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H Tanimura

Publications and source records attributed to H Tanimura.

At least 37 records · Page 2Linked to original sources

[New therapeutic strategy against colon cancer based on a tumor-specific approach].

To develop a new therapy against colon cancer, we investigated two kinds of strategy using a cancer-specific approach. First, we employed the Cre/loxP regulation system to enhance the specific expression by carcinoembryonic antigen (CEA) promotor in CEA-producing tumor cells, and examined whether sufficient enhancement to transcriptional activity of CEA promotor, which maintains its specificity in vitro and in vivo, could be obtained. Next, using dendritic cells pulsed with HLA-A24 epitope peptides of CEA, we performed a Phase I study of active immunotherapy in patients with advanced colon cancer. These results suggest that the newly developed therapy for colon cancer is a promising strategy; however, minor modification may be necessary.

Antigen-Presenting Cells↗

P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer.

The resistance to doxorubicin (DOX) by some tumor cells is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. We tried to prove the correlations between P-glycoprotein expression and the sensitivity for anticancer drugs including DOX and other cytotoxic drugs that are currently used for gastrointestinal cancer patients. We quantified the P-glycoprotein expression by flow cytometry techniques, and the sensitivity for anticancer drugs using a tetrazolium salt, 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), assay in highly purified fresh human tumor cells obtained from 25 cancer patients. The inhibition rates were the lowest in DOX and mitomycin C (MMC), compared with other drugs. The most significant correlation between DOX and MMC was seen in the inhibition rates. A significant correlation was also seen between the inhibition rates for DOX and P-glycoprotein expression, whereas only a slight correlation between the sensitivity for MMC and P-glycoprotein expression was observed. We should therefore pay close attention to the effect of P-glycoprotein when treating cancer patients, especially if both the inhibition rates of DOX and MMC are low based on the findings of an MTT assay.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Establishment and analysis of biological characteristics of a human duodenal carcinoma cell line, WDC-1.

BACKGROUND: Duodenal carcinoma is very rare and its culture cell lines have rarely been established. METHODS: Tumor cells separated from a surgically resected primary tumor of duodenal carcinoma were put into culture. The patient was an 81-year-old female and had metastatic lymph nodes. We investigated the biological characteristics of the culture cells including in vitro cell kinetics, karyotype, expression of tumor markers and integrins and tumorigenicity and histology in nude mice. RESULTS: A new cell line, designated WDC-1, was established. This duodenal carcinoma cell line proliferated in a monolayered sheet with a doubling time of 50 h. The histological findings of the xenograft in nude mice were similar to those of the primary tumor. WDC-1 cells produced carcinoembryonic antigen and expressed 1 integrin and very late antigen (VLA)-4d in vitro. CONCLUSIONS: A duodenal carcinoma cell line was established, which is rare and may contribute to progress in understanding the biological features of duodenal cancer.

Adenocarcinoma↗

Antitumor effects of interleukin-2 gene-modified fibroblasts in an orthotopic colon cancer model.

We transduced the interleukin-2 (IL-2) gene into murine fibroblasts BALBCL7 or murine colon cancer CT26 using a retroviral vector. BALBCL7 transduced with IL-2 gene secreted 748 pg/ml of IL-2, whereas IL-2 gene-modified CT26 secreted 1,167 pg/ml of IL-2 (48 h incubation, 1x10(6)/ml). Then, we inoculated gene-modified BALBCL7 and/or CT26 cells into BALB/c female mice, and observed the tumor growth. The tumor growth was inhibited in mice inoculated with parental CT26 plus IL-2 gene-modified BALBCL7, compared with that in mice given parental CT26 alone (P<0.01). Moreover, we investigated the cytotoxic activity of spleen cells derived from mice treated with gene-modified cells, and performed phenotypic analysis of the effector cells. The killer cells derived from mice inoculated with IL-2 gene-modified BALBCL7 plus parental CT26 showed higher cytotoxic activity than those from mice inoculated with CT26 alone. The cytotoxic activity was almost completely blocked by anti-CD8 antibody (Ab), and partially blocked by anti-asialo GM1 Ab. Next, we inoculated CT26 tumor tissue into murine cecum orthotopically, and treated the animals with gene-modified BALBCL7 plus parental CT26. The tumor size in the cecum was significantly decreased, compared with parental CT26 alone (P<0.01).

