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Background: There is little information available related to the reproductive health of people with intellectual disability (ID). The aims of the present study are to describe caregiver attitudes and to examine determinants of gynaecological health for women with ID., Method: We recruited 1152 caregivers (response rate=71.87%) and analysed their responses to a mailed-out, self-administered, structured questionnaire. We divided attitudinal perceptions of reproductive health into 4 domains: menstruation, menopause, sex education, and preventive healthcare. Each domain in turn had 5 issues (questions), with scores of 1 to 4 given according to the level of agreement with each issue (low to high score: strongly disagree, disagree, agree, and strongly agree). The total sum score for each domain was 5-20 (total score range: 20-80)., Results: The respondents' attitudinal mean score was 57.78±4.64 (range: 48-75). The multiple logistic regression model revealed that the factors of "workplace training in reproductive health" (OR=1.793, 95% CI=1.31-2.46), "felt satisfied with public reproductive health services for the client" (OR=0.694, 95% CI=0.53-0.92), and "scores of reproductive health knowledge" (OR=1.735, 95% CI=1.29-2.34) were significantly correlated with attitudinal score level toward gynaecological health for women with ID., Conclusions: The study highlights that service authorities should address health policy initiatives to continue providing workplace training in reproductive health, public reproductive health services. There is also a need for caregivers to increase their knowledge of reproductive health.

Purpose of Review: The present review examines the most recent published references to epidemiology, healthcare needs and utilization and social and health policy relating to people with intellectual disability in Taiwan., Method: Electronic searches of Medline, PubMed and PsychInfo literature using the key terms of epidemiology, etiology, welfare policy, health policy, health services, intellectual disability, learning disability and mental retardation as well as a thorough manual search for relevant literature., Recent Findings: The administrative prevalence of intellectual disability was 0.318-0.396%, and men accounted for a higher percentage of cases than women in Taiwan. Institutionalized care still dominates disability services provided in this society, and the number of institutions and staff working therein has increased steadily in recent years. Many studies also identify the high risk for ill health accompanied by physical/mental diseases in people with intellectual disability, with this group also requiring more healthcare services than the general population in Taiwan. There are still many barriers to accessibility and availability of health and social services confronting people with intellectual disability and their caregivers under the National Health Insurance scheme in Taiwan., Summary: As a result of this review process, this paper suggests that future study should focus on an evaluation of the efficacy of current health and social policies related to people with intellectual disability, and that supportive health environments be initiated for this group of people living in institutions or in the community.

The present paper aims to explore awareness and acceptability of human papillomavirus (HPV) vaccination and to identify factors influencing HPV acceptability among women with physical disabilities in Taiwan. The study participants were 438 adult women with physical disabilities, aged 18-69 years. The participants were all officially registered as having physical disabilities in Taipei County, Taiwan, in March 2009. The major findings were that 54.5% of the participants had previously heard about the HPV vaccine and that vaccine acceptability was very low (3.2%) if the participants would have had to pay for the vaccine but would increase to 60% if the government were to provide the vaccine for free. We found that those participants who had had a Pap smear test within the past 1 year or 3 years were significantly more likely to be aware of and willing to receive the HPV vaccine than those who had not. To increase the HPV vaccination rate among women with physical disabilities, the study suggests that the current health care system in Taiwan should consider implementing free immunization for this group of women., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The paper aims to analyze the hospital inpatient care use and medical fee of people with ID co-occurring with schizophrenia in Taiwan. A nationwide data were collected concerning hospital admission and medical expenditure of people with ID (n = 2565) among national health insurance beneficiaries in Taiwan. Multiple regression analyses were undertaken to determine the role of the explanatory variables to hospital psychiatric inpatient care and medical expenditure. We found that there were 2565 individuals with ID used hospital psychiatric inpatient care among people with ID in 2005, and 686 cases (26.7%) co-occurring with schizophrenia according to hospital discharge claims. Those ID patients co-occurring with schizophrenia consumed more annual inpatient fee than those without schizophrenia (251,346 vs. 126,666 NTD) (p < 0.001). We found factors of female cases, longer hospital stay in chronic ward and general ward users among ID patients co-occurring with schizophrenia used more hospital inpatient care (R(2) = 0.417). Annual hospital inpatient days were significantly affected by factors of severe illness card holder, annual inpatient care fee, longer hospital stay in acute or chronic ward (R(2) = 0.746). Those factors of female cases, high inpatient care users, longer hospital stay in acute ward and general ward were consuming more medical care fee than their counterparts (R(2) = 0.620). The study highlights the future study should examine the efficacy of hospital inpatient care for people with ID and schizophrenia., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Although many previous studies have begun to address the reproductive health needs of women with intellectual disabilities; however, the supportive behaviors of caregivers to assist their reproductive health is not well understood. Data from a cross-sectional survey of "2009 National Survey on Reproductive Health Care Needs and Health Education Strategies for Women with Intellectual Disabilities in Taiwan" were analyzed. Study sample consisted of 1152 caregivers who working in 32 disability institutions have been analyzed in the study. The results showed that the caregiver did not have adequate supportive behaviors towards reproductive health care for women with ID (mean score was 29.84 out of 60), particularly in the arrangement of preventive reproductive health services. We analyzed the potential significant variables in a multiple linear regression model to examine the factors which affect the caregiver's supportive behaviors of reproductive health for women with ID. The model revealed that the factor of respondent's gender, job category, working years in disability setting, helping experience of reproductive health for women with ID, perception of reproductive health knowledge, in-job training of reproductive health, perceived adequacy of public reproductive health service for the client, scores of reproductive health knowledge and reproductive health attitude were significantly correlated to their supportive behavioral score of reproductive health for women with ID. These factors can explain 23.6% of the variation of supportive behavioral score. The present study suggests the reproductive health interventions need to take into account the perspectives of health workers, caregivers and women, as well as the constraints they face in providing and receiving services, respectively., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We collected self reported rate of cervical smear testing and to examine the affecting factors in women with physical disabilities in the study, to define the reproductive health care for this group of people. The study population recruited 521 women with physical disabilities aged more than 15 years who were officially registered as having physical disabilities in Taipei County, Taiwan. Those people with physical disabilities include following: upper and low limb, spinal cord injury and other nervous system impairments. Results found that there were 71.5% participants had ever used the Pap smear tests in their life time and mean age of the first screening was 39.21±10.16 years (range=20-85 years). Nearly 41% of participants expressed that they had accepted the screening within 1 year and 28.1% reported they used the Pap smear screening regularly. Our study also found women with physical disabilities have higher use of Pap smear tests than does the general population in Taiwan (74% vs. 64% in aged≥30 years). Logistic regression model for the use of Pap smear test indicated that those married women (OR=12.06, 95% CI=6.85-21.22), with mild level of disability (OR=2.10, 95% CI=1.05-4.21) and high cognitive level toward Pap smear information were factors to affect the use of Pap smear in the study participants. We suggest the further study should conduct to examine the quality perception and follow-up service of Pap smear test for women with physical disabilities, to ensure the health care right for this group of women., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Limited attention has been paid to the issue of reproductive health as it affects women with intellectual disabilities, despite reproductive health being a vital issue in public health policy for women in the general population. This paper describes caregiver awareness of reproductive health issues relative to women with intellectual disabilities who are being cared for in welfare institutions in Taiwan., Methods: The study employed a cross-sectional, questionnaire-based study which recruited 1,152 caregivers (response rate = 71.87%) from 32 registered disability welfare institutions in Taiwan. We classified their understanding/awareness of reproductive health issues into four domains: menstrual (1) and menopause (2) issues, sex education (3), and reproductive health services (4). Each domain had five associated yes/no questions and the total score for the four domains was out of a maximum of 20. Data were analyzed using SPSS 15.0 software., Results: We found that most of the caregivers were familiar with matters concerning sex education, menopause, and reproductive health services, but they lacked adequate understanding of issues associated with menstruation in women with ID. Many aspects of reproductive health such as "menstrual pain", "age at menarche", "masturbation", "diet during perimenopause", and "publicly available reproductive health services" were issues in which caregivers lacked adequate knowledge and required further instruction. Logistic regression analysis revealed that female caregivers with a university degree, and those who had experience assisting with reproductive health care were more inclined to have higher reproductive health awareness scores than their counterparts., Conclusions: This study highlights that service providers should offer appropriate reproductive health education to institutional caregivers, and that more attention be focused on the personal experiences and concerns of intellectually disabled women in future research.

