Lung carcinoma is the most commonly diagnosed cancer and the leading cause of cancer deaths in the US. It accounts for 12% of all cancers diagnosed worldwide, making it the most common malignancy, other than nonmelanoma skin cancer. A new focus has emerged involving the role of race and ethnicity in lung carcinoma. Current health statistics data demonstrate striking disparities, which are most evident between African American patients and their white counterparts. This disparity is greatest among male patients, where statistically significant differences are seen not only in lung cancer incidence and risk, but also in survival and treatment outcomes. Several hypotheses that attempt to explain this disparity include genetic, cultural and socioeconomic differences, in addition to differences in tobacco use and exposure. Current evidence does not clearly identify the reasons for this observed disparity, or the role the aforementioned factors play in the development and overall outcomes of people with lung cancer in these populations. This disease continues to pose a considerable public health burden and more research is needed to improve understanding of the disparity of lung carcinoma statistics among African Americans. This review summarizes the existing body of knowledge regarding lung carcinoma in African Americans and attempts to identify promising areas for future investigation and intervention.
"Lung cancer is a devastating illness with an overall survival of 17% in NSCLC. NSCLC has differential histological classification (adeno carcinoma, squamous cell carcinoma and large cell carcinoma) and prognosis is dependent considerably on the stage of the cancer at the time of diagnosis . In order to make an impact on the disease, understanding key molecular changes is crucial. "
[Show abstract][Hide abstract] ABSTRACT: Non-small cell lung cancers (NSCLC) are highly heterogeneous at the molecular level and comprise 75% of all lung tumors. We have previously shown that the receptor tyrosine kinase (RTK) MET frequently suffers gain-of-function mutations that significantly promote lung tumorigenesis. Subsequent studies from our lab also revealed that PAX5 transcription factor is preferentially expressed in small cell lung cancer (SCLC) and promotes MET transcription. PAX8, however, is also expressed in NSCLC cell lines. We therefore investigated the role of PAX8 in NSCLC.
Using IHC analysis, PAX8 protein expression was determined in archival NSCLC tumor tissues (n = 254). In order to study the effects of PAX8 knockdown on NSCLC cellular functions such as apoptosis and motility, siRNA against PAX8 was used. Confocal fluorescence microscopy was used to monitor the localization of MET, RON and PAX8. The combinatorial effect of PAX8 knockdown and MET inhibition using SU11274 was investigated in NSCLC cell viability assay.
Relative levels of PAX8 protein were elevated (>= + 2 on a scale of 0-3) in adenocarcinoma (58/94), large cell carcinoma (50/85), squamous cell carcinoma (28/47), and metastatic NSCLC (17/28; lymph node). Utilizing early progenitors isolated from NSCLC cell lines and fresh tumor tissues, we observed robust overexpression of PAX8, MET, and RON. PAX8 knockdown A549 cells revealed abrogated PAX8 expression with a concomitant loss in MET and the related RON kinase expression. A dramatic colocalization between the active form of MET (also RON) and PAX8 upon challenging A549 cells with HGF was visualized. A similar colocalization of MET and EGL5 (PAX8 ortholog) proteins was found in embryos of C. elegans. Most importantly, knockdown of PAX8 in A549 cells resulted in enhanced apoptosis (~ 6 fold) and decreased cell motility (~45%), thereby making PAX8 a potential therapeutic target. However, the combinatorial approach of PAX8 knockdown and treatment with MET inhibitor, SU11274, had marginal additive effect on loss of NSCLC cell viability.
PAX8 provides signals for growth and motility of NSCLC cells and is necessary for MET and RON expression. Further investigations are necessary to investigate the therapeutic potential of PA8 in NSCLC.
