Port-side forceps technique: a new technique for laparoscopic cholecystectomy.
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Cholecystectomy, Laparoscopic↗
Biomedical subjects
M Sowa
Publications and source records attributed to M Sowa.
Identification and characterization of motility stimulating factor secreted from pancreatic cancer cells: role in tumor invasion and metastasis.
Cell motility is an important factor in the process of invasion and metastasis of tumor. In this study, the relationship between cell motility and experimental metastatic potential was examined using two human pancreatic cancer cell lines, SW1990 and PANC-1. Serum-free conditioned medium from the highly metastatic cell line SW1990 was found to contain a factor that stimulated the migration of and induced a fibroblast-like morphological change in the weakly metastatic cell line PANC-1. Preincubation of PANC-1 cells with SW1990 conditioned medium (SW-C.M.) induced liver metastasis following splenic injection of PANC-1 cells in nude mice, although no liver metastasis was observed without pretreatment of SW-C.M. This factor, temporarily termed PDMF (pancreatic cancer-derived motility factor) is a heparin non-binding protein having a molecular weight of 40 kDa calculated by gel-filtration HPLC which acts not only chemotactically but also chemokinetically, and also acts mainly in a paracrine fashion. However, this factor had no effect on the proliferation of PANC-1 cells; it therefore appears to be a so-called motility factor. Only TGF-beta1 and IL-6 were recognized in the SW-C.M. among cytokines thought to stimulate cell motility. These cytokines stimulated the motility of PANC-1 cells, but differed from PDMF in the neutralizing test with antibody against these cytokines. Results of characterization and preliminary purification suggest that this factor may be a novel motility factor. The above findings suggest that this motility factor may play an important role in the invasion and metastasis of pancreatic cancer, and complete purification of it will be useful in elucidating the mechanism of progression of cancer and designing a strategy for inhibition of invasion and metastasis of pancreatic cancer.
Animals↗
Loss of p21WAF1/CIP1 expression correlates with disease progression in gastric carcinoma.
Previous studies have shown that tumour-suppressor genes play an important role in the progression of solid tumours. Recently, the p21WAF1/CIP1 tumour-suppressor protein has been reported to work as a critical downstream effector of p53 and a potent inhibitor of cyclin-dependent kinases. Thus, the p21WAF1/CIP1 gene is thought to play a central role in tumour suppression. In this study we investigated p21 protein expression in gastric carcinomas. A total of 172 primary gastric carcinoma specimens were immunohistochemically stained for p21 protein expression. Correlations between p21 expression and clinicopathological features were examined. Loss of p21 expression was observed in 104 of 172 tumour tissues (60.4%), and the frequency of p21 loss increased as the stage progressed. Expression of p21 in the primary tumour was frequently lost in patients with either lymph node, liver or peritoneal metastases as compared with patients without metastases. In patients with p21-negative tumours, the risk of recurrence following curative surgery was significantly higher, and the prognosis was significantly poorer than in patients with p21-positive tumours. Loss of p21 expression in primary gastric carcinoma correlates with disease progression. The status of p21 gene expression may have prognostic value in this disease.
Adult↗
Increased sialyl Lewis A expression and fucosyltransferase activity with acquisition of a high metastatic capacity in a colon cancer cell line.
A human colon cancer cell line, OCUC-LM1(LM), was established from a liver metastasis in our laboratory. Intrasplenic injection of LM into nude mice was repeated three and five times, and the daughter cell lines were designated as LM-H3 and LM-H5 respectively. The level of sialyl Lewis A (SLA) in the supernatant of LM-H3 and LM-H5 was 3 and 4.5 times higher than that of LM respectively. Flow cytometric analysis of SLA expression showed that the peak channel for LM was 113; for LM-H3, 126; and for LM-H5, 146. The mean fluorescence intensity of LM was 102.3 +/- 43.5; for LM-H3, 126.2 +/- 28.4; and for LM-H5, 144.8 +/- 23.4. In endothelial cell adhesion assays, the percentages of adherent LM-H3 and LM-H5 cells were significantly higher than for LM. The activity of alpha1-->4 fucosyltransferase was higher in LM-H3 and LM-H5 than in LM, but there was no difference in alpha2-->3 sialyltransferase activities for type 1 chain among the cell lines. Our results suggest that SLA expression is associated with acquisition of a high capacity for liver metastasis of colon cancer; increased SLA expression is due mainly to increased fucosyltransferase activity.
