A peptide factor originally identified by its ability to stimulate the phosphorylation the erbB-2 receptor (RECEPTOR, ERBB-2). It is a ligand for the erbB-3 receptor (RECEPTOR, ERBB-3) and the erbB-4 receptor. Variant forms of NEUREGULIN-1 occur through alternative splicing of its mRNA.
A family of peptides originally found as factors that stimulate the phosphorylation of the erbB-2 receptor (RECEPTORS, ERBB-2). Multiple variant forms of NEUREGULINS occur due to alternative splicing of their mRNAs. The NEUREGULINS include products from the three known genes (NGR1; NGR2 and NGR3).
A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF RECEPTOR and the ERBB-2 RECEPTOR. Overexpression of the erbB-3 receptor is associated with TUMORIGENESIS.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
Retrovirus-associated DNA sequences (erbB) originally isolated from, or related to, the avian erythroblastosis virus (AEV). These genes code for the epidermal growth factor receptor (EGFR) family of receptors which is important in the control of normal cell proliferation and in the pathogenesis of human cancer. The genes include erbB-1 (GENES, ERBB-1), erbB-2 (GENES, ERBB-2), and erbB-3, all of which show abnormalities of expression in various human neoplasms.
Transforming proteins encoded by erbB oncogenes from the avian erythroblastosis virus. The protein is a truncated form of the EGF receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) whose kinase domain is constitutively activated by deletion of the ligand-binding domain.
The erbB-2 gene is a proto-oncogene that codes for the erbB-2 receptor (RECEPTOR, ERBB-2), a protein with structural features similar to the epidermal growth factor receptor. Its name originates from the viral oncogene homolog (v-erbB) which is a truncated form of the chicken erbB gene found in the avian erythroblastosis virus. Overexpression and amplification of the gene is associated with a significant number of adenocarcinomas. The human c-erbB-2 gene is located at 17q21.2.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Tumors or cancer of the human BREAST.
A cell line derived from cultured tumor cells.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A transmembrane mucin that is found in a broad variety of epithelial tissue. Mucin-4 may play a role in regulating cellular adhesion and in cell surface signaling from the ERBB-2 RECEPTOR PROTEIN-TYROSINE KINASE. Mucin-4 is a heterodimer of alpha and beta chains. The alpha and beta chains result from the proteolytic cleavage of a precursor protein.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)
Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)
Antibodies produced by a single clone of cells.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Authoritative treatises on drugs and preparations, their description, formulation, analytic composition, physical constants, main chemical properties used in identification, standards for strength, purity, and dosage, chemical tests for determining identity and purity, etc. They are usually published under governmental jurisdiction (e.g., USP, the United States Pharmacopoeia; BP, British Pharmacopoeia; P. Helv., the Swiss Pharmacopoeia). They differ from FORMULARIES in that they are far more complete: formularies tend to be mere listings of formulas and prescriptions.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed)
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
Component of the NATIONAL INSTITUTES OF HEALTH. Through basic and clinical biomedical research and training, it conducts and supports research with the objective of cancer prevention, early stage identification and elimination. This Institute was established in 1937.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
An operating division of the US Department of Health and Human Services. It is concerned with the overall planning, promoting, and administering of programs pertaining to health and medical research. Until 1995, it was an agency of the United States PUBLIC HEALTH SERVICE.
Cellular proteins encoded by the H-ras, K-ras and N-ras genes. The proteins have GTPase activity and are involved in signal transduction as monomeric GTP-binding proteins. Elevated levels of p21 c-ras have been associated with neoplasia. This enzyme was formerly listed as EC 3.6.1.47.
Transforming protein encoded by ras oncogenes. Point mutations in the cellular ras gene (c-ras) can also result in a mutant p21 protein that can transform mammalian cells. Oncogene protein p21(ras) has been directly implicated in human neoplasms, perhaps accounting for as much as 15-20% of all human tumors. This enzyme was formerly listed as EC 3.6.1.47.

Immune responses to all ErbB family receptors detectable in serum of cancer patients. (1/5700)

Employing NIH3T3 transfectants with individual human ErbB receptor coding sequences as recombinant antigen sources, we detected by immunoblot analysis specific immunoreactivity against all four ErbB receptors among 13 of 41 sera obtained from patients with different types of epithelial malignancies. Overall, serum positivity was most frequently directed against ErbB2 followed by EGFR, ErbB3 and ErbB4. Specificity patterns comprised tumor patients with unique serum reactivity against ErbB2 or ErbB4. Moreover, approximately half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB2, EGFR and ErbB4, ErbB2 and ErbB3 or EGFR, ErbB2 and ErbB3. Serum reactivity was confirmed for the respective ErbB receptors expressed by human tumor cells and corroborated on receptor-specific immunoprecipitates. Positive sera contained ErbB-specific antibodies of the IgG isotype. Representative immunohistochemical analysis of tumor tissues suggested overexpression of ErbB receptors for which serum antibodies were detectable in five of six patients. These findings implicate multiple ErbB receptors including ErbB3 and ErbB4 in addition to EGFR and ErbB2 in primary human cancer. Heterogeneity of natural ErbB-specific responses in cancer patients warrants their evaluation in light of immunotherapeutic approaches targeting these receptors.  (+info)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (2/5700)

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.  (+info)

An intramembrane modulator of the ErbB2 receptor tyrosine kinase that potentiates neuregulin signaling. (3/5700)

The ErbB2 receptor tyrosine kinase plays a critical role in a variety of developmental processes, and its aberrant activation may contribute to the progression of some breast and ovarian tumors. ASGP2, a transmembrane glycoprotein found on the surface of the highly metastatic ascites 13762 rat mammary adenocarcinoma cell line, is constitutively associated with ErbB2 in these cells and in mammary tissue from pregnant rats. Expression studies indicate that ASGP2 interacts directly and specifically with ErbB2 through one of its epidermal growth factor-like domains and that the co-expression of the two proteins in the same cell dramatically facilitates their direct stable interaction. Ectopic expression of ASGP2 in human melanoma tumor cells potentiates the response of endogenous ErbB2 to the neuregulin-1 growth factor. These observations point to a novel intramembrane mechanism for the modulation of receptor tyrosine kinase activity.  (+info)

Immunohistochemical analysis of c-yes and c-erbB-2 oncogene products and p53 tumor suppressor protein in canine mammary tumors. (4/5700)

In order to evaluate the involvement of c-yes and c-erbB-2 oncogene products, and p53 tumor suppressor protein in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 79 mammary tumors were analyzed immunohistochemically using antibodies against human c-yes p62 and c-erbB-2 products and p53. These 79 tumors were divided into 2 groups: 32 benign (2 adenosis, 7 simple adenomas, 14 complex adenomas, and 9 benign mixed mammary tumors) and 47 malignant tumors (26 simple adenocarcinomas, 7 complex adenocarcinomas, 5 solid carcinomas, 2 sclerosing carcinomas, 6 malignant mixed mammary tumors, and 1 malignant myoepithelioma). As a result of immunostaining, 40.6% (13/32) of the benign tumors and 21.3% (10/47) of the malignant tumors expressed the c-Yes oncogene product, ErbB-2 expression was detected in 50% (16/32) of the benign tumors and in 19.1% (9/47) of the malignant tumors. P53 expression was detected in 16% (4/25) of the benign tumors and in 30.6% (11/36) of the malignant tumors. Co-expression of c-Yes and ErbB-2, ErbB-2 and p53, and all 3 products was detected in 6, 1 and 7 tumors, respectively.  (+info)

Tyrosine kinase inhibitor emodin suppresses growth of HER-2/neu-overexpressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel. (5/5700)

Overexpression of the HER-2/neu proto-oncogene, which encodes the tyrosine kinase receptor p185neu, has been observed in tumors from breast cancer patients. We demonstrated previously that emodin, a tyrosine kinase inhibitor, suppresses tyrosine kinase activity in HER-2/neu-overexpressing breast cancer cells and preferentially represses transformation phenotypes of these cells in vitro. In the present study, we examined whether emodin can inhibit the growth of HER-2/neu-overexpressing tumors in mice and whether emodin can sensitize these tumors to paclitaxel, a commonly used chemotherapeutic agent for breast cancer patients. We found that emodin significantly inhibited tumor growth and prolonged survival in mice bearing HER-2/neu-overexpressing human breast cancer cells. Furthermore, the combination of emodin and paclitaxel synergistically inhibited the anchorage-dependent and -independent growth of HER-2/neu-overexpressing breast cancer cells in vitro and synergistically inhibited tumor growth and prolonged survival in athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of p185neu. Both immunohistochemical staining and Western blot analysis showed that emodin decreases tyrosine phosphorylation of HER-2/neu in tumor tissue. Taken together, our results suggest that the tyrosine kinase activity of HER-2/neu is required for tumor growth and chemoresistance and that tyrosine kinase inhibitors such as emodin can inhibit the growth of HER-2/neu-overexpressing tumors in mice and also sensitize these tumors to paclitaxel. The results may have important implications in chemotherapy for HER-2/neu-overexpressing breast tumors.  (+info)

Trimodality therapy in stage III non-small cell lung cancer: prediction of recurrence by assessment of p185neu. (6/5700)

In a trimodality treatment approach for stage III non-small cell lung cancer the prognostic impact of pretherapeutic p185neu assessment was evaluated. Fifty-four patients were admitted to chemotherapy followed by twice-daily radiation with concomittant low-dose chemotherapy and subsequent surgery. Immunohistochemical assessment of p185neu expression was performed in paraffin-embedded mediastinal lymph node metastases, by mediastinoscopy biopsy prior to therapy. Paraffin-embedded biopsies of mediastinal lymph node metastases were available in 33 cases. Seven out of eight patients with positive p185neu staining developed distant metastases, in contrast to seven out of 25 negative cases. Expression of p185neu in mediastinal lymph node metastases was a significant predictor for progression-free survival (p=0.047) and resulted mainly from significant differences in metastases-free survival (p185neu-positive versus p185neu-negative: median, 11 versus 19 months; 2- and 3-yr rates, 13% and 0% versus 40% and 32%; p=0.04). On the basis of these preliminary results it was concluded that further evaluation of p185neu expression in trials on neoadjuvant and adjuvant therapy is warranted. When the prognostic impact of p185neu in such trials with larger patient numbers is confirmed, this may contribute to the identification of stratification variables for future treatment approaches of non-small cell lung cancer.  (+info)

Inhibition of aberrant proliferation and induction of apoptosis in HER-2/neu oncogene transformed human mammary epithelial cells by N-(4-hydroxyphenyl)retinamide. (7/5700)

Epithelial cells from non-cancerous mammary tissue in response to exposure to chemical carcinogens or transfection with oncogenes exhibit hyperproliferation and hyperplasia prior to the development of cancer. Aberrant proliferation may, therefore, represent a modifiable early occurring preneoplastic event that is susceptible to chemoprevention of carcinogenesis. The synthetic retinoid N-(4-hydroxyphenyl)retinamide (HPR), has exhibited preventive efficacy in several in vitro and in vivo breast cancer models, and represents a promising chemopreventive compound for clinical trials. Clinically relevant biochemical and cellular mechanisms responsible for the chemopreventive effects of HPR, however, are not fully understood. Experiments were performed on preneoplastic human mammary epithelial 184-B5/HER cells derived from reduction mammoplasty and initiated for tumorigenic transformation by overexpression of HER-2/neu oncogene, to examine whether HPR inhibits aberrant proliferation of these cells and to identify the possible mechanism(s) responsible for the inhibitory effects of HPR. Continuous 7-day treatment with HPR produced a dose-dependent, reversible growth inhibition. Long-term (21 day) treatment of 184-B5/HER cells with HPR inhibited anchorage-dependent colony formation by approximately 80% (P < 0.01) relative to that observed in the solvent control. A 24 h treatment with cytostatic 400 nM HPR produced a 25% increase (P = 0.01) in G0/G1 phase, and a 36% decrease (P = 0.01) in S phase of the cell cycle. HPR treatment also induced a 10-fold increase (P = 0.02) in the sub-G0 (apoptotic) peak that was down-regulated in the presence of the antioxidant N-acetyl-L-cysteine. Treatment with HPR resulted in a 30% reduction of cellular immunoreactivity to tyrosine kinase, whereas immunoreactivity to p185HER remained essentially unaltered. HPR exposure resulted in time-dependent increase in cellular metabolism of the retinoid as evidenced by increased formation of the inert metabolite N-(4-methoxyphenyl)-retinamide (MPR) and progressive increase in apoptosis. Thus, HPR-induced inhibition of aberrant proliferation may be caused, in part, by its ability to inhibit HER-2/neu-mediated proliferative signal transduction, retard cell cycle progression and upregulate cellular apoptosis.  (+info)

Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6. (8/5700)

A new human breast cancer cell line, KPL-4, was recently isolated from the malignant pleural effusion of a breast cancer patient with an inflammatory skin metastasis. This cell line can be cultured under serum-free conditions and is tumorigenic in female athymic nude mice. Flow cytometric analysis revealed the expression of Erb B-1, -2 and -3. Dot blot hybridization showed a 15-fold amplification of the erb B-2. Reverse transcription-polymerase chain reaction analysis showed a detectable level of mRNA expression of all the Erb B family receptors. In addition, all the receptors were autophosphorylated under a serum-supplemented condition. Unexpectedly, transplanted KPL-4 tumours induced cachexia of recipient mice. A high concentration of interleukin-6 (IL-6) was detected in both the culture medium and the serum of mice. The weight of tumours significantly correlated with the serum IL-6 level. The antiproliferative effect of a humanized anti-Erb B-2 monoclonal antibody, rhuMAbHER2, was investigated. This antibody significantly inhibited the growth of KPL-4 cells in vitro but modestly in vivo. Loss of mouse body weight was partly reversed by rhuMAbHER2. These findings suggest that KPL-4 cells may be useful in the development of new strategies against breast cancer overexpressing the Erb B family receptors and against IL-6-induced cachexia.  (+info)

