Psychosocial measures reported by parents in studies of skin cancer prevention

Background. Because it is important to minimize children's sun exposure to reduce skin cancer risk, much of the extensive skin cancer prevention literature consists of studies of children's sun protection, sun avoidance and ultraviolet radiation (UVR) exposure. Little attention has been focused on the measurement of psychosocial constructs in these studies. Identification of the psychosocial correlates or determinants of children's skin cancer risk or risk-reduction behavior is critical to more fully understand and predict behavior. Furthermore, psychosocial variables may be influenced by interventions to reduce risk. Thus, it is important to examine the psychosocial measures used in studies of children's skin cancer prevention. Information on the validity and reliability of psychosocial measures may increase confidence in study findings based on these measures. In particular, self-efficacy and barriers are key constructs in several major theoretical frameworks and parental measures have been associated with children's sun protection. However, there is conceptual overlap of self-efficacy and barriers measures and little is known about the psychometric properties of these measures.^ Study Aims and Methods. The overall goal of this dissertation was to examine the measurement of psychosocial constructs relevant to children's skin cancer prevention. Because children depend primarily on their parents for skin cancer prevention, measures of parents' psychosocial constructs are the focus. Study 1 was a systematic review of parental psychosocial measures used in studies of children's sun protection, sun avoidance and UVR exposure. The specific aims of Study 1 were to (1) describe psychosocial measures reported by parents, including available information on the psychometric properties of these measures and their use in analyses and (2) provide recommendations for the development, refinement and standardized reporting of measures. ^ Study 2 examined the psychometric properties of measures of parental self-efficacy and barriers regarding children's sun protection. Melanoma patients (N=205) who were parents of children ≤ 12 years of age completed a telephone interview that included self-efficacy and barriers measures specific to sunscreen, clothing, shade and limiting time outdoors. The specific aims of Study 2 were to (1) use a confirmatory factor analytic approach to examine the factorial validity of parental self-efficacy and barriers measures, (2) examine the convergent and discriminant validity of behavior-specific measures of self-efficacy and barriers and (3) assess the reliability of item and scale measures.^ Results. In Study 1, a search of standard databases yielded 48 eligible studies. Most studies assessed only one or two psychosocial constructs. Knowledge was measured most frequently. There was little discussion of measure source, development, theoretical background or psychometric properties, besides internal consistency reliability. There was conceptual overlap of some measures. In Study 2, confirmatory factor analytic findings supported the factorial validity of the self-efficacy and barriers measures. When all eight self-efficacy and barriers measures were included in the same model, a modified eight-factor model adequately fit the data, providing preliminary evidence that the measures are distinct. Measure associations supported the convergent validity of all measures and the discriminant validity of most measures. The self-efficacy and barriers measures were reliable.^ Conclusions. Recommendations based on the literature review include developing and refining psychosocial measures based on theory. Describing a measure's theoretical basis and psychometric properties would facilitate critical evaluation. Standardized reporting of source, development, theory, construct, items and analytic role would facilitate comparison of findings, continual refinement and future applications of measures. In the validation study, self-efficacy and barriers measures were examined in a sample of parents with a personal history of melanoma. Findings suggested that these measures are valid and reliable for use in studies of children's sun protection. There was preliminary evidence that these measures are distinct but additional study is needed. ^

