Biomedical subjects

Masaichi Ohira

Publications and source records attributed to Masaichi Ohira.

12 recordsLinked to original sources

PubMed2002

Very low incidence of microsatellite instability in intraductal papillary-mucinous neoplasm of the pancreas.

Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas, a new entity of pancreatic cancer with a favorable prognosis, has shown a gradual increase in the number of reported cases. Patients with high-frequency microsatellite instability (MSI-H) tumors have been shown to survive longer than those with low-frequency MSI (MSI-L) or microsatellite stable (MSS) tumors in colorectal and gastric cancer. We investigated whether MSI-H in patients with IPMC can contribute to a good prognosis. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from 10 patients with IPMCs and 16 with intraductal papillary-mucinous adenomas (IPMAs) were provided for DNA extraction after microdissection. Polymerase chain reaction (PCR) was carried out using 8 microsatellite primer marker sets. The mixed PCR samples were analyzed using a genetic analyzer. MSI-H was determined by assessment of microsatellite variations in 3 or more of the 8 tested markers. Immunohistochemical staining of the MSI-responsible proteins hMLH1 and hMSH2 was conducted for both the IPMC and IPMA samples. Ten percent of IPMC harbored MSI-H tumors, whereas no MSI-H tumors were detected in the IPMAs. Thirty percent of IPMC tumors and 25% of IPMA tumors showed MSI-L. All IPMCs and IPMAs showed normal expression of both hMLH1 and hMSH2. MSI-H and loss of hMLH1 and hMSH2 are very rare events in both IPMCs and IPMAs. We conclude that a good prognosis for patients with IPMC is not associated with MSI-H.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Inhibitory effect of a selective cyclooxygenase-2 inhibitor on liver metastasis of colon cancer.

COX-2 overexpression is recognized in various cancers, but the role of COX-2 in the progression of cancer, including the liver metastasis of colon cancer, is not clearly understood. We examined the role of COX-2 in the mechanism of liver metastasis of colon cancer, using a highly metastasizable colon carcinoma cell line, LM-H3. A COX-2 inhibitor, JTE-522, inhibited cell proliferation and invasion of LM-H3 in vitro and clearly reduced the number of metastatic nodules on the surface of nude mouse livers in vivo. We also examined the effects of JTE-522 on the production of growth factors and MMPs through the use of ELISA and gelatin zymography, respectively. JTE-522 downregulated PDGF production by LM-H3 but had no influence on VEGF production. JTE-522 also inhibited MMP-2 secretion by LM-H3. JTE-522 downregulated PGE(2) production, but the associated changes in PGE(2) did not affect PDGF and VEGF production by LM-H3. We conclude that JTE-522 downregulated the cell proliferation and invasive potential of LM-H3 by reducing the production of PDGF and MMP-2 and hypothesize that these inhibitory effects on the production of PDGF and MMP-2 can lead to inhibition of liver metastasis of colon cancer. These data indicate that the COX-2 inhibitor JTE-522 has a high potential for use as a clinical agent for the treatment of liver metastasis of colon cancer.

Animals↗

PubMed2002

Lymphangioma of the lesser omentum associated with abdominal esophageal carcinoma: report of a case.

A case of lymphangioma of the lesser omentum associated with abdominal esophageal carcinoma is described herein. The patient was a 54-year-old man who initially presented with dysphagia. Gastrointestinal fiberscopy (GIF) revealed an esophageal carcinoma and abdominal computed tomography (CT) detected a 3-cm, low-density lesion on the median aspect of the fornix, which was diagnosed as a metastatic lymph node. A radical operation was performed to resect the esophageal carcinoma, and a cystic lesion the size of a hen's egg was found in the lesser omentum of the stomach. The cystic lesion, which contained serous fluid, was unilocular and attached to the serosa of the stomach. The histological diagnosis was omental lymphangioma. Our review of the Japanese literature revealed 29 cases of lesser omental lymphangioma, but only two of these were associated with an advanced malignant tumor. Although the etiology of omental lymphangioma is unclear, the findings in our case suggested that obstruction of the lymphatic vessels invaded by the esophageal carcinoma may be one of the causes of this disease.

