ABSTRACT
Background: Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous group of lymphoid malignancies with distinct oncogenic events and clinical behavior that cannot be unraveled by morphology and immunophenotype alone. Simple biological segregation such as the Hans classifier helps to explain the heterogeneous responses to standard treatment and provides a rationale for the investigation of novel targeted therapies. Aims and Objectives: In this study, we tried to estimate immunohistochemical (IHC) features of nodal and extranodal DLBCL using cell-of-origin classification (Hans Algorithm) with the markers CD10, Bcl-6, MUM1. Materials and Methods: Blocks of the patients with a histological diagnosis of DLBCL over the past 3 years were retrieved and submitted for IHC analysis to classify into germinal center B cell type (GCB) and non-GCB type. Results: Mean age for nodal DLBL was 48.19 � 14.68 years, extranodal were 55.7 � 13.22 years. Mean age for GCB were 56.6 � 15.66 years whereas for non-GCB were 51.45 � 12.85 years. Among nodal lymphomas cervical was the most common site and among extranodal lymphomas, intestinal lymphomas were commonest (including colorectal). Relative proportion of GCB among extranodal was 28.78%, whereas in nodal DLBCL it was 16.67%, relative risk of getting GCB type DLBCL was 1.72 times higher in extranodal compared to nodal DLBCL (P = 0.081). Total positivity of MUM1 was 17%, whereas for Bcl6 and CD10 it was 29% and 15% respectively. Ki67 was considerably higher in GCB type and for extranodal DLBCL in our study. Conclusion: Proportion of extranodal GCB type DLBCL compared to nodal DLBCL is considerably higher in our study population, though it varies greatly among Asian and world data. Uniform meta-analysis and systematic review is necessary to stratify.
ABSTRACT
PURPOSE: Prolactin (PRL) plays a critical role in breast cancer progression by activating its cognate receptor and promotes the growth and differentiation of breast cancer cells. Studies have shown that B-cell lymphoma 6 (BCL6) is the target gene of microRNA-339-5p (miR-339-5p) and that BCL6 expression contributes to breast cancer progression. Herein, we identified PRL as a potent suppressor of BCL6 expression in human breast cancer cells. METHODS: Western blotting and quantitative reverse transcription-polymerase chain reaction were used to investigate molecular mechanisms underlying miR-339-5p expression and BCL6 manipulation in MCF-7, T47D, and SKBR3 breast cancer cells. Phenotypic changes in these breast cancer cell lines were assessed by performing cell viability (MTT), colony formation, migration, and invasion assays. RESULTS: PRL suppressed BCL6 protein and mRNA expression and upregulated miR-339-5p expression in MCF-7 and T47D breast cancer cells. Selective downregulation of miR-339-5p expression significantly reversed PRL-induced suppression of BCL6 mRNA and protein expression. Exogenous PRL stimulation significantly decreased the proliferation, colony formation, migration, and invasion of breast cancer cells, and suppression of miR-339-5p expression reversed these processes in vitro. CONCLUSION: These results indicated that PRL inhibited BCL6 expression and regulated breast cancer progression through a miR-339-5p-dependent pathway.
Subject(s)
Humans , Blotting, Western , Breast Neoplasms , Breast , Cell Line , Cell Survival , Down-Regulation , Lymphoma, B-Cell , Prolactin , RNA, MessengerABSTRACT
Objective To explore the impact of ketogenic diet (KD) on follicular helper T cells(TFH) in children with intractable epilepsy.Methods Thirty-three cases with intractable epilepsy were selected between Jul.2013 and Jan.2014 in Shenzhen Children's Hospital,19 boys and 14 girls; average age was 39.6 months,and seventeen age-matched healthy children who took a physical examination in the same hospital were assigned as the healthy control group.Blood samples were collected from the children with refractory epilepsy before and after 1 week of KD treatment.The proportions of the various stages of B cells and TFH cells were detected by flow cytometry.The plasma concentration of interleukin-21 (IL-21) was determined by enzyme-linked immunosorbent assay(ELISA),and realtime quantitative PCR(RT-PCR) was performed to detect the levels of peroxisome proliferator-activated receptor gamma (PPAR-γ),B-lymphocyte-induced maturation protein-1 (Blimp-1),B-cell lymphoma 6 (Bcl6) and IL-21 mRNA expression in CD4 + T cells.Results (1) The number of TFH cells in children with intractable epilepsy [(3.57 ± 0.58) ％] was remarkably decreased after KD treatment(P ＜ 0.01),while there were no difference between after KD treatment and healthy control group[(4.93 ±0.70)％ vs (5.03 ±0.63)％,P ＞0.05].(2) The levels of transcription factor Bcl6 expression after treatment were significantly decreased,while inhibitory factor Blimp-1 expression increased (P ＜ 0.05).(3)The plasma concentration of IL-21 had a trend to decrease (P ＞ 0.05),while there were no difference before and after KD treatment,and levels of IL-21 mRNA expressions in CD4 +T cells were significantly decreased after the treatment (8.28 × 10-3 ± 1.19 × 10-3 vs 1.72 × 10-2 ± 0.81 × 10-2,t =3.08,P ＜ 0.05).(4) There was no significant difference in CD27-IgD + B cells before and after KD treatment (P ＞ 0.05),CD27 + IgD + B cell and CD27-IgD-B cells had a trend to decrease after KD treatment(P ＞0.05),and CD27 + IgD-B cells and CD27 + IgD-CD38 high plasma cells were significantly decreased after KD treatment (P ＜ 0.05).(5) The number of TFH cells were correlated positively with the number of CD27 + IgD-B cells and CD27 + IgD-CD3g high plasma cells (r =0.785,0.745,P ＜ 0.05).(6) The levels of PPAR-γmRNA in CD4 + T cells expression were significantly up-regulated after KD treatment (3.49 × 10-3 ± 1.10 × 10-3 vs 2.28 ± 10-3 ± 1.30 × 10-3,t =3.41,P ＜0.05),and the number of TFH cells and PPAR-γgene expression was correlated negatively (r =-0.619,P ＜ 0.05).Conclusions KD might down regulate TFH cell number and function through inducing PPAR-γexpression and could inhibit B cell differentiation,which might be one of the factors for hypogammaglobuinemia by KD treatment.