tbuckley/cabot-search huggingface dataset:
Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial
Authors: T.E. Witzig, K. Tobinai, L. Rigacci, T. Ikeda, A. Vanazzi, M. Hino, Y. Shi, J. Mayer, L.J. Costa, C.D. Bermudez Silva, J. Zhu, D. Belada, K. Bouabdallah, J.G. Kattan, J. Kuruvilla, W.S. Kim, J.-F. Larouche, M. Ogura, M. Ozcan, L. Fayad, C. Wu, J. Fan, A.-L. Louveau, M. Voi, F. Cavalli
Journal: Annals of Oncology (2017)
Incorporating blood-based liquid biopsy information into cancer staging: time for a TNMB system?
Authors: M. Yang, M.E. Forbes, R.L. Bitting, S.S. O'Neill, P -C Chou, U. Topaloglu, L.D. Miller, G.A. Hawkins, S.C. Grant, B.R. DeYoung, W.J. Petty, K. Chen, B.C. Pasche, W. Zhang
Journal: Annals of Oncology (2017)
Increased Inflammation in Pericardial Fluid Persists 48 Hours After Cardiac Surgery
Authors: Brittany Butts, Lee A. Goeddel, David J. George, Chad Steele, James E. Davies, Chih-Chang Wei, Jasmina Varagic, James F. George, Carlos M. Ferrario, Spencer J. Melby, Louis J. Dell’Italia
Journal: Circulation (2017)
CD19-negative relapse of pediatric B-cell precursor acute lymphoblastic leukemia following blinatumomab treatment
Authors: E. Mejstríková, O. Hrusak, M. J. Borowitz, J. A. Whitlock, B. Brethon, T. M. Trippett, G. Zugmaier, L. Gore, A. von Stackelberg, F. Locatelli
Journal: Blood Cancer Journal (2017)
Fc-independent immune thrombocytopenia via mechanomolecular signaling in platelets
Authors: M. Edward Quach, Matthew A. Dragovich, Wenchun Chen, Anum K. Syed, Wenpeng Cao, Xin Liang, Wei Deng, Simon F. De Meyer, Guangheng Zhu, Jun Peng, Heyu Ni, Carolyn M. Bennett, Ming Hou, Jerry Ware, Hans Deckmyn, X. Frank Zhang, Renhao Li
Journal: Blood (2017)
Peptide‐Functionalized Polyurethane Coatings Prepared via Grafting‐To Strategy to Selectively Promote Endothelialization
Authors: Xin Ding, Willy Chin, Chuen Neng Lee, James L. Hedrick, Yi Yan Yang
Journal: Advanced Healthcare Materials (2017)

Abstract Endothelialization, formation of endothelial cells (ECs) layer on cardiovascular implant surface, is considered an ideal approach to prevent restenosis (renarrowing of blood vessel mainly due to the accumulation of proliferated vascular smooth muscle cells, SMCs) and thrombosis. In this study, the possibility of using polyurethane (PU) as a coating platform for functionalization with peptide to enhance endothelialization on implants is explored. PUs are synthesized through metal‐free organocatalytic polymerization followed by chemical conjugation with an EC‐specific REDV peptide through thiol–ene reaction. Meanwhile, the free isocyanate groups of PU allow for covalent grafting of REDV‐functionalized PU (PU/REDV) to silanize implant materials (nitinol and PET). PU/REDV coating with peptide grafting density of ≈2 nmol cm −2 selectively accommodates primary human umbilical vein ECs (HUVECs) and retards spreading of primary human umbilical artery SMCs (HUASMCs). In addition, a layer of HUVECs is formed within 3 d on PU/REDV‐coated surfaces, while proliferation of HUASMCs is inhibited. The selectivity is further confirmed by coculture of HUVECs and HUASMCs. Moreover, the PU/REDV‐coated surfaces are less thrombogenic as evidenced by reduced number and activity of adhered platelets. Therefore, PU/REDV can be potentially used as a coating of cardiovascular implants to prevent restenosis and thrombosis by promoting endothelialization.
Plasma Inflammatory Protein Profiles Distinguish Hemophagocytic Lymphohistiocytosis from Sepsis and SIRS
Authors: Harshal Abhyankar, Carl E. Allen, Howard Lin, Baruch Goldberg, Brooks Scull, Kenneth L. McClain, Jordana Goldman, Trung Nguyen, Michael B. Jordan, Tsz-kwong Man, Olive S. Eckstein, Joseph Lubega, Dalia Bashir, Rikhia Chakraborty, Hector Wong, Eyal Muscal, Daniel Zinn
Journal: Blood (2017)
Abstract IA09: Comprehensive genomic characterization of head and neck squamous cell carcinomas
Authors: Jennifer R. Grandis
Journal: Clinical Cancer Research (2017)

