Project description:Analysis of diffuse large B-cell lymphoma (DLBCL) from primary sites (named as S1, S2 and S3) and metastatic lymph nodes (named as L1, L2 and L3). Results provide insight into the targets involved in t DLBCL dissemination.
Project description:Angiogenesis plays a key role in tumor metastasis. Many genes may act in this process including formation of vessels, immune evasion,etc. Different gene expression profiles between lymphoma endothelium cells and reactive lymph node-derived endothelium cells may uncover these genes. And intensive mechanism researches on such key genes may explain the mechanisim of tumor-specific angiogenesis and help to explore effective treatment strategies to prevent/reverse tumor metastasis. We use microarrays to detail gene expression profiles of human lymphoma endothelium and reactive lymph node-derived endothelium. Lymph nodes were taken from surgery samples of cases pathologically diagnosed DLBCL (diffuse large B-cell lymphoma), PTL (peripheral T cell lymphoma) and reactive lymph nodes. The pure endothelium cells were isolated by LCM after immunohistochemical staining of CD34. We found Tim-3 was preferentially expressed on lymphoma-derived ECs via different expression profiles between lymphoma ECs and reactive lymph node-derived ECs. Intensive researches were carried out on Tim-3-expressing -ECs and we found that Tim-3 -expressing-Ecs may play important role on EC-mediated tumor evasion.
Project description:In this study, we present the first comparison of global transcriptional changes taking place in canine lymphoma and human diffuse large B-cell lymphoma (DLBCL), with particular reference to the nuclear factor-kappaB (NF-κB) pathway. Microarray data generated from lymph nodes diagnosed with canine DLBCL and healthy lymph nodes were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa. A considerable number of differentially expressed genes between canine lymphoma and healthy lymph node samples were also found differentially expressed between human DLBCL and healthy lymph node samples. Principal component analysis (PCA) using a literature derived 120 NF-κB target gene set mapped to 199 orthologous canine array probesets and 259 human array probesets clearly separated the healthy and cancer samples in both canine and human datasets. The analysis demonstrated that for both human and canine DLBCL there is activation of the NF-κB/p65 canonical pathway rather than the alternative pathway. This has therapeutic implications for the use of specific pathway inhibitors for the treatment of DLBCL for both species and also indicates that naturally occurring canine lymphoma could be used as a model to study therapeutic strategies for human lymphoma. The model was further validated by the identification of molecular signatures that could sub-classify canine DLBCL into activated B-cell-like (ABC) or germinal centre B-cell-like (GCB) types equivalent to human subtypes.
Project description:to screen and identify differentially expressed microRNAs (miRNAs) between diffuse large B-cell lymphoma (DLBCL) and control (lymph node reactive hyperplasia, LRH) groups, investigate whether miRNAs associated with DLBCL and could serve as potential therapeutic targets.
Project description:Gene expression profiling of biopsied human lymph node (LN) tissue comparing each patient sample against mobilised peripheral blood stem cells (PBSC), the reference channel Evaluate whether gene expression microarray can diagnose lymph node biopsies as reactive or as one of three main types of lymphoma: classical Hodgkin’s lymphoma (cHL), diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL).
Project description:In this study, we present the first comparison of global transcriptional changes taking place in canine lymphoma and human diffuse large B-cell lymphoma (DLBCL), with particular reference to the nuclear factor-kappaB (NF-?B) pathway. Microarray data generated from lymph nodes diagnosed with canine DLBCL and healthy lymph nodes were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa. A considerable number of differentially expressed genes between canine lymphoma and healthy lymph node samples were also found differentially expressed between human DLBCL and healthy lymph node samples. Principal component analysis (PCA) using a literature derived 120 NF-?B target gene set mapped to 199 orthologous canine array probesets and 259 human array probesets clearly separated the healthy and cancer samples in both canine and human datasets. The analysis demonstrated that for both human and canine DLBCL there is activation of the NF-?B/p65 canonical pathway rather than the alternative pathway. This has therapeutic implications for the use of specific pathway inhibitors for the treatment of DLBCL for both species and also indicates that naturally occurring canine lymphoma could be used as a model to study therapeutic strategies for human lymphoma. The model was further validated by the identification of molecular signatures that could sub-classify canine DLBCL into activated B-cell-like (ABC) or germinal centre B-cell-like (GCB) types equivalent to human subtypes. Canine DLBCL patients were recruited via the clinical oncology service of the University of Edinburgh Royal (Dick) School of Veterinary Studies (DJA), and the University of Wisconsin-Madison School of Veterinary Medicine (DMV). Lymph node biopsy samples were taken, as part of normal diagnostic procedures, from dogs newly diagnosed with lymphoma (naïve) and samples from dogs that had relapsed following standard of care CHOP chemotherapy. Only dogs with confirmed DLBCL after pathological grading were used in this study. This included standard histopathological grading by two independent pathologists and CD3/PAX5 marker analysis. Normal lymph node samples were obtained from canines that were euthanized for non-lymphoma conditions. Microarray data were generated from 35 canine samples (25 DLBCL and 10 healthy) in total. However, data from 2 canine DLBCL samples did not meet our required quality and were removed from further analysis. Only data from 33 (23 DLBCL and 10 healthy) samples were used for analysis. The generated data were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data (GSE12195) from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa.
Project description:To understand the biological function of GSTT1 deletion in diffuse large B cell lymphoma (DLBCL), we identified genes that are expressed differently in lymph node tissues from DLBCL patients collected at diagnosis with GSTT1 deletion (4 cases) compared to those without GSTT1 deletion (4 cases).
Project description:Gene expression profiling of biopsied human lymph node (LN) tissue comparing each patient sample against mobilised peripheral blood stem cells (PBSC), the reference channel Evaluate whether gene expression microarray can diagnose lymph node biopsies as reactive or as one of three main types of lymphoma: classical Hodgkin’s lymphoma (cHL), diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL). Two condition experiment, LN vs mobilised PBSC, 116 cases assayed, 1 replicate per array
Project description:Follicular lymphoma (FL) is one of the most common types of indolent B-cell lymphoma in Western countries. FL commonly transforms to more aggressive diffuse large B-cell lymphoma (DLBCL) at reported frequencies between 15 - 60%. We have used microarray comparative genomic hybridisation (aCGH) at 1 Mb resolution to study copy number changes in paired tumor samples (primary FL and a subsequent tDLBCL) as well as de novo DLBCL cases to outline genetic mechanisms of transformation from follicular lymphoma to diffuse large B-cell lymphoma.
Project description:Follicular lymphoma (FL) is one of the most common types of indolent B-cell lymphoma in Western countries. FL commonly transforms to more aggressive diffuse large B-cell lymphoma (DLBCL) at reported frequencies between 15 - 60%. We have used microarray comparative genomic hybridisation (aCGH) at 1 Mb resolution to study copy number changes in paired tumor samples (primary FL and a subsequent tDLBCL) as well as de novo DLBCL cases to outline genetic mechanisms of transformation from follicular lymphoma to diffuse large B-cell lymphoma. Single hybridization per case. 21 FL, 31 transformed DLBCL, 29 de novo DLBCL (10 GC and 19 non-GC DLBCL). Tumor labelled with Cy5 and reference with Cy3. Mixture of 20 normal male or female genomic DNA was used in sex-mismatched hybridization.