bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tobacco epidemic in Syria
Authors: Ward K D , Eissenberg T , Rastam S , Asfar T , Mzayek F , Fouad M F , Hammal F , Mock J , Maziak W 
Published: May 2006

Background:The Syrian Center for Tobacco Studies (SCTS) was established in response to the smoking epidemic in Syria and lack of local knowledge and expertise to confront it.Objectives:To (1) study tobacco use and local smoking practices using both qualitative and quantitative research methods; (2) develop and test an effective smoking cessation intervention for the Syrian environment; and (3) train Syrian researchers.Methods and results:The Aleppo Household Survey involved a representative sample of adults in Aleppo (2038 subjects, 45.2% men, mean age 35.3 years, response rate 86%). The prevalence of cigarette smoking was 56.9% among men and 17.0% among women, while the prevalence of waterpipe smoking was 20.2% among men and 4.8% among women. Daily use predominated for cigarettes (29.0%), while the opposite was seen in waterpipe use with 10.6% smoking occasionally. Interest in quitting was greater for cigarette than waterpipe smokers (74.0%v48.6%), while quit rates were higher for waterpipe compared to cigarettes (28.2%v16.5%). In-depth ethnographic interviews with smokers show that smoking waterpipe is often viewed as an aesthetic enjoyable experience, while smoking cigarettes is viewed as a mundane anxiety-relieving addiction. Clinical laboratory studies reveal that both waterpipe and cigarette smokers in Syria are exposed to smoke toxicants and exhibit dependence symptoms.Conclusions:All these data have been used iteratively to adapt smoking cessation interventions from developed countries to suit the local Syrian environment. Research conducted in the SCTS to date has provided a fertile training ground for Syrian researchers, as well as for the building of regional collaborations.
Personal, interpersonal, and cultural predictors of stages of cigarette smoking among adolescents in Johannesburg, South Africa
Authors: Brook J S , Morojele N K , Brook D W , Zhang C , Whiteman M 
Published: May 2006

Objective:This study examined the personal, parental, peer, and cultural predictors of stage of smoking among South African urban adolescents.Design:A cross-sectional design was employed. A stratified random approach based on census data was used to obtain the sample. Analyses were conducted using logistic regression.Setting:The study took place in communities in and around Johannesburg, South Africa.Subjects:Participants consisted of 731 adolescents in the age range of 12–17 years old. The sample was 47% male and 53% female, and contained four ethnic classifications: white, black, Indian, and “coloured” (a South African term for mixed ancestry).Methods:A structured, in-person interview was administered to each participant in private by a trained interviewer, after obtaining consent.Main outcome measures:The dependent variables consisted of three stages of smoking: non-smoking, experimental smoking, and regular smoking. The independent measures were drawn from four domains: personal attributes, parental, peer, and cultural influences.Results:Factors in all four domains significantly predicted three different stages of smoking. Personal attributes (internalising and externalising) distinguished among the three stages. Parental factors (for example, affection) reduced the odds of being a regular smoker compared with an experimental smoker or non-smoker, but did not differentiate experimental smokers from non-smokers. Findings from the peer domain (for example, peer substance use) predicted an increase in the risk of being a regular smoker compared with an experimental smoker or non-smoker. In the cultural domain, ethnic identification predicted a decrease in the risk of being a regular smoker compared with an experimental smoker, whereas discrimination and victimisation predicted an increase in the risk of being an experimental smoker compared with a non-smoker.Conclusions:All the domains were important for all four ethnic groups. Four psychosocial domains are important in distinguishing among the three stages of smoking studied. Some predictors differentiated all stages of smoking, others between some of the stages of smoking. Therefore, intervention and prevention programmes which are culturally and linguistically sensitive and appropriate should consider the individual’s stage of smoking.
Vulnerability to smoking after trying a single cigarette can lie dormant for three years or more
Authors: Fidler J A , Wardle J , Henning Brodersen N , Jarvis M J , West R 
Published: May 2006

