原发性肝癌雄激素受体表达的临床病理研究

 目的探讨原发性肝癌患者雄激素受体的改变对肝癌发生发展的影响.方法应用放射配体结合分析法(RBA)对36例行手术切除的肝癌组织、癌周组织及外周血白细胞雄激素受体(Androgen receptor,AR)的含量进行测定,同时用放射免疫法(RIA)测定肝癌患者及正常人血浆雄激素(睾酮T)的水平,结合临床病理资料进行统计分析.结果(1)癌组织与癌周组织相比,AR含量明显升高(P＜0.01),且与肿瘤直径大小有关;(2)高分化的肝癌组织AR含量明显高于低分化者(P＜0.01);(3)肝癌患者血浆睾酮水平增加不明显(P＞0.05),但白细胞AR表达明显升高(P＜0.01).结论肝癌的发生可能与癌组织中AR含量升高有关,AR的含量与肿瘤的大小及分化程度存在相关性.     

肝癌患者雄激素受体的测定及其与临床病理特征关系的研究

应用放射配体结合分析法（ＲＢＡ）测定３６例手术治疗的肝癌组织、癌周组织及外周血白细胞雄激素受体（ＡＲ）的含量，同时用放射免疫法（ＲＩＡ）测定肝癌患者及正常人血浆雄激素（睾酮Ｔ）的水平，结合临床病理资料进行统计分析。结果（１）癌组织与癌周组织相比，ＡＲ含量明显升高（Ｐ＜０．０１），且与肿瘤直径大小有关；（２）高分化的肝癌组织ＡＲ含量明显高于低分化者（Ｐ＜０．０１）；（３）肝癌患者血浆睾酮水平轻度增加（Ｐ＞０．０５），但白细胞ＡＲ表达明显升高（Ｐ＜０．０１）。提示：肝癌的发生可能与癌组织中ＡＲ含量升高有关，ＡＲ的含量与肿瘤的大小及分化程度存在相关性     

复方木尼孜其对女性迟发性痤疮血清睾酮的影响及疗效观察

目的观察复方木尼孜其对女性迟发性痤疮血清睾酮的影响及疗效。方法将128名痤疮患者随机分为两组。治疗组(A组)65例口服复方木尼孜其颗粒。对照组(B组)63例口服一清胶囊和维生素B6,治疗时间为28 d。另设62例相应年龄段非痤疮患者作对照组(C组)。于治疗前后采用电化学发光免疫分析法检测其卵泡期血清睾酮水平,并进行疗效评价。结果 A组和B组的总有效率分别为89.2%和61.9%,差异有统计学意义(P<0.05)。A组治疗前血清睾酮水平较C组明显升高(P<0.05),而治疗后血清睾酮水平与C组相比差异无统计学意义(P>0.05)。结论女性迟发性痤疮发病的主要原因与雄激素分泌增多有关。复方木尼孜其颗粒具有抗雄激素作用,对女性迟发性痤疮的疗效确切,且无明显不良反应。     

过度训练状态下大鼠骨骼肌总蛋白含量和雄激素受体结合容量的变化

在建立过度训练动物模型的基础上，通过测定过度训练状态下，大鼠血浆总睾酮（TT），股四头肌、腓肠肌总蛋白百分含量及胞浆雄激素受体（AR）的最大结合容量，探讨骨骼肌中总蛋白和AR的变化及其相互关系。结果显示，过度训练状态下，大鼠股四头肌、腓肠肌总蛋白百分含量和胞浆AR的最大结合容量显著下降（P<0.01），骨骼肌胞浆AR最大结合容量的下降幅度约为血浆TT的2倍。提示低血T及低骨骼肌AR水平协同作用，共同导致骨骼肌总蛋白含量的下降，而其中AR可能起到更重要的作用。     

