Influence of the neural microenvironment on prostate cancer.
Influence of the neural microenvironment on prostate cancer.
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DOI：
10.1002/pros.23454
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Ayala G
中科院分区：
文献类型：
--
作者：
Coarfa C;Florentin D;Putluri N;Ding Y;Au J;He D;Ragheb A;Frolov A;Michailidis G;Lee M;Kadmon D;Miles B;Smith C;Ittmann M;Rowley D;Sreekumar A;Creighton CJ;Ayala G
神经是前列腺癌（PCa）的关键因素，但神经支配在前列腺癌中的功能作用知之甚少。PCa诱导的神经发生和神经周侵袭（PNI）与侵袭性疾病相关。在原位植入癌细胞之前，我们用化学和物理方法切除了啮齿动物前列腺的神经。我们还进行了人类新辅助临床试验，使用肉毒杆菌毒素A型（肉毒杆菌毒素）和生理盐水在同一患者，前列腺切除术前。双侧去神经导致小鼠肿瘤发生率和大小降低。在人类中，肉毒杆菌素治疗导致肉毒杆菌素治疗侧的癌细胞凋亡增加。在去神经啮齿动物前列腺、脊髓损伤患者和肉毒杆菌治疗侧的肿瘤中鉴定出类似的去神经基因阵列谱。诱导的去神经支配表现出标志性基因谱，表明翻译和生物能量关闭。神经还调节非肿瘤性上皮细胞的基本细胞功能。神经在正常上皮组织的稳态中起作用，并参与前列腺癌肿瘤的存活。这项研究证实，人类癌症和神经之间的相互作用对疾病进展至关重要。这项工作可能会对一般癌症治疗策略产生重大影响，因为神经/癌症相互作用在其他癌症中也可能很重要。靶向神经微环境可能代表治疗人前列腺癌的治疗方法。
Nerves are key factors in prostate cancer (PCa), but the functional role of innervation in prostate cancer is poorly understood. PCa induced neurogenesis and perineural invasion (PNI), are associated with aggressive disease. We denervated rodent prostates chemically and physically, before orthotopically implanting cancer cells. We also performed a human neoadjuvant clinical trial using botulinum toxin type A (Botox) and saline in the same patient, before prostatectomy. Bilateral denervation resulted in reduced tumor incidence and size in mice. Botox treatment in humans resulted in increased apoptosis of cancer cells in the Botox treated side. A similar denervation gene array profile was identified in tumors arising in denervated rodent prostates, in spinal cord injury patients and in the Botox treated side of patients. Denervation induced exhibited a signature gene profile, indicating translation and bioenergetic shutdown. Nerves also regulate basic cellular functions of non‐neoplastic epithelial cells. Nerves play a role in the homeostasis of normal epithelial tissues and are involved in prostate cancer tumor survival. This study confirms that interactions between human cancer and nerves are essential to disease progression. This work may make a major impact in general cancer treatment strategies, as nerve/cancer interactions are likely important in other cancers as well. Targeting the neural microenvironment may represent a therapeutic approach for the treatment of human prostate cancer.
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影响因子：
2.4
作者：
Bitoh, Y;Shimotake, T;Iwai, N
通讯作者：
Iwai, N
影响因子：
3.3
作者：
Dai, Hong;Li, Rile;Ayala, Gustavo E.
通讯作者：
Ayala, Gustavo E.
DOI：
10.1007/bf00496704
发表时间：
1968-01-01
期刊：
ZEITSCHRIFT FUR ZELLFORSCHUNG UND MIKROSKOPISCHE ANATOMIE
影响因子：
--
作者：
BAUMGARTEN, HG;FALCK, B;OWMAN, T
通讯作者：
OWMAN, T
影响因子：
1.6
作者：
JUNGBLUT, T;AUMULLER, G;MELCHIOR, H
通讯作者：
MELCHIOR, H
影响因子：
64.8
作者：
BAPTISTA, CA;GERSHON, TR;MACAGNO, ER
通讯作者：
MACAGNO, ER