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.

Proposal for Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials: The STEEP System

Abstract: Purpose Standardized definitions of breast cancer clinical trial end points must be adopted to permit the consistent interpretation and analysis of breast cancer clinical trials and to facilitate cross-trial comparisons and meta-analyses. Standardizing terms will allow for uniformity in data collection across studies, which will optimize clinical trial utility and efficiency. A given end point term (eg, overall survival) used in a breast cancer trial should always encompass the same set of events (eg, death attributable to breast cancer, death attributable to cause other than breast cancer, death from unknown cause), and, in turn, each event within that end point should be commonly defined across end points and studies. Methods A panel of experts in breast cancer clinical trials representing medical oncology, biostatistics, and correlative science convened to formulate standard definitions and address the confusion that nonstandard definitions of widely used end point terms for a breast cancer clinical tr...

Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors

Abstract: We used bioluminescence imaging to reveal patterns of metastasis formation by human breast cancer cells in immunodeficient mice. Individual cells from a population established in culture from the pleural effusion of a breast cancer patient showed distinct patterns of organ-specific metastasis. Single-cell progenies derived from this population exhibited markedly different abilities to metastasize to the bone, lung, or adrenal medulla, which suggests that metastases to different organs have different requirements. Transcriptomic profiling revealed that these different single-cell progenies similarly express a previously described “poor-prognosis” gene expression signature. Unsupervised classification using the transcriptomic data set supported the hypothesis that organ-specific metastasis by breast cancer cells is controlled by metastasis-specific genes that are separate from a general poor-prognosis gene expression signature. Furthermore, by using a gene expression signature associated with the ability of these cells to metastasize to bone, we were able to distinguish primary breast carcinomas that preferentially metastasized to bone from those that preferentially metastasized elsewhere. These results suggest that the bone-specific metastatic phenotypes and gene expression signature identified in a mouse model may be clinically relevant.

Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets

Abstract: We have shown that coculture of bone marrow microvascular endothelial cells with hematopoietic progenitor cells results in proliferation and differentiation of megakaryocytes In these long-term cultures, bone marrow microvascular endothelial cell monolayers maintain their cellular integrity in the absence of exogenous endothelial growth factors Because this interaction may involve paracrine secretion of cytokines, we evaluated megakaryocytic cells for secretion of vascular endothelial growth factor (VEGF) Megakaryocytes (CD41a+) were generated by ex vivo expansion of hematopoietic progenitor cells with kit-ligand and thrombopoietin for 10 days and further purified with immunomagnetic microbeads Using reverse transcription–PCR, we showed that megakaryocytic cell lines (Dami, HEL) and purified megakaryocytes expressed mRNA of the three VEGF isoforms (121, 165, and 189 amino acids) Large quantities of VEGF (>1 ng/106 cells/3 days) were detected in the supernatant of Dami cells, ex vivo-generated megakaryocytes, and CD41a+ cells isolated from bone marrow The constitutive secretion of VEGF by CD41a+ cells was stimulated by growth factors of the megakaryocytic lineage (interleukin 3, thrombopoietin) Western blotting of heparin–Sepharose-enriched supernatant mainly detected the isoform VEGF165 In addition, immunohistochemistry showed intracytoplasmic VEGF in polyploid megakaryocytes Thrombin stimulation of megakaryocytes and platelets resulted in rapid release of VEGF within 30 min We conclude that human megakaryocytes produce and secrete VEGF in an inducible manner Within the bone marrow microenvironment, VEGF secreted by megakaryocytes may contribute to the proliferation of endothelial cells VEGF delivered to sites of vascular injury by activated platelets may initiate angiogenesis

Long-Term Survival After Curative Resection for Pancreatic Ductal Adenocarcinoma: Clinicopathologic Analysis of 5-Year Survivors

Abstract: Objective The authors reviewed the clinicopathologic characteristics of patients who underwent resection with curative intent for ductal adenocarcinoma of the pancreas between 1983 and 1989. Summary Background Data Recent studies have demonstrated a reduction in the morbidity and mortality of pancreatic resection and improvement in the actuarial 5-year survival for patients with resected ductal adenocarcinoma. Methods Resection with curative intent was performed on 118 of 684 patients (17%) with pancreatic cancer admitted to the authors' institution. Clinical, demographic, treatment, and pathologic variables were analyzed. The original pathologic material for all cases was reviewed ; nonductal cancers were excluded. Results The head of the gland was the predominant tumor site (n = 102), followed by the body (n = 9), and tail (n = 7). Seventy-two percent of the patients underwent pancreaticoduodenectomies, 15% underwent total pancreatectomies, 10% underwent distal pancreatectomies, and 3% underwent distal subtotal pancreatectomies. Operative mortality was 3.4%. Median survival was 14.3 months after resection compared with 4.9 months if patients did not undergo resection (p < 0.0001). Twelve patients survived 5 years after surgery (10.2% overall actual 5-year survival rate). Three of the tumors were well differentiated, five were moderately differentiated, and four were poorly differentiated. Extrapancreatic invasion occurred in nine cases (75%), and perineural invasion was present in ten cases (83%). Five tumors exhibited invasion of duodenum, ampulla of Vater, and/or common bile duct, and an additional tumor invaded the portal vein. Lymph node involvement by carcinoma was noted in five cases (42%). Six patients remain alive without evidence of disease at a median follow-up of 101 months (range, 82-133 months). Five patients died of recurrent or metastatic pancreatic cancer at 60, 61, 62, 64, and 64 months, respectively. One patient died at 84 months of metastatic lung cancer without evidence of recurrent pancreatic disease. Conclusions This paper emphasizes the grim prognosis of pancreatic ductal adenocarcinoma. Five-year survival cannot be equated to cure. Although pancreatectomy offers the only chance for long-term survival, it should be considered as the best palliative procedure currently available for the majority of patients. This emphasizes the need for the development of novel and effective adjuvant therapies for this disease.