Early life risk factors and puberty implications for cancer prevention

Earlier age at puberty is a known risk factor for breast cancer and suspected to influence prostate cancer; yet few studies have assessed early life risk factors for puberty. The overall objectives was to determine the relationship between birth-weight-for-gestational-age (BWGA), weight gain in infancy and pubertal status in girls and boys at 10.8 and 11.8 years and who were born of preeclamptic (PE) and normotensive (NT) mothers. Data for this study were collected from hospital and public health medical records and at a follow-up visit at 10.8 and 11.8 years for girls and boys, respectively. We used stratified analysis and multivariable logistic regression modeling to assess effect measure modifier and to determine the relationship between BWGA, weight gain in infancy and childhood and pubertal status, respectively. ^ There was no difference in the relationship between BWGA and pubertal status by maternal PE status for girls and boys; however, there was a non-significant increase in the odds of having been born small-for-gestational-age (SGA) in girls who were pubertal for breast or pubic hair Tanner stage 2+ compared to those who B1 or PH1. In contrast, boys who were pubertal for genital and pubic hair Tanner stage 2+ had lower odds of having been born SGA than those who were prepubertal for G1 or PH1. ^ In girls who were pubertal for breast development, the odds of having gained one additional unit SD for weight was highest between 3 to 6 months and 6-12 months for those who were B2+ vs. B1. For pubic hair development, weight gain between 6-12 months had the greatest effect for girls of PE mothers only. In boys, there were no statistically significant associations between weight gain and genital Tanner stage at any of the intervals; however, weight gain between 3-6 months did affect pubic hair tanner stage in boys of NT mothers. This study provide important evidence regarding the role of SGA and weight gain at specific age intervals on puberty; however, larger studies need to shed light on modifiable exposures for behavioral interventions in pregnancy, postpartum and in childhood.^

Cancer patients' attitudes toward cancer trials

Background. Accurate measurement of attitudes toward participation in cancer treatment trials (CTs) and cancer prevention trials (CPTs) across varied groups could assist health researchers and educators when addressing attitudinal barriers to participation in these trials. ^ Methods. The Attitudes toward Cancer Trials Scales (ACTS) instrument development was based on a conceptual model developed from research literature, clinical practice experience, and empirical testing of items with a sample of 312 respondents. The ACTS contains two scales, the Cancer Trials (CT) scale (4 components; 18 items) and the Cancer Prevention Trials (CPT) scale (3 components; 16 items). Cronbach's alpha values for the CT and CPT scales, respectively, were 0.86 and 0.89. These two scales along with sociodemographic and cancer trial history variables were distributed in a mail survey of former patients of a large cancer research center. The disproportionate stratified probability sampling procedure yielded 925 usable responses (54% response rate). ^ Results. Prevalence of favorable attitudes toward CTs and CPTs was 66% and 69%, respectively. There were no significant differences in mean scale scores by cancer site or gender, but African Americans had more favorable attitudes toward CTs than European Americans. Multiple regression analysis indicated that older age, lower education level, and prior CT participation history were associated with more favorable attitudes toward CTs. Prior CT participation and prior CPT participation were associated with more favorable attitudes toward CPTs. Results also provided evidence of reliability and construct validity for both scales. ^ Conclusions. Middle age, higher education, and European American ethnicity are associated with less positive attitudes about participating in cancer treatment trials. Availability of a psychometrically sound instrument to measure attitudes may facilitate a better understanding decision making regarding participation in CTs and CPTs. It is this author's intention that the ACTS' scales will be used by other investigators to measure attitudes toward CTs and CPTs in various groups of persons, and that the many issues regarding participation in trials might become more explicit. ^

Prophylactic mastectomy and oophorectomy for women at risk of breast and ovarian cancer: Incorporating preferences in a decision analysis

The discoveries of the BRCA1 and BRCA2 genes have made it possible for women of families with hereditary breast/ovarian cancer to determine if they carry cancer-predisposing genetic mutations. Women with germline mutations have significantly higher probabilities of developing both cancers than the general population. Since the presence of a BRCA1 or BRCA2 mutation does not guarantee future cancer development, the appropriate course of action remains uncertain for these women. Prophylactic mastectomy and oophorectomy remain controversial since the underlying premise for surgical intervention is based more upon reduction in the estimated risk of cancer than on actual evidence of clinical benefit. Issues that are incorporated in a woman's decision making process include quality of life without breasts, ovaries, attitudes toward possible surgical morbidity as well as a remaining risk of future development of breast/ovarian cancer despite prophylactic surgery. The incorporation of patient preferences into decision analysis models can determine the quality-adjusted survival of different prophylactic approaches to breast/ovarian cancer prevention. Monte Carlo simulation was conducted on 4 separate decision models representing prophylactic oophorectomy, prophylactic mastectomy, prophylactic oophorectomy/mastectomy and screening. The use of 3 separate preference assessment methods across different populations of women allows researchers to determine how quality adjusted survival varies according to clinical strategy, method of preference assessment and the population from which preferences are assessed. ^

Predictors of participation in genetic testing for hereditary breast and ovarian cancer

