tbuckley/cabot-search huggingface dataset:
Abstract LB-179: Next-generation epitope prediction using mass spectrometry and integrative genomics
Authors: Michael S. Rooney, Jenn Abelin, Siranush Sarkizova, Derin Keskin, Christine Hartigan, Wandi Zhang, John Sidney, William Lane, Jonathan Stevens, Guang L. Zhang, Karl Clauser, Nir Hacohen, Steve Carr, Cathy Wu
Journal: Cancer Research (2017)

Abstract Personalized neoantigen therapies for cancer require accurate epitope selection. However, most Class I prediction algorithms in common use today are based on biochemical binding assays that are difficult to scale and do not address processing steps upstream of peptide-MHC binding. Here we present an alternative approach based on the LC-MS/MS identification of MHC Class I-bound peptides. While MS-based profiling is not new, we optimized the system for rule learning by focusing on cell lines expressing only a single HLA-A or HLA-B allele and by collecting parallel transcriptomic and proteomic measurements. Identifying over 24,000 peptides across 16 individual alleles, we were able to discover novel binding motifs, which were validated biochemically, and develop novel neural network algorithms. Furthermore, we systematically interrogated processing rules - discovering a novel motif conserved across multiple cell types - and developed a principled framework for integrating epitope cleavability, expression, and MHC binding potential into an overall ranking. Validating on external datasets, we saw a doubling in positive predictive value with respect to standard approaches. We thus demonstrate a scalable strategy for systematically learning the rules of endogenous antigen presentation that can be deployed for the optimal selection of patient-specific cancer neoantigens. Citation Format: Michael S. Rooney, Jenn Abelin, Siranush Sarkizova, Derin Keskin, Christine Hartigan, Wandi Zhang, John Sidney, William Lane, Jonathan Stevens, Guang L. Zhang, Karl Clauser, Nir Hacohen, Steve Carr, Cathy Wu. Next-generation epitope prediction using mass spectrometry and integrative genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-179. doi:10.1158/1538-7445.AM2017-LB-179
Cell-Specific Pathways Supporting Persistent Fibrosis in Heart Failure
Authors: Stephen D. Farris, Creighton Don, Deri Helterline, Christopher Costa, Tabitha Plummer, Susanne Steffes, Claudius Mahr, Nahush A. Mokadam, April Stempien-Otero
Journal: Journal of the American College of Cardiology (2017)
THE EFFECTS OF SERIAL SPORTS TRAINING RISK ASSESSMENT AND COUNSELLING IN KIDS (T.R.A.C.K.)
Authors: Neeru Jayanthi
Journal: British Journal of Sports Medicine (2017)

Background Training recommendations in young athletes have been published by various authors and organizations to help reduce future injury risk. No previous study has evaluated a randomized intervention of counselling using evidence-based recommendations in a population of young athletes. Objective To determine if serial interactive on-line evidence-based counselling reduce the future rate of injury in young athletes. Design Multi-Center Double-blind Prospective Randomized Interventional Trial. Setting Academic institutions treating young athletes in sports medicine or primary care clinics. Patients (or Participants) Young athletes 8–17 years old presenting with or without a prior injury to either of these institutions. Interventions (or Assessment of Risk Factors) After completing the baseline risk assessment tool, young athletes were randomized to: (1) a control group who are monitored every 3 months for exposures for one year and (2) an intervention group of athletes who are similarly monitored and also receive a counselling checklist intervention every 3 months for one year. Training characteristics such as training volume, degree of specialization, and adherence to recommendations were evaluated in each group. Main Outcome Measurements Injury rates were compared at baseline and after the intervention in control and intervention. Compliance to recommendations and barriers to compliance were also assessed. Results 362 subjects were enrolled with 350 subjects adequate for analysis (170 control, 180 intervention). Baseline demographics and injury rates (71% vs. 75%, p&lt;0.1) were similar between groups. At baseline, injured athletes were older, had higher hrs/week of organized sports, less free play, and were more likely to do year round sports specialization then uninjured athletes. At 6 months of follow up, athletes in the counselling group had lower rates of injury then those in the control group (48.0% vs. 27.7%, p=0.003). Conclusions Serial on-line based evidence-based counselling on training in young athletes may help to reduce future injury risk.
Abstract IA24: The role of CCL18 signaling in breast tumor associated macrophages promoting cancer progression
Authors: Erwei Song
Journal: Cancer Research (2016)

