PubMed Health⌕ Search

Biomedical subjects

S Fushida

Publications and source records attributed to S Fushida.

At least 55 records · Page 3Linked to original sources

[A new strategy for the therapy of pancreatic cancer by proton pump inhibitor].

Bafilomycin A1 is a specific inhibitor of vacuolar type proton pump (V-ATPase). This study was designed to examine the effect of bafilomycin A1 on the growth of Capan-1 human pancreatic cells which overexpress V-ATPase. Nude mice bearing a xenografted tumor of Capan-1 cell line were treated for 4 weeks with bafilomycin A1 (1.0 mg/kg/day). This treatment inhibited tumor growth, which was significantly reduced as compared with controls after 21 days (p < 0.05). However, there were no significant differences in body weights between groups. Microscopically, a large number of tumor cells in the treated group showed signs of apoptosis. These findings suggest that apoptosis induced by bafilomycin A1 was the event involved in suppression of tumor growth in vivo.

Animals↗

[Clinical usefulness of serum CYFRA21-1 in colorectal cancer].

Serum CYFRA21-1 levels were studied in 127 cases of colorectal cancer. The positive rates for serum CYFRA21-1 were 34.6% in primary colorectal cancer. There was a significant correlation between the positive rates of serum CYFRA21-1 and liver metastases, peritoneal dissemination, lymph node metastases, or clinical stage. The survival rate for patients in the CYFRA21-1 positive group was lower than those with CYFRA21-1 negative group. Among patients who underwent curative operation, patients is the CYFRA21-1 positive group gave a recurrence rate of 26.6%, against 9.4% in the CYFRA21-1 negative group. There was no correlation between serum CYFRA21-1 levels and serum CEA levels. These findings suggest that Serum CYFRA21-1 levels may be a useful indicator in estimating the prognosis for colorectal cancer.

Adenocarcinoma↗

[Analysis of the p16INK4, p15INK4B genes abnormality and the amplification of cyclin D1 gene in esophageal cancer].

To evaluate the prognostic significance of gene amplification and overexpression of cyclin D1 in the patients of esophageal squamous cancer, slot blot hybridization and immunohistochemical staining were performed. The patients with gene amplification or overexpression of cyclin D1 were significantly poorly prognosis than patients these were negative. And to investigate abnormality of p16 and p15 genes in 12 squamous cell carcinoma of esophagus, PCR and SSCP analysis were performed. In only one of 12 tumors, complete deletion of p16 and p15 genes was detected. But in other 11 tumors, no abnormality could be detected. Besides to evaluate the prognostic significance of expression of p16 in patients of esophageal squamous cancer, immunohistochemical staining for p16 was performed. The patients with overexpression of p16 were significantly better prognosis than patients that was negative, and this result was opposite contrast with the result of cyclin D1.

Carcinoma, Squamous Cell↗

[Chemohyperthermic peritoneal perfusion and subtotal peritonectomy for peritonitis carcinomatosa in gastroenteric cancer].

A new operative procedure, called subtotal peritonectomy (SP), in combination with chemohyperthermic peritoneal perfusion, was developed for the treatment of peritonitis carcinomatosa in gastrointestinal cancer. SP includes resection of primary lesion, colon, small bowel, spleen, and gall bladder and parietal peritonectomy. Six patients with gastric cancer and two patients with colon cancer underwent these procedures. A great deal of discharge from the peritoneal cavity, an increase in systemic vascular resistance index, and a decrease in central venous pressure represented much decrease in circulatory volume on days 1 to 2 postoperatively. This state improved at 3 to 4 days after operation. Histopathological study revealed multiple peritoneal seedings with negative surgical margins in all patients. There were no related deaths though bleeding, perforation, and abscess occurred in two patients each. One patient died of peritoneal recurrence after one year, but the other have survived.

Adult↗

[Correlation between the expression of urokinase-type plasminogen activator, E-cadherin and malignancy in gastric cancer].

