Memorial Sloan Kettering Cancer Center

About: Memorial Sloan Kettering Cancer Center is a healthcare organization based out in New York, New York, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 30293 authors who have published 65381 publications receiving 4462534 citations. The organization is also known as: MSKCC & New York Cancer Hospital.

Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies.

Abstract: Summary Background Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Methods Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. Findings 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p Interpretation Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. Funding Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

Gene-Panel Sequencing and the Prediction of Breast-Cancer Risk

Abstract: An international group of cancer geneticists review the level of evidence for the association of gene variants with the risk of breast cancer. It is difficult to draw firm conclusions from the data because of ascertainment bias and the lack of data from large populations.

A Human Telomeric Protein

Abstract: Telomeres are multifunctional elements that shield chromosome ends from degradation and end-to-end fusions, prevent activation of DNA damage checkpoints, and modulate the maintenance of telomeric DNA by telomerase. A major protein component of human telomeres has been identified and cloned. This factor, TRF, contains one Myb-type DNA-binding repeat and an amino-terminal acidic domain. Immunofluorescent labeling shows that TRF specifically colocalizes with telomeric DNA in human interphase cells and is located at chromosome ends during metaphase. The presence of TRF along the telomeric TTAGGG repeat array demonstrates that human telomeres form a specialized nucleoprotein complex.

Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor

Abstract: Members of the transforming growth factor β (TGFβ) family of cytokines, which also includes activins and the bone morphogenetic proteins (BMPs), initiate signaling from the cell surface by interacting with two distinct serine/threonine kinase receptors (Massague and Weis-Garcia 1996; ten Dijke et al. 1996). Ligand binding induces the formation of a complex in which the type II receptor phosphorylates and activates the type I receptor; this protein then propagates the signal by phosphorylating a family of signal transducers, the Smad proteins (Massague et al. 1997). To date, eight vertebrate Smad proteins, Smad1–Smad-7 and Smad-9, are cloned (Massague et al. 1997; Topper et al. 1997; Watanabe et al. 1997). The members of this family have conserved amino- and carboxy-terminal domains, hereafter referred to as the N-domain and the C-domain. The C-domain has effector function, as it participates in homomeric and heteromeric interactions (Hata et al. 1997; Shi et al. 1997; Wu et al. 1997) and acts as a transcriptional activator (Chen et al. 1996; Liu et al. 1996). Although Smads display common structural features, recent studies have revealed that their functions in the signaling pathway are diverse and can be divided into three classes: (1) receptor-regulated Smad proteins, which act as direct substrates of the receptors; (2) Smads that act as functional partners of the receptor-regulated Smads; and (3) antagonistic Smads or anti-Smads. Smad1, Smad2, Smad3, Smad5, and Smad9 belong to the first class: Smad 1 and presumably its closely related members Smad5 and Smad9 mediate BMP signaling (Graff et al. 1996; Hoodless et al. 1996; Lechleider et al. 1996; Liu et al. 1996; Thomsen 1996; Yingling et al. 1996; Kretzschmar et al. 1997; Suzuki et al. 1997; Watanabe et al. 1997) whereas Smad2 and Smad3 mediate TGFβ/activin signaling (Baker and Harland 1996; Eppert et al. 1996; Graff et al. 1996; Macias-Silva et al. 1996; Zhang et al. 1996). These Smads are directly phosphorylated on serine residues at their carboxy-terminal ends (SSXS motif) by the specific type I receptor (Macias-Silva et al. 1996; Kretzschmar et al. 1997), and their phosphorylation leads to formation of a heteromeric complex with the second Smad class, which includes Smad4 in vertebrates (Lagna et al. 1996; Zhang et al. 1997). Unlike receptor-regulated Smads, which are specific for each pathway, the tumor suppressor Smad4/DPC4 (Hahn et al. 1996) acts as a shared partner for both BMP-specific and TGFβ/activin-specific Smads (Lagna et al. 1996; Zhang et al. 1997) and plays an essential role as a transcriptional activator in the nucleus (Liu et al. 1997). Recently, a third class of Smads has been reported, whose members act as antagonists of these signaling pathways (Hayashi et al. 1997; Imamura et al. 1997; Nakao et al. 1997; Topper et al. 1997; Tsuneizumi et al. 1997). When overexpressed, these Smads can interact with various type I receptors and nonselectively inhibit signaling by various TGFβ superfamily members, leading to the notion that antagonistic Smads act as general blockers of type I receptors (Hayashi et al. 1997; Imamura et al. 1997; Nakao et al. 1997). In contrast to this model, the results presented here show that both in Xenopus and in mammalian cells, Smad6 efficiently blocks Smad1 signaling, without inhibiting Smad2 signaling. Consistently, we observe a direct, BMP-dependent interaction of Smad6 with Smad1, but not with Smad2 or Smad4. The Smad1–Smad6 interaction can prevent the formation of the Smad1–Smad4 complex, which is required for BMP signaling. Although Smad6 can associate with type I receptors, it does so indiscriminately and inhibits Smad1 signaling without inhibiting receptor-mediated phosphorylation. Thus, we conclude that Smad6 inhibits BMP/Smad1 signaling in vivo by acting as a selective Smad4 decoy.