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

Alkaloids ; pharmacology ; Animals ; Liver Neoplasms, Experimental ; enzymology ; prevention & control ; Quinolizines ; pharmacology ; Rats ; Selenium ; pharmacology ; Telomerase ; metabolism ; Yeast, Dried ; pharmacology

Oral administration of red ginseng extracts (1% in diet for 40 weeks) resulted in the significant suppression of spontaneous liver tumor formation in C3H/He male mice. Average number of tumors per mouse in control group was 1.06, while that in red ginseng extracts-treated group was 0.33 (p<0.05). Incidence of liver tumor development was also lower in red ginseng extracts-treated group, although the difference from control group was not statistically significant. Anti-carcinogenic activity of white ginseng extracts, besides red ginseng extracts, was also investigated. In the present study, the administration of white ginseng extracts was proven to suppress tumor promoter-induced phenomena in vitro and in vivo. It is of interest that oral administration of the extracts of Ren-Shen-Yang- Rong-Tang, a white ginseng-containing Chinese medicinal prescription, resulted in the suppression of skin tumor promotion by 12-o-tetradecanoylphorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated CD-1 mice. These results suggest the usefulness of ginseng in the field of cancer prevention.
Animal ; Anticarcinogenic Agents/*pharmacology ; Female ; Liver Neoplasms, Experimental/*prevention & control ; Male ; Mice ; Mice, Inbred C3H ; *Panax ; Plant Extracts/pharmacology ; Plant Roots ; Skin Neoplasms/*prevention & control

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

OBJECTIVETo study the effects of murine angiostatin, which was transfected into the human hepatocellular cancer cell line SMMC-7721, on the implant carcinoma of nude mouse.

METHODSThe human hepatocellular cancer cell line SMMC-7721, which could express murine angiostatin gene stably, was constructed. The animals were divided into three groups: SMMC-7721 cell was implanted into control group, SMMC-7721/pcDNA3.1 (+) cell was implanted into vector group, and SMMC-7721/pcDNA3.1-mAST cell was implanted into angiostatin group. The carcinoma volume, weight, and microvessel density (MVD) of each group were compared.

RESULTSThe implant carcinoma volume in 35 days was (3 538.1 +/- 643.3) mm(3), (3 128.5 +/- 546.6) mm(3), and (755.8 +/- 198.2) mm(3) in the control group, vector group, and angiostatin group. The carcinoma weight of the control group, vector group, and angiostatin group was (6.0 +/- 0.7) g, (5.9 +/- 0.5) g, (2.1 +/- 0.5) g, respectively. The carcinoma MVD was 52.2 +/- 6.6, 49.4 +/- 7.0, and 25.5 +/- 4.1 accordingly. The carcinoma volume, weight, and MVD of the angiostatin group were significantly smaller than those of the control group and vector group (P < 0.01). The inhibitory rate of carcinoma reached 78.6%.

CONCLUSIONSNude mouse experiments showed that the tumorigenic capacity of cells transfected had been reduced greatly, and that the carcinoma volume, weight and MVD were significantly lower than those of the control group. We conclude that angiostatin inhibits the growth of carcinoma by its inhibition of carcinoma angiogenesis.

Angiostatins ; Animals ; Genetic Therapy ; methods ; Liver Neoplasms, Experimental ; blood supply ; prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neovascularization, Pathologic ; prevention & control ; Peptide Fragments ; genetics ; Plasminogen ; genetics ; Tumor Cells, Cultured

To observe the pharmacokinetic and tissue-distribution characters of 5-flourouracil magnetic albumin deuto-microsphere (5-Fu-MAD) in normal and tumor-bearing mice, HPLC method for the determination of 5-Fu in plasma and tissues was established and applied to determine 5-Fu in mouse plasma and tissue samples. A Flame atomic absorption spectrometer was used to detect the iron concentration in mouse tissue. Plasma concentration-time curves of free 5-Fu, 5-Fu-MAD and 5-Fu-MAD plus the magnetic frame (MF) conformed to two compartment model of first order absorption and they had C(max) of 34.9, 7.95 and 5.97 mg x L(-1); T1/2 (Ke) of 22.26, 76.0 and 124.6 min, V(d) of 3.28, 30.7 and 66.1 L x kg; AUC(0-t), of 233.9, 78.3 and 50.2 mg x min x L(-1); AUC(0-infinity) of 237.2, 89.3 and 68.1 mg x min x L(-1), respectively. The distribution of 5-Fu and iron was the highest in the plenty blood perfusion organs like the liver, tumor, spleen and lung, while lower in the kidney and heart and lowest in brain and muscle. The tissue distribution of muscle and tumor increased significantly when a magnetic frame was inserted there. The pharmacokinetics and tissue distribution of 5-Fu-MAD exhibited sustained-release and target characteristics.
Albumins ; chemistry ; Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Cell Line, Tumor ; Delayed-Action Preparations ; Female ; Fluorouracil ; administration & dosage ; pharmacokinetics ; Liver ; metabolism ; pathology ; Liver Neoplasms, Experimental ; metabolism ; pathology ; prevention & control ; Magnetics ; Male ; Mice ; Microspheres ; Random Allocation ; Tissue Distribution

OBJECTIVETo study whether the ethanol extract of Phellinus merrillii (EPM) has chemopreventive potential against liver carcinogenesis.

