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Biomedical subjects

M Sowa

Publications and source records attributed to M Sowa.

At least 91 records · Page 5Linked to original sources
PubMed1995

Establishment of two new scirrhous gastric cancer cell lines: analysis of factors associated with disseminated metastasis.

Determination of the differences between cell lines which are derived from a primary tumour and a disseminated metastatic lesion from the same patient may aid in elucidating the factors associated with disseminated metastases. We report on the establishment and characterisation of two new scirrhous gastric cancer cell lines, designated OCUM-2M and OCUM-2D, derived from a 49-year-old female. OCUM-2M was derived from a primary gastric tumour, and OCUM-2D was derived from a sample of disseminated metastasis. The two cell lines were derived from the same patient. We investigated biological differences between the two cell lines to study mechanisms involved in disseminated metastasis. The growth activity of OCUM-2D cells as determined by doubling time and tumorigenicity was greater than that of OCUM-2M cells. The level of epidermal growth factor receptor (EGFR) expression in OCUM-2D cells was about twice that of OCUM-2M cells and the growth of OCUM-2D cells was stimulated more by epidermal growth factor (EGF) than that of OCUM-2M cells. The invasive activity of OCUM-2D cells was higher than that of OCUM-2M cells and was increased after addition of transforming growth factor-beta 1 (TGF-beta 1). An increase in the number of attached and spreading cells was found following the addition of 10 ng ml-1 TGF-beta 1. These findings suggest that high growth and invasive activity may play an important role in disseminated metastasis and that EGF and TGF-beta 1, which affect the growth and invasive activity of OCUM-2D cells, might be factors associated with metastasis in scirrhous gastric carcinoma. The two cell lines OCUM-2M and OCUM-2D should be beneficial for analysing mechanisms of tumour progression.

Adenocarcinoma, Scirrhous↗
PubMed1995

Auditory P3 event related potentials (ERP) and brainstem auditory evoked responses (BAER) after spinal cord injury in humans.

Previous studies have observed altered somatotopic sensory fields after experimental deafferentation in animals as well as enhanced somatosensory evoked potentials and altered cortical motor pathways following spinal cord injury (SCI) in humans. These observations indicate that cortical reorganization may occur subsequent to SCI. In earlier work, we have observed attenuated amplitudes for both tactile P3 and auditory N1/P2 orienting event-related potentials (ERP) in spinal cord injured groups. These results suggest that the reorganization process may have functional perceptual and cognitive consequences. In an effort to determine if deafferentation affects the P3 ERP using stimuli other than somatosensory, we measured brain activity from central recording sites during an auditory "oddball" task. Additionally, we obtained brainstem auditory evoked responses (BAER) in order to assess subcortical primary auditory pathways as well. Results show that the SCI groups produced significantly attenuated N1/P2 complexes and P3 when compared to controls. Also, the quadriplegic group exhibited increased latencies of the P3 at frontal and central sites. There were no differences between groups in BAER results. These findings suggest that primary subcortical auditory information processing stages remain intact after SCI although later stages may be significantly altered.

Adult↗
PubMed1995

Intratumoral injection of an adriamycin immunoconjugate against human pancreatic cancer xenografts.

We have evaluated the effect of an adriamycin conjugate of monoclonal antibody Nd2 (ADM-Nd2) on the growth rate of SW1990 xenografts grown subcutaneously in athymic nude mice. Intravenous or intraperitoneal administration of radiolabeled Nd2 resulted in a maximum tumor accumulation of approximately 45% of the initial dose/g of tumor 3-7 days after administration. However, administration into the tumor produced retention of 1200%ID/g 1 day after, with 50% of this high value remaining even at 7 days after administration. In contrast, intratumoral administration of a non-specific immunoglobulin showed a lower initial retention and rapid loss of label. Both intravenously and intratumorally administered ADM-Nd2 reduced the growth rate of SW1990 xenografts. While a single intravenous administration arrested growth for about two weeks, a single intratumoral injection prevented any increase in tumor size even 45 days after administration. Xenografts treated with ADM-Nd2 showed degenerative changes at the histological level. Neither Nd2 alone nor Adriamycin alone inhibited growth when administered at the same dose as the conjugate.

Animals↗
PubMed1995

[Contribution of carbohydrate antigens to endothelial E-selectin binding in cancer cells].

