Analysis of urinary retention after endoscopic prostate enucleation and its subsequent impact on surgical outcomes.

PURPOSE: Postoperative urinary retention (PUR) is a common complication after prostate enucleation, which leads to an increased length of hospital stay and decreased postoperative satisfaction. This study determined the predictive factors of postoperative urine retention within 1 month after prostate enucleation and investigated whether PUR influences surgical outcomes at the 2-week, 3-month, and 6-month follow-up time points. METHODS: Data were collected from the electronic medical records of 191 patients with benign prostatic obstruction (BPO) during October 2018 to September 2021. Of them, 180 patients who underwent thulium laser or plasma kinetic enucleation of the prostate (ThuLEP, PKEP) were separated into the PUR group (n = 24) and the non-PUR (NPUR) group (n = 156). Uroflowmetry and the International Prostate Symptom Score (IPSS) questionnaire were followed up at 2 weeks, 3 months, and 6 months postoperatively. RESULTS: The PUR group had a significantly higher percentage of patients with type 2 diabetes mellitus (DM) than the NPUR group. Postoperatively, compared with the NPUR group, the PUR group had significantly less improvement in changes in the IPSS Quality of Life scores at 2 weeks, the total IPSS(International Prostate Symptom Score) at all follow-up times, the IPSS-S(IPSS storage subscores) at 2 weeks and 3 months, and the IPSS-V(IPSS voiding subscores) at all follow-up times. Predictive factors for PUR include lower preoperative maximum urinary flow (Qmax), lower preoperative total IPSS, and higher operation time. CONCLUSION: Lower preoperative Qmax, lower IPSS scores, and longer operation time were risk factors for PUR. Furthermore, PUR could be a prognostic factor for prostatic enucleation surgical outcomes.

Impact of age and anterior fibromuscular stroma preservation on post-enucleation voided volume.

PURPOSE: This study is centered on the critical role of anterior fibromuscular stroma (AFS) preservation in prostate enucleation, an emerging strategy aimed at minimizing postoperative urinary incontinence-a common concern in benign prostatic hyperplasia (BPH) surgeries. By focusing on postoperative voiding volumes (VV), our research investigates the efficacy of AFS preservation. This approach, distinct in its methodology, is hypothesized to improve urinary function post-surgery, thereby offering a potentially significant advancement in BPH surgical treatments. MATERIALS AND METHODS: A retrospective analysis was conducted, comparing patients who underwent prostate enucleation in 2017 without intentional AFS preservation to those in 2019 with this technique. We examined variables including age, BMI, diabetes, hypertension, and preoperative VV to assess their effect on post-catheter removal VV. The study's methodology includes a thorough review of the primary statistical analysis methods employed. RESULTS: Our analysis indicates that while the 2017 and 2019 cohorts were similar in most preoperative parameters, the 2019 group that underwent AFS-preserved surgery showed a significant improvement in postoperative VVs. This was less pronounced in the patient group aged over 70, underscoring the importance of this demographic in our study. CONCLUSIONS: The study concludes that intentional preservation of AFS during prostate enucleation positively impacts early postoperative VVs, with limited improvement in older patients. These findings highlight the potential of AFS preservation not only in enhancing urinary outcomes post-surgery but also in shaping future BPH surgical procedures and research directions.

Surgical outcomes of endoscopic enucleation of the prostate in community aging males with or without preoperative urinary retention.

OBJECTIVES: This study aims to investigate the surgical outcomes of endoscopic enucleation of the prostate in older males with or without preoperative urinary retention (UR). MATERIAL AND METHODS: We conducted a study on selected patients with symptomatic benign prostatic hyperplasia (BPH) who underwent either thulium:YAG laser (vela XL) prostate enucleation (ThuLEP) or bipolar plasma enucleation of the prostate (B-TUEP) at the geriatric urology department of our institution. The studied patients were categorized into two groups, namely the UR group and the non-UR group, on the basis of whether they experienced UR in the 1 month preceding their surgery. Their clinical outcomes following prostate endoscopic surgery were evaluated and analyzed. RESULTS: Our results revealed comparable outcomes for operation time, length of hospital stay, percentage of tissue removed, re-catheterization rate, and urinary tract infection rate within the 1 month between the B-TUEP and ThuLEP surgery groups, regardless of UR history. However, the non-UR B-TUEP group experienced more blood loss relative to the non-UR ThuLEP group (P = .004). Notably, patients with UR exhibited significantly greater changes in IPSS total, IPSS voiding, and prostate-specific antigen values relative to those without UR. CONCLUSIONS: Both ThuLEP and B-TUEP were effective in treating BPH-related bladder outlet obstruction. Our study identified more pronounced changes in IPSS total, IPSS voiding, and prostate-specific antigens within the UR group. Moreover, the rate of postoperative UR in this group was not higher than that observed in the non-UR group. Our study also revealed that the presumed benefits of laser surgery in reducing blood loss were less pronounced for patients with UR.