Human Epidermal growth factor Receptor type 2 (HER2) is over expressed in 20.0-30.0% of breast cancers and is currently evaluated histopathologically. Immunohistochemistry and fluorescence in situ hybridization require invasive enucleation of the tumor tissue and may be affected by heterogeneity. Serum marker tests are more objective because of the uniformity of the study material. Serum HER2 levels are important for breast cancer care. However, the clinical utility of serum HER2 testing is unclear. We evaluated serum HER2 as a marker of therapeutic response in breast cancer.
TY - JOUR. T1 - Survival of HER2-positive primary breast cancer patients treated by neoadjuvant chemotherapy plus trastuzumab. T2 - A multicenter retrospective observational study (JBCRG-C03 study). AU - Takada, M.. AU - Ishiguro, H.. AU - Nagai, S.. AU - Ohtani, S.. AU - Kawabata, H.. AU - Yanagita, Y.. AU - Hozumi, Y.. AU - Shimizu, C.. AU - Takao, S.. AU - Sato, N.. AU - Kosaka, Y.. AU - Sagara, Y.. AU - Iwata, H.. AU - Ohno, S.. AU - Kuroi, K.. AU - Masuda, N.. AU - Yamashiro, H.. AU - Sugimoto, M.. AU - Kondo, M.. AU - Naito, Yasuhiro. AU - Sasano, H.. AU - Inamoto, T.. AU - Morita, S.. AU - Toi, M.. PY - 2014. Y1 - 2014. N2 - We investigated the disease-free survival (DFS) of HER2-positive primary breast cancer patients treated with neoadjuvant chemotherapy plus trastuzumab, as well as predictive factors for DFS and pathologic response. Data from 829 female patients treated between 2001 and 2010 were collected from 38 institutions in Japan. Predictive factors were evaluated using ...
Overexpression of the oncogene HER2/neu (c-erbB-2) occurs in up to 30% of breast cancers and is correlated with reduced survival, especially in node-positive disease. The aim of this study was to identify genes associated with the aggressive phenotype of HER2/neu-positive breast cancer cells using cDNA microarrays. RNA was extracted from three HER2/neu-positive and three HER2/neu-negative breast cancer cell lines. Pooled RNA was hybridized in duplicate to the breast specific microarray filters from Research Genetics containing 5184 unique cDNAs. Subsequently, a similar comparison was performed for pooled RNAs from 10 node-positive, ER-positive invasive ductal carcinomas, half of which were HER2/neu overexpressers. In HER2/neu overexpressing breast cancer cell lines, 90 (1.7%) genes were up-regulated and 46 (0.9%) were down-regulated, compared to cell lines with low HER2/neu protein levels. In contrast, in HER2/neu overexpressing primary breast cancers, more genes were down-regulated (N = 132, 2.5%) than
TY - JOUR. T1 - Lapatinib plus capecitabine resolved human epidermal growth factor receptor 2-positive brain metastases. AU - Glück, Stefan. AU - Castrellon, Aurelio. PY - 2009/11/1. Y1 - 2009/11/1. N2 - Brain metastases affect 25%-30% of women with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and are associated with a high burden of disease and poor prognosis. A 55-year-old woman presented with HER2-positive, hormone receptor-positive, locally advanced infiltrating ductal carcinoma. She received 4 cycles of neoadjuvant docetaxel (75 mg/m2) plus trastuzumab (6 mg/kg) on a 21-day cycle, resulting in complete pathologic response at the time of surgery. Trastuzumab (6 mg/kg every 21 days) plus anastrozole (1 mg/d) was continued for 1 year. Two years later, the patient progressed with pulmonary nodules and a large pleural effusion. Computed tomography and positron emission tomography revealed multiple lesions in the liver and thoracic spine but no evidence of ...
in Breast Cancer (2014), 6. Many systemic treatment options are available for advanced breast cancer, including endocrine therapy, chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, and other targeted agents ... [more ▼]. Many systemic treatment options are available for advanced breast cancer, including endocrine therapy, chemotherapy, anti-human epidermal growth factor receptor 2 (HER2) therapy, and other targeted agents. Recently, everolimus, a mammalian target of rapamycin (mTOR) inhibitor, combined with exemestane, an aromatase inhibitor, has been approved in Europe and the USA for patients suffering from estrogen receptor-positive, HER2-negative advanced breast cancer previously treated by a nonsteroidal aromatase inhibitor, based on the results of BOLERO-2 (Breast cancer trials of OraL EveROlimus). This study showed a statistically significant and clinically meaningful improvement in median progression-free survival. Results concerning the impact on overall ...
Clinical studies have suggested that human epidermal growth factor receptor-2 (HER2) provide a useful target for antitumor therapy. We previously described the generation of a chimeric HER2-targeted immunocasp-3 protein. In this study, we extend the repertoire of chimeric proapoptotic proteins with …
Single-agent poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been approved as the first targeted therapy available for patients with BRCA-mutated HER2-negative metastatic breast cancer. This meta-analysis aimed to better evaluate activity, efficacy and safety of single-agent PARPi in this population. A systematic search of Medline, Embase and conference proceedings up to 31 January 2018 was conducted to identify randomised controlled trials (RCTs) investigating single-agent PARPi versus monochemotherapy in patients with BRCA-mutated HER2-negative metastatic breast cancer. Using the random-effect model, we calculated summary risk estimates (pooled HR and OR with 95% CI) for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), any grade and grade 3-4 adverse events (AEs), treatment discontinuation rate and time to deterioration in quality of life (QoL). Two RCTs (n=733) were included. As compared with monochemotherapy, single-agent PARPi significantly ...
New life-saving treatments for HER-2 Negative Metastatic Breast Cancer in clinical trial on Phase II Study of Pembrolizumab and Nab-paclitaxel in HER-2 Negative Metastatic Breast Cancer
TY - JOUR. T1 - Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer. T2 - A case-control study. AU - Haffty, Bruce G.. AU - Brown, Felix. AU - Carter, Darryl. AU - Flynn, Stuart. PY - 1996/7/1. Y1 - 1996/7/1. N2 - Purpose: The purpose of this study is to determine the prognostic significance of overexpression of the HER-2 neu oncoprotein with respect to local relapse following conservative surgery and radiation therapy (CS+RT). Methods and Materials: Twenty consecutive patients who sustained a local recurrence as the first and only site of failure following CS+RT comprised the case population base for this study. Only patients who received no adjuvant systemic chemotherapy or tamoxifen were selected for analysis. Following the identification of 20 consecutive local-relapse patients, the patient database was searched for 20 matching control patients who did not sustain a local relapse. Each control patient was ...
TY - JOUR. T1 - Eribulin in triple negative metastatic breast cancer. T2 - Critic interpretation of current evidence and projection for future scenarios. AU - Pizzuti, Laura. AU - Krasniqi, Eriseld. AU - Barchiesi, Giacomo. AU - Mazzotta, Marco. AU - Barba, Maddalena. AU - Amodio, Antonella. AU - Massimiani, Gioia. AU - Pelle, Fabio. AU - Kayal, Ramy. AU - Vizza, Enrico. AU - Grassadonia, Antonino. AU - Tomao, Silverio. AU - Venuti, Aldo. AU - Gamucci, Teresa. AU - Marchetti, Paolo. AU - Natoli, Clara. AU - Sanguineti, Giuseppe. AU - Ciliberto, Gennaro. AU - Vici, Patrizia. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Triple negative breast cancer (TNBC) is characterized by distinctive biological features that confer an aggressive clinical behavior. In TNBC patients, the absence of well-defined driver pathways such as hormonal receptor expression or hyperactivation of the human epidermal growth factor receptor 2 (HER2) significantly reduce the spectrum of therapeutic options, which are currently mainly ...
Objective: To assess the safety/tolerability of the combination lapatinib (L) and docetaxel (D) in patients with Her 2/neu overexpressing breast cancer (BC). This study is important as it will define how to deliver lapatinib with taxotere, a highly active drug in breast cancer. Patients and Methods: Female patients (pts) with locally advanced, inflammatory or large operable BC were treated with escalating doses of L from 1000 to 1250 mg/day, in combination with D given IV every 21 days at doses ranging from 75 to 100 mg/m2 for 4 cycles. At least 3 pts were treated at each dose level. The definition of dose limiting toxicity (DLT) is based on the toxicity assessed at cycle 1 as follows: any grade 3−4 non hematological toxicity, ANC < 0.5 G/L lasting for 7 days or more, febrile neutropenia or thrombocytopenia
Triple-negative breast cancer (TNBC) which is defined by the lack of expression of estrogen receptor (ER) and progesterone receptor (PR) and absence of human epidermal growth factor receptor type 2 (H
Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and ...
Carcinoma of the breast and ovary account for one-third of all cancers occurring in women and together are responsible for approximately one-quarter of cancer-related deaths in females. The HER-2/neu proto-oncogene is amplified in 25 to 30 percent of human primary breast cancers and this alteration is associated with disease behavior. In this report, several similarities were found in the biology of HER-2/neu in breast and ovarian cancer, including a similar incidence of amplification, a direct correlation between amplification and over-expression, evidence of tumors in which overexpression occurs without amplification, and the association between gene alteration and clinical outcome. A comprehensive study of the gene and its products (RNA and protein) was simultaneously performed on a large number of both tumor types. This analysis identified several potential shortcomings of the various methods used to evaluate HER-2/neu in these diseases (Southern, Northern, and Western blots, and ...
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Additional file 1: Figure S1. of Palmitate-induced ER stress increases trastuzumab sensitivity in HER2/neu-positive breast cancer cells
PRIMARY OBJECTIVES:. I. To determine the recommended phase II dose of veliparib along with carboplatin on a 14-day and 21-day schedule in patients with Her2 negative metastatic breast cancer that are estrogen receptor (ER)/progesterone receptor(PR) negative or ER and/or PR positive with defects in Fanconi Anemia (FA) pathway repair genes.. II. To determine the safety and tolerability of combining veliparib on a 14-day and 21-day schedule with carboplatin in this patient population.. III. To determine the preliminary efficacy of this combination in this patient population.. SECONDARY OBJECTIVES:. I. To determine the pharmacodynamic endpoints of poly(ADP-ribose) polymerase (PARP) inhibition in the tumor by using, A) 3-[F-18]fluoro-3-deoxythymidine positron emission tomography (FLT-PET) of the target lesions, B) circulating tumor cells to detect the induction of the histone variant gamma H2AX, and C) peripheral blood mononuclear cells to assess poly ADP-Ribose (PAR) levels.. II. To determine ...
Clinical benefit rate (CR, PR, or SD = 24 weeks) for women For ErbB2 Positive Advanced Breast Cancer. Clinical benefit rate was the percentage of subjects who achieved overall tumor response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), ,=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.. Clinical Benefit (CB) = CR + PR + SD ,= 24 weeks. ...
CancerConnect News: In patients with human epidermal growth factor receptor (HER2)-positive advanced breast cancer, the combination of Herceptin® (trastuzumab) plus a taxane resulted in delayed time to cancer progression and was associated with fewer side effects than Tykerb® (lapatinib) plus a taxane, according to final clinical trial results reported in the Journal of Clinical Oncology. The HER2 pathway is a biological pathway involved in cellular replication and growth. Approximately 20-25% of breast cancers overexpress the HER2 protein and are referred to as HER2-positive. Herceptin and Tykerb both target and block the HER2-protein, and are used for the treatment of both early-stage and more advanced HER2-positive breast cancer.. The NCIC Clinical Trials Group enrolled and evaluated 537 patients in 21 countries with centrally confirmed HER2-postive advanced breast cancer that were treated with a taxane plus Tykerb or Herceptin. These individuals have now been followed a median of 21.5 ...
With the increasing availability of agents that target individual ErbB receptors, the possible combinations incorporating these agents are numerous. This discussion will be limited to combinations employing trastuzumab and EGFR tyrosine kinase inhibitors in the treatment of HER-2-positive breast cancer. HER-2-positive metastatic breast cancer may be the best setting in which to test the concurrent inhibition of multiple ErbB receptors, because the pathogenesis and progression of the disease are driven by amplification of the HER-2/neu gene, and breast cancer patients can be selected for targeted therapy based on the presence of this molecular abnormality. Trastuzumab, the prototypical ErbB-targeted therapy, has a single agent response rate of 34% in women with metastatic HER-2/neu-positive breast cancer as measured by fluorescence in situ hybridization (47). Preclinical experiments have shown that trastuzumab has synergistic activity when combined with chemotherapeutic agents such as ...
PHILADELPHIA, Jan. 7, 2021 /PRNewswire/ - CARISMA Therapeutics Inc., a biopharmaceutical company focused on discovering and developing innovative immunotherapies, announced today that it has completed its Series B equity financing providing for gross proceeds of $47 million, bringing CARISMAs total capital raised to nearly $109 million. The funding will be used to advance current pipeline and discovery programs, including the Phase I clinical trial of CARISMAs lead candidate, CT-0508, an anti-human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M), which recently initiated trial enrollment and patient screening for the first-of-its-kind, first-in-human study of CAR-M. The funding will also allow CARISMA to further develop its proprietary engineered-macrophage platform, continue pipeline expansion in cancer indications and enable the platforms application to disease areas outside of cancer.. Full news article here.. ...
Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/Epidermal Growth Factor Receptor (HER1/EGFR) tyrosine kinase inhibitor. It is marketed as Tarceva for the treatment of locally advanced or metastatic non-small cell lung cancer or pancreatic cancer.
We are at the beginning of Personalized Medicine. This concept can take many forms. It can mean an evaluation the DNA of a breast cancer that predicts a poor prognosis. (Overexpression of the human epidermal growth factor receptor type 2, HER2) It can also mean a diagnostic test to determine if a patient will response to a specific type of cancer treatment like Gleevec (imatinib). Recently, several companies have started offering over the counter DNA tests. These are presently being evaluated by the FDA because of concerns for consistently and how they will be interpreted ...
Lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in the treatment of HER-2-overexpressing locally advanced or metastatic breast cancer: systematic review and meta-analysis Tobias Engel Ayer Botrel, Luciano Paladini, Otávio Augusto C Clark Evidencias Scientific Information, Campinas, São Paulo, Brazil Background: This paper reports a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of lapatinib plus chemotherapy or endocrine therapy (CET) versus CET alone in human epidermal growth factor receptor 2-overexpressing (HER-2+) locally advanced or metastatic breast cancer. Methods: Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were progression-free survival and overall survival. The side effects of each treatment were analyzed. The data extracted from the studies were combined by using the hazard ratio or risk ratio with their corresponding 95% confidence interval (CI).
Overexpression of the HER2/Neu (ErbB2) proto-oncogene is associated with breast cancer progression and poor patient prognosis. Herceptin (trastuzumab) is a humanized IgG1 against the ectodomain of the HER2 receptor. In combination with chemotherapy, it induces regression of HER2-overexpressing metas …
Amplification or overexpression of HER-2/neu in cancer cells confers resistance to apoptosis and promotes cell growth. The cellular localization of p21Cip1/WAF1 has been proposed to be critical either in promoting cell survival or in inhibiting cell growth. Here we show that HER-2/neu-mediated cell growth requires the activation of Akt, which associates with p21Cip1/WAF1 and phosphorylates it at threonine 145, resulting in cytoplasmic localization of p21Cip1/WAF1. Furthermore, blocking the Akt pathway with a dominant-negative Akt mutant restores the nuclear localization and cell-growth-inhibiting activity of p21Cip1/WAF1. Our results indicate that HER-2/neu induces cytoplasmic localization of p21Cip1/WAF1 through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt.
Treatment of human epidermal growth factor receptor 2 (HER2)-driven breast cancer with the HER-targeting tyrosine kinase inhibitor lapatinib can lead to a rapid compensatory increase in expression, signaling activity and relocalization of HER3 to the plasma membrane, which may attenuate the response to lapatinib. This might imply a potential role for a more dynamic assessment of HER3 tumor status using molecular imaging techniques, such as positron emission tomography (PET), instead of immunohistochemical HER3 staining on tumor biopsies. Here, we explored the feasibility of a dynamic assessment of HER3 status during lapatinib treatment in human breast cancer xenografts using zirconium-89 labeled anti-human HER3 monoclonal antibody (mAb) as a potential tracer for animal PET imaging.. The anti-human HER3 mouse mAb MAB3481 was used for all experiments. The effect of lapatinib treatment on HER3 expression and HER3 mAb internalization in human breast cancer cell lines SKBR3 and BT474 was determined ...
These studies in a rat model of LM human breast cancer demonstrated that regional IT therapy with MAb 4D5, directed against the HER2/neu receptor, inhibits growth of HER2/neu overexpressing xenografts. Metastatic breast cancer lesions outside of the CNS respond to therapy with i.v. anti-HER2/neu antibody (9 , 10) , but MAbs administered i.v. do not cross the blood-brain barrier and cannot be detected in the CSF or in LM tumor tissue (26 , 27) . A recently completed clinical trial using chemotherapy plus anti-HER2/neu antibody to treat metastatic breast cancer that overexpresses HER2 (10) found that in patients with progressive disease, the CNS was the only site of disease progression in 23 of 153 (15%) of those treated with chemotherapy plus antibody compared with 16 of 200 (8%) of those treated with chemotherapy alone. In the current study, continuous IVent infusion produced therapeutic concentrations of the antibody in the CSF and resulted in antibody attachment to LM human breast cancer ...
Introduction: Despite improvements in treatment with newly approved HER2-targeted therapies, safe and effective treatments are still needed, not only for HER2-positive metastatic breast cancer (MBC), but also for MBC expressing intermediate levels of HER2 that are still considered HER2-negative (e.g. IHC 2+, FISH-negative). MM-302 is a liposomal antibody drug conjugate (ADC) designed to target doxorubicin to HER2-overexpressing cancer cells. MM-302 is currently being evaluated in HER2-positive locally advanced breast cancer (LABC)/MBC patients in the registration-directed HERMIONE trial. The objective of this study was to compare the relative efficacy of MM-302 and PLD in treating HER2-intermediate MBC (corresponding to 1+/2+ by IHC) using models that closely mimic how HER2-overexpressing metastatic tumors are established in humans.. Methods: To establish metastatic disease, the murine 4T1-HER2 cell line engineered to express intermediate levels of Her2 (median of ∼1×105 HER2 receptors/cell), ...
Trastuzumab is by far the drug of choice for treatment of human epidermal growth factor receptor 2 (Her2) overexpressing breast cancer patients. However, frequently, the therapy remains ineffective...
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Health,Researchers Edith Perez and Edward Romond reported from two separate trials that Breast cancer patients with Her2-positive were effectively treated with Herceptin therapy using trastuzumab. //The results of their study were published in the journal The New England Journal of Medicine. The researchers compiled results from two clinical trials which compared patients getting only chemotherapy with,Trastuzumab,therapy,effective,for,Breast,cancer,patients,with,Her-2/neu,positive,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Doxorubicin has been an integral part of the treatment of women with breast cancer for many years. Since amrubicin may have more activity than doxorubic
This study will evaluate the efficacy and safety of 2 doses of Avastin in combination with docetaxel, versus docetaxel plus placebo, in patients with me
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The discovery of Human Epidermal growth factor Receptor 2 (HER2) positive breast cancer subtypes is not yet complete, according to Mark D. Pegram, MD, who will be delivering a presentation on the different clinical outcomes of these subtypes at the Miami Breast Cancer Conference this week.
