Biomedical subjects

M Sowa

Publications and source records attributed to M Sowa.

At least 73 records · Page 4Linked to original sources

PubMed1996

Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma.

It is known that angiogenesis plays an important role in the growth and metastasis of solid tumours. Several angiogenic factors have been identified and platelet-derived endothelial cell growth factor (PD-ECGF) is thought to be one such factor. Recently, it was reported that thymidine phosphorylase (dThdPase) is identical to PD-ECGF. Using immunohistochemical staining with an anti-dThdPase antibody, we investigated the correlation between dThdPase expression and the microvessel density in 120 gastric carcinomas. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in dThdPase-positive tumours than in dThdPase-negative tumors. There was a significant correlation between dThdPase expression and the increment of microvessel density. Moreover, regarding distant organ metastasis, the frequency of hepatic metastasis was significantly higher (P < 0.01) in patients with dThdPase-positive tumours than in those with dThdPase-negative tumors. In summary, it was suggested that dThdPase expression is closely associated with the promotion of angiogenesis and hepatic metastasis in gastric carcinoma.

Adult↗

PubMed1996

Clinical significance of serum CYFRA 21-1 in gastric cancer.

We studied the clinical significance of the soluble cytokeratin 19 fragment detected with monoclonal antibody CYFRA 21-1 in the sera of patients with histologically proven gastric cancer. Sera of 110 patients with gastric cancer were analysed for CYFRA 21-1 levels by a two-step sandwich enzyme immunoassay. There were no significant differences between CYFRA 21-1 levels and the histotype, depth of invasion or vessel invasion. However, CYFRA 21-1 was significantly higher in the presence of peritoneal metastases, liver metastases and extensive nodal involvement. When the positive cut-off value was defined as 5 ng ml-1, the CYFRA 21-1 in the stage IV and recurrent cases was 55.6% and 66.7%, respectively, which was as high as carcinoembryonic antigen (CEA) and greater than carbohydrate antigen 19-9 (CA 19-9). The positivities in stage I/II and III were zero and 5.9%, respectively, and false-positive rate in 76 patients with benign gastrointestinal disorders was 2.6%. There appeared to be no correlation between CYFRA 21-1 and CEA or CA 19-9. The patients with above 5 n ml-1 of CYFRA 21-1 had a significantly poorer prognosis. Multivariate analysis indicated that CYFRA 21-1 was an independent prognostic factor, while CEA and CA 19-9 failed to be of prognostic value. In conclusion, CYFRA 21-1 is a reliable tumour marker for gastic cancer in predicting very advanced cases, recurrence of the disease and overall poor prognosis.

Antibodies, Monoclonal↗

PubMed1996

Differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts.

Scirrhous gastric cancer cells proliferate rapidly with fibrosis, when the cancer cells invade into the submucosa of the stomach. To investigate the mechanisms responsible for the rapid proliferation, the growth interaction between gastric cancer cells and fibroblasts was examined. Human gastric cancer cell lines established from scirrhous carcinoma or well-differentiated adenocarcinoma were used. Human fibroblast cell lines were obtained from various organs. The growth interaction between gastric cancer cells and fibroblasts was examined by calculating the number of cancer cells or by measuring [3H]thymidine incorporation of cancer cells. Gastric fibroblasts specifically stimulated the growth of scirrhous gastric cancer cells, but not that of well-differentiated adenocarcinoma cells. The growth factor(s) produced from gastric fibroblasts were then partially purified and characterised. The growth-promoting factor(s) had apparent molecular weights of 10000 dalton and was sensitive both to heat and proteinase treatment. No inhibition for the factor(s) was achieved with defined anti-growth factor antibodies. In this study, differential responses of scirrhous and well-differentiated gastric cancer cells to orthotopic fibroblasts were shown. Rapid proliferation of scirrhous gastric carcinoma should be partly controlled by orthotopic fibroblasts. The growth factor(s) from gastric fibroblasts, which was distinct from various defined growth factors such as epidermal growth factor (EGF), basic fibroblast growth factor (b-FGF), transforming growth factor-alpha (TGF-alpha), keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), insulin-like growth factor I (IGF-I), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF) and transforming growth factor beta 1 (TGF-beta 1) may play an important role in the progression of scirrhous gastric cancer cells.

Adenocarcinoma, Scirrhous↗

PubMed1996

Role of alpha 2 beta 1- and alpha 3 beta 1-integrin in the peritoneal implantation of scirrhous gastric carcinoma.

