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H Tanimura

Publications and source records attributed to H Tanimura.

At least 19 recordsLinked to original sources

Helicobacter bilis infection in biliary tract cancer.

BACKGROUND: Biliary tract cancer is a highly fatal disease with poor prognosis, but the aetiology is poorly understood. AIM: We aimed to identify Helicobacter bilis infection in the gallbladder in patients with biliary tract disease. METHODS: Archival gallbladder specimens from 34 patients (14 males and 20 females) with an average age of 61.4 +/- 12.2 years (mean +/- SE) were retrieved, consisting of 11 cases of gallbladder cancer, three of bile duct cancer, 16 of cholecystolithiasis and four of pancreatic cancer. DNA was extracted and nested PCR using primers specific for 16S rRNA of H. bilis was performed. RESULTS: Amplification was observed in 3 of 11 gallbladder cancer cases (27.2%) and one of three cases with biliary duct cancer (33.3%). In total, four of 14 cases with biliary tract cancer were positive for H. bilis (28.6%). In addition, the presence of H. bilis was shown in two of 16 cases (12.5%) with cholecystolithiasis. Notably, although the number of cases examined was small, none of the four cases with pancreatic cancer showed the presence of H. bilis infection in the gallbladder without apparent abnormalities. CONCLUSION: H. bilis infection may play a role in biliary tract disease, particularly in biliary tract cancer.

Biliary Tract Neoplasms↗

Specific T-cell immunity against Ki-ras peptides in patients with pancreatic and colorectal cancers.

Mutations of codon 12 in the Ki-ras gene are frequently found in pancreatic and colorectal cancers. It has been demonstrated that human T-cells have the potential to recognise tumours expressing mutated ras-derived peptides. However, it remains unclear whether T-cells from a given individual can recognise the mutant peptides, which are expressed in that individual's tumour tissues. Mutations of the Ki-ras oncogene were analysed by the mutant-allele-specific amplification (MASA) method in pancreatic and colorectal tumour tissues, and T-cell responses against mutated Ki-ras-derived peptides were measured by [(3)H]thymidine incorporation and IFN-gamma production assays. Specific T-cell responses against Ki-ras-products were found in cancer patients, whereas no immune response was observed in normal individuals (P<0.01). Six of the eight pancreatic cancer patients (75%) and nine of 26 colorectal cancer patients (35%) had T-cell responses to mutated Ki-ras-derived-peptides. T-cell response in a given individual cannot recognise the same mutated ras peptide, which is expressed in that individual's tumour tissues. However, pancreatic and colorectal cancer patients have T-cell immunity against Ki-ras-peptides, and this provides potential target for cancer immunotherapy.

Cell Division↗

Carcinoembryonic antigen-specific suicide gene therapy of cytosine deaminase/5-fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric carcinoma model.

Tumor-specific gene delivery is crucial to achieving successful effects in suicide gene therapy. Carcinoembryonic antigen (CEA) promoter has been widely used for this purpose, but the expression level of tumor-specific promoters such as CEA promoter is generally low. In the previous study, we used the Cre/loxP system and showed that LacZ expression by the CEA promoter was remarkably enhanced and maintained its specificity using the Cre/loxP regulation system. In this study, the Cre/loxP system was first applied to augmentation of selective expression of the cytosine deaminase (CD) gene as a suicide gene therapy in CEA-producing cells. The double infection with AxCEANCre expressing Cre recombinase under the control of the CEA promoter and AxCALNLCD expressing the CD gene under the control of the CAG promoter by the Cre switching system rendered CEA-producing tumor cells 13-fold more sensitive to 5-fluorocytosine (5-FC) compared with the single infection with AxCEACD expressing CD gene driven by the CEA promoter. The therapeutic efficacy of the enhanced CD/5-FC suicide gene therapy was evaluated in orthotopic implantation models of human gastric carcinoma. Adenovirus vectors (1 x 10(9) plaque-forming units) were administered i.p. into mice three times, and then 5-FC was administered i.p. for the next 10 days. Tumor volume and weight in mice treated with AxCEANCre and AxCALNLCD/5-FC were significantly reduced as compared with those in mice treated not only with Mock (AxCALacZ) but also with AxCEACD/5-FC (P < 0.0001). This beneficial effect on tumor burden was also reflected in the overall survival. The survival periods of the mice treated with AxCEANCre and AxCALNLCD/5-FC were longer than those of mice treated with Mock or AxCEACD/5-FC (P < 0.01). These results suggested that application of the Cre/loxP system could provide a new approach for enhanced selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma.

