Biomedical subjects

M Sowa

Publications and source records attributed to M Sowa.

At least 37 records · Page 2Linked to original sources

PubMed1998

Globotriaosyl ceramide and globoside as major glycolipid components of fibroblasts in scirrhous gastric carcinoma tissues.

Scirrhous gastric cancer is characteristic in that cancer cells proliferate and invade with prominent fibrosis. To search for the expression of specific carbohydrate chains in scirrhous gastric cancer, we have examined the glycosphingolipid composition of scirrhous cancer tissues (n=10) in comparison with that of non-scirrhous cancer tissues (n=10) by means of two-dimensional thin layer chromatography, followed by fast atom bombardment mass spectrometry of the individual glycolipids and immunostaining analysis. The major neutral glycosphingolipids from scirrhous gastric cancer tissues were identified as ceramide monohexoside, ceramide dihexoside, globotriaosyl ceramide (Gb3) and globoside (Gb4), while the major acidic glycosphingolipids were II3 NeuAcalpha-LacCer, II3 NeuAcalpha2-LacCer and sulfatide. Relative concentrations of Gb3 and Gb4 in scirrhous gastric cancer tissues (Gb3 + Gb4 = 58%) were two times higher than those in non-scirrhous gastric cancer tissues (29%). Orthotopic fibroblasts cloned from scirrhous gastric cancer tissues showed similar high concentrations of Gb3 and Gb4 to scirrhous gastric cancer tissues. Furthermore, immunohistochemical study revealed that Gb3 and Gb4 were expressed intensely on the fibroblasts. On the other hand, analysis of glycosphingolipids in four scirrhous gastric cancer cell lines yielded the following results. i) The contents of Gb3 and Gb4 were low (6%), compared with orthotopic fibroblasts (62%). ii) Significant amounts of Le(a) (pentaglycosylceramide) and Le(b) (hexa- and heptaglycosylceramides), which could not be detected in scirrhous cancer tissues, were observed. The results show that the major neutral glycosphingolipids such as Gb3 and Gb4 of scirrhous gastric cancer tissues were derived from orthotopic fibroblasts and not from the cancer cells.

Adenocarcinoma, Scirrhous↗

PubMed1998

Multiple early gastric stump carcinomas after gastrectomy for peptic ulcer.

The remnant stomach after partial gastrectomy is considered to have a predilection for the development of primary gastric carcinoma. However, early gastric stump carcinomas are uncommon because the diagnosis of gastric stump carcinoma is more difficult than that of carcinoma in the intact stomach. Triple early gastric stump carcinomas, as in the present case, are exceedingly rare and may provide some clues for further investigation of carcinogenesis in the gastric stump. We studied about the histological appearance, genetic alterations (P-53 gene, c-erbB-2 gene and K-ras gene), and expression of tumor-associated antigens (carcinoembryonic antigen, carbohydrate antigen 19-9, and sialyl-Tn) in this rare case. The three carcinomas differed from each other histologically. With respect to genetic alterations, c-erbB-2 was amplified in one lesion, but no mutations of K-ras and P-53 gene were detected. The three carcinomas also differed from each other on the expression of tumor-associated antigens. In noncancerous mucosal epithelium at the anastomosis showing hyperplasia and cystic formation of glandular epithelial cells, no genetic alterations were detected, but sialyl-Tn and carbohydrate antigen 19-9 were expressed. These results suggest that there may be different processes of carcinogenesis of the three carcinomas even though they occurred under identical environmental conditions to those that have increased cancer risk.

Adenocarcinoma↗

PubMed1998

Granular cell tumor of the duodenum: a case report.

Granular cell tumor (GCT) in the duodenum is an extremely rare disease: only one case has been listed in a review, to date. We reported a 47-yr-old Japanese male case with GCT of the duodenum. Clinically, melena caused by bleeding from the tumor was the only symptom. The tumor cells showed abundant, granular eosinophilic cytoplasm. Although this tumor was clinically and histologically benign, highly developed tumor microvessels were demonstrated both angiographically and histologically, suggesting malignant potential of the tumor.

Duodenal Neoplasms↗

PubMed1998

Thymidine phosphorylase activity in tumor correlates with venous invasion.

