tbuckley/cabot-search huggingface dataset:
Abstract SY26-01: Targeting natural ligands for TCR engineering
Authors: Stephen P. Schoenberger
Journal: Cancer Research (2021)

Abstract Neoantigens (NeoAg) offer the potential to directtherapeutic T cell responses to immunogenic mutations exclusively expressed bytumors. Most strategies for their identification select potentialligands for CD8+ T cells rather than for CD4+ T cells,despite the extensive literature showing functional cooperation between thesesubsets. To better understand CD4-CD8synergy in anti-tumor immunity, we have applied a novel functional approach toidentify the subset of expressed mutations targeted as NeoAg by natural CD4+and CD8+ T cell responses to a poorly-immunogenic spontaneoussquamous cell tumor, SCC VII. We demonstrate that a single mutation (Cltc H129&amp;gt;Q) that is recognized byboth subsets is capable of eradicating large established SCCVII tumors in thesetting of therapeutic vaccination provided the relevant epitopes whenphysically linked. Single-cell TCR analysis revealed that the endogenous CD4+T cell response against this epitope comprises both low-affinity CD4+-dependentand high-affinity CD4+-independent receptors, with the latterdisplaying superior capacity in promoting prophylactic and therapeutic CD8+T cell-mediated immunity against the MHC class I+ class II−tumors in the setting of adoptive cellular therapy. These findings demonstratethat linked CD4+ T cell help enables potent therapeuticNeoAg-specific vaccination and provides instructive insights into the qualityof TCRs mediating this effect. Citation Format: Stephen P. Schoenberger. Targeting natural ligands for TCR engineering [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY26-01.
Clinical interpretation of whole-genome and whole-transcriptome sequencing for precision oncology
Authors: Vaidehi Jobanputra, Kazimierz O. Wrzeszczynski, Reinhard Buttner, Carlos Caldas, Edwin Cuppen, Sean Grimmond, Torsten Haferlach, Charles Mullighan, Anna Schuh, Olivier Elemento
Journal: Seminars in Cancer Biology (2021)
A Race-Conscious Analysis of the Use of Transvaginal Ultrasonography in the Evaluation of Postmenopausal Bleeding
Authors: Eloise Chapman-Davis, Dineo Khabele
Journal: JAMA Oncology (2021)

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 Oncology 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 Oncology journal
Neurosurgical resection for locally recurrent brain metastasis
Authors: Alexander F C Hulsbergen, Abdullah M Abunimer, Fidelia Ida, Vasileios K Kavouridis, Logan D Cho, Ishaan A Tewarie, Rania A Mekary, Philippe Schucht, John G Phillips, Joost J C Verhoeff, Marike L D Broekman, Timothy R Smith
Journal: Neuro-Oncology (2021)

In patients with locally recurrent brain metastases (LRBMs), the role of (repeat) craniotomy is controversial. This study aimed to analyze long-term oncological outcomes in this heterogeneous population.Craniotomies for LRBM were identified from a tertiary neuro-oncological institution. First, we assessed overall survival (OS) and intracranial control (ICC) stratified by molecular profile, prognostic indices, and multimodality treatment. Second, we compared LRBMs to propensity score-matched patients who underwent craniotomy for newly diagnosed brain metastases (NDBM).Across 180 patients, median survival after LRBM resection was 13.8 months and varied by molecular profile, with >24 months survival in ALK/EGFR+ lung adenocarcinoma and HER2+ breast cancer. Furthermore, 102 patients (56.7%) experienced intracranial recurrence; median time to recurrence was 5.6 months. Compared to NDBMs (n = 898), LRBM patients were younger, more likely to harbor a targetable mutation and less likely to receive adjuvant radiation (P < 0.05). After 1:3 propensity matching stratified by molecular profile, LRBM patients generally experienced shorter OS (hazard ratio 1.67 and 1.36 for patients with or without a mutation, P < 0.05) but similar ICC (hazard ratio 1.11 in both groups, P > 0.20) compared to NDBM patients with similar baseline. Results across specific molecular subgroups suggested comparable effect directions of varying sizes.In our data, patients with LRBMs undergoing craniotomy comprised a subgroup of brain metastasis patients with relatively favorable clinical characteristics and good survival outcomes. Recurrent status predicted shorter OS but did not impact ICC. Craniotomy could be considered in selected, prognostically favorable patients.
Abstract 1180: A novel synthetic lethality treatment strategy for metastatic breast cancer
Authors: Justin Zonneville, Moyi Wang, Mohammed Alruwaili, Kevin Eng, Thomas Melendy, Ben Ho Park, Renuka Iyer, Christos Fountzilas, Andrei V. Bakin
Journal: Cancer Research (2021)

