Search results for "cancer cell"

Abstract 1907: Claudin 6 is a carcinoembryonic antigen with cancer stem cell marker features

2018

Abstract Background Claudin 6 (CLDN6) is a tight junction membrane protein whose expression in normal tissue is confined to embryonic cells, but is aberrantly expressed in various human cancers, such as ovarian cancer (OC) and testicular cancer (TC). A monoclonal antibody against CLDN6, IMAB027, has shown promising antitumor activity in preclinical human CLDN6-positive (CLDN6+) cancer models. In this series of nonclinical studies, we investigated CLDN6 expression in normal and cancer tissues, as well as the localization and possible function of CLDN6 in cancer cells. Methods Expression of CLDN6 was assessed in a wide range of human tissues (eg, lung, colon, skin, ovary) and cultured cells b…

Abstract B154: A first-in-human trial of GDC-0068: A novel, oral, ATP-competitive Akt inhibitor, demonstrates robust suppression of the Akt pathway i…

2011

Abstract GDC-0068 is a highly selective ATP-competitive small molecule that inhibits all three isoforms of Akt with IC50 values of 5 to 30 nM. GDC-0068 selectively inhibits cancer cells with activated Akt signaling (e.g. via PTEN loss or PIK3CA mutations). Patients with advanced solid tumors were treated with GDC-0068 using a 3+3 escalation design. GDC-0068 was dosed PO QD on a 21-day on, 7-day off schedule; endpoints included safety, pharmacokinetics (PK) and determination of pathway knockdown. Pharmacodynamics (PD) endpoints in surrogate tissue [platelet rich plasma (PRP)] were evaluated in all patients. In addition, at least two patients per cohort had pre- and on-treatment (day 15) tumo…

Abstract LB-099: Metabolic vulnerabilities of mesenchymal-like EGFR-mutant NSCLC cells with acquired resistance to tyrosine kinase inhibitors

2018

Abstract Despite the availability of the effective targeted therapies in lung cancer, such as EGFR tyrosine kinase inhibitors (TKIs), drug tolerance and acquired resistance are two common problems that negatively impact lung cancer patient survival. Consequently it is important to understand the molecular basis of the drug tolerance and resistance so that we could formulate effective strategies to ameliorate the efficacy of existing drug and to suppress the emergence of drug resistance. A burgeoning body of literature demonstrated that epigenetic changes by the methylation of DNA and histones are critical in acquired drug resistance, especially in those cancer cells with stem cell-like prop…

Comprehensive Analysis of VEGFR2 Expression in HPV-Positive and -Negative OPSCC Reveals Differing VEGFR2 Expression Patterns

2021

VEGF signaling regulated by the vascular endothelial growth factor receptor 2 (VEGFR2) plays a decisive role in tumor angiogenesis, initiation and progression in several tumors including HNSCC. However, the impact of HPV-status on the expression of VEGFR2 in OPSCC has not yet been investigated, although HPV oncoproteins E6 and E7 induce VEGF-expression. In a series of 56 OPSCC with known HPV-status, VEGFR2 expression patterns were analyzed both in blood vessels from tumor-free and tumor-containing regions and within tumor cells by immunohistochemistry using densitometry. Differences in subcellular colocalization of VEGFR2 with endothelial, tumor and stem cell markers were determined by doub…

Colon Cancer Stem Cells: Bench-to-Bedside—New Therapeutical Approaches in Clinical Oncology for Disease Breakdown

2011

It is widely accepted by the scientific community that cancer, including colon cancer, is a “stem cell disease”. Until a few years ago, common opinion was that all neoplastic cells within a tumor contained tumorigenic growth capacity, but recent evidences hint to the possibility that such a feature is confined to a small subset of cancer-initiating cells, also called cancer stem cells (CSCs). Thus, malignant tumors are organized in a hierarchical fashion in which CSCs give rise to more differentiated tumor cells. CSCs possess high levels of ATP-binding cassette (ABC) transporters and anti-apoptotic molecules, active DNA-repair, slow replication capacities and they produce growth factors tha…

Ethanol-Mediated Stress Promotes Autophagic Survival and Aggressiveness of Colon Cancer Cells via Activation of Nrf2/HO-1 Pathway

2019

Epidemiological studies suggest that chronic alcohol consumption is a lifestyle risk factor strongly associated with colorectal cancer development and progression. The aim of the present study was to examine the effect of ethanol (EtOH) on survival and progression of three different colon cancer cell lines (HCT116, HT29, and Caco-2). Our data showed that EtOH induces oxidative and endoplasmic reticulum (ER) stress, as demonstrated by reactive oxygen species (ROS) and ER stress markers Grp78, ATF6, PERK and, CHOP increase. Moreover, EtOH triggers an autophagic response which is accompanied by the upregulation of beclin, LC3-II, ATG7, and p62 proteins. The addition of the antioxidant N-acetyl…

Epigenetic changes and nuclear factor-κB activation, but not microRNA-224, downregulate Raf-1 kinase inhibitor protein in triple-negative breast canc…

2015

Raf-1 kinase inhibitor protein (RKIP) is a tumor suppressor and metastasis inhibitor, which enhances drug-induced apoptosis of cancer cells. Downregulation of RKIP may be significant in the biology of highly aggressive and drug-resistant tumors, for example triple-negative breast cancers (TNBCs). Potential causes for the low levels of RKIP expressed by SUM 159 TNBC cells were investigated in the present study. Bisulphite modification, methylation specific-polymerase chain reaction (PCR) and a TransAM NF-κB assay were performed and the results suggested that various mechanisms, including methylation of the gene promoter, histone deacetylation and nuclear factor-κB (NF-κB) activation, but not…

Next-Generation Genomic Profiling of Hepatocellular Adenomas: A New Era of Individualized Patient Care

2014

Hepatocellular adenomas (HCAs) are clinically relevant benign liver lesions that commonly occur in women on hormonal contraceptives. In this issue of Cancer Cell, Pilati and colleagues present an integrative multi-“omics”-based analysis of HCA and identify recurrent genetic alterations associated with adenoma-carcinoma transition and new drugable targets.

Stomach signet-ring cancer cell line (MZ-STO-1), established in tissue culture: Morphological characterization and antigenic profile

1986

Intermittent and Periodic Fasting, Hormones, and Cancer Prevention

2021

Simple Summary Hormonal and growth factor alterations, related to an elevated food consumption and excessive adiposity, affect the regulation of genes involved in cellular processes including proliferation, differentiation and DNA repair, allowing cells to survive and proliferate despite the accumulation of mutations which lead to malignant transformation. The growth hormone/insulin growth factor-1 (GH/IGF-1)/ insulin pathway and its downstream effectors, in fact, are known to promote aging and/or age-related diseases, including cancer, in many model organisms. The restriction of nutrients is established to have strong effects on levels of hormones and growth factors, delaying the incidence…