Zhao, Q., Huo, X., Sun, F., Dong, R.[Retracted] Polyphenol‑rich extract of ,em,Saliva chinensis,/em, exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G0/G1‑phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells. Molecular Medicine Reports 23, no. 6 (2021): 462. https://doi.org/10.3892/mmr. ...
298168476 - EP 0869803 B1 20030416 - ALLOGENEIC PARACRINE CYTOKINE TUMOR VACCINES - [origin: WO9724132A1] The present invention provides a method of treating cancer comprising (a) obtaining a tumor cell line, (b) modifying the tumor cell line to render it capable of producing an increased level of a cytokine relative to the unmodified tumor cell line, and (c) administering the tumor cell line to a mammalian host having at least one tumor that is the same type of tumor as that from which the tumor cell line was obtained, wherein the tumor cell line is allogeneic and is not MHC-matched to the host. The present invention also provides a pancreatic tumor cell line, a method and medium for obtaining such a tumor cell line, and a composition comprised of cells of a purified pancreatic tumor cell line.[origin: WO9724132A1] The present invention provides a method of treating cancer comprising (a) obtaining a tumor cell line, (b) modifying the tumor cell line to render it capable of producing an increased level
Polyamines (PAs) are involved in regulation of cell growth and cellular survival by interacting with processes like translation, transcription or ion transport. It is described that polyamines can induce apoptosis in mesenchymal cell lines. The aim of our study was to analyze whether the physiological PAs (putrescine, spermidine or spermine) or the PA-derivate deoxyspergualin (DSG), a novel immunosuppressant, induce apoptosis in immunocompetent cells. Furthermore, we wanted to investigate which molecular mechanisms are involved in the execution of the cell death program. By means of flow cytometric analysis we found an induction of apoptosis by spermine (Spm) and DSG in quiescent and activated PBMCs, PHA generated lymphoblasts, and various tumor cell lines (Jurkat, SKW-3, U937). Moreover, DSG and Spm triggered apoptosis in human Fas-deficient cells and in cell lines MV4.11. and RS4.11., which are described to be resistant to apoptosis induction by many conventional chemotherapeutic agents. ...
Figure s2. Metformin (MET) effects on proliferation of human lung embryonic fibroblast cell line. Human lung embryonic fibroblast cell line was treated with an increasing concentrations of MET (0µmol-25µmol) for a period of 48 hours. Cells were subsequently fixed with ethanol and DNA content was used as a marker for proliferation rate determined by crystal violet staining. Results of three independent experiments are shown. Values represented are Mean±SEM.
TY - JOUR. T1 - Overcoming cancer cell resistance to Smac mimetic induced apoptosis by modulating cIAP-2 expression. AU - Petersen, Sean L.. AU - Peyton, Michael. AU - Minna, John D.. AU - Wang, Xiaodong. PY - 2010/6/29. Y1 - 2010/6/29. N2 - Smac mimetics target cancer cells in a TNFα-dependent manner, partly via proteasome degradation of cellular inhibitor of apoptosis 1 (cIAP1) and cIAP2. Degradation of cIAPs triggers the release of receptor interacting protein kinase (RIPK1) from TNF receptor I (TNFR1) to form a caspase-8 activating complex together with the adaptor protein Fas-associated death domain (FADD). We report here a means through which cancer cells mediate resistance to Smac mimetic/TNFα-induced apoptosis and corresponding strategies to overcome such resistance. These human cancer cell lines evades Smac mimetic-induced apoptosis by up-regulation of cIAP2, which although initially degraded, rebounds and is refractory to subsequent degradation. cIAP2 is induced by TNFα via NF-κB ...
Plant polyphenols have been highlighted not only as chemopreventive, but also as potential anticancer substances. Flavones are a subclass of natural flavonoids reported to have an antioxidant and anticancer activity. The aim of our study was to evaluate antioxidant and anticancer activity of seventeen trihydroxyflavone derivatives, including apigenin (API) and baicalein (BCL). Also, we wanted to find out if there is a correlation between those two effects. Cell growth inhibition testing was carried out using MTT assay in three different human cancer cell lines: lung (A549), breast (MCF-7) and brain epithelial (U87). Antioxidant activity was determined by the DPPH radical scavenging method. Thirteen trihydroxyflavones possessed anticancer activity against at least one tested cancer cell line. They were more active against the MCF-7 cell line, and the lowest activity was determined against the U87 cell line. The majority of compounds inhibited cancer cell growth at EC50 values between 10-50 µM. The most
2075 American ginseng extract (GE) has been shown to have anti-proliferative effects on breast cancer cells, possibly mediated by induction of the cyclin inhibitor protein p21. Little is known regarding the effects of GE in other cancer cell lines or its anti-cancer mechanism(s) of action. The goals of the present study were to determine the effects of water-extracted GE on the proliferation of human colon cancer cells and to examine the role of p21 in mediating these effects using wild-type and p21-null HCT116 cells (courtesy of Dr. B. Vogelstein). Cells were treated with a wide concentration-range of GE (0-2.0 mg/ml) every two days for a total of six days and total cell number was determined. Although proliferation was inhibited by GE in both wild-type and p21-null cells, the IC50 in p21-null cells (0.42 mg/ml) was nearly two fold lower than that in wild-type cells (0.8 mg/ml). Cells were then treated with an inhibitory concentration of GE (1.0 mg/ml) and viability was assessed by trypan blue ...
The systemic balance of angiogenic and anti-angiogenic factors has been proposed to play a key-role in primary tumor growth dependent growth suppression of secondary tumors. Despite the importance of the organ microenvironment to angiogenesis and microcirculation, the influence of a primary tumor on secondary bone tumors has not been investigated so far. Since breast cancer has a high propensity to spread to bone, we used an in vivo xenograft model to determine the impact of growing breast cancer cells (MCF-7) in the mammary fat pad on the microvascular properties of subsequently inoculated secondary breast cancer tumors in bone. Mice were either treated with a resection of the primary tumor (n = 10) or no surgery (n = 9) and intravital microscopy was performed over 25 days in bone tumors. Tumor growth in bone was temporarily suppressed by the primary tumor on days 10 and 14. While microvascular permeability and vascular diameter decreased in both groups over time, the presence of the primary ...
Distant metastasis and drug resistance represent the two major causes for breast cancer mortality. The majority of breast cancer patients who develop metastases also demonstrate multi-drug resistance. The presence of breast cancer stem cells (BCSCs) in these patients might be the underlying key elements for their clinical manifestations. Hence, targeting BCSCs represents an ideal goal for therapeutic development. Recently, cadherin 11 (CDH11) has been shown to be a key mediator for breast-to-bone metastasis; disrupting CDH11-mediated signaling represents an ideal target for drug development. Using bioinformatics approach, our team has identified two known small molecules (temporarily named RD-1 and RD-2) which can down-regulate CDH11 expression in different cancer cell lines including breast. In parallel, we have teamed up with an industrial partner developed who has produced a line of monoclonal anti-CDH11 antibodies with high specificity and neutralizing ability in suppressing breast cancer ...
Despite extensive investigations on the monocyte response to cancer cells, the data available are not sufficient to complete the picture of the molecular mechanisms underlying this phenomenon. When monocytes/macrophages contact a tumor, they activate an inflammatory response within a few hours (12, 40, 41). Nevertheless, monocytes become deactivated after their first exposure to cancer cells (12, 41). This kind of tolerance is characterized by a down-regulation in the expression of several cytokines, and might be termed cancer-induced tolerance. Indeed, the transcription of TNF-α, IL-12, and other proinflammatory molecules is negatively regulated following the initial monocyte contact with tumor cells (12).. Our current observations confirm these previous reports regarding down-regulation of inflammatory responses when monocytes are re-exposed to a particular tumor cell line. In our hands, the inflammatory responses of human monocytes exposed to six different human cancer cell lines were ...
