193 results on '"Horng-Heng Juang"'
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2. Investigating the Genetic Diversity of Hepatitis Delta Virus in Hepatocellular Carcinoma (HCC): Impact on Viral Evolution and Oncogenesis in HCC
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Horng-Heng Juang, Chao-Wei Hsu, Kang-Shuo Chang, Shan-Bei Iang, Yang-Hsiang Lin, and Mei Chao
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hepatitis delta virus ,hepatocellular carcinoma ,RNA recombination ,delta antigen ,cell migration and invasion ,Microbiology ,QR1-502 - Abstract
Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV’s involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan’s National Health Research Institutes, 2.7% (8/300) tested anti-HDV positive, with 62.7% (5/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial–mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.
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- 2024
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3. Caffeic acid phenethyl ester inhibits the growth of bladder carcinoma cells by upregulating growth differentiation factor 15
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Chen-Pang Hou, Ke-Hung Tsui, Kang-Shuo Chang, Hsin-Ching Sung, Shu-Yuan Hsu, Yu-Hsiang Lin, Pei-Shan Yang, Chien-Lun Chen, Tsui-Hsia Feng, and Horng-Heng Juang
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Bladder ,GDF15 ,CAPE ,AMPK ,MAPK ,NDRG1 ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
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.
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- 2022
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4. Anterior fibromuscular stroma: The possible role for transient incontinence after endoscopic enucleation of prostate
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Yu-Hsiang Lin, Ke-Hung Tsui, and Horng-Heng Juang
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Diseases of the genitourinary system. Urology ,RC870-923 - Published
- 2023
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5. Comparative Analysis of Surgical Outcomes of Flexible Ureteroscopy and Da Vinci Robotic Surgery in Community Patients with Renal Pelvic Stones Larger than 2 cm
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Yu-Ju Yeh, Shu-Chuan Weng, Yu-Hsiang Lin, Chien-Lun Chen, Shu-Han Tsao, Han-Yu Tsai, Horng-Heng Juang, Phei-Lang Chang, and Chen-Pang Hou
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stones ,RIRS ,RAPL ,robotic ,ureteroscopy ,Medicine (General) ,R5-920 - Abstract
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.
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- 2023
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6. Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells
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Kang-Shuo Chang, Syue-Ting Chen, Hsin-Ching Sung, Shu-Yuan Hsu, Wei-Yin Lin, Chen-Pang Hou, Yu-Hsiang Lin, Tsui-Hsia Feng, Ke-Hung Tsui, and Horng-Heng Juang
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prostate ,androgen receptor ,ARv7 ,MALT1 ,PSA ,NDRG1 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
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.
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- 2023
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7. Simple and Convenient Method for Assessing the Severity of Bleeding during Endoscopic Prostate Surgery and the Relationships between Its Corresponding Surgical Outcomes
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Shu-Chuan Weng, Shu-Han Tsao, Han-Yu Tsai, Horng-Heng Juang, Yu-Hsiang Lin, Phei-Lang Chang, Chien-Lun Chen, and Chen-Pang Hou
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prostate ,endoscopic ,thulium laser ,enucleation ,bleeding ,hematuria ,Medicine (General) ,R5-920 - Abstract
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.
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- 2023
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8. Prostate-Specific Antigen Velocity Predicts Surgical Outcome of Thulium Laser Enucleation of the Prostate
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Po-You Chen, Shao-Ming Chen, Horng-Heng Juang, Chen-Pang Hou, Yu-Hsiang Lin, Pei-Shan Yang, Chien-Lun Chen, Phei-Lang Chang, Kuo-Yen Lin, and Ke-Hung Tsui
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prostatic hyperplasia ,laser ,prostate-specific antigen velocity ,quality of life ,outcome ,Medicine (General) ,R5-920 - Abstract
Background: We determined the effect of prostate-specific antigen velocity (PSAV) on the surgical outcome of thulium laser enucleation of the prostate (ThuLEP) in patients with benign prostatic hyperplasia (BPH).Methods: A retrospective review was performed of prospectively collected data of patients with BPH who underwent ThuLEP at any time from 2017 to 2019. Patients who had undergone BPH surgery or had prostate cancer previously were excluded, and patients with prostate-specific antigen (PSA) > 4 ng/ml were examined through transrectal ultrasound-guided prostate biopsy to rule out prostatic malignancy. Furthermore, patients were excluded if prostatic malignancy was diagnosed during postsurgery follow-up.Results: The PSA level, International Prostate Symptom Score (IPSS), and quality of life (QoL) of 27 male patients at 3 and 15 months postsurgery differed significantly from those at presurgery; the maximum flow rate (Qmax) and postvoid residual (PVR) significantly differed between 3 months postsurgery and presurgery; and 22 and 5 patients had good to excellent and fair to poor outcomes, respectively, at 15 months postsurgery. Patients were divided into two groups (fair and poor vs. good and excellent outcomes at 15 months postsurgery), which significantly differed with respect to PSAV at 3 months postsurgery (P = 0.04), IPSS presurgery (P < 0.02), surgical length (P = 0.01), and hospitalization duration (P = 0.04). In a receiver operating characteristic (ROC) analysis, the optimal cutoff value of PSAV of −0.52 ng/ml characterized effectiveness at 15 months after ThuLEP, and the area under the curve (AUC), sensitivity, and specificity were 0.82 (P < 0.02), 0.80, and 0.82, respectively. For PSAV < -0.52 and ≥-0.52 ng/ml, the percentages of reduction for IPSS, QoL, Qmax, and PVR were −78.6 and −71.4%, −33.3 and 0.0%, 94.4 and 40.0%, and −85.1 and −38.7%, respectively.Conclusions: Postsurgical PSAV was positively correlated with surgical success, and the PSAV cutoff was −0.52 ng/ml. PSAV can, thus, be used to guide the postsurgical follow-up treatment at 3 months after BPH surgery.
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- 2022
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9. Antioxidation and Antiapoptosis Characteristics of Heme Oxygenase-1 Enhance Tumorigenesis of Human Prostate Carcinoma Cells
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Kun-Chun Chiang, Ke-Hung Tsui, Yu-Hsiang Lin, Chen-Pang Hou, Kang-Shuo Chang, Hsin-Han Tsai, Yi-Syuan Shin, Chiu-Chun Chen, Tsui-Hsia Feng, and Horng-Heng Juang
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Heme oxygenase-1 (HO-1) has antiinflammatory and antioxidant properties and is deemed as a tissue protector. However, effects of HO-1 in prostate cancer remain in controversy. We evaluated the role of HO-1 in prostate carcinoma in vitro and in vivo.Overexpression of HO-1 did not affect prostate cell proliferation in the normal condition but enhanced cell proliferation under serum starvation. HO-1 overexpression enhanced cell invasion of PC-3 cells through epithelial–mesenchymal transition (EMT) induction, which was supported by increased Slug, N-cadherin, and vimentin expressions. In the xenograft animal study, HO-1 overexpression enhanced PC-3 cell tumor growth in vivo. HO-1 attenuated reactive oxygen species induced by H2O2 or pyocyanin treatment in PC-3 and DU145 cells. HO-1 further reduced PC-3 and DU145 cell apoptosis induced by H2O2 or serum starvation. Our results suggested that HO-1 was able to increase prostate carcinoma cell invasion in vitro and tumor growth in vivo. The EMT induction and antioxidant and antiapoptotic effects of HO-1 in the prostate carcinoma cells may be responsible for these findings.
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- 2020
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10. Clinical Outcome of Endoscopic Enucleation of the Prostate Compared With Robotic-Assisted Simple Prostatectomy for Prostates Larger Than 80 cm in Aging Male
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Chen-Pang Hou, Yu-Hsiang Lin, Pei-Shan Yang, Phei-Lang Chang, Chien-lun Chen, Kuo-Yen Lin, Horng-Heng Juang, Shu-Chuan Weng, and Ke-Hung Tsui
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Medicine - Abstract
This study investigated and compared the surgical outcomes of using endoscopic enucleation (thulium: YAG laser and bipolar plasma; ThuLEP) with robotic-assisted simple prostatectomy (RASP) in the treatment of prostates larger than 80 cm 3 . Records were obtained for the period from January 2014 to December 2020 for selected patients with BPO who underwent RASP, ThuLEP, or bipolar transurethral enucleation of the prostate (B-TUEP). Patients were excluded if they had active malignant disease, neurogenic bladder, lower urinary tract syndrome for reasons other than BPO, and a history of prostate surgery. Data of 396 patients who underwent B-TUEP, ThuLEP, and RASP were examined. A total of 112 patients met the including criteria, 85 of whom (B-TUEP: 29; ThuLEP: 41; RASP: 15) completed the final visit. The mean operation time and duration of postoperative hospital stays in the RASP group were significantly longer than those of the B-TUEP and ThuLEP groups. Only 1 patient in the RASP group required blood transfusion. The RASP group was superior to the other groups in voiding improvement including Qmax and IPSS voiding score. The pain score of the ThuLEP group after surgery was significantly lower than that of the other two groups during hospitalization, whereas the QoL scores were identical between the three groups at 2 weeks, 3 months, and 6 months post operation. The rates of returning to ER within the first postoperative month did not differ significantly between the three groups, and all the reasons for return involved minor complications that required no additional invasive treatment. These three surgical methods (B-TUEP, ThuLEP, and RASP) are all effective and safe for treating prostates larger than 80 cm3, with each having its particular advantages. B-TUEP requires the shortest operation time, ThuLEP causes the lowest postoperative pain, and RASP results in superior voiding function improvement.
