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A study used somatic cell genetics to locate the determinants of resistance of squamous carcinoma cell lines to transforming growth factor beta 1 (TGF beta 1), because a majority of human squamous carcinoma cell lines of the aerodigestive and genital tructs are refractory to the antiproliferative action of TGF beta 1 in nitro. Recessive genes concerned with TGF beta 1 signaling may be regionalized to the distal part of chromosome 18q. The level of the mutant p53 protein expressed by the hybrid cell lines was lowered, suggesting that mutant p53 lowers the responsiveness of keratinocytes to TGF beta 1. The loss of one or more post-receptor elements of the signaling pathway may cause the recessive nature of TGF beta resistance of FaDu cells.

Objective Resistance to transforming growth factor (TGF)-β-mediated cell growth inhibition is a well-known pathogenic mechanism in epithelial neoplasia. TGF-β signaling requires normal function of downstream mediators such as TGF-β receptors (TβRs) and Smad proteins. The goal of this study is to investigate the expression of components of the TGF-β signaling pathway in follicular tumors of the thyroid. Study Design Twenty follicular thyroid neoplasms were classified as adenomas (11) or minimally invasive follicular carcinomas (9) according to current pathological criteria. Protein expression was evaluated to identify differences between benign and malignant tumors that could be used as an adjunct to histopathological analysis. Methods Paraffin-embedded tissue sections containing tumor and adjacent nonneoplastic parenchyma were analyzed by immunohistochemistry for the expression of TβR type II (TβR-II) and Smad2, Smad4, Smad6, and Smad7. Expression of each protein in the tumor was compared with that of the corresponding adjacent nonneoplastic thyroid parenchyma. Results TβR-II expression was lost in 78% of the carcinomas. In the remaining 22%, TβR-II was preserved but Smad2 expression was lost. In all conventional adenomas, however, TβR-II expression was maintained. Furthermore, all tumors with normal expression of all proteins were adenomas. Conclusions Downregulation of TβR-II is a consistent abnormality in follicular carcinomas and can be used to differentiate minimally invasive carcinomas from adenomas. Also, downregulation of Smad proteins is another mechanism by which carcinomas can become independent from TGF-β-mediated growth inhibition. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most common cancer in the world. In addition to the geographical and sex-specific differences in the incidence, mortality, and survival rates of lung cancer, growing evidence suggests that racial and ethnic differences exist., Methods: We reviewed published data related to racial and ethnic differences in lung cancer., Results: Current knowledge and substantive findings related to racial and ethnic differences in lung cancer were summarized, focusing on incidence, mortality, survival, cigarette smoking, prevention and early detection, and genomics. Systems-level and health care professional-related issues likely to contribute to specific racial and ethnic health disparities were also reviewed to provide possible suggestions for future strategies to reduce the disproportionate burden of lung cancer., Conclusions: Although lung carcinogenesis is a multifactorial process driven by exogenous exposures, genetic variations, and an accumulation of somatic genetic events, it appears to have racial and ethnic differences that in turn impact the observed epidemiological differences in rates of incidence, mortality, and survival.

Background: The scarcity of tissues from racial and ethnic minorities at biobanks poses a scientific constraint to research addressing health disparities in minority populations., Methods: To address this gap, the Minority Biospecimen/Biobanking Geographic Management Program for region 3 (BMaP-3) established a working infrastructure for a "biobanking" hub in the southeastern United States and Puerto Rico. Herein we describe the steps taken to build this infrastructure, evaluate the feasibility of collecting formalin-fixed, paraffin-embedded tissue blocks and associated data from a single cancer type (breast), and create a web-based database and tissue microarrays (TMAs)., Results: Cancer registry data from 6 partner institutions were collected, representing 12,408 entries from 8,279 unique patients with breast cancer (years 2001-2011). Data were harmonized and merged, and deidentified information was made available online. A TMA was constructed from formalin-fixed, paraffin-embedded samples of invasive ductal carcinoma (IDC) representing 427 patients with breast cancer (147 African Americans, 168 Hispanics, and 112 non-Hispanic whites) and was annotated according to biomarker status and race/ethnicity. Biomarker analysis of the TMA was consistent with the literature., Conclusions: Contributions from participating institutions have facilitated a robust research tool. TMAs of IDC have now been released for 5 projects at 5 different institutions.