Influence of testosterone on pup killing in the rat is modified by prior experience.

The usual response of the adult male rat which is placed together with newborn rat pups for the first time is to kill and eat the pups. In past experiments castration of the male blocked this behavior, and replacement therapy with testosterone propionate (TP) maintained the behavior. In the present experiments this relationship between testosterone and pup-killing behavior was modified by giving the animals prior killing or nonkilling experience. In general, experienced killers continued to kill on a retest after 30 days of testosterone deprivation, and experienced nonkillers tended not to kill on the retest even though they were given daily treatment with testosterone for thirty days prior to retesting.     

Development of olfactory-guided behavior in the golden hamster.

Hamster pups were tested for an odor preference every day from 1-16 days of age with shavings from their home cage and with clean wood shavings. The hamster pups showed a clear preference for their home cage shavings by 8 days of age. They were then tested for preferences with other odor combinations. Tests for preference with other odor pairs indicate that this preference is due to a change in the hamsters rather than a change in the stimulus. In these tests the hamster pups did not demonstrate a preference for their home shavings over shavings in which a nonlactating female had lived. Further tests will have to be done to determine how specific the hamster pup's olfactory preferences are.     

Effects of hormonal replacement with androgens and estrogens on male sexual behavior and plasma levels of these steroids in gonadectomized golden hamsters (Mesocricetus auratus)

Because the endocrine control of sexual behavior in male hamsters remains controversial, this study analyzed the influence of different androgens and estrogens in the regulation of masculine, sexual behavior (MBS). Aromatizable androgens: androstenedione (A) and testosterone (T), a non-aromatizable androgen: 5α-dihydrotestosterone (DHT), as well as estrogens (E₂ and E₁) alone or in combination with DHT, were administered in gonadectomized, sexually experienced males, for 3 weeks. In addition, plasma levels of these steroids were determined. Gonadectomy completely suppressed masculine sexual behavior (MSB) after 4 weeks. Both A and T replacements restored all the sexual behavior parameters in castrated hamsters by the 3rd week of treatment, with A being more potent in restoring all copulatory series and maintaining all MSB parameters, including long intromissions. Castrated males treated with DHT showed little interest in the female and did not display any copulatory behavior. Gonadectomized males treated with estrogens alone showed active anogenital investigation and displayed some mounts, but did not ejaculate. Males treated with estrogens combined with DHT had longer latencies and less number of ejaculations than males treated with aromatizable androgens. Long intromissions were observed only in males treated with T or A. Plasma levels of A were significantly higher than T levels in intact males. In males treated with A both androgens and estrogens were present in plasma. These results support the notion that aromatizable androgens, mainly A, but not non-aromatizable androgens or even estrogens in combination with DHT, play a relevant role in the endocrine regulation of MSB in the golden hamster.     

阉割和睾酮替代对大鼠应激免疫抑制蛋白的影响

目的 :研究阉割和睾酮替代对束缚应激模型大鼠血清中应激免疫抑制蛋白的影响。方法 :成年雄性SD大鼠随机分为正常对照组、假手术组、阉割组、阉割后睾酮替代组。每组 10～ 12只。以上各组随机抽出一半给予束缚应激 ,另一半作为不应激对照。观察各组大鼠血清对ConA诱导的淋巴细胞转化的作用 ,作为反映血清中应激免疫抑制蛋白含量的指标。在离体实验中观察不同浓度的睾酮对淋巴细胞转化的直接作用。结果 :阉割可促进应激大鼠血清中应激免疫抑制蛋白的产生 ,睾酮替代可对抗这一作用。结论 :睾酮可在一定范围内对抗应激免疫抑制蛋白的产生。     