Objective:To examine the development of smoking behaviour among adolescents who, at age 11, had tried cigarettes just once.Design:A five-year prospective study.Setting:36 schools in South London, England.Subjects:A socioeconomically and ethnically diverse sample of students completed questionnaires annually from age 11–16. A total of 5863 students took part, with an annual response rate ranging from 74–85%. 2041 (35%) provided smoking status data every year.Main outcome measures:Current smoking (smoking sometimes or more often) for the first time. Cotinine assays provided biochemical verification of smoking status.Results:Students who at age 11 reported having tried smoking cigarettes just once (n = 260), but were not smoking at the time, were more likely to take-up smoking at a later age than those that had not tried smoking (n = 1719), even after a gap of up to three years of not smoking. The odds of starting to smoke at age 14 were 2.1 times greater (95% confidence interval 1.2 to 3.5) in the age 11 “one time triers” than the “non-triers”, even once sex, ethnicity, deprivation, parental smoking and conduct disorder were adjusted for.Conclusions:This is the first clear demonstration of a “sleeper effect” or period of dormant vulnerability. Our findings have implications for understanding the development of cigarette use and for policies to reduce smoking in young people. Preventing children from trying even one cigarette may be important, and the design of interventions should recognise adolescents who have smoked just once, several years previously, as potentially vulnerable to later smoking uptake.
Role of snus in initiation and cessation of tobacco smoking in Sweden
Authors: Ramström L M , Foulds J 
Published: May 2006

Objective:To examine patterns of smoking and snus use and identify individual pathways of Swedish tobacco users in order to clarify whether snus use is associated with increased or decreased smoking.Methods:Retrospective analysis of data from a cross-sectional survey completed by 6752 adult Swedes in 2001–2 focusing on identifying tobacco use history by survey items on current and prior tobacco use and smoking initiation and cessation procedures.Results:15% of the men and 19% of the women completing the survey were daily smokers. 21% of the men and 2% of the women were daily snus users. Almost all (91%) male daily smoking began before the age of 23 years, whereas initiation of daily snus use continued throughout the age range (33% of initiation after age 22). 20% of male primary snus users started daily smoking compared to 47% of non-primary snus users. Thus, the odds of initiating daily smoking were significantly lower for men who had started using snus than for those who had not (odds ratio (OR) 0.28, 95% confidence interval (CI) 0.22 to 0.36). Among male primary smokers, 28% started secondary daily snus use and 73% did not. 88% of those secondary snus users had ceased daily smoking completely by the time of the survey as compared with 56% of those primary daily smokers who never became daily snus users (OR 5.7, 95% CI 4.9 to 8.1). Among men who made attempts to quit smoking, snus was the most commonly used cessation aid, being used by 24% on their latest quit attempt. Of those men who had used one single cessation aid 58% had used snus, as compared with 38% for all nicotine replacement therapy products together. Among men who used snus as a single aid, 66% succeeded in quitting completely, as compared with 47% of those using nicotine gum (OR 2.2, 95% CI 1.3 to 3.7) or 32% for those using the nicotine patch (OR 4.2, 95% CI 2.1 to 8.6). Women using snus as an aid were also significantly more likely to quit smoking successfully than those using nicotine patches or gum.Conclusion:Use of snus in Sweden is associated with a reduced risk of becoming a daily smoker and an increased likelihood of stopping smoking.
Mentoring Cambodian and Lao health professionals in tobacco control leadership and research skills
Authors: Ferry L Hyder , Job J , Knutsen S , Montgomery S , Petersen F , Rudatsikira E , Singh P 
Published: May 2006

