tbuckley/cabot-search huggingface dataset:
Breast cancer wait times: Use of breast screening clinics affect presenting stage
Authors: J. Hodgins, C. Hamm
Journal: Journal of Clinical Oncology (2006)

10686 Background: Wait times in the navigation of the diagnostic and therapeutic system of breast cancer have been increasingly investigated. It is inherently apparent that an earlier diagnosis would lead to an improved prognosis in breast cancer. In Ontario (Canada) Breast Screening Clinics (OBSC) allow direct access of patients to mammograms. Methods: A retrospective review of all breast cancer patients seen in the regional cancer centre in the year 2003 was performed. Wait times between the following events were recorded: first symptom to presentation to medical system, presentation to mammogram, mammogram to biopsy, biopsy to surgery, surgery to consultation at cancer centre. Results: In 2003, 277 new cases of breast cancer were seen at the regional cancer centre. Identified median waiting times were as follows: mammogram to diagnostic biopsy - 18.5 days, diagnostic biopsy to definitive surgery - 28 days; surgical consultation to definitive surgery - 13 days; definitive surgery to oncology consultation - 31 days. Some wait times were longer in those patients who did not have close geographic access to OBSC and a regional cancer centre: mammography to diagnostic biopsy was doubled (17 to 34 days) and surgical consult to surgical date was doubled (12 vs 26.5 days). Eighty per cent (n = 27) of patients identified by OBSC presented with Stage I or less breast cancer vs 37% of all other patients. Seventeen per cent of patients seen at the regional cancer centre were less than 50 years of age and not eligible for the OBSC. Conclusions: The wait times reported are in keeping with the current experience in Ontario, Canada.[1] It is most likely that access to a breast-screening clinic allows self-selection of a more highly motivated population. This population of patients consistently presented with earlier stage and more curable disease. The challenge that remains is to increase the number of patients that access breast-screening clinics. Presently, only 13% of presenting patients seen at the regional cancer centre were identified by the OBSC. We are identifying barriers to the use of this very effective strategy. [1] Cancer Care Ontario. Ontario Wait Times Strategy. www.health.gov.on.ca. [Table: see text]
Conflicts of interest compromise US public health agency’s mission, say scientists
Authors: Jeanne Lenzer
Journal: BMJ (2016)

Scientists at the United States’ public health agency have urged their employers to “clean up this house,” claiming that conflicts of interest are undermining trust in the agency.1

The scientists at the Centers for Disease Control and Prevention in Atlanta, Georgia, sent an anonymous letter at the end of August to Carmen S Villar, chief of staff at the CDC’s Office of the Director. They wrote, “It appears that our mission is being influenced and shaped by outside parties and rogue interests.

“This ‘climate of disregard’ puts many of us in difficult positions. We are often directed to do things we know …
GW26-e5470 The role of circulating miRNAs in diagnosis of acute myocardial infarction and the pathological significance
Authors: Ali Sheikh Md Sayed, Ping Zhu, Li Chuanchang, Ke Xia, Fei Li, Xu Deng, Umme Salma, TianLun Yang, Jun Peng
Journal: Journal of the American College of Cardiology (2015)
Subgroups of T-Cell Prolymphocytic Leukemia (T-PLL) Discovered By High-Throughput Ex Vivo Drug Testing and Genetic Profiling
Authors: Emma I Andersson, Shady Adnan, Leopold Sellner, Dorine Bellanger, Alexandra Schrader, Giuliano Crispatzu, Henan Zhang, Carlos C Mateos, Edgar Faber, Steffen Koschmieder, Tim H. Brummendorf, Krister Wennerberg, Wei Ding, Marc-Henri Stern, Marco Herling, Simon Anders, Wolfgang Huber, Thorsten Zenz, Satu Mustjoki
Journal: Blood (2015)
MicroRNAs as specific biomarkers for distinguishing between primary and metastatic brain tumors
Authors: D. Nass, S. Rosenwald, E. Sitbon, G. Lithwick, E. Elyakim, H. Cholakh, Y. Spector, N. Rosenfeld, R. Aharonov, I. Barshack, Z. Bentwich
Journal: Journal of Clinical Oncology (2008)

