tbuckley/cabot-search huggingface dataset:
Association of IL17-expressing γδ t cells with acute radiation-induced pneumonitis.
Authors: Winston W. P. Liao, K. S. Clifford Chao, Tom K Hei, Simon Cheng
Journal: Journal of Clinical Oncology (2012)

e21097 Background: Radiation pneumonitis is a substantial cause of morbidity and mortality with thoracic radiation for lung cancer. Little is known about the crucial mechanisms of the inflammatory response. We seek to determine if a key mediator of organ-specific inflammatory disorders and innate immune response, IL-17 + γδ T cells, is associated with radiation pneumonitis. Methods: C3HBe/FeJ mice (7 mice/group) were sham-irradiated as controls or exposed to a single dose of 15 Gy thoracic X-ray to develop pneumonitis. We have previously shown that TGFβ has an immunosuppressive activity in radiation pneumonitis. To potentiate the radiation pneumonitis, one group of mice was administered anti-TGFβ therapy with inhibitory TGFβ mAb (1D11, i.p.10 mg/kg/wk). Bronchoalveolar lavage fluid was assessed for cytology and inflammatory cytokine level. Lung tissues were examined for cell infiltration and histopathological changes. Cell surface marker and intracellular cytokine staining were performed on lymphocytes from the digested lungs by flow cytometry. Results: At 10 weeks post-irradiation, the lungs of the irradiated mice showed substantially more alveolar wall edema and increased infiltration of inflammatory cells compared with sham controls. Pneumonitis-involved lungs contained more IL-17 + γδ T cells (0.85% ± 0.00%) compared with sham controls (0.33% ± 0.02%), p&lt;0.001. Furthermore increased IL-17 + γδ T cells were associated with potentiated radiation pneumonitis with anti-TGFβ therapy. There was a significant increased alveolar inflammation in irradiated mice injected with anti-TGFβ mAb. Anti-TGFβ irradiated lungs also contained significantly more IL-17 + γδ T cells (1.17% ± 0.13%) compared with irradiated controls (0.72% ± 0.13%), p&lt;0.001. There was no increase of other TGFβ-dependent T cell subtypes such as IFNγ + αβ T cells (Th1), IL-17 + αβ T cells (Th17), CD25 + Foxp3 + Tregs, nor activated macrophages in the potentiated pneumonitis lungs. Conclusions: Our findings implicate a novel role for IL17-expressing γδ T cells in radiation pneumonitis. This study reveals this innate immune response pathway as a potential target for therapeutic intervention in radiation lung injury
Nucleolus and rRNA Gene Chromatin in Early Embryo Development
Authors: Jelena Kresoja-Rakic, Raffaella Santoro
Journal: Trends in Genetics (2019)

The nucleolus is the largest substructure in the nucleus and forms around the nucleolar organizer regions (NORs), which comprise hundreds of rRNA genes. Recent evidence highlights further functions of the nucleolus that go beyond ribosome biogenesis. Data indicate that the nucleolus acts as a compartment for the location and regulation of repressive genomic domains and, together with the nuclear lamina, represents the hub for the organization of the inactive heterochromatin. In this review, we discuss recent findings that have revealed how nucleolar structure and rRNA gene chromatin states are regulated during early mammalian development and their contribution to the higher-order spatial organization of the genome.
