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T Kamigaki

Publications and source records attributed to T Kamigaki.

At least 19 recordsLinked to original sources

Randomized clinical trial of preoperative intranasal mupirocin to reduce surgical-site infection after digestive surgery.

BACKGROUND: Compromised patients subjected to major digestive surgery frequently develop infective complications caused by methicillin-resistant Staphylococcus aureus (MRSA), which may have dangerous consequences. This was a prospective randomized study to determine whether intranasal mupirocin could reduce postoperative infective complications in patients having digestive surgery. METHODS: A total of 395 patients who underwent abdominal digestive surgery were assigned randomly into two groups: a treated group (193 patients) and controls (202). Patients in the treated group were given 30 mg mupirocin calcium hydrate ointment topically to each nostril three times a day on each of the 3 days before operation. The untreated group received no mupirocin treatment. RESULTS: Most infections were due to Gram-negative bacteria in both groups. There were 21 Gram-positive infections detected at the surgical site, ten in the treated group and 11 in control patients. The incidence of pneumonia was significantly different between the groups (none in the treated group and five in control patients; P = 0.028). Four of five patients with pneumonia had a sputum culture containing MRSA. CONCLUSION: Intranasal mupirocin treatment had no significant impact on surgical-site infection after digestive surgery.

Administration, Intranasal↗

High expression of thymidylate synthase leads to resistance to 5-fluorouracil in biliary tract carcinoma in vitro.

To evaluate the effect of chemotherapy of 5-fluorouracil (5-FU) in human biliary tract carcinoma, we studied 5-FU sensitivity, thymidylate synthase (TS) content, and dihydropyrimidine dehydrogenase (DPD) activity in 4 human biliary tract carcinoma cell lines compared to 12 various digestive carcinoma cell lines of human organs in vitro. 5-FU sensitivity in the cell lines was analyzed by MTT assay. TS content was analyzed by the [6-(3)H]FdUMP binding assay method, and DPD activity was analyzed by thin-layer chromatography (TLC). 5-FU IC(50) values of biliary tract carcinoma cell lines were significantly higher than those of the carcinoma cell lines of the other digestive organs: 97, 45, 119, and 194 times the concentration of the other digestive, pancreas, colon, and gastric carcinoma cell lines, respectively. TS content of biliary tract carcinoma cell lines was also significantly greater than that of the carcinoma cell lines of the other organs. No difference in DPD activity, however, was recognized between the carcinoma cell lines of each organ. TS content in the cell lines significantly correlated with 5-FU sensitivity, but DPD activity did not. Therefore, in the present study, TS expression was concluded to influence the high resistance to 5-FU of biliary tract carcinoma in comparison with the carcinomas of the other digestive organs.

Biliary Tract Neoplasms↗

Optimal duration of oral adjuvant chemotherapy with Carmofur in the colorectal cancer patients: the Kansai Carmofur Study Group trial III.

A multi-institutional study was performed to evaluate the appropriate duration of oral administration of Carmofur (1-hexylcarbamoyl-5-fluorouracil, HCFU), a 5-fluorouracil (5-FU) derivative, for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative operation. Patients were divided into two: i) short duration group receiving 6 months of HCFU administration and ii) long duration group receiving 1 year of the administration, using a centralized registration system. Among 364 patients entered in this study, 293 evaluable cases were analyzed to investigate the appropriate duration of adjuvant oral chemotherapy. No statistical differences were found in the cumulative 5-year disease-free or survival rates between the groups. However, the actual duration of oral HCFU administration differed in the patients of short and long duration groups from the protocol. Namely, more than 70% of the patients received a different duration of oral adjuvant chemotherapy in each of the groups. Therefore, apart from this division of two groups, correlation between the actual duration of oral HCFU administration and the prognosis was examined in these patients. As a result, it was suggested that oral adjuvant chemotherapy with HCFU would be effective in colon cancer patients when the duration of administration exceeded 330 days. In rectal cancer patients, however, adjuvant chemotherapy with HCFU alone was considered to be not sufficient to affect the prognosis.

Administration, Oral↗

[Two cases of multiple liver metastases of colon cancer with systemic irinotecan and hepatic arterial injection of 5-FU].