13002 Background: A recurring challenge for brain pathologists is to diagnose whether a brain malignancy is a primary tumor or a metastasis from some other origin. The accurate diagnosis of brain malignancies is essential for selection of proper treatment. MicroRNAs are a class of small non-coding RNA species that regulate gene expression; many exhibit tissue-specific expression and are involved in oncogenesis. In this study we examined whether the specific expression of microRNAs may be utilized in the identification and diagnosis of brain malignancies. Methods: We studied the expression profile of human microRNAs in 260 FFPE tumor samples including brain primary tumor samples, non-brain primary tumors, and 50 brain metastases from various tissue origins. We used proprietary protocols for RNA extraction that preserve the microRNA fraction, and profiled microRNA expression on proprietary microRNA microarrays. Results: We identified microRNAs that are differentially expressed specifically in brain primary tumors, as compared to primary tumors from other tissues and their metastases to the brain. By considering the expression of only two of these microRNAs, previously linked to brain development, it was possible to distinguish between primary and metastatic brain tumors with very high accuracy. Conclusions: We identified microRNAs that represent excellent biomarkers for brain primary tumors. Previous reports have found these microRNAs expressed more strongly in developing neurons and brain than in adult brain. Thus, their specific over-expression in brain primary tumors supports a mechanistic role for these microRNAs or a link between neuronal stem cells and brain tumorigenesis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Rosetta Genomics Ltd Rosetta Genomics Ltd
Thrombus Formation at High Shear Rates
Authors: Lauren D.C. Casa, David N. Ku
Journal: Annual Review of Biomedical Engineering (2017)

The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. A high-shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Thrombosis at high shear rates depends primarily on the long protein von Willebrand factor (vWF) and platelets, with hemodynamics playing an important role in each stage of thrombus formation, including vWF binding, platelet adhesion, platelet activation, and rapid thrombus growth. The prediction of high-shear thrombosis is a major area of biofluid mechanics in which point-of-care testing and computational modeling are promising future directions for clinically relevant research. Further research in this area will enable identification of patients at high risk for arterial thrombosis, improve prevention and treatment based on shear-dependent biological mechanisms, and improve blood-contacting device design to reduce thrombosis risk.
Relevance of cardiac parvovirus <scp>B19</scp> in myocarditis and dilated cardiomyopathy: review of the literature
Authors: Job Verdonschot, Mark Hazebroek, Jort Merken, Yannick Debing, Robert Dennert, Hans‐Peter Brunner‐La Rocca, Stephane Heymans
Journal: European Journal of Heart Failure (2016)
PPARα Activation Bypasses the Transcription Elongation Defect in Mutant tif1γ Erythroid Differentiation
Authors: Marlies P. Rossmann, Xiaoying Bai, Bilguujin Dorjsuren, Lauren Krug, Chang-Ying Chiang, Erika Lee, Wahaj Chaudhry, Shakkaura Kemet, Isaac Adatto, Leonard I. Zon
Journal: Blood (2014)
Serum gamma-glutamyl transferase levels affect the prognosis of patients with intrahepatic cholangiocarcinoma who receive postoperative adjuvant transcatheter arterial chemoembolization: A propensity score matching study
Authors: Zhufeng Lu, Shuang Liu, Yong Yi, Xiaochun Ni, Jiaxing Wang, Jinlong Huang, Yipeng Fu, Ya Cao, Jian Zhou, Jia Fan, Shuangjian Qiu
Journal: International Journal of Surgery (2016)
Lapatinib and paclitaxel in HER2-negative, extracellular domain (ECD) positive metastatic breast cancer (MBC) in a randomized phase III study
Authors: R. S. Finn, R. Gagnon, A. Di Leo, M. F. Press, M. Arbushites, M. Koehler
Journal: Journal of Clinical Oncology (2008)