Using Pb(2+) as ion perturber, phenosafranine (PF) and fluorescein isothiocyanate (FITC) could emit strong and stable room temperature phosphorescence (RTP) signal on the filter paper, respectively. When they were mixed, the phenomenon that the RTP signal of PF and FITC enhanced significantly was found. And 1.12 ag DNA spot(-1) (sample volume was 0.40 μL, corresponding concentration was 2.8 × 10(-15) g mL(-1)) could cause the RTP signal of both PF and FITC to enhance sharply. The content of DNA was proportional to the ΔI(p) of PF and FITC in the system at 634 and 659 nm. Thus, a new solid substrate room temperature phosphorimetry (SSRTP) for the determination of trace DNA was established by using FITC-PF as double-luminescent phosphorescence probe. The detection limit (LD) of this method calculated by 3S(b)/k was 14 zg DNA spot(-1) for PF and 18 zg DNA spot(-1) for FITC, respectively, showing high sensitivity. It has been applied to the determination of trace DNA in practical samples and the analysis results were in accordance with those of fluorescence probe. The reaction mechanism of SSRTP for the determination of trace DNA was also discussed.

The present study aimed to describe the kidney function profile - serum creatinine and estimated glomerular filtration rate (eGFR), and to examine the relationships of predisposing factors to abnormal serum creatinine in people with intellectual disabilities (ID). Data were collected by a cross-sectional study of 827 aged 15-18 years adolescents with ID who participated in annual health examinations as they enrolled into special education schools in Taiwan. We used serum samples to determine participants' creatinine profiles, and the Cockcroft-Gault formula to calculate the data of eGFR to present the chronic kidney disease. The results found 22% of the participants have abnormal serum creatinine value (creatinine>1.0mg/dl) and 59.6%, 36.4% and 4.0% at chronic kidney disease (CKD) stage 1, 2 and 3 cases accordingly based on the Cockcroft-Gault formula. No CKD stage 4 and 5 cases in this study. That is, there were 4% CKD cases (eGFR <60 mL/min/1.73 m(2); CKD stage 3, 4 and 5) in adolescents with ID in this study. The results also indicated that gender and BMI could significantly predict abnormal creatinine condition in multivariate logistic regression analysis. Those boys with ID were more likely to have abnormal creatinine value than girls with ID (OR=10.13, 95% CI=5.96-17.23). In term of BMI, those underweight adolescents with ID were less likely to have high creatinine value compared to normal weight group (OR=0.45, 95% CI=0.28-0.72). In summary, this study provides the preliminary information of creatinine and estimated GFR in people with ID; we suggest the public health policy should initiate appropriate management strategies to monitor kidney function and to improve treatment outcomes of chronic kidney disease for this vulnerable population., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The present study analyzed national data from "Domestic Violence Report System" derived primarily from the Council of Domestic Violence and Sexual Assaults Prevention, Ministry of the Interior, Taiwan, to describe the reported prevalence of domestic violence in people with disabilities and to examine the time-effect on the prevalence from years 2006 to 2009. The annual reported prevalence of domestic violence victims in people with disabilities was slightly lower than the general population. However, the reported rate changed significantly in people with disabilities over the period of 2006-2009, the victim number and rate (per ten-thousand) of reported cases in different years were 1260 (12.84), 1725 (16.90), 2163 (20.79) and 3157 (29.48). People with voice or speech disability, chronic psychosis and intellectual disability were the most domestic violence reported prevalence among the disabilities in the study. Those disabilities, such as chronic psychosis, intellectual disability, vision disability, hearing disability and multi-disabilities show increased significantly in annual reported rate in curve estimation for linear model over the period of 2006-2009. Finally, we found the average increase rate of annual reported prevalence in people of disabilities was 3.7 times of the general population (9.79% vs. 36.08%). Intellectual disability (41.52%), vision or speech disability (38.59%) and chronic psychosis (37.96%) were the most increasing disability type in average of annual reported prevalence of domestic violence among disabilities during the period of 2006-2009. The present study suggests health and welfare authorities should play vital roles in identifying and providing appropriate services for people with disabilities who encounter domestic violence., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The active -OH group in fullerol (F-ol) could react with the dissociated -COOH group in fluorescein isothiocyanate (FITC) to form F-ol-(FITC)(n), which could emit room temperature phosphorescence (RTP) signal of F-ol and FITC on acetate cellulose membrane (ACM), respectively. Their RTP signals were enhanced by N,N-dimethylaniline (DMA). The labeling reaction between the -NCS group of FITC in DMA-F-ol-(FITC)(n) and the -NH2 group in wheat germ agglutinin (WGA) produced DMA-F-ol-(FITC)(n)-WGA, which could further take affinity adsorption (AA) reaction with bioactive substances (BS), such as glucose and alkaline phosphatase (AP), to produce DMA-F-ol-(FITC)(n)-WGA-BS. Both of these two products could maintain the good RTP characteristics of F-ol and FITC. Based on the facts above, a new phosphorescent labeling reagent, DMA-F-ol-FITC, was developed, and a new affinity adsorption solid substrate room temperature phosphorimetry (AASSRTP) for the determination of BS was established. This method was applied to the determination of BS in human serum and the diagnosis of diseases, with the results agreeing very well with those of enzyme-linked immunosorbent assay (ELISA). The mechanism of DMA-F-ol-(FITC)(n) labeling of WGA and AASSRTP for the determination of BS is discussed., (2010 Elsevier Inc. All rights reserved.)

The macrolide compound MFTZ-1 has been identified as a novel topoisomerase II (Top2) inhibitor with potent in vitro and in vivo anti-tumour activities. In this study, we further examined the effects of MFTZ-1 on hypoxia-inducible factor-1α (HIF-1α) accumulation, vascular endothelial growth factor (VEGF) secretion and angiogenesis. MFTZ-1 reduced HIF-1α accumulation driven by hypoxia or growth factors in human cancer cells. Mechanistic studies revealed that MFTZ-1 did not affect the degradation of HIF-1α protein or the level of HIF-1α mRNA. By contrast, MFTZ-1 apparently inhibited constitutive and inducible activation of both phosphatidylinositol-3-kinase (PI3K)-Akt and p42/p44 mitogen-activated protein kinase (MAPK) pathways. Further studies revealed that MFTZ-1 abrogated the HIF-1α-driven increase in VEGF mRNA and protein secretion. MFTZ-1 also lowered the basal level of VEGF secretion. The results reveal an important feature that MFTZ-1 can reduce constitutive, HIF-1α-independent VEGF secretion and concurrently antagonize inducible, HIF-1α-dependent VEGF secretion. Moreover, MFTZ-1 disrupted tube formation of human umbilical vein endothelial cells (HUVECs) stimulated by hypoxia with low-concentration serum or by serum at normoxia, and inhibited HUVECs migration at normoxia. MFTZ-1 also prevented microvessel outgrowth from rat aortic ring. These data reflect the potent anti-angiogenesis of MFTZ-1 under different conditions. Furthermore, using specific small interfering RNA targeting Top2α or Top2-defective HL60/MX2 cells, we showed that MFTZ-1 affected HIF-1α accumulation and HUVECs tube formation irrelevant to its Top2 inhibition. Taken together, our data collectively reveal that MFTZ-1 reduces constitutive and inducible HIF-1α accumulation and VEGF secretion possibly via PI3K-Akt and MAPK pathways, eliciting anti-angiogenesis independently of its Top2 inhibition., (© 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