We aim to elucidate the correlation between clinicopathological parameters and uPA and ECD expression in gastric cancer. Some 125 patients with primary gastric cancer, who were treated at the Second Department of Surgery, Kanazawa University, between 1988 and 1993, were enrolled in this study. The expression of uPA and ECD was evaluated by immunohistochemical staining using a anti-uPA and an anti-ECD monoclonal antibody. The nuclear DNA contents were measured by flow cytometry. Among 125 tumors, 42 (34%) were found to have preserved ECD expression (ECD (+)), and 83 (66%) reduced ECD expression (ECD (-)). uPA immunoreactivity was observed in 82 (65%) of 125 tumors. According to the expression of uPA and ECD status, groups of 22 uPA (-)/ECD (+), 21 uPA (+)/ECD (+), 17 uPA (-)/ECD (-) and 65 uPA (+)/ECD (-) were identified. There was a significant correlation between uPA (+)/ECD (-) status and depth of invasion, liver metastasis, peritoneal dissemination, lymph node metastasis, and venous invasion. Patients with uPA (+)/ECD (-) tumors showed the poorest prognosis and the highest rate of recurrence, as compared with the other groups of patients. No significant correlations were found between uPA (+)/ECD (-) status and DNA ploidy patterns, and histological type. Immunohistochemical analysis of the combination of uPA and ECD expression could be a useful method for the evaluation of metastasis and prognosis in gastric cancer patients. Our results indicate that uPA may have an important role in cancer infiltration and ECD in cancer infiltration and metastasis.

Cadherins↗

Lymph node metastasis and surgical management of gastric cancer invading the esophagus.

In 88 resected patients with esophagus-invading gastric cancer, the factors determining the prognosis of this disease were investigated by multivariate analysis. Neither, age, sex, macroscopic type, thoracotomy, nor histological type proved to be independent prognostic factors. The presence or absence of lymph node metastasis, serosal invasion, tumor size, and the extent of esophageal invasion were found to be significant independent prognostic factors. Among lymph node metastases, involvement of para-aortic lymph nodes was especially important. The prognosis was significantly better in cases in which these nodes were carefully dissected (R4 gastrectomy), than in cases in which selected dissection was performed (R2). However, no patient with mediastinal lymph node metastasis survived for any lengthy period, and thus the mediastinal lymph nodes seemed to be nodes, the dissection of which brought little effect. Postoperative results were very poor in cases in which the extent of the esophageal invasion was 3 cm or more. These patients should be treated with multi-modal therapy such as neoadjuvant chemotherapy.

Adenocarcinoma↗

Lymph node metastases from carcinoma of the gastric stump.

The incidence of metastases from gastric stump cancer to various regional lymph node stations was studied after meticulous node dissection in 87 patients, who had undergone curative resection. Fifty-five (63%) patients had microscopically involved nodes. The incidence of node metastases varied between 17% and 30% in the perigastric nodes (n 1), with the same incidence in second-station lymph nodes (n 2; nodes along the left gastric, common hepatic and splenic artery, or nodes at the splenic hilus) With respect to third-station lymph nodes (n 3), metastases in nodes in the hepatoduodenal ligament (No 12) and retropancreatic nodes (No 13) were found only in 2% and 8% of the cases, respectively, but there was a high incidence of metastases (14/54, 31%) in the nodes along the mesenteric root. The overall 5-year survival rate was 48% and those for n 1 and n 2 patients were 78%, and 41%, respectively. With regard to the third level lymph node station, no 5-year survivors were seen when there was nodal involvement in node station No. 12 or No. 13. However, involvement of nodes at the root of the mesentery was associated with a 5-year survival rate of 25%. These results suggest that resection of the second level lymph nodes station must be combined with total gastrectomy and distal pancreatectomy, and that the resection of the mesenteric root is very important in patients with a tumor invading the jejunum.

Female↗

Analysis of proliferative activity using anti-proliferating cell nuclear antigen antibody in gastric cancer tissue specimens obtained by endoscopic biopsy.

BACKGROUND: Proliferative activities of tumors are thought to be prognostic features of malignant tumors, but their value as measured by proliferating cell nuclear antigen (PCNA) labeling remains unclear in gastric cancer. METHODS: PCNA labeling rates (LR) were quantified in 121 paraffin-embedded biopsy specimens from primary tumors by immunocytochemistry. RESULTS: Immunohistochemical analyses have demonstrated that PCNA presents an intense staining in the nuclei of tumor cells and mucous neck cells of gastric glands. The PCNA LR ranged from 12% to 79% (mean +/- standard deviation), and a significant correlation was found between bromodeoxyuridine labeling indices and PCNA LR: PCNA LR were closely associated with tumor size, serosal invasion, and nodal involvement. The patients with tumors with high PCNA LR (greater than 40%) were dead significantly earlier than were those with tumors with low PCNA LR: When the PCNA LR and all the clinicopathologic parameters were entered into a Cox regression model, PCNA LR emerged as an independent prognostic factor. CONCLUSION: These results indicate that PCNA LR may be a potentially useful prognostic factor for gastric cancer.