F the soft agar colony formation in comparison with vector control cells exposed to arsenite for eight weeks. A single explanation of these information is the
Previously (Liu et al., Cancer Res., 56: 3371-3379, 1996), we isolated a novel serine protease-like gene-Normal Epithelial Cell Specific-1 (NES1)-that is expressed in normal mammary epithelial cells but is down-regulated in most breast cancer cell lines. Here, we demonstrate that stable expression of NES1 in the NES1-negative MDA-MB-231 breast cancer cell line suppressed the oncogenicity as revealed by inhibition of the anchorage-independent growth and tumor formation in nude mice. Fluorescence in situ hybridization localized the NES1 gene to chromosome 19q13.3, a region that contains genes for related proteases (including the prostate-specific antigen) and is rearranged in human cancers. Similar to breast cancer cell lines, prostate cancer cell lines also lacked NES1 mRNA and protein expression. Together, these results strongly suggest a tumor-suppressor role for NES1 in breast and prostate cancer.. ...
Pazopanib and Sorafenib delay tumor growth in vivo and prolong the survival of mice bearing intracranial human medulloblastomaIn a orthotopic xenograft mouse mo
Effect of Cav-1 expression in prostate cancer cells on in vitro lymphangiogenesis(A) LEC differentiation into tube-like structures was investigated by plating t
Panelists Suresh S. Ramalingam, MD; Marina Garassino, MD; Benjamin Besse, MD, PhD; and Giorgio Scagliotti, MD, PhD, explain what promising molecular targets are emerging for non–small cell lung cancer, particularly |em|HER2|/em| and |em|MET|/em|.
Preclinical validation of potential therapeutic targets via the use of in vivo models is traditionally regarded as an obligatory step of anticancer drug development, but it is also considered a problematic issue. There is now increasing concern that what is still deemed a successful end point at the preclinical level-positive performance of a drug in xenografts of different human cancer cell lines-is in fact not predictive of a compounds efficacy in the clinical setting (44). The obvious objection is that immortalized cancer cells, which are commonly used in xenograft experiments, have been adapted to grow on plastic in the laboratory for decades and thus exhibit a genetic drift, a biologic compliance, and phenotypic features different from original cancers in patients.. Besides this evident flaw, another (often underestimated) drawback of such an approach is that the catalog of currently available cell lines is inevitably finite and possibly poor for some tumor types. The main reason for this ...
Preclinical validation of potential therapeutic targets via the use of in vivo models is traditionally regarded as an obligatory step of anticancer drug development, but it is also considered a problematic issue. There is now increasing concern that what is still deemed a successful end point at the preclinical level-positive performance of a drug in xenografts of different human cancer cell lines-is in fact not predictive of a compounds efficacy in the clinical setting (44). The obvious objection is that immortalized cancer cells, which are commonly used in xenograft experiments, have been adapted to grow on plastic in the laboratory for decades and thus exhibit a genetic drift, a biologic compliance, and phenotypic features different from original cancers in patients.. Besides this evident flaw, another (often underestimated) drawback of such an approach is that the catalog of currently available cell lines is inevitably finite and possibly poor for some tumor types. The main reason for this ...
This study is for patients with breast, prostate, ovarian, non-small cell lung (NSCL) or bladder cancer who have failed potentially curative treatments or for whose disease a curative treatment does not exist.. OGX-427 is a second-generation ASO that inhibits expression of Hsp27. Hsp27 is one of the heat shock proteins. Hsp27 increases with cell stress, including cytotoxic chemotherapy, radiation therapy and hormone therapy and has been shown to inhibit cell death. Thus, decreasing Hsp27 as a cancer therapy is attractive as a therapy as it should result in down regulation of pathways implicated in cancer progression and development of resistance to treatment.. A number of in vitro and in vivo pharmacological studies have demonstrated that OGX-427 has single-agent activity in reducing Hsp27, inhibiting cell growth and inducing cell death in several human cancer cell lines. OGX-427 has also demonstrated chemosensitizing activity in studies using cell lines and animal models in combination with ...
In this study, we showed that SPARCL1 suppresses the proliferation, migration, invasion, and anchorage-independent growth of colon cancer cells (Fig. 1). The expression of SPARCL1 also induces the differentiation of colon cancer cells (Fig. 4). The results are consistent with previously conducted in vitro studies (8, 22). Here, we further report the in vivo findings obtained using xenograft animal models. In the subcutaneous xenograft mouse model, the expression of SPARCL1 retarded tumor growth, which points to its anti-proliferation potential (Supplementary Fig. S4). We used an intrasplenic injection mouse model mimicking liver metastasis of CRC at the later stages. This was based on the anatomy assumption that colon cancer cells migrate mostly through vena porta hepatic (23). The liver metastasis animal model indicated that SPARCL1 significantly reduces the liver metastasis by RKO cells (Fig. 2). These in vitro and in vivo studies validate that the expression of SPARCL1 has potential ...
Hypoxia plays an important role in the resistance of tumour cells to chemotherapy. However, the exact mechanisms underlying this process are not well understood. Moreover, according to the cell lines, hypoxia differently influences cell death. The study of the effects of hypoxia on the apoptosis induced by 5 chemotherapeutic drugs in 7 cancer cell types showed that hypoxia generally inhibited the drug-induced apoptosis. In most cases, the effect of hypoxia was the same for all the drugs in one cell type. The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then investigated. In HepG2 cells that are strongly protected against cell death by hypoxia, hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 cells that are not protected against cell death by hypoxia. In HepG2 cells, hypoxia decreased NOXA and BAD abundance and modified the electrophoretic mobility of BIMEL. BIM
We used the cancer-intrinsic property of oncogene-induced DNA damage as the base for a conditional synthetic lethality approach. To target mechanisms important for cancer cell adaptation to genotoxic stress and thereby to achieve cancer cell-specific killing, we combined inhibition of the kinases ATR and Wee1. Wee1 regulates cell cycle progression, whereas ATR is an apical kinase in the DNA-damage response. In an orthotopic breast cancer model, tumor-selective synthetic lethality of the combination of bioavailable ATR and Wee1 inhibitors led to tumor remission and inhibited metastasis with minimal side effects. ATR and Wee1 inhibition had a higher synergistic effect in cancer stem cells than in bulk cancer cells, compensating for the lower sensitivity of cancer stem cells to the individual drugs. Mechanistically, the combination treatment caused cells with unrepaired or under-replicated DNA to enter mitosis leading to mitotic catastrophe. As these inhibitors of ATR and Wee1 are already in phase ...
Background:. Esophageal cancer (EC) is an aggressive malignancy with increasing incidence and poor outcome (1). New therapeutic strategies are urgently required. The phosphatidylinositol 3-kinase (PI3K)/AKT signal pathway has been documented as a central hub for the malignant behaviors of cancer cells (2). However, the functional role and therapeutic effect of PI3K/AKT inhibitors in esophageal cancer metastasis is underappreciated.. Aim:. We aim to study the clinical significance of PI3K/AKT signaling pathway in EC metastasis and evaluate the therapeutic effect of PI3K/AKT-targeted therapy.. Methods:. A highly invasive cancer cell line (KYSE410-I3) was established by serial selection of the EC cells invading through the matrigel-coated Boyden chamber. Cell migration and invasion were determined using Boyden chamber migration and invasion assays. Western blot and immunohistochemistry were used to detect protein expressions in cell lysates and in a tissue microarray containing 40 pairs of ...
Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
An isogenic cell line ATCC CCL-185IG was created by using CRISPR gene editing technology, and contains EML4-ALK fusion variant 1 (E13; A20).
An isogenic cell line ATCC CCL-185IG was created by using CRISPR gene editing technology, and contains EML4-ALK fusion variant 1 (E13; A20).
