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Diffuse large B-cell lymphoma (DLBCL) includes two prognostically-important subtypes, the germinal center B-cell (GCB) and the non-GCB types. The aim of this study was to evaluate immunohistochemical approaches for predicting the survival of patients with DLBCL following autologous hematopoietic stem cell transplantation (AHSCT). We identified 62 patients with DLBCL who either had an initial complete remission (17 patients) or received salvage chemotherapy for relapsed or refractory disease (45 patients), followed by AHSCT. Tissue microarrays were immunostained with monoclonal antibodies against GCET1, CD10, BCL6, MUM1, FOXP1 and LMO2. Using the Hans algorithm, we classified 50% of the cases as GCB type, whereas the Choi algorithm classified 58% as GCB type and LMO2 was positive in 69%. However, no significant differences were found in the five-year overall or event-free survivals using any of these approaches. In conclusion, cell-of-origin fails to predict survival of DLBCL patients treated with AHSCT.

A frequent chromosomal translocation in mature B-cell non-Hodgkin lymphoma affects band 3q27 and results in deregulation of the B-cell lymphoma 6 (BCL6) gene. Two breakpoint clusters have been described thus far, the major breakpoint region (MBR) and an alternative breakpoint region (ABR) that is located 245 - 285 kb 5' to BCL6. Translocation at the MBR predominates in diffuse large B-cell lymphoma, whereas translocation at the ABR is reported to be frequently associated with grade 3B follicular lymphoma. However, translocation at the ABR has not been studied in a large series of follicular lymphomas, particularly t(14;18)-negative follicular lymphomas. Therefore, we studied BLC6 rearrangements at the MBR and ABR by using break-apart fluorescence in situ hybridization (FISH) probes in 142 cases of follicular lymphomas, including 63 t(14;18)-negative and 79 t(14;18)-positive cases. Conventional cytogenetic (karyotype) analysis was also performed in 58 of the 63 t(14;18)-negative cases. BCL6 rearrangement was found in 26% of t(14;18)-negative and 19% of t(14;18)-positive follicular lymphoma. t(14;18)-negative cases showed a high frequency of rearrangement at the ABR (12%) with an ABR:MBR ratio of 0.86, compared to only 5% with an ABR:MBR ratio of 0.36 in the t(14;18)-positive cases. BCL6 rearrangements were found in all grades of follicular lymphoma but were most frequent in grade 3 t(14;18)-negative follicular lymphoma (60%). FISH analysis had a higher sensitivity for detecting BCL6 rearrangements than conventional cytogenetics. In conclusion, BCL6 rearrangements occur at a similar frequency in t(14;18)-negative follicular lymphoma and diffuse large B-cell lymphoma. However, t(14;18)-negative follicular lymphoma appears to have a higher frequency of rearrangement at the ABR compared with t(14;18)-positive follicular lymphoma and diffuse large B-cell lymphoma. Therefore, it is important to perform FISH analysis with ABR to determine possible involvement of BCL6 rearrangement in follicular lymphoma, especially in t(14;18)-negative cases.

The objective of this study was to investigate the clinical pathological characteristics of breast cancer (BC) patients with secondary diabetes after systemic therapy without preexisting diabetes. A total of 1434 BC patients received systemic therapy and were analyzed retrospectively. Fasting plasma glucose (FPG) levels were monitored prior to the treatments, during the course of systemic therapy, and at the follow-up visits. Cox regression models were used to estimate the associations between the clinical pathological characteristics of BC and the cause-specific hazard of developing secondary diabetes. Among the 1434 BC patients, 151 had preexisting type 2 diabetes. Of the remaining 1283 patients with normal FPG levels prior to the systemic therapy, 59 developed secondary diabetes and 72 displayed secondary impaired fasting glucose (IFG) over a mean follow-up of 41 months. The prevalence of secondary type 2 diabetes in BC patients was 4.6 % (59/1283), which was obviously higher than that of the normal control group (1.4 %, P < 0.001). The percentage of older patients (P < 0.05), menopausal patients (P < 0.001), and obese patients (P < 0.01) tended to be lower in the secondary diabetic group. In addition, these patients with secondary diabetes had later pathological stages (P < 0.01), more lymph node metastasis (P < 0.05), negative estrogen receptor (ER) expression (P < 0.05), and smaller size of tumors (P < 0.05). After adjusting for age and BMI, the risk of developing secondary diabetes and IFG in subjects with later pathological stage BC (hazard ratio (HR) = 1.623; 95 % confidence interval (CI) 1.128–2.335 (P < 0.01)), negative progesterone receptor (PR) expression (HR = 0.530; 95 % CI 0.372–0.755 (P < 0.001)), positive human epidermal growth factor receptor 2 (HER2) expression (HR = 1.822; 95 % CI 1.230–2.700 (P < 0.01)), and more lymph node metastasis (HR = 1.595; 95 % CI 1.128–2.258 (P < 0.01)) was significantly higher. In conclusion, this study shows that an increase in the incidence of diabetes among breast cancer survivors after systemic therapy, especially the patients with later pathological stages, more lymph node metastasis, negative hormone receptor expression, and positive HER2 expression. Our study suggests that greater diabetes screening and prevention strategies among breast cancer patients after systemic treatment are needed in China.

