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, Prostate cancer, Radiation therapy
Papers published on a yearly basis
Papers
More filters
••
TL;DR: The results suggest that compounds that exploit the distinctive inactivation mechanisms of individual protein kinases can achieve both high affinity and high specificity.
Abstract: The inadvertent activation of the Abelson tyrosine kinase (Abl) causes chronic myelogenous leukemia (CML). A small-molecule inhibitor of Abl (STI-571) is effective in the treatment of CML. We report the crystal structure of the catalytic domain of Abl, complexed to a variant of STI-571. Critical to the binding of STI-571 is the adoption by the kinase of an inactive conformation, in which a centrally located "activation loop" is not phosphorylated. The conformation of this loop is distinct from that in active protein kinases, as well as in the inactive form of the closely related Src kinases. These results suggest that compounds that exploit the distinctive inactivation mechanisms of individual protein kinases can achieve both high affinity and high specificity.
1,694 citations
••
TL;DR: The Multiple Outcomes of Raloxifene Evaluation (MORE) as discussed by the authors was a multicenter, randomized, double-blind trial, in which women taking raloxion hydrochloride or placebo were followed up for a median of 40 months at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.
Abstract: ContextRaloxifene hydrochloride is a selective estrogen
receptor modulator that has antiestrogenic effects on breast and
endometrial tissue and estrogenic effects on bone, lipid metabolism,
and blood clotting.ObjectiveTo determine whether women taking raloxifene have a
lower risk of invasive breast cancer.Design and SettingThe Multiple Outcomes of Raloxifene Evaluation
(MORE), a multicenter, randomized, double-blind trial, in which women
taking raloxifene or placebo were followed up for a median of 40 months
(SD, 3 years), from 1994 through 1998, at 180 clinical centers composed
of community settings and medical practices in 25 countries, mainly in
the United States and Europe.ParticipantsA total of 7705 postmenopausal women, younger than 81
(mean age, 66.5) years, with osteoporosis, defined by the presence of
vertebral fractures or a femoral neck or spine T-score of at least 2.5
SDs below the mean for young healthy women. Almost all participants
(96%) were white. Women who had a history of breast cancer or who were
taking estrogen were excluded.InterventionRaloxifene, 60 mg, 2 tablets daily; or raloxifene, 60
mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.Main Outcome MeasuresNew cases of breast cancer, confirmed by
histopathology. Transvaginal ultrasonography was used to assess the
endometrial effects of raloxifene in 1781 women. Deep vein thrombosis
or pulmonary embolism were determined by chart review.ResultsThirteen cases of breast cancer were confirmed among the
5129 women assigned to raloxifene vs 27 among the 2576 women assigned
to placebo (relative risk [RR], 0.24; 95% confidence interval
[CI], 0.13-0.44; P<.001). To prevent 1 case of breast
cancer, 126 women would need to be treated. Raloxifene decreased the
risk of estrogen receptor–positive breast cancer by 90% (RR, 0.10;
95% CI, 0.04-0.24), but not estrogen receptor–negative invasive
breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the
risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but
did not increase the risk of endometrial cancer (RR, 0.8; 95% CI,
0.2-2.7).ConclusionAmong postmenopausal women with osteoporosis, the
risk of invasive breast cancer was decreased by 76% during 3 years of
treatment with raloxifene.
1,692 citations
••
TL;DR: Evaluating several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota and the mechanisms of action of these markers clarify.
Abstract: PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable antitumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic, and biological studies focused on the human cancer microenvironment have yielded substantial insight into this issue. Here, we focus on tumor microenvironment and evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota. We further clarify the mechanisms of action of these markers and their roles in shaping, being shaped, and/or predicting therapeutic responses. We also discuss a variety of combinations with PD pathway blockade and their scientific rationales for cancer treatment.
1,690 citations
••
TL;DR: Cetuximab on this once-weekly schedule has modest activity and is well-tolerated as a single agent in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor.
Abstract: Purpose To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapyrefractory colorectal cancer whose tumors express the epidermal growth factor receptor. Patients and Methods Phase II, open-label clinical trial. Patients were required to have EGFr expression demonstrated on formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining before study participation. Patients were required to have received irinotecan, either alone or in a combination regimen, and to have demonstrated clinical failure on this regimen before study entry. Cetuximab was administered weekly by intravenous infusion. The first dose of 400 mg/m 2 was given during the course of 2 hours. Subsequent weekly treatments were given at a dose of 250 mg/m 2 during the course of 1 hour. Results
1,690 citations
••
TL;DR: The purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A is reported, and it is linked to Polycomb silencing, which is important in regulating chromatin dynamics and transcription.
Abstract: Covalent modification of histones is important in regulating chromatin dynamics and transcription1,2. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B3. Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination4,5,6 and a ‘cross-talk’ between H2B ubiquitination and histone methylation7,8, the responsible enzymes and the functions of H2A ubiquitination are unknown. Here we report the purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A. The complex, termed hPRC1L (human Polycomb repressive complex 1-like), is composed of several Polycomb-group proteins including Ring1, Ring2, Bmi1 and HPH2. hPRC1L monoubiquitinates nucleosomal histone H2A at lysine 119. Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. Chromatin immunoprecipitation analysis demonstrated colocalization of dRing with ubiquitinated H2A at the PRE and promoter regions of the Drosophila Ubx gene in wing imaginal discs. Removal of dRing in SL2 tissue culture cells by RNA interference resulted in loss of H2A ubiquitination concomitant with derepression of Ubx. Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing.
1,685 citations
Authors
Showing all 30708 results
Name | H-index | Papers | Citations |
---|---|---|---|
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 |