1017 Background: It has been hypothesized that women with HER2-negative MBC respond to HER2-targeted drugs if the circulating baseline HER2 ECD is >16 ng/ml. Lapatinib, an oral, dual inhibitor of HER2 and EGFR, is effective in women with HER2+ MBC. We retrospectively examined this hypothesis using tissue and serum data from women with MBC who were enrolled in a randomized clinical trial of lapatinib and paclitaxel. Methods: Patients (pts, n=579) with newly diagnosed MBC were randomized to paclitaxel with placebo (P) or lapatinib (L+P). HER2 status was evaluated by fluorescence in situ hybridization or immunohistochemistry in archival tissue. Serum ECD was centrally measured by ELISA in available samples at baseline (bECD, n=473), Week 9, and every 12 weeks thereafter. Pts were stratified by HER2 and bECD status. Results: bECD was positive only in 62% (50/81) of HER2+ pts and in as many as 24% (96/392) of HER2-negative pts. It is known that PFS increased in L+P in HER2+ patients. In HER2-negative pts, bECD status had no effect on response (see Table). PFS within L+P or P was not significantly different across bECD strata. Follow-up median ECD levels were stable in bECD- pts, and decreased (up to 9 ng/mL) in bECD+ pts. Decreases were similar between treatment arms. Additional correlations (response rate, time, tumor burden) and descriptive statistics for HER2+ pts will be reported. Conclusions: This is the largest reported randomized ECD dataset for HER2-negative MBC pts. bECD+ levels were observed in 24% of HER2-negative MBC pts. We conclude that in HER2-negative MBC: (1) bECD is not predictive of benefit of L+P or P, (2) higher bECD may not indicate more refractory tumors as PFS with L+P and P was similar across bECD strata, (3) bECD may not contribute to treatment decisions for pts with HER2-negative MBC since PFS was similar in bECD strata. bECD+ (n=96) bECD- (n=296) L+P P p L+P P p Median PFS, wks, HER2- 17.3 24.0 0.7948 23.9 22.9 0.3598 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline Genentech, GlaxoSmithKline Genentech, GlaxoSmithKline
Quality of life, autonomy, satisfaction, and costs associated with mental health supported accommodation services in England: a national survey
Authors: Helen Killaspy, Stefan Priebe, Stephen Bremner, Paul McCrone, Sarah Dowling, Isobel Harrison, Joanna Krotofil, Peter McPherson, Sima Sandhu, Maurice Arbuthnott, Sarah Curtis, Gerard Leavey, Geoff Shepherd, Sandra Eldridge, Michael King
Journal: The Lancet Psychiatry (2016)
Impact of CTLA4 Genotype and Other Immune Response Gene Polymorphisms on Outcomes after Umbilical Cord Blood Transplantation - a Eurocord, CBC-Ctiwb-EBMT, Netcord and FMRP-USP Study
Authors: Renato Cunha, Marco A. Zago, Sergio Querol, Fernanda Volt, Annalisa Ruggeri, Guillermo Sanz, Fabienne Pouthier, Gesine Koegler, Jose L Vicario, Paola Bergamaschi, Riccardo Saccardi, Carmen H Lamas, Cristina Heredia, Gerard Michel, Henrique Bittencourt, Marli Tavella, Rodrigo A Panepucci, Francisco Fernandes, Julia Pavan, Eliane Gluckman, Vanderson Rocha
Journal: Blood (2015)
ARRY-649, a member of a novel class of Eg5 kinesin inhibitors
Authors: M. R. Miglarese, E. Wallace, R. Woessner, S. Allen, J. Hans, C. Lemieux, W. Dewolf, J. Lyssikatos, P. Lee, K. Koch
Journal: Journal of Clinical Oncology (2006)

13045 Background: Inhibitors of the Eg5 motor kinesin selectively disrupt mitotic spindles in dividing cells. This selective targeting of microtubule dynamics in dividing cells is expected to translate to broad-spectrum anti-tumor activity while avoiding neuropathic side effects caused by taxanes. To date, quinazolinone Eg5 inhibitors, exemplified by ispinesib, represent the only Eg5 inhibitors reported in clinical trials. Methods: We used X-ray crystallography, biochemical and cell-based assays, pharmacokinetic profiling and in vivo efficacy studies to identify and optimize a potent series of Eg5 inhibitors. Results: We have discovered a distinct series of potent Eg5 inhibitors, exemplified by ARRY-649. ARRY-649 inhibited Eg5 with an IC 50 of 0.7 nM, blocked phosphorylation of histone H3 in HeLa cells with an IC 50 of 0.3 nM and showed sub-nanomolar activity against a broad panel of human tumor cells lines in in vitro viability assays. Further evaluation of mechanism-of-action in tumor cell lines revealed that ARRY-649 induced a monopolar spindle phenotype and subsequent apoptosis characteristic of Eg5 inhibition. In contrast to paclitaxel, ARRY-649 retained potent activity against multi-drug resistant human tumor cells lines selected to overexpress P-glycoprotein. ARRY-649 demonstrated robust efficacy in the HT-29 human colon tumor xenograft model and was well-tolerated at efficacious doses and schedules. Durable complete- and partial-regressions were observed upon intraperitoneal administration on a 5 mg/kg q4dx3 schedule in the HT-29 model. Similar results were obtained using the HL-60 myelomonocytic xenograft model. Conclusions: ARRY-649 represents a distinct class of potent Eg5 inhibitors with robust activity in preclinical models of human cancer. Based on these observations, we have progressed novel Eg5 inhibitors toward clinical development. [Table: see text]
Response to: ‘Helmet use and risk of head injuries in alpine skiers and snowboarders: changes after an interval of one decade’
Authors: Gerhard Ruedl, Irving Scher, Martin Burtscher
Journal: British Journal of Sports Medicine (2016)

