{"title":"Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent.","authors":"Haruna Satoh, Kazuhiro Nishikawa, Kazuyuki Suzuki, Ryuji Asano, Nantiga Virgona, Tomio Ichikawa, Kiyokazu Hagiwara, Tomohiro Yano","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Genistein is a major component of soybean isoflavone and has preventive effect against breast cancer. In breast cancer, the over-expression of HER-2 contributes to malignant transformation of the cancer cells. The present study was undertaken to estimate if genistein could act as a useful anti-cancer agent against a breast cancer cell overexpressing HER-2 in combination with a conventional chemotherapy agent, adriamycin (ADR). Genistein enhanced cytotoxic effect of ADR at low doses less than IC50 against the human breast cancer cell. The enhancing effect was mainly dependent on the elevation of necrotic-like cell death but not apoptotic cell death. In conjugation with this event, remarkable inactivation of HER-2 and Akt in the breast cancer cell was caused by the combination of genistein and ADR. These results suggest that genistein enhances necrotic-like cell death of the breast cancer cells through the inactivation of HER-2 receptor and Akt in combination with ADR.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"149-58"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24935446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hilary P Benton, Angelica V Esquivel, Amber D Rice, Shri N Giri
{"title":"Modulation of articular chondrocyte activity by pirfenidone.","authors":"Hilary P Benton, Angelica V Esquivel, Amber D Rice, Shri N Giri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pirfenidone is under investigation as an anti-inflammatory and anti-fibrotic agent in several organs including lung. Since important features of arthritic conditions include inflammation and long-term damage to articular cartilage, we have investigated whether PD can suppress chondrocyte responses to bacterial lipopolysaccharide (LPS) and interleukin 1 (IL-1); modulators that induce a cascade of inflammatory responses that lead to articular joint tissue damage. PD (0 - 5microM) showed no effect on cell number or viability when incubated with high density primary equine chondrocyte cultures for a 24 hr period. PD did not stimulate nitric oxide (NO) release by chondrocytes when added alone but LPS and IL-1-induced NO release was inhibited by PD, in a dose-dependent manner. PD did not significantly influence GAG release from cartilage matrix nor did it stimulate or suppress the GAG releasing actions of LPS or IL-1. We conclude that PD is capable of attenuating the cytokine-induced production of the inflammatory mediator, NO by chondrocytes, without stimulating matrix glycosaminoglycan loss from cartilage. PD may have potential as an anti-inflammatory agent in the joint.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"275-88"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Accelerated acetylcholine metabolism in the lung after infusion of phenylephrine in dogs.","authors":"Tsutomu Nakahara, Hiroaki Nejishima, Koichi Nakayama, Kunio Ishii","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We investigated whether continuous administration of an a-adrenergic agonist, phenylephrine, could affect acetylcholine metabolism within the pulmonary circulation in anesthetized dogs. Infusions of phenylephrine at 3 microg/kg/min for 120 min shifted the dose-response curve for the depressor responses produced by acetylcholine (0.03-10 micro g/kg) injected into the right atrium to the right by about 30-fold. In contrast, the magnitude of the rightward shift in the dose-response curve for the depressor responses produced by acetylcholine injected into the left ventricle was only 3-fold. These results suggest that continuous administration of alpha-adrenergic agonists accelerate acetylcholine metabolism within the pulmonary circulation.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"201-6"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anastasios A Mihas, Vijaya K Kanji, Thanos A Mihas, Roy M Joseph, Angel K Markov, Douglas M Heuman
{"title":"Fructose diphosphate attenuates the acetaminophen-induced liver injury in the rat evidence for involvement of nitric oxide.","authors":"Anastasios A Mihas, Vijaya K Kanji, Thanos A Mihas, Roy M Joseph, Angel K Markov, Douglas M Heuman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have previously shown that fructose-1,6-diphosphate (FDP) stimulates the synthesis of nitric oxide probably by stimulating the hepatic inducible nitric oxide synthase (iNOS). The aim of the present study was to evaluate the hepatoprotective role of FDP in acetaminophen-induced liver injury and whether this hepatoprotective effect is mediated by nitric oxide. Liver injury was induced in adult Sprague-Dawley rats by the administration of acetaminophen (1.6 g/kg by gavage) 10 min prior to the intraperitoneal injection of either FDP or normal saline. Liver injury was assessed by alanine aminotransferase (ALT) activity in the serum. iNOS and malondialdehyde (MDA) levels were determined in liver homogenates. Acetaminophen produced striking elevations of serum ALT, high MDA levels and a profound decrease in the liver iNOS. Administration of FDP attenuated the ALT and MDA elevations and prevented the liver iNOS depletion caused by acetaminophen. Pretreatment of the animals with the iNOS inhibitor L-NAME abolished this hepatoprotection. These findings suggest that FDP protects against acetaminophen-induced liver injury, at least partly, by stimulating production of nitric oxide.