Antibodies↗

Inverse association of nm23-H1 expression by colorectal cancer with liver metastasis.

The expression of nm23-H1 mRNA and protein was studied in colorectal cancers by Northern blotting and immunohistochemistry. All 21 colorectal cancers studied by Northern blotting had increased levels of nm23-H1 mRNA relative to the adjacent normal colonic mucosa. Increased nm23-H1 protein expression was also observed in all 36 colorectal cancer cases including those studied by Northern blotting. There was no significant correlation between nm23-H1 expression and tumour histology, serosal invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the expression of both mRNA and protein was significantly lower in tumours associated with liver metastasis than in those without such metastasis. These observations indicate that the nm23 gene may play a role in the suppression of liver metastasis of colorectal cancer.

Antibodies, Monoclonal↗

Correlation of p53 expression and proliferative activity in gastric cancer.

We analyzed immunohistochemically the association between p53 tissue status and prognostic parameters of 357 gastric cancer patients, using endoscopically obtained biopsy materials, embedded in paraffin. Using PAb1801, an anti-p53 monoclonal antibody p53 immunoreactivity was detected in the nuclei of cancer cells in 113 cases (32%). The nuclear p53 immunoreaction was closely associated with positive lymph node metastasis, serosal invasion, and liver metastasis. For the estimation of proliferative activity, proliferating cell nuclear antigen (PCNA) labeling rates (LRs) of biopsy specimens were immunohistochemically measured. A significant positive correlation was found between PCNA LRs and p53 tissue status. In addition, a positive nuclear p53 immunoreaction was found to be significantly associated with shorter overall survival. Especially, in the group of patients with stages III and IV, the prognosis of patients with p53-positive tumours was significantly poorer than that of patients with p53-negative tumours. These results indicate that immunohistochemical staining for nuclear p53 in biopsied materials may be useful in deciding the therapeutic schedule of patients with gastric cancer, preoperatively.

Antibodies, Monoclonal↗

[Evaluation regarding effect and quality of life after distal pancreatectomy combining total gastrectomy].

Distal pancreatectomy combined with total gastrectomy for gastric carcinoma was evaluated in regard to the availability and quality of life for patients. We performed a question-naire survey of their daily life, especially regarding postpancreatectomy diabetes, for 67 patients passed 5 years after total gastrectomy inclusive of five cases without pancreatectomy as control. Eleven cases developed diabetes mellitus which needed insulin injection after distal pancreatectomy excluding three patients with glucose intolerance before operation. These were 19% of cases performed pancreatectomy, while there was no diabetes in cases without pancreatectomy. The incidence of postpancreatectomy diabetes was 60 per cent of the cases which underwent Appleby operation (65% pancreas resection), while it was 50 percent of the cases which underwent total gastrectomy combined with distal pancreatectomy (50% resection). There is significant difference at < 0.05 level. The incidence of postpancreatectomy diabetes was increased as passing of years after operation. These results suggest that distal pancreatectomy combining total gastrectomy improves the prognosis of patients with nodal metastasis. But considering the occurrence of postpancreatectomy diabetes, it should be emphasized the adequate indication is needed for the operation, and close and long-term follow up is essential for keeping QOL.

Diabetes Mellitus↗

Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis.

BACKGROUND AND METHODS: The expression of p53 protein in 100 large bowel cancers was studied immunohistochemically by use of a monoclonal antibody (PAb1801). RESULTS: Immunoreactivity was found in 61.0% of specimens from 100 patients with colorectal cancer. The pattern of p53 expression was mainly detected in the nuclei of the cancer cells. There was no significant correlation between the expression of p53 and the histologic grade, tumor size, serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, or liver metastasis. However, patients with p53-positive tumors had a greater relative risk of death compared with those with p53-negative tumors. The p53 negative-tumors showed a recurrence rate of 5.9%; for the p53 positive-tumors, a recurrence rate of 23.8% was recorded. The 3-year survival rate was 96.7% of 39 patients with p53-negative carcinomas and 61.8% for the patients with p53-positive tumors; there was a significant difference in the rate between the two groups of patients (P < 0.05). The growth fraction of p53-positive tumors determined with a monoclonal antibody against DNA polymerase alpha (49.0%) was significantly higher than that of p53-negative tumors (40.7%, P < 0.01). CONCLUSIONS: These results suggest that the immunoreactivity of p53 may be a biologic marker of prognostic significance.

Analysis of Variance↗

Intraperitoneal hyperthermic treatment for peritoneal dissemination of colorectal cancers.

