Jong-Khing Huang

Ying-Huei Lee; Wann-Chu Huang; Jeng-Yu Tsai; Chih-Ming Lu; Wei-Chuan Chen; Ming-Huei Lee; Hueih-Shing Hsu; Jong-Khing Huang; Luke S. Chang

Introduction: A nationwide survey was conducted to investigate the prevalence of upper urinary calculi in Taiwan. Materials and Methods: A postal questionnaire was mailed to 27,758 people, 0.2% of the adults in Taiwan. Results: Of the 4,588 valid respondents, 440 had at least one episode of upper urinary calculus disease. The overall prevalence was 9.6% (14.5% in males and 4.3% in females). Men were more prone to nephrolithiasis than women (age-adjusted prevalence of 12.2% in men and 3.1% in women, p = 0). The ‘stone belt’ was localized in the Midwest region of Taiwan. A gender- and age-adjusted multivariate analysis revealed that alcohol consumption and family history of kidney stone were significant risk factors for stone occurrence. Compared with general population, the odds ratios for stone disease in inhabitants whose father, mother and both parents with stone history were 3.44 [95% confidence interval (CI), 2.33–5.07], 4.79 (95% CI, 2.85–8.07) and 10.40 (95% CI, 3.75–28.84), respectively. The subtropical temperature and gradually higher socioeconomic standards of living may contribute to the high prevalence. Inhabitants in the Midwest region have higher risk to develop stones. Conclusions: Further studies are needed to investigate the exact cause of these regional variations of stone prevalence. Nevertheless, the present study provides an additional piece of information on worldwide epidemiology of urolithiasis.

Chung-Ren Jan; Chin-Man Ho; Sheng-Nan Wu; Jong-Khing Huang; Ching-Jiunn Tseng

We have studied the effects of La3+ on ATP-evoked rises in intracellular calcium levels ([Ca2+]i) measured by fura-2 fluorimetry in Madin Darby canine kidney (MDCK) cells. ATP evoked [Ca2+]i rises dose-dependently with an EC50 of 2.5 microM. The trigger for the Ca2+ signal was a release of Ca2+ from the inositol-1,4,5-trisphosphate (IP3)-sensitive stores because the signal was completely blocked by pretreatment with the endoplasmic reticulum (ER) Ca2+ pump inhibitor thapsigargin (TG) or the phospholipase C (PLC) inhibitor U73122. Both the peak height and area under the curve of 10 microM ATP-evoked Ca2+ signal was reduced by approximately 50% by extracellular Ca2+ removal, suggesting that ATP induced capacitative Ca2+ entry. La3+ inhibited the ATP-evoked Ca2+ signal dose-dependently when added before or after ATP. Pretreatment of 0.1 mM La3+ inhibited approximately 90% of the Ca2+ signal induced by 10 microM ATP. The mechanisms underlying the La3+ inhibition appear to involve not only block of capacitative Ca2+ entry but also interference with ATP binding to the ATP receptors.

Chih-Ming Lu; Shou-Jen Lan; Ying-Huei Lee; Jong-Khing Huang; Chun-Hsiung Huang; Chung-Cheng Hsieh

OBJECTIVES To determine whether tea consumption and intake of other beverages increases bladder cancer risk. METHODS A case-control study was conducted in Kaohsiung, Taiwan between August 1996 and June 1997. Index patients studied were consecutive patients with histologically confirmed, newly diagnosed bladder cancer in two major hospitals. For each patient, 4 controls were selected from patients with non-neoplastic and nonurologic diseases undergoing surgical operations in the same hospital and individually matched by sex, age, and date of admission. Using a structured questionnaire, a trained interviewer interviewed 40 patients and 160 controls. Conditional logistic regression analysis adjusting for ethnicity, family history, and smoking status and matching variables were used to estimate the odds ratio (OR) and 95% confidence interval (CI). RESULTS Tea consumption overall was associated with increased bladder cancer risk (OR 3.29, 95% CI 1.34 to 8.05). Compared with non-tea drinkers, the odds ratios of bladder cancer for oolong tea drinkers was 3.00 (95% CI 1.20 to 7.47); for non-oolong tea drinkers (black and/or other green tea), it was 14.86 (95% CI 2.13 to 103.83). The risk was greater among those who began to drink tea before age 40 (OR 9.50, 95% CI 2.39 to 37.75) and those who had been drinking tea for more than 30 years (OR 17.75, 95% CI 3.00 to 105.17). Coffee, tap water, and alcohol consumption were associated with a slightly increased risk, and both soy juice and rice juice consumption were associated with reduced risk; none of these odds ratio estimates were statistically significant, however. CONCLUSIONS Our results suggest that tea consumption is associated with an increased risk of bladder cancer.

