tbuckley/cabot-search huggingface dataset:
Relaxin-expressing oncolytic adenovirus induces remodeling of physical and immunological aspects of cold tumor to potentiate PD-1 blockade
Authors: Bo-Kyeong Jung, Hae Young Ko, Hyunji Kang, JinWoo Hong, Hyo Min Ahn, Youjin Na, Hyeongi Kim, Jin Su Kim, Chae-Ok Yun
Journal: Journal for ImmunoTherapy of Cancer (2020)

Currently, several antibody (Ab)-based therapies have shown excellent therapeutic effects in the clinic. Nonetheless, Ab penetration into tumor tissues is limited due to abnormal vasculature, tumor interstitial pressure, and excessive extracellular matrix (ECM) accumulation, thus demanding novel strategies to overcome these barriers.The intratumoral distribution of therapeutic Abs were detected by fluorescence microscopy or positron emission tomography in both human gastric xenograft and syngeneic pancreatic hamster tumor models. The antitumor efficacy by combination of oncolytic adenovirus (Ad), which coexpresses relaxin (RLX), interleukin (IL)-12, and granulocyte macrophage colony-stimulating factor (GM-CSF) (oAd/IL12/GM-RLX) and antibody against the programmed cell death protein 1 (αPD-1) was examined in hamster subcutaneous and orthotopic pancreatic tumor models. The immunological aspects of these combination therapy regimen were assessed by flow cytometry or immunohistochemistry in subcutaneous hamster tumor models.Relaxin-expressing oncolytic Ad effectively degraded tumor ECM and enhanced the tumor penetration of trastuzumab in comparison with trastuzumab monotherapy. Based on these results, an oAd/IL12/GM-RLX was used to enhance the potency of immune checkpoint blockade. The combination of the oAd/IL12/GM-RLX and αPD-1 promoted a concomitant degradation of the tumor ECM and amelioration of the immunosuppressive tumor niches, ultimately enhanced intratumoral infiltration of both αPD-1 and activated T cells. Of note, the combination therapy was able to elicit a potent and durable antitumor immune response against cold tumors that were refractory to immune checkpoint inhibitor monotherapy.Our findings are the first to demonstrate that expression of four genes (IL-12p35, IL-12p40, GM-CSF, and RLX) mediated by a single oncolytic Ad vector can promote remodeling of both physical and immunological aspects of the tumor niches to overcome the major limitations of Ab-based therapies that have emerged in recent clinical trials.
Persistence of rT-PCR-SARS-CoV-2 infection and delayed serological response, as a possible effect of rituximab according to the hypothesis of Schulze-Koops<i>et al</i>
Authors: Maurizio Benucci, Luca Quartuccio, Francesca Li Gobbi, Arianna Damiani, Valentina Grossi, Maria Infantino, Mariangela Manfredi
Journal: Annals of the Rheumatic Diseases (2020)