Abstract Breast carcinomas commonly carry mutations in the tumor suppressor p53, while therapeutic efforts to target mutant p53 were largely unfruitful. Here we present preclinical data supporting a novel combination therapy strategy for treatment of p53-deficient cancers. Genomic data revealed a high expression activity of Base-Excision Repair (BER) pathways in p53-deficient breast cancers. However, we found that BER-mediated repair was significantly dysregulated in p53-mutant cancer cells. Treatment with deoxyuridine analogues induced accumulation of DNA damage in p53-mutant cells and inhibitors of poly (ADP-ribose) polymerase (PARPi) greatly enhanced this response. In contrast, normal cells responded to PARPi with activation of the p53-p21 axis and cell cycle arrest. Inactivation of either p53 or p21/CDKN1A in p53 wild-type cells conferred the p53-mutant phenotype. Preclinical breast cancer studies revealed that the combination of deoxyuridine analogue with PARPi was more effective in inhibition of tumor growth and metastases than either drug alone. This work illustrates a novel combination therapy strategy that may improve survival rates and outcomes for thousands of breast cancer patients. Citation Format: Justin Zonneville, Moyi Wang, Mohammed Alruwaili, Kevin Eng, Thomas Melendy, Ben Ho Park, Renuka Iyer, Christos Fountzilas, Andrei V. Bakin. A novel synthetic lethality treatment strategy for metastatic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1180.
Clinical trials: regulators’ inaction has left EU registry “riddled with inaccurate and missing data”
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Nearly 6000 clinical trial results are currently missing from the European trial registry, despite transparency rules requiring countries to upload results within 12 months of trial completion, a report has found.1

Researchers from the University of Oxford said the findings show that medicines regulators in the 14 European countries included in the report have failed to ensure that important data on new drugs and vaccines are rapidly and consistently made public.

The report, published 5 July, found that the largest gaps were in Italy (1221 results missing), Spain (884), the Netherlands …
Projecting the risk of mosquito-borne diseases in a warmer and more populated world: a multi-model, multi-scenario intercomparison modelling study
Authors: Felipe J Colón-González, Maquins Odhiambo Sewe, Adrian M Tompkins, Henrik Sjödin, Alejandro Casallas, Joacim Rocklöv, Cyril Caminade, Rachel Lowe
Journal: The Lancet Planetary Health (2021)