The 8-quinolineboronic acid phosphorescent molecular switch (abbreviated as PMS-8-QBA. Thereinto, 8-QBA is 8-quinolineboronic acid, and PMS is phosphorescent molecular switch) was found for the first time. PMS-8-QBA, which was in the "off" state, could only emit weak room temperature phosphorescence (RTP) on the acetyl cellulose membrane (ACM). However, PMS-8-QBA turned "on" automatically for its changed structure, causing that the RTP of 8-QBA in the system increased, after PMS-8-QBA-WGA (WGA is wheat germ agglutinin) was formed by reaction between -OH of PMS-8-QBA and -COOH of WGA. More interesting is that the -NH(2) of PMS-8-QBA-WGA could react with the -COOH of alkaline phosphatase (AP) to form the affinity adsorption (AA) product WGA-AP-WGA-8-QBA-PMS (containing -NH-CO- bond), which caused RTP of the system to greatly increase. Thus, affinity adsorption solid substrate room temperature phosphorimetry using PMS-8-QBA as labelling reagent (PMS-8-QBA-AA-SSRTP) for the determination of trace AP was established. The method had many advantages, such as high sensitivity (the detection limit (LD) was 2.5zgspot(-1). For sample volume of 0.40mulspot(-1), corresponding concentration was 6.2x10(-18)gml(-1)), good selectivity (the allowed concentration of coexisting material was higher, when the relative error was +/-5%), high accuracy (applied to detection of AP content in serum samples, the result was coincided with those obtained by enzyme-linked immunoassay), which was suitable for the detection of trace AP content in serum samples and the forecast of human diseases. Meanwhile, the mechanism of PMS-8-QBA-AASSRTP was discussed. The new field of analytical application and clinic diagnosis technique of molecule switch are exploited, based on the phosphorescence characteristic of PMS-8-QBA, the AA reaction between WGA and AP, as well as the relation between AP content and human diseases. The research results promote the development and interpenetrate among molecule switch technique, lectin science and SSRTP., (Copyright 2009 Elsevier B.V. All rights reserved.)

A new phosphorescence-labelling reagent (3.5-G-D-P labelling reagent) was developed, based on 3.5-generation polyamidoamine dendrimers (3.5-G-D) as internal acceptor to capture porphyrin (P) molecular. In the disturber of heavy atom, 3.5-G-D-P could emit room temperature phosphorescence (RTP) of 3.5-G-D and P on the surface of polyamide membrane (PAM), respectively. Products (3.5-G-D-P-WGA) of 3.5-G-D-P labelling triticum vulgaris lectin (WGA) could emit strong and stable RTP signal on the surface of PAM, and it also could take specific affinity adsorption reaction (AA) with alkaline phosphatase (ALP). The product of the AA reaction (3.5-G-D-P-WGA-ALP) could keep the RTP characteristics of 3.5-G-D-P very well, and the DeltaI(p) of the system was linear correlation to the content of ALP. The DeltaI(p) of the system with Tween-80 was once for P and twice for 3.5-G-D more than that without Tween-80. Thus, the affinity adsorption solid substrate-room temperature phosphorimetry (AA-SS-RTP) for the determination of trace ALP has been established using Tween-80-3.5-G-D-P to label WGA. The detection limit (LD) of this method was 0.12fgspot(-1) for 3.5-G-D and 0.18fgspot(-1) for P with direct method, 0.14fgspot(-1) for 3.5-G-D and 0.17fgspot(-1) for P with sandwich method, respectively, and the sensitivity was obviously high. This research showed that either using 3.5-G-D or P excitation/emission wavelength to determine the content of ALP in human serum, the results were coincided with ELISA, and the flexibility of AA-SS-RTP was obviously improved and the applicability was wider. Meanwhile, the reaction mechanism of determining ALP by direct method AA-SS-RTP was discussed., (Copyright 2009. Published by Elsevier B.V.)

A novel solid substrate-room temperature phosphorimetry (SS-RTP) was developed for determination of bumetanide (BMTN). It was validated by determining selectivity, linearity, accuracy, precision, and signal to noise ratio (S/N) for analysis. And all the experiments presented in this work were based on that BMTN inhibited the formation of [Fe-morin](3+) ([FeR](3+)) complex by the reaction between Fe(3+) and R, which led to severe quenching of room temperature phosphorescence (RTP) signal. The rate constant of the reaction (k) was 2.44 x 10(-4) s(-1), the activation energy (E) was 21.39 kJ mol(-1). Detection limit of this method (LD, 5.0 ag spot(-1), corresponding concentration was 1.2 x 10(-14) g mL(-1)) was evaluated and compared with other methods, indicating better sensitivity for BMTN determination using this technique. And due to the high sensitivity of the method, it has been successfully applied to determine BMTN in human urine samples. The linear range was from 0.040 pg mL(-1) to 4.0 pg mL(-1), allowing wide determined range of BMTN. Meanwhile, the mechanism of this method was also discussed.

Artemisinin and its derivatives (ARTs) are effective antimalarial drugs and also possess profound anticancer activity. However, the mechanism accounted for its distinctive activity in tumor cells remains unelucidated. We computed Pair wise Pearson correlation coefficients to identify genes that show significant correlation with ARTs activity in NCI-55 cell lines using data obtained from studies with HG-U133A Affymetrix chip. We found c-myc is one of the genes that showed the highest positive correlation coefficients among the probe sets analyzed (r=0.585, P<0.001). Dihydroartemisinin (DHA), the main active metabolite of ARTs, induced significant apoptosis in HL-60 and HCT116 cells that express high levels of c-MYC. Stable knockdown of c-myc abrogated DHA-induced apoptosis in HCT116 cells. Conversely, forced expression of c-myc in NIH3T3 cells sensitized these cells to DHA-induced apoptosis. Interestingly, DHA irreversibly down-regulated the protein level of c-MYC in DHA-sensitive HCT116 cells, which is consistent to persistent G1 phase arrest induced by DHA. Further studies demonstrated that DHA accelerated the degradation of c-MYC protein and this process was blocked by pretreatment with the proteasome inhibitor MG-132 or GSK 3beta inhibitor LiCl in HCT116 cells. Taken together, ARTs might be useful in the treatment of c-MYC-overexpressing tumors. We also suggest that c-MYC may potentially be a biomarker candidate for prediction of the antitumor efficacies of ARTs., ((c) 2010 Elsevier Inc. All rights reserved.)

Multi-wall carbon nanotubes (MWNTs) could be modified as water soluble MWNTs (it was called as MWNTs-A and MWNTs-B) by chemical methods. MWNTs-A and MWNTs-B could emit room temperature phosphorescence (RTP) signal on the surface of nitrocellulose membrane (NCM). A new solid substrate-room temperature phosphorimetry (SS-RTP) for the determination of trace alkaline phosphatase (ALP) was established based on the signal magnification effect of tween-80 and ALP on MWNTs-B's RTP intensity and the linear relationship between the content of ALP and the DeltaI(P) of the system. The linear range of this method was 0.0020-0.80 (fg spot(-1), sample volume: 0.40 microl spot(-1)), the regression equation of working curve was DeltaI(P) = 0.8170 + 96.84m(ALP) (fg spot(-1)), correlation coefficient (r) was 0.9986. This method had high sensitivity (detection limit (LD): 1.4 ag spot(-1)), good selectivity (Er < or = +/- 5 in-care-of, coexistence species were of no interference), high precision (RSDs were 4.4%-1.2%) and accuracy. It was applied to the determination of trace ALP in human serum and the diagnosis of human diseases. The results were tallied with those of enzyme-linked immunosorbent assay (ELISA). The mechanism of new SS-RTP for the determination of trace ALP was discussed, which laid the theory foundation for the analytical application of MWNTs in life science.

