Papers by Daisuke Matsubara
Hepatology Research, 2002
Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway in ca... more 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/cofactor for cell proliferation, oxidoreductase enzymes, and retinol metabolism, respectively.
This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmer... more This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Cancer science, Jan 15, 2016
YAP1, the main hippo pathway effector, is a potent oncogene and is overexpressed in non-small-cel... more YAP1, the main hippo pathway effector, is a potent oncogene and is overexpressed in non-small-cell lung cancer (NSCLC); however, the YAP1 expression pattern in small-cell lung cancer (SCLC) has not yet been elucidated in detail. We herein demonstrated that the loss of YAP1 is a special feature of high-grade neuroendocrine lung tumors. A hierarchical cluster analysis of 15 high-grade neuroendocrine tumor cell lines containing 14 SCLC cell lines that depended on the genes of hippo pathway molecules and neuroendocrine markers clearly classified these lines into two groups: the YAP1-negative and neuroendocrine marker-positive group (n=11), and YAP1-positive and neuroendocrine marker-negative group (n=4). Among the 41 NSCLC cell lines examined, the loss of YAP1 was only observed in one cell line showing the strong expression of neuroendocrine markers. Immunostaining for YAP1, using the sections of 189 NSCLC, 41 SCLC and 30 large cell neuroendocrine carcinoma (LCNEC) cases, revealed that ...
Journal of Digestive Diseases, Aug 1, 2012
OBJECTIVE: Adenosquamous carcinoma originating in the stomach is an unusual neoplasm with few exi... more OBJECTIVE: Adenosquamous carcinoma originating in the stomach is an unusual neoplasm with few existing histological studies. This study was aimed to gain insight into the histogenetic and clinicopathological characteristics of gastric cancer with squamous cell carcinoma (SCC) components.METHODS: From January 2001 to June 2010 a total of 1735 patients underwent a resection of gastric cancer. Histopathologically, eight patients had adenocarcinoma containing SCC components, in which the proportion of SCC components was above 25% of the total tumor mass in four patients. The immunohistochemical and clinicopathological characteristics of these eight patients were analyzed.RESULTS: The median survival duration was 22 months. Adenocarcinoma was present at the superficial layer of all tumors and SCC was primarily present at sites with deep invasion. Immunohistochemically, adenocarcinoma components were positive for cytokeratin (CK) 8/18/19 and CK7 in all cases. SCC components were positive for carcinoembryonic antigen and CK7 in more than 60% of patients. Expression patterns of p53 product were identical in both components. SCC components were positive for 34βE12 and adenocarcinoma components were negative for 34βE12 in all patients.CONCLUSIONS: SCC components are derived from squamous metaplasia in a pre-existing adenocarcinoma. A gastric adenocarcinoma with SCC components is associated with various patterns of metastasis and both SCC and adenocarcinoma components have the potential for metastasis. Gastric cancer with SCC components is a clinically aggressive tumor.© 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.
Journal of Allergy and Clinical Immunology, 2016
Pathology international, Jan 8, 2015
The switch/sucrose non-fermenting (SWI/SNF) complex has recently emerged as a novel tumor suppres... more The switch/sucrose non-fermenting (SWI/SNF) complex has recently emerged as a novel tumor suppressor in various human cancers. In the present study, we analyzed the expression of multiple SWI/SNF subunits in primary non-small cell lung cancer (NSCLC). A total of 133 NSCLC, consisting of 25 squamous cell carcinomas (SCC), 70 adenocarcinomas (AD), 16 large cell carcinomas (LC), and 22 pleomorphic carcinomas (PL), were immunohistochemically examined for the expression of BRG1, BRM, BAF47, ARID1A, and ARID1B. The frequency at which reductions in the expression of BRG1 were observed was significantly higher in the LC-PL group (13/38, 34.2%) than in the SCC-AD group (7/95, 7.4%). Similarly, the frequency at which reductions in the expression of BRM were observed was significantly higher in the LC-PL group (17/38, 44.7%) than in the SCC-AD group (14/95, 14.7%). The loss of the expression of ARID1A, ARID1B, and BAF47 was observed only in a fraction of NSCLC cases. Furthermore, the frequency...
BMC Cancer, 2015
Background: Although advanced esophageal squamous-cell carcinoma (ESCC) is treated using a multid... more Background: Although advanced esophageal squamous-cell carcinoma (ESCC) is treated using a multidisciplinary approach, outcomes remain unsatisfactory. The microenvironment of cancer cells has recently been shown to strongly influence the biologic properties of malignancies. We explored the effect of supernatant from esophageal fibroblasts on the cell growth and chemo-resistance of ESCC cell lines.