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- 2021
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11. Endoscopic Enucleation of Prostate Could Increase Testosterone Levels in Hypotestosteronemic Patients with Bladder Outlet Obstruction
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Yun-Ren Li, Shu-Han Tsao, Chien-Lun Chen, Chen-Pang Hou, Ke-Hung Tsui, Horng-Heng Juang, and Yu-Hsiang Lin
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benign prostatic hyperplasia ,secondary hypogonadism ,testosterone ,circadian rhythm ,BipolEP ,ThuLEP ,Medicine - Abstract
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 (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.
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- 2022
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12. The Clinical Experiences of Urine Metabolomics of Genitourinary Urothelial Cancer in a Tertiary Hospital in Taiwan
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Horng-Heng Juang, Shao-Ming Chen, Gigin Lin, Meng-Han Chiang, Chen-Pang Hou, Yu-Hsiang Lin, Pei-Shan Yang, Phei-Lang Chang, Chien-lun Chen, Kuo-Yen Lin, and Ke-Hung Tsui
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genitourinary urothelial cancer ,urine metabolomics ,bladder ,urothelium ,neoplasia ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Few studies have addressed the impact of diagnostic urine metabolites and the clinical outcomes associated with genitourinary urothelial (GU) cancer to date. Furthermore, longitudinal analysis of the dynamics of urine metabolites contributing to the detection of GU cancer has not yet been fully investigated; therefore, the discovery of novel diagnostic urine biomarkers is of enormous interest. We explored the correlation of the urine metabolomic profiles to GU cancers. The aqueous metabolites of the GU cancer and the control were also identified and analyzed through high-resolution1H nuclear magnetic resonance (NMR) spectroscopy. Compared with the control, the urine metabolites of the tumor were studied in relation to changes over time in a linear mixed model for repeated measures. The urine metabolites of sixty-three (44 male and 19 female) patients with GU cancers were systemically analyzed. The urine metabolite profile in GU cancer was significantly higher than those in the control group (p
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- 2021
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13. WNT1 Inducible Signaling Pathway Protein 1 Is a Stroma-Specific Secreting Protein Inducing a Fibroblast Contraction and Carcinoma Cell Growth in the Human Prostate
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Kang-Shuo Chang, Syue-Ting Chen, Hsin-Ching Sung, Shu-Yuan Hsu, Wei-Yin Lin, Chen-Pang Hou, Yu-Hsiang Lin, Tsui-Hsia Feng, Ke-Hung Tsui, and Horng-Heng Juang
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prostate ,WISP1 ,stroma ,contraction ,proliferation ,tumorigenesis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
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.
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- 2022
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14. Metallothionein 2A with Antioxidant and Antitumor Activity Is Upregulated by Caffeic Acid Phenethyl Ester in Human Bladder Carcinoma Cells
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Hsin-Ching Sung, Kang-Shuo Chang, Syue-Ting Chen, Shu-Yuan Hsu, Yu-Hsiang Lin, Chen-Pang Hou, Tsui-Hsia Feng, Ke-Hung Tsui, and Horng-Heng Juang
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antioxidation ,metallothionein 2A ,HO-1 ,bladder cancer ,apoptosis ,ROS ,Therapeutics. Pharmacology ,RM1-950 - Abstract
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.
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- 2022
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15. The Upregulation of Caffeic Acid Phenethyl Ester on Growth Differentiation Factor 15 Inhibits Transforming Growth Factor β/Smad Signaling in Bladder Carcinoma Cells
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Chen-Pang Hou, Ke-Hung Tsui, Syue-Ting Chen, Kang-Shuo Chang, Hsin-Ching Sung, Shu-Yuan Hsu, Yu-Hsiang Lin, Tsui-Hsia Feng, and Horng-Heng Juang
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bladder ,TGFβ ,Smad ,CAPE ,GDF15 ,maspin ,Biology (General) ,QH301-705.5 - Abstract
Growth differentiation factor 15 (GDF15) is known as a TGFβ-like cytokine acting on the TGFβ 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 TGFβ/Smads signaling in the human bladder carcinoma cells remain unexplored. Results revealed that TGFβ 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 TGFβ/Smad pathways. Moreover, TGFβ blocked the CAPE-inducing expressions of GDF15, maspin, and NDRG1. Pretreatment of TGF receptor kinase inhibitor not only blocked the activation of TGFβ but also attenuated the activation of GDF15 on the expressions of maspin and NDRG1. The CAPE treatment attenuated the activation of TGFβ on cell proliferation and invasion. Our findings indicate that TGFβ downregulated the expressions of GDF15, maspin, and NDRG1 via TGFβ/Smad signaling. Whereas, CAPE acts as an antagonist on TGFβ/Smad signaling to block the effect of TGFβ on the GDF15 expression and cell proliferation and invasion in bladder carcinoma cells.
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- 2022
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16. Surgery for Xanthogranulomatous Pyelonephritis: A Comparison of Midline Transperitoneal and Flank Retroperitoneal Laparotomy Approaches to Nephrectomy
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Shu-Han Tsao, Chien-Ho Wang, Horng-Heng Juang, Yu-Hsiang Lin, Pei-Shan Yang, Phei-Lang Chang, Chien-Lun Chen, and Chen-Pang Hou
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xanthogranulomatous pyelonephritis ,XGP ,nephrectomy ,transperitoneal ,retroperitoneal ,Medicine - Abstract
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.
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- 2022
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17. 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
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Kang-Shuo Chang, Ke-Hung Tsui, Shu-Yuan Hsu, Hsin-Ching Sung, Yu-Hsiang Lin, Chen-Pang Hou, Pei-Shan Yang, Chien-Lun Chen, Tsui-Hsia Feng, and Horng-Heng Juang
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MALT1 ,CAPE ,prostate cancer ,AR ,NF-κB ,p53 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
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.
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- 2022
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18. Transurethral resection of the prostate provides more favorable clinical outcomes compared with conservative medical treatment in patients with urinary retention caused by benign prostatic obstruction
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Yu-Hsiang Lin, Chen-Pang Hou, Tien-Hsing Chen, Horng-Heng Juang, Phei-Lang Chang, Pei-Shan Yang, Chien-lun Chen, and Ke-Hung Tsui
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Alfa-blocker ,Benign prostate hyperplasia ,Urine retention ,Outcome ,Prostatectomy ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background To evaluate the long-term surgical outcomes of patients with urinary retention (UR) caused by a benign prostatic obstruction (BPO) who underwent transurethral resection of the prostate (TURP), and compare their outcomes with those of patients who received medication without surgical intervention. Methods This retrospective cohort study analyzed claims data collected during the period of 1997–2012 from Taiwan’s National Health Insurance Research Database. We examined geriatric adverse events among patients who had received a diagnosis of symptomatic benign prostatic hyperplasia and whom experienced UR, and compared those who received TURP and medication only. Primary outcomes included urinary tract infection (UTI), UR, inguinal hernia, hemorrhoids, stroke, acute myocardial infarction, and bony fracture. We excluded patients who had concomitant prostate cancer, bladder cancer, or a long-term urinary catheter indwelling, as well as those who did not receive α-blocker medication regularly. Those aged 90 years were also excluded. The enrolled patients were categorized into TURP (n = 1218) and medication only (n = 795) groups. After 1:1 propensity score matching, we recorded and compared patients’ characteristics, postoperative clinical outcomes, and geriatric adverse events. Results The TURP cohort had a lower incidence of UTI and UR during the postoperative follow-up period from 2 months to 3 years than did the medication only group (20.7% vs. 28.9% and 12.5% vs. 27.6%, respectively, p
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- 2018
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19. Mucosa-Associated Lymphoid Tissue 1 Is an Oncogene Inducing Cell Proliferation, Invasion, and Tumor Growth via the Upregulation of NF-κB Activity in Human Prostate Carcinoma Cells
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Ke-Hung Tsui, Kang-Shuo Chang, Hsin-Ching Sung, Shu-Yuan Hsu, Yu-Hsiang Lin, Chen-Pang Hou, Pei-Shan Yang, Chien-Lun Chen, Tsui-Hsia Feng, and Horng-Heng Juang
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prostate ,MALT1 ,NF-κB ,CXCL5 ,IL-6 ,proliferation ,Biology (General) ,QH301-705.5 - Abstract
Prostate cancer is one of the most common seen malignancies and the leading cause of cancer-related death among men. Given the importance of early diagnosis and treatment, it is worth to identify a potential novel therapeutic target for prostate cancer. Mucosa-associated lymphoid tissue 1 (MALT1) is a novel gene involved in nuclear factor κB (NF-κB) signal transduction by acting as an adaptor protein and paracaspase, with an essential role in inflammation and tumorigenesis in many cancers. This study investigated the functions and the potential regulatory mechanisms of MALT1 in the human prostate cancer cells. We found that MALT1 is abundant in prostate cancer tissues. MALT1 facilitated NF-κB subunits (p50 and p65) nuclear translocation to induce gene expression of interleukin 6 (IL-6) and C-X-C motif chemokine 5 (CXCL5) in prostate carcinoma cells. MALT1 promoted cell proliferation, invasion, and tumor growth in vitro and in vivo. MALT1 enhanced NF-κB activity in prostate carcinoma cells; moreover, NF-κB induced MALT1 expression determined by reporter and immunoblot assays, implying there is a positive feedback loop between MALT1 and NF-κB. In conclusion, MALT1 is a NF-κB-induced oncogene in the human prostate carcinoma cells.