Continuous hyperthermic peritoneal perfusion (CHPP) combined with administration of anticancer drugs was performed in eight colorectal cancer patients with peritoneal dissemination. An overall response rate of 50 percent was achieved in the eight patients. Two of three complete responders are long, recurrence-free survivors for 15 and 30 months. The two-year survival has been achieved in 18.8 percent of the patients receiving CHPP, and this rate is significantly higher than the rates in P2 and P3 patients who did not receive CHPP. The complications of CHPP with administration of anticancer drugs were mild bone marrow suppression in two (25 percent) of the eight patients and also a mild grade of renal dysfunction in one (12.5 percent), though not lethal. The results suggest that the combination of CHPP with the administration of anticancer drugs is a safe and effective therapy for peritoneal dissemination of colorectal cancers.

Adult↗

DNA polymerase alpha positive-cell rate in colorectal cancer and its relationship to prognosis.

A total of 63 patients with colorectal cancer were studied for proliferative activity by an immunohistochemical technique using a monoclonal antibody against DNA polymerase alpha. The DNA polymerase alpha positive cell rates ranged from 24.0% to 74.6%. There was a correlation between the DNA polymerase alpha positive cell rates of biopsies and resected specimens. There was no significant correlation between DNA polymerase alpha positive cell rates and histological type, tumour size, invasion of bowel wall, lymphatic invasion, venous invasion, lymph node metastasis or peritoneal metastasis. Tumours with a high growth fraction (a DNA polymerase alpha positive cell rate greater than or equal to 42%) were more frequently associated with liver metastasis than those with a low growth fraction (a DNA polymerase alpha positive cell rate less than 42%). Patients with high growth fraction tumours had significantly poorer prognoses than those with low growth fraction tumours. The results of multivariate analysis using the proportional hazard model of Cox indicated that the DNA polymerase alpha positive cell rates, liver metastasis, and peritoneal metastasis were independent prognostic factors. The results indicate that the DNA polymerase alpha positive cell rate may be a useful prognostic marker of colorectal cancers.

Antibodies, Monoclonal↗

Interrelationship between transforming growth factor-alpha and epidermal growth factor receptor in advanced gastric cancer.

An immunohistochemical study for transforming growth factor-alpha (TGF alpha) and epidermal growth factor receptor (EGFR) was made with 167 primary tumors of advanced gastric cancer to demonstrate the potential existence of autocrine mechanism. TGF alpha stained positively in 87 (52%), and EGFR in 68 (41%) of the tumors. The authors classified the tumors into the following three groups: group 1 with neither TGF alpha nor EGFR staining positively (63 tumors); group 2 with either TGF alpha or EGFR staining positively (53 tumors); group 3 with both TGF alpha and EGFR staining positively (51 tumors). The incidence rates of macroscopically infiltrative tumors and large tumor measuring 6 cm or more in diameter were significantly higher for group 3 than for groups 1 and 2. The patients of group 3 had the poorest prognosis, with a 5-year survival rate of only 12%, while the 5-year survival rates were 45 and 36% for groups 1 and 2. There was a significant difference in survival between the patients of group 1 and those of group 3. Bromodeoxyuridine labeling indices were significantly higher in the tumors belonging to group 3 (median 15.8%) than in those of group 1 (median 10.8%). The results suggest that the autocrine mechanism between TGF alpha and EGFR may play an important role in the progression of gastric cancer, and that when such a mechanism becomes operative, prognosis may be poor.

Adenocarcinoma↗

Correlation of c-erbB-2 protein expression and lymph node status in early gastric cancer.

For the prediction of nodal status of early gastric cancer, sections of formalin-fixed, paraffin-embedded tissue from 220 early gastric cancers were analyzed immunohistochemically, using a polyclonal antibody against erbB-2 protein. The data of erbB-2 protein expression have been correlated with pathologic data, and a logistic regression analysis was made for the estimation of the significant factors responsible for lymph node metastasis. A pattern consistent with cell membrane staining was regarded as most specific for the erbB-2 expression. There were 22 (10%) cancers with evidence of erbB-2 protein expression. Positive staining was associated with only lymph node metastasis. The risk of lymph node metastasis was 3-fold greater in tumors having erbB-2 protein expression than in tumors without the expression. When the erbB-2 tissue status and clinicopathological parameters were entered into the logistic regression analysis, erbB-2 protein expression emerged as one of the independent significant factors for lymph node metastasis. These results indicate that early gastric cancer with erbB-2 protein expression may represent a potential risk of lymph node metastasis.

Biomarkers, Tumor↗