tbuckley/cabot-search huggingface dataset:
Abstract 553: Personalized circulating tumor DNA analysis in head and neck squamous cell carcinoma: Preliminary results of the Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and NeckSquamous Cell Carcinoma (LIONESS) study
Authors: Susanne Flach, Karen Howarth, Sophie Hackinger, Christodoulos Pipinikas, Kirsten McLay, Giovanni Marsico, Christoph Walz, Olivier Gires, Martin Canis, Philipp Baumeister
Journal: Cancer Research (2021)

Abstract Introduction Head and neck squamous cell carcinoma (HNSCC) remains a substantial burden to global health. Despite evolving therapies, 5-year survival is less than 50% and unlike other cancers, reliable biomarkers to monitor treatment response do not exist. Cell-free circulating tumor DNA (ctDNA) is an emerging biomarker but has not yet been studied sufficiently for HNSCC. The detection of ctDNA as a marker of minimal residual disease following curative-intent treatment holds promise for identifying patients at an increased risk of relapse, who may benefit from adjuvant radio(chemo)therapy or facilitate close monitoring with repeat resection if needed. Methods We conducted a single-center prospective experimental evidence-generating cohort study to assess ctDNA in 30 patients with p16-negative HNSCC (stages I-IVB) who received primary surgical treatment with curative intent at our institution. Whole exome sequencing (WES) was performed on formalin-fixed paraffin-embedded tumor tissue to a median depth of 250x. For each patient, we selected up to 48 somatic variants for personalized ctDNA assay design. We used the RaDaRTM assay to analyze serial pre- and post-operative plasma samples (range 2-6) for evidence of minimal residual disease or recurrence. Results In a subset of patients analyzed to evaluate the performance of RaDaR, personalized panels were designed with between 34 and 48 somatic variants (median 48). Preliminary data shows 100% ctDNA detection in baseline samples taken prior to surgery at tumor fractions ranging from 312 ppm (equivalent to 0.03% AF) to 7579 ppm (equivalent to 0.76% AF). In post-surgery samples, ctDNA could be detected at levels as low as 26 ppm (equivalent to 0.0026% AF). Analysis of follow-up plasma samples will be presented along with data from the full patient cohort. Conclusions This study illustrates the potential of ctDNA as a biomarker in HNSCC and demonstrates the feasibility of personalized ctDNA assays for the detection of minimal residual disease post-treatment and for monitoring for early detection of relapse. Citation Format: Susanne Flach, Karen Howarth, Sophie Hackinger, Christodoulos Pipinikas, Kirsten McLay, Giovanni Marsico, Christoph Walz, Olivier Gires, Martin Canis, Philipp Baumeister. Personalized circulating tumor DNA analysis in head and neck squamous cell carcinoma: Preliminary results of the Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and NeckSquamous Cell Carcinoma (LIONESS) study [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 553.
脊椎転移の管理のための統合多領域アルゴリズム:国際脊椎腫瘍コンソーシアム報告【Powered by NICT】
Authors: Spratt Daniel E, Beeler Whitney H, de Moraes Fabio Y, Rhines Laurence D, Gemmete Joseph J, Chaudhary Neeraj, Shultz David B, Smith Sean R, Berlin Alejandro, Dahele Max, Slotman Ben J, Younge Kelly C, Bilsky Mark, Park Paul, Szerlip Nicholas J
Journal: The Lancet Oncology (2017)
Abstract 2006: The contributions of iron regulatory proteins 1 and 2 to ferroptosis activation and ferroptotic cell death
Authors: Evan Hermann, Thais Oliveira, McKale Montgomery
Journal: Cancer Research (2021)