Animals↗
Transforming growth factor-beta and hepatocyte growth factor produced by gastric fibroblasts stimulate the invasiveness of scirrhous gastric cancer cells.
Scirrhous gastric carcinoma is characterized by cancer cells that infiltrate rapidly in the stroma with extensive growth of fibroblasts. In the present study, we examined the effect of gastric fibroblasts on the invasiveness of a scirrhous gastric cancer cell line, OCUM-2D, using an invasion assay. Gastric fibroblast-derived conditioned medium (CM) significantly stimulated the invasiveness of OCUM-2D cells, as did transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF). The stimulating activity of gastric fibroblast-derived CM was inhibited significantly by anti-TGF-beta neutralizing antibody or anti-HGF neutralizing antibody. TGF-beta and HGF were detected in the gastric fibroblast-derived CM, and TGF-beta receptor and C-met (HGF receptor) were expressed on OCUM-2D cells. Thus, TGF-beta and HGF produced by gastric fibroblasts appear to affect the invasiveness of scirrhous gastric cancer cells. TGF-beta was also detected in the conditioned medium derived from OCUM-2D cells, though HGF was not. TGF-beta appears to affect the invasiveness of OCUM-2D cells in both paracrine and autocrine fashions.
Adenocarcinoma, Scirrhous↗
Radioimmunodetection with 111In-labeled monoclonal antibody Nd2 in patients with pancreatic cancer.
This report summarizes results from an initial clinical evaluation of radioimmunodetection (RAID) in patients with pancreatic cancer using murine monoclonal antibody Nd2, directed against mucins from pancreatic cancer. Nd2 (2 mg) was labeled with 111In (2 mCi) and injected into 19 patients suspected of having pancreatic cancer. Planar scintigrams were taken 3 days post-infusion. As for final diagnoses after surgery, 14 cases were pancreatic cancer, and one case each was chronic pancreatitis, neurilemmoma, islet cell carcinoma, cholangioma, and apparent absence of suspected recurrent lesion of pancreatic cancer. Of 14 patients with pancreatic cancer, RAID was positive in 10 cases (71.4%). Cases other than pancreatic cancer were all negative, so the specificity was 100%. These results demonstrate that RAID using 111In-Nd2 can be useful in differentiating exocrine pancreatic cancer from benign conditions and other types of carcinomas in the pancreatoduodenal regions.
Adenocarcinoma↗
Therapeutic strategies for early gastric cancer.
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Adult↗
[Malignancy of colorectal cancer analyzed by expression of cyclin D1].
We evaluated the clinical significance of cyclin D1 expression in colorectal adenocarcinoma. One hundred twenty-three specimens resected from patients with colorectal cancers were investigated by staining with a monoclonal antibody against cyclin D1. The possible correlations among cyclin D1 expression, clinicopathologic factors and prognosis were studied. There was no significant association between cyclin D1 expression and various clinicopathological factors. However, disease-free survival was significantly worse in the patients with cyclin D1 strongly positive tumors than in those with cyclin D1 negative tumors. Cyclin D1 overexpression may be useful as a predictor of disease recurrence in patients with colorectal adenocarcinoma.
Adenocarcinoma↗
[Immunohistochemical study of p21 expression in gastric carcinoma].
In this study, the expression of p21 protein was investigated immunohistochemically in 152 patients with gastric cancer. Expression of p21 was detected in 64 tumors (42.1%). There were significant differences among the expression of p21, histologic type, depth of invasion, lymph node metastasis, liver metastasis, and peritoneal metastasis. The deeper the tumor invaded, the more frequent p21 expression increased. Of the 152 patients, lymph node, liver and peritoneal metastasis were found in 86, 13 and 23 patients, respectively. p21 expression was more frequently lost in tumors from patients with metastasis. In relation to prognosis, patients with p21-positive tumors had a significantly better prognosis than those with p21-negative tumors. In conclusion, this study suggested that expression of p21 has a prognostic value in gastric cancer.
