Chemopreventive Action by Ethanol-extracted Brazilian Green Propolis on Post-initiation Phase of Inflammation-associated Rat Colon Tumorigenesis.

BACKGROUND/AIM: Propolis has since long been utilized in numerous folk medicines with a variety of medicinal properties. In this study, the effects of ethanol-extracted (EEP) and water-extracted (WEP) Brazilian green propolis on the post-initiation phase of inflammation-associated rat colon tumorigenesis were directly compared. MATERIALS AND METHODS: Male F344 rats at 6 weeks of age were subcutaneously injected with 1,2-dimethylhydrazine (DMH) at 40 mg/kg body weight twice during the first week, followed by 1% dextran sodium sulfate (DSS) in drinking water for one week. After a 1-week no-treatment period, animals were administered either basal Oriental MF powdered diet, or 1% EEP or 1% WEP in the basal diet until week 32. RESULTS: Post-initiation treatment with EEP significantly reduced the multiplicity of colorectal carcinomas compared to the control (0.40±0.13/rat vs. 2.29±0.84/rat, respectively, p<0.05), and EEP also reduced the tumor volume. Immunohistochemically, expression of inflammation-associated proteins inducible nitric oxide synthase, tumor necrotic factor alpha, nuclear factor kappa B and glutathione peroxidase-2 were significantly diminished in colorectal tumors from EEP-treated rats. CONCLUSION: Suppression of inflammation and oxidative stress, which had been triggered by DMH and promoted by DSS, was a primary mechanism by which EEP suppressed carcinogenesis.

Determination of Hepatotoxicity and Its Underlying Metabolic Basis of 1,2-Dichloropropane in Male Syrian Hamsters and B6C3F1 Mice.

1,2-Dichloropropane (1,2-DCP) has recently been reclassified from not classifiable as to its carcinogenicity to humans (Group 3) to carcinogenic to humans (Group 1) by the International Agency for Research on Cancer. This was based on the findings of epidemiological studies in Japan that occupational exposure to paint stripers containing 1,2-DCP was associated with increased cholangiocarcinomas. It is known that 1,2-DCP is negative for cholangiocarcinogenicity in rats and mice. However, its toxicity and carcinogenicity has not been examined in hamsters and little is known about the regulation of its metabolism in hamsters. The purpose of this study was to determine the hepatobiliary toxicity of 1,2-DCP in hamsters and to characterize and compare the altered patterns of hepatic xenometabolic enzymes in hamsters and mice. Male Syrian hamsters and male B6C3F1 mice were treated with various doses of 1,2-DCP for 4 h or 3 days or 4 weeks. These experiments demonstrated that a high dose of 1,2-DCP induced centrilobular hepatocellular necrosis in hamsters. CYP2E1 is possibly the key enzyme responsible for bioactivation and the consequent hepatocytotoxicity of 1,2-DCP, and GSH conjugation catalyzed by GST-T1 may exert a cytoprotective role in hamsters and mice. Notably, the expression pattern of GST-T1 in bile duct epithelial cells differed between hamsters and mice: GST-T1 was expressed in bile duct epithelial cells of mice but not hamsters. This indicates that responses to 1,2-DCP in the bile duct of hamsters might differ from that of mice, and suggests that long-term studies are necessary to clarify the chalangiocarcinogenicity of 1,2-DCP in hamsters, though no biliary toxicity was observed in the present short-term experiments.

L-Leucine and L-isoleucine enhance growth of BBN-induced urothelial tumors in the rat bladder by modulating expression of amino acid transporters and tumorigenesis-associated genes.

We investigated the underlying mechanisms of L-leucine and L-isoleucine mediated promotion of bladder carcinogenesis using an initiation-promotion model. Rats were administered N-butyl-N-(4-hydroxybutyl) nitrosamine for 4 weeks and then fed AIN-93G basal diet or diet supplemented with L-leucine or L-isoleucine for 8 weeks followed by the basal diet for another 8 weeks. At the end of the experiment, week 20, there was a significant elevation of papillary and nodular (PN) hyperplasia multiplicity in the amino acid groups. L-Leucine and L-isoleucine transporters were up-regulated in PN hyperplasias and/or bladder tumors compared with concomitant normal-appearing bladder urothelium at weeks 12 and/or 20 in all groups. In addition, in normal-appearing bladder urothelium, significantly increased mRNA levels of y+LAT1, LAT2, LAT4, and 4F2hc were observed in the amino acid groups compared with the BBN control group at both weeks 12 and 20, and increased mRNA levels of LAT1 were observed at week 20. Furthermore, up-regulation of TNF-α, c-fos, ß-catenin, p53, p21(Cip1/WAF1), cdk4, cyclin D1 and caspase 3 in the amino acid groups was detected in normal-appearing bladder urothelium. Overall, our results indicate that supplementation with l-leucine or l-isoleucine enhanced growth of bladder urothelial tumors by triggering expression of amino acid transporters and tumorigenesis-associated genes.

A case of malignant pheochromocytoma with early intense uptake and immediate rapid washout of 99mTc-tetrofosmin characterizing the overexpression of anti-apoptotic Bcl-2.

Defective apoptotic program due to the overexpression of the anti-apoptotic Bcl-2 protein of the outer mitochondrial membrane may be a cause of the poor response of malignant pheochromocytoma to 131I-MIBG therapy. We report a case of malignant pheochromocytoma which showed early intense uptake and immediate rapid washout of 99mTc-tetrofosmin characterizing the overexpression of anti-apoptotic Bcl-2 and which was refractory to 131I-MIBG therapy.

Usefulness of a pulse oximeter for enhancing breath holding in hepatic subtraction angiography.

This study examined the usefulness of a pulse oximeter in hepatic digital subtraction angiography (DSA) with oxygen administration for breath holding. Oxygen saturation and dissociation times were measured using a pulse oximeter. Twenty-eight patients inhaled oxygen at a rate of 3 liters/min through a nasal tube. Saturation times ranged from 0 to 140 seconds to achieve arterial oxygen-hemoglobin saturation of almost 100%. Dissociation times ranged from 0 to 600 seconds after oxygen termination.