Abstract Large and comprehensive genomic analyses of head and neck squamous cell carcinomas (HNSCC) are greatly increasing our understanding of the heterogeneity of this disease and identifying the key genomic changes that drive these tumors. HNSCC tumors associated with HPV are distinct from HNSCC disease linked to tobacco exposure (HPV-positive versus HPV-negative). HPV- tumors are characterized by: 1) amplification of receptor tyrosine kinases (RTK); 2) genomic loss of TP53 and loss of CKDN2A/RB1 by a variety of mechanisms including truncating mutation, deletion, and/or alternative splicing; 3) amplification of CCND1/CDK4/CDK6; 4) activation of NFE2L2/KEAP1/CUL3; and 5) loss of NOTCH1/FAT1/AJUBA. In contrast, HPV-positive HNSCCs harbor: 1) RTK amplification; 2) FGFR2/3 mutations and/or FGFR3-TACC3 fusions; 3) CDKN2A loss; and 4) E2F1 amplification. Interestingly, activating mutations in the PIK3CA oncogene are found in approximately one third of HPV-negative HNSCC and in over fifty percent of HPV-positive tumors. Mutually exclusive mutations in RAS family genes, specifically RHOA, KRAS, and HRAS, are present but infrequently found in HNSCC (6% of TCGA cases). Amplification of chromosome 3q, a region containing the TP63, SOX2, and PIK3CA genes, is seen in the majority of both HPV-negative and HPV-positive HNSCC. HPV-negative HNSCCs demonstrate clear evidence of molecular heterogeneity, as demonstrated by expression profiling studies indicating diverse biologic subclasses within HPV-negative disease, including a class of tumors without EGFR amplification and/or overexpression, previously termed “atypical” HNSCCs, which consist of approximately 20% of HPV-negative cases and the majority of HPV-positive HNSCCs. An intriguing mutational pattern identified by TCGA was a subset of HPV-negative HNSCC originating in the oral cavity with few to no copy-number alterations statistically enriched for HRAS, CASP8, and PIK3CA mutations and lack of TP53 mutation. With increasing genetic profiling of HNSCC cell lines and patient-derived xenografts, there is increasing opportunity to rationally select preclinical models to test specific precision medicine hypotheses. Citation Format: Jennifer R. Grandis. Comprehensive genomic characterization of head and neck squamous cell carcinomas [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA09.
Abstract #2345: Comparative oncology modeling of rapalog development
Authors: Melissa Paoloni, Christina Mazcko, Duane Currier, Yunkai Yu, Liang Cao, Chand Khanna
Journal: Cancer Research (2009)