We first investigated the difference in carbohydrate antigens' expression between primary tumors and matched metastatic liver lesions of colorectal carcinomas, using immunohistochemical methods. Regarding the degree of expression, SLA, SLX and SPan-1 antigens were found to be expressed on a larger proportion of tumor cells in liver metastases than in primary tumors. Second, comparing the expression of carbohydrate antigens on highly metastatic colon cancer cell line to the parental line, the expression of SLA on the surface of highly metastatic variant was increased more intensively than the parental line. Finally, we investigated the contribution of carbohydrate antigens to endothelial E-selectin binding in colon and pancreatic cancer cells, and the results indicated that SLA might play a significant role in this binding. These findings suggest that the expression of carbohydrate antigens on the surface of cancer cells obviously contributed to E-selectin binding and also to metastatic potential.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1995

[Role of carbohydrate antigens in cell-cell and cell to extracellular matrix adhesion on pancreatic cancer].

We investigated the variable adhesiveness of pancreatic cancer cells by glycosylation inhibitor to elucidate the role of carbohydrate antigens in cell-cell and cell to extracellular matrix adhesion. Various carbohydrate antigens were strongly expressed on pancreatic cancer cell (SW1990) by ELISA, and these expression correlated to its in vitro invasiveness and in vivo metastatic potential. Cellular adhesion to Matrigel, laminin and collagen type IV and homotypic cellular aggregation in SW1990 were enhanced by reducing O-linked glycosylation with its inhibitor (Bzl-GalNAc), and these effect were reversed by additional purified mucins. These results suggested that O-linked glycoproteins on SW1990 cell surface may inhibit its adhesiveness to the substratum and aggregation properties by hindering surface receptors, and this variability of adhesiveness induced by altered glycosylation may have an another important role in highly metastatic potential of well glycosylated cancer cells.

Adenocarcinoma↗
PubMed1995

[The changes in nuclear DNA content in acquisition of a high capacity for metastasis of human cell lines].

Quantification of nuclear DNA content in cancer is considered a prognostic factor, and several investigators have demonstrated that aneuploid tumors are more aggressive than diploid tumors. In this report, we investigated the relationship between metastatic capacity and nuclear DNA content using gastric and colon cancer cell lines. We established a highly peritoneal metastatic cell line (2M-D3) from a gastric cancer cell line (2M) and a highly liver metastatic cell line (LM-H3) from colon cancer cell line (LM) in our laboratory. Both the highly metastatic cell lines have more capacity for growth and metastasis, but lower nuclear DNA content and chromosome numbers than these parental cell lines. The results indicated that metastatic capacity was inversely proportional to nuclear DNA content. We cannot provide a satisfactory explanation for this inverse correlation between metastatic capacity and nuclear DNA content, but it is supposed that each cancer cell may have suitable and stable nuclear DNA content in metastasis.

Animals↗
PubMed1995

[Correlation between malignancy of gastric cancer and c-myc DNA amplification or overexpression of c-myc protein].

The amplification of c-myc DNA for fresh frozen tissue of 31 gastric adenocarcinomas was examined with dot blot hybridization method. Using the avidin-biotin peroxidase complex method, the expression of c-myc protein was examined immunohistochemically for formalin-fixed paraffin embedded tissue of 51 gastric adenocarcinomas including the same cases for c-myc DNA analysis. c-myc DNA amplification was detected in only 4 cases (12.9%). However, c-myc protein overexpression was recognized in 21 cases (41.2%). Only one of 4 cases showing c-myc DNA amplification indicated overexpression of c-myc protein. There was no statistically significant relation of c-myc protein overexpression with clinicopathological factors (histology, depth of invasion, invasion of the vessels, metastasis, intraabdominal dissemination and histological staging). These results suggest overexpression of c-myc protein could be recognized even in early gastric cancer indicating the relation of this gene product with proliferation of gastric cancer cells, although its role in the progression and metastasis of gastric adenocarcinoma might be minimal.

Adenocarcinoma↗
PubMed1995

[Role of tripeptide Arg-Gly-Asp (RGD) on adhesiveness of human pancreatic cancer cell, PANC-1 to extracellular matrix].

Tumor cell invasion and metastasis are likely to be complex processes involving a variety of cell surface receptors mediating interactions with a number of extracellular matrix molecules, including fibronectin, laminin, and collagen. We have applied this interaction of receptors for specific adhesive substrates in vitro, using specific monoclonal antibody and biologically active synthetic peptides with human pancreatic carcinoma cell, PANC-1. Tripeptide Arg-Gly-Asp (RGD) inhibited adhesion on PANC-1 cells to fibronectin but less effective in blocking adhesion to laminin and collagen, although anti beta 1-integrin antibody significantly inhibited adhesion of fibronectin but less inhibited to laminin, collagen. Our studies emphasize the importance of synthetic tripeptide RGD in adhesion on PANC-1 to extracellular matrix protein, as well as indicating the specificity of cell surface receptor, beta 1 integrin.

Amino Acid Sequence↗
PubMed1995

[Malignancy of gastric cancer analyzed by the expression of thymidine phosphorylase].