Ovarian cancer stem cells and macrophages reciprocally interact through the WNT pathway to promote pro-tumoral and malignant phenotypes in 3D engineered microenvironments
Authors: Shreya Raghavan, Pooja Mehta, Yuying Xie, Yu L. Lei, Geeta Mehta
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Innate immune cells such as macrophages are abundantly present within malignant ascites, where they share the microenvironment with ovarian cancer stem cells (CSC). <h3>Methods</h3> To mimic this malignant ascites microenvironment, we created a hanging-drop hetero-spheroid model to bring CSCs and macrophages in close association. Within these hetero-spheroids, CD68<sup>+</sup> macrophages (derived from U937 or peripheral blood monocytes) make up ~ 20% of the population, while the rest are ovarian cancer cells and ovarian cancer stem cells (derived from the high grade serous ovarian cancer cell line, OVCAR3). <h3>Results</h3> Our results indicate that CSCs drive the upregulation of M2 macrophage marker CD206 within hetero-spheroids, compared to bulk ovarian cancer cells, implying an inherently more immuno-suppressive program. Moreover, an increased maintenance of elevated aldehyde dehydrogenase (ALDH) activity is noted within hetero-spheroids that include pre-polarized CD206<sup>+</sup> M2 macrophages, implying a reciprocal interaction that drives pro-tumoral activation as well as CSC self-renewal. Consistent with enriched CSCs, we also observe increased levels of pro-tumoral IL-10 and IL-6 cytokines in the CSC/M2-macrophage hetero-spheroids. CSC/M2-macrophage hetero-spheroids are also less sensitive to the chemotherapeutic agent carboplatin and are subsequently more invasive in transwell assays. Using inhibitors of WNT secretion in both CSCs and macrophages, we found that CSC-derived WNT ligands drove CD206<sup>+</sup> M2 macrophage activation, and that, conversely, macrophage-derived WNT ligands enriched ALDH<sup>+</sup> cells within the CSC compartment of hetero-spheroids. Upon examination of specific WNT ligand expression within the monocyte-derived macrophage system, we observed a significant elevation in gene expression for <i>WNT5B</i>. In CSCs co-cultured with macrophages within hetero-spheroids, increases in several WNT ligands were observed, and this increase was significantly inhibited when WNT5B was knocked down in macrophages. <h3>Conclusions</h3> Our data implies that macrophage- initiated WNT signaling could play a significant role in the maintenance of stemness, and the resulting phenotypes of chemoresistance and invasiveness. Our results indicate paracrine WNT activation during CSC/M2 macrophages interaction constitutes a positive feedback loop that likely contributes to the more aggressive phenotype, which makes the WNT pathway a potential target to reduce the CSC and M2 macrophage compartments in the tumor microenvironment.
Radiotherapy plus the anti-EGFR mAb nimotuzumab or placebo for the treatment of high-grade glioma patients.
Authors: Maria Teresa Solomon, Julio Cesar Selva, Javier Figueredo, Jose Vaquer, Carolina Toledo, Nelson Quintanal, Silvia Salva, Rafael Dominguez, Jose Alert, Jorge Juan Marinello, Mauricio Catala, Martha Gonzalez Griego, Patrcia Lorenzo Luaces, Normando Iznaga, Ferdinand Bach, Tania Crombet Ramos
Journal: Journal of Clinical Oncology (2012)

2515 Background: Despite remarkable advances in multimodal therapy, high grade glioma (HGG) patients still face a poor prognosis. EGFR is well validated as a primary contributor of HGG initiation and progression. Nimotuzumab is a humanized monoclonal antibody (mAbs) that recognizes the EGFR extracellular domain. While it has similar preclinical and clinical activity when compared to other anti-EGFR mAbs, it does not induce skin toxicity or hypomagnesemia. Methods: A randomized, double blind, multicentric clinical trial was conducted in 70 anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) patients that received radiotherapy (RT) plus nimotuzumab or placebo. Patients received 6 weekly doses of nimotuzumab or placebo together with radiotherapy. Treatment was maintained every 3 weeks, until completing 1 year of treatment. GBM patients did not receive temozolomide since the drug cannot be sold to Cuba. The objectives of this study were to assess the overall survival, progression free survival (PFS), response rate, immunogenicity and safety in both treatment groups. Results: Seventy patients were included in the study: 41 AA and 29 GBM. The median cumulative dose was 3600 mg of nimotuzumab and the median antibody number of doses was 16. The combination of nimotuzumab and radiotherapy was very safe. The most prevalent related adverse events included grade 1-2 nausea, fever, tremors and anorexia. There was no increasing toxicity with repeated drug exposure. No anti-idyotipic response was detected. The mean and median survival time for subjects treated with nimotuzumab and RT was 31.06 and 17.76 months while the mean and median survival time for controls was 21.07 and 12.63 months, respectively. For the evaluable patients of the AA stratum, the median survival time was 44.56 months (active drug) vs. 14.6 months (control). For the evaluable patients in the GBM cohort, the median survival time was 16.06 months (nimotuzumab arm) vs. 8.36 months (placebo arm). Median PFS was 18.23 vs. 6.25 months. Conclusions: In this randomized trial, nimotuzumab continues showing an excellent safety profile and positive efficacy results in patients with high grade glioma in combination with irradiation.
