Search results for "NOS"
showing 10 items of 30869 documents
Epigenetic Silencing of CDR1as Drives IGF2BP3-Mediated Melanoma Invasion and Metastasis.
2018
Summary Metastasis is the primary cause of death of cancer patients. Dissecting mechanisms governing metastatic spread may uncover important tumor biology and/or yield promising therapeutic insights. Here, we investigated the role of circular RNAs (circRNA) in metastasis, using melanoma as a model aggressive tumor. We identified silencing of cerebellar degeneration-related 1 antisense (CDR1as), a regulator of miR-7, as a hallmark of melanoma progression. CDR1as depletion results from epigenetic silencing of LINC00632, its originating long non-coding RNA (lncRNA) and promotes invasion in vitro and metastasis in vivo through a miR-7-independent, IGF2BP3-mediated mechanism. Moreover, CDR1as le…
Differential distribution and enrichment of non-coding RNAs in exosomes from normal and Cancer-associated fibroblasts in colorectal cancer.
2018
Exosome production from cancer-associated fibroblasts seems to be an important driver of tumor progression. We report the first in-depth biotype characterization of ncRNAs, analyzed by Next Generation Sequencing and Bioinformatics, expressed in established primary human normal and cancer-associated fibroblasts (CAFs) from cancer and normal mucosa tissues from 9 colorectal cancer patients, and/or packaged in their derived exosomes. Differential representation and enrichment analyses based on these ncRNAs revealed a significant number of differences between the ncRNA content of exosomes and the expression patterns of the normal and cancer-associated fibroblast cells. ncRNA regulatory elements…
Melanoma Lesions Independently Acquire T-cell Resistance during Metastatic Latency
2016
Abstract Melanoma often recurs after a latency period of several years, presenting a T cell–edited phenotype that reflects a role for CD8+ T cells in maintaining metastatic latency. Here, we report an investigation of a patient with multiple recurrent lesions, where poorly immunogenic melanoma phenotypes were found to evolve in the presence of autologous tumor antigen–specific CD8+ T cells. Melanoma cells from two of three late recurrent metastases, developing within a 6-year latency period, lacked HLA class I expression. CD8+ T cell–resistant, HLA class I–negative tumor cells became clinically apparent 1.5 and 6 years into stage IV disease. Genome profiling by SNP arrays revealed that HLA …
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, …
Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential…
2016
e23035Background: NSCLC patients harboring EGFR mutations are able to receive approved tyrosine kinase inhibitors (TKIs) but to better assess the treatment responses new tools are needed. Liquid bi...
Molecular Basis of Mismatch Repair Protein Deficiency in Tumors from Lynch Suspected Cases with Negative Germline Test Results
2020
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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…
Hereditary breast and ovarian cancer in families from southern Italy (Sicily)—Prevalence and geographic distribution of pathogenic variants in BRCA1/…
2020
Recent advances in the detection of germline pathogenic variants (PVs) in BRCA1/2 genes have allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. Because little is known about this in the Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy. We retrospectively collected and analyzed all clinical information of 1346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs at University Hospital Policlini…
High numbers of circulating CD57+ NK cells associate with resistance to HER2-specific therapeutic antibodies in HER2+ primary breast cancer.
2019
Abstract Natural killer (NK) cells can orchestrate effective antitumor immunity. The presence of tumor-infiltrating NK cells in diagnostic biopsies predicts pathologic complete response (pCR) to HER2-specific therapeutic antibodies in patients with primary breast cancer. Here, we analyzed whether diversity in circulating NK cells might influence tumor infiltration and HER2-specific therapeutic antibody efficacy. We found that numbers of circulating CD57+ NK cells inversely correlated with pCR to HER2-specific antibody treatment in patients with primary breast cancer independently of age, traditional clinicopathologic factors, and CD16A 158F/V genotype. This association was uncoupled from th…