The modifying potential of capsaicin (CAP) on lesion development was examined in a rat multiorgan carcinogenesis model. Groups 1 and 2 were treated sequentially with diethylnitrosamine (DEN) (100 mg/kg, ip, single dose at commencement), N-methylnitrosourea (MNU) (20 mg/kg, ip, 4 doses at days 2, 5, 8, and 11), and N,N-dibutylnitrosamine (DBN) (0.05% in drinking water during weeks 3 and 4). Group 3 received vehicles without carcinogens during the initiation period. Group 4 served as the untreated control. After this initiating procedure, Groups 2 and 3 were administered a diet containing 0.01% CAP. All surviving animals were killed 20 weeks after the beginning of the experiment and the target organs examined histopathologically. The induction of GST-P+ hepatic foci in rats treated with carcinogens was significantly inhibited by treatment with CAP. CAP treatment significantly decreased the incidence of adenoma of the lung but increased the incidence of papillary or nodular (PN) hyperplasia of the urinary bladder. The tumor incidence of other organs, such as the kidney and thyroid, was not significantly different from the corresponding controls. These results demonstrated that concurrent treatment with CAP not only can inhibit carcinogenesis but can also enhance it depending on the organ. Thus, this wide-spectrum initiation model could be used to confirm organ-specific modification potential and, in addition, demonstrate different modifying effects of CAP on liver, lung, and bladder carcinogenesis.
Animals ; Capsaicin/pharmacology/*toxicity ; Cocarcinogenesis ; Diethylnitrosamine ; Liver Neoplasms, Experimental/chemically induced/prevention & control ; Lung Neoplasms/chemically induced/prevention & control ; Male ; Methylnitrosourea ; Neoplasms, Experimental/*chemically induced/prevention & control ; Nitrosamines ; Rats ; Rats, Inbred F344 ; Urinary Bladder Neoplasms/chemically induced

OBJECTIVETo evaluate the toxicity of Radix Aristolochiae supplied experimental evidence of rational use of drug in clinic.

METHODAfter treatment with small dose Radix Aristolochiae, Guanxin Suhe Wan (with Radix Aristolochiae) and Guanxin Suhe Wan (without Radix Aristolochiae) in different group for a long- term, respectively, the biochemical indicator of PT, ALT, AST, ALB, ALP, Crea and BUN were detected, and the kidney, liver, stomach and urinary bladder were examined by pathologic assaying.

RESULTIn Radix Aristolochiae group and Guanxin Suhe Wan (with Radix Aristolochiae) group, all of biochemical indicator were changed significantly, and hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered.

CONCLUSIONRadix Aristolochiae and Guanxin Suhe Wan (with Radix Aristolochiae) can damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity.

Animals ; Aristolochia ; chemistry ; toxicity ; Drugs, Chinese Herbal ; toxicity ; Kidney ; drug effects ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Stomach Neoplasms ; chemically induced ; Urinary Bladder ; drug effects ; metabolism ; pathology ; Urinary Bladder Neoplasms ; chemically induced

The purpose of this study was to review occupational reproductive abnormalities and occupational bladder cancer in Korea and to discuss their toxicological implications. Reproductive dysfunction as a result of 2-bromopropane poisoning was first reported in Korean workers. In 1995, 23 of the 33 workers (25 female and 8 male workers) who were exposed to 2-bromopropane during the assembly of tactile switch parts developed reproductive and/or hematopoietic disorders. A total of 17 (68%) workers were diagnosed with ovarian failure. Two of the eight male workers experienced azoospermia and four workers experienced some degree of oligospermia or reduced sperm motility. In summary, 2-bromopropane poisoning caused severe reproductive effects in Korean workers. The prognosis was poor for reproductive dysfunction. A few cases of occupational bladder cancer have been reported in Korea, whereas other cancers of the urinary tract have not been reported after occupational exposure. A few cases of benzidine-induced cancer have been reported in Korea and 592 workers in Japan have received compensation for benzidine and beta-naphthylamine-induced cancer. In conclusion, a few cases of benzidine-induced occupational bladder cancer have been reported in Korea. However, benzidine-induced bladder cancer will likely be an important occupational health issue in Korea in the coming years.
2-Naphthylamine/toxicity ; Azoospermia/chemically induced/epidemiology ; Benzidines/toxicity ; Female ; Humans ; Hydrocarbons, Brominated/toxicity ; Infertility/*chemically induced/*epidemiology ; Male ; Occupational Diseases/*chemically induced/*epidemiology ; Occupational Exposure/adverse effects ; Oligospermia/chemically induced/epidemiology ; Primary Ovarian Insufficiency/chemically induced/epidemiology ; Republic of Korea ; Sperm Motility/drug effects ; Urinary Bladder Neoplasms/*chemically induced/*epidemiology

OBJECTIVETo evaluate the toxicity of Radix Aristolochiae and Radix Inulae, and to supply the toxicity experimental data that Radix Inulae supersedes Radix Aristolochiae in clinic.

METHODA long dose of Radix Aristolochice and Radix Inulae was given intragastrically to rats for six months, then drug withdrawal for a month. The hematology and biochemical indicators were measured, and the pathologic changes of kidney, liver, stomach and urinary bladder were examined.