Abstract Tumor-associated macrophages (TAMs) play critical roles in cancer progression. We focus on dissecting their underlying molecular mechanisms by applying human sample-based approaches, which include humanized mice, clinical samples and online clinical databases. Our data showed that CCL18, one of the most abundantly produced cytokines from human breast TAMs, is closely associated with advanced histopathological grading, triple negative breast cancer subtype, lymphovascular invasion, distant metastasis and poor prognosis of breast cancer patients. Mechanistic studies revealed that CCL18 induces epithelial-mesenchymal transition (EMT) and inflammatory cytokine secretion of tumor cells by activating NFkB pathway. Among the cytokines induced by CCL18, GM-CSF released from tumor cells undergone EMT in turn enhances the CCL18 production from TAMs and forms a positive feedback loop, which is essential to breast cancer metastasis, especially in the triple negative subtype. In addition, our recent study demonstrated that CCL18 could also mediate the activation and functions of other stromal cells in tumor microenvironment, leading to angiogenesis, recruitment of naïve T cells and activation of a special subset of chemoresistance-inducing fibroblasts. Previously, the receptor of CCL18 remained unknown. By using immunoprecipitation and mass spectra of the membrane extracts, cell-free isotope binding assays, [Ca2+]I mobilization and cAMP assays, we identified PITPNM3 as a functional receptor for CCL18. RNAi silencing of PITPNM3 in either cancer cells or stromal cells significantly inhibited the tumor progression in vivo. In conclusion, we define CCL18 from TAMs as the axis of a novel inflammatory signaling network in tumor microenvironment and imply the potential clinical application by targeting its receptor. Citation Format: Erwei Song. The role of CCL18 signaling in breast tumor associated macrophages promoting cancer progression. [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 IA24.
Review: Dapagliflozin increases, and empagliflozin reduces, adverse renal events in type 2 diabetes
Authors: John T. Nguyen, Donald A. Molony
Journal: Annals of Internal Medicine (2017)

Source Citation Tang H, Li D, Zhang J, et al. Sodium–glucose cotransporter 2 inhibitors and risk of adverse renal outcomes among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2017 Feb 27 [Epub ahead of print]. 28240446
Diagnosis of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) with or without Multi-Organ Dysfunction (MOD) after Hematopoietic Stem Cell Transplantation (HSCT): Analysis of a Multicenter Chart Review
Authors: Tina Doede, Anusha Viddam, Kathleen F. Villa, Alison L. Hannah, Charles H. Weaver, William Tappe
Journal: Blood (2016)
Microglia in steady state
Authors: Katrin Kierdorf, Marco Prinz
Journal: Journal of Clinical Investigation (2017)

Microglial cells are the resident tissue macrophages of the CNS and are widely recognized for their immune surveillance of the healthy CNS. In addition to this well-accepted function, recent findings point to major roles for microglia in instructing and regulating the proper function of the neuronal networks in the adult CNS, but these cells are also involved in creating neuronal networks by orchestrating construction of the whole network during development. In this Review, we highlight recent findings about the steady-state functions of microglial cells, the factors that are important for physiological microglial function, and how microglia help to maintain tissue homeostasis in the CNS.
The prevalence and morphometry of an accessory spleen: A meta-analysis and systematic review of 22,487 patients
Authors: Jens Vikse, Beatrice Sanna, Brandon Michael Henry, Dominik Taterra, Silvia Sanna, Przemysław A. Pękala, Jerzy A. Walocha, Krzysztof A. Tomaszewski
Journal: International Journal of Surgery (2017)
Aspirin plus clopidogrel was not linked to risk for cancer compared with aspirin alone or no antiplatelets
Authors: Mitchell Levine
Journal: Annals of Internal Medicine (2017)