We established a highly peritoneal-seeding cell line, OCUM-2MD3, from a poorly peritoneal-seeding cell line, OCUM-2M, of human scirrhous gastric carcinoma. The intraperitoneal inoculation of OCUM-2MD3 cells produced peritoneal dissemination in nude mice, whereas that of OCUM-2M cells did not. We then investigated the correlation between seeding potential and adhesion molecule beta 1-integrins or alpha 6 beta 4-integrin. alpha 2 beta 1- and alpha 3 beta 1-integrin expression on OCUM-2MD3 cells (91.6% and 93.6%) was increased compared with that of OCUM-2M cells (47.8% and 34.3%) by flow cytometric analysis, and the expression level of the other integrins was not different between the two cell lines. The binding ability of OCUM-2MD3 cells to matrigel, fibronectin, laminin and type I collagen was significantly increased, approximately seven times, three times, eight times, and three times greater than that of OCUM-2M cells respectively. The invasiveness of OCUM-2MD3 cells was also significantly increased 8-fold over OCUM-2M cells. The binding and invasive ability of OCUM-2MD3 cells was significantly decreased following the addition of anti-alpha 2 beta 1- and alpha 3 beta 1-integrin antibody, but not by anti-alpha 6 beta 1- and alpha 6 beta 4-integrin antibody. These results suggest that adhesiveness and invasiveness in peritoneal implantation of scirrhous gastric carcinoma might be closely associated with alpha 2 beta 1- and alpha 3 beta 1-integrin.

Adenocarcinoma, Scirrhous↗

PubMed1996

Radioimmunotherapy for pancreatic carcinoma using (131)I-labeled monoclonal antibody Nd2 in xenografted nude mice.

We investigated the biodistribution, radiolocalization, and radioimmunotherapeutic potential of (131)I-labeled Nd2 in athymic nude mice bearing human pancreatic carcinoma xenografts. (131)I-Nd2 was accumulated at high levels in the tumor, in contrast to blood, liver, spleen, and other normal organs. The tumor was clearly delineated in scintigraphs. The volumes of tumors of mice injected with 7.4 MBq of (131)I-Nd2 were 80% less than those of tumors before injection of radiolabeled Nd2. Fibrous or vacuolar degeneration was seen in histological sections of tumors of 7-week-treated mice. The growth of tumors in mice treated with misonidazole, a hypoxic cell radiosensitizer, and then injected twice with 3.7 MBq of (131)I-Nd2 was suppressed over 7 weeks. Neither leucocytopenia nor thrombocytopenia was severe after injection of radiolabeled Nd2. Thus (131)I-labeled Nd2 may have clinical application in the radioimmunotherapy of pancreatic cancer.

Animals↗

PubMed1996

CD44H plays an important role in peritoneal dissemination of scirrhous gastric cancer cells.

The role of the adhesion molecule CD44H in the peritoneal adhesion and invasion of cancer cells was assessed using cell lines with low and high peritoneal seeding ability, OCUM-2M (2M) and OCUM-2MD3 (2MD3), respectively. The in vitro binding ability to peritoneal components (mesothelial cells, fibronectin and type I collagen) and invasive ability of 2MD3 cells were higher than those of 2M cells. The expression level of CD44H on 2MD3 cells was higher than that on 2M cells as determined by western blot analysis and flow cytometry. The adhesiveness of 2MD3 cells to hyaluronic acid, which is expressed on the surfaces of mesothelial cells, was greater than that of 2M cells. The binding ability of 2MD3 cells to mesothelial cells was inhibited in the presence of anti-CD44H monoclonal antibody, but that of 2M cells was not. These results suggested that the 2MD3 cell binding to mesothelial cells is regulated by the CD44-hyaluronic acid dependent system. The in vitro binding to submesothelial components and the invasiveness of 2MD3 cells were also inhibited in the presence of anti-CD44H antiody. The in vivo inoculation of 2MD3 cells treated with an anti-CD44H antibody resulted in a significiant prolongation of survival time as compared with control mice that were inoculated with 2MD3 cells alone. In conclusion, CD44H was associated with attachment not only to hyaluronic acid on mesothelial cells, but also to peritoneal stromal components. Thus, CD44H may play an important role in cancer cell binding and invasion in the peritoneal dissemination of scirrhous gastric cancer cells.

Adenocarcinoma, Scirrhous↗

PubMed1996

Overexpression of c-myc messenger RNA in primary and metastatic lesions of carcinoma of the stomach.

