Prostate stem cells and benign prostatic hyperplasia
Prostate stem cells and benign prostatic hyperplasia
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DOI：
10.1002/pros.20763
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发表时间：
2008-06-15
期刊：
影响因子：
2.8
通讯作者：
Isaacs, John T.
中科院分区：
文献类型：
--
作者：
Isaacs, John T.
在需要手术干预之前，药物治疗可用于治疗有症状的BPH患者。这些包括每日单独或联合使用α-受体阻滞剂和5-α-还原酶抑制剂治疗。这些医疗方法有两个主要问题。首先，治疗是慢性的，必须每天服用。其次，这种慢性治疗存在显著的财务成本和生活质量问题。是否有可能开发出有效的急性治疗有症状的BPH，而没有长期雄激素剥夺诱导的副作用？沃尔什[Peters，沃尔什：新英格兰医学杂志317：599- 604，1987]和科菲等人[Sufrin等人：Invest Urol 13：418- 423，1976]，结合对前列腺基质（S）和上皮（E）隔室的干细胞组织及其相互旁分泌和自分泌相互作用的日益增长的理解，提供了急性方法的基本原理。（1）雄激素剥夺破坏了前列腺S和E之间的相互作用，从而降低了两个区室的重量，和（2）一旦BPH发展，雄激素剥夺不会减少S或E区室中的干细胞单位的数量，因为随后的雄激素恢复完全恢复了增大的腺体。Coffey研究证明，急性雄激素剥夺使S-E相互作用对辐射诱导的破坏敏感，因此在辐射后，雄激素恢复不会诱导完全的腺体再生。因此，对症状性BPH的有效治疗应该是通过在有限的时间内进行可逆性雄激素剥夺的急性治疗，然后在允许该男子恢复其正常血清睾酮之前进行单剂量的适形外照射来实现的。
Pharmacological approaches are available to medically-managed patients with symptomatic BPH before surgical intervention is required. These include daily treatment with alpha-blockers and 5-alpha-reductase inhibitors alone or in combination. These medical approaches have two major problems. First, treatments are chronic and must be taken daily. Second, there are significant financial costs and quality of life issues for such chronic treatments. Is it possible to develop effective acute therapy for symptomatic BPH without the long-term androgen deprivation-induced side effects? Two seminal but rarely cited studies of Walsh [Peters, Walsh: N Engl J Med 317:599-604,1987] and Coffey et al. [Sufrin et al.: Invest Urol 13:418-423,1976], combined with the growing understanding of the stem cell organization of the prostate stromal (S) and epithelial (E) compartments and their reciprocal paracrine and autocrine interactions provides the rationale for an acute approach.The Walsh study documents that: (1) androgen deprivation disrupts the reciprocal interaction between the prostate S and E thereby decreasing the weight of both compartments and (2) once BPH develops, androgen deprivation does not decrease the number of stem cell units in either the S or E compartments since subsequent androgen restoration fully restores the enlarged gland. The Coffey study documents that acute androgen deprivation sensitizes S-E interactions to radiation induced disruptions so that following radiation, androgen restoration does not induce full gland regrowth. Therefore, effective therapy for symptomatic BPH should be achievable by acute treatment with reversible androgen deprivation for a limited period followed by a single dose of conformal external beam radiation before allowing the man to recovery his normal serum testosterone.