Correspondencerituximab schedule, our patient undergoing a retreatment regimen at B cell recovery showed a good outcome.Notably, IgG levels before the last rituximab infusion were low, but over the dangerous threshold of 400 mg/dL.Therefore, it might be argued that rituximab retreatment regimen at B cell recovery rather than fixed retreatment schedule might be safer.Moreover, dexamethasone may have contributed to the favourable outcome of our patient. 5According to European League Against Rheumatism recommendations, 6 patients undergoing cyclophosphamide or rituximab-mediated immunosuppression should represent the population of patients with rheumatic disease at highest risk of COVID-19 infection and its most severe consequences at this time; therefore, administration of these treatments should be based on a careful risk-benefit ratio.If needed, retreatment with rituximab should be based on B cell recovery or clinical (or laboratory) relapse, according to the disease, rather than with a fixed time schedule.Finally, a deeper analysis of the effect of each biological agent on COVID-19 infection is warranted.
AB0050 DETECTION OF SERUM AND SYNOVIAL FLUID LEVELS OF VISFATIN DURING FLARE-UPS AND REMISSION OF PRIMARY OSTEOARTHRITIS OF THE KNEES
Authors: Haytham Abd elaal, Hassan Bassiouni, Khaled Zaky
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> OA is the most common form of joint disease and a major contributor of disability in older people. OA is a chronic joint disease characterized by cartilage breakdown, bone remodeling, osteophyte development and synovial inflammation [1]. Adipose tissue expresses and secretes a large number of proteins that often share functional and structural properties of cytokines and are there classified as adipokines [2]. These include leptin, adiponectin, resistin, visfatin, and others. These factors are associated with inflammation and immune response. Visfatin is an adipokines identified in 2004 and was identified first as Pre B cell Colony Enhancing Factor [3]. Visfatin is a potent inducer of PGE2 release in both human and immature mouse articular chondrocytes, as a result of increased messenger prostaglandin E synthase and decreased 15 15prostaglandine dehydrogenase syntheses [4]. <h3>Objectives</h3> The aim of the study was to measure the level of visfatin in serum and synovial fluid from patients with knee osteoarthritis in flare-up and after they enter in remission. Methods: to achieve the target of our study 20 patients with OA of the knee in flare-up were selected from out-patients clinic. The patients were followed up every two weeks after the first setting until they entered into remission. Twenty normal controls age, sex and body mass index (BMI) matched were recruited. In the first setting all patients had their sera, and synovial fluid measured for Visfatin, in the second setting sera and synovial fluid (if any) was drawn for visfatin measurement. Measurement of Visfatin by (ELISA) for quantitative determination of human visfatin in biological fluids. <h3>Results</h3> <h3>Conclusion</h3> Visfatin was elevated both systemically and locally in the patients with knee OA, was elevated during flare-ups and decrease during remission, was higher in serum than in synovial fluid of patients and There was no difference in the level of visfatin in relation to aging or gender difference. <h3>References</h3> [1] Lorenz H, Richter W (2006) Osteoarthritis: cellular and molecular changes in degenerating cartilage. Prog Histochem Cytochem40(3):135–163. [2] Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab89(6):2548–2556. [3] O. Gualillo, J. R. Gonźalez-Juanatey, and F. Lago,(2007) "The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives," Trends in Cardiovascular Medicine, vol. 17, no. 8, pp. 275–283, 2007. [4] Duan Y, Hao D, Li M, et al. (2012) Increased synovial fluid visfatin is positively linked to cartilage degradation biomarkers in osteoarthritis. Rheumatol Int2012; 32:985–90. <h3>Disclosure of Interests</h3> None declared
Cost-Effectiveness of Implantable Cardioverter Defibrillators (ICDs) Compared with Amiodarone for Prevention of Sudden Cardiac Death
Authors: Douglas K. Owens, Gillian D. Sanders, RA Harris, Kathryn M. McDonald, Paul A. Heidenreich, Anne Dembitzer, Mark A. Hlatky
Journal: Annals of Internal Medicine (1997)
3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice
Authors: Athri D. Rathnayake, Jian Zheng, Yunjeong Kim, Krishani Dinali Perera, Samantha Mackin, David K. Meyerholz, Maithri M. Kashipathy, Kevin P. Battaile, Scott Lovell, Stanley Perlman, William C. Groutas, Kyeong-Ok Chang
Journal: Science Translational Medicine (2020)

Optimized small-molecule 3C-like protease inhibitors show potency against human coronaviruses in both cell culture and a mouse model.
Methods matter and the ‘too much, too soon’ theory (part 2): what is the goal of your sports injury research? Are you describing, predicting or drawing a causal inference?
Authors: Rasmus Oestergaard Nielsen, Nina Sjoerup Simonsen, Marti Casals, Emmanuel Stamatakis, Mohammad Ali Mansournia
Journal: British Journal of Sports Medicine (2020)

Imagine a sports injury researcher who gets a bright idea in relation to the ‘too much, too soon’ theory (too much training, too soon, leads to injury).1 Then, the researcher proposes the following aim: to examine the association between workload and sports injury. Think twice: Does the word ‘association’ truly assist you, the reader, in understanding the underlying goal?

Every researcher should be clear on the goal of their research. The goal should be immediately clear to the intended readers. Failure to be clear about goals may lead to inappropriate, misleading and flawed conclusions.2 Hernan, an expert epidemiologist, declared in 2018 that ‘…being explicit about the goal of the analysis is a prerequisite for good science ’ ,3 since being explicit about the objective of a study reduces ambiguity in the scientiﬁc question, errors in the data analysis, and excesses in the interpretation of the results. Possibly, using the term ‘association’ (above) is ambiguous as we are unaware of the underlying goal.

