OBJECTIVETo investigate the anticancer efficacy and the hepatic and renal toxicity of As2O3-lipiodol emulsion via transarterial embolization in a rabbit VX2 liver tumor model.

METHODSVX2 tumors were implanted in rabbit livers successfully, followed by transarterial embolization with high-dose As2O3(5 mg/kg with 0.2 mL lipiodol, n=10), low-dose As2O3(1 mg/kg with 0.2 mL lipiodol, n=10), and control(0.2 mL lipiodol, n=10). The growth ratios and microvessel densities(MVDs) of the tumors were estimated by multi-row spiral CT and CD34 immunohistochemical staining, respectively. Hepatic and renal function was also evaluated by means of blood biochemical analysis.

RESULTSThe growth ratios of the tumors differed significantly among three groups(P<0.01). The high-dose and low dose group showed significantly lower tumor growth ratios[44.05%(-36.40%~64.60%), 95.20%(-11.60%~159.40%)] than control group[145.55%(98.90%~250.30%), all P<0.05]. The MVDs of the tumors were significantly lower in the high-dose(21.4±10.6) and low-dose group(34.1±12.0) than those in control group(57.9±16.1,all P<0.05). The levels of blood ALT and AST obtained 28 days after transarterial embolization were significantly lower in the high-dose[(25.50±12.37)U/L,(24.25±10.89)U/L] and low-dose group[(45.00±14.04)U/L,(35.22±11.86)U/L] than in control group[(79.12±30.52)U/L,(75.25±25.89)U/L, all P<0.05].

CONCLUSIONAs2O3-lipiodol emulsion via transarterial embolization has anticancer effect without significant hepatic and renal functional damage in rabbit VX2 liver tumors.

Animals ; Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Embolization, Therapeutic ; Emulsions ; pharmacology ; Ethiodized Oil ; pharmacology ; Liver Neoplasms, Experimental ; drug therapy ; Oxides ; pharmacology ; Rabbits ; Tomography, Spiral Computed

OBJECTIVETo study the effect of spleen lymphocytes on the splenomegaly by hepatocellular carcinoma-bearing mouse model.

METHODSCell counts, cell cycle distribution, the percentage of lymphocytes subsets and the levels of IL-2 were measured, and two-dimensional gel electrophoresis (2-DE) was used to investigate the relationship between spleen lymphocytes and splenomegaly in hepatocellular carcinoma-bearing mice.

RESULTSCompared with the normal group, the thymus was obviously atrophied and the spleen was significantly enlarged in the tumor-bearing group. Correlation study showed that the number of whole spleen cells was positively correlated with the splenic index. The cell diameter and cell-cycle phase distribution of splenocytes in the tumor-bearing group showed no significant difference compared to the normal group. The percentage of CD3+ T lymphocytes and CD8+ T lymphocytes in spleen and peripheral blood of tumor-bearing mice were substantially higher than that in the normal mice. Meanwhile, the IL-2 level was also higher in the tumor-bearing group than in the normal group. Furthermore, two dysregulated protein, β-actin and S100-A9 were identified in spleen lymphocytes from H22-bearing mice, which were closely related to cellular motility.

CONCLUSIONIt is suggested that dysregulated β-actin and S100-A9 can result in recirculating T lymphocytes trapped in the spleen, which may explain the underlying cause of splenomegaly in H22-bearing mice.

Animals ; Carcinoma, Hepatocellular ; complications ; Cell Cycle ; Female ; Liver Neoplasms ; complications ; Lymphocytes ; physiology ; Mice ; Mice, Inbred ICR ; Neoplasms, Experimental ; therapy ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Spleen ; cytology ; pathology ; Splenomegaly ; etiology ; therapy ; Thymus Gland

OBJECTIVETo assess the application of gray-scale contrast-enhanced ultrasound (CEUS) and contrast-enhanced spiral computed tomography (CECT) in detection of residual tumor after high intensity focused ultrasound (HIFU) ablation with microbubbles on rabbit hepatic VX2 tumors.

