MYC-dependent MiR-7-5p regulated apoptosis and autophagy in diffuse large B cell lymphoma by targeting AMBRA1.

Diffuse large B-cell lymphoma (DLBCL) is the leading cause of mortality from invasive hematological malignancies worldwide. MicroRNA-7-5p (miR-7-5p) has been shown to be a tumor suppressor in several types of tumors. However, its role in DLBCL is not fully understood. This study explored the role of miR-7-5p in the progression of DLBCL and pursued the underlying mechanism. Quantitative real-time PCR and transfection of miRNA mimic and inhibitors were used to assess the effects of miR-7-5p on autophagy and apoptosis in SU-DHL-4 and SU-DHL-10 cells. Dual-luciferase reporter assay was used to identify target genes of miR-7-5p. Immunofluorescence, flow cytometry, and western blotting (WB) were performed to explore the underlying mechanism and downstream pathways of miR-7-5p and AMBRA1 in DLBCL cells. MiR-7-5p was upregulated in DLBCL cells. Luciferase reporter assays implicated AMBRA1 as a downstream target of miR-7-5p in DLBCL. WB and flow cytometry showed that an increase in miR-7-5p level and a decrease in AMBRA1 expression led to a decrease in autophagy and apoptosis-related protein expression. Furthermore, miR-7-5p prevented c-MYC dephosphorylation through AMBRA1 downregulation. On the contrary, c-MYC increased the expression of miR-7-5p, thereby establishing positive feedback on miR-7-5p transcription. The addition of hydroxychloroquine, an autophagy inhibitor, reduced autophagy and increased apoptosis in DLBCL cells. In vivo experiments further proved that the increase of miR-7-5p played a regulatory role in the expression of downstream AMBRA1 and c-MYC. These results demonstrate that c-MYC-dependent MiR-7-5p suppressed autophagy and apoptosis by targeting AMBRA1 in DLBCL cells. MiR-7-5p also suppressed autophagy and apoptosis by targeting AMBRA1 in DLBCL cells. Therefore, these data suggest that targeting miR-7-5p may be a promising strategy in DLBCL therapy.

Onychopathy Following Durvalumab Treatment for Extensive-Stage Small-Cell Lung Cancer: A Case Report.

Patients treated with immune checkpoint inhibitors (ICIS) are prone to immune related adverse events (irAEs), making it important to pay attention to these adverse events. Herein, we report a case of onychopathy after treatment of extensive small cell lung cancer (ES-SCLC) with durvalumab; this is the first report of onychopathy caused by durvalumab in a patient with lung cancer. The change in the patient's nails mainly manifested in the form of pigmentation and the thickening of the nails. Antifungal ointment was ineffective, and these changes were unrelated to malnutrition or any other factors. In addition, this case shows that onychopathy may occur within 2 years after treatment, indicating that these patients need long-term follow-up.

Surgical therapy and survival in young patients with stage I-II hepatocellular carcinoma: a retrospective cohort study.

Background: Hepatocellular carcinoma (HCC) is regarded as a high-mortality cancer, but the effectiveness of surgical strategies for young patients with early-stage HCC remains controversial. We aimed to analyze the survival in young patients with stage I-II HCC who underwent different kinds of surgical treatments. Methods: Overall survival (OS) and cancer-specific survival (CSS) were compared among patients aged 18-45 years with stage I-II HCC from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013) who underwent local tumor destruction (LTD), wedge or segmental resection (WSR), lobectomy resection (LR), liver transplantation (LT), or non-surgery. Univariate and multivariate analyses and Kaplan-Meier method were used to examine the OS and CSS of the patients. A stratification analysis of CSS was also conducted among the subgroups. Results: Data from 664 patients were extracted. The median survival time was 46 months. In the multivariate analysis of OS, compared with non-surgery, LTD [hazard ratio (HR), 0.37; 95% confidence interval (CI): 0.25-0.54; P<0.0001], LR (HR, 0.29; 95% CI: 0.19-0.45; P<0.0001), and WSR (HR, 0.26; 95% CI: 0.17-0.39; P<0.0001) had better outcomes, and LT had the best survival benefit (HR, 0.24; 95% CI: 0.16-0.36; P<0.0001), which was similar to CSS. In the stratification analysis, compared with the non-surgery group, among patients with chemotherapy, LT reduced the risk of CSS by 64% (HR, 0.36; 95% CI: 0.19-0.66; P interaction=0.0004). Conclusions: Surgery offers a survival benefit compared with non-surgery for young patients with stage I-II HCC. LT is associated with better survival than WSR, LR, and LTD.

First-line treatments for patients with advanced ALK gene rearrangements in NSCLC: a systematic review and network meta-analysis.