Cyclin-Dependent Kinase Inhibitor p21↗
Laparoscopic adrenalectomy: comparison with the conventional approach.
Laparoscopic adrenalectomy (LA) was performed on 14 patients with adrenal tumors. Herein we describe the laparoscopic procedure and the patients' clinical course compared with those of patients who underwent the conventional posterior or transabdominal approach (PA, TA). The 14 patients included four men and 10 women aged 28 to 69 years. Clinical diagnoses in this series were primary aldosteronism in seven patients, Cushing's adenoma in four patients, and nonfunctioning tumor in three patients. Maximum diameters of the adrenal tumors ranged from 10 to 48 mm. In all patients, the adrenal tumors were removed successfully. The mean operating time was longer for LA- than for PA- or TA-treated patients (185 versus 99 and 143 min), whereas the mean blood loss was smaller for LA- or PA-treated (92 and 126 ml) than for TA-treated patients (407 ml). The patients' postoperative condition, as assessed in terms of the number of febrile days, leucocytosis, and elevation of C-reactive protein value, was significantly better with LA. In addition, the frequency of administration of analgesics was lower and the time required until the patient could walk were shorter after LA than after PA and TA. In conclusion, laparoscopic adrenalectomy appears to be a minimally invasive and safe therapeutic option that may become a standard procedure for adrenal surgery.
Adrenal Gland Neoplasms↗
A case of membranous glomerulonephritis associated with gastric cancer.
We describe a patient with gastric cancer and membranous glomerulonephritis (MGN). The patient, a 61-year-old male, was admitted to our Hospital in May, 1996, because of proteinuria and hyperlipidemia persisting for a year. Laboratory examination filled the criteria of nephrotic syndrome and renal biopsy revealed MGN of stage II. Prednisolone therapy (40 mg/day p.o.) was started, followed by a gradual decrease in proteinuria from 4.5 g/day to 0.1 g/day. Endoscopic examination was performed because of stomach-ache revealed advanced gastric cancer of Borrmann 4. Desiring for a conservative therapy, he was discharged and moved to a hospice. In literature review, MGN is the most frequent lesion among various glomerular diseases associated with malignancy, such as the lung, stomach, and colon, particularly at an elderly ages, and sometimes antedates the detection of malignancy, as in the present case. In several cases with MGN, immune-complexes composed of tumor antigens, such as carcino-embryonic antigen, and antibodies have been reported to deposit in basement membrane of glomeruli, causing MGN. In the renal and gastric cancer tissues of the present case, the presence of three novel tumor-associated antigens, Span-1, Thomsen-Friedenreich antigen (T antigen) and F1 alpha antigen, was examined, using a immuno-peroxidase method. Although none of these three antigens were immuno-stained in the renal tissue, clinical course and literature review suggest that MGN in this patient seems to be associated with gastric cancer, which may have produced MGN-causing tumor antigens other than the three antigens. It should be emphasized that malignancy should be carefully and routinely examined in patients with MGN, particularly at elderly ages.
Glomerulonephritis, Membranous↗
[Current status of low-dose CDDP. 5-FU therapy for solid malignant tumors--nationwide questionnaire survey].
A nation-wide questionnaire survey was undertaken concerning low-dose anticancer therapy of CDDP plus 5-FU, which involves (5-10 mg CDDP/body/day + 300-500 mg/body/day) for 4-6 weeks. Out of 1,525 cases from 130 institutions, 847 cases with evaluable lesions were collected from 79 institutions. The response rate was 56.4% in esophageal cancer, 34.3% in gastric cancer, 35.3% in colorectal cancer, 47.2% in liver cancer and 35.9% in lung cancer, respectively. Adverse effects were found to be fewer and compliance was much better than the conventional therapy. Such figures suggest that the present regimen may be more effective than any so far. Problems for medical administration such as unlicensed CDDP for colorectal cancer were pointed out, which hinder the forthcoming third phase study.