Design:The aim of the programme was to ultimately affect public health practice and policy in the Kingdom of Cambodia and Lao People’s Democratic Republic (Lao PDR) by training key health professionals to conduct tobacco control research.Setting:Encouraged by the World Health Organization’s Framework Convention on Tobacco Control, a global partnership formed to build effective leadership to develop and guide national tobacco control agendas. The partners were the Ministries of Health (Cambodia and Lao PDR), non-government organisations (Adventist Development and Relief Agency in Cambodia and Laos) and an academic institution (Loma Linda University, Loma Linda, California, USA).Subjects:16 health professionals, 10 from Cambodia and 6 from Lao PDR, were selected by local advisory committees to enter a two-year, intensive tobacco research graduate certificate and research training programme.Intervention:We developed a “Global Tobacco Control Methods” (GTCM) 28 unit certificate programme that was offered in five sessions from September 2003 to September 2005 at the National Institute of Public Health, Phnom Penh, Cambodia. As part of their coursework, the 16 trainees actively participated in the development and implementation of two research projects. In the first project, “Healthy Doc Healthy Patient” (HDHP), trainees adapted an existing, self-administered questionnaire designed to assess health practices and beliefs of medical students in Cambodia and Lao PDR. The second project involved the design of a national prevalence of tobacco use and health beliefs study in Cambodia using a multi-stage, cluster sample method. Trainees were sponsored to attend and present at international tobacco control conferences to enhance their awareness of the tobacco epidemic.Results:As of September 2005, 14 trainees (8 from Cambodia and 6 from Lao PDR) completed the courses in the GTCM certificate programme. The HDHP study sampled four medical school classes (years 3, 4, 5 and 6) in both Cambodia (n  =  330, 71.1% response rate) and Lao PDR (n  =  386, 87.3% response rate). As part of the Cambodian adult tobacco prevalence study in Cambodia, 13 988 adults (ages ⩾ 18 years) were interviewed from all 22 provinces during the summer of 2005. Over the two years, more than half of the trainees participated substantially in local and regional tobacco control and research activities. Programme challenges included the trainees’ limited English language and computer proficiency skills, both of which improved during the two years.Conclusions:With the successful completion of the certificate programme, the remaining two years of the grant will be used to prepare the trainees for positions of leadership within their Ministries of Health and other agencies to implement effective tobacco control policies based on locally-derived research findings.
Economic burden of smoking in China, 2000
Authors: Sung H-Y , Wang L , Jin S , Hu T-W , Jiang Y 
Published: May 2006

Objective:To assess the health-related economic burden attributable to smoking in China for persons aged 35 and older.Methods:A prevalence-based, disease-specific approach was used to estimate the smoking attributable direct costs, indirect morbidity costs, and costs of premature deaths caused by smoking-related diseases. The primary data source was the 1998 China National Health Services Survey, which contains the smoking status, medical utilisation, and expenditures for 216 101 individuals.Results:The economic costs of smoking in 2000 amounted to $5.0 billion (measured in 2000, US$) in total and $25.43 per smoker (⩾ age 35). The share of the economic costs was greater for men than women, and greater in rural areas than in urban areas. Of the $5.0 billion total costs, direct costs were $1.7 billion (34% of the total), indirect morbidity costs were $0.4 billion (8%), and indirect mortality costs were $2.9 billion (58%). The direct costs of smoking accounted for 3.1% of China’s national health expenditures in 2000.Conclusion:The adverse health effects of smoking constitute a huge economic burden to the Chinese society. To reduce this burden in the future, effective tobacco control programmes and sustained efforts are needed to curb the tobacco epidemic and economic losses.
Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248
Authors: Potapova Olga , Laird A. Douglas , Nannini Michelle A. , Barone Angela , Li Guangmin , Moss Katherine G. , Cherrington Julie M. , Mendel Dirk B. 
Published: May 2006

