Zobrazení zdroje stránky Bertramcollins6744

Retinol plays a significant role in several physiological processes through their nuclear receptors, whose expression depends on retinol cytoplasmic concentration. Loss of expression of nuclear receptors and low retinol levels have been correlated with lung cancer development. Stimulated by retinoic acid 6 (STRA6) is the only described cell membrane receptor for retinol uptake. Some chronic diseases have been linked with specific polymorphisms in STRA6. This study aimed to evaluate four STRA6 single nucleotide polymorphisms (SNPs) (rs4886578, rs736118, rs351224, and rs97445) among 196 patients with locally-advanced and metastatic non-small cell lung cancer (NSCLC) patients. Genotyping, through a validated SNP assay and determined using real time-PCR, was correlated with clinical features and outcomes. NSCLC patients with a TT SNP rs4886578 and rs736118 genotype were more likely to be &gt;60 years, non-smokers, and harboring EGFR mutations. Patients with a TT genotype compared with a CC/CT SNP rs974456 genotype had a median progression-free survival (PFS) of 3.2 vs. 4.8 months, p = 0.044, under a platinum-based regimen in the first-line. Furthermore, patients with a TT rs351224 genotype showed a prolonged overall survival (OS), 47.5 months vs. 32.0 months, p = 0.156. This study showed a correlation between clinical characteristics, such as age, non-smoking history, and EGFR mutational status and oncological outcomes depending on STRA6 SNPs. The STRA6 TT genotype SNP rs4886578 and rs736118 might be potential biomarkers in locally-advanced and metastatic NSCLC patients.Nuclear factor erythroid-2-related factor-2 (NFE2L2/Nrf2) is a transcription factor that regulates the expression of antioxidant genes. Both Kelch-like ECH-associated protein 1 (Keap1) mutations and Nrf2 mutations contribute to the activation of Nrf2 in non-small cell lung cancer (NSCLC). Nrf2 activity is associated with poor prognosis in NSCLC. Metabolic reprogramming represents a cancer hallmark. Increasing studies reveal that Nrf2 activation promotes metabolic reprogramming in cancer. In this review, we discuss the underlying mechanisms of Nrf2-mediated metabolic reprogramming and elucidate its role in NSCLC. Inhibition of Nrf2 can alter metabolic processes, thus suppress tumor growth, prevent metastasis, and increase sensitivity to chemotherapy in NSCLC. In conclusion, Nrf2 may serve as a therapeutic target for the treatment of NSCLC.Poly (ADP-ribose) polymerase (PARP) inhibitors are a therapeutic milestone exerting a synthetic lethal effect in the treatment of cancer involving BRCA1/2 mutation. Theoretically, PARP inhibitors (PARPi) eliminate tumor cells by disrupting DNA damage repair through either PARylation or the homologous recombination (HR) pathway. However, resistance to PARPi greatly hinders therapeutic effectiveness in triple-negative breast cancer (TNBC). Owing to the high heterogeneity and few genetic targets in TNBC, there has been limited therapeutic progress in the past decades. In view of this, there is a need to circumvent resistance to PARPi and develop potential treatment strategies for TNBC. We present, herein, a review of the scientific progress and explore the mechanisms underlying PARPi resistance in TNBC. The complicated mechanisms of PARPi resistance, including drug exporter formation, loss of poly (ADP-ribose) glycohydrolase (PARG), HR reactivation, and restoration of replication fork stability, are discussed in detail in this review. Additionally, we also discuss new combination therapies with PARPi that can improve the clinical response in TNBC. The new perspectives for PARPi bring novel challenges and opportunities to overcome PARPi resistance in breast cancer.The primary aim of the present retrospective study was to investigate lipid profiles and kinetics in acute promyelocytic leukemia (APL) patients. We analyzed 402 newly diagnosed APL patients and 201 non-APL patients with acute myeloid leukemia (as control). Incidence of hypertriglyceridemia in APL patients and non-APL patients was 55.82% and 28.4% (p = 0.0003). The initial levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were higher in APL patients than in control (all p less then 0.0001). In APL patients, triglyceride levels were significantly increased during induction treatment with all-trans retinoic acid and arsenic. Multivariable analysis showed that age, being overweight (body mass index ≥25) and APL were independent risk factors for hypertriglyceridemia in all patients before treatment. High triglyceride levels were not significantly associated with disease-free survival or overall survival in the APL patients. In summary, in the current study triglyceride levels were significantly elevated in APL patients before treatment, and they increased during induction treatment, but there were no significant corresponding effects on survival.Neuroblastoma (NB) is one of the most common solid tumors in childhood. To date, targeting MYCN, a well-established driver gene in high-risk neuroblastoma, is still challenging. In recent years, inhibition of bromodomain and extra terminal (BET) proteins shows great potential in multiple of Myc-driven tumors. ARV-825 is a novel BET inhibitor using proteolysis-targeting chimera (PROTAC) technology which degrades target proteins by the proteasome. In this study, we investigated the effect of ARV-825 in neuroblastoma in vitro and in vivo. Our results showed that ARV-825 treatment robustly induced proliferative suppression, cell cycle arrest, and apoptosis in NB cells. Moreover, ARV-825 efficiently depleted BET protein expression, subsequently repressing the expression of MYCN or c-Myc. In the NB xenograft model, ARV-825 profoundly reduced tumor growth and led to the downregulation of BRD4 and MYCN expression in mice. Taken together, these findings provide evidence that PROTAC BET inhibitor is an efficient way to achieve MYCN/c-Myc manipulation, and ARV-825 can be used as a potential therapeutic strategy for the treatment of neuroblastoma.Glioblastoma is the most common primary brain tumor in adults with poor overall outcome and 5-year survival of less than 5%. Treatment has not changed much in the last decade or so, with surgical resection and radio/chemotherapy being the main options. Glioblastoma is highly heterogeneous and frequently becomes treatment-resistant due to the ability of glioblastoma cells to adopt stem cell states facilitating tumor recurrence. Therefore, there is an urgent need for novel therapeutic strategies. The ubiquitin system, in particular E3 ubiquitin ligases and deubiquitinating enzymes, have emerged as a promising source of novel drug targets. In addition to conventional small molecule drug discovery approaches aimed at modulating enzyme activity, several new and exciting strategies are also being explored. [https://www.selleckchem.com/products/ccg-203971.html CCG-203971] Among these, PROteolysis TArgeting Chimeras (PROTACs) aim to harness the endogenous protein turnover machinery to direct therapeutically relevant targets, including previously considered "undruggable" ones, for proteasomal degradation.