We read with great interest the article of Sulheim et al .1 We agree with their conclusion that wearing a helmet while skiing or snowboarding is recommended strongly. We are troubled by the authors' conclusion in their abstract that there was an ‘unexpected reduction in protective effect of a skiing helmet’ when comparing the winter seasons 2002 and 2011. We feel that this wording is misleading, as there was no measure of the physical abilities of helmets in their study. Ski helmets typically …
Phase II study of recombinant IL-21 (rIL-21) plus sorafenib as second- or third-line therapy for metastatic renal cell cancer (mRCC): Final results
Authors: S. Bhatia, E. Heath, I. Puzanov, W. Miller, B. Curti, M. Gordon, M. Ernstoff, D. Hausman, N. Hunder, J. Thompson
Journal: Journal of Clinical Oncology (2009)

3023 Background: Despite the positive impact of targeted therapies on treatment for mRCC, the efficacy of these agents appears to decrease beyond the first-line setting. There is an unmet need for novel therapies after failure of vascular endothelial growth factor (VEGF)-directed agents. rIL-21, a cytokine that enhances CD8+ T-cell and NK cell activity, has single-agent antitumor activity (J Clin Oncol. 2008;26:2034). Based on promising results of a phase I study of rIL-21 plus sorafenib, we initiated a phase II study to explore the safety and efficacy of this combination as second- or third-line treatment for mRCC. Methods: Patients with mRCC received second- or third-line therapy with sorafenib 400 mg PO BID continuously plus rIL-21 30 μg/kg IV on days 1–5 and 15–19 of each 7-week treatment course (TC). Efficacy endpoints included progression-free survival (PFS) and overall response rate (ORR) per RECIST. Response was assessed by the investigator and by independent radiologic review (IRR). Results: 33 patients were enrolled from 14 sites in the U.S. and Canada. Median age was 61 years (range, 46–75); ECOG performance status was 0 (n=15) or 1 (n=18). Patients had received 1 (n=25) or 2 (n=8) prior lines of therapy, including sunitinib (n=19), temsirolimus (n=5), bevacizumab (n=3), everolimus (n=2), IL-2 (n=11), or other (n=4). Grade ≥3 adverse events considered at least possibly related to study drug and occurring in ≥3 patients included hypophosphatemia (33%), hand-foot syndrome (24%), rash (24%), thrombocytopenia (8%), and neutropenia (8%). Twelve patients remain on study; 13 withdrew for progressive disease (PD), 6 for toxicity, and 2 for other reasons. IRR has been performed for the first 23 patients who completed at least 1 full TC, with 6 confirmed PR (26%), 1 unconfirmed PR (4%), 14 SD (61%), and 2 PD (9%). While median PFS cannot yet be determined, 14 of the first 29 patients have completed at least 3 TCs, equivalent to approximately 21 weeks, with SD or better. Conclusions: rIL-21 plus sorafenib is associated with an acceptable safety profile and promising antitumor efficacy in previously treated patients with mRCC. The observed ORR to date compares favorably with the rate previously reported for sorafenib in the first and second-line setting. [Table: see text]
Minimal Residual Disease (MRD) and Risk of Relapse in Acute Promyelocytic Leukemia (APL): Insights from the North American Intergroup Phase III Trial C9710.
Authors: Wendy Stock, Richard Harvey, Barry Moser, Dorie Sher, Esther Schachter-Tokarz, Matthew Myers, James Slack, Bayard Powell, Clara D. Bloomfield, Richard A. Larson, Martin S. Tallman, Frederick R. Appelbaum, James Feusner, Cheryl Willman, Robert Gallagher
Journal: Blood (2006)
The role of DNA methylation in dyslipidaemia: A systematic review
Authors: Kim V.E. Braun, Trudy Voortman, Klodian Dhana, Jenna Troup, Wichor M. Bramer, John Troup, Rajiv Chowdhury, Abbas Dehghan, Taulant Muka, Oscar H. Franco
Journal: Progress in Lipid Research (2016)
The Analgesic Effect of Magnetic Acupressure During Bone Marrow Aspiration and Biopsy Procedure in Cancer Patients: A Randomized, Blinded, Placebo Controlled Trial.
Authors: Ting Bao, Xiaobu Ye, Janice Skinner, Bing Cao, Joy Fisher, Suzanne Nesbit, Stuart A. Grossman
Journal: Blood (2009)
A MicroRNA302-367-Erk1/2-Klf2-S1pr1 Pathway Prevents Tumor Growth via Restricting Angiogenesis and Improving Vascular Stability
Authors: Jingjiang Pi, Ting Tao, Tao Zhuang, Huimin Sun, Xiaoli Chen, Jie Liu, Yu Cheng, Zuoren Yu, Helen He Zhu, Wei-Qiang Gao, Yuanzhen Suo, Xunbin Wei, Paul Chan, Xiangjian Zheng, Ying Tian, Edward Morrisey, Lin Zhang, YuZhen Zhang
Journal: Circulation Research (2016)