OBJECTIVE: To conduct a network meta-analysis of randomised controlled trials to determine the optimal clinical choice of first-line therapy for patients with ALK receptor tyrosine kinase (ALK) gene rearrangement non-small cell lung cancer (NSCLC). METHODS: Clinical trials in patients with histologically confirmed ALK gene rearrangement NSCLC, that included ALK inhibitors as first-line therapy, were identified using database searches. A Bayesian network meta-analysis was conducted to calculate the efficacy and safety of the included first-line treatments. RESULTS: Nine trials with 2,407 patients were included for analyses. Lorlatinib was better than brigatinib for progression-free survival (PFS) (hazard ratio 0.79, 95% confidence interval 0.63, 0.98). In subgroup analyses, lorlatinib exhibited the highest probability of best PFS ranking in patients with or without baseline brain metastases (38% and 80%, respectively); brigatinib had the highest probability of best PFS ranking among Asian patients (47%). Alectinib offered the highest survival advantage (57% probability), while lorlatinib was likely to be the best treatment for an objective response (41% probability). Alectinib displayed the highest probability of being ranked lowest for grade ≥3 adverse events (86%). CONCLUSIONS: Lorlatinib was associated with the best PFS overall, and was suitable for patients with or without brain metastases. Brigatinib was associated with the best PFS in Asian patients.

The impact of surgery on long-term survival of patients with primary intestinal non-Hodgkin lymphomas based on SEER database.

Evidence regarding the need for surgery for primary intestinal non-Hodgkin lymphoma (PINHL) patients with chemotherapy is limited and controversial. We aimed to investigate the specific impact of surgery on survival of PINHL patients. Data from PINHL patients (aged > 18 years) with chemotherapy between 1983 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We concerned about overall survival (OS) and improved cancer-specific survival (CSS). Propensity score matching (PSM) analysis was also used to explore the reliability of the results to further control for confounding factors. Finally, we screened 3537 patients. Multivariate regression analysis showed that patients with surgery and chemotherapy had better OS (hazard ratio [HR] 0.83; 95% confidence interval [CI] 0.75-0.93; p = 0.0009) and CSS (HR 0.87; 95% CI 0.77-0.99; p = 0.0404) compared with the non-operation group after adjusting for confounding factors. After PSM analysis, compared with non-surgery, surgery remained associated with improved OS (HR 0.77; 95% CI 0.68-0.87; p < 0.0001) and improved CSS (HR 0.82; 95% CI 0.72-0.95; p = 0.008) adjusted for baseline differences. In the large cohort of PINHL patients with chemotherapy older than 18 years, surgery was associated with significantly improved OS and CSS before and after PSM analysis.

Development and External Validation of a Nomogram to Predict Cancer-Specific Survival in Patients with Primary Intestinal Non-Hodgkin Lymphomas.

PURPOSE: Primary intestinal non-Hodgkin lymphoma (PINHL) is a biologically and clinically heterogeneous disease. Few individual prediction models are available to establish prognoses for PINHL patients. Herein, a novel nomogram was developed and verified to predict long-term cancer-specific survival (CSS) rates in PINHL patients, and a convenient online risk calculator was created using the nomogram. MATERIALS AND METHODS: Data on PINHL patients from January 1, 2004, to December 31, 2015, obtained from the Surveillance, Epidemiology, and End Results (SEER) database (n = 2372; training cohort), were analyzed by Cox regression to identify independent prognostic parameters for CSS. The nomogram was internally and externally validated in a SEER cohort (n = 1014) and a First Affiliated Hospital of Guangzhou University of Chinese Medicine (FAHGUCM) cohort (n = 37), respectively. Area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to evaluate nomogram performance. RESULTS: Five independent predictors were identified, namely, age, marital status, Ann Arbor Stage, B symptoms, and histologic type. The nomogram showed good performance in discrimination and calibration, with C-indices of 0.772 (95% CI: 0.754-0.790), 0.763 (95% CI: 0.734-0.792), and 0.851 (95% CI: 0.755-0.947) in the training, internal validation, and external validation cohorts, respectively. The calibration curve indicated that the nomogram was accurate, and DCA showed that the nomogram had a high clinical application value. AUC values indicated that the prediction accuracy of the nomogram was higher than that of Ann Arbor Stage (training cohort: 0.804 vs 0.630; internal validation cohort: 0.800 vs 0.637; external validation cohort: 0.811 vs 0.598), and Kaplan-Meier curves indicated the same. CONCLUSION: A nomogram was developed to assist clinicians in predicting the survival of PINHL patients and in making optimal treatment decisions. An online calculator based on the nomogram was made available at https://cuifenzhang.shinyapps.io/DynNomapp/.