Abstract The essentiality of iron for cell growth and proliferation, coupled with its capacity to promote damaging free radical production, has made it a desirable target for cancer treatment and prevention. One such approach may be through the activation of ferroptosis, a form of iron-mediated programmed cell death. However, we must first understand how cancer cells manipulate the homeostatic regulators of iron metabolism to promote malignancy before we can fully harness iron's therapeutic potential. The iron regulatory proteins 1 and 2 (IRP1 and IRP2) are the master regulators of intracellular iron homeostasis because they coordinate the expression of proteins involved in iron storage, uptake, and utilization. Yet, the roles and regulation of IRPs during cellular ferroptosis remain unknown. The primary objective of this work was to examine the reciprocal relationship between ferroptosis activation and IRP mRNA binding activity. Utilizing tetracycline-inducible plasmids, we found that overexpression of IRP1 or IRP2 significantly increases sensitivity to ferroptotic cell death in HEK293T cells. Intriguingly however, ferroptosis induction by erastin treatment differentially influences IRP1 and IRP2 mRNA binding activity in a cell-type dependent manner, with those cell types expressing higher levels IRP2 exhibiting increased sensitivity to ferroptosis activation. Yet, IRP2 knockout cells are still subject to ferroptotic cell death, as are cells that lack IRP1 expression. Collectively, our findings suggest that while increased expression of IRP1 and IRP2 can promote ferroptotic cell death, expression of IRP1 or IRP2 is sufficient to convey sensitivity to ferroptosis activation. To identify mechanism driving increased IRP mRNA binding activity during cellular ferroptosis, we are currently assessing both iron-dependent and -independent regulators of IRP1 and IRP2 function and stability. As iron is an essential, yet potentially toxic nutrient, such findings will be important because they are expected to provide novel insights for exploiting the toxic nature of iron without compromising the essential homeostatic control mechanisms. Citation Format: Evan Hermann, Thais Oliveira, McKale Montgomery. The contributions of iron regulatory proteins 1 and 2 to ferroptosis activation and ferroptotic cell death [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 2006.
Abstract 337: p16INK4A-deficiency predicts for response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
Authors: Jing Ni, Sheheryar Kabraji, Shaozhen Xie, Yanzhi Wang, Peichen Pan, Xiaofang He, Zongming Liu, Henry Long, Myles Brown, Eric P. Winer, Deborah Dillon, Nancy Lin, Jean Zhao
Journal: Cancer Research (2021)

Abstract Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). To identify predictors of response and resistance to brain-penetrant, small molecule targeted therapies, we performed whole exome sequencing, RNAseq and quantitative immunohistochemistry of HER2+ BCBM tissues from 21 patients. We found that the tumor suppressor p16INK4A (p16) was deficient in the majority of HER2+ BCBMs. Orthotopic HER2+ BCBM patient-derived xenograft (PDX) models with p16 deficiency were resistant to the brain-penetrant HER2 inhibitor, tucatinib or the brain penetrant CDK4/6 inhibitor, abemaciclib, when used as single agents. However, p16-deficiency predicted response to combined tucatinib and abemaciclib in orthotopic HER2+ BCBM PDX models. These data establish the rationale for a biomarker-driven clinical trial of combined CDK4/6- and HER2-targeted agents for patients with HER2+ BCBM. Citation Format: Jing Ni, Sheheryar Kabraji, Shaozhen Xie, Yanzhi Wang, Peichen Pan, Xiaofang He, Zongming Liu, Henry Long, Myles Brown, Eric P. Winer, Deborah Dillon, Nancy Lin, Jean Zhao. p16INK4A-deficiency predicts for response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases [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 337.
Abstract 2597: Non-clinical studies of systemic delivery of oncolytic virus arms with IL-12 and anti-PD-1 antibody
Authors: Yanxin Zheng, Runbin Yan, Yuxin Tang, Borui Zhan, Yue Huang, Dongyao Ni, Xiaoqing Chen, Grace Zhou
Journal: Cancer Research (2021)