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Cyclin-dependent kinase (CDK4/6) inhibitors in combination with endocrine therapy are currently the optimal first line treatment for hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) non-amplified metastatic breast cancer (MBC). However, not all patients benefit from this treatment and all patients will inevitably progress. Identifying therapeutic strategies in this setting is therefore of immediate clinical importance. We present an overview of the mechanisms of resistance to CDK4/6 inhibitors and review potential biomarkers that may guide therapy selection. We also discuss the use of CDK4/6 inhibitors in the context of non-HR-positive/HER2-non-amplified breast cancer and in combination with therapies other than endocrine therapy.
OBJECTIVES: Brain metastases (BM) are a significant complication of metastatic breast cancer (MBC). The high incidence of BM in HER2 overexpressing MBC is now well recognized, however, the optimal management of such patients is not yet clearly defined. We aimed to analyze factors affecting survival after diagnosis of BM in patients treated in our center. MATERIALS AND METHODS: Retrospective analysis of survival in all patients treated with antineoplastic therapy for BM from MBC in our institution between May 1st 2002 and April 30th 2005, according to HER2 expression and use of trastuzumab after diagnosis of BM. RESULTS: The median survival of the 26 patients with HER2 overexpressing disease after diagnosis of BM was significantly longer than that of the 60 patients with HER2 nonoverexpressing disease (6.2 vs. 3.8 months, P = 0.027). Further analysis revealed that this seems to be due to the favorable outcome of the 70% (n = 18) of HER2 overexpressing patients who received trastuzumab after BM were
Background: Testing for human epidermal growth factor receptor-2 (HER-2) is routinely performed after breast cancer diagnosis by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). FISH is more accurate and reproducible, often considered the gold standard, and a more reliable predictor of a patients response to HER-2 directed therapies in clinical practice. The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule located in close proximity to HER-2 on chromo some 17q11-12 and has been shown to be an independent adverse prognostic marker in breast cancer. Methods: We performed western blotting analysis of protein extracts from 563 annotated frozen breast tumors, collected from 1988 - 1998. GRB7 and HER-2 bands were assigned low or high values compared to specific protein controls, and tubulin bands. HER-2 FISH was performed on a subset of these tumors using an FDA approved Path Vysion kit on 4 μm frozen sections. ...
Methods for the detection, monitoring and treatment of malignancies in which the HER-2/neu oncogene is associated are disclosed. Detection of specific T cell activation (e.g., by measuring the proliferation of T cells) in response to in vitro exposure to the HER-2/neu protein, or detection of immunocomplexes formed between the HER-2/neu protein and antibodies in body fluid, allows the diagnosis of the presence of a malignancy in which the HER-2/neu oncogene is associated. The present invention also discloses methods and compositions, including peptides, for treating such malignancies.
1. Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature. 2003;421:756-760 2. Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U. et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science. 1985;230:1132-1139 3. Hudis CA. Trastuzumab-mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39-51 4. Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol. 2009;27:1323-1333 5. Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med. 2008;358:1409-1411 6. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival ...
|p|erbB-2|strong| |/strong|is a transmembrane, tyrosine kinase (TK) receptor whose overexpression is associated with adverse prognosis in breast cancer|sup|1|/sup|.|/p| |p|The human epidermal growth factor receptor (erbB-2) is a transmembrane receptor th
Approximately a quarter of women with HER2 positive breast cancer, who were treated with a combination of the targeted drugs lapatinib and trastuzumab before surgery and chemotherapy, saw their tumours shrink significantly or even disappear, according to results from a clinical trial. The University of Manchesters Professor Nigel Bundred tol...
TY - JOUR. T1 - Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer. T2 - Results of the randomized phase II CHER-LOB study. AU - Guarneri, Valentina. AU - Frassoldati, Antonio. AU - Bottini, Alberto. AU - Cagossi, Katia. AU - Bisagni, Giancarlo. AU - Sarti, Samanta. AU - Ravaioli, Alberto. AU - Cavanna, Luigi. AU - Giardina, Giovanni. AU - Musolino, Antonino. AU - Untch, Michael. AU - Orlando, Laura. AU - Artioli, Fabrizio. AU - Boni, Corrado. AU - Generali, Daniele Giulio. AU - Serra, Patrizia. AU - Bagnalasta, Michela. AU - Marini, Luca. AU - Piacentini, Federico. AU - DAmico, Roberto. AU - Conte, PierFranco. PY - 2012/6/1. Y1 - 2012/6/1. N2 - Purpose: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II ...
TY - JOUR. T1 - Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy. AU - Lipton, Allan. AU - Leitzel, Kim. AU - Ali, Suhail M.. AU - Carney, Walter. AU - Platek, Greg. AU - Steplewski, Klaudia. AU - Westlund, Ron. AU - Gagnon, Robert. AU - Martin, Anne Marie. AU - Maltzman, Julie. PY - 2011/11/1. Y1 - 2011/11/1. N2 - BACKGROUND: Changes in serum human epidermal growth factor receptor 2 (HER2) levels associated with clinical outcomes, including objective response rate, progression-free survival (PFS), and overall survival have been reported in patients with metastatic breast cancer (MBC) receiving trastuzumab and chemotherapy. This study investigated whether baseline or changes in serum HER2 correlated with overall response rate (ORR) and/or PFS in patients with MBC receiving first-line lapatinib monotherapy. METHODS: The EGF20009 study ...
TY - JOUR. T1 - Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. AU - Carey,Lisa A.. AU - Berry,Donald A.. AU - Cirrincione,Constance T.. AU - Barry,William T.. AU - Pitcher,Brandelyn N.. AU - Harris,Lyndsay N.. AU - Ollila,David W.. AU - Krop,Ian E.. AU - Henry,Norah Lynn. AU - Weckstein,Douglas J.. AU - Anders,Carey K.. AU - Singh,Baljit. AU - Hoadley,Katherine A.. AU - Iglesia,Michael. AU - Cheang,Maggie Chon U.. AU - Perou,Charles M.. AU - Winer,Eric P.. AU - Hudis,Clifford A.. PY - 2016/2/20. Y1 - 2016/2/20. N2 - Purpose Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (PCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, ...
Breast cancer is a heterogeneous disease encompassing a number of phenotypically diverse tumours. Expression levels of the oestrogen, progesterone and HER2/neu receptors which characterize clinically distinct breast tumours have been shown to change during disease progression and in response to systemic therapies. Mi(cro)RNAs play critical roles in diverse biological processes and are aberrantly expressed in several human neoplasms including breast cancer, where they function as regulators of tumour behaviour and progression. The aims of this study were to identify miRNA signatures that accurately predict the oestrogen receptor (ER), progesterone receptor (PR) and HER2/neu receptor status of breast cancer patients to provide insight into the regulation of breast cancer phenotypes and progression. Expression profiling of 453 miRNAs was performed in 29 early-stage breast cancer specimens. miRNA signatures associated with ER, PR and HER2/neu status were generated using artificial neural networks (ANN), and
CancerConnect News: The CDK4/6 inhibitor Kisqali (ribociclib) has been given breakthrough status by the US Food and Drug Administration as an initial endocrine-based treatment for of pre- or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer in combination with tamoxifen or an aromatase inhibitor.. Results from the Phase III MONALEESA-7 trial evaluating Kisqali® in combination endocrine-based therapy in premenopausal or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer are the basis for the breakthrough status designation.1. About Kisqali® Kisqali is a selective cyclin-dependent kinase inhibitor-this class of drugs helps slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow ...
Breast cancer is the most common cancer among women in China. Amplification of the Human epidermal growth factor receptor type 2 (HER2) gene is present and overexpressed in 18-20% of breast cancers and historically has been associated with inferior disease-related outcomes. There has been increasing interest in de-escalation of therapy for low-risk disease. This study analyzes the cost-effectiveness of Doxorubicin/ Cyclophosphamide/ Paclitaxel/ Trastuzumab (AC-TH) and Docetaxel/Carboplatin/Trastuzumab(TCH) from payer perspective over a 5 year time horizon. A half-cycle corrected Markov model was built to simulate the process of breast cancer events and death occurred in both AC-TH and TCH armed patients. Cost data came from studies based on a Chinese hospital. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed.The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were
Looking for online definition of c-erb B2/neu protein in the Medical Dictionary? c-erb B2/neu protein explanation free. What is c-erb B2/neu protein? Meaning of c-erb B2/neu protein medical term. What does c-erb B2/neu protein mean?
BACKGROUND: The mechanisms of resistance to anti-human epidermal growth factor receptor 2 (HER 2) therapies are unclear but may include the tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor (VEGF) and AXL pathways. Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms-like tyrosine kinase 3 (FLT3), angiopoiten receptor (TIE-2), RET and RON kinases. This phase Ib study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phase II doses (RP2D) of foretinib and lapatinib in a cohort of HER-2-positive patients with metastatic breast cancer (MBC). METHODS: Women with HER-2 positive MBC, Performance status (PS 0-2), and no limit on number of prior chemotherapies or lines of anti-HER-2 therapies were enrolled. A 3 + 3 dose escalation design was utilized. Four dose levels were intended with starting doses of foretinib 30 mg and lapatinib 750 mg orally once a day (OD) on a ...
Background: Development of a multidrug resistance (MDR) phenotype to chemotherapy remains a major barrier in the treatment of cancer. Gankyrin (p28, p28GANK or PSMD10) is an oncoprotein overexpressed in different carcinoma cell lines. The aim of this study was to compare Gankyrin expression level in MDR cells (MCF-7/ADR and MCF-7/ MX) and non-MDR counterparts (MCF-7). Methods: Gankyrin, MDR1 (also known as ABCB1; the ATP-binding cassette sub-family B member 1) and ABCG2 (also known as BCRP; the human breast cancer resistance protein) mRNA levels were analyzed by real-time RT-PCR. Western blot analysis was used to detect the protein expression levels of Gankyrin. Results: The PCR results showed that the expression of Gankyrin was significantly lower in the ABCG2 overexpressing cell line MCF-7/MX than in non-resistanct MCF-7 cells. In contrast, there were no significant differences in mRNA expression of Gankyrin in the MDR1 overexpressing cell line MCF-7/ADR in comparison with MCF-7 cells. Similarly,
BACKGROUND: Adjuvant trastuzumab has been routinely used in HER2-positive operable breast cancer patients. Prognostic factors remain to be well characterized in these patients and might correlate with primary and/or acquired resistance to trastuzumab.. PATIENTS AND METHODS: The study subjects were 78 HER2-positive operable breast cancer patients treated with adjuvant chemotherapy followed by 1-year trastuzumab between 2005 and 2010 in our institute. All breast tumors showed a HercepTest score of 3+ or that of 2+ and positive fluorescence in situ hybridization. Expression levels of HER1, phosphorylated HER2 (pY1248), HER3, HER4, and p53 were assessed by immunohistochemistry. Prognostic factors were investigated with univariate and multivariate analyses using the Kaplan-Meier/log-rank test and Cox proportional hazards model, respectively.. RESULTS: The median age and follow-up period of the patients were 54 years and 39 months, respectively. The mean tumor size was 2.1 cm and the node-positive ...
A new study has revealed that a combination of chemotherapy and treatment with two drugs lengthens survival of patients with HER2-positive metastatic breast cancer.
The study is being done as a follow-up to a recent clinical trial that showed HER2-positive breast cancer patients using a combination of trastuzumab (Herceptin) and lapatinib (Tykerb) for 12 weeks - without chemotherapy - showed a significant benefit in the eradication of breast cancer tumors.. The study results were released in May 2011 by the American Society of Clinical Oncology.. Certain subgroups in the study (those that were estrogen receptor positive or negative) showed different complete pathologic response rates (no cancer cells found in the tumor after treatment), so we hypothesized that longer treatment may be more effective for some, said Dr. Mothaffar Rimawi, medical director of the Lester and Sue Smith Breast Center at BCM and study chair. There may be a group that does not need chemotherapy. It will still be helpful for some, but maybe not for all.. The study will randomize patients to receive 12 vs. 24 weeks of trastuzumab and lapatinib. Patients whose tumors are also ...
06 Dec 2017. A combination of pembrolizumab and trastuzumab, tested in patients with trastuzumab-resistant advanced HER2-positive breast cancer, was well tolerated and had clinical benefit in patients whose tumors were positive for a biomarker for pembrolizumab, according to data presented from the phase Ib/II PANACEA trial at the 2017 San Antonio Breast Cancer Symposium, held Dec. 5-9.. We wanted to investigate if immunotherapy approaches can work in patients with advanced HER2-positive breast cancer that is resistant to trastuzumab, said Sherene Loi, MD, PhD, associate professor at Peter MacCallum Cancer Centre in Melbourne, Australia, working with the International Breast Cancer Study Group (IBCSG).. It is estimated that approximately 20 percent of invasive breast cancers are HER2-positive, and some of these patients develop resistance to trastuzumab, a HER2-specific monoclonal antibody utilized for treatment of the disease.. Loi and colleagues hypothesized that immunotherapy may help to ...
Widespread use of mammography in breast cancer screening has led to the identification of increasing numbers of patients with ductal carcinoma in situ (DCIS). DCIS of the breast with an area of focal invasion 1 mm or less in diameter is defined as DCIS with microinvasion, DCIS-Mi. Identification of biological differences between DCIS and DCIS-Mi may aid in understanding of the nature and causes of the progression of DCIS to invasiveness. In this study, using resected breast cancer tissues, we compared pure DCIS (52 cases) and DCIS-Mi (28 cases) with regard to pathological findings of intraductal lesions, biological factors, apoptosis-related protein expression, and proliferative capacity through the use of immunohistochemistry and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. There were no differences in biological factors between DCIS and DCIS-Mi, with respect to levels of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The frequency of
Herceptin is a humanized monoclonal antibody targeted against the human epidermal growth factor receptor c-erbB-2 (HER-2) which is overexpressed in approximately 25-30% of invasive breast cancer. Herceptin recognizes an epitope on the extracellular domain of c-erbB-2 and blocks downstream signaling. Approximately 50% of patients respond to Herceptin therapy; however, the majority of these will demonstrate disease progression within 1 year of treatment initiation. Several molecular mechanisms contributing to Herceptin resistance have been proposed. This research aims to define the effects of Herceptin on subcellular c-erbB-2 receptor trafficking.. We have created a c-erbB-2 plasmid fused to Yellow Fluorescent Protein (c-erbB-2-YFP) and an epidermal growth factor receptor fused to Green Fluorescent Protein (EGFR-GFP). Both constructs were sequenced and the correct sequence obtained. Both constructs were shown to react with specific antibodies and to have the predicted molecular weight using ...
Not only four but rather seven different human epidermal growth factor receptor related (Her) receptor tyrosine kinases (RTKs) have been described to be expressed in a variety of normal and neoplastic tissues: Her1, Her2, Her3, and additionally four Her4 isoforms have been identified. A differential expression of Her4 isoforms does not, however, play any role in either the molecular diagnostics or treatment decision for breast cancer patients. The prognostic and predictive impact of Her4 expression in breast cancer is basically unclear. We quantified the Her4 variants JM-a/CYT1, JM-a/CYT2, JM-b/CYT1, and JM-b/CYT2 by isoform-specific polymerase chain reaction (qPCR) in (i) triple-negative, (ii) Her2 positive breast cancer tissues and (iii) in benign breast tissues. In all three tissue collectives we never found the JM-b/CYT1 or the JM-b/CYT2 isoform expressed. In contrast, the two JM-a/CYT1 and JM-a/CYT2 isoforms were always simultaneously expressed but at different ratios. We identified a positive
The product of the HER2/Neu oncogene is a receptor tyrosine kinase that is amplified in 25-30% of human primary breast tumors. In this project? we have isolated the HER2/Neu kinase from Sf9 cells infected with a baculovirus expression vector. We probed the substrate specificity of the HER2/Neu kinase using two peptide libraries: (1) a soluble peptide library containing three degenerate positions N-terminal to tyrosine; and (2) a bead-supported combinatorial library possessing sis degenerate positions at P - 1, P - 2, P - 3, P + 1, P + 2, and P + 3. We identified four novel substrate sequences for HER2/Neu from the two peptide libraries. We synthesized these peptides as individual sequences and measured steady-state kinetic properties for phosphorylation by HER2/Neu. One of the peptides, AAEEIYAARRG, is the best synthetic peptide substrate reported to date for HER2/Neu. All of the sequences bear a resemblance to sites of autophosphorylation on HER2/Neu and related epidermal growth factor (EGF) ...
Breast cancer is one of the most common types of cancer affecting women, and approximately 15-30 % of breast cancer patients have a particularly aggressive type called HER2 positive breast cancer. These patients have tumors that overexpress human epidermal growth factor receptor 2 (HER2). HER2 is a glycoprotein found on the cell surface, and the extracellular domain (ECD) of this protein can be proteolytically cleaved and released into the blood circulation where it could be useful as a tumor marker to monitor the treatment response in HER2 positive patients. However, there are few assays available for HER2. The aim of this master thesis was therefore to develop a robust and sensitive immunoassay specific for HER2 ECD. Six monoclonal antibodies (M75, M77, M79, M83, M84 and M89) that recognise both recombinant and native HER2 were utilized to develop an immunometric assay for serum HER2. The antibodies were characterized, and antibody pair combinations were evaluated in a two-site assay to find ...
Trastuzumab is a drug used for the treatment of metastatic breast cancer patients. Due to blockage of the human epidermal growth factor receptor 2 signaling in cardiac myocytes, cardiotoxicity has been observed. There are many studies that investigated risk factors for trastuzumab-induced cardiotoxicity, but no study has been published for factors on the time to cardiotoxicity. This study aimed to investigate the factors for the time to occur trastuzumab-induced cardiotoxicity. From January 2014 to December 2015, a retrospective study was performed with breast cancer patients who were treated with trastuzumab. Associations between presence of and time to cardiotoxicity and various factors were analyzed. Based on multivariate models, it was found that baseline left ventricular ejection fraction (LVEF) < 62.5% (AHR 5.96, 95% CI 2543-13.95) and anthracycline-based chemotherapy (AHR 7.90, 95% CI 1.05-59.71) were significant factors for time to cardiotoxicity after adjusting other confounding ...
Author(s): Yardley, Denise A; Kaufman, Peter A; Brufsky, Adam; Yood, Marianne Ulcickas; Rugo, Hope; Mayer, Musa; Quah, Cheng; Yoo, Bongin; Tripathy, Debu | Abstract: Improvements in screening and adjuvant therapy for breast cancer are associated with decreased recurrence, which may have the effect of increasing the proportion of patients presenting with first-line de novo versus recurrent metastatic breast cancer (MBC). Here, we describe and compare patients with de novo versus recurrent human epidermal growth factor 2 (HER2)-positive MBC. registHER was a prospective observational cohort study (late 2003-early 2006) of 1,023 patients with HER2-positive MBC. Baseline characteristics, treatment patterns, and clinical outcomes were examined in patients with newly diagnosed de novo (n = 327) compared with recurrent HER2-positive MBC after prior treatment for early-stage disease (n = 674). Patients with de novo HER2-positive MBC were less likely to have lung metastases, more likely to have lymph node, bone,
Trastuzumab (Herceptin; Genentech/Roche, South San Francisco, CA, USA), the first available HER2-targeted therapy, is a humanized murine IgG monoclonal antibody that binds to the HER2 ECD. Its antitumor activity has not been completely ascertained, however, it is thought to result from a combination of antibody-dependent cell-mediated cytotoxicity, inhibition of cleavage of the ECD of the HER2 (8), decreased DNA repair, decreased intracellular signal transduction and anti-angiogenic effects (9,10). Trastuzumab-based treatment strategy has established a milestone in the therapy of HER2-positive breast cancer with attractive clinical benefits in the treatment of metastatic breast cancer, as well as adjuvant chemotherapy and neoadjuvant chemotherapy.. Adding trastuzumab to chemotherapy in the first-line treatment of HER2-positive metastatic breast cancer (MBC) was based on the pivotal phase III trial in which 469 women with HER2-positive MBC were randomized to receive standard chemotherapy ...