ACP Journal Club18 July 2017Aspirin plus clopidogrel was not linked to risk for cancer compared with aspirin alone or no antiplateletsMitchell Levine, MDMitchell Levine, MDMcMaster University, Hamilton, Ontario, Canada (M.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2017-167-2-010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLeader A, Zelikson-Saporta R, Pereg D, et al. The effect of combined aspirin and clopidogrel treatment on cancer incidence. Am J Med. 2017 Feb 14. [Epub ahead of print]. https://pubmed.ncbi.nlm.nih.gov/28213047Clinical Impact RatingsGIM/FP/GP: Cardiology: Oncology: Reference1 Serebruany VL1, Cherepanov V, Cabrera-Fuentes HA, Kim MH. Solid cancers after antiplatelet therapy: Confirmations, controversies, and challenges. Thromb Haemost. 2015;114:1104-12. [PMID: 26559427] Google Scholar Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, Canada (M.L.)This article was published at Annals.org on 4 July 2017. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCYP2C19 and ABCB1 genetic polymorphisms correlate with the recurrence of ischemic cardiovascular adverse events after clopidogrel treatment 18 July 2017Volume 167, Issue 2Page: JC10KeywordsAntiplatelet therapyAspirinBody mass indexCancer detection and diagnosisCancer treatmentCohort studiesDrugsHealth maintenance organizationsMedical servicesMelanoma ePublished: 18 July 2017 Issue Published: 18 July 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Unravelling the pharmacologic opportunities and future directions for targeted therapies in gastro-intestinal cancers part 2: Neuroendocrine tumours, hepatocellular carcinoma, and gastro-intestinal stromal tumours
Authors: Cindy Neuzillet, Louis de Mestier, Benoît Rousseau, Olivier Mir, Mohamed Hebbar, Hemant M. Kocher, Philippe Ruszniewski, Christophe Tournigand
Journal: Pharmacology & Therapeutics (2017)
Updated results of a phase I/II study of inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-hyper-CVD) as frontline therapy for older patients with acute lymphoblastic leukemia.
Authors: Nicholas James Short, Hagop M. Kantarjian, Susan Mary O'Brien, Farhad Ravandi, Deborah A. Thomas, Guillermo Garcia-Manero, Naval Guastad Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Koji Sasaki, Naveen Pemmaraju, Yesid Alvarado, Jovitta Jacob, Rebecca Garris, Philip A. Thompson, Jorge E. Cortes, Elias Jabbour
Journal: Journal of Clinical Oncology (2017)

7014 Background: Inotuzumab ozogamicin (InO) is an anti-CD22 antibody-toxin conjugate that is effective in patients (pts) with relapsed/refractory ALL. Given the poor tolerance of elderly pts to intensive chemotherapy, we evaluated the safety and efficacy of low-intensity chemotherapy (mini-hyper-CVD) plus InO as frontline treatment for older pts with newly diagnosed ALL. Methods: Pts ≥60 years of age with newly diagnosed Ph-negative pre-B ALL received mini-hyper-CVD (no anthracycline, dose reductions of cyclophosphamide, dexamethasone, MTX and Ara-C). Pts received InO 1.3-1.8 mg/m2 on day 3 of cycle 1 and 0.8-1.3 mg/m2 on day 3 of cycles 2-4. Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles. Responding pts received POMP maintenance for up to 3 years. Results: 47 pts have been treated, 4 of whom were in CR at enrollment. Median age was 68 years (range, 60-81) and median CD22 expression was 97% (range, 72-100%). Among 43 pts evaluable for response, 41 (95%) achieved CR or CRp (CR, n = 36, CRp, n = 5). 1 pt achieved CRi and 1 did not respond. MRD negativity by 6-color flow cytometry was achieved in 31/41 pts (76%) after 1 cycle and in 44/46 pts (96%) overall. Median times to platelet and ANC recovery in cycle 1 were 23 and 16 days, respectively, and for subsequent cycles were 22 and 17 days, respectively. Prolonged thrombocytopenia ( &gt; 6 weeks) occurred in 37 pts (79%). 4 pts (9%) developed VOD, 1 after allogeneic stem cell transplant (ASCT) and 3 unrelated to ASCT. Only 1 pt developed severe VOD. Among 46 responders, 6 (13%) relapsed, 3 (7%) underwent ASCT in CR1, 27 (59%) remain on treatment or have completed maintenance, and 10 (22%) died in CR/CRp. With a median follow-up of 24 months, the 3-year continued remission and OS rates were 72% and 54%, respectively. Compared to a historical cohort of older pts treated with hyper-CVAD ± rituximab (n = 79), mini-hyper-CVD + InO resulted in significantly higher 3-year OS (54% vs 31%; P = 0.007). Conclusions: Mini-hyper-CVD plus InO is safe and effective in elderly pts with newly diagnosed ALL and appears to improve outcomes compared to hyper-CVAD in this population. Clinical trial information: NCT01371630.
Long Noncoding RNA and Cancer: A New Paradigm
Authors: Arunoday Bhan, Milad Soleimani, Subhrangsu S. Mandal
Journal: Cancer Research (2017)

