RESUMO
Chromophobe (Ch) renal cell carcinoma (RCC) arises from the intercalated cell in the distal nephron. There are no proven treatments for metastatic ChRCC. A distinguishing characteristic of ChRCC is strikingly high levels of reduced (GSH) and oxidized (GSSG) glutathione. Here, we demonstrate that ChRCC-derived cells exhibit higher sensitivity to ferroptotic inducers compared with clear-cell RCC. ChRCC-derived cells are critically dependent on cystine via the cystine/glutamate antiporter xCT to maintain high levels of glutathione, making them sensitive to inhibitors of cystine uptake and cyst(e)inase. Gamma-glutamyl transferase 1 (GGT1), a key enzyme in glutathione homeostasis, is markedly suppressed in ChRCC relative to normal kidney. Importantly, GGT1 overexpression inhibits the proliferation of ChRCC cells in vitro and in vivo, suppresses cystine uptake, and decreases levels of GSH and GSSG. Collectively, these data identify ferroptosis as a metabolic vulnerability in ChRCC, providing a potential avenue for targeted therapy for these distinctive tumors.
Assuntos
Sistema y+ de Transporte de Aminoácidos , Carcinoma de Células Renais , Cistina , Ferroptose , Glutationa , Neoplasias Renais , Sistema y+ de Transporte de Aminoácidos/metabolismo , Transporte Biológico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Cistina/metabolismo , Glutationa/metabolismo , Dissulfeto de Glutationa/deficiência , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Terapia de Alvo Molecular , gama-Glutamiltransferase/metabolismoRESUMO
Many biomarkers indicate prognosis in chronic lymphocytic leukemia; such as fluorescence in situ hybridization testing: 17p or 11q deletions have a worse prognosis than trisomy 12, 13q deletion or normal result, or the mutational status of the immunoglobulin heavy chain (IGHV): unmutated IGHV have a worse prognosis than mutated IGHV. Recently, many gene mutations (TP53, NOTCH1 etc.,) have been linked to a worse prognosis. With the new era of high-throughput sequencing, it has become easier to study gene mutations and their implication in predicting prognosis. In this review, we aim to review all the studies that performed whole-exome sequencing or whole-genome sequencing on chronic lymphocytic leukemia cells and explore the implication of various genes in disease prognosis.
Assuntos
Biomarcadores Tumorais/genética , Leucemia Linfocítica Crônica de Células B/genética , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Mutação/genética , Prognóstico , Trissomia/genética , Sequenciamento do Exoma/métodosRESUMO
As soon as they get accepted into medical school, students find themselves facing numerous expectations: coping with tremendous study burden, competing with others for the best rank, completing internships and participating in the race for publishing are only to name a few. This big juggle makes it hard for the medical student to focus on research. It is often easier to postpone publication and involvement in research to "later". In fact there are many advantages to publishing in the current publication system but there are many disadvantages as well. With the widespread of social media and open access systems, new challenges have arisen. The aim of this paper is to discuss the advantages and disadvantages of publishing in the current system while highlighting the new challenges that the students might need to overcome. Its aim is to provide medical students with information to enhance their understanding of the current publication system and thus most importantly, probe their desire to publish.
Assuntos
Editoração , Estudantes de Medicina , HumanosRESUMO
Driving molecular mutations such as rearrangement of ALK and EGFR mutation is present in 5-10% of non-small-cell lung cancer. Tyrosine kinase inhibitors have shown good efficacy and thus become the standard of care. However, tumors have developed several resistance mechanisms against tyrosine kinase inhibitors, including transformation to small-cell lung carcinoma (SCLC). Transformation to SCLC after administration of anti-EGFR in EGFR-mutated adenocarcinoma has been well documented. Similarly, it appears that the same transformation happens in ALK-rearranged adenocarcinoma after the use of anti-ALK. In fact, to date eight cases have been reported in the literature. We aimed in this paper to focus on the characteristics, prognosis and treatment of these transformed SCLC.