Yen Ta Chen

Suppression Versus Induction of Androgen Receptor Functions by the Phosphatidylinositol 3-Kinase/Akt Pathway in Prostate Cancer LNCaP Cells with Different Passage Numbers

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway controls several important biological functions, such as cell growth regulation, apoptosis, and migration. However, the way in which PI3K/Akt controls androgen receptor (AR)-mediated prostate cancer cell growth remains unclear and controversial. Here, we demonstrate that the PI3K/Akt pathway regulates AR activity in a cell passage number-dependent manner. Specifically, PI3K/Akt pathway can suppress AR activity in androgen-dependent LNCaP cells with low passage numbers. In contrast, it can also enhance AR activity in LNCaP cells with high passage numbers. Furthermore, we also demonstrate that insulin-like growth factor-1 can activate the PI3K/Akt pathway that results in the phosphorylation of AR at Ser210 and Ser790. The consequence of these events may then change the stability of AR protein. Together, our results demonstrate that the PI3K/Akt pathway may have distinct mechanisms to modulate AR functions in various stages of prostate cancer cells and that a combined therapy of antiandrogens and anti-PI3K/Akt inhibitors may be worth considering as a future therapeutic approach to battle prostate cancer.

Interleukin-6 differentially regulates androgen receptor transactivation via PI3K-Akt, STAT3, and MAPK, three distinct signal pathways in prostate cancer cells

The effects of IL-6 on prostate cancer cells are well documented yet remain controversial. Some reports suggested that IL-6 could promote prostate cancer cell growth, while others showed that IL-6 could repress prostate cancer cell growth. Here, we systemically examined various IL-6 signaling pathways in prostate cancer cells and found that IL-6 could go through at least three distinct pathways to modulate the functions of androgen receptor (AR), a key transcriptional factor to control the prostate cancer growth. Our results show that IL-6 can enhance AR transactivation via either the STAT3 or MAPK pathways. In contrast, IL-6 can suppress AR transactivation via the PI3K-Akt pathway. Co-existence of these various signaling pathways may result in either additive or conflicting effects on AR transactivation. Together, our results indicate that the balance of these various pathways may then determine the overall effect of IL-6 on AR transactivation.

Is Hand-Assisted Retroperitoneoscopic Nephroureterectomy Better Than Transurethral Bladder Cuff Incision-Assisted Nephroureterectomy?

PURPOSE To compare the perioperative and oncologic outcome between hand-assisted nephroureterectomy (HARNU) and transurethral bladder cuff incision-assisted nephroureterectomy (TUINU), which manage the bladder cuff with different methods. PATIENTS AND METHODS From January 2005 to December 2008, 325 patients with upper urinary tract urothelial carcinoma (UUT-UC) underwent nephroureterectomy at our institution. A total of 208 patients were enrolled in this retrospective study. RESULTS A total of 208 patients, including 102 men and 106 women, were analyzed in this retrospective study. Ninety-eight patients underwent HARNU for UUT-UC, and110 patients underwent TUINU. The HARNU group has less operative time and hospital stay, and fewer postoperative ileus episodes. There were trends of less blood loss in the HARNU group. There were no statistical differences in the total bladder tumor recurrence, local recurrence, contralateral recurrence, distant metastasis, and cancer-specific survival between HARNU and TUINU. There was a significantly higher incidence of bladder tumor recurrence in TUINU group, however, than in the HARNU group (P=0.008) if the tumor was located at the low third of the ureter. CONCLUSION There were more oncologic concerns about bladder tumor recurrence for the low third ureteral tumor in the TUINU group. In addition, the perioperative outcomes such as operative time, blood loss, hospital stay, and ileus rate were better in the HARNU group. Therefore, surgeons can manage UUT tumor with less oncologic concern and better perioperative results with HARNU.

Oncological impact of endoscopic bladder cuff management during nephroureterectomy varies according to upper urinary tract tumor location

To compare the oncological outcome between extravesical excision and transurethral excision for bladder cuff management in patients undergoing nephroureterectomy with upper urinary tract urothelial cancer.

Severity of hydronephrosis correlates with tumour invasiveness and urinary bladder recurrence of ureteric cancer.

To explore the prognostic role of hydronephrosis grade in patients with pure ureteric cancer.