There are not many studies pertaining to the spinal or limb abnormalities in people with intellectual disabilities, without a clear profile of these deformities of them, efforts to understand its characters and improve their quality of life will be impossible. Therefore, this paper aims to describe the prevalence and related factors of spinal and limb abnormalities in adolescents with intellectual disabilities. The participants who participated in health examinations as they enrolled into special schools at the first year, a total of 822 aged 15-18 years adolescents with ID were recruited to this study. The results showed that there were 14.5% and 8.5% cases had spinal and limb abnormalities based on the physician's observation and X-ray test. Factors of BMI level and limb abnormalities were significantly predicted the spinal abnormality occurrence in those adolescents with ID. Gender, disability level and have a spinal abnormality were variables that can statistically correlate to limb abnormality condition. The study highlights that in order to ensure people with intellectual disabilities receive an appropriate quality of care, it is important to have a precise understanding of the ways in which the needs of them who have spinal or limb deformities differ from the sole intellectual disability and the general population as a whole., (2010 Elsevier Ltd. All rights reserved.)

8-Quinolineboronic acid phosphorescent molecular switch (8-QBA-PMS) in the "off" state emitted weak room temperature phosphorescence (RTP) of 8-QBA on the acetylcellulose membrane (ACM) with the perturbation of Pb(2+). When 8-QBA-PMS was used to label concanavalin agglutinin (Con A) to form 8-QBA-PMS-Con A based on the reaction between -OH of 8-QBA-PMS and -COOH of Con A, 8-QBA-PMS turned "on" automatically due to its structure change, and RTP of the system increased 2.7 times. Besides, -NH(2) of 8-QBA-PMS-Con A could carry out affinity adsorption (AA) reaction with the -COOH of alpha-fetoprotein variant (AFP-V) to form the product Con A-AFP-V-Con A-8-QBA-PMS containing -NH-CO- bond, causing the RTP of the system to further increase. Moreover, the amount of AFP-V was linear to the DeltaI(p) of the system in the range of 0.012-2.40 (fg spot(-1)). Thus, a new affinity sensitive adsorption solid substrate room temperature phosphorimetry using 8-QBA-PMS as labelling reagent (8-QBA-PMS-AASSRTP) for the determination of AFP-V was proposed with the detection limit (LD) of 9 x 10(-15) g mL(-1). It had been used to determine AFP-V in human serum with the results agreeing with enzyme-link immunoassay (ELISA), showing promise for the prediction of PHC due to the intimate association between AFP-V and primary hepatocellular carcinoma (PHC). The mechanism of the promethod was also discussed., (Copyright 2010. Published by Elsevier B.V.)

Background: Echinoside A was isolated from sea cucumber. This study demonstrates its anticancer effects and its mechanisms of action., Materials and Methods: Anticancer effects of echinoside A were evaluated in vitro and in vivo. TUNEL and DNA fragmentation assays were applied to examine its ability to induce apoptosis. A series of biochemical assays were applied to investigate the inhibition of echinoside A on topoisomerase2alpha (Top2alpha). Molecular docking analyses were used to demonstrate the direct interaction between echinoside A and Top2alpha., Results: Echinoside A inhibited the growth of tumors in mouse models and human prostate carcinoma xenografts in nude mouse models. Echinoside A shows the unique characteristics of inhibiting the noncovalent binding of Top2alpha to DNA by competing with DNA for the DNA-binding domain of the enzyme and of interfering predominantly with the Top2alpha-mediated prestrand passage cleavage/religation equilibrium over with the poststrand passage one. These features distinguish echinoside A from other known Top2alpha inhibitors. As a result, echinoside A induced DNA double-strand breaks in a Top2-dependent manner., Conclusion: Echinoside A targets Top2alpha by unique interference with the binding of Top2 to DNA and by imparing the Top2-mediated DNA cleavage and religation, exerting potent in vitro and in vivo antitumor activities.

Aim: JG3, a novel marine-derived oligosaccharide, significantly inhibits angiogenesis and tumor metastasis by blocking heparanase activity. It also arrests tumor growth, an effect that is not fully explained by its anti-heparanase activity. Here we sought to identify the mechanisms underlying JG3-mediated inhibition of tumor growth., Methods: Heparanase expression was assessed by RT-PCR and Western blotting. NF-kappaB activation status was determined using immunofluorescence, Western blotting, DNA-binding and transcription-activity assays. The effect of JG3 on upstream components of the NF-kappaB pathway and on selected transcription factors were monitored by Western blotting. The antitumor effect of JG3 and its relation to NF-kappaB activation were evaluated using four different tumor xenograft models., Results: We found that JG3 effectively inhibited NF-kappaB activation independent of heparanase expression. Our results indicate that JG3 inactivated NF-kappaB by interfering with the activation of upstream components of the NF-kappaB pathway without generally affecting the nuclear translocation of transcription factors. Further, in vivo studies demonstrated that JG3 effectively arrested the growth of tumors derived from cell lines in which NF-kappaB was constitutively active (BEL-7402 liver carcinoma and MDA-MB-435s breast carcinoma), but did not affect the growth of tumors derived from NF-kappaB-negative cell lines (SGC-7901 gastric cancer and HO-8910 ovarian carcinoma)., Conclusion: Our data indicate that NF-kappaB mediates the JG3-induced arrest of tumor growth. These results define a new mechanism of action of JG3 and highlight the potential for JG3 as a promising lead molecule in cancer therapy.

This study aims to establish evidence-based data to explore the perceptions and experience of primary care physicians in the Pap smear screening provision for women with intellectual disabilities (ID), and to analyze the associated factors in the delivery of screening services to women with ID in Taiwan. Data obtained by a cross-sectional survey by a structured, self-administered questionnaire (12 perceptional issues), and were posted to all primary care settings (N=168) which provided Pap smear tests for women with ID in Taichung and I-Lan counties in Taiwan, Republic of China during the period of 2009. The vital primary care physician of each healthcare setting was the main respondent of the questionnaire. Finally, there were 69 valid questionnaires returned, giving a response rate of 41.7%. The main findings showed that 72.5% medical care settings provide Pap smear services and 51.5% have practical experience on conducting the tests for women with ID. Among the respondents, nearly 90% primary care physicians expressed that women with ID need Pap smear test regularly. With regard to the associated factors in the delivery of Pap smear screening services to women with ID. The study found that experienced healthcare settings in Pap smear tests for women with ID were more likely to be in public healthcare settings, felt confident in providing screening tests, having a rapid screening program and having a reminding follow-up system. Those respondents felt necessity in Pap smear test for women with ID were more likely to express it is needed to set up a special screening clinic for this group of women. The present study suggests that women with ID need thoughtful, well-coordinated care from primary care physicians, to increase access to health care providers may be helpful in improving Pap screening tests for this population., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Although little is known about the incidence of cervical cancer in women with intellectual disabilities (ID), Pap smear screening is an effective public health program to prevent cervical cancer to this group of people. The purposes of this study were to identify and evaluate the factors regarding the utilization of the Pap smears in women with ID seen in the preventive health screening program. We employed a cross-sectional survey "2009 National Survey on Preventive Health Use and Determinants among People with Disabilities", with the study sample 508 women with ID (aged > or =15 years) participated in the research in Taiwan. Results showed that there were 22.1% women with ID had ever used Pap smear screening previously and mean age of the first screening was nearly 40 years old. Comparing to the general population in Taiwan, the ID women at age group <35 years was less likely to use screening and the age group > or =35 years was more likely to use Pap smears than did the general women. Finally, a logistic regression analysis showed that marital status and had experience of accepted tubal ligation surgery were two factors which predicted Pap smear test use in the study. Those women with ID who had marital status were 8.99 times (95% CI=1.65-49.15) more likely than those had not marital status to use Pap smear test. Women with ID had experience on tubal ligation surgery were 10.48 times (95% CI=1.40-78.26) more likely to use Pap smear test than their counterparts. This study highlights that to acknowledge the rights of women with ID to access Pap smear screening service, health professionals will need to become more flexible and competent in the service that they provide., (Copyright 2009 Elsevier Ltd. All rights reserved.)