Adenoviridae↗

Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide derived from wild-type p53.

Mutations in the p53 gene are the most common genetic alterations found in human tumours, and these mutations result in high levels of p53 protein in the tumour cells. Since the expression levels of wild-type p53 in nonmalignant tissue are usually much lower in contrast, the p53 protein is an attractive target for cancer immunotherapy. We tested p53 encoded HLA-A24 binding peptides for their capacity to elicit anti-tumour cytotoxic T lymphocytes (CTL) in vitro. These peptides were in murine p53-derived cytotoxic peptides, which were being presented to CTL by H-2K(d)and H-2K(b)molecules, because the HLA-A24 peptide binding motifs were similar to the H-2K(d)and H-2K(b). For CTL induction, we used CD8(+)T lymphocytes from the peripheral blood mononuclear cells (PBMC) of healthy donors and the peptides from pulsed dendritic cells as antigen-presenting cells. We identified the peptide, p53-161 (AIYKQSQHM), which was capable of eliciting CTL lines that lysed tumour cells expressing HLA-A24 and p53. The effectors lysed C1RA24 cells (p53(+), HLA-A*2402 transfectant), but not their parental cell lines C1R (p53(+), HLA-A,B null cell). These results strongly indicate that the CTL exerts cytotoxic activity in HLA-A24's restricted manner. The identification of this novel p53 epitope for CTL offers the possibility to design and develop specific immunotherapeutic approaches for treating tumours with p53 mutation in HLA-A24-positive patients.

Animals↗

Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER2 / neu: possible immunotherapy for colorectal carcinomas.

HER2 / neu is a potential antigen candidate for immunotherapy because of its correlation to a poor prognosis and high expressions in many kinds of epithelial tumours. Especially in the colorectal carcinomas, the higher expression of HER2 / neu is recognized in metastatic regions as well as in primary sites. Several CTL epitopes restricted by HLA-A2.1 and -A3 were identified so far, however epitopes restricted by HLA-A24, that is one of the most common allele in Japanese and Caucasians, have not been identified. In this paper, we showed identification of a CTL epitope peptide of HER2 / neu restricted by HLA-A24. HLA-A24 binding peptides selected by an analysis based on HLA-A24 binding motifs were determined for their binding affinities to HLA-A24 molecules. The peptide with a sequence of RWGLLLALL (position 8-16) named HE1 showed the highest affinity. We induced CTLs from CD8(+)cells of HLA-A24 healthy donors by stimulation with HE1-pulsed autologous dendritic cells. The CTLs showed cytotoxic activity against not only the peptide-pulsed target cells but also HLA-A24 colorectal tumour cell lines that endogenously overexpressed HER2 / neu. The antigen-specificity was confirmed by cold target inhibition assay using HE1-pulsed target cells. In summary, HER2 / neu peptide, RWGLLLALL, may contribute to the induction of antitumour immunity with the peptide-based immunotherapy for the colorectal carcinomas.

Colorectal Neoplasms↗

Clinical features and management of hepatic portal venous gas: four case reports and cumulative review of the literature.

HYPOTHESIS: Hepatic portal venous gas (HPVG) has been considered a rare entity associated with a grave prognosis. Since 1978, when Liebman et al reviewed 64 cases of HPVG and reported a mortality of 75%, the number of reported cases has been increasing. DESIGN: Case series. PATIENTS AND METHODS: We reviewed the literature on 182 cases of HPVG in adults, including 4 of our patients, (transplantation and abdominal trauma cases were excluded) and analyzed the cause, pathogenesis, and clinical features. RESULTS: In this series, the underlying clinical events associated with HPVG were bowel necrosis (43%), digestive tract dilatation (12%), intraperitoneal abscess (11%), ulcerative colitis (4%), gastric ulcer (4%), Crohn disease (4%), complications of endoscopic procedures (4%), intraperitoneal tumor (3%), and other (15%). The overall mortality was 39% but varied depending on the underlying disease. CONCLUSIONS: Hepatic portal venous gas is a lethal or curable entity caused by various diseases. The underlying disease associated with HPVG determines the clinical features and prognosis of the patients. The treatment of patients with HPVG should be directed to the underlying disease.

Aged↗

Complete response of highly advanced gastric cancer with peritoneal dissemination after new combined chemotherapy of S-1 and low-dose cisplatin: report of a case.