Shu-Pin Huang; Chao-Yuan Huang; Wen-Jeng Wu; Yeong-Shiau Pu; Jun Chen; Yun-Yun Chen; Chia-Cheng Yu; Tony T. Wu; Jyh-Seng Wang; Ying-Huei Lee; Jong-Khing Huang; Chun-Hsiung Huang; Ming-Tsang Wu

To investigate the effect of vitamin D receptor (VDR) FokI polymorphism on susceptibility to prostate cancer and the outcome of the disease in a Taiwanese population, we genotyped a total of 416 prostate cancer patients, 502 age‐matched male controls and 189 non age‐matched symptomatic benign prostatic hyperplasia. Although we did not find a significant association between VDR FokI genotypes and overall prostate cancer risk, we found that in men aged less than or equal to the median age of 73 years with VDR FokI F allele specifically had an increased risk of prostate cancer with a marginal significant trend (OR, 2.08; 95% CI, 1.00–4.34, p for trend = 0.056). The FF genotype was also highly associated with more aggressive prostate cancer (Gleason score 8–10) (OR, 2.47; 95% CI, 1.20–5.08) than did the Ff and ff genotypes. After adjusting other covariates, we found that in patients who had localized prostate cancer for which a radical prostatectomy was performed (n = 131), the VDR FokI FF genotype was associated with worse prostate‐specific antigen (PSA) recurrence‐free survival (hazard ratio = 3.25, 95% CI = 1.32–8.00, p = 0.010). Our findings suggest that the VDR FF genotype may increase the risk of early‐onset prostate cancer and is associated with more aggressive disease. Furthermore, the VDR polymorphism could be used as a prognostic marker for localized prostate cancer after radical prostatectomy.

Jong-Khing Huang; Chung-Ren Jan

Linoleamide is an endogenous lipid that has been shown to induce sleep in cats, rats and humans. However, its physiological function remains unclear. In this study the effect of linoleamide on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) tubular cells was examined, by using fura-2 as a Ca2+ probe. In a concentration-dependent manner, linoleamide induced increases in [Ca2+]i between 10-500 microM with an EC50 of 20 microM. The signal comprised a slow rise and a persistent phase, and was a result of internal Ca2+ release and external Ca2+ influx because it was partly inhibited by external Ca2+ removal. In Ca2+-free medium, depletion of the endoplasmic reticulum Ca2+ store with 1 microM thapsigargin abolished 100 microM linoleamide-induced internal Ca2+ release, and conversely, pretreatment with linoleamide prevented thapsigargin from releasing internal Ca2+. This demonstrates that the internal source of linoleamide-induced [Ca2+]i increase is located in the endoplasmic reticulum. This discharge of internal Ca2+ caused capacitative Ca2+ entry because after incubation with 100 microM linoleamide in Ca2+-free medium for 8 min readmission of 3 mM CaCl2 induced increases in [Ca2+]i. After the formation of inositol-1,4,5-trisphosphate (IP3) was blocked by the phospholipase C inhibitor U73122 (1 microM), linoleamide still induced an increase in [Ca2+]i but the shape of the increase was altered. Similar results were found for another sleep-inducing lipid 9,10-octadecenoamide. Together, the present study shows that the endogenous sleep-inducing lipid linoleamide was able to cause significant increases in [Ca2+]i in renal tubular cells, by releasing the endoplasmic reticulum Ca2+ store and triggering capacitative Ca2+ entry in a manner independent of IP3.

