The role of TFEB in tumor cell autophagy: Diagnostic and therapeutic opportunities
Publication date: Available online 21 January 2020Source: Life SciencesAuthor(s): Afsane Bahrami, Vanessa Bianconi, Matteo Pirro, Hossein M. Orafai, Amirhossein SahebkarAbstractAutophagy is a conserved “self-eating” recycling process which removes aggregated or misfolded proteins, or defective organelles, to maintain cellular hemostasis. In the autophagy-lysosome pathway (ALP), clearance of unwanted debris and materials occurs through the generation of the autophagosome, a complex of double-membrane bounded vesicles that form around cytosolic cargos and catabolize their contents by fusion to lysosomes. In tumors, autophagy has dichotomous functions via preventing tumor initiation but promoting tumor progression. The basic helix-loop-helix leucine zipper transcription factor EB (TFEB) activates the promoters of genes encoding for proteins, which participate in this cellular degradative system by regulating lysosomal biogenesis, lysosomal acidification, lysosomal exocytosis and autophagy. In humans, disturbances of ALP are related to various pathological conditions. Recently, TFEB dysregulation was found to have a crucial pathogenic role in different tumors by modulating tumor cell autophagy. Notably, in renal cell carcinomas, different TFEB gene fusions were reported to promote oncogenic features. In this review, we discuss the role of TFEB in human cancers with a special focus on potential diagnostic and therapeutic implications.Graphical abstract
A provision in the Affordable Care Act (ACA) expanded Medicaid eligibility in participating states to low-income individuals with incomes up to 138% of the federal poverty level. Medicaid expansion has been associated with earlier cancer stage at diagnosis, which we hypothesized may alter treatment patterns for patients with early stage renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and non-small lung cancer (NSCLC).
The objective of this study was to address those limitations and rigorously assess long-term oncologic outcomes in a prospective cohort after cryoablation for Stage 1 RCC.
While percutaneous ablation of renal masses has matured in the treatment of stage T1a renal cell carcinomas, less is known about the outcomes of percutaneous ablation in stage T1b renal tumors. Multiple groups have found high rates of cancer free, progression free, and overall survival after percutaneous thermal ablation of T1b tumors. A comparison of percutaneous ablation versus partial nephrectomy in T1b tumors by Chang and by Caputo demonstrated comparable overall and cancer specific survival rates.
To determine the feasibility, perioperative outcomes and cancer-free survival of morbidly obese patients who underwent thermal ablation for renal cell carcinoma (RCC).
Paraneoplastic neurologic syndromes are rare but well described presentation of certain malignancies in both children and adults. Cerebellar dysfunction is a common paraneoplastic presentation and has been previously reported in association with small cell lung cancer, breast cancers, ovarian tumors, renal cell carcinoma, follicular lymphoma, and Hodgkin ’s lymphoma. There are only a handful of case reports with the association of paraneoplastic neurologic presentation with Non-Hodgkin lymphoma including Diffuse Large B-cell Lymphoma (DLBCL).
Once thought to be"undruggable," a target in renal cell carcinoma now has a drug aimed at it, and initial results from a small clinical trial are promising.Medscape Medical News
In this study, we aim at identifying genes indicating chRCC progression. A bioinformatic approach was used to correlate chromosomal loss and mRNA expression from 15287 genes from The Cancer Genome Atlas (TCGA) database. All genes in TCGA chromophobe renal cancer dataset (KICH) for which a significant correlation between chromosomal loss and mRNA expression was shown, were identified and their associations with outcome was assessed. Genome-wide DNA copy-number alterations were analyzed by Affymetrix OncoScan® CNV FFPE Microarrays in a second cohort of Swiss chRCC. In both cohorts, tumors with loss of chromosomes 2, ...
In this study, we aim at evaluation the role of the Asp148Glu (rs1130409) variant at apurinic/apyrimidinic endonuclease (APE) gene in renal cell carcinoma (RCC) risk and the contribution of different genotypes to its transcriptional mRNA levels. In the case-control study, 92 RCC patients and 580 cancer-free patients matched by age and gender were recruited. The apurinic/APE genotyping work was conducted with typical restriction fragment length polymorphism methodology after polymerase chain reaction. At the meanwhile, thirty renal tissue samples with variant genotypes were examined for their apurinic/APE mRNA and protein e...
In this report, we describe the case of a 66-year-old male who presented with mRCC with lung and cardiac metastases treated with cabozantinib, a multikinase inhibitor that was administered in second line after disease progression with sunitinib. To date, there are no data about the safety and efficacy of cabozantinib in mRCC with cardiac metastasis. In a real word analysis, cabozantinib demonstrated to be associated to a modest risk of developing left ventricular heart failure. It is unknown if this risk is higher in mRCC population with cardiac metastases. We report the first evidence of efficacy and safety of cabozantini...
ConclusionsSeveral TKIs are standard of care at different settings. Among those approved TKIs, tivozanib has similar efficacy than others with a better safety profile. The use of prognostic factors is critical to the selection of optimal therapy.