tbuckley/cabot-search huggingface dataset:
Abstract A20: Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of macrophage-derived IL1beta
Authors: Kelly Kersten, Seth B. Coffelt, Niels J. Verstegen, Kim Vrijland, Metamia Ciampricotti, Chris W. Doornebal, Cheei-Sing Hau, Parul Doshi, Karin E. de Visser
Journal: Cancer Research (2016)

Abstract Metastatic breast cancer remains a major cause of cancer-related death among women. Metastasis is regulated by extensive crosstalk between cancer cells and immune cells. Besides the onset of a local inflammatory microenvironment, tumors frequently induce a systemic inflammatory state characterized by the release of various cytokines, chemokines and growth factors to mobilize myeloid cells that support metastasis, emphasizing the notion that cancer should be regarded as a systemic disease. Utilizing the K14cre;Cdh1F/F;Trp53F/F (KEP) conditional mouse model of metastatic breast cancer, we have recently unraveled a novel mechanistic link between mammary tumor-induced IL17-producing gamma delta T cells, systemic expansion of immunosuppressive neutrophils and metastasis formation. We identified tumor-derived IL1beta as one of the drivers of this cascade by inducing IL17 release from gamma delta T cells. However, it remains unclear how other inflammatory mediators are involved in this systemic inflammatory cascade. In the current study, we identified the pro-inflammatory cytokine CCL2 as a key regulator of the gamma delta T cell IL17 neutrophil axis. CCL2 blockade resulted in reduced IL17-production by gamma delta T cells, decreased systemic neutrophil accumulation and enhanced CD8+ T cell activity. We show that activation of this cascade relies on CCL2-mediated release of IL1beta from CCR2+ tumor-associated macrophages. These results indicate that CCL2, via IL1beta, acts as a key player in regulating the pro-metastatic gamma delta T cell IL17 neutrophil systemic inflammatory cascade and might be an interesting candidate for therapeutic targeting. Citation Format: Kelly Kersten, Seth B. Coffelt, Niels J. Verstegen, Kim Vrijland, Metamia Ciampricotti, Chris W. Doornebal, Cheei-Sing Hau, Parul Doshi, Karin E. de Visser. Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of macrophage-derived IL1beta. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A20.
Abstract IA38: Viral cancers: The forgotten culprits in the African cancer problem
Authors: Patrick S. Moore
Journal: Cancer Research (2017)

Abstract Infection is responsible for approximately one-fifth of cancer cases worldwide. Causes and rates of cancer vary dramatically throughout the world. While infection is often overlooked as a cancer cause in the United States and Europe, it is often the main driving force for cancer in other parts of the world. The first human cancer virus discovered, Epstein-Barr virus (EBV), was isolated from a Ugandan Burkitt lymphoma in 1964. Infectious cancers including hepatocellular carcinoma, cervical carcinoma, Kaposi's sarcoma and gastric carcinoma represent the majority of cancer cases among men and women in some world regions, particularly in Africa. This lecture will focus on how new cancer viruses can be discovered, using Kaposi sarcoma herpesvirus and Merkel cell polyomavirus found in our lab as examples. The common characteristics--as well as the diverse nature--of viral cancers will be described. The extraordinary public health success of vaccines in preventing cancers of particular importance in Africa will be highlighted, and missed opportunities for low-cost, effective prevention and treatment of infectious cancers will be discussed. As with discovery of EBV, it is quite possible that the next cancer agent will be discovered in cancers unique to African countries but will have important implications to public health throughout the world. Citation Format: Patrick S. Moore. Viral cancers: The forgotten culprits in the African cancer problem [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 IA38.
The role of extracellular matrix stiffness in megakaryocyte and platelet development and function
Authors: Orly Leiva, Catherine Leon, Seng Kah Ng, Pierre Mangin, Christian Gachet, Katya Ravid
Journal: American Journal of Hematology (2017)

