OBJECTIVETo establish a modified rat model of liver cancer with concurrent cirrhosis for the study of carcinogenesis characteristics and drug intervention of liver cancer.

METHODSFifty male Wistar rats weighing 100-120 g were randomly divided into normal control group (20 rats) and model group (30 rats). In the model group, the rats were subjected to intraperitoneal injection of 50 mg/kg DEN N-diethylnitrosamine (DEN) twice a week for 4 consecutive weeks, followed then by weekly injections for another 10 weeks. The control rats received injections of 0.1 ml saline in the same manner. At 2, 4, 8, 12, 14, and 18 weeks, 3 rats from each group were sacrificed for assessing tumor formation and liver cirrhosis.

RESULTSLiver cancer with concurrent cirrhosis was induced successfully after 14 weeks of DEN injections. At the 14th week, 3 out of the 5 rats were found to have cirrhosis and LC, and at the 18th week, all the 3 rats examined had cirrhosis and liver cancer. The total carcinogenesis rate in the rats was 75% at 18 weeks with an overall mortality of 33%.

CONCLUSIONThis approach to establishing rat models of liver cancer with concurrent cirrhosis requires simple operation, shortens the time of carcinogenesis, and ensures a high success rate of carcinogenesis and a low mortality rate. The carcinogenesis characteristics in this model are similar to those in human.

Animals ; Liver Cirrhosis, Experimental ; complications ; pathology ; Liver Neoplasms, Experimental ; etiology ; pathology ; Male ; Rats ; Rats, Wistar

Animals ; Neoplasm Metastasis ; genetics ; Neoplasms, Experimental ; genetics ; pathology

Animals ; Humans ; Microchip Analytical Procedures ; Neoplasms ; pathology ; Neoplasms, Experimental ; pathology ; Pathology ; Periodicals as Topic ; RNA Interference

OBJECTIVETo investigate the malignant tendency of liver basophilic cells in rats by examining the liver dynamic pathological changes during the hepatocarcinogenesis induced by diethylnitrosamine (DEN).

METHODSOne hundred forty male Sprague-Dawley rats, about 200 g each, were randomly divided into a normal group and a model group. The model group rats were administered 1% DEN intragastrically once a week for 14 weeks. The normal control group rats were given saline instead of DEN. Seven to ten rats of the model group were sacrificed at 2, 3, 5, 8, 10, 12, 14, 18 weeks. The remaining rats were followed to the end of the experiment at 26 weeks. Histopathological changes of the livers were analyzed, and the localization of GST-P and PCNA in the livers were detected in situ by immunohistochemistry.

RESULTSAccording to the characteristics of the lesions in the model group, histological liver change patterns were categorized into three phases: (1) liver injury phase (2 to 5 weeks) with centrilobular necrosis, a small amount of collagen deposition in the necrotic regions with fibrous septa development and cell proliferation; (2) the cirrhosis phase (8 to 12 weeks) with significant hepatocellular regeneration and collagen deposition. As the regenerative nodules and fibrous septa formed, cirrhosis with uniform sized nodules developed in all the rats at 12 weeks. In the regenerative nodules, significant hepatocellular metamorphosis was seen; (3) In the carcinomatous transformation and nodular remodeling phase (after 14 weeks), two types of cancer, namely hepatocellular carcinoma and cholangiocarcinoma were found. Incidence of the cancer was 62.5% at 18 weeks. Basophilic cell lesions appeared beginning at 10 weeks. Pale bodies were seen in some basophilic cells. Small cell changes appeared starting at 12 weeks. Some of these cells containing droplets like lipid vacuoles, invaded into the surrounding liver tissues. Both basophilic cell lesions and small cell changes were all positive for proliferating cell nuclear antigen (PCNA).

CONCLUSIONDevelopment of foci of basophilic small cells, with cells containing lipid vacuoles and pale bodies, and invading into the surrounding liver tissues are the changes highly suggestive of an early hepatocellular carcinoma transformation.