Signaling through the mTOR pathway has been shown to contribute to the growth, progression and chemoresistance of several cancers. Accordingly, agents that inhibit this pathway have been developed as potentially valuable therapeutics for cancer. Preclinical studies of rapamycin in mice as well as recent data using novel rapalogs in human patients suggest that mTOR blockade may be efficacious in several cancers including osteosarcoma. The development of mTOR inhibitors as cancer agents will require optimization of dose and regimen as well rationale selection of appropriate agents to be used in combination therapies. The NCI-directed and centrally managed, Comparative Oncology Trials Consortium (COTC), provides the advanced infrastructure, via electronically reported data and serial tumor and surrogate biomarker collections, to ask biologically intensive mechanistic questions in a clinically relevant population of dogs with naturally occurring cancers. To this end, in a recently completed dose escalation study, COTC003, with doses ranging from 0.01 mg/kg to 0.08 mg/kg we demonstrated that dogs with osteosarcoma could receive rapamycin safely and yield pharmacokinetic exposures similar to those seen in human patients. The study period was 15 days, with dogs receiving seven consecutive IM doses of rapamycin then having limb removal surgery on day 8. A serial PK assessment over the initial 48 hours was completed, as well as trough levels on Day 8, 9 and 15. These doses were well tolerated through seven consecutive doses of rapamycin and no MTD was reached. Pharmacokinetic data from this study showed a dose dependent relationship with exposure, reaching exposures similar to those seen in human patients. Tumor biopsies were obtained pre-treatment and post-treatment on the day of surgery. Furthermore, at these exposures, modulation of mTOR targets (pS6RP/S6RP) in matched tumor tissue and PBMCs was demonstrated. However modulation of these conventional mTOR targets was not dose-dependent and occurred at even the lowest exposures. Ongoing studies will now use these tissue reagents to identify pharmacodynamic targets that are reflective of relevant exposures to mTOR inhibitors like rapamycin. Results from this study provide the basis for now ongoing studies that will identify optimal rapamycin treatment schedules using novel pharmacodynamic profiles, assessment of immunosuppression, and pharmacokinetic exposures. Future efforts for this comparative oncology approach that includes pet dogs with cancer are to assess rapamycin in combination with targeted and cytotoxic agents in microscopic disease to evaluate its activity in the most likely effective setting. These data will collectively inform the development path of rapamycin and rapalogs for human sarcoma patients.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2345.
Recent Trends in Chemotherapy Use and Oncologists’ Treatment Recommendations for Early-Stage Breast Cancer
Authors: Allison W Kurian, Irina Bondarenko, Reshma Jagsi, Christopher R Friese, M Chandler McLeod, Sarah T Hawley, Ann S Hamilton, Kevin C Ward, Timothy P Hofer, Steven J Katz
Journal: JNCI Journal of the National Cancer Institute (2017)

There is growing concern about overtreatment of breast cancer as outcomes have improved over time. However, little is known about how chemotherapy use and oncologists' recommendations have changed in recent years.
Bright spots, physical activity investments that work: Active Everyday, Sheffield’s physical activity service for all people living with and beyond cancer
Authors: Liam Humphreys, Helen Crank, Gabbi Frith, Helen Speake, Lindsey J Reece
Journal: British Journal of Sports Medicine (2017)

### Programme card

#### Country/locality/coverage

Sheffield, South Yorkshire, UK, which has a total estimated population of 551 800.

#### Target population

The estimated 18 235 people in Sheffield, South Yorkshire, UK, who are currently living with or beyond cancer. This number is expected to increase to 28 450 people by 2030.

#### What modes/types/domains of physical activity does the programme promote?

Functional physical activity sessions in community venues aimed at improving rehabilitation and recovery.

#### Which of the seven best investments does the programme address?

Community-wide programme and healthcare.

#### What sectors does it involve?

The project involves health professionals and exercise specialists by embedding physical activity within routine cancer care and developing a pathway that bridges the gap between clinical services and community physical activity opportunities.

#### Estimated programme reach

The programme has engaged over 300 people so far.

#### What is special about this programme?

The programme aims to integrate a pragmatic physical activity service for people affected by cancer within existing services, enabling all patients to be supported to move more for health and well-being benefits.