Abstract Background: Limited success has been reported with intravenous delivery of oncolytic viruses because of dilution of viruses in the blood volume, rapid clearance of viral particles and sequestration in non-target organs. We have reported construction of MVR-T3011, a recombinant oncolytic herpes virus embodies immunotherapeutic genes encoding IL-12 and anti-PD-1 antibody. Intratumoral Injection of MVR-T3011 has entered into clinical stage for the study of its safety and preliminary efficacy. Here we propose systemic delivery of MVR-T3011 by intravenous (IV) injection to treat tumor types that are not easily accessible by local injection. Methods: The pharmacological activity, safety and biodistribution of MVR-T3011 by intravenous injection have been studied in immune deficient and competent mouse model. Results: (i) In immune deficient mice, MVR-T3011 is enriched in tumor following tail vein injection. MVR-T3011 inhibits tumor growth of A549 xenograft. (ii) In immune competent mice, MVR-T1013L, the virus backbone carries a reporter gene encodes luciferase was enriched in upper abdomen and thorax 24hr following IV injection. (iii) IV administration of mouse surrogate oncolytic virus MVR-T3855 extended survival of mice in B16-F10 mouse melanoma lung metastasis model, LLC mouse orthotopic lung cancer model and H22 mouse orthotopic hepatocarcinoma model significantly. (iv) IV administration of MVR-T3855 delayed the onset of peritoneal effusion in H22 mouse hepatocarcinoma model significantly. (v) The biodistribution studies showed: following IV injection, tumor viral DNA reached peak level at 24hr, and dropped to baseline at 48hr; Subsequent injection showed similar patterns with lower peak levels. Consistent virus DNA level in the blood was detected without spike of viral DNA in other tissues probably due to non-complete virus genome circulating following virus clearance. Both IL-12 and anti-PD-1 antibody were detected in tissue and/or blood with low level 24hr following injection. Conclusions: MVR-T3011 is a suitable herpes oncolytic virus agent for intravenous injection through studies of pharmacological activity, safety and biodistribution. The significant finding reported in this article is clinical potential of herpes oncolytic virus for extensive metastatic tumors. Citation Format: Yanxin Zheng, Runbin Yan, Yuxin Tang, Borui Zhan, Yue Huang, Dongyao Ni, Xiaoqing Chen, Grace Zhou. Non-clinical studies of systemic delivery of oncolytic virus arms with IL-12 and anti-PD-1 antibody [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 2597.
Approaches for corneal endothelium regenerative medicine
Authors: Pere Català, Gilles Thuret, Heli Skottman, Jodhbir S. Mehta, Mohit Parekh, Sorcha Ní Dhubhghaill, Rob W.J. Collin, Rudy M.M.A. Nuijts, Stefano Ferrari, Vanessa L.S. LaPointe, Mor M. Dickman
Journal: Progress in Retinal and Eye Research (2021)

The state of the art therapy for treating corneal endothelial disease is transplantation. Advances in the reproducibility and accessibility of surgical techniques are increasing the number of corneal transplants, thereby causing a global deficit of donor corneas and leaving 12.7 million patients with addressable visual impairment. Approaches to regenerate the corneal endothelium offer a solution to the current tissue scarcity and a treatment to those in need. Methods for generating corneal endothelial cells into numbers that could address the current tissue shortage and the possible strategies used to deliver them have now become a therapeutic reality with clinical trials taking place in Japan, Singapore and Mexico. Nevertheless, there is still a long way before such therapies are approved by regulatory bodies and become clinical practice. Moreover, acellular corneal endothelial graft equivalents and certain drugs could provide a treatment option for specific disease conditions without the need of donor tissue or cells. Finally, with the emergence of gene modulation therapies to treat corneal endothelial disease, it would be possible to treat presymptomatic patients or those presenting early symptoms, drastically reducing the need for donor tissue. It is necessary to understand the most recent developments in this rapidly evolving field to know which conditions could be treated with which approach. This article provides an overview of the current and developing regenerative medicine therapies to treat corneal endothelial disease and provides the necessary guidance and understanding towards the treatment of corneal endothelial disease.
Associations of Community Water Lead Concentrations with Hemoglobin Concentrations and Erythropoietin-Stimulating Agent Use among Patients with Advanced CKD
Authors: John Danziger, Kenneth J. Mukamal, Eric Weinhandl
Journal: Journal of the American Society of Nephrology (2021)