BACKGROUND: Although c-myc expression in carcinoma of the stomach has been reported to be involved in progression of the disease, little is known about the mechanism or significance of its expression. STUDY DESIGN: We measured c-myc messenger RNA (mRNA) levels by Northern blot hybridization in 51 primary gastric carcinoma lesions and 15 metastatic lesions accompanied by normal mucosal tissues from the same patients. The extent of c-myc mRNA expression in malignant lesions was determined and compared with that in normal mucosal tissues. The clinical and pathologic significance of c-myc mRNA expression was investigated. RESULTS: In 35 (68.6 percent) of 51 primary gastric carcinomas c-myc mRNA was overexpressed. Expression was found to be more frequent and stronger in early lesions than in advanced lesions (90 percent, 6.15-fold compared with 54.8 percent, 2.42-fold, p < 0.05). However, c-myc mRNA expression in the primary lesions showed little influence on either the histologic features or the disease progression. C-myc mRNA levels were higher in every metastatic lesion than in the primary lesions (9.89-fold compared with 3.04-fold, p < 0.05). CONCLUSIONS: These observations suggest that c-myc mRNA overexpression may play a role in the early development of primary lesions as well as in the formation of metastatic lesions of carcinomas of the stomach.

Blotting, Northern↗

PubMed1996

[Correlation between expression of RB protein and prognosis of gastric cancer].

In this study, the expression of retinoblastoma (RB) protein was investigated immunohistochemically in 94 patients with gastric cancer. Overexpression of RB was detected in 48 tumors (51.1%). There was no significant association among the expression of RB, histologic type, lymph node metastasis, and liver metastasis. However, a significant difference was noted with respect to depth of invasion and peritoneal metastases. Among 94 patients, peritoneal metastases were observed in 11 patients. RB expression was detected in only two of these cases with peritoneal metastases, which was significantly less than those without peritoneal metastases. In relation to prognosis, patients with RB-positive tumors had a significantly better prognosis than those with RB-negative tumors. In conclusion, this study suggested that expression of RB has a prognostic value in gastric cancer.

Adenocarcinoma↗

PubMed1996

[Association between p53 expression and chemosensitivity in advanced and recurrent gastric cancer].

Fifteen cases with very advanced and recurrent gastric carcinoma were treated by 5-FU plus cisplatin. Among them, 6 cases were responder (CR + PR) and 9 cases were nonresponder (NC). In order to select the responder, p53 protein status in the tissue obtained by endoscopical biopsy before chemotherapy was studied. The immunohistochemical method was by the avidin-biotin complex method using anti-p53 protein monoclonal antibody. One CR case showed negative p53 staining and 2 of 5 cases of PR cases exhibited positive p53 staining. The staining of all 9 NC cases was positive. Significantly high p53 protein overexpression in the nonresponder cases was indicated. In conclusion, our result suggested that the immunohistochemical method detecting p53 protein in the biopsy specimen may be useful to predict the effect by chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

[Mechanism of peritoneal metastasis and the possibility of therapeutic agents].

Peritoneal metastasis has been clinically considered to be a terminal stage, so aggressive therapy has not been performed. Recently, the molecular biologic study of cancer metastasis has progressed, so it should be important in the future to examine new therapies based on the mechanism of metastasis. In this paper, the mechanism of peritoneal metastasis, especially adhesion to peritoneum, was investigated using a scirrhous gastric cancer cell line, OCUM-2MD3. The possibility of therapeutic agents for the metastasis based on the mechanism was discussed.

Animals↗

PubMed1996

[New therapeutic approach to pancreatic cancer by monoclonal antibodies].

The prognosis of pancreatic cancer is extremely poor in digestive cancers even with systemic therapy including surgery. Thus development of a new therapeutic approach is awaited. Recently, new trials of cancer treatments using monoclonal antibodies conjugated with anti-cancer drugs or labeled with isotopes have been reported. Here, we discuss the possible therapeutic application for pancreatic cancer of adriamycin-conjugated and 131I-labeled Nd2, which is produced against pancreatic cancer mucin.

Animals↗

PubMed1995

Characterization and biodistribution of a mouse/human chimeric antibody directed against pancreatic cancer mucin.