The extracellular matrix (ECM) is a key acellular structure in constant remodeling to provide tissue cohesion and rigidity. Deregulation of the balance between matrix deposition, degradation, and crosslinking results in fibrosis. Bone marrow fibrosis (BMF) is associated with several malignant and nonmalignant pathologies severely affecting blood cell production. BMF results from abnormal deposition of collagen fibers and enhanced lysyl oxidase-mediated ECM crosslinking within the marrow, thereby increasing marrow stiffness. Bone marrow stiffness has been recently recognized as an important regulator of blood cell development, notably by modifying the fate and differentiation process of hematopoietic or mesenchymal stem cells. This review surveys the different components of the ECM and their influence on stem cell development, with a focus on the impact of the ECM composition and stiffness on the megakaryocytic lineage in health and disease. Megakaryocyte maturation and the biogenesis of their progeny, the platelets, are thought to respond to environmental mechanical forces through a number of mechanosensors, including integrins and mechanosensitive ion channels, reviewed here.
Abstract IA12: Targeting DNA repair in cancer therapy
Authors: Alan D. D'Andrea
Journal: Cancer Research (2017)

Abstract Human cancer cells have genomic instability resulting from germline or acquired defects in DNA repair. One DNA repair pathway - the Fanconi Anemia/BRCA pathway (D'Andrea, A., N Engl J Med 362:1909, 2010) - is defective in many human cancers, including breast, ovarian, and pancreatic neoplasms. Disruption of the FA/BRCA Pathway results in the characteristic chromosome instability and radiation/crosslinker hypersensitivity of these tumors. In general, loss of one DNA repair pathway often leads to hyperdependence on another pathway for tumor cell survival. This hyperdependence offers a unique opportunity for the development of anticancer therapeutics. For instance, FA/BRCA pathway deficient tumors are hyperdependent on Base Excision Repair (BER) and, accordingly, these tumors are hypersensitive to single agent treatment with PARP1 inhibitors, which block BER, or with ATM inhibitors. Our research program is focused on profiling the FA/BRCA pathway and the other five major DNA repair pathways in tumor cells (Kennedy and D'Andrea, JCO 24: 3799, 2006). Each DNA repair pathway has a characteristic biomarker and repairs a specific type of DNA lesion. By profiling these pathways in primary tumor samples with activation-specific antibodies to DNA repair proteins, we have been able (1) to predict the sensitivity of tumors to conventional chemotherapy and radiation (2) to subset tumors for their sensitivity to novel classes of DNA repair inhibitors, (i.e., PARP1, Chk1, ATM, and proteasome inhibitors) and (3) to screen for new small molecule inhibitors of other DNA repair pathways. This combination of novel DNA repair inhibitors, conventional DNA damaging agents, and DNA repair biomarkers offers new opportunities for developing more effective anticancer therapy. In my presentation, I will also discuss novel approaches to sensitizing Triple Negative Breast Cancers (TNBCs) and Ovarian Tumors (OCs) to PARP1 inhibitors. We have previously shown that exposure of these tumors to either a CDK inhibitor or a proteasome inhibitor can block homologous recombination (HR) repair and thereby sensitize the tumor cells to PARP1 inhibitor. The CDK inhibitor/PARP1 inhibitor combination has been examined in orthotopic primary TNBC and OC xenograft models. Finally, we have identified an additional PARP1-dependent DNA repair mechanism in TNBCs and OCs. This pathway is driven by a novel alternative end-joining polymerase, POL. These tumors are hypersensitive to inhibitors of this new pathway, suggesting a new target for DNA repair therapies. Citation Format: Alan D. D'Andrea. Targeting DNA repair in cancer therapy [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 IA12.
Vijver op Ooidonk
Authors: Elizabeth Rasche González
Journal: JAMA (1980)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Ipilimumab plus Lenalidomide after Allogeneic and Autologous Stem Cell Transplantation for Patients with Lymphoid Malignancies
Authors: Issa F. Khouri, Irina Fernandez Curbelo, Francesco Turturro, Elias J. Jabbour, Denái R. Milton, Roland L. Bassett, Luis M. Vence, James P. Allison, Alison M. Gulbis, Padmanee Sharma
Journal: Clinical Cancer Research (2017)