抗雄激素药物应用于女性中、重度迟发型痤疮治疗临床效果分析

目的：探讨抗雄激素药物应用于女性中、重度迟发型痤疮治疗临床效果。方法选取皮肤科2010年1月～2012年12月收治中、重度迟发型痤疮女性患者250例,采用随机抽样方法分为对照组（125例）和治疗组（125例）;两组患者均给予小剂量甲泼尼龙口服,对照组患者加用螺内酯治疗,治疗组患者则加用达英-35治疗;比较两组患者近期疗效、治疗前后血清睾酮（ T）、雌二醇（ E2）水平。结果治疗组近期疗效显著优于对照组,组间比较差异有统计学意义（ P＜0.05）;两组患者治疗后血清T水平较治疗前显著下降,且治疗组患者治疗后下降程度优于对照组,组间比较差异有统计学意义（ P＜0.05）;但两组患者治疗前后血清E2水平组间比较差异无统计学意义（ P＞0.05）。结论抗雄激素药物应用于女性中、重度迟发型痤疮治疗可有效改善皮疹症状,调节激素水平。     

老年男性肥胖患者性激素及其受体的变化

 目的 研究老年男性肥胖患者的性激素及其受体水平的变化,探讨性激素及其受体与肥胖的关系.方法 共调查老年(≥60岁)男性314例.其中健康人104例,年龄62～92岁,平均(71.38±5.15)岁;肥胖者74例,61～87岁,平均(71.32±4.74)岁.超重者111例,年龄60～85岁,平均(71.43±5.03)岁,采集其晨起静脉血,低温离心后取血清,测定总睾酮(TT)、游离睾酮(FT)、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇(E2)、黄体生成素(LH)、卵泡刺激素(FSH)水平,并采用流式细胞术检测外周血白细胞雄激素受体(AR).结果 (1)肥胖人群TT、SHBG均值低于非肥胖人群,E2/TT则高于非肥胖人群;(2)BMI与TT、SHBG、HDL呈负相关.结论 肥胖人群的睾酮较非肥胖者明显降低,且睾酮与肥胖程度、血糖和血脂都有相关性,在肥胖的发展中起保护性作用.     

运动时骨骼肌雄激素受体表达和活性改变及其对运动能力的影响

机体运动能力与雄激素水平呈较高的正相关。雄激素通过与雄激素体受体(AR)结合发挥其促进骨骼生长、肌肉肥大和刺激促红细胞生成素分泌的作用。本文综述了耐力运动、抗阻运动对骨骼肌AR表达水平和转录激活活性的影响,即适度的耐力和抗阻运动均会增加骨骼肌等组织AR的蛋白表达、结合容量和转录激活活性,而过度运动或力竭运动会降低骨骼肌AR的蛋白水平、结合容量和转录激活活性,并进一步从睾酮的作用(睾酮增加AR的mRNA水平、延长AR的半衰期)、胰岛素生长因子-1信号通路(IGF-1通过MAPK通路,包括p38,ERK1/2和JNK,以及通过PI3K/Akt-Foxo1通路来实现其增加AR蛋白表达和促进核转位的作用)和胰岛素生长因子-1受体信号通路(IGF-1R通过PI3K激活AR的转录激活活性)来阐述运动对骨骼肌AR表达水平和转录激活活性影响的机制。本文还综述了AR表达水平对运动能力的影响,但这方面相关的研究还比较少,仍有许多问题有待解决。     

雄激素受体对结直肠癌预后的意义

为探讨雄激素受体对结直肠癌病人的预后意义 ,作者以放射配基结合分析法测定结直肠癌及癌旁粘膜AR水平 ,结合 30例病人年龄、性别、肿瘤部位 (结、直肠 )、分化程度 (高、中、低 )、Dukes分期 (A、B、C、D)以及结直肠癌DNA及CEA水平 ,与随访结果一起纳入生存资料的Cox回归模型分析。结果显示 ,直肠癌较结肠癌预后差 (P <0 0 1)。Dukes分期与生存期呈负相关 (P <0 0 1)。结直肠癌旁粘膜AR水平与病人生存期呈正相关 (P <0 0 5 )。其他因素如性别、年龄、分化程度、癌组织AR、DNA及CEA水平与生存期不相关。提示结直肠癌旁粘膜AR水平为结直肠患者生存的保护性因素 ,具有重要的预后意义     

