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Takashi Kamigaki

Publications and source records attributed to Takashi Kamigaki.

18 recordsLinked to original sources
PubMed2006

Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma.

Cancer immunotherapy by dendritic cell (DC)/tumor cell fusion hybrids (DC/TC hybrids) has been shown to elicit potent anti-tumor effects via the induction of immune responses against multiple tumor-associated antigens. In the present study, we compared the anti-tumor effects of vaccinating Balb/c mice (H-2(d)) with CT26CL25 colon carcinoma cells that had been fused with either syngeneic DCs from Balb/c mice, allogeneic DCs from C57BL/6 mice (H-2(b)) or semiallogeneic DCs from B6D2F1 mice (H-2(b/d)). Preimmunization with either semiallogeneic or allogeneic DC/TC hybrids induced complete protection from tumor challenge, whereas mice preimmunized with syngeneic DC/TC hybrids were only partially protected (75% tumor rejection). The average number of pulmonary metastases after intravenous tumor injection decreased significantly following immunization with semiallogeneic or allogeneic DC/TC hybrids (8.3 +/- 7.9 or 16.3 +/- 3.5, mean +/- SD) relative to syngeneic DC/TC hybrids (67.8 +/- 6.3). These data demonstrate that vaccination with semiallogeneic DC/TC hybrids resulted in the greatest anti-tumor efficacy. Anti-tumor effects showed by in vivo studies were virtually accomplished by the frequency of induced CTLs specific to both gp70 and beta-galactosidase assessed by using pentameric assay. Among the fusion vaccines tested, semiallogeneic DC/TC hybrids induced the highest ratio of Th1 cytokine IFN-gamma to Th2 cytokine IL-10. In addition, allogeneic or semiallogeneic DC/TC hybrids elicited a significantly stronger NK activity than syngeneic DC/TC hybrids. These findings suggest that in clinical settings, DCs derived from a healthy donor (which are generally characterized as more semiallogeneic than allogeneic) may be more capable than autologous DCs of inducing promising anti-tumor effects in vaccinations with DC/TC hybrids.

Adenocarcinoma↗
PubMed2006

Adenocarcinoma arising in gastric inverted hyperplastic polyp: a case report and review of the literature.

A 54-year-old man, found to have a submucosal tumor in the stomach by double contrast roentgenography, endoscopy, and endoscopic ultrasonography, underwent a laparoscopic partial gastrectomy. The pathological examination revealed that the lesion, measuring 45 mm x 35 mm, was an inverted hyperplastic polyp (IHP) located in the submucosal layer and consisting mostly of columnar cells resembling foveolar epithelium and pyloric gland cells. Notably, adenocarcinoma with adjacent dysplasia was observed in the submucosal glands. Transition from hyperplasia to dysplasia and from dysplasia to adenocarcinoma was noted. The adenocarcinoma component was intensely and diffusely positive for p53 overexpression, while the dysplasia component showed only weak and focal positivity, suggesting a role of p53 mutation in the dysplasia-carcinoma sequence. Gastric IHP is very rare, and only 31 cases (in 29 patients) have been reported. Five of these IHPs coexisted with gastric adenocarcinomas, which had all developed separately from the IHP lesions. Therefore, this is the first case of adenocarcinoma arising within gastric IHP itself.

Adenocarcinoma↗
PubMed2006

MDR1 T-129C polymorphism can be predictive of differentiation, and thereby prognosis of colorectal adenocarcinomas in Japanese.

The expression level of MDR1 mRNA was evaluated in colorectal adenocarcinomas and adjacent noncancerous colorectal tissues obtained from 21 Japanese patients. It was lower in the former than in the latter (p=0.012), suggesting its down-regulation as a consequence of malignant transformation of colorectal tissues, possibly with the suppression of differentiation. Relatively lower expression was suggested in moderately-differentiated colorectal adenocarcinomas than well-differentiated ones, but there was no statistical difference (p=0.111). MDR1 mRNA up-regulation was found in a colorectal adenocarcinoma cell line, HCT-15, after treatment with two typical differentiating agents, sodium butyrate and all-trans retinoic acid, suggesting its involvement in the cellular events, resulting in differentiation without malignant transformation. MDR1 T-129C, but not G2677A,T and C3435T, was associated with the lower expression of MDR1 mRNA both in colorectal adenocarcinomas (p=0.040) and adjacent noncancerous colorectal tissues (p=0.023), possibly being an useful invasive marker predicting poorly-differentiated colorectal adenocarcinomas and thereby the poor prognosis of the patients, especially when no extra biopsy samples will be obtained. Further investigations with relatively large number of patients should be undertaken to confirm these preliminary results.