Up to 10% of all breast and ovarian cancers are attributable to mutations in cancer susceptibility genes. Clinical genetic testing for deleterious gene mutations that predispose to hereditary breast and ovarian cancer (HBOC) syndrome is available. Mutation carriers may benefit from following high-risk guidelines for cancer prevention and early detection; however, few studies have reported the uptake of clinical genetic testing for HBOC. This study identified predictors of HBOC genetic testing uptake among a case series of 268 women who underwent genetic counseling at The University of Texas M. D. Anderson Cancer Center from October, 1996, through July, 2000. Women completed a baseline questionnaire that measured psychosocial and demographic variables. Additional medical characteristics were obtained from the medical charts. Logistic regression modeling identified predictors of participation in HBOC genetic testing. Psychological variables were hypothesized to be the strongest predictors of testing uptake—in particular, one's readiness (intention) to have testing. Testing uptake among all women in this study was 37% (n = 99). Contrary to the hypotheses, one's actual risk of carrying a BRCA1 or BRCA2 gene mutation was the strongest predictor of testing participation (OR = 15.37, CI = 5.15, 45.86). Other predictors included religious background, greater readiness to have testing, knowledge about HBOC and genetic testing, not having female children, and adherence to breast self-exam. Among the subgroup of women who were at ≥10% risk of carrying a mutation, 51% (n = 90) had genetic testing. Consistent with the hypotheses, predictors of testing participation in the high-risk subgroup included greater readiness to have testing, knowledge, and greater self-efficacy regarding one's ability to cope with test results. Women with CES-D scores ≥16, indicating the presence of depressive symptoms, were less likely to have genetic testing. Results indicate that among women with a wide range of risk for HBOC, actual risk of carrying an HBOC-predisposing mutation may be the strongest predictor of their decision to have genetic testing. Psychological variables (e.g., distress and self-efficacy) may influence testing participation only among women at highest risk of carrying a mutation, for whom genetic testing is most likely to be informative. ^

Development and preliminary validation of the cancer family impact scale for colorectal cancer

This study aimed to develop and validate The Cancer Family Impact Scale (CFIS), an instrument for use in studies investigating relationships among family factors and colorectal cancer (CRC) screening when family history is a risk factor. We used existing data to develop the measure from 1,285 participants (637 families) across the United States who were in the Johns Hopkins Colon Cancer Genetic Testing study. Participants were 94% white with an average age of 50.1 years, and 60% were women. None had a personal CRC history, and eighty percent had 1 FDR with CRC and 20% had more than one FDR with CRC. The study had three aims: (1) to identify the latent factors underlying the CFIS via exploratory factor analysis (EFA); (2) to confirm the findings of the EFA via confirmatory factor analysis (CFA); and (3) to assess the reliability of the scale via Cronbach's alpha. Exploratory analyses were performed on a split half of the sample, and the final model was confirmed on the other half. The EFA suggested the CFIS was an 18-item measure with 5 latent constructs: (1) NEGATIVE: negative effects of cancer on the family; (2) POSITIVE: positive effects of cancer on the family; (3) COMMUNICATE: how families communicate about cancer; (4) FLOW: how information about cancer is conveyed in families; and (5) NORM: how individuals react to family norms about cancer. CFA on the holdout sample showed the CFIS to have a reasonably good fit (Chi-square = 389.977, df = 122, RMSEA= 0.058 (.052-.065), CFI=.902, TLI=.877, GF1=.939). The overall reliability of the scale was α=0.65. The reliability of the subscales was: (1) NEGATIVE α = 0.682; (2) POSITIVE α = 0.686; (3) COMMUNICATE α = 0.723; (4) FLOW α = 0.467; and (5) NORM α = 0.732. ^ We concluded the CFIS to be a good measure with most fit levels over 0.90. The CFIS could be used to compare theoretically driven hypotheses about the pathways through which family factors could influence health behavior among unaffected individuals at risk due to family history, and also aid in the development and evaluation of cancer prevention interventions including a family component. ^

The association of area socioeconomic status and cancer screening: A systematic review and multilevel study

