tbuckley/cabot-search huggingface dataset:
Abstract PR05: Familial cancer patient specific iPSCs based study of a potential oncogenic factor, sFRP2, in osteosarcoma
Authors: Huen Suk Kim, Ye X. Yuan, Jeffrey M. Bernitz, Andreia Gomes, Christopher Schaniel, Dung-Fang Lee, Ihor R. Lemischka
Journal: Clinical Cancer Research (2018)

Abstract Osteosarcoma (OS), despite being a serious pediatric cancer with the lowest survival rate, is not well studied due to its rare occurrence. For this reason, studying OS in a patient-specific manner is more challenging. In an attempt to establish a method to study OS in a patient-specific manner, we previously generated Li-Fraumeni syndrome (LFS---a germline P53 mutation disease) patient specific iPSCs, and demonstrated that the LFS-iPSC derived mesenchymal stem cells (MSCs) and osteoblasts (OBs) can recapitulate tumorigenic phenotypes in vitro and in vivo (Lee, Kim, et al., Cell 2015). Taking advantage of this new platform, we focused on finding potential therapeutic targets. We found SFRP2 (secreted frizzled related protein 2) to be highly expressed in LFS iPSC-derived MSCs and OBs by global RNA-seq gene expression analysis. Using global transcript profiling of ectopic overexpression (OE) of sFRP2 in wild-type MSCs, we discovered that sFRP2 regulates osteoblast differentiation, cell adhesion, cell proliferation, and apoptosis-related gene sets. Further functional assays revealed that sFRP2 OE contributes to the generation of abnormal osteoblast cells, which are the cause of OS, by suppressing osteogenic alkaline phosphatase activity, mineralization, and osteogenic BMP and WNT signaling. Furthermore, ectopic OE of sFRP2 is associated with LFS mediated tumorigenesis. sFRP2 OE in MSCs and OBs facilitates cell proliferation through cell cycle alteration and increases anchorage independency. In in ovo and in vivo xenograft assays (subcutaneous and intratibial injections), the tumor size is significantly increased in sFRP2 OE group and decreased in knockdown sFRP2 group. Interestingly, we also found that sFRP2 OE augments angiogenesis in vitro and in vivo, suggesting sFRP2 has a role as a paracrine factor. In the future, we will analyze sFRP2 expression levels in human OS tissue samples to determine whether sFRP2 OE has clinical relevance. Conclusively, this study demonstrates that P53 mutation-mediated osteosarcoma exerts oncogenicity through sFRP2 overexpression and that targeting of sFRP2 is a potential therapeutic strategy for OS treatment. This abstract is also being presented as Poster A22. Citation Format: Huen Suk Kim, Ye X. Yuan, Jeffrey M. Bernitz, Andreia Gomes, Christopher Schaniel, Dung-Fang Lee, Ihor R. Lemischka. Familial cancer patient specific iPSCs based study of a potential oncogenic factor, sFRP2, in osteosarcoma [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR05.
Abstract 18139: Neurological Favorable Outcome Associated EMS Compliance With On-Scene Resuscitation Time Protocol
Authors: Jeong Ho Park, Tae Han Kim, Sang Do Shin, Ki Jeong Hong, Gwan Jin Park, Youngsun Ro, Kyoung Jun Song, Yong Ju Park, Kyung Won Lee, Eui Jung Lee
Journal: Circulation (2016)

Introduction: Korean national emergency care protocol for EMS providers recommends minimum of 5 minutes of on-scene resuscitation before transport to hospital in cases of OHCA (Out-of-Hospital Card...
Anorexia, vomiting and weight loss in a 22-year-old woman
Authors: Vincent Ting Fung Cheung, Eve Fryer, Miranda J Payne, Oliver Brain
Journal: Gut (2018)

A 22-year-old woman presented in December 2017 with a 2-month history of postprandial abdominal pain, nausea, vomiting, early satiety and 4 kg weight loss. She had entirely normal bowel habit. She did not use non-steroidal anti-inflammatory drugs and omeprazole had not helped her symptoms. Her medical history included resection of 1.8 mm Spitz melanoma in June 2010 and left axillary dissection in November 2012 (3/22 nodes positive). She received first-line ipilimumab and nivolumab starting November 2016. Cycle 2 was complicated by grade 2 hepatotoxicity that resolved spontaneously; cycle 4 by grade 3 hepatotoxicity requiring steroids and mycophenolate mofetil (discontinued in August 2017). She had stereotactic radiosurgery for a right temporal lobe metastasis in June 2017 and restarted on maintenance nivolumab monotherapy in July 2017. In December …
Abstract #4181: Hu proteins and small-cell lung cancer-associated autoantibodies as tools for early SCLC detection
Authors: Meleeneh Kazarian, Joaquim Calbo Angrill, Anton Berns, Dana Aswad, Ite Laird-Offringa
Journal: Cancer Research (2009)

Early detection is essential for decreasing cancer-related mortality. Small-cell lung cancer (SCLC), which accounts for up to 15% of all lung cancers, currently lacks effective methods for early detection and is the most aggressive lung cancer subtype. Associated with this lethal disease are several rare autoimmune disorders, including paraneoplastic encephalomyelitis/sensory neuronopathy (PEM/SN), a condition characterized by neuronal death, inflammation of the brain and spinal cord, dementia, and sensory loss. Most patients with this autoimmune disease have underlying SCLC and harbor high titers of antibodies against Hu proteins. Anti-Hu reactivity is also present in approximately 16% of SCLC patients without PEM/SN. HuD, one member of the Hu protein family, is normally expressed in the nervous system. In SCLC, however, it is abnormally expressed in the tumor and results in autoantibody generation. The mechanism by which this occurs is unknown. Our efforts are aimed at elucidating the basis for immune reactivity in order to devise tools for antibody-based early detection of SCLC. We have evidence that the HuD protein may undergo an unusual modification which could render it foreign to the immune system and result in an autoimmune response. Previous studies have demonstrated that certain proteins modified in this way are highly immunogenic and cause autoimmune disorders. We hypothesize that modification of a variety of neuronal proteins in SCLC tumors triggers an immune response that results in autoantibody production and, in extreme cases, may lead to paraneoplastic disease in which the immune response extends to native proteins in the nervous system. Using a unique SCLC-prone mouse model, we observe that 13% of these mice harbor elevated titers of anti-Hu antibodies, a situation very similar to that in human SCLC patients. Interestingly, anti-Hu reactivity is detected prior to the clinical diagnosis of SCLC in these mice. Thus, the mice are an excellent model to study anti-Hu reactivity and whether the modification of HuD causes the observed immune response. Additionally, we plan to use this mouse model system to determine whether autoantibodies are generated against other SCLC-related autoantigens which could potentially serve as diagnostic markers for SCLC. Using anti-Hu reactivity as a model to study the etiology of SCLC-related autoimmunity will enhance our understanding of diseases like PEM/SN and help in devising antibody-based early detection diagnostic tools for SCLC, the first step in effectively treating this fatal disease.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4181.
Abstract 3390: Comprehensive analysis of tumor immunity by integrating transcriptome and methylome
Authors: Xuefeng Wang, Cong Liang
Journal: Cancer Research (2018)

Abstract Immunotherapy has produced promising results in treating cancers. Further understanding of the crosstalk between tumor and its immune microenvironment is likely to have an immediate impact on therapeutic intervention as well as the development of markers of drug resistance. One main difficulty in quantifying the components of tumor microenvironment is that currently there are considerable technological and analytical barriers to assessing and measuring tumor immunity in situ. In this work, we propose to improve the prediction of cell mixtures by both gene expression and epigenetic information. The vast amount of DNA methylation data has been collected in public domain but remains under-analyzed and largely disconnected. No studies have yet investigated the value of using existing methylation panels for immune cell deconvolution in tumor tissues. In our preliminary data, we have observed a strong association between DNA methylation probes and immune signatures such as total TCR expression and tumor infiltrates estimation in melanoma and breast cancer. We have built a more rigorous prediction model based on methylation markers and to extend the analyses to all major cancer types. The results will be externally validated with pooled data from published studies with eligible methylation assay and immune signature measurements. We work closely with immunology scientists to perform a critical evaluation of the robustness and reproducibility of the predictive models. Results of the study, if validated, will have immediate clinical application in screening patient immunity, and will further support the hypothesis that the DNA methylome adds a new dimension to the pan-omic snapshot of cancer immunity and tumor microenvironment. Based on the proposed analytical framework, future prospective studies can be developed using newer methylation platforms—to compare patient groups with different immune conditions and patients in different stages of treatment. Citation Format: Xuefeng Wang, Cong Liang. Comprehensive analysis of tumor immunity by integrating transcriptome and methylome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3390.
Adiponectin Reduces Atherosclerosis in Apolipoprotein E-Deficient Mice
Authors: YoshihisaOkamoto, ShinjiKihara, NoriyukiOuchi, MakotoNishida, YukioArita, MasahiroKumada, KojiOhashi, NaohikoSakai, IichiroShimomura, HidekiKobayashi, NaokiTerasaka, ToshimoriInaba, TohruFunahashi, YujiMatsuzawa
Journal: Circulation (2002)