Hong-Chiang Chang; Chorng-Chih Huang; Chun-Jen Huang; Jin-Shiung Cheng; Shiuh-In Liu; Jeng-Yu Tsai; Hong-Tai Chang; Jong-Khing Huang; Chiang-Ting Chou; Chung-Ren Jan

The antidepressant desipramine has been shown to induce a rise in cytosolic Ca2+ levels ([Ca2+]i) and cytotoxicity in human PC3 prostate cancer cells, but the mechanisms underlying its cytotoxic effect is unclear. Cell viability was examined by WST-1 assays. Apoptosis was assessed by propidium iodide staining and an increase in caspase-3 activation. Phosphorylation of protein kinases was analyzed by immunoblotting. Desipramine caused cell death via apoptosis in a concentration-dependent manner. Immunoblotting data revealed that desipramine activated the phosphorylation of c-Jun NH2-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK). SP600125 (a selective JNK inhibitor) partially prevented cells from apoptosis. Pretreatment with BAPTA/AM, a Ca2+ chelator, to prevent desipramine-induced [Ca2+]i rises worsened desipramine-induced cytotoxicity. Immunoblotting data suggest that BAPTA/AM pretreatment enhanced desipramine-evoked JNK phosphorylation and caspase-3 cleavage. The results suggest that in PC3 cells, desipramine caused apoptosis via inducing JNK-associated caspase-3 activation, and [Ca2+]i rises may slow down or alleviate desipramine-induced cytotoxicity.

Chung-Ren Jan; Bang-Ping Jiann; Yih-Chau Lu; Hong-Tai Chang; Warren Su; Wei-Chung Chen; Chia-Cheng Yu; Jong-Khing Huang

The effects of triethyltin on Ca2+ mobilization in human PC3 prostate cancer cells have been explored. Triethyltin increased [Ca2+]i at concentrations larger than 3 microM with an EC50 of 30 microM. Within 5 min, the [Ca2+]i signal was composed of a gradual rise and a sustained phase. The [Ca2+]i signal was reduced by half by removing extracellular Ca2+. The triethyltin-induced [Ca2+]i increases were inhibited by 40% by 10 microM nifedipine, nimodipine and nicardipine, but were not affected by 10 microM of verapamil or diltiazem. In Ca2+-free medium, pretreatment with thapsigargin (1 microM), an endoplasmic reticulum Ca+ pump inhibitor, reduced 200 microM triethyltin-induced Ca+ increases by 50%. Pretreatment with U73122 (2 microM) to inhibit phospholipase C did not alter 200 microM triethyltin-induced [Ca2+]i increases. Incubation with triethyltin at a concentration that did not increase [Ca2+]i (1 microM) in Ca2+-containing medium for 3 min potentiated ATP (10 microM)- or bradykinin (1 microLM)-induced [Ca2+]i increases by 41 +/- 3% and 51 +/- 2%, respectively. Collectively, this study shows that the environmental toxicant triethyltin altered Ca2+ handling in PC3 prostate cancer cells in a concentration-dependent manner: at higher concentrations it increased basal [Ca2+]i; and at lower concentrations it potentiated agonists-induced [Ca2+]i increases.

Hong-Tai Chang; Jong-Khing Huang; Jue-Long Wang; Jin-Shiung Cheng; Kam-Chung Lee; Yuk-Keung Lo; Chun-Pin Liu; Kang-Ju Chou; Wei-Chung Chen; Warren Su; Yee-Ping Law; Chung-Ren Jan

