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.
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 ...
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 ...
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, ...
... (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 ...
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 ...
BioAssay record AID 83769 submitted by ChEMBL: The compound was tested in vitro for antiproliferative activity against HT-29 tumor cell lines.
Cell culture is practiced extensively throughout the world today. The techniques required to allow cells to grow and be maintained outside the body have been developed throughout the 20th century. In the 50 years since the publication of the first human cancer cell line, HeLa (1), thousands of cell lines representing most of the spectrum of human cancer have been derived. These have provided tools to study in depth the biochemistry and molecular biology associated with individual cancer types and have helped enormously in our understanding of normal as well as cancer cell physiology. ...
In this study, we performed a high‐throughput TEAD‐luciferase reporter screen to uncover genes that modulate YAP/TAZ activity upon overexpression and identified multiple members of MAP/microtubule regulating kinase (MARK) family as top hits. We demonstrate that expression of MARK family members leads to robust activation of the TEAD reporter, an indicator of YAP/TAZ transcriptional activity, and that depletion of MARK4 expression in breast cancer cells results in loss of YAP/TAZ nuclear localization and a marked decrease in target gene expression. Mechanistically, we show that MARK4 binds to and phosphorylates the core components of the Hippo pathway, MST and SAV, and that MARK4, in a kinase‐dependent manner, inhibits the assembly of core the Hippo kinase cassette by disrupting the interaction of MST and SAV with LATS.. The mammalian MARK family is comprised of four kinases, MARK1-4 (also referred to Par‐1c, Par‐1b, Par‐1a, and Par‐1d, respectively) which are orthologs of the ...
Circulating Tumor Cells can be found in the blood of patients with primary tumor. These cells are extraordinarily rare and their detection presents a major challenge. But collaboration between bioengineers, molecular biologists and clinicians, many technologies have been developed which can detect CTCs. There are many ongoing research on this which are facilitated by the reports generated earlier. Because of the circulating tumor cells clinical significance, there has been a lot of stress on developing methods that can allow detailed studies across multiple types of cancer and its detection. Detailed study on CTC technologies shows that this field of biotechnology can offer unique opportunities for the detection of tumor cells in patients with early stage cancer. It also confirms the ability to genetically characterize tumor cells without needing an invasive biopsy, and determine responsiveness to the new generation targeted cancer drugs. Some of the latest reports even discuss the ability of ...
Background: 14‐3‐3 sigma (σ) is a negative regulator of the cell cycle and contributes to G2/M arrest. In many malignant tumors, the 14‐3‐3 σ is considered to be an important tumor suppressor of which the decreased expression has been reported. The level of the 14‐3‐3 σ was reported to be decreased either by hypermethylation at its promoter site or ubiquitin‐mediated proteolysis by the estrogen‐responsive ring finger protein (Efp). In this study, we tried to investigate which mechanism plays more important role in the 14‐3‐3 σ regulation, how the change of the 14‐3‐3 σ expression affect the biology of human breast cancer, and hence to extend our understanding of the role of the 14‐3‐3 σ in human breast cancer.. Materials and Methods: In order to examine the role of ubiquitin‐associated proteolysis by the Efp, we examined the change of the level of 14‐3‐3 σ protein after Efp silencing using siRNA in MCF‐7 breast cancer cell line. We also examined the Efp ...
Applied StemCell has engineered a series of cell lines that feature diverse mutations in EGFR, KRAS, and BRAF. Click here to learn more.
We want to genotype one of cancer cell lines studies in the lab. Are there any concerns or recommendations specifically for cancer cell lines?
Ionizing radiation (IR) is a non-specific but highly effective way to kill malignant cells. However, tumor recurrence sustained by a minor fraction of surviving tumor cells is a commonplace phenomenon caused by the activation of both cancer cell intrinsic resistance mechanisms, and also extrinsic intermediaries of therapy resistance, represented by non-malignant cells and structural components of the tumor stroma. The improved accuracy offered by advanced radiotherapy (RT)-technology permits reduced volume of healthy tissue in the irradiated field, and has been triggering an increase in the prescription of high-dose oligo-fractionated regimens in the clinics. Given the remarkable clinical success of high-dose RT and the current therapeutic shift occurring in the field, in this review we revise the existing knowledge on the effects that different radiation regimens exert on the different compartments of the tumor microenvironment, and highlight the importance of anti-tumor immunity and other ...