There are now an estimated 2.5 million people living with cancer in the UK, with this figure projected to rise to 4 million by 2030.1 Cancer and its treatment can negatively impact physical and psychological well-being.2 Regular physical activity throughout the cancer journey can preserve or improve physical function, quality of life, cardiorespiratory fitness and weight management.3 That said, …
Personalised diet advice could tackle obesity, report advises
Authors: Anne Gulland
Journal: BMJ (2017)

Personalised nutrition and self monitoring of food consumption could be one way to deal with obesity, a report has said.1

The European Academies Science Advisory Council’s report looks at the future of nutrition and food security in Europe, saying that research and innovation will be central to tackling malnutrition in all forms, including undernutrition and micronutrient deficiencies as well as overweight and obesity.

The report warned against concentrating attention on obesity at the “expense of the continuing recognition of the substantial burden of undernutrition in an unequal …
Abstract IA17: New ways of targeting Ras
Authors: Frank McCormick
Journal: Cancer Research (2017)

Abstract Activating K-Ras mutations occur frequently in many cancers, and account for about one million cancer deaths per year worldwide. Currently, no therapies exist that target K-Ras directly, and K-Ras cancers are very difficult to treat. Indeed, they are excluded from treatment with targeted agents such as tarceva and vemurafenib. The K-Ras protein is a member of a large family of related proteins, of which H-Ras and N-Ras are the closest relatives. Ablation of all three Ras genes is likely to be toxic, as these proteins are essential in most signaling transduction pathways. We therefore need to target the mutant oncoprotein itself, or target K-Ras, without affecting H-Ras or N-Ras. The striking similarity of these proteins makes this task challenging, together with the fact that the K-Ras gene expresses two splice variants, K-Ras 4A and K-Ras 4B, each of which can contribute to cancer. Nevertheless, differences do exist between these proteins, and ways in which these can be exploited will be discussed. One approach takes advantage of unique properties of K-Ras 4B, the other targets an amino acid that is shared between K-Ras isoforms, but is not present in H-Ras or N-Ras, or other members of the Ras family. K-Ras processing can be prevented by compounds that block the CAAX box cysteine. We have identified compounds that interact covalently with this cysteine and block prenylation by farnesyl transferase or geranylgeranyl transferase. These compounds reduce expression of K-Ras in cells and have specificity for K-Ras relative to H-Ras and N-Ras and represent another approach to targeting K-Ras specifically. We have also used new biophysical methods to target K-Ras, including second harmonic generation. This method detects small allosteric changes in proteins, and thus allows identification of small molecules that bind to K-Ras at novel allosteric sites. Drug resistance is likely to be a problem with Ras inhibitors, as it is for all types of cancer therapies. We have identified an approach to killing drug resistant cells that appears effective against a wide range of resistance mechanisms. This was achieved by targeting persister cells that survive targeted agents, but have unique properties that make them vulnerable to attack. The implications of this new strategy will be discussed. Citation Format: Frank McCormick. New ways of targeting Ras [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA17.
Biased Estimates in Mendelian Randomization Studies Conducted in Unrepresentative Samples
Authors: Marcus Munafò, George Davey Smith
Journal: JAMA Cardiology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Abstract 10954: Clinical and Angiographic Predictors of Adverse Outcomes After Percutaneous Coronary Intervention in Patients With Radiation Associated Coronary Artery Disease
Authors: Grant W Reed, Ahmad Masri, Brian P Griffin, Samir R Kapadia, Stephen G Ellis, Milind Y Desai
Journal: Circulation (2015)