BackgroundMosquito-borne diseases are expanding their range, and re-emerging in areas where they had subsided for decades. The extent to which climate change influences the transmission suitability and population at risk of mosquito-borne diseases across different altitudes and population densities has not been investigated. The aim of this study was to quantify the extent to which climate change will influence the length of the transmission season and estimate the population at risk of mosquito-borne diseases in the future, given different population densities across an altitudinal gradient.MethodsUsing a multi-model multi-scenario framework, we estimated changes in the length of the transmission season and global population at risk of malaria and dengue for different altitudes and population densities for the period 1951–99. We generated projections from six mosquito-borne disease models, driven by four global circulation models, using four representative concentration pathways, and three shared socioeconomic pathways.FindingsWe show that malaria suitability will increase by 1·6 additional months (mean 0·5, SE 0·03) in tropical highlands in the African region, the Eastern Mediterranean region, and the region of the Americas. Dengue suitability will increase in lowlands in the Western Pacific region and the Eastern Mediterranean region by 4·0 additional months (mean 1·7, SE 0·2). Increases in the climatic suitability of both diseases will be greater in rural areas than in urban areas. The epidemic belt for both diseases will expand towards temperate areas. The population at risk of both diseases might increase by up to 4·7 additional billion people by 2070 relative to 1970–99, particularly in lowlands and urban areas.InterpretationRising global mean temperature will increase the climatic suitability of both diseases particularly in already endemic areas. The predicted expansion towards higher altitudes and temperate regions suggests that outbreaks can occur in areas where people might be immunologically naive and public health systems unprepared. The population at risk of malaria and dengue will be higher in densely populated urban areas in the WHO African region, South-East Asia region, and the region of the Americas, although we did not account for urban-heat island effects, which can further alter the risk of disease transmission.FundingUK Space Agency, Royal Society, UK National Institute for Health Research, and Swedish Research Council.
多数手術癌施設での若年女性における子宮内膜癌の解析【Powered by NICT】
Authors: Biler Alper, Solmaz Ulas, Erkilinc Selcuk, Gokcu Mehmet, Bagci Mustafa, Temel Orhan, Karadeniz Tugba, Sanci Muzaffer
Journal: International Journal of Surgery (2017)
Isocitrate dehydrogenase 2 regulates intracellular metabolic reprogramming in chemo-resistant urothelial carcinoma
Authors: K. Shigeta, M. Hasegawa, T. Kosaka, T. Hishiki, M. Ryuichi, A. Miyajima, M. Suematsu, E. Kikuchi, M. Oya
Journal: European Urology (2021)
Abstract 2037: Targeting chromosome rearrangements in cancer with CRISPR
Authors: Huibin Yang, Radhika Suhas-Hulbatte, Mats Ljungman
Journal: Cancer Research (2021)

Abstract Background: We have developed a novel precision and personalized cancer therapeutic approach to specifically target cancer cells using CRISPR technology. This approach is universal to all cancers and not dependent on the unique biology of the tumor. The innovation of this approach is that chromosome rearrangement junctions (CRJs), which typically exist in the hundreds in each tumor cell, are targeted by guide RNAs that bring together two parts of a dCas9-fused endonuclease, Fok1, leading to the induction of DNA double strand breaks (DSBs) at sites of the targeted CRJs in cancer cells specifically. Materials and Methods: HCT116 colon cancer cells and UMUC-3 bladder cancer cells were engineered to express Fok1-dCas9 and two pairs of CRJ-targeting gRNA under doxycycline regulation. Induction of DSBs at CRJs were assessed by γH2AX foci and γH2AX ChIP-PCR and cell death was assessed by apoptosis (PARP1 &amp; caspase cleavage and flow cytometry for sub-G1 DNA content and Annexin V staining) and clonogenic survival. Results: Induction of Fok1-dCas9 lead to the induction of 1-2 DSBs per cell and promoted cell death when accompanied with the expression of pairs of CRJ-targeting gRNAs. However, no DSBs or cell death was observed with expression of Fok1-dCas9 alone or in combination with non-targeting gRNAs. Conclusions: We have shown that we can direct two parts of a dCas9-fused Fok1 endonuclease to sites of CRJs in cancer cells using CRISPR gRNAs leading to the induction of DSBs and loss of cell survival specifically in cancer cells. Recent breakthroughs in CRISPR delivery using lipid nanoparticles will allow us to next explore the utility of our precision CRISPR approach in animal models. If successfully implemented, the impact of our universal approach targeting CRJs in cancer with CRISPR could be transformative for cancer therapy. Citation Format: Huibin Yang, Radhika Suhas-Hulbatte, Mats Ljungman. Targeting chromosome rearrangements in cancer with CRISPR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2037.
The role of precision nutrition in the modulation of microbial composition and function in people with inflammatory bowel disease
Authors: Alexa N Sasson, Richard J M Ingram, Zhengxiao Zhang, Lorian M Taylor, Ashwin N Ananthakrishnan, Gilaad G Kaplan, Siew C Ng, Subrata Ghosh, Maitreyi Raman
Journal: The Lancet. Gastroenterology & hepatology (2021)
Long-term activity of tandem CD19/CD20 CAR therapy in refractory/relapsed B-cell lymphoma: a single-arm, phase 1–2 trial
Authors: Yajing Zhang, Yao Wang, Yang Liu, Chuan Tong, Chunmeng Wang, Yelei Guo, Dongdong Ti, Qingming Yang, Shen Qiao, Zhiqiang Wu, Weidong Han
Journal: Leukemia (2021)

