Animals ; Diethylnitrosamine/toxicity* ; Liver ; Liver Neoplasms/chemically induced* ; Rats

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 study farm compost polluted water that may induce pharyngo-esophageal, gastric and liver carcinoma in chickens.

METHODS280 chickens were randomized into 4 groups: experiment group 100 chickens fed with compost water + NaNO(2) by stomach tube. The other 180 were evenly randomized into 3 control groups (60 each), fed with compost water, NaNO(2) and tap water in the same way. The farm compost was prepared with corn stalks, rice straws, excreta of men and livestock. The compost water, after being nitrosified and acidified, was fed through stomach tube 5 - 7.5 ml/session, twice a week. Besides, a solution consisting of the respective formula of each group added with 3 - 4 L water with pH adjusted to 3 - 4 by 1N HCL was given ad lib to all chickens in each group for 26.5 months.

RESULTSIn the experiment group, there were pharyngo-esophageal carcinoma 16 (16.3%), gastric adenocarcinoma 5 (10.4%) and liver carcinoma 3 (6.3%), in contrast to none in the 3 control groups, showing significant differences (P < 0.01, P < 0.01, P < 0.05).

CONCLUSIONSuccessful simulation of the layout of esophageal carcinoma high morbidity area and the mimic of chicken gastric fluid strongly support our compost etiological hypothesis that the nitrosified and acidified compost water are carcinogenic, very well causing esophageal, gastric and liver carcinoma.

Adenocarcinoma ; chemically induced ; pathology ; Animals ; Carcinoma, Squamous Cell ; chemically induced ; pathology ; Chickens ; Esophageal Neoplasms ; chemically induced ; pathology ; Feces ; Female ; Liver Neoplasms ; chemically induced ; pathology ; Male ; Pharyngeal Neoplasms ; chemically induced ; pathology ; Random Allocation ; Sewage ; adverse effects ; Sodium Nitrite ; toxicity ; Stomach Neoplasms ; chemically induced ; pathology ; Water Pollution, Chemical ; adverse effects

OBJECTIVETo explore the hepatic injury induced by CCl4in SD rat.

METHOD40 SD rats were allocated to male and female group, consisting of 20 animals/sex/group. SD rats were given at 2 mL x kg(-1) of 10% CCl4 through celiac injection per 3 day for 12 days. All rats were killed by anaesthesia of ethyl ether and bleeding through abdominal aorta at 12th day. Liver tissue was fixed in 10% neutral formalin, embedded in paraffin, cut at a nominal thickness of 3 microm, stained with hematoxylin and eosin ( H&E) , evaluated at by microscopic examination.

RESULT19 cases with local necrosis, 8 cases with fatty degeneration, 9 cases with cystic degeneration and 2 cases with fibrosis were seen in group male. 20 cases with local necrosis, 9 cases with fatty cases degeneration, 1 case with cystic degeneration and 1 case with fibrosis were seen in group female. The incidence of cystic degeneration in male group was found significantly higher than that in female group (P < 0. 05) , but the incidence of other lesions was no significant difference between male and female group.

CONCLUSIONCCl4 induces local necrosis , fatty degeneration, fibrosis and cystic degeneration in SD rat. The incidences of local necrosis , fatty degeneration and fibrosis were no significantly difference between male and female rat, but the incidence of cystic degeneration in male rats was significant higher than that in female rats.