复方丹参健力浓缩颗粒对模拟高强度训练大鼠内分泌功能的影响

目的 研究复方丹参健力浓缩颗粒对模拟高强度海训大鼠内分泌功能的影响及其可能的机制.方法 40只SD雄性大鼠按数字表法随机分为5组,分别为安静对照组(对照组),大负荷运动对照组(运动组)及低剂量(48 mg/kg)、中剂量(144 mg/kg)、高剂量(686 mg/kg)给药大负荷运动组(分别称为低剂量组、中剂量组、高剂量组),灌胃给药4周后考察各组大鼠体质量及血清中内分泌因子含量的变化.结果 与对照组相比,运动组大鼠体质量下降,白细胞、淋巴细胞、中性粒细胞数显著下降,血浆中睾酮(T)含量降低,皮质酮(C)含量升高,睾酮/皮质酮(T/C)大幅降低,干扰素γ(INF-γ)和白细胞介素-4(IL-4)含量升高,INF-γ/IL-4显著下降.与运动组比较,中、高剂量组各种血细胞数量升高(P＜0.05或P＜0.01),C含量降低(P＜0.05或P＜0.01),T/C和INF-γ/IL-4升高(P＜0.05或P＜0.01).结论 中、高剂量复方丹参健力浓缩颗粒能显著提高模拟高强度训练大鼠的内分泌功能,改善其免疫抑制状态.     

胃癌患者血浆睾酮含量的改变及其意义

41例男性胃癌患者和35例男性健康人血浆睾酮含量测定的结果发现,胃癌组血浆睾酮含量显著低于健康对照组(P<0.01),但胃癌患者手术后血浆睾酮含量比手术前显著增高(P<0.01),而与健康对照组相比无显著差异(P>0.05)。提示雄性激素可能与胃癌的发生有关。     

Androgen deprivation-mediated cytoreduction before interstitial brachytherapy for prostate cancer does not abrogate the elevated risk of urinary morbidity associated with larger initial prostate volume

PURPOSE: We examined whether prostate volume reduction after a short course of androgen deprivation (AD) lowered the risks of acute and chronic urinary morbidity related to radioactive seed implantation for low-risk prostate cancer. METHODS AND MATERIALS: Eighty-one patients received AD for cytoreduction before interstitial brachytherapy alone. Urinary morbidity was carefully assessed for all patients during a median followup of 53 (range, 23-78) months after treatment. Outcomes were then compared with those of a control group of 81 patients who were matched 1:1 based on identical prostate volume measured at the time of radioactive seed implant, but who had not received AD. RESULTS: Despite effective cytoreduction (median, 30% prostate volume reduction) with AD, prolonged catheterization was required significantly more often for patients who had received AD when compared with the control group of patients who were implanted at identical prostate volumes but who had not received AD (27% vs. 9%, p = 0.02). This finding remained statistically significant on multivariate analysis (p = 0.04). Surgical intervention (9% vs. 4%, p = 0.09) and subsequent urinary incontinence (4% vs. 1%, p = 0.16) were also more frequent among patients who had received AD when compared with implant volume-matched controls. CONCLUSIONS: Patients who achieved smaller prostate volumes through the use of AD maintained a significantly elevated risk (threefold) for urinary complications, commensurate with their initially large prostate volume, when compared with a control group of patients who were implanted at identical prostate volumes but who had not received AD. Therefore, patients presenting with larger prostate glands that would warrant a short course of AD before implant should be counseled accordingly when discussing options for local therapy.     