Although definitions may vary depending on the source,4 5 research into sports injury usually has one of three goals: To describe, to predict or to explain. To describe, for example, how athletes train and/or how many athletes sustains sports injury over time (eg, injury risk), without investigating their relationship. In contrast to describing, researchers can also examine relationships, or so-called associations, which can have two vastly different goals: to predict groups at risk of sustaining sport injury (here referred to as predicting) or to explain why some athletes sustain workload-related injury (here referred to as causal inference).

In the first educational piece in this ‘too much, too soon’ series,6 we provided readers with examples of causal research questions, described analytical concepts and outlined the main differences between population-based prevention and personalised prevention. This …
Estrogen receptor α controls metabolism in white and brown adipocytes by regulating <i>Polg1</i> and mitochondrial remodeling
Authors: Zhenqi Zhou, Timothy M. Moore, Brian G. Drew, Vicent Ribas, Jonathan Wanagat, Mete Civelek, Mayuko Segawa, Dane M. Wolf, Frode Norheim, Marcus M. Seldin, Alexander R. Strumwasser, Kate A. Whitney, Ellen Lester, Britany R. Reddish, Laurent Vergnes, Karen Reue, Prashant Rajbhandari, Peter Tontonoz, Jason Lee, Sushil K. Mahata, Sylvia C. Hewitt, Orian Shirihai, Craig Gastonbury, Kerrin S. Small, Markku Laakso, Jorgen Jensen, Sindre Lee, Christian A. Drevon, Kenneth S. Korach, Aldons J. Lusis, Andrea L. Hevener
Journal: Science Translational Medicine (2020)

ERα gene expression is heritable in humans and prevents obesity in mice by improving mitochondrial function via adipocyte Polg1 expression.
Abstract B06: Candidate differentiation stall in epithelial mesenchymal transition in H3K27M diffuse midline glioma
Authors: Allison R. Cheney, Lauren M. Sanders, Lucas Seninge, Holly C. Beale, Ellen Towle Kephart, Jacob Pfeil, Katrina Learned, A. Geoffrey Lyle, Isabel Bjork, David Haussler, Sofie R. Salama, Olena M. Vaske
Journal: Cancer Research (2020)

Abstract The purpose of our study was to elucidate the molecular mechanisms by which the histone H3 K27M mutation drives tumorigenesis of pediatric gliomas. Though it has potential implications on the treatment of diffuse midline glioma as a disease driver, the timing, cell type of origin, and effect of the H3K27M mutation on early embryonic brain development are not fully characterized. Here, we performed differential expression analysis on a cohort of H3K27M and H3WT pediatric gliomas, revealing that genes in the epithelial-mesenchymal transition (EMT) pathway were significantly differentially expressed. SNAI1, the EMT master regulator, was significantly overexpressed in the H3K27M tumor cohort. Overall, pre-EMT genes were overexpressed in H3K27M tumors while post-EMT genes were underexpressed. We hypothesized that H3K27M may lead to gliomagenesis by stalling an EMT in early brain development and employed single-cell and bulk RNA sequencing data from cerebral organoids at multiple developmental timepoints to test this hypothesis. We observed that a long noncoding RNA (lncRNA) signature identified as transiently expressed in early brain development was preferentially expressed in H3K27M tumors. Cell type-specific lncRNA signatures had higher expression in H3K27M tumors for pre-EMT cell types, and higher expression in H3WT tumors for post-EMT cell types. Finally, t-SNE clustering of single-cell glioma RNA sequencing data with single-cell organoid data revealed transcriptional similarities between H3K27M and pre-EMT neural stem cells. In conclusion, we observed aberrant activity of the EMT in H3K27M gliomas. Our data suggest that the H3K27M mutation is associated with a pre-EMT cell phenotype, and that this mutation may cause EMT arrest or de-differentiation. Citation Format: Allison R. Cheney, Lauren M. Sanders, Lucas Seninge, Holly C. Beale, Ellen Towle Kephart, Jacob Pfeil, Katrina Learned, A. Geoffrey Lyle, Isabel Bjork, David Haussler, Sofie R. Salama, Olena M. Vaske. Candidate differentiation stall in epithelial mesenchymal transition in H3K27M diffuse midline glioma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr B06.
Prophylactic Modified Donor Lymphocyte Infusion after Allogeneic Peripheral Blood Stem Cell Transplantation for Very High-Risk Hematological Malignancies: Low Incidence of Relapse without Increasing the Risk of Graft-Versus-Host Disease
Authors: Xiaoning Gao, Shuhong Wang, Wenrong Huang, Honghua Li, Yu Jing, Liping Dou, Fei Li, Lili Wang, Xiaolin Lu, Jing Chen, Lijun Wang, Xiangshu Jin, Li Yu, Daihong Liu
Journal: Blood (2017)
Same Name, Different Game: EGFR Drives Intrinsic KRASG12C Inhibitor Resistance in Colorectal Cancer
Authors: Mohamad Karim Koleilat, Lawrence N. Kwong
Journal: Cancer Discovery (2020)