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"253-66"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toshiyuki Kimura, Tomomi Shimizu, Tatsuya Funahashi, Mayumi Nagakura, Kazuhito Watanabe, Kuniomi Tachibana, Shigemi Kondo, Ing Kang Ho, Ikuo Yamamoto
{"title":"N3-phenacyluridine as a new type of antinociceptive compound in mice.","authors":"Toshiyuki Kimura, Tomomi Shimizu, Tatsuya Funahashi, Mayumi Nagakura, Kazuhito Watanabe, Kuniomi Tachibana, Shigemi Kondo, Ing Kang Ho, Ikuo Yamamoto","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The antinociceptive activity of N3-phenacyluridine, a novel hypnotic, was examined with tail pinch, hot plate and acetic acid-induced abdominal constriction methods by intracerebroventricular (i.c.v.) injection to mice. In the first method, N3-phenacyluridine exerted antinociceptive activity after the i.c.v. injection at a dose of 0.5 micromol/mouse, although this activity was comparable to the activity of morphine (0.01 micromol/mouse, i.c.v.). In the second method, the activity of N3 -phenacyluridine was continued until 120 min after the injection at a dose of 0.5 micromol/mouse. In last, N3-phenacyluridine (0.1 micromol/mouse, i.c.v.) significantly decreased in the numbers of acetic acid-induced abdominal constriction as compared to the control (1% Tween 80 saline). The ED50 value of the antinociceptive activity of N3-phenacyluridine was 0.02 imol/mouse, i.c.v. The present paper demonstrated for the first time that N3-phenacyluridine belonging to oxopyrimidine nucleoside analogue possesses not only the hypnotic and sedative activities previously reported, but also antinociceptive activity.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"57-65"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhanced expression of PP1gamma1, a catalytic subunit isoform of protein phosphatase type1 and expression of telomerase activity in Ewing's sarcoma cells.","authors":"Satoshi Mori, Yongping Cao, Takahisa Yamadab, Kenichi Sogawa, Kazuya Kondo, Norifumi Hino, Tatsuhiko Miyazaki, Yoji Kawaguchi, Shiro Oka, Kojiro Kawasaki, Tasuku Mashiba, Hiromichi Norimatsu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We previously reported that PP1gamma1 is highly expressed in osteosarcoma and chondrosarcoma, and suggested that this protein plays a role in malignancy of osteogenic tumors. In this study, we investigated the correlation of the expression of PP1gamma1 with telomerase activity. PP2A protein was not positive in any of the 5 cases of Ewing's sarcoma, but PP1gamma1 protein was strongly positive in all cases. Furthermore, malignant cells had high telomerase activity. We investigated the correlation of the expression of PP1gamma1 with telomerase activity, and showed that telomerase activity is regulated by protein phosphorylation in Ewing's sarcoma cells.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"269-74"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fas/Fas-ligand expressions in peripheral-blood mononuclear cells of patients with myelodysplastic syndromes.","authors":"Toshihiko Hirano, Noriko Hiratsuka, Tohru Iwahori, Kitaro Oka, Kazunori Wakasugi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Increased expressions of Fas and Fas-ligand (Fas-L) in bone marrow cells of myelodysplastic syndromes (MDS) have been reported, and large number of these \"cell-death signals\" might explain molecular basis for exacerbation of apoptosis in marrow cells of these syndromes. However, expression of these molecules or progression of apoptosis in peripheral-blood mononuclear cells (PBMCs) in MDS has little been investigated. In the present study, we compared expression of these cell-death molecules and percentages of apoptotic cells in PBMCs between MDS patients and healthy subjects. PBMCs were obtained from 7 MDS patients and 8 age-matched healthy controls. Five out of 7 patients were MDS with refractory anemia (RA) type, while the other 2 were MDS-RA with excess of blasts (MDS-RAEB) type. Percentages of PBMCs expressing Fas, Fas-L, and phosphatidylserine as a cell apoptosis-marker were determined by staining cells with FITC-labeled anti-CD95 (Fas) antibody, biotinyl anti Fas-L antibody, and annexin