Angiogenic hypersprouting and leaky vessels are essential for tumor growth. MicroRNAs have unique therapeutic advantages by targeting multiple pathways of tumor-associated angiogenesis, but the function of individual miRNAs of miR302-367 cluster in angiogenesis and tumors has not yet been fully evaluated.To investigate the functions of miR302-367 in developmental angiogenesis and tumor angiogenesis and explore the molecular mechanisms of microRNA for the treatment of pathological neovascularization-related diseases.Here, we show that miR302-367 elevation in endothelial cells reduces retinal sprouting angiogenesis and promotes vascular stability in vivo, ex vivo, and in vitro. Erk1/2 is identified as direct target of miR302-367, and downregulation of Erk1/2 on miR302-367 elevation in endothelial cells increases the expression of Klf2 and in turn S1pr1 and its downstream target VE-cadherin, suppressing angiogenesis and improving vascular stability. Conversely, both pharmacological blockade and genetic deletion of S1pr1 in endothelial cells reverse the antiangiogenic and vascular stabilizing effect of miR302-367 in mice. Tumor angiogenesis shares features of developmental angiogenesis, and endothelial specific elevation of miR302-367 reduces tumor growth by restricting sprout angiogenesis and decreasing vascular permeability via the same Erk1/2-Klf2-S1pr1 pathways.MiR302-367 regulation of an Erk1/2-Klf2-S1pr1 pathway in the endothelium advances our understanding of angiogenesis, meanwhile also provides opportunities for therapeutic intervention of tumor growth.
Predictors of survival in patients with transformed chronic lymphocytic leukemia (TC).
Authors: Lorenzo Falchi, Michael J. Keating, Xuemei Wang, Ellen J. Schlette, Rachel L. Sargent, Edith M. Marom, Mylene Truong, William G. Wierda, Alessandra Ferrajoli
Journal: Journal of Clinical Oncology (2013)

7098 Background: Patients with CLL that develop Richter’s syndrome (RS) have a very poor prognosis. Similarly, pts with CLL that have clinical and histological features (increased large cells/prolymphocytes in CLL tissue biopsy) of increased aggressiveness (defined as accelerated phase CLL, AP) have a poor prognosis. In order to identify prognostic factors in pts with AP and RS, collectively referred to as TC, we reviewed our center experience. Methods: Pts with TC and complete evaluation including biopsy and concomitant FDG/PET were included. Pts with de novo TC were excluded as their prognosis is substantially superior versus previously treated pts. Pts with N+ or M+ concurrent solid tumors were also excluded. Since FDG/PET-derived SUV reflects tumor proliferative rate, we used SUVmax≥10 to indicate high-risk disease (Falchi, Blood. 2012;120: abstr # 927). We identified factors associated with outcome and performed a multivariable model for OS. Results: One hundred eighty-three consecutive pts with TC (99 with AP and 84 with RS) were evaluated at MDACC between 2002 and 2012. Demographic and clinical characteristics were similar between pts with AP and pts with RS. 30% and 77% of pts with AP and RS, respectively had an SUVmax≥10. Approximately half of the pts were treated with intensive chemoimmunotherapy after the TC diagnosis. CR rates were 21% and 16% and overall response rates were 37% and 26% for pts with AP and RS, respectively. At the time of this analysis 144/183 pts have died, for a median OS of 9.6 months (7.9-14.7). Age ≥65, B symptoms, LDH, β2-microglobulin, del17p, SUVmax≥10, extensive disease by FDG/PET (SUVmax≥5 on both sides of the diaphragm), PS≥2 bulky disease and high Ki67 correlated with shorter OS. In multivariable analysis SUV uptake (max≥10), PS higher than 1 and bulky nodal disease (&gt;5 cm) retained independent significance. Conclusions: Based on our experience, an SUVmax of 10 or higher, PS higher than 1 and bulky nodal disease (&gt;5 cm) are the most important factors predicting outcome in pts with TC. A prognostic model for survival is being developed for pts with TC.