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF), an angiogenesis factor. We investigated the correlation between dThdPase activity in gastric cancer tissue and clinicopathological factors. Thirty-three cancer tissue specimens and 23 adjacent normal gastric mucosal specimens were obtained from surgery. Measurement of dThdPase activity was based on the amount of 5-fluorouracil formed from 5'-deoxy-5-fluorouridine by dThdPase. Mean dThdPase activity in cancer tissue was approximately 3.2 times higher than that in normal tissue. Cancerous tissues with venous invasion had about twice the dThdPase activity as cancerous tissues without venous invasion. Other clinicopathological features were not related to dThdPase activity. A correlation between dThdPase activity and immunosuppressive acidic protein level was observed (r = 0.532, P = 0.005). dThdPase activity in gastric cancer cells was found to be correlated with venous invasion, supporting previous findings that it plays a role in tumor angiogenesis.

Adult↗

PubMed1998

TGF-beta1 produced by gastric cancer cells affects mesothelial cell morphology in peritoneal dissemination.

In vitro morphologic change of mesothelial cells was observed following the addition of serum-free conditioned medium (SF-CM) from peritoneal dissemination cell line OCUM-2MD3. The same morphologic change of mesothelial cells was observed following the addition of 10 ng/ml TGF-beta1, but not following the addition of b-FGF, IGF-I, VEGF or PDGF-AA. In the in vivo study, mesothelial cells of mice treated with SF-CM from OCUM-2MD3 and TGF- beta1 were separated from one another, resulting in exposure of the submesothelial connective tissue. The molecular size of the mesothelial morphology changing activity was estimated by running the SF-CM from OCUM-2MD3 through a gel filtration column TSK-gel G2000SW. The mesothelial morphology changing activity was recognized at positions equivalent of Mr 6, 500-30,000. 25 kDa TGF-beta1 was detected in the active fraction from the TSK-gel G2000SW column and the SF-CM of OCUM-2MD3 by Western blotting using a monoclonal antibody against TGF-beta1. These findings suggest that TGF-beta1 produced by gastric cancer cells changes the morphology of mesothelial cells and may thus be closely associated with peritoneal dissemination.

Animals↗

PubMed1998

Expression of the mismatch repair gene hMSH2 in sporadic colorectal cancer.

At least four genes involved in DNA mismatch repair (MMR), hMSH2, hMLH1, hPMS1 and hPMS2, have been cloned and characterized. These genes have been demonstrated to be altered in the germline of patients with hereditary non-polyposis colorectal cancer (HNPCC). HNPCC is an autosomal dominant disease characterized by a preponderance of proximal colon, young age of onset, increased multiplicity, and improved stage-specific survival. In this study, we examined the expression of hMSH2 protein in sporadic colorectal cancer (CRC). As a result, the frequency of right-sided CRC and multiple CRCs were significantly higher in the patients with hMSH2-negative CRC than in those with hMSH2-positive CRC. The rate of p53 positivity was significantly lower in the hMSH2-negative tumours than that in the hMSH2-positive tumours. The disease-free survival rate tended to be higher in the patients with hMSH2-negative CRC than in the patients with hMSH2-positive CRC. Our findings suggest that both the clinicopathological and biological features of hMSH2-negative sporadic CRC seemed to be similar to those of HNPCC. To clarify the mechanism of carcinogenesis in HNPCC and sporadic CRC, further investigations of genetic alterations caused by MMR genes will be needed.

Adult↗

PubMed1998

Tranilast and cisplatin as an experimental combination therapy for scirrhous gastric cancer.

We examined the effect of Tranilast on the reduction of the administered dose of cisplatin using a scirrhous gastric cancer model. Scirrhous gastric cancer cell line, OCUM-2M, and gastric fibroblasts, NF-10, were used. The IC50 values of CDDP to OCUM-2M cells were decreased by Tranilast in vitro. The combination treatment with Tranilast and CDDP decreased the xenografted tumor size. The combination therapy decreased fibrosis and mitosis, and increased apoptosis. These findings suggest that Tranilast increased the CDDP response on scirrhous gastric cancer. The combination treatment with Tranilast and CDDP may be useful as a new therapy for scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗

PubMed1998

Expression of intercellular adhesion molecule-1 in invasive breast cancer reflects low growth potential, negative lymph node involvement, and good prognosis.

To understand the role of intercellular adhesion molecule-1 (ICAM-1) in tumor progression in the host, we examined ICAM-1 expression in breast cancer by immunohistochemistry. This study included 274 female patients with invasive breast cancer, with a median follow-up of 98 months. The molecule was identified in formalin-fixed, paraffin-embedded primary tumors, and the relationship to clinicopathological factors and prognosis was analyzed. ICAM-1 expression occurred in 50.3% of patients. ICAM-1 expression had negative correlation to tumor size (P = 0.003), lymph node metastasis (P < 0.0001), tumor infiltration (P = 0.003), nuclear pleomorphism (P = 0.004), and nuclear grade (P = 0.042). Patients with ICAM-1-positive tumors had better relapse-free and overall survival than those with negative tumors (P < 0.0001 and P = 0.0003, respectively). These results suggest that expression of ICAM-1 on cancer cells might have a role as a suppressor of tumor progression under the host immune surveillance system.

