, 2006; Ma et al., 2004; Yu et al., 2002). A large subset of Chinese American males is less likely to report consideration of physician Temsirolimus CCI-779 advice to quit smoking and hence is less likely to have adequate knowledge of early cancer symptoms (Fu et al.; Yu et al.). Typically, Chinese American smoking behaviors are culturally bound with adverse health issues related to smoking being dealt within the context of Chinese culture and traditional medicine (Hu et al., 2006; Yu et al.). There is a dearth of culturally appropriate smoking intervention programs to promote cessation within Chinese American communities. Accessibility to culturally unfamiliar intervention programs has not led to significant changes in smoking behaviors (Spigner, Yip, Huang, & Tu, 2007).

Research to date, however, has identified intervention strategies that could effect better quit and cessation outcomes. Two studies have shown that physician-led smoking interventions may lead to higher quit and cessation rates among Chinese Americans (Ferketich et al., 2004; Spigner et al.). Although knowledge about the adverse impact of tobacco use on the health of Chinese Americans in NYC is low, general awareness of the city’s restrictive ordinances against smoking in public places has created a need in the community for culturally and linguistically specific smoking prevention and cessation programs. The city’s Chinese community is composed largely of new immigrants, who, like their predecessors, adhere to Chinese cultural norms (Shelley et al., 2004). Two studies by Spigner et al. (2007) and Yu et al.

(2002) found that former Chinese smokers may not consider prevailing approaches to prevention and cessation, particularly nicotine replacement therapy (NRT), to be effective, which may have led to limited uptake in comparison with ��cold turkey�� methods. The authors note that the effectiveness of culturally appropriate therapies, especially those that relate to introduction of NRT, need further study. Prochaska and DiClemente’s (1983) Transtheoretical Model (TTM) has often been applied to smoking cessation programs to stimulate behavior change. The core constructs of TTM, around which other dimensions are organized, are the stages of change: precontemplation, contemplation, preparation, action, and maintenance. These represent ordered categories to change problem behavior along a continuum of motivational readiness.

Matching interventions to the specific stage of change is important to promoting retention in smoking cessation interventions (Prochaska, 1996). Few intervention studies, however, have targeted Chinese Americans, the largest subset of Asian ethnic groups in the United States. A generic Asian QUIT program Batimastat was first developed and later tailored to specifically meet the cultural and linguistic needs of several Asian American ethnic communities, including Chinese (Ma, 1999).

25, which Volasertib aml has been suggested for nonpregnant smokers. FUNDING The original Smoking, Nicotine and Pregnancy (SNAP) randomized control trial was supported by a grant from the National Institute for Health Research (NIHR) Health Technology Assessment Programme (grant number 06/07/01). DECLARATION OF INTERESTS The views and opinions expressed in this article are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health. T.C. and S.L. are members of the UK Centre for Alcohol and Tobacco Studies; T.C. and S.C. are members of the NIHR National School for Primary Care Research, and J.T. is funded via an NIHR fellowship. ACKNOWLEDGMENTS We would like to thank Mira V. Doig and ABS Laboratories for their contribution in blood cotinine analyses and interpretation of the blood cotinine values.

We would also like to thank Dr Sheila Sharp and the University of Dundee for their contribution in analyzing the salivary cotinine samples.
Nearly all adults who smoke start smoking before the age of 26, making tobacco use a pediatric problem (U.S. Department of Health and Human Services, 2012). In the United States, each year, over a million adolescents become regular users of tobacco (Stevens, Barron, Ledbetter, Foarde, & Menard, 2001). The decline in youth smoking during the 1990s has stalled, and the Surgeon General��s 2012 report on smoking among adolescents called for greater attention to this national epidemic (U.S. Department of Health and Human Services, 2012). According to recent U.S.

surveys, 23% of high school students and 36% of young adults aged 18�C25 use tobacco, the latter being the highest smoking rate among all age groups (Centers for Disease Control and Prevention, 2012; Substance Abuse and Mental Health Services Administration, 2010). Smoking rates are further elevated among youth with psychiatric disorders such as attention deficit, conduct disorder, depression, anxiety, and alcohol or illicit drug dependencies (Mermelstein, 2003). A study of adolescent psychiatric inpatients found that 60% were current smokers with 40% smoking a pack or more daily (Ramsey, Brown, Strong, & Sales, 2002). Another study reported that half of 14- to 17-year olds with anxiety symptoms and two thirds of those with depressive symptoms used tobacco (Dudas, Hans, & Barabas, 2005). The reciprocal also is true.