TY - JOUR. T1 - High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy. AU - Fujita, Hayato. AU - Ohchida, Kenoki. AU - Mizumoto, Kazuhiro. AU - Itaba, Soichi. AU - Ito, Tetsuhide. AU - Nakata, Kohei. AU - Yu, Jun. AU - Kayashima, Tadashi. AU - Hayashi, Akifumi. AU - Souzaki, Ryota. AU - Tajiri, Tatsuro. AU - Onimaru, Manabu. AU - Manabe, Tatsuya. AU - OHTSuka, Takao. AU - Tanaka, Masao. PY - 2011/3. Y1 - 2011/3. N2 - Pancreatic ductal adenocarcinoma (PDAC) still presents a major therapeutic challenge and a phase III clinical trial has revealed that the combination of gemcitabine and a human epidermal growth factor receptor type I (HER1/EGFR) targeting agent presented a significant benefit compared to treatment with gemcitabine alone. The aim of this study was to investigate EGFR mRNA expression in resected PDAC tissues and its correlation with patient prognosis. We obtained formalin-fixed paraffin-embedded (FFPE) ...
PubMed journal article The role of human epidermal growth factor receptor 2 in the survival of women with estrogen and progesterone receptor-negative, invasive breast cancer: the California Cancer Registry, 1999-200 were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android
TY - JOUR. T1 - Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2). AU - Feilchenfeldt, J.. AU - Varga, Z.. AU - Siano, M.. AU - Grabsch, H. I.. AU - Held, U.. AU - Schuknecht, B.. AU - Trip, A.. AU - Hamaguchi, T.. AU - Gut, P.. AU - Balague, O.. AU - Khanfir, K.. AU - Diebold, J.. AU - Jochum, W.. AU - Shoji, H.. AU - Kushima, R.. AU - Wagner, D.. AU - Shimada, Y.. AU - Cats, A.. AU - Knuth, A.. AU - Moch, H.. AU - Aebi, S.. AU - Hofer, S.. PY - 2015/9/1. Y1 - 2015/9/1. KW - HER2. KW - gastro-oesophageal adenocarcinoma. KW - CNS metastases. KW - lepto-meningeal carcinomatosis. KW - brain. KW - ethnicity. U2 - 10.1038/bjc.2015.279. DO - 10.1038/bjc.2015.279. M3 - Article. C2 - 26313663. VL - 113. SP - 716. EP - 721. JO - British Journal of Cancer. JF - British Journal of Cancer. SN - 0007-0920. IS - 5. ER - ...
The c-erbB-2 proto-oncogene encodes a receptor tyrosine kinase (RTK) closely related to the epidermal growth factor receptor (EGFR). Overexpression of erbB-2 occurs in approximately 20% of human breast tumours, where increased expression correlates with poor patient prognosis. The EGFR is coupled to the Ras signalling pathway by interaction with the adaptor protein Grb2, and Sos, a Ras GDP-GTP exchange factor. In this study, activation of the erbB-2 receptor and its association with Grb2 and Sos was investigated in breast cancer cell lines which overexpress erbB-2. The receptor was found to be tyrosine phosphorylated in all cell lines in which it is overexpressed. Western blotting of Grb2 and Sos immuneprecipitates from such cells revealed co-precipitation of erbB-2, demonstrating association of the Grb2/Sos complex with erbB-2 in vivo. Furthermore, a fusion protein containing only the SH2 domain of Grb2 bound to erbB-2 immobilized on nitrocellulose, indicating that association with Grb2 is direct and
Amplification of the Neu/c-erbB-2 receptor tyrosine kinase has been implicated as an important event in the genesis of human breast cancer. Indeed, transgenic mice bearing either an activated form of neu or the wild-type proto-oncogene under the transcriptional control of the mouse mammary tumor virus promoter-enhancer frequently develop mammary carcinomas (L. Bouchard, L. Lamarre, P. J. Tremblay, and P. Jolicoeur, Cell 57:931-936, 1989; C. T. Guy, M. A. Webster, M. Schaller, T. J. Parson, R. D. Cardiff, and W. J. Muller, Proc. Natl. Acad. Sci. USA 89:10578-10582, 1992; W. J. Muller, E. Sinn, R. Wallace, P. K. Pattengale, and P. Leder, Cell 54:105-115, 1988). Induction of mammary tumors in transgenic mice expressing the wild-type Neu receptor is associated with activation of the receptors intrinsic tyrosine kinase activity (Guy et al., Proc. Natl. Acad. Sci. USA 89:10578-10582, 1992). Here, we demonstrate that activation of Neu in these transgenic mice occurs through somatic mutations located ...
The proto-oncogene HER-2/neu is the human homologue of the rat neu oncogene and is mapped on chromosome 17 at q21. It has been clinically demonstrated that gene protein overexpression assessed by immunohistochemistry, which has been shown to be associated with gene amplification, is related to worse prognosis and differential treatment responsiveness and is correlated with high tumor grade, large size, positive nodal status, ductal infiltration, histological type, and low values of estrogen and progesterone receptors (5 , 17 , 18) . Whether HER-2/neu status can help to identify etiologically distinct subgroups of breast cancer cases has received only limited attention (8 , 9 , 19) .. In the study reported here, the OR for breast cancer in relation to OC use before age 18 was elevated among women with HER-2/neu-positive tumors and decreased among women with HER-2/neu-negative tumors. The 2-fold heterogeneity in the ORs was statistically significant in age-adjusted models but not in ...
Background: Overexpression of the human epidermal growth factor receptor (HER) 2 is associated with poor prognosis and shortened survival in breast cancer patients. HER2 is a potent activator of several signaling pathways that support cell survival, proliferation and metabolism. In HER2- positive breast cancer there are most likely unexplored proteins that act directly or indirectly downstream of well established pathways and take part in tumor development and treatment response.. Methods: In order to identify novel copy number variations (CNVs) in HER2-positive breast cancer whole-genome single nucleotide polymorphism (SNP) arrays were used. A PCR-based loss of heterozygosis (LOH) assay was conducted to verify presence of deletion in HER2-positive breast cancer cases but also in HER2 negative breast cancers, cervical cancers and lung cancers. Screening for mutations was performed using single-strand conformation polymorphism (SSCP) followed by PCR sequencing. Protein expression was evaluated ...
Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2; also known as HER-2/neu), is indicated for the treatment of women with either early stage or metastatic HER2+ breast cancer. It kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Strategies that enhance the activity of ADCC effectors, including NK cells, may improve the efficacy of trastuzumab. Here, we have shown that upon encountering trastuzumab-coated, HER2-overexpressing breast cancer cells, human NK cells become activated and express the costimulatory receptor CD137. CD137 activation, which was dependent on NK cell expression of the FcγRIII receptor, occurred both in vitro and in the peripheral blood of women with HER2-expressing breast cancer after trastuzumab treatment. Stimulation of trastuzumab-activated human NK cells with an agonistic mAb specific for CD137 killed breast cancer cells (including an intrinsically trastuzumab-resistant cell line) ...
HER2 expression in breast cancer tissue is indicative of an aggressive pathology. HER2 expression is therefore considered a marker of poor prognosis and results from clinical trials have demonstrated a significant benefit for HER2-targeted therapy in patients with HER2-positive EBC [8] and MBC [7]. Therapeutic inhibition of the HER2 pathway has the potential to counteract the prognostic risk associated with HER2 positivity. Currently, four HER2-directed agents are available for use in the treatment of HER2-positive breast cancer: the antibodies trastuzumab, pertuzumab and trastuzumab emtansine, and the tyrosine kinase inhibitor lapatinib. However, the benefit of HER2-targeted therapies is restricted to patients with HER2 gene amplification or protein overexpression. All HER2-directed therapies can cause severe adverse events and have a heightened risk of causing significant patient harm when used in error. Therefore, they must only be administered to eligible patients most likely to respond. ...
1. Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 2009;14:320-368. 2. Nahta R, Hung MC, Esteva FJ. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res 2004;64:2343-2346. 3. Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M. Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on HER2-positive human xenograft tumor models. Cancer Res 2009;69:9330-9336. 4. Baselga J, Cortes J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366:109-119. 5. Swain SM, Kim SB, Cortes J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet ...
There are a number of different kinds of breast cancer and each is treated differently. Patients with Her2+ breast cancer are generally classified as high risk. As a result, current treatment guidelines recommend adjuvant trastuzumab (Herceptin®, Genentech, 1 DNA Way South San Francisco, CA 94080-4990, co-marketed by F. Hoffmann-La Roche, Grenzacherstrasse 124, CH-4070 Basel, Switzerland) and chemotherapy as the best treatment option for all HER2-positive breast cancer patients at high risk of relapse, increasing their chance of living longer. At the same time, results from the HERA-trial (HERceptin Adjuvant), a randomized, two-arm, open label study of the efficacy, safety and tolerability of trastuzumab compared to observation in women who have completed standard adjuvant treatment of HER2 positive primary breast cancer, showed that 74% of patients remained distant recurrence-free at 3 years without trastuzumab ...
It is reported that pertuzumab and trastuzumab bind to different domains of HER2. A previous study showed that pertuzumab and trastuzumab were oriented at different angles with respect to HER2 after binding to HER2, by using a 3D structure model of the Fab region of pertuzumab and trastuzumab and p185HER2 (27). As shown in Figure 1A, binding of whole IgG to HER2 ECD protein, pertuzumab would not interfere with the binding of trastuzumab on HER2, even though both antibodies are displayed in their whole IgG conformation. This result indicates that pertuzumab and trastuzumab could have combination effects on antitumor activity.. We examined the efficacy of pertuzumab and trastuzumab in vivo. The reason for in vivo study is that the in vivo models indicate the efficacy of this antitumor activity more accurately because trastuzumab or pertuzumab have a mechanism through ADCC activity. We used NCI-N87 and 4-1ST as HER2-positive models. NCI-N87 and 4-1ST were determined as HER2 2+ and 3+, respectively ...
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... receptor, erbb-3 MeSH D12.776.624.664.700.800 - receptor, macrophage colony-stimulating factor MeSH D12.776.624.664.700.830 - ... estrogen receptor alpha MeSH D12.776.826.750.350.262 - estrogen receptor beta MeSH D12.776.826.750.350.350 - receptors, ... Retinoid X receptor alpha MeSH D12.776.826.701.500.625 - Retinoid X receptor beta MeSH D12.776.826.701.500.750 - Retinoid X ... thyroid hormone receptors alpha MeSH D12.776.624.664.700.830.750 - thyroid hormone receptors beta MeSH D12.776.624.664.700.915 ...
... has been shown to interact with: ErbB-2 receptor tyrosine kinase MK5 HSPA9 HSPA8, JAK2, and RASA1 ENSG00000103423 GRCh38 ... In neuromuscular junctions, only the short isoform clusters acetylcholine receptors for efficient synaptic transmission. The ... 2.0.CO;2. ISSN 1466-1268. PMC 312896. PMID 11147971. Sarkar S, Pollack BP, Lin KT, et al. (2002). "hTid-1, a human DnaJ protein ... 278 (1-2): 201-10. doi:10.1016/S0378-1119(01)00720-X. PMID 11707338. Cheng H, Cenciarelli C, Shao Z, et al. (2002). "Human T ...
PCI inhibits tumor cell growth.a Mechanism of action is inhibition of receptor dimerization and receptor trans- ... PCI blocks the formation and activation of ErbB1/ErbB-2 (EGFR and HER2) heterodimers that have a prominent role in carcinoma ... 226 (2): 169-84. doi:10.1016/j.canlet.2005.01.025. PMID 16039955. ^a Nagashima M, Werner M, Wang M, et al. (May 2000). "An ... 2 (10): 835-7. doi:10.1038/nsb1095-835. PMID 7552703. ^a Blanco-Aparicio C, Molina MA, Fernández-Salas E, et al. (May 1998). " ...
... receptor, erbb-3 MeSH D12.776.543.750.060.468 - receptor, igf type 1 MeSH D12.776.543.750.060.484 - receptor, insulin MeSH ... receptor, erbb-3 MeSH D12.776.543.750.750.400.370 - receptors, fibroblast growth factor MeSH D12.776.543.750.750.400.370.500 - ... receptor, epidermal growth factor MeSH D12.776.543.750.750.400.350 - receptor, erbb-2 MeSH D12.776.543.750.750.400.360 - ... receptor, epidermal growth factor MeSH D12.776.543.750.060.374 - receptor, erbb-2 MeSH D12.776.543.750.060.437 - ...
The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor ... The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members ... Zhang H, Berezov A, Wang Q, Zhang G, Drebin J, Murali R, Greene MI (August 2007). "ErbB receptors: from oncogenes to targeted ... Olayioye MA, Beuvink I, Horsch K, Daly JM, Hynes NE (June 1999). "ErbB receptor-induced activation of stat transcription ...
The ErbB protein family consists of 4 members ErbB-1, also named epidermal growth factor receptor (EGFR) ErbB-2, also named ... Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. ErbB-1 and ErbB-2 are ... The figure below shows the tridimensional structure of the ErbB family proteins, using the pdb files 1NQL (ErbB-1), 1S78 (ErbB- ... "Transactivation of ErbB Family of Receptor Tyrosine Kinases Is Inhibited by Angiotensin-(1-7) via Its Mas Receptor". PLOS ONE. ...
Receptor tyrosine-protein kinase erbB-4 is a receptor tyrosine kinase that is a member of the epidermal growth factor receptor ... Receptor tyrosine-protein kinase erbB-4 is an enzyme that in humans is encoded by the ERBB4 gene. Alternatively spliced ... Chang H, Riese DJ, Gilbert W, Stern DF, McMahan UJ (May 1997). "Ligands for ErbB-family receptors encoded by a neuregulin-like ... Chow NH, Liu HS, Yang HB, Chan SH, Su IJ (Jun 1997). "Expression patterns of erbB receptor family in normal urothelium and ...
... epidermal growth factor receptor - Epidiorite - epigenetics - Epinephrine - equine gonadotropin - erbA gene - erbB gene - erbB- ... G protein-coupled receptor - G3P - GABA - GABA receptor - GABA-A receptor - gag-onc fusion protein - galanin - gamete - gamma- ... CXCR4 receptor - cyclic AMP receptor - cyclic AMP receptor protein - cyclic AMP-responsive DNA-binding protein - cyclic ... leukotriene B4 receptor - LH - LH receptor - LHRH receptor - life - life form - Ligand - light reactions - Lineweaver-Burke- ...
Dreux AC, Lamb DJ, Modjtahedi H, Ferns GA (May 2006). "The epidermal growth factor receptors and their family of ligands: their ... "Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display". Biochemistry. 41 (27): ... Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. ... Harris RC, Chung E, Coffey RJ (March 2003). "EGF receptor ligands". Experimental Cell Research. 284 (1): 2-13. doi:10.1016/ ...
... receptor, erbb-2 MeSH D23.101.840.721 - receptor, erbb-3 MeSH D23.101.840.800 - synaptophysin MeSH D23.101.840.870 - tissue ... receptors, complement 3b MeSH D23.050.301.264.035.610 - receptors, complement 3d MeSH D23.050.301.264.035.690 - receptors, ige ... receptors, complement 3b MeSH D23.101.100.110.610 - receptors, complement 3d MeSH D23.101.100.110.690 - receptors, ige MeSH ... receptors, interleukin-7 MeSH D23.050.301.264.035.782 - receptors, interleukin-8a MeSH D23.050.301.264.035.850 - receptors, ...
Receptor tyrosine-protein kinase erbB-3, also known as HER3 (human epidermal growth factor receptor 3), is a membrane bound ... ErbB3 is a member of the epidermal growth factor receptor (EGFR/ERBB) family of receptor tyrosine kinases. The kinase-impaired ... Epidermal growth factor receptor family Epidermal growth factor receptor Receptor tyrosine-kinases GRCh38: Ensembl release 89: ... 1997). "Ligands for ErbB-family receptors encoded by a neuregulin-like gene". Nature. 387 (6632): 509-12. doi:10.1038/387509a0 ...
... supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB ... in estrogen receptor negative/androgen receptor positive cancers) androgen receptor signaling. These studies suggest that GATA3 ... Marine J, Winoto A (Aug 1991). "The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements ... Wilson BJ, Giguère V (2008). "Meta-analysis of human cancer microarrays reveals GATA3 is integral to the estrogen receptor ...
... supports existence of molecular apocrine breast cancer with a role for androgen receptor and implies interactions with ErbB ... 2009). "Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor ... 2009). "Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours". ... "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer". Nature. 481 (7381): 389-93. doi: ...
RTK class I (EGF receptor family) (ErbB family) RTK class II (Insulin receptor family) RTK class III (PDGF receptor family) RTK ... NGF receptor family) RTK class VIII (HGF receptor family) RTK class IX (Eph receptor family) RTK class X (AXL receptor family) ... RYK receptor family) RTK class XIII (DDR receptor family) RTK class XIV (RET receptor family) RTK class XV (ROS receptor family ... The ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor ...
"Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1". Oncogene. 21 (36): 5609-18. doi: ... "Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1". Oncogene. 21 (36): 5609-18. doi: ... Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW (May 2001). "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb ... Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW (May 2001). "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb ...
Abl gene Androgen receptor Apoptosis-antagonizing transcription factor ARID4A Aryl hydrocarbon receptor BRCA1 BRF1 C-jun C-Raf ... Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW (May 2001). "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb ... July 1998). "Retinoblastoma, a tumor suppressor, is a coactivator for the androgen receptor in human prostate cancer DU145 ... Ge NL, Elferink CJ (August 1998). "A direct interaction between the aryl hydrocarbon receptor and retinoblastoma protein. ...
"Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3". The Journal ... GRB7 has been shown to interact with: EPH receptor B1, Insulin receptor, PTK2, RET proto-oncogene, and Rnd1 Model organisms ... This gene encodes a growth factor receptor-binding protein that interacts with epidermal growth factor receptor (EGFR) and ... Growth factor receptor-bound protein 7, also known as GRB7, is a protein that in humans is encoded by the GRB7 gene. The ...
The EGF pathway includes the receptors HER1 (EGFR), HER2, HER3, and HER4; the binding of ligands (e.g. EGF etc.) to HER ... Jennings, B; Hadfield JE; Worsley SD; Girling A; Willis G. (1997). "A differential PCR assay for the detection of c-erbB 2 ... It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy ... Trastuzumab works by binding to the HER2 receptor and slowing down cell duplication. Trastuzumab was approved for medical use ...
1994). "Characterization of mouse non-receptor tyrosine kinase gene, HYL.". Oncogene 9 (11): 3371-4. PMID 7936664. CS1 ... 2002). "Csk homologous kinase (CHK) and ErbB-2 interactions are directly coupled with CHK negative growth regulatory function ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ... 1999). "The Csk homologous kinase associates with TrkA receptors and is involved in neurite outgrowth of PC12 cells.". J. Biol ...
Receptor tyrosine kinase. *ErbB: HER1/EGFR (Cetuximab. *Panitumumab). *HER2/neu (Trastuzumab. *Trastuzumab emtansine) ... anti-NMDA receptor encephalitis and Devic's disease,[23] Graves' ophthalmopathy,[24] autoimmune pancreatitis,[25] Opsoclonus ... 3 (2): 86-90. doi:10.1186/bcr276. PMC 138676. PMID 11250751.. *^ Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, ... with enhanced binding to Fc gamma receptors, which increase ADCC (antibody-dependent cellular cytotoxicity).[55] This strategy ...
Receptor tyrosine kinase. *ErbB: HER1/EGFR (Cetuximab. *Panitumumab). *HER2/neu (Trastuzumab. *Trastuzumab emtansine) ... It is mainly used to treat cases of NSCLC that harbour mutations in the epidermal growth factor receptor (EGFR) gene.[5] ... Afatinib covalently binds to cysteine number 797 of the epidermal growth factor receptor (EGFR) via a Michael addition (IC50 = ... Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive ...
"Microfluidics-assisted fluorescence in situ hybridization for advantageous human epidermal growth factor receptor 2 assessment ... "Defining the sister rat mammary tumor cell lines HH-16 cl.2/1 and HH-16.cl.4 as an in vitro cell model for Erbb2". PLOS ONE. 7 ... Paraspeckles visualized by single-molecule FISH against NEAT1 (Quasar 570) in U-2 OS cells (DAPI). ... 2] FISH can also be used to detect and localize specific RNA targets (mRNA, lncRNA and miRNA) in cells, circulating tumor cells ...
The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and ... receptor binding. • neurotrophin TRKB receptor binding. • growth factor activity. • GO:0001948 protein binding. ... regulation of receptor activity. • activation of phospholipase C activity. • neurotrophin TRK receptor signaling pathway. • ... NMDA receptor activity[edit]. NMDA receptor activation is essential to producing the activity-dependent molecular changes ...
Receptor/signaling modulators. Signaling peptide/protein receptor modulators. Growth factor receptor modulators. ... This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, ... transmembrane signaling receptor activity. • tumor necrosis factor-activated receptor activity. • nerve growth factor binding. ... TNFRSF8, CD30, D1S166E, Ki-1, tumor necrosis factor receptor superfamily member 8, TNF receptor superfamily member 8. ...
Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture). See also. Receptor/signaling modulators. ... RNA, ((2'-deoxy-2'-fluoro)C-Gm-Gm-A-A-(2'-deoxy-2'-fluoro)U-(2'-deoxy-2'-fluoro)C-Am-Gm-(2'-deoxy-2'-fluoro)U-Gm-Am-Am-(2'- ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... Study 2: 61% pegaptanib vs. 34% placebo. Regulatory information[edit]. Pegaptanib (pegaptanib sodium injection) has been ...
G protein-spregnuti receptor (Hedgehog, Wnt) • RTK (TGF beta, MAPK/ERK) • Notch • JAK-STAT • Akt/PKB • Fas apoptoza • Hippo • ... RTK klasa I (EGF receptorska) familija (ErbB familija). *RTK klasa II (Insulinska receptorska familija) ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ...
The receptor for PDGF, PDGFR is classified as a receptor tyrosine kinase (RTK), a type of cell surface receptor. Two types of ... Receptor tyrosine kinase. ONCO. *ErbB/c-ErbB *HER2/neu. *Her 3. *c-Met ... Like many other growth factors that have been linked to disease, PDGF and its receptors have provided a market for receptor ... "Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes". Science. 243 (4892): 800-4. doi: ...
insulin receptor binding. • hormone activity. • GO:0001948 protein binding. • growth factor activity. • insulin-like growth ... insulin receptor signaling pathway. • positive regulation of protein kinase B signaling. • regulation of transcription, DNA- ... regulation of receptor activity. • negative regulation of transcription from RNA polymerase II promoter. • osteoblast ... insulin receptor signaling pathway via phosphatidylinositol 3-kinase. • positive regulation of multicellular organism growth. • ...
Receptor tyrosine kinase. *ErbB: HER1/EGFR (Cetuximab. *Panitumumab). *HER2/neu (Trastuzumab. *Trastuzumab emtansine) ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... 46 (2): 101-110. doi:10.1046/j.1365-2125.1998.00764.x. ISSN 0306-5251. PMC 1873672. PMID 9723817.. ... 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)- 5-(trifluoromethyl)phenyl]-3- [(4-pyridin-3-ylpyrimidin-2-yl) amino]benzamide ...
transmembrane-ephrin receptor activity. • protein binding. • ephrin receptor binding. Cellular component. • anchored component ... The ephrins and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases and have been ... Zhou R (1998). "The Eph family receptors and ligands". Pharmacol. Ther. 77 (3): 151-81. doi:10.1016/S0163-7258(97)00112-5. PMID ... Wilkinson DG (2001). "Multiple roles of EPH receptors and ephrins in neural development". Nat. Rev. Neurosci. 2 (3): 155-64. ...
Receptor tyrosine kinase. ONCO. *ErbB/c-ErbB *HER2/neu. *Her 3. *c-Met ... 264 (2): 457-64. doi:10.1006/bbrc.1999.1516. PMID 10529385.. *^ a b c Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta ... vitamin D receptor and cyclin-dependent kinase inhibitors, p21 and p27". Nephrol. Dial. Transplant. 18 Suppl 3 (90003): iii9-12 ... 117 (2): 473-81. doi:10.1172/JCI28971. PMC 1783820. PMID 17273559.. *^ Chen H, Li C, Huang J, Cung T, Seiss K, Beamon J, ...
Receptor tyrosine kinase. *ErbB: HER1/EGFR (Cetuximab. *Panitumumab). *HER2/neu (Trastuzumab. *Trastuzumab emtansine) ... Active targeting uses biological molecules (antibodies, proteins, DNA and receptor ligands) to preferentially target the ... doi:10.1016/0163-7258(91)90086-2.. *^ a b c d Yue QX, Liu X, Guo DA (Aug 2010). "Microtubule-binding natural products for ... 56 (2): 185-229. PMID 15169927. doi:10.1124/pr.56.2.6.. *^ Sobell HM (Aug 1985). "Actinomycin and DNA transcription". ...
Hepatocitni faktor rasta - ErbB/Epidermalni faktor rasta - Fibroblast faktor rasta (1, 2, 3, 4) - Trombocit-izvedeni faktor ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ... Ligand-receptor complex. ]. {\displaystyle \left[\mathrm {Ligand} \right]\cdot \left[\mathrm {Receptor} \right]\;\;{\overset {K ... ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • IFI (16, 35) • MLL (2, 3, T1) • MNDA • NFY (A, B, C) • Ro/Sigma ...
epidermal growth factor receptor binding. • ربط بروتيني. • growth factor activity. • protein tyrosine kinase activity. • ... Révillion F، Lhotellier V، Hornez L، Bonneterre J، Peyrat JP (January 2008). "ErbB/HER ligands in human breast cancer, and ... epidermal growth factor receptor signaling pathway. • peptidyl-tyrosine phosphorylation. • phosphatidylinositol phosphorylation ... positive regulation of epidermal growth factor-activated receptor activity. • تمايز خلوي. • positive regulation of cytokine ...
Receptor tyrosine kinase. ONCO. *ErbB/c-ErbB *HER2/neu. *Her 3. *c-Met ... Davies G, Jiang WG, Mason MD (April 2001). "HGF/SF modifies the interaction between its receptor c-Met, and the E-cadherin/ ... Hazan RB, Norton L (April 1998). "The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin ... Besco JA, Hooft van Huijsduijnen R, Frostholm A, Rotter A (October 2006). "Intracellular substrates of brain-enriched receptor ...
Receptors[edit]. Main article: Nerve growth factor receptor. There are two classes of receptors for neurotrophins: p75 and the ... given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB). Mice born without the ... 2010). "Neurotrophin receptor TrkA and TrkC cause neuronal death whereas TrkB does not". Nature. 467: 59-63. doi:10.1038/ ... The expression of TrkA or TrkC receptors in the absence of neurotrophins can lead to apoptosis, but the mechanism is poorly ...
neurotrophin TRKA receptor binding. • ephrin receptor binding. • chemorepellent activity. • neurotrophin TRKB receptor binding ... neurotrophin TRKC receptor binding. • transmembrane receptor protein tyrosine kinase activator activity. • ... 1998). "Eph receptor-ligand interactions are necessary for guidance of retinal ganglion cell axons in vitro". Eur. J. Neurosci ... activation of transmembrane receptor protein tyrosine kinase activity. • axon guidance. • synaptic membrane adhesion. ...
Receptor tyrosine kinase. *ErbB: HER1/EGFR (Cetuximab. *Panitumumab). *HER2/neu (Trastuzumab. *Trastuzumab emtansine) ... It is a receptor tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor (EGFR). ... It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor.[28] For the signal to be ... Blum G, Gazit A, Levitzki A (2000). "Substrate competitive inhibitors of IGF-1 receptor kinase". Biochemistry. 39 (51): 15705- ...
... the agonist of formyl peptide receptor 3". Journal of Immunology. 187 (3): 1475-85. doi:10.4049/jimmunol.1003545. PMID 21709160 ... 105 (2): 179-82. doi:10.1002/ajmg.1204. PMID 11304834.. *^ Haidar B, Kiss RS, Sarov-Blat L, Brunet R, Harder C, McPherson R, ... Kim SJ, Kim KH, Ahn ER, Yoo BC, Kim SY (January 2013). "Depletion of cathepsin D by transglutaminase 2 through protein cross- ... erbB-3 receptor. *NMP22. Breast cancer. *CA 15-3. *erbB-2 receptor ...
signaling receptor activity. • transmembrane receptor protein tyrosine kinase activity. • receptor tyrosine kinase. • ... Receptor tyrosine kinase. ONCO. *ErbB/c-ErbB *HER2/neu. *Her 3. *c-Met ... The co-receptors themselves are classified as members of the GDNF receptor-α (GFRα) protein family. Different members of the ... receptor complex. • integral component of plasma membrane. • axon. • neuronal cell body. • dendrite. • early endosome. • ...
Receptor tyrosine kinase. *ErbB: HER1/EGFR (Cetuximab. *Panitumumab). *HER2/neu (Pertuzumab, Trastuzumab (+hyaluronidase) ... There are a large number of TK enzymes in the body, including the insulin receptor. Imatinib is specific for the TK domain in ... It blocks the activity of Abelson cytoplasmic tyrosine kinase (ABL), c-Kit and the platelet-derived growth factor receptor ( ... by inhibiting its receptor (PDGF-Rβ). One of its effects is delaying atherosclerosis in mice without[76] or with diabetes.[77] ...
Additional growth factor receptor modulators: Cerebrolysin (neurotrophin mixture). See also. Receptor/signaling modulators. ... 274 (2): 337-43. doi:10.1006/bbrc.2000.3142. PMID 10913340.. *^ Koga C, Adati N, Nakata K, Mikoshiba K, Furuhata Y, Sato S, Tei ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ... 2] cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene was shown to be expressed in normal brain, ...
auditory receptor cell fate commitment. • B cell differentiation. • regulation of gene expression. • Notch signaling pathway. • ... positive regulation of ERBB signaling pathway. • blood vessel endothelial cell fate specification. • negative regulation of ... positive regulation of transcription of Notch receptor target. • positive regulation of Notch signaling pathway. • ... positive regulation of ephrin receptor signaling pathway. • epithelial to mesenchymal transition involved in endocardial ...
neurotrophin p75 receptor binding. • receptor binding. • protein binding. • growth factor activity. Cellular component. • ... Tropomyosin receptor kinase B § Agonists. References[edit]. *^ a b c GRCh38: Ensembl release 89: ENSG00000225950 - Ensembl, May ... transmembrane receptor protein tyrosine kinase signaling pathway. • ganglion mother cell fate determination. • epidermis ... 2006). "Tyrosine kinase B receptor and its activated neurotrophins in ovaries from human fetuses and adults". Mol. Hum. Reprod ...
9,0 9,1 Olayioye, M A; Beuvink I, Horsch K, Daly J M, Hynes N E (June 1999). "ErbB receptor-induced activation of stat ... Aryl hydrocarbon receptor,[7] PDE6G,[8] STAT1,[9][10] EPH receptor B2,[11][12] Androgenski receptor,[13][14][15] Proteinska ... B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, ... Estrogenski receptor alfa,[13][31][32][33] Estrogenski receptor beta,[13][33] HNF1A,[34] KHDRBS1,[35][36][37][38][39] DDEF1,[40 ...
androgen receptor binding. • identical protein binding. • enzyme binding. • ubiquitin protein ligase binding. • importin-alpha ... Xia X, Cheng A, Lessor T, Zhang Y, Hamburger AW (May 2001). "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb ... androgen receptor signaling pathway. • chromatin remodeling. • negative regulation of smoothened signaling pathway. • negative ... Ge NL, Elferink CJ (August 1998). "A direct interaction between the aryl hydrocarbon receptor and retinoblastoma protein. ...
The GDNF family receptor-α (GFRα) proteins are a group of co-receptors which form complexes with GDNF-family ligands (GFLs) to ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ...
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ... Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ... ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the ...
Receptor tyrosine-protein kinase erbB-2. P04626. Details. Drug Relations. Drug Relations. DrugBank ID. Name. Drug group. ... Receptor tyrosine-protein kinase erbB-2. Details. Name. Receptor tyrosine-protein kinase erbB-2. Kind. protein. Organism. Human ...
Receptor tyrosine-protein kinase er.... Receptor tyrosine-protein kinase erbB-2, EC 2.7.10.1 (Metastatic lymph node gene 19 ... Receptor tyrosine-protein kinase er.... Receptor tyrosine-protein kinase erbB-2 (cDNA FLJ59426, highly similar to Receptor ... Receptor tyrosine-protein kinase erbB-2Imported. ,p>Information which has been imported from another database using automatic ... tr,J3KTI5,J3KTI5_HUMAN Receptor tyrosine-protein kinase erbB-2 (Fragment) OS=Homo sapiens OX=9606 GN=ERBB2 PE=1 SV=1 ...
Systematic reviews of Receptor tyrosine-protein kinase erbB-2. Receptor tyrosine-protein kinase erbB-2 in N Eng J Med, Lancet, ... Receptor tyrosine-protein kinase erbB-2. From Ganfyd. (Redirected from Human epidermal growth factor receptor 2 protein) ... NHS Evidence on Receptor tyrosine-protein kinase erbB-2 Centre for Reviews and Dissemination databases -DARE & NHS EED ( ... ChemSpider on Receptor tyrosine-protein kinase erbB-2. CTD (Comparative Toxicogenomics Database) on Receptor tyrosine-protein ...
Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy ... Antibodies targeted to TRAIL receptor-2 and ErbB-2 synergize in vivo and induce an antitumor immune response John Stagg, ... We thus demonstrated that the combination of anti-DR5 and anti-ErbB2 mAbs might be an effective form of treatment for ErbB-2- ... Remarkably, treatment with a combination of anti-DR5 and anti-ErbB-2 mAbs induced complete response in a majority of mice. In ...
c-erbB-4 expression was associated with a more favourable outcome. Co-expression of c-erbB-2 and EGFR was associated with a ... c-erbB-4 expression, however, showed an antagonistic effect on the clinical influence of c-erbB-2 expression. In conclusion, c- ... However, c-erbB-4 antagonizes the c-erbB-2 effect on clinical course in breast carcinomas. To achieve best results with ... c-erbB-3, and c-erbB-4. All the immunoreactive tumours were confirmed positive by RT-PCR. Tumour size, histological grade, ...
... c-erb-B-2, which has been identified in the human genome, maps to human chromosome 17 at q21 (ref. 40), and seems to encode a ... A novel v-erb-B-related gene, c-erb-B-2, which has been identified in the human genome, maps to human chromosome 17 at q21 (ref ... receptor. The c-erb-B-2 gene is conserved in vertebrates and it has been suggested that the neu gene, detected in a series of ... Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor Nature. 1986 Jan 16-22;319(6050): ...
... Br J Cancer. 1996 Dec;74(11):1749-56. ... In vitro binding of [3H]cholesteryl ether ([3H]Chol ether) labelled anti-erbB-2 conjugated liposomes to N-87 cells (erbB-2- ... No difference in binding to OV1063 cells (erbB-2-negative human ovary carcinoma) was observed. These results indicate highly ... Despite increased cell binding, doxorubicin (DOX) loaded in anti-erbB-2-conjugated liposomes did not cause increased in vitro ...
It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. ... Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member. ... A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. ... Receptor, ErbB-2, Proto-Oncogene Protein HER-2 (More). A cell surface protein-tyrosine kinase receptor that is overexpressed in ...
ErbB-2, NEU, or HER2) in serum, buffered solution or cell culture medium. ... AlphaLISA no-wash assay kit for detection and quantitation of Human epidermal growth factor receptor 2 ( ... is a type I membrane glycoprotein that is a member of the ERBB family of tyrosine kinase receptors. It serves as a receptor for ... Receptor Tyrosine-Protein Kinase ERbB-2 (HER2) AlphaLISA Detection Kit, 5,000 Assay Points ...
With the exception of ErbB-3, which acts as a noncatalytic partner to other erbB family members, the type I receptors have ... Inhibition of Receptor Autophosphorylation in Cells. The ability of GW2016 to inhibit the activity of EGFR and ErbB-2 in intact ... Receptors were immunoprecipitated using either EGFR or ErbB-2 antibodies and blotted for phosphotyrosine content. Treatment ... Receptors were immunoprecipitated with antibodies to EGFR or ErbB-2 and blotted for phosphotyrosine. This representative ...
ErbB-2 is a receptor tyrosine kinase (RTK) that is amplified/overexpressed in 20-30% of all invasive breast malignancies; it ... In this study, female MMTV-erbB-2 transgenic mice at 6-weeks of age were treated weekly by oral gavage with either 1.0 mg DMBA ... In addition to its well known mutational effect, DMBA induced deregulation of ER and erbB-2 pathways plays a critical role in ... DMBA promotes erbB-2 mediated carcinogenesis through activation of estrogen receptor and receptor tyrosine kinase pathways. [ ...
Death receptors of the TNF 3 receptor family (e.g., TNF receptor and Fas receptor) induce apoptosis on binding to their ... Both Akt kinase and MAPK are activated in response to growth factor receptor activation and up-regulated when erbB-2 receptor ... Pan G., Ni J., Wei Y. F., Yu G., Gentz R., Dixit V. M. An antagonist decoy receptor and a death domain-containing receptor for ... A, the erbB-2-overexpressing cancer cell line SKBr-3 was transfected with antisense ODNs (AS) at 1 μm or sense ODNs (S) at 1 μm ...
... with monoclonal antibodies to either ErbB-3 or ErbB-4, and with normal mouse serum (NMS), transiently transfected with 2 μg of ... ErbB-2 (green) and Stat3 (red) were localized as described in Materials and Methods. The same cells are shown in each row, and ... ErbB-2 Tyr 877 phosphorylation is required for Stat3 activity. SK-BR-3 cells were treated or not treated with HRG for 10 min or ... ErbB-2 phosphorylation was studied as described in the legend to Fig. 6B, and Stat3 and c-Src phosphorylation was studied as ...
2001 Feb;2(2):127-37. Research Support, Non-U.S. Govt; Research Support, U.S. Govt, Non-P.H.S.; Review ... When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling ... Untangling the ErbB signalling network.. Yarden Y1, Sliwkowski MX.. Author information. 1. Department of Biological Regulation ... a recombinant antibody designed to block the receptor ErbB2. Likewise, small-molecule enzyme inhibitors and monoclonal ...
The human epidermal growth factor receptor (erbB-2) is a transmembrane receptor th ... receptor whose overexpression is associated with adverse prognosis in breast cancer,sup,1,/sup,.,/p, ,p, ... p,erbB-2,strong, ,/strong,is a transmembrane, tyrosine kinase (TK) ... The human epidermal growth factor receptor (erbB-2) is a transmembrane receptor that is overexpressed in 15%-25% of breast ...
... the CXC chemokine receptor 4 (CXCR4), estrogen receptor (ER), Proliferating Cell Nuclear Antigen (PCNA), DNA topoisomerase II ( ... Biological molecular markers such as proto-oncogene erbB-2 (HER-2/neu, c-erbB-2), ... 0/Receptors, CXCR4; 0/estrogen receptor alpha, human; EC 2.7.10.1/ERBB2 protein, human; EC 2.7.10.1/Receptor, erbB-2 ... Estrogen Receptor alpha / metabolism. Female. Humans. Immunohistochemistry. Middle Aged. Receptor, erbB-2 / metabolism*. ...
The EGFR is a member of four proteins in the ErbB family of receptor tyrosine kinases. The other members are ErbB-2/HER2, ErbB- ... suggest that cancer cell lines driven by a member of the ErbB receptor system often couple to ErbB-3 to activate the PI3K/Akt ... ErbB-3 is unique among the ErbB family members in that it is has been shown to have weak or no tyrosine kinase activity (5). ... For example, in a subclone of NIH 3T3 cells that does not express endogenous ErbB receptors, EGFR expression alone is unable to ...
ProViz is an interactive protein exploration tool, which searches several databases for information about a given query protein. Data relevant to the protein like an alignment of homologues, linear motifs, post translational modifications, domains, secondary structure, sequence variations and others are graphically represented relative to their position in the protein.
This Timeline article focuses on the ERBB (also known as HER) network of receptor tyrosine kinases (RTKs), which exemplifies ... This Timeline article focuses on the ERBB network of receptor tyrosine kinases, which exemplifies how a constant dialogue ... Differential expression of NDF/neuregulin receptors ErbB-3 and ErbB-4 and involvement in inhibition of neuronal differentiation ... The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 229, 976-978 ( ...
Herceptin is active in a subset of patients over-expressing the epidermal growth factor receptor (EGFR) c-erbB-2 (HER2) but it ... These studies indicate that Herceptin applied to cells expressing only c-erbB-YFP induces receptor internalisation into a ... Preliminary results to determine the effect of the antibody SGP1 on the c-erbB-3 receptor have shown induced phosphorylation of ... Both constructs c-erbB-2-YFP and EGFR-GFP were used to transiently transfect COS-7 cells to determine their biosynthesis and ...
Monoclonal Anti-c-erbB-4 antibody produced in mouse for your research needs. Find product specific information including CAS, ... ErbB-4 also refers as HER4 is a 180-185kD oncogene that belongs to epidermal growth factor receptor family and is expressed ... Monoclonal anti-c-erbB-4 antibody can be used to study the role of erbB-4 and its interaction with other erbB family members as ... It plays a crucial role as a cell surface receptor for neuregulins. It can also bind with erbB -2 to forms heterodimers and can ...
Epidermal growth factor (EGF) binds with high affinity to the EGF receptor, also known as ErbB-1, but upon replacement of the N ... However, these chimeras weakly bind to ErbB-3 alone. To further dissect the ligand binding selectivity of the ErbB network, we ... Role of the N-terminus of epidermal growth factor in ErbB-2/ErbB-3 binding studied by phage display. Stortelers, C.; Souriau, C ... These data show that the linear N-terminal region of EGF-like growth factors is directly involved in binding to ErbB-3. ...
An immunological approach reveals biological differences between the two NDF/heregulin receptors, erbB-3 and erbB-4. J Biol ... Neu differentiation factor activation of erbB-3 and erbB-4 is cell specific and displays a differential requirement for erbB-2 ... EGF binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB-2 protein in the mammary tumor cell line SK- ... Beerli R.R., Graus-Porta D., Hynes N.E. (1998) Intracellular Antibodies as Tools to Study ErbB Receptor Tyrosine Kinases. In: ...
... cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology. ... neu gene is accompanied by overexpression of its cell surface receptor product, c‐erbB2 protein. To investigate the degree of ... Evaluation of C-ErbB-2 Overexpression and Her-2/neu Gene Copy Number Heterogeneity in Barretts Adenocarcinoma. Axel Walch,1 ... In conclusion, we observed marked intratumoural heterogeneity of c‐erbB2 protein overexpression and Her‐2/neu gene copy number ...
Laboratory of Receptor Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021. ... Monoclonal antibody (MAb) 4D5 was used to analyze the phosphorylation of p185HER2, the gene product of c-erbB-2/HER2, in SK-BR- ... Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human ... Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human ...
