Identifying the role of apolipoprotein A-I in prostate cancer.

Although localized prostate cancer (PCa) can be cured by prostatectomy and radiotherapy, the development of effective therapeutic approaches for advanced prostate cancer, including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), is lagging far behind. Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need. Here, we report that apolipoprotein A-I (ApoA-I), the major component of high-density lipoprotein (HDL), is upregulated in PCa based on both bioinformatics and experimental evidence. The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells. Molecularly, ApoA-I is regulated by MYC, a frequently amplified oncogene in late-stage PCa. Altogether, our findings have revealed a novel indicator to predict prognosis and recurrence, which would benefit patients who are prone to progress to metastasis or even NEPC, which is the lethal subtype of PCa.

VHL-HIF-2α axis-induced SMYD3 upregulation drives renal cell carcinoma progression via direct trans-activation of EGFR.

It has been well established that the von Hippel-Lindau/hypoxia-inducible factor α (VHL-HIFα) axis and epidermal growth factor receptor (EGFR) signaling pathway play a critical role in the pathogenesis and progression of renal cell carcinoma (RCC). However, few studies have addressed the relationship between the two oncogenic drivers in RCC. SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase involved in gene transcription and oncogenesis, but its expression and function in RCC remain unclear. In the present study, we found that SMYD3 expression was significantly elevated in RCC tumors and correlated with advanced tumor stage, histological and nuclear grade, and shorter survival. Depletion of SMYD3 inhibited RCC cell proliferation, colony numbers, and xenograft tumor formation, while promoted apoptosis. Mechanistically, SMYD3 cooperates with SP1 to transcriptionally promote EGFR expression, amplifying its downstream signaling activity. TCGA data analyses revealed a significantly increased SMYD3 expression in primary RCC tumors carrying the loss-of-function VHL mutations. We further showed that HIF-2α can directly bind to the SMYD3 promoter and subsequently induced SMYD3 transcription and expression. Taken together, we identify the VHL/HIF-2α/SMYD3 signaling cascade-mediated EGFR hyperactivity through which SMYD3 promotes RCC progression. Our study suggests that SMYD3 is a potential therapeutic target and prognostic factor in RCC.

[Alpha-blockers and bioflavonoids in men with chronic nonbacterial prostatitis (NIH-IIIa): a prospective, placebo-controlled trial].

OBJECTIVE: The National Institutes of Health (NIH) category IIIa chronic prostatitis syndromes (non bacterial chronic prostatitis) were common disorders but with few effective therapies. Alpha-blockers and bioflavonoids had recently been reported in randomized controlled trials to improve the symptom of these disorders in a significant proportion of men. The aim of this study was to confirm these findings in a prospective randomized, placebo-controlled trial. METHODS: Forty-five men with category IIIa chronic non bacterial protatitis were randomized into three groups as follows: (1) placebo; (2) phenoxybenzamine-hydrochloride:10 mg two times a day for one month; (3) flavoxate HCI-neptumus: 200 mg three times a day for one month. The NIH chronic prostatitis symptom score was used to grade symptoms at the beginning and conclusion of the study. RESULTS: All the patients in three groups completed the study except three dropout patients in placebo group because of sever symptoms. The three groups were similar in age, duration of symptoms and initial symptom score. Patients taking placebo had a mean improvement in NIH-CPSI from 21.85 to 19.55 (not significant), while the phenoxybenzamine-hydrochloride group had a mean improvement from 21.95 to 13.75 (P < 0.01), and those taking flavoxate HCI-neptumus had a mean improvement from 21.75 to 16.95 (P < 0.05). The decrease in NIH-CPSI was associated with significant improvement in patients' clinical manifestations. CONCLUSION: Therapy with alpha-blockers was well tolerated with significant symptomatic improvement in most men having chronic non-bacterial chronic protatitis while the bioflavonoids group had no significant improvement. Mechanism of both medicines needs further study.