Youth who smoke are at increased risk of developing mental illness compared with nonsmokers, including major depressive disorder, agoraphobia, generalized anxiety disorder, and panic disorder (Chang, Sherritt, & Knight, 2005; Choi, Patten, Gillin, Kaplan, & Pierce, 1997; Hanna & Grant, 1999; Johnson et al., 2000). Carfilzomib Decreasing youth smoking is imperative for addressing chronic use and the incidence of tobacco-related illnesses (Al-Delaimy, White, & Pierce, 2006).

Finally, we were interested in the possibility that tobacco dependence (i.e., the HSI) might lie along the causal pathway and at least partially account for any significant relations of menthol use status and smoking abstinence. To address this possibility, we used a nonparametric bootstrapping procedure to estimate the significance of an indirect things effect in single mediation models with 5,000 resamples with replacement from the dataset (MacKinnon, 2008). Continuous abstinence was treated as an ordinal variable with one observation (i.e., abstinent through which postquit week) for every participant. Therefore, the bootstrapping was performed by resampling individual ordinal outcomes from the dataset.

Because the CR logit model operates through a logistic regression approach for a binary smoking abstinence variable, with observations conditional on being continuously abstinent through each time point (thus, each individual contributes a varied number of binary observations), the corresponding estimates of the coefficients were standardized in calculating the indirect effect and the proportion of total effect that was mediated [] (MacKinnon, Lockwood, Brown, Wang, & Hoffman, 2007). These analyses were conducted using R version 2.13.0 (R Core Team, 2012) and were adjusted for age, gender, total annual household income, educational level, employment status, partner status, and stage. RESULTS Participant Characteristics Participants (N = 183; 95 non-Hispanic White and 88 non-Hispanic Black smokers) were 45.9 years of age (��10.31) on average. In the overall sample, continuous abstinence rates were 25.

7% at week 1, 19.1% at week 2, and 15.9% at week 3. There were fewer menthol than nonmenthol using participants (83 menthol users vs. 100 nonmenthol users). Among menthol users, continuous short-term smoking abstinence rates were 19.3% at week 1, 14.5% at week 2, and 12.1% at week 3. Among nonmenthol users, continuous short-term smoking abstinence rates were 31.0% at week 1, 23.0% at week 2, and 19.0% at week 3. Among White participants, 18.9% (n = 18) endorsed current menthol cigarette use, whereas 73.9% (n = 65) of Black participants endorsed current menthol cigarette use. White menthol smokers had higher HSI scores (4.28��1.53) as compared with Black menthol (3.42��1.27) smokers (t = ?2.43, p = .02). Likewise, White menthol smokers had higher HSI scores than White nonmenthol smokers (3.

75��1.30), although this difference was not statistically significant (p = .14). Participant characteristics by menthol use Carfilzomib status are in Table 1. Table 1. Participant Characteristics by Menthol Use Status Preliminary Analyses Preliminary analyses indicated significant differences between menthol and nonmenthol users by race and employment status. Specifically, most menthol users were Black, whereas most nonmenthol users were White participants.

As antismoking overnight delivery advocate Godshall (1999) has asserted, ��[W]ith unprecedented future legal protection granted by the state [attorneys general] in exchange for money, it appears that the tobacco industry has emerged from the state lawsuits even more powerful.�� The Food and Drug Administration With regulation of the industry (the Family Smoking Prevention and Tobacco Control Act), a new experiment in tobacco control may begin (Kennedy, Cornyn, Waxman, & Davis, 2007). Theoretically, such regulation would eliminate nicotine and toxic agents from cigarettes. However, it is unlikely that the Food and Drug Administration (FDA) will be allowed to eliminate the industry. Thus, the outcome of regulation, based on the BEM, will involve new contingencies that may limit the industry’s life or prolong it.

