A novel podocyte protein, R3h domain containing-like, inhibits TGF-β-induced p38 MAPK and regulates the structure of podocytes and glomerular basement membrane.

Not only in kidney glomerular physiological function but also glomerular pathology especially in diabetic condition, glomerular podocytes play pivotal roles. Therefore, it is important to increase our knowledge about the genes and proteins expressed in podocytes. Recently, we have identified a novel podocyte-expressed gene, R3h domain containing-like (R3hdml) and analyzed its function in vivo as well as in vitro.

Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy.

IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN.

STX11 functions as a novel tumor suppressor gene in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Their molecular pathogenesis has not been entirely elucidated. We previously showed that 6q24 is one of the most frequently deleted regions in primary thyroid T-cell lymphoma.

Molecular characterization of chronic-type adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type-1-induced neoplasm with four clinical subtypes: acute, lymphoma, chronic, and smoldering. Although the chronic type is regarded as indolent ATL, about half of the cases progress to acute-type ATL. The molecular pathogenesis of acute transformation in chronic-type ATL is only partially understood.

Clonal heterogeneity of lymphoid malignancies correlates with poor prognosis.

Clonal heterogeneity in lymphoid malignancies has been recently reported in adult T-cell lymphoma/leukemia, peripheral T-cell lymphoma, not otherwise specified, and mantle cell lymphoma. Our analysis was extended to other types of lymphoma including marginal zone lymphoma, follicular lymphoma and diffuse large B-cell lymphoma. To determine the presence of clonal heterogeneity, 332 cases were examined using array comparative genomic hybridization analysis.

SegAnnDB: interactive Web-based genomic segmentation.

Motivation: DNA copy number profiles characterize regions of chromosome gains, losses and breakpoints in tumor genomes. Although many models have been proposed to detect these alterations, it is not clear which model is appropriate before visual inspection the signal, noise and models for a particular profile.

Results: We propose SegAnnDB, a Web-based computer vision system for genomic segmentation: first, visually inspect the profiles and manually annotate altered regions, then SegAnnDB determines the precise alteration locations using a mathematical model of the data and annotations.

Clonal heterogeneity of mantle cell lymphoma revealed by array comparative genomic hybridization.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t(11;14)(q13;q32). This lymphoma exhibits a poor prognosis and remains incurable with standard chemotherapy approaches. Recently, we have shown that a majority of patients with acute-type adult T-cell leukemia/lymphoma (ATLL) have multiple subclones that were likely produced in lymph nodes.

Gene expression profiling of diffuse large B-cell lymphoma supervised by CD21 expression.

This study investigated the gene expression profiles of 40 cases of diffuse large B-cell lymphoma (DLBCL) according to CD21 expression, a favourable prognostic factor in DLBCL. Signature genes were analysed by Gene Ontology Tree Machine, and genes concerned with the immune system and related categories were significantly upregulated in CD21- DLBCLs. Of 40 DLBCLs, four were germinal centre B cell-like (GCB) and 36 non-GCB.

Expression profiling analysis of the CD5+ diffuse large B-cell lymphoma subgroup: development of a CD5 signature.

Diffuse large B-cell lymphoma (DLBCL) accounts for 30% of non-Hodgkin's lymphomas and is known to comprise heterogeneous groups. We previously reported that CD5+ DLBCL is a clinically distinct subgroup of these tumors that is associated with poor prognosis. In our current study, we have used gene expression profiling technology in an attempt to identify new markers and to further characterize the biological features of CD5+ DLBCL.

Selection of causal gene sets for lymphoma prognostication from expression profiling and construction of prognostic fuzzy neural network models.

To assess the response of lymphomas to chemotherapy, gene expression profiling data from DNA microarrays were analyzed using the fuzzy neural network (FNN) modeling method. We used the FNN modeling method to produce 10 noninferior models. Using these models, we were able to predict diffuse large B-cell lymphoma (DLBCL) patient outcome with 93% accuracy.

Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) comprises molecularly distinct subgroups such as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) DLBCLs. We previously reported that CD5(+) and CD5(-)CD10(+) DLBCL constitute clinically relevant subgroups. To determine whether these 2 subgroups are related to ABC and GCB DLBCLs, we analyzed the genomic imbalance of 99 cases (36 CD5(+), 19 CD5(-)CD10(+), and 44 CD5(-)CD10(-)) using array-based comparative genomic hybridization (CGH).

Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma.

Deletions of the 3p arm have been detected in various solid tumors, but no study to date has investigated this deletion in diffuse large B-cell lymphoma (DLBCL). Recently, we demonstrated that 3p14.2 was deleted in approximately 30% of DLBCL cases by use of a genome-wide array-comparative genomic hybridization (CGH).

Genome-wide array-based comparative genomic hybridization of diffuse large B-cell lymphoma: comparison between CD5-positive and CD5-negative cases.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma and exhibits aggressive and heterogeneous clinical behavior. To genetically characterize DLBCL, we established our own array-based comparative genomic hybridization and analyzed a total of 70 cases [26 CD-positive (CD5+) DLBCL and 44 CD5-negative (CD5-) DLBCL cases]. Regions of genomic aberrations observed in >20% of cases of both the CD5+ and CD5- groups were gains of 1q21-q31, 1q32, 3p25-q29, 5p13, 6p21-p25, 7p22-q31, 8q24, 11q23-q24, 12q13-q21, 16p13, 18, and X and losses of 1p36, 3p14, 6q14-q25, 6q27, 9p21, and 17p11-p13.

Analysis of chromosomal imbalances in de novo CD5-positive diffuse large-B-cell lymphoma detected by comparative genomic hybridization.

We recently demonstrated that the prognosis for de novo CD5-positive (CD5+) diffuse large-B-cell lymphoma (DLBCL) is markedly worse than that for CD5-negative (CD5-) DLBCL. Our findings also suggested that on the basis of its clinical features CD5+ DLBCL may constitute a unique disease category. However, the genetic basis for these two categories has not been established.

Multiple fuzzy neural network system for outcome prediction and classification of 220 lymphoma patients on the basis of molecular profiling.

A fuzzy neural network (FNN) using gene expression profile data can select combinations of genes from thousands of genes, and is applicable to predict outcome for cancer patients after chemotherapy. However, wide clinical heterogeneity reduces the accuracy of prediction. To overcome this problem, we have proposed an FNN system based on majoritarian decision using multiple noninferior models.

Fuzzy neural network applied to gene expression profiling for predicting the prognosis of diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the largest category of aggressive lymphomas. Less than 50% of patients can be cured by combination chemotherapy. Microarray technologies have recently shown that the response to chemotherapy reflects the molecular heterogeneity in DLBCL.

Prognostic factors in elderly patients with acute myelogenous leukemia: a single center study in Japan.

We retrospectively analyzed data of 47 patients aged 60 years or older, hospitalized in our institution with the diagnosis of acute myelogenous leukemia (AML), and searched for prognostic factors. Induction with anthracyclines significantly correlated with better complete remission (CR) rate (P = 0.0016) and overall survival (OS) (P < 0.