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Previous studies have indicated that the intrauterine growth retardation (IUGR) fetus is faced with a high susceptibility to adult metabolic syndrome (MS). Non-alcoholic simple fatty liver (NAFL) is considered to be the hepatic manifestation of MS. In the present study, we evaluated the susceptibility of high-fat dietinduced NAFL in female adult IUGR offspring rats, induced by prenatal nicotine exposure, and we further explored the underlying intrauterine programming mechanism for this phenomenon. The IUGR rat model was established by prenatal exposure to nicotine (2 mg kg −1 d −1 ), the liver tissues from female fetuses and female adult offspring fed with normal or high-fat diets were collected. The female adult offspring in the nicotine-exposed group showed low birth weights and postnatal catch-up growth, as well as severe NAFL under high-fat diets. Moreover, increased gene expression involved in the hepatic insulin-like growth factor 1 (IGF1) pathway, gluconeogenesis and lipid synthesis, and decreased gene expression of lipid output accompanied with elevated serum triglyceride levels, was observed. The female fetuses in the nicotine-exposed group showed down-regulated hepatic IGF1 pathways, and also exhibited similar patterns of increased gluconeogenesis, lipid synthesis and decreased lipid output to those in the adults. The present study demonstrates the intrauterine origin of increased susceptibility to high-fat diet-induced NAFL in female offspring rats by prenatal nicotine exposure, which is most likely mediated by "two intrauterine programming". That is, the first glucocorticoid-IGF1 axis programming induces postnatal catch-up growth, aggravates glucose and lipid metabolic disorders, and leads to an increased susceptibility to adult NAFL, while the second hepatic glucose and lipid metabolic programming enhances hepatic lipogenesis and reduces lipid oxidation and output, promoting NAFL. † Electronic supplementary information (ESI) available. See

Astragaloside is a monomer isolated from Astragalus membranaceus, a flowering plant in the family Fabaceae. The aim of the present study was to investigate the anti-apoptotic affect of astragaloside on myocardial cells through the TLR4/NF-κB signaling pathway. Astragaloside, NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and Toll-like receptor 4 (TLR4) blocking antibody solution were prepared in vitro, and myocardial cells were incubated and cultured in serum-free medium overnight. Cells were divided into five groups: the normal control group, serum-free group, astragaloside group, TLR4 blocking antibody group and NF-κB inhibitor PDTC group. The myocardial cell apoptosis in each group was detected using flow cytometry, and the expression levels of TLR4 and NF-κB were detected via western blotting. The apoptosis rate in the serum-free group was significantly higher than that in the normal control group. The apoptosis rate of myocardial cells in the TLR4 blocking antibody group and NF-κB inhibitor PDTC group was lower than that in the serum-free group. In addition, the myocardial cell apoptosis was more obviously decreased in the astragaloside group, and the protein expression levels of TLR4 and NF-κB in the serum-free group were significantly higher than those in normal control group. The protein expression levels of TLR4 and NF-κB in the astragaloside group were obviously lower than those in the serum-free group, and the protein expression levels of TLR4 and NF-κB in the TLR4 blocking antibody group and NF-κB inhibitor PDTC group were decreased. In conclusion, astragaloside reduced myocardial cell apoptosis and protected myocardial cells, which may be one of the mechanisms of a traditional Chinese medicine monomer in treating heart failure.