Complex contingencies produce dependence Since the World Health Organization tobacco treaty (Framework Convention Alliance, 2008), the processes now unfolding are a function of changes in the antitobacco subculture in the United States, western Europe, and other nations. This suggests future curtailments as nations develop antitobacco cultures, but the timing and degree remain uncertain. One reason for this is that the industry actively pursues systems that guarantee long-term existence. Its ability to lobby legislators is partially based on incredible wealth acquired by selling an addictive product. The industry has also systematically supported all levels of society, from funding local fire departments to funding science in our most prestigious universities (Chapman & Shatenstein, 2001).

Its business success attracts investors, including pension funds. Thus, efforts to curtail the industry may hurt the retirement and health services of thousands of workers in the United States alone. Theoretically, such contingencies cause legislators to pause in their efforts to curtail a deadly industry. Research to confirm this is warranted. The tobacco industry funds academic research in the context of academic freedom norms, offering the public possible ��cures�� for cancer, heart disease, and so forth. By targeting treatment first and smoking cessation second, the industry ensures minimal effect on its business. These industry contingencies support research and clinical care by the very professionals who should be leading efforts against a harmful industry.

Potentially biased behavior of academics is supported by cultural contingencies of academic freedom. Recognizing these interacting contingencies is a step toward altering them. More research should focus on the direct and indirect effects of industry support for civil governments as well as academic investigators. The right to smoke guarantees new addicts Concepts Entinostat of self-control and personal decision making prevail in most cultures.

Measures Demographics Information this research was collected on demographics and medical history. Women used a calendar to report the timing of their menstrual cycles for the past three months. Smoking History Participants were asked to report their frequency of smoking, preferred brand of cigarette, years of smoking, and number of quit attempts. Biochemical Confirmation of Smoking CO levels were measured using a Vitalograph Breath CO (Vitalograph, Inc., Lenexa, KS). Urine cotinine was analyzed on site by reversed-phase high-performance liquid chromatography with ultraviolet detection modified from the literature (Hariharan, VanNoord, & Greden, 1988) to include a micro acid back extraction cleanup step. The lower limit of quantitation for cotinine was set to 25 ng/ml.

Nicotine Dependence Nicotine Dependence was assessed using the six-item Fagerstr?m Test for Nicotine Dependence (range = 1�C10; Heatherton, Kozlowski, Frecker, & Fagerstr?m, 1991). Cravings to Smoke Participants evaluated their current cravings to smoke using a Visual Analogue Scale (VAS, range 1�C100). Current Mood Participants were asked to report their current mood in response to bipolar adjectives assessing positive affect (i.e., cheerful, happy) and negative affect (i.e., sad, depressed; Mongrain & Tramabakoulos, 1997) using VAS-mood scales (range 1�C100). Lifestyle Questionnaire The Lifestyle Questionnaire included measures of nicotine dependence, cravings to smoke, and current mood as described above. The Lifetime Questionnaire also included questions assessing alcohol use, caffeine consumption, exercise patterns, and eating behaviors in order to reduce demand characteristics.

Mood Induction Similar to our previous work (McKee, Wall, Hinson, Goldstein, & Bissonnette, 2003), a prerecorded cassette of segments of musical pieces was played during the 10-min mood induction and the 50-min mood-maintenance phase. Examples of musical pieces used to induce a positive mood were Beethoven��s ��Symphony No. 3, Eb Major�� and Yanni��s ��Aria.�� Selections used to induce a negative mood included Beethoven��s ��Piano Trio No 4, D Major�� and Pink Floyd��s ��Shine on You Crazy Diamond.�� Statistical Analyses Analyses of variance (ANOVAs) were run to determine whether baseline differences existed across gender and treatment condition.

In order to ensure that the mood manipulation was effective, a repeated measures multivariate analysis of variance (MANOVA) was performed with mood condition (Negative Mood Induction, Positive Mood Dacomitinib Induction, Neutral Mood) and gender as the between-subjects independent variables and ratings of positive affect and negative affect at two timepoints (pre-mood induction, post-mood induction) as the two dependent variables. To test the primary research questions, univariate ANOVAs were used to analyze the main and interactive effects of mood conditions and gender on smoking behavior.