Animals ; Basophils ; pathology ; Carcinoma, Hepatocellular ; pathology ; Hepatocytes ; pathology ; Liver Neoplasms, Experimental ; pathology ; Male ; Precancerous Conditions ; pathology ; Rats ; Rats, Sprague-Dawley

No abstract available.
Animals ; Female ; Lymphatic Metastasis/*pathology ; Magnetic Resonance Imaging/*methods ; Mammary Neoplasms, Experimental/*pathology

Animals ; Cell Line, Tumor ; Disease Models, Animal ; Neoplasms, Experimental ; pathology ; Pathology

OBJECTIVETo investigate the relationship between the extracellular matrix (ECM) and neoplastic progression in hamster with tongue cancer.

METHODSForty-eight specimens of hamster tongue cancer were divided into control group (n=6) and experimental group (n=42). The pathological grade of the specimens was assessed (including 3 stages, namely atypical hyperplasia, carcinoma in situ and early invasive carcinoma). The sections of the tongue were stained with Masson and aldehyde-fuchsin (AF) staining for microscopic observation of the elastic fiber and collagen fiber changes.

RESULTSWithin the connective tissue cores (CTC) of the papillae in the control group was a framework of numerous and fine Gomrori's aldehyde fuchsin-positive elastic fibers. But in the stages of dysplasia and carcinoma in situ, these elastic fibers decreased and further diminished in the CTC in early invasive carcinoma. In dysplasia and carcinoma in situ stages, most of the elastic fibers collapsed with scattered elastic fibers, and the elastic fibers decreased significantly in early invasive carcinoma. The control group showed a significantly greater number of elastic fibers in the experimental group. The collagen fiber was obviously increased and irregularly arranged in dysplasia and carcinoma in situ stage; in early invasive carcinoma, the collagen fibers became thicker with deposition in the lamina propria.

CONCLUSIONAn excessive deposition of collagen fiber and reduction of the elastic fibers is an important factor contributing to the development of tongue carcinoma in hamsters.

Animals ; Carcinoma ; pathology ; Collagen ; metabolism ; Connective Tissue ; pathology ; Cricetinae ; Elastic Tissue ; pathology ; Extracellular Matrix ; pathology ; Neoplasms, Experimental ; pathology ; Tongue Neoplasms ; pathology

OBJECTIVETo evaluate the efficacy of energy controllable steep pulses (ECSP) in the treatment of rabbit VX2 cancer implanted in livers.

METHODSA tumor model was successfully established using 30 rabbits. ECSP were applied to liver cancer in half of these rabbits and the rest were used as controls. After exposure to ECSP, tissues were obtained and subjected by routine HE and transmission electron microscopic (TEM) observation. The survival time of the animals and the statuses of each group were recorded.

RESULTSFrom pathological observations, ECSP showed effectively destructive action compared with that of the unexposed group. A clear borderline can be seen between necrotic cancer and its surrounding normal tissue. Irreversible cell changes were present under TEM. The survival periods of the experimental and control group were 83.1 days and 39.0 days respectively, and there was a significant difference between the two groups (Z = -2.943, P < 0.01).

CONCLUSIONECSP can effectively treat rabbit VX2 cancer implanted in the liver; also it is safe for its surrounding normal tissues. ECSP can be a useful method for local treatment of liver cancer.

Animals ; Electric Conductivity ; Electromagnetic Fields ; Electroporation ; methods ; Female ; Liver Neoplasms, Experimental ; pathology ; Male ; Rabbits

OBJECTIVESTo evaluate the efficacy of recombinant human adenovirus p53 gene therapy (rAd-p53) in the rabbit VX2 liver cancer model using different interventional therapy approach.

METHODSThirty New Zealand rabbits implanted with VX2 tumor in the liver were randomized into five groups with six of each. The tumor volumes (V1) were measured by MRI and CT scan 11 days after tumors implanted. The interventional therapy scheme performed as below: intraarterial 0.9% saline solution perfusion in group A, transcatheter arterial embolization with 0.5 ml ultrafluid lipiodol in group B, intraarterial rAd-p53 gene perfusion in group C (1 x 10(6)/VP); intraarterial rAd-p53 gene perfusion (1 x 10(6)/VP) in combination with transcatheter arterial embolization (ultrofluid lipiodol, 0.5 ml) in group D and intratumoral rAd-p53 gene (1 x 10(6)/VP) injection in group E. The tumor volumes (V2) were measured by MRI and CT scan, and the tumor growth ratios were calculated 14 days after interventional procedures. Then all animals were sacrificed.