Breast Neoplasms↗

PubMed1998

[p53 and Bax protein expression as predictor of chemotherapeutic effect in gastric carcinoma].

This study was performed to estimate p53 and Bax overexpression as a predictor of the response to chemotherapy of patients with gastric cancer. The subjects were 20 patients with stage IV gastric cancer and 3 with locally recurrent lesions treated with 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) for 4 weeks. Of the total 23 patients, there were 10 responders: 2 showing complete response (CR) and 8, partial response (PR). Carcinoma biopsy specimens of all were obtained endoscopically with anti-p53 and anti-Bax antibodies. Of the 10 responders, 7 were in the negative p53 staining group, while of the 13 non-responders, 11 were in the positive p53 staining group (p = 0.013). But no correlation was demonstrated between the chemotherapeutic effect and Bax staining alone. Moreover, among the p-53-positive cases, the patients with Bax-negative tumors were all chemoresistant. Therefore, immunohistochemical identification of p-53 and Bax prior to chemotherapy may be a useful predictor for choice of non-responders to chemotherapy.

Adenocarcinoma↗

PubMed1998

[A cooperative study on concomitant with low-dose divided administration of cisplatin (CDDP) and sustained drip infusion of 5-fluorouracil (5-FU) for unresectable advanced gastric cancer. Osaka Cisplatin Gastric Cancer Study Group].

For patients with unresectable gastric cancer registered between July 1994 and September 1995, the following dosage regimen was examined: a drip infusion of cisplatin (CDDP) at 7 mg/m2/day for 5 consecutive days and 2-day withdrawal a week for 3 weeks with concomitant sustained drip infusion of 5-FU at 300 mg/m2/day for 21 days. The whole cycle was repeated again after 2-week withdrawal. The antitumor effect was seen in 39.4% among 33 cases. With respect to histological classification, there was no difference in appearance of the effect between the moderately differentiated type at 62.5% and the low-differentiated type at 42.9%. The cases which became resectable after the administration included those in which the tumor disappeared completely in the resected specimens. As adverse reactions encountered in the cases above Grade 3, anorexia, nausea and vomiting and diarrhea were seen as clinical symptoms in 10, 5.3 and 11.8%, respectively. As laboratory test values, decrease in hemoglobin, leukocytopenia and thrombocytopenia were seen in 16.7, 15.8 and 5%, respectively, while renal or liver dysfunction did not occur. This dosage regimen was considered useful for unresectable advanced gastric cancer, although myelosuppression should be watched carefully.

Adult↗

PubMed1998

[Correlation between pyrimidine nucleoside phosphorylase (PyNPase)/platelet-derived endothelial cell growth factor and histological prognostic factor, and influences of 5'-deoxy-5-fluorouridine (5'-DFUR) administration on PyNPase levels. 5'-DFUR Joint Research Group in the Osaka Area for Gastric Cancer].

PURPOSE: Pyrimidine nucleoside phosphorylase (PyNPase), among which thymidine phosphorylase (dThdPase) exists mainly in human tumor tissues, is an enzyme to convert 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil. Recently, it was reported that dThdPase was identical to platelet-derived endothelial cell growth factor, angiogenetic factor. Therefore, we expect that there is possibility of dThdPase being a prognostic factor. METHODS: We investigated for a possible correlation between PyNPase activities in tumor tissues and prognostic factors of histological findings, examined the influences of preoperative oral 5'-DFUR administration to PyNPase levels and investigated for a correlation between HPLC methods and ELISA methods in patients with gastric cancer. RESULTS: Higher levels of PyNPase were observed in patients with advanced t,n,v, and ly factors. PyNPase levels decreased by 5'-DFUR in patients with differentiated cases. A high correlation was found between HPLC and ELISA methods. CONCLUSION: This study suggests that we must investigate possibility of PyNPase being a prognostic factor in more detail.

Antineoplastic Agents↗

PubMed1997

Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis.

Recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel density to investigate the role of p53 in the regulation of angiogenesis and its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immunohistochemical staining for p53 protein, VEGF and factor VIII-related antigen. Positive p53 protein accumulation and VEGF expression was found in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining status was identical in 65.6% of tumors. The incidence of p53- or VEGF-positive tumors was significantly higher in patients with venous invasion and liver metastases than in those without. The microvessel count (MVC) in p53- or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53- and VEGF-positive tumors was significantly higher than that in the other subgroups. Neither synchronous nor metachronous hepatic metastases were found in patients with p53- and VEGF-negative tumors, while 52.2% of patients with both-positive tumors had liver metastases and had a poorer prognosis than those with both-negative tumors. Our findings suggest the presence of a p53-VEGF pathway regulating tumor angiogenesis in human colorectal carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this disease.

Adult↗

PubMed1997

Combined analysis of vascular endothelial growth factor and platelet-derived endothelial cell growth factor expression in gastric carcinoma.

Solid tumours require neovascularization for growth and metastasis. Both vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) are well-characterized inducers of angiogenesis. In this study we examined the expressions of these antigens and their relationship with microvessel density and also determined their prognostic significance. Ninety-five specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. Microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in tumours that were both VEGF+ and PD-ECGF+ than in tumours that were both VEGF- and PD-ECGF-. According to prognosis, patients with VEGF+ tumours had a significantly worse prognosis than did those with VEGF- tumours. Although there was no significant correlation between PD-ECGF expression and prognosis, patients with PD-ECGF+ tumours tended to have a shorter survival than did those with PD-ECGF- tumours. Moreover, the frequency of hepatic recurrence was significantly higher in patients with tumours that were both VEGF-positive and PD-ECGF+ than in all other patients.

Adult↗

PubMed1997

Expression of mucin-associated tumor antigens is altered by cell density.

Mucin-associated sialylated Lewis antigens are implicated in tumor cell metastasis and are used in several tests for pancreatic cancer. Despite their clinical importance, little is known about the structures of the oligosaccharides of pancreatic cancer mucins or about the regulation of their synthesis or of the synthesis of their protein cores. In this study, we examined the effects of culture at high cell density on the expression of these antigens in the SW1990 human pancreatic cancer cell line. Mucins from cells that were 2.5 weeks post-confluent had increased expression of sialyl-Lewis(a) and Lewis(x) antigens but reduced expression of the DU-PAN-2 antigen (NeuAc alpha2,3Galbeta1,3GlcNAc-Gal-R) when compared to mucins from 1 day post-confluent cells. Sialyl-Lewis antigens differ from the DU-PAN-2 antigen by the presence of an additional fucose. Mucins from 2.5-week cells also had increased binding to lectins specific for fucose, such as AAL and UEAI, with no apparent change in the binding of lectins specific for sialic acids. Metabolically radiolabeled O-linked oligosaccharides with sialyl-Lewis(a) antigenic reactivity eluted from Bio-Gel P-10 in the region of sialylated and sulfated oligosaccharides. Oligosaccharides eluted from QAE-Sephadex (2 mM Tris base) in a pattern suggesting the presence of 1, 2 and 3 or more negative charges per oligosaccharide. Even after desialylation and desulfation, oligosaccharides eluted from Bio-Gel P-10 with apparent molecular sizes greater than glucose oligomers of 12 units. Culture of SW 1990 cells at high density also increased the steady-state levels of mRNA for mucins MUC1, 2, 4, 5 and 6. In summary, after prolonged culture at high cell density, SW1990 cells have qualitative changes in their oligosaccharides that may be due to up-regulation of fucosyltransferases.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1997

Continuous infusion of 5-fluorouracil and low dose cisplatin infusion for the treatment of advanced and recurrent gastric adenocarcinoma.

BACKGROUND: Several chemotherapy studies have suggested that continuous infusion of 5-fluorouracil (5-FU) is more effective than bolus 5-FU. In addition, 5-FU and cis-Diamminedichloroplatinum-II (cisplatin) in combination have been shown to have synergistic cytotoxicity against several human neoplasms. In this study, the authors evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion (FP therapy) in the treatment of advanced and recurrent gastric adenocarcinoma. The relationship between the response to FP therapy and several factors was also examined. METHODS: A total of 26 patients fulfilling standard eligibility criteria were enrolled in the trial. FP therapy consisted of 5-FU (350 mg/m2/day every day by continuous infusion) and cisplatin (7.5 mg/m2/day in 100 mL of normal saline infused over 1 hour on Days 1-5 every week) for 4 weeks. RESULTS: A complete response was observed in 2 cases and a partial response in 11 cases, for an overall response rate of 50%. Patients with good performance status (PS) (0-1) and differentiated histologic type showed higher response rates (50.0% and 63.6%, respectively) than patients with poor PS (2 or 3) and undifferentiated histologic type (28.6% and 35.3%, respectively), although there were no significant differences. Patients with low serum levels of immunosuppressive acidic protein (IAP) showed a significantly higher response rate (71.4%) than those with high IAP levels (0%). Toxic effects included leukopenia, thrombocytopenia, nausea, and vomiting; these were not life-threatening and did not require treatment interruption. CONCLUSIONS: FP therapy is a promising regimen for patients with advanced and recurrent gastric adenocarcinoma. Serum levels of IAP may predict chemosensitivity.

