tbuckley/cabot-search huggingface dataset:
Investigation of Antigen-Specific T-Cell Receptor Clusters in Human Cancers
Authors: Hongyi Zhang, Longchao Liu, Jian Zhang, Jiahui Chen, Jianfeng Ye, Sachet Shukla, Jian Qiao, Xiaowei Zhan, Hao Chen, Catherine J. Wu, Yang-Xin Fu, Bo Li
Journal: Clinical Cancer Research (2019)

Cancer antigen-specific T cells are key components in antitumor immune response, yet their identification in the tumor microenvironment remains challenging, as most cancer antigens are unknown. Recent advance in immunology suggests that similar T-cell receptor (TCR) sequences can be clustered to infer shared antigen specificity. This study aims to identify antigen-specific TCRs from the tumor genomics sequencing data.We used the TRUST (Tcr Repertoire Utilities for Solid Tissue) algorithm to assemble the TCR hypervariable CDR3 regions from 9,700 bulk tumor RNA-sequencing (RNA-seq) samples, and developed a computational method, iSMART, to group similar TCRs into antigen-specific clusters. Integrative analysis on the TCR clusters with multi-omics datasets was performed to profile cancer-associated T cells and to uncover novel cancer antigens.Clustered TCRs are associated with signatures of T-cell activation after antigen encounter. We further elucidated the phenotypes of clustered T cells using single-cell RNA-seq data, which revealed a novel subset of tissue-resident memory T-cell population with elevated metabolic status. An exciting application of the TCR clusters is to identify novel cancer antigens, exemplified by our identification of a candidate cancer/testis gene, HSFX1, through integrated analysis of HLA alleles and genomics data. The target was further validated using vaccination of humanized HLA-A*02:01 mice and ELISpot assay. Finally, we showed that clustered tumor-infiltrating TCRs can differentiate patients with early-stage cancer from healthy donors, using blood TCR repertoire sequencing data, suggesting potential applications in noninvasive cancer detection.Our analysis on the antigen-specific TCR clusters provides a unique resource for alternative antigen discovery and biomarker identification for cancer immunotherapies.
Incidence and Risk Factors of Second Malignancies Among Medicare Beneficiaries with Newly-Diagnosed Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms Receiving Cytoreductive Therapy with Hydroxyurea
Authors: Rong Wang, Rory M Shallis, Scott F. Huntington, Amer M. Zeidan, Steven D. Gore, Amy J Davidoff, Xiaomei Ma, Nikolai A. Podoltsev
Journal: Blood (2019)
Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline
Authors: Bryan J. Schneider, Nofisat Ismaila, Joachim Aerts, Caroline Chiles, Megan E. Daly, Frank C. Detterbeck, Jason W.D. Hearn, Sharyn I. Katz, Natasha B. Leighl, Benjamin Levy, Bryan Meyers, Septimiu Murgu, Larissa Nekhlyudov, Edgardo S. Santos, Navneet Singh, Joan Tashbar, David Yankelevitz, Nasser Altorki
Journal: Journal of Clinical Oncology (2019)

PURPOSE To provide evidence-based recommendations to practicing clinicians on radiographic imaging and biomarker surveillance strategies after definitive curative-intent therapy in patients with stage I-III non–small-cell lung cancer (NSCLC) and SCLC. METHODS ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, radiology, primary care, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2000 through 2019. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 14 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Patients should undergo surveillance imaging for recurrence every 6 months for 2 years and then annually for detection of new primary lung cancers. Chest computed tomography imaging is the optimal imaging modality for surveillance. Fluorodeoxyglucose positron emission tomography/computed tomography imaging should not be used as a surveillance tool. Surveillance imaging may not be offered to patients who are clinically unsuitable for or unwilling to accept further treatment. Age should not preclude surveillance imaging. Circulating biomarkers should not be used as a surveillance strategy for detection of recurrence. Brain magnetic resonance imaging should not be used for routine surveillance in stage I-III NSCLC but may be used every 3 months for the first year and every 6 months for the second year in patients with stage I-III small-cell lung cancer who have undergone curative-intent treatment.
Success of stent-in-stent deployment after intraductal radiofrequency ablation for hepatic hilar obstruction
Authors: Takeshi Ogura, Saori Ueno, Nobu Nishioka, Masanori Yamada, Kazuhide Higuchi
Journal: Endoscopy (2019)