Ideal cancer targets should have the following features: (a) they play an essential role in carcinogenesis, and/or are required for the maintenance of cancer cell phenotype, and/or are survival proteins that confer resistance to cancer cells against apoptosis; (b) they are overexpressed in cancer cells, which is associated with a poor prognosis of patient survival; (c) inhibition of their expression or activity induces growth suppression and/or apoptosis in cancer cells, but not in normal cells, achieving a potential therapeutic window; and (d) it is druggable, that is, it is an enzyme (e.g., kinase) or a cell surface molecule (e.g., membrane-bound receptor) that can be easily screened for small-molecule inhibitors or being targeted by a specific antibody (27, 28). In this study, we validated SAG, a dual-function protein with antioxidant and ligase activities, as a potential anticancer target. We showed here that (a) SAG is overexpressed in several human cancers originated from different ...
We here show that the physiological estrogen metabolite 2-Methoxyestradiol (2-ME) has a very strong growth inhibitory effect on cell lines from different solid cancer types. The tumors investigated were hepatocellular carcinome (HCC), pancreatic cancer, and lung cancer. All three tumor types present with a very poor prognosis, which did not improve significantly the last 20 years in spite of new operation techniques, new anticancer drugs, or new molecular approaches. Using several different cell lines of each cancer type we studied, we could confirm a generalized phenomenon of cancer growth inhibition by 2-ME. We found up to 90% growth inhibition in all cell lines with the exception of one pancreatic cancer cell line. This effect could even be increased using combination therapies of 2-ME and Gemcitabine, 5-FU, Taxol or a monoclonal antibody against the EGF receptor. We found an additive growth inhibition when all of these anticancer agents were combined with 2-ME. Our studies on lung cancer ...
We here show that the physiological estrogen metabolite 2-Methoxyestradiol (2-ME) has a very strong growth inhibitory effect on cell lines from different solid cancer types. The tumors investigated were hepatocellular carcinome (HCC), pancreatic cancer, and lung cancer. All three tumor types present with a very poor prognosis, which did not improve significantly the last 20 years in spite of new operation techniques, new anticancer drugs, or new molecular approaches. Using several different cell lines of each cancer type we studied, we could confirm a generalized phenomenon of cancer growth inhibition by 2-ME. We found up to 90% growth inhibition in all cell lines with the exception of one pancreatic cancer cell line. This effect could even be increased using combination therapies of 2-ME and Gemcitabine, 5-FU, Taxol or a monoclonal antibody against the EGF receptor. We found an additive growth inhibition when all of these anticancer agents were combined with 2-ME. Our studies on lung cancer ...
Raji Xenograft Model. What is a Xenograft?. Development of an anti-cancer therapeutic requires intense, well planned studies that follow a streamlined path for success. Primary studies are performed in an in vitro setting that allows for high throughput screening and analysis of multiple compounds of interest. This method enables a focused compound screening approach of multiple cell lines within a specific cancer type, or a divergent approach across a broad range of cancer types. Ultimately, in vitro screening results need to be confirmed in an animal model due to in vitro inadequacies of cells cultured on plastic, as this method is far removed from the microenvironment of a tumor.. As the logical next step in therapeutic development is the administration of the test compound in a living animal, a cell line derived xenograft model (CDX) is created by inoculating human cancer cell lines in test animals. The injected cell lines grow into established tumors, thus, permitting efficacy studies of ...
Interleukin-15 (IL-15) is a common γ-chain cytokine that plays a significant role in the activation and proliferation of T and NK cells and holds great potential in fighting cancer. We have previously shown that bioactive IL-15 in vivo comprises a complex of the IL-15 chain with the soluble or cell-associated IL-15 receptor alpha chain that are together termed heterodimeric IL-15 (hetIL-15). We investigated the anti-tumor efficacy of hetIL-15 in several mouse cancer models. Repeated injections of hetIL-15 were effective in delaying tumor growth in the MC38 colon carcinoma and the B16 melanoma models. The beneficial effects of hetIL-15 therapy included a significantly reduced onset of lung metastasis in 4T1 breast cancer-bearing mice. We study the mechanisms of antitumor effects of hetIL-15 in several tumor models. hetIL-15 administration promoted a dramatic increase of tumor infiltration and persistence of CD8+ T cells, including tumor specific T cells, and resulted in an increased CD8+/Treg ...
Development of novel and effective therapeutics for treating various cancers is probably the most congested and challenging enterprise of pharmaceutical companies. Diverse drugs targeting malignant and nonmalignant cells receive clinical approval each year from the FDA. Targeting cancer cells and nonmalignant cells unavoidably changes the tumor microenvironment, and cellular and molecular components relentlessly alter in response to drugs. Cancer cells often reprogram their metabolic pathways to adapt to environmental challenges and facilitate survival, proliferation, and metastasis. While cancer cells dependence on glycolysis for energy production is well studied, the roles of adipocytes and lipid metabolic reprogramming in supporting cancer growth, metastasis, and drug responses are less understood. This Review focuses on emerging mechanisms involving adipocytes and lipid metabolism in altering the response to cancer treatment. In particular, we discuss mechanisms underlying cancer-associated ...
IL-13Rα2 chain has been shown to play a unique role in tumor biology. It is overexpressed in a variety of primary tumor cell cultures and tumor cell lines (13, 15-18, 25, 34), whereas normal cells including lymphoid cells, endothelial cells, and astrocytes (13, 15, 17, 26) do not express or express low levels of this cytokine receptor chain. Recent studies have demonstrated that overexpression of IL-13Rα2 chain in certain breast and pancreatic cancer cell lines resulted into loss of tumorigenicity, whereas unmodified control tumor cells formed enlarging tumor nodules when injected in immunodeficient mice (46). In another study, Terabe et al. (47) have demonstrated that the soluble form of IL-13Rα2 chain (5) can modulate immune environment and shift Th2 phenotype to a dominant Th1 phenotype. This shift resulted into resistance of 15-12RM cell-derived tumor recurrence. Thus, further investigation of the role of IL-13Rα2 chain in tumor immunology and targeting has become extremely ...
Abstract: The synthesis of an innovative delivery system for targeted cancer therapy which combines the drug controlled release ability of Molecularly Imprinted Polymers (MIPs) with magnetic properties of magnetite is described herein. In the present study, an easy and smart synthetic strategy, involving new engineered precipitation photo-polymerization, was developed with the aim to obtain Magnetic Molecularly Imprinted Polymers (MMIPs) for 9H-carbazole derivative sustained delivery in cancer treatment. Both in vitro drug release and cytotoxicity studies on different cancer cell lines, such as HeLa and MCF-7, were performed in order to evaluate the controlled release ability and the potential application as a drug carrier in targeted cancer therapy. The synthesized polymeric materials have shown not only good selective recognition and controlled release properties, but also high magnetic responding capacity. The performed cytotoxicity studies highlighted the high inhibitory activity against the ...
Researchers at the University of Washington have blended the past with the present in the fight against cancer, synthesizing a promising new compound from an ancient Chinese remedy that uses cancer cells rapacious appetite for iron to make them a target.
Bao et al. uncover that the subpopulation of CD133+ cells isolated from mind tumors exhibit CICs houses, are refractory to chemo- or radiotherapy, and market
Certain compounds in cancerous cells - derivatives of the chemical phenanthridine - end up disrupting the spindle, as the team found, preventing cell chromosomes from splitting, and stopping the cell from dividing.. The growth of the cancer is essentially mitosis out of control, but with the division halted thanks to the new protein mechanism, these cancer cells can die off instead of spreading throughout the body.. According to the mechanism we discovered, the faster cancer cells proliferate, the faster and more efficiently they will be eradicated, says Cohen-Armon.. This technique was tested with positive results on a variety of tumour types in human cancer cell cultures, including breast, lung, ovary, colon, pancreas, blood, and brain cancer.. This is one of many researches currently exploring ways to kill off cancer cells with minimum damage to the body.. Last year, a protein called ProAgio that could trigger cancer cell death was identified from researchers from Georgia State University. ...