We describe two patients with multiple liver metastases of colon cancer, who simultaneously received systemic irinotecan and hepatic arterial injection of 5-FU. In both cases, a notable partial response (more than 80%) in the hepatic metastases was observed. The patients could undergo chemotherapy without remarkable side-effects as out-patients. In the future, we shall perform a clinical study to evaluate the safety and dose limiting toxicity for the present combined chemotherapy.

Aged↗

[A case of gastric cancer with liver metastasis responding to low-dose CDDP/5-FU combination chemotherapy].

We reported a case of a 62-year-old female with gastric cancer accompanied by liver, Virchow and paraaortic lymph nodes, and bone metastasis (taken low-dose cisplatin (CDDP)/5-fluorouracil (5-FU) combination chemotherapy). CDDP (10 mg/body/day) was injected on 1-5 days i.v. and 5-FU (500 mg/body/day) was injected i.v. continuously on 1-7 days. This treatment cycle was repeated for 4 weeks. After 4 cycles, liver metastasis disappeared without severe side effects. Primary lesion and Virchow's lymph nodes metastasis were reduced. However, bone and paraaortic lymph node metastasis showed no response. It was considered that low-dose CDDP/5-FU combination chemotherapy was effective for liver and lymph nodes metastasis of gastric cancer in this case.

Adenocarcinoma↗

Enhancement of tumor uptakes by stabilized Fab homo-oligomers of a chimeric monoclonal antibody against carcinoembryonic antigen.

We investigated the effect of stabilized Fab oligomerization by disuccinimidyl suberate on tumor uptake in a pancreatic carcinoma xenograft model in nude mice. Recombinant mouse/human chimeric Fab of the anti-carcinoembryonic antigen (CEA) monoclonal antibody A10, which was previously shown to react specifically with gastrointestinal cancers was used in this study. Fab homo-oligomers (dimers and trimers) chemically linked with ethylene bonds (C-C oligomers) were produced by linkage of chimeric Fab. Oligomers with C-C bonds had similar immunoreactivity against human CEA to parental Fab monomer. In biodistribution studies in animals bearing pancreatic carcinoma xenografts, at 12 and 24 h after infusion, C-C oligomers showed significantly greater uptakes in tumors than Fab or F(ab')2 but lower than IgG. However, oligomers with C-C bonds maintained higher tumor to normal tissue specificity ratios than IgG 24 h post-infusion. In conclusion, tumor uptake was enhanced by Fab oligomerization with C-C bonds, compared to Fab or F(ab')2, perhaps due to the larger molecular size. It was also shown that C-C Fab oligomers could have a potency to deliver high-dose radionuclides with reduced radio-uptakes in normal tissues for the radioimmunotherapy of gastrointestinal carcinomas.

Animals↗

Proliferating cell nuclear antigen as a predictor of therapeutic effect of continuous 5-fluorouracil administration in gastric cancer.

The change of proliferating cell nuclear antigen (PCNA) expression was examined in three gastric cancer cell lines, MKN28, MKN45 and MKN74, during continuous or bolus exposure to 5-fluorouracil (5-FU). The cytotoxic effect of 5-FU was almost the same in all the cells. PCNA expression was higher at 24 and 72 h after continuous 5-FU treatment than before treatment. Continuous 5-FU treatment of cells revealed higher expression of PCNA protein and mRNA than did bolus treatment. Flow cytometry revealed that 5-FU increased cell population at the late G1 or S phase 24 and 72 h after treatment. PCNA values at the late G1 and S phase were significantly higher than those at other phases 24 h after treatment. These results suggest that PCNA expression increased due to cell cycle accumulation at late G1 and S phases. Thus PCNA values just after chemotherapy of gastric cancer may be useful in predicting the therapeutic effects of continuous 5-FU administration.

Antimetabolites, Antineoplastic↗

[KMO1].

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Antigens, Tumor-Associated, Carbohydrate↗

Improved tumor detection by anti-CEA chimeric Fab oligomers with disulfide linkages in a pancreatic-carcinoma-xenograft model.