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- 2021
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20. The Correlation between Chitin and Acidic Mammalian Chitinase in Animal Models of Allergic Asthma
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Chia-Rui Shen, Horng-Heng Juang, Hui-Shan Chen, Ching-Jen Yang, Chia-Jen Wu, Meng-Hua Lee, Yih-Shiou Hwang, Ming-Ling Kuo, Ya-Shan Chen, Jeen-Kuan Chen, and Chao-Lin Liu
- Subjects
allergy ,asthma ,chitinase ,promoter ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase) may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA)-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression.
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- 2015
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21. Human Heme Oxygenase-1 Induced by Interleukin-6 via JAK/STAT3 Pathways Is a Tumor Suppressor Gene in Hepatoma Cells
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Kun-Chun Chiang, Kang-Shuo Chang, Shu-Yuan Hsu, Hsin-Ching Sung, Tsui-Hsia Feng, Mei Chao, and Horng-Heng Juang
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ho-1 ,il-6 ,ros ,stat3 ,jak ,luteolin ,ag490 ,hepg2 ,hep3b ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Heme oxygenase-1 (HO-1) has several important roles in hepatocytes in terms of anti-inflammation, anti-apoptosis, and antioxidant properties. Interleukin-6 (IL-6) is a pleiotropic cytokine associated with liver regeneration and protection against injury. The aim of this study was to determine the potential crosstalk between HO-1 and IL-6, and to elucidate the signaling pathways involved in the induction of HO-1 by IL-6 in human hepatoma cells. Ectopic overexpression of HO-1 not only attenuated cell proliferation in vitro and in vivo, but also blocked the reactive oxygen species (ROS) induced by H2O2 and the pyocyanin in HepG2 or Hep3B cells. IL-6 expression was negatively regulated by HO-1, while IL-6 induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and HO-1 gene expression in HepG2 cells. The co-transfected HO-1 reporter vector and a protein inhibitor of the activated STAT3 (PIAS3) expression vector blocked the IL-6-induced HO-1 reporter activity. Both interferon γ and interleukin-1β treatments induced STAT1 but not STAT3 phosphorylation, which had no effects on the HO-1 expression. Treatments of AG490 and luteolin blocked the JAK/STAT3 signaling pathways which attenuated IL-6 activation on the HO-1 expression. Our results indicated that HO-1 is the antitumor gene induced by IL-6 through the IL-6/JAK/STAT3 pathways; moreover, a feedback circuit may exist between IL-6 and HO-1 in hepatoma cells.
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- 2020
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22. Migration and Invasion Enhancer 1 Is an NF-ĸB-Inducing Gene Enhancing the Cell Proliferation and Invasion Ability of Human Prostate Carcinoma Cells In Vitro and In Vivo
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Kang-Shuo Chang, Ke-Hung Tsui, Yu-Hsiang Lin, Chen-Pang Hou, Tsui-Hsia Feng, and Horng-Heng Juang
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prostate ,mien1 ,akt ,nf-b ,il-6 ,ndrg1 ,tumorigenesis ,jsh-23 ,mk2206 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. We determined the expression, biological functions, and regulatory mechanisms of MIEN1 in the prostate. The results of immunohistochemical analysis indicated that MIEN1 was expressed specifically in epithelial cells and significantly higher in adenocarcinoma as compared to in normal tissues. MIEN1 enhanced in vitro cell proliferation, invasion, and in vivo tumorigenesis. Meanwhile, MIEN1 attenuated cisplatin-induced apoptosis in PC-3 cells. Overexpression of NF-ĸB-inducing kinase (NIK) enhanced MIEN1 expression, while overexpression of NF-ĸB inhibitor α (IĸBα) blocked MIEN1 expression in PC-3 cells. In prostate carcinoma cells, MIEN1 provoked Akt phosphorylation; moreover, MIEN1 downregulated N-myc downstream regulated 1 (NDRG1) but upregulated interleukin-6 (IL-6) gene expression. MK2206, an Akt inhibitor, impeded the modulation of MIEN1 on NDRG1 and IL-6 expressions. Our studies suggest that MIEN1 is an NF-ĸB downstream oncogene in the human prostate. Accordingly, the modulation of Akt signaling in the gene expressions of NDRG1 and IL-6 may account for the functions of MIEN1 in cell proliferation, invasion, and tumorigenesis in prostate carcinoma cells.
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- 2019
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23. Transgelin, a p53 and PTEN-Upregulated Gene, Inhibits the Cell Proliferation and Invasion of Human Bladder Carcinoma Cells In Vitro and In Vivo
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Ke-Hung Tsui, Yu-Hsiang Lin, Kang-Shuo Chang, Chen-Pang Hou, Pin-Jung Chen, Tsui-Hsia Feng, and Horng-Heng Juang
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bladder ,tagln ,f-actin ,pten ,p53 ,tumorigenesis ,proliferation ,invasion ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Transgelin (TAGLN/SM22-α) is a regulator of the actin cytoskeleton, affecting the survival, migration, and apoptosis of various cancer cells divergently; however, the roles of TAGLN in bladder carcinoma cells remain inconclusive. We compared expressions of TAGLN in human bladder carcinoma cells to the normal human bladder tissues to determine the potential biological functions and regulatory mechanisms of TAGLN in bladder carcinoma cells. Results of RT-qPCR and immunoblot assays indicated that TAGLN expressions were higher in bladder smooth muscle cells, fibroblast cells, and normal epithelial cells than in carcinoma cells (RT-4, HT1376, TSGH-8301, and T24) in vitro. Besides, the results of RT-qPCR revealed that TAGLN expressions were higher in normal tissues than the paired tumor tissues. In vitro, TAGLN knockdown enhanced cell proliferation and invasion, while overexpression of TAGLN had the inverse effects in bladder carcinoma cells. Meanwhile, ectopic overexpression of TAGLN attenuated tumorigenesis in vivo. Immunofluorescence and immunoblot assays showed that TAGLN was predominantly in the cytosol and colocalized with F-actin. Ectopic overexpression of either p53 or PTEN induced TAGLN expression, while p53 knockdown downregulated TAGLN expression in bladder carcinoma cells. Our results indicate that TAGLN is a p53 and PTEN-upregulated gene, expressing higher levels in normal bladder epithelial cells than carcinoma cells. Further, TAGLN inhibited cell proliferation and invasion in vitro and blocked tumorigenesis in vivo. Collectively, it can be concluded that TAGLN is an antitumor gene in the human bladder.
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- 2019
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24. Structural Pattern Differences in Unbranched Rod-Like RNA of Hepatitis Delta Virus Affect RNA Editing
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Chao-Wei Hsu, Horng-Heng Juang, Chien-Yi Kuo, Hsin-Pai Li, Shan-Bei Iang, Siao-Han Lin, Chau-Ting Yeh, and Mei Chao
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hepatitis delta virus ,rna editing ,delta antigen ,adar1 ,Microbiology ,QR1-502 - Abstract
Hepatitis delta virus (HDV) RNA forms an unbranched rod-like structure and complexes with the delta antigen (HDAg). Host ADAR1-catalyzed RNA editing at the amber/W site of the small HDAg leads to the production of the large HDAg, which inhibits replication and is required for virion assembly. For HDV genotype 1, amber/W editing is controlled by HDAg and the RNA structure immediate vicinity and downstream of the editing site. Here, the effects of 20 mutants carrying an increased length of consecutive base-pairing at various sites in HDV RNA on amber/W site editing were examined. All nine mutants carrying genomic regions that formed up to 15 consecutive base pairs, which is also the maximum length observed in 41 naturally occurring HDV genomes, showed normal editing rate. However, mutants carrying a 16 or 17 consecutive base-paired antigenomic segment located as far as 114 nt upstream could increase editing efficiency, possibly by interfering with HDAg binding. These data show for the first time that extended base-pairing upstream of the amber/W site could increase HDV RNA editing efficiency. Furthermore, it appears that the naturally occurring HDV RNA structures have been selected for suboptimal amber/W RNA editing, which favors the HDV replication cycle.