Downregulate phosphorylation of STAT3, increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values. Furthermore, HJC-0123 significantly suppressed estrogen receptor (ER)-negative breast cancer MDA-MB-231 xenograft tumor growth in vivo (p.o.), indicating its great potential as an efficacious and orally bioavailable drug candidate for human cancer therapy.
Panel of tumor cell lines with variable get Pleuromutilin expression of this receptor. To examine this experimentally, we utilized a shRNA construct to stably
Cancer cells demand large nutrient supplies and thus reprogram their metabolic pathways to ensure metabolic flexibility, cellular homeostasis, energy production, cell proliferation, and survival. In addition to direct modulation of signal transduction pathways causing oncogenic addiction, alterations in oncogenes also contribute to metabolic rewiring in cancer cells, resulting in the promotion of cancer cell proliferation, survival, and metastatic dissemination. Accordingly, metabolic reprogramming is now considered an important characteristic of several types of cancer, including NSCLC. Despite several ongoing approaches to target cancer metabolism, metabolic reprogramming should be therapeutically explored in additional studies. In addition, the influence of metabolic rewiring on the interaction between cancer cells and the tumor microenvironment needs to be extensively investigated to comprehensively understand the course of cancer development and progression, providing mechanistic insights ...
Our Cancer Biology program conducts research to discover biochemical, metabolic, and genetic abnormalities in tumor cells and nonmalignant cells in the tumor microenvironment, and exploit these findings to develop more effective ways to prevent, diagnose, and treat cancer.
Working in a mouse model, the LSUHSC research team studied LKB1, an enzyme that functions as a tumor suppressor in the small intestine, and Nischarin, a novel protein that regulates breast cancer cell migration and movement discovered by Dr. Alahari in 2000. Thirty percent of lung adenocarcinomas have an LKB1 gene mutation, and high levels of the LKB1 protein in breast cancer cells have been shown to significantly inhibit tumor growth. The LKB1-interacting protein is also structurally similar to Nischarin. The researchers suspected that the two suppressors might relate to each other, and they did in fact discover a functional and biochemical link between them ...
Working in a mouse model, the LSUHSC research team studied LKB1, an enzyme that functions as a tumor suppressor in the small intestine, and Nischarin, a novel protein that regulates breast cancer cell migration and movement discovered by Dr. Alahari in 2000. Thirty percent of lung adenocarcinomas have an LKB1 gene mutation, and high levels of the LKB1 protein in breast cancer cells have been shown to significantly inhibit tumor growth. The LKB1-interacting protein is also structurally similar to Nischarin. The researchers suspected that the two suppressors might relate to each other, and they did in fact discover a functional and biochemical link between them ...
NexusPharma is dedicated to the discovery of novel anti-cancer treatments. Novel drug candidates are tested in patient derived xenograft tumor models or patient derived tumor cell lines that are derived from such PDX models - we are creating these models to reflect human disease in the most predictable ways. Please ask us if we could help you in your dicsovery projects with these technologies - creating drug candidates wit a higher chance of success in clinical trials!. ...
Targeted therapies are a promising option for cancer treatments, offering the ability to specifically target cancer cells through inhibition of a signaling molecule responsible for oncogenesis. The major drawback of this type of treatment is the development of drug resistance, which can occur through activation of a bypass pathway, or by mutation of the targeted protein (47, 48). The gatekeeper mutation is a devastating mechanism of the latter form of resistance in established kinase targets such as BCR-ABL, EGFR, PDGFR, and Src (23). Thus, identifying corresponding gatekeeper mutations in novel targets allows an understanding of their consequences before they reach the clinic. FGFRs are a relatively recent family of proteins to be addressed through targeted therapy, with multiple inhibitors in clinical trials for the treatment of cancers such as NSCLC and breast cancer (20, 49). In addition, the V561M mutation of FGFR1 has been observed in humans (50) and requires only a single-nucleotide ...
Cell migration is of paramount importance in physiological processes such as immune surveillance, but also in the pathological processes of tumor cell migration and metastasis development. The factors
Thought to be genetically stable and identical, cancer cell lines harbor significant levels of genetic variation, which may help explain why it can be hard to reproduce findings in cell line-based research.