In this study, the expression of thymidine phophorylase (dThdPase) was investigated immunohistochemically in 73 patients with gastric cancer. dThd Pase was mainly distributed at the apical portion, or cytoplasm of cancer cells and its expression was detected in 52 tumors (71.2%). There were no significant association among the expression of dThdPase, histologic type, depth of invasion, and lymph node metastasis. However, a significant difference was noted with respect to liver metastases. Among 73 patients, liver metastases were observed in 11 patients. dThdPase expression was detected in all of these cases with liver metastases, which was significantly more common than those without such metastases. In relation to the prognosis, patients with dThdPase-positive tumors had a significantly worse prognosis than those with dThdPase-negative tumors. In conclusion, the expression of dThdPase may be useful as a predictor of malignant potential in gastric cancer.

Adult↗
PubMed1995

[Establishment of a new scirrhous gastric cancer cell line OCUM-2M from a primary gastric tumor].

We report on the establishment and characterization of a scirrhous gastric cancer cell line, designated OCUM-2M, derived from a 49-year-old Japanese female. OCUM-2M was derived from a primary tumor of stomach taken by total gastrectomy. The cell line grew singly or in clusters in the cultured medium. The cell line continued to multiply for more than one year. Doubling time was 37.3 hours, chromosomal mode was 70. The DNA ploidy pattern was aneuploid and DNA index was 1.59. It produced several tumor-associated antigens such as CEA, CA19-9, SLX and SPan-1. The cell line was transplantable in athymic BALB/c nude mice, and histological findings of the xenografted tumor showed poorly differentiated adenocarcinoma. The growth of OCUM-2M was stimulated following the addition of EGF, b-FGF and KGF, and decreased following the addition of TGF-beta 1. This cell line is useful in vitro and in vivo systems for studies of the biology of scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗
PubMed1995

[Clinical significance of argyrophilic nucleolar organizer regions (AgNOR) and microvessel quantitation by staining for factor VIII-related antigen as prognostic indicators in stage I breast cancer].

The clinical significance of AgNOR and microvessel quantitation as prognostic indicators in Stage I breast cancer were examined. This study included 99 patients with Stage I breast cancer, with a median follow-up period of 119 months. AgNOR was stained by Crocker's method and microvessels were identified by immunohistochemical staining for Factor VIII-related antigen in formalin-fixed, paraffin-embedded primary tumors. AgNOR score related with tumor size. Microvessel count was related to estrogen receptor status. When patients were classified into two groups by the mean AgNOR score, higher scores had a tendency to be correlated with shorter overall survival. And when classified by microvessel count, higher counts were significantly associated with shorter overall, survival (p < 0.01). The microvessel count might be a useful predictor and the AgNOR score could be used to corroborate predictions for identifying patients at high risk for relapse and death in Stage I breast cancer.

Breast Neoplasms↗
PubMed1995

[A late phase II trial of l-leucovorin and 5-fluorouracil in advanced colorectal cancer. l-Leucovorin and 5-FU Study Group (Japan Western Group)].

A multicentral cooperative study was conducted to evaluate the clinical efficacy and toxicity of l-Leucovorin (l-LV) and 5-fluorouracil (5-FU) in advanced colorectal cancer. The administration schedule was a two-hour intravenous infusion of l-LV (250 mg/m2) and an intravenous bolus injection of 5-FU (600 mg/m2), given one hour after the beginning of the l-LV infusion. Sixty-four patients were treated weekly for six weeks followed by two-weeks rest, and then evaluated for response. Complete response and partial response were obtained in 21 patients (32.8%). The median survival time was 12.8 months. The most prominent side effects were anorexia (57.8%), nausea and vomiting (56.3%), diarrhea (48.4%) and myelosuppression such as leucopenia (54.7%), thrombocytopenia (18.8%) and decreased hemoglobin (40.6%). These side effects, however, were within permissible levels. Severe toxicity was prevented by discontinuance of the treatment. From the present study, l-LV and 5-FU combination therapy seems to be a very promising and useful treatment for patients with advanced colorectal carcinoma.

Adult↗
PubMed1995

Increased expression of sialyl Lewis A and sialyl Lewis X in liver metastases of human colorectal carcinoma.

Sialyl Lewis A (SLA) and sialyl Lewis X (SLX) have been shown to be specific ligands for endothelial leukocyte adhesion molecule-1 (ELAM-1), and may be involved in the process of adhesion between cancer cells and endothelium. We used immunohistochemical methods to study the expression of SLA, SLX and CEA in both primary tumors and matched metastatic liver lesions of colorectal carcinomas. Specimens from primary tumors and matched liver metastases from 24 patients with colorectal carcinomas were studied immunohistochemically. The degree of expression of CEA in liver metastases was similar to that in primary tumors, but SLA and SLX were expressed on a larger proportion of tumor cells in liver metastases than in primary tumors. Our findings suggest that colorectal carcinoma cells expressing SLA and/or SLX form metastatic liver tumors. They also suggest that expression of SLA and SLX in primary of colorectal carcinoma can be used as a prognostic indicator of metastasis.

