Examining The Effectiveness Of Interventions Designed To Increase Mammography Adherence Among African American Women

The objective of this paper was to assess and synthesize the key findings, conclusions, and recommendations of mammography interventions targeting African American women conducted between 1999 and 2010. Collection of materials for this study included searches of academic databases using the following inclusion criteria: 1) publication in the English language, 2) between 1999 and 2010, 3) conducted in the United States, 4) targeting African American women. Titles and abstracts of identified studies were evaluated independently by two researchers. A total of 24 studies met the inclusion criteria. Interventions were categorized as either practice-based or community-based. Classifications were then sub-categorized based on the employment of targeted or tailored strategies. Culturally-appropriate tailored and targeted messages are an effective approach to increase screening mammography adherence. Community-wide interventions that employ lay health advisors were found to assist in offsetting issues related to trust and access. Interventions delivered in faith-based settings were effective mediums for increasing adherence to screening guidelines. Stepped-care interventions were an efficient, cost-effective method for increasing adherence among non-compliant populations. The majority of the identified studies relied upon theoretical frameworks to guide the intervention. Community-based interventions should progress from atheoretical to theory-based intervention frameworks

Social Cognitive Models of Fruit and Vegetable Consumption, Moderate Physical Activity, and Sleep Behavior in Overweight and Obese Men

Background. Approximately 35% of men in the United States are obese, though little theoretical work examining predictors correlates of obesity exists for this population. The purpose of this study was to test the capacity of Bandura’s social cognitive model of health behavior to account for variance in fruit and vegetable consumption, moderate physical activity, and sleep behavior in overweight and obese men. Methods. Data were collected from overweight and obese men using previously validated questionnaires. Structural equation models were built to examine the direct and indirect effects the social cognitive theory constructs of self-efficacy, outcome expectation, socio-structural factors, and goals on the behaviors under investigation. Results. A total of 305 men participated in this study (Mage=44.52; SD=6.95). Overall fit for the social cognitive models of health behavior were adequate, accounting for 35.0%, 31.2%, and 21.1% of the variance in the fruit and vegetable consumption, moderate physical activity, and sleep behavior correlates, respectively. Self-efficacy had the greatest total effect on fruit and vegetable consumption (βtotal=.500) and sleep behavior (βtotal=.406), while goals has the greatest total effect on moderate physical activity (βtotal=.495). The indirect effects of self-efficacy on the three behaviors demonstrates the relative importance of self-efficacy as a mediator for health behavior change. Discussion. Men are underrepresented in behavioral obesity prevention and treatment research. This study provides support for the social cognitive model of health behavior as a theoretical framework for predicting behaviors hypothesized to protect against and treat obesity in men. Additionally, this study represents the first attempt to model correlates social cognitive constructs on sleep behavior

Modeling Risk Factors for Sleep- and Adiposity-Related Cardiometabolic Disease: Protocol for the Short Sleep Undermines Cardiometabolic Health (SLUMBRx) Observational Study

Background: Obesity and short sleep duration are significant public health issues. Current evidence suggests that these conditions are associated with cardiovascular disease, metabolic syndrome, inflammation, and premature mortality. Increased interest in the potential link between obesity and short sleep duration, and its health consequences, has been driven by the apparent parallel increase in the prevalence of both conditions in recent decades, their overlapping association with cardiometabolic outcomes, and the potential causal connection between the two health issues. The SLUMBRx (Short Sleep Undermines Cardiometabolic Health) study seeks to contribute to the development of a comprehensive adiposity-sleep model while laying the groundwork for a future research program that will be designed to prevent and treat adiposity- and sleep-related cardiometabolic disease risk factors. Objective: This SLUMBRx study aims to address 4 topics pertinent to the adiposity-sleep hypothesis: the relationship between adiposity and sleep duration; sex-based differences in the relationship between adiposity and sleep duration; the influence of adiposity indices and sleep duration on cardiometabolic outcomes; and the role of socioecological factors as effect modifiers in the relationship between adiposity indices, sleep, and cardiometabolic outcomes. Methods: SLUMBRx will employ a large-scale survey (n=1000), recruiting 159 participants (53 normal weight, 53 overweight, and 53 obese) to be assessed in 2 phases. Results: SLUMBRx was funded by the National Institutes of Health, Heart, Lung, and Blood Institute through a K01 grant award mechanism (1K01HL145128-01A1) on July 23, 2019. Institutional Review Board (IRB) approval for the research project was sought and obtained on July 10, 2019. Phase 1 of SLUMBRx, the laboratory-based component of the study, will gather objective adiposity indices (air displacement plethysmography and anthropometrics) and cardiometabolic data (blood pressure, pulse wave velocity and pulse wave analysis, and a blood-based biomarker). Phase 2 of SLUMBRx, a 1-week, home-based component of the study, will gather sleep-related data (home sleep testing or sleep apnea, actigraphy, and sleep diaries). During phase 2, detailed demographic and socioecological data will be collected to contextualize hypothesized adiposity and sleep-associated cardiometabolic disease risk factors. Collection and analyses of these data will yield information necessary to customize future observational and intervention research. Conclusions: Precise implementation of the SLUMBRx protocol promises to provide objective and empirical data on the interaction between body composition and sleep duration. The hypotheses that will be tested by SLUMBRx are important for understanding the pathogenesis of cardiometabolic disease and for developing future public health interventions to prevent its conception and treat its consequences

Polymorphism rs4919510:C>G in Mature Sequence of Human MicroRNA-608 Contributes to the Risk of HER2-Positive Breast Cancer but Not Other Subtypes