Animals↗

Overexpression of multidrug resistance genes MDR1 and cMOAT in human hepatocellular carcinoma and hepatoblastoma cell lines.

Overexpression of either of the multidrug resistance genes MDR1 and MRP is associated with resistance of tumors to multiple chemotherapeutic agents. Overexpression of MDR1 has been reported in some cell lines derived from human hepatocellular carcinomas (HCC) and hepatoblastomas (HB). The human gene for cMOAT ( ), a homologue of MRP, is thought to mediate hepatobiliary excretion of organic anions and to be associated with cisplatin resistance. In this study, expression levels of MDR1 and cMOAT were examined in 9 human HCC and HB cell lines and 10 other human cancer cell lines. Overexpression of the cMOAT gene was observed in all 9 HCC and HB cell lines and 3 of 10 other cancer cell lines. Co-overexpression of the cMOAT and MDR1 genes was observed in 7 of 9 HCC and HB cell lines, but in none of the 10 other cancer cell lines. Seven of the HCC and HB cell lines that had overexpression of the cMOAT gene were shown to be highly resistant to cisplatin compared to 2 HCC cell lines with low levels of cMOAT expression. These findings suggest that overexpression of cMOAT could contribute to cisplatin resistance in HCC and HB.

Biological Transport, Active↗

Tumor specific CTL therapy for advanced cancer and development for cancer vaccine.

BACKGROUND/AIMS: Advanced gastrointestinal (GI) cancer is a virulent disease with a poor prognosis despite multidisciplinary treatment. The present study was designed to clarify the clinical effects of tumor specific cytotoxic T Lymphocyte (CTL) therapy as multidisciplinary treatment for patients with advanced cancer. METHODOLOGY: The enrolled advanced cancer patients had distant metastases derived from gastric cancer, colon cancer and bilio-pancreatic cancer. The patients had received the chemotherapy according to the results of chemosensitivity test and adoptive immunotherapy by various kinds of the activated killer cells. RESULTS: There was no severe toxicity, except fever and mild myelo-suppression. Six patients had complete response, and 18 patients had partial response out of 38 enrolled patients. The performance status was improved in responders (p<0.01); however, it was not changed in non-responders. Furthermore, the ratio of discharge of the responders was higher than that of non-responders. CONCLUSIONS: It was clarified that tumor-specific CTL therapy as multidisciplinary treatment is clinically valuable, especially in terms of quality of life. For developing the new strategy against cancer, CEA specific cancer vaccine trials have just started.

Antineoplastic Combined Chemotherapy Protocols↗

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents: special references to bacteria isolated between July 1996 and June 1997].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 20 facilities in Japan since July 1982. This paper describes the results obtained during period from July 1996 to June 1997. The number of cases investigated as objectives was 217 for one year. A total of 406 strains were isolated from 177 cases (81.6% of total cases). From primary infections 162 strains were isolated, and from postoperative infections 244 strains were isolated, respectively. From primary infections, anaerobic bacteria were predominant, while from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was the highest. In postoperative infections, the majority of them were Enterococcus faecalis, while in primary infections, many of them were Enterococcus avium. The isolation rate of Staphylococcus spp., especially from postoperative infections, followed that of Enterococcus spp. 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 the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by E. coli and Enterobacter cloacae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. The isolation rate of aerobic Gram-negative bacillus has decreased with time, while those of anaerobes like B. fragilis group and of aerobic Gram-positive bacteria have gradually increased in both types of infections. We found vancomycin-resistant strains of neither Staphylacoccus aureus nor Enterococcus spp.; however, the MIC of arbekacin for one of strains of S. aureus was 100 micrograms/ml. Both the MIC90's of meropenem and imipenem/cilastatin against P. aeruginosa isolated in this term were 25 micrograms/ml, which were higher than those against the strains isolated in the previous years. Compared with the isolated strains in the year 1995, progress of resistance against carbapenem antibiotics was confirmed.