Carcinoma, Squamous Cell↗

PubMed2002

Primary leiomyosarcoma of the breast: report of a case.

We describe herein a case of primary leiomyosarcoma of the breast in a 59-year-old woman. Preoperative clinical examination and cytology findings indicated a benign breast tumor, but intraoperative histopathological examination of the tumor revealed malignant spindle cells, and a modified radical mastectomy was performed. Immunohistochemical analysis subsequently confirmed a diagnosis of leiomyosarcoma. Primary leiomyosarcoma of the breast is extremely rare and difficult to diagnose before surgery because of the need for mitotic figures and immunohistochemical staining to confirm the diagnosis. When pre- and intraoperative examinations indicate the possibility of a leiomyosarcoma, an extended excision with sufficient margins should be performed to remove all of the affected tissue. A review of the literature on this unusual tumor of the breast is presented.

Breast Neoplasms↗

PubMed2002

[Chemoradiation therapy for esophageal cancer].

The current status and future prospects of chemoradiation therapy (CRT) for esophageal cancer are reviewed herein. In Western countries, CRT is performed for every stage of esophageal cancer and it has been reported that in definitive CRT series the complete response rate is 30 to 50%, the mean survival rate more than twelve months, and the in 2-year survival rate about 30%, while in neoadjuvant CRT series the pathological response rate is 20 to 50%, the mean survival period more than twenty months, and the 3-year survival 30 to 40%. On the other hand, as esophageal cancer is treated mainly by surgery in Japan, CRT is applied in patients with tumors invading adjacent organs, and a high pathological complete response rate is reported in some neoadjuvant studies. Although both definitive and neoadjuvant CRT increases the response rate and improves local tumor control, CRT is associated with substantial mortality and morbidity, especially in neoadjuvant series. More effective and less toxic CRT regimens, using new chemotherapeutic agents such as nedaplatin and paclitaxel and new irradiation protocol such as accelerated hyperfractionation, are needed to improve the prognosis of patients with advanced esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils.

Nd2 is a monoclonal antibody against pancreatic cancer. We have previously reported that human/mouse chimeric antibody Nd2 (c-Nd2) can induce antibody-dependent cell-mediated cytotoxicity (ADCC) with peripheral blood mononuclear cells (PBMs) as effectors. In this study, we investigated whether c-Nd2 can induce ADCC with poly-morphonuclear neutrophils (PMNs) as effector cells and the effects of granulocyte-colony stimulating factor (G-CSF) in enhancing this cytotoxicity. Cytotoxicities for pancreatic cancer cell line, SW1990 were dose-dependently increased by c-Nd2 during co-culture with PMNs and these cytotoxicities were significantly suppressed by the addition of neutralizing antibodies against CD16, which is Fcgamma receptor expressed on PMN membranes. PMNs treated with G-CSF significantly enhanced in vitro ADCC activity against SW1990 induced by c-Nd2. The in vivo growth of subcutaneously transplanted SW1990 tumor in nude mouse was significantly inhibited by i.p. administration of c-Nd2 compared to control (non-specific IgG1). In addition, this inhibitory effect was enhanced by the combination of c-Nd2 and G-CSF. Immunohistochemical study with anti-mouse neutrophil elastase antibody demonstrated strong infiltrations of PMNs into and around the transplanted tumor, treated with c-Nd2 and G-CSF. These results suggest that PMNs play an important role in c-Nd2 inducing ADCC and that combination immunotherapy of c-Nd2 with G-CSF may have clinical applications in the treatment of patients with pancreatic cancer by enhancing ADCC.

Animals↗

PubMed2002

Prognostic value of microsatellite instability in resectable pancreatic cancer.