RESULTSThe tumor tissues were explanted for immunohistochemistry to observe the expressions of vascular endothelial cell growth factor (VEGF) and factor VIII. Microvessel density (MVD) of the tumor tissues was assessed by factor VIII immunohistochemical analysis. In addition, apoptotic index was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The tumor volumes before therapy were (79.4+/-8.2), (75.3+/-7.8), (74.6+/-6.6), (78.7+/-9.1), (75.8+/-8.4) mm(3) respectively, without differences found among them (F = 12.248, P = 0.0636). But the tumor volumes after therapy were (564.7+/-96.7), (176.5+/-83.2), (239.6+/-42.8), (159.8+/-58.6), (334.7+/-32.6) mm(3) respectively (F = 24.537, P = 0.0218). The tumor growth ratios were 6.9, 2.6, 3.1, 1.6 and 4.1 respectively. The mean apoptosis index were 12.0%+/-1.1%, 14.5%+/-2.1%, 17.6%+/-2.3%, 18.6%+/-2.3% and 19.6%+/-2.5% respectively. with significant differences in group E in comparison with the other four groups. Mean positive ratio of VEGF was 50.0%, 83.3%, 83.3%, 50.0% and 50.0% respectively, with significant differences observed in group B and group C compared with the other three groups (F = 7.84, P = 0.019). The differences of VIII factor positive expression ratio among each group were significant (F = 0.854, P = 0.018). Statistical analysis showed a positive correlation between the expression of VEGF and MVD (r = 2.400, P = 0.0233).

CONCLUSIONThe rAd-p53 has effective treatment outcomes in VX2 rabbit liver cancer, and intra-arterial rAd-p53 gene perfusion in combination with transcatheter arterial embolization is the best approach in comparison with intra-arterial rAd-p53 gene perfusion, transcatheter arterial embolization and intratumoral rAd-p53 gene injection alone.

Adenoviruses, Human ; genetics ; Animals ; Genes, p53 ; Genetic Therapy ; Liver Neoplasms, Experimental ; pathology ; therapy ; Rabbits ; Treatment Outcome

OBJECTIVETo observe effects of cold- and hot-property herbs and effects of hot and cold constitutions on the tumor growth of tumor bearing rats, and to observe the effect of Cinobufacini Injection (CI) on the tumor growth of tumor bearing rats of different constitutions.

METHODSEighty healthy male Wistar rats were randomly divided into eight groups, i.e., the tumor bearing control group, the tumor bearing heat syndrome group, the tumor bearing cold syndrome group, the heat syndrome tumor bearing group, the cold syndrome tumor bearing group, the tumor bearing CI group, the heat syndrome tumor bearing CI group, and the cold syndrome tumor bearing CI group, respectively. The weight and volume of rats' subcutaneous tumor were measured 14 days after tumor inoculation.

RESULTSThe weight and volume of tumor in the heat syndrome tumor bearing CI group [(3.55 +/- 1.12) g, (2864.44 +/- 1430.51) mm3] and the tumor bearing CI group [(4.29 +/- 1.14) g, (3397.19 +/- 1701.13) mm3] were significantly lower than those of the tumor bearing control group [(6.01 +/- 2.45) g, (6218.91 +/- 3837.64) mm3] and the cold syndrome tumor bearing CI group [(6.90 +/- 1.57) g, (6168.42 +/- 2457.03) mm3], showing statistical difference (P<0.05). There was insignificant difference among other groups.

CONCLUSIONSCI showed better tumor inhibition effects on tumor bearing rats of heat syndrome constitution, which indicated CI was of cold property. It might be possibly used in tumor bearing rats of heat syndrome constitution.

Animals ; Bufanolides ; pharmacology ; therapeutic use ; Injections ; Male ; Neoplasms, Experimental ; drug therapy ; pathology ; Rats ; Rats, Wistar