Lifestyle and Diet as Risk Factors for Urinary Stone Formation: A Study in a Taiwanese Population.

Background and Objectives: Urinary tract stones have long been a common ailment afflicting the population, with a high incidence and a wide distribution across different age groups. Effectively preventing the occurrence of urinary tract stones is of paramount importance. The primary aim of this study is to investigate the correlations between individual characteristics, water consumption habits, dietary habits, exercise habits, and the occurrence of urinary tract stones in a Taiwanese population. Materials and Methods: This study is cross-sectional research conducted over one month in 2022. One hundred eligible urinary stone cases were recruited through physician screening at outpatient clinics, and an additional one hundred samples from surgical outpatients without urinary tract stones were included as the control group. A questionnaire survey was employed to gather information on demographic variables, dietary habits, water consumption, and exercise habits of the cases. Descriptive statistics, chi-square tests, and logistic regression were used to explore the impact of relevant factors on urinary stone formation. Results: The analysis results revealed that among the demographic variables, males exhibited a higher risk of contracting urinary tract stones than females, and the majority of cases fell within the 40- to 49-year-old age group. Unhealthy lifestyle habits such as smoking and betel nut chewing also demonstrated a higher susceptibility to urinary tract stones. A logistic regression analysis showed that individuals who engaged in physical activity more than three times per week and those with inadequate water intakes had a higher risk of developing urinary tract stones. Conclusions: There is a close relationship between lifestyle and urinary tract stones. It is recommended that individuals continue to hydrate adequately during exercise.

Comparative Analysis of Surgical Outcomes of Flexible Ureteroscopy and Da Vinci Robotic Surgery in Community Patients with Renal Pelvic Stones Larger than 2 cm.

Background and Objectives: This study evaluated and compared the surgical outcomes of retrograde intrarenal surgery (RIRS) lithotripsy versus robot-assisted laparoscopic pyelolithotomy (RAPL) in community patients with renal pelvic stones larger than 2 cm. Materials and Methods: A total of 77 patients who underwent RIRS (RIRS group, n = 50) or RAPL (RAPL group, n = 27) at our institution between December 2016 and July 2022 were recruited. A single surgeon performed all surgical operations. Preoperative, operative, and postoperative data were recorded. The study evaluated various clinical outcomes, namely, urinary tract infections, analgesic use, emergency room readmissions, stone clearance rates, surgical complications, and medical expenditures associated with the treatment courses, and compared them between the groups. Results: The RAPL group had a larger mean stone diameter and higher degree of hydronephrosis than the RIRS group did. The RIRS group had superior outcomes regarding operative time, length of postoperative hospital stay, surgical wound pain, and medical expenditures. Regarding postoperative outcomes, comparable rates of postoperative urinary tract infection, prolonged analgesic use, and emergency room readmissions were observed between the groups. However, the RAPL group had a higher stone clearance rate than the RIRS group did (81.5% vs. 52.0%, p = 0.014). Conclusions: For the surgical treatment of renal pelvis stones larger than 2 cm, RAPL has a superior stone clearance rate than RIRS; however, RIRS achieves superior outcomes in terms of medical expenditures, length of hospital stay, and surgical wound pain. Both procedures were equally safe.

Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells.

The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.

Can the Sandwich Method Be an Alternative Treatment Choice for BPH Patients With Large Prostates?

