Prostate--an extrapituitary source of follicle-stimulating hormone (FSH): occurrence, localization, and de novo biosynthesis and its hormonal modulation in primates and rodents.

A comparative study on the immunocytochemical localization, de novo biosynthesis, and hormonal modulation of follicle-stimulating hormone (FSH) was carried out in the prostates of man, monkey, dog, guinea pig, hamster, rat, and mouse. FSH was localized in the cytoplasm of the prostatic epithelial cells. In some specimens, staining was also observed in the nucleus. Both pituitary as well as prostatic FSH were coeluted on a Sephadex G-100 column and high-performance liquid chromatography (HPLC) indicating physicochemical similarities of FSH in both the tissues. Surprisingly, the modulation of pituitary and prostatic FSH by inhibin and its related peptides were comparable. The intensity and grandularity of FSH staining was stronger in the case of benign prostatic hyperplasia as compared with normal prostatic specimens. In view of the well-known effects of FSH on the cellular growth, differentiation, and function of gonadal tissues, a similar role for FSH in pathophysiology of prostate is postulated.     

前列腺癌与良性前列腺增生细胞株差异核基质蛋白的鉴定

目的:鉴定人前列腺癌雄激素依赖性细胞株LNCaP、前列腺癌雄激素非依赖性细胞株PC-3与良性前列腺增生细胞株BPH-1之间差异表达的核基质蛋白(nuclear matrix proteins,NMPs)。方法:常规制备各细胞株NMPs,应用双向凝胶电泳对其进行分离;对差异表达的蛋白质点行MALDI-TOF-MS/MS质谱分析,数据库搜索并鉴定。结果:成功获得了分辨率高、重复性好的不同细胞株NMPs双向凝胶电泳图谱;初步鉴定出包含酶、调节蛋白、RNA结合蛋白及各种因子在内的12个差异表达的蛋白质,在癌细胞株中3个NMPs表达上调,9个下调。结论:人前列腺癌细胞与良性前列腺增生细胞之间NMPs表达存在明显差异;初步筛选出12个差异NMPs,其表达水平及功能与疾病的联系需进一步研究。     

Effects of the Bowman-Birk inhibitor on growth, invasion, and clonogenic survival of human prostate epithelial cells and prostate cancer cells

BACKGROUND: The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor with demonstrated anticarcinogenic activity in both in vitro and in vivo systems. METHODS: The effects of BBI and BBI Concentrate (BBIC), a soybean concentrate enriched in BBI, on cell growth, invasion, and/or survival were evaluated by the sulforhodamine B assay, a colony formation assay, the trypan blue dye exclusion assay and an in vitro invasion assay. The cells used in these studies were normal human prostate epithelial cells and prostate epithelial cell lines derived from embryonic prostate tissue (267B1) or benign prostatic hyperplasia (BPH) tissue (BRF-55T) and human prostate cancer cells established by Ki-ras oncogene transfection of 267B1 cells (267B1/Ki-ras) or from metastatic lesions of human prostate cancer (LNCaP and PC-3). RESULTS: BBIC had a statistically significant inhibitory effect on the growth and clonogenic survival of BRF-55T, 267B1/Ki-ras, LNCaP, and PC-3 cells. BBI also inhibited the growth of LNCaP cells and the clonogenic survival of BRF-55T and 267B1/Ki-ras cells and decreased the ability of LNCaP cells to invade across reconstituted basement membrane (Matrigel) when PC-3 cell-conditioned medium was utilized as the chemoattractant. BBI or BBIC did not affect the growth of normal prostate epithelial cells. CONCLUSION: BBI and/or BBIC could be a useful agent for treatment of prostate diseases.     

Single case report of prostate adenocarcinoma in a dog castrated three months previously. Morphological, biochemical, and endocrine determinations

During the course of another investigation, three dogs had been castrated 3 months previously. Upon completion of the experiment, it was discovered that one dog presented a spontaneous prostatic adenocarcinoma of intraalveolar proliferative type at histology. Prostate weight of this dog before castration was estimated to be 22 g by tridimensional measurement at laparotomy and remained relatively constant (19 g) 3 months after castration. These results indicate that if regression had occurred in some cell populations (androgen-dependent) it was only partial and masked by growth of androgen-independent cells. Analysis of 12 individual steroids in peripheral blood and in prostatic tissue attested of a normal adrenal secretory activity. A series of 15 hydrolytic enzymes along with receptors for androgen, estrogen, and progesterone, were determined in prostatic tissue obtained at sacrifice. Enzymatic activities were those of typical epithelial cells, and most of them remained relatively high despite low levels of circulating testosterone. However, two markers of androgen action in dog prostate, acid phosphatase and arginine esterase, were significantly reduced. Receptor levels were similar to those of castrated animals. Thus, cancer cells had probably retained some androgen sensitivity.     

Current treatment strategies for advanced prostate cancer

During the past decade, treatment strategies for patients with advanced prostate cancer involving stage IV (T4N0M0, N1M0 or M1) hormone‐sensitive prostate cancer and recurrent prostate cancer after treatment with curative intent, as well as castration‐resistant prostate cancer, have extensively evolved with the introduction and approval of several new agents including sipuleucel‐T, radium‐223, abiraterone, enzalutamide and cabazitaxel, all of which have shown significant improvement on overall survival. The appropriate use of these agents and the proper sequencing of these agents are still not optimized. The results of several recently reported randomized controlled trials and retrospective studies could assist in developing a treatment strategy for advanced prostate cancer. In addition, prospective studies and molecular characterization of tumors to address these issues are ongoing.     

Low dose of ketoconazole in patients with prostate adenocarcinoma resistant to pharmacological castration

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Ketoconazole is an inhibitor of adrenal androgen synthesis which carries on the anti‐tumour activity by interfering with different enzymes, cytochrome P450 14‐α‐demethylase, C 17,20 lyase and C 17 α‐hydroxylase. Some studies have shown an anti‐tumour activity of ketoconazole employed at different dose levels following the failure of androgen‐suppressive therapies. Patients refractory to pharmacological castration and/or chemotherapy could have an additional benefit in terms of disease control from the use of low dose of ketoconazole. The safety profile was good.

OBJECTIVE

• ? To assess the efficacy of ketoconazole in patients with castration‐resistant prostate cancer (CRPC).

PATIENTS AND METHODS

• ? From April 2008 to November 2009, 37 patients with CRPC have been treated with ketoconazole. The primary endpoint was the prostate‐specific antigen (PSA) response; the secondary endpoints were progression‐free survival and safety profile.
• ? Ketoconazole was administered by oral route at a dose of 200 mg every 8 h continuous dosing until the onset of serious adverse events or disease progression.
• ? The study was based on a two‐step design with an interim efficacy analysis carried out on the first 12 patients accrued.

RESULTS

• ? Main characteristics of population were: median age 75 years (range 60–88); baseline mean PSA 28.8 ng/mL (4.3–1000); 30 patients previously challenged with at least two lines of hormone therapy; 15 patients previously treated with chemotherapy.
• ? Biochemical responses accounted for: two complete responses (5%), six partial responses (16%), 13 patients with stable disease (35%), and 14 with progressive disease (38%). Of 15 patients resistant to chemotherapy, overall disease control (complete plus partial responses plus stable disease) was recorded in seven of them.
• ? Treatment was feasible without inducing grade 3–4 adverse events. The most common grade 1–2 adverse events were asthenia (27%), vomiting (8%) and abdominal pain (8%).

CONCLUSION

• ? Treatment with low‐dose ketoconazole is feasible and well tolerated. The efficacy was satisfactory in patients previously treated with chemotherapy.

     

Phase II study of docetaxel re‐treatment in docetaxel‐pretreated castration‐resistant prostate cancer

Study Type – Therapy (cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? We show that (i) docetaxel re‐treatment, after a treatment‐free interval, preserves activity; (ii) the treatment is especially well tolerated in patients who were effectively pretreated with docetaxel; and (iii) it could be speculated that combining docetaxel with other agents in this setting might be safe and result in greater activity.

OBJECTIVE

To determine the activity and tolerability of docetaxel re‐treatment after first‐line therapy with docetaxel in castration‐resistant prostate cancer (CRPC).

PATIENTS AND METHODS

Between November 2005 and January 2009, 45 patients initially responding to docetaxel and then experiencing disease progression after a period of biochemical remission of at least 5 months were enrolled in a prospective multicenter study and re‐treated with docetaxel. The primary endpoint was the biochemical response (biochemical partial response defined as >50% prostate‐specific antigen [PSA] decline); secondary endpoints were objective response, toxicity, progression‐free survival (PFS) and overall survival (OS).

RESULTS

Partial PSA responses were observed in 11 patients (24.5%), 4 (25%) of whom also had an objective response. The treatment was well tolerated, with grade 1–2 neutropenia, thrombocytopenia, vomiting and peripheral neuropathy noted in 18 (40%), 11 (24.5%), 8 (17.8%), and 6 (13.3%) patients, respectively. The most common grade 3 toxicity was neutropenia, which was observed in 8 patients (17.8%). Median PFS was 5 months and median OS was 13 months.

CONCLUSIONS

Docetaxel re‐treatment preserves anti‐tumour activity and is well tolerated in a selected population of pretreated patients with CRPC. Further randomized trials are needed to confirm our preliminary results.     

TRPC6在人良性与恶性前列腺组织中的表达

观察瞬时受体电位通道C6（TRPC6）在人良性与恶性前列腺组织及前列腺癌细胞系中的表达,进一步探讨TRPC6的表达与前列腺癌分期、分级及激素依赖性的关系。利用免疫组织化学技术,检测发现45．0％的前列腺增生和86．6％的前列腺癌病例表达TRPC6,两者比较有显著性差异沪〈0．01）。TRPC6的表达与前列腺癌分级和前列腺外转移有关（P〈0．01）。前列腺癌分期增高,TRPC6表达增多,但在T2、T3和DT4期肿瘤病例中,TRPC6表达无显著差异。此外TRPC6在激素依赖性前列腺癌与激素非依赖性前列腺癌中的表达也无显著差异。应用RT-PCR及Westernblot,检测到TRPC6在前列腺癌细胞系中的表达。本研究发现,TRPC6在良性与恶性前列腺组织及前列腺癌细胞系中表达。TRPC6的表达与前列腺癌的组织分级、Gleason评分及前列腺外转移有关。     

Idiopathic intracranial hypertension: A possible complication in the natural history of advanced prostate cancer

Idiopathic intracranial hypertension is a variety of intracranial hypertension that is extremely rare in men. Obesity and hypogonadism are the most important predictive factors. Etiological hypotheses include increased central venous pressure, and various hormonal and metabolic changes commonly found in obese patients. We described the case of an obese man with prostate cancer who showed a consistent bodyweight increase during treatment with taxanes and prednisone. He was hospitalized because of a severe loss of vision as a consequence of idiopathic intracranial hypertension. A complete symptom remission was obtained after 3 weeks of anti‐edema therapies (steroids, acetazolamide). Castration‐resistant prostate cancer is a risk factor for idiopathic intracranial hypertension. Long‐term androgen deprivation therapy, bodyweight increase, and fluid retention during chronic steroid administration and taxane chemotherapy might favor the disease onset. This severe complication has a good outcome, and should be suspected in the presence of symptoms and signs of intracranial hypertension.