Abstract Increasing the remission rate and reducing the recurrence rate can improve the clinical efficacy of chimeric antigen receptor (CAR) T cell therapy in recurrent/refractory non-Hodgkin lymphoma (r/rNHL). In this open-label, single-arm phase I/II trial, 87 patients with r/rNHL, including 58 patients with aggressive diffuse large B-cell lymphoma and 24 with high tumour burden, received an infusion at doses of 0.5 × 10 6 –8 × 10 6 TanCAR7 T cells per kilogram of body weight after conditioning chemotherapy. The best overall response rate was 78% (95% confidence interval [CI], 68–86); response rates were consistent across prognostic subgroups. The median follow-up was 27.7 months. The median progression-free survival was 27.6 months (95% CI, 11 to not reached). Cytokine release syndrome (CRS) occurred in 61 patients (70%) with 60% of cases being grade 1 or 2 and 10% being grade 3 or greater. Grade 3 CAR T cell-related encephalopathy syndrome (CRES) occurred in 2 patients (2%). Two patients died from treatment-associated severe pulmonary infection, and one died from CRS-related pulmonary injury between 1 and 3 months post infusion. Long-term remissions were observed following the use of TanCAR7 T cells in r/rNHL with a safety profile that included CRS but few cases of CRES.
Standardized Reference Diets for Zebrafish: Addressing Nutritional Control in Experimental Methodology
Authors: Stephen A. Watts, Louis R. D'Abramo
Journal: Annual Review of Nutrition (2021)

The ideal of experimental methodology in animal research is the reduction or elimination of environmental variables or consistency in their application. In lab animals, diet has been recognized as a very influential response variable. Reproducibility in research using rodents required the development of a unique diet of consistent ingredient and nutrient composition to allow for cross-comparisons of lab results, spatially and temporally. These diets are commonly referred to as standard reference diets (SRDs). The established validity of published nutritional requirements combined with the cooperation of commercial partners led to species-specific reference diets commonly used by the research community. During the last several decades, zebrafish ( Danio rerio) have become a widespread alternative animal model, but specific knowledge of their nutrition is lacking. We present a short-term approach for developing an SRD for zebrafish, similar to that eventually attained for rodents over decades. Imminent development of an open-formulation, commercially produced SRD for zebrafish will notably advance translational biomedical science.
Erratum: CATMoS: Collaborative Acute Toxicity Modeling Suite
Authors: Kamel Mansouri, Agnes L. Karmaus, Jeremy Fitzpatrick, Grace Patlewicz, Prachi Pradeep, Domenico Alberga, Nathalie Alepee, Timothy E.H. Allen, Dave Allen, Vinicius M. Alves, Carolina H. Andrade, Tyler R. Auernhammer, Davide Ballabio, Shannon Bell, Emilio Benfenati, Sudin Bhattacharya, Joyce V. Bastos, Stephen Boyd, J. B. Brown, Stephen J. Capuzzi, Yaroslav Chushak, Heather Ciallella, Alex M. Clark, Viviana Consonni, Pankaj R. Daga, Sean Ekins, Sherif Farag, Maxim Fedorov, Denis Fourches, Domenico Gadaleta, Feng Gao, Jeffery M. Gearhart, Garett Goh, Jonathan M. Goodman, Francesca Grisoni, Christopher M. Grulke, Thomas Hartung, Matthew Hirn, Pavel Karpov, Alexandru Korotcov, Giovanna J. Lavado, Michael Lawless, Xinhao Li, Thomas Luechtefeld, Filippo Lunghini, Giuseppe F. Mangiatordi, Gilles Marcou, Dan Marsh, Todd Martin, Andrea Mauri, Eugene N. Muratov, Glenn J. Myatt, Dac-Trung Nguyen, Orazio Nicolotti, Reine Note, Paritosh Pande, Amanda K. Parks, Tyler Peryea, Ahsan H. Polash, Robert Rallo, Alessandra Roncaglioni, Craig Rowlands, Patricia Ruiz, Daniel P. Russo, Ahmed Sayed, Risa Sayre, Timothy Sheils, Charles Siegel, Arthur C. Silva, Anton Simeonov, Sergey Sosnin, Noel Southall, Judy Strickland, Yun Tang, Brian Teppen, Igor V. Tetko, Dennis Thomas, Valery Tkachenko, Roberto Todeschini, Cosimo Toma, Ignacio Tripodi, Daniela Trisciuzzi, Alexander Tropsha, Alexandre Varnek, Kristijan Vukovic, Zhongyu Wang, Liguo Wang, Katrina M. Waters, Andrew J. Wedlake, Sanjeeva J. Wijeyesakere, Dan Wilson, Zijun Xiao, Hongbin Yang, Gergely Zahoranszky-Kohalmi, Alexey V. Zakharov, Fagen F. Zhang, Zhen Zhang, Tongan Zhao, Hao Zhu, Kimberley M. Zorn, Warren Casey, Nicole C. Kleinstreuer
Journal: Environmental Health Perspectives (2021)
The Coverage in England of US-Approved Cancer Drugs—Reply
Authors: Avi Cherla, Huseyin Naci, Elias Mossialos
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine 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 Internal Medicine journal
Abstract 2099: EM-seq enables accurate and precise methylome analysis of challenging DNA samples
Authors: V K Chaithanya Ponnaluri, Louise Williams, Matthew A. Campbell, Vaishnavi Panchapakesa, Romualdas Vaisvila, Bradley Langhorst, Eileen Dimalanta, Theodore B. Davis
Journal: Cancer Research (2021)