Antineoplastic Combined Chemotherapy Protocols↗
Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect mesothelial cell morphology and promote peritoneal dissemination.
Mesothelial cell monolayers have been reported to prevent infiltration of cancer cells into the peritoneum. We have previously reported that peritoneal fibrosis induced by gastric cancer cells prior to metastatization may provide a congenial environment for peritoneal metastases. In this study, we investigated the effects of peritoneal fibroblasts on peritoneal mesothelial cell morphology. Human gastric cancer (OCUM-2MD3), peritoneal fibroblast (NF-2P) and mesothelial (MS-1) cell lines were established in our laboratory. Histology of the peritoneum was investigated following intraperitoneal inoculation of serum-free conditioned media (SF-CM) from OCUM-2MD3 cells into nude mice. SF-CM from peritoneal fibroblasts was added to monolayer-cultured mesothelial cells, and their morphology was examined by phase-contrast microscopy. This experiment was conducted in the presence and absence of neutralizing antibodies against various factors. Mesothelial cells exposed to fibroblasts proliferation became hemispherical and separated from each other, while unexposed mesothelium remained as a flat monolayer. Cultured-mesothelial cells rounded up or exhibited a fibroblast-like shape following the addition of peritoneal fibroblast SF-CM. Anti-hepatocyte growth factor (HGF) neutralizing antibody partly inhibited this effect. We suggest that soluble factors, such as HGF, produced by peritoneal fibroblasts affect the morphology of mesothelial cells in monolayers so that the resulting environment may become prone to the peritoneal dissemination of cancer cells.
Animals↗
Prognostic significance of T antigen expression in patients with gastric carcinoma.
BACKGROUND: Thomsen-Freidenreich (T) antigen, the immediate precursor antigen of the human blood MN system, has been detected in malignant cells, but not in most normal cells in which it is cryptic but can be unmasked by desialylation. In this study, we determined the prognostic significance of T antigen in specimens with gastric carcinoma. METHODS: Expression of T antigen was studied immunohistochemically in 157 gastric carcinoma tissue specimens obtained at surgery from the First Department of Surgery, Osaka City University Medical School between 1983 and 1987. RESULTS: T antigen expression was detected in 72 of the tumors (45.9%). The staining pattern was inclined to change from a luminal surface type to a cytoplasmic type in accordance with decreasing degree of cell differentiation. The rate of expression of T antigen significantly increased (P < 0.05) with serosal invasion, and was significantly higher (P < 0.01) in patients with hepatic or lymph node metastasis or peritoneal dissemination than in those without such metastasis or dissemination. Furthermore, among patients with Stage III or IV disease, those with T antigen-positive tumors had a significantly poorer prognosis than those with T antigen-negative tumors. CONCLUSIONS: Our findings suggest that relationships exist between expression of T antigen and depth of invasion, hepatic metastasis, lymph node metastasis, or peritoneal dissemination, and that T antigen may be a good indicator of the prognosis of patients with gastric carcinoma.
Antigens, Neoplasm↗
Fibrosis in the peritoneum induced by scirrhous gastric cancer cells may act as "soil" for peritoneal dissemination.
BACKGROUND: Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer. However, the mechanism of peritoneal metastasis remains unclear. We therefore investigated the interaction between gastric cancer cells and peritoneal fibroblasts, in vivo and in vitro. METHODS: A human scirrhous gastric cancer cell line, OCUM-2MD3, and a human peritoneal fibroblast cell line, NF-2P, were established in our laboratory. We then investigated the effect of OCUM-2MD3 cells on the peritoneum of nude mice and on the proliferation of NF-2P cells, the effect of NF-2P cells on the migratory capability of OCUM-2MD3 cells, and the peritoneal fibrosis on the development of peritoneal metastasis. RESULTS: The proliferation of peritoneal fibroblasts was recognized in areas with and without cancer cell infiltration. Serum-free conditioned medium from the OCUM-2MD3 cells had induced peritoneal fibrosis in vivo and significantly stimulated the proliferation of NF-2P cells in vitro. The molecular weight (molecular weight ratio 25,000-43,000) of the growth factors produced by the OCUM-2MD3 cells was estimated by gel filtration high performance liquid chromatography. The migratory capability of the OCUM-2MD3 cells was significantly increased by the presence of NF-2P cells. Tumorigenicity in mice with peritoneal fibrosis was greater than in mice with normal peritoneum. CONCLUSIONS: Peritoneal fibrosis, formed by a factor secreted by scirrhous gastric cancer cells, may be congenial environment ("soil") for peritoneal metastases of scirrhous gastric carcinoma.