Adenocarcinoma↗

PubMed1997

Overexpression of cyclin D1 and p53 associated with disease recurrence in colorectal adenocarcinoma.

Multiple genetic changes occur during the evolution of normal cells into cancer cells. It has been reported that both cyclin D1 and p53 genes play major roles in oncogenesis and/or cell cycle control in various cancers. In this study, we examined the overexpression of cyclin D1 and p53 by the immunohistochemical method and investigated the correlation between expression of these antigen and prognosis in patients with colorectal adenocarcinoma. Disease-free survival was significantly lower in the patients with cyclin D1-strongly positive tumors than in those with cyclin D1-negative tumors. Similarly, disease-free survival of the patients with p53-strongly positive tumors was significantly lower than that of those with p53-negative tumors. Moreover, multivariate analysis indicated that both cyclin D1 and p53 overexpression are independent prognostic factors in patients with colorectal adenocarcinoma. In conclusion, both cyclin D1 and p53 overexpression may be useful predictors of disease recurrence in patients with colorectal adenocarcinoma.

Adenocarcinoma↗

PubMed1997

18F-fluorodeoxyglucose positron emission tomography and the prognosis of patients with pancreatic adenocarcinoma.

BACKGROUND: Fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) can be used to measure the glycolytic activity of tumor cells. Though the prognosis of patients with pancreatic adenocarcinoma is usually poor, a subset of patients with good prognoses may be discovered by determining the degree of FDG integration into tumors. METHODS: Fourteen patients with histologically proven pancreatic adenocarcinoma underwent 18F-FDG PET. The standardized uptake value (SUV) of 18F-FDG was calculated, and the patients were divided into high (> or = 3.0) and low (< 3.0) SUV groups. RESULTS: The two groups were not significantly different in terms of age, tumor location and size, staging, and treatment. However, analysis by the Kaplan-Meier method revealed that the groups had different prognoses (log rank test, P < 0.05). The mean survival of patients with high SUV was 5 months, whereas that of patients with low SUV was 14 months. There were not strong correlations between the SUVs and tumor size (0.56), serum carbohydrate antigen 19-9 (0.39), or carcinoembryonic antigen (0.52). CONCLUSIONS: SUV calculated with 18F-FDG can be utilized as a prognostic factor for patients with pancreatic adenocarcinoma.

Adenocarcinoma↗

PubMed1997

Establishment of a cisplatin-resistant gastric carcinoma cell line OCUM-2M/DDP.

A cis-diamminedichloroplatinum (CDDP)-resistant scirrhous gastric cancer cell line, OCUM-2M/DDP, was established by chronic exposure of cells of the parent scirrhous gastric cancer cell line, OCUM-2M, to CDDP at progressively increasing concentrations. The OCUM-2M/DDP cell line had an 11.3-fold higher level of resistance relative to its parent cell line as determined by a succinate dehydrogenase inhibition test. The biological and biochemical characteristics of the resistant and parent cell line were compared. There were differences in the modal chromosome number and DNA index, suggesting that some alterations of the DNA in the CDDP-resistant cells had occurred. Neither the parent nor resistant cell line expressed mdr-1 mRNA. After exposure to CDDP for 4 h, the intracellular platinum content of OCUM-2M cells was significantly higher than that of OCUM-2M/DDP cells (51.9 +/- 1.8 vs 16.4 plus 1.0 ng/mg protein, mean +/- SD, respectively). The GSH levels in OCUM-2M cells and OCUM-2M/DDP cells were 3.5 +/- 1.0 micrograms/mg protein and 16.8 +/- 1.2 micrograms/mg protein, respectively. These levels were also significantly different. These findings suggest that the possible mechanisms of acquired resistance to CDDP in OCUM-2M/DDP cells may be a decrease in intracellular CDDP accumulation and detoxication by GSH. This OCUM-2M/DDP cell line could be used in further investigations of the mechanism of CDDP resistance in gastric cancer.

Antineoplastic Agents↗