Abstract
Recent achievements in the development of multitargeted molecular inhibitors necessitate a better understanding of the contribution of activity against individual targets to their efficacy. SU11248, a small-molecule inhibitor targeting class III/V receptor tyrosine kinases, including the platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors, KIT and FLT3, exhibits direct effects on cancer cells as well as antiangiogenic activity. Here, we investigated the contributions of inhibiting individual SU11248 target receptors to its overall antitumor efficacy in tumor models representing diverse signaling paradigms. Consistent with previous results, SU11248 was highly efficacious (frequently cytoreductive) in all models tested. To elucidate the specific contributions of inhibition of PDGF and VEGF receptors to the in vivo efficacy of SU11248, we employed two selective inhibitors, SU10944 (VEGF receptor inhibitor) and Gleevec (PDGF receptor inhibitor). SU10944 alone induced a tumor growth delay in all models evaluated, consistent with a primarily antiangiogenic mode of action. In contrast, Gleevec resulted in modest growth inhibition in tumor models in which the cancer cells expressed its targets (PDGFRβ and KIT), but was not efficacious against tumors not driven by these target receptor tyrosine kinases. Strikingly, in all but one tumor model evaluated, the antitumor efficacy of SU10944 combined with Gleevec was similar to that of single-agent SU11248, and was greatly superior to that of each compound alone, indicating that the antitumor potency of SU11248 in these models stems from combined inhibition of both PDGF and VEGF receptors. The one exception was a model driven by an activated mutant of FLT3, in which the activity of SU11248, which targets FLT3, was greater than that of SU10944 plus Gleevec. Moreover, SU10944 combined with Gleevec inhibited tumor neoangiogenesis to an extent comparable to that of SU11248. Thus, the potent efficacy of SU11248 in models representing diverse signaling paradigms results from simultaneous inhibition of individual target receptors expressed both in cancer cells and in the tumor neovasculature, supporting the hypothesis that multitargeted inhibitors have the cumulative antitumor efficacy of combined single-target inhibitors. [Mol Cancer Ther 2006;5(5);1280–9]
Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells
Authors: Saab Raya , Bills Jennifer L. , Miceli Alexander P. , Anderson Colleen M. , Khoury Joseph D. , Fry David W. , Navid Fariba , Houghton Peter J. , Skapek Stephen X. 
Published: May 2006

AbstractMyoblast cell cycle exit and differentiation are mediated in part by down-regulation of cyclin D1 and associated cyclin-dependent kinase (Cdk) activity. Because rhabdomyosarcoma may represent a malignant tumor composed of myoblast-like cells failing to exit the cell cycle and differentiate, we considered whether excess Cdk activity might contribute to this biology. Cyclin D–dependent Cdk4 and Cdk6 were expressed in most of a panel of six human rhabdomyosarcoma-derived cell lines. Cdk4 was expressed in 73% of alveolar and embryonal rhabdomyosarcoma tumors evaluated using a human tissue microarray. When challenged to differentiate by mitogen deprivation in vitro, mouse C2C12 myoblasts arrested in G1 phase of the cell cycle, whereas four in the panel of rhabdomyosarcoma cell lines failed to do so. C2C12 myoblasts maintained in mitogen-rich media and exposed to a Cdk4/Cdk6 inhibitor PD 0332991 accumulated in G1 cell cycle phase. Similar treatment of rhabdomyosarcoma cell lines caused G1 arrest and prevented cell accumulation in vitro, and it delayed growth of rhabdomyosarcoma xenografts in vivo. Consistent with a role for Cdk4/Cdk6 activity as a regulator of myogenic differentiation, we observed that PD 0332991 exposure promoted morphologic changes and enhanced the expression of muscle-specific proteins in cultured myoblasts and in the Rh30 cell line. Our findings support the concept that pharmacologic inhibition of Cdk4/Cdk6 may represent a useful therapeutic strategy to control cell proliferation and possibly promote myogenic differentiation in rhabdomyosarcoma. [Mol Cancer Ther 2006;5(5):1299–308]
Exisulind and guanylyl cyclase C induce distinct antineoplastic signaling mechanisms in human colon cancer cells
Authors: Pitari Giovanni Mario , Li Tong , Baksh Ronnie I. , Waldman Scott A. 
Published: May 2006

AbstractThe nonsteroidal anti-inflammatory drug sulindac is metabolized to sulindac sulfone (exisulind), an antineoplastic agent that inhibits growth and induces apoptosis in solid tumors. In colon cancer cells, the antineoplastic effects of exisulind have been attributed, in part, to induction of cyclic guanosine 3′,5′-monophosphate (cGMP) signaling through inhibition of cGMP-specific phosphodiesterases, which elevates intracellular cGMP, and novel expression of cGMP-dependent protein kinase (PKG) Iβ, the presumed downstream effector mediating apoptosis. Here, inhibition of proliferation and induction of cell death by exisulind was dissociated from cGMP signaling in human colon cancer cells. Accumulation of intracellular cGMP produced by an exogenous cell-permeant analogue of cGMP or a potent agonist of guanylyl cyclase C yielded cytostasis without cell death. Surprisingly, the antiproliferative effects of induced cGMP accumulation were paradoxically less than additive, rather than synergistic, when combined with exisulind. Further, although exisulind induced expression of PKG Iβ, it did not elevate intracellular cGMP and its efficacy was not altered by inhibition or activation of PKG I. Rather, PKG I induced by exisulind may mediate desensitization of cytostasis induced by cGMP. Thus, cytotoxic effects of exisulind are independent of cGMP signaling in human colon cancer cells. Moreover, combination therapies, including exisulind and agents that induce cGMP signaling, may require careful evaluation in patients with colon cancer. [Mol Cancer Ther 2006;5(5):1190–6]
Enhancement of the radiosensitivity of cervical cancer cells by overexpressing p73α
Authors: Liu Stephanie Si , Chan Kelvin Yuen-Kwong , Leung Rebecca Ching-Yu , Law Helen Ka-Wai , Leung Tsin-Wah , Ngan Hextan Yuen-Sheung 
Published: May 2006

