Institution
Memorial Sloan Kettering Cancer Center
Healthcare•New York, New York, United States•
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.
Topics: Cancer, Population, Breast cancer, Radiation therapy, Prostate cancer
Papers published on a yearly basis
Papers
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TL;DR: This is the first report demonstrating that the ectopic overexpression of a Cdk inhibitor such as p21 or p27 directly leads to a terminal differentiation program, suggesting that ligand-modulated transcriptional induction of the p21 gene facilitates the induced differentiation of this monoblastic cell line.
Abstract: The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, acting through its cognate nuclear receptor (vitamin D3 receptor, VDR) will induce myeloid leukemic cell lines to terminally differentiate into monocytes/macrophages. Because VDR acts by transcriptionally regulating responsive genes in a ligand-dependent manner, we sought target genes of the receptor that initiate, the differentiation process in response to ligand. We screened a cDNA library prepared from the myelomonocytic U937 cell line with probes generated from either 1,25-dihydroxyvitamin D3-treated or untreated cells. We report here that a candidate clone that hybridized differentially is the Cdk inhibitor p21WAF1, CIP1. Furthermore, we show that p21 is transcriptionally induced by 1,25-dihydroxyvitamin D3 in a VDR-dependent, but not p53-dependent, manner, and we identify a functional vitamin D response element in the p21 promoter. Transient overexpression of p21 and/or the related Cdk inhibitor p27 in U937 cells in the absence of 1,25-dihydroxyvitamin D3 results in the cell-surface expression of monocyte/macrophage-specific markers, suggesting that ligand-modulated transcriptional induction of the p21 gene facilitates the induced differentiation of this monoblastic cell line. We believe that this is the first report demonstrating that the ectopic overexpression of a Cdk inhibitor such as p21 or p27 directly leads to a terminal differentiation program.
897 citations
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TL;DR: Diverse interventions were employed to manage these pains, with variable efficacy, and this data clarify the spectrum of breakthrough pains and indicate their importance in cancer pain management.
Abstract: In the cancer population, the term breakthrough pain typically refers to a transitory flare of pain in the setting of chronic pain managed with opioid drugs. The prevalence and characteristics of this phenomenon have not been defined, and its impact on patient care is unknown. We developed operational definitions for breakthrough pain and its major characteristics, and applied these in a prospective survey of patients with cancer pain. Data were collected during a 3 month period from consecutive patients who reported moderate pain or less for more than 12 h daily and stable opioid dosing for a minimum of 2 consecutive days. Of 63 patients surveyed, 41 (64%) reported breakthrough pain, transient flares of severe or excruciating pain. Fifty-one different pains were described (median 4 pains/day; range 1-3600). Pain characteristics were extremely varied. Twenty-two (43%) pains were paroxysmal in onset; the remainder were more gradual. The duration varied from seconds to hours (median/range: 30 min/1-240 min), and 21 (41%) were both paroxysmal and brief (lancinating pain). Fifteen (29%) of the pains were related to the fixed opioid dose, occurring solely at the end of the dosing interval. Twenty-eight (55%) of the pains were precipitated; of these, 22 were caused by an action of the patient (incident pain), and 6 were associated with a non-volitional precipitant, such as flatulence. The pathophysiology of the pain was believed to be somatic in 17 (33%), visceral in 10 (20%), neuropathic in 14 (27%), and mixed in 10 (20%). Pain was related to the tumor in 42 (82%), the effects of therapy in 7 (14%), and neither in 2 (4%). Diverse interventions were employed to manage these pains, with variable efficacy. These data clarify the spectrum of breakthrough pains and indicate their importance in cancer pain management.
896 citations
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TL;DR: Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas.
Abstract: Background We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas, which are precursors of most large-bowel cancers. Methods We randomly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before randomization to one of two groups: an intervention group given intensive counseling and assigned to follow a diet that was low in fat (20 percent of total calories) and high in fiber (18 g of dietary fiber per 1000 kcal) and fruits and vegetables (3.5 servings per 1000 kcal), and a control group given a standard brochure on healthy eating and assigned to follow their usual diet. Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps; they remained in the study for approximately four years, undergoing colonoscopy one and four years after randomization. Results A total of 1905 of the randomized subjects (91....
895 citations
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Fox Chase Cancer Center1, University of Utah2, University of Texas MD Anderson Cancer Center3, University of California, San Diego4, University of South Florida5, Brigham and Women's Hospital6, University of Alabama at Birmingham7, Roswell Park Cancer Institute8, Case Western Reserve University9, Ohio State University10, University of Colorado Boulder11, University of Nebraska Medical Center12, Johns Hopkins University13, University of California, San Francisco14, University Of Tennessee System15, City of Hope National Medical Center16, University of Washington17, Duke University18, Northwestern University19, Memorial Sloan Kettering Cancer Center20
TL;DR: This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.
Abstract: Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.
894 citations
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TL;DR: The results provide genetic evidence that H-RasV12G is important in both the genesis and maintenance of solid tumours, and the failure of persistent endogenous and enforced VEGF expression to sustain tumour viability indicates that the tumour-maintaining actions of activated Ras extend beyond the regulation of V EGF expression in vivo.
Abstract: Advanced malignancy in tumours represents the phenotypic endpoint of successive genetic lesions that affect the function and regulation of oncogenes and tumour-suppressor genes. The established tumour is maintained through complex and poorly understood host-tumour interactions that guide processes such as angiogenesis and immune sequestration. The many different genetic alterations that accompany tumour genesis raise questions as to whether experimental cancer-promoting mutations remain relevant during tumour maintenance. Here we show that melanoma genesis and maintenance are strictly dependent upon expression of H-RasV12G in a doxycycline-inducible H-Ras12G mouse melanoma model null for the tumour suppressor INK4a. Withdrawal of doxycycline and H-RasV12G down-regulation resulted in clinical and histological regression of primary and explanted tumours. The initial stages of regression involved marked apoptosis in the tumour cells and host-derived endothelial cells. Although the regulation of vascular endothelial growth factor (VEGF) was found to be Ras-dependent in vitro, the failure of persistent endogenous and enforced VEGF expression to sustain tumour viability indicates that the tumour-maintaining actions of activated Ras extend beyond the regulation of VEGF expression in vivo. Our results provide genetic evidence that H-RasV12G is important in both the genesis and maintenance of solid tumours.
894 citations
Authors
Showing all 30708 results
Name | H-index | Papers | Citations |
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Gordon H. Guyatt | 231 | 1620 | 228631 |
Edward Giovannucci | 206 | 1671 | 179875 |
Irving L. Weissman | 201 | 1141 | 172504 |
Craig B. Thompson | 195 | 557 | 173172 |
Joan Massagué | 189 | 408 | 149951 |
Gad Getz | 189 | 520 | 247560 |
Chris Sander | 178 | 713 | 233287 |
Richard B. Lipton | 176 | 2110 | 140776 |
Richard K. Wilson | 173 | 463 | 260000 |
George P. Chrousos | 169 | 1612 | 120752 |
Stephen J. Elledge | 162 | 406 | 112878 |
Murray F. Brennan | 161 | 925 | 97087 |
Lewis L. Lanier | 159 | 554 | 86677 |
David W. Bates | 159 | 1239 | 116698 |
Dan R. Littman | 157 | 426 | 107164 |