Mechanisms navigating the TGF-βpathway in prostate cancer

Few pharmacotherapies are currently available to treat castration resistant prostate cancer(CRPC),with low impact on patient survival.Transforming growth factor-b(TGF-b)is a multi-functional peptide with opposite roles in prostate tumorigenesis as an inhibitor in normal growth and early stage disease and a promoter in advanced prostate cancer.Dysregulated TGF-b signaling leads to a cascade of events contributing to oncogenesis,including upregulated proliferation,decreased apoptosis,epithelial-to-mesenchymal transition(EMT)and evasion of immune surveillance.TGF-b signaling pathway presents an appropriate venue for establishing a therapeutic targeting platform in CRPC.Exploitation of TGF-b effectors and their cross talk with the androgen axis pathway will provide new insights into mechanisms of resistance of the current antiandrogen therapeutic strategies and lead to generation of new effective treatment modalities for CRPC.Points of functional convergence of TGF-b with key oncogenic pathways,including mitogen-activated protein kinase(MAPK)and androgen receptor(AR),are discussed as navigated within the EMT landscape in the tumor microenvironment.In this context the emerging anti-TGF-b pharmacotherapies for prostate cancer treatment are considered.Targeting the functional cross-talk between the TGF-b signaling effectors with the androgen axis supports the development of novel therapeutic strategies for treating CRPC with high specificity and efficacy in a personalized-medicine approach.

Cancer/testis antigens： novel tools for discerning aggressive and non-aggressive prostate cancer

The introduction of serum prostate-specific antigen （PSA） in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens （CTAs） are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.

Prostate stromal tumor with prostatic cysts after transurethral resection of the prostate: A case report

BACKGROUND A prostatic stromal tumor is deemed to be a rare oncology condition.Based on the retrospective analysis of clinical data and scientific literature review,a case of prostatic stromal tumor was reported in this article to explore the diagnosis,treatment and prognosis of this rare disease.CASE SUMMARY The present case involved an older male patient who was admitted to our department for a medical consultation of dysuria.Serum prostate-specific antigen was 8.30 ng/mL,Ultrasound and magnetic resonance imaging suggested evident enlargement of the prostate and multiple cystic developments internally.Considering that the patient was an elderly male with a poor health status,transurethral resection of the prostate was performed to improve the symptoms of urinary tract obstruction.Furthermore,based on histopathologic examination and immunohistochemical staining,the patient was pathologically diagnosed with prostatic stromal tumor.The patient did not receive any further adjuvant therapy following surgery leading to a clinical recommendation that the patient should be followed up on a long-term basis.However,during the recent follow-up assessment,the patient demonstrated recurrence of lower urinary tract symptoms and gross hematuria.CONCLUSION Referring to scientific literature review,we believe that the management of these lesions requires a thorough assessment of the patient.Furthermore,the treatment of prostate stromal tumors should be based on the imaging examination andpathological classification. Active surgical treatment is of great significance to theprognosis of patients, and subsequent surveillance after the treatment iswarranted.

Clinicopathologic characteristics of prostatic stromal sarcoma with rhabdoid features: A case report

BACKGROUND Prostatic stromal sarcoma presenting with rhabdoid features is extremely rare,and only four cases have been reported in the English-language literature to date.Accordingly, there is no absolute definition of this group of tumors as yet, and our overall understanding of its morphological features, therapeutic regimen and prognosis is limited.CASE SUMMARY A 34-year-old male patient was referred to our hospital to address a 2-mo history of hematuria and progressive dysuria. Pelvic computed tomography scan revealed a 6.0 cm × 5.2 cm × 7.2 cm mass in the prostate, with bladder invasion.The patient underwent transurethral prostatectomy as upfront therapy. He refused further treatment and died of uncontrollable tumor growth 3 mo after surgery. Pathology analysis revealed the stroma to be pleomorphic, with a huge number of atypical spindle cells. Rhabdomyoblastic cells, with abundant eosinophilic cytoplasm, were detected. The spindle cells were positive for vimentin, INI1 and β-catenin, and the rhabdomyoblastic cells were positive for MyoD1, myogenin and INI1. The spindle cells and epithelial cells were sporadically positive for P53.CONCLUSION The prostatic stromal sarcoma tumor was immunoreactive for β-catenin,suggesting a role for the Wnt/β-catenin pathway in this tumor type.

Percent free prostate-specific antigen is effective to predict prostate biopsy outcome in Chinese men with prostate-specific antigen between 10.1 and 20.0 ng ml^-1

Percent free prostatic-specific antigen （%fPSA） has been introduced as a tool to avoid unnecessary biopsies in patients with a serum PSA level of 4.0-10.0 ng ml^-1, however, it remains controversial whether %fPSA is effective in PSA range of 10.1-20.0 ng ml^-1 in both Chinese and Western population. In this study, the diagnostic performance of %fPSA and serum PSA in predicting prostate cancer （PCa） and high-grade PCa （HGPCa） was analyzed in a multi-center biopsy cohort of 5915 consecutive Chinese patients who underwent prostate biopsy in 22 hospitals across China from January 1, 2010 to December 31, 2013. The indication for biopsy was PSA〉4.0 ng ml^-1 or/and suspicious digital rectal examination. Total and free serum PSA determinations were performed by three types of electrochemiluminescence immunoassays with recalibration to the World Health Organization standards. The diagnostics accuracy of PSA, %fPSA and %fPSA in combination with PSA （%fPSA ＋ PSA） was determined by the area under the receivers operating characteristic curve （AUC）. %fPSA was more effective than PSA in men aged ≥60 years old. The AUC was 0.584 and 0.635 in men aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1, respectively. The AUC of %fPSA was superior to that of PSA in predicting HGPCa in patients ≥60 years old in these two PSA range. Our results indicated that %fPSA is both statistically effective and clinical applicable to predict prostate biopsy outcome in Chinese patients aged ≥60 years old with a PSA of 4.0-10.0 ng ml^-1 and 10.1-20.0 ng ml^-1.

Glucocorticoids suppress tumor angiogenesis and growth of prostate cancer

Hormone-refractory prostate cancer ( HRPC) sometimes is responsive to treatment with glucocorticoids, such as prednisolone, hydrocortisone and dexamethasone, but the underlying mechanisms are not well established. In a recent paper (Clin Cancer Res, 2006, 12:3003-3009), Yano et al. Hypothesized and confirmed that the therapeutic effect of glucocorticoids on HRPC is attributed to inhibition of angiogenesis. A prostate cancer cell line DU145 that expresses glucocorticoid receptor was used to study the effect of dexamethasone (Dex) on the expres-