The present paper aims to assess the hypertension, hyperglycemia and hyperlipidemia prevalence of adolescents with intellectual disabilities, and to recognize the health disparities between the study participants and the general population. This study conducted a cross-sectional medical chart analysis of 856 students who participated in school enrolment health examinations in three special schools in Taiwan from 2005 to 2007. We found there were 11.7% cases had hypertension. The biochemical analyses results showed that the elevated or abnormal rates of each exam were the following: triglyceride (9.1%), total cholesterol (1.1%), and fasting plasma glucose (0.3%). The study found the prevalence of hypertension and elevated triglyceride were significantly higher than the general population at the same age, and the body mass index had significantly correlated to hypertension and elevated triglyceride tests. Based on the study findings, many potential risks for metabolic syndrome in adolescents with intellectual disabilities were higher than the general population. The present study suggests that it is necessary to monitor and set up a follow-up health policy for students with intellectual disabilities in healthcare system., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background: This study provides a perspective on the mental health status and analyses the effectiveness of a stress-relief program for primary caregivers of adolescents with intellectual disability (ID)., Method: Seventy-seven primary caregivers of people with ID were recruited (intervention group, n = 31; non-intervention group, n = 46) to the study, which involved participation in one stress management workshop (intervention group only) and both groups reading an education booklet on stress management., Results: We found that 22.1% of caregivers in the study were at high risk of depressive stress and in need of mental health consultation; this prevalence was nearly six times that of the general population. The effectiveness of mental health initiatives resulted in a significant reduction in depressive stress for the intervention group., Conclusions: The study highlights that a "face-to-face" workshop is an effective way to decrease levels of depressive stress.

There is little information of hepatitis B vaccination coverage for people with intellectual disabilities (ID). The present paper aims to examine the completed hepatitis B vaccination coverage rate and its determinants of children and adolescents with ID in Taiwan. A cross-sectional questionnaire survey, with the entire response participants was composed of 495 primary caregivers of children and adolescents with ID (age 3-24 years) who studying in 3 special education schools in Taiwan. The results showed that coverage rate of completed hepatitis B vaccination was 74.34% in children and adolescents with ID. Although hepatitis B vaccination is a universal health policy in Taiwan, the uncompleted coverage rate of our study subjects was 2 times of the Taiwan general population at the same age. In the logistic regression analysis of hepatitis B vaccination coverage, we found that the factors of household income and ID individual's age were variables that can significantly predict they did not accept a completed vaccination. The present study suggests that parents and providers should routinely review immunizations of children and adolescents with ID., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Anemia is known to be a significant public health problem in many countries. Most of the available information is incomplete or limited to special groups such as people with intellectual disability. The present study aims to provide the information of anemia prevalence and associated risk factors of children and adolescents with intellectual disability in Taiwan. We analyzed physical examination charts of 937 children and adolescents with intellectual disability at the age of 6-18 years from three special schools. We collected information on their demographic characteristics (age and gender), disability condition (type and level), BMI (weight and height) and measured blood hemoglobin concentration (Hb). There were 11.6% of children and adolescents with intellectual disability with anemia (boy <13 g/dl, girl <12 g/dl), and the factors of gender, age, disability level and BMI are significantly correlated to anemia in bivariant analyses in the study. In the logistic regression analysis, the model revealed that the factors of gender (OR=0.63, 95% CI=0.41-0.95), and age (OR=3.21, 95% CI=1.77-5.82) were variables that could significantly predict the anemia occurrence of the participants. The study highlights the anemia prevalence in children and adolescents with ID is a mild public health problem among people with intellectual disabilities, but to prevent the problems become worst; the health authority should include providing children and adolescents with adequate nutrition and appropriate health protections during early childhood.

Physical inactivity is a global public health problem, and it has been linked to many of the most serious illnesses facing many industrialized nations. There is little evidence examining the physical activity profile and determinants for the vulnerable population such as people with intellectual disabilities (ID). The present paper aims to describe the regular physical activity prevalence and to examine its determinants among adolescents with intellectual disabilities in Taiwan. Participants were recruited from 3 special education schools in Taiwan, with the entire response participants composed of 351 primary caregivers of adolescents with ID (age 16-18 years). There were 29.9% ID individuals had regular physical activity habits, and the main physical activities were walking, sports, and jogging. There were only 8% individuals with ID met the national physical activity recommendation in Taiwan which suggests at least exercise 3 times per week and 30 min per time. In a stepwise logistic regression analysis of regular physical activity habit, we found that the factors of caregiver's educational level and preference toward physical activity were variables that can significantly predict ID individuals who had regular physical activity habit in their daily livings after controlling other factors. To maximize the positive effect of physical activity on people with ID, the present study suggests that it is needed to initiate appropriate techniques used for motivation to participate in physical activity for this population.

The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or adolescents with ID. A cross-sectional design was conducted in three Taiwanese public special schools to analyze annual health examination chart of students with ID. There were 1041 aged 3-21 years children and adolescents with ID participated in the study. The results show elevated rate of GOT and GPT were 3.7% and 7.2%, the study indicates the elevated GPT in children and adolescents with ID is higher than the general school aged children in Taiwan. In multiple linear regression models show that the factors of BMI, HBsAg, TC and UA can significantly explain the GOT value (R(2)=0.275). Those factors of gender, BMI, HBsAg, TC and UA can significantly explain 44.4% variation of GPT value (R(2)=0.444). To prevent the further liver disease burden in people with ID, the study highlights that the health care professionals should assess liver functions of this group of people, and to inform their caregivers the importance of implement regular liver health check-up.

The aims of the preset study were to describe the profile of serum uric acid, the prevalence of hyperuricemia and its risk factors among children and adolescents with intellectual disabilities. We conducted a cross-sectional study of 941 children and adolescents with intellectual disabilities (aged 4-18 years) who participated in annual health examinations in three special schools in Taiwan. This study indicated 30.6% boys and 17.9% girls with intellectual disabilities were with hyperuricemia in Taiwan. The factors of gender, age and BMI were variables that can significantly predict the hyperuricemia occurrence in this vulnerable population. Those children and adolescents with intellectual disabilities were boys (OR=2.93, 95% CI=2.02-4.26) and older age (OR=6.49, 95% CI=2.19-19.21) were more likely to be hyperuricemia. With regard to BMI to hyperuricemia occurrence, those children and adolescents with intellectual disabilities were overweight (OR=1.16-3.21, 95% CI=1.16-3.21) and being obese (OR=4.95-11.58, 95% CI=4.95-11.58) was more likely to have a hyperuricemia than the normal weight group. This study provides the general profile of serum uric acid, hyperuricemia and its risk factors of children and adolescents with intellectual disabilities. Medical professionals should be highly alert to the possible consequences of hyperuricemia and provide useful information about the clinical manifestation of this condition for caregivers of children and adolescents with intellectual disabilities.