Adenocarcinoma↗
PubMed2006

Correlation between expression of major histocompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the pancreas, biliary tract and colon.

To elicit a tumor immune response, tumor antigens represented by major histocompatibility (MHC) class I complex on the cell surface is indispensable. Some investigators demonstrated that many cancer cells reduce expression of beta2-microglobulin, a transporter of antigen presenting (TAP) or low molecular protein (LMP), due to the deletion mutant or point mutation. We investigated gene expression levels of antigen presenting machineries in 13 cell lines of the pancreas, biliary tract and colon cancer by using real-time quantitative PCR. We also evaluated the correlation between expression of MHC class I and that of antigen-processing molecules in these gastrointestinal cancer cell lines. Flow cytometric analysis showed that expression of MHC class I for the pancreatic cancer cell lines was generally lower than that for the biliary tract or colon cancer cell lines. It was further found that the colon cancer cell lines HCT-15/DLD-1 showed no MHC class I expression and lack of protein expression for beta2-microglobulin. Transfection of the wild-type beta2-microglobulin gene restored MHC class I antigen expression on the cell surface for DLD-1. Quantitative real-time PCR demonstrated lower expression for TAP1, TAP2, LMP2 and LMP7 gene in five cancer cell lines. Partial correlation analysis demonstrated that LMP2 was the only antigen presenting machinery which was significantly associated with MHC class I expression. Our results suggest that beta2-microglobulin and LMP2 are important for the expression of MHC class I in 13 gastrointestinal cancer cell lines, while the combined but complex expression of antigen presenting mechanisms was related to MHC class I expression level on the surface of cancer cells.

ATP-Binding Cassette Transporters↗
PubMed2006

[A case of unknown primary cancer responding to TS-1].

A 65-year-old male showed elevated tumor marker and intra-abdominal lymph node (LN) swelling. PET revealed an accumulation of FDG at para-aortic LNs from the mediastinum to the inguinal region. Although many different examinations were performed to detect primary cancer, none was found. We diagnosed unknown primary cancer (UPC), and administered TS-1 (100 mg/day). Six months later, the tumor marker lowered and the LN swelling reduced. PET showed a little accumulation of FDG at intra-abdominal LN. An intra-abdominal LN biopsy was performed, and an adenocarcinoma was seen at a lymph vessel. Then, 15 months later, brain metastasis was recognized and 18 months later the patient died of systematic metastasis. Autopsy was not performed, and primary cancer was not seen till the end. TS-1 proved effective for the UPC.

Adenocarcinoma↗
PubMed2006

Dendritic cell-tumor cell hybrids enhance the induction of cytotoxic T lymphocytes against murine colon cancer: a comparative analysis of antigen loading methods for the vaccination of immunotherapeutic dendritic cells.

Dendritic cells (DCs) have been used successfully for inducing effective anti-tumor immune responses in advanced cancer patients undergoing tumor-specific immunotherapy. Appropriate antigen pulsing is a crucial parameter for optimizing the efficacy of immunotherapy as well as anti-tumor protection therapy. Using a murine colon cancer model, we evaluated the anti-tumor efficacy of four different preparations of DC vaccines that contained either a whole tumor or its derivatives, including i) DCs pulsed with tumor lysate, ii) DCs pulsed with necrotic tumor cells, iii) DCs pulsed with apoptotic tumor cells, and iv) DC-tumor cell fusion hybrids. Our data show that DC-tumor cell fusion hybrids and DCs pulsed with irradiated apoptotic tumor cells were more potent than DCs with freeze-thawed necrotic tumor cells for the induction of protective anti-tumor responses. The vaccination of DCs pulsed with tumor lysate failed to elicit any anti-tumor effect. In animals administered with higher doses of a tumor-cell challenge, DC-tumor cell fusion hybrids elicited the most effective anti-tumor response. Among the preparations tested, mice immunized with DC-tumor cell fusion hybrids resulted in the greatest induction of cytotoxicity as measured by the cytotoxic T lymphocyte activity of both the splenocytes and the Thy1.2-positive T lymphocytes. Furthermore, the in vitro production of IFN-gamma polarized to the Th1 cytokine responses was highest in the splenocytes derived from mice vaccinated with DC-tumor cell fusion hybrids. Our results suggest that DC-tumor cell fusion hybrids are more potent inducers of protection against solid tumors, such as colon cancer, than other antigen-loading strategies using whole tumor cell materials.

Animals↗
PubMed2005

[KMO1].

