Biomedical subjects

Daisuke Matsubara

Publications and source records attributed to Daisuke Matsubara.

5 recordsLinked to original sources

PubMed2006

Decrease in Epstein-Barr virus-positive AIDS-related lymphoma in the era of highly active antiretroviral therapy.

Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced the incidence of lymphoma among HIV-infected individuals. A clinicopathological study was performed on 86 AIDS-related lymphoma patients who were treated in Tokyo area from 1987 to 2005. The incidence of lymphoma detected by autopsy was 27% (53 cases/198 autopsies). Diffuse large B cell lymphoma was the most predominant histological subtype throughout the period (78%). Burkitt's lymphoma (BL) increased from 2% in the pre-HAART era (before end-1997) to 13% in the HAART era, whereas incidence of BL did not vary between HAART users and non-users. Epstein-Barr virus (EBV)-positive lymphoma decreased from 88% in the pre-HAART era to 58% in the HAART era, but did not differ significantly between HAART users (73%) and non-users (74%). Nodal involvement of lymphoma increased from 14% in the pre-HAART era to 50% in the HAART era; however, central nervous system involvement decreased from 62 to 38%. Kaposi's sarcoma-associated herpesvirus infection was rare (4%) among all cases. These data suggest that HAART might play a partial role in these changes, and the alteration in immunological backgrounds, such as EBV prevalence, is suggested as another leading cause of these changes in Japanese AIDS-related lymphoma.

Adolescent↗

PubMed2006

Distinct expression of Kaposi's sarcoma-associated herpesvirus-encoded proteins in Kaposi's sarcoma and multicentric Castleman's disease.

The expression of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)-encoded proteins is herein demonstrated in Kaposi's sarcoma (KS) and multicentric Castleman's disease (MCD) in a single lymph node derived from a patient with acquired immunodeficiency syndrome. Immunohistochemistry revealed that both lytic and latent KSHV proteins were expressed in cells of the MCD lesion. KSHV-encoded viral interleukin-6 was also detected in follicular dendritic cells of the germinal center. Cytoplasmic localization of open reading frame 59 protein and latency-associated nuclear antigen suggested KSHV activation in the MCD lesion. Moreover, a high copy number of KSHV was detected in the blood. Clinically, pegylated-liposomal doxorubicin induced regression of not only KS, but also lymphadenopathy of the MCD lesion with a decrease in KSHV load and human interleukin-6 in the blood. To the best of the authors' knowledge this is the first case demonstrating differential expression of virus proteins in two KSHV-associated diseases, KS and MCD, in the same section. The case confirms lytic KSHV infection in MCD, and suggests that clinical symptoms of MCD might be closely linked with KSHV activation.

Adult↗

PubMed2005

Loss of TSLC1 expression in lung adenocarcinoma: relationships with histological subtypes, sex and prognostic significance.

The TSLC1 (tumor suppressor in lung cancer 1) gene is a tumor suppressor recently identified through functional complementation in a lung adenocarcinoma cell line A549. In this study we immunohistochemically examined the loss of TSLC1 expression in 93 cases of surgically resected lung adenocarcinoma, and investigated its correlation with clinicopathological parameters, including histological subtypes of tumors. The prognostic significance of loss of TSLC1 expression was analyzed by univariate and multivariate analyses, in parallel with other prognostic markers such as p53, p27, and Ki-67. In non-cancerous lung tissue, TSLC1 was weakly positive in bronchial and bronchiolar epithelial cells, type II pneumocytes and bronchial glands. Overall, TSLC1 was negative in 60 of 93 lung adenocarcinomas. TSLC1 was mainly localized in the cytoplasm of the cells, but cell membrane staining was also observed, especially at sites of cell-cell adhesion. TSLC1-negative tumors were more frequently observed in male cases (41/54 cases, 70.0%) than in female cases (19/39 cases, 48.7%) (P < 0.01). Notably, TSLC1 expression was preserved in a non-invasive, bronchiolo-alveolar histological pattern of tumor cells (P < 0.0001). Survival analyses showed that loss of TSLC1 expression was associated with lower patient survival in univariate and multivariate analyses (P < 0.05 and P = 0.059, respectively). Subset analyses further showed that the prognostic impact of loss of TSLC1 was significant for male patients (P = 0.0089), but not for female patients. We conclude that TSLC1 is expressed in a subset of lung adenocarcinomas, especially in those with bronchiolo-alveolar spread pattern. Loss of TSLC1 is associated with lower patient survival, supporting its role as a tumor suppressor.

Adenocarcinoma↗

PubMed2005

Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathological significance, relationship to p53 and identification of their target genes.

Previous studies suggest that some S100 proteins are involved in the progression of certain types of cancer. However, no comprehensive data is currently available on the expression of S100 family genes in lung adenocarcinomas. Oligonucleotide array, quantitative reverse transcription-polymerase chain reaction and western blot analyses of lung adenocarcinoma cell lines and bronchiolar epithelial cells (SAEC and NHBE) revealed that S100A2 and S100A4 were the most strikingly downregulated and upregulated members of the S100 family, respectively. Immunohistochemical analyses of 94 primary lung adenocarcinomas showed that positive S100A2 expression (33/94, 35.1%) was significantly associated with lymphatic invasion (P=0.0233) and positive S100A4 expression (19/94, 20.2%) with vascular invasion (P=0.0454). Interestingly, a strong inverse relationship was found between S100A4 and p53 expression (P=0.0008). Survival analyses showed that S100A4 positivity was associated with poor patient prognosis (P=0.042). S100A2 positivity was not associated with patient survival when the whole patient group was analyzed; however, S100A2 positivity was a favorable prognostic indicator in patients with p53-negative tumors (P=0.0448). Finally, we used oligonucleotide array analyses and identified potential S100A2 and S100A4 target genes involved in cancer progression: S100A2 induced RUNX3 and REPRIMO; S100A4 induced EZRIN, RUNX1 and WISP1; S100A2 repressed EGFR, NFKB2 and RELA2; and S100A4 repressed ANXA10 and IL1RN. Thus, the present study demonstrates involvement of S100A2 and S100A4 in the progression of lung adenocarcinomas and an inverse association between S100A4 and p53 expression, and provides a list of targets regulated by S100A2 and S100A4.

Adenocarcinoma↗

PubMed2002

Glucose-6-phosphate dehydrogenase in rat hepatic stellate cells: an ultrastructural enzyme-cytochemical study.

Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism. This enzyme plays an important role in various cell functions, including cell proliferation, lipid/retinol metabolism, etc. Although marked cell proliferation and retinol metabolism take place in hepatic stellate cells (HSCs), it has not been determined whether cytochemically detectable G6PD is present in HSCs. The distribution pattern of G6PD within these cells, if it is present, is also unknown. The purpose of this study was to investigate the subcellular localization of G6PD in rat HSCs using a newly developed enzyme-cytochemistry (copper-ferrocyanide) method. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of HSCs. The cytochemical controls ensured specific detection of the enzyme activity. HSCs possessed enzyme-cytochemically detectable G6PD activity. This enzyme may play a role in normal liver biology and liver disease pathophysiology, by supplying HSCs with NADPH and ribose-5-phosphate as a substance/substrate/co-factor for cell proliferation, oxidoreductase enzymes, and retinol metabolism, respectively.

Journal Article↗