BioAssay record AID 103734 submitted by ChEMBL: Compound was tested for cancer cell line growth inhibition against human breast (MCF-7) cell line.
Pdf is an enzyme that, during protein production, removes a modification called an N-formyl group from the first amino acid, a methionine, in the protein chain. While work began on the development of antibiotics against what was thought to be a bacterial-exclusive enzyme, genome-based data searches identified several classes of Pdf-like sequences in parasites, plants and mammals. Subsequent studies showed that the Pdfs were active both in culture and in the living organism, thus potentially derailing the usefulness of these antibiotics for specifically combating infectious agents. In previous studies, Scheinberg and colleagues had found that actinonin had an antiproliferative effect on human cancer cell lines and on tumor growth in a mouse model. They theorized this growth inhibitory activity might be related to actinonin s inhibition of human Pdf ...
METHODS ARE NOW AVAILABLE FOR IDENTIFYING AND PURIFYING A VAST ARRAY OF ANTIGENS EXPRESSED ON TUMOR CELLS. THE PURPOSE OF THE PROPOSED STUDIES IS TO DEVELOP METHODS FOR SENSITIZING T CELLS TO ANTIGENS THAT CAN BE PURIFIED FROM TUMOR CELL MEMBRANES, RATHER THAN SENSITIZING WITH INTACT TUMOR CELLS EXPRESSING THE ANTIGEN. PHASE I STUDIES WILL UTILIZE A MURINE TUMOR EXPRESSING A WELL-DEFINED TUMOR ASSOCIATED ANTIGEN (TAA), WHICH CAN BE READILY PURIFIED AND IS KNOWN TO ELICIT A MEASURABLE T-CELL RESPONSE. THESE STUDIES SHOULD PROVIDE INSIGHT INTO HOW TO HANDLE TAA SO AS TO RETAIN IMMUNOGENICITY AND TO PERMIT GENERATION OF BOTH CYTOTOXIC EFFECTOR T CELLS AND HELPER/DTH EFFECTOR T CELLS REACTIVE WITH THE TUMOR. STUDIES PERFORMED WITH BIOCHEMICALLY PROCESSED TAA AND BIOSYNTHETIC PLANAR LIPID MEMBRANES AS AN ANTIGEN-PRESENTING SURFACE SHOULD HELP DEVELOP METHODOLOGY FOR BYPASSING THE REQUIREMENT FOR BOTH INTACT TUMOR CELLS AND ANTIGEN-PRESENTING CELLS FROM THE PATIENT FOR IN VITRO SENSITIZATION OF T ...
CD146, a marker of endothelial cells, promotes tumor progression of many cancers including melanoma and the prostate. Strikingly, several lines of evidence suggest that it is a suppressor of breast cancer (BC) progression. In addition, not only the ligand(s) has not been identified, but CD146-downstream mechanisms remain unknown. Here, we report a novel molecular mechanism by which CD146 acts as a suppressor of breast tumor growth. A novel transcriptional target of CD146-suppressed BC, TimpV, the only endogenous protein inhibitor known for metallocarboxypeptidases, was identified and validated using novel validated Enhanced Green Fluorescent Protein (EGFP)-inducible systems of CD146 expression in both, the weakly and the highly invasive BC cell lines MCF-7 and MDA-MB-231, respectively. CD146/TimpV association was validated by quantitative PCR and immunoblotting experiments in a range of BC cells. In functional experiments, both CD146 induction and siRNA experimental approaches revealed that, ...
Circulating Tumor Cells Circulating Tumor Cells (CTC) • Metastasis: the spread of cancer from its primary site to other places in the body. Metastatic disease is the most common cause of cancer-related death in patients with solid tumors. Metastasis Process CTCs • Standard definition of a CTC: - Epithelial tumor cell which has adopted genetic mutations that enable migration through the basement membrane and the extracellular matrix, and is free to circulate in the blood stream - confirmed by: 1) visualization of an intact nucleus (using DAPI, 4′,6-diamidino-2phenylindole, a DNA-binding fluorescent stain) 2) expression of cytokeratin 3) lack of expression of the white blood cell marker, CD45, the leukocyte-common antigen gene - Invasive tumor cells tend to loose their epithelial antigens by the epithelial to mesenchymal transition (EMT) process, so CTCs cannot be diagnosed based on the expression of epithelial-specific transcripts or antigens Clinical Usefulness • Many metastatic lesions ...
Ski, the transforming protein of the avian Sloan-Kettering retrovirus, inhibits transforming growth factor-β (TGF-β)/Smad signaling and displays both pro-oncogenic and anti-oncogenic activities in human cancer. Inhibition of TGF-β signaling is likely responsible for the pro-oncogenic activity of Ski. We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. TAZ and YAP are transcriptional coactivators that can contribute to cancer by promoting proliferation, tumorigenesis, and cancer stem cell expansion. Hippo signaling activates the the Lats family of kinases, which phosphorylate TAZ and YAP, resulting in cytoplasmic retention and degradation and inhibition of their transcriptional activity. We showed that Ski interacted with multiple components of the Hippo pathway to facilitate activation of Lats2, resulting in increased phosphorylation and ...
Macrophages within the tumor microenvironment facilitate angiogenesis and extracellular-matrix breakdown and remodeling and promote tumor cell motility. Recent studies reveal that direct communication between macrophages and tumor cells leads to invasion and egress of tumor cells into the blood vess …
As combining therapeutic agents with different action mechanisms may enhance efficacy, YSC-02, an oncolytic adenovirus with multi targets was loaded with five different genes, which were designed with the expectation that different action mechanisms would cooperate. In spite of concerns regarding many APIs, YSC-02 was constructed to be an adenovirus-based anti-cancer drug. By using our own established mouse model system suitable for efficient adenoviral infection and replication, immune activity as well as survival potential could be precisely estimated for anti-cancer drug efficacy. YSC-02 was designed to decrease tumor cell survival, metastasis and to increase tumor cell death, and immune activation. It is composed of five different target genes, including one fused form and two shRNAs, but each of these genes functions is closely linked to produce the maximal antitumor effect. YSC-02 is like an organic complex designed to be applied primarily to heterogeneous liver cancer and melanoma. The ...
Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of antioxidative properties. Punica granatum (PG) (pomegranate) is a well known fruit in this context, but its cytotoxicity in cancer cells has not been extensively studied. Here, we investigated the antiproliferative properties of a peel extract of PG from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate peel (PPE) was prepared. Total phenolic content(TPC) and total flavonoid conetnt (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. The cytotoxicity of different doses of PPE (0, 5, 20, 100, 250, 500, |TEX|$1000{\mu}g/ml$|/TEX|) was evaluated by MTT assays with A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P|0.01) or very significant (P|0.0001)
TY - JOUR. T1 - Enhancement of sensitivity of human lung cancer cell line to TRAIL and gefitinib by IGF-1R blockade. AU - Lee, Yoon Jin. AU - Park, Mi Young. AU - Young, Ae Kang. AU - Kwon, Sung Youn. AU - Yoon, Ho Il. AU - Lee, Jae Ho. AU - Lee, Choon Taek. PY - 2007/7. Y1 - 2007/7. N2 - Background: TRAIL is a cytokine that selectively induces apoptosis in various cancer cell lines. Gefitinib is new targeted drug applied in lung cancer that selectively inhibits EGFR tyrosine kinase. However, lung cancers have shown an initial or acquired resistance to these drugs. This study examined the effect of IGF-1R and its blockade on enhancing the sensitivity of lung cancer cell lines to TRAIL and gefitinib. Methods: Two lung cancer cell lines were used in this study. NCI H460 is very sensitive to TRAIL and gefitinib. On the other hand, A549 shows moderate resistance to TRAIL and gefitinib. The IGF-1R blockade was performed using adenoviruses expressing the dominant negative IGF-1R and shRNA to IGF-1R ...