BACKGROUND: Nd2 is a murine monoclonal antibody (MoAb) directed against purified mucins of the human pancreatic cancer cell line SW1990. The authors previously reported promising results with Nd2 for immunotargeting pancreatic cancer. However, murine MoAbs induce human anti-mouse antibodies (HAMAs), a serious problem for clinical use. Mouse/human chimeric antibodies may be less immunogenic and therefore reduce the incidence of HAMAs. In this study, the binding affinity, tumor specificity, biodistribution, and immunoimaging of chimeric Nd2 were evaluated. METHODS: The affinity of chimeric Nd2 was evaluated by competition radioimmunoassay and Scatchard analysis using 125I-chimeric Nd2, 125I-murine Nd2, and SW1990 mucin. Immunoreactivity against pancreatic cancer tissues was examined histochemically by the avidin-biotin peroxidase complex method. The biodistribution of the MoAbs was examined in athymic nude mice bearing SW1990 xenografts that were administered intravenous 125I-labeled chimeric or murine Nd2. 111In-chimeric Nd2 was injected into the same xenograft models, and scintigrams were obtained on day 3. RESULTS: Affinity analysis and immunohistochemical studies showed that chimeric Nd2 had the same affinity to SW1990 mucin and the same specificity for pancreas cancer tissues as murine Nd2. Intravenous administration of 125I-chimeric Nd2 resulted in a maximum tumor accumulation of 43% of the initial dose/gram of tumor, which was almost identical to the accumulation of 125I-murine Nd2. Distinct immunoscintigrams of tumors in nude mice were obtained with 111In-chimeric Nd2. CONCLUSION: Chimeric Nd2 may have clinical potential in the radioimmunodetection and immunotherapy of pancreatic cancer.

Animals↗

PubMed1995

Alterations in gastric mucin with malignant transformation: novel pathway for mucin synthesis.

BACKGROUND: Mucins are high-molecular-weight glycoproteins produced by both normal and cancer cells. However, in cancer cells, abnormal mucins are synthesized and potentially can be used as markers for the development and progression of certain malignancies. In a previous study, we reported the production of a new monoclonal antibody directed against a mucin antigen termed F1 alpha, an O-linked oligosaccharide similar to sialyl Tn and Thomsen-Friedenreich (T) antigens, that has not been previously detected in human cancers. F1 alpha is expressed in a high percentage (80.2%; 89/111) of gastric cancers. PURPOSE: In the present study, we compared the expression of F1 alpha with that of sialyl Tn and T antigens in human gastric cancer tissues to determine how differences in the expression of these cancer-associated antigens correlated with the biological properties of cancer cells. METHODS: A total of 141 cases of gastric cancer were studied. Sections of formalin-fixed, paraffin-embedded tissue were immunostained for F1 alpha, sialyl Tn, and T antigens. The relationship between the expression of these antigens and the patient's clinicopathologic characteristics was studied. The chi-square test (two-sided) was used for statistical analyses. RESULTS: F1 alpha was expressed in a high percentage of the cases of early to advanced cancers, irrespective of the degree of malignant progression. The rate of expression of sialyl Tn antigen in early carcinoma was low, but it increased significantly as depth of invasion increased (P < .05) and was significantly higher in patients with hepatic or lymph node metastasis than in those without such metastasis (P < .01). Expression of T antigen significantly increased with depth of invasion (P < .01) and was significantly higher in patients with hepatic metastasis (P < .05), lymph node metastasis (P < .05), or peritoneal dissemination (P < .01) than in those without such metastasis or dissemination. In consecutive sections of the same specimen, the sites of staining for F1 alpha and sialyl Tn antigens seldom coincided. In many cases, F1 alpha staining was predominant, but the sialyl Tn-dominant region tended to increase as gastric cancer progressed. Regions of T-antigen staining were usually circumscribed by those of F1 alpha staining. CONCLUSION: Our findings indicate that the expression of F1 alpha begins almost at the same time as does carcinogenesis in gastric epithelial cells. Moreover, in association with progression of gastric carcinoma, synthetic pathways for sialyl Tn antigen and T antigen probably are activated independently.

Antigens, Surface↗

PubMed1995

Mucoepidermoid carcinoma of the pancreas: report of a case.

We present herein the case of a 64-year-old man diagnosed as having a mucoepidermoid carcinoma of the pancreas. The tumor originated in the tail of the pancreas and invaded the spleen, left adrenal gland, left kidney, and transverse colon. Liver and peritoneal metastases were also noted. Despite surgical treatment and adjuvant chemotherapy, the disease progressed rapidly and the patient died of cachexia 4 months after his initial diagnosis. Mucoepidermoid carcinoma of the pancreas is a rare entity, and is believed to be a form of adenosquamous carcinoma known as adenoacanthoma. However, in this patient, no differentiated squamous cell component could be detected. In fact, the tumor was composed of mucin-producing cells, epidermoid cells, and intermediate cells. Immunohistochemical staining for the carcinoembryonic antigen, CA19-9, and SPan-1 demonstrated a production of cancerous mucin in the epidermoid cells, suggesting that mucoepidermoid carcinoma may arise from the squamoid metaplasia of an adenocarcinoma.