Adenocarcinoma, Scirrhous↗
Prognostic value of vascular endothelial growth factor expression in gastric carcinoma.
BACKGROUND: Many studies have shown that angiogenesis plays an important role in the growth, progression, and metastasis of solid tumors. Recently, several angiogenic factors have been identified. Vascular endothelial growth factor (VEGF) is thought to be one such angiogenic factor and is also thought to be a selective mitogen for endothelial cells. We investigated the correlation between the expression of VEGF and the progression of gastric carcinoma. METHODS: One hundred twenty-nine specimens resected from patients with gastric carcinoma were investigated by staining with a polyclonal antibody against VEGF. Correlations between the expression of VEGF, microvessel density, and various clincopathologic factors were studied. RESULTS: Microvessel density, determined by immunostaining for Factor VIII related antigen, was significantly higher in VEGF-positive tumors than in VEGF-negative tumors. VEGF positivity was correlated with vessel involvement, lymph node metastasis, and liver metastasis. Moreover, patients with VEGF-positive tumors had a significantly poorer prognosis than those with VEGF-negative tumors. Multivariate analysis indicated that the expression of VEGF is an independent prognostic factor in patients with gastric cancer. According to the mode of recurrence, the frequency of hepatic metastases was significantly increased among patients with VEGF-positive tumors. CONCLUSIONS: The expression of VEGF may be a good prognostic indicator for patients with gastric carcinoma and may also be useful as a predictor of the mode of recurrence in patients with gastric carcinoma.
Adult↗
Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice.
We established a peritoneal-metastatic model for scirrhous gastric carcinoma. Peritoneal metastasis had developed after intraperitoneal inoculation of OCUM-2MD3 cells in nude mice. This cell line was derived from a peritoneal-metastatic nodule at the mesenterium after orthotopic implantation of OCUM-2M cells which developed no peritoneal metastasis after intraperitoneal inoculation. The histologic findings of orthotopic-implanted tumor in the stomach show scirrhous type while those of subcutaneous-implanted tumor show medullary type. There might be factors, in OCUM-2MD3 cells, which are responsible for peritoneal metastasis. We next investigated the differences in the biological behavior of the original OCUM-2M and the derived variant OCUM-2MD3. Morphology and growth activity of the two cell lines were similar to each other. The specific chromosomes, add(6)(q13), del(7)(q21.2) and inv(11)(p13q21), were found in OCUM-2MD3 cells but not in OCUM-2M cells. While the oncogenes amplification by OCUM-2M cells was found in K-sam and c-myc, that by OCUM-2MD3 cells was found only in c-myc. The expression of E-cadherin by OCUM-2MD3 cells was decreased compared with that of OCUM-2M cells. Expression level of beta 1-integrin of OCUM-2MD3 cells were higher than that of OCUM-2M cells. The binding and invasion activity of OCUM-2MD3 cells were higher than those of OCUM-2M cells, and were decreased by anti-beta 1-integrin antibody. The invasion activity of OCUM-2MD3 cells was increased in the presence of peritoneal fibroblast. In this study, it was suggested that orthotopic implantation of cancer cells might have an effect on the acquisition of metastatic ability. beta 1-integrin and peritoneal fibroblasts might be correlated with peritoneal metastasis. This peritoneal-metastatic model should be useful for analysing the mechanism of peritoneal metastasis of human scirrhous gastric cancer.
Adenocarcinoma, Scirrhous↗
Prognostic value of angiogenesis in gastro-intestinal tumours.
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Cells, Cultured↗