Although patients with kidney disease may be particularly susceptible to the adverse health effects associated with lead exposure, whether levels of lead found commonly in drinking water are associated with adverse outcomes in patients with ESKD is not known.To investigate associations of lead in community water systems with hemoglobin concentrations and erythropoietin stimulating agent (ESA) use among incident patients with ESKD, we merged data from the Environmental Protection Agency (EPA) Safe Drinking Water Information System (documenting average 90th percentile lead concentrations in community water systems during 5 years before dialysis initiation, according to city of residence) with patient-level data from the United States Renal Data System.Among 597,968 patients initiating dialysis in the United States in 2005 through 2017, those in cities with detectable lead levels in community water had significantly lower pre-ESKD hemoglobin concentrations and more ESA use per 0.01 mg/L increase in 90th percentile water lead. Findings were similar for the 208,912 patients with data from the first month of ESKD therapy, with lower hemoglobin and higher ESA use per 0.01 mg/L higher lead concentration. These associations were observed at lead levels below the EPA threshold (0.015 mg/L) that mandates regulatory action. We also observed environmental inequities, finding significantly higher water lead levels and slower declines over time among Black versus White patients.This first nationwide analysis linking EPA water supply records to patient data shows that even low levels of lead that are commonly encountered in community water systems throughout the United States are associated with lower hemoglobin levels and higher ESA use among patients with advanced kidney disease.
進行性固形腫瘍患者における熱ショック蛋白質90阻害剤である17-ジメチルアミノエチルアミノ-17-デメトキシゲルダナマイシンに対する第I相薬物動態・薬力学的試験
Authors: K Ramanathan Ramesh, J Egorin Merrill, Erlichman Charles, C Remick Scot, S Ramalingam Suresh, Naret Cynthia, L Holleran Julianne, J Teneyck Cynthia, Ivy S. Percy, P Belani Chandra
Journal: Journal of Clinical Oncology (2010)
Trauma Laparotomies Result in Incisional Hernias, So What Is Next?
Authors: Lucas Beffa, Michael Rosen
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Artificial intelligence with fuzzy logic algorithms approach for target prostate biopsy outcomes prediction
Authors: E. Checcucci, S. Rosati, S. De Cillis, M. Vagni, N. Giordano, A. Piana, S. Granato, D. Amparore, P. Alessio, A. Pecoraro, A. Piana, F. Piramide, G. Volpi, M. Sica, D. Zamengo, M. Manfredi, S. De Luca, C. Fiori, G. Balestra, F. Porpiglia
Journal: European Urology (2021)
Abstract 10706: The Interplay Between Leukocyte Integrin Mac-1 And Estrogen Receptors Protects Against Atherosclerosis
Authors: Elzbieta Pluskota, Dorota Szpak, Lahoucine Izem, Dmitriy Verbovetskiy, Dmitry Soloviev, Edward F Plow
Journal: Circulation (2019)

Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by accumulation of lipid-loaded macrophages and fibrous material in developing lesions. Integrin αMβ2 (Mac-1) i...
Abstract 3046: In situ analysis of microenvironmental glycogen in Ewing's sarcoma patient samples by mass spectrometry imaging
Authors: Lyndsay E. Young, Lindsey R. Conroy, Harrison A. Clarke, Derek B. Allison, Richard R. Drake, Matthew S. Gentry, Ramon C. Sun
Journal: Cancer Research (2021)