Background. The gap between actual and ideal rates of routine cancer screening in the U.S., particularly for colorectal cancer screening (CRCS) (1;2), is responsible for an unnecessary burden of morbidity and mortality, particularly for disadvantaged groups. Knowledge about the effects of individual and area influences is being advanced by a growing body of research that has examined the association of area socioeconomic status (SES) and cancer screening after controlling for individual SES. The findings from this emerging and heterogeneous research in the cancer screening literature have been mixed. Moreover, multilevel studies in this area have not yet adequately explored the possibility of differential associations by population subgroup, despite some evidence suggesting gender-specific effects. ^ Objectives and methods. This dissertation reports on a systematic review of studies on the association of area SES and cancer screening and a multilevel study of the association between area SES and CRCS. The specific aims of the systematic review are to: (1) describe the study designs, constructs, methods, and measures; (2) describe the association of area SES and cancer screening; and (3) identify neglected areas of research. ^ The empiric study linked a pooled sample of respondents aged ≥50 years without a personal history of colorectal cancer from the 2003 and 2005 California Health Interview Surveys with a comprehensive set of census-tract level area SES measures from the 2000 U.S. Census. Two-level random intercept models were used to test 2 hypotheses: (1) area SES will be associated with adherence to two modalities of CRCS after controlling for individual SES; and (2) gender will moderate the relationship between area socioeconomic status and adherence to both modalities of CRCS. ^ Results. The systematic review identified 19 eligible studies that demonstrated variability in study designs, methods, constructs, and measures. The majority of tested associations were either not statistically significant or significant and in the positive direction, indicating that as area SES increased, the odds of CRCS increased. The multilevel study demonstrated that while multiple aspects of area SES were associated with CRCS after controlling for individual SES, associations differed by screening modality and in the case of endoscopy, they also differed by gender. ^ Conclusions. Conceptual and methodologic heterogeneity and weaknesses in the literature to date limit definitive conclusions about the underlying relationships between area SES and cancer screening. The multilevel study provided partial support for both hypotheses. Future research should continue to explore the role of gender as a moderating influence with the aim of identifying the mechanisms linking area SES and cancer prevention behaviors. ^

Cancer perceptions: Implications from the 2007 Health Information National Trends Survey

Background. Research has demonstrated associations between sociodemographic characteristics and illness perceptions; however, the impact of cancer exposure through personal or family diagnoses is not well-studied. The purposes of this study were to examine the prevalence of different cancer beliefs and the disparity in cancer beliefs across groups of individuals with distinct cancer histories; and to identify whether, when adjusted for sociodemographic characteristics, cancer history predicts a set of cancer beliefs.^ Methods. Using Leventhal’s Common Sense Model and data from the 2007 Health Information National Trends Survey (N=7172), we constructed multivariable logistic regressions to evaluate the effect of different stimuli, including cancer experience, on cancer perceptions (e.g., risk, worry, causation, outcome).^ Results. Findings indicate significant associations between cancer history and cancer perceptions. Individuals with family and personal cancer histories were more likely than individuals without any cancer history to worry about getting cancer (OR=3.55, P<0.01), agree they will develop cancer in the future (OR=8.81, P<0.01), and disagree that cancer is most often caused by a person’s behavior or lifestyle (OR=1.24, P=0.03). Additionally, results support education’s role in forming cancer perceptions. Individuals with high levels of education were more likely to endorse cancer prevention (OR=1.68, P<0.01) and higher 5-year survival rates (OR=1.41, P<0.01). ^ Conclusions. Results indicate cancer history affects cancer perceptions throughout the cancer continuum. Additionally, cancer history may influence coping behaviors and outcomes related to cancer.^ Impact. Cancer education and survivorship programs should assess important variables (e.g., cancer history) to more effectively tailor services and monitor evolving needs throughout cancer care.^

