Exploration of intrinsic and extrinsic apoptotic pathways in zearalenone-treated rat sertoli cells.

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin produced mainly by Fusarium. ZEA causes reproductive disorders and is both cytotoxic and genotoxic in animals; however, little is known regarding the molecular mechanism(s) leading to ZEA toxicity. Sertoli cells are somatic cells that support the development of spermatogenic cells. The objective of this study was to explore the effects of ZEA on the proliferation, apoptosis, and necrosis of rat Sertoli cells to uncover signaling pathways underlying ZEA cytotoxicity. ZEA reduced the proliferation of rat Sertoli cells in a dose-dependent manner, as indicated by a CCK8 assay, while flow cytometry revealed that ZEA caused both apoptosis and necrosis. Immunoblotting revealed that ZEA treatment increased the ratio of Bax/Bcl-2, as well as the expression of FasL and caspases-3, -8, and -9, in a dose-dependent manner. Collectively, these data suggest that ZEA induced apoptosis and necrosis in rat Sertoli cells via extrinsic and intrinsic apoptotic pathways. This study provides new insights into the molecular mechanisms by which ZEA exhibits cytotoxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1731-1739, 2016.

Diagnostic accuracy of pelvic magnetic resonance imaging for the assessment of bone marrow involvement in diffuse large B-cell lymphoma.

PURPOSE: We investigated the efficacy of pelvic magnetic resonance imaging (MRI) in the diagnosis of bone marrow involvement (BMinv) in diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS: This was a retrospective study of data from a previous study (NCT02733887). We included 171 patients who underwent bone marrow biopsy (BMB) and bone marrow smear (BMS), pelvic MRI, and whole-body positron emission tomography-computed tomography (PET/CT) from January 2016 to December 2019 at a single center. BMB/BMS and whole-body PET/CT results were used as reference standards against which we calculated the diagnostic value of pelvic MRI for BMinv in DLBCL patients. A chi-square test was used to compare detection rates, and a receiver operating characteristic curve was used to evaluate diagnostic value of pelvic MRI. Propensity-score matching was performed according to clinical information, and Kaplan-Meier curves were constructed to compare progression-free survival (PFS) and overall survival (OS) of patients. RESULTS: The BMinv detection rate of pelvic MRI (42/171) was higher (P = 0.029) than that of BMB/BMS (25/171), and similar to that of PET/CT (44/171; P = 0.901). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of pelvic MRI were 83.33%, 98.37%, 94.15%, 95.24%, and 93.80%, respectively. Median PFS values were as follows: BMB/BMS-positive, 17.8 months vs. BMB/BMS-negative, 26.9 months (P = 0.092); PET/CT-positive, 24.8 months vs. PET/CT-negative, 33.0 months (P = 0.086); pelvic MRI-positive, 24.9 months vs. pelvic MRI-negative, 33.1 months (P<0.001). Median OS values were as follows: BMB/BMS-positive, 22.3 months vs. BMB/BMS-negative, 29.8 months (P = 0.240); PET/CT-positive, 27.9 months vs. PET/CT-negative, 33.9 months (P = 0.365); pelvic MRI-positive, 27.3 months vs. pelvic MRI-negative, 35.8 months (P = 0.062). CONCLUSION: Pelvic MRI is effective for detecting BMinv in DLBCL patients, providing a more accurate indication of PFS than BMB/BMS and PET/CT do. It may ultimately be used to improve the accuracy of clinical staging, guide patient treatment, and evaluate prognosis.

A novel prognostic model for angioimmunoblastic T-cell lymphoma: A retrospective study of 55 cases.

OBJECTIVE: To explore prognostic factors and develop an accurate prognostic prediction model for angioimmunoblastic T-cell lymphoma (AITL). METHODS: Clinical data from Chinese patients with newly diagnosed AITL were retrospectively analysed. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier method survival curves; prognostic factors were determined using a Cox proportional hazards model. The sensitivity and specificity of the predicted survival rates were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves. RESULTS: The estimated 5-year OS and PFS of 55 eligible patients with AITL were 22% and 3%, respectively. Multivariate analysis showed that the presence of pneumonia, and serous cavity effusions at initial diagnosis were significant prognostic factors for OS. Based on AUC ROC values, our novel prognostic model was superior to IPI and PIT based models and suggested better diagnostic accuracy. CONCLUSIONS: Our prognostic model based on pneumonia, and serous cavity effusions at initial diagnosis enabled a balanced classification of AITL patients into different risk groups.

