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Biomedical subjects

S Fushida

Publications and source records attributed to S Fushida.

At least 73 records · Page 4Linked to original sources

[Immunohistochemical detection of p53 in colorectal cancer and its relationship to prognosis].

The expression of p53 in colorectal tumors was studied immunohistochemically by monoclonal antibody (PAb1801). No nuclear staining was evident in the tumor cells of colorectal adenomas. p53 immunoreactivity was found in 59 (61.5%) of 96 colorectal cancers. There was no significant correlation between the p53 immunoreactivity and histologic type, tumor size, invasion of bowel wall, lymphatic invasion, venous invasion, lymph node metastasis, peritoneal dissemination, or liver metastasis. However, the p53 negative tumors showed a recurrence rate of 3.3%, while for the p53 positive tumors a recurrence rate of 20.9%. p53 negative tumors were associated with favorable prognosis, whereas those with p53 positive tumors were related to poor prognosis. DNA polymerase alpha positive cells rate in p53 positive tumors was significantly higher than in p53 negative tumors. The results suggested that p53 immunoreactivity might possibly be a useful prognostic marker of colorectal cancers.

Biomarkers, Tumor↗

[PMUE therapy (CDDP, MMC, UFT, etoposide) for advanced gastric cancer--a case report].

CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was given to a 62-year-old man with advanced gastric carcinoma. PMUE therapy consists of i.v. injection of CDDP 75 mg/m2 and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. He was admitted for Borrmann type 3 gastric carcinoma with multiple liver metastasis, lymph node metastases and peritoneal dissemination, the underwent total gastrectomy with R2 lymph node dissection. He was treated four times with this therapy after sensitivity test for carcinostatic agents (SDI test), which resulted in complete remission, as confirmed by CT scan and second-look operation. The patient has currently been free of disease, and we conclude that this PMUE therapy is extremely effective for advanced gastric carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

[Serum sialyl-Tn antigen in colorectal cancer and its relationship to prognosis].

Serum sialyl-Tn antigen level was studied in 117 cases of colorectal cancer. The positive rates for serum sialyl-Tn antigen were 23.1% in primary colorectal cancer. There is a significant correlation between the positive rates of serum sialyl-Tn antigen and liver metastases, peritoneal dissemination, or lymph node metastases. The survival rate for patients with sialyl-Tn antigen positive sera was lower than those with sialyl-Tn antigen negative. Among patients who underwent curative operation, patients with sialyl-Tn positive sera gave a recurrence rate of 35.7%, while those with sialyl-Tn negative sera recorded a recurrence rate of 14.7%. There is no correlation between the positive rates of serum sialyl-Tn antigen and DNA ploidy pattern. Serum sialyl-Tn antigen levels may be a useful indicator in projecting the prognosis of colorectal cancer.

Antigens, Neoplasm↗

Heterogeneity of DNA ploidy in gastric cancer.

Heterogeneity of DNA content was analyzed in 389 samples from 65 resected gastric cancers. Analysis of the samples revealed that there were 14 homogeneously diploid tumours. Six tumours were uniformly DNA aneuploid, each tissue block containing the same DNA index. The other 45 tumours (69%) varied in DNA content heterogeneity. In 39 of 45 tumours, there was a mixture of diploid and aneuploid samples, and 25 of the 39 tumours had a single aneuploid stemline. In 14 out of 39 tumours, there was also a mixture of diploid and aneuploid samples having two or more DNA aneuploid stemlines. In the remaining six tumours, different DNA aneuploid stemlines were contained in different samples without evidence of diploidy. When four or fewer samples were analyzed, only 50% of the tumours were diagnosed as having DNA content heterogeneity. On the other hand, 78% of the tumours showed DNA heterogeneity when 5 or more samples were analyzed. If the tumours had not been widely sampled, about a quarter of the tumours would have been mislabeled as diploid. The patients with tumours showing homogeneous diploidy survived longer than those with tumours showing a mixture of diploid and aneuploid stemlines. The survival rate was lowest for the patients with tumours having a mixture of diploid and multiple aneuploid stemlines, compared with those showing homogeneous diploid or a mixture of diploid and single aneuploid stemlines. The data from the current study clearly demonstrate the importance of adequate sampling in assessing the ploidy status of gastric cancers to identify groups of patients running different clinical course and prognosis.

DNA, Neoplasm↗

Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma.

