基因治疗ppt课件

State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xian, P.R.China,Xin-min Zhou,rAd-P53 gene therapy for advanced hepatocellular carcinoma,Parkin DM, et al. CA Cancer J Clin 2005;55:74-108,HCC is the sixth most common cancer worldwide and the third most common cause of death from cancer,China is the most prevalent region of HCC,Global Cancer Statistics, 2002. CA Cancer J Clin 2005;55:74-108,There were 626,162 new cases of HCC worldwide in 2002 China accouts for 55 of all cases Male-to-female ratios are around 3,Distribution of HCC patient according to BCLC staging in China,Data from Chinese HCC status survey initiated by Chinese Anti-cancer Association,stage A,stage B,stage C,stage D,53.9,27.1,15.3,2.6,BCLC staging and treatment strategy,Stage 0 PST 0, Child-Pugh A,Portal pressure/bilirubin,RFA = radiofrequency ablation; PEI = percutaneous ethanol injection.,HCC,Stage AC Okuda 12, PST 02, Child-Pugh AB,Stage D PST 2, Child-Pugh C,Very early stage (0) Single 2 cm carcinoma in situ,Early stage (A) 13 nodules 3 cm, PS 0,Intermediate stage (B) Multinodular, PS 0,Advanced stage (C) Portal invasion, N1, M1, PS 12,End stage (D),Single,3 nodules 3 cm,Increased,Associated diseases,Normal,No,Yes,Resection,Liver transplantation,PEI/RFA,Chemoembolization,Sorafenib,Curative treatments,Bruix J, et al. Hepatology 2011; 53(3):1020-1022.,TP53 gene, widely regarded as the genome guardian of cells, plays a key role in cell cycle control, apoptosis, and inhibition of tumor cell proliferation. Mutations in the TP53 gene are a feature of 50% of all reported cancer cases.,TP53: the most commonly mutated gene in human cancer,Christian Frezza , et, al . Drug Resistance Updates Volume 15, Issues 5?6 2012 258 - 267,p53 restoration strategies for cancer treatment,Restoring TP53 functions: gene therapy,9,CDK,VEGF,damage repair gene,MDM2,feedback,cutting tumor blood supply,GD-AIF,BAI-1,TSP,p53,Ku70,DNA-PK,ATM,reverse RT sensitivity,MDR,reverse chemoresistance,cell cycle arrest,MMP,Inhibit invasion and metastasis,NK,bystander effect,a(II)PH,cell apoptosis,Ad-p53 antitumor mechanismsthrough multiple pathways,adenoviral delivery vehicle antitumor mechanisms,regulate patients physiological function,reduce the side effects caused by conventional radio- and chemotherapy,improve appetite and general health status,improve patients quality of life,adenoviral delivery vehicle,trigger immune response,induce cytokines and lymphocytes,increase humoral immunity and cellular immunity,nerveendocrine system,Immune system,Ad-p53A promising treatment modality for advanced HCC,Recombinant human adenovirusp53 injection (GendicineTM) has shown encouraging results in clinical applications for treatment of advanced HCC. Gendicine could be administered via intravenous injection, intraperitoneal infusion and hepatic artery infusion. Gendicine could be applied in combination with conventional therapies such as radiotherapy, chemotherapy, and surgery.,Male, 63y, CT indicated a low density, space-occupying lesion, sized 1613.5 cm in the right lobe of the liver Tumor stage C(BCLC), AFP 12947 ng/mL. Treatment regimen: intratumoral injection of Gendicine via transcatheter perfusion at a dose of 21012 VP, once per week for 4 weeks, 2 days after TACE was carried out, TACE was repeated after two months Result: After two sessions of treatment, CT indicated a much smaller lesion sized 32 cm, and serum AFP level decreased to 6075 ng/mL,Case 1,Before treatment,After treatment,Case 2,Female, 56y, CT depicted intrahepatic multinodular HCC, Tumor stage C(BCLC), AFP 3565 ng/mL. Treatment regimen: Intravenous injection of Gendicine at a dose of 21012 VP, once every other day for 5 times after TACE was carried out. Result: After one sessions of treatment, CT indicated a smaller lesions compared with last time, and serum AFP level decreased to 2127 ng/mL,Before treatment,After treatment,Ongoing clinical trial,1 : 1 randomization （n = 80）,rAd-P53+ FOLFX4,FOLFX4,Inclusion criteria Staging B-C HCC Karnofsky 60 Child Pugh A status,Effect assessment Response Rate Life quality Safety assessment Adverse effect,21012 rAd-p53 VP per 2 days for 10 times,Response rates by Response Evaluation Criteria in Solid Tumors,Response rates by Response Evaluation Criteria in Solid Tumors,Response rates by Response Evaluation Criteria in Solid Tumors,Life of quality by Karnofsky,Safety,No severe side effects have been observed. Overall, Gendicine is safe