Abstract Summary: The discovery of covalent inhibitors of KRASG12C has led to promising clinical results in lung cancer, but disappointing response rates in colon cancer. In this issue of Cancer Discovery, Misale and colleagues identify high endogenous EGFR activity as the underlying mechanism of intrinsic resistance, which can be overcome by anti-EGFR antibody coadministration. See related article by Amodio et al., p. 1129.
Assessing Expression of PD-L1 in Tumor-Associated Macrophages—Reply
Authors: Salma Jabbour, Charles B. Simone, Jyoti Malhotra
Journal: JAMA Oncology (2020)

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
VIABLE TUMOUR TISSUE ADHERENT TO NEEDLE APPLICATORS AFTER LOCAL ABLATION: A RISK FACTOR FOR LOCAL RECURRENCE
Authors: N. Snoeren, J. Huiskens, M. Jansen, A. Rijken, R. van Hillegersberg, G. Slooter, J. Klaase, P. van den Tol, A. van Erkel, F. ten Kate
Journal: Annals of Oncology (2010)
BNC105P is a vascular disruption agent that exhibits dual mode of action in a number of cancer indications and works additively in combination with bevacizumab.
Authors: Gabriel Kremmidiotis, Tina Lavranos, Donna Beaumont, Annabell Leske, Julian Adams, Michael O'Callaghan, Allison Hall, Deanna Bueti, Jelena Gasic, Bernard Flynn
Journal: Cancer Research (2008)

1445  Tumor vascular disruption is a therapeutic strategy of great potential. A number of vascular disrupting agents (VDA) are currently in clinical development. Discovery of VDA compounds that display a wide therapeutic margin will enable exploitation of the therapeutic potential of blocking tumor vasculature. Bionomics has discovered and is developing BNC105P as a VDA. We have previously shown BNC105P displays selectivity for tumor endothelium and exhibits strong efficacy in breast and colon tumor models. We have further evaluated the vascular disruption capacity of BNC105P in other tumor types. Subcutaneous lung, prostate and brain tumors were grown in Balb/c nu/nu mice. Dose response of tumor vasculature to BNC105P treatment was evaluated. Vascular disruption was assessed histologically using H33342 perfusion. BNC105P disrupts vasculature in lung, prostate and brain xenograft tumors following a single administration. Vascular disruption was observed at 5mg/kg in lung and brain tumors and 20mg/kg in prostate tumors. Vascular disruption led to corresponding increases in tumor necrosis. The consequences of BNC105P action in the tumor microenvironment were evaluated. Expression of laminin and CD31 decreased suggesting disruption of vessel integrity and endothelial cell death. There was increased expression of VEGF and apoptosis 30 hours post-administration of the drug. Tumor re-vascularisation occurs 48hrs following BNC105P treatment. Treatment of tumors with BNC105P in combination with bevacizumab prevented tumor re-vascularisation and prolonged vascular shutdown up to 5 days post treatment. Low dose BNC105P in combination with bevacizumab produced additive effects in human breast cancer xenografts. High dose levels of BNC105P treatment produced considerable inhibition of tumor growth in a number of models suggesting VDA and anti-proliferative modes of action. BNC105 exhibits anti-proliferative activity at 0.1-1nM against cancer cells in vitro. Distribution of the active drug BNC105 was investigated in tumor-bearing animals at 15 minutes, 2, 6 and 24 hours post-administration. At 24 hours BNC105 is cleared from all organs but remains at high levels within the tumor. BNC105 shuts down tumor blood vessels “locking itself” inside the tumor were it exerts anti-proliferative pressure on the cancer cells. BNC105 is currently under investigation in Phase I clinical trials.
Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology
Authors: Kimberly Davies, Matthew Barth, Saro Armenian, Anthony N. Audino, Phillip Barnette, Branko Cuglievan, Hilda Ding, James B. Ford, Paul J. Galardy, Rebecca Gardner, Rabi Hanna, Robert Hayashi, Alexandra E. Kovach, Andrea Judit Machnitz, Kelly W. Maloney, Lianna Marks, Kristin Page, Anne F. Reilly, Joanna L. Weinstein, Ana C. Xavier, Nicole R. McMillian, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2020)

Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.
THU0155 Impact of rheumatoid arthritis on the outcomes of 1093 patients, and the use of disease modifying anti rheumatic drugs since diagnosis
Authors: T Sokka, P Hannonen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Severe long-term consequences of rheumatoid arthritis (RA) are well known, while the existing evidence suggests that early and active use of disease modifying anti rheumatic drugs (DMARDs) may improve the outcomes. <h3>Objectives</h3> To study the impact of disease on the outcomes of patients with RA, and to describe their use of DMARDs over time. <h3>Methods</h3> In August 2000, a questionnaire was sent to 1500 patients with RA who had been seen in Jyvaskyla Central Hospital since 1995 and were included in the RA database of the hospital. A total of 1093 (73%) patients replied and were included in the study. The overall impact of RA was assessed by asking "How much does RA impact your life?". Response alternatives were 1)"Not at all", 2)"Some", 3)"Much", and 4)"Very much". The questionnaire also assessed functional capacity by Health Assessment Questionnaire (HAQ, range 0–3), pain and general health by 10 cm visual analogue scale (VAS, range 0–100), and current usage of DMARDs. Data concerning demographics, "diagnostic delay", and previous use of DMARDs were available through the RA database. The intensity of the use of DMARDs was calculated as the percentage of the time on DMARDs from the total time elapsed since the diagnosis to August 2000. <h3>Results</h3> A total of 13% of the patients did not experience any impact from RA, while 48% experienced "some", 27% "much", and 12% were impacted "very much". Those experiencing "very much" level of impact by RA were older, had longer disease duration, had less education, were more often rheumatoid factor positive, had worse HAQ and general health scores, had more pain, and also had longer diagnostic delay, and less use of DMARDs over time than those experiencing "no" or "some" impact by the disease (Table 1: mean values for variables are shown except median for DMARD%.) <h3>Conclusion</h3> In spite of extensive therapy with DMARDs, RA causes considerable impact in the majority of patients in the long term. Shortening of diagnostic delay (improvement in the cooperation between primary and specialist care) and continuous active therapy with available DMARDs should be emphasised to decrease disease impact.
Regulatory T cells: A potential weapon to combat COVID‐19?
Authors: Yu Liu, Guangying Qi, Joseph A. Bellanti, René Moser, Bernhard Ryffel, Song Guo Zheng
Journal: MedComm (2020)

Since the end of December 2019, a novel coronavirus SARS-CoV-2 began to spread, an infection disease termed COVID-19. The virus has spread throughout the world in a short period of time, resulting in a pandemic. The number of reported cases in global reached 5 695 596 including 352 460 deaths, as of May 27, 2020. Due to the lack of effective treatment options for COVID-19, various strategies are being tested. Recently, pathologic studies conducted by two teams in China revealed immunopathologic abnormalities in lung tissue. These results have implications for immunotherapy that could offer a novel therapy strategy for combating lethal viral pneumonia. This review discusses the clinical and pathological features of COVID-19, the roles of immune cells in pathological processes, and the possible avenues for induction of immunosuppressive T regulatory cells attenuating lung inflammation due to viral infection. It is our hope that these proposals may both be helpful in understanding the novel features of SARS-CoV-2 pneumonia as well as providing new immunological strategies for treating the severe sequelae of disease manifestations seen in people infected with SARS-CoV-2.
Architectural Decay of the Skeleton and Accumulation of Visceral Abdominal Fat Following Androgen Deprivation Therapy for Prostate Cancer.
Authors: EJ Hamilton, EJ Gianatti, BJ Strauss, J Wentworth, A Ghasem-Zadeh, R Zebase, D Lim Joon, D Bolton, E Seeman, JD Zajac, M Grossmann
Journal: Endocrine Reviews (2010)