The present study based on World Health Organization quality of life (WHOQOL-BREF) scale to examine quality of life of the caregivers caring for their children/adolescents with intellectual disabilities in Taiwan, and the factors contributing to their quality of life. Structured interviews were conducted with 597 caregivers of children/adolescents with intellectual disabilities. The results found that the mean scores in each domain of WHOQOL-BREF of the caregivers as the followings: physical capacity (PC) was 13.71+/-2.35, psychological well-being (PW) was 12.21+/-2.55, social relationship (SR) was 12.99+/-2.43 and environment (EN) was 12.32+/-2.38. These mean scores were lower than the general population and slight higher than the caregivers of adults with intellectual disabilities in Taiwan. Finally, multiple stepwise regressions were conducted to examine the characteristics of caregiver and children/adolescents with intellectual disabilities will more likely explained the WHOQOL-BREF mean scores. The study found the following three factors: self-perceived health status, household income and stress from insufficient family support were significantly correlated to all four domains in multiple stepwise regression analyses. The results highlights that caregivers of children and adolescents with intellectual disabilities seem to display a lower WHOQOL-BREF mean score than the general population, probably for a combination of stress, health and household income factors. These finding must be taken into account in policy making to provide better and more specific supports and interventions for the caregivers of people with intellectual disabilities.

The present study was to describe the input/process and evaluate the effectiveness of Taiwanese Workplace Health Promotion Initiatives based on employees' perspectives. This study employed a cross-sectional design by a structured questionnaire that was completed by 842 employees in 30 workplaces that participated in the Taiwan Workplace Health Promotion (WHP) Initiatives which supported by Ministry of Health from 2004 to 2006. The results found that the employees generally agreed that WHP improved their personal health skills. There was a lower level of agreement with respect to other input/process domains such as workplace healthy policy, workplace supportive health environments and WHP activities and services and the WHP effectiveness. With regard to the prediction of WHP effectiveness, the domain of workplace health activities/services could only predict 50.5% of the variation of the effectiveness in a regression model. Three domains of workplace - health activities/services, personal health skills and supportive health environments - were significantly correlated to the agree level of health promotion effectiveness. The results suggest that companies that intend initiating health promotion programs need to conduct a detailed assessment of the nature of the workplace settings and the perceptions of employees.

Sexual violence against people with disabilities is widespread and linked to negative public health and social outcomes. The objectives of the present study were to describe and analyze and thus provide an overview of the current state of affairs concerning sexual assault among people with disabilities, including reported prevalence and trends, over the period from 2002 through 2007 in Taiwan. The present study analyzed nationwide data from the 2002-2007 "Sexual assaults report system" derived primarily from the Council of Domestic Violence and Sexual Assaults Prevention, Ministry of the Interior, Taiwan. The data took into account the number of cases and disability type in persons reported to have been sexually assaulted, and to analyze the reported rate of sexual assaults among this section of the population in Taiwan. In addition, the study used a linear estimation model to examine with time (2002-2007) in the rate of reported sexual assaults. The rate of increase of sexual assault reported among people with disabilities was 2.7 times that of the general population (469-173%) during the period of 2002-2007. Government statistics showed that intellectually disabled persons accounted for the largest proportion (>50%) of reported sexual assault cases among the disabled, followed by persons with chronic psychosis, who accounted for one-third of the reported sexual assault cases among the disabled population. The reported rate of sexual assault increased from 0.9 to 2.42 per ten-thousand people in the general population and from 1.24 to 5.74 per ten-thousand disabled persons. Intellectual disability, chronic psychosis and voice and speech impairments were consistently associated with a higher prevalence of sexual assault than the general population. The line of best fit estimated from a linear model showed a significant change over the study period in the reported number of sexual assault cases among disabled people. The results highlight the requirement for further study to explore the needs of people with disabilities with regards to education and other strategies to prevent sexual assault, particularly in the most vulnerable group-those with intellectual disability.

Aberrant activation of the epidermal growth factor receptor (EGFR) is closely associated with malignant progression of tumors. EGFR inhibitors have been used successfully in clinic in the treatment of solid tumors. In the present study, we revealed that BB, a new synthetic quinonazoline derivative, was a potent EGFR inhibitor. BB selectively inhibited EGFR with a IC(50) value of 50 +/- 37 nM, at least 32-fold more potent than suppressed all other ten tested receptor tyrosine kinases including the same family member ErbB2 (IC(50) = 5.6 +/- 3.2 microM). BB effectively abrogated autophosphorylation of the EGF-stimulated EGFR and phosphorylation of its key downstream signaling molecules ERK and AKT in A549 cells. BB was shown to suppress EGF-stimulated proliferation of A549 cells with an apparently lower IC(50) value (0.33 +/- 0.07 microM) than that (2.7 +/- 0.4 microM) for the serum-stimulated cells. BB also inhibited the EGF-independent proliferation of a panel of tumor cells. In addition, BB exhibited anti-angiogenesis activity, as evidenced by antagonizing EGF-induced HMEC-1 migration in vitro, blocking HMEC-1 tube formation, and inhibiting microvessel sprouting from rat aortic rings. Most importantly, BB prominently inhibited in vivo tumorigenesis of NIH3T3 cells specifically driven by the activation-mutated EGFR genes. As reported, normal NIH3T3 cells lack tumorigenicity in nude mice. NIH3T3 cells transfected with the EGFR gene with activating mutation (A750P or L858R) produced rapidly growing xenografts in nude mice. BB, when given orally at 100 mg/kg consecutively for 2 w, prominently inhibited the growth of the xenografts and reduced the number of microvessels. Taken together, the data indicate that BB is a new selective EGFR inhibitor with potent antitumor activity, revealing its potential as a promising anticancer candidate.

It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.

Although many studies have explored emergency services for children, there are few published reports of the utilization of emergency services by children with disabilities. The present study attempts to provide data regarding the utilization of, and factors affecting, emergency department visits by disabled children in Taipei. A general census of 1006 children with disabilities, identified from the Taiwan National Disability Registry System in Taipei, was conducted. The overall response rate was 38%, yielding a sample of 340 disabled children. The results showed that 30.1% of children with disabilities had utilized emergency department services over the past 4 months with an average of 1.4 visits per child. The most common reasons for emergency visits were fever (34.7%), respiratory symptoms (24.2%), abdominal pain (15.8%), injury (7.4%), and epilepsy seizures (7.4%). This study also found, using a logistic regression model, that emergency department utilization may be associated with household economic status and the reported physical health of children with disabilities. The 'deficit' and 'balance' household economic status groups gave odds ratios of 3.902 (95% CI=1.469-10.364) and 3.311 (95% CI=1.249-8.779), relative to the 'surplus' group. The model also indicated that those children with disabilities who were reported as being in poor physical health had 11.359 times (95% CI=2.968-43.469) the likelihood of using emergency care than those whose physical health was in excellent condition. The study suggests that in order to maximize the health of children with disabilities, medical care stakeholders should consider who are the most likely groups to use emergency department services and develop anticipatory guidance or preventive services for this vulnerable population.

The purposes of the present study were to describe the welfare expenditure for people with disabilities and examine its relation to national economic growth from 1991 to 2006 in Taiwan. We analyzed data mainly from the information of population with disabilities, disability welfare expenditure and national economic growth and gross national product (GNP) per capita in Taiwan from 1991 to 2006. The percentage and overtime trend were used to examine the change in disability welfare expenditure, national economic growth and GNP per capita. Taiwan's economy continued its steady expansion on record an annual average growth of 5.4% and GNP per capita of 5.7% for the year 1991-2006. At the same period of time, the registered population with disabilities increased nearly five times (204,158 persons in 1991 to 981,015 persons in 2006), the government disability welfare expenditure was dramatically increasing to over 10 times from 1991 to 2006 (US$ 74 million to US$ 784 million). Although the total disability budget increased, the beneficiary of the individual with disability increased only 2.2 times. In the content of annual welfare budget for people with disabilities, it is difficult to figure out the increase pattern of the budget growth. However, the local government plays a vital role in disability welfare services gradually, it provides more than 85% welfare budget for people with disabilities. Finally, the author emphasizes that government should examine the long term effects of welfare budget allocation shifting from central government to local government to ensure the right of people with disabilities.