OBJECTIVE: To compare the efficacy and safety of the sandwich method with GreenLight photoselective vaporization (GLPVP) and bipolar transurethral resection (B-TURP) with those of the enucleation method in patients with BPH and a prostate volume ≥ 80 g. METHODS: Patients with BPH who underwent either the sandwich method with GLPVP and B-TURP or the enucleation method between 2014 and 2021 were included in the analysis. The primary outcome was the comparison of uroflowmetry results between the 2 groups. Safety analysis of the complication rates was also compared. RESULTS: The cohort included 55 patients in the sandwich group and 41 patients in the enucleation group. In the efficacy analysis, both groups showed comparable uroflowmetry results, except for a higher postoperative average flow rate in the enucleation group. Regarding perioperative parameters, the sandwich method required a longer operating time, and the enucleation group had a higher incidence of manual Foley irrigation. Both groups demonstrated similar postoperative complications. CONCLUSION: The sandwich method exhibited comparable efficacy and safety to the enucleation method in patients with BPH with a prostate volume ≥ 80 g. Thus, for surgeons who are familiar with GLPVP and B-TURP, the sandwich method may be an alternative surgical approach for BPH patients with large prostates.

Simple and Convenient Method for Assessing the Severity of Bleeding during Endoscopic Prostate Surgery and the Relationships between Its Corresponding Surgical Outcomes.

Bleeding during endoscopic prostate surgery is often overlooked, and appropriate measurement techniques are rarely applied. We proposed a simple and convenient method for assessing the severity of bleeding during endoscopic prostate surgery. We determined the factors affecting bleeding severity and whether they affected the surgical results and functional outcomes. Records from March 2019 to April 2022 were obtained for selected patients who underwent endoscopic prostate enucleation through either 120-W Vela XL Thulium:YAG laser or bipolar plasma enucleation of the prostate. The bleeding index was measured using the following equation: irrigant hemoglobin (Hb) concentration (g/dL) × irrigation fluid volume (mL)/preoperative blood Hb concentration (g/dL) × enucleated tissue (g). Our research revealed that patients who underwent surgery employing the thulium laser, those aged over 80 years, and those with a preoperative maximal flow rate (Qmax) of more than 10 cc/s experienced less surgical bleeding. The patients' treatment outcomes differed depending on the severity of the bleeding. Enucleating prostate tissue was easier in the patients with less severe bleeding, who also had a lower risk of developing urinary tract infections and an improved Qmax.

Anterior fibromuscular stroma-preserved endoscopic enucleation of the prostate: a precision anatomical approach.

BACKGROUND: Benign prostate obstruction (BOO) is becoming increasingly important in this aging society. Some urge/stress urinary incontinence (UUI/SUI) still occurs after endoscopic enucleation of the prostate (EEP). It remains unclear how post-EEP incontinence can be avoided. Currently, early apical release to ameliorate the traction of the external sphincter is the best technique for incontinence prevention. OBJECTIVE: To describe our surgical technique of anterior fibromuscular stroma (AFS)-preserved EEP for BOO. DESIGN, SETTING, AND PARTICIPANTS: The medical records of 60 consecutive patients who underwent AFS-preserved EEP for BOO in our center from September 2019 to December 2019 were retrospectively reviewed. SURGICAL PROCEDURE: AFS-preserved EEP starts at the 12 o'clock position of the urethra, and the junction between the AFS and transitional zone (T-zone) was identified. The AFS and T-zone were separated first to protect the AFS in the initial operative procedure. Then, following the usual enucleation procedure, AFS-preserved EEP could be achieved. MEASUREMENTS: Postoperative prostate-specific antigen (PSA), testosterone, urethral stricture, and voiding status, such as incontinence, uroflow, and postvoiding residual urine were assessed. RESULTS AND LIMITATIONS: The data show that AFS-preserved EEP could achieve similar surgical outcomes as other early apical release approaches. CONCLUSIONS: The preserved AFS provides a nice landmark at the 12 o'clock position during EEP.

The Impact of Exercise on Improving Body Composition and PSA in High-Risk Prostate Cancer Patients on Androgen-Deprivation Therapy.

This prospective study investigated how exercise impacted chronological changes in anthropometrics, body composition, prostate-specific antigen (PSA) level and prognostic nutrition index (PNI) in high-risk prostate cancer (PCa) patients on androgen deprivation therapy (ADT). The patients were divided into either the usual care or exercise group. All patients received measurements a week before ADT initiation, six- and twelve months after treatment. The exercise group received both aerobic and resistance training. The analysis was conducted using appropriate statistical methods. There were 45 males enrolled (age 67.4 ± 8 years and BMI 25.5 ± 3.6 kg/m2). Profound changes were observed at six months follow-up. The exercise group showed a significant increase in the trunk and leg lean mass, and a lesser loss of total and arm lean mass. A significant decrease in PSA was also observed among the exercise group. PNI and PSA were significantly associated with regional lean mass. Exercise can prevent loss or even increase lean mass in high-risk PCa, especially in the early stage of ADT treatment. Moreover, a strong bond between lean mass and PNI and PSA further underscores the importance of early and continuous exercise interventions.