RESULTThe rats of Radix Aristolochice showed serious toxic responses of renal tubule atrophy and necrosis, meanwhile, the levels of BUN, Cr and NAG were increased obviously. Hepatonecrosis, renal tubular necrosis, gastric carcinoma and bladder carcinoma were discovered with pathologic assaying. But the rats of Radix Inulae did not.

CONCLUSIONRadix Aristolochiae could damage kidney and liver, and cause gastric carcinoma and bladder carcinoma by intensive toxicity. Radix Inulae could take the place of Radix Aristolochiae to use in clinic.

Acetylglucosaminidase ; urine ; Animals ; Aristolochia ; chemistry ; Blood Urea Nitrogen ; Creatinine ; blood ; Drugs, Chinese Herbal ; isolation & purification ; toxicity ; Female ; Inula ; chemistry ; Kidney Tubules ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Male ; Necrosis ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach ; drug effects ; pathology ; Stomach Neoplasms ; chemically induced ; Urinary Bladder ; drug effects ; pathology ; Urinary Bladder Neoplasms ; chemically induced

Animals ; Carcinoma, Squamous Cell ; genetics ; Colorectal Neoplasms ; genetics ; metabolism ; Enzyme Activation ; Esophageal Neoplasms ; genetics ; Genome-Wide Association Study ; Head and Neck Neoplasms ; genetics ; Humans ; Neoplasms ; chemically induced ; enzymology ; genetics ; Phosphoinositide Phospholipase C ; chemistry ; genetics ; metabolism ; physiology ; Signal Transduction ; Skin Neoplasms ; chemically induced ; enzymology ; Stomach Neoplasms ; genetics ; Urinary Bladder Neoplasms ; metabolism ; pathology ; ras Proteins ; metabolism

This study was aimed to establish rat bladder tumor animal models to investigate the in viva antitumor effect of polyanhydride-pirarubicin (PAD-THP), a long-lasting anti-cancer implant, in the bladder tumor of animal models. The model of bladder cancer was set up with N-butly-N-(4 hydroxybutyl) nitrosamine (BBN) feeding into rats. The PAD-THP long-acting anti-cancer implants containing the drugs and the same dose of the THP naked drug were placed under the bladder mucosa of bladder tumor model in vivo. The pirarubicin plasma concentration was measured with high performance liquid chromatography (HPLC) detection in vivo. The effective drug concentration and lasting period were observed and compared in the animal bodies. The tumor sizes were measured before and after the treatment. The in viva antitumor effects were analyzed and compared. The results showed that more significant antitumor effect of PAD-THP implants on the local drug release characteristics were presented compared with that of the same dose of THP bare drug group and there were significant differences (P<0. 05) between the two methods. All the results indicated that the PAD-THP anti-cancer implants in the postoperative local treatment of bladder tumors would show prosperous in the future for clinical application.
Animals ; Antineoplastic Agents ; administration & dosage ; Butylhydroxybutylnitrosamine ; Delayed-Action Preparations ; administration & dosage ; Disease Models, Animal ; Doxorubicin ; administration & dosage ; analogs & derivatives ; Female ; Implants, Experimental ; Polyanhydrides ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder Neoplasms ; chemically induced ; drug therapy ; pathology

OBJECTIVEThe aim of this study was to analyze the clinical characteristics, treatment and prognosis of advanced urothelial carcinoma of the bladder (AUCB).

METHODSThe clinicopathological data of 117 patients with AUCB admitted in our hospital from 1998 to 2009 were reviewed. All patients received first-line chemotherapy. The survival rate was calculated by Kaplan-Meier analysis and log-rank test.

RESULTSThe median age of all patients was 56 years and the male-to-female ratio was 3.33:1. Their 6-, 12-, 24-, 36- and 60-month survival rates were 90.3%, 61.3%, 32.3%, 24.2% and 8.1%, respectively. In the first-line chemotherapy regimen, the effectiveness rate of gemcitabine + platinum drugs was 49.3% (37/75), the median progression-free survival(PFS) was 7.9 months and overall survival (OS) was 18.7 months. The effectiveness of cyclophosphamide + epirubicin + platinum drug regimen was 45.5% (10/22), Median PFS was 7.1 months and OS was 15.3 months. The effectiveness of paclitaxel + platinum drug regimen was 47.1% (8/17), median PFS was 6.5 months and OS was 13.7 months. Among them, the effectiveness rate of the gemcitabine + cisplatin regimen in 67 patients was 47.8%, the median PFS was 7.0 months and OS was 15.3 months. In the 13 patients who received paclitaxel + carboplatin regimen, the effectiveness rate was 53.8%, median PFS was 7.7 months and OS was 16.0 months. The major side effects were leucopenia and thrombocytopenia, mostly were tolerable, of grade I to II.

CONCLUSIONSIn advanced unresectable and metastatic urothelial carcinoma of the bladder, GC regimen is recognized as a standard first-line chemotherapy, with a higher effectiveness and tolerable side effects. Taxane and molecular targeted drugs may further improve the therapeutic effect of the treatment of advanced urothelial carcinomas of the bladder in the future.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Transitional Cell ; drug therapy ; pathology ; secondary ; Cisplatin ; administration & dosage ; adverse effects ; Cyclophosphamide ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Disease-Free Survival ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Retrospective Studies ; Survival Rate ; Thrombocytopenia ; chemically induced ; Urinary Bladder Neoplasms ; drug therapy ; pathology ; Urothelium ; pathology