The significance of microsatellite instability (MSI) as a prognostic predictor for resectable pancreatic cancer patients was examined. Forty-six histologically confirmed pancreatic cancer patients who had undergone resection were studied. DNA was extracted from the paraffin block sections by means of the microdissection method. PCR was performed using eight microsatellite primer marker sets. The mixed PCR sample was analyzed by a genetic analyzer. The number of MSI-positive patients was eight (17.4%) as determined by assessment of microsatellite variations in three or more of the eight tested markers. Univariate analysis revealed that patients with MSI-positive tumors had significantly longer survival times than patients with MSI-negative tumors, although there were no significant differences in clinicopathological factors between the two groups (median survival term, 62 months versus 10 months, respectively; P = 0.011). According to univariate survival analysis, patients with T3/T4, N1, or M1 tumors, as classified by Union Internationale Contre le Cancer staging, had significantly shorter survival times than patients with less progressive tumors. Multivariate survival analysis indicated that MSI status had an independent predictive value (hazard ratio = 5.577; P = 0.007). The tumor-infiltrating leukocyte intensity in MSI-positive tumors was significantly larger than that in MSI-negative tumors, suggesting that MSI-positive tumors may induce stronger antitumor immunity. In conclusion, a patient with MSI-positive pancreatic cancer may have a comparatively better prognosis after resection, possibly due to intensive immunoreaction to the tumor.

Aged↗

PubMed2002

Genetic alterations in adenoma-carcinoma sequencing of intraductal papillary-mucinous neoplasm of the pancreas.

We investigated the adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm from the aspect of genetic changes. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from patients with 16 intraductal papillary-mucinous adenoma of the pancreas (IPMA) and 10 intraductal papillary-mucinous carcinoma of the pancreas (IPMC) were provided for DNA extraction after microdissection. SSCP-DNA sequencing analysis demonstrated K-ras mutations at codon 12 in 75% of IPMA and 70% of IPMC, while those at codon 13 were observed neither in IPMA nor IPMC. There were no characteristic K-ras mutation types in IPMA and IPMC and no significant differences in incidence of K-ras mutations between the two categories. The frequencies of p53 mutations analyzed by SSCP-DNA sequencing were not high in IPMA (18.8%) and IPMC (30%), showing no significant difference between them. LOHs of APC in IPMA and IPMC were infrequent (6.3 and 20%, respectively) and showed no significant difference in incidence between the two categories. The LOH frequencies of DCC in IPMA and IPMC were 31.3 and 40%, respectively, and were not statistically different from each other. Taken together, genetic changes such as K-ras, p53, APC and DCC mutations may not be associated with adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm of pancreas.

Adenocarcinoma, Mucinous↗

PubMed2002

Lipid-mediated gene transfection of intercellular adhesion molecule-1 suppresses the peritoneal metastasis of gastric carcinoma.

We have previously reported that a decreased expression level of ICAM-1 in cancer cells frequently led to the development of lymph node metastasis, and suggested that ICAM-1 gene transfection may inhibit lymph node metastasis. In the present study, we investigated whether ICAM-1 gene therapy for the peritoneal metastasis of gastric carcinoma is useful as a new immuno-gene therapy. ICAM-1 gene was transfected into a gastric cancer cell line, OCUM-2MD3 (2MD3), which has a high metastatic ability to the peritoneum. A transfectant cancer cell line, 2MD3/ICAM-1, had high ICAM-1 expression on the cell surface. The adhesion and cytotoxicity abilities of peripheral blood mononuclear cells were significantly increased against 2MD3/ICAM-1 cells in comparison with 2MD3 cells. Mice inoculated with 2MD3/ICAM-1 cells in the peritoneal cavity had a significantly better survival rate than those inoculated with 2MD3 cells (log-rank test, p<0.05). Histologic findings revealed that more mononuclear cells existed around the metastatic nodules in 2MD3/ICAM-1. Although gastric carcinoma frequently causes peritoneal metastasis, no useful therapy for the metastasis of gastric carcinoma has been developed. These findings revealed that ICAM-1 gene transfection to cancer cells could be a useful immuno-gene therapy for the peritoneal metastasis of gastric carcinoma.

Animals↗

PubMed1999

Decrease in ICAM-1 expression on gastric cancer cells is correlated with lymph node metastasis.

