基因治疗课件(同名102).ppt

1、 State Key Laboratory of Cancer Biology&Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xian,P.R.ChinaXin-min Zhou.tumor typetumor typeCasesCases（10,00010,000）RankRankDeathsDeaths（10,00010,000）RankRanklung cancer135.01118.01breast cancer115.0241.15colorectal cancer100.0352.9

2、4stomach cancer93.4470.02prostate cancer67.9522.16liver cancer62.6659.83 Parkin DM,et al.CA Cancer J Clin 2005;55:74-108 .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 ar

3、ound 3.Data from Chinese HCC status survey initiated by Chinese Anti-cancer Associationstage Astage Astage Bstage Bstage Cstage Cstage Dstage D53.927.115.32.6.Stage 0PST 0,Child-Pugh APortal pressure/bilirubinRFA=radiofrequency ablation;PEI=percutaneous ethanol injection.HCCStage ACOkuda 12,PST 02,C

4、hild-Pugh ABStage DPST 2,Child-Pugh CVery early stage(0)Single 2 cmcarcinoma in situEarly stage(A)13 nodules 3 cm,PS 0Intermediate stage(B)Multinodular,PS 0Advanced stage(C)Portal invasion,N1,M1,PS 12End stage(D)Single3 nodules 3 cmIncreasedAssociated diseasesNormalNoYesResectionLiver transplantatio

5、nPEI/RFAChemoembolizationSorafenibCurative treatmentsPalliative treatmentsSymptomatictreatmentBruix 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

6、in the TP53 gene are a feature of 50%of all reported cancer cases.Christian Frezza,et,al.Drug Resistance Updates Volume 15,Issues 5?6 2012 258-267.p53:17p13.1.9CDKVEGFdamage repair genefeedbackp21 cutting tumor blood supplyGD-AIFBAI-1TSPp53Ku70 DNA-PK ATM reverse RT sensitivityMDRreverse chemoresist

7、ancecell cycle arrestMMPInhibit invasion and metastasisNKbystander effecta(II)PHcell apoptosisAd-p53 antitumor mechanismsthrough multiple pathways.adenoviral delivery vehicle antitumor adenoviral delivery vehicle antitumor mechanismsmechanisms regulate patients physiological functionreduce the side

8、effects caused by conventional radio-and chemotherapyimprove appetite and general health statusimprove patients quality of lifeadenoviral delivery vehicletrigger immune responseinduce cytokines and lymphocytesincrease humoral immunity and cellular immunitynerveendocrine systemImmune system.Recombina

9、nt 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

10、 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

11、VP,once per week for 4 weeks,2 days after TACE was carried out,TACE was repeated after two monthsResult:After two sessions of treatment,CT indicated a much smaller lesion sized 32 cm,and serum AFP level decreased to 6075 ng/mL,Case 1Case 1.Before treatmentAfter treatment.Case 2Case 2 Female,56y,CT d

12、epicted 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 tim

13、e,and serum AFP level decreased to 2127 ng/mL,.Before treatmentAfter treatment.1:1 randomization （n=80）rAd-P53+FOLFX4 FOLFX4 Inclusion criterian Staging B-C HCCn Karnofsky 60 n Child Pugh A statusEffect assessmentResponse RateLife qualitySafety assessmentAdverse effect21012 rAd-p53 VP per 2 days for

14、 10 times.groupnCRPRMRSDPDCR+PR(%)treatment 40018118345.0control 40011815627.5Response rates by Response Evaluation Criteria in Solid TumorsResponse rates by Response Evaluation Criteria in Solid Tumors.groupnimprovedStableprogressive CR+PR(%)treatment 402410685.0control 401571855.0.No severe side effects have been observed.Overall,Gendicine is safe and well tolerated by patients.the most common side effects were pain at the injection site,fatigue,and development of self-limited fever,which could be alleviated by symptomatic treatment.