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Antigens, Tumor-Associated, Carbohydrate↗
PubMed2004

Association of VEGF genotype with mRNA level in colorectal adenocarcinomas.

The mRNA expression of vascular endothelial growth factor (VEGF) was evaluated in colorectal adenocarcinomas and adjacent noncancerous colorectal tissues in 18 Japanese patients. The expression was confirmed to be up-regulated in the colorectal adenocarcinomas, when compared with the noncancerous tissues. Twelve genotypes of VEGF: six positions in the promoter region, two in the 5'UTR, and four in the 3'UTR, and their association with the expression of VEGF mRNA were evaluated. While G-1877A, T-1455C, G-1154A, C702T, and G1612A were not detected, C-2578A, T-1498C, G-1190A, C-634G, C-7T, C936T, and C1451T were found at allele frequencies of 4/36, 15/36, 15/36, 20/36, 8/36, 6/36, and 6/36, respectively, suggesting that C-2578A, G-1154A, and G1612A were associated with a decreased risk for colorectal adenocarcinoma. T-1498C (G-1190A) and C-7T were found to be associated with higher levels of VEGF mRNA, and may be a risk factor for the development of liver metastasis and/or prognosis of colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed2004

Chemosensitivity assessed by collagen gel droplet embedded culture drug sensitivity test, and MDR1, MRP1, and MRP2 mRNA expression in human colorectal adenocarcinomas.

PURPOSE: To evaluate chemosensitivity and its correlation with expression levels of the multidrug resistant transporter (MDR1) and the multidrug resistance-associated proteins 1 and 2 (MRP1, MRP2) mRNA in human colorectal adenocarcinomas. METHODS: Colorectal adenocarcinomas were obtained as surgical samples from 25 patients. The chemosensitivity of 12 anticancer drugs was assessed by the collagen gel droplet embedded culture drug sensitivity test (CD-DST). The expression levels of MDR1, MRP1, and MRP2 mRNA in colorectal adenocarcinomas were also evaluated by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The chemosensitivity was successfully evaluated for 16 of 25 patients, and the anticancer drugs were effective against the samples showing a relatively high growth rate. Gemcitabine hydrochloride was found to be more promising than those often prescribed for the treatment of colorectal adenocarcinoma. There was no correlation of the mRNA expression levels of MDR1 and MRP1 with the chemosensitivity of any anticancer drugs tested, but mitomycin C was found to be more effective for the colorectal adenocarcinoma with relatively high expression of MRP2 mRNA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Prevention of irinotecan-induced diarrhea by oral sodium bicarbonate and influence on pharmacokinetics.

Alkalization of the intestinal tract by oral administration of sodium bicarbonate has been reported to be a promising method for preventing delayed diarrhea, a dose-limiting toxicity in patients receiving chemotherapy with irinotecan hydrochloride. However, it is feared that this method may adversely affect the pharmacokinetics of irinotecan by inhibiting its intestinal absorption and that of its active metabolites. We compared the pharmacokinetics and toxicity of irinotecan with and without oral alkalization in a cross-over study that enrolled 10 colorectal cancer patients. We found that alkalization did not decrease the blood levels of irinotecan and its active metabolite. In fact, the area under concentration versus time curves (AUCs) of irinotecan and 7-ethyl-10-hydroxycamptothecin glucuronide (SN-38G) were statistically equivalent both with and without oral alkalization. Also, the AUC of SN-38 with alkalization was statistically equivalent or larger than that without alkalization. Oral alkalization reduced the incidence of diarrhea and gastrointestinal symptoms, and these adverse effects were not worsened by long-term administration. These results suggest that oral alkalization can control diarrhea and gastrointestinal toxicity without decreasing the blood levels of irinotecan and its active metabolites, thus improving the tolerability of long-term chemotherapy without reducing efficacy.

Administration, Oral↗
PubMed2004

MDR1, MRP1 and MRP2 genotypes and in vitro chemosensitivity in Japanese patients with colorectal adenocarcinomas.