METHODSThirty male Spraque-Dawley rats were randomly divided into control group, EPM control group, hepatocarcinoma control group, low-dose EPM group and high-dose EPM group, 6 in each group. Using the Solt and Farber protocol in a rat model of hepatocarcinogenesis, the chemopreventive effect of EPM on diethylnitrosamine (DEN)-initiated, 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH)-promoted liver carcinogenesis in rats was evaluated. Basic pathophysiological and histological examinations, together with the serum levels of glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT) and gamma-glutamyl transpeptidase (γ-GT) were measured.

RESULTSTreatment of EPM at the concentration of 2 g/kg body weight in the diet for 8 weeks clearly prevented the development of carcinogenesis and reduced the levels of sGOT, sGPT, and serum γ-GT of rats as compared with the hepatocarcinoma control group (P<0.05 or P<0.01). These phenotypes were accompanied by a significant increase in natural killer cell activity.

CONCLUSIONEPM showed a strong liver preventive effect against DEN+2-AAF+PH-induced hepatocarcinogenesis in a rat model.

2-Acetylaminofluorene ; Animals ; Basidiomycota ; chemistry ; Carcinogenesis ; chemically induced ; Cytoprotection ; drug effects ; Diethylnitrosamine ; Ethanol ; chemistry ; Liver Neoplasms, Experimental ; chemically induced ; prevention & control ; Male ; Plant Extracts ; chemistry ; pharmacology ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the dynamic expressions of TGF-beta 1 and TGF-beta 1 mRNA at different stages of hepatocellular carcinoma (HCC) development and their use in clinical diagnosis.

METHODSHepatoma models were developed with 2-FAA using male Sprague-Dawley (SD) rats. Morphological changes of the rat liver histological preparations (H and E stained) were studied. The fragment of TGF-beta 1 gene obtained was amplified by nested RT-PCR. Dynamic change of TGF-beta 1 level was quantitatively analyzed by ELISA. The distribution of TGF-beta 1 in the cells and its gene expression were detected in human HCC tissues.

RESULTSThe progressive increases of hepatic TGF-beta 1 and TGF-beta 1 mRNA were observed in rat hepatocytes which progressed from granular degeneration, atypical hyperplasia and finally to HCC development induced by 2-FAA. The expression levels in HCC tissues were significantly higher than those in the normal and degenerative ones. TGF-beta 1 was shown in rat hepatocytes by immunohistochemistry. Plasma TGF-beta 1 was detected in 89.5% of all the patients with HCC, but it was detected in 93.3% of them who had an AFP less than 400 microg/L. TGF-beta 1 mRNA showed a stronger expression in HCC tissues. TGF-beta 1 mRNA was found in peripheral blood mononuclear cells from all HCC patients with extrahepatic metastasis.

CONCLUSIONTGF-beta 1 may participate in hepatocyte canceration. The overexpression of TGF-beta 1 and TGF-beta 1 mRNA could be useful markers for early diagnosis and predicting prognosis of HCC.

Adult ; Aged ; Animals ; Biomarkers, Tumor ; blood ; Carcinoma, Hepatocellular ; blood ; diagnosis ; pathology ; Female ; Humans ; Liver Neoplasms, Experimental ; blood ; diagnosis ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; prevention & control ; Prognosis ; RNA, Messenger ; blood ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; blood

OBJECTIVETo study the effects of 4-1BBL on antitumor immunity induced in vivo by murine 4-1BBL gene transfected Hepa1-6.

METHODSRetrovirus vector was used to transfer the 4-1BBL gene into syngeneic murine heptocellular carcinoma cell line Hepa1-6. The products were termed as Hepa1-6/4-1BBL, and then the TCV4-1BBL was obtained by treating them with mitomycin (MMC). Three models (immunological model, early model, and later model) were established to study the antitumor effects of TCV4-1BBL.

RESULTS(1)In immunological models, the syngeneic mice were completely protected by inoculation with TCV4-1BBL, survived free from tumor for a long period (over 100 days). (2)In early models (7 days after inoculation), Hepa1-6 tumor cells showed strong immunogenicity effects and (3) In later models (14 days after inoculation), they had obvious antitumor effects and most of the tumors were disappeared.

CONCLUSIONSThe antitumor effect against syngeneic murine hepatocellular carcinoma in vivo is obviously enhanced by treating them with TCV4-1BBL

4-1BB Ligand ; Animals ; Cell Division ; immunology ; Female ; Liver Neoplasms, Experimental ; immunology ; pathology ; prevention & control ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Plasmids ; genetics ; immunology ; Transfection ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha ; genetics ; immunology

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Liver Neoplasms, Experimental ; drug therapy ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Metastasis ; prevention & control ; Neoplasm Transplantation ; Phytotherapy ; Qi ; Spleen