Abstract In addition to mutations or aberrant expression in the protein-coding genes, mutations and misregulation of noncoding RNAs, in particular long noncoding RNAs (lncRNA), appear to play major roles in cancer. Genome-wide association studies of tumor samples have identified a large number of lncRNAs associated with various types of cancer. Alterations in lncRNA expression and their mutations promote tumorigenesis and metastasis. LncRNAs may exhibit tumor-suppressive and -promoting (oncogenic) functions. Because of their genome-wide expression patterns in a variety of tissues and their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. In this article, we have reviewed the emerging functions and association of lncRNAs in different types of cancer and discussed their potential implications in cancer diagnosis and therapy. Cancer Res; 77(15); 3965–81. ©2017 AACR.
Improved survival rate in patients with glioblastoma who underwent more than six cycles of temozolomide in a multimodal treatment scheme.
Authors: Rodica Anghel, Laurentia Minea Gales, Ionela Bizu, Carmen Ragan, Radu Mitrica, Oana Gabriela Ion
Journal: Journal of Clinical Oncology (2014)

e13008 Background: Glioblastoma (GBM) is the most common and aggressive primary brain tumour. Despite aggressive treatment, the prognosis of patients with GBM remains poor. The study aimsto assess the outcome of patients with GBM treated in our centre after combined treatment (surgery, radiotherapy and multiple cycle of chemotherapy). Methods: Data from medical files of 90 patients (43M/47F), with confirmed GBM and Karnofsky Performance Status >70, treated in our department between 2008-2013 were retrospectively reviewed. Median age at diagnosis was 54 years (range 21-74). Post-operative chemo-radiotherapy [60Gy with temozolomide (75 mg/mp/day)] and cycles of chemotherapy consisting of temozolomide (150-200 mg/mp day 1-5, every 4 weeks) until disease progression or unacceptable toxicity were planned. Results: The most frequent primary localization of GBM was in the frontal lobe (n=37, 41%). The median tumour’s dimension was 5.2 cm. All patients were referred for surgical ablation: total ablation was performed in 30 patients (33.3%), subtotal ablation in 50 patients (55.6%); in 10 patients (11.1%) surgery could not be performed and the patient underwent only biopsy. 3D-conformational radiotherapy was administered to all 90 patients to a mean total dose 57.9 Gy. After radiotherapy the mean number of cycles of temozolomide delivered was 4.7 (range 0-13). The progression free survival rate at 6 months was 62.2%. Median overall survival was 14 months (95% CI 11.55-16.44), and 1 and 2 years survival rates of 55.5% and 36.6% respectively. Multivariate analysis regarding the outcome showed advantage for either total ablation or subtotal ablation vs.biopsy (p<0.001). Regarding the number of cycles of chemotherapy, median survival in patients with no chemotherapy, less than 6 cycles, 6 cycles, and more than 6 cycles was 4, 10, 28, and 53 months respectively. In our study there was a significant advantage of more than 6 cycles of temozolomide (HR=0.38, p<0.0001, 95% CI 0.29-0.51). Conclusions: Chemo-radiotherapy followed by chemotherapy with temozolomide is an effective treatment for patient with GBM and more than 6 cycles of chemotherapy significantly improves survival.
Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor–Modified T Cells After Failure of Ibrutinib
Authors: Cameron J. Turtle, Kevin A. Hay, Laïla-Aïcha Hanafi, Daniel Li, Sindhu Cherian, Xueyan Chen, Brent Wood, Arletta Lozanski, John C. Byrd, Shelly Heimfeld, Stanley R. Riddell, David G. Maloney
Journal: Journal of Clinical Oncology (2017)

Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 × 105, 2 × 106, or 2 × 107 CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib. Six patients were venetoclax refractory, and 23 had a complex karyotype and/or 17p deletion. Results Four weeks after CAR-T cell infusion, the overall response rate (complete response [CR] and/or partial response [PR]) by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria was 71% (17 of 24). Twenty patients (83%) developed cytokine release syndrome, and eight (33%) developed neurotoxicity, which was reversible in all but one patient with a fatal outcome. Twenty of 24 patients received cyclophosphamide and fludarabine lymphodepletion and CD19 CAR-T cells at or below the maximum tolerated dose (≤ 2 × 106 CAR-T cells/kg). In 19 of these patients who were restaged, the overall response rate by IWCLL imaging criteria 4 weeks after infusion was 74% (CR, 4/19, 21%; PR, 10/19, 53%), and 15/17 patients (88%) with marrow disease before CAR-T cells had no disease by flow cytometry after CAR-T cells. Twelve of these patients underwent deep IGH sequencing, and seven (58%) had no malignant IGH sequences detected in marrow. Absence of the malignant IGH clone in marrow of patients with CLL who responded by IWCLL criteria was associated with 100% progression-free survival and overall survival (median 6.6 months follow-up) after CAR-T cell immunotherapy. The progression-free survival was similar in patients with lymph node PR or CR by IWCLL criteria. Conclusion CD19 CAR-T cells are highly effective in high-risk patients with CLL after they experience treatment failure with ibrutinib therapy.
Clinical and prognostic significance of e1a2 BCR-ABL1 transcript subtype in chronic myeloid leukemia
Authors: Z Gong, L J Medeiros, J E Cortes, L Zheng, J D Khoury, W Wang, G Tang, S Loghavi, R Luthra, W Yang, H M Kantarjian, S Hu
Journal: Blood Cancer Journal (2017)

Clinical and prognostic significance of e1a2 BCR-ABL1 transcript subtype in chronic myeloid leukemia
How to design efficient cluster randomised trials
Authors: K Hemming, S Eldridge, G Forbes, C Weijer, M Taljaard
Journal: BMJ (2017)

Cluster randomised trials have diminishing returns in power and precision as cluster size increases. Making the cluster a lot larger while keeping the number of clusters fixed might yield only a very small increase in power and precision, owing to the intracluster correlation. Identifying the point at which observations start making a negligible contribution to the power or precision of the study—which we call the point of diminishing returns—is important for designing efficient trials. Current methods for identifying this point are potentially useful as rules of thumb but don't generally work well. We introduce several practical aids to help researchers design cluster randomised trials in which all observations make a material contribution to the study. Power curves enable identification of the point at which observations begin to make a negligible contribution to a study for a given target difference. Under this paradigm, the number needed per arm under individual randomisation gives an upper bound on the cluster size, which should not be exceeded. Corresponding precision curves can be useful for accommodating flexibility in the choice of target difference and show the point at which confidence intervals around the estimated effect size no longer decrease. To design efficient trials, the number of clusters and cluster size should be determined concurrently, not independently. Funders and researchers should be aware of diminishing returns in cluster trials. Researchers should routinely plot power or precision curves when performing sample size calculations so that the implications of cluster sizes can be transparent. Even when data appear to be "free," in the sense that few resources are needed to obtain the data, excessive cluster sizes can have important ramifications
Rapid <i>In Situ</i> MRI Traceable Gel-forming Dual-drug Delivery for Synergistic Therapy of Brain Tumor
Authors: Feng-Wei Lin, Pin-Yuan Chen, Kuo-Chen Wei, Chiung-Yin Huang, Chih-Kuang Wang, Hung-Wei Yang
Journal: Theranostics (2017)

Preventing tumor recurrence after surgical resection of a brain tumor is a significant clinical challenge because current methods deliver chemotherapeutic agents in a rapid manner and are not effective against the residual tumor cells.To overcome this drawback, we report a simple method to prepare magnetic resonance imaging (MRI) traceable ultra-thermosensitive hydrogels with rapid gelation ability from aqueous solution within 4 s at 28 °C for hydrophilic (epirubicin, EPI) and hydrophobic (paclitaxel, PTX) drugs co-delivery with bovine serum albumin nanoparticles (BSA NPs) incorporation.The results showed the average survival of gliosarcoma-bearing (MBR 614 or U87) mice receiving BSA/PTX NPs incorporated hydrogelGd/EPI increased to 63 days or 69 days with no tumor recurrence observed.Our synergistic strategy presents a new approach to the development of a local drug delivery system for the prevention of brain tumor recurrence.