Animals ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; Cysts ; chemically induced ; pathology ; Disease Models, Animal ; Female ; Liver ; pathology ; Liver Cirrhosis ; chemically induced ; pathology ; Liver Diseases ; pathology ; Liver Neoplasms ; chemically induced ; pathology ; Male ; Precancerous Conditions ; chemically induced ; pathology ; Rats ; Rats, Sprague-Dawley ; Sex Factors

Iron is essential for the growth of all living cells. One of the most important intracellular roles of iron is the activation of ribonucleotide reductase, which is indispensible to the production of deoxyribonucleotide necessary for DNA synthesis. Deferoxamine (DFO) is an iron chelating agent and has been known to have an antiproliferative effect in various malignant cells including hepatocellular carcinoma and the effect seems to be related to depletion of iron. This study was undertaken to investigate the effect of DFO on preneoplastic lesions in chemically induced hepatocarcinogenesis. The resistant hepatocyte model was used and Sprague Dawley rats were divided into the following groups; I: normal control, II: carcinogen administered group, III: carcinogen and DFO administered group. Rats were sacrificed at 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks and 8 weeks after partial hepatectomy (PH). DFO (50 mg/kg/day, I.P.) was daily injected from 3 weeks before administration of carcinogen to the time when rats were sacrificed. Hepatic iron content was higher in group II than in group III, especially at 3 days and 1 week after PH. Hyperplastic lesions of resistant hepatocytes were less well developed in group III than in group II. Bromodeoxyuridine labelling indices of oval cells and hyperplastic lesions of resistant hepatocytes were higher in group II than in group III except for rats examined at 3 days after PH. The results suggest that DFO has an antiproliferative effect on preneoplastic lesions in hepatocarcinogenesis and it might be related to reduction of the hepatic iron.
Animal ; Deferoxamine/*pharmacology ; Diethylnitrosamine ; Liver Neoplasms, Experimental/chemically induced/*prevention & control ; Male ; Precancerous Conditions/chemically induced/*prevention & control ; Rats ; Rats, Sprague-Dawley ; Support, Non-U.S. Gov't

Recently, Ng et al. reported that the A:T > T:A substitutions, proposed to be a signature of aristolochic acid (AA) exposure, were detected in 76/98 (78%) of patients with hepatocellular carcinoma (HCC) from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients' exposure history is the key to determine the "culprit" of the A:T > T:A mutations. Apparently, without estimation of the patients' exposure history, the conclusion of Ng et al. is unpersuasive and misleading.
Aristolochic Acids ; toxicity ; Carcinogens ; toxicity ; Carcinoma, Hepatocellular ; chemically induced ; genetics ; China ; Environment ; Humans ; Liver Neoplasms ; chemically induced ; genetics ; Mutation ; Taiwan ; Tobacco ; toxicity ; Vinyl Chloride ; toxicity

Although various combinations of chemotherapy regimens have been tried for patients with esophageal cancer, their duration of survival is extremely poor. In this study, we investigated the safety and clinical efficacy of paclitaxel and cisplatin chemotherapy in metastatic or recurrent esophageal cancer. 32 patients enrolled in this study and the median age was 60 yr. Of all the 32, 28 patients (88%) had been treated previously, 22 of them with chemotherapy or radiation therapy. All patients in the study received biweekly paclitaxel (90 mg/m2) followed by cisplatin (50 mg/m2). One patient (3%) responded completely, and 12 patients (38%) showed a partial response; in 9 patients (28%) the disease remained stable, and in 10 patients (31%) it progressed. The objective response rate was 41%. The median duration of response was 4.8 months, and the median overall survival in all patients was 7 months. The 1-yr and 2-yr survival rates were 28.1% and 7.1%, respectively. Grade 3 or 4 of neutropenia and anemia were observed in 6 (19%) and 5 (16%) patients, respectively. The major non-hematologic toxicity was fatigue, but most of them could manageable. In conclusion, biweekly paclitaxel and cisplatin is effective in patients with metastatic or recurrent esophageal cancer.
Aged ; Anemia/chemically induced ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Bone Neoplasms/drug therapy/secondary ; Cisplatin/administration & dosage/adverse effects ; Diarrhea/chemically induced ; Esophageal Neoplasms/*drug therapy/pathology ; Fatigue/chemically induced ; Humans ; Liver Neoplasms/drug therapy/secondary ; Lung Neoplasms/drug therapy/secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea/chemically induced ; Neoplasm Recurrence, Local ; Paclitaxel/administration & dosage/adverse effects ; Survival Analysis ; Thrombocytopenia/chemically induced ; Time Factors ; Treatment Outcome ; Vomiting/chemically induced

OBJECTIVETo evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC).