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- 2019
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25. Association between Bladder Outlet Obstruction and Bladder Cancer in Patients with Aging Male
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Yu-Hsiang Lin, Chen-Pang Hou, Horng-Heng Juang, Phei-Lang Chang, Tien-Hsing Chen, Chien-Lun Chen, and Ke-Hung Tsui
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benign prostate hyperplasia ,bladder outlet obstruction ,diabetes mellitus ,prostatectomy ,urinary tract infection ,lower urinary tract symptoms ,Medicine - Abstract
The associations between the treatment outcomes of benign prostatic hyperplasia/benign prostatic obstruction and lifelong health status, including urologic cancer incidence as well as geriatric adverse events (AEs), are unknown. This retrospective cohort study analyzed claims data collected during the period of 1997–2012 from Taiwan’s Longitudinal Health Insurance Database 2000. Patients who received transurethral resection of the prostate (TURP) were prioritized, and the remaining patients who were prescribed alpha-blockers were, subsequently, identified. Patients in the TURP and medication-only groups were further divided into two groups, according to the presence or absence of AEs during the first six-month follow-up. Outcomes of primary interest were all-cause mortality, occurrence of prostate cancer, transurethral resection of the bladder tumor, and radical cystectomy for bladder cancer. Compared with patients in the AE-free TURP group, those in the TURP with AEs had a higher risk of lifelong bladder cancer (subdistribution hazard ratio: 2.3, 95% confidence interval (CI): 1.56–3.39), whereas the risk of prostate cancer was comparable between the two groups (SHR: 1.2, 95% CI: 0.83–1.74). In the medication cohorts, patients undergoing alpha-blocker treatment who had AEs had a higher risk of all-cause mortality (hazard ratio: 1.63, 95% CI: 1.49–1.78) and a higher risk of lifelong bladder cancer (SHR: 2.72, 95% CI: 1.99–3.71) when compared with those without AE. Our study reveals that unfavorable treatment outcomes of benign prostate hyperplasia, whether caused by medication or surgical treatment, are associated with a higher incidence of bladder cancer. Unfavorable outcomes of surgical treatment are associated with higher risk of geriatric AEs, and unfavorable outcomes of medication treatment are associated with a higher risk of all-cause mortality.
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- 2019
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26. Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells
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Ke-Hung Tsui, Chen-Pang Hou, Kang-Shuo Chang, Yu-Hsiang Lin, Tsui-Hsia Feng, Chiu-Chun Chen, Yi-Syuan Shin, and Horng-Heng Juang
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metallothionein 3 ,bladder ,tumorigenesis ,NDRG1 ,MASPIN ,hypoxia ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Metallothioneins have been viewed as modulators in a number of biological regulations regarding cancerous development; however, the function of metallothionein 3 (MT3) in bladder cancer is unexplored. We determined the regulatory mechanisms and potential function of MT3 in bladder carcinoma cells. Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-qPCR) assays revealed that TSGH-8301 cells expressed more MT3 levels than RT-4, HT1376, and T24 cells. Immunoblot and RT-qPCR assays showed that arsenic (AS2O3) treatments enhanced the gene expression of MT3. Hypoxia induced HIF-1α, HIF-2α, and MT3 expression; furthermore, HIF-2α-knockdown attenuated hypoxic activation on MT3 expression. Ectopic overexpression of MT3 increased cell proliferation, invasion, and tumorigenesis significantly in T24 and HT1376 cells in vitro and in vivo; however, MT3-knockdown in TSGH-8301 cells had the reverse effect. Moreover, knockdown of MT3 enhanced arsenic-induced apoptosis determined by the Annexin V-FITC apoptosis assay. MT3-overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (NDRG1), N-myc downstream regulated gene 2 (NDRG2), and the mammary serine protease inhibitor (MASPIN) in HT1376 and T24 cells, whereas MT3-knockdown in TSGH-8301 cells had the opposite effect. The experiments indicated that MT3 is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of NDRG1, NDRG2, and MASPIN expressions.
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- 2019
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27. Caffeic Acid Phenethyl Ester Induces N-myc Downstream Regulated Gene 1 to Inhibit Cell Proliferation and Invasion of Human Nasopharyngeal Cancer Cells
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Kun-Chun Chiang, Shih-Wei Yang, Kai-Ping Chang, Tsui-Hsia Feng, Kang-Shuo Chang, Ke-Hung Tsui, Yi-Syuan Shin, Chiu-Chun Chen, Mei Chao, and Horng-Heng Juang
- Subjects
CAPE ,NDRG1 ,MAPK ,nasopharyngeal cancer ,STAT3 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis, is widely studied due to its anti-cancer effect. Nasopharyngeal carcinoma (NPC) is distinct from other head and neck carcinomas and has a high risk of distant metastases. N-myc downstream regulated gene 1 (NDRG1) is demonstrated as a tumor suppressor gene in several cancers. Our result showed that CAPE treatment could repress NPC cell growth, through induction of S phase cell cycle arrest, and invasion. CAPE treatment stimulated NDRG1 expression in NPC cells. NDRG1 knockdown increased NPC cell proliferation and invasion and rendered NPC cells less responsive to CAPE growth-inhibiting effect, indicating CAPE repressed NPC cell growth partly through NDRG1indcution. CAPE treatment increased phosphorylation of ERK, JNK, and p38 in a dose- and time-dependent manner. Pre-treatments by inhibitors of ERK (PD0325901), JNK (SP600125), or p38 (SB201290), respectively, all could partly inhibit the CAPE effect on NDRG1 induction in NPC cells. Further, STAT3 activity was also repressed by CAPE in NPC cells. In summary, CAPE attenuates NPC cell proliferation and invasion by upregulating NDRG1 expression via MAPK pathway and by inhibiting phosphorylation of STAT3. Considering the poor prognosis of NPC patients with metastasis, CAPE could be a promising agent against NPC.
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- 2018
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28. Topoisomerase inhibitors modulate gene expression of B-cell translocation gene 2 and prostate specific antigen in prostate carcinoma cells.
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Kun-Chun Chiang, Ke-Hung Tsui, Li-Chuan Chung, Chun-Nan Yeh, Phei-Lang Chang, Wen-Tsung Chen, and Horng-Heng Juang
- Subjects
Medicine ,Science - Abstract
Camptothecin (CPT) and doxorubicin (DOX) have been demonstrated to have potent anti-tumor activity. The B-cell translocation gene 2 (BTG2) is involved in the regulation of cell cycle progression. We evaluated the molecular mechanisms of CPT and DOX on cell proliferation and the expressions of BTG2 and prostate specific antigen (PSA) in prostate carcinoma cells. Our results indicated that CPT or DOX treatments induced Go/G1 cell cycle arrest in LNCaP cells and apoptosis at higher dosage. Immunoblot and transient gene expression assay indicated that CPT or DOX treatments induced p53 and BTG2 gene expression, with the later effect dependent on the p53 response element within BTG2 promoter area since mutation of the p53 response element from GGGAAAGTCC to GGAGTCC or from GGCAGAGCCC to GGCACC by site-directed mutagenesis abolished the stimulation of CPT or DOX on the BTG2 promoter activity, which is also supported by our results that cotreatments of pifithrin-α, an inhibitor of p53 dependent transcriptional activation, blocked the induction of CPT or DOX on BTG2 gene expression. CPT or DOX also downregulated the protein expressions of androgen receptor (AR) and PSA. Transient gene expression assays suggested that CPT or DOX's attenuation of PSA promoter activity is dependent on both the androgen and p53 response elements within of the PSA promoter. Our results indicated that CPT and DOX attenuate cell proliferation via upregulation of BTG2 gene expression through the p53-dependent pathway. The CPT and DOX block the PSA gene expression by upregulation of p53 activity and downregulation of androgen receptor activity.
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- 2014
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29. Celastrol blocks interleukin-6 gene expression via downregulation of NF-κB in prostate carcinoma cells.