尼尔雌醇作用下去势雌兔骨组织形态计量学改变

目的：评估尼尔雌醇对绝经后骨质疏松症的疗效，并探讨其机理。方法：将３０只雌性新西兰兔随机分成３组（每组１０只）：治疗组［摘除卵巢＋尼尔雌醇（每月２ｍｇ）］、模型组（摘除卵巢）和正常对照组（假手术），６个月后处死取材，并在处死前行四环素标记，ＶＩＤＡＳ图象分析系统下作骨组织形态计量学测定。结果：治疗组的单位体积骨小梁骨量（ＢＶ／ＴＶ）、相对类骨质量（ＯＶ／ＢＶ）、成骨细胞指数（ＯＢＩ）和组织水平的骨形成速率［ＢＦＲ（Ｔ）］明显高于模型组和（或）正常对照组。结论：尼尔雌醇能增加成骨细胞数量，可能是一种成骨细胞募集和（或）增殖的刺激剂。     

四种补肾中药对去卵巢大鼠骨质疏松骨形态的作用

目的 比较骨碎补、锁阳、淫羊藿和狗脊４种补肾中药对去卵巢（ＯＶＸ）大鼠骨质疏松的作用。方法 将５４只３月龄雌性Ｗｉｓｔａｒ大鼠随机分成模型组和中药治疗组。模型组包括非手术组、假手术组和去卵巢组,每组１０只;中药组包括骨碎补组、锁阳组、淫羊藿组和狗脊组,每组６只。去卵巢手术后１周,中药组分别用上述４种中药喂养,８周后放血外死全部小鼠,用骨形态主坦学方法比较４种中药对ＯＶＸ大鼠骨质疏松的防治作用。结果     

Battling resistance mechanisms in antihormonal prostate cancer treatment: Novel agents and combinations

Prostate cancer (PCa) is a hormone-sensitive disease. Androgen deprivation therapy lowers serum testosterone levels (castration) or blocks the androgen receptor (AR) ligand-binding domain. Especially in metastatic disease, hormonal therapy has been able to delay disease progression, reduce symptoms, and improve overall survival. Despite subsequent disease progression and development of castration resistance, PCa remains AR driven. Secondary hormonal treatments such as abiraterone acetate or enzalutamide have demonstrated increased overall survival. However, new resistance mechanisms to these agents have been identified, and systemic chemotherapy is still needed especially in fast-progressing castration-resistant PCa. Several promising androgen synthesis inhibitors (orteronel and galeterone), AR inhibitors (ARN-509, EPI-001, AZD3514, and ODM-201), and heat shock protein modulators (AT11387, 17-DMAG, STA-9090, and OGX-427) are currently under investigation. The wide variety in upcoming systemic agents underlines the molecular heterogeneity of castration-resistant PCa. This article reviews antihormonal therapy in PCa and resistance mechanisms and focuses on novel and upcoming agents currently in clinical testing.     

AR-V7表达与去势抵抗性前列腺癌阿比特龙治疗敏感性的相关性研究

目的:探讨去势抵抗性前列腺癌(CRPC)患者中雄激素受体剪切变异体7(AR-V7)的表达与阿比特龙治疗敏感性的相关性。方法:采用前瞻性队列研究对2016年1月至2019年1月北京大学肿瘤医院收治的年龄≥18岁,存在1≥处全身转移,拟使用阿比特龙治疗的新发CRPC患者行外周血循环肿瘤细胞(CTCs)AR-V7检测,根据检测结果将患者分为AR-V7阳性组和AR-V7阴性组,对两组患者PSA下降时间、PSA无进展生存(PFS)、临床状态PFS、影像学PFS以及总生存进行统计分析。结果:共入组77例患者,其中AR-V7阴性组49例,AR-V7阳性组28例。AR-V7阴性组PSA下降时间[(72.04±66.92)d与(190.11±102.44)d,P=0.000]、PSA无应答率[6.12%(3/49)与21.4%(6/28),P=0.040]明显小于AR-V7阳性组,而PSA PFS[(489.17±269.39)d与(130.56±120)d,P=0.010]、临床状态PFS[(551.91±322.05)d与(261.44±200.85)d,P=0.018]、影像学PFS[(523.7±223.28)d与(247.56±202.80)d,P=0.003]明显长于AR-V7阳性组。AR-V7阳性组和AR-V7阴性组的肿瘤特异性生存时间分别为(1246.89±375.65)d和(1001.42±248.94)d(P=0.159),总生存率分别为89.8%(44/49)和89.3%(25/28)(P=0.176),差异均无统计学意义。结论:CRPC患者中,AR-V7表达与阿比特龙治疗敏感性及患者预后密切相关,阳性表达患者阿比特龙治疗效果及预后较差。     