5%), and at delivery 84 (8.8%) of the participants achieved validated cessation. Table 1. Participant Characteristics for Cessation inhibitor Carfilzomib at 1 Month and Delivery Factors Associated With Smoking Cessation at 1 Month At 1 month, in the univariate analysis, women who finished full time education when they were >16 years had greater odds of cessation; women who had a higher baseline cotinine levels, and those who were recruited from trial site 4, were found to have lower odds of cessation (Table 2). The final multivariable model shows which baseline variables were independently associated with validated cessation at 1 month. Women who were aged >16 years when they finished full time education (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.24�C2.67, p = .002) had significantly increased odds of achieving validated cessation.

Participants who had a higher baseline cotinine (OR = 0.94, 95% CI = 0.91�C0.96, p < .001 for a 10ng/ml increase) had significantly lower odds of cessation at 1 month after quit date. The effect of trial recruitment site 4 did not remain significant when added to the multivariable model (OR = 0.69, 95% CI = 0.36�C1.34, p = .277). Table 2. Univariate and Multivariate Associations With Validated Cessation at 1 Month Factors Associated With Smoking Cessation at Delivery Table 3 shows the univariable and multivariable associations with validated cessation at delivery; the univariable results found women who finished full time education at >16 years and had lower baseline cotinine levels had increased odds of cessation and those with higher baseline cotinine levels had lower odds of cessation.

In the final multivariable model, women who continued school beyond the compulsory minimum age (16 years) were more likely to stop smoking (OR = 1.89, 95% CI = 1.16�C3.07, p = .010) and women with a higher baseline cotinine level were less likely to achieve cessation (OR = 0.96, 95% CI = 0.92�C0.99, p < .010). Table 3. Univariate and Multivariate Associations With Validated Cessation at Delivery DISCUSSION Main Findings We found that, among participants in a trial of transdermal nicotine patches in pregnancy, smoking cessation of 1-month duration and also until delivery were positively associated with finishing full time education beyond the compulsory age of 16 years and negatively associated with baseline cotinine levels.

Leaving school at 16 years is a marker of social disadvantage and also an indicator of lower socioeconomic status, which is associated with decreased probability of quitting. Strengths and Limitations The main limitation of this study was that a relatively restricted variety of variables were collected in the trial; in particular, there were few Cilengitide behavioral or socioeconomic measures, which, in some studies have been shown to influence cessation (Schneider et al., 2010). It also remains possible that differences in cessation rates observed in early and late pregnancy might be explained by unmeasured factors.

The sample may be underpowered to resolve the nonreplication, and more work is needed to be done to resolve the results. In conclusion, our results provide further evidence that chromosome 20 harbors genetic www.selleckchem.com/products/U0126.html elements influencing ND. The comparison of our results with the literature supports the hypothesis that the locus has multiple mutant alleles influencing smoking behavior. Funding National Institutes of Health (DA12854 to P.A.F.M., DA024722 to S.F.S., DA019951 to M.L.P.); the Doctoral Programs of Public Health, University of Helsinki to U.B.; Helsinki Biomedical Graduate School to J.H.; Academy of Finland Postdoctoral Fellowship to A.L.; and the Center of Excellence in Complex Disease Genetics, Academy of Finland to J.K.

Declaration of Interests JK has served as a consultant to Pfizer in 2008 on pharmacogenetics of smoking cessation and has received a GRAND award funded by Pfizer Inc. UB has served as a consultant to Pfizer in 2008 on ND measurements. Supplementary Material Supplementary Figure 1 can be found online at http://www.ntr.oxfordjournals.org. Supplementary Data: Click here to view. Acknowledgments KK-V and JH contributed to the manuscript equally. The authors would like to thank the personnel of the FIMM Technology Center (Microsatellite Genotyping Group) for excellent technical assistance and to pay tribute to two recently deceased project collaborators, Professor Leena Peltonen and Dr. Richard D. Todd.
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality in the United States (Hurd, 2000). In 1996, 6.

0% of the United States population was estimated to have COPD (Mannino, 2002). The economic burden of COPD in the United States is calculated at greater than $14 billion and in 1998, was responsible for 14.2 million ambulatory visits to hospitals or physician offices (Mannino, 2002). However, this figure is likely to be higher now, as the prevalence of COPD in the United States has been increasing (Hurd, 2000; Mannino, Homa, Akinbami, Ford, & Redd, 2002). Understanding the key preventable risk factors for COPD is therefore essential to reducing the impact of this disease on the community. Cigarette smoking is known to be the single most important preventable risk factor for COPD (Mannino, 2002; Mannino et al., 2002). In recent years, there has been growing interest in the relationship between mental disorders and COPD among adults.