Lymphovascular invasion is a pathological feature related to aggressive cancer behavior and predicts early recurrence in prostate cancer

In order to determine the prognostic impact of lymphovascular invasion (LVI) in patients after radical prostatectomy, the retrospective data from our institution has been analyzed. From 1998 to 2010, 117 patients underwent radical prostatectomy. A total of 87 patients were included in this retrospective study. The relationship between LVI and advanced prostate cancer characteristics was evaluated by χ2 test. The Kaplan‐Meier method and meta‐analysis were used to describe the impact of LVI invasion upon early biochemical failure after radical prostatectomy. LVI was observed in patients with clinically or pathologically aggressive prostate cancer including patients of higher preoperative risk group, higher preoperative PSA, advanced Gleason grade, and pathological T3 disease. LVI is also associated with early biochemical failure rate both in our report and in the literature. Therefore, LVI is a pathological feature which indicates prognosis correlates with aggressive prostate cancer behavior and results in early biochemical failure after radical prostatectomy.

Re: Thomas Seisen, Benoit Peyronnet, Jose Luis Dominguez-Escrig, et al. Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel. Eur Urol 2016;70:1052–68: Preoperative Bladder Cancer History and Chronic Kidney Disease Are Associated with Occult Renal Pelvis Cancer in Preoperative Solitary Ureteral Cancer

Follow-up duration Gender, n (%) 0.054 Male 12 (32) 110 (49) Female 26 (68) 115 (51) Mean age (yr) 64.63 67.62 0.088 Preoperative CKD stage, n (%) 0.005 Stage I 0 11 (5) Stage II 2 (5) 44 (20) Stage III 14 (37) 95 (42) Stage IV 5 (13) 31 (13) Stage V 17 (45) 44 (20) Smoking history, n (%) 5 (13) 41 (18) 0.447 Bladder cancer history, n (%) 16 (42) 45 (20) 0.003 Hydronephrosis, n (%) 0.533 Grade 2 14 (37) 72 (32) >Grade 2 24 (63) 153 (68) Pathology stage 5 (13) 51 (23) 0.185 T0–1 T2 T3–4

Re: Xiao-Dong Jin, Simone Roethlisberger, Fiona C. Burkhard, Frédéric Birkhaeuser, Harriet C. Thoeny, Urs E. Studer. Long-term Renal Function After Urinary Diversion by Ileal Conduit or Orthotopic Ileal Bladder Substitution. Eur Urol 2012;61:491–7

Jin et al. reported that diabetes and hypertension increase the risk of impaired renal function for ileal conduit rather than orthotopic ileal bladder substitution in patients surviving >10 yr [1]. However, patients with multiple comorbidities and newly developed chronic kidney disease [2] may seldom survive>10 yr due to subsequent mortality, and they may be excluded for analysis by such selection criteria. Ku et al. suggested that the multiple variables affecting renal function after ileal-based urinary diversion should be assessed [3]. Thus the factors causing postoperative renal function deterioration for patients with shortto intermediate-term observation are worthy of investigation. We analyzed data concerning renal function outcome between ileal conduit and ileal neobladder from 2005 to 2011 in our single institution. There were 147 patients who underwent ileal-based urinary diversion (101 for ileal conduit and 46 for ileal neobladder). The average followup duration was 20.7 18.7 mo. The reasons for renal function deterioration were multifactorial and overlapped in our observation. Urinary tract infection, emptying dysfunction, hydronephrosis, postoperative chemotherapy, diabetes, and hypertension were the most common factors affecting renal function. Emptying dysfunction happened only in patients with ileal neobladder urinary reconstruction (two patients had bladder outlet obstruction and nine patients could not void spontaneously due to cerebrovascular accident or other medical events). Multivariate analysis was used for examination of the impact of multiple factors (sex, age, urinary reconstruction type, postoperative chemotherapy, diabetes, and hypertension). Ileal neobladder reconstruction seems to be an independent significant factor for renal function deterioration in univariate and multivariate analysis. More factors affected renal function after ileal neobladder reconstruction than after ileal conduit because of emptying concern. Thurairaja et al. reported that surgical technique modification could enhance the spontaneous voiding rate of ileal neobladder [4]. However, valsalva maneuver while voiding in patients who had undergone ileal