Abstract DNA isolated from blood draws (cell-free DNA (cfDNA)) or from archival material like formalin fixed paraffin embedded (FFPE) tissues have advanced the field of cancer genetics. DNA methylation (5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC)) is a key epigenetic factor that plays an important role in cellular processes and it's misregulation results in diseased states like cancer. Advances in the field of sample preparation from biological matrices and genomics have enabled cancer biomarker identification based on methylation profiling. Bisulfite sequencing has been the gold standard for detection of methylation and is employed for both targeted and whole genome methylation analysis. However, the chemical based bisulfite conversion of cytosines to uracils leads to DNA damage which subsequently translates to shorter DNA insert sizes as well as biases in the data. DNA obtained from cfDNA and FFPE samples is typically of low quality and quantity making DNA methylation profiling using the harsh bisulfite conversion challenging. Robust biomarker detection relies primarily on the ability to profile methylation accurately. To overcome the drawbacks of bisulfite sequencing, we developed an enzyme based methylation detection technology, called NEBNext® Enzymatic Methyl-Seq (EM-Seq™), that minimizes damage to DNA enabling longer insert sizes, lower duplication rates and minimal GC bias resulting in more accurate quantification of methylation in the sample DNA. Using EM-Seq, we profiled cfDNA and lung FFPE DNA. Results for these challenging DNA types showed that the EM-Seq libraries had longer inserts, lower duplication rates, higher percentages of mapped reads and less GC bias compared to WGBS libraries. EM-seq libraries also identified a higher number of CpG's with even coverage facilitating accurate methylation calling. In conclusion, EM-Seq libraries have superior sequencing metrics resulting in robust methylation profiling for these types of challenging DNA samples. Citation Format: V K Chaithanya Ponnaluri, Louise Williams, Matthew A. Campbell, Vaishnavi Panchapakesa, Romualdas Vaisvila, Bradley Langhorst, Eileen Dimalanta, Theodore B. Davis. EM-seq enables accurate and precise methylome analysis of challenging DNA samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2099.
Abstract 10958: B-type Natriuretic Peptide Level is Associated with Dietary Salt Intake in Patients with Compensated Heart Failure: Evaluated by Casual Spot Urine
Authors: Tsuneaki Sadanaga, Shinji Ichimori
Journal: Circulation (2010)

Introduction: Dietary salt restriction is a mainstay in the management of patients with hypertension and heart failure. However, the effect of salt intake on heart failure status is not well elucid...