METHODSForty rabbits with hepatic VX2 tumors were randomly divided into three groups before ablation. Group I (n=10) served as sham ablation controls, rabbits in group II (n=15) and group III (n=15) were ablated using HIFU under the manipulation of computer. A bolus of 0.2 ml SonoVue solution was injected via ear marginal vein of rabbits in group III before ablation. Tumors were examined with CEUS and CECT before and within 3h after HIFU ablation. Necropsy and histopathological assessment were performed immediately after the completion of images evaluation.

RESULTSBefore ablation, intense arterial feeding vessels was detected in the tumors (77.5%,31/40 Compared with 52.5%,21/40) or the periphery of the tumors (22.5%,9/40 Compared with 47.5%,19/40) by CEUS and CECT, respectively. The tumors were characterized by quick wash-in and wash-out (high and rapid peak of enhancement in the arterial phase,followed by a fast decrease in enhancement level). The dose parameters used to achieve therapeutic effect in group III were significantly lower than those in group II(P<0.01). There were local residual viable tumor tissues due to incomplete ablation in 60.0% (9/15) of group II and 13.3% (2/15) of group III revealed by histopathology(P<0.05). The concordance rate of CECT and CEUS with histopathology on residual tumor detection was 27.3% and 81.8% (P<0.05), respectively.

CONCLUSIONThe administration of microbubble agent enhances the efficacy of HIFU on rabbit hepatic VX2 tumors. CEUS is more sensitive than CECT in detection of residual viable rabbit VX2 tumor after HIFU.

Animals ; Female ; High-Intensity Focused Ultrasound Ablation ; Liver Neoplasms, Experimental ; therapy ; Male ; Microbubbles ; Neoplasm, Residual ; diagnostic imaging ; pathology ; Phospholipids ; Rabbits ; Sulfur Hexafluoride ; Tomography, Spiral Computed ; Ultrasonography

OBJECTIVE: Arsenic trioxide (As2O3) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As2O3 on RF-induced ablation in an experimentally induced liver tumor. MATERIALS AND METHODS: VX2 carcinoma was grown in the livers of 30 rabbits. As2O3 (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA +/- 35; 90 +/- 5degrees C). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. RESULTS: The overall ablation areas were 156 +/- 28.9 mm2 (group A), 119 +/- 31.7 (group B), and 92 +/- 17.4 (group C, p < 0.04). The ablation area of the tumor was significantly larger in group A (73 +/- 19.7 mm2) than both group B (50 +/- 19.4, p = 0.02) and group C (28 +/- 2.2, p < 0.01). The ratios of the tumoral ablation area to the overall ablation area were larger in group A (47 +/- 10.5%) than that of the other groups (42 +/- 7.3% in group B and 32 +/- 5.6% in group C) (p < 0.03). CONCLUSION: Radiofrequency-induced ablation area can be increased with intraarterial or intravenous administration of As2O3. The intraarterial administration of As2O3 seems to be helpful for the selective ablation of the tumor.
Animals ; Arsenicals/*pharmacology ; Catheter Ablation/*methods ; Combined Modality Therapy ; Contrast Media/diagnostic use ; Disease Models, Animal ; Liver/radiography ; Liver Neoplasms, Experimental/*drug therapy/radiography/*surgery ; Oxides/*pharmacology ; Rabbits ; Statistics, Nonparametric ; Tomography, X-Ray Computed

OBJECTIVETo find out the anticancer effect of Indigofera aspalathoides (I. aspalathoides) on 20-methylcholanthrene induced fibrosarcoma in rats.

METHODSFibrosarcoma was induced in Wistar strain male albino rats by 20-methylcholanthrene. Intraperitoneous (i.p.) administration of 250 mg/kg body weight/day of aqueous extract of I. aspalathoides for 30 d effectively suppressed chemically induced tumors. Parameters such as body weight, liver and kidney weight, tumor weight, mean survival time, behavioral changes, blood glucose, blood glycogen and marker enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), acid phosphatase (ACP) and 5'-nucleiotidase (5'-NT) in serum, liver and kidney and lipid profiles such as total cholesterol, phospholipids, free fatty acids in liver and kidney of control and experimental animals were studied.

