1.Manganese antagonizes iron blocking mitochondrial aconitase expression in human prostate carcinoma cells.
Ke-Hung TSUI ; Phei-Lang CHANG ; Horng-Heng JUANG
Asian Journal of Andrology 2006;8(3):307-315
AIMTo investigate the possible role of manganese in the regulation of mitochondrial aconitase (mACON) activity human prostate carcinoma cell line PC-3 cells.
METHODSThe mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dinucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the mACON. The putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays.
RESULTSIn vitro study revealed that manganese chloride (MnCl2) treatment for 16 h inhibited the enzymatic activity of mACON, which induced the inhibition of citrate utility and cell proliferation of PC-3 cells. Although results from transient gene expression assays showed that MnCl2 treatment upregulated gene translation by approximately 5-fold through the iron response element pathway, immunoblot and reporter assays showed that MnCl2 treatments inhibited protein and gene expression of mACON. This effect was reversed by co-treatment with ferric ammonium citrate. Additional reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays suggested that a putative metal response element in the promoter of the mACON gene was involved in the regulation of MnCl2 on the gene expression of mACON.
CONCLUSIONThese findings suggest that manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.
Aconitate Hydratase ; antagonists & inhibitors ; genetics ; Actins ; genetics ; Adenosine Triphosphate ; metabolism ; Cell Line, Tumor ; Chlorides ; pharmacology ; Citrates ; metabolism ; DNA Primers ; Gene Expression Regulation, Enzymologic ; drug effects ; Gene Expression Regulation, Neoplastic ; drug effects ; Genes, Reporter ; Humans ; Iron ; metabolism ; Male ; Manganese Compounds ; pharmacology ; Mitochondria ; enzymology ; Prostatic Neoplasms ; enzymology
2.Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China.
Ke-Hung TSUI ; Shao-Ming CHEN ; Ta-Ming WANG ; Horng-Heng JUANG ; Chien-Lun CHEN ; Guang-Huan SUN ; Phei-Lang CHANG
Asian Journal of Andrology 2007;9(5):711-715
AIMTo compare the results of bladder tumor associated antigen (BTA TRAK), nuclear matrix protein 22 (NMP 22) and voided urine cytology (VUC) in detecting bladder cancer.
METHODSA total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups: (i) 93 patients with bladder cancer; (ii) 42 patients with urinary benign conditions; and (iii) 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests.
RESULTSThe sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer.
CONCLUSIONThe NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.
Aged ; Humans ; Male ; Nuclear Proteins ; urine ; Taiwan ; Urinary Bladder Neoplasms ; diagnosis ; urine ; Urine ; cytology
3.Skin Exposure Contributes to Chemical-Induced Asthma: What is the Evidence? A Systematic Review of Animal Models
Hung-Chang TSUI ; Steven RONSMANS ; Laurens J De SADELEER ; Peter H. M. HOET ; Benoit NEMERY ; Jeroen A. J. VANOIRBEEK
Allergy, Asthma & Immunology Research 2020;12(4):579-598
It is generally assumed that allergic asthma originates primarily through sensitization via the respiratory mucosa, but emerging clinical observations and experimental studies indicate that skin exposure to low molecular weight (LMW) agents, i.e. “chemicals,” may lead to systemic sensitization and subsequently develop asthma when the chemical is inhaled. This review aims to evaluate the accumulating experimental evidence that adverse respiratory responses can be elicited upon inhalation of an LMW chemical sensitizer after previous sensitization by dermal exposure. We systematically searched the PubMed and Embase databases up to April 15, 2017, and conducted forward and backward reference tracking. Animal studies involving both skin and airway exposure to LMW agents were included. We extracted 6 indicators of “selective airway hyper-responsiveness” (SAHR)—i.e. respiratory responses that only occurred in previously sensitized animals—and synthesized the evidence level for each indicator into strong, moderate or limited strength. The summarized evidence weight for each chemical agent was graded into high, middle, low or “not possible to assess.” We identified 144 relevant animal studies. These studies involved 29 LMW agents, with 107 (74%) studies investigating the occurrence of SAHR. Indicators of SAHR included physiological, cytological/histological and immunological responses in bronchoalveolar lavage, lung tissue and airway-draining lymph nodes. Evidence for skin exposure-induced SAHR was present for 22 agents; for 7 agents the evidence for SAHR was inconclusive, but could not be excluded. The ability of a chemical to cause sensitization via skin exposure should be regarded as constituting a risk of adverse respiratory reactions.