Thuja, a bioactive derivative of Thuja occidentalis, has been widely accredited for its antitumorigenic potential (25,26). Although reports have verified the anticancer effect of this remedy (8-10), detailed reports elucidating the molecular mechanisms underlying the anticancer effect of thuja are needed. The present study demonstrated that the antitumorigenic effect of thuja on breast cancer cells was not a placebo effect as the placebo (potentized hydro-alcoholic solution)-treated cells failed to induce significant cell death when compared to the control cells. The present study further revealed that thuja asserted its effects by re-orienting the molecular choreography of cancer cells. Importantly, the preferential induction of the cytotoxic effects in breast cancer cells, as compared to normal cells, suggests a safe and non-toxic therapeutic opportunity.. It was shown that thuja is a potent inducer of apoptosis in mammary epithelial carcinoma cells, with a more pronounced effect in ...
TY - JOUR. T1 - Determinants of drug response in a cisplatin-resistant human lung cancer cell line. AU - Fujiwara, Yasuhiro. AU - Sugimoto, Yoshikazu. AU - Kasahara, Kazuo. AU - Bungo, Masami. AU - Yamakido, Michio. AU - Tew, Kenneth D.. AU - Saijo, Nagahiro. PY - 1990/5. Y1 - 1990/5. N2 - To elucidate the mechanism(s) of cisplatin resistance, we have characterized a human non-small cell lung cancer cell line ( PC-9 CDDP) selected from the wild type (PC-9) for acquired resistance to cisplatin. PC-9 CDDP demonstrated 28-fold resistance to cisplatin, with cross resistance to other chemotherapeutic drugs including chlorambucil (×6.3), melphalan (×3.7) and 3-[(4-amino-2-methyl-5-pyrimidinyl)]methyl-1-(2-chloroethyl)-1-nitrosourea (ACNU) (×3.9). There was no expression of mdr-1 mRNA in either wild-type or resistant cells. The mRNA and protein levels of glutathione S-transferase (GST) π were similar in the two lines. A GST-μ isozyme was present in equal amounts and the activities of ...
Lung cancer is the commonest type of cancer with the highest fatality rate worldwide. There is continued research that experiments on drug development for lung cancer patients by assessing their responses to chemotherapeutic treatments to select novel targets for improved therapies. This study aims to analyze the anticancer drug sensitivity in human lung cancer cell lines by using machine learning techniques. The data for this analysis is extracted from the National Cancer Institute (NCI). This experiment uses 408,291 human small molecule lung cancer cell lines to conclude. The values are drawn from describing the raw viability values for 91 human lung cancer cell lines treated with 354 different chemical compounds and 432 concentration points tested in each replicate experiments. Our analysis demonstrated the data from a considerable amount of cell lines clustered by using Simple K-means, Filtered clustering and by calculating sensitive drugs for each lung cancer cell line. Additionally, our analysis
The aim of this study was the evaluation of the effects of strawberry anthocyanin extracts treatment on two in vitro models of murine breast cancer cell line, trying to detect a specific pathway (AMP-activated protein kinase, or AMPK) through which strawberries exert their anticancer activity. The anticancer
There is increasing evidence for the involvement of miRNAs in mammalian biology and breast cancer. For instance, the levels of MiR-206 have been found to be higher in ERalpha-negative MB-MDA-231 cells than in ERalpha-positive MCF-7 cells [12], and enforced expression of miR-125a or miR-125b leads to coordinate suppression of ERBB2 and ERBB3 in the human breast cancer cell line SKBR3 [13]. Furthermore, MiR-27b, which is expressed in MCF-7 cells, may be one of the causes of high expression of the drug-metabolising enzyme CYP1B1 in cancerous tissues [14]. Finally, as a tumor suppressor in breast cancer cells, miR-17-5p regulates breast cancer cell proliferation by inhibiting the translation of AIB1 mRNA [15].. Research on the roles of BCSC-related miRNAs in breast cancer has great significance. Ponti [16] isolated tumorigenic breast cancer cells with stem/progenitor cell properties from a breast cancer cell line, and Huang [17] screened side population (SP) cells from a breast cancer cell line. ...
Focal adhesion kinase, FAK is a 125 kDa nonreceptor tyrosine kinase that localizes to focal adhesions. FAK is overexpressed in human tumors and regulates cellular adhesion and survival signaling. We have shown previously that the dominant-negative FAK, C-terminal FAK-CD, caused detachment and apoptosis in human breast cancer cells, and that overexpression of an activated form of Src tyrosine kinase or epidermal growth factor receptor, EGFR, suppressed FAK-CD induced apoptotic effects in breast cancer cells. In the present study, we studied the effect of a novel FAK inhibitor, TAE226 (Novartis, Inc.), on the breast cancer cell lines. We used stable breast cancer cell lines overexpressing Src (MCF-7-Src and BT474-Src) or overexpressing EGFR (BT474-EGFR), and control breast cancer cell lines for the treatment with different doses of TAE226 drug. The detachment and apoptosis caused by TAE226 was analyzed and compared with the effect of the dominant-negative adenoviral FAK-CD. The TAE226 drug caused ...
The genus Stachys belongs to Lamiaceae family with about 300 species and worldwide distribution. In the present study, the cytotoxic activity of four fractions of different Satchys species (S. byzatina C. Koch., S. inflata Benth., S. setifera Ten. and S. persica Gmel.), has been investigated against HT-29 (colon carcinoma), Caco-2 (colorectal adenocarcinoma), T-47D (breast ductal carcinoma) and NIH-3T3 (Swiss mouse embryo fibroblast) cell lines by MTT test. The samples were extracted by percolation method with four solvents; petroleum ether (60-80 ºC), chloroform, ethyl acetate and 80% aqueous methanol, susseccively. All cell lines were cultured in proper medium. Concentrations of 62.5-750 μg/mL from partition fractions of all samples, dissolved in 1% (v/v) DMSO were tested on each cell line. Cells with no treatment and methotrexate were examined as negative and positive controls, respectively. Cell viability was determined by MTT assay. Some fractions showed good cell inhibitory activity with IC50S.
Research highlights: {yields} PPAR{gamma} ligands increased the rate of apoptosis and inhibition of proliferation in ovarian cancer cells. {yields} PPAR{gamma} ligands induced p63 and p73 expression, but not p53. {yields} p63 and p73 leads to an increase in p21 expression and apoptosis in ovarian cancer cells with treatment PPAR{gamma} ligands. {yields} These findings suggest that PPAR{gamma} ligands suppressed growth of ovarian cancer cells through upregulation of p63 and p73. -- Abstract: Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) agonists, including thiazolidinediones (TZDs), can induce anti-proliferation, differentiation, and apoptosis in various cancer cell types. This study investigated the mechanism of the anticancer effect of TZDs on human ovarian cancer. Six human ovarian cancer cell lines (NIH:OVCAR3, SKOV3, SNU-251, SNU-8, SNU-840, and 2774) were treated with the TZD, which induced dose-dependent inhibition of cell growth. Additionally, these cell lines exhibited ...