BACKGROUND: Lymph node metastasis is a frequent type of metastasis in patients with gastric cancer. The mechanisms responsible for this type of metastasis, however, are not clearly understood. We hypothesize that the immunosurveillance system between cancer cells and lymphocytes may be associated with the lymph node metastatic process. In this study, we examined the correlation between lymph node metastasis and intercellular adhesion molecule-1 (ICAM-1), which mediates the immunosurveillance system between tumor cells and cytotoxic lymphocytes, in gastric cancer.METHODS: One hundred and forty-three specimens resected from patients with gastric cancer were investigated by staining with a monoclonal antibody against ICAM-1. We studied the correlation between the expression of ICAM-1 and various clinicopathologic factors, as well as infiltration of tumor-infiltrating lymphocytes (TILs).RESULTS: ICAM-1 expression on gastric cancer cells was significantly decreased in patients with lymph node metastasis. The infiltration of TILs was associated with ICAM-1 expression level. The prognosis of patients with ICAM-1-negative tumors was poorer than the prognosis of those with ICAM-1-positive tumors.CONCLUSIONS: These findings suggest that ICAM-1 expression on cancer cells is closely associated with lymph node metastasis in gastric cancer, under the influence of the host immunosurveillance system.

Journal Article↗

PubMedDate not supplied

Expression of intercellular adhesion molecule-1 and prognosis in colorectal cancer.

Intercellular adhesion molecule-1 (ICAM-1) is a 90-kDa cell surface glycoprotein and is known to be a member of the immunoglobulin gene superfamily of adhesion molecules. It has been suggested that ICAM-1 expression on cancer cells might have a role as a suppressor of tumor progression under the host immune surveillance system. We studied the correlation between the expression of ICAM-1 and clinicopathological factors, as well as infiltration of tumor infiltrating lymphocytes (TILs) in colorectal cancer. Resected specimens from 96 patients with colorectal carcinoma were investigated using immunohistochemical staining with a monoclonal antibody against ICAM-1. As a result, the incidence of lymph node or liver metastasis was significantly lower in patients with ICAM-1-positive tumors than in those with ICAM-1-negative tumors. Infiltration of TILs was more frequently observed in the ICAM-1-positive tumors than in the ICAM-1-negative tumors. The prognosis of the patients with ICAM-1-negative tumors was significantly poorer than that of those with ICAM-1-positive tumors. In conclusion, these findings suggested that ICAM-1 expression is closely associated with metastasis and may be a useful indicator of prognosis in patients with colorectal cancer.

Adult↗

PubMedDate not supplied

Negative hMSH2 protein expression in pancreatic carcinoma may predict a better prognosis of patients.

The prognostic values of immunohistochemical staining for hMSH2 and hMLH1 in patients with pancreatic carcinomas were investigated. Fifty-five patients with histologically proven pancreatic carcinomas were studied. Immunohistochemical staining for hMSH2 and hMLH1 was performed by avidin-biotin-peroxidase complex method with a catalyzed signal amplification system. Tumor cells that exhibited an absence of nuclear staining in the presence of non-neoplastic cells with nuclear staining were considered to have an abnormal pattern. Four tumors (7.3%) demonstrated abnormal hMS2-negative staining. One tumor (1.8%) had abnormal hMLH1-negative staining and this tumor showed negative hMSH2 staining. No particular clinicopathologic factor such as tumor location, histology, T-factor, N-factor and TNM-stage were observed in patients with negative hMSH2 staining tumors. Median survival time (MST) of patients with hMSH2-negative tumors was comparatively longer than that of patients with hMSH2-positive tumors, however, there was no significant difference between MSTs of the two groups (56 months vs. 14 months; p=0.16). We concluded that negative hMSH2 immunohistochemical staining in the pancreatic carcinomas may demonstrate certain patients, but not all, who had microsatellite instability-positive tumors. The patients with hMSH2-negative tumors may have better prognoses than those with hMSH2-positive tumors. To clarify these findings, further large number of pancreatic carcinomas must be investigated.

Adaptor Proteins, Signal Transducing↗