Abstract Ewing's sarcoma (ES) is a rare pediatric cancer of the bone and soft tissues affecting adolescents and young adults, with peak incidence from ages 10 to 15 years. A clinical feature of ES is the accumulation of Periodic acid-Schiff positive (PAS+) aggregates. PAS+ staining in ES histopathology analysis has been speculated to be glycogen accumulation, however, this has not been confirmed. To interrogate these aggregates, we developed a novel workflow for the high-sensitive detection of in situ glycogen via enzymatic release of glycogen substrates coupled to matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) from formalin-fixed patient tissues. We utilized this method to study the nature of PAS+ staining in a cohort of ES patient samples surgically removed from tibia, rib, chest, shoulder, abdomen and testicle tissues. Using this innovative technique, we discovered profound intra-tumoral glycogen accumulation compared to adjacent stroma, normal, muscle and/or necrotic tissue. Further, intra-tumoral glycogen also has an increased phosphate content and distinct chain length profile compared to normal glycogen found in adjacent and patient-matched tissue. Notably, genetic manipulation and pharmacological inhibition of glycogen synthesis, or removal of glycogen phosphates, blunted ES tumor growth in xenografted mouse models. These findings suggest an important role of ES glycogen aggregates in tumor growth. Together, application of this novel MALDI-IMS technique, and the insights provided by formalin-fixed ES patient samples, reveals a distinct role of ES glycogen aggregates and uncovers a new therapeutic opportunity for this rare pediatric cancer. Citation Format: Lyndsay E. Young, Lindsey R. Conroy, Harrison A. Clarke, Derek B. Allison, Richard R. Drake, Matthew S. Gentry, Ramon C. Sun. In situ analysis of microenvironmental glycogen in Ewing's sarcoma patient samples by mass spectrometry imaging [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 3046.
KIR3DL3-HHLA2 is a human immunosuppressive pathway and a therapeutic target
Authors: Yao Wei, Xiaoxin Ren, Phillip M. Galbo, Scott Moerdler, Hao Wang, R. Alejandro Sica, Bijan Etemad-Gilbertson, Lei Shi, Liqiang Zhu, Xudong Tang, Qi Lin, Mou Peng, Fangxia Guan, Deyou Zheng, Jordan M. Chinai, Xingxing Zang
Journal: Science Immunology (2021)

The B7 family ligand HERV-H LTR-associating protein 2 (HHLA2) is an attractive target for cancer immunotherapy because of its coinhibitory function, overexpression in human cancers, and association with poor prognoses. However, the knowledge of the HHLA2 pathway is incomplete. HHLA2 has an established positive receptor transmembrane and immunoglobulin (Ig) domain containing 2 (TMIGD2) but a poorly characterized negative receptor human killer cell Ig-like receptor, three Ig domains, and long cytoplasmic tail (KIR3DL3). Here, KIR3DL3 and TMIGD2 simultaneously bound to different sites of HHLA2. KIR3DL3 was mainly expressed on CD56
Covid-19: Doctors criticise government’s plan to make mask wearing a personal choice
Authors: Abi Rimmer
Journal: BMJ (2021)

The BMA has spoken out against plans to allow people to make their own decisions on whether to wear a face covering as part of easing covid-19 restrictions in England.

Speaking on 5 July, Prime Minister Boris Johnson set out plans for the final stage of easing covid-19 restrictions in England. The fourth stage was previously delayed by four weeks, from 21 June to 19 July, to allow more people to be vaccinated.1

Johnson said that the plans—which are subject to a final decision by the government on 12 July—would shift from legal restrictions to allowing people to make their own informed decisions about how to manage the virus.

“From step four we will remove all legal limits on the numbers meeting indoors and outdoors, we will allow all business to reopen including nightclubs, and we will lift the limit on named visitors to care homes …
急性心筋梗塞患者の院内死亡率における郊外および都市の性差-MIYAGI-AMI登録研究からの報告-
Authors: Itoh Yoshitaka, Yasuda Satoshi, Takii Toru, Takahashi Jun, Itoh Kenta, Shiba Nobuyuki, Shimokawa Hiroaki
Journal: Circulation (2011)
Endoscopic exploration directly impacts clinical decision making in the management of patients with suspected upper tract urothelial carcinoma following radical cystectomy
Authors: J. Aumatell Ovide, J. Huguet Pérez, J.D. Subiela, A. Mercadé Sánchez, J. Balañà Lucena, J.M. Gaya Sopena, O. Rodríguez-Faba, A. Territo, A. Breda, J. Palou Redorta
Journal: European Urology (2021)