Endoscopic Enucleation of Prostate Could Increase Testosterone Levels in Hypotestosteronemic Patients with Bladder Outlet Obstruction.

Background: We evaluated the impact of endoscopic enucleation of the prostate on testosterone levels in hypotestosteronemic patients with bladder outlet obstruction. Methods: We enrolled 294 men with lower urinary tract symptoms (LUTS) who received surgery between January 2019 and December 2020 in simple tertiary centre. The inclusion criteria were as follows: being a male patient aged 45−95 years and having recurrent urinary tract infection, having previously failed medical treatment for LUTS or urine retention, and undergoing bipolar or thulium laser enucleation of the prostate. The preoperative and postoperative data were retrospectively reviewed. Results: This study included 112 men with a mean age of 69.4 years. The mean preoperative and postoperative testosterone levels were 4.8 and 4.98, respectively. Of the patients, 88 (78.6%) received ThuLEP and 24 received BipolEP. We divided the patients into two groups according to preoperative serum testosterone levels: normal-testosterone (≥3 ng/mL) and low-testosterone (<3 ng/mL) groups. A significant change in testosterone levels (p = 0.025) was observed in the low-testosterone group. In contrast, no significant difference in testosterone levels was noted in the normal-testosterone group (p = 0.698). Conclusions: Endoscopic enucleation surgery of the prostate could improve postoperative testosterone levels in hypotestosteronemic patients with bladder outlet obstruction.

WNT1 Inducible Signaling Pathway Protein 1 Is a Stroma-Specific Secreting Protein Inducing a Fibroblast Contraction and Carcinoma Cell Growth in the Human Prostate.

The WNT1 inducible signaling pathway protein 1 (WISP1), a member of the connective tissue growth factor family, plays a crucial role in several important cellular functions in a highly tissue-specific manner. Results of a RT-qPCR indicated that WISP1 expressed only in cells of the human prostate fibroblasts, HPrF and WPMY-1, but not the prostate carcinoma cells in vitro. Two major isoforms (WISP1v1 and WISP1v2) were identified in the HPrF cells determined by RT-PCR and immunoblot assays. The knock-down of a WISP1 blocked cell proliferation and contraction, while treating respectively with the conditioned medium from the ectopic WISP1v1- and WISPv2-overexpressed 293T cells enhanced the migration of HPrF cells. The TNFα induced WISP1 secretion and cell contraction while the knock-down of WISP1 attenuated these effects, although TNFα did not affect the proliferation of the HPrF cells. The ectopic overexpression of WISP1v1 but not WISP1v2 downregulated the N-myc downstream regulated 1 (NDRG1) while upregulating N-cadherin, slug, snail, and vimentin gene expressions which induced not only the cell proliferation and invasion in vitro but also tumor growth of prostate carcinoma cells in vivo. The results confirmed that WISP1 is a stroma-specific secreting protein, enhancing the cell migration and contraction of prostate fibroblasts, as well as the proliferation, invasion, and tumor growth of prostate carcinoma cells.

Metallothionein 2A with Antioxidant and Antitumor Activity Is Upregulated by Caffeic Acid Phenethyl Ester in Human Bladder Carcinoma Cells.

Functions of metallothionein 2A (MT2A) in bladder cancer have not been extensively explored even though metallothioneins are regarded as modulators in several biological regulations including oxidation and cancerous development. We evaluated MT2A in bladder carcinoma cells in terms of the mechanisms of regulation and the underlying functions. MT2A overexpression not only downregulated endogenous ROS but also blocked ROS induced by H2O2. We used the annexin V-FITC apoptosis assay to determine the modulation of H2O2-induced cell apoptosis by MT2A expression. Results of immunoblot and reporter assays indicated that caffeic acid phenethyl ester (CAPE) treatment induced MT2A and heme oxygenase-1 (HO-1) expressions; moreover, the involvement of CAPE in either upregulation of the HO-1 expression or downregulation of endogenous ROS is MT2A dependent in bladder carcinoma cells. Knockdown of MT2A increased invasion and cell growth in vitro and in vivo, whereas ectopic overexpression of MT2A had the reverse effect in bladder carcinoma cells. Unlike bladder cancer tissues, the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) analysis showed a significant level of MT2A mRNA in the normal bladder tissues. Collectively, our results indicated that MT2A is acting as an antioxidant and also a tumor suppressor in human bladder carcinoma cells.