Customizing surveillance of patients with esophageal or esophagogastric junction adenocarcinoma (E-EGA) after trimodality therapy (TMT).
Authors: Takashi Taketa, Arlene M. Correa, Kazuki Sudo, Mariela A. Blum, Roopma Wadhwa, Heath D. Skinner, Ritsuko Komaki, Jeffrey H. Lee, Manoop S. Bhutani, Brian Weston, Zhongxing X. Liao, David C. Rice, Stephen Swisher, Wayne Lewis Hofstetter, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2013)

4085 Background: Follow-up strategy for E-EGA patients after TMT has varied and is debated often due to the lack of evidence. It is an expensive endeavor and the literature provides little guidance. Methods: Between 2000 and 2010, we identified 518 E-EGA patients who had TMT. We reviewed the timing/pattern of recurrence after TMT and grouped them as local-regional (LR) or metastatic (M). Results: The median follow-up time from date of surgery was 29.3 months (range, 0.8 to 149.2 months). 215 (41.5%) had a relapse (M=188 [87.5%] and LR=27 [12.5%]). Among LRs, regional node only in 16 (7.4%) and intra-luminal only occurred in 11 (5.1%). The frequency of relapses was highly associated with the surgical stage (p&lt;0.001). &gt;90% of all relapses occurred within 29.2 months of surgery. In addition, almost all intra-luminal only relapses occurred within 24 months (see Table). Conclusions: Our data suggest that it may be possible to customize surveillance of patients after TMT based on the surgical stage. Additionally, intra-luminal only relapse are rare and are unlikely after 24 months. Our data can contribute to the development of an evidence-based surveillance strategy. [Table: see text]
What is taken for granted in autism research?
Authors: Michele Ilana Friedner
Journal: Behavioral and Brain Sciences (2019)

Abstract This commentary focuses on three points: the need to consider semiotic ideologies of both researchers and autistic people, questions of commensurability, and problems with “the social” as an analytical concept. It ends with a call for new research methodologies that are not deficit-based and that consider a broad range of linguistic and non-linguistic communicative practices.
The 1918 influenza pandemic: 100 years of questions answered and unanswered
Authors: Jeffery K. Taubenberger, John C. Kash, David M. Morens
Journal: Science Translational Medicine (2019)

The 2018-2019 period marks the centennial of the "Spanish" influenza pandemic, which caused at least 50 million deaths worldwide. The unprecedented nature of the pandemic's sudden appearance and high fatality rate serve as a stark reminder of the threat influenza poses. Unusual features of the 1918-1919 pandemic, including age-specific mortality and the high frequency of severe pneumonias, are still not fully understood. Sequencing and reconstruction of the 1918 virus has allowed scientists to answer many questions about its origin and pathogenicity, although many questions remain. This Review summarizes key findings and still-to-be answered questions about this deadliest of human events.