We have investigated the effect of Fab oligomerization on imaging efficacy in a pancreatic-carcinoma xenograft model in mice. Recombinant mouse/human chimeric Fab of the anticarcinoembryonic antigen (CEA) monoclonal antibody A10, which has been shown to react specifically with gastrointestinal cancers, was used in this study. Fab homo-oligomers (dimers and trimers) were prepared by linkage of chimeric Fab with N-succinimidyl-3-(2-pyridyldithio)-propionate. Oligomers with S-S bonds showed 10-fold higher binding activity against human CEA than Fab, while the binding activity of oligomers was similar to that of F(ab')2. In mice bearing pancreatic-carcinoma xenografts, tumor uptake of S-S oligomers was significantly greater than that of monomeric Fab, while there was no difference in tumor uptake between S-S Fab trimers and F(ab')2. S-S oligomers showed more rapid clearance rates and uniform percolation in the tumor nodules than F(ab')2. At 18 hr after injection, clear scintigraphic detection of the pancreatic-carcinoma tumors was obtained with 123I-labeled S-S Fab dimers. At 24hr, improved tumor imaging was shown for 123I-labeled S-S Fab oligomers with slightly visible uptake in normal tissues, similar to that of F(ab')2. S-S oligomers of chimeric A10 Fab may be useful as rapid diagnostic tools of pancreatic carcinomas.

Animals↗

Synthetic lipid A produces antitumor effect in a hamster pancreatic carcinoma model through production of tumor necrosis factor from activated macrophages.

The antitumor effect and biological activities of a newly synthesized lipid A analogue (ONO-4007) were investigated in a hamster pancreatic carcinoma model. Marked and dose-dependent inhibition of tumor growth was achieved by i.p. injection twice a week for 3 weeks of 10, 30 or 50 mg/kg of ONO-4007. Endogenous tumor necrosis factor (TNF) activities induced by ONO-4007 were significantly greater in tumor than in serum, spleen and liver. TNF production by macrophages stimulated with ONO-4007 after culture was much greater when culture was performed in the presence of hamster pancreatic carcinoma cells (no cell-to-cell contact). It was further found that the cytotoxic activity of TNF secreted by macrophages cultured with cancer cells was inhibited in the presence of anti-TNF neutralizing antibodies. These findings suggest that ONO-4007 displays antitumor effects by stimulating production of endogenous TNF in tumor macrophages, possibly through activation by soluble macrophage-stimulating factors in cancer cells.

Animals↗

Radiolocalization of pancreatic carcinoma xenografts in nude mice with radiolabeled chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal antibody A10.

Recombinant mouse-human chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal antibody (MAb) A10 react with various GI carcinomas. We tested radiolocalization of pancreatic carcinoma xenografts in nude mice using radiolabeled chimeric A10 Fab fragments, comparing them with murine Fab fragments and parental MAb. For mice injected with chimeric A10 Fab fragments, we obtained significantly higher uptake in tumors than in normal tissues at 24 and 48 h after injection. In addition, tumor/normal tissues labeling ratios for chimeric A10 Fab fragment were significantly greater than those for murine MAb at 24 h postinfusion. However, no significant difference in biodistribution was observed between chimeric and murine Fab fragments. In autoradiography imaging studies, we obtained clearer tumor detection without visible uptake in normal organs for chimeric Fab fragments than for murine MAb. These results suggest that chimeric Fab fragments of A10 could be a potentially useful candidate for radioimmunodetection of pancreatic carcinomas.

Animals↗

Therapy and imaging of pancreatic carcinoma xenografts with radioiodine-labeled chimeric monoclonal antibody A10 and its Fab fragment.

