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Biomedical subjects

T Kamigaki

Publications and source records attributed to T Kamigaki.

15 recordsLinked to original sources
PubMed2000

[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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

[KMO1].

Explore the source record for details and available documents.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

[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↗
PubMed1994

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↗
PubMed1992

[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↗