Animals ; Carcinoma, Hepatocellular ; genetics ; therapy ; Genetic Therapy ; methods ; Humans ; Liver Neoplasms, Experimental ; genetics ; therapy ; Treatment Outcome

OBJECTIVETo construct and express secretive endostatin eukaryotic plasmid for treatment of hepatoma.

METHODSMouse Igk signal peptide sequence was synthesized and cloned into pcDNA3.1 with endostatin gene. The supernant of BHK-21 transfected with recombinant was used to culture ECV304. The proliferation of latter was evaluated by MTT assay. H22 was inoculated intramusclely, then naked DNA of endostatin plasmid was injected into the inoculation site. Tumors were dissected and weighted after treatments. All data was analyzed by SPSS10.0.

RESULTSThe supernant of BHK-21 transfected with recombinant can inhibit the proliferation of ECV304 by 29.2%. Tumor weight lighter after injected with naked pSecES (1.34 g+/-0.96g) compared with naked pcDNA3.1 (2.70g+/-0.82g) and saline (3.73g+/-1.41g).

CONCLUSIONThe endostatin eukaryotic plasmid was constructed and it can be used for gene therapy on hepatoma.

Animals ; Endostatins ; genetics ; secretion ; Genetic Therapy ; Liver Neoplasms, Experimental ; therapy ; Male ; Mice ; Plasmids

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

*Chemoembolization, Therapeutic/methods ; Drugs, Chinese Herbal/*administration & dosage ; Hepatic Artery ; Liver Neoplasms, Experimental/pathology ; Liver Neoplasms, Experimental/*therapy ; Orchidaceae ; Phytotherapy ; Rats, Inbred ACI

*Chemoembolization, Therapeutic ; Liver Neoplasms, Experimental/*therapy ; Microspheres ; Polyglactin 910/*therapeutic use ; Rats, Inbred ACI

Animals ; Combined Modality Therapy ; Endostatins ; genetics ; Genetic Therapy ; Liver Neoplasms, Experimental ; radiotherapy ; therapy ; Mice ; Mice, Nude ; Neoplasm Transplantation

Animals ; Carcinoma in Situ ; therapy ; Cell Line, Tumor ; Genetic Therapy ; methods ; Interleukin-12 ; genetics ; Liver Neoplasms, Experimental ; therapy ; Mice ; Neoplasm Transplantation

BACKGROUNDElectrochemical therapy (ECT) has been used to treat unresectable hepatic tumor. In order to improve its efficacy, we combined ECT with hyperthermia induced by electrothermal needle (ETN) (ETECT). The aim of this study is to investigate the destructive effect of ETECT on normal rat liver.

METHODSTwenty rats were randomized into 4 treatment groups (n=5 in each group): control, ECT alone, hyperthermia alone and ETECT. Following the treatment, sections of the livers were histologically examined by light microscopy and the destructive volumes were measured with micrometer.

RESULTSWe found that the destructive volumes in ETECT group were the largest (P<0.01). In ETECT group coagulative necrosis was found in both anode and cathode areas, around which transition zones existed. The transition zones can only be seen when coulomb was increased in ECT group.

CONCLUSIONETECT was demonstrated to enhance the destructive effect of ECT. This study provides theoretical and experimental basis for a new local ablative treatment for unresectable primary liver tumor.

Animals ; Electric Stimulation Therapy ; methods ; Electrochemistry ; Female ; Hyperthermia, Induced ; methods ; Liver Neoplasms, Experimental ; pathology ; therapy ; Rats ; Rats, Sprague-Dawley

Animals ; Chemoembolization, Therapeutic ; Liver Neoplasms, Experimental ; therapy ; Male ; Microspheres ; Polyglactin 910 ; therapeutic use ; Rats ; Rats, Inbred ACI

OBJECTIVETo investigate the therapeutic effects of adenovirus-mediated transfer of the herpes simplex virus thymidine rinase gene (HSV-tk) used by several methods and the dose-effect relationship.

METHODSDiverse doses (1 x 10(9) PFU, 1 x 10(10) PFU, 1 x 10(11) PFU) of adenovirus-mediated transfer of HSV-tk were given by intraparenchymatous, intravenous and intraperitoneal injection, and ganciclovir (GCV) (100 mg.kg(-1).d(-1)) was injected into the cavity of the peritoneum to treat human hepatocarcinoma. The change of tumors size was observed and the fragments of HSV-tk gene were tested.

RESULTSIn nude mice after intraparenchymatous injection and high-dose (1 x 10(11) PFU) intravenous injection, the tumors were suppressed significantly (t = 13.1, 12.4, P < 0.01) and lots of fragments of HSV-tk gene were observed. In mice after intraperitoneal injection and low-dose (1 x 10(9) PFU, 1 x 10(10) PFU) intravenous injection, no suppressive effect was observed (t = 1.8, 1.0, 2.1, 1.1, 0.8, P > 0.05) with few or without fragments in the tumors.

CONCLUSIONSAdenovirus-mediated transfer of the HSV-tk by intraparenchymatous or intravenous injection is effective in treatment of hepatocarcinoma in nude mice, but intraperitoneal injection has no therapeutic effect.

Adenoviridae ; genetics ; Animals ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Humans ; Liver Neoplasms, Experimental ; therapy ; Mice ; Mice, Inbred BALB C ; Simplexvirus ; enzymology ; Thymidine Kinase ; genetics ; Tumor Cells, Cultured