METHODSFrom January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1, 8, 15 every 4 weeks. Carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5.

RESULTSThe median number of cycles was 3 (range, 2-6). The overall response rate was 62.2%. Median time to progression was 7.0 months (95% CI: 5.1-8.9). Median overall survival was 29.0 months (95% CI: 20.1-37.9). One year survival rate was 73.3%. Response rate for first line and second line treatment were 62.1% and 62.5% , respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade III to IV adverse events included nausea/vomiting in 2 cases (4.4%), leukopenia in 17 cases (37.8%) , and alopecia in 6 cases (13.3%).

CONCLUSIONCombination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

Alopecia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; mortality ; pathology ; Carboplatin ; administration & dosage ; Drug Administration Schedule ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Metastasis ; Paclitaxel ; administration & dosage ; Postmenopause ; Premenopause ; Soft Tissue Neoplasms ; drug therapy ; secondary ; Survival Rate ; Vomiting ; chemically induced

OBJECTIVETo evaluate the efficacy and safety of combination chemotherapy of Docetaxel (Taxotere, TXT) combined with cisplatin (DDP) for anthracycline (ANT)-resistant advanced breast cancer (ABC).

METHODSFrom April 2000 to March 2005, 31 patients with ANT-resistant advanced breast cancer were treated with combination chemotherapy of TXT and DDP. TXT 75 mg/m2 and DDP 75 mg/m2 were used on day 1 every three weeks. The median number of cycles was 4 (range: 2 - 8 cycles).

RESULTSThe overall combination chemotherapy response rate was 54.9% with a median time to progression of 5 months. One-year survival rate was 66.7%. The main side effects were gastrointestinal and hematologic toxicities, including grade 3 to 4 nausea and vomiting in 3 patients (9.7%), leukopenia in 6 (19.3%), and neutropenia in 3 (9.7%).

CONCLUSIONTaxotere and displatin combination is active in the treatment for anthracycine-resistant advanced breast cancer patient with an acceptable toxicity, and may be a therapeutic alternative after anthracycline regimen has failed.

Adult ; Aged ; Anthracyclines ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; adverse effects ; Drug Resistance, Neoplasm ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Middle Aged ; Nausea ; chemically induced ; Neutropenia ; chemically induced ; Remission Induction ; Survival Analysis ; Taxoids ; administration & dosage ; adverse effects ; Treatment Outcome ; Vomiting ; chemically induced

OBJECTIVETo understand the molecular mechanism and find out the responsible genes for liver cancer by exploring the regulation of gene expression during hepatocarcinogenesis in tree shrew induced by aflatoxin B1 (AFB1).

METHODSThe tissues from tree shrew of different stages during the pathogenesis and development of hepatocellular carcinoma (HCC), liver cancer tissue, para-cancerous tissues, pre-cancerous liver tissues, liver tissues of the same stage from normal controls and the liver tissues taken before AFB1-treatment were analyzed for gene expression by cDNA array.

RESULTSFour patterns of gene expression were observed during AFB1-induced hepatocarcinogenesis. They were: genes up-regulated in HCC tissue and para-cancerous tissue, especially in HCC tissues; genes with similar expressing level in both HCC tissue and para-cancerous tissue, but higher than that in pre-cancerous tissue; genes down-regulated in HCC tissue; genes up-regulated before HCC appeared but down-regulated after HCC appeared.

CONCLUSIONDynamic observation of gene expression will be beneficial to elucidate the mechanisms of AFB1- induced hepatocarcinogenesis and locate the responsible genes.

Aflatoxin B1 ; toxicity ; Animals ; Gene Expression Profiling ; Liver Neoplasms, Experimental ; chemically induced ; genetics ; Oligonucleotide Array Sequence Analysis ; methods ; Tupaiidae