Behavioral facets of cancer chemoprevention trials

Few studies have explored factors related to participation in cancer chemoprevention trials. The purpose of this dissertation was to conduct investigations in this emerging field by studying aspects of participation at three phases of cancer chemoprevention trials: at enrollment, during a placebo run-in period, and post-trial. In all three studies, subjects had a history of cancer and were at high risk of recurrence or second primary tumors.^ The first study explored correlates of enrollment in a head and neck cancer chemoprevention trial by comparing participants and eligible nonparticipants. Of 148 subjects who met the trial's preliminary eligibility criteria, 40% enrolled. In multivariate analysis, enrollment was positively associated with being male (OR 2.36) and being employed (OR 2.73). The most commonly cited reason for declining participation among nonparticipants was transportation.^ The second study examined outcomes of an eight-week placebo run-in period in a head and neck cancer chemoprevention trial. Of 391 subjects, 91.3% were randomized after the run-in. Adherence to drug capsules ranged from 0% to 120.3% (mean $\pm$ SD, 95.8% $\pm$ 15.1). In multivariate analysis, the main variable predicting run-in outcome was race; white subjects were 3.45 times more likely to be randomized than non-white subjects. Subjects with Karnofsky scores of 100 were 2.13 times more likely to be randomized than were subjects with lower scores.^ The third study used post-trial questionnaires to assess subjects' (n = 64) perceptions of participation in a cancer chemoprevention trial. The most highly rated trial benefit was the perception of potential colon cancer prevention, and the most troublesome barrier was erroneous billing for study visits. Perceived benefits were positively associated with interest in participating in future trials of the same (p = 0.05) and longer (p = 0.02) duration, and difficulty with trial pills and procedures was inversely related to interest in future placebo-controlled trials (p = 0.01).^ These are among the first behavioral studies to be completed in the rapidly growing field of cancer chemoprevention. Much work has yet to be done, however, to advance our understanding of the complex issues relating to chemoprevention trial participation. ^

Identification of micro-RNAs targeting genes of PI3K/AKT pathway in ovarian cancer

Ovarian cancer is the leading cause of cancer-related death for females due to lack of specific early detection method. It is of great interest to find molecular-based biomarkers which are sensitive and specific to ovarian cancer for early diagnosis, prognosis and therapeutics. miRNAs have been proposed to be potential biomarkers that could be used in cancer prevention and therapeutics. The current study analyzed the miRNA and mRNA expression data extracted from the Cancer Genome Atlas (TCGA) database. Using simple linear regression and multiple regression models, we found 71 miRNA-mRNA pairs which were negatively associated between 56 miRNAs and 24 genes of PI3K/AKT pathway. Among these miRNA and mRNA target pairs, 9 of them were in agreement with the predictions from the most commonly used target prediction programs including miRGen, miRDB, miRTarbase and miR2Disease. These shared miRNA-mRNA pairs were considered to be the most potential genes that were involved in ovarian cancer. Furthermore, 4 of the 9 target genes encode cell cycle or apoptosis related proteins including Cyclin D1, p21, FOXO1 and Bcl2, suggesting that their regulator miRNAs including miR-16, miR-96 and miR-21 most likely played important roles in promoting tumor growth through dysregulated cell cycle or apoptosis. miR-96 was also found to directly target IRS-1. In addition, the results showed that miR-17 and miR-9 may be involved in ovarian cancer through targeting JAK1. This study might provide evidence for using miRNA or miRNA profile as biomarker.^

Risk factors for inflammatory breast cancer

Background: Inflammatory breast cancer (IBC) is rare and accounts for 2.5% of all invasive breast cancers. The 5-year survival rates are significantly lower than for other types of breast cancer, highlighting the significance of cancer prevention in IBC. The comprehensive multi-disciplinary team Morgan Welch Inflammatory Breast Cancer Research Program and Clinic at University of Texas MD Anderson Cancer Center treats the largest number of Inflammatory Breast patients in a single center. Because of this unique center, large patient resources, and good medical and epidemiological records, we were able to conduct the largest single center case-control and case-case study on IBC. Methods: We identified 246 patients diagnosed with IBC and 397 cancer free patients seen at the Dan L Duncan Cancer Prevention Clinic. Breast cancer reproductive risk factors and lifestyle risk factors were compared between tumor subtypes of IBC patients (Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+), Human Epidermal Growth Factor 2 positive (HER2+)), and (ER -/PR-/HER2-)) and cancer free controls. Results: Breastfeeding was the only significant risk factor (p<0.01) between tumor subtypes in IBC patients. In the case-control study that included all IBC patients and cancer free patients the descriptive statistics indicate significant difference in BMI, history of smoking, number of children, age of first pregnancy, any breastfeeding and total time breastfeeding (p<0.05). No differences were found in the frequency of other breast cancer risk factors. Conclusion: The associations determined between cancer free controls and IBC patients have identified previously unknown risk factors for IBC. The risk factors identified by the case control study suggest BMI, history of smoking, and the protective effect of breastfeeding as potential modifiable risk factors that can be used to decrease the incidence of IBC. Impact: These results highlight the importance of evaluating epidemiologic risk factors of IBC, which could lead to the identification of distinct etiologic pathways that could be targeted for prevention.^

