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.

Transcriptional control by the TGF‐β/Smad signaling system

Abstract: The deployment of a cell's genetic program in a multicellular organism must be tightly controlled for the sake of the organism as a whole. Over the past 20 years the transforming growth factor‐β (TGF‐β) family of secretory polypeptides has emerged as a major source of signals exerting this type of control. This family includes various forms of TGF‐β, the bone morphogenetic proteins (BMPs), the Nodals, the Activins, the anti‐Mullerian hormone, and many other structurally related factors in vertebrates, insects and nematodes (Massague, 1998). Produced by diverse cell types, these factors regulate cell migration, adhesion, multiplication, differentiation and death throughout the life span of the organism. Many of these responses result from changes in the expression of key target genes. Hence, transcriptional control by the TGF‐β family has become a subject of intense investigation in recent years. The present knowledge of these mechanisms is reviewed here. One basic concept concerning the role of the TGF‐β family as hormonally active agents warrants mention at the outset. Unlike classical hormones, whose actions are few and concrete, the members of the TGF‐β family have many different effects depending on the type and state of the cell. For example, in the same healing wound TGF‐β may stimulate or inhibit cell proliferation depending on whether the target is a fibroblast or a keratinocyte (Ashcroft et al ., 1999); in mammary epithelial cells TGF‐β will cause growth arrest or metastatic behavior depending on the level of oncogenic Ras activity present in the cell (Oft et al ., 1996); and human BMP4 and its Drosophila ortholog, DPP, can signal dorsalization in the fly (Padgett et al ., 1993) yet bone formation in a vertebrate (Sampath et al ., 1993). TGF‐β family members are multifunctional hormones, the nature of their effects depending on what has been called ‘the cellular context’. It was plausible …

Cardiovascular Risk Associated With Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention

Abstract: background Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern. methods We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme. results

Histone demethylation by a family of JmjC domain-containing proteins

Abstract: Covalent modification of histones has an important role in regulating chromatin dynamics and transcription. Whereas most covalent histone modifications are reversible, until recently it was unknown whether methyl groups could be actively removed from histones. Using a biochemical assay coupled with chromatography, we have purified a novel JmjC domain-containing protein, JHDM1 (JmjC domain-containing histone demethylase 1), that specifically demethylates histone H3 at lysine 36 (H3-K36). In the presence of Fe(ii) and alpha-ketoglutarate, JHDM1 demethylates H3-methyl-K36 and generates formaldehyde and succinate. Overexpression of JHDM1 reduced the level of dimethyl-H3-K36 (H3K36me2) in vivo. The demethylase activity of the JmjC domain-containing proteins is conserved, as a JHDM1 homologue in Saccharomyces cerevisiae also has H3-K36 demethylase activity. Thus, we identify the JmjC domain as a novel demethylase signature motif and uncover a protein demethylation mechanism that is conserved from yeast to human.

Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer

Abstract: Purpose: A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining the prognostic utility of CTC measurement before initiating therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes and OS at these and other time points. Experimental Design: Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetermined Favorable or Unfavorable groups ( Results: Two hundred thirty-one of 276 enrolled patients (84%) were evaluable. Patients with Unfavorable pretreatment CTC (57%) had shorter OS (median OS, 11.5 versus 21.7 months; Cox hazard ratio, 3.3; P P P = 0.0218). Prognosis for patients with ( a ) Unfavorable baseline CTC who converted to Favorable CTC improved (6.8 to 21.3 months); ( b ) Favorable baseline CTC who converted to Unfavorable worsened (>26 to 9.3 months). Conclusions: CTC are the most accurate and independent predictor of OS in CRPC. These data led to Food and Drug Administration clearance of this assay for the evaluation of CRPC.

Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver

Abstract: Lyden and colleagues report that pancreatic cancer-derived exosomes induce a pre-metastatic niche in the liver by promoting TGFβ secretion from Kupffer cells, leading to fibronectin production in hepatic stellate cells and macrophage recruitment.