Notes

Sodium-Glucose Cotransporter (SGLT2) inhibitors: A brand new Time inside renovascular safety.
rest in DUSP6-overexpressing ovarian cancer cells. This suggests that overexpression of DUSP6 promotes chemotherapy-resistance through the negative regulation of the ERK signaling pathway, increasing the G0/G1 phase ratio among ovarian cancer cells, and leading to cellular quiescence. © The author(s).Background Platinum-based therapy (PBT) can be limited by gastrointestinal adverse events, particularly PBT-related colitis and diarrhea (PCD). We studied clinical features, treatments, and outcomes of PCD. Methods This was a retrospective study of cancer patients who received PBT and colonoscopic evaluation for PCD symptoms from 2009 to 2018. Results Of 36,595 patients who received PBT, 86 (0.2%) met inclusion criteria. Median time from PBT initiation to PCD was 66 days. Regarding PBT type, 47% of the patients received carboplatin, 31% cisplatin, and 22% oxaliplatin. Median duration of PCD symptoms was 20 days. Colonoscopy revealed mucosal ulceration in 34% of the patients and nonulcerative inflammation in 33%. Half of the cohort needed hospitalization for PCD (49%). The majority received treatment for PCD (59%) immunosuppressive therapy in 21%, antibiotics in 27%, antimotility agents in 22%, and intravenous fluids in 51%. Eight patients (9%) were admitted to the intensive care unit for PCD management. Six patients (7%) experienced colonic perforation that required surgical intervention; two of them had gastrointestinal tumors. Physicians restarted PBT in 37 (43%) patients; 8 (22%) of them had PCD recurrence that was managed expectantly. Colonic perforation occurred more frequently with use of oxaliplatin and cisplatin than carboplatin (P=0.05). The median duration of PCD symptoms was longer in patients receiving carboplatin or cisplatin than in those receiving oxaliplatin (P=0.182). Conclusions PCD is rare, but in a small subset of patients, it can lead to serious complications. Treatment of PCD is mainly supportive, but immunosuppressive therapy may be required. © The author(s).Background Peroxiredoxins (PRDXs) were reported to be associated with inflammation response in previous studies. In colon adenocarcinoma (COAD), however, their correlations and clinical significance were unclear. Methods The RNA-seq data of 452 COAD patients with clinical information was downloaded from The Cancer Genome Atlas (TCGA) and transcripts per million (TPM) normalized. Comparisons of relative expressions of PRDXs between COAD tumor and normal controls were applied. PRDXs dy-regulations in COAD were validated via Oncomine, Human Protein Atlas (HPA) and Gene Expression Omnibus (GEO) repository. Through Tumor Immune Estimation Resource (TIMER), the immune estimation of TCGA-COAD patients was downloaded and the dy-regulated PRDXs were analyzed for their correlations with immune infiltrations in COAD. The TCGA-COAD patients were divided into younger group (age≤65 years) and older group (age>65 years) to investigate the prognostic roles of age, TNM stage, dy-regulated PRDXs and the immune infiltrations inr its early diagnosis. Age was prognostic and should be considered in the treatments of the older patients. Dy-regulated PRDXs were negatively correlated with immune infiltration levels. CD4+ T cell and CD8+ T cell infiltrations were prognostic in COAD and their potential as immune targets needed further investigation. © The author(s).Gallbladder cancer is one of the most common malignant tumors in the biliary tract. In recent years, the chemotherapy treatment for gallbladder carcinoma has exhibited obvious characteristics of drug resistance and insensitivity, and one of the main factors is the existence of cancer stem cells. Here in this study, the effect of Bufalin on gallbladder cancer (GBC-SD) cells and the related mechanism were studied. The results indicated that Bufalin could inhibit the growth of gallbladder carcinoma both in vivo and in vitro. According to the biological behavior analysis, Bufalin induced apoptosis, inhibited the propagation, migration and invasion of GBC-SD cells, and blocked cell cycle at the G2/M stage. Besides, Bufalin inhibited the tumor sphere formation capability of gallbladder carcinoma in matrigel, reduced the expression of multiple stemness-associated proteins, including Oct4, Sox2 and the stem cell-surface marker proteins CD133 and CD44. Western blot assay showed that Bufalin inhibited MEK/ERK and PI3-K/AKT signaling pathways by inhibiting the expression of p-c-Met, which in turn affected the expression of apoptosis-related protein Mcl-1, and the invasion-associated proteins E-cadherin, MMP9 and Snail. Bufalin was found to have an inhibitory effect on the GBC-SD cell growth and reduce the self-renewal and characteristic of gallbladder cancer stem cells. It enhanced the chemotherapeutic sensitivity and reduced the metastasis of gallbladder carcinoma. In conclusion, Bufalin can be used as a new promising anticancer drug for gallbladder cancer patients who are resistant to traditional chemotherapy. © The author(s).Background and Purpose Pervious studies have demonstrated that the loss of EGFR T790M after Osimertinib treatment may be the cause of Osimertinib resistance. Here, we conducted a meta-analysis to evaluate the association between the persistence of EGFR T790M and the clinical benefits of Osimertinib in non-small cell lung cancer (NSCLC) patients with baseline EGFR T790M mutation. Experimental design and Methods PUBMED, EMBASE, and Cochrane databases were searched for eligible studies that provided the survival outcomes including overall survival (OS), progression-free survival (PFS) or time to