Surgery for Xanthogranulomatous Pyelonephritis: A Comparison of Midline Transperitoneal and Flank Retroperitoneal Laparotomy Approaches to Nephrectomy.

Xanthogranulomatous pyelonephritis (XGP) is a rare inflammatory disease often associated with high morbidity and mortality. Whether the midline transperitoneal or the flank retroperitoneal approach is superior remains unknown. We searched through pathology databases and reviewed 86 patients with an XGP diagnosis from 2000 to 2021 at our institution. After the patients who did not meet the inclusion criteria were excluded, 35 patients who had undergone nephrectomy through the midline transperitoneal or the flank retroperitoneal laparotomy approach were recruited. Nine (25.71%) of the thirty-five patients underwent nephrectomy through a midline approach, whereas twenty-six (74.29%) received a flank approach. Patients in the midline approach group had a longer surgical time (p = 0.03) than those in the flank approach group. In addition, patients in the flank approach group took less time after surgery to resume oral intake than those in the midline approach group (p = 0.01). No significant differences in the rates of intraoperative and postoperative complications such as peritonitis or intraabdominal infection were observed between the groups. For the patients with XGP who are good candidates for surgery, nephrectomy is a relatively safe surgical treatment method. Both surgical methods produced favorable surgical outcomes, and the patients who received these methods had similar complication rates.

The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor ß/Smad Signaling in Bladder Carcinoma Cells.

Growth differentiation factor 15 (GDF15) is known as a TGFß-like cytokine acting on the TGFß receptor to modulate target genes. GDF15 is regarded as a tumor suppressor gene in the human bladder and the caffeic acid phenethyl ester (CAPE) induces GDF15 expression to inhibit the tumor growth in vitro and in vivo. However, the interactions among GDF15, CAPE, and TGFß/Smads signaling in the human bladder carcinoma cells remain unexplored. Results revealed that TGFß downregulated the expression of GDF15 via the activation of Smad 2/3 and Smad 1/5. Induction of GDF15 on its downstream genes, NDRG1 and maspin, is dependent on the TGFß/Smad pathways. Moreover, TGFß blocked the CAPE-inducing expressions of GDF15, maspin, and NDRG1. Pretreatment of TGF receptor kinase inhibitor not only blocked the activation of TGFß but also attenuated the activation of GDF15 on the expressions of maspin and NDRG1. The CAPE treatment attenuated the activation of TGFß on cell proliferation and invasion. Our findings indicate that TGFß downregulated the expressions of GDF15, maspin, and NDRG1 via TGFß/Smad signaling. Whereas, CAPE acts as an antagonist on TGFß/Smad signaling to block the effect of TGFß on the GDF15 expression and cell proliferation and invasion in bladder carcinoma cells.

Comparison of Outcome and Quality of Life Between Thulium Laser (VelaTM XL) Enucleation of Prostate and Bipolar Transurethral Enucleation of the Prostate (B-TUEP).

BACKGROUND AND PURPOSE: In this study, we compared patient outcomes between the 120-W thulium laser (Vela™XL) prostate enucleation (ThuLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) techniques. METHODS: We excluded patients with concomitant prostate cancer and bladder cancer and prospectively analyzed patients with benign prostatic obstruction (BPO) who underwent ThuLEP and B-TUEP from October 2018 to January 2021 in our institution. Patients' demographics, comorbidities, prostate volumes, prostate-specific antigen (PSA) levels, and International Prostate Symptoms Score (IPSS) were recorded. Perioperative outcomes including intraoperative blood loss, prostate resection percentage of the transition zone, postoperative pain score (numeric rating scale, NRS), complications, changes in postoperative uroflowmetry parameters, IPSS, and the rate of reuse of BPH medications were also evaluated. RESULTS: The data of a total of 111 patients (ThuLEP: 49, B-TUEP: 62) met the inclusion criteria were collected and analyzed prospectively. Our results revealed no significant differences between ThuLEP and B-TUEP in terms of operation time, prostate tissue enucleated, and days of hospitalization. However, patients in the ThuLEP group reported less pain after surgery than those in the B-TUEP group, and a higher proportion of patients in the B-TUEP group returned to the emergency department due to complications within one month postoperatively, with hematuria being the main cause. No significant differences were observed between the groups in changes in uroflowmetry parameters and IPSS at 2 weeks, 3 months, and 6 months postoperatively. CONCLUSION: The efficacy of ThuLEP was comparable to that of B-TUEP in terms of maximal flow rate, voiding volume, IPSS, and quality of life. ThuLEP also had several advantages over B-TUEP, including less blood loss and less postoperative pain. Therefore, ThuLEP can be considered a treatment of choice for BPH/bladder outlet obstruction, specifically for patients with a bleeding tendency and fear of pain.