RESULTSFibrosarcoma bearing animals were ferocious and anxious. The mean survival time was found to increase after the treatment. The body weights were significantly decreased (P<0.001) in group II fibrosarcoma animals which steadily increased after the treatment with I. aspalathoides. The liver and kidney weights were significantly increased whereas the tumor weights decreased as compared to the weights in untreated fibrosarcoma bearing rats. The blood glucose and the liver and kidney glycogen levels were found to decrease significantly (P<0.001) in group II animals. Elevated activities of marker enzymes were observed in serum, liver and kidney of fibrosarcoma bearing Group II animals which were normalize after I. aspalathoides treatment. In the liver and kidney of Group II animals the total cholesterol increased whereas the phospholipids and free fatty acid levels decreased (P<0.001) which were normalized after treatment.

CONCLUSIONSThe treatment by I. aspalathoides on fibrosarcoma bearing rats has improved the levels of various parameters indicating its antiproliferative and anticancer activity.

Animals ; Antineoplastic Agents ; pharmacology ; Chemoprevention ; Fibrosarcoma ; drug therapy ; pathology ; Indigofera ; chemistry ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Liver Neoplasms, Experimental ; chemically induced ; pathology ; prevention & control ; Male ; Methylcholanthrene ; Phytotherapy ; methods ; Plant Extracts ; pharmacology ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Rats ; Rats, Wistar ; Seeds ; chemistry

To evaluate the changes induced in tumor tissue, the feeding artery, and neovascularization upon pingyangmycin-lipiodol emulsion treatment via transcatheter arterial chemoembolization (TACE) using the rabbit VX2 liver cancer model. The VX2 liver tumor model was established in 28 rabbits, and baseline tumor volume (V1, in mm3) was measured by spiral scan computed tomography (CT). Then, the rabbits were randomly divided into four groups (n = 7 each) and administered intraarterial therapies of: ultrafluid lipoidol embolization (group A); pingyangmycin (group B); pingyangmycin-lipiodol emulsion (group C); or saline (group D). All rabbits were sacrificed seven days later, and the response to therapy was determined by measuring the tumor volume (V2, in mm3), calculating the tumor growth rate, detecting expression of the vascular endothelial growth factor (VEGF) tumor biomarker, and performing histological analysis of the microvessel density (MVD) in the liver. Prior to therapy, the average V1 of the groups was statistically similar (A: 389.8+/-167.3, B: 404.1+/-184.9, C: 355.1+/-158.3, D: 378.1+/-189.0; (F = 0.257, P more than 0.05). In contrast, after therapy the average V2 of the groups was significantly different (A: 922.6+/-32.9, B: 665.9+/-99.9, C: 349.5+/-177.8, D: 1403.5+/-411.2; F = 26.23, P less than 0.05), as was the tumor growth ratio (A: 1.4, B: 0.6, C: -0.02, D: 2.7) and the mean positive ratio of VEGF (A: 57.1%, B: 42.9%, C: 28.6%, D: 100%; F = 8.407, P less than 0.05). MVD was highest in group D and lowest in group C (all, P less than 0.05). Bivariate correlation analysis revealed a positive correlation between VEGF expression and MVD (r = 0.743, P less than 0.01). Pingyangmycin exerts anti-tumor effects in the rabbit VX2 liver cancer model, but is more effective when administered as the combination therapy of pingyangmycin-lipiodol emulsion with TACE.
Animals ; Antibiotics, Antineoplastic ; administration & dosage ; therapeutic use ; Bleomycin ; administration & dosage ; analogs & derivatives ; therapeutic use ; Chemoembolization, Therapeutic ; methods ; Emulsions ; Ethiodized Oil ; administration & dosage ; therapeutic use ; Female ; Iodized Oil ; administration & dosage ; therapeutic use ; Liver Neoplasms, Experimental ; blood supply ; drug therapy ; pathology ; Male ; Microvessels ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Rabbits ; Random Allocation ; Tumor Burden ; drug effects ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo observe the inhibitory effect of 4-chlorobenzoyl berbamine (BBD9) on imatinib-resistant cell line K562 (K562/IR) in vitro and in vivo and explore the mechanisms.