To address the role of β(1) integrins in pancreatic cancer progression, we stably knocked down β(1) integrin subunit expression in human FG-RFP pancreatic cancer cells using lentiviral-based RNA interference. We then examined the effects of β(1) integrin subunit knockdown on pancreatic cancer cell adhesion, migration and proliferation on tumor microenvironment-specific extracellular matrix proteins in vitro and on tumor progression in vivo using a clinically relevant fluorescent orthotopic mouse model of pancreatic cancer. Knockdown of the β(1) integrin subunit inhibited cell adhesion, migration and proliferation on types I and IV collagen, fibronectin and laminin in vitro. In vivo, knockdown of the β(1) integrin subunit reduced primary tumor growth by 50% and completely inhibited spontaneously occurring metastasis. These observations indicate a critical role for the β(1) integrin subunit in pancreatic cancer progression and metastasis in particular. Our results suggest the β(1) integrin
Using a broad panel of 44 human breast cancer cell lines and 3 immortalized breast epithelial lines, we have shown that HER2 amplification status was a strong predictor of response to dacomitinib, with IC50 values below 1 μmol/L in the vast majority of HER2-amplified lines. MDA-MB-453 and UACC-732 were the only HER2-amplified lines that were resistant to dacomitinib. Of note, these 2 lines have some of the lowest levels of HER2 DNA copy number by comparative genomic hybridization (data not shown) and HER2 mRNA among the HER2-amplified lines. In addition, these 2 lines express low baseline levels of total and phosphorylated HER2 (25) and total and phosphorylated EGFR (data not shown). These 2 cell lines were also previously shown to be resistant to trastuzumab (25) and lapatinib (25, 26). These findings may have potential clinical implications for selecting the patients for clinical trials with dacomitinib.. Dacomitinib showed an antiproliferative activity superior to trastuzumab in vitro. The ...
There has been a long‐standing debate over the role of LNs in promoting cancer malignancy. Some clinical evidence has suggested that metastasis to the LNs in breast cancer patients is strongly associated with distant organ metastasis, poor disease‐free survival, and shorter overall survival (Rouzier et al, 2002; Ran et al, 2010). Although breast cancer cell‐induced lymphangiogenesis in TDLNs is important to distant organ metastasis in mouse model, there is no direct evidence to demonstrate that breast cancer cells metastasized to LNs was required for further distant organ metastasis (Hirakawa et al, 2007; Shibata et al, 2008). Several clinical trials showed no survival benefits for patients underwent lymphadenectomy (Gervasoni et al, 2007). Thus, whether TDLNs involved in the progression of systemic metastasis remain controversial (Ran et al, 2010; Pereira et al, 2015). Using a syngeneic mouse model, we observed that breast tumor cells derived from TDLN gained higher malignancy compared ...
HMGB3 silence inhibits breast cancer cell proliferation and tumor growth by interacting with hypoxia-inducible factor 1alpha Jun Gu, Tao Xu, Qin-Hua Huang, Chu-Miao Zhang, Hai-Yan ChenDepartment of Health Check-Up Center, Jinshan Hospital, Fudan University, Shanghai 201508, Peoples Republic of ChinaBackground: Breast cancer is the most common malignant tumor that affects women with higher incidence. High-mobility group box 3 (HMGB3) plays critical functions in DNA repair, recombination, transcription and replication. This study aimed to investigate the effects of HMGB3 silence on mammosphere formation and tumor growth of breast cancer.Methods: LV5-HMGB3 and LV3-siHMGB3 vectors were transfected into MCF10A, MDA-MB-231, HCC1937, ZR-75-1 and MCF7 cells. Cell counting kit-8 (CCK-8) assay was used to evaluate cell proliferation. Xenograft tumor mice model was established by injection of MDA-MB-231. qRT-PCR and western blot were used to examine the expression of Nanog, Sox2 and OCT-4. Mammosphere forming
ARHI is a Ras-related imprinted gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of breast cancers, and loss of its expression is associated with its progression from ductal carcinoma in situ (DCIS) to invasive disease. In ovarian cancer, re-expression of ARHI induces autophagy and leads to autophagic death in cell culture; however, ARHI re-expression enables ovarian cancer cells to remain dormant when they are grown in mice as xenografts. The purpose of this study is to examine whether ARHI induces autophagy in breast cancer cells and to evaluate the effects of ARHI gene re-expression in combination with paclitaxel. Re-expression of ARHI was achieved by transfection, by treatment with trichostatin A (TSA) or by a combination of TSA and 5-aza-2-deoxycytidine (DAC) in breast cancer cell cultures and by liposomal delivery of ARHI in breast tumor xenografts. ARHI re-expression induces autophagy in breast cancer cells, and ARHI is essential for the induction of
Brain metastasis is an increasingly common complication for breast cancer patients; approximately 15- 30% of breast cancer patients develop brain metastasis. However, relatively little is known about how these metastases form, and what phenotypes are characteristic of cells with brain metastasizing potential. In this study, we show that the targeted knockdown of MMP-1 in breast cancer cells with enhanced brain metastatic ability not only reduced primary tumor growth, but also significantly inhibited brain metastasis. Two variants of the MDA-MB-231 human breast cancer cell line selected for enhanced ability to form brain metastases in nude mice (231-BR and 231-BR3 cells) were found to express high levels of matrix metalloproteinase-1 (MMP-1). Short hairpin RNA-mediated stable knockdown of MMP-1 in 231-BR and 231-BR3 cells were established to analyze tumorigenic ability and metastatic ability. Short hairpin RNA-mediated stable knockdown of MMP-1 inhibited the invasive ability of MDA-MB 231 variant cells
HE4, also known as WFDC2, is a useful biomarker for ovarian cancer when either used alone or in combination with CA125. HE4 is also overexpressed in endometrial cancer (EC), but its function in cancer cells is not clear. In this study, we investigate the role of HE4 in EC progression. An HE4-overexpression system was established by cloning the HE4 prototypic mRNA variant (HE4-V0) into a eukaryotic expression vector. Following transfection, stable clones in two EC cell lines were selected. The effects of HE4 overexpression on cell growth and function were measured with the use of cell proliferation assay, matrigel invasion, and soft agar gel colony formation assays. HE4-induced cancer cell proliferation in vivo was examined in a mouse xenograft model. HE4 overexpression significantly enhanced EC cell proliferation, matrigel invasion, and colony formation in soft agar. Moreover, HE4 overexpression promoted tumor growth in the mouse xenograft model. HE4 overexpression enhanced several malignant phenotypes
TY - JOUR. T1 - Amphiregulin is a potent mitogen in human pancreatic cancer cells. T2 - Correlation with patient survival. AU - Yokoyama, M.. AU - Ebert, M.. AU - Funatomi, H.. AU - Friess, H.. AU - Buchler, M. W.. AU - Johnson, G. R.. AU - Korc, Murray. PY - 1995. Y1 - 1995. N2 - The epidermal growth factor (EGF) receptor (EGFR) is activated by EGF and other EGF-like growth factors, including amphiregulin (AR). We characterized the localization and mitogenic action of AR in T3M4 and COLO-357 human pancreatic cancer cell lines and determined whether the presence of AR in human pancreatic cancers correlates with patient survival. Both T3M4 and COLO-357 cells were found to be extremely sensitive to AR, one-half maximal stimulation occurring at a concentration of 70 and 50 pM, respectively. The magnitude of the stimulatory effect was greater with AR than with EGF. Both cell lines exhibited AR immunostaining, which was present in a variable manner in the cytoplasm, nucleus and nucleoli. ...