Epidermal growth factor receptor erbB1 Homo sapiens 1.000 CHEMBL1824 Receptor protein-tyrosine kinase erbB-2 Homo sapiens 1.000 ... Receptor protein-tyrosine kinase erbB-4 Homo sapiens 1.000 CHEMBL279 Vascular endothelial growth factor receptor 2 Homo sapiens ... Epidermal growth factor receptor erbB1 Homo sapiens 1.000 CHEMBL1913 Platelet-derived growth factor receptor beta Homo sapiens ... Receptor protein-tyrosine kinase erbB-2 Homo sapiens 1.000 CHEMBL203 ...
T1 - C-erbB-2 oncogene product expression depends on tumour type and is related to oestrogen receptor and lymph node status in ... C-erbB-2 oncogene product expression depends on tumour type and is related to oestrogen receptor and lymph node status in human ... C-erbB-2 oncogene product expression depends on tumour type and is related to oestrogen receptor and lymph node status in human ... C-erbB-2 oncogene product expression depends on tumour type and is related to oestrogen receptor and lymph node status in human ...
Steroid hormone receptors, estrogen receptors, progesterone receptors, and c-erbB2 expression of breast cancer tissue samples ... Effect of postoperative ischemia on steroid hormone receptors and c-erbB-2 levels in breast cancer tissue. Turk J Surg. 1950;1( ... Estrogen receptors, PRs, and c-erbB2 receptors remain stable in a medium at pH 7.4, but ischemia shifts pH value to acidosis, ... Effect of postoperative ischemia on steroid hormone receptors and c-erbB-2 levels in breast cancer tissue. ...
Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. p53 staining tended to be ... These results suggest that expressions of p53 and c-erbB-2 protein are heterogeneous and that p53 and c-erbB-2 overexpressions ... This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein ... Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an ...
  • The HER2 protein , also known amongst other names as, ErbB2 or neu, and coded for by the ERBB2 gene at 17q12 derives its name from human epidermal growth factor receptor 2 , indicating its similarity to epidermal growth factor receptor (EGFR). (ganfyd.org)
  • HER2 interacts with other members of the EGFR family and functions as a co-receptor for epidermal growth factor or equivalent ligands. (ganfyd.org)
  • HER2 can be blocked using a synthetic humanised monoclonal antibody called trastuzumab , although the mechanisms of action may be more complex than just receptor antagonism. (ganfyd.org)
  • Despite the development of human epidermal growth factor receptor-2 (ErbB-2/HER2)-targeted therapies, there remains an unmet medical need for breast cancer patients with ErbB-2 overexpression. (pnas.org)
  • The AlphaLISA ® Human epidermal growth factor receptor 2 (ErbB-2, NEU, or HER2) Detection Kit is designed for detection and quantitation of human ErbB-2 in serum, buffered solution or cell culture medium in a homogeneous (no-wash steps, no separation steps) assay. (perkinelmer.com)
  • The antibodies target the extracellular domain of the HER2 receptor. (perkinelmer.com)
  • Human epidermal growth factor receptor 2 (ERBB2, NEU, or HER2) is a type I membrane glycoprotein that is a member of the ERBB family of tyrosine kinase receptors. (perkinelmer.com)
  • The other members are ErbB-2/HER2, ErbB-3, and ErbB-4. (pnas.org)
  • Herceptin is active in a subset of patients over-expressing the epidermal growth factor receptor (EGFR) c-erbB-2 (HER2) but it is not possible to predict which individuals will respond. (biomedcentral.com)
  • The biology of erbB-2/neu/HER2 and its role in cancer. (springer.com)
  • Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. (asm.org)
  • Monoclonal antibody (MAb) 4D5 was used to analyze the phosphorylation of p185HER2, the gene product of c-erbB-2/HER2, in SK-BR-3 cells. (asm.org)
  • The HR cells exhibited higher levels of phosphorylated epidermal growth factor receptor (EGFR) and EGFR/HER2 heterodimers. (aacrjournals.org)
  • These results are consistent with the inability of trastuzumab to block the heterodimerization of HER2 and suggest that amplification of ligand-induced activation of ErbB receptors is a plausible mechanism of acquired resistance to trastuzumab that should be investigated in primary mammary cancers. (aacrjournals.org)
  • Although HER2 does not bind any of the ErbB ligands directly, its catalytic activity can potently amplify signaling by ErbB-containing heterodimers via increasing ligand binding affinity and/or receptor recycling and stability ( 2 - 5 ). (aacrjournals.org)
  • For example, overexpression of the insulin-like growth factor-I receptor or increased levels of insulin-like growth factor-I receptor/HER2 heterodimers ( 14 , 15 ), which potently activate phosphatidylinositol 3-kinase (PI3K) and its downstream effector Akt, abrogate trastuzumab action when transfected into antibody-sensitive human breast cancer cells. (aacrjournals.org)
  • The ErbB protein family consists of 4 members ErbB-1, also named epidermal growth factor receptor (EGFR) ErbB-2, also named HER2 in humans and neu in rodents ErbB-3, also named HER3 ErbB-4, also named HER4 v-ErbBs are homologous to EGFR, but lack sequences within the ligand binding ectodomain. (wikipedia.org)
  • We have developed and evaluated a selectedreaction monitoring assay for the human receptor tyrosine-protein kinase erbB-2 (HER2) in formalin-fixed paraffin-embedded breast tumors. (mcponline.org)
  • OBJECTIVE: The purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional 'clinical' immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in 'clinical luminal' [HR+/human epidermal growth factor receptor 2-negative (HER2-)] breast cancer patients to predict treatment sensitivity. (bireme.br)
  • ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. (nature.com)
  • ErbB2, also called Neu and Her2 (human epidermal growth factor receptor 2), is a type I transmembrane glycoprotein member of the ErbB family of tyrosine kinase receptors. (rndsystems.com)
  • We study signal transduction by growth factor receptor tyrosine kinases, focusing on the EGFR/HER2/ErbB family, including the impact of signaling by these receptors on clinical outcomes and response to targeted therapies for cancer, and their potential as therapeutic targets in novel combination therapies. (yalecancercenter.org)
  • A major focus in our laboratory has been the interaction of HER2 signaling with estrogen receptor (ER) signaling in breast cancer, and more recently with IGF-I receptor signaling, and the effects of inhibitors of these receptors in combination targeted therapies. (yalecancercenter.org)
  • ErbB2, also called Neu and Her2, is a transmembrane glycoprotein in the ErbB family of tyrosine kinase receptors for EGF superfamily growth factors. (rndsystems.com)
  • The aim of this study was to determine whether human epidermal growth factor receptor 2 (HER2)/erbB-2, p-glycoprotein, or p53 expression correlated with histologic response to preoperative chemotherapy or event-free survival. (uni-bonn.de)
  • Paraffin-embedded tissue was identified from 53 patients (73% of patients enrolled onto protocol) and stained for HER2/erbB-2, p53, and p-glycoprotein expression using standard monoclonal antibodies and methods. (uni-bonn.de)
  • At the time of initial biopsy, 20 (42.6%) of 47 samples demonstrated high levels of HER2/erbB-2 expression. (uni-bonn.de)
  • Expression of HER2/erbB-2 correlated with a significantly worse histologic response (P =.03). (uni-bonn.de)
  • In patients presenting with nonmetastatic disease, expression of HER2/erbB-2 at the time of initial biopsy was associated with a significantly decreased event-free survival (47% v 79% at 5 years, P =.05). (uni-bonn.de)
  • The correlation of HER2/erbB-2 expression with histologic response to preoperative chemotherapy and event-free survival in this study suggests that HER2/erbB-2 should be evaluated prospectively as a prognostic indicator. (uni-bonn.de)
  • HER2 (erbB-2/neu) is a member of the erbB receptor tyrosine kinase family. (clinicaltrials.gov)
  • ERBB2 gene which encodes human epidermal growth factor 2 (HER2) is a major proliferative driver activating downstream signaling through PI3K-AKT and MEK-ERK. (clinicaltrials.gov)
  • breast cancer and HER2 overexpression.Therefore, patients with tumors that demonstrate EGFR expression and clear-cut erbB-2 overexpression (3+) or limited erbB-2 overexpression (+ or 2+) will be included in the study. (bioportfolio.com)
  • In human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer, Src, a non-recep. (bioportfolio.com)
  • HER2 a proto-oncogenic receptor tyrosine kinase of the EGFR family. (phosphosite.org)
  • In conclusion, α -mangostin may be useful as a therapeutic agent for breast cancer carrying a p53 mutation and having HER2- and hormone receptor-negative subtypes. (hindawi.com)
  • Trastuzumab is a monoclonal antibody against human epidermal growth factor (HER/ErbB) receptor 2 (HER2/ErbB2). (hindawi.com)
  • protein phosphatase magnesium-dependent 1D) have a delay in HER2/neu (human epidermal growth factor 2), but not Wnt1-induced mammary tumor formation. (nih.gov)
  • The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. (uptodate.com)
  • The erbB-2/HER2 oncogene is overexpressed in a significant fraction of human carcinomas of the breast, ovary, and lung in a manner that correlates with poor prognosis. (uptodate.com)
  • This study showed less aggressive tumour biology in older women and a comparable clinical outcome with that of the younger patients, where a considerable number received chemotherapy.Introduction There is dearth of literature reporting the prevalence and biological characteristics as well as the long-term clinical outcome of human epidermal growth factor receptor-2 (HER2) overexpressing tumours in older women. (ebscohost.com)
  • Background This study was conducted to determine the frequency of PIK3CA mutations and human epidermal growth factor receptor-2 (HER2) phosphorylation status (pHER2-Tyr1221/1222) and if PIK3CA, phosphatase and tensin homolog (PTEN), or pHER2 has an impact on outcome in HER2-positive early-stage. (ebscohost.com)
  • The epidermal growth factor receptor 2 (HER2) is a tyrosine kinase overexpressed in nearly 20% to 25% of invasive breast cancers. (ebscohost.com)
  • Clinical relevance of ErbB-2/HER2 nuclear expression in breast cancer. (ebscohost.com)
  • The article offers information on a study conducted by the authors related to relevance of human epidermal growth factor receptor 2 (ErbB-2/HER2) in breast cancer. (ebscohost.com)
  • Ligand binding to the four closely related members of this RTK family -epidermal growth factor receptor (EGFR, also known as ErbB-1 or HER1), ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4)-induces the formation of receptor homo- and heterodimers and the activation of the intrinsic kinase domain, resulting in phosphorylation on specific tyrosine residues (pY) within the cytoplasmic tail. (genome.jp)
  • We investigated the therapeutic activity of an agonist mAb to mouse tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 (DR5) against ErbB2-driven breast cancer. (pnas.org)
  • We thus demonstrated that the combination of anti-DR5 and anti-ErbB2 mAbs might be an effective form of treatment for ErbB-2-overexpressing breast cancer. (pnas.org)
  • The network is often dysregulated in cancer and lends credence to the mantra that molecular understanding yields clinical benefit: over 25,000 women with breast cancer have now been treated with trastuzumab (Herceptin), a recombinant antibody designed to block the receptor ErbB2. (nih.gov)
  • erbB-2 overactivity is associated with adverse biological characteristics and poor clinical outcomes 1 .Overexpression of erbB2 in cell lines leads to transformation in the absence of a ligand 2 . (apexbt.com)
  • Therefore, in a technical sense, ErbB2 remains an orphan receptor. (apexbt.com)
  • We have chemically labelled Herceptin immunoglobulin (Genentech Inc., South San Francisco, CA, USA) with Alexa Fluor 568 (Invitrogen Molecular Probes, Inc., CA, USA) and have shown that this binds only to cells expressing the c-erbB2-YFP receptor. (biomedcentral.com)
  • Postoperative ischemia could affect the evaluation of breast cancer tissue for steroid hormone receptors and c-erbB2 levels until fixation using formalin. (turkjsurg.com)
  • The misevaluation of steroid hormone receptors and c-erbB2 levels, which are important prognostic factors in the treatment of breast cancer, could change treatment options. (turkjsurg.com)
  • The aim of this study was to investigate the effects of postoperative ischemia on a breast cancer tissue sample, particularly on steroid hormone receptors and c-erbB2 expression level. (turkjsurg.com)
  • Steroid hormone receptors, estrogen receptors, progesterone receptors, and c-erbB2 expression of breast cancer tissue samples were evaluated using both techniques. (turkjsurg.com)
  • Two groups were created based on the results of steroid hormone receptors and c-erbB2 expression levels using the two histopathological techniques. (turkjsurg.com)
  • A mastectomy specimen should be examined at once to ensure accurate detection of steroid hormone receptors and c-erbB2 levels for the proper treatment of breast cancer patients. (turkjsurg.com)
  • The presence of estrogen receptors (ERs), progesterone receptors (PRs), and c-erbB2 oncogene are accepted as the most important prognostic factors ( 2 - 4 ). (turkjsurg.com)
  • Eventually, all processes may lead to the misevaluation of steroid hormone receptors and c-erbB2 levels, which have high prognostic value for the treatment of breast cancer, and thus, misevaluation may cause alteration in treatment options. (turkjsurg.com)
  • Two groups were created based on steroid hormone receptors and c-erbB2 results: the first group for results of the frozen technique (n=20) and the second group for results of the regular follow-up technique (n=20). (turkjsurg.com)
  • 1-4 Its biological effects are mediated by a set of tyrosine kinase receptors (ErbB2, ErbB3, and ErbB4) that dimerize on ligand binding, leading to phosphorylation and downstream signaling. (ahajournals.org)
  • ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2) is a Protein Coding gene. (genecards.org)
  • The following product was used in this experiment: ErbB2 (HER-2) Monoclonal Antibody (6C2) from Thermo Fisher Scientific, catalog # MA5-15702, RRID AB_10985801. (thermofisher.com)
  • Most frequent is overexpression of ErbB2, a ligandless co-receptor that amplifies ErbB signalling. (nature.com)
  • Figure 3: Signalling by ErbB homodimers in comparison with ErbB2-containing heterodimers. (nature.com)
  • Among the ErbB family members, ErbB2 is unique in that it has no identified ligands. (rndsystems.com)
  • Rather, ErbB2 heterodimerizes with the other members of the ErbB family (ErbB1 (EGFR), ErbB3, ErbB4) to form higher affinity signaling complexes. (rndsystems.com)
  • In the present study, it was hypothesized that signal transducer and activator of transcription 3 (STAT3) and erbB‑2 receptor tyrosine kinase 2 (ERBB2) may be involved in the regulation of hypoxia‑induced VEGF in the retina. (spandidos-publications.com)
  • Hypoxia‑induced phosphorylation of STAT3 and ERBB2 in ARPE‑19 cells was decreased by AG490, an inhibitor of Janus kinase 2, as were hypoxia‑induced VEGF release and tube formation in human umbilical vein endothelial cells. (spandidos-publications.com)
  • In the present study, a Janus kinase 2 (JAK2) inhibitor that blocks STAT3 activation ( 16 ) was used to investigate whether STAT3 and ERBB2 may regulate VEGF release in an RPE cell line. (spandidos-publications.com)
  • The vector of anti-ErbB2 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human ErbB2. (creative-biolabs.com)
  • 3] Lee KF, Simon H, Chen H, Bates B, Hung MC, Hauser C. Requirement for neuregulin receptor erbB2 in neural and cardiac development. (mh-hannover.de)
  • Statistical analysis of EGFR family members in these tumours showed a significant association between c-erbB-2 expression and reduced disease-free and cancer-specific survival. (nih.gov)
  • Co-expression of c-erbB-2 and EGFR was associated with a worse prognosis. (nih.gov)
  • In conclusion, c-erbB-2 expression in breast carcinomas is associated with an unfavourable clinical course and EGFR expression has a synergistic effect. (nih.gov)
  • The epidermal growth factor receptor (EGFR) and ErbB-2 transmembrane tyrosine kinases are currently being targeted by various mechanisms in the treatment of cancer. (aacrjournals.org)
  • GW2016 is a potent inhibitor of the ErbB-2 and EGFR tyrosine kinase domains with IC 50 values against purified EGFR and ErbB-2 of 10.2 and 9.8 n m , respectively. (aacrjournals.org)
  • This report describes the efficacy in cell growth assays of GW2016 on human tumor cell lines overexpressing either EGFR or ErbB-2: HN5 (head and neck), A-431 (vulva), BT474 (breast), CaLu-3 (lung), and N87 (gastric). (aacrjournals.org)
  • Inhibition of EGFR and ErbB-2 receptor autophosphorylation and phosphorylation of the downstream modulator, AKT, was verified by Western blot analysis in the BT474 and HN5 cell lines. (aacrjournals.org)
  • Together, these results indicate that GW2016 achieves excellent potency on tumor cells with selectivity for tumor versus normal cells and suggest that GW2016 has value as a therapy for patients with tumors overexpressing either EGFR or ErbB-2. (aacrjournals.org)
  • The EGFR 2 and ErbB-2 are members of the type I receptor tyrosine kinase family and have been investigated as potential targets for cancer therapy because of their overexpression in a variety of neoplastic tissues ( 1 ). (aacrjournals.org)
  • EGFR and ErbB-2 are known to signal through the Ras pathway, stimulating cell division ( 3 ), and through the PI3K pathway, resulting in cell growth and survival ( 1 ). (aacrjournals.org)
  • Because these effects on cell growth and survival are dependent on the catalytic activity of EGFR and ErbB-2, it is believed that inhibition of this activity could provide a therapeutic opportunity for patients with tumors expressing elevated levels of EGFR and ErbB-2. (aacrjournals.org)
  • Recent efforts to design small molecule inhibitors of EGFR have generated encouraging preclinical and clinical results ( 2-8 ). (aacrjournals.org)
  • We have reported previously the discovery of a number of small molecule, dual EGFR/ErbB-2, tyrosine kinase inhibitors with activity in preclinical tumor models ( 9 , 10 ). (aacrjournals.org)
  • GW2016 is a potent inhibitor of EGFR and ErbB-2 tyrosine kinase catalytic activity and is selective for EGFR and ErbB-2 versus other proliferative kinases. (aacrjournals.org)
  • Western blot analysis of mammary tissues at 14 weeks of age showed that ERα, p-ERα, cyclin D1, Bcl-2, c-myc, EGFR, erbB-2 and erbB-3 protein levels were significantly increased in DMBA treated mice, which was accompanied by increased phosphorylation/activation of erbB-2, EGFR, ERK and Akt1. (aacrjournals.org)
  • Therapies that target the EGF receptor (EGFR), such as gefitinib (IRESSA), are effective in a subset of patients with advanced non-small cell lung cancer (NSCLC). (pnas.org)
  • Two gefitinib-sensitive NSCLC cell lines with endogenous distinct activating EGFR mutations (L858R and Del747-749), frequently observed in NSCLC patients who respond to gefitinib, also use ErbB-3 to couple to PI3K. (pnas.org)
  • Down-regulation of ErbB-3 by means of short hairpin RNA leads to decreased phospho-Akt levels in the gefitinib-sensitive NSCLC cell lines, Calu-3 (WT EGFR) and H3255 (L858R EGFR), but has no effect on Akt activation in the gefitinib-resistant cell lines, A549 and H522. (pnas.org)
  • We conclude that ErbB-3 is used to couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and mutant EGFRs. (pnas.org)
  • The EGF receptor (EGFR) is one such target, because it is known to promote growth of cells and function as an oncogene and is expressed in up to 80-90% of non-small cell lung cancer (NSCLC) (reviewed in ref. 3 ). (pnas.org)
  • The EGFR is a member of four proteins in the ErbB family of receptor tyrosine kinases. (pnas.org)
  • We have created a plasmid containing c-erbB-2 fused to Yellow Fluorescent Protein (c-erbB-2-YFP) and an epidermal growth factor receptor fused to Green Fluorescent Protein (EGFR-GFP). (biomedcentral.com)
  • Both constructs c-erbB-2-YFP and EGFR-GFP were used to transiently transfect COS-7 cells to determine their biosynthesis and transport to the cell surface. (biomedcentral.com)
  • However, cotransfection of c-erbB-2 (unlabelled) with EGFR tagged to GFP gave the unexpected result that the EGFR was internalised over about 1 hour (significantly slower than the effect of adding EGFR-Alexafluor). (biomedcentral.com)
  • We showed that cotransfection with c-erbB-2-YFP and EGFR labelled (or not) with GFP and addition of the labelled Herceptin is affected by the presence of EGFR. (biomedcentral.com)
  • This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. (kisti.re.kr)
  • Overall, 34% of gastric carcinomas had nuclear-staining for p53 protein, 34% of carcinomas membrane staining for the c-erbB-2 and 74% of carcinomas membrane and cytoplasmic staining for EGFr, showing distribution in a heterogeneous fashion. (kisti.re.kr)
  • The aim of this study was to investigate how trafficking of (111)In-labeled human epidermal growth factor ((111)In-DTPA-hEGF) relates to that of the EGF receptor (EGFR) and whether coadministration of agents that modulate EGFR signaling alters the efficacy of (111)In-DTPA-hEGF. (ox.ac.uk)
  • METHODS: The spatiotemporal interaction between AlexaFluor488-EGF (AF488-EGF) and Cy3-conjugated anti-EGFR antibody (Cy3-anti-EGFR) was studied in the breast cancer cell line MDA-MB-468 using fluorescence resonance energy transfer and 2-photon fluorescence lifetime imaging. (ox.ac.uk)
  • The cytotoxicity of (111)In-DTPA-hEGF (0-64 nM) plus trastuzumab (0-50 μg/mL) or L-778,123 (0-22.5 μM) was measured using clonogenic assays in a panel of breast cancer cell lines that express different levels of EGFR and ErB-2. (ox.ac.uk)