Several epidemiologic and clinical studies have found high rates of mood and anxiety disorders among adults with COPD (Di Marco et al., 2006; Goodwin, Chuang, Simuro, Davies, & Pine, 2007; Janson, Bjornsson, Hetta, & Boman, 1994; Karajgi, Rifkin, Doddi, & Kolli, 1990; Light, Merrill, Despars, Gordon, & Mutalipassi, 1985; van Manen GSK-3 et al., 2002; Yellowlees, Alpers, Bowden, Bryant, & Ruffin, 1987; Yohannes, Baldwin, & Connolly, 2000).

Interestingly, virtually all the intrahepatic COR93-specific CD8+ T cells in HBV transgenic mice strongly expressed the co-inhibitory molecule compound library PD-1 on day 1.5 ex vivo and remained so until day 28 (Figure 2E), while PD-1 expression was virtually absent in their counterparts in cVac infected nontransgenic animals (Figure 2J), suggesting that PD-1 signaling may have contributed to the functional impairment of intrahepatic COR93-specific CD8+ T cell responses in HBV transgenic mice. To determine if the dysfunctional T cell responses in the HBV transgenic liver reflect active suppression of functional differentiation by PD-1 signaling, the COR93-specific TCR transgene was crossed for two generations onto a MHC class I matched PD-1 deficient background (kindly provided by Dr.

Arlene Sharpe, Harvard Medical School) [31], yielding PD-1 deficient COR93-specific TCR transgenic animals. Equal numbers of PD-1 deficient and wild type COR93-specific na?ve CD8+ T cells were adoptively transferred into HBV-transgenic mice, and analyzed for expansion, IFN�� producing ability and Granzyme B (GrB) expression on day 7 after adoptive transfer. The results were correlated with the degree of liver damage and HBV gene expression monitored by serum alanine aminotransferase (ALT) activity and HBV gene Northern Blot (NB) analysis, respectively. As shown in Figure 3A, PD-1 deficient COR93-specific CD8+ T cells expanded much more vigorously in the liver than wild type COR93-specific CD8+ T cells, and a larger fraction of PD-1 deficient T cells expressed IFN�� and Granzyme B (Figure 3B and C) and they induced a more severe liver disease, monitored as serum alanine aminotransferase (ALT) activity (Figure 3D).

Furthermore, HBV gene expression was significantly reduced in the recipients of PD-1 deficient COR93-specific CD8+ T cells but not in the wild type T cell recipients (Figure 3E), reflecting the superior cytolytic and interferon gamma-producing activity of the PD-1 deficient cells. Collectively, these results indicate that PD-1 signaling suppresses the expansion and functional differentiation of HBV-specific CD8+ T cells after antigen recognition in the liver. Figure 3 PD-1 deficient COR93-specific CD8+ T cells develop cytolytic ability in the liver of HBV transgenic mice.

Intrahepatic priming of HBV-Specific na?ve T cells after adoptive transfer into HBV transgenic mice Because the hepatocytes in HBV transgenic mice replicate HBV at high level and release viral particles and subviral antigens into the circulation [19], HBV derived antigen could be presented to na?ve T cells either by the hepatocytes themselves or by professional antigen Drug_discovery presenting cells (pAPCs) that acquire virus particles and/or subviral antigens in the liver or in peripheral lymphoid organs.

Because it is a more common outcome than alternative measures (Keely, Hughes, & Carpenter, 2001), it enhances statistical power. Continuous abstinence may not capture those who quit later in the process, which is a particular problem in cessation-induction studies (Velicer, Prochaska, selleckchem Nilotinib Rossi, & Snow, 1992). Most people who achieve point prevalence abstinence in a typical aid-to-cessation study have achieved long-term abstinence (Keely et al., 2001). The point prevalence rate provides an unbiased estimate of the rate of prolonged abstinence (Keely et al., 2001; Stead, Perera, Bullen, Mant, & Lancaster, 2008). For these reasons, the U.S. Public Health Service guideline on tobacco dependence uses point prevalence as the preferred outcome (Fiore et al., 2008).