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Kun-Chun Chiang, Ke-Hung Tsui, Li-Chuan Chung, Chun-Nan Yeh, Wen-Tsung Chen, Phei-Lang Chang, and Horng-Heng Juang
- Subjects
Medicine ,Science - Abstract
Interleukin-6 (IL-6), a multifunctional cytokine, contributes to proliferation or differentiation of prostate carcinoma cells in a highly cell type-specific manner. Celastrol (3-hydroxy-24-nor-2oxo-1(10),3,5,7-friedelatetrane-29-oic acid), also named as tripterine, is extracted from root of Chinese traditional herb Tripterygiumwilfordii Hook f with potent anti-inflammatory and anti-cancer activities. In this study, we evaluated the molecular mechanisms of celastrol on cell proliferation and IL-6 gene expression in prostate carcinoma cells. 3H-thymidine incorporation and flow cytometric analysis indicated that celastrol treatments arrested the cell cycle at the G0/G1 phase, thus attenuating cell proliferation in prostate carcinoma PC-3 cells; moreover, celastrol induced cell apoptosis at higher dosage. Knockdown of IL-6 attenuated the anti-proliferative effect of celastrol on PC-3 cells. Results from ELISA and 5'-deletion transient gene expression assays indicated that celastrol treatment decreased IL-6 secretion and gene expression, and this effect is dependent on the NF-κB response element within IL-6 promoter area since mutation of the NF-κB response element from AAATGTCCCATTTTCCC to AAATGTTACATTTTCCC by site-directed mutagenesis abolished the inhibition of celastrol on the IL-6 promoter activity. Celastrol also attenuated the activation of PMA and TNFα on the gene expression and secretion of IL-6 in PC-3 cells. Immunoblot assays revealed that celastrol treatment downregulated the expressions of IKKα, p50 and p65, supporting the 5'-deletion transient gene expression assay result that celastrol blocked IL-6 expression through the NF-κB pathway in PC-3 cells. For the first time, our results concluded that celastrol attenuates PC-3 cell proliferation via downregulation of IL-6 gene expression through the NF-κB-dependent pathway.
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- 2014
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30. Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma.
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Chun-Nan Yeh, Kun-Chun Chiang, Horng-Heng Juang, Jong-Hwei S Pang, Chung-Shan Yu, Kun-Ju Lin, Ta-Sen Yeh, and Yi-Yin Jan
- Subjects
Medicine ,Science - Abstract
Cholangiocarcinoma (CCA), a lethal disease, affects many thousands worldwide yearly. Surgical resection provides the best chance for a cure; however, only one-third of CCA patients present with a resectable tumour at the time of diagnosis. Currently, no effective chemotherapy is available for advanced CCA. Cyclooxygenase-2 (COX-2) is a potential oncogene expressing in human CCA tissues and represents a candidate target for treatment; however, COX-2 inhibitors increase the risk of negative cardiovascular events as application for chemoprevention aim. Here, we re-evaluated the effectiveness and safety of celecoxib, one widely used COX-2 inhibitor, in treating CCA. We demonstrated that celecoxib exhibited an anti-proliferative effect on CGCCA cells via cell cycle arrest at G2 phase and apoptosis induction. Treatment for 5 weeks high dose celecoxib (160 mg/kg) significantly repressed thioacetamide-induced CCA tumour growth in rats as monitored by animal positron emission tomography through apoptosis induction. No obviously observable side effects were noted during the therapeutic period. As retrospectively reviewing 78 intrahepatic mass-forming CCA patients, their survival was strongly and negatively associated with a positive resection margin and high COX-2 expression. Based on our result, we concluded that short-term high dose celecoxib may be a promising therapeutic regimen for CCA. Yet its clinical application still needs more studies to prove its safety.
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- 2013
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31. The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo
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Jehn-Chuan Lee, Kun-Chun Chiang, Tsui-Hsia Feng, Yu-Jen Chen, Sung-Ting Chuang, Ke-Hung Tsui, Li-Chuan Chung, and Horng-Heng Juang
- Subjects
NDRG1 ,NDRG3 ,Maspin ,DFO ,deferasirox ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Oral squamous cell carcinoma (OSCC) is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG) family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin) gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment.
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- 2016
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32. 25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)2D3
- Author
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Kun-Chun Chiang, Chun-Nan Yeh, Cheng-Cheng Huang, Ta-Sen Yeh, Jong-Hwei S. Pang, Jun-Te Hsu, Li-Wei Chen, Sheng-Fong Kuo, Atsushi Kittaka, Tai C. Chen, and Horng-Heng Juang
- Subjects
cholangiocarcinoma ,25(OH)D ,CYP27B1 ,1α-OHase ,vitamin D ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)2D3, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)2D3, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)2D3 has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)2D3 concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 μg/kg or 20 μg/kg, significantly inhibited SNU308 cells’ growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)2D3 and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA.
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- 2016
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33. The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential
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Kun-Chun Chiang, Ta-Sen Yeh, Shin-Cheh Chen, Jong-Hwei S. Pang, Chun-Nan Yeh, Jun-Te Hsu, Li-Wei Chen, Sheng-Fong Kuo, Masashi Takano, Atsushi Kittaka, Tai C. Chen, Chi-Chin Sun, and Horng-Heng Juang
- Subjects
triple negative breast cancer ,TNBC ,MART-10 ,EMT ,vitamin D ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3), the newly-synthesized 1α,25(OH)2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)2D3 induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin) and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition) process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH)2D3 and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9) activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH)2D3 and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC.
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- 2016
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34. The role of prostatic urethral angle and intravesical prostatic protrusion on surgical capsule calculi formation in the prostate: A retrospective study.
- Author
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Chen, Jonathan Y. J., Han-Yu Tsai, Chen-Pang Hou, Shu-Han Tsao, Yu-Ting Chen, Horng-Heng Juang, and Yu-Hsiang Lin
- Abstract
Purpose: To investigate the relationship between prostatic urethral angle (PUA) and the development of surgical capsule calculi (SCC) within the prostate, and to examine the presence and impact of intravesical prostatic protrusion (IPP). Materials and Methods: A retrospective analysis was conducted on 90 patients who underwent radical prostatectomy, with preoperative assessments using both transrectal ultrasound of the prostate (TRUS) and magnetic resonance imaging. Patients were divided into groups with and without SCC and further categorized into type 1 and type 2 stones based on the location and severity of the calculi. Statistical analysis included chi-square and independent sample t-tests, with p<0.05 considered significant. Results: Of the patients, 82.2% were diagnosed with SCC. No significant difference in PUA was found between patients with and without SCC. However, a notable disparity in IPP presence was observed, suggesting an inverse correlation with SCC development. Additionally, no significant differences were identified when comparing the two types of SCC based on PUA and IPP measurements. Conclusions: The presence of IPP exhibited an inverse relationship with SCC, suggesting diminished urine flow pressure over the prostatic urethra may reduce the likelihood of SCC formation. However, no direct association between PUA and the presence or severity of SCC was identified. These findings highlight the complexity of factors contributing to prostatic calculi development and the potential role of IPP in this context. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Ultrasound-guided extracorporeal shock wave lithotripsy with minimal x-ray exposure prevented genitourinary tract injury patients with urolithiasis in Taiwan.
- Author
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Yi-Te Chiang, Shao-Ming Chen, Hsuan-Mao Tsui, Horng-Heng Juang, Chia-Wei Lin, Meng-Han Chiang, Chia-Hung Liu, Su-Wei Hu, Wei-Tang Kao, Kuan-Chou Chen, Kai-Yi Tzou, Chia-Chang Wu, Wen-Ling Wu, and Ke-Hung Tsui
- Abstract
Background: This study investigated the use of ultrasound-guided extracorporeal shock wave lithotripsy (ESWL) to break stones in the genitourinary tract and prevent genitourinary injury. Our goals were to achieve accurate focusing and minimal X-ray exposure for the benefit of the patients. Methods: The LiteMed LM-9200 lithotripter with ultrasonography and fluoroscopy was used for two different procedures: autoaimed and autoperiodical. These procedures enabled dual focusing on stone localization and tracking. Results: Out of 108 patients who underwent autoperiodical procedures, 29 had no gross hematuria. Among the 335 patients who received autoaimed procedures, 194 had no gross hematuria. The average duration of X-ray exposure during autoperiodical and autoaimed procedures was 120 and 50 s, respectively. Conclusion: The ultrasound-guided ESWL with minimal X-ray exposure was found to be useful in treating genitourinary upper-tract urolithiasis in the autoaimed procedure. Patients who underwent the autoaimed procedure experienced less gross hematuria compared to those who underwent the autoperiodical procedure. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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36. Anterior fibromuscular stroma-preserved endoscopic enucleation of the prostate: a precision anatomical approach
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Yu-Hsiang Lin, Shin-Yuan Chang, Shu-Han Tsao, Chen-Pang Hou, Chien-Lun Chen, Wen-Chou Lin, Ke-Hung Tsui, and Horng-Heng Juang
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Urology - Abstract
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.To describe our surgical technique of anterior fibromuscular stroma (AFS)-preserved EEP for BOO.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.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.Postoperative prostate-specific antigen (PSA), testosterone, urethral stricture, and voiding status, such as incontinence, uroflow, and postvoiding residual urine were assessed.The data show that AFS-preserved EEP could achieve similar surgical outcomes as other early apical release approaches.The preserved AFS provides a nice landmark at the 12 o'clock position during EEP.