Unresectable malignant hepatic hilar biliary obstruction (MHBO) is often treated by deploying several uncovered self-expandable metal stents (UCSEMS) [1] [2] [3] [4]. Bilateral UCSEMS can be deployed using either side-by-side or stent-in-stent (SIS) procedures. However, SIS might not be as widely appropriate for MHBO because the procedure is technically complex. Furthermore, the risk of complications such as focal cholangitis can increase if bilateral SIS deployment fails after contrast medium is injected. However, a recent meta-analysis found that intraductal radiofrequency ablation (RFA) for malignant biliary obstruction might be associated with improved stent patency [5]. Here, we describe bile duct dilation using intraductal RFA to improve the technical success of subsequent UCSEMS deployment using SIS ([Video 1]).
miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1
Authors: Hui Jing, Xiaoyang Zhang, Kai Luo, Qiancheng Luo, Meng Yin, Wei Wang, Zhongqun Zhu, Jinghao Zheng, Xiaomin He
Journal: Biomaterials (2019)
Self‐Albumin Camouflage of Carrier Protein Prevents Nontarget Antibody Production for Enhanced LDL‐C Immunotherapy
Authors: Haiying Ji, Guangxi Wu, Yongyong Li, Kun Wang, Xiaomei Xue, Shasha You, Shengming Wu, Tianbin Ren, Bin He, Xueyin Shi
Journal: Advanced Healthcare Materials (2019)

Abstract Elevated low‐density lipoprotein cholesterol (LDL‐C) increases the risk of atherosclerotic cardiovascular disease. Peptide‐based PCSK9 vaccines have shown a promising prospect of reducing LDL‐C. In peptide vaccine (pVax) design, the peptide antigens need to conjugate with carrier protein (CP). However, CP incorporation can induce undesirable anti‐CP antibodies, which sterically mask peptide epitopes from being recognized by specific B cells and impair subsequent therapeutically antibody production. This epitopic suppression has posed a barrier in clinical translation of conjugate vaccines all along. A model CP (keyhole limpet hemocyanin, KLH) is herein camouflaged with serum albumin (SA) into hybrid nanocarriers (SA@N), with PCSK9 peptide being anchored onto the surface to form nanovaccine (SA@NVax). Such camouflage of KLH via high “self” SA coverage is able to inhibit KLH from extracellular immune recognition and prevent detectable anti‐KLH antibody production. Furthermore, the nanovaccine around 70 nm stabilized by intermolecular disulfide network is ideal for internalization and biodegradation by antigen presenting cells as well as better retention in draining lymph nodes and spleen. As expected, the SA@NVax efficiently primes higher anti‐PCSK9 IgG antibody titer than PCSK9 pVax.
Mitigating smoothened inhibitor-induced growth plate closure with parathyroid hormone.
Authors: Yoav E Timsit, Diane E Gunson, Thomas Krucker, Judit E Markovits, Silvia Buonamici, Anthony Boral, Dereck Dokyi Amakye, Aaron L Nelson, Francois Pognan, Salah-Dine Chibout, Nancy A Turner
Journal: Journal of Clinical Oncology (2012)