Expression of programmed cell death ligand 1 (PD-L1) is an important process by which tumor cells suppress antitumor immunity in the tumor microenvironment. Bone marrow (BM)-derived immune cells are an important component of the tumor microenvironment. However, the link between PD-L1 induction on tumor cells and communication with BM cells is unknown. This study demonstrates that BM cells have a direct effect in inducing PD-L1 expression on tumor cells, which contributes to the tumor cells drug resistance. This novel discovery was revealed using a co-incubation system with BM cells and tumor cells. BM cells from wild-type C57BL6 mice and the immune-deficient mouse strains B-cell−/−, CD28−/−, perforin−/−, and Rag2−/− but not CD11b−/− dramatically increased the expression of tumor cell surface PD-L1. This PD-L1 induction was dependent on CD11b-positive BM cells through direct contact with tumor cells. Furthermore, p38 signaling was activated in tumor cells after co-incubation with BM
Expression of programmed cell death ligand 1 (PD-L1) is an important process by which tumor cells suppress antitumor immunity in the tumor microenvironment. Bone marrow (BM)-derived immune cells are an important component of the tumor microenvironment. However, the link between PD-L1 induction on tumor cells and communication with BM cells is unknown. This study demonstrates that BM cells have a direct effect in inducing PD-L1 expression on tumor cells, which contributes to the tumor cells drug resistance. This novel discovery was revealed using a co-incubation system with BM cells and tumor cells. BM cells from wild-type C57BL6 mice and the immune-deficient mouse strains B-cell−/−, CD28−/−, perforin−/−, and Rag2−/− but not CD11b−/− dramatically increased the expression of tumor cell surface PD-L1. This PD-L1 induction was dependent on CD11b-positive BM cells through direct contact with tumor cells. Furthermore, p38 signaling was activated in tumor cells after co-incubation with BM
Natural products, especially supplementary metabolites produced by plants under stressed conditions, are shown to have different pharmacological impacts from one to another. cell lines. The existing study aims to research the power of crude nonpolar, semi-polar, and polar components of leaves to activate different required mechanisms that may prevent tumor cell proliferation or stimulate tumor cell apoptosis. 2. Outcomes: 2.1. Cytotoxicity The ready crude components had been examined against different tumor cell lines: MCF-7, HCT-116, and HepG2. The outcomes exposed that hexane and ethyl acetate components produced a substantial impact in comparison to in solid tumor cell lines MCF-7, HCT-116, and HepG2. Cells had been subjected to the components for 72 h. Cell viability was determined using SRB-U SulphoRhodamine-B data and assay are expressed as mean S.D. (n = 3). Desk 1 IC50 (g/mL) of different components of in various solid tumor cell lines. for 48 h, stained with AO/EB. The pictures had been ...
Cell lines and culture conditions. Human breast cancer cell lines (MDA-MB-231 and MCF-7) and 293T were purchased from the American Type Culture Collection (ATCC). These cell lines were authenticated at ATCC before purchase by standard short tandem repeat DNA-typing methodology. The murine mammary carcinoma cell line E0771 was purchased from BeNa Culture Collection. The Py8119 cell line was provided by Suling Liu (Fudan University, Shanghai, China). The MDA-MB-231, E0771, and 293T cell lines were maintained in Dulbeccos modified Eagle medium (DMEM; Invitrogen) supplemented with 10% FBS (Invitrogen Corp.). The MCF-7 cell line was maintained in Eagles minimum essential medium (Invitrogen Corp.) supplemented with 10% FBS and 0.01 mg/ml human recombinant insulin. The Py8119 cell line was maintained in F12K nutrient media (HyClone) supplemented with 5% FBS. Each cell line was cultured in standard medium as recommended by ATCC. All cells were incubated at 37°C in a humidified incubator containing 5% ...
Most human cancers have CNVs, which impact upon gene dosage through loss or gain of whole chromosomes or chromosome segments (Hanahan and Weinberg 2011). Previous studies have described CNVs in PC3 and LNCaP using targeted techniques, such as exome sequencing. However, WGS, together with continuously updated gene annotations, offers improved detection of copy number changes (Meynert et al. 2014; Belkadi et al. 2015; Warr et al. 2015).. CNVs were identified using the R package cn.mops (Klambauer et al. 2012). In particular, we wished to identify genes that are lost in PC3 and LNCaP. The absence of this information can misinform even the most well-designed in vitro or cell line xenograft experiment (e.g., where a gene in an important pathway is lost). In the context of CNV analysis, we were interested in identifying putative homozygous deletions (CNV = 0; CNV0 events), i.e., genes that are inactivated by partial or complete gene deletion. To inform this analysis, we also considered the ...
The invasive, mesenchymal phenotype of CD44posCD24neg breast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44neg/lowCD24pos breast cancer cells lack the ability to give rise to their invasive CD44posCD24neg counterpart. Here we demonstrate that noninvasive, epithelial-like CD44posCD24pos cells readily give rise to invasive, mesenchymal CD44posCD24neg progeny in vivo and in vitro. This interconversion was found to be dependent upon Activin/Nodal signaling. Breast cancer cell lines were sorted into CD44posCD24pos and CD44posCD24neg populations to evaluate their progeny for the expression of CD44, CD24, and markers of a mesenchymal phenotype. The populations, separated by fluorescence activated cell sorting (FACS) were injected into immunocompromised mice to evaluate their tumorigenicity and invasiveness of the resulting xenografts. CD24 expression was dynamically regulated in vitro in all evaluated breast
The invasive, mesenchymal phenotype of CD44posCD24neg breast cancer cells has made them a promising target for eliminating the metastatic capacity of primary tumors. It has been previously demonstrated that CD44neg/lowCD24pos breast cancer cells lack the ability to give rise to their invasive CD44posCD24neg counterpart. Here we demonstrate that noninvasive, epithelial-like CD44posCD24pos cells readily give rise to invasive, mesenchymal CD44posCD24neg progeny in vivo and in vitro. This interconversion was found to be dependent upon Activin/Nodal signaling. Breast cancer cell lines were sorted into CD44posCD24pos and CD44posCD24neg populations to evaluate their progeny for the expression of CD44, CD24, and markers of a mesenchymal phenotype. The populations, separated by fluorescence activated cell sorting (FACS) were injected into immunocompromised mice to evaluate their tumorigenicity and invasiveness of the resulting xenografts. CD24 expression was dynamically regulated in vitro in all evaluated breast
TY - JOUR. T1 - Rad51b activity and cell cycle regulation in response to DNA damage in breast cancer cell lines. AU - Lee, Phoebe S.. AU - Fang, Jun. AU - Jessop, Lea. AU - Myers, Timothy. AU - Raj, Preethi. AU - Hu, Nan. AU - Wang, Chaoyu. AU - Taylor, Philip R.. AU - Wang, Jianjun. AU - Khan, Javed. AU - Jasin, Maria. AU - Chanock, Stephen J.. PY - 2014/10/12. Y1 - 2014/10/12. N2 - Common genetic variants mapping to two distinct regions of RAD51B, a paralog of RAD51, have been associated with breast cancer risk in genome-wide association studies (GWAS). RAD51B is a plausible candidate gene because of its established role in the homologous recombination (HR) process. How germline genetic variation in RAD51B confers susceptibility to breast cancer is not well understood. Here, we investigate the molecular function of RAD51B in breast cancer cell lines by knocking down RAD51B expression by small interfering RNA and treating cells with DNA-damaging agents, namely cisplatin, hydroxyurea, or ...
Podocalyxin (gene name PODXL) is a CD34-related sialomucin implicated in the regulation of cell adhesion, migration and polarity. Upregulated expression of podocalyxin is linked to poor patient survival in epithelial cancers. However, it is not known if podocalyxin has a functional role in tumor progression. We silenced podocalyxin expression in the aggressive basal-like human (MDA-MB-231) and mouse (4T1) breast cancer cell lines and also overexpressed podocalyxin in the more benign human breast cancer cell line, MCF7. We evaluated how podocalyxin affects tumorsphere formation in vitro and compared the ability of podocalyxin-deficient and podocalyxin-replete cell lines to form tumors and metastasize using xenogenic or syngeneic transplant models in mice. Finally, in an effort to develop therapeutic treatments for systemic cancers, we generated a series of antihuman podocalyxin antibodies and screened these for their ability to inhibit tumor progression in xenografted mice. Although deletion of
Fibroblast growth factors (FGFs) and their high-affinity receptors contribute to the autocrine growth stimulation in several human malignancies. Here, we describe that FGF18 expression is up-regulated in 34/38 colorectal tumours and is progressively enhanced during colon carcinogenesis reaching very high levels in carcinoma. Moreover, our data suggest that FGF18 affects both tumour cells and tumour microenvironment in a pro-tumorigenic and pro-metastatic way. Addition of recombinant FGF18 to the culture media of slowly growing colorectal tumour cell lines LT97 and Caco-2 stimulated proliferation. Phosphorylation of externally regulated kinase 1/2 and S6 was increased already 5 min after growth factor addition. SW480 cells, endogenously producing large amounts of FGF18, were not affected in this setting, but recombinant FGF18 supported tumour cell survival under conditions of serum starvation. Down-modulation of endogenous FGF18 production by small interference RNA (siRNA) significantly reduced ...