Breast cancer risk factors among Mexican-American women

Introduction: The average age of onset of breast cancer among Hispanic women is 50 years, more than a decade earlier than non-Hispanic white women. Age at diagnosis is an important prognostic factor for breast cancer; younger age at onset is more likely to be associated with advanced disease, poorer prognosis, hormone receptor negative breast tumors, and a greater likelihood of hereditary breast cancer. Studies of breast cancer risk factors including reproductive risk factors, family history of breast cancer, and breast cancer subtype have been conducted predominately in non-Hispanic whites. Breast cancer is a heterogeneous disease with the presence of clinically, biologically, and epidemiologically distinct subtypes that also differ with respect to their risk factors. The associations between reproductive risk factors and family history of breast cancer have been well documented in the literature. However, only a few studies have assessed these associations with breast cancer subtype in Hispanic populations. Methods: To assess the associations between reproductive risk factors and family history of breast cancer we conducted three separate studies. First, we conducted a case-control study of 172 Mexican-American breast cancer cases and 344 age matched controls residing in Harris County, TX to assess reproductive and other risk factors. We conducted logistic regression analysis to assess differences in cases and controls adjusted for age at diagnosis and birthplace and then we conducted a multinomial logistic regression analysis to compare reproductive risk factors among the breast tumor subtypes. In a second study, we identified 139 breast cancer patients with a first- or second-degree family history of breast cancer and 298 without a family history from the ELLA Bi-National Breast Cancer Study. In this analysis, we also computed a multinomial logistic regression to evaluate associations between family history of breast cancer and breast cancer subtypes, and logistic regression to estimate associations between breast cancer screening practices with family history of breast cancer. In the final study, we employed a cross-sectional study design in 7279 Mexican-American women in the Mano a Mano Cohort Study. We evaluated associations with family history of breast cancer and breast cancer risk factors including body mass index (BMI), lifestyle factors, migration history, and adherence to American Cancer Society (ACS) guidelines. Results: In the results of our first analyses, reproductive risk factors differed in the magnitude and direction of associations when stratified by age and birthplace among cases and controls. In our second study, family history of breast cancer, and having at least one relative diagnosed at an early age (<50 years) was associated with triple negative breast cancer (TNBC). Mammography prior to receiving a breast cancer diagnosis was associated with family history of breast cancer. In our third study that assessed lifestyle factors, migration history and family history of breast cancer; we found that women with a first-degree family history of breast cancer were more overweight or obese compared with their counterparts without a family history. There was no indication that having a family history contributed to women practicing healthier lifestyle behaviors and/or adhering to the ACS guidelines for cancer prevention. Conclusions: We observed that among Mexican-American women, reproductive risk factors were associated with breast cancer where the woman was born (US or Mexico). Having a family history of breast cancer, especially having either a first- or second-degree relative diagnosed at a younger age, was strongly associated with TNBC subtype. These results are consistent with other published studies in this area. Further, our results indicate that women with strong family histories of breast cancer are more likely to undertake mammography but not to engage in healthier lifestyle behaviors.^

Significance of signal transducer and activator of transcription 3 during multistage mouse skin carcinogenesis

