Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1)

Abstract. Thomas J‐A II, Gerber L, Moreira DM, Hamilton RJ, Bañez LL, Castro‐Santamaria R, Andriole GL, Isaacs WB, Xu J, Freedland SJ (Durham VA Medical Center, Durham, NC, USA; Duke University School of Medicine, Durham, NC, USA; The Author Smith Institute for Urology, New Hyde Park, NY, USA; Memorial Sloan‐Kettering Cancer Center, New York, NY, USA; GlaxoSmithKline, Research Triangle Park, NC, USA; Washington University School of Medicine, St. Louis, MO, USA; Johns Hopkins Hospital, Baltimore, MD, USA; Wake Forest University, Winston‐Salem, NC, USA; and Duke University School of Medicine, Durham, NC, USA). Prostate cancer risk in men with prostate and breast cancer family history: results from the REDUCE study (R1). J Intern Med 2012; 272 : 85–92. Background. To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases. Methods. Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5–10.0 ng mL^?1 and a negative prestudy biopsy. Among men undergoing at least one on‐study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics. Results. A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22–1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73–1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38–2.15) (P‐interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72–3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84–1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region. Conclusions. In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification.     

Rapid molecular diagnosis of pulmonary tuberculosis in children using nasopharyngeal specimens

Background.?A rapid diagnosis of pediatric pulmonary tuberculosis (PTB) using Xpert MTB/RIF (Mycobacterium tuberculosis/rifampicin) automated testing on induced sputum (IS) is possible, but the capacity for performing IS is limited. The diagnosis using a nasopharyngeal aspirate (NPA), which can be non-invasively obtained, is desirable. Methods.?Paired specimens (NPA and IS) were tested using smear, liquid culture and Xpert. The diagnostic accuracy of Xpert and smear was compared with culture for different specimens in children with suspected PTB. Results.?There were 535 children [median age 19 months, 117 (21·9%) HIV-infected] who had one IS and one NPA specimen; 396 had two paired specimens. A positive smear, Xpert test or culture occurred in 30 (5.6%), 81 (15.1%) and 87 children (16.3%), respectively. The culture yield was higher from IS (84/87, 96.6%) vs NPA (61/87, 70.1%, P?相似文献   

Integrin‐mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc

The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin‐mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM‐111 and LM‐511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM‐binding integrins was quantified for human NP cells using flow cytometry. The cell‐ECM attachment mechanism was determined by quantifying cell attachment to LM‐111, LM‐511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM‐111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell‐based therapeutics. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1661–1667, 2013