TS-1(S-1) has been developed as a new oral anticancer drug based on the biological modulation of 5-fluorouracil. We treated a patient with highly advanced gastric carcinoma with a new combination chemotherapy of S-1 and low-dose cisplatin. Remarkable tumor reduction was observed after two cycles of this therapy in the primary tumor and metastatic lymph nodes, and the ascites disappeared. This was concluded to be a partial response. The only adverse effect was skin pigmentation of the fingers (grade 1), leading to early timing of operation after chemotherapy. The gastric tumor showed evident invasion to the serosa. Lymph nodes around the stomach were swollen. Peritoneal dissemination was also recognized in the omentum and mesocolon. Total gastrectomy with regional lymph node dissection was performed. Disseminated tumors were all resected. Histological examination showed that no tumor cells were detected in the gastric primary lesion, metastatic lymph nodes or disseminated peritoneal tumors, suggesting pathological complete remission. It was suggested that this regimen could be a potent combined therapy for the treatment of patients with highly advanced gastric carcinoma, and it could be useful as neoadjuvant chemotherapy. Further studies are necessary to evaluate the efficacy of this therapy.

Adenocarcinoma↗

Adenosquamous carcinoma of the pancreas: successful treatment with extended radical surgery, intraoperative radiation therapy, and locoregional chemotherapy.

BACKGROUND: Adenosquamous carcinoma of the pancreas is a rare tumor with an extremely poor survival rate. No obvious evidence that multidisciplinary treatments improves the prognosis and survival has been reported. PATIENT AND RESULTS: A 63-yr-old female with adenosquamous carcinoma of the pancreas underwent extended radical surgery, intraoperative radiation therapy, postoperative intraarterial chemotherapy, and external beam radiation therapy. The patient is alive at 40 mo after surgery with no recurrence. CONCLUSIONS: Multidisciplinary treatments including aggressive surgery, intraoperative radiation therapy, and locoregional chemotherapy might improve the survival of patients with adenosquamous carcinoma of the pancreas to inhibit liver metastasis and local recurrence.

Antineoplastic Agents↗

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1998 and March 1999].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in Japan since July 1982. This paper describes the results obtained in fiscal 1998 (from April 1998 to March 1999). The number of cases investigated as objectives was 225 for one year. A total of 429 strains (121 strains from primary infections and 308 strains from postoperative infections) were isolated from 183 cases (81.3% of total cases). In primary infections, the isolation rates of anaerobes and Escherichia coli were higher than in postoperative infections, while in postoperative infections, those of Gram-positive aerobes and Pseudomonas aeruginosa were higher than in primary infections. On the whole, among Gram-positive aerobes, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus with high frequency in isolation from postoperative infections. Among Gram-positive anaerobes, Peptostreptococcus spp. and Streptococcus spp. were predominantly isolated. Among Gram-negative aerobes, E. coli, P. aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae were frequently isolated. Among Gram-negative anaerobes, Bacteroides fragilis group was the majority of isolates. In primary infections, the percentage of Gram-negative aerobes has gradually increased since fiscal 1995 or 1996 with these years as the turning point, while those of Gram-positive and Gram-negative anaerobes have gradually declined. In postoperative infections, the percentage of Gram-negative anaerobes has increased continuously since the mid-1980s. The percentage of MRSA among S. aureus rose to 89.7%, which was the highest level since the beginning of this study. The susceptibilities of B. fragilis, which did not show apparent changes, were recognized to have decreased against cephems in fiscal 1998. Among other bacteria in B. fragilis group, development of resistance to cephems has continued on a long-term basis since the mid-1980s. E. coli and K. pneuminiae have obviously not changed in susceptibilities, however, the susceptibilities of isolated strains in fiscal 1998 against high-generation cephems, oxacephems and monobactams have declined. We found neither vancomycin-resistant nor teicoplanin-resistant strains of S. aureus and Enterococcus spp.

Anti-Bacterial Agents↗

[Guidelines for adequate antibiotic prophylaxis after hepatic, biliary, and pancreatic surgery].

The recent spectrum of bacteria isolated from patients with hepatic, biliary, and pancreatic infections mostly consists of Gram negative rods translocated from their intestinal flora. Cephem or carbapenem antibiotics should be selected based on the severity of surgical infection and risk to each patient to prevent postoperative infections. Once postoperative infection occurs, surgical procedures such as ultrasonography-guided percutaneous biliary drainage should be performed to reduce inflammation and to obtain samples for bacterial culture. The most commonly identified bacteria after hepatic, biliary, and pancreatic surgery are Pseudomonas species, MRSA, and Enterococcus species. Previously administered antimicrobial agents should be immediately interrupted and empiric antibiotic therapy with carbapenem started. Vancomycin or teicoplanin is selected when MRSA or Enterococcus faecium infection is suspected. Infection control systems should be in place for prevention of postoperative MRSA infections.