Genome-wide genetic information in about 1,000 cancer cell lines is available on COSMIC DB(Sanger Center, UK), and on recent NGS analyses(Klijin C et al., Nat Biotechnol 2015); however, among them, only 28 cell lines are derived from GC. Since driver gene mutation frequency in a certain cancer is often less than 5%, the establishment of cell lines from each patient to be analyzed is desired for functional selection of driver gene mutations. Furthermore, almost all of the 28 GC cell lines were established many years ago, thereby, the clinical and pathological information is insufficient. The wait is on for the establishment of new GC cell lines, especially from metastatic sites after therapy. Peritoneal metastasis is most frequent in GCs, especially diffuse-type GCs. In 2016, we successfully established 13 diffuse-type GC cell lines from the cancer ascites of 12 patients. In collaboration with the Division of Genetics, we have totally established 84 diffuse-type GC cell lines(National ...
In addition to serving as a physical support, the extracellular matrix (ECM) actively influences cell behavior. However, the definitive effects of different chemical structures present in the ECM on cell behavior remain obscure. The current study aimed to investigate the effects of different chemical structures present in the ECM on cellular physiology using the ovarian cancer cell line SKOV-3 as a model. Self-assembled monolayers (SAMs) with different chemical modifications, including methyl (-CH|sub|3|/sub|), hydroxyl (-OH), amino (-NH|sub|2|/sub|), carboxyl (-COOH), and mercapto (-SH) groups, were used as microenvironmental models to explore the effects of different structures on SKOV-3 cells. The cell morphology, cell adhesion, cytotoxicity, and functional alterations in cancer cells cultured on different SAMs were analyzed. The results showed that SKOV-3 cells cultured on -NH|sub|2|/sub| surfaces exhibited the largest contact area, whereas those on -CH|sub|3|/sub| surfaces exhibited the smallest
The apoptosis-stimulating protein of p53 (ASPP) family comprises three members, namely, ASPP1, ASPP2, and iASPP. They regulate the promotive effect of p53 on apoptosis. Breast cancer (BC) remains as one of the leading causes of cancer or cancer-related mortality among women. However, the relationship between the ASPP family members and p53, as well as the dissemination and expression pattern of ASPP family members in p53+ BC, has not been elucidated. Our objectives are to detect the expression of ASPP family members in p53+ BC cell lines and determine its significance in tumor cell apoptosis. The mRNA expression of ASPP family members in five p53+ BC cell lines was detected through RT-PCR and assayed using Quality-one software. The p53 protein expression was detected by immunohistochemistry. Afterward, the apoptosis indices of the five BC cell lines were detected by flow cytometry. The iASPP mRNA was expressed in Bcap-37, MCF-7, and HBL-100. Compared with the human peripheral blood mononuclear cells,
Breast cancer, which derives from the epithelium of the mammary glands, is one of the most common cancers diagnosed in women globally. To date, the authors of many studies have reported that the deregulation of microRNAs (miRNAs) plays a crucial role in the occurrence, development, and metastasis of tumors. Here, we discovered that miR-660-5p was upregulated in the breast cancer cell lines MCF7 and MDA-MB-231 compared with that in the normal control cell line CCD-1095Sk. We then inhibited the expression of miR-660-5p to investigate its biological function in cancer development, progression, and metastasis. We determined the changes in the levels of expression of transcription factor CP2 (TFCP2) and CDKN1A to further clarify the specific mechanism involved. The results showed that downregulation of miR-660-5p significantly suppressed the proliferation, migration, and invasion of MCF7 breast cancer cell. Moreover, inhibition of miR-660-5p promoted cell cycle G1 arrest and reduced apoptosis in ...
Pancreatic cancer (PC) remains a major cause of cancer-related deaths primarily due to its inherent potential of therapy resistance. Checkpoint inhibitors have emerged as promising anti-cancer agents when used in combination with conventional anti-cancer therapies. Recent studies have highlighted a critical role of the Greatwall kinase (microtubule-associated serine/threonine-protein kinase-like (MASTL)) in promoting oncogenic malignancy and resistance to anti-cancer therapies; however, its role in PC remains unknown. Based on a comprehensive investigation involving PC patient samples, murine models of PC progression (Kras;PdxCre-KC and Kras;p53;PdxCre-KPC), and loss and gain of function studies, we report a previously undescribed critical role of MASTL in promoting cancer malignancy and therapy resistance. Mechanistically, MASTL promotes PC by modulating the epidermal growth factor receptor protein stability and, thereupon, kinase signaling. We further demonstrate that combinatorial therapy targeting
Our objective was to evaluate the cancer suppression activity of extracts from a commercial variety of yellow-fleshed peach Rich Lady (RL) and a red-fleshed plum Black Splendor (BS) and identify the phenolic fractions that may possess potential as chemopreventive and/or chemotherapeutic natural compounds. The peach RL extract effectively inhibited the proliferation of the estrogen-independent MDA-MB-435 breast cancer cell line. The concentration to inhibit 50% of cell proliferation (IC(50)) was approximately 42 mg/L for this cell line compared to an IC(50) of approximately 130 and approximately 515 mg/L for the noncancerous breast cell line MCF-10A and the estrogen-dependent breast cancer cell line MCF-7, respectively. Similarly, BS extracts showed greater effects on MDA-MB-435 cells as compared to the other breast cancer or the normal breast cell lines. In general, BS extracts were less effective than RL extracts. Within all RL and BS fractions, fraction 3 (F3, flavonoids) and fraction 4 ...
Enhanced anticancer activity and intracellular uptake of paclitaxel-containing solid lipid nanoparticles in multidrug-resistant breast cancer cells Wenting Xu, Eun Ju Bae, Mi-Kyung Lee Department of Pharmaceutical Sciences, Woosuk University, Jeonbuk, South Korea Purpose: The aim of this study was to show enhanced anticancer activity of paclitaxel (Ptx) incorporated into solid lipid nanoparticles (SLNs) and reveal reversal of multidrug resistance (MDR) by SLNs mediated by increased uptake through different entry mechanisms from that in drug-sensitive cells.Methods: Anticancer activity of Ptx incorporated in SLNs (Ptx-SLNs) was measured in the drug-sensitive human breast cancer cell line MCF7 and its MDR variant MCF7/ADR. Cellular uptake of cargo molecules in SLNs was compared using Ptx-SLNs and rhodamine 123-loaded SLNs (Rho-SLNs) in both cell lines. In addition, endocytic uptake was evaluated using genistein (Gen) and chlorpromazine (Cpz) as inhibitors of clathrin- and caveola-mediated
BioAssay record AID 21 submitted by DTP/NCI: NCI human tumor cell line growth inhibition assay. Data for the EKVX Non-Small Cell Lung cell line.
By using sophisticated gene sequencing methods to demonstrate a regulatory link between the stem cell factor Lin28 and the signaling molecule bone morphogenic protein 4, Yale researchers are creating a path for developing new targeted ovarian cancer therapies.. Researchers at Yale School of Medicine have identified a key link between stem cell factors that fuel ovarian cancers growth and patient prognosis. The study, which paves the way for developing novel targeted ovarian cancer therapies, is published online in the current issue of Cell Cycle.. Lead author Dr. Yingqun Huang, associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, and her colleagues have demonstrated a connection between two concepts that are revolutionizing the way cancer is treated.. First, the cancer stem cell idea suggests that at the heart of every tumor there is a small subset of difficult-to-identify tumor cells that fuel the growth of the bulk of the tumor. This concept predicts that ...