Correlations of c-erbB-2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c-erbB-2 protein in which the reaction was localized to the cell membrane. There was no significant association between c-erbB-2 staining and the macroscopic or histologic type of the carcinomas. c-erbB-2-stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c-erbB-2-unstained ones. In addition, c-erbB-2 was stained in none of early gastric carcinomas. The 5-year survival rates of the c-erbB-2 protein-positive and the protein-negative group were 11% and 50%, respectively. When the c-erbB-2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis, nodal status, and c-erbB-2 tissue status emerged as independent prognostic variables. The results suggested that c-erbB-2 protein expression might be enhanced in advanced stages during the progression of gastric carcinoma. In this particular group of patients, immunoreactivity for c-erbB-2 protein is an indicator of poor short-term prognosis.

Adult↗

Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer.

Using a polyclonal antibody that is monospecific for the erbB-2 oncogene product, an immunohistochemical study of the expression of erbB-2 protein was performed in formalin-fixed paraffin-embedded tissue sections from 260 primary gastric cancers. erbB-2 protein expression in which the reaction was localized to the cell membranes was observed in 31 (11.9%) cancers. All nontumor cells and normal gastric epithelium were negative for membrane staining. There was not a significant association between erbB-2 staining and histological type or venous invasion. erbB-2 protein expression was associated with serosal invasion, lymph node metastasis, and lymphatic invasion. In addition, erbB-2 protein expression correlated with a high number of lymph node metastases. Furthermore, the risk of recurrence in lymph node was over 3 times higher in patients with erbB-2 protein-positive tumors than in those with erbB-2 protein-negative ones. When erbB-2 protein expression and the clinical parameters were entered simultaneously into the Cox regression model, erbB-2 protein expression emerged as an independent prognostic indicator. Patients with erbB-2 protein-positive tumors had 5-fold greater relative risk of death, as compared with those with erbB-2 protein-negative tumors. These results indicate that erbB-2 protein expression is an important independent prognostic indicator in gastric cancer. The high malignant potential of erbB-2 protein-positive tumors may be associated with the very high potential for lymph node metastasis.

Biomarkers, Tumor↗

Tissue status of epidermal growth factor and its receptor as an indicator of poor prognosis in patients with gastric cancer.

An immunohistological study of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) was made with 157 specimens of stomach cancer. EGF stained positively in 70 specimens (45%), and EGFR in 53 specimens (34%). The cancers were classified into three groups; Group 1 with neither EGF nor EGFR staining positively (67 tumors); Group 2 with either EGF or EGFR staining positively (57 tumors); and Group 3 with both EGF and EGFR staining positively (33 tumors). The incidence rates of tumors of macroscopically infiltrative, poorly differentiated, deep invading and node-positive types were significantly higher for Group 3 than for Groups 1 and 2. The bromodeoxyuridine labeling indices (BrdU LIs) were significantly higher for Group 3 (median: 15.1%) than for Group 1 (median: 10.7%) or Group 2 (median: 11.4%). Patients with synchronous expression of EGF and EGFR (Group 3) had the poorest prognosis. From the results, it may be concluded that tumors with synchronous expression of EGF and EGFR have the highest malignant potentials and this phenomenon may cause autocrine secretion for self-replication.

Adult↗

[Clinical experiences with hyperthermochemotherapy of hepatic metastasis from gastric cancer].

Thermochemotherapy was performed on gastric cancer cases of hepato-metastasis. The subjects were 12 gastric cancer cases having hepato-metastatic lesions (10 synchronous, 2 heterochronous). Using 8 or 13.58 MHz-dielectric heating apparatus, thermotherapy was carried out for 40-60 min (twice a week, 5-35 times, averaging 12.8 per case) at an intra-tumoral temperature greater than 42 degrees C. Chemotherapy consisted of hepato-arterial infusion of MMC 10 mg/BW, CDDP 75 mg/m2 once per 3-4 weeks and consecutive daily administration p.o. of UFT 800 mg/BW. Effect greater than PR was noted in 75% (9/12) on the whole and in 100% (5/5) and 57% (4/7) for H1-2 and H3, respectively. Mean and 50% survival periods were 9.3 and 7.2 months, respectively, with a one-year survival rate of 38%. Chemotherapy-induced side effects were nausea and vomiting in 83% and leukopenia and thrombopenia in 67%, while the only thermotherapy-induced side effect was subcutaneous fatty tissue necrosis in 3 cases. The above results suggested the effectiveness of the present thermochemotherapy in the treatment of hepato-metastasis of gastric cancer.

Administration, Oral↗

[Blood kinetics of free-platinum in CDDP hepato-arterial injection therapy].

