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Titolo:
Enhanced therapeutic effect of HSV-tk plus GCV gene therapy and ionizing radiation for prostate cancer
Autore:
Chhikara, M; Huang, HX; Vlachaki, MT; Zhu, XH; Teh, B; Chiu, KJ; Woo, S; Berner, B; Smith, EO; Oberg, KC; Aguilar, LK; Thompson, TC; Butler, EB; Aguilar-Cordova, E;
Indirizzi:
Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 , Dept Pediat, Houston, TX 77030 USA Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 Gene Therapy, Houston, TX 77030 USA Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 , Dept Radiol, Houston, TX 77030 USA Baylor Coll Med, Vet Affairs Med Ctr, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 fairs Med Ctr, Houston, TX 77030 USA Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 , Dept Pathol, Houston, TX 77030 USA Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 ott Dept Urol, Houston, TX 77030 USA Loma Linda Univ, Sch Med, Div Human Anat, Loma Linda, CA 92350 USA Loma Linda Univ Loma Linda CA USA 92350 an Anat, Loma Linda, CA 92350 USA Advantagene Inc, San Diego, CA 92024 USA Advantagene Inc San Diego CA USA92024 agene Inc, San Diego, CA 92024 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 4, volume: 3, anno: 2001,
pagine: 536 - 542
SICI:
1525-0016(200104)3:4<536:ETEOHP>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
VIRUS THYMIDINE KINASE; RANDOMIZED COMPARATIVE TRIAL; ONCOLOGY GROUP; GANCICLOVIR THERAPY; CLINICAL-TRIAL; MOUSE MODEL; RADIOTHERAPY; CARCINOMA; ADENOVIRUS; IRRADIATION;
Keywords:
gene therapy; radiotherapy; herpes simplex virus thymidine kinase; adenoviral vector; prostate cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Aguilar-Cordova, E Harvard Univ, Sch Med, Harvard Gene Therapy Initiat, 4 Blackfan Circle,Suite 407, Boston, MA 02115 USA Harvard Univ 4 Blackfan Circle,Suite 407 Boston MA USA 02115
Citazione:
M. Chhikara et al., "Enhanced therapeutic effect of HSV-tk plus GCV gene therapy and ionizing radiation for prostate cancer", MOL THER, 3(4), 2001, pp. 536-542

Abstract

Standard therapies for prostate cancer including radiation, prostatectomy,and hormone ablation have significant toxicities and recurrence risk. HSV-tk gene therapy may be effective in combination with radiation therapy due to complementary mechanisms and distinct toxicity profiles. Mouse prostate tumors transplanted subcutaneously were treated by either gene therapy involving intratumoral injection of AdV-tk followed by systemic ganciclovir or local radiation therapy or the combination of gene and radiation therapy. Both single-therapy modalities showed a 38% decrease in tumor growth compared to controls. The combined treatment resulted in a decrease of 61%. In addition the combined-therapy group had a mean survival of 22 days versus 16.6days for single therapy and 13.8 days for nontreated controls. To analyze systemic anti-tumor activity, lung metastases were generated by tail vein injection of RM-1 prostate cancer cells on the same day that they were injected subcutaneously. The primary tumors were treated as before with AdV-tk followed by ganciclovir, radiation, or the combination. The number of lung nodules was reduced by 37% following treatment with AdV-tk, whereas radiotherapy alone had no effect on metastatic growth. The combination led to an additional 50% reduction in lung colonization. Primary tumors that received the combination therapy had a marked increase in CD4 T cell infiltrate. Thisis the first report showing a dramatic systemic effect following the localcombination treatment of radiation and AdV-tk. A clinical study using thisstrategy has been initiated and patient accrual is ongoing.

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Documento generato il 04/04/20 alle ore 21:36:02