V, respectively. The cells were subsequently analyzed with flow cytometry. The mean (SD) percentage of Fas-expressing PBMCs in MDS group was 55.3 (13.9), whereas the value in healthy subjects was 30.6 (8.8) %, and thus the ratio of Fas positive cells in PBMCs of MDS was significantly higher than that of healthy subjects (p < 0.002). In contrast, the mean (SD) of Fas-L expressing PBMCs in MDS (n=5) was 18.4 (12.2) %, which was significantly lower (p < 0.02) than that in healthy subjects (34.4 +/- 8.1%; n=7). The mean (SD) of apoptotic PBMCs detected as annexin V-positive, non-necrotic cells in MDS (n=7) was 23.3 (7.5) %, which was not significantly different from that in healthy subjects (22.2 +/- 7.8%; n=8). Thus, PBMCs in MDS express high levels of Fas, whereas they conversely exhibit low levels of Fas-L, which may result in prevention of apoptosis by the death signals, and in cell-survival in these cells.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"315-28"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The relationship between oxidative metabolism and lipid peroxidation in rat liver microsomes.","authors":"Bin Ji, Y Masubuchi, T Horie","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>7-ethoxycoumarin was not found to induce lipid peroxidation in rat liver microsomes, although it was reported to cause lipid peroxidation in rat cultured hepatocytes. The productions of thiobarbituric acid reactive substances (TBARS) and chemiluminescence (CL) in the presence of some drugs including tolbutamide, naproxen and salicylic acid and their oxidation activities were determined. There was a negative correlation between extent of oxidative stress and oxidation activities. These results suggested that the oxidative metabolism of these drugs did not directly contribute to the microsomal peroxidation reaction. In addition, naproxen-induced microsomal lipid peroxidation was found to occur in rat, but did not in guinea pig.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"181-92"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of intravenous torasemide in rats.","authors":"Ae K Lee, Eun J Kim, Myung G Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Pharmacokinetic and pharmacodynamic parameters were evaluated after an intravenous administration of torasemide at a dose of 10 mg/kg to control rats and rats with acute renal failure induced by uranyl nitrate (U-ARF). In rats with U-ARF, the total area under the plasma concentration-time curve from time zero to time infinity (AUC) was significantly smaller (6380 versus 4450 microg min/ml) than that in control rats. This was due to significantly faster total body clearance (1.57 versus 2.25 ml/min/kg) in the rats. The faster total body clearance in rats with U-ARF could be due to significantly faster nonrenal clearance (1.51 versus 2.22 ml/min/kg due to faster metabolism) since renal clearance (0.0365 versus 0.00199 ml/min/kg) was significantly slower (due to impaired kidney function) than that in control rats. The 8-h urine output was significantly smaller in rats with U-ARF (178 versus 22.0 ml/kg), however, the 8-h urinary excretion of sodium, potassium, and chloride were not significantly different between two groups of rats.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"193-200"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of different de-endothelization procedures in the isolated rat thoracic aorta: a short communication.","authors":"C Uluoglu, H Zengil","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The aim of this study was to compare the effects of different techniques used for deendothelization on responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators and vasoconstrictor (phenylephrine) in the isolated rat thoracic aorta. Four different methods were used for de-endothelization: (1) mechanical (wire), (2) physical (distilled water), (3) chemical (Triton X-100 and saponin) and (4) enzymatic (trypsin). The results showed that mechanical rubbing with rough-surfaced wire was the most effective procedure amongst five different techniques used for deendothelization in the isolated rat thoracic rings. Denudation by wire abolished endothelium-dependent relaxation successfully without much interfering smooth muscle vasodilating and contracting properties of the agonists. It seems that physical, chemical and enzymatic techniques are not suitable for endothelial denudation in the isolated thoracic rat aorta preparations. These endothelium removing methods may be useful for studying the role of endothelium in vascular beds or small diameter vessels whose endothelial cells can not be removed mechanically.</p>","PeriodicalId":21045,"journal":{"name":"Research communications in molecular pathology and pharmacology","volume":"113-114 ","pages":"289-97"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24936308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}