Biomedical subjects

Michio Ogawa

Publications and source records attributed to Michio Ogawa.

79 records · Page 5Linked to original sources

PubMedDate not supplied

Hepatic injury induced by interleukin-18 administration: importance of preceding priming effect.

The priming effects of obstructive jaundice by bile duct ligation on interleukin (IL)-18-induced hepatic injury are investigated. The production of IL-12 and tumor necrosis factor-alpha increased 3 days after bile duct ligation. Subsequent IL-18 injection to rats with obstructive jaundice caused by BDL resulted in prominent interferon-gamma production and hepatic injury. These results suggest that IL-18 with IL-12 and/or tumor necrosis factor-alpha have synergistic effects on the induction of hepatic injury via interferon-gamma production on this model.

Animals↗

PubMedDate not supplied

Increased concentrations of plasma interleukin-18 in patients with hepatic failure 1 week after surgery.

We investigated the dynamic aspects of circulatory interleukin (IL)-18 in patients who underwent a hepatectomy. In patients with hepatic failure after surgery, plasma concentrations of IL-6 and IL-10 increased in the early phase; however, the plasma concentrations of IL-18 increased in the later phase after 1 week. Interestingly, the increase in the plasma IL-18 concentration was correlated with that in serum bilirubin levels in hepatectomized patients. Hence, the decrease in the hepatic metabolism of IL-18 may cause the plasma accumulation of IL-18. This mechanism was confirmed using rat experiments. Intravenously administrated human IL-18 was excreted in bile. Furthermore, the plasma clearance of human IL-18 was prolonged in bile-duct-ligated rats. These results suggest that IL-18 is metabolized in the liver and excreted in bile, and an increase in plasma IL-18 in patients with hepatic failure reflects the decreased metabolism in the liver.

Biomarkers↗

PubMedDate not supplied

Immunohistochemical expression of SKALP/elafin in squamous cell carcinoma of human lung.

The immunohistochemical expression of skin-derived anti-leukoproteinase (SKALP)/elafin in lung squamous cell carcinoma (SqCC) and in uninvolved bronchial epithelium was studied. The results were compared with the immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and the TDT-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. SKALP/elafin was expressed in SqCC with high incidence (82.6%). By contrast, the expression was not observed in uninvolved bronchial epithelium. SKALP/elafin expression was located in the cell layers just underneath the cornified envelope of each cell nest, and DNA fragmentation was observed in the same cell layers. PCNA was expressed in the basal layer of each cornified envelope, and both expressions were clearly separated. Immunoreactive score of SKALP/elafin expression was significantly correlated with the differentiation and it tended to increase in accordance with the degree of differentiation. These results suggested that SKALP/elafin was possibly involved in the cell differentiation program, finally leading to keratinization in SqCC of human lung. SKALP/elafin may be a beneficial molecular target for detection or even the development of a new therapeutic method against cancer.

Aged↗

PubMedDate not supplied

Outpatient therapy with irinotecan and low-dose cisplatin for metastatic colorectal cancer resistant to 5-fluorouracil.

Chemotherapy with irinotecan hydrochloride and low-dose cisplatin was tested for the treatment of metastatic colorectal cancer showing resistance to 5-fluorouracil. Eleven consecutive patients with advanced metastatic colorectal cancer (performance status: 0 to 2), who had shown tumor progression on chemotherapy with 5-fluorouracil/leucovorin, were treated with irinotecan (60 mg/m2) plus cisplatin (6 mg/m2) by 90-min intravenous infusion. Treatment was repeated weekly for 3 weeks during admission and then fortnightly on an outpatient basis. Objective responses were observed in four patients (36%; 95% confidence interval: 11%-69%). The median duration of response was 5.5 months and six patients are still alive. The time to disease progression was longer in the no change group (7.0+/-3.6 months: mean +/- SD) than in the responder group (5.5+/-1.9 months), and there was no difference of median survival between the two groups (10.0 versus 10.3 months). The overall median survival was 8.2 months (range: 4 to 12+ months). This treatment was well tolerated. Six patients experienced grade 1 or 2 leucopenia, while grade I diarrhea and nausea occurred in three and five patients, respectively. Based on the good response, excellent quality of life, and convenience, the present regimen seems to be reasonable second-line outpatient chemotherapy for patients with metastatic colorectal cancer showing resistance to 5-fluorouracil.