Abstract
Radiation therapy is the most effective therapy for cervical cancer in advanced stages. p53 plays a critical role in the cellular response to radiation-induced DNA damage. However, p53 function is often impaired in the presence of the oncoprotein E6 from human papillomavirus, which is often associated with the development of cervical cancer. p73, a p53 family member, is highly similar to p53, but is resistant to the degradation by human papillomavirus E6. In this study, we investigated the role of p73α in relation to cellular radiosensitivity in the p53-impaired cervical cancer cells. Radiosensitivity and irradiation-induced apoptotic cell death were examined in the exogenous overexpressed p73α- and p53-impaired cells. Our results showed that the endogenous p73α expressed only in the radiosensitive cervical cancer C4-1 cells, but not in the radioresistant SiHa, Caski, and HeLa cells. Overexpression of exogenous p73α by transfection in the radioresistant cells resulted in a significant increase of cellular sensitivity to radiation. Enhanced radiosensitivity in p73α-transfected cells was attributed by increase of cellular apoptosis. Coactivation of p21 was also observed in the p73α-transfected cells upon radiation treatment. In summary, our findings suggested that p73α is an important determinant of cellular radiosensitivity in the p53-impaired cervical cancer cells. [Mol Cancer Ther 2006;5(5):1209–15]
DNA mismatch repair and p53 function are major determinants of the rate of development of cisplatin resistance
Authors: Lin Xinjian , Howell Stephen B. 
Published: May 2006

Abstract
As opposed to factors that control sensitivity to the acute cytotoxic effect of cisplatin, little is known about the factors that determine the rate at which resistance develops. This study examined how loss of p53 or DNA mismatch repair (MMR) function affected the rate of development of resistance to cisplatin in human colon carcinoma cells during sequential cycles of cisplatin exposure that mimic the way the drug is used in the clinic. We used a panel of sublines molecularly engineered to express either the MMR- and p53-proficient phenotype or singly or doubly deficient phenotypes. Loss of either MMR or p53 alone increased the rate of development of resistance to cisplatin by 1.8- and 2.4-fold, respectively; however, loss of both MMR and p53 increased the rate by 4.8-fold. Inhibition of DNA polymerase ζ by suppression of the expression of its REV3 subunit eliminated the increased rate of development of resistance observed in the MMR-deficient cells. Loss of p53 or MMR increased the steady-state level of REV3 and of REV1 mRNA; loss of both functions increased these levels much further by a factor of 20.2-fold for REV3 and 10.3-fold for REV1. The basal level of homologous recombination measured using a reporter vector was 1.3- to 1.7-fold higher in cells that had lost either p53 or MMR function, and 2.6-fold higher in cells that had lost both. In the p53- and MMR-proficient cells, cisplatin induced a 17-fold increase in homologous recombination even when the recombining sequences that did not contain cisplatin adducts; the magnitude of induction was even greater in cells that had lost either one or both functions. We conclude that separate from effects on sensitivity to the acute cytotoxic effect of cisplatin, loss of MMR, especially when combined with loss of p53, results in rapid evolution of cisplatin resistance during sequential rounds of drug exposure that is likely mediated by enhanced mutagenic translesion synthesis. The DNA damage response activated by cisplatin is accompanied by a p53- and MMR-dependent increase in homologous recombination even between adduct-free sequences. [Mol Cancer Ther 2006;5(5):1239–47]