Recombinant mouse/human chimeric monoclonal antibody A10 (ch-A10) and its Fab fragment (ch-Fab) react with carcinoembryonic antigen on various gastrointestinal carcinomas. We performed biodistribution studies with 125I-labeled ch-A10 and ch-Fab in an antigen-positive human pancreatic carcinoma (BxPC-3) xenograft model. We also evaluated the anti-tumor effect of 131I-labeled ch-A10, and studied the detection of BxPC-3 xenografts with 123I-labeled ch-Fab in whole body scintigraphy. In comparative biodistribution studies, the tumor uptake of 125I-labeled ch-A10 was significantly greater than that of 125I-labeled ch-Fab 24 h post-injection. However, the tumor-to-blood ratio was 46.8 for ch-Fab at 24 h post-injection, while it was only 1.4 for ch-A10. Microautoradiography studies showed that ch-Fab penetrated more uniformly into the tumor nodules than did ch-A10. In mice given a therapeutic dose of 131I-labeled ch-A10, a significant inhibition of tumor growth was seen, while control 131-I-labeled human IgG did not affect tumor growth. Leukocyte toxicity was observed within 3 weeks after injection of 131I-labeled ch-A10, but leukocyte counts recovered to normal levels at 8 weeks post-injection. In whole-body scintigraphy, clear and rapid tumor imaging was obtained with 200 microCi of 123I-labeled ch-Fab 24 h post-injection. These results suggest that radioiodine-labeled chimeric A10 antibodies could potentially be useful candidates for radioimmunotherapy and radioimmunodetection of pancreatic carcinomas.

Adult↗

[Retrospective analysis of postoperative chemotherapy with UFT against pancreatic cancer].

The retrospective study was carried out to evaluate the effect of UFT given orally in patients with histologically proven pancreatic cancer in our institutions for 6 years. The study regimen was designed as follows: 400 or 600 mg/body UFT per day after the patients having something solid evidences of tumor. For 6 years, 78 patients were entered in this protocol. Further details of the patients characteristics were as follows: head 47 (60.3%) cases, tail & body 31; resection cases 26 (33.3%), palliative 52; Stage IV 62 (79.5%) cases. Resection, P (peritoneal dissemination). H (liver metastasis) and T (tumor size) were statistically proven to be significant prognostic factors. The median survival time of UFT group was 204 days and that of non UFT group was 123 days. According to the retrospective analysis, there was a significant difference in the cumulative survival rate between UFT group and non UFT group with 1.98 of Hazard's proportional ratio (p = 0.009). However, further clinical investigations-prospective study are necessary to confirm these data.

Antineoplastic Combined Chemotherapy Protocols↗

Development and characterization of chimeric anti-carcinoembryonic antigen monoclonal antibodies and their Fab fragments.

In an attempt to reduce the immunogenicity of two different murine anti-carcinoembryonic antigen (CEA) monoclonal antibodies (MAbs), KM10 and A10, we produced recombinant mouse/human chimeric MAbs and the respective Fab fragments carrying the variable regions of the murine MAbs. Chimeric A10 Fab fragment was expressed in Escherichia coli, and produced in large quantities in a mini-jar fermentation system. In competitive binding assays, chimeric MAbs and their Fab fragments showed identical specificity to human CEA epitopes, as compared to the parental MAbs or Fab fragments. Both chimeric Fab fragments exhibited strong immunohistochemical reactivity with various gastrointestinal carcinomas and no reactivity with CEA-related antigens, such as NCA (nonspecific cross-reacting antigen) or BGPI (biliary glycoprotein I). Furthermore, chimeric KM10 MAb elicited substantially higher antibody-dependent cellular cytotoxicity than the murine MAb. Complement-dependent cytotoxicity in vitro was much weaker with chimeric KM10 MAb. These results indicate that chimeric MAbs or Fab fragments could potentially replace the parental murine antibodies or their Fab fragments in therapy or diagnosis of human gastrointestinal carcinomas.

Animals↗

[Treatment and present status of pancreatic cancer].

The Pancreatic Cancer Registry of the Japan Pancreas Society registered 11,317 patients of pancreatic cancer during these ten years. Among these patients, resectional procedures were performed on only 3,743 cases (33.1%). The actual 5-year survival rate of the patients who underwent resection was 16.6%. As for small cancer which was less than 2cm, the 5-year survival rate was 41.0%. In pancreatic cancer local recurrence was more frequent than other cancers of pancreatic head lesions. Extended operation which means lymphangiectomy more than R2 has not improved survival rate generally But some patients who underwent extended operation have survived long period. Multi-disciplinary treatment of pancreatic cancer has been tried.

Combined Modality Therapy↗