Pathology international, 2014
We performed an immunohistochemical analysis of the expression of zinc-finger E-box binding homeo... more We performed an immunohistochemical analysis of the expression of zinc-finger E-box binding homeobox 1 (ZEB1), a master regulator of epithelial-mesenchymal transition (EMT), and determined its relationship with E-cadherin in 157 non-small cell lung carcinomas (93 adenocarcinomas, 36 squamous cell carcinomas, 18 large cell carcinomas, and 10 pleomorphic carcinomas). Although the expression of E-cadherin was low in the subset of adenocarcinomas (10%) and squamous cell carcinomas (11%), ZEB1 expression was only observed in one case of squamous cell carcinoma and none of the adenocarcinomas. In contrast, the low expression of E-cadherin (50% and 90%, respectively) and the positive expression of ZEB1 (11% and 50%, respectively) were more frequently observed in poorly differentiated carcinomas (large cell carcinomas and pleomorphic carcinomas). Overall, the expression of ZEB1 was inversely correlated with that of E-cadherin. Furthermore, the distribution of ZEB1-positive cancer cells was ...
Oncology reports, 2014
The growth, invasiveness and metastasis of human cancers are determined not only by cancer cells,... more The growth, invasiveness and metastasis of human cancers are determined not only by cancer cells, but also by their microenvironment. Activated stromal fibroblasts promote tumor progression by secreting growth factors. In the present study, we focused on interrelations between cancer and fibroblasts, the main component of tumor stroma. We retrospectively analyzed the relations of mortality to clinical, pathological, and α-smooth muscle actin (α-SMA) characteristics in 97 consecutive patients with esophageal squamous cell carcinoma (ESCC). In vitro, we used TE-11, KYSE150 and KYSE220 ESCC cell lines and isolated esophageal stromal fibroblasts, some of which were immortalized. Migration assays were conducted to assess the effects of fibroblasts on cancer-cell migration and 3-dimensional organotypic cultures. In vivo, TE-11 and KYSE220 cells plus immortalized fibroblasts were co-transplanted subcutaneously in Nod/Scid mice to assess the effects of fibroblasts on tumorigenicity. Clinico...
Diagnostic pathology, 2012
Glomerular crescents are most commonly associated with rapidly progressive crescentic glomerulone... more Glomerular crescents are most commonly associated with rapidly progressive crescentic glomerulonephritis; however, they also develop in response to a wide range of primary and secondary glomerular injuries. Since various kind of glomerulopathies occasionally overlay diabetic glomerular injuries, the presence of crescents in renal biopsy specimens of diabetics may have stimulated a search for etiologies other than diabetes. In this report, we describe an unusual case of diabetic glomerulosclerosis with peculiar extracapillary proliferation. Although such a relationship has so far been ignored in most of the literature, the etiological linkage between diabetic glomerulosclerosis and the development of crescents may not be exceptional. We have reviewed the previous literature and herein discuss the pathological implications of the development of crescents in patients with diabetic glomerulosclerosis. The virtual slide(s) for this article can be found here: http://www.diagnosticpatholog...
Pediatrics international : official journal of the Japan Pediatric Society, 2011
Esophagus, 2009
Abstract We reviewed the clinicopathological characteristics of 14 patients who underwent resecti... more Abstract We reviewed the clinicopathological characteristics of 14 patients who underwent resection of basaloid squamous carcinoma (BSC) of the esophagus. The mean age was 65.3 years, and all patients were male. Seven patients had superficial BSCs and 7 had ...
Respirology, 2007
Low dose weekly administration of methotrexate has been thought to be effective for both rheumato... more Low dose weekly administration of methotrexate has been thought to be effective for both rheumatoid arthritis (RA) and psoriasis. However, there is a possibility that methotrexate therapy may be oncogenic. This report presents a case of pulmonary lymphoma developed during long-term methotrexate therapy for psoriasis. Physicians should be aware that Epstein-Barr virus-associated lymphoproliferative disorders that occur during treatment with methotrexate are not specific to patients with RA.
Pathology International, 2006
load and human interleukin-6 in the blood. To the best of the authors' knowledge this is the firs... more 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 KSHVassociated 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.
Pathology International, 2010
In this study we explored the distribution of nestin-positive cells in extraneural human tissues ... more In this study we explored the distribution of nestin-positive cells in extraneural human tissues with special reference to stromal myofibroblasts. Tissue microarrays were constructed from various tissues with normal histology and tissues with fibrosing disorders. Sections were immunostained for nestin, alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, CD34, and other stromal markers. Nestin was expressed in the myoepithelium of the breast, podocytes of the renal glomerulus, and endothelial cells of most organs. Nestin was also expressed in the stroma of several organs, including the intestine, uterine cervix, and endometrium. Nestin-positive fibroblast-like cells appeared in the stroma of the kidney, pancreas, lung, and skin in fibrosing conditions. With the notable exception of endometrial stromal cells, most of these nestin-positive stromal cells were alpha-SMA-positive. Interestingly, we observed a concomitant appearance of nestin- and CD34-positive myofibroblasts under fibrosing conditions. Further investigation showed that nestin was expressed by stromal fibroblasts in cervical squamous cell carcinoma, but not in lung adenocarcinoma, pointing to heterogeneity of cancer stroma. In conclusion, nestin was expressed in variable proportions of stromal myofibroblasts in human tissues. The differential expression of nestin may indicate phenotypic and functional heterogeneity. Nestin-positive myofibroblast may represent a relatively immature subpopulation of cells with multipotentiality.
