Halmos G, Schally A V, Sun B, Davis R, Bostwick D G, Plonowski A
Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center and Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
J Clin Endocrinol Metab. 2000 Jul;85(7):2564-71. doi: 10.1210/jcem.85.7.6698.
To evaluate the potential application of somatostatin (SST) analogs as an adjuvant treatment for prostate cancer, we characterized the binding sites for SST octapeptide analogs on prostate cancers in patients treated with radical prostatectomy. The affinity and density of binding sites for SST analog RC-160 on 80 surgical specimens of prostate cancers were determined by ligand competition assays. The expression of messenger ribonucleic acid (mRNA) for SST receptor subtype 1 (SSTR1), subtype 2 (SSTR2), and subtype 5 (SSTR5) was also investigated in 22 samples by RT-PCR. Fifty-two of 80 specimens (65%), showed a single class of specific binding sites for RC-160 with a mean dissociation constant (K(d)) of 9.44 nmol/L and a mean maximal binding capacity of 754.8 fmol/mg membrane protein. The mRNA for SSTR1 was detected in 86% of samples, whereas the incidences of mRNA for SSTR2 and SSTR5 were 14% and 64%, respectively. The expression of SSTR2 and/or SSTR5 was 100%, consistent with the presence of RC-160 binding. In patients at high risk of cancer recurrence (stage pT3 and/or Gleason score of 8-10), the incidence of RC-160 binding (65.7%) was similar to that observed in the low risk group (64.3%). The demonstration of the high incidence of octapeptide-preferring SSTRs in organ-confined and locally advanced prostate cancers supports the merit of further investigations of the application of SST analogs and their radionuclide and cytotoxic derivatives for adjuvant treatment of patients at high risk of cancer recurrence after radical prostatectomy. Such approaches could be also considered for patients with advanced prostate cancer at the time of relapse.
为评估生长抑素(SST)类似物作为前列腺癌辅助治疗的潜在应用,我们对接受根治性前列腺切除术患者的前列腺癌中SST八肽类似物的结合位点进行了表征。通过配体竞争试验确定了SST类似物RC - 160在80份前列腺癌手术标本上结合位点的亲和力和密度。还通过逆转录聚合酶链反应(RT - PCR)在22份样本中研究了生长抑素受体1型(SSTR1)、2型(SSTR2)和5型(SSTR5)信使核糖核酸(mRNA)的表达。80份标本中有52份(65%)显示出一类针对RC - 160的特异性结合位点,平均解离常数(K(d))为9.44 nmol/L,平均最大结合容量为754.8 fmol/mg膜蛋白。86%的样本中检测到SSTR1的mRNA,而SSTR2和SSTR5的mRNA发生率分别为14%和64%。SSTR2和/或SSTR5的表达率为100%,与RC - 160结合的存在一致。在癌症复发高危患者(pT3期和/或Gleason评分为8 - 10分)中,RC - 160结合的发生率(65.7%)与低风险组(64.3%)相似。在器官局限性和局部进展性前列腺癌中八肽偏好性SSTRs的高发生率表明,进一步研究SST类似物及其放射性核素和细胞毒性衍生物在根治性前列腺切除术后癌症复发高危患者辅助治疗中的应用具有价值。对于晚期前列腺癌复发时的患者也可考虑采用此类方法。