BMC Cancer 03/2014; 14(1):185. DOI:10.1186/1471-2407-14-185 · 3.36 Impact Factor
"Socioeconomic factors like account for some proportion of breast cancer outcome disparities, but a majority of pooled and population-based studies show a persistence of survival differences in black patients and white patients after adjustment for socioeconomic factors [7, 29]. Interestingly, despite the observed increase in breast cancer mortality in African American breast cancer patients, these patients are more likely to experience delays in completion of adjuvant chemotherapy, are more likely to receive potentially inappropriate and substandard healthcare, are less likely to undergo preventive cancer screening, and are less likely to participate in clinical trials [7, 30]. "
[Show abstract][Hide abstract] ABSTRACT: Data characterizing demographics, treatment patterns, and clinical outcomes in black patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) are limited. registHER is a large, observational cohort study of patients (n = 1,001) with HER2-positive MBC diagnosed ≤6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up of 27 months). Demographics, treatment patterns, and clinical outcomes were described for black (n = 126) and white patients (n = 793). Progression-free survival (PFS) following first-line therapy and overall survival (OS) were examined. Multivariate analyses adjusted for baseline and treatment factors. Black patients were more likely than white patients to be obese (body mass index ≥30), to have diabetes, and to have a history of cardiovascular disease; they were also less likely to have estrogen receptor or progesterone receptor positive disease. In patients treated with trastuzumab, the incidence of cardiac safety events (grade ≥3) was higher in black patients (10.9 %) than in white patients (7.9 %). Unadjusted median OS and PFS (months) were significantly lower in black patients than in white patients (OS: black: 27.1, 95 % confidence interval [CI] 21.3-32.1; white: 37.3, 95 % CI 34.6-41.1; PFS: black: 7.0, 95 % CI 5.7-8.2; white: 10.2, 95 % CI 9.3-11.2). The adjusted OS hazard ratio (HR) for black patients compared with white patients was 1.29 (95 % CI 1.00-1.65); adjusted PFS HR was 1.29 (95 % CI 1.05-1.59). This real-world evaluation of a large cohort of patients with HER2-positive MBC shows poorer prognostic factors and independently worse clinical outcomes in black versus white patients. Further research is needed to identify potential biologic differences that could have predictive impact for black patients or that could explain these differences.
Breast Cancer Research and Treatment 09/2013; 141(3). DOI:10.1007/s10549-013-2697-5 · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectif : Examiner l’association entre la consommation alimentaire de caroténoïdes (β-carotène, α-carotène, β-cryptoxanthine, lutéine/zéaxanthine, lycopène) et de vitamine C et le risque de cancer du poumon, selon le sexe, l’intensité de tabagisme et le sous-type histologique de la tumeur. Méthodes : Les données proviennent d’une étude cas-témoins menée à Montréal, Canada. Des entrevues ont été effectuées auprès de 1 105 cas incidents de cancer du poumon et 1 449 témoins issus de la population générale. Leur fréquence de consommation moyenne de 49 fruits et légumes deux ans auparavant a été convertie en apports en antioxydants. Les rapports de cotes (RC) et les intervalles de confiance (IC) à 95% caractérisant l’association entre les antioxydants et le risque de cancer du poumon ont été estimés à l’aide de modèles de régression logistique et polytomée, en tenant compte de facteurs de confusion potentiels. Résultats : Une consommation élevée en antioxydants était généralement associée à une diminution du risque de cancer du poumon de l’ordre de 30%. Un effet protecteur a été observé chez les hommes et les femmes, pour les non fumeurs, les fumeurs quelque soit l’intensité de tabagisme, ainsi que pour les carcinomes à petites cellules, épidermoïde et l’adénocarcinome. Conclusions : Plusieurs antioxydants alimentaires protégeraient du cancer du poumon. Les efforts de prévention bénéficieraient de cibler la promotion de la consommation de fruits et de légumes riches en caroténoïdes et en vitamine C. Objective: To investigate the association between dietary intake of carotenoids (β-carotene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene) and vitamin C, and risk of lung cancer according to sex, smoking intensity and tumor histological subtype. Methods: In the course of a case-control study conducted in Montreal, Canada, in-person interviews elicited dietary data from 1,105 incident lung cancer cases and 1,449 population controls. Usual frequency of intake of 49 fruit and vegetables two years prior to diagnosis or interview was estimated and converted to antioxidant intakes. Odds ratios (OR) and 95% confidence intervals (CI) between intake variables and lung cancer were estimated using logistic and polytomous regression models, adjusting for potential confounding factors. Results: High intakes of antioxidants were generally associated with some 30% reduction in lung cancer risk. A protective effect was observed among men and women, among never smokers, smokers regardless of intensity, and for small cell carcinoma, squamous cell carcinoma and adenocarcinoma. Conclusions: Results from this study suggest several dietary antioxidants may protect against lung cancer. Prevention programs should promote increased intakes of fruit and vegetables rich in carotenoids and vitamin C.
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