9562 Background: The Hedgehog pathway plays an important role in regulating growth plate patency by activating PTH/PTHrP signaling, and loss of PTH/PTHrP signaling is an expected pharmacological effect of smoothened (Smo) inhibition. LDE225, a Smo inhibitor currently in phase I/II trials for the treatment of basal cell carcinoma (BCC) and medulloblastoma (MB), causes closure of the epiphyseal (growth) plate in rodents and dogs. As a therapeutic strategy to mitigate these effects, we investigated whether administration of human parathyroid hormone (PTH amino acids 1-34 or PTH 1-34 ) could prevent premature growth plate closure caused by LDE225. Methods: Oral LDE225 was given once daily to rapidly growing male rats (starting at 4 or 6 weeks of age) in combination with hPTH 1-34 administered subcutaneously as a continuous infusion (to mimic signaling by locally-produced PTHrP) or as once-daily injections. Femur and tibial growth plates were scanned by microCT and growth plate volumes were calculated. Growth plates were also assessed histologically. Results: Continuous delivery of hPTH 1-34 provided the greatest effect for maintaining patent growth plates compared to once-daily subcutaneous injections. However, the dose of continuous hPTH 1-34 giving the greatest protection was not well-tolerated beyond 1 week due to PTH-induced hyperparathyroidism, confirmed by clinical chemistry and histological assessment. Reduction in the dose of continuous hPTH 1-34 improved tolerability, but provided less protection to the growth plate. Once-daily hPTH 1-34 injection for two weeks was well-tolerated, with anabolic effects clearly observed by histology and microCT. The extent of closure in animals co-treated with LDE225 and once-daily hPTH 1-34 injections was less compared to that caused by LDE225 treatment alone. Conclusions: As shown in this preclinical model, hPTH 1-34 administration mitigates LDE225-induced growth plate closure. Although hPTH 1-34 shows promise experimentally, current use is restricted in pediatric patients and further study will be needed before considering hPTH 1-34 treatment concurrent with LDE225 therapy in children or adolescents.
Targeting uptake transporters for cancer imaging and treatment
Authors: Yuchen Zhang, Joanne Wang
Journal: Acta Pharmaceutica Sinica B (2019)

Cancer cells reprogram their gene expression to promote growth, survival, proliferation, and invasiveness. The unique expression of certain uptake transporters in cancers and their innate function to concentrate small molecular substrates in cells make them ideal targets for selective delivering imaging and therapeutic agents into cancer cells. In this review, we focus on several solute carrier (SLC) transporters known to be involved in transporting clinically used radiopharmaceutical agents into cancer cells, including the sodium/iodine symporter (NIS), norepinephrine transporter (NET), glucose transporter 1 (GLUT1), and monocarboxylate transporters (MCTs). The molecular and functional characteristics of these transporters are reviewed with special emphasis on their specific expressions in cancers and interaction with imaging or theranostic agents [e.g., I-123, I-131, 123I-iobenguane (mIBG), 18F-fluorodeoxyglucose (18F-FDG) and 13C pyruvate]. Current clinical applications and research areas of these transporters in cancer diagnosis and treatment are discussed. Finally, we offer our views on emerging opportunities and challenges in targeting transporters for cancer imaging and treatment. By analyzing the few clinically successful examples, we hope much interest can be garnered in cancer research towards uptake transporters and their potential applications in cancer diagnosis and treatment.
Addressing Challenges and Implications of National Surveillance for Racial/Ethnic Disparities in Diabetes
Authors: Kunihiro Matsushita, Olive Tang, Elizabeth Selvin
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Pifithrin-μ incorporated in gold nanoparticle amplifies pro-apoptotic unfolded protein response cascades to potentiate synergistic glioblastoma therapy
Authors: Haitao Zhu, Xiongfeng Cao, Xiaojie Cai, Ying Tian, Dongqing Wang, Jianchen Qi, Zhaogang Teng, Guangming Lu, Qianqian Ni, Shouju Wang, Longjiang Zhang
Journal: Biomaterials (2019)

