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.

Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain.

Abstract: Short RNAs mediate gene silencing, a process associated with virus resistance, developmental control and heterochromatin formation in eukaryotes. RNA silencing is initiated through Dicer-mediated processing of double-stranded RNA into small interfering RNA (siRNA). The siRNA guide strand associates with the Argonaute protein in silencing effector complexes, recognizes complementary sequences and targets them for silencing. The PAZ domain is an RNA-binding module found in Argonaute and some Dicer proteins and its structure has been determined in the free state. Here, we report the 2.6 A crystal structure of the PAZ domain from human Argonaute eIF2c1 bound to both ends of a 9-mer siRNA-like duplex. In a sequence-independent manner, PAZ anchors the 2-nucleotide 3' overhang of the siRNA-like duplex within a highly conserved binding pocket, and secures the duplex by binding the 7-nucleotide phosphodiester backbone of the overhang-containing strand and capping the 5'-terminal residue of the complementary strand. On the basis of the structure and on binding assays, we propose that PAZ might serve as an siRNA-end-binding module for siRNA transfer in the RNA silencing pathway, and as an anchoring site for the 3' end of guide RNA within silencing effector complexes.

Pancreatic adenocarcinoma, version 2.2017: Clinical practice guidelines in Oncology

Abstract: Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

Screening for psychologic distress in ambulatory cancer patients

Abstract: BACKGROUND Based on evidence that psychologic distress often goes unrecognized although it is common among cancer patients, clinical practice guidelines recommend routine screening for distress. For this study, the authors sought to determine whether the single-item Distress Thermometer (DT) compared favorably with longer measures currently used to screen for distress. METHODS Patients (n = 380) who were recruited from 5 sites completed the DT and identified the presence or absence of 34 problems using a standardized list. Participants also completed the 14-item Hospital Anxiety and Depression Scale (HADS) and an 18-item version of the Brief Symptom Inventory (BSI-18), both of which have established cutoff scores for identifying clinically significant distress. RESULTS Receiver operating characteristic (ROC) curve analyses of DT scores yielded area under the curve estimates relative to the HADS cutoff score (0.80) and the BSI-18 cutoff scores (0.78) indicative of good overall accuracy. ROC analyses also showed that a DT cutoff score of 4 had optimal sensitivity and specificity relative to both the HADS and BSI-18 cutoff scores. Additional analyses indicated that, compared with patients who had DT scores < 4, patients who had DT scores ≥ 4 were more likely to be women, have a poorer performance status, and report practical, family, emotional, and physical problems (P ≤ 0.05). CONCLUSIONS Findings confirm that the single-item DT compares favorably with longer measures used to screen for distress. A DT cutoff score of 4 yielded optimal sensitivity and specificity in a general cancer population relative to established cutoff scores on longer measures. The use of this cutoff score identified patients with a range of problems that were likely to reflect psychologic distress. Cancer 2005. © 2005 American Cancer Society.

Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer

Abstract: Importance BRAF V600E is a prominent oncogene in papillary thyroid cancer (PTC), but its role in PTC-related patient mortality has not been established. Objective To investigate the relationship between BRAF V600E mutation and PTC-related mortality. Design, Setting, and Participants Retrospective study of 1849 patients (1411 women and 438 men) with a median age of 46 years (interquartile range, 34-58 years) and an overall median follow-up time of 33 months (interquartile range, 13-67 months) after initial treatment at 13 centers in 7 countries between 1978 and 2011. Main Outcomes and Measures Patient deaths specifically caused by PTC. Results Overall, mortality was 5.3% (45/845; 95% CI, 3.9%-7.1%) vs 1.1% (11/1004; 95% CI, 0.5%-2.0%) (P Conclusions and Relevance In this retrospective multicenter study, the presence of the BRAF V600E mutation was significantly associated with increased cancer-related mortality among patients with PTC. Because overall mortality in PTC is low and the association was not independent of tumor features, how to use BRAF V600E to manage mortality risk in patients with PTC is unclear. These findings support further investigation of the prognostic and therapeutic implications of BRAF V600E status in PTC.