Weld Kyle J, Mayher Brant E, Allay James A, Cockroft Jody L, Reed Christopher P, Randolph Mildred M, Lu Yi, Steiner Mitchell S, Gingrich Jeffrey R
Urologic Research Laboratories, University of Tennessee, Memphis, Tennessee 38163, USA.
Cancer Gene Ther. 2002 Feb;9(2):189-96. doi: 10.1038/sj.cgt.7700425.
Direct transrectal delivery of therapeutic genes utilizing adenoviral vectors for advanced prostate cancer may offer effective treatment at the molecular level. Large animal models to assess feasibility and the intraprostatic and systemic dissemination patterns of these vectors have not been reported. For these studies, a replication-deficient (E1(-)/E3(-)) recombinant adenovirus (AdRSVlacZ) expressing bacterial beta-galactosidase (beta-gal) was delivered under transrectal ultrasound guidance. Two prostate biopsies, followed by concurrent injection of 4.8 x 10(9) pfu of the adenoviral vector divided into either 1 or 2 mL of diluent, were performed (n=4). Swabs of the rectum, sputum, and urine were collected and after 72 hours, the animals were sacrificed. Specimens were assayed for the presence of virus and beta-gal activity. Rectal swabs were transiently positive, whereas urine and sputum samples showed no detectable vector throughout the experiment. Beta-gal activity was observed at the prostate injection sites with detectable activity noted up to 7.5 mm away from the injection site. Systemic dissemination was observed regardless of the injected volume. In conclusion, transrectal prostate biopsy with concurrent prostate injection is a feasible method to deliver therapeutic adenoviral vectors for the treatment of prostate cancer; however, systemic distribution and temporary rectal shedding of virus should be anticipated.
利用腺病毒载体经直肠直接递送治疗性基因用于晚期前列腺癌，可能在分子水平提供有效的治疗方法。尚未见有评估这些载体的可行性以及前列腺内和全身扩散模式的大型动物模型的报道。在这些研究中，在经直肠超声引导下递送表达细菌β-半乳糖苷酶（β-gal）的复制缺陷型（E1(-)/E3(-)）重组腺病毒（AdRSVlacZ）。进行两次前列腺活检，随后将4.8×10(9) pfu的腺病毒载体分为1或2 mL稀释剂进行同时注射（n = 4）。收集直肠、痰液和尿液拭子，72小时后处死动物。对标本进行病毒存在情况和β-gal活性检测。直肠拭子呈短暂阳性，而在整个实验过程中尿液和痰液样本未检测到载体。在前列腺注射部位观察到β-gal活性，在距注射部位7.5 mm处仍可检测到活性。无论注射体积如何，均观察到全身扩散。总之，经直肠前列腺活检同时进行前列腺注射是递送治疗性腺病毒载体治疗前列腺癌的一种可行方法；然而，应预计到病毒的全身分布和暂时的直肠排出。