Little explicit attention has been given to the generic health profile of staff working for people with intellectual disability in institutions. This study aimed to provide a profile of physical and mental health of staff working in disability welfare institutions, and to examine the possible demographic and organizational factors that explain an association with their health. A cross-sectional questionnaire survey was conducted to analyze 1243 staff (76% response rate) working in 24 institutions in Taiwan. The 36-Item Short-Form (SF-36) Taiwan version was used to measure their generic health status. The mean of Physical component scores (PCS) was slightly higher than Mental component scores (MCS) (50.83 vs. 45.12). With regard to each dimension among PCS, the mean score of Physical functioning (PF) was 57.14 (S.D.=5.93), Role limitations-physical (RP) was 49.88 (S.D.=9.69), Bodily pain (BP) was 52.14 (S.D.=8.09) and General medical health (GH) was 51.50 (S.D.=8.28). Among the MCS, Vitality (VT) was 46.19 (S.D.=6.71); Social functioning (SF) was 46.44 (S.D.=7.58); Role limitations-emotional (RE) was 47.30 (S.D.=11.89) and Mental health (MH) was 43.58 (S.D.=8.81). We found the generic health of staff working for people with intellectual disabilities were significantly lower in PCS and MCS than the Taiwan general population. Influences of staff's demographic and organizational characteristics on their health were also analyzed in the content. This study highlights the authorities and service providers need to continue to develop their awareness and understanding of the experiences that their staff encounters in the organizations, so that they can receive resources to support their positive health in working for people with intellectual disabilities.

Background and Purpose: The critical role of blood supply in the growth of solid tumours makes blood vessels an ideal target for anti-tumour drug discovery. The anti-angiogenic and vascular disrupting activities of C9, a newly synthesized microtubule-depolymerizing agent, were investigated with several in vitro and in vivo models. Possible mechanisms involved in its activity were also assessed., Experimental Approach: Microtubule-depolymerizing actions were assessed by surface plasmon resonance binding, competitive inhibition and cytoskeleton immunofluorescence. Anti-angiogenic and vascular disrupting activities were tested on proliferation, migration, tube formation with human umbilical vein endothelial cells, and in rat aortic ring, chick chorioallantoic membrane and Matrigel plug assays. Western blots and Rho activation assays were employed to examine the role of Raf-MEK-ERK (mitogen-activated ERK kinase, extracellular signal-regulated kinase) and Rho/Rho kinase signalling., Key Results: C9 inhibited proliferation, migration and tube formation of endothelial cells and inhibited angiogenesis in aortic ring and chick chorioallantoic membrane assays. C9 induced disassembly of microtubules in endothelial cells and down-regulated Raf-MEK-ERK signalling activated by pro-angiogenic factors. In addition, C9 disrupted capillary-like networks and newly formed vessels in vitro and rapidly decreased perfusion of neovasculature in vivo. Endothelial cell contraction and membrane blebbing induced by C9 in neovasculature was dependent on the Rho/Rho kinase pathway., Conclusions and Implications: Anti-angiogenic and vascular disruption by C9 was associated with changes in morphology and function of endothelial cells, involving the Raf-MEK-ERK and Rho/Rho kinase signalling pathways. These findings strongly suggest that C9 is a new microtubule-binding agent that could effectively target tumour vasculature.

Aim: Gambogic acid (GA) is the major active ingredient of gamboge, which is secreted from a Chinese traditional medicine, Garcinia hanburyi, which possesses potent antitumor activity. GA3, a new GA derivative, has been shown to possess better water solubility than GA. The aim of the present study was to examine the antitumor activity of GA3 and the mechanism underlying it., Methods: The growth inhibition of cancer cell lines induced by GA3 was assessed using the SRB assay. DAPI staining, flow cytometry, a DNA fragment assay, and Western blot analysis were used to study the apoptotic mechanisms of GA3., Results: GA3 displayed wide cytotoxicity in diversified human cancer cell lines with a mean IC(50) value of 2.15 micromol/L. GA3 was also effective against multidrug resistant cells, with an average resistance factor (RF) that was much lower than that of the reference drug, doxorubicin. Mechanistic studies revealed that GA3-induced apoptosis in HL-60 cells proceeded via both extrinsic and intrinsic pathways, with caspase-8 functioning upstream of caspase-9. In addition, GA3-driven apoptotic events were associated with up-regulation of Bax, down-regulation of Bcl-2 and cleavage of Bid. Moreover, GA3 triggered cytochrome c release from the mitochondria, in particular bypassing the involvement of the mitochondrial membrane potential., Conclusion: Better solubility and a potential anti-MDR activity, combined with a comparable antitumor efficacy, make GA3 a potential drug candidate in cancer therapy that deserves further investigation.

Aim: To design and synthesize a novel class of antitumor agents, featuring the 3-nitroquinoline framework., Methods: Based on the enzyme-binding features of Ekb1, introducing a nitro group at the 3-position of the quinoline core, a series of novel 3-nitroquinolines was designed and synthesized. The inhibition of epidermal growth factor receptor (EGFR) activity by these compounds was evaluated and analyzed by the sulforhodamine B assay for their inhibitory activities toward human epidermoid carcinoma (A431) cells and breast cancer (MDA-MB-468) cells, which are known to overexpress the EGFR kinase., Results: A series of novel 3-nitroquinoline derivatives were synthesized and evaluated for their antiproliferative effect against the EGFR-overexpressing tumor cell lines. Several compounds for concentration-response studies showed prominent inhibitory activities with IC50 values in the micromolar or nanomolar range. The structure-activity relationship was discussed in terms of the inhibitory activity against the proliferation of 2 human carcinoma cell lines., Conclusion: This study was the first to identify new structural types of antiproliferative agents against the EGFR-overexpressing tumor cell lines by the incorporation of the nitro group at the 3-position of the quinoline core structure, providing promising new templates for the further development of anticancer agents.

Glutathione (GSH), as the major small-molecule antioxidant in cells, has been implicated in the regulation of cell proliferation and apoptosis. Salvicine (SAL), a novel diterpenoid quinone compound, exhibits potent antitumor activities both in vitro and in vivo by poisoning topoisomerase II (Topo II) and has entered Phase II clinical trials for cancer therapy. Herein, we provide further evidence that SAL-induced DNA double-strand breaks (DSBs) and apoptosis by GSH depletion drives H2O2 generation and Topo II inhibition. Our data reveal that treatment with SAL results in a pronounced increase in intracellular H2O2 and is accompanied by the occurrence of DNA DSBs and apoptosis in epithelial HeLa cells. Furthermore, SAL was also noted to trigger a dramatic depletion of intracellular GSH via its direct reaction with GSH. Importantly, the introduction of GSH and overexpression of catalase antagonized SAL-mediated DNA DSBs and apoptosis, and the GSH synthesis inhibitor dl-buthionine-[S,R]-sulfoximine reduced SAL-mediated H2O2 generation, indicating that SAL-mediated H2O2 generation is derived from intracellular GSH depletion. Notably, SAL-mediated Topo II inhibition was also concentration-dependently reversed by GSH. Furthermore, we found that Topo II-defective HL-60/MX2 cells were almost completely resistant to SAL-induced DNA DSBs, suggesting that, in addition to its direct inhibitory effect on Topo II, SAL-mediated H2O2 generation may also trigger DNA DSBs via poisoning of Topo II. All these findings together suggest that GSH-depletion-driven H2O2 generation and Topo II inhibition are both critical for SAL-induced DNA DSBs and apoptosis.