The effect of oral contraceptive use on salivary testosterone concentrations and athlete performance during international field hockey matches

Objectives

To investigate the effect of oral contraceptive (OC) use on salivary testosterone (sal-T) concentrations and performance-related statistics in international field hockey matches.

Positron tomographic assessment of androgen receptors in prostatic carcinoma

Purpose The purpose of this study was to evaluate the feasibility of androgen receptor (AR) imaging with 16-[¹⁸F]fluoro-5-dihydrotestosterone (FDHT) by positron emission tomography (PET) and to assess the binding selectivity of FDHT to AR in patients with prostate cancer.Methods Twenty men (age range 56–87 years) with advanced prostate cancer were studied. All except one had metastatic disease confirmed by biopsy and/or radiological studies. One patient who had radiological findings suggesting a single hepatic metastasis was found to have focal fatty infiltration on biopsy obtained after FDHT-PET and was excluded from further data analysis. FDHT uptake was assessed semiquantitatively by determination of the standardized uptake value (SUV) and tumor-to-muscle ratio (T/M). Additionally, to assess the AR binding selectivity of FDHT, patients with one or more foci of abnormally increased FDHT accumulation were studied after administration of an AR antagonist (flutamide).Results Conventional imaging demonstrated innumerable lesions in two patients and 43 lesions in the remaining 17 patients with advanced prostate cancer. FDHT-PET was positive in 12 of 19 patients (sensitivity of 63%), including the two patients with innumerable lesions. FDHT-PET detected 24 of 28 known lesions (86%) in the remaining ten patients. In addition, FDHT-PET detected 17 unsuspected lesions in five of these ten patients. All 12 patients with positive FDHT-PET underwent a repeat PET study after receiving flutamide for 1 day (250 mg t.i.d.). In all of these patients, there was a decrease in tumor FDHT uptake after flutamide; the mean (± standard deviation) SUV and T/M decreased from 7.0±4.7 and 6.9±3.9, respectively, to 3.0±1.5 and 3.0±1.6, respectively (p=0.002). The mean PSA in patients with positive FDHT-PET was significantly higher than that in patients with negative FDHT-PET (p=0.006).Conclusion Our results document the feasibility of PET imaging of prostate cancer with FDHT and suggest that tumor uptake of FDHT is a receptor-mediated process. Positive PET studies were associated with higher PSA levels and thus, presumably, with greater tumor burden.     

前列腺癌CT表现与癌组织中雄激素受体的相关性研究

目的 探讨前列腺癌CT表现与病理改变及癌组织中雄激素受体(AR)表达的相关性,为前列腺癌临床治疗及估计预后提供影像学依据.资料与方法 搜集40例经CT检查和病理证实的前列腺癌患者资料,应用免疫组织化学法检测病理组织中AR表达,并行肿瘤组织学病理分级,再与CT表现对照分析.结果 AR表达阴性10例(25%),阳性30例(75%).不同病理分级癌组织中AR表达率有显著性差异(P<0.05),其中高分化阳性表达率为100%,中分化为87%,低分化为60%.CT分期评估A/B期22例,C期10例,D期8例.不同CT分期的前列腺癌组织中AR表达率有显著性差异(P<0.05).CT分期与临床分期无显著性差异(P>0.05).CT上肿块外形、密度改变与AR表达无关(P>0.05),而肿瘤的大小与AR的表达呈负相关.结论 前列腺癌组织中AR表达与前列腺癌的病理分级呈负相关;AR阳性表达随CT分期的升高而减少,CT上前列腺外形和肿瘤密度不能反映前列腺癌组织中AR的表达情况.     

Dosimetric outcomes in prostate brachytherapy: Is downsizing the prostate with androgen deprivation necessary?

ObjectivesA large prostate volume has historically been a relative contraindication to prostate brachytherapy (PB) because of concerns of toxicity and potential pubic arch interference. Common practice has been to downsize large prostates with androgen deprivation therapy (ADT) before proceeding with brachytherapy. The present study compares postimplant dosimetry in patients with prostate volumes >50 cc with those with prostate volumes ≤50 cc.MethodsA review of all patients who underwent PB at our institution from 2001 to 2006 was performed. Postimplant dosimetry was obtained approximately 4 weeks after brachytherapy.ResultsOne-hundred forty-five out of a total of 148 patients had available dosimetry. In the 113 patients with prostate volumes ≤50 cc (mean, 35.4 cc, range, 14.2–49.7 cc); the mean D₉₀ (dose which covers 90% of the prostate), V₁₀₀ (volume of prostate receiving 100% of the prescribed dose), V₁₅₀ (volume of prostate receiving 150% of the prescribed dose), and V₂₀₀ (volume of prostate receiving 200% of the prescribed dose) was 128.9%, 95.6%, 73.9%, and 51.2%, respectively. In the 32 patients with prostate volumes >50 cc (mean 58.1 cc, range 50.2–86.0 cc); the mean D₉₀, V₁₀₀, V₁₅₀, and V₂₀₀ was 125.1%, 95.2%, 68.2%, and 41.7%, respectively. The rectal V₁₀₀ was 1.0 cc for both cohorts. There was no statistically significant difference between the cohorts with respect to postimplant dosimetry for D₉₀, V₁₀₀, and V₁₅₀. The V₂₀₀ for prostate volumes >50 cc was significantly lower (p < 0.05).ConclusionsIn the present study, patients with prostate volumes >50 cc have postimplant dosimetry parameters similar to patients with prostate volumes ≤50 cc for D₉₀, V₁₀₀, and V₁₅₀; and significantly lower values for V₂₀₀. These results suggest that patients with large prostate volumes may not need to be routinely placed on hormonal therapy; sparing patients the side effects of hormonal therapy, and sparing the health care system the costs of luteinizing hormone-releasing hormone agonist injections.     

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer

PurposeRetrospective data suggest less benefit from androgen deprivation therapy (ADT) in the setting of dose-escalated definitive radiation for prostate cancer, especially when a combination of external beam radiotherapy (EBRT) and brachytherapy approaches are used. This study aimed to test the hypothesis that patients with prostate cancer with intermediate- or high-risk disease undergoing extreme dose escalation with a brachytherapy boost are less likely to receive ADT.Methods and MaterialsData from the National Cancer Database were extracted for men aged 40–90 years diagnosed with node-negative, non-metastatic prostate cancer from 2004 to 2015. Only patients with intermediate- or high-risk disease who were treated with definitive radiotherapy were included. The association and patterns of care between dose escalated radiotherapy and ADT receipt were assessed using multivariable logistic regression.ResultsPatients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive ADT if they underwent dose escalation with a combination of EBRT and brachytherapy (odds ratio 0.67, p < 0.0001). Over time, this decrease in ADT utilization has widened for patients with unfavorable intermediate-risk disease. There was no difference in ADT utilization when comparing patients treated with non–dose-escalated EBRT to those treated with dose-escalated EBRT (without brachytherapy).ConclusionIn this large national database, patients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive guideline-indicated ADT if they underwent extreme dose escalation with combined radiation modalities. As we await prospective data guiding the utility of ADT with dose escalated radiation, these findings suggest potential underutilization of ADT in patients at higher risk of advanced disease.     

Identification of pubic arch interference in prostate brachytherapy: simplifying the transrectal ultrasound technique

PURPOSE: We report a simplified technique allowing identification of pubic arch interference (PAI) using transrectal ultrasound (TRUS). METHODS AND MATERIALS: Fifty consecutive brachytherapy patients implanted using a two-stage technique were studied. The pubic arch was outlined using a marker pen on the ultrasound monitor screen during the dose planning ultrasound. Where pubic arch interference (PAI) was identified attempted needle passage was used to confirm PAI (n = 3). RESULTS: Mean time to perform PAI assessment was 90 s. Three of 50 patients had PAI, which was confirmed by attempted needle passage. No patients required modification to the implant plan during the implant procedure. CONCLUSIONS: TRUS reliably identifies PAI. This simple technique may be used with any TRUS scanner and avoids the need for CT scanning or specific software to identify PAI. Our low incidence of PAI may be related to lower prostate volumes at implantation due to patient selection, neoadjuvant androgen deprivation, or improved patient positioning.     

雄激素抑制对出血创伤后免疫反应影响的研究

目的探讨雄激素抑制对出血创伤后免疫功能的影响与作用机制. 方法建立不同方式雄激素抑制与出血创伤的雄鼠动物模型,出血创伤后24 h检测胸腺细胞凋亡、脾细胞增殖与其产生的白细胞介素(IL)-2、IL-3. 结果出血创伤加速雄鼠胸腺细胞凋亡,干扰胸腺细胞选择与凋亡的正常程序,雄激素抑制对此有保护作用,且不同雄激素抑制措施具有协同效应;出血创伤使雄鼠脾细胞增殖及产生IL-2、IL-3均受到显著抑制,而抑制雄激素可使之提高. 结论抑制雄激素,在中枢免疫器官及外周免疫细胞水平均有保护作用,暂时的雄激素抑制措施是保护出血创伤后雄鼠免疫功能的简单而有效的方法.     

MicroPET assessment of androgenic control of glucose and acetate uptake in the rat prostate and a prostate cancer tumor model

PET has been used to monitor changes in tumor metabolism in breast cancer following hormonal therapy. This study was undertaken to determine whether PET imaging could evaluate early metabolic changes in prostate tumor following androgen ablation therapy. Studies were performed comparing two positron-emitting tracers, ¹⁸F-FDG and ¹¹C-acetate, in Sprague-Dawley male rats to monitor metabolic changes in normal prostate tissue. Additional studies were performed in nude mice bearing the CWR22 androgen-dependent human prostate tumor to evaluate metabolic changes in prostate tumor. In rats, for the androgen ablation pretreatment, 1 mg diethylstilbestrol (DES) was injected subcutaneously 3 and 24 hours before tracer injection. For androgen pretreatment, 500 μg dihydrotestosterone (DHT) was injected intraperitoneally 2 and 6 hours before tracer injection. The rats were divided into three groups, Group A (no-DES, no-DHT, N = 18), Group B (DES, no-DHT, N = 18) and Group C (DES, DHT, N = 18). In each group, 10 animals received ¹⁸F-FDG, whereas the remaining eight animals were administered ¹¹C-acetate. Rats were sacrificed at 120 min post-injection of ¹⁸F-FDG or 30 min post-injection of ¹¹C-acetate. Pretreatment of the mouse model using DHT (200 μg of DHT in 0.1 mL of sunflower seed oil) or DES (200 μg of DES in 0.1 mL of sunflower seed oil) was conducted every 2 days for one week. Mice were imaged with both tracers in the microPET scanner (Concorde Microsystems Inc.). DES treatment caused a decrease in acetate and glucose metabolism in the rat prostate. Co-treatment with DHT maintained the glucose metabolism levels at baseline values. In the tumor bearing mice, similar effects were seen in ¹⁸F-FDG study, while there was no significant difference in ¹¹C-acetate uptake. These results indicate that changes in serum testosterone levels influence ¹⁸F-FDG uptake in the prostate gland, which is closely tied to glucose metabolism, within 24 hours of treatment and in the prostate tumor within 1 week. These early metabolic changes could enable monitoring metabolic changes in prostate tumor following treatment by imaging using ¹⁸F-FDG PET. Further studies are needed to clarify the reason for the insensitivity of ¹¹C-acetate for measuring metabolic change in prostate tumor.