Search results for "54"
showing 10 items of 2200 documents
PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.
2018
The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as those caused by BRCA1 mutations or ERCC1 defects. Using isogenic cell lines and patient-derived samples, we showed that ERCC1-defective non-small cell lung cancer (NSCLC) cells exhibit an enhanced type I IFN transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration. We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-autonomous immunomodulatory properties in ERCC1-defecti…
Comprehensive Analysis of SWI/SNF Inactivation in Lung Adenocarcinoma Cell Models
2020
Simple Summary: Mammalian SWI/SNF complexes regulate gene expression by reorganizing the way DNA is packaged into chromatin. SWI/SNF subunits are recurrently altered in tumors at multiple levels, including DNA mutations as well as alteration of the levels of RNA and protein. Cancer cell lines are often used to study SWI/SNF function, but their patterns of SWI/SNF alterations can be complex. Here, we present a comprehensive characterization of DNA mutations and RNA and protein expression of SWI/SNF members in 38 lung adenocarcinoma (LUAD) cell lines. We show that over 85% of our cell lines harbored at least one alteration in one SWI/SNF subunit. In addition, over 75% of our cell lines lacked…
Are Long Noncoding RNAs New Potential Biomarkers in Gastrointestinal Stromal Tumors (GISTs)? The Role of H19 and MALAT1
2019
Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be cor…
Targeting BRAF and RAS in Colorectal Cancer
2021
Simple Summary In colorectal cancer, mutations of the KRAS and BRAF genes are quite common and can contribute to the activation of cell signaling pathways that lead to cell proliferation and differentiation. These processes promote cancer growth, and in some cases, they may cause cells to develop resistance to certain types of treatment, notably EGFR inhibitors. We summarize recent knowledge regarding the effects of KRAS and BRAF mutations in the setting of colorectal cancer and discuss the new therapies under development. Abstract Colorectal cancer (CRC) is still one of the most frequent forms of cancer in the world in terms of incidence. Around 40% of CRC patients carry a mutation of the …
Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.
2019
Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…
Intratumoral immunosuppression profiles in 11q-deleted neuroblastomas provide new potential therapeutic targets
2021
In this issue, Coronado et al. attempt to improve our understanding of the factors affecting the response to immunotherapy in a large subset of high‐risk neuroblastoma with hemizygous deletion of chromosome 11q. By using several computational approaches, the authors study potential transcriptional and post‐transcriptional pathways that may affect the response to immunotherapy and further be leveraged therapeutically in a biomarker‐directed fashion.
Δ133p53α enhances metabolic and cellular fitness of TCR-engineered T cells and promotes superior antitumor immunity
2021
BackgroundTumor microenvironment-associated T cell senescence is a key limiting factor for durable effective cancer immunotherapy. A few studies have demonstrated the critical role of the tumor suppressor TP53-derived p53 isoforms in cellular senescence process of non-immune cells. However, their role in lymphocytes, in particular tumor-antigen (TA) specific T cells remain largely unexplored.MethodsHuman T cells from peripheral blood were retrovirally engineered to coexpress a TA-specific T cell receptor and the Δ133p53α-isoform, and characterized for their cellular phenotype, metabolic profile and effector functions.ResultsPhenotypic analysis of Δ133p53α-modified T cells revealed a marked …
Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation an…
2020
Background/Objective Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD). The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on prolifer…
Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells
2018
Background It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. Methods Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. …
Effect of nutritional supplementations on physical performance and muscle strength parameters in older people: A systematic review and meta-analysis
2019
Malnutrition plays a role in the development of poor physical performance, frailty and sarcopenia. The use of nutritional supplementations for improving physical performance and muscle strength parameters in older people is unclear. We therefore aimed to summarize the effect of nutritional supplementations compared to placebo on physical performance (i.e. tests more investigating physical function, utilising aerobic capacity & muscle power) and muscle strength (i.e. tests depending on muscle power) outcomes in older people in randomized controlled trials (RCTs). A literature search in major databases was undertaken until the 01st September 2018. Eligible studies were RCTs investigating …