METHODSThe IC50 of BBD9 and berbamine (BBM) was determined by MTT assay. The expressions of p210(Bcr-Abl), IKKa, cytoplasmic and nuclear NF-κBp65 were determined using Western blotting in K562/IR cells following a 48-h exposure to 0.5 µg/ml BBD9 or 8 µg/ml BBM. Flow cytometry was used to analyze the cell viability, apoptosis and necrosis; Western blotting was employed to determine the expressions of PARP, caspase-3, caspase-9 and LC3II in K562/IR cells exposed to different concentrations of BBD9 for 48 h. In nude mouse models bearing K562/IR cell xenograft, the tumor weight, tumor regression, and body weight changes of the mice were measured after treatments with 15 mg/kg and 30 mg/kg BBD9 and 100 mg/kg imatinib.

RESULTSThe IC50 of BBD9 and BBM was 0.73 µg/ml and 5.43 µg/ml, respectively. In K562/IR cell cultures, the expressions of p210(Bcr-Abl), IKKa and nuclear NF-κB p65 were all decreased following BBD9 and BBM treatments, but BBD9 produced more potent effect; cytoplasmic NF-κB p65 showed no obvious changes after the treatments. The cell apoptosis and necrosis increased with the concentrations of BBD9, which also dose-dependently increased the levels of cleaved caspase-3, csapase-9, PARP, and LC3II expression. In the tumor-bearing mouse model, BBD9 showed stronger effects than imatinib in reducing the tumor weight, promoting tumor regression, and increasing the body weight.

CONCLUSIONBBD9 can effectively inhibit the growth of K562/IR cells in vitro and in vivo by activating cell apoptosis, necrosis and autophage pathways, down-regulating expressions of p210(Bcr-Abl) and IKKa and suppressing the cytoplasm-to- nucleus translocation of NF-κBp65.

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Benzamides ; Benzylisoquinolines ; pharmacology ; therapeutic use ; Drug Resistance, Neoplasm ; Female ; Fusion Proteins, bcr-abl ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; I-kappa B Kinase ; metabolism ; Imatinib Mesylate ; K562 Cells ; Liver Neoplasms, Experimental ; drug therapy ; metabolism ; Mice ; Mice, Nude ; Piperazines ; pharmacology ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Pyrimidines ; pharmacology ; Transcription Factor RelA ; metabolism ; Xenograft Model Antitumor Assays

OBJECTIVETo study the therapeutic effect adenovirus-mediated apoptin gene transfer combined with ADM and CDDP on hepatocellular carcinoma in mice.

METHODSIn c57BL/ 6 mice bearing hepatocellular carcinoma, the changes of tumor volume, histomorphology, tumor inhibition rate and the side effects were observed after intratumoral injection of adenovirus containing apoptin gene and ADM and CDDP.

RESULTSSeven days after the treatment, the mean volume of the tumor in the mice receiving intratumoral apoptin-containing adenovirus injection combined with ADM and CDDP reduced significantly as compared with that in mice treated with adenovirus vehicle and control group. The tumor inhibition rate in the combined treatment group was 90.13%, significantly higher than that in the control group. No adverse effect of the treat was observed in the course of the experiment.

CONCLUSIONThe adenovirus vectors containing apoptin gene combined with ADM and CDDP may serve a safe treatment of hepatocellular carcinoma.

Adenoviridae ; genetics ; metabolism ; Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Capsid Proteins ; biosynthesis ; genetics ; therapeutic use ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Doxorubicin ; administration & dosage ; Gene Transfer Techniques ; Genetic Therapy ; Liver Neoplasms, Experimental ; therapy ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Random Allocation

OBJECTIVETo investigate the inhibitory effect of survivin antisense oligodeoxynuleotides (ASODN) mediated by polyethylenimine (PEI) on hepatocelluar carcinoma SMMC-7721 cell proliferation and its effect on chemosensitivity to 5-FU in tumor-bearing mice.

METHODSThe inhibitory effect of PEI-ASODN on SMMC-7721 cell proliferation was assayed by WST-8 test, Trypan blue exclusion test, and cell clone formation assay. In mouse models of transplanted H22 cell hepatocarcinoma and ascites tumor, the effect of 5-FU combined with PEI-ASODN on the weight and volume of the subcutaneous tumors was examined. The tumor inhibition rate in the tumor-bearing mice was calculated and the average survival time recorded.

RESULTSSMMC-7721 cells incubated with different concentrations of PEI-ASODN for 48 h showed significantly reduced cell proliferation in comparison with the control cells, while PEI or ASODN alone produced no such inhibitory effect. Incubation of SMMC-7721 cells with 0.75 micromol/L PEI-ASODN for 24, 48, 72, and 96 h resulted in significantly suppressed cell proliferation, and a 7-day incubation of the cells with PEI-ASODN at different concentrations (0.25-0.75 micromol/L) significantly inhibited the cell clone formation. In the tumor-bearing mice, the tumor weight and volume were obviously reduced with a tumor inhibition rate of 56.91% and volume inhibition rate of 57.83%, significantly different from those in saline-treated mice (P<0.01). In the mice bearing ascites tumor, the average survival time was 22.0 days in saline group and 42.7 days in 5-FU+PEI-ASODN treatment group, showing a a life-prolonging rate of 94.09% in the latter group. A synergetic effect was noted between 5-FU and PEI-ASODN.

CONCLUSIONPEI-ASODN complex can significantly inhibit the proliferation of hepatocarcinoma SMMC-7721 cells and enhance 5-FU chemosensitivity of the tumor cells in vitro and transplanted H22 tumors in mice.

Animals ; Antimetabolites, Antineoplastic ; pharmacology ; therapeutic use ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Synergism ; Female ; Fluorouracil ; pharmacology ; therapeutic use ; Inhibitor of Apoptosis Proteins ; genetics ; pharmacology ; therapeutic use ; Liver Neoplasms, Experimental ; drug therapy ; pathology ; Male ; Mice ; Oligodeoxyribonucleotides, Antisense ; pharmacology ; therapeutic use ; Repressor Proteins ; genetics ; pharmacology ; therapeutic use

OBJECTIVETo research the microemulsion preparation of Ganoderma lucidum polysaccharides and triterpenes and investigate its properities. Evaluate the effects of polysaccharides and triterpenes microemulsions against transplant tumor growth.

METHODThe microemulsion formula was optimized by constructing the pseudo-ternary phase diagrams of blank microemulsion. The polysaccharides and triterpenes microemulsions were prepared on the blank microemulsions. The appearance, particle distribution and Zeta potential were investigated by transmission electron microscope and grain size analyzer. The Heps mice were randomly administered with polysaccharides and triterpenes microemulsions (114.5, 57.25 mg x kg(-1) x d(-1)) for 7 days. The effectiveness was assessed based on tumor inhibitory ratio of mice with Heps tumors. The toxicity was evaluated by measurements of the mice weight, immune organ weight.

RESULTThe optimal microemulsion formula was composed of tween 20, dimethyl carbinol, water and 9-octadecenoic acid with the ratio of 14.3: 14.3: 33. 3:2. Polysaccharides and triterpenes microemulsions in transmission electron microscope were consisted of small spherical drop. The average particle size was 32.43 nm and the Zeta potential was -3.41 mV. The polysaccharides and triterpenes microemulsions showed an inhibition rate of 37.66% (57.25 mg x kg(-1) x d(-1)) and 52.34% (114.5 mg x kg(-1) x d(-1)) respectively against Heps tumor growth.

CONCLUSIONThe acquired microemulsion with small particle size is stable. It significantly inhibits the tumor growth in Heps mice.

Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Emulsions ; Female ; Liver Neoplasms, Experimental ; drug therapy ; Male ; Mice ; Neoplasm Transplantation ; Particle Size ; Polysaccharides ; therapeutic use ; Reishi ; chemistry ; Triterpenes ; therapeutic use