Purpose: Prevention or treatment of relapsed lymphoid malignancies after hematopoietic stem cell transplantation (HSCT) requires novel strategies. We hypothesized that antitumor-cell responses could be enhanced by the addition of lenalidomide to the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab.Experimental Design: We conducted a phase II investigator-initiated trial to assess the safety and activity of ipilimumab and lenalidomide in patients with lymphoid malignancies that relapsed after allogeneic HSCT and in high-risk patients after autologous HSCT. Patients received 10 mg of oral lenalidomide daily for 21 days followed by intravenous ipilimumab at 3 mg/kg bodyweight. The regimen was repeated 4 weeks later for a total of four treatments.Results: We enrolled 17 patients (10 allogeneic and seven autologous transplant recipients). Immune-mediated toxicity was limited to one patient with asymptomatic hypothyroidism and one with dermatitis in the allogeneic and autologous groups, respectively. One allogeneic transplant recipient had a flare of prior GVHD while taking lenalidomide that precluded further treatment. All others finished treatment without GVHD. Four of 10 patients in the allogeneic group had complete responses (three of which were durable at 19+, 21+, and 32+ months), and three had partial responses. The disease in six of seven patients in the autologous group remains in remission. The groups had similar immune responses, including a two- to threefold increase in inducible ICOS+CD4+FoxP3- T-cell number.Conclusions: Our early-phase data suggested that ipilimumab plus lenalidomide is well tolerated after HSCT. Adverse events did not differ significantly between the allogeneic and autologous groups. Clin Cancer Res; 24(5); 1011-8. ©2017 AACR.
PS04.05 ElevatION NET 201:Ph II Study of PDR001 in Metastatic, Well Differentiated NET of Pancreatic/GI/Thoracic Origin or Poorly Differentiated GEP NEC
Authors: J.C. Yao, N. Fazio, M.E. Pavel, J.R. Strosberg, E. Bergsland, P. Ruszniewski, M. Voi, C. Wu, E. Degtyarev, P. Aimone, S. Singh
Journal: Journal of Thoracic Oncology (2017)
Reduction in Hypoglycemia With the Predictive Low-Glucose Management System: A Long-term Randomized Controlled Trial in Adolescents With Type 1 Diabetes
Authors: Mary B. Abraham, Jennifer A. Nicholas, Grant J. Smith, Janice M. Fairchild, Bruce R. King, Geoffrey R. Ambler, Fergus J. Cameron, Elizabeth A. Davis, Timothy W. Jones
Journal: Diabetes Care (2017)

OBJECTIVE Short-term studies with automated systems that suspend basal insulin when hypoglycemia is predicted have shown a reduction in hypoglycemia; however, efficacy and safety have not been established in long-term trials. RESEARCH DESIGN AND METHODS We conducted a 6-month, multicenter, randomized controlled trial in children and adolescents with type 1 diabetes using the Medtronic MiniMed 640G pump with Suspend before low (predictive low-glucose management [PLGM]) compared with sensor-augmented pump therapy (SAPT) alone. The primary outcome was percentage time in hypoglycemia with sensor glucose (SG) &amp;lt;3.5 mmol/L (63 mg/dL). RESULTS In an intent-to-treat analysis of 154 subjects, 74 subjects were randomized to SAPT and 80 subjects to PLGM. At baseline, the time with SG &amp;lt;3.5 mmol/L was 3.0% and 2.8% in the SAPT and PLGM groups, respectively. During the study, PLGM was associated with a reduction in hypoglycemia compared with SAPT (% time SG &amp;lt;3.5 mmol/L: SAPT vs. PLGM, 2.6 vs. 1.5, P &amp;lt; 0.0001). A similar effect was also noted in time with SG &amp;lt;3 mmol/L (P &amp;lt; 0.0001). This reduction was seen both during day and night (P &amp;lt; 0.0001). Hypoglycemic events (SG &amp;lt;3.5 mmol/L for &amp;gt;20 min) also declined with PLGM (SAPT vs. PLGM: events/patient-year 227 vs. 139, P &amp;lt; 0.001). There was no difference in glycated hemoglobin (HbA1c) at 6 months (SAPT 7.6 ± 1.0% vs. PLGM 7.8 ± 0.8%, P = 0.35). No change in quality of life measures was reported by participants/parents in either group. There were no PLGM-related serious adverse events. CONCLUSIONS In children and adolescents with type 1 diabetes, PLGM reduced hypoglycemia without deterioration in glycemic control.
European normative values for physical fitness in children and adolescents aged 9–17 years: results from 2 779 165 Eurofit performances representing 30 countries
Authors: Grant R Tomkinson, Kevin D Carver, Frazer Atkinson, Nathan D Daniell, Lucy K Lewis, John S Fitzgerald, Justin J Lang, Francisco B Ortega
Journal: British Journal of Sports Medicine (2017)