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- 2022
37. Comparison of Outcome and Quality of Life Between Thulium Laser (VelaTM XL) Enucleation of Prostate and Bipolar Transurethral Enucleation of the Prostate (B-TUEP)
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Yu-Ting Chen, Chen-Pang Hou, Horng-Heng Juang, Yu-Hsiang Lin, Pei-Shan Yang, Phei-Lang Chang, Chien-Lun Chen, Shu-Chuan Weng, and Ke-Hung Tsui
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Chemical Health and Safety ,Therapeutics and Clinical Risk Management ,Pharmacology (medical) ,General Medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Safety Research - Abstract
Yu-Ting Chen,1,* Chen-Pang Hou,1â 3,* Horng-Heng Juang,1,4 Yu-Hsiang Lin,1,2 Pei-Shan Yang,1,4 Phei-Lang Chang,1 Chien-lun Chen,1 Shu-Chuan Weng,3 Ke-Hung Tsui1,5 1Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 3Health and Management, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 4Department of Anatomy, School of Medicine, Chang Gung University, Tao-Yuan, Taipei, Taiwan; 5Department of Urology, Shuang Ho Hospital, TMU Research Center of Urology and Kidney, School of Medicine, College of Medical, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Ke-Hung Tsui, Taiwan Innovative Medical Association, Department of Urology, Shuang Ho Hospital, College of Medical, Taipei Medical University, Taipei, Taiwan, Email t2130@s.tmu.edu.tw Shu-Chuan Weng, Department of Healthcare Management, Yuanpei University of Medical Technology, Hsinchu, Taipei, Taiwan, Email scweng303@mail.ypu.edu.twBackground and Purpose: In this study, we compared patient outcomes between the 120-W thulium laser (Velaâ¢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. Patientsâ 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.Keywords: prostate, laser, prostatectomy, prostatic hyperplasia, quality
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- 2022
38. Clinical outcome of transurethral enucleation of the prostate using the 120-W thulium Laser (Vela™ XL) compared to bipolar transurethral resection of the prostate (TURP) in aging male
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Chen-Pang Hou, Yu-Hsiang Lin, Chien-Lun Chen, Phei-Lang Chang, Pei-Shan Yang, Ke-Hung Tsui, and Horng-Heng Juang
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Laser surgery ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Enucleation ,Urology ,Prostatic Hyperplasia ,Comorbidity ,urologic and male genital diseases ,Bladder outlet obstruction ,Quality of life ,Prostate ,Surveys and Questionnaires ,benign prostate hyperplasia ,medicine ,Humans ,Transurethral resection of the prostate ,Aged ,Aged, 80 and over ,business.industry ,aging ,Age Factors ,Transurethral Resection of Prostate ,Cell Biology ,Middle Aged ,Prognosis ,laser ,medicine.anatomical_structure ,Treatment Outcome ,bladder outlet obstruction ,Quality of Life ,International Prostate Symptom Score ,Prostate surgery ,business ,Research Paper - Abstract
This study compared the surgical outcomes of the 120-W Thulium laser (Vela™ XL) enucleation of the prostate and bipolar transurethral resection of the prostate (TURP) in terms of efficacy, safety, and improvements of quality of life (QoL) in patients with benign prostate hyperplasia (BPH). Records were obtained from January 2014 to September 2018 for selected patients with symptomatic BPH who underwent 120-W Thulium laser (Vela™XL) prostate enucleation and bipolar TURP in our institution. All the patients selected met the surgical criteria for TURP and had received medical treatment for at least 3 months. Patients were excluded if their ECOG performance status was >1, if they had active malignant disease, of if they had a history of prostate surgery or reconstruction surgery of the urinary system. Patients decided which treatment option would be performed. Both the procedures were conducted by a single surgeon. Clinical outcomes such as changes in the International Prostate Symptom Score (IPSS) score, urodynamic parameters, drug consumption, pain scores, and QoL were evaluated. The rate of urinary tract infection, recatheterization, additional analgesic requirement, return to the emergency department for treatment, and other surgical complications was analyzed and compared between the two cohorts. A total of 276 patients met the inclusion criteria. Among them, 141 patients received bipolar TURP, where as 135 decided to receive laser vaporesection. No significant difference was observed in age, PSA level, prostate volume, and comorbidities between the two cohorts. Pre-operative (pre-op) urodynamic parameters were also identical, except that the laser surgery group had a higher rate of admission with a urinary catheter (24.4% vs. 14.2%, p=0.044). The operating time was longer in the laser surgery group (79.3 minutes vs. 62.4 minutes, p
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- 2020
39. Antioxidation and Antiapoptosis Characteristics of Heme Oxygenase-1 Enhance Tumorigenesis of Human Prostate Carcinoma Cells
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Chen-Pang Hou, Yi-Syuan Shin, Tsui-Hsia Feng, Horng-Heng Juang, Hsin-Han Tsai, Kun-Chun Chiang, Yu-Hsiang Lin, Kang-Shuo Chang, Ke-Hung Tsui, and Chiu-Chun Chen
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0301 basic medicine ,Cancer Research ,Original article ,biology ,Cell growth ,Chemistry ,Vimentin ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease_cause ,medicine.disease ,lcsh:RC254-282 ,Heme oxygenase ,03 medical and health sciences ,Prostate cancer ,030104 developmental biology ,0302 clinical medicine ,Oncology ,DU145 ,In vivo ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,medicine ,Carcinogenesis - Abstract
Heme oxygenase-1 (HO-1) has antiinflammatory and antioxidant properties and is deemed as a tissue protector. However, effects of HO-1 in prostate cancer remain in controversy. We evaluated the role of HO-1 in prostate carcinoma in vitro and in vivo. Overexpression of HO-1 did not affect prostate cell proliferation in the normal condition but enhanced cell proliferation under serum starvation. HO-1 overexpression enhanced cell invasion of PC-3 cells through epithelial–mesenchymal transition (EMT) induction, which was supported by increased Slug, N-cadherin, and vimentin expressions. In the xenograft animal study, HO-1 overexpression enhanced PC-3 cell tumor growth in vivo. HO-1 attenuated reactive oxygen species induced by H2O2 or pyocyanin treatment in PC-3 and DU145 cells. HO-1 further reduced PC-3 and DU145 cell apoptosis induced by H2O2 or serum starvation. Our results suggested that HO-1 was able to increase prostate carcinoma cell invasion in vitro and tumor growth in vivo. The EMT induction and antioxidant and antiapoptotic effects of HO-1 in the prostate carcinoma cells may be responsible for these findings.
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- 2019
40. Comparison of Outcome and Quality of Life Between Thulium Laser (Vela
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Yu-Ting, Chen, Chen-Pang, Hou, Horng-Heng, Juang, Yu-Hsiang, Lin, Pei-Shan, Yang, Phei-Lang, Chang, Chien-Lun, Chen, Shu-Chuan, Weng, and Ke-Hung, Tsui
- Abstract
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.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.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.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.
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- 2021
41. The Clinical Experiences of Urine Metabolomics of Genitourinary Urothelial Cancer in a Tertiary Hospital in Taiwan
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Gigin Lin, Shao-Ming Chen, Yu-Hsiang Lin, Horng-Heng Juang, Chen-Pang Hou, Pei-Shan Yang, Meng-Han Chiang, Chien-Lun Chen, Phei-Lang Chang, Ke-Hung Tsui, and Kuo-Yen Lin
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Cancer Research ,medicine.medical_specialty ,Metabolite ,Urine ,Gastroenterology ,genitourinary urothelial cancer ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,Valine ,Internal medicine ,medicine ,bladder ,RC254-282 ,030304 developmental biology ,Original Research ,0303 health sciences ,Genitourinary system ,business.industry ,Cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,urothelium ,medicine.disease ,neoplasia ,chemistry ,Oncology ,030220 oncology & carcinogenesis ,urine metabolomics ,Leucine ,Isoleucine ,business - Abstract
Few studies have addressed the impact of diagnostic urine metabolites and the clinical outcomes associated with genitourinary urothelial (GU) cancer to date. Furthermore, longitudinal analysis of the dynamics of urine metabolites contributing to the detection of GU cancer has not yet been fully investigated; therefore, the discovery of novel diagnostic urine biomarkers is of enormous interest. We explored the correlation of the urine metabolomic profiles to GU cancers. The aqueous metabolites of the GU cancer and the control were also identified and analyzed through high-resolution1H nuclear magnetic resonance (NMR) spectroscopy. Compared with the control, the urine metabolites of the tumor were studied in relation to changes over time in a linear mixed model for repeated measures. The urine metabolites of sixty-three (44 male and 19 female) patients with GU cancers were systemically analyzed. The urine metabolite profile in GU cancer was significantly higher than those in the control group (p
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- 2021
42. Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival
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Jun-Te Hsu, Ta-Sen Yeh, Sheng-Fong Kuo, Ho-Yen Chueh, Kun-Chun Chiang, Shuen-Iu Hung, Sheng-Teng Huang, Li-Wei Chen, Ren-Chin Wu, Jong-Hwei S. Pang, Chun-Nan Yeh, Horng-Heng Juang, Ming-Huang Chen, and Shih-Chiang Huang
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0301 basic medicine ,Gene knockdown ,Cell growth ,Angiogenesis ,fungi ,Cell ,Cell migration ,Cell cycle ,Biology ,Filamentous actin ,Vascular endothelial growth factor ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,parasitic diseases ,Cancer research ,medicine - Abstract
Objective Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA. Materials and methods Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied. Results IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial-mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients. Conclusion Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment.