Biomarkers, Tumor↗

PubMed1995

A case of primary Hodgkin's disease of the stomach.

A case of primary Hodgkin's disease, a lymphocyte-predominant entity, occurring in the stomach is described. The patient was a 37-year-old man who complained of general fatigue. Endoscopic biopsy revealed gastric malignant lymphoma. Subtotal gastrectomy and postoperative chemotherapy following a modified CHOP regimen were performed. The patient has been free of recurrence during a follow-up period of 15 months. The preoperative diagnosis of gastric Hodgkin's disease is difficult. Thus far, of 100 cases of gastric Hodgkin's disease reported in Japan, only 3 were diagnosed correctly preoperatively. We also misdiagnosed our case, as B cell type malignant lymphoma, preoperatively. The final diagnosis of Hodgkin's disease of the stomach was made on the basis of histopathological and immunohistochemical examinations. Hodgkin's disease of the stomach is rare, and there are histologically similar diseases; Ki-1 lymphoma, adult T cell lymphoma, malignant histiocytosis, and infectious monocytosis. Careful diagnosis is essential thus for Hodgkin's disease of the stomach.

Adult↗

PubMed1995

Role of SPan-1 antigen in adhesion of human colon cancer cells to vascular endothelium.

Recently E-selectin (ELAM-1, endothelial leukocyte adhesion molecule-1) was shown to recognize not only sialyl Lewis X but also sialyl Lewis A, and these carbohydrate antigens may be involved in the process of the adhesion between cancer cells and endothelial cells in cancer metastasis. To investigate the contribution of sialylated carbohydrate antigen, SPan-1, and sialic acid to the adhesion of human colon cancer cells to endothelial cells, adhesion assay using HUVECs (human umbilical vein endothelial cells) was performed. The adhesion was significantly inhibited by pretreatment with anti-E-selectin antibody, indicating that this adhesion was thought to be mediated by E-selectin. When these cancer cells were pretreated with SPan-1 antibody, the adhesion was significantly inhibited in a concentration-dependent manner. The adhesion was also inhibited by pretreatment with neuraminidase. These findings suggest that the SPan-1 antigen plays a significant role in the adhesion of human colon cancer cells to endothelial cells, and sialylation of the terminal structure of carbohydrate antigens is important in this adhesion.

Antigens, Neoplasm↗

PubMed1995

Establishment of a new human extrahepatic bile duct carcinoma cell line (OCUCh-LM1) and experimental liver metastatic model.

A new human extrahepatic bile duct carcinoma cell line, designated OCUCh-LM1, was established from a liver metastatic lesion in a 61-year-old male. OCUCh-LM1 cells proliferated in a monolayered sheet with a population doubling time of 31 h. OCUCh-LM1 cells had an aneuploid pattern with a DNA index of 1.76, and chromosome counts showed a unimode of 63. OCUCh-LM1 cells expressed various carbohydrate antigens, including sialyl Lewis X, carbohydrate antigen 19-9 and SPan-1 antigen. Subcutaneous injections of OCUCh-LM1 cells induced tumour formation in nude mice. The reconstituted tumours were classified as well-differentiated adenocarcinoma. A daughter line, designated OCUCh-LM1-H1, was also established from liver metastatic colonies induced by splenic injection of OCUCh-LM1. OCUCh-LM1-H1 cells showed a higher potential for liver metastasis than OCUCh-LM1 (100% vs 20%). Since OCUCh-LM1 retains the initial characteristics (as of 93 passages at present) and expresses various carbohydrate antigens, the OCUCh-LM1 cell line and liver metastatic model established here will be useful for the study of the biological nature of extrahepatic bile duct carcinoma and the relationship between the expression of carbohydrate antigens and metastatic potential.

Animals↗

PubMed1995

Microvessel quantitation in invasive breast cancer by staining for factor VIII-related antigen.

The clinical importance of microvessel quantitation as a prognostic indicator in invasive breast cancer was examined. This study included 155 patients with invasive breast cancer, with a median follow-up of 82 months. Microvessels were identified by immunohistochemical staining for factor VIII-related antigen in formalin-fixed, paraffin-embedded primary tumours. For each tumour, microvessels were counted within a 200 x magnification field in the area of highest microvessel density. Microvessel counts (MVCs) had no correlation with tumour size, lymph node status or histological grade. When patients were classified by MVC, higher counts were associated with shorter disease-free survival and overall survival (P < 0.025 and P < 0.01 respectively). Multivariate analysis showed that MCV is an independent prognostic factor. Microvessel quantitation may be a useful predictor for identifying breast cancer patients at high risk for relapse and death.

Breast Neoplasms↗