Adenocarcinoma↗

PubMedDate not supplied

Second-line chemotherapy with combined irinotecan and low-dose cisplatin for patients with metastatic gastric carcinoma resistant to 5-fluorouracil.

Although 5-fluorouracil (5-FU) is still the mainstay of systemic treatment for patients with metastatic gastric cancer, many patients do not show satisfactory response to this drug. We treated patients with metastatic gastric cancer resistant to 5-FU with a combination of irinotecan hydrochloride (I) and low-dose cisplatin (P). Twenty-one consecutive patients with advanced metastatic gastric cancer and performance status of 0-2, who had received prior chemotherapy with S-1, but had nonetheless shown unrelenting tumor progression, were treated with 60 mg/m(2) of I combined with 6 mg/m(2) of P, administered by intravenous infusion over 90 min following premedication with azasetron (I/low-P). I/low-P was repeated weekly for 3 weeks with the patient admitted to hospital, and thereafter, fortnightly on an outpatient basis. Seven, eight and six of the total of 21 patients had liver metastases, lymph node metastases and peritoneal dissemination, respectively. Objective response was observed in 11 of the 21 patients (52%; 95% confidence interval: 31-78%). Two (18%) and nine (82%) of these 11 patients exhibited complete and partial response, respectively. The median duration of the response was 7.9 months. The treatment regimen under study was tolerated very well by the patients. Thirteen of the 21 patients (62%) developed grade 1 or 2 leucopenia, which was the most common adverse reaction recorded. Diarrhea and nausea, grade I in all of the cases, occurred in five (22%) and nine (43%) patients, respectively. Based on its remarkable effectiveness, marked improvement in the quality of life of the patients, and the convenience of its administration, the I/low-P regimen is recommended as a promising second-line chemotherapeutic regimen for patients with metastatic gastric cancer resistant to 5-FU.

Adult↗

PubMedDate not supplied

Immunohistochemical analysis of estrone sulfatase and aromatase in human breast cancer tissues.

We examined, by immunohistochemical analysis, the expression of aromatase and estrone sulfatase (E1-STS) which are the two major enzymes involved in in situ estrogen synthesis in breast cancer tissue. In the 83 cases examined, E1-STS, which hydrolyses estrone sulfate (E1S) to estrone (E1), was dominantly detected in tumor cells in 43 (59.0%) cases. Aromatase, which converts androgens to estrogens, was dominantly detected in stromal cells of the tumor. It was detected in 39 (47.0%) of the 83 cases. There was no significant correlation between the expression of these two enzymes and clinicopathological factors. We found a tendency for a correlation between aromatase expression and E1-STS expression in breast tumor (p=0.075). In terms of the possible use of these enzymes as prognostic indicators, patients who had aromatase in their tumor showed longer relapse-free survival than those lacking aromatase (p=0.045). Significant correlations between the expression of aromatase and the angiogenesis regulators, vascular endothelial growth factor and thymidine phosphorylase, were found (p=0.047 and p=0.046, respectively), though the presence of aromatase did not correlate with intratumoral microvessel density. This may indicate that aromatase is involved in vascular permeability and recruitment of endothelial cells rather than neovascularization. It may be useful to study the expression of aromatase and E1-STS using immunocytochemical analysis for understanding the tumor characteristics in breast cancer.

Adult↗

PubMedDate not supplied

Heat shock protein 105 is overexpressed in a variety of human tumors.

We earlier reported that heat shock protein 105 (hsp105), which we identified by serological analyses of recombinant cDNA expression libraries (SEREX), was overexpressed in human colon and pancreatic adenocarcinoma. We went on to examine hsp105 expression in various colorectal cancers and adenomas, using immunohistochemical analysis. The 44 of 53 patients with colorectal cancers (83.0%) and only 2 of 21 (9.5%) with colorectal adenomas had an evident overexpression of hsp105, which means that overexpression of hsp105 is a late event in the colorectal adenoma-carcinoma sequence. Subsequently, we asked if hsp105 was overexpressed in other human tumors. During immunohistochemical studies, we discovered that overexpression of hsp105 occurred not only in cases of colorectal and pancreatic adenocarcinoma, but also thyroid, esophageal, breast, and bladder carcinoma and islet cell tumor, gastric malignant lymphoma, pheochromocytoma, and seminoma. On the other hand, hsp105 was evidently overexpressed only in the testis in human adult normal tissues. Thus, hsp105 is a useful marker of a variety of human tumors and hsp105 may prove to be a target molecule for designing anti-tumor immunotherapy.

Blotting, Northern↗