  • RESULTS: Using fluorescence resonance energy transfer, we showed that EGF interacts with EGFR in the cytoplasm and nucleus after internalization of the ligand-receptor complex in MDA-MB-468 cells. (ox.ac.uk)
  • The ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. (wikipathways.org)
  • Epidermal growth factor receptor (EGFR) signaling in cancer. (wikipathways.org)
  • The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. (wikipedia.org)
  • This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. (cancerindex.org)
  • This study aimed to investigate the expression of the ErbB family of receptor tyrosine kinases in pulmonary typical carcinoid and atypical carcinoid tumors and to understand the role of epidermal growth factor receptor (EGFR) signaling in pulmonary carcinoid tumor proliferation. (aacrjournals.org)
  • Our findings of the overexpression of epidermal growth factor receptor (EGFR), ErbB3, and ErbB4 suggests that signaling by the ErbB family of receptor tyrosine kinases is important for the transmission of growth signals during pulmonary carcinoid tumor growth. (aacrjournals.org)
  • The c-erbB-2 proto-oncogene encodes a receptor tyrosine kinase (RTK) closely related to the epidermal growth factor receptor (EGFR). (garvan.org.au)
  • Prior therapy with an EGFR (Endothelial Growth Factor Receptor) and/or erbB-2 inhibitor. (clinicaltrials.gov)
  • The neural progenitor cells of these regions express the epidermal growth factor receptor (EGFR, ErbB-1 or HER1). (frontiersin.org)
  • We summarize the current data regarding the role of EGFR and ErbB family signaling on neural stem cells and the downstream cascades involved in oligodendrogenesis in the neurogenic niches of the adult brain. (frontiersin.org)
  • Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. (rcsb.org)
  • GP30 is a potential ligand for this receptor. (rcsb.org)
  • It is an orphan receptor with no known ligand, as it acts as a heterodimer with other members of the EGF receptors family. (perkinelmer.com)
  • When ligand binds to type I receptors, dimerization occurs. (aacrjournals.org)
  • Whereas ErbB-2 is generally thought to be orphaned from a high-affinity ligand, it participates in signaling by heterodimerization with ligand-bound members of the type I receptor family. (aacrjournals.org)
  • We investigated whether combined treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and trastuzumab could enhance the specific killing of cells that overexpress the erbB-2 receptor. (aacrjournals.org)
  • These receptors homodimerize or heterodimerize upon ligand binding. (pnas.org)
  • To further dissect the ligand binding selectivity of the ErbB network, we have applied the phage display technique to examine the role of the linear N-terminal region in EGF for interaction with ErbB-2/ErbB-3 heterodimers. (cnrs.fr)
  • For example, the phenotypic knock-out of growth factor receptors by scFv mediated intracellular retention provides an attractive tool for investigating complex receptor-ligand interactions. (springer.com)
  • We have downregulated cell surface expression of individual erbB receptors via intracellular antibody expression prior to analyzing ligand induced signaling. (springer.com)
  • The ability ('+') or inability ('-') of each growth factor to activate each of the ErbB receptors is shown in the table below: The dimerization occurs after ligand bind to the extracellular domain of the ErbB monomers and monomer-monomer interaction establishes activating the activation loop in a kinase domain, that activates the further process of transphosphorylation of the specific tyrosine kinases in the kinase domain of ErbB's intracellular part. (wikipedia.org)
  • The heregulin receptor tyrosine kinase ErbB-4 is constitutively cleaved, in the presence or absence of ligand, by an exofacial proteolytic activity producing a membrane-anchored cytoplasmic domain fragment of 80 kD. (rupress.org)
  • Hence, proteasome activity is essential to prevent the accumulation of a significant level of ligand-independent, active ErbB-4 tyrosine kinase generated by metalloprotease activity. (rupress.org)
  • Coincidentally, activated ligand- receptor complexes are subject to less defined processes that alter their activity and cell surface distribution, and/or number. (rupress.org)
  • Most all ligand-occupied growth factor receptor tyrosine kinases are rapidly internalized by receptor-mediated endocytosis through clathrin-coated pits ( Sorkin and Waters, 1993 ). (rupress.org)
  • Internalized ligand-receptor complexes subsequently are sorted to lysosomes where both receptor and ligand are degraded. (rupress.org)
  • However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. (genecards.org)
  • c-Ret/dok fusion proteins, in which Y1062 of c-Ret is deleted and replaced by the sequences of dok-4 or dok-5, induce ligand-dependent axonal outgrowth of PC12 cells, whereas a c-Ret fusion containing dok-2 sequences does not elicit this response. (rupress.org)
  • In the absence of Wip1, hormone-receptor-positive cells have significantly reduced transcription of RANKL (receptor activator of nuclear factor kappa-B ligand) and IGF2 (insulin-like growth factor 2), paracrine stimulators of alveolar development. (nih.gov)
  • Although the encoded protein resembles several receptors for growth factors, no high affinity ligand of ErbB-2 has so far been fully characterized. (uptodate.com)
  • Thus, oncogenicity of ErbB-2 in human epithelia may not rely on the existence of a specific ligand but rather on its ability to act as a coreceptor for multiple stroma-derived growth factors. (uptodate.com)
  • A new bispecific ligand-directed toxin (BLT) was created in which 2 human cytokines-epidermal growth factor ([EGF], targeting overexpressed EGF receptor) and amino acid terminal fragment ([ATF], targeting urokinase plasminogen activator receptor)-were cloned onto the same single-chain molecule with truncated Pseudomonas exotoxin with a terminal lysyl-aspartyl-glutamyl-leucine (KDEL) sequence. (thejns.org)
  • Amplification and overexpression of the erbB-2 gene product, being unique to malignancy, confer onto this antibody-mediated therapy high tumour specificity. (nih.gov)
  • erbB-2 is a transmembrane, tyrosine kinase (TK) receptor whose overexpression is associated with adverse prognosis in breast cancer 1 . (apexbt.com)
  • 2. Di Fiore PP, Pierce JH, Fleming TP, Hazan R, Ullrich A, King CR, Schlessinger J, Aaronson SA: Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells. (apexbt.com)
  • Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an independent prognostic variable in gastric carcinoma. (kisti.re.kr)
  • Amplifiction of the Her-2/ neu gene is accompanied by overexpression of its cell surface receptor product, c‐erbB‐2 protein. (hindawi.com)
  • In conclusion, we observed marked intratumoural heterogeneity of c‐erbB‐2 protein overexpression and Her‐2/neu gene copy number in the majority of the primary BCA analyzed. (hindawi.com)
  • c-erbB-2 overexpression was very common (83%) in OSC, and was not associated with pathologic findings or clinical outcome. (semanticscholar.org)
  • Overexpression of erbB-2 occurs in approximately 20% of human breast tumours, where increased expression correlates with poor patient prognosis. (garvan.org.au)
  • The degree of association between the erbB-2 receptor and Grb2 in vivo was related to erbB-2 overexpression, and MAP kinase, which functions downstream from Ras, displayed markedly increased activity in cell lines overexpressing erbB-2. (garvan.org.au)
  • These results demonstrate that erbB-2 is coupled to Ras signalling via the Grb2/Sos complex, and that overexpression of this receptor in breast cancer cells leads to amplification of the Ras signalling pathway. (garvan.org.au)
  • This causes a conformational change in the receptor that activates the kinase domain and results in autophosphorylation and initiation of divergent signal transduction cascades ( 2 ). (aacrjournals.org)
  • We have studied the possible association between receptor signal transduction and cispla-tin-mediated cytotoxicity utilizing the SKBR-3 human breast cancer cell line and the anti-pl85 TAb 250 IgGl. (elsevier.com)
  • Taken together these data support a direct association between pl85c-erbB-2 signal transduction and inhibition of cisplatin-induced DNA repair. (elsevier.com)
  • Signal transduction and oncogenesis by ErbB/HER receptors. (wikipathways.org)
  • W hen growth factor ligands bind to their cognate receptors, tyrosine kinase activity is activated, and results in the initiation of multiple signal transduction pathways. (rupress.org)
  • However, several lines of evidence have raised the possibility that ErbB-2 can augment signal transduction initiated by binding of certain growth factors to their direct receptors. (uptodate.com)
  • A further five- to tenfold increase in its expression under influence of the long terminal repeat of Moloney murine leukemia virus was associated with activation of erbB-2 as a potent oncogene. (apexbt.com)
  • erbB-2 is a Potent Oncogene When Overexpressed in NIH/3T3 Cells. (apexbt.com)
  • BACKGROUND: Biological molecular markers such as proto-oncogene erbB-2 (HER-2/neu, c-erbB-2), the CXC chemokine receptor 4 (CXCR4), estrogen receptor (ER), Proliferating Cell Nuclear Antigen (PCNA), DNA topoisomerase II (topo II), P-glycoprotein (P-gp) and glutathione S-transferase (GST) were observed for changes after administration of neochemotherapy and whether these protein expression changes were correlated with response to chemotherapy. (biomedsearch.com)
  • Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. (nature.com)
  • C-erbB-2 oncogene product expression depends on tumour type and is related to oestrogen receptor and lymph node status in human breast carcinoma. (qub.ac.uk)
  • The ErbB-2 oncogene was detected using a monoclonal anti ErbB-2 antibody (AO485). (biomedcentral.com)
  • 0,007), and in transgenic mice carrying the rat HER-2/neu oncogene. (biomedcentral.com)
  • The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. (wikipedia.org)
  • lthough c-erbB-2 expression is, in general terms, an ominous prognostic indicator in breast carcinomas, there are suggestions that lack of this oncogene, when combined with analogous lack of estrogen (ER negative) and progesterone receptors (PgR negative)â€"“triple-negative phenotype†, is linked with an equally poor prognosis. (ebscohost.com)
  • c-erbB-2 oncogene has a complex biological role in early breast carcinomas for its expression characterizes subgroups of patients with both favorable (triple-positive phenotype) and unfavorable prognosis (c-erb-B2 positive cases after excluding triple-positive and triple-negative tumors)â€"a phenomenon presumably due to activation of different biological pathways. (ebscohost.com)
  • These data suggest that DMBA induced activation of both ER and receptor tyrosine kinase (RTK) pathways. (aacrjournals.org)
  • In addition to its well known mutational effect, DMBA induced deregulation of ER and erbB-2 pathways plays a critical role in this process. (aacrjournals.org)
  • These death receptor pathways offer an attractive method to induce apoptosis in cancer cells and may thereby serve as a treatment of cancer. (aacrjournals.org)
  • When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion. (nih.gov)
  • Hynes, N. E. & MacDonald, G. ErbB receptors and signaling pathways in cancer. (nature.com)
  • Anne Goriely ( [email protected]) suggested adding the MRAS (RRAS3) -SHOC2.PPP1CA pathways that activate RAF kinase and ERF, an ETS-family protein that inhibits ERK1 (aka MAPK3) and 2 (MAPK1). (cancer.gov)
  • Activation of the tyrosine kinase domain leads to the activation of the whole range of downstream signaling pathways like PLCγ, ERK 1/2, p38 MAPK, PI3-K/Akt and more with the cell. (wikipedia.org)
  • Among its related pathways are Trk receptor signaling mediated by the MAPK pathway and Development HGF signaling pathway . (genecards.org)
  • Figure 2: Crosstalk between the ErbB network and other signalling pathways. (nature.com)
  • Other ErbB receptors also activate several intracellular pathways for oligodendrocyte specification, migration and survival. (frontiersin.org)
  • The ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including proliferation, differentiation, cell motility, and survival. (genome.jp)
  • Signaling effectors containing binding pockets for pY-containing peptides are recruited to activated receptors and induce the various signaling pathways. (genome.jp)
  • A novel v-erb-B-related gene, c-erb-B-2, which has been identified in the human genome, maps to human chromosome 17 at q21 (ref. 40), and seems to encode a polypeptide with a kinase domain that is highly homologous with, but distinct from, that of the epidermal growth factor (EGF) receptor. (nih.gov)
  • The c-erb-B-2 gene is conserved in vertebrates and it has been suggested that the neu gene, detected in a series of rat neuro/glioblastomas, is, in fact, the rat c-erb-B-2 gene. (nih.gov)
  • Amplification of the c-erb-B-2 gene in a salivary adenocarcinoma and a gastric cancer cell line MKN-7 suggests that its over-expression is sometimes involved in the neoplastic process. (nih.gov)
  • Its sequence shows that the c-erb-B-2 gene encodes a possible receptor protein and allows an analysis of the similarity of the protein to the EGF receptor and the neu product. (nih.gov)
  • A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. (semanticscholar.org)
  • A wide variety of human tumors contain an amplified or overexpressed erbB-2 gene, which encodes a growth factor receptor-like protein. (apexbt.com)
  • When erbB-2 complementary DNA was expressed in NIH/3T3 cells under the control of the SV40 promoter, the gene lacked transforming activity despite expression of detectable levels of the erbB-2 protein. (apexbt.com)
  • The high levels of the erbB-2 product associated with malignant transformation of NIH/3T3 cells were observed in human mammary tumor cells that overexpressed this gene 3 . (apexbt.com)
  • Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. (nature.com)
  • Postnatal disruption of NRG-1/ErbB signaling by gene targeting in mice leads to dilated cardiomyopathy. (ahajournals.org)
  • More specifically, we investigated the prognostic value of four Notch receptors in breast cancer patients through "the Kaplan-Meier plotter" (KM plotter) database, in which updated gene expression data and survival information are from a total of 3554 breast cancer patients. (springer.com)
  • This chromosomal region carries several loci implicated in human proliferation disorders, including the tuberous sclerosis 2 gene (TSC2), polycystic kidney disease 1 gene ( PKD1 ), and the CREB binding protein ( CBP ) locus (Yin and Rozakis-Adcock, 2001). (atlasgeneticsoncology.org)
  • The 5' flanking region contains several consensus binding sites for transcription factors that regulate gene expression during tissue and organ development, such as myeloid zinc finger ( MZF1 ), Ikaros 2 and homeodomain proteins, as well as factors implicated in cell growth and survival responses, including AP-1 , PEA3 , E2F and NF-kB . (atlasgeneticsoncology.org)
  • Subsequent sequencing of a primary tumor from this patient and of a metastatic lesion revealed several drivers - an amplification of the FGFR2 locus (encoding fibroblast growth factor receptor 2) that was found exclusively in the primary, and a deletion in the gene TGFBR2 (encoding TGF-beta receptor type-2) found exclusively in the metastasis. (biomedcentral.com)
  • Aggressive brain tumors were intracranially established in nude rats by using human U87 glioma genetically marked with a firefly luciferase reporter gene (U87-luc), and the rats were stereotactically treated with 2 intracranial injections of deimmunized EGFATFKDEL via convection-enhanced delivery (CED). (thejns.org)
  • Preliminary results to determine the effect of the antibody SGP1 on the c-erbB-3 receptor have shown induced phosphorylation of a 60 kDa protein that is probably Shc, which already has been identified as one of the main second messenger proteins recruited by HER3. (biomedcentral.com)
  • EGF binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB-2 protein in the mammary tumor cell line SK-BR-3. (springer.com)
  • TAb 250 induced tyrosine phosphorylation of pl85 and the receptor substrate phospholipase C-yl, as well as rapid association of these molecules in vivo. (elsevier.com)
  • Phosphorylation of p185HER2 in the presence of newborn calf serum was not attributable to stimulation of the epidermal growth factor receptor by epidermal growth factor or by transforming growth factor-alpha. (asm.org)
  • Phosphorylation of CrkII adaptor protein at tyrosine 221 by epidermal growth factor receptor. (wikipathways.org)
  • On dimerization, the intrinsic kinase domain is activated, resulting in phosphorylation of specific tyrosine residues within the cytoplasmic tail of the receptor and subsequent downstream signaling. (ahajournals.org)
  • The intracellular/cytoplasmic region of the ErbB receptor consists mainly of three subdomains: A juxtamembrane with approximately 40 residues, a kinase domain containing approximately 260 residues and a C-terminal domain of 220-350 amino acid residues that become activated via phosphorylation of its tyrosine residues that mediates interactions of other ErbB proteins and downstream signaling molecules. (wikipedia.org)
  • Established tumors in BALB/c transgenic mice expressing a constitutively active ErbB-2/neuT were treated with anti-DR5 mAb and/or anti-ErbB-2 mAb and monitored for tumor progression. (pnas.org)
  • Combined therapy with anti-DR5 and anti-ErbB-2 mAbs further significantly suppressed the growth of advanced spontaneous tumors in ErbB-2/neuT transgenic mice, even when treatment was delayed until tumors were palpable. (pnas.org)
  • By the endpoint (first tumor ∼1.5cm 3 ), the average number of palpable tumors per mouse were 1.15 and 2 for control and DMBA groups, respectively. (aacrjournals.org)
  • an addition to chromosome 4 and trisomy 5 in the control mouse, trisomy 2, trisomy 3 and a deletion to chromosome 4 were detected from tumors of the DMBA mice, suggesting that DMBA induced chromosomal instability contributed to tumor promotion in this model. (aacrjournals.org)
  • These data suggest that the combination of trastuzumab and TRAIL may allow enhanced therapeutic efficacy and specificity in the treatment of erbB-2-overexpressing tumors. (aacrjournals.org)
  • Comparative analysis of h tid and HER-2 expression in breast and non breast tumors . (biomedcentral.com)
  • One of the molecular ligands of the cytosolic hTid-L and hTid-I forms is the ErbB-2 receptor variably over expressed in diverse solid tumors. (biomedcentral.com)
  • We evaluated h tid and HER-2 expression by quantitative real time PCR in tumors of different TNMG status and by immunohistochemistry in a cohort of breast tumors of the Luminal A, B, HER-2 and triple negative subtype. (biomedcentral.com)
  • In contrast h tid expression is significantly lower in tumors of the Luminal B (20%) and HER-2 (18%) subtype over expressing the receptor and in the triple negative (40%) more aggressive malignancies. (biomedcentral.com)
  • Thus, in the context of the functional link between the h tid encoded proteins and ErbB-2 in the present study we addressed the question whether in human sporadic breast tumors the in vivo expression profiles of the two tumor genes provide support for h tid function as a negative regulator of ErbB-2 activity. (biomedcentral.com)
  • ErbB-1 and ErbB-2 are found in many human cancers and their excessive signaling may be critical factors in the development and malignancy of these tumors. (wikipathways.org)
  • A total of 116 specimens with early breast cancer, defined as tumors of ≤2 cm in size and clinically negative axilla, were studied immunohistochemically for ER, PgR, and c-erbB-2 expression. (ebscohost.com)
  • However, if triple-positive and triple-negative cases were excluded from the original sample, the remaining c-erbB-2 positive cases were connected with poor prognosis, relative to the remaining c-erbB-2 negative tumors. (ebscohost.com)
  • Pulmonary carcinoid tumors are malignant neoplasms comprising neuroendocrine cells that account for 2% to 5% of all lung cancers ( 2 ). (aacrjournals.org)
  • PURPOSE: Hormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. (bireme.br)
  • Figure 2: LIF promotes proliferation and anchorage-independent growth of breast cancer cells and promotes the growth of xenograft breast tumors. (amazonaws.com)
  • Activation of the co-receptor complex transduces a signal, which in turn, stimulates tyrosine kinase activity in the intracellular domain. (ganfyd.org)
  • A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. (semanticscholar.org)
  • Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2. (semanticscholar.org)
  • Polyubiquitination and proteasomal degradation of the p185c-erbB-2 receptor protein-tyrosine kinase induced by geldanamycin. (semanticscholar.org)
  • With the exception of ErbB-3, which acts as a noncatalytic partner to other erbB family members, the type I receptors have functional tyrosine kinase catalytic domains. (aacrjournals.org)
  • Down-regulation of the erbB-2 receptor protein by trastuzumab or antisense oligodeoxynucleotides decreased Akt kinase activation but not mitogen-activated protein kinase activation. (aacrjournals.org)
  • Expression of a constitutively active form of Akt kinase in an erbB-2-overexpressing cell line completely abrogated the increase in TRAIL-mediated apoptosis by trastuzumab and significantly reduced the biological effect of either reagent alone. (aacrjournals.org)
  • Therefore, down-regulation of the erbB-2 receptor by trastuzumab enhances TRAIL-mediated apoptosis by inhibiting Akt kinase activity. (aacrjournals.org)