The Antitumor Effect of Caffeic Acid Phenethyl Ester by Downregulating Mucosa-Associated Lymphoid Tissue 1 via AR/p53/NF-κB Signaling in Prostate Carcinoma Cells.

Caffeic acid phenethyl ester (CAPE), a honeybee propolis-derived bioactive ingredient, has not been extensively elucidated regarding its effect on prostate cancer and associated mechanisms. The mucosa-associated lymphoid tissue 1 gene (MALT1) modulates NF-κB signal transduction in lymphoma and non-lymphoma cells. We investigated the functions and regulatory mechanisms of CAPE in relation to MALT1 in prostate carcinoma cells. In p53- and androgen receptor (AR)-positive prostate carcinoma cells, CAPE downregulated AR and MALT1 expression but enhanced that of p53, thus decreasing androgen-induced activation of MALT1 and prostate-specific antigen expressions. p53 downregulated the expression of MALT in prostate carcinoma cells through the putative consensus and nonconsensus p53 response elements. CAPE downregulated MALT1 expression and thus inhibited NF-κB activity in p53- and AR-negative prostate carcinoma PC-3 cells, eventually reducing cell proliferation, invasion, and tumor growth in vitro and in vivo. CAPE induced the ERK/JNK/p38/AMPKα1/2 signaling pathways; however, pretreatment with the corresponding inhibitors of MAPK or AMPK1/2 did not inhibit the CAPE effect on MALT1 blocking in PC-3 cells. Our findings verify that CAPE is an effective antitumor agent for human androgen-dependent and -independent prostate carcinoma cells in vitro and in vivo through the inhibition of MALT1 expression via the AR/p53/NF-κB signaling pathways.

Caffeic acid phenethyl ester inhibits the growth of bladder carcinoma cells by upregulating growth differentiation factor 15.

BACKGROUND: Caffeic acid phenethyl ester (CAPE), a bioactive component of propolis, has beneficial effects on cancer prevention. Growth differentiation factor 15 (GDF15) is an antitumor gene of bladder cancer. Therefore, this study investigated the anti-cancer effect of CAPE on bladder carcinoma cells and related mechanisms. METHODS: The expressions of GDF15, N-myc downstream-regulated gene 1 (NDRG1), and maspin, and the activations of extracellular signal regulated kinase (ERK), c-jun Nterminal kinase (JNK), p38, and 50 adenosine monophosphate-activated protein kinase (AMPK) α1/2 in human bladder cells after gene transfection or knockdown were determined by immunoblot, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), and reporter assays. The assays of 5-ethynyl-2'-deoxyuridine (EdU), CyQUANT cell proliferation, and Matrigel invasion, and the xenograft animal study were used to assess the cell proliferation, invasion, and tumorigenesis. RESULTS: GDF15 expression in epithelial cells was negatively correlated with neoplasia in vitro. Also, GDF15 exhibits in bladder fibroblasts and smooth muscle cells. CAPE-induced expressions of NDRG1 and maspin decreased cell proliferation and invasion of bladder carcinoma cells in a GDF15-dependent manner in vitro. The xenograft animal study suggesting CAPE attenuated tumor growth in vivo. CAPE increased phosphorylation of ERK, JNK, p38, and AMPKα1/2 to modulate the GDF15 expressions. Pretreatments with ERK, JNK, or p38 inhibitors partially inhibited the CAPE effects on the inductions of GDF15, NDRG1, or maspin. Knockdown of AMPKα1/2 attenuated the CAPE-induced GDF15 expression and cell proliferation in bladder carcinoma cells. CONCLUSIONS: Our findings indicate that CAPE is a promising agent for anti-tumor growth in human bladder carcinoma cells via the upregulation of GDF15.