In our previous paper, the chemosensitivity of human colorectal adenocarcinoma was evaluated against 12 anticancer drugs including 5-fluorouracil (5-FU), 7-ethyl-10-hydroxycamptothecin (SN-38), mitomycin C (MMC) and cisplatin (CDDP), and it was found that the anticancer drugs were effective against those with a relatively high growth rate. MMC was effective for those with a relatively high mRNA expression of the multidrug resistance-associated protein 2 (MRP2), whereas no correlation was found for the multidrug resistant transporter MDR1 and MRP1. In this study, 3 genotypes of MDR1, 4 genotypes of MRP1, and 6 genotypes of MRP2 were additionally evaluated, and it was suggested that MDR1 C3435T and MRP2 G1249A were related with the susceptibility to colorectal adenocarcinoma. The chemosensitivity against 5-FU, SN-38, MMC and CDDP was independent of MDR1 C3435T, MRP1 G2168A, and MRP2 C-24T (C3972T), possibly due to no association with the growth rate of and mRNA expression levels of MDR1, MRP1 and MRP2 in the adenocarcinoma, however, MDR1 C3435T tended to be accompanied with a higher expression of MDR1 mRNA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

An experimental study on the pharmacokinetics of 5-fluorouracil regional chemotherapy for pancreatic cancer.

BACKGROUND: Recently a few centers reported promising results of regional intra-arterial chemotherapy for pancreatic cancer. However, the detailed pharmacokinetics and the side effects of anticancer agents remain unclear. METHODS: Catheters were introduced into the gastroduodenal artery and the splenic artery of dogs. In group I, arterial infusion of 5-fluorouracil (5-FU) was performed over 10 minutes. In group II, 5-FU was infused systemically. In group III, an intra-arterial infusion was repeated weekly three times. Blood samples and liver and pancreas tissue samples were obtained to determine 5-FU levels. In a subset of each group, the pancreas, duodenum, and liver were excised for histological analyses. RESULTS: Immediately after the infusion of 5-FU, the portal level in group I was higher than that in group II. However, the mean systemic level in group I was lower than in group II. The mean tissue concentration in the pancreas in group I was significantly higher than that of group II. Histological examination revealed no microscopic alterations after treatment in all groups, including group III. CONCLUSIONS: This fundamental study suggested that intra-arterial chemotherapy of 5-FU for pancreatic cancer allows higher regional drug delivery without adverse effects on normal regions of the pancreas, the duodenum, and the liver.

Animals↗
PubMed2002

Suppression of human pancreatic carcinoma cell growth and invasion by epigallocatechin-3-gallate.

INTRODUCTION: The consumption of green tea is associated with a lower risk of several types of human carcinomas. A number of studies have focused on the possible mechanisms of cancer prevention by tea extracts, especially polyphenols such as epigallocatechin-3-gallate (EGCG). AIMS AND METHODOLOGY: Green tea-derived EGCG was tested in human pancreatic carcinoma cells. The cells (PANC-1, MIA PaCa-2, and BxPC-3) were treated with different doses of EGCG (0, 25, 50, 100, and 200 micromol/L) for 48 hours in culture medium. Proliferation of pancreatic carcinoma cells was measured by means of the WST-1 colorimetric assay. For the study of cell invasion, the cells were incubated with 100 micromol/L EGCG for 2 hours. Then, the cells were added into the cell insert, coated with Matrigel basement membrane matrix. After incubation at 37 degrees C for 24 hours, the cells that had invaded through the Matrigel were counted visually under the microscope. RESULTS: The growth of all three pancreatic carcinoma cells was significantly suppressed by EGCG treatment in a dose-dependent manner. EGCG treatment caused significant suppression of the invasive ability of pancreatic carcinoma cells PANC-1, MIA PaCa-2, and BxPC-3 but did not affect the cell cycle protein cyclin D1. CONCLUSION: EGCG may be a potent biologic inhibitor of human pancreatic carcinomas, reducing their proliferative and invasive activities.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Real-time quantitative polymerase chain reaction for MDR1, MRP1, MRP2, and CYP3A-mRNA levels in Caco-2 cell lines, human duodenal enterocytes, normal colorectal tissues, and colorectal adenocarcinomas.

The expression levels of mRNAs for MDR1 (P-glycoprotein), multidrug resistance-associated proteins (MRP1, MRP2), and cytochrome P450 3A (CYP3A) in Caco-2 cells were quantitatively compared with those in human duodenal enterocytes, normal colorectal tissues, and colorectal adenocarcinomas. Caco-2 cells (passages 36-88) were kindly supplied by several laboratories in Japan. Human duodenal enterocytes were obtained from five healthy male volunteers. Normal colorectal tissues and colorectal adenocarcinomas were simultaneously obtained from seven patients with primary colorectal adenocarcinoma. MDR1, MRP1, MRP2, and CYP3A mRNA levels were determined by real-time quantitative polymerase chain reactions (PCR). Relative concentrations of mRNAs for target proteins (MDR1, MRP1, MRP2, and CYP3A) and glyceraldehyde-3-phosphate dehydrogenase in Caco-2 cells were 1.00 +/- 0.15, 1.02 +/- 0.06, 0.94 +/- 0.10, and 0.68 +/-0.60, respectively, and those in human enterocytes were about 12-, 3-, 7-, and 8000-fold higher than in the Caco-2 cells, respectively. In contrast, MDR1, MRP1, and CYP3A mRNA levels in Caco-2 cells were comparable to those in normal colorectal tissue and colorectal adenocarcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Prognostic significance of S100A4 expression in gallbladder cancer.