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- 2019
43. Caffeic acid phenethyl ester inhibits the growth of bladder carcinoma cells by upregulating growth differentiation factor 15
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Yu-Hsiang Lin, Chen-Pang Hou, Pei-Shan Yang, Kang-Shuo Chang, Hsin-Ching Sung, Horng-Heng Juang, Shu-Yuan Hsu, Chien-Lun Chen, Ke-Hung Tsui, and Tsui-Hsia Feng
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MAPK/ERK pathway ,Gene knockdown ,Bladder cancer ,Growth Differentiation Factor 15 ,Chemistry ,Cell growth ,Urinary Bladder ,Carcinoma ,Maspin ,Epithelial Cells ,General Medicine ,Transfection ,medicine.disease_cause ,medicine.disease ,Gene Expression Regulation, Neoplastic ,chemistry.chemical_compound ,Urinary Bladder Neoplasms ,Cell Line, Tumor ,medicine ,Cancer research ,Animals ,Humans ,Caffeic acid phenethyl ester ,Carcinogenesis - Abstract
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.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.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.Our findings indicate that CAPE is a promising agent for anti-tumor growth in human bladder carcinoma cells via the upregulation of GDF15.
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- 2021
44. Proteomic characterization of arsenic and cadmium exposure in bladder cells
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Cheng-Han Tsai, Ke-Hung Tsui, Horng-Heng Juang, Wei-Chao Liao, Wei-Ting Ou Yang, Hsiao-Wei Chen, Ying-Hsu Chang, Chuen Hsueh, Chien-Lun Chen, and Yi-Ting Chen
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Proteomics ,Urinary Bladder ,Cell ,Taiwan ,Arsenic ,Analytical Chemistry ,Biological pathway ,Promyelocytic leukemia protein ,Tandem Mass Spectrometry ,Cell Line, Tumor ,Biomarkers, Tumor ,Carcinoma ,medicine ,Humans ,Protein Interaction Maps ,Spectroscopy ,biology ,Chemistry ,Organic Chemistry ,Proteins ,Cancer ,medicine.disease ,Blot ,medicine.anatomical_structure ,Urinary Bladder Neoplasms ,Cell culture ,Proteome ,Cancer research ,biology.protein ,Cadmium ,Signal Transduction - Abstract
Rationale Accumulating evidence has linked prolonged exposure to heavy metals to cancer occurrence in the urinary system. However, the specific biological mechanisms responsible for the association of heavy metals with the unusually high incidence of upper tract urothelial carcinoma in Taiwan are complex and incompletely understood. Methods To elucidate the specific biological mechanism and identify molecular indicators of the unusually high association of upper tract urothelial carcinoma with heavy metal exposure, protein expression following the treatment of T24 human bladder carcinoma and RT4 human bladder papilloma cell line models with arsenic (As) and cadmium (Cd) was studied. Proteomic changes in these cell models were integrated with data from a human bladder cancer (BLCA) tissue proteome to identify possible protein indicators of heavy metal exposure. Results After mass spectrometry based proteomic analysis and verification by Western blotting procedures, we identified 66 proteins that were up-regulated and 92 proteins that were down-regulated in RT4 cell extracts after treatment with As or Cd. Some 52 proteins were up-regulated and 136 proteins were down-regulated in T24 cell extracts after treatment with Cd. We further confirmed that down-expression of the PML (promyelocytic leukemia) protein was sustained for at least 75 days after exposure of bladder cells to As. Dysregulation of these cellular proteins by As was associated with three biological pathways. Immunohistochemical analyses of paraffin-embedded BLCA tissue slides confirmed that PML protein expression was decreased in BLCA tumor cells compared with adjacent noncancerous epithelial cells. Conclusions These data suggest that PML may play an important role in the pathogenesis of BLCA and may be an indicator of heavy metal exposure in bladder cells.
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- 2020
45. Human Heme Oxygenase-1 Induced by Interleukin-6 via JAK/STAT3 Pathways Is a Tumor Suppressor Gene in Hepatoma Cells
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Horng-Heng Juang, Kun-Chun Chiang, Mei Chao, Tsui-Hsia Feng, Kang-Shuo Chang, Hsin-Ching Sung, and Shu-Yuan Hsu
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0301 basic medicine ,HepG2 ,Tumor suppressor gene ,Physiology ,Clinical Biochemistry ,HO-1 ,Biochemistry ,Article ,STAT3 ,03 medical and health sciences ,0302 clinical medicine ,STAT1 ,luteolin ,Molecular Biology ,AG490 ,IL-6 ,Expression vector ,biology ,Chemistry ,lcsh:RM1-950 ,ROS ,Cell Biology ,Hep3B ,Cell biology ,JAK ,Heme oxygenase ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,030220 oncology & carcinogenesis ,STAT protein ,biology.protein ,Phosphorylation ,Signal transduction - Abstract
Heme oxygenase-1 (HO-1) has several important roles in hepatocytes in terms of anti-inflammation, anti-apoptosis, and antioxidant properties. Interleukin-6 (IL-6) is a pleiotropic cytokine associated with liver regeneration and protection against injury. The aim of this study was to determine the potential crosstalk between HO-1 and IL-6, and to elucidate the signaling pathways involved in the induction of HO-1 by IL-6 in human hepatoma cells. Ectopic overexpression of HO-1 not only attenuated cell proliferation in vitro and in vivo, but also blocked the reactive oxygen species (ROS) induced by H2O2 and the pyocyanin in HepG2 or Hep3B cells. IL-6 expression was negatively regulated by HO-1, while IL-6 induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and HO-1 gene expression in HepG2 cells. The co-transfected HO-1 reporter vector and a protein inhibitor of the activated STAT3 (PIAS3) expression vector blocked the IL-6-induced HO-1 reporter activity. Both interferon &gamma, and interleukin-1&beta, treatments induced STAT1 but not STAT3 phosphorylation, which had no effects on the HO-1 expression. Treatments of AG490 and luteolin blocked the JAK/STAT3 signaling pathways which attenuated IL-6 activation on the HO-1 expression. Our results indicated that HO-1 is the antitumor gene induced by IL-6 through the IL-6/JAK/STAT3 pathways, moreover, a feedback circuit may exist between IL-6 and HO-1 in hepatoma cells.
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- 2020
46. Gassless Single-Port Retroperitoneoscopic Surgery for Urologic Disease: Case Series Reports
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Chen-Che Lee, Pei-Shan Yang, Yu-Hsiang Lin, Ke-Hung Tsui, Horng-Heng Juang, Phei-Lang Chang, Kuo-Jen Lin, Chien-Lun Chen, and Chen-Pang Hou
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Laparoscopic surgery ,Retrospective review ,medicine.medical_specialty ,Ureter stricture ,business.industry ,medicine.medical_treatment ,General Medicine ,medicine.disease ,Surgery ,Port (medical) ,Renal mass ,medicine ,Urologic disease ,business ,Adrenal tumors - Abstract
Introduction: The effects of Gassless single port retroperitoneoscopic surgery with urologic diseaseremain unclear. In this retrospective review, we aim to elucidate the effect of the Gassless retroperitoneoscopy for urologic disease. Methods: We retrospectively enrolled five consecutive patients who visited the urologic department for urologic disease from January 2016 to October 2016. All cases were followed up at least 12 months postoperatively. Of these, two renal mass, two adrenal tumors and one ureter stricture were reports. Result: There were no significant differences between the characteristics of these groups. (p
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- 2020
47. Maspin is a PTEN-Upregulated and p53-Upregulated Tumor Suppressor Gene and Acts as an HDAC1 Inhibitor in Human Bladder Cancer
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Chen-Pang Hou, Horng-Heng Juang, Yu-Hsiang Lin, Kang-Shuo Chang, Ke-Hung Tsui, and Tsui-Hsia Feng
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p53 ,bladder, maspin, HDAC1, p53, PTEN, tumorigenesis ,Cancer Research ,Gene knockdown ,PTEN ,Bladder cancer ,Tumor suppressor gene ,biology ,Chemistry ,Maspin ,Vimentin ,medicine.disease_cause ,medicine.disease ,Article ,HDAC1 ,tumorigenesis ,Cyclin D1 ,Oncology ,medicine ,biology.protein ,Cancer research ,maspin ,Carcinogenesis ,bladder - Abstract
Maspin is a member of the clade B serine protease inhibitor superfamily and exhibits diverse regulatory effects in various types of solid tumors. We compared the expressions of maspin and determined its potential biological functions and regulatory mechanisms in bladder carcinoma cells in vitro and in vivo. The results of RT-qPCR indicated that maspin expressed significantly lower levels in the bladder cancer tissues than in the paired normal tissues. The immunohistochemical assays of human bladder tissue arrays revealed similar results. Maspin-knockdown enhanced cell invasion whereas the overexpression of maspin resulted in the opposite process taking place. Knockdown of maspin also enhanced tumorigenesis in vivo and downregulated protein levels of acetyl-histone H3. Moreover, in bladder carcinoma cells, maspin modulated HDAC1 target genes, including cyclin D1, p21, MMP9, and vimentin. Treatment with MK2206, which is an Akt inhibitor, upregulated maspin expression, whereas PTEN-knockdown or PTEN activity inhibitor (VO-OHpic) treatments demonstrated reverse results. The ectopic overexpression of p53 or camptothecin treatment induced maspin expression. Our study indicated that maspin is a PTEN-upregulated and p53-upregulated gene that blocks cell growth in vitro and in vivo, and may act as an HDAC1 inhibitor in bladder carcinoma cells. We consider that maspin is a potential tumor suppressor gene in bladder cancer.