Adult↗
PubMed1994

E-selectin binding by pancreatic tumor cells is inhibited by cancer sera.

Tumor cells interact with endothelial cells during both intra- and extravasation. Understanding how these interactions are modulated could lead to the development of ways to alter the metastatic potential of tumor cells. Three pancreatic cancer cell lines, SW1990, CAPAN-2 and PANC-I, were examined for their ability to bind to the endothelial cell adhesion molecule E-selectin (ELAM-1). SW1990 cells exhibited highest binding, highest surface expression of the carbohydrate antigens sialylated Lewis(a) (sLe(a)) and sialylated Lewis(x) (sLe(x)) and released the most high m.w. sLe(a) and sLe(x) antigens. Expression of sLe(a) and sLe(x) antigens and binding to E-selectin were reduced by pre-treatment of SW1990 cells with the O-linked glycosylation inhibitor benzyl-alpha-GalNAc but not with the N-linked glycosylation inhibitor tunicamycin. Expression of peptide epitopes associated with MUC1 apomucins was increased by benzyl-alpha-GalNAc. Cell binding was greatly reduced by mucins purified from SW1990 xenografts and by an antibody against sLe(a). An antibody against sLe(x) had a much less marked effect. Sera from pancreatic cancer patients reduced SW1990 cell binding to E-selectin but sera from normals did not. The degree of inhibition was related to the sLe(x) level in the sample. When cancer serum was separated by column chromatography on Sephacryl S-400, the void volume fractions contained most of the sLe(a) and sLe(x) antigens and most of the inhibitory activity to E-selectin binding. Differences in the relative availability of sLe(a) and sLe(x) ligands on serum molecules and on the SW1990 cell surface may account for the differences between antibody and serum inhibition results. Thus SW1990 cell adhesion to E-selectin is mediated by ligands on mucinous glycoproteins, and adhesion can be inhibited by mucins, high blood levels of sLe(x) and reduction of cellular O-linked glycosylation.

Acetylgalactosamine↗
PubMed1994

Proliferating cell nuclear antigen labeling index of preoperative biopsy specimens in gastric carcinoma with special reference to prognosis.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is an auxiliary protein of DNA polymerase delta and is considered to correlate with the cell's proliferative state. Immunohistochemical methods with a anti-PCNA antibody (PC10) have particular advantages compared with other techniques because of the maintenance of the tissue architecture and simplicity of the methodology. The authors investigated the correlation between the tumor's proliferative activity and progression of gastric carcinoma using immunohistochemical staining with PC10. METHODS: One hundred eighty-nine endoscopic biopsy specimens from patients with gastric carcinoma before operation were investigated by immunohistochemical study, using anti-PCNA monoclonal antibody (PC10). The correlation of PCNA labeling index (percentage of positive cells in more than 500 tumor cells) with various clinicopathologic factors and prognosis was studied. RESULTS: The PCNA labeling index became higher as the histologic stage increased. In patients with lymph node metastasis, vascular invasion, liver metastasis, and peritoneal metastasis, the labeling index was significantly higher. In patients with high PCNA labeling index (50% or greater), prognosis was significantly poorer than in those with a low index (less than 50%). The rate of disease recurrence after curative resection was significantly higher in patients with high PCNA grade group. CONCLUSION: As a result of this study, PCNA labeling index is suggested to be correlated with the depth of invasion, organ metastasis, vascular invasion, and tumor stage and to be effective as a prognostic factor.

Adult↗
PubMed1994

Emotional sequelae of stroke: a longitudinal perspective.

This study investigated emotional change following stroke at acute (2-week), 2-month, and 6-month time intervals. Five dimensions of emotional functioning were examined in a sample of 19 stroke subjects: indifference, inappropriateness, depression, mania, and pragnosia (a defect in the pragmatics of social communicative style). Results showed that, at the 2-month point, differential recovery rates become apparent depending on hemispheric side of the stroke lesion. Increased indifference, inappropriateness, and depression appear to account for these results and suggest a slower rate of recovery on these variables in the left hemisphere group (LH n = 9) compared to the right (RH n = 10). Results further indicate that, at the 6-month point, emotional functioning in RH subjects appears to worsen. In contrast, emotional recovery in LH subjects seems to stabilize at this time. Clinical implications of these findings in terms of type and timing of intervention are discussed.

Affective Symptoms↗