Counterarguments in favor of prolonged abstinence are that the aim of smoking cessation is to get smokers to quit and stay quit forever, the only outcome known to improve health (Peto & Doll, 2006). One third of those who achieve point prevalence abstinence are not long-term abstainers (Keely et al., 2001), and this proportion might be much higher in cessation-induction studies than in aid-to-cessation studies (e.g., Aveyard, Griffin, Lawrence, & Cheng, 2003). There also has been disagreement about how to count enrolled participants who defaulted on follow-up. Some researchers advocate counting such people as smokers (Hughes et al., 2003; West, Hajek, Stead, & Stapleton, 2005), and some evidence indicates that in typical aid-to-cessation studies this is the case (Foulds et al., 1993).

Others have argued that this assumption is probably not appropriate for cessation-induction studies (Velicer, Prochaska, Fava, Laforge, & Rossi, 1999), although no empirical evidence has identified the smoking status of defaulters to follow-up in cessation-induction studies. In an effort to reconcile such differences, the SRNT working group examined these issues and the evidence and recommended that prolonged abstinence, meaning abstinence for either 6 or 12 months, be used as the primary outcome in smoking cessation studies (Hughes et al., 2003). In cessation-induction trials, outcomes should be measured at some (arbitrary) point after the start of the intervention. The period chosen should allow enough time for the intervention to induce initially unwilling quitters to begin a quit attempt.

In aid-to-cessation studies, abstinence measures are tied to the quit day. West AV-951 et al. (2005) proposed the Russell Standard measure of prolonged abstinence. The present paper describes a process for defining how prolonged abstinence is measured and what counts as a treatment success, extending the recommendations of the SRNT working group. Recently, a new approach to treating smokers has been tested in clinical trials. Smokers who did not intend to quit were randomized to either long-term nicotine replacement therapy (NRT) or placebo and given advice on how to cut down on cigarettes.

In recent years, oral fluoropyrimidines have been evaluated in oesophagogastric cancer. Capecitabine has been shown to have equivalent activity to 5-FU, with a different selleck bio safety profile (Cunningham et al, 2008). It is likely that modification of the wTCF regimen by substituting an oral fluoropyrimidine for 5-FU would maintain activity, while potentially improving safety and convenience. Novel biological targeted agents, such as bevacizumab, cetuximab, and panitumumab, have also improved outcomes in a range of cancers including colorectal, breast, and lung cancer (Hurwitz et al, 2004; Sandler et al, 2006; Jonker et al, 2007; Miller et al, 2007; Van Cutsem et al, 2007). Some of these agents are currently being evaluated in advanced oesophagogastric cancer.

Weekly docetaxel-based chemotherapy provides a useful chemotherapy backbone for evaluation of targeted agents, and the AGITG is currently evaluating the efficacy and safety of adding the epidermal growth factor receptor-targeted antibody, panitumumab, to wTCF chemotherapy as treatment for this disease. Acknowledgments This study was supported by an unrestricted educational grant by Sanofi-Aventis. Drugs were provided by Sanofi-Aventis and Roche. Numerous individuals from many institutions participated to complete this study. We thank everyone involved for their efforts.
Liver cancer, especially hepatocellular carcinoma (HCC), is a malignancy of worldwide significance (1,2). Although the increased global incidence of HCC is correlated with the increasing prevalence of chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) (2,3), some of the mechanisms associated with the initiation and progression of this disease remain elusive.

Dysregulation of the hedgehog (HH) pathway is implicated in the carcinogenesis of multiple tissue types (1,4). HH was first identified in Drosophila during screening of genes that are important in early embryonic development (5). This pathway is activated during binding of sonic HH (SHH) or Indian hedgehog (IHH) ligand to their receptors, Patched (PTCH). The unbound PTCH acts as a tumor suppressor that can bind to and repress smoothened (SMOH), thereby preventing the SMOH proto-oncoprotein from activating downstream of the transcription factors, such as glioma-associated oncogene-1 (GLI1). By contrast, the ligand-bound PTCH facilitates the release of SMOH and activation of GLI1 resulting in the transcription of target genes including PTCH and GLI1 (1). The HH activation AV-951 has been observed in other types cancers such as basal cell carcinomas of the skin (6-9), prostate cancer (10,11), lung cancer (12,13), gastrointestinal cancers (14-19), breast cancer (20,21), and ovarian cancer (22).