Modern Pathology, 2009
We report here the presence of subepithelial myofibroblasts in pure bronchioloalveolar carcinoma ... more We report here the presence of subepithelial myofibroblasts in pure bronchioloalveolar carcinoma and a subset of invasive lung adenocarcinoma. The subepithelial myofibroblasts we describe were observed in a peculiar location beneath the cancer cells in the alveolar septa. Immunohistochemically, they were positive for a-smooth muscle actin and calponin, but negative for desmin and h-caldesmon. To gain insight into their biological significance, we examined 116 surgically resected lung adenocarcinomas. The resected tumors included 13 bronchioloalveolar carcinomas, 20 mixed type adenocarcinomas with bronchioloalveolar carcinoma components, 57 papillary adenocarcinomas, 22 solid adenocarcinomas with mucin, and 4 acinar adenocarcinomas. All specimens were immunostained for a-smooth muscle actin to visualize the myofibroblasts. In all of the pure bronchioloalveolar carcinomas observed, the subepithelial myofibroblasts were completely preserved adjacent to the cancer cells. In mixed adenocarcinomas with bronchioloalveolar carcinoma components, subepithelial myofibroblasts were present in the bronchioloalveolar carcinoma components, but scanty in the invasive areas, where stromal myofibroblasts emerged between the cancer cell nests. Subepithelial myofibroblasts were retained, however, in the invasive areas of a subset of invasive adenocarcinomas. Survival analysis showed that the retention of subepithelial myofibroblasts in these invasive tumors was associated with low rates of lymphatic and vascular invasion, a low rate of lymph node involvement, and an excellent patient survival. These results suggest that subepithelial myofibroblasts increase in bronchioloalveolar carcinomas, but are gradually replaced by typical stromal myofibroblasts during progression into invasive cancer. A subset of invasive adenocarcinomas retains subepithelial myofibroblasts. Analysis of subepithelial myofibroblasts may be helpful in identifying a subset of lung adenocarcinoma with excellent prognosis.
Microbes and Infection, 2006
Recent introduction of highly active antiretroviral therapy (HAART) is reported to have reduced t... more 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.
Journal of Thoracic Oncology, 2010
No comprehensive data are available on the molecular predictors of sensitivity to MET inhibitor i... more No comprehensive data are available on the molecular predictors of sensitivity to MET inhibitor in lung carcinomas. We examined the efficacy of the MET inhibitor PHA665752 in 41 cell lines of non-small lung carcinoma to determine whether sensitivity to the MET inhibitor is correlated with the (1) genetic statuses of MET, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, and KRAS, (2) MET phosphorylation and its downstream signaling pathways, or (3) epithelial-mesenchymal transition. Of the 41 cells, 8 were highly or intermediately sensitive to PHA665752, and the remainder were PHA665752 resistant. The sensitive cells (n = 8) included not only 4 of 4 MET-amplified cell lines but also 2 of 11 KRAS-mutated cell lines and 1 of 6 EGFR-mutated cell lines. Unlike the MET-amplified cell lines, both the MET-mutated cell lines were PHA665752 resistant. High phospho-MET was not restricted to the four MET-amplified cell lines. To the contrary, it was also found in 9 of 37 MET-nonamplified cell lines, including 3 of 6 EGFR-mutated cell lines and 4 of 11 KRAS-mutated cell lines. High phospho-MET was correlated with PHA665752 sensitivity in the entire panel of cell lines, especially in the KRAS-mutated cells. The AKT and ERK pathways in the high phospho-MET cell lines were dependent on MET activation in MET-amplified and KRAS-mutated cells but not in EGFR-mutated and human epidermal growth factor receptor 2-amplified cells. MET amplification is an excellent predictor of PHA665752 sensitivity but not the sole predictor. High phospho-MET and dependence of the AKT and ERK pathways on MET activation may predict sensitivity to PHA665752, especially in KRAS-mutated cell lines.
Journal of Thoracic Oncology, 2007
Materials and Methods: A total of 75 cases of surgically resected lung adenocarcinomas were exami... more Materials and Methods: A total of 75 cases of surgically resected lung adenocarcinomas were examined. There were 9 cases of BAC, 14 cases of mixed type adeno-carcinoma with a BAC component, and 52 cases of pure invasive adenocarcinomas. All cases were ...
Journal of Thoracic Oncology, 2012
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Papers by Daisuke Matsubara