Objective To develop sex-specific and age-specific normative values for the nine Eurofit tests in European children and adolescents aged 9–17 years. Methods A systematic review was undertaken to identify papers that explicitly reported descriptive results for at least one of nine Eurofit tests (measuring balance, muscular strength, muscular endurance, muscular power, flexibility, speed, speed-agility and cardiorespiratory fitness (CRF)) on children and adolescents. Data were included on apparently healthy (free from known disease/injury) children and adolescents aged 9–17 years. Following harmonisation for methodological variation where appropriate, pseudodata were generated using Monte Carlo simulation, with population-weighted sex-specific and age-specific normative centiles generated using the Lambda Mu Sigma (LMS) method. Sex-specific and age-specific differences were expressed as standardised differences in means, with the percentage of children and adolescents with healthy CRF estimated at the sex-age level. Results Norms were displayed as tabulated centiles and as smoothed centile curves for the nine Eurofit tests. The final dataset included 2 779 165 results on children and adolescents from 30 European countries, extracted from 98 studies. On average, 78% of boys (95% CI 72% to 85%) and 83% of girls (95% CI 71% to 96%) met the standards for healthy CRF, with the percentage meeting the standards decreasing with age. Boys performed substantially (standardised differences &gt;0.2) better than girls on muscular strength, muscular power, muscular endurance, speed-agility and CRF tests, but worse on the flexibility test. Physical fitness generally improved at a faster rate in boys than in girls, especially during the teenage years. Conclusion This study provides the largest and most geographically representative sex-specific and age-specific European normative values for children and adolescents, which have utility for health and fitness screening, profiling, monitoring and surveillance.
Geographic Variation of Adjuvant Breast Cancer Therapy Initiation in the United States: Lessons From Medicare Part D
Authors: John A. Charlson, Emily L. McGinley, Ann B. Nattinger, Joan M. Neuner, Liliana E. Pezzin
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Drug utilization under Medicare Part D varies significantly by geographic region. This study examined the extent to which geographic variation in Part D plan characteristics contributes to the variation in choice of initial endocrine therapy agent among women with incident breast cancer. Methods: Two-stage multivariate regression analyses were applied to the 16,541 women identified from Medicare claims as having incident breast cancer in 2006–2007. The first stage determined the effect of state of residence on the probability of having an aromatase inhibitor (AI), as opposed to tamoxifen, as initial endocrine therapy. The second stage provided estimates of the impact of state-specific Part D plan characteristics on variation in choice of initial therapy. Results: There was substantial residual geographic variation in the likelihood of using an AI as initial endocrine therapy, despite controlling for socioeconomic status, breast cancer treatment, and other factors. Regression-adjusted probabilities of starting an AI ranged from 57.3% in Wyoming to 92.6% in the District of Columbia. Results from the second stage revealed that variation in characteristics of Part D plans across states explained approximately one-third (30%) of the state-level variability in endocrine therapy. A higher number of plans with cost-sharing above the mean, greater spread in deductibles, and a greater spread in monthly drug premiums were associated with lower adjusted state probabilities of initiating an AI. In contrast, a higher number of drug plans with monthly premiums above the state mean and higher mean cost-sharing (in dollars) were both positively associated with likelihood of starting on an AI. Conclusions: Study findings suggest that variation in benefit design of Part D plans accounts for an important share of the large and persisting variability in use of AIs—the preferred oral therapy for breast cancer.
Importance of recognition and improved treatment for antimelanoma differentiation‐associated protein 5‐associated dermatomyositis
Authors: A. Caplan, S. Imadojemu, V.P. Werth
Journal: British Journal of Dermatology (2017)

