Targeting Btk/Etk of prostate cancer cells by a novel dual inhibitor.

Btk and Etk/BMX are Tec-family non-receptor tyrosine kinases. Btk has previously been reported to be expressed primarily in B cells and has an important role in immune responses and B-cell malignancies. Etk has been shown previously to provide a strong survival and metastasis signal in human prostate cancer cells, and to confer androgen independence and drug resistance. While the role of Etk in prostate carcinogenesis is well established, the functions of Btk in prostate cancer have never been investigated, likely due to the perception that Btk is a hematopoietic, but not epithelial, kinase. Herein, we found that Btk is overexpressed in prostate cancer tissues and prostate cancer cells. The level of Btk in prostate cancer tissues correlates with cancer grades. Knockdown of Btk expression selectively inhibits the growth of prostate cancer cells, but not that of the normal prostate epithelial cells, which express very little Btk. Dual inhibition of Btk and Etk has an additive inhibitory effect on prostate cancer cell growth. To explore Btk and Etk as targets for prostate cancer, we developed a small molecule dual inhibitor of Btk and Etk, CTN06. Treatment of PC3 and other prostate cancer cells, but not immortalized prostate epithelial cells with CTN06 resulted in effective cell killing, accompanied by the attenuation of Btk/Etk signals. The killing effect of CTN06 is more potent than that of commonly used inhibitors against Src, Raf/VEGFR and EGFR. CTN06 induces apoptosis as well as autophagy in human prostate cancer cells, and is a chemo-sensitizer for docetaxel (DTX), a standard of care for metastatic prostate cancer patients. CTN06 also impeded the migration of human prostate cancer cells based on a 'wound healing' assay. The anti-cancer effect of CTN06 was further validated in vivo in a PC3 xenograft mouse model

Ectopic ureter associated with uterine didelphys and obstructed hemivagina: preoperative diagnosis by MRI

Uterine didelphys with obstructed hemivagina and ipsilateral renal anomalies is a rare congenital malformation of the female urogenital tract. While the urinary anomalies almost always involve renal agenesis, we report a rare case of a 17-year-old girl with the malformation associated with ectopic ureteral insertion into the obstructed hemivagina, which was diagnosed preoperatively by MR imaging. To the best of our knowledge, preoperative MR imaging diagnosis of the ectopic ureter associated with this syndrome has not been previously reported. Accurate preoperative diagnosis of ectopic ureteral insertion associated with this syndrome is important for surgical planning

Bacteremic community-acquired pneumonia due to Klebsiella pneumoniae: Clinical and microbiological characteristics in Taiwan, 2001-2008

<p>Abstract</p> <p>Background</p> <p><it>Klebsiella pneumoniae </it>is the major cause of community-acquired pyogenic infections in Taiwan. This retrospective study evaluated the clinical and microbiological characteristics of bacteremic community-acquired pneumonia due to <it>K. pneumoniae </it>in Taiwanese adults.</p> <p>Methods</p> <p>The clinical characteristics of bacteremic community-acquired pneumonia (CAP) in adults due to <it>K. pneumoniae </it>were compared to those of adults with bacteremic CAP due to <it>Streptococcus pneumoniae </it>at a tertiary medical center in Taiwan from 2001-2008. Risk factors for mortality of bacteremic CAP due to <it>K. pneumoniae </it>were analyzed. All clinical isolates of <it>K. pneumoniae </it>were examined for capsular serotypes, hypermucoviscosity phenotype, aerobactin and <it>rmpA </it>gene.</p> <p>Results</p> <p><it>K. pneumoniae </it>was the dominant cause of bacteremic CAP and was associated with a more fulminant course and a worse prognosis than bacteremic CAP due to <it>Streptococcus pneumoniae</it>. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality. Serotype K1 and K2 comprised around half of all isolates. There were no significant differences in the clinical characteristics of patients with bacteremic CAP due to K1/K2 and non-K1/K2 isolates. Hypermucoviscosity phenotype as well as the aerobactin and <it>rmpA </it>genes were highly prevalent in the <it>K. pneumoniae </it>isolates.</p> <p>Conclusions</p> <p><it>K. pneumoniae </it>continued to be the dominant cause of bacteremic CAP in Taiwanese adults during 2001-2008. Initial presentation with septic shock and respiratory failure were independent risk factors for both early and total mortality from <it>K. pneumoniae </it>bacteremic CAP. Serotypes K1/K2 comprised around half of all isolates, but did not predispose patients to a poor clinical outcome. Physicians should be aware of the poor prognosis of any patient with bacteremic <it>K. pneumoniae </it>CAP and monitor these patients more closely.</p

Determinants of formation of aflatoxin-albumin adducts: a seven-township study in Taiwan

Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma. Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism. A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin (AFB1-albumin adducts). A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case–control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan, were employed in this study. Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay, as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction. The detection rate of AFB1-albumin adducts was significantly higher in males (42.5%) than in females (21.6%) (multivariate-adjusted odds ratio=2.6, 95% confidence interval=1.4–5.0). The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers (42.8%) than in non-carriers (36.6%) (multivariate-adjusted odds ratio=1.4, 95% confidence interval=1.0–2.1). In addition, the detection rate of AFB1-albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione S-transferase T1-1. In conclusion, this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB1-albumin adducts in a well characterised Chinese adult population. This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection

An Algorithm Informed by the Parathyroid Hormone Level Reduces Hypocalcemic Complications of Thyroidectomy

Ó The Author(s) 2010. This article is published with open access at Springerlink.com Background Measurement of the parathyroid hormone (PTH) level following total thyroidectomy (TTx) may allow prediction of postoperative hypocalcemia. We present an algorithmic method of managing hypocalcemia preemptively, based on the PTH level 1 h after operation. Materials and methods We examined 423 consecutive patients undergoing TTx at a single institution. A subset of patients were managed using an algorithm involving routine postoperative oral calcium administration and the early addition of oral calcitriol in patients with a low 1-h postoperative PTH level. Algorithm patients were compared to a concurrent, conventionally managed group. Outcomes measured included serum calcium levels, symptoms of hypocalcemia, postoperative complications, and receipt of intravenous (IV) calcium. Results The algorithm was applied in 135 patients, and 288 patients were managed conventionally. Critically low calcium levels (total calcium \7.5 mg/dl [1.88 mmol/l] or ionized calcium \0.94 mmol/l) were less common in algorithm patients (10.6 % vs. 25.3%; p \ 0.005). Much of this difference was attributable to the protective impact of the algorithm on patients undergoing TTx for cancer, 30% of whom developed critically low calcium levels when managed conventionally. Among patients requiring IV calcium, algorithm patients received fewer doses (1.29 vs

Do Neutrophils Play a Role in Establishing Liver Abscesses and Distant Metastases Caused by Klebsiella pneumoniae?

Serotype K1 Klebsiella pneumoniae is a major cause of liver abscesses and endophthalmitis. This study was designed to identify the role of neutrophils in the development of distant metastatic complications that were caused by serotype K1 K. pneumoniae. An in vitro cellular model was used to assess serum resistance and neutrophil-mediated killing. BALB/c mice were injected with neutrophils containing phagocytosed K. pneumoniae. Serotype K1 K. pneumoniae was significantly more resistant to serum killing, neutrophil-mediated phagocytosis and intra-cellular killing than non-K1 isolates (p<0.01). Electron microscopic examination had similar findings as in the bioassay findings. Intraperitoneal injection of neutrophils containing phagocytosed serotype K1 K. pneumoniae led to abscess formation in multiple sites including the subcutaneous tissue, lung, and liver, whereas no abscess formation was observed in mice injected with non-K1 isolates. The resistance of serotype K1 K. pneumoniae to complement- and neutrophil-mediated intracellular killing results in the dissemination of K. pneumoniae via the bloodstream. Escape from neutrophil intracellular killing may contribute to the dissemination and establishment of distant metastases. Thus, neutrophils play a role as a vehicle for helping K. pneumoniae and contributing to the establishment of liver abscess and distant metastatic complications

Effect of Qigong on quality of life: a cross-sectional population-based comparison study in Taiwan

<p>Abstract</p> <p>Background</p> <p>Qigong, similar to Tai Chi Chuan, is beneficial to health. In Taiwan, Waitankung, a type of Qigong, is as popular as Tai Chi Chuan. This population-based comparison study compares the health-related quality of life between people practicing Waitankung and their comparable community residents.</p> <p>Methods</p> <p>A total of 165 individuals practicing Waitankung were matched by age and sex with 660 general individuals for comparison. Information about health-related quality of life, measured by the SF-36, and other basic and health conditions was obtained from the questionnaires. This study used the linear mixed-effect regression model to examine the association between health-related quality of life and the practice of Waitankung.</p> <p>Results</p> <p>Compared with either sedentary individuals or individuals practicing other types of exercise, the Waitankung group scored higher for eight and five out of ten SF-36 components, respectively. The Waitankung group scored better in general health, vitality, and physical component summary compared to individuals participating in other types of exercise, even when considering the energy expended by exercise.</p> <p>Conclusion</p> <p>The results suggest that Waitankung exercising is significantly associated with health-related quality of life. Waitankung may serve as an exercise choice for middle-aged and older people to improve overall quality of life.</p

Long-Term Mortality of Patients with Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess: A Population-Based Study

Background: Taiwan is endemic for pyogenic liver abscess (PLA). Septic ocular or central nervous system (CNS) complications derived from PLA can result in catastrophic disability. We investigated the epidemiology and long-term prognosis of PLA patients with septic ocular or CNS complications over an 8-year period. Methodology/Principal Findings: We extracted 21,307 patients with newly diagnosed PLA from a nationwide health registry in Taiwan between 2000 and 2007. The frequency of and risk factors for PLA with septic ocular or CNS complications were determined. The 2-year survival of these patients was compared between those with and without septic ocular or CNS complications. Septic ocular or CNS complications accounted for 2.1 % of all PLA patients. Age and the Charlson comorbidity index were significantly lower in PLA patients with ocular or CNS complications than those without. Diabetes and age,65 years were independent predictors of septic ocular or CNS complications. The 2-year mortality of patients with septic ocular or CNS complications was similar to those without complications (24.8 % vs. 27.5%, p = 0.502). However, among patients,65 years old and a Charlson index #1, the 2-year mortality was significantly higher in those with than without complications (18.6 % vs. 11.8%, p = 0.001). Conclusions/Significance: Physicians should recognize that catastrophic disability due to ocular or neurologica