Anti-Bacterial Agents↗

Limitations of differential display.

Since its original description, differential display PCR (DD-PCR) has been extensively used in attempts to identify novel genes under a variety of circumstances. Despite its widespread use, however, few novel genes of interest have been identified. In the present study we describe a set of experiments examining reasons for failure of differential display. Evidence is presented that aberrant priming at both the 5' and 3' ends results in competition in the PCR, precluding detection of messages other than those which are abundantly expressed. Appropriate calculations are discussed which indicate this was predictable and unlikely to be overcome. While DD may be successfully applied in some settings, the evidence indicates that only abundantly expressed messages can be detected. This limitation is emphasized.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Does Helicobacter pylori eradication depend on the period of amoxicillin treatment? A retrospective study.

In this study, the effect of different periods of amoxicillin (AMPC) treatment on the eradication rate of Helicobacter pylori in 173 patients with peptic ulcers (gastric ulcer, 109; duodenal ulcer, 64) was investigated. AMPC (1.5 g/day) was administered for 2, 4, or 6 weeks with omeprazole (20mg/day) and plaunotol (240mg/day), a mucoprotective drug, for 8 weeks. The H. pylori eradication rate was 46.7% for 2 weeks' treatment, 83.4% for 4 weeks' treatment, and 100% for 6 weeks' treatment. The eradication rate had a good correlation with the period of AMPC treatment. The healing rates of peptic ulcer at 4 and 8 weeks were 93.3% and 100%, respectively, in the 2-week group, 98.0% and 99.3% in the 4-week group, and 85.7% and 100% in the 6-week group. The recurrence rate of gastric and duodenal ulcers was 3.5% and 0% respectively, in the patients in whom H. pylori was eradicated and 30.0% and 40%, respectively, in the patients in whom H. pylori was not eradicated for 12 months after the H. pylori eradication treatment. Adverse effects of this regimen were observed in 5 (2.9%) of the 173 patients. Diarrhea was observed in 3 patients and eruption in 2. These adverse effects disappeared within a few days after only AMPC was withdrawn. Therefore, these may be caused by AMPC. The eradication rate of H. pylori depends on the period of AMPC treatment. This regiment, AMPC (1.5g/day) + omeprazole (20mg/day) + plaunotol (240mg/day), is safe and well tolerated for eradication of H. pylori.

Adult↗

Altered hepatic hemodynamics and improved liver function following intrahepatic vascular infusion of prostaglandin E1.

Prostaglandin E1 (PGE1) has cytoprotective effects in the liver. To find how PGE1 influenced hepatic hemodynamics, oxygen metabolism, and hepatic function, we carried out an experimental and a clinical study. PGE1 was continuously administered into the hepatic artery (n = 5) or portal vein (n = 5) at a rate of 0.01 micrograms/kg per min in healthy mongrel dogs. In the clinical study, in eight patients PGE1 was administered through the hepatic artery at a rate of 0.01 micrograms/kg per min after hepatic lobectomy. In the experimental study, hepatic hemodynamics and oxygen metabolism did not change during the administration of PGE1 into the portal vein. During administration of PGE1 into the hepatic artery, hepatic arterial flow increased 1.5-fold after administration compared to the rate before administration (P < 0.01). Hepatic arterial pressure, hepatic arterial resistance, and post-sinusoidal resistance significantly decreased after administration (P < 0.01, P < 0.01, and P < 0.05, respectively). Hepatic oxygen supply increased significantly (P < 0.01). In the patients, serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels remained low after surgery, and the recovery of protein synthesis was improved compared with that in eight hepatectomized patients without PGE1 administration (controls). The intrahepatic arterial infusion of PGE1 was considered useful for the recovery of liver function.

Aged↗

Intraoperative radiation therapy for a patient with bulky disease of mesenteric non-Hodgkin's lymphoma.