Conventional radiotherapy has a pivotal role in the treatment of glioblastoma; nevertheless, its clinical utility has been limited by radiation resistance. There is emerging evidence that upregulated heat shock protein A5 (HSPA5) in cancer cells maintains or restores the homeostasis of a cellular microenvironment and results in cancer resistance in various treatments. Therefore, we describe a bioresponsive nanoplatform that can deliver a HSPA5 inhibitor (pifithrin-μ, PES) and radiosensitizer (gold nanosphere, AuNS), to expand the synergistic photothermal therapy and radiotherapy, as well as to monitor the progression of cancer therapy using computer tomography/magnetic resonance imaging. The nanoplatform ([email protected], 63.3 ± 3.1 nm) comprises AuNS coated with the photothermal conversion agent polydopamine (PDA) for enhanced radiotherapy and photothermal therapy, as well as PES (loading efficiency of PES approximately 40%), a small molecular inhibitor against HSPA5 to amplify the pro-apoptotic unfolded protein response (UPR). The reported nanoplatform enables hyperthermia-responsive release of PES. Results from in vitro and in vivo studies demonstrate that [email protected] can specially activate pro-apoptotic UPR cascades, leading to remarkably improved radiotherapy and photothermal therapy efficiencies. Considered together, a versatile theranostic nanosystem is reported for promoting the synergistic radiophotothermal therapy by selectively activating pro-apoptotic UPR cascade pathways.
In Search of Historical Insight Into the Problem of Military Suicide
Authors: David S. Jones
Journal: JAMA Network Open (2019)

According to the latest data from the US Department of Defense, 541 service members died by suicide in 2018. 1 The suicide rate for the active component of the military, 24.8 per 100 000 service members, has increased to the highest level since before World War II.How can this be reversed?Smith et al 2 have provided a major contribution to the effort to understand military suicide.They
High-sensitivity troponin I and all-cause mortality in patients with stable COPD: an analysis of the COSYCONET study
Authors: Benjamin Waschki, Peter Alter, Tanja Zeller, Christina Magnussen, Johannes T. Neumann, Raphael Twerenbold, Christoph Sinning, Christian Herr, Kathrin Kahnert, Sebastian Fähndrich, Stefan Blankenberg, Klaus F. Rabe, Tobias Welte, Rudolf A. Jörres, Claus F. Vogelmeier, Robert Bals, Henrik Watz
Journal: European Respiratory Journal (2019)

Chronic obstructive pulmonary disease (COPD) is a leading cause of death with a considerable part of the population dying from cardiovascular diseases. High-sensitivity troponin I (hs-TnI) might help to better identify COPD patients at high risk of mortality. We aimed to study the predictive value of hs-TnI for all-cause mortality beyond established COPD assessments, and after consideration of relevant cardiovascular risk factors and prevalent cardiovascular diseases, in a broad population with stable COPD. Circulating hs-TnI concentrations together with a wide range of respiratory and cardiovascular markers were evaluated in 2085 patients with stable COPD across all severity stages enrolled in the multicentre COSYCONET cohort study. The primary outcome was all-cause mortality over 3 years of follow-up. Hs-TnI was detectable in 2020 (96.9%) patients. The median hs-TnI concentration was 3.8 ng·L −1 (interquartile range 2.5–6.6 ng·L −1 ), with levels above the 99th percentile reference limit of 27 ng·L −1 observed in 1.8% of patients. In Cox regression analyses including adjustments for airflow limitation, dyspnoea grade, exercise capacity and history of severe exacerbations, as well as traditional cardiovascular risk factors, estimated glomerular filtration rate, ankle–brachial index, N-terminal pro-brain natriuretic peptides and prevalent cardiovascular diseases, hs-TnI was a significant predictor for all-cause mortality, both as a continuous variable (hazard ratio (HR) for log hs-TnI 1.28, 95% CI 1.01–1.62) and categorised according to the cut-off of 6 ng·L −1 (HR 1.63, 95% CI 1.10–2.42). In patients with stable COPD, hs-TnI is a strong predictor of all-cause mortality beyond established COPD mortality predictors, and independent of a broad range of cardiovascular risk factors and prevalent cardiovascular diseases. Hs-TnI concentrations well below the upper reference limit provide further prognostic value for all patients with COPD when added to established risk assessments.
Spatiotemporally controllable diphtheria toxin expression using a light-switchable transgene system combining multifunctional nanoparticle delivery system for targeted melanoma therapy
Authors: Muye He, Yan Wang, Xianjun Chen, Yuzheng Zhao, Kaiyan Lou, Yujie Wang, Lei Huang, Xinyu Hou, Jiajun Xu, Xiaoran Cai, Yi Cheng, Minbo Lan, Yi Yang, Feng Gao
Journal: Journal of Controlled Release (2019)
Digital light processing 3D printed silk fibroin hydrogel for cartilage tissue engineering
Authors: Heesun Hong, Ye Been Seo, Do Yeon Kim, Ji Seung Lee, Young Jin Lee, Hanna Lee, Olatunji Ajiteru, Md Tipu Sultan, Ok Joo Lee, Soon Hee Kim, Chan Hum Park
Journal: Biomaterials (2019)
Anti-α Gal Antibodies in the Context of Blood Group and Stool and Tumour-Adjacent Microbiome in Colorectal Cancer Patients
Authors: I. Selingerova, E. Budinska, B. Zwinsova, B. Mazalova, B. Bencsikova, D. Valik, L. Zdrazilova Dubska
Journal: Annals of Oncology (2019)
Cell-free Circulating Tumor DNA Variant Allele Frequency Associates with Survival in Metastatic Cancer
Authors: Seyed Pairawan, Kenneth R. Hess, Filip Janku, Nora S. Sanchez, Kenna R. Mills Shaw, Cathy Eng, Senthilkumar Damodaran, Milind Javle, Ahmed O. Kaseb, David S. Hong, Vivek Subbiah, Siqing Fu, David R. Fogelman, Victoria M. Raymond, Richard B. Lanman, Funda Meric-Bernstam
Journal: Clinical Cancer Research (2019)

