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Gleason 6 Prostate Tumors Diagnosed in the PSA Era Do Not Demonstrate the Capacity for Metastatic Spread at the Time of Radical Prostatectomy

Donin, Nicholas M; Laze, Juliana; Zhou, Ming; Ren, Qinghu; Lepor, Herbert
OBJECTIVE: To elucidate the probability that Gleason 6 tumors diagnosed in the prostate-specific antigen (PSA) era treated with radical prostatectomy (RP) develop metastasis. METHODS: Between October 2000 and June 2012, 1781 men underwent open RP by a single surgeon. Biochemical recurrence (BCR) was defined as a serum PSA value >/=0.2 ng/mL, or 2 progressively rising PSA values >0.14 ng/mL. Significant BCR (sBCR) was defined as a BCR with a PSA doubling time (PSADT) <36 months. Insignificant BCR (iBCR) was defined as BCR with a PSADT >/=36 months. RESULTS: Eight hundred fifty-seven of men (48.1%) undergoing open RP had a pathologic diagnosis of Gleason 6. Twenty-three of 857 of these men (2.7%) developed BCR, 7 were designated as iBCR (mean PSADT 81 months, range 36 to 100), 16 were sBCR (mean PSADT 8 months, range 1.5-20 months). There was a 10-fold difference in PSADT between the sBCR and iBCR groups (P <.001). All men with sBCR underwent salvage radiation therapy (SRT) and all demonstrated a subsequent PSA decline to
PMID: 23706588
ISSN: 0090-4295
CID: 415042

Prostate Cancer Multifocality and Heterogeneity: Implications for Gleason Grading, Tumor Volume Measurement and Tissue Sampling for Research [Meeting Abstract]

Huang, C. C.; Kong, M.; Ren, Q.; Deng, F-M; Melamed, J.; Zhou, M.
ISI:000314444401308
ISSN: 0893-3952
CID: 227142

Role of Long-Chain Fatty Acyl-CoA Synthetase 4 (ACSL4) in Prostate Cancer Progression [Meeting Abstract]

Ren, Q.; Kong, M. X.; Wu, X.; Deng, F-M; Melamed, J.; Monaco, M. E.; Lee, P.
ISI:000314444401414
ISSN: 0893-3952
CID: 227182

Role of Long-Chain Fatty Acyl-CoA Synthetase 4 (ACSL4) in Prostate Cancer Progression [Meeting Abstract]

Ren, Q.; Kong, M. X.; Wu, X.; Deng, F-M; Melamed, J.; Monaco, M. E.; Lee, P.
ISI:000314789301334
ISSN: 0023-6837
CID: 241022

Prostate Cancer Multifocality and Heterogeneity: Implications for Gleason Grading, Tumor Volume Measurement and Tissue Sampling for Research [Meeting Abstract]

Huang, C. C.; Kong, M.; Ren, Q.; Deng, F-M; Melamed, J.; Zhou, M.
ISI:000314789301228
ISSN: 0023-6837
CID: 241172

Gleason 6 Prostate Tumors Diagnosed in the PSA Era Do Not Demonstrate the Capacity for Metastatic Spread at the Time of Radical Prostatectomy REPLY [Editorial]

Donin, Nicholas M; Laze, Juliana; Lepor, Herbert; Zhou, Ming; Ren, Qinghu
ISI:000321036200043
ISSN: 0090-4295
CID: 2245722

Over-expression of TIF1 gamma is a common event in hepatocellular carcinoma irrespective of viral etiology and neoadjuvant therapy [Meeting Abstract]

Kong, M. X.; Ligr, M.; Sarpel, U.; Lee, L.; Ren, Q.; Cho, M.; Hadju, C.; Konno, F.; Taboada, S.; Lee, P.; Xu, R.
ISI:000308126900242
ISSN: 0309-0167
CID: 178294

The Occurrence of Papillary Thyroid Carcinoma in Patients Undergoing Thyroidectomy for Hurthle Cell Adenoma: A Comparative Study [Meeting Abstract]

Kong, M. X.; Ren, Q.; Wang, B.; Cangiarella, J.; Sun, W.
ISI:000308126900401
ISSN: 0309-0167
CID: 178295

Accurate assessment of HER2 status in 'triple-negative' breast cancer requires both IHC and FISH testing [Meeting Abstract]

Ren, Q.; Samdani, R.; Singh, B.
ISI:000308126900087
ISSN: 0309-0167
CID: 178293

Regulation of a novel androgen receptor target gene, cyclin B1, through androgen-dependent E2F family member switching

Li, Y; Zhang, DY; Ren, Q; Ye, F; Zhao, X; Daniels, G; Wu, X; Dynlacht, B; Lee, P
Malignant transformation of human prostatic epithelium is associated with loss of androgen receptor (AR) in the surrounding stroma. However, the function and mechanisms of AR signaling in prostate cancer (PCa) stroma remain elusive. Here we report that androgen and its receptor inhibit proliferation of prostate stromal cells through transcriptional suppression of cyclin B1 by Proteomics Pathway Array Analysis (PPAA), confirmed at mRNA and protein levels using AR negative or positive primary prostate stromal cells. Furthermore, AR showed a negative correlation with cyclin B1 expression in stroma of human PCa samples in vivo. Mechanistically, we identify cyclin B1 as a bona fide AR target gene in prostate stromal cells. The negative regulation of cyclin B1 by AR is mediated through switching between E2F1 and E2F4 on the promoter of cyclin B1. E2F1 binds to cyclin B1 promoter and maintains its expression and subsequent cell cycle progression in AR negative stromal cells or AR positive stromal cells when androgens are depleted. Upon stimulation with androgen in AR positive stromal cells, E2F1 is displaced from the binding site by AR and replaced with E2F4, leading to recruitment of the SMRT/HDAC3 co-repressor complex and repression of cyclin B1 at chromatin level. The switch between E2F1 and E2F4 at the E2F binding site of the cyclin B1 promoter coincides with an androgen-dependent interaction between AR and E2F1 as well as cytoplasmic to nuclear translocation of E2F4. Thus, we identified a novel mechanism for E2F factors in the regulation of cell cycle gene expression and cell cycle progression under the control of AR signaling.
PMCID:3434485
PMID: 22508987
ISSN: 0270-7306
CID: 164476