A long survival is rarely observed in patients demonstrating recurrent malignant lymphoma with bulky disease because of the appearance of chemoresistant tumor cells after extensive chemotherapy, and moreover the presence of bulky disease has also been consistently associated with a poorer response rate and a shortened survival, due to the fact that tumor size is the most significant factor for the treatment of non-Hodgkin's lymphoma. We herein describe a case of a 53-year-old woman presenting with the chief complaint of abdominal fullness, who underwent intraoperative radiation therapy (IORT) for recurrent bulky non-Hodgkin's lymphoma in the mesenterium. The patient has had no evidence of tumor recurrence, based on the findings of regular abdominal computed tomographic scans, 60 months after initial chemotherapy and 28 months after IORT.

Female↗

Successful immunochemotherapy for patients with malignant mesothelioma: report of two cases.

Malignant mesothelioma is a clinically aggressive tumor and has a poor prognosis; therefore, the selection of therapeutic strategies is important to improve the prognosis. Two patients with intraperitoneal malignant mesothelioma received combination therapy as follows: (1) case-oriented chemotherapy according to the results of a chemosensitivity test, and (2) adoptive immunotherapy using cytotoxic T lymphocytes (CTL). The chemosensitivity test was assessed by an MTT colorimetric assay. CTL was generated by a mixed culture with autologous tumor cells, and activated by immobilized anti-CD3 monoclonal antibody and interleukin-2. The MTT assay indicated that cisplatin and adriamycin were sensitive drugs in both patients, and they thus received the case-oriented chemotherapy according to the MTT assay. The activated CTL exhibited a high cytotoxicity against autologous malignant mesothelioma cells, and were transferred intraperitoneally. The patients were controllable for ascites, and the tumor masses gradually vanished (partial response). Chemoimmunotherapy is thus considered to be an effective treatment for intraperitoneal malignant mesothelioma, especially to improve the quality of life.

Adult↗

Clinical effect of immunochemotherapy for a patient with advanced gallbladder cancer: report of a case.

A 56-year-old woman was admitted presenting with a sensation of abdominal fullness. She was diagnosed to have advanced gallbladder cancer with carcinomatous peritonitis, as well as lymph node and liver metastases. We obtained highly purified tumor cells and tumor-infiltrating lymphocytes (TIL) from extirpated cervical lymph nodes and peritoneal effusion, and the chemosensitivity of these cells was tested with an MTT assay. Intensive chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU) was then performed according to the results of the MTT assay. Thereafter, cytotoxic T-lymphocytes (CTL) were induced in mixed cultures of autologous tumor cells and peripheral blood lymphocytes, and adoptive immunotherapy was performed with TIL and CTL. The malignant ascites and metastatic lesions disappeared after the intraperitoneal administration of CDDP and the transfer of TIL and CTL, and subsequently the patient's quality of life improved. This patient could return to work; however, liver metastasis was later observed, and she died 14 months after the initial diagnosis. Combination therapy with anticancer drugs and activated killer cells was thus found to be effective in a patient with advanced gallbladder cancer.

Adenocarcinoma↗

Perigastric lymph node status as a prognostic indicator in patients with gastric cancer.

BACKGROUND: The extent of lymph node dissection and histological examination of dissected lymph nodes varies among countries, which leads to the erroneous nodal stage and different surgical results in gastric cancer (stage migration, 'Will Rogers effect'). The aim of this study was to clarify the prognostic significance of the number of positive perigastric lymph nodes, which could be evaluated simply after D1 gastrectomy. METHODS: A consecutive series of 106 patients with histologically node-positive gastric cancer treated by radical gastrectomy and lymph node dissection (D2 or D3) was studied. The number of metastatic perigastric nodes (level I, nos 1-6) was examined, and its influence on the survival of patients was analysed. RESULTS: The overall 5-year survival rate was 50.9 per cent; the 5-year survival rate was significantly decreased when positive perigastric nodes exceeded six (62 per cent for one to six nodes versus 23 per cent for seven or more nodes, P< 0.001). Tumours having one to six positive perigastric nodes compared with those having seven or more positive perigastric nodes were more likely to have a size less than 4 cm (29 per cent versus one of 30, P< 0.001), grossly localized type (45 per cent versus seven of 30, P=0.042), absence of serosal invasion (32 per cent versus none of 30, P=0.002) and metastasis limited to the perigastric lymph nodes (70 per cent versus seven of 30, P < 0.001). CONCLUSION: The results indicate that the number of positive perigastric nodes correlates with tumour progression and patient survival. This parameter is a simple and useful prognostic indicator for node-positive gastric cancer, and is available not only for D2 and D3 gastrectomy but also for D1 gastrectomy.

Adult↗

[Deep-seated fungal infection in surgery].

In surgery, deep-seated fungal infection is not rare. In our institute, fungal infection was analyzed during postoperative periods. As pathogen, fungus was the second frequent pathogen after the operations for esophageal cancer and gastric cancer, and the third pathogen after hepatobiliopancreatic cancer and colon cancer. Furthermore, fungus was found more frequently pathogen from distant infection than that from local foci. Especially in CV catheter sepsis, fungus was main pathogen (60 %). In order to inhibit CV catheter sepsis, nutrition support team (NST) has been induced in our institute for prevention of external pathway of fungus. After NST, the frequency of CV catheter sepsis decreased from 12 % to 3.6 %, and the isolated frequency of fungus in catheter sepsis patients also decreased from 84 % to 16 %, respectively. It demonstrates that the activity of NST successfully prevents the external pathway of fungus in CV catheter indwelling patients. However, internal pathway (fungal translocation) still remains, and that issue has to be overcome. Molecular biological technique was applied for diagnosis of fungemia. PCR-RFLPs was performed by using specific primer of 18s rRNA in V4 region. Clinical samples were applied for PCR-RFLPs, and antifungal therapy was performed according as the results of PCR-RFLPs. It indicated that molecular biological technique was useful for diagnosis of fungemia.

Catheterization↗

[Adverse effects of intravenous fat emulsion administration].

Fat emulsion has been widely accepted a parenteral nutrient for the prevention of essential fatty acid deficiency and the supply of a high energy source. The following problems associated with the administration of fat emulsion are, however, well recognized: 1) The soy protein detected slightly in soy bean oil may induce allergic reactions. 2) Although administered in small quantities emulsified fat particles over 5 microns in diameter can cause fat emboli, including as pulmonary, splenic, placental, and cerebral emboli. 3) Hyperlipidemia may cause pulmonary hypertension and hemophagocytosis when triglycerides contained in the fat emulsion are intravenously administered at a rate greater than 0.1g/kg/hour. 4) Fat emulsion may have immunosuppressive effects, because emulsified fat particles phagocytized by the reticuloendothelial system reduce its functions. Long-chain triglyceride of the omega-6 series can suppress the functions of lymphocytes and neutrophils through prostaglandins. 5) Fungal infections, especially with Malassezia furfur which requires fat for growth, are sometimes associated with intravenous fat emulsion infused through a central venous catheter.

Fat Emulsions, Intravenous↗

Tumor size of colorectal cancer: indication for laparoscopic surgery.

Port site metastasis often occurs after laparoscopic colorectal resection of Dukes B and Dukes C tumors. To evaluate the feasible indication for laparoscopic surgery for the cure of colorectal cancer, we performed a clinicopathologic study with special reference to tumor size. A total of 233 patients who underwent curative resection of colorectal cancer at our department during 15 years were examined. There were 59 Dukes A tumors, and their mean size was 2.86 cm. Tumors < 2 cm, compared with tumors > 2 cm, were characterized by grossly superficial type (68% vs. 9%, p < 0.01), negative serosal invasion (95% vs. 24%, p < 0.01), and absence of lymph node metastasis (91% vs. 60%, p < 0.01). Among tumors < 3 cm, node-negative cases were distinguished by location in the colon (73% vs. 22%, p < 0.05) and by histologically well-differentiated type (75% vs. 11%, p < 0.01) in comparison with node-positive cases. All 14 patients with Dukes A tumor undergoing laparoscopic colectomy were free of recurrence during a mean follow-up period of 34 months. The results indicate that all cancers < 2 cm and well-differentiated colon cancers < 3 cm are good candidates for laparoscopic colorectal surgery for cure.

Adenocarcinoma↗