Physicians are expected to assess prognosis both for patient counseling and for determining suitability for clinical trials. Increasingly, cell-free circulating tumor DNA (cfDNA) sequencing is being performed for clinical decision making. We sought to determine whether variant allele frequency (VAF) in cfDNA is associated with prognosis.
Long-term survival and clinical efficacy in patients with advanced pancreatic and small bowel metastatic neuroendocrine tumors (GEP-NET) after I.V. 90Y DOTATATE.
Authors: Wojciech Rogowski, Ewa Wachula, Jolanta Zok, Anna Lewczuk, Jaroslaw Cwikla, Piotr Wysocki
Journal: Journal of Clinical Oncology (2013)

e15045 Background: Current therapeutic options for patients with progressive metastatic gastroenteropancreatic neuroendocrine tumour/neoplasm (GEP-NET/NEN) are limited. Treatment with SST analogues is method of choice, due to good symptoms control. [DOTA0, D-Phe1,Tyr3] octreotate[DOTATATE] has a higher affinity for SST2 receptors and thus is able to achieve longer disease control. The aim of this study was to evaluate long term radiological and clinical therapeutic effect of 90Y-DOTATATE in patients with progressive somatostatin receptor–positive small bowel and pancreatic neuroendocrine tumour/neoplasm (GEP-NET/NEN).The primary end point was assessing OS and PFS in long term follow-up. Methods: 67 patients progressing after treatment with SST analogues were inlcuded in the study. The mean treatment activity was 3.8GBq. The mean interval between therapies was 7 weeks (range 6 -9 weeks). Patients were treated up to mean a cumulative activity of 11.2 GBq. Due to pure beta emission (90Y) internal dosimetry was evaluated. Results: Median overall survival (OS) and progression-free survival (PFS) are shown in the Table. In univariate analysis Ki-67 (p=0.048) was the only significant factor influencing OS in pancreatic tumors. That was not confirmed in multivariate analysis. In small bowel tumors we defined three factors influencing survival in univariate analysis. These were: female gender (p=0.023), performance status at the beginning of therapy (p=0.031) and presence of liver metastases (p=0.026). Female gender (HR=0.30, 95% CI 0.11-0.81; p=0.018) was confirmed as positive prognostic factor in multivariate analysis. Factos influencing PFS were also assessed and will be presented as well. Conclusions: 90Y DOTATATE PRRT is effective in long term outcome (OS and PFS) in patient with advances progressive pancreatic and small bowel GEP-NET. This therapy is relatively safe as initial systemic therapy and after previous treatment with chemotherapy or somatostatine analogues as well. [Table: see text]