In CDDP hepato-arterial injection therapy, platinum (Pt) concentration in hepatic and peripheral venous blood were determined in two groups with different injection rates, and the blood kinetics of Pt was examined. Seven cases of digestive cancers having liver metastases were given CDDP (100 mg) selectively into the proper hepatic artery at a constant rate (10 or 40 min). After injection, concentration of non-protein-bound Pt in hepatic and peripheral venous blood were determined. Pt concentration and AUC value were higher in hepatic venous blood at injection rate than peripheral venous blood. On the other hand, Pt concentration in hepatic venous blood in the cases 10 min-injection were higher than those received 40 min-injection, but neither Pt concentration in peripheral venous blood nor incidences of the side effects and abnormal clinical findings were influenced by the injected rates.

Adult↗

Continuous hyperthermic peritoneal perfusion for the treatment of peritoneal dissemination in gastric cancers and subsequent second-look operation.

A total of 31 patients with gastric cancer showing peritoneal dissemination received continuous hyperthermic peritoneal perfusion (CHPP) in combination with the administration of cisplatin (CDDP) and mitomycin C (MMC). The authors developed a new special device named the peritoneal cavity expander (PCE) for sufficient perfusion and direct temperature measurement in the peritoneal cavity. As complications of CHPP three patients presented with bone marrow suppressions (leukocytes less than or equal to 3000/mm3 and/or platelets less than or equal to 30,000/mm3): one, leakage of intestinal anastomosis; one, intestinal perforation; and one, acute renal failure. But none of them was lethal. Twelve of 31 patients who had received CHPP during the initial operation underwent second-look operation (SLO) for the assessing the effects of CHPP and for resecting residual or recurrent tumors. Among 12 patients who received SLO complete response (CR) was observed in four patients, partial response (PR) in one, no change (NC) in three, and progressive disease (PD) in four, with the overall response rates (%CR + %PR) standing at 41%. Two-year survival rate of the complete and partial responders was 50%, which was significantly higher than 0% of the other responders (NC + PD). The survival curves of the two groups were significantly different (P less than 0.05, generalized Wilcoxon test). These results supported that CHPP was well tolerated and effective for the treatment of patients with peritoneal dissemination in gastric cancer when combined with anti-cancer drugs having synergism with hyperthermia. Since the outcome of SLO was one of prognostic factors it was important to follow up these patients by SLO.

Adult↗

Gastric cancer heterogeneity.

This study was carried out on 222 samples from 37 gastric carcinomas to assess the incidence of multiple stem lines in primary tumors and metastasis as reflected by multiple DNA stem lines and their relationship to epidermal growth factor (EGF) receptor expression, histologic grade, tumor size, and degree of wall infiltration. Fifteen primary tumors (40.5%) were homogeneously diploid/peridiploid whereas 22 (59.5%) were aneuploid. In the lymph node metastasis, seven patients (29.2%) had an homogeneous diploid/peridiploid pattern in all metastatic lymph nodes. On the other hand, 17 (70.8%) had at least one aneuploid peak in the lymph node metastasis. DNA content heterogeneity was seen in 12 (33%) of primary tumors whereas 14 (66.6%) of 21 patients had multiple cell clones in the metastasis. Therefore, 12 patients had a metastatic clone which was not observed in the primary tumor. DNA content heterogeneity was seen even in tumors with submucosal invasion suggesting that this phenomenon is also present at earlier stages. No correlation between the histologic grade and the DNA distribution was observed. Furthermore, histologic heterogeneity was independent of DNA content heterogeneity. The EGF receptor expression was observed in six of the 23 patients in whom this analysis was done. The EGF receptor expression was constant in all samples which were studied and even samples with a different DNA content and histologic grade were stables for the EGF receptor expression.

Carcinoma↗

Correlation of DNA ploidy and clinical outcome in Borrmann type 4 gastric carcinoma.

The correlation between DNA ploidy pattern and clinical outcome was studied in 76 patients with Borrmann type 4 gastric carcinomas. Twenty-six tumors were diploid, and 50 tumors were aneuploid. There was no correlation among DNA ploidy and histologic type, lymph-node status, wall invasion, or clinical stage. The incidence of vascular invasion in the aneuploid tumors was significantly higher than that in the diploid tumors. Five year survival was achieved in 28% of the patients with diploid tumors and 8% of those with aneuploid tumors, respectively. Among the patients undergoing curative resection, 5 year survival rate was 54% in the patients with diploid tumors compared to 28% with aneuploid tumors. There was a significant survival advantage in patients with diploid tumors. These results indicate that DNA ploidy might be an important prognostic factor in Borrmann type 4 gastric carcinomas.

Adult↗

Epidermal growth factor receptor status and S-phase fractions in gastric carcinoma.