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- 2019
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48. MART-10, a 1α,25(OH)2D3 Analog, Potently Represses Metastasis of ER+ Breast Cancer Cells with VEGF-A Overexpression
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Masashi Takano, Sheng-Fong Kuo, Chun-Nan Yeh, Horng-Heng Juang, Atsushi Kittaka, Jong-Hwei S. Pang, Li-Wei Chen, Kun-Chun Chiang, Tai C. Chen, Ta-Sen Yeh, and Ming-Huang Chen
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Cancer Research ,030219 obstetrics & reproductive medicine ,Angiogenesis ,Chemistry ,Cell migration ,General Medicine ,medicine.disease ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Oncology ,MCF-7 ,Neuropilin 1 ,Cancer cell ,medicine ,Cancer research ,030212 general & internal medicine ,Autocrine signalling - Abstract
Background Breast cancer ranks second in the list of cancer-related deaths for women. Even under multidisciplinary treatment, 25-50% of patients with breast cancer still ultimately develop metastasis, leading to poor prognosis. In addition to inducing angiogenesis, vascular endothelial growth factor-A (VEGF-A) is believed to directly increase cancer cell metastatic potential and overexpression of VEGF-A is associated with higher invasiveness of breast cancer. 1α,25(OH)2D3, the active form of vitamin D, and its analogs have been widely applied as anticancer agents in the past. Material and methods Western blot, migration and invasion assays, enzyme-linked immunosorbent assay, and immunofluorescent stain were applied in this study. Result VEGF-A increased cell migration and invasion in estrogen receptor-positive (ER+) breast cancer MCF-7 cells. VEGF-A induced an autocrine loop in MCF-7 cells as VEGF-A treatment increased both VEGF-A expression and secretion. The expression of VEGF receptor type 2 (VEGFR2) and neuropilin 1 was also up-regulated by VEGF-A in MCF-7 cells. In addition, F-actin synthesis and LIM domain kinase 1 (LIMK-1) phosphorylation were increased by VEGF-A. VEGF-A also increased β-catenin expression and nuclear translocation of both β-catenin and nuclear factor-ĸB (NF-ĸB), indicating increased β-catenin and NF-ĸB activity. 1α,25(OH)2D3 and MART-10, an analog of 1α,25(OH)2D3, effectively repressed VEGF-A-induced MCF-7 cell migration and invasion and other VEGF-A-induced effects on MCF-7 cells, with MART-10 being more potent than 1α,25(OH)2D3 Conclusion: MART-10 can be deemed as a promising agent for prevention and treatment of metastasis of ER+ breast cancer with VEGF-A overexpression.
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- 2018
49. Migration and Invasion Enhancer 1 Is an NF-ĸB-Inducing Gene Enhancing the Cell Proliferation and Invasion Ability of Human Prostate Carcinoma Cells In Vitro and In Vivo
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Ke-Hung Tsui, Kang-Shuo Chang, Yu-Hsiang Lin, Tsui-Hsia Feng, Chen-Pang Hou, and Horng-Heng Juang
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Cancer Research ,medicine.disease_cause ,lcsh:RC254-282 ,Article ,NF-κB ,Prostate cancer ,medicine ,MK2206 ,Enhancer ,Protein kinase B ,IL-6 ,prostate ,Oncogene ,Cell growth ,Chemistry ,Kinase ,NDRG1 ,Akt ,JSH-23 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,MIEN1 ,tumorigenesis ,Oncology ,Apoptosis ,NF-B ,Cancer research ,Carcinogenesis - Abstract
Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. We determined the expression, biological functions, and regulatory mechanisms of MIEN1 in the prostate. The results of immunohistochemical analysis indicated that MIEN1 was expressed specifically in epithelial cells and significantly higher in adenocarcinoma as compared to in normal tissues. MIEN1 enhanced in vitro cell proliferation, invasion, and in vivo tumorigenesis. Meanwhile, MIEN1 attenuated cisplatin-induced apoptosis in PC-3 cells. Overexpression of NF-ĸB-inducing kinase (NIK) enhanced MIEN1 expression, while overexpression of NF-ĸB inhibitor &alpha, (IĸB&alpha, ) blocked MIEN1 expression in PC-3 cells. In prostate carcinoma cells, MIEN1 provoked Akt phosphorylation, moreover, MIEN1 downregulated N-myc downstream regulated 1 (NDRG1) but upregulated interleukin-6 (IL-6) gene expression. MK2206, an Akt inhibitor, impeded the modulation of MIEN1 on NDRG1 and IL-6 expressions. Our studies suggest that MIEN1 is an NF-ĸB downstream oncogene in the human prostate. Accordingly, the modulation of Akt signaling in the gene expressions of NDRG1 and IL-6 may account for the functions of MIEN1 in cell proliferation, invasion, and tumorigenesis in prostate carcinoma cells.
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- 2019
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50. BTG2 is a tumor suppressor gene upregulated by p53 and PTEN in human bladder carcinoma cells
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Kun-Chun Chiang, Ke-Hung Tsui, Kang-Shuo Chang, Horng-Heng Juang, Yu-Hsiang Lin, and Tsui-Hsia Feng
- Subjects
0301 basic medicine ,p53 ,Male ,Cancer Research ,PTEN ,Biopsy ,urologic and male genital diseases ,Mice ,0302 clinical medicine ,Gene expression ,BTG2 ,tumor suppressor gene ,RNA, Small Interfering ,Original Research ,Cancer Biology ,Mice, Inbred BALB C ,biology ,Chemistry ,Bladder cancer ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Tumor suppressor gene ,Urinary Bladder ,Response Elements ,Immediate-Early Proteins ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Protein kinase B ,Cell growth ,Tumor Suppressor Proteins ,Carcinoma ,PTEN Phosphohydrolase ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,030104 developmental biology ,Urinary Bladder Neoplasms ,Mutation ,biology.protein ,Cancer research ,Tumor Suppressor Protein p53 - Abstract
Although widely deemed as a tumor suppressor gene, the role of B‐cell translocation gene 2 (BTG2) in bladder cancer is still inconclusive. We investigated the role and regulatory mechanism of BTG2 in bladder cancer. BTG2 expression in human bladder tissues was determined by RT‐qPCR and immunoblotting assays. Expressions of BTG2 and PTEN in bladder carcinoma cells were determined by immunoblotting, RT‐qPCR, or reporter assays. The 3H‐thymidine incorporation assay, flow cytometry, and the xenograft animal model were used to determine the cell growth. BTG2 expression was lower in human bladder cancer tissues than normal bladder tissues. Highly differentiated bladder cancer cells, RT4, expressed higher BTG2 than the less‐differentiated bladder cancer cells, HT1376 and T24. Overexpression of BTG2 in T24 cells inhibited cell growth in vitro and in vivo. Camptothecin and doxorubicin treatments in RT‐4 cells or transient overexpression of p53 into p53‐mutant HT1376 cells induced p53 and BTG2 expression. Further reporter assays with site‐mutation of p53 response element from GGGAAAGTCC to GGAGTCC within BTG2 promoter area showed that p53‐induced BTG2 gene expression was dependent on the p53 response element. Ectopic PTEN overexpression in T24 cells blocked the Akt signal pathway which attenuated cell growth via upregualtion of BTG2 gene expression, while reverse effect was found in PTEN‐knockdown RT‐4 cells. PTEN activity inhibitor (VO‐OHpic) treatment decreased BTG2 expression in RT‐4 and PTEN‐overexpressed T24 cells. Our results suggested that BTG2 functioned as a bladder cancer tumor suppressor gene, and was induced by p53 and PTEN. Modulation of BTG2 expression seems a promising way to treat human bladder cancer.
- Published
- 2017
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