Search results for "Down"
showing 10 items of 1658 documents
Partial restoration of pre-transformation levels of lysyl oxidase and transin mRNAs in phenotypic ras revertants.
1995
Neoplastic transformation mediated by ras oncogenes is associated with deregulated expression of genes encoding, for example, various proteases, lysyl oxidase, and smooth-muscle α-actin. To define the role of these genes in the initiation or maintenance of the ras-transformed state, we compared their steady-state mRNA levels in two different sets of preneoplastic fibroblast lines, ras-transformed clones, and phenotypic revertants derived from them. Compared with the preneoplastic fibroblasts, the ras-transformed derivatives exhibited elevated levels of cathepsin L (major excreted protein), transin (stromelysin I, matrix metalloproteinase–3), and collagenase I (matrix metalloproteinase–1) mR…
MUC1 oncoprotein promotes refractoriness to chemotherapy in thyroid cancer cells.
2007
Abstract Overexpression of MUC1 oncoprotein is frequently observed in cancer and contributes to confer resistance to genotoxic agents. Papillary, follicular, and anaplastic thyroid carcinomas are the three forms of thyroid epithelial cancer. Anaplastic tumors are less differentiated and extremely aggressive, characterized by a poor prognosis. Little is known about the role of MUC1 in thyroid cancer. We recently showed that autocrine production of interleukin (IL)-4 and IL-10 controls thyroid cancer cell survival, growth, and resistance to chemotherapy through activation of Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositide 3′-OH ki…
Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma
2021
Simple Summary Colorectal cancer (CRC) belongs to the most common cancer types. It is well known that half of all CRC possess missense mutations in the TP53 tumor suppressor gene. However, the entire signaling cascade upstream and downstream of the p53 protein may also contribute to CRC development, if relevant players in this signaling cascade lost their function. Besides p53 loss-of-function by mutations, epigenetic changes (DNA methylation, post translational modifications of histones, micro-RNAs) play a vital role in CRC development. In the present review, we concentrated on the epigenetic modifications related to the entire p53 signal transduction cascade upstream and downstream of p53…
Parthenolide generates reactive oxygen species and autophagy in MDA-MB231 cells. A soluble parthenolide analogue inhibits tumour growth and metastasi…
2013
Triple-negative breast cancers (TNBCs) are clinically aggressive forms associated with a poor prognosis. We evaluated the cytotoxic effect exerted on triple-negative MDA-MB231 breast cancer cells both by parthenolide and its soluble analogue dimethylamino parthenolide (DMAPT) and explored the underlying molecular mechanism. The drugs induced a dose- and time-dependent decrement in cell viability, which was not prevented by the caspase inhibitor z-VAD-fmk. In particular in the first hours of treatment (1–3 h), parthenolide and DMAPT strongly stimulated reactive oxygen species (ROS) generation. The drugs induced production of superoxide anion by activating NADPH oxidase. ROS generation caused…
Abstract 968: β-catenin plays an important role in lung tumor development induced by EGFR mutations
2014
Abstract The discovery of somatic mutations in epidermal growth factor receptor (EGFR) and the development of EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, have revolutionized treatment for non-small cell lung cancer (NSCLC). Resistance to TKIs emerges in almost all patients, but currently no effective treatment is available.Therefore, novel strategies to either prevent or overcome resistance are sorely needed. Here we show that β-catenin is essential for development of EGFR mutated lung cancers. We found that β-catenin was upregulated, translocated to the nucleus, and subsequently activated in both EGFR mutated lung cancer cell lines and EGFR mutation driven lung…
Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue
2021
Acromegaly is a disease mainly caused by pituitary neuroendocrine tumor (PitNET) overproducing growth hormone. First-line medication for this condition is the use of somatostatin analogs (SSAs), that decrease tumor mass and induce antiproliferative effects on PitNET cells. Dopamine agonists (DAs) can also be used if SSA treatment is not effective. This study aimed to determine differences in transcriptome signatures induced by SSA/DA therapy in PitNET tissue. We selected tumor tissue from twelve patients with somatotropinomas, with half of the patients receiving SSA/DA treatment before surgery and the other half treatment naive. Transcriptome sequencing was then carried out to identify diff…
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…
A first-in-human trial of RG7116, a glycoengineered monoclonal antibody targeting HER3, in patients with advanced/metastatic tumors of epithelial cel…
2013
2522 Background: The Human Epidermal Growth Factor Receptor 3 (HER3) is a key heterodimerization partner for other HER family members thereby acting as a downstream signal amplifier. This is a first in human study evaluating the safety of RG7116, a humanized anti-HER3 monoclonal antibody with potent HER3 signal inhibition. Due to a glycoengineered Fc-part this antibody displays enhanced antibody-dependent cellular cytotoxicity as compared to conventional antibodies. Methods: Patients (pts) with advanced or metastatic carcinomas with centrally confirmed HER3 protein expression were included. A “3+3” dose escalation design was performed starting at 100 mg flat dosing in a q2w regimen. In add…
Dexamethasone lacks effect on blood pressure in mice with a disrupted endothelial NO synthase gene.
2003
Cushing's syndrome and systemic administration of glucocorticoids are associated with hypertension, but the underlying molecular mechanism is only partially understood. We have shown previously that dexamethasone downregulates the expression of the endothelial NO synthase (eNOS) gene in human endothelial cells and in the rat and that this may contribute to the blood pressure-raising effect of the steroid [Proc. Natl. Acad. Sci. USA 96 (1999) 13357]. In the current communication, we demonstrated that dexamethasone increased mean arterial blood pressure in wild-type C-57 Bl6 mice (eNOS+/+ mice), but had no effect on blood pressure in mice with a disrupted eNOS gene (eNOS-/- mice) derived from…
Hypoxia-induced epithelial VEGF-C/VEGFR-3 upregulation in carcinoma cell lines
2008
Adaptation to hypoxia, a universal hallmark of carcinomas, is a critical step for tumor cell survival and growth. One of the principal regulators of hypoxia-responsive pathways is the transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha). Currently, it is known that tumoral production of members of the vascular endothelial growth factor (VEGF)-family (VEGFs) may promote tumor growth and progression by acting on carcinoma cells that express the cognate receptors (VEGFRs). However, the influence of hypoxia in the formation of such a tumoral VEGF/VEGFR loop is not completely understood. In the present study we examined the potential existence of a HIF-1 alpha/VEGF/VEGFR autocrine…