The calcium-binding protein S100A4 has been characterized as a metastasis-inducing molecule, and regulates cell motility and invasiveness of cancer cells. In order to clarify the significance of the expression of S100A4 as a prognostic factor in gallbladder cancer, S100A4 expression in resected gallbladder cancers were examined using an immunohistochemical staining technique. The relationship between S100A4 expression and clinicopathological factors including prognosis were evaluated. Twenty-five of 60 cases (42%) demonstrated positive staining for S100A4. There was no statistically significant association between S100A4 and histological grade, T, N, M factor, presence of stone, or stage. Kaplan-Meier method showed the 5-year survival rate of the group staining positive for S100A4 (31.5%) to be statistically poorer than that of the group staining negative for S100A4 (78.2%). Also in T2 cases, the 5-year survival rate of the group staining positive for S100A4 (57.1%) was statistically poorer than that of the group staining negative for S100A4 (83.3%). On univariate analysis, positive staining for S100A4 was a significant prognostic factor, and the hazard ratio was 4.05. On multivariate analysis, positive staining for S100A4 is also a significant predictor of prognosis second to T factor. These results indicate that positive staining for S100A4 is useful in assessing the prognosis of patients with gallbladder cancer as well as TNM factors.

Aged↗
PubMed2001

New pancreatic duct-invagination anastomosis using ultrasonic dissection for nonfibrotic pancreas with a nondilated duct.

Nonfibrotic pancreases with a nondilated duct are susceptible to pancreatic fistula or leakage following pancreaticoduodenectomy. We developed a novel pancreatic duct-invagination anastomosis using an ultrasonic dissector and applied this technique to 14 consecutive pancreaticoduodenectomies and 1 segmental pancreatectomy for otherwise normal pancreases. With the aid of an ultrasonic dissector, even branch pancreatic ducts were skeletonized, ligated securely, and divided during pancreatic transection. Moreover, the main duct was exposed (> 1 cm) easily by ultrasonic dissection and a small-caliber pancreatic tube was inserted into the duct on the stump. Subsequently, pancreatic duct invagination could be easily done through a 10 G intravenous catheter passed through the gastrointestinal tract. The main duct was anchored to the adjacent serosa, but any pancreatic parenchymal sutures, possibly leading to internal laceration and/or parenchymal ischemia particularly in soft nonfibrotic pancreases, were avoidable during the procedures. All the anastomoses were done within 10 minutes. Only 1 patient (6.7%)developed pancreatic fistula, which resolved spontaneously in 21 days postoperatively. Neither anastomotic leakage nor remnant pancreatitis was seen in this series. Although a prospective, randomized study is needed, this technique may contribute to reduced morbidity after pancreaticoduodenectomy for a nonfibrotic pancreas with a nondilated main duct.

Aged↗
PubMedDate not supplied

Thymidylate synthase and dihydropyrimidine dehydrogenase expressions in gallbladder cancer.

BACKGROUND: Although 5-Fluorouracil (5-FU) is widely used in chemotherapeutic treatment for gallbladder cancer, there is little evidence of its effectiveness. Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are the major determinants of individual sensitivity to 5-FU, and the impact of TS and DPD expression on prognosis and 5-FU efficacy has been studied in gastrointestinal carcinomas. MATERIALS AND METHODS: TS and DPD enzymatic activities in frozen samples of 7 gallbladder cancer tissues and immunohistochemical TS and DPD protein expressions in 53 resected gallbladder cancers were evaluated. RESULTS: The DPD activity of gallbladder cancers was significantly higher than that of gastric and colon cancers (p=0.041). TS and DPD protein expressions increased in pT2 and pT3 cases compared to those in pT1 cases, and cases both with high TS and DPD expressions had a worse prognosis than both low TS and DPD expressions. However, TS and DPD expressions were not independent prognostic factors. CONCLUSION: TS and DPD protein expressions in gallbladder cancers were frequently high in pT2 and pT3 gallbladder cancers and control of high TS or DPD levels may be important for advanced gallbladder cancer therapy.

Aged↗