The correlation with epidermal growth factor (EGF) receptor expression and clinicopathologic findings were studied in 242 gastric carcinomas. They were stained for EGF receptor by means of an immunohistochemical technique using a monoclonal antibody against the receptor. S-Phase fractions were measured by in vivo bromodeoxyuridine (BrdU) labeling and indirect immunohistochemical staining using anti-BrdU monoclonal antibody. In normal gastric epithelium, EGF receptor immunoreactivity could not be found. EGF receptor was found in 76 (31.4%) of 242 gastric carcinomas. Diffusely infiltrating types of carcinomas were more likely than localized tumors to be EGF receptor-positive. In addition, EGF receptor-positive tumors had significantly higher values of BrdU labeling indices than EGF receptor-negative tumors. The patients with EGF receptor-positive carcinomas also had a poorer prognosis than did negative cases. These results suggested that EGF receptor-positive tumors may have higher proliferative activity and local extension may progress more rapidly, and also seem to show that EGF receptor status may possibly be a useful prognostic marker for gastric carcinomas.

Bromodeoxyuridine↗

[Correlation of epidermal growth factor receptor status and clinical outcome in gastric carcinoma].

Analysis of epidermal growth factor receptor (EGFR) was performed on 242 primary gastric carcinomas and the results correlated with histologic findings and S-phase fractions measured by bromodeoxyuridine (BrdU) labeling. They were stained for EGFR by means of an indirect immunoperoxidase technique using a monoclonal antibody against the receptor. Seventy-six of these cancer tissues exhibited EGFR reactivities. All the cancer cell membranes were stained and sometimes the stroma were stained. These EGFR status were then compared on the basis of pathologic findings including macroscopic type, depth of invasion, differentiation type, vascular invasion and lymph node metastasis. Staining for EGFR in Borrmann's 3 or 4 type was significantly stronger than those in other macroscopic types. The staining for EGFR was closely related to the poorly differentiated type and frequent serosal involvement. BrdU labeling index was studied in 25 cases. These values were from 2.3% to 18.6%, with a mean of 10.4%. The mean BrdU labeling index of EGFR positive cases was 12.2%, of negative cases 7.6%, respectively. There was a good correlation between BrdU labeling index and EGFR status. In addition, There was a signifiCANT 8P less than 0.05) correlation between the presence of the EGFR and poor prognosis. However, EGFR status was not significantly correlated with the lymph node metastasis, vessel invasion and size of the tumors. These results indicate that demonstration of EGFR status may be useful in prognosis and this receptor may be a suitable target for therapy.

Adenocarcinoma, Scirrhous↗

[Human epidermal growth factor (h-EGF) in gastric carcinomas].

Two hundred and twenty one gastric carcinomas were immunohistochemically stained for h-EGF and we examined the correlation between h-EGF immunoreactivities and histologic findings. Regarding macroscopic and histologic types, incidence of h-EGF immunoreactivities in infiltrating type and in poorly differentiated type was significantly higher than those in localized type and in differentiated type, respectively. In addition, h-EGF producing carcinomas showed high positive rate in prognostic serosal involvement and scirrhous type in stroma. Prognosis in patients with h-EGF producing tumors was poorer than that in those with h-EGF non-producing tumors, especially in stages II and III. These results suggest that h-EGF immunoreactivities serves as a biological marker of high malignancy.

Adenocarcinoma↗

[Multimodal therapy using hyperthermia for gastric cancer--with special reference to histological studies].

We carried out a combination preoperative therapy involving radiofrequency hyperthermia (8 MHz or 13.56 MHz) with radiation (10-MV X-ray) or chemotherapy (Mitomycin C, CDDP or UFT) for 24 advanced gastric cancers with the aim of preventing local recurrence and improving resectability. The tumor and histological effects were evaluated in each case. Furthermore, an agar phantom possessing a cavity, for simulating the stomach, was employed in an experiment to evaluate temperature distribution upon RF-heating. In the experiment using the agar phantom, the rising temperature around the cavity at 3 o'clock was higher than at 5' and 6 o'clock. This suggested that gastric juice and air must be aspirated when treating a patient by RF-heating. Of the 24 tumors, 4 (17%) showed partial response. Histological effects were observed in 67% of 21 primary tumors. The rate of histological effects in metastases of lymph nodes, liver and peritoneum were 29% (4/14), 100% (2/2) and 0% (0/4), respectively. Tumor response was closely correlated with irradiation and the temperature in the stomach cavity (over 42.5 degrees C). Almost all patients showed good tolerance of this combined therapy. These results show that combined treatment involving radiation, chemotherapy and hyperthermia appears to be a potentially useful from of preoperative therapy for patients with advanced gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