discontinuation (TTD) data for each patient treated with Osimertinib with the status of the T790M mutation tested after Osimertinib resistance. The hazard ratios (HRs) and their 95% confidence intervals (CI) were calculated for each study. Results In total, eight eligible studies were included in the analysis, among which six studies provided the data on PFS, and the other two studies provided the TTD data. Overall, 312 patients (151 patients with the persistence of T790M) were identified. The persistence of T790M was associated with longer PFS (HR, 0.40; 95% CI, 0.19-0.84; P=0.01) and TTD (HR, 0.54; 95% CI, 0.39-0.76; P=0.0004). Furthermore, overall analysis the survival outcomes including PFS and TTD subgroups also showed preferable clinical benefits for patients with the T790M persistence (HR, 0.57; 95%CI, 0.45-0.73; P less then 0.00001). Conclusions Our findings confirm the persistence of T790M is associated with the clinical benefits of Osimertinib in NSCLC patients with baseline EGFR T790M mutation treated with Osimertinib. © The author(s).The microenvironment of solid tumors plays an essential role in tumor progression. In lung cancer, the stromal cells produce a fibronectin rich extracellular matrix which is known to contribute to both tumor metastasis and drug resistance. Due to its conformational lability, fibronectin is considerably remodeled by the contractile forces of the fibrotic microenvironment within the tumor stroma. As a result, the secondary structure of fibronectin's Type III domains is disrupted and the molecule becomes highly stretched. The contribution/impact of these strained forms of fibronectin on tumor growth and metastasis is not known. In the current study we show that the partially unfolded first Type III domain of fibronectin, III-1c, activates a toll-receptor/NF-κB pathway leading to an increase in the expression of IL-8. Using a 3-D model of tumor-associated extracellular matrix, we demonstrate that lung cancer cells seeded onto this matrix activate a TLR4/NF-κB signaling pathway leading to a robust increase in the release of IL-8. Cytokine release by these cells is completely dependent on the presence of fibronectin in the extracellular matrix. These findings suggest that paracrine signaling between the tumor and the stromal myofibroblasts causes a remodeling of the matrix fibronectin into a strained conformation which supports the activation of a TLR4/NF-κB signaling pathway resulting in the upregulation of fibro-inflammatory cytokines. © The author(s).Riluzole is approved by the FDA as an amyotrophic lateral sclerosis (ALS) drug. Previous studies showed that treatment with riluzole suppressed the proliferation of many cancer cells. However, little is known about its effects on nasopharyngeal carcinoma (NPC) and its molecular mode of action. In this study, we determined the effect of riluzole on apoptosis, cell cycle, migration, and invasion in NPC cell lines and investigated its mechanism at the molecular level. By using the human NPC cell lines CNE1, CNE2, and HNE1, we revealed that riluzole effectively inhibited viability of the NPC cell lines in dose- and time-dependent manners. Furthermore, riluzole dose-dependently induced apoptosis and G2/M cell cycle arrest in the NPC cell lines. After combination with radiotherapy (RT), greater cytotoxicity was achieved than with riluzole or RT alone in vitro and vivo. This was associated with the activation of ataxia telangiectasia mutated (ATM) and phosphoinositide p53 pathways. P53 silencing reduced cell reactiveness to riluzole therapy. These observations demonstrate that the riluzole-activated ATM/P53 pathway is directly involved in radiation-induced apoptosis of NPC cells. Given the acceptable side effect, combining of riluzole and radiotherapy is promising in NPC treatment. © The author(s).Background Tamoxifen (TAM) and aromatase inhibitor (AI) therapies have been associated with increased risk of thromboembolic and cardiovascular events, respectively, in addition to other side effects. This study analysed the risk of these events and the overall survival (OS) benefit in breast cancer patients treated with AI, compared with TAM-treated patients, in a large population-based cohort. Methods This observational cohort study included women diagnosed with breast cancer and treated with TAM or AI. Data were extracted from primary care records in a population database (SIDIAP, System for the Development of Research in Primary Care). Incidence rates of study outcomes are reported. Survival analyses included Kaplan-Meier estimation and Cox proportional hazards models. Sensitivity analysis was carried out, using Fine and Gray models to account for competing risk of death. Confounding was minimized using propensity score adjustment and inverse probability weighting (IPW) adjustment. Results Data from 3082 postmenopausal women treated with TAM, and 18,455 treated with AI, were available. Adjusted hazard ratios (HRs) [95% confidence interval (CI)] for AI users, compared with TAM group, were 0.93 (95%CI 0.69-1.26) for thromboembolic events (TEEs); 1.13 (95%CI 0.79-1.63) for cardiovascular events, and 0.76 (95%CI 0.70-0.82) for mortality. Additional analyses using competing risk analysis had similar results, while IPW adjustment showed a potential risk of pulmonary embolism (PE) [2.26 (95%CI 1.02-4.97)] in AI-treated patients. Conclusions AI users had >20% lower all-cause mortality compared with TAM users, without increasing risk to experience cardiovascular and TEEs. This would locate AI therapy on the first line in clinical practice. Thus, AI might be the most preferable option in adjuvant hormonal therapy choice. © The Author(s), 2020.
Homepage: