The standard first-line treatment of castration-resistant prostate cancer (CRPC) is docetaxel-based chemotherapy. However, CRPC may not respond to docetaxel due to drug resistance or other causes. Several new therapeutic agents have been developed, some of which are approved by FDA or on clinical trials. The mechanisms of action of these agents include stabilizing microtubules, inhibiting hormone synthesis, blocking androgen receptor, bone targeting or immune regulation. In this article we review the novel therapeutic options for CPRC after docetaxel failure.
Bone Neoplasms ; drug therapy ; secondary ; Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Taxoids ; therapeutic use

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male ; Humans ; Prostatic Neoplasms/pathology* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen ; Castration ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

OBJECTIVETo discuss the novel biomarkers of microRNAs in prostate cancer.

DATA SOURCESThe literatures about microRNAs and prostate cancer cited in this review were obtained mainly from Pubmed published in English from 2004 to 2012.

STUDY SELECTIONOriginal articles regarding the novel role of microRNAs in prostate cancer were selected.

RESULTSMicroRNAs play an important role in prostate cancer such as cell differentiation, proliferation, apoptosis, and invasion. Especially microRNAs correlate with prostate cancer cell epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), drug sensitivity, cancer microenvironment, energy metabolism, androgen independence transformation, and diagnosis prediction.

CONCLUSIONSMicroRNAs are involved in various aspects of prostate cancer biology. The role of microRNA in the initiation and development of prostate cancer deserves further study.

Biomarkers ; analysis ; Drug Resistance, Neoplasm ; Humans ; Male ; MicroRNAs ; analysis ; physiology ; Prostatic Neoplasms ; diagnosis ; drug therapy ; pathology

In China, the incidence of prostate cancer has been increasing in recent years. Hormonal therapy has been the mainstay of the therapeutic options for metastatic diseases for many years. But many metastatic tumors progress at a median of two to five years and become hormonal refractory prostate cancer (HRPC). This article summarizes in the advances of diagnostic criteria, molecular biological features, prediction markers, new therapeutic agents and further researches to be undertaken concerning HRPC.
Aged ; Androgen Antagonists ; pharmacology ; Biomarkers, Tumor ; analysis ; Drug Resistance, Neoplasm ; Humans ; Male ; Prostatic Neoplasms ; diagnosis ; drug therapy ; pathology

OBJECTIVETo study the action mechanism of a Chinese herbal mixture PC-SPES II inducing the apoptosis of androgen independent prostate adenocarcinoma cell line (PC-3).

METHODSThe growth of PC-3 was shown by MTT. Immunofluorescence staining of acridine orange (AO) and flow cytometry were used to detect the apoptosis. The expressions of the apoptosis-related proteins were analyzed with their monoclonal or polyclonal antibodies after Western blotting.

RESULTSPC-SPES II not only inhibited the growth of PC-3 cells but also induced their death. The apoptosis of PC-3 cells treated with PC-SPES II was detected by immunofluorescence staining of AO and flow cytometry, which showed the apoptotic cells to be (29.8 +/- 5.6)%, but the untreated control cells (0.06 +/- 0.014)%, (P < 0.01). The expression of Bcl-2 and Bcl-xL, two antiapoptosis proteins, was decreased while Bax, a pro apoptosis protein, was elevated in the cells treated with PC-SPES II as compared with the untreated control (P < 0.01). Accordingly, the expression of the activated fragments of caspase-3 was also increased (P < 0.01).

CONCLUSIONThe Chinese herbal mixture PCSPES II can induce the apoptosis of PC-3. Its mechanism may lie in the up-regulation of Bax expression and down-regulation of Bcl-2 and Bcl-xL expressions, which induce the activated fragments of caspase-3 by mitochondria.

Apoptosis ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Male ; Phytotherapy ; Prostatic Neoplasms ; drug therapy ; pathology

OBJECTIVETo study the clinicopathological characteristics of primary Non-Hodgkin's Lymphoma (NHL) of the prostate.

METHODSTwo cases of primary NHL of the prostate were studied by analyzing the clinical data, pathological features, prognosis and review of the literature.

RESULTSHE showed that the normal prostatic tissues were replaced by diffuse-type cancer tissues composed of oval or round medium- to large- size lymphoid cells, with vesicular nuclei, fine chromatin, 2-4 membrane-bound nucleoli and scanty cytoplasm, with either amphophilic or basophilic. Immunohistochemistry revealed: CD20 +, CD79a +, CD10 -, CD5 -, CD3 - and CD45 - in Case 1 and CD20+ + +, PSA +/-, CKpan -, Syn -, CgA -, 34betaE12 -, P504S - and CD3 - in Case 2. Case 1 received chemotherapy combined with radiotherapy, relapsed 4 years later and stabilized by repeated chemotherapy. Case 2 experienced no recurrence after treated by chemotherapy.

CONCLUSIONSurgical treatment could be avoided by preoperative pathological diagnosis of primary NHL of the prostate, for which combined chemotherapy should be the first preference.

Aged ; Antigens, CD20 ; analysis ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymphoma, Non-Hodgkin ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology

We reviewed and analyzed the clinical data for a patient with metastatic castration-resistant prostate cancer (mCRPC) from September, 2009 to December, 2014. After the treatment with abiraterone, patient's performance status improved, pain relieved, total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) markedly decreased. tPSA or fPSA fluctuated between 
30 and 50 ng/mL or between 10 and 20 ng/mL. MRI showed the left peripheral zone reduced. MRI and bone single photon emission computed tomography (SPECT) scan showed no new metastasis. These results indicated that application of abiraterone for patient with mCRPC not only decreased prostate specific antigen (PSA) levels and tumor volume, but also blocked bone metastasis progression and enhanced pain relief.
Androstenes ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Disease Progression ; Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology

Androgens ; metabolism ; Antineoplastic Agents, Hormonal ; therapeutic use ; Humans ; Integrative Medicine ; Male ; Medicine, Chinese Traditional ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology

OBJECTIVETo analyze the influence of benign prostatic hyperplasia (BPH) drugs on incidence and pathology grading of prostate cancer in China.

METHODSRetrospectively investigated the history of drug treatment in 1029 cases of BPH in patients from February 1998 to December 2004. According to the history of drug use, the patients were divided into 4 groups: finasteride group, alpha-receptor inhibitor group, finasteride and alpha-receptor inhibitor combination group and control group (untreated group). We gathered pathology sections of patients in all groups, and gave Gleason Score to each. The difference of incidence and pathology grading of prostate cancer were analyzed by Stata 7.0.

RESULTSThe incidence of prostate cancer in the population of our study was 13.5%; The incidence in finasteride group, alpha-receptor inhibitor group, combination group and control group was 9.8%, 16.0%, 10.3% and 18.6%, respectively. There was significant difference between the two groups with the use of finasteride and the two groups without it (P < 0.05). In our study, the ratio of middle or high level pathology grading (Gleason ≥ 7) in prostate cancer patients was 58.3%, the ratio of middle or high level pathology grading prostate cancer patients in the four groups was 71.4%, 59.6%, 67.7% and 40.0%, respectively. In the comparison of composition ratio of middle or high level prostate cancer, there was significant difference between the two groups with the use of finasteride and the two groups without it (P < 0.05).

CONCLUSIONSFinasteride can lower the risk of prostate cancer, but increase the pathology grade of the prostate cancer which has occurred in the same time. The alpha-receptor inhibitor does not have the same effect.

Adrenergic alpha-Antagonists ; therapeutic use ; Aged ; Aged, 80 and over ; Finasteride ; therapeutic use ; Humans ; Incidence ; Male ; Middle Aged ; Prostatic Hyperplasia ; drug therapy ; Prostatic Neoplasms ; epidemiology ; pathology ; Retrospective Studies

Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments.
Animals ; Bone Neoplasms ; drug therapy ; metabolism ; radiotherapy ; secondary ; surgery ; Breast Neoplasms ; metabolism ; pathology ; Disease Models, Animal ; Drug Delivery Systems ; Female ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Prostatic Neoplasms ; metabolism ; pathology ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism