Search results for "OSiS"
showing 10 items of 15931 documents
Relevance of the natural HDAC inhibitor sulforaphane as a chemopreventive agent in urologic tumors.
2018
Due to an increased understanding of molecular biology and the genomics of cancer, new and potent agents have been approved by the Food and Drug Administration (FDA) to fight this disease. However, all of these drugs cause severe side effects and resistance inevitably develops, re-activating tumor growth and dissemination. For this reason, patients turn to natural compounds as alternative or complementary treatment options, since it has been found that natural plant products may block, inhibit, or reverse cancer development. The present review focusses on the role of the natural compound sulforaphane (SFN) as an anti-tumor agent in urologic cancer. SFN is a natural compound found in crucife…
The importance of transmembrane domain interactions in the viral control of apoptosis
2021
Viral control of apoptosis occurs through the expression of viral encoded anti-apoptotic B-cell lymphoma 2 (BCL2) analogs. These proteins are thought to restrain apoptosis by interacting with cellular BCL2 family members. We identified that protein-protein interactions between cellular and viral BCL2 transmembrane domains are crucial for the viral protein’s function.
Hypoxia-Inducible Factor-1α Activity as a Switch for Glioblastoma Responsiveness to Temozolomide
2018
Rationale: The activity of the transcription factor, hypoxia-inducible factor (HIF)-1?, is a common driver of a number of the pathways involved in the aggressiveness of glioblastomas (GBMs), and it has been suggested that the reduction in this activity observed, soon after the administration of temozolomide (TMZ), can be a biomarker of an early response in GBM models. As HIF-1? is a tightly regulated protein, studying the processes involved in its downregulation could shed new light on the mechanisms underlying GBM sensitivity or resistance to TMZ. Methods: The effect of HIF-1? silencing on cell responsiveness to TMZ was assessed in four genetically different human GBM cell lines by evaluat…
Targeting Immune Modulators in Glioma While Avoiding Autoimmune Conditions
2021
Simple Summary Glioblastoma multiforme is a futile disease usually leading to the patient’s death within one year post-diagnosis; therefore, novel treatment options are desperately needed. In this regard, activation of the inert immune system has moved into focus in recent years. Malignant brain tumors, as well as autoimmune diseases, elicit aberrant immune responses. In this way, glioma escapes the host’s immune system and, thus, activation of the immune response in order to reduce tumor tolerance can serve as an alternative treatment option. Immune checkpoint modulators in combination with traditional therapies have gained attention in both glioma and autoimmune diseases. In this review, …
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results
2020
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Genetic variations in the PSMA6 and PSMC6 proteasome genes are associated with multiple sclerosis and response to interferon‑β therapy in Latvians
2021
Several polymorphisms in genes related to the ubiquitin-proteasome system exhibit an association with pathogenesis and prognosis of various human autoimmune diseases. Our previous study reported the association between multiple sclerosis (MS) and the PSMA3-rs2348071 polymorphism in the Latvian population. The current study aimed to evaluate the PSMA6 and PSMC6 genetic variations, their interaction between each other and with the rs2348071, on the susceptibility to MS risk and response to therapy in the Latvian population. PSMA6-rs2277460, -rs1048990 and PSMC6-rs2295826, -rs2295827 were genotyped in the MS case/control study and analysed in terms of genotype-protein correlation network. The …
Roles of TP53 in determining therapeutic sensitivity, growth, cellular senescence, invasion and metastasis.
2016
TP53 is a critical tumor suppressor gene that regulates cell cycle progression, apoptosis, cellular senescence and many other properties critical for control of normal cellular growth and death. Due to the pleiotropic effects that TP53 has on gene expression and cellular physiology, mutations at this tumor suppressor gene result in diverse physiological effects. T53 mutations are frequently detected in numerous cancers. The expression of TP53 can be induced by various agents used to treat cancer patients such as chemotherapeutic drugs and ionizing radiation. Radiation will induce Ataxia telangiectasia mutated (ATM) and other kinases that results in the phosphorylation and activation of TP53…
Pattern of Invasion in Human Pancreatic Cancer Organoids Is Associated with Loss of SMAD4 and Clinical Outcome
2020
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by extensive local invasion and systemic spread. In this study, we employed a three-dimensional organoid model of human pancreatic cancer to characterize the molecular alterations critical for invasion. Time-lapse microscopy was used to observe invasion in organoids from 25 surgically resected human PDAC samples in collagen I. Subsequent lentiviral modification and small-molecule inhibitors were used to investigate the molecular programs underlying invasion in PDAC organoids. When cultured in collagen I, PDAC organoids exhibited two distinct, morphologically defined invasive phenotypes, mesenchymal an…
Impact of glucocorticoids on systemic sirtuin 1 expression and activity in rats with adjuvant-induced arthritis
2020
The class III histone deacetylase sirtuin 1 (SIRT1) plays a pivotal role in numerous biological and physiological functions, including inflammation. An association between SIRT1 and proinflammatory cytokines might exist. In addition to their important role in inflammation associated with rheumatoid arthritis (RA), proinflammatory cytokines mediate the development of systemic effects. Here, we evaluated systemic SIRT1 expression and enzymatic activity, in peripheral blood mononuclear cells (PBMCs) and in liver isolated from rats with adjuvant-induced arthritis (AIA), treated or not with low or high doses of glucocorticoids (GCs). We also measured the production of tumour necrosis factor alph…
Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions
2019
Purpose: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma arising from the skin. We aimed to review and deal with some of the most relevant controversial topics on the correct use of immunotherapy for the treatment of MCC. Methods: The primary search was carried out via PubMed, EMBASE, and the Cochrane Library (until 31st May, 2018), while other articles and guidelines were retrieved from related papers or those referenced in these papers. Additionally, we performed an extensive search on ClinicalTrials.gov to gather information on the ongoing clinical trials related to this specific topic. Results: We performed an up-to-date critical review taking into account the…