CIC-DUX4 oncoprotein drives sarcoma metastasis and tumorigenesis via distinct regulatory programs
Authors: Ross A. Okimoto, Wei Wu, Shigeki Nanjo, Victor Olivas, Yone K. Lin, Rovingaile Kriska Ponce, Rieko Oyama, Tadashi Kondo, Trever G. Bivona
Journal: Journal of Clinical Investigation (2019)

Transcription factor fusion genes create oncoproteins that drive oncogenesis and represent challenging therapeutic targets. Understanding the molecular targets by which such fusion oncoproteins promote malignancy offers an approach to develop rational treatment strategies to improve clinical outcomes. Capicua–double homeobox 4 (CIC-DUX4) is a transcription factor fusion oncoprotein that defines certain undifferentiated round cell sarcomas with high metastatic propensity and poor clinical outcomes. The molecular targets regulated by the CIC-DUX4 oncoprotein that promote this aggressive malignancy remain largely unknown. We demonstrated that increased expression of ETS variant 4 (ETV4) and cyclin E1 (CCNE1) occurs via neomorphic, direct effects of CIC-DUX4 and drives tumor metastasis and survival, respectively. We uncovered a molecular dependence on the CCNE-CDK2 cell cycle complex that renders CIC-DUX4–expressing tumors sensitive to inhibition of the CCNE-CDK2 complex, suggesting a therapeutic strategy for CIC-DUX4–expressing tumors. Our findings highlight a paradigm of functional diversification of transcriptional repertoires controlled by a genetically aberrant transcriptional regulator, with therapeutic implications.
Hospital Readmission of Adolescents and Young Adults With Complex Chronic Disease
Authors: Peter Dunbar, Matt Hall, James C. Gay, Clarissa Hoover, Jessica L. Markham, Jessica L. Bettenhausen, James M. Perrin, Karen A. Kuhlthau, Morgan Crossman, Brigid Garrity, Jay G. Berry
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Adolescents and young adults (AYA) who have complex chronic disease (CCD) are a growing population that requires hospitalization to treat severe, acute health problems. These patients may have increased risk of readmission as demands on their self-management increase and as they transfer care from pediatric to adult health care practitioners. <h3>Objective</h3> To assess variation across CCDs in the likelihood of readmission for AYA with increasing age. <h3>Design, Setting, and Participants</h3> Retrospective 1-year cross-sectional study of the 2014 Agency for Healthcare Research and Quality Nationwide Readmissions Database for all US hospitals. Participants were 215 580 hospitalized individuals aged 15 to 30 years with cystic fibrosis (n = 15 213), type 1 diabetes (n = 86 853), inflammatory bowel disease (n = 48 073), spina bifida (n = 7819), and sickle cell anemia (n = 57 622) from January 1, 2014, to December 1, 2014. <h3>Exposures</h3> Increasing age at index admission. <h3>Main Outcomes and Measures</h3> Unplanned 30-day hospital readmission. Readmission odds were compared by patients’ ages in 2-year epochs (with age 15-16 years as the reference) using logistic regression, accounting for confounding patient characteristics and data clustering by hospital. <h3>Results</h3> Of 215 580 participants, 115 982 (53.8%) were female; the median (interquartile range) age was 24 (20-27) years. Across CCDs, multimorbidity was common; the percentages of index hospitalizations with 4 or more coexisting conditions ranged from to 33.4% for inflammatory bowel disease to 74.2% for spina bifida. Thirty-day hospital readmission rates varied significantly across CCDs: 20.2% (cystic fibrosis), 19.8% (inflammatory bowel disease), 20.4% (spina bifida), 22.5% (type 1 diabetes), and 34.6% (sickle cell anemia). As age increased from 15 to 30 years, unadjusted, 30-day, unplanned hospital readmission rates increased significantly for all 5 CCD cohorts. In multivariable analysis, age trends in the adjusted odds of readmission varied across CCDs. For example, for AYA who had cystic fibrosis, the adjusted odds of readmission increased to 1.9 (95% CI, 1.5-2.3) by age 21 years and remained elevated through age 30 years. For AYA who had type 1 diabetes, the adjusted odds of readmission peaked at ages 23 to 24 years (odds ratio, 2.3; 95% CI, 2.1-2.6) and then declined through age 30 years. <h3>Conclusions and Relevance</h3> These findings suggest that hospitalized AYA who have CCDs have high rates of multimorbidity and 30-day readmission. The adjusted odds of readmission for AYA varied significantly across CCDs with increasing age. Further attention is needed to hospital discharge care, self-management, and prevention of readmission in AYA with CCD.