This study investigates the influence of microbes on fluid transport in sedimentary and igneous host rock environments. It particularly focuses on granodiorite rock (Äspö; Sweden) and mudstone (Horonobe; Japan) that were utilised during laboratory-based column experiments. The results showed that biofilms fo
The Twist1 gene is highly expressed in many different tumor types and regulates several different stages of tumor development, from initiation through metastasis. Loss of Twist1 can prevent tumor progression, and therefore Twist1 represents a promising target for the development of anti-cancer drugs. Dr. Spicer and his team have identified specific protein interactions that are required for Twist1 function.
Poly A Plus RNA, Human Cancer & Cell Line. Poly A Plus RNA samples are enriched through two rounds of oligo(dT) chromatography. Representative populations with a high percentage of full-length transcripts.
Poly A Plus RNA, Human Cancer & Cell Line. Poly A Plus RNA samples are enriched through two rounds of oligo(dT) chromatography. Representative populations with a high percentage of full-length transcripts.
seven months later on. Thinking of the generally poor prognosis of SCCB, novel therapeutic strategies are desired to improve outcomes of individuals. Targeted
To facilitate access of the broader research community to cancer proteomics datasets, we have developed a user-friendly data portal, TCPA (The Cancer Proteome Atlas). The current data release contains 4,495 tumor samples in total, and mainly consists of three parts. (i) TCGA tumor tissue sample sets; (ii) independent tumor tissue sample set; and (iii) ,500 cell-line samples. TCPA currently provides six modules: Summary, My Protein, Download, Visualization, Analysis and Cell line. Importantly, this resource provides a unique opportunity to validate the findings from TCGA data and identify model cell lines for functional investigation ...
Circulating tumor cells (CTCs) are very important targets for cancer research. Their detection and molecular characterization enable researchers to gain new insights in the mechanism of cancer. However, detecting them against the background of normal cells in whole blood can be challenging, as it requires selective enrichment of CTCs or removal of other nucleated cells while maintaining the variability of tumor cell expression. ...
Combinations of conventional and new drugs have been found to enhance the rate of tumor cell death during a study resolving the role of CDKs in esophageal tumor cell mortality.
Evolutionary thought will only on occasion directly affect individual therapeutic decisions. Yet it will form a critical part of the worldview for the practice of medicine. Evolutionary reasoning provides a conceptual framework within which to situate the profusion of facts that constitute medicine, and so helps organise knowledge of biological systems.4 It allows the physician to answer patients questions about the origin of symptoms and disease in a more holistic and often more meaningful manner. It can be of particular value in understanding psychiatric symptoms such as phobias, and can be used as part of their clinical management.18 Evolutionary thinking also provides an evaluative context in which to consider individual clinical decisions and the medical scientific literature. For example, what is the plausibility and therapeutic significance of selection arguments used to explain ethnic differences in the origin of hypertension?19 What is the appropriate approach to antibiotic use to ...
kRAS is one of, if not the, most prevalent oncogenic aberrations identified to date, and has been well validated as a therapeutic target. It is either upregulated or mutationally activated in ∼30% of all cancers, including 60-90% of pancreatic cancer, and contributes to malignant transformation, tumorigenicity, and a corresponding poor prognosis. Our therapeutic approach to transcriptionally downregulate kRAS is innovate and promising because we are focused on ablating the oncogenic protein, rather than previously unsuccessful attempts focused on modulating its function. Numerous literature reports validate the downregulation of kRAS expression to as an anti-cancer approach, but there has yet to be a concerted effort in this area, primarily due to lack of a molecular target. This is where our findings are exceptionally pioneering, as we focus on globular higher order DNA (G4) formations within the core kRAS promoter as druggable targets with great promise. G4s occur in G/C-rich DNA and are ...
Top 10 cell-lines for Q9ULL0 (Homo sapiens, UniProt): MX-1, NCI-H1963, SK-MEL-2, UACC-812, MCF-7-con, NCI-H1048, MCF-7-TP53 KD, NC-37, NALM-1, Hs 695T
This unit describes protocols for culturing and subsequently enriching cancer stem cells (CSCs), also referred to as tumor‐initiating cells (TICs), from human established cell lines
EpithelialCmesenchymal transition (EMT) is thought to be a crucial event during the early metastasis of tumor cells. with GM6001 was shown to attenuate TGF-1-induced EMT. Furthermore, the exposure of EC-1 cells to TGF-1 increased the expression and activity of MMP-9, while knockdown blocked TGF-1-induced EMT and inhibited cell invasiveness and migration. Additionally, treatment with the …. ...