Tamoxifen has been shown to increase cytoplasmic free Ca2+ levels [Ca2+]i in renal tubular cells and bladder cancer cells, and to alter Ca2+ signaling in MCF-7 breast cancer cells. The present study examined the effect of tamoxifen on [Ca2+]i in ZR-75-1 human breast cancer cells using fura-2 as an indicator. Tamoxifen increased [Ca2+]i at a concentration above 2 μM with an EC50 of 5 μM. Removing extracellular Ca2+ reduced the response by 48 ± 2%. In Ca2+-free medium, after tamoxifen-induced [Ca2+]i increased had returned to baseline, adding 3 mM Ca2+ increased [Ca2+]i in a concentration-dependent manner. Further, pretreatment with 10 μM tamoxifen abolished the [Ca2+]i increase induced by 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor); and conversely, pretreatment with thapsigargin prevented tamoxifen from releasing more Ca2+. Tamoxifen (10 μM)-induced Ca2+ release was not changed by inhibiting phospholipase C activity with 2 μM U73122. Trypan blue exclusion assay revealed that tamoxifen (1–10 μM) did not alter viability after 1 min of incubation, but killed 10% of cells after 3–10 min of incubation. Together, this study shows that tamoxifen (>2 μM) induced a significant, immediate increase in [Ca2+]i in ZR-75-1 breast cancer cells. Tamoxifen acted by releasing Ca2+ from the endoplasmic reticulum Ca2+ stores in a manner independent of phospholipase C activity, and by inducing Ca2+ entry from extracellular medium. Tamoxifen may be of mild cytotoxicity after acute exposure.

Wei-Chuan Chen; Ying-Huei Lee; Jong-Khing Huang; Ming-Tsun Chen; Luke S. Chang

Seventeen patients with urolithiasis in problem kidneys which comprised horseshoe kidneys, medullary sponge kidneys (MSKs), polycystic kidneys and duplex kidneys presented to our hospital and were evaluated for treatment with extracorporeal shock-wave lithotripsy (ESWL). A total of 21 renal units were treated with ESWL. Auxiliary procedures included preoperative retrograde ureteral catheterization (1 horseshoe kidney) placement of a retrograde double-J catheter stent (1 MSK), percutaneous nephrolithotomy (PCNL; 2 MSKs) and postoperative PCNL (1 MSK). The outcome showed that 5 renal units (23.8%) were stone free, 15 renal units (71.4%) had a decreased stone load with residual stone and improved symptoms, and 1 renal unit (4.8%) had residual stone with persistent symptoms. We conclude that ESWL can be used as a primary management tool for calculi in problem kidneys.

Bang-Ping Jiann; Yih-Chau Lu; Hong-Tai Chang; Jong-Khing Huang; Chung-Ren Jan

Abstract The effect of clomiphene, an ovulation-inducing agent, on cytosolic free Ca 2+ levels ([Ca 2+ ] i ) in populations of PC3 human prostate cancer cells was explored by using fura-2 as a Ca 2+ indicator. Clomiphene at concentrations between 10-50 μM increased [Ca 2+ ] i in a concentration-dependent manner. The [Ca 2+ ] i signal was biphasic with an initial rise and a slow decay. Ca 2+ removal inhibited the Ca 2+ signal by 41%. Adding 3 mM Ca 2+ increased [Ca 2+ ] i in cells pretreated with clomiphene in Ca 2+ -free medium, confirming that clomiphene induced Ca 2+ entry. In Ca 2+ -free medium, pretreatment with 50 μM brefeldin A (to permeabilize the Golgi complex), 1 μM thapsigargin (to inhibit the endoplasmic reticulum Ca 2+ pump), and 2 μM carbonylcyanide m-chlorophenylhydrazone (to uncouple mitochondria) inhibited 25% of 50 μM clomiphene-induced store Ca 2+ release. Conversely, pretreatment with 50 μM clomiphene in Ca 2+ -free medium abolished the [Ca 2+ ] i increase induced by brefeldin A, thapsigargin or carbonylcyanide m-chlorophenylhydrazone. The 50 μM clomiphene-induced Ca 2+ release was unaltered by inhibiting phospholipase C with 2 μM 1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Trypan blue exclusion assay suggested that incubation with clomiphene (50 μM) for 2-15 min induced time-dependent decrease in cell viability by 10-50%. Collectively, the results suggest that clomiphene induced [Ca 2+ ] i increases in PC3 cells by releasing store Ca 2+ from multiple stores in an phospholipase C-independent manner, and by activating Ca 2+ influx; and clomiphene was of mild cytotoxicity.