Linked Article: Koguchi‐Yoshioka et al. Br J Dermatol 2017; 177: 1442–1446.
Osteosarcoma, Chondrosarcoma, and Chordoma
Authors: Jeremy S. Whelan, Lara E. Davis
Journal: Journal of Clinical Oncology (2017)

Osteosarcoma (OS), chondrosarcoma, and chordoma are characterized by multiple challenges to the investigator, clinician, and patient. One consequence of their rarity among sarcomas, as well as their biologic and clinical heterogeneity, is that management guidelines are inadequate to inform the range of individual patient-treatment decisions from diagnosis, approaches to surgery, chemotherapy, radiotherapy, treatment of recurrence, palliative care, and quality of survivorship. Of high-grade sarcomas, OSs are among the most curable, with more than two-thirds of patients with localized disease likely to achieve long-term survival. Neoadjuvant chemotherapy comprising cisplatin, doxorubicin, and methotrexate with intercalated surgery is the standard of care for resectable OS in those younger than 40 years. Outcomes for OS presenting with unresectable metastases or recurrent disease, or in those older than 40 years are generally poor. Overall results have improved little for all patients with OS, and new treatments are needed. Surgical resection remains the cornerstone of management for chondrosarcoma and chordoma. However, the application of new biologic insights to therapeutic development indicates that improved treatments may soon be routine for patients with chondrosarcoma and chordoma for whom surgery alone is inadequate. For all these uncommon diseases, patients should be offered specialist expert care delivered by experienced multidisciplinary teams in high-volume centers.
Randomized split-face, controlled comparison of treatment with 1565-nm nonablative fractional laser for enlarged facial pores
Authors: W. Yu, J. Zhu, G. Ma, J. Yang, Y. Qiu, Y. Chen, H. Chen, Y. Jin, X. Yang, X. Hu, T. Wang, L. Chang, X. Lin
Journal: British Journal of Dermatology (2017)
Will STPs lead to further cuts to health and social care?
Authors: Jeremy P Wight
Journal: BMJ (2017)

Sutaria and colleagues provide an account of the damaging cuts that have been made to health and social care by local authorities, but they fail to make the case that sustainability and transformation partnerships (STPs) will lead to further cuts in services.1

The Editor’s Choice on the topic is, therefore, misleading, saying that “rather than being about integration of health and social care . . …
Development of the gingival sulcus at the time of tooth eruption and the influence of genetic factors
Authors: Luigi Nibali
Journal: Periodontology 2000 (2017)

Abstract Tooth eruption is characterized by a concert of mechanisms that result in the emergence of teeth in the oral cavity. Genetic variants seem to regulate this process and the formation of a gingival sulcus around the teeth. Interindividual variability in the response to microbial triggers in the sulcus plays an important role in the onset and progression of periodontal diseases. Host genetic variants can influence this variability, affecting the response of the host to the subgingival biofilm. Genetic factors affecting tooth eruption could potentially influence susceptibility to periodontal diseases and, specifically, susceptibility to localized aggressive periodontitis. This review aims to discuss the evidence available for the role of host genetic variants in tooth eruption and to and to give some directions for prospective research in this topic.
Bidirectional Associations Between Child Sleep Problems and Internalizing and Externalizing Difficulties From Preschool to Early Adolescence
Authors: Jon L. Quach, Cattram D. Nguyen, Kate E. Williams, Emma Sciberras
Journal: JAMA Pediatrics (2017)

Although multiple cross-sectional and longitudinal studies have established that sleep problems and behavioral difficulties are associated in children, the directionality of this association and whether sleep problems are differentially associated with different types of childhood behavioral difficulties are unclear. Understanding these associations will inform the focus and timing of interventions.
Quality and Safety in Health Care, Part XXXIV
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2017)

There is an important opportunity for improvement in the care of cardiology outpatients by having greater compliance with published guidelines, and the PINNACLE (Practice Innovation and Clinical Excellence) Registry seeks to do that. One of the major areas studied by this registry is the use of secondary prevention medications for patients with coronary artery disease. Appropriate use of these medications decreases later myocardial infarctions and death from a cardiac cause.