Dog vaccination with EgM proteins against Echinococcus granulosus.

BACKGROUND: Dogs play a pivotal role in the transmission of cystic echinococcosis (CE), a zoonosis caused by the tapeworm Echinococcus granulosus. We showed previously that dogs vaccinated with two E. granulosus adult-worm specific proteins, EgM9 and EgM123, emulsified with Freund's adjuvants induced significant protective efficacy in terms of reduction in worm burden and egg production after 45 days post-infection. It was not known whether this protection can be sustained using adjuvants suitable for use in dogs. METHODS: Recombinant EgM9 and EgM123 were mixed with Quil A or ISCOMs for vaccinating dogs. After three vaccine injections, all the dogs were orally challenge-infected with 200 000 protoscoleces of E. granulosus. After 45 days of infection, all the dogs were euthanized and necropsied for collecting and counting E. granulosus worms. Immunoglobins, including the IgG subclasses IgG1 and IgG2, were detected in the sera of vaccinated dogs by ELISA. To determine whether the protection efficacy could be maintained after 45 days post-infection, we implemented a longevity trial to count eggs in dog faeces for 170 days after infection. RESULTS: The dogs vaccinated with EgM9 and EgM123 mixed with Quil A and ISCOMs showed similar protective efficacy as the proteins emulsified with Freund's adjuvants in our previous study in terms of reduction of worms and eggs at 45 days post-infection. The longevity trial showed that EgM9 protein-vaccinated group released lower number of eggs per gram compared with the egg counts in the control dogs during the dog trial study. CONCLUSION: EgM9 and EgM123 are thus suitable vaccine candidates against E. granulosus infection in dogs.

Prognostic significance of Tet methylcytosine dioxygenase 2 (TET2) gene mutations in adult patients with acute myeloid leukemia: a meta-analysis.

Tet methylcytosine dioxygenase 2 (TET2) gene mutations have recently been recognized in acute myeloid leukemia (AML). We performed a meta-analysis to evaluate the controversial prognostic significance of TET2 mutations in AML. Eight studies, covering 2552 patients with AML, were included in this analysis. Pooled hazard ratios (HRs) indicated that TET2 mutations had a poor prognostic impact on the survival of patients with AML. The combined HR for overall survival (OS) was 1.53 and the summary HR for event-free survival (EFS) was 1.64. Additionally, TET2 mutations appeared to be an adverse prognostic indicator in both patients with cytogenetically normal (CN)-AML (HR for OS: 1.43 and HR for EFS: 1.76) and subgroups of patients with favorable-risk genotypes (HR for EFS: 2.35) and intermediate-I-risk genotypes (HR for EFS: 1.57). These findings indicate that TET2 mutations have an adverse impact on prognosis and may help to justify risk-adapted therapeutic strategies for patients with AML.

Associations between RASSF1A promoter methylation and NSCLC: a meta-analysis of published data.

BACKGROUND: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features. METHODS: Eligible studies were identified through searching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. RESULTS: Nineteen studies involving 2,063 cases of NSCLC and 1,184 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and NSCLC in the complete data set (OR = 19.42, 95% CI: 14.04- 26.85, P < 0.001). Pooling the control tissue subgroups (heterogeneous/autologous) gave pooled ORs of 32.4 (95% CI, 12.4-84.5) and 17.7 (95% CI, 12.5-25.0) respectively. Racial subgroup (Caucasian/Asian) analysis gave pooled ORs of 26.6 (95% CI, 10.9-64.9) and 20.9 (95% CI, 14.4-30.4) respectively. The OR for RASSF1A methylation in poorly-differentiated vs. moderately/well-differentiated NSCLC tissues was 1.88 (95% CI, 1.32- 2.68, P<0.001), whereas there were no significant differences in RASSF1A methylation in relation to gender, pathology, TNM stage and smoking behavior among NSCLC cases. CONCLUSION: This meta-analysis suggests a significant association between RASSF1A methylation and NSCLC, confirming the role of RASSF1A as a tumor suppressor gene. Large-scale and well-designed case-control studies are needed to validate the associations identified in the present meta-analysis.