Anti-Bacterial Agents↗

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer.

BACKGROUND AND OBJECTIVES: Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells. METHODS: Freshly isolated cancer cells from 20 patients with colorectal cancer and the established colon cancer cell lines were used in this study. The augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy-CPT (SN-38) was analyzed in combination with other anticancer agents. Furthermore, the antitumor effectiveness using lower concentrations of anticancer agents was measured to understand the mechanism of the augmentation. RESULTS: The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer. CDDP also had a synergistic effect in combination with SN-38 according to the fractional product concept. At lower than plasma peak concentrations of SN-38, the anticancer effects were augmented in combination with lower concentrations of CDDP for freshly isolated colorectal cancer. This augmentation showed a strong synergistic effect. CONCLUSIONS: These results may be supportive to ongoing clinical studies of chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer.

Adenocarcinoma↗

Enhanced selective gene expression by adenovirus vector using Cre/loxP regulation system for human carcinoembryonic antigen-producing carcinoma.

Selective gene targeting using the carcinoembryonic antigen (CEA) promoter is useful in gene therapy for gastrointestinal cancer. However, the expression of the CEA promoter is not sufficient. In this study, we tried to enhance CEA promoter activity using the Cre/loxP system. The double infection of CEA-producing cells such as MKN45 and LoVo with AxCEANCre and AxCALNLZ at a total multiplicity of infection (MOI) of 50 achieved 7-fold higher expression level of beta-galactosidase activity than single infection of those cells with AxCEALacZ at 50 MOI. On the other hand, the double infection of CEA-nonproducing cells such as MKN1 and HeLa cells showed a very low expression of beta-galactosidase activity. In the subcutaneous tumor models, the administration of AxCEANCre and AxCALNLZ into the CEA-producing tumor showed stronger expression of the LacZ gene in tumor tissue than that of AxCEALacZ. In the experiment using orthotopic models of CEA-producing gastric cancer, intraperitoneal double administration of AxCEANCre and AxCALNLZ caused evident LacZ gene expression in transplanted gastric tumors, but no LacZ gene expression in the normal stomach or liver. It was confirmed that enhanced tissue-specific gene transduction under control of CEA promoter using the Cre/loxP system was useful not only in vitro, but also in vivo, especially in orthotopic models.

Adenoviridae↗

Solid and cystic tumor of the pancreas: clinicopathologic and genetic studies of four cases.

BACKGROUND: Solid and cystic tumor (SCT) of the pancreas can be distinguished from other pancreatic neoplasms by its nearly exclusive occurrence in young women, and its favorable prognosis after complete resection. METHODS: We experienced four cases with SCT of the pancreas, and analyzed these tumors by immunohistochemical and electron microscopic studies, as well as genetic analysis of ras oncogene mutation. RESULTS: The presented cases expressed the neuron-specific enolase in two cases, alpha1-antitrypsin and alpha1-antichymotrypsin in two cases, and vimentin in one case, which indicated that this tumor originates from pleuripotential embryonic stem cells. No patients had mutations of K-ras gene in codon 12, and further genetic analysis is required to predict the malignant potential. CONCLUSION: SCT of the pancreas appears to have limited malignant potential and the metastatic ratio is not high, although the tumor has local invasion. Therefore, an aggressive surgical approach seems fully justified.

Adult↗

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1997 and March 1998].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 19 facilities in Japan since July 1982. This paper describes the results obtained during the period from April 1997 to March 1998. The number of cases investigated as objectives was 215 for one year. A total of 420 strains (170 strains from primary infections and 250 strains from postoperative infections) were isolated from 174 cases (80.9% of total cases). In primary infections, the isolation rate of anaerobic bacteria was higher than in postoperative infections, while in postoperative infections, those of aerobic Gram-positive bacteria and Pseudomonas aeruginosa were higher than in primary infections. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus, which was frequently isolated from postoperative infections. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by P. aeruginosa, Klebsiella pneumoniae in this order, and from postoperative infections, P. aeruginosa was most predominantly isolated, followed by E. coli and K. pneumoniae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. We found neither vancomycin nor arbekacin resistant strains of S. aureus, and found no vancomycin resistant strains of Enterococcus spp. The susceptibility of P. aeruginosa against carbapenems did not decline in the year 1997, while resistance of B. fragilis group against cephems advanced increasingly.

Anti-Bacterial Agents↗