BACKGROUND: A few polymorphisms are located in the mature microRNA sequences. Such polymorphisms could directly affect the binding of microRNA to hundreds of target mRNAs. It remains unknown whether rs4919510:C>G located in the mature miR-608 alters breast cancer susceptibility. METHODS: The association of rs4919510:C>G with risk and pathologic features of breast cancer were investigated in two independent case-control studies, the first set including 1,138 sporadic breast cancer patients (including 927 invasive ductal carcinoma patients, 777 of them with known subtypes: 496 luminal-like, 133 HER2-positive, and 148 triple-negative) and 1,434 community-based controls, and the second set including 294 familial/early-onset breast cancer patients and 500 hospital-based cancer-free controls. Odds ratios (ORs) were estimated by logistic regression. Predicted targets of miR-608 and complementary sequences containing rs4919510:C>G were surveyed to reveal potential pathological mechanism. RESULTS: In the first set, although rs4919510:C>G was unrelated to breast cancer in general patients, variant genotypes (CG/GG) were specifically associated with increased risk of HER2-positive subtype (Adjusted OR = 1.97, 95% CI, 1.34-2.90 in the recessive model). Variant G-allele was the risk allele with OR of 1.62 (95% CI, 1.23-2.15). Patients carrying GG-genotype also had larger HER2-positive tumors (P for Kruskal-Wallis test = 0.006). The relationship between rs4919510:C>G and risk of HER2-positive subgroup was validated in the second set (Bonferroni corrected P = 0.06). The adjusted combined OR (total 164 HER2-positive cases) in the recessive model was 1.97 (95% CI, 1.43-2.72) for GG genotype (corrected P = 1.1 × 10(-4)). Bioinformatic analysis indicated that, HSF1, which is required for HER2-induced tumorigenesis, might be a target of miR-608. The minimum free-energy of ancestral-miR-608 (C-allele) binding to HSF1 is -35.9 kcal/mol, while that of variant-form (G-allele) is -31.5 kcal/mol, indicating a lower affinity of variant-miR-608 to HSF1 mRNA. CONCLUSION: rs4919510:C>G in mature miR-608 may influence HER2-positive breast cancer risk and tumor proliferation

PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study

<p>Abstract</p> <p>Background</p> <p>The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression. The aim of this study was to determine whether PAR1 expression could be used as predictor of metastases and mortality.</p> <p>Methods</p> <p>In a cohort of patients with infiltrating ductal carcinoma studied longitudinally since 1996 and until 2007, PAR1 over-expression was assessed by immunoblotting, immunohistochemistry, and flow citometry. Chi-square and log rank tests were used to determine whether there was a statistical association between PAR1 overexpression and metastases, mortality, and survival. Multivariate analysis was performed including HER1, stage, ER and nodes status to evaluate PAR1 as an independent prognostic factor.</p> <p>Results</p> <p>Follow up was 95 months (range: 2–130 months). We assayed PAR1 in a cohort of patients composed of 136 patients; we found PAR1 expression assayed by immunoblotting was selectively associated with high grade patients (50 cases of the study cohort; P = 0.001). Twenty-nine of 50 (58%) patients overexpressed PAR1, and 23 of these (46%) developed metastases. HER1, stage, ER and PAR1 overexpression were robustly correlated (Cox regression, P = 0.002, P = 0.024 and P = 0.002 respectively). Twenty-one of the 50 patients (42%) expressed both receptors (PAR1 and HER1 P = 0.0004). We also found a statistically significant correlation between PAR1 overexpression and increased mortality (P = 0.0001) and development of metastases (P = 0.0009).</p> <p>Conclusion</p> <p>Our data suggest PAR1 overexpression may be involved in the development of metastases in breast cancer patient and is associated with undifferentiated cellular progression of the tumor. Further studies are needed to understand PAR1 mechanism of action and in a near future assay its potential use as risk factor for metastasis development in high grade breast cancer patients.</p

Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients

BACKGROUND: Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy. METHODS: The patients were genotyped using PCR followed by cleavage with restriction enzymes. RESULTS: Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11–0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21–1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19–0.74, P = 0.0041). CONCLUSION: The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort

FADD phosphorylation is critical for cell cycle regulation in breast cancer cells

Anti-oestrogen therapy is effective for control of hormone receptor-positive breast cancers, although the detailed molecular mechanisms, including signal transduction, remain unclear. We demonstrated here that long-term tamoxifen treatment causes G2/M cell cycle arrest through c-jun N-terminal kinase (JNK) activation, which is dependent on phosphorylation of Fas-associated death domain-containing protein (FADD) at 194 serine in an oestrogen (ER) receptor-positive breast cancer cell line, MCF-7. Expression of a dominant negative mutant form of MKK7, a kinase upstream of JNK, or mutant FADD (S194A) in MCF-7 cells suppressed the cytotoxicity of long-term tamoxifen treatment. Of great interest, similar signallings could be evoked by paclitaxel, even in an ER-negative cell line, MDA-MB-231. In addition, immunohistochemical analysis using human breast cancer specimens showed a close correlation between phosphorylated JNK and FADD expression, both being significantly reduced in cases with metastatic potential. We conclude that JNK-mediated phosphorylation of FADD plays an important role in the negative regulation of cell growth and metastasis, independent of the ER status of a breast cancer, so that JNK/FADD signals might be promising targets for cancer therapy

Cytosolic phospholipase A2-α expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours

BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)α (cPLA(2)α) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)α expression correlated with EGFR/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)α activity in clinical breast cancer was established by relating the expression of cPLA(2)α in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)α mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)α expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)α expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)α in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker

GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Aromatase inhibitors (AI) that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER⁺) breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88), also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER⁺breast cancer cells</p> <p>Methods</p> <p>We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined.</p> <p>Results</p> <p>GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole.</p> <p>Conclusion</p> <p>Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER⁺breast cancer.</p