Salud ósea en pacientes con cáncer de próstata

ContextIn patients with prostate cancer, bone health is compromised by advanced age at diagnosis, androgen suppression treatments and the developmentofbone metastases. In this paper the medical literature is reviewed in order to update the state of the art on their incidence, prevention and management.Evidence acquisitionA literature review about bone involvement in patients with prostate cancer in different clinical settings is performed.Synthesis of the evidenceDecreased bone mineral density is higher in patients diagnosed of prostate cancer before starting treatment than in healthy men with the same age. During the first year of treatment, a severe loss bone density is reported due to androgen suppression therapy. From then on, loss bone density seems to slow down, persisting at long-term. It is important to know the starting point and the dynamics of loss bone in order to prevent its progression. The skeletal events have an important impact on quality of life in patients with prostate cancer. Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone.ConclusionsThe prevention and management of bone involvement in patients with prostate cancer is critical to quality of life in these patients and requires an individualized approach. Before starting a prolonged androgen deprivation, baseline risk of fracture should be evaluated in order to adopt the proper protective measures. In patients with metastases, early treatments reducing the risk of bone events should be taken into account.     

去势联合125I粒子近距离放疗治疗中晚期前列腺癌

目的 探讨去势联合125I粒子近距离放疗治疗中晚期前列腺癌的临床疗效.方法 回顾性分析2004-2009年经病理证实的66例中晚期前列腺癌患者资料.年龄61～85岁,平均72岁.其中C期40例,D期26例;G2 42例,G3 24例.采用药物去势联合抗雄激素药物的全雄性激素阻断治疗,3个月后行手术去势及近距离放疗,通过三维治疗计划系统,在经直肠超声引导下将125I放射性粒子均匀植入前列腺内.比较治疗前后血PSA水平、前列腺体积及IPSS评分变化情况.结果 66例手术均顺利完成.每例植入粒子35～87枚,平均55枚.术后随访10～62个月,平均49个月.患者术前血PSA(67.5±11.1)ng/ml,前列腺体积(51.4±10.0)ml,IPSS评分0.8±2.3;术后6个月PSA(1.50±0.50)ng/ml,前列腺体积(18.7±10.7)ml,IPSS评分5.1±3.5,手术前后差异有统计学意义(P＜0.05).结论 去势联合125I粒子近距离放疗是综合治疗中晚期前列腺癌的有效手段.

Abstract：

Objective To investigate the therapeutic efficacy of castration with 125I brachtherapy in middle and late stage prostate cancer. Methods Sixty-six patients with prostate cancer from 2004 to 2009 were analyzed, 40 were at clinical stage C and 26 were at clinical stage D, 42 had a pathologic grade G2 and 24 had a pathologic grade G3. The first endocrinal therapy used was total androgen blockade (chemical castration and anti-androgen drugs). The therapeutic time was three months before bilateral orchidectomy and brachtherapy. A 3D radiotherapy planning system was used for brachtherapy with transrectal ultrasound-guided radioactive 125I seed uniform implantation. Follow-up endocrinal therapy was decided according to a monthly check of serum PSA (prostate specific antigen) levels. After six months, serum PSA, IPSS and volume of the prostate before and after treatment were compared. Results The operations were completed successfully in all cases. The mean number of 125I seeds implanted was 55. The mean follow-up was 10 to 62 months, with an average of 49 months. Serum PSA, IPSS and the volume of the prostate was reduced significantly six months after operation (P<0.05). Conclusions Castration with 125I brachtherapy is an effective approach in combination therapy for treating middle and late stage prostate cancer.