  • ErbB-3 is unique among the ErbB family members in that it is has been shown to have weak or no tyrosine kinase activity ( 5 ). (pnas.org)
  • In particular, ErbB-3 effectively couples to the phosphoinositide 3-kinase (PI3K)/Akt pathway. (pnas.org)
  • Cohen, S., Fava, R. A. & Sawyer, S. T. Purification and characterization of epidermal growth factor receptor/protein kinase from normal mouse liver. (nature.com)
  • The c-erbB-2 (HER-2/neu) protooncogene encodes an Mr 185,000 transmembrane glycoprotein with intrinsic tyrosine kinase activity. (elsevier.com)
  • Preincubation of SKBR-3 cells with the tyrosine kinase inhibitor tyrphostin 50864-2 abrogated the enhancement of drug-mediated cell kill induced by TAb 250. (elsevier.com)
  • Phosphotyrosine interactome of the ErbB-receptor kinase family. (wikipathways.org)
  • Mike Nickerson ( [email protected] ) included negative feedback to IRS1 and 2 from the PI3 kinase pathway. (cancer.gov)
  • For the activation of kinase domain in the ErbB dimer, asymmetric kinase domain dimer of the two monomers is required with the intact asymmetric (N-C lobe) interface at the site of adjoining monomers. (wikipedia.org)
  • However, it does form heterodimers with other EGF receptor family members which do have kinase activity. (cancerindex.org)
  • When proteasome activity is inhibited for 6 h, the kinase-active 80-kD ErbB-4 fragment accumulates to a level equivalent to 60% of the initial amount of native ErbB-4 (∼10 6 receptors per cell). (rupress.org)
  • Tyrosine-kinase activity, as well as internalization sequences in the receptor carboxyl terminus, are essential for this step in receptor trafficking. (rupress.org)
  • This article focuses on a protein kinase C-independent basal or constitutive mechanism that generates a similar hydrolysis of ErbB-4. (rupress.org)
  • Here we found that p62dok family members act as substrates for the c-Ret receptor tyrosine kinase. (rupress.org)
  • The specificity of receptor tyrosine kinase signaling has been investigated in great detail. (rupress.org)
  • Receptor Tyrosine Protein Kinase ERBB 3 market is segmented by Type, and by Application. (reportsnreports.com)
  • Players, stakeholders, and other participants in the global Receptor Tyrosine Protein Kinase ERBB 3 market will be able to gain the upper hand as they use the report as a powerful resource. (reportsnreports.com)
  • The Receptor Tyrosine Protein Kinase ERBB 3 market is analysed and market size information is provided by regions (countries). (reportsnreports.com)
  • The key regions covered in the Receptor Tyrosine Protein Kinase ERBB 3 market report are North America, Europe, Asia Pacific, Latin America, Middle East and Africa. (reportsnreports.com)
  • Receptor Tyrosine Protein Kinase ERBB 3 market competitive landscape provides details and data information by players. (reportsnreports.com)
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  • Sunitinib, sorafenib, and bevacizumab are multitargeted tyrosine kinase inhibitors that inhibit tumor neovascularization and are currently in clinical trials [ 2 , 3 ]. (hindawi.com)
  • 82 MAP/microtubule Affinity-Regulating Kinase 2 (MARK2) Antikörper von 14 Herstellern verfügbar auf www.antikoerper-online.de. (antikoerper-online.de)
  • The Shc- and/or Grb2-activated mitogen-activated protein kinase (MAPK) pathway is a common target downstream of all ErbB receptors. (genome.jp)
  • These results indicate highly selective binding of antibody-targeted liposomes to erbB-2-overexpressing cells. (nih.gov)
  • We have made a monoclonal antibody called SGP1 that recognises the extracellular domain of HER3 receptor [ 1 ] and we would like to see whether addition of a HER3-specific monoclonal antibody to Herceptin will increase its anticancer activity. (biomedcentral.com)
  • Our preliminary results using monoclonal antibody SGP1 have shown that the presence of HER3 receptor can affect the extent of downregulation. (biomedcentral.com)
  • Monoclonal anti-c-erbB-4 antibody can be used to study the role of erbB-4 and its interaction with other erbB family members as well as the cellular and molecular mechanisms underlying tumor growth. (sigmaaldrich.com)
  • Monoclonal anti-c-erbB-4 antibody can be used in immunoprecipitation (4-8 μg/test) using RIPA lysate of cultured CB4 cells (CHO cell line transfected with erbB-4). (sigmaaldrich.com)
  • The supraadditive drug/antibody effect was not seen in SKBR-3 cells with TAb 263, an anti-pl85 IgGl that does not induce receptor signaling or with TAb 250 in MDA-468 breast cancer cells which do not overexpress c-erbB-2. (elsevier.com)
  • At the top of the diagram are the receptors and messengers to the three RAS proteins. (cancer.gov)
  • Type III NRGs, containing a cysteine-rich domain, are 2-pass transmembrane proteins. (ahajournals.org)
  • The figure below shows the tridimensional structure of the ErbB family proteins, using the pdb files 1NQL (ErbB-1), 1S78 (ErbB-2), 1M6B (ErbB-3) and 2AHX (ErbB-4): The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher-order oligomers upon activation by a subset of potential growth factor ligands. (wikipedia.org)
  • Notably, the ErbB1 and ErbB4 are the two most studied and intact among the family of ErbB proteins, Which forms functional intracellular tyrosine kinases. (wikipedia.org)
  • There are a few exceptions to this, such as tissue-bound receptors that must be measured in a biopsy from the solid tumor or proteins that are secreted into the urine. (encyclopedia.com)
  • In addition, specific docking proteins of receptor tyrosine kinases have been discovered which mediate particular biological responses. (rupress.org)
  • These docking proteins contain NH 2 -terminal membrane-targeting elements, pleckstrin homology (PH) domains or myristylation sites, and receptor-targeting sequences, PTB or PTB-like domains. (rupress.org)
  • CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins which are expressed on antigen-presenting cells (APC). (creative-biolabs.com)
  • Several cytoplasmic docking proteins appear to be recruited by specific ErbB receptors and less exploited by others. (genome.jp)
  • Altered ErbB-2 signalling is associated with an unfavourable prognosis in about 30% of human breast malignancies. (biomedcentral.com)
  • Estrogen receptor beta 2 is associated with poor prognosis in estrogen receptor alpha-negative breast carcinoma. (ebscohost.com)
  • Insulin-like growth factor-I receptor/human epidermal growth factor receptor 2 heterodimerization contributes to trastuzumab resistance of breast cancer cells. (semanticscholar.org)
  • Trastuzumab treatment resulted in down-regulation of the erbB-2 receptor in all erbB-2-overexpressing cell lines. (aacrjournals.org)
  • Inhibition of IGF1R activity enhances response to trastuzumab in HER-2-positive breast cancer cells. (springer.com)
  • Figure 2: Combination of neratinib and trastuzumab has an additive effect and prevents re-activation of pHER3 and pAkt. (amazonaws.com)
  • Evaluation of the Insulin-like Growth Factor Receptor Pathway in Patients with Advanced Breast Cancer Treated with Trastuzumab. (bioportfolio.com)
  • Anthocyanins potentiate the activity of trastuzumab in human epidermal growth factor receptor 2-positive breast cancer cells in vitro and in vivo. (ebscohost.com)
  • A MAb (N-12A5) directed against erbB-2 oncoprotein, a functional surface antigen, was used. (nih.gov)
  • Sebaceous carcinoma of the eyelids: frequent expression of c-erbB-2 oncoprotein. (semanticscholar.org)
  • To compare the desmoplastic reactions against biological markers, such as estrogen and progesterone receptors, oncoprotein c-erbB-2 and oncoprotein p53, with the objective of studying the relationship between the tumoral stroma and epithelial cancer cells. (scielo.br)
  • Immunohistochemical methods were used to determine the expression of the hormonal receptors and c-erbB-2/p53 oncoprotein. (scielo.br)
  • Extent of desmoplastic reaction versus expression of estrogen and progesterone receptors, oncoprotein c-erbB-2, and oncoprotein p53. (scielo.br)
  • c-erbB-2 oncoprotein. (scielo.br)
  • Second, by using antibodies that block inter-ErbB interactions and cells devoid of surface ErbB-2, we learned that signaling by all ligands examined, except those derived from the precursor of EGF, was enhanced by the oncoprotein. (uptodate.com)
  • development of hematopoietic stem cells and T-cells activity during aging as well as understanding antigen recognition mechanisms by their receptors and its coupling to cellular response in mast cells as a model. (weizmann.ac.il)
  • [5] [11] Although IGF-1 is responsible for most of the role of GH in mediating breast development, GH itself has been found to play a direct, augmenting role as well, as it increases estrogen receptor (ER) expression in breast stromal (connective) tissue , while IGF-1, in contrast, has been found to not do this. (wikipedia.org)
  • In mice loss of signaling by any member of the ErbB family results in embryonic lethality with defects in organs including the lungs, skin, heart and brain. (wikipathways.org)
  • A) C4HD (left) and T47D (right) cells were preincubated for 90 min with AG825, with monoclonal antibodies to either ErbB-3 or ErbB-4, and with normal mouse serum (NMS), transiently transfected with 2 μg of DN Jak1 or DN Jak2 vector for 2 days, and preincubated with PP2 for 90 min. (asm.org)
  • Figure 3: Drug flood: antibodies and small molecules intercepting ERBB signalling. (nature.com)
  • Genes encoding single-chain Fv domains (scFvs) directed to the extracellular portion of these receptors were derived from hybridoma cells producing the corresponding monoclonal antibodies. (springer.com)
  • Agonistic antibodies against pl85c-erbB-2 enhance the cytotoxic effect of the DNA alkylator, cisplatin, against c-erB-2-overexpressing human carcinoma cells (Hancock et al. (elsevier.com)
  • Remarkably, treatment with a combination of anti-DR5 and anti-ErbB-2 mAbs induced complete response in a majority of mice. (pnas.org)
  • In this study, female MMTV-erbB-2 transgenic mice at 6-weeks of age were treated weekly by oral gavage with either 1.0 mg DMBA in peanut oil or vehicle alone for 6 weeks. (aacrjournals.org)
  • Aberrant neural and cardiac development in mice lacking the erbB4 neuregulin receptor. (springer.com)
  • Strain-dependent epithelial defects in mice lacking the EGF receptor. (springer.com)
  • For example, ErbB-2 and ErbB-4 knockout mice die at midgestation leads to deficient cardiac function associated with a lack of myocardial ventricular trabeculation and display abnormal development of the peripheral nervous system. (wikipedia.org)
  • In ErbB-3 receptor mutant mice, they have less severe defects in the heart and thus are able to survive longer throughout embryogenesis. (wikipedia.org)
  • Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. (mh-hannover.de)
  • This is exemplified by our studies of the erbB signaling network with its four related receptors and multiple activating ligands. (springer.com)
  • The four members of the ErbB protein family are capable of forming homodimers, heterodimers, and possibly higher order oligomers upon activation by a subset of potential growth factor ligands. (wikipathways.org)
  • The four ErbB receptors and their many neuregulins and EGF-like ligands form a layered signalling network. (nature.com)
  • In mammals, specific ligands and their respective homo- or heterodimeric ErbB complexes specify different cell lineages. (nature.com)
  • Here, we contrasted these two models of ErbB-2 function: First, examination of a large series of epidermal growth factor (EGF)-like ligands and neuregulins, including virus-encoded ligands as well as related motifs derived from the precursor of EGF, failed to detect interactions with ErbB-2 when this protein was singly expressed. (uptodate.com)
  • A library of EGF variants was constructed in which residues 2, 3, and 4 were randomly mutated, followed by selection for binding to intact MDA-MB-453 cells that overexpress ErbB-2 and ErbB-3 but lack ErbB-1. (cnrs.fr)
  • In this study, activation of the erbB-2 receptor and its association with Grb2 and Sos was investigated in breast cancer cell lines which overexpress erbB-2. (garvan.org.au)
  • Untangling the ErbB signalling network. (nih.gov)
  • Epidermal growth factor (EGF) binds with high affinity to the EGF receptor, also known as ErbB-1, but upon replacement of the N-terminal linear region by neuregulin (NRG) 1 or transforming growth factor (TGF) alpha sequences it gains in addition high affinity for ErbB-2/ErbB-3 heterodimers. (cnrs.fr)
  • In contrast to previously characterized chimeras of EGF with NRG-1 or TGF-alpha, these variants did not only show high binding affinity for ErbB-2/ErbB-3 heterodimers but also for ErbB-3 alone. (cnrs.fr)
  • Controlled dimerization of ErbB receptors provides evidence for differential signaling by homo- and heterodimers. (wikipathways.org)
  • c-erbB-4 expression was associated with a more favourable outcome. (nih.gov)
  • c-erbB-4 expression, however, showed an antagonistic effect on the clinical influence of c-erbB-2 expression. (nih.gov)
  • To achieve best results with immunotherapy against the c-erbB-2 receptor, clarifying the status of c-erbB-4 expression may be of significance. (nih.gov)
  • Pathological expression of human ErbB-2 protein, also known as HER-2, is common in many types of cancer. (semanticscholar.org)
  • A) ErbB-2 expression and activation were blocked using ASODNs and AG825 respectively, as described in the legend to Fig. 2 , and cells were treated with HRG for 10 min or left untreated. (asm.org)
  • Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy. (biomedsearch.com)
  • In fact, abundant ErbB-3 expression is detected only in gefitinib-sensitive NSCLC cell lines. (pnas.org)
  • Epidermal growth factor (EGF) receptor and erbB-2, two receptors whose aberrant expression is frequently involved in human cancer, were chosen as targets. (springer.com)
  • Intracellular expression of an scFv that competes with EGF was found to inhibit EGF receptor function in an autocrine manner. (springer.com)
  • Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. (kisti.re.kr)
  • Expression of monocyte chemoattractant protein-1 and CC chemokine receptor 2 in non-small cell lung cancer and its significance. (ebscohost.com)
  • Some characteristics of sebaceous carcinoma, such as female preponderance, shown in the present series during 11-year period at Korea Cancer Center Hospital, led us to study their hormone receptors and c-erbB-2 expression. (semanticscholar.org)
  • The present study addresses the question of the relationship between the desmoplastic reaction and some of the most important biological markers in DC, such as hormone receptors, expression of c-erbB-2 and p53 oncoproteins. (scielo.br)
  • Autocrine loops, mutant ErbB1 molecules and enhanced expression of ErbB receptors are frequently observed in human cancers of epithelial and neuronal origins. (nature.com)
  • In seiner Dissertationsarbeit beschäftigte er sich mit der Expression der erbB-Rezeptoren im Endothelsystem von Reif- und Frühgeborenen [1]. (mh-hannover.de)
  • Eighteen genes regulating metabolism of fatty acids, lipid second messengers and gangliosides were 2-9 fold upregulated in melanomas of GDS-1375. (cancerindex.org)
  • In addition we have fluorescently labelled Herceptin, and its ability to bind c-erbB-2 is retained. (biomedcentral.com)
  • However, these chimeras weakly bind to ErbB-3 alone. (cnrs.fr)
  • Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's Disease. (wikipathways.org)
  • The latter transcript presumably encodes only the extracellular domain of the putative receptor. (nih.gov)
  • The human epidermal growth factor receptor (erbB-2) is a transmembrane receptor that is overexpressed in 15%-25% of breast cancers. (apexbt.com)
  • However, about 10 to 15% of breast cancers do not express either estrogen or progesterone receptor (ER and PgR, resp. (hindawi.com)
  • These studies indicate that Herceptin applied to cells expressing only c-erbB-YFP induces receptor internalisation into a compartment apparently just under the surface of the plasma cell membrane, supporting the observations of Austin and colleagues [ 2 ] who explored this by electron microscopy. (biomedcentral.com)
  • Betacellulin activates the epidermal growth factor receptor and erbB-4, and induces cellular response patterns distinct from those stimulated by epidermal growth factor or neuregulin. (springer.com)
  • [2] [3] GnRH induces the secretion of the gonadotropins , follicle-stimulating hormone (FSH) and luteinizing hormone (LH), from the pituitary gland . (wikipedia.org)
  • Immunohistochemistry is the first-line modality with recourse to FISH only in scores of 2. (ganfyd.org)
  • The expressions of C-erbB-2, CXCR4 and ER-α were measured by immunohistochemistry (IHC) on full tissue sections and on tissue microarrays (TMAs). (biomedsearch.com)
  • Recombinant fragment, corresponding to amino acids 676-end of Human ErbB 2. (abcam.com)
  • Analysis of the selected phage EGF variants revealed clones with high binding affinity to ErbB-2/ErbB-3 while maintaining high affinity to ErbB-1. (cnrs.fr)
  • In NIH/3T3 fibroblasts transformed by a mutated, constitutively active erbB-2, scFv-mediated intracellular retention of erbB-2 led to complete reversion of the transformed phenotype. (springer.com)
  • It serves as a receptor for the epidermal growth factor (EGF) family of growth factors. (perkinelmer.com)
  • However, it is believed to couple with other ErbB family members to activate intracellular signaling. (pnas.org)
  • Figure 1: Family portrait: functional and structural features that are unique to each receptor. (nature.com)
  • It may be that multiple targeting of the HER-family receptors will help to increase the number of patients that respond to the therapy. (biomedcentral.com)
  • We have used this approach to test two alternative strategies for the inactivation of individual members of the erbB family of receptor tyrosine kinases (RTKs). (springer.com)
  • Analysis of signaling emanating from this receptor family is complicated by the extensive crosstalk which occurs among the individual receptors. (springer.com)
  • The results from these experiments have allowed us to draw some important conclusions concerning erbB receptor interplay and to show that erbB-2 is the key member of this family. (springer.com)
  • Proteolytic cleavage by a member of the ADAM family results in the release of a bioactive fragment containing the EGF-like receptor binding domain. (ahajournals.org)
  • ErbB protein family signaling is important for development. (wikipedia.org)
  • All four ErbB receptor family members are nearly same in the structure having single-chain of modular glycoproteins. (wikipedia.org)
  • It is a complex process due to the domain specificity and nature of the members of ErbB family. (wikipedia.org)
  • Within neural tissues, the plexin family serves as transmembrane receptors for Semaphorins. (wikipedia.org)
  • ErbB family members serve as receptors for the epidermal growth factors. (rndsystems.com)
  • In addition to dok-1, dok-2, and dok-3, we identified two new family members, dok-4 and dok-5, that can directly associate with Y1062 of c-Ret. (rupress.org)
  • ErbB-2 blockade and prenyltransferase inhibition alter epidermal growth factor and epidermal growth factor receptor trafficking and enhance (111)In-DTPA-hEGF Auger electron radiation therapy. (ox.ac.uk)
  • Fanti WJ, Johnson DE, Williams LT. Signaling by receptor tyrosine kinases. (springer.com)
  • Excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. (wikipathways.org)
  • A comprehensive pathway map of epidermal growth factor receptor signaling. (wikipathways.org)
  • ErbB receptors: directing key signaling networks throughout life. (wikipathways.org)
  • The ErbB signaling network: receptor heterodimerization in development and cancer. (wikipathways.org)
  • Since the discovery that neuregulin-1 (NRG-1)/ErbB signaling is indispensable in cardiac development, evidence has shown that this system also plays a crucial role in the adult heart. (ahajournals.org)
  • In vivo studies, however, did not uniformly reinforce a role for apoptosis in the development of cardiomyopathy induced by impaired NRG-1/ErbB signaling. (ahajournals.org)
  • On the other hand, pharmacological activation of ErbB signaling is likely an unrecognized and beneficial effect of currently used drugs in heart failure and a promising therapeutic approach to prevent or reverse myocardial dysfunction. (ahajournals.org)
  • NRG-1/ErbB signaling. (ahajournals.org)
  • Despite the apparent necessity of GH/IGF-1 signaling in pubertal breast development however, women with Laron syndrome , in whom the growth hormone receptor (GHR) is defective and insensitive to GH and serum IGF-1 levels are very low, puberty, including breast development, is delayed, although full sexual maturity is always eventually reached. (wikipedia.org)
  • We continue to study how signaling by these receptors impacts responses to different types of therapies and explore targeting these receptors in combination with other novel targeted therapeutics. (yalecancercenter.org)
  • LIF binds to its receptor complex composed of LIFR and gp130 to activate the LIF signaling pathway. (amazonaws.com)
  • However, the prognostic value of individual Notch receptors in breast cancer (BC) patients remains elusive. (springer.com)
  • In the current study, we investigated the prognostic value of Notch receptors in human BC patients. (springer.com)
  • p53 staining tended to be associated with positive nodal status and metastasis, and c-erbB-2 staining with positive nodal status only. (kisti.re.kr)
  • Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. (rcsb.org)
  • Requirement for neuregulin receptor erbBz in neural and cardiac development. (springer.com)