4.Skin Exposure Contributes to Chemical-Induced Asthma: What is the Evidence? A Systematic Review of Animal Models
Hung-Chang TSUI ; Steven RONSMANS ; Laurens J De SADELEER ; Peter H. M. HOET ; Benoit NEMERY ; Jeroen A. J. VANOIRBEEK
Allergy, Asthma & Immunology Research 2020;12(4):579-598
It is generally assumed that allergic asthma originates primarily through sensitization via the respiratory mucosa, but emerging clinical observations and experimental studies indicate that skin exposure to low molecular weight (LMW) agents, i.e. “chemicals,” may lead to systemic sensitization and subsequently develop asthma when the chemical is inhaled. This review aims to evaluate the accumulating experimental evidence that adverse respiratory responses can be elicited upon inhalation of an LMW chemical sensitizer after previous sensitization by dermal exposure. We systematically searched the PubMed and Embase databases up to April 15, 2017, and conducted forward and backward reference tracking. Animal studies involving both skin and airway exposure to LMW agents were included. We extracted 6 indicators of “selective airway hyper-responsiveness” (SAHR)—i.e. respiratory responses that only occurred in previously sensitized animals—and synthesized the evidence level for each indicator into strong, moderate or limited strength. The summarized evidence weight for each chemical agent was graded into high, middle, low or “not possible to assess.” We identified 144 relevant animal studies. These studies involved 29 LMW agents, with 107 (74%) studies investigating the occurrence of SAHR. Indicators of SAHR included physiological, cytological/histological and immunological responses in bronchoalveolar lavage, lung tissue and airway-draining lymph nodes. Evidence for skin exposure-induced SAHR was present for 22 agents; for 7 agents the evidence for SAHR was inconclusive, but could not be excluded. The ability of a chemical to cause sensitization via skin exposure should be regarded as constituting a risk of adverse respiratory reactions.
5.Synchronous primary carcinomas of the bladder and prostate.
Sheng-Hui LEE ; Phei-Lang CHANG ; Shao-Ming CHEN ; Guang-Huan SUN ; Chien-Lun CHEN ; Biing-Yir SHEN ; Ya-Shen WU ; Ke-Hung TSUI
Asian Journal of Andrology 2006;8(3):357-359
AIMTo determine the incidence of adenocarcinoma of the prostate for patients undergoing radical cystoprostatectomy for bladder cancer in Taiwan.
METHODSA total of 248 patients in Taiwan who were histologically confirmed for transitional cell carcinoma of the bladder underwent cystoprostatectomy. Histopathologic evaluation of the prostate specimens sectioned at 5 mm intervals was performed.
RESULTSOf the 248 patients, 10 (4.03%) were found to have prostate cancer. Of the 10 cases of unsuspected prostate cancer, eight proved to be at stage T1 or T2, and two at T3 and T4, respectively. This rate of incidentally found prostate cancer amongst our bladder cancer patients appeared to be lower than that found in bladder cancer patients in similar studies in USA.
CONCLUSIONAlthough the incidence of incidental prostate cancer in patients in Taiwan with bladder cancer is not high compared with that in Western countries, we suggest that digital rectal examination and prostate-specific antigen (PSA) are important screening tools for men with bladder cancer, especially for those aged 60 years and older in Taiwan.
Carcinoma, Transitional Cell ; pathology ; surgery ; Humans ; Male ; Neoplasm Staging ; Prostatectomy ; Prostatic Neoplasms ; complications ; surgery ; Urinary Bladder Neoplasms ; complications ; pathology ; surgery