Protein tyrosine kinase (PTK) inhibitors represent emerging therapeutics for cancer chemoprevention. In our study, hematoxylin (26) was identified as one of the most remarkable c-Src inhibitors in an orthogonal compound-mixing library (32200 compounds) by using an ELISA-based automated high-throughput screening (HTS) strategy. Interestingly, hematoxylin was found to be an ATP competitive broad-spectrum PTK inhibitor in vitro, with IC50 values ranging from nanomolar to micromolar level. Further studies showed that such inhibition was associated with the PTK phosphorylation and subsequent downstream signaling pathways. The structure-activity relationship assessment of the PTK inhibitory potency of hematoxylin analogues isolated from Heamatoxylon campechianum was in good agreement with the result of concurrent molecular docking simulation: the catechol moiety in ring A and the hematoxylin-like three-dimensional structure were essential for c-Src-targeted activities. Hematoxylin and its natural analogues were substantially validated to function as a new class of PTK inhibitors.

Dihydroartemisinin (DHA), the main active metabolite of artemisinin derivatives, is one of the most effective anti-malarial analogs of artemisinin. In the current study, we found that DHA inhibited the proliferation of a panel of tumor cells originated from different tissue types. DHA effectively induced apoptosis in human promyelocytic leukemia HL-60 cells, which was accompanied with mitochondrial dysfunction and caspases activation. Further studies indicated that DHA-induced apoptosis was iron-dependent. Though DHA slightly elicited superoxide anion, these reactive oxygen species (ROS) contribute little to DHA-induced apoptosis in HL-60 cells. Moreover, DHA time-dependently activated mitogen-activeted protein kinases (MAPKs) and specific inhibition of p38 MAPK, but not c-Jun-NH2-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK), abolished DHA-induced apoptosis, indicating that activation of p38 MAPK is required for DHA-induced apoptosis in HL-60 cells. Altogether, our data uncover that DHA induces apoptosis is dependent of iron and p38 MAPK activation but not ROS in HL-60 cells.

Three new coumarins containing a C(10) terpenoid side chain, clauslactones R - T (1 - 3), together with 14 known coumarins (4 - 17) and 11 known carbazole alkaloids (18 - 28), were isolated from the leaves and stems of Clausena excavata. Their structures were established by detailed spectroscopic analyses. Furthermore, the stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis, which was the first example among coumarins with a C(10) terpenoid side chain. Additionally, compounds 22 and 27 were found to show moderate topoisomerase II inhibitory effects at 50 microM.

Two new sesquiterpenoids, vernobockolides A (1) and B (2), along with five known ones, piptocarphin C (3), piptocarphin F (4), piptocarphin A (5), hirsutolide (6), and beta-d-glucopyranosyl taraxinic ester (7), were isolated from the aerial part of Vernonia bockiana. Their structures were determined by spectroscopic analysis, especially 2D NMR. Among them, compounds 2-6 showed strong cytotoxic activities against mouse lymphoid tumor cell line P388 with the IC(50) values of 1.81, 1.32, 0.77, and 0.73 microM, respectively.

Aim: The molecular mechanisms of the affinity regulation of alphavbeta3 integrin are important in tumor development, wound repairing, and angiogenesis. It has been established that the cytoplasmic domains of alphavbeta3 integrin play an important role in integrin-ligand affinity regulation. However, the relationship of structure-function within these domains remains unclear., Methods: The extracellular and transmembrane domain of alphaIIb was fused to the alphav integrin cytoplasmic domain, and the chimeric alpha subunit was coexpressed in Chinese hamster ovary (CHO) cells with the wild-type beta3 subunit or with 3 mutant beta3 sequences bearing truncations at the positions of T741, Y747, and F754, respectively. The CHO cells expressing these recombinant integrins were tested for soluble fibrinogen binding and the cell adhesion and spreading on immobilized fibrinogen., Results: All 4 types of integrins bound soluble fibrinogen in the absence of agonist stimulation, and only the cells expressing the chimeric alpha subunit with the wild-type beta3 subunit, but not those with truncated beta3, could adhere to and spread on immobilized fibrinogen., Conclusion: The substitution alphaIIb at the cytoplasmic domain with the alphav cytoplasmic sequence rendered the extracellular alphaIIbbeta3 a constitutively activated conformation for ligands without the need of pinside-outq signals. Our results also indicated that the COOH-terminal sequence of beta3 might play a key role in integrin alphaIIb/alphavbeta3-mediated cell adhesion and spreading on immobilized fibrinogen. The cells expressing alphaIIb/alphavbeta3 have enormous potential for facilitating drug screening for antagonists either to alphavbeta3 intracellular interactions or to alphaIIbbeta3 receptor functions.

Pseudolaric acid B (PAB), discovered as a promising angiogensis inhibitor, was served as the anticancer drug lead, and a series of its derivatives were synthesized. Among them, some derivatives, such as 13c- 13k, exhibited potent inhibition on the HMEC-1 cell proliferation and strong cytotoxic activities against the tested six tumor cell lines. The PAB derivatives 13c- 13k also showed significant and specific inhibition on HMEC-1 cell migration in vitro, and only 13d expressed moderate activity against HMEC-1 cell tube formation. The in vitro anticancer tests of the selected natural PAB analogs and the structurally modified PAB derivatives have led to the establishment of a clear structure-activity relationship.

By the guidance of bioassay, one new cytotoxic triterpenoid saponin, 3-O-[beta-D-galactopyranosyl-(1-->2)-beta-D-glucuronopyranosyl] quillaic acid 28-O-beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-fucopyranosyl-(1-->4)]-beta-D-fucopyranoside (1), and five known cytotoxic triterpenoid saponins, vaccaroside E (2), vaccaroside G (3), vaccaroside B (4), segetoside H (5) and segetoside I (6), were isolated from Vaccaria segetalis. Their structures were established on the basis of ESI-MS, IR, extensive NMR ((1)H NMR, (13)C NMR, TOCSY, (1)H-(1)H COSY, DEPT, HMQC, HMBC and ROESY) analyses, chemical degradation, and by comparing with previously reported data. Compounds 1-6 showed moderate cytotoxic activities against LNcap, P-388 and A-549 cell lines with IC(50) values in the range 0.1-12.9 microM.

Human ADAM15 is unique among the A disintegrin and metalloprotease domain (ADAM) family because of the integrin binding motif Arg-Gly-Asp (RGD) within its disintegrin domain. Integrin alpha5beta1 has been reported to bind to ADAM15 in an RGD-dependent manner, but the biological significance of the interaction between ADAM15 and alpha5beta1 is unknown. To characterize the effects of ADAM15 on alpha5beta1-mediated cell adhesion and migration and elucidate the potential mechanism, CHO cells which express endogenous integrin alpha5beta1 were transfected with human ADAM15 cDNA. ADAM15 overexpression led to enhanced cell adhesion and decreased migration on fibronectin, which were suppressed by down-regulation of integrin alpha5. Overexpression of ADAM15 not only increased the cell surface expression of integrin alpha5 but also resulted in a more clustered staining of alpha5 on cell surface, while the beta1 subunit remained unchanged. Unexpectedly, results from immunoprecipitation and immunofluorescence indicated that ADAM15 and alpha5beta1 integrin did not interact directly in CHO cells. We found that ADAM15 expression decreased the phosphorylation of Erk1/2. Consistently, down-regulation of Erk1/2 phosphorylation by MEK inhibitor PD98059 or siRNA against Erk1/2 enhanced the expression of alpha5 on cell surface. By using a B16F10 pulmonary metastasis model, we revealed that overexpression of ADAM15 significantly reduced the number of metastatic nodules on the lung. Taken together, this study reveals for the first time that ADAM15 could drive alpha5 integrin expression on cell surface via down-regulation of phosphorylated Erk1/2. This presents a novel mechanism by which ADAM15 regulates cell-matrix adhesion and migration.