Adjuvant hormone strategies in postmenopausal women with breast cancer: An economic evaluation based on the EBCTCG meta-analyses
Authors: T. Younis, D. Rayson, C. Skedgel
Journal: Journal of Clinical Oncology (2009)

6574 Background: Meta-analyses conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) demonstrated significant improvements in breast cancer (BC) outcomes associated with tamoxifen (TAM) and/or aromatase inhibitor (AI) therapy. We conducted an economic evaluation, based on these meta-analyses, to examine the cost-effectiveness (CE) of adjuvant TAM, sequential TAM-AI and upfront AI in post menopausal (PM) women with BC. Methods: A generic model was developed to calculate cumulative costs and quality adjusted life year gains (QALYG) over 25-year horizon in hypothetical cohorts of PM women with BC undergoing 5-year treatment with TAM alone, upfront AI, or sequential TAM-AI. We examined different cohorts with varying 10-year baseline recurrence risk (RR) without adjuvant hormonal treatments to reflect the natural spectrum of breast cancer disease encountered (low = 25%; average = 38%; high = 50%; very high = 75%). The efficacy outcomes were derived from the EBCTCG meta-analyses, with 10-year duration of benefit assumed for all strategies. Costs and utilities were derived from the literature, and local resources. The analysis took a direct payer perspective and reports costs in 2008 Cdn$. Costs and benefits were discounted at 3%. CE was based on the $50,000/QALY gained threshold. Adverse events were not included in the primary analysis. Sensitivity analyses were conducted. Results: Adjuvant hormonal treatments with TAM and/or AI are CE strategies in PM women with BC. The costs and QALYG associated with hormonal treatments were dependent on the baseline RR: CE estimates were more favorable in cohorts with higher as opposed to lower RR. The baseline RR also influenced the choice of the optimal economic strategy. Upfront AI was associated with higher costs and more QALY gains compared to TAM-AI. CE however was favorable in patients with average to very high RR and unfavorable in patients with low RR. Conclusions: Adjuvant treatments with TAM and/or AI are associated with favorable CE in PM women with BC. The optimal CE strategies, however, are dependent on the baseline RR without hormonal treatment. A risk-tailored hormonal treatment choice could optimize the overall health system efficiency. [Table: see text]
The Use of e-Cigarettes in Patients With Cancer—A Double Shipwreck—In Reply
Authors: Nina N. Sanford, Brandon A. Mahal
Journal: JAMA Oncology (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 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
Addressing the Cardiovascular Disease Burden in China—Is It Possible Without Surgery?
Authors: Dominique Vervoort, Xiya Ma, Jessica G. Y. Luc
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Barriers to Successful Implementation of Precision Medicine to the Treatment of Refractory AML: Lessons Learned
Authors: Evandro D Bezerra, Sylvia Chien, Timothy Martins, Cody Hammer, Kelda M Gardner, Taylor Sekizaki, Anna Rosen, Carole Shaw, Vivian Oehler, Carl Tony Blau, Su-In Lee, Paul C. Hendrie, Roland B. Walter, Mary-Elizabeth M. Percival, Ryan D. Cassaday, Bradley Patay, Andrew Carson, Soheil Meshinchi, Katherine Tarlock, Frederick R. Appelbaum, Jerald P. Radich, Elihu H. Estey, Pamela S. Becker
Journal: Blood (2017)
Myeloma Patient-Derived Bone Marrow Serum Negatively Regulates Natural Killer Cell Activity
Authors: Tarun K. Garg, Katie Stone, Hongwei Wang, Antje Hoering, Brian A Walker, Maurizio Zangari, Sharmilan Thanendrarajan, Carolina D. Schinke, Faith E. Davies, Gareth Morgan, Frits van Rhee
Journal: Blood (2018)