EpithelialCmesenchymal transition (EMT) is thought to be a crucial event during the early metastasis of tumor cells. with GM6001 was shown to attenuate TGF-1-induced EMT. Furthermore, the exposure of EC-1 cells to TGF-1 increased the expression and activity of MMP-9, while knockdown blocked TGF-1-induced EMT and inhibited cell invasiveness and migration. Additionally, treatment with the …. ...
Top 10 cell-lines for Q96LK0 (Homo sapiens, UniProt): My-La CD4+, NCI-H1581, Sez-4, A2058, NCI-H841, MFE-280, MFE-296, SK-UT-1B, U-251MG-PARK2, Kasumi-6
Given this role in accelerating growth, the team considered that miR-31 may also be involved in tumor promotion. Indeed, chemicals that mimic miR-31 increased growth of bowel cancer cell lines, and caused larger tumor volume in mice. Of greatest significance, however, was the observation that mice with tumors caused by loss of a gene called Apc developed far fewer tumors when miR-31 was deleted. As loss of Apc is a hallmark of human bowel cancer, miR-31 could be a potential therapeutic target for the disease.. "We have shown that miR-31 is a master regulator of the normal and pathological growth of intestinal stem cells and acts as a promoter of tumor growth," said senior author Zhengquan Yu, Professor of Biochemistry and Molecular Biology at China Agricultural University. "The next steps will be to build on our insights into the signaling pathways through which miR-31 exerts its effects to fully evaluate its potential as a therapeutic target in cancer." ...
Sensitive, specific, and accurate methods to assay chemosensitivity are needed to (1) screen new therapeutic agents, (2) identify patterns of chemosensitivity for different tumor types, (3) establish
... : polyA tails and parenthood In an age where scientific research is increasingly framed and measured by its translational potential, Lori
Manassas, VA (PRWEB) February 07, 2012 -- Searching for appropriate tumor cell models often entails a time-intensive review of the literature and genomic
Global circulating tumor cells technologies market is segmented based on the method of enrichment and detection, and application areas. Based on methods of enrichment, the report includes market analysis
Circulating Tumor Cell (CTC) Diagnostics Market Driven by Increasing incidences of cancer : Size, Share, Trends, Growth and Forecast 2021
Harvesting lab-raised zebrafish based on their size led to differences in the activity of more than 4,000 genes, as well as changes in allele frequencies of those genes, in the fish that remained.. 0 Comments. ...
There are currently a hundred approved anti-cancer drugs. Holbeck and her colleagues were interested in whether any of these drugs would be more effective against specific types of tumor if the drugs were used in combination. To that end, they tested all 5000 different drug combinations in 60 cell lines over the course of 300,000 experiments. The cell lines were chosen both because they were derived from nine distinct types of cancer and because they are well characterized (gene expression and other parameters are well understood in these cells ...
Researchers have found that a gene they call THOR produces a long, non-coding RNA that has a role in cancer, and whose silencing stops tumor growth.
Research published earlier this year sheds light on a fundamental process which drives cell growth and death among epithelial tissues such as gut lining and skin [1]. A disruption to the processes governing the growth and death of cells is at the root of tumor formation and health conditions associated with inflammation. Researchers led by Dr. Jody Rosenblatt at…
Rare stem-like tumor cells play a critical role in the spread of breast cancer, but a vulnerability in the pathway that powers them offers a strategy to target
Researchers have developed new nanorobotic agents capable of navigating through the bloodstream to administer a drug with precision by specifically targeting the active cancerous cells of tumours.
Disabling a single enzyme associated with the formation of lipids significantly disrupts the ability of aggressive cancer cells to spread and grow tumors, according to a new study.
Abstract DNA from cancer cells can enter surrounding fluid after apoptosis or necrosis. This DNA can be identified by sampling and sequencing the fluid looking for the mutations that gave rise to the cancer, referred to ...
Okay, so I take our boys to the YMCA almost every morning so that they can socialize with other kids and I can get a mommy break. At that time of day, ther...
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)
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
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
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