Signal transducer and activator of transcription 3 (Stat3) is a signaling molecule that transduces signal from cell surface receptors, itself translocates into the nucleus, binds to consensus promoter sequences and activates gene transcription. Here, we showed that Stat3 is constitutively activated in both premalignant tumors (papillomas) and squamous cell carcinomas of mouse skin that is induced by topical treatment with an initiator 7,12-dimethylbenz[a]anthracene (DMBA) followed by a tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Additional data demonstrated that epidermal growth factor signaling contributes to the activation of Stat3 in this model. Using mice where Stat3 function is abrogated in keratinocytes via the Cre-LoxP system (K5Cre.Stat3 flox/flox), we demonstrated that Stat3 is required for de novo carcinogenesis since Stat3 deficiency leads to a complete abrogation of skin tumor development induced by DMBA and TPA. We subsequently showed that Stat3 plays a role in both the initiation and promotion stages of carcinogenesis. During initiation, Stat3 functions as an anti-apoptotic molecule for maintaining the survival of DNA-damaged keratinocyte stem cells. During promotion, Stat3 functions as a critical regulator for G1 to S phase cell cycle progression to confer selective clonal expansion of initiated cells into papillomas. On the other hand, using transgenic mice over-expressing a constitutively dimerized form of Stat3 (Stat3C) in keratinocytes (K5.Stat3C), we revealed a role for Stat3 in tumor progression. After treatment with DMBA and TPA, K5.Stat3C transgenic mice developed skin tumors with a shorter latency when 100% bypassed the premalignant stage and became carcinoma in situ. Histological and immunohistochemical analysis revealed these tumors as highly vascularized and poorly differentiated. More strikingly, these tumors exhibited invasion into surrounding mesenchymal tissue, some of which metastasized into lung. The tumor-mesenchymal front was characterized by partial loss of E-cadherin and elevation of vimentin, markers characterizing epithelial-mesenchymal transition. On the other hand, inhibition of Stat3 via a decoy oligonucleotide led to a significant reduction of tumor size in approximately 50% of all papillomas tested. In conclusion, we demonstrated that Stat3 plays a critical in all three stages (initiation, promotion and progression) of skin carcinogenesis, and it may potentially become a good target for cancer prevention and anti-cancer therapy. ^

Reducing liver cancer disparities: a community-based hepatitis-B prevention program for Asian-American communities

OBJECTIVES: Several Asian-American groups are at a higher risk of dying of liver diseases attributable to hepatitis-B infection. This culturally diverse community should be well informed of and protected against liver diseases. The present study assesses the knowledge of hepatitis B before and after a hepatitis-B educational program and determines the infection status of an Asian community. METHODS: Nine Asian communities of Montgomery County, MD, enrolled in the hepatitis-B prevention program between 2005 and 2006. They attended culturally tailored lectures on prevention, completed self-administered pre- and posttests, and received blood screening for the disease. RESULTS: More than 800 Asian Americans participated in the study. Knowledge of prevention was improved after educational delivery. The average infection rate was 4.5%, with Cambodian, Thai, Vietnamese, Chinese and Korean groups having higher infection rates. The age group of 36-45 had the highest percentage of carriers (9.1%). CONCLUSION: Many Asian groups, particularly those of a southeast Asian decent, were subject to a higher probability of hepatitis-B infection. At an increased risk are first-generation Asian immigrants, groups with low immunization rates and those aged 36-45. The findings provide potential directions for focusing preventive interventions on at-risk Asian communities to reduce liver cancer disparities.

The Role of Cancer-Associated Fibroblasts in Lung Tumorigenesis

The extracellular milieu is rich in growth factors that drive tumor progression,but the mechanisms that govern tumor cell sensitivity to those ligands have notbeen fully defined. In this study, we address this question in mice that developmetastatic lung adenocarcinomas through the suppression of the microRNA-200 (miR-200) family. Cancer-associated fibroblasts (CAF) enhance tumorgrowth and invasion by secreting VEGF-A that binds to VEGFR1, a processrequired for tumor growth and metastasis in mice and correlated with a poorprognosis in lung adenocarcinoma patients. In this study, we discovered thatmiR-200 blocked CAF-induced tumor cell invasion by directly targetingVEGFR1 in tumor cells. In the context of previous studies, our findings suggestthat the miR-200 family is a point of convergence for diverse biologic processesthat regulate tumor cell proliferation, invasion, and metastasis; its target genesixdrive epithelial-to-mesenchymal transition (ZEB1 and ZEB2) and promotesensitivity to a potent tumor growth factor emanating from the microenvironment(VEGFR1). Clinical trials should focus not only on the role of VEGFR1 inangiogenesis but also on the expression and activation of VEGFR1 in tumorcells by stromal sources of VEGF-A in the tumor microenvironment as a targetfor metastasis prevention.