Background: The clinical and angiographic predictors of outcomes after percutaneous coronary intervention (PCI) in patients with cancer and radiation associated coronary artery disease (CAD) are not well established. Methods: In this retrospective cohort study, 157 patients with thoracic malignancy and external beam radiation therapy (XRT) prior to PCI were identified. The rates of major adverse cardiovascular and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, repeat revascularization, or stroke) were compared across patient characteristics. Results: During follow-up of 5.4±4.5 years, 91 (58%) patients had MACCE; 59 (38%) died, of which 23 (39%) were cardiac deaths, 23 (39%) due to cancer or other causes, and 13 (22%) unknown. By Kaplan-Meier analysis, MACCE were more frequent with coronary artery calcification (p=0.023), ostial stenosis (p=0.049), target vessel diameter ≥ 3.0 mm (p=0.018), a SYNTAX score ≥ the median of 11 (p=0.014), or bare metal stenting (BMS) compared to drug-eluting stenting (DES) (p=0.006) (Figure). Cardiac death was more frequent in patients with SYNTAX score ≥ 11 (p=0.028) or BMS (p=0.043). After multivariable adjustment, independent predictors of MACCE were chronic kidney disease (CKD) (p=0.006), New York Heart Association (NYHA) class ≥ 3 (p=0.024), and BMS (p=0.008) (Table). Conclusions: In patients with radiation associated CAD treated with PCI, MACCE is more frequent in those with target vessel calcification, ostial stenosis, large vessel diameter, or SYNTAX score ≥ 11. BMS placement is independently associated with greater MACCE than DES, and other risk factors for MACCE include CKD and NYHA class ≥ 3.
Quality of life in patients with advanced epithelial ovarian cancer (EOC) randomized to maintenance pazopanib or placebo after first-line chemotherapy in the AGO-OVAR 16 trial. Measuring what matters—patient-centered end points in trials of maintenance therapy
Authors: M. Friedlander, J. Rau, C.K. Lee, W. Meier, A. Lesoin, J.-W. Kim, A. Poveda, M. Buck, G. Scambia, M. Shimada, F. Hilpert, M.T. King, P. Debruyne, A. Bologna, S. Malander, B.J. Monk, E. Petru, P. Calvert, T.J. Herzog, C. Barrett, A. du Bois
Journal: Annals of Oncology (2017)
Emerging Targeted and Immune-Based Therapies in Sarcoma
Authors: Seth M. Pollack, Matthew Ingham, Matthew B. Spraker, Gary K. Schwartz
Journal: Journal of Clinical Oncology (2017)

Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials. Indeed, the spectrum of targeted drug development in sarcoma now spans many of the most active paradigms in cancer research and includes agents that target cancer-related vulnerabilities in receptor tyrosine kinases and intracellular signaling pathways, epigenetics, metabolism, nuclear-cytoplasmic transport, and many others. Our understanding of the sarcoma immune microenvironment and heterogeneous mechanisms of tumor immune evasion has also expanded. Although a subset of sarcomas appears inflamed and responsive to immune checkpoint blockade with programmed death 1 (PD-1) targeted agents, novel immunotherapies and combinations likely will be needed for most subtypes. A variety of approaches-including targeting immune checkpoints other than PD-1; modulating tumor-associated macrophage phenotype from tumor-promoting to tumor-suppressive status; using cellular-based therapies, such as chimeric antigen and high-affinity T-cell receptors to deepen the adaptive immune response; and reinvigorating older approaches, such as vaccines and oncolytic virus-based treatments-are being investigated. The goal of these new approaches is to harness subtype-specific insights into cancer and immune biology to bring more effective and less toxic treatments to the clinic for the benefit of patients with sarcoma.
Putting innovation to the test
Authors: Fiona Godlee
Journal: BMJ (2017)

NHS staff and patients face the prospect of continued austerity after the chancellor fell short of meeting NHS England’s request for at least £4bn to meet growing demand (doi:10.1136/bmj.j5422). How should we respond? (Watch The BMJ ’s Facebook Live event at http://bit.ly/2AtfCGS for health policy experts’ response to the autumn budget.)

Tight budgets can, of course, stimulate innovation, as Caroline White found when investigating the effect of cuts to England’s sexual health services (doi:10.1136/bmj.j5395). Local authorities have responded innovatively, absorbing rising demand within fixed budgets through efficiencies and new ways of working, says White’s …
INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12) immunotherapy in biochemically relapsed prostate cancer
Authors: I. Csiki, N. Shore, K. Bhatt, M. Morrow, K. Kraynyak, L. Liu, T. McMullan, J. Lee, B. Sachetta, S. Rosencranz, E. Heath, M. Bagarazzi
Journal: Annals of Oncology (2017)