Background— Dysregulation of adipocyte-derived bioactive molecules plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the injured artery from the plasma and suppressed endothelial inflammatory response and vascular smooth muscle cell proliferation, as well as macrophage-to-foam cell transformation in vitro. The current study investigated whether the increased plasma adiponectin could actually reduce atherosclerosis in vivo. Methods and Results— Apolipoprotein E-deficient mice were treated with recombinant adenovirus expressing human adiponectin (Ad-APN) or β-galactosidase (Ad-βgal). The plasma adiponectin levels in Ad-APN–treated mice increased 48 times as much as those in Ad-βgal treated mice. On the 14th day after injection, the lesion formation in aortic sinus was inhibited in Ad-APN–treated mice by 30% compared with Ad-βgal–treated mice (P<0.05). In the lesions of Ad-APN–treated mice, the lipid dr...
Therapeutic Targeting of TFE3/IRS-1/PI3K/mTOR Axis in Translocation Renal Cell Carcinoma
Authors: Nur P. Damayanti, Justin A. Budka, Heba W.Z Khella, Mary W. Ferris, Sheng Yu Ku, Eric Kauffman, Anthony C. Wood, Khunsha Ahmed, Venkata Nithinsai Chintala, Remi Adelaiye-Ogala, May Elbanna, Ashley Orillion, Sreenivasulu Chintala, Chinghai Kao, W. Marston Linehan, George M. Yousef, Peter C. Hollenhorst, Roberto Pili
Journal: Clinical Cancer Research (2018)

Translocation renal cell carcinoma (tRCC) represents a rare subtype of kidney cancer associated with various
Lepirudin (Recombinant Hirudin) for Parenteral Anticoagulation in Patients With Heparin-Induced Thrombocytopenia
Authors: AndreasGreinacher, UweJanssens, GuntherBerg, MarkusBöck, HaraldKwasny, BettinaKemkes-Matthes, PetraEichler, HeikoVölpel, BerndPötzsch, MatthiasLuz
Journal: Circulation (1999)

Background—We prospectively investigated lepirudin for further parenteral anticoagulation in patients with heparin-induced thrombocytopenia (HIT). Methods and Results—Patients with confirmed HIT (n=112) received lepirudin according to need for 2 to 10 days (longer if necessary): A1, treatment: 0.4 mg/kg IV bolus, followed by 0.15 mg · kg−1 · h−1 intravenous infusion, n=65; A2, treatment in conjunction with thrombolysis: 0.2 mg/kg, followed by 0.10 mg · kg−1 · h−1, n=4; and B, prophylaxis: 0.10 mg · kg−1 · h−1, n=43. Outcomes from 95 eligible lepirudin-treated patients were compared with those of historical control patients (n=120). Complete laboratory response (activated partial thromboplastin time ratio >1.5 with ≤2 dose increases and platelet count normalization by day 10) was achieved in 65 lepirudin-treated patients (69.1%; 95% CI, 59.3% to 78.3%). At 2 weeks after cessation of lepirudin, 11 patients died (9.8%), 10 underwent limb amputation (8.9%), and 20 suffered a new thromboembolic complication (1...
Clear Morphological Depiction of Cor Triatriatum in a Child by Transthoracic 3-Dimensional Echocardiography
Authors: Wan-LingChih, Jou-KouWang, Yih-SharngChen, Shyh-JyeChen, Mei-HwanWu, Chun-AnChen
Journal: Circulation (2013)
Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Radoslav Chekerov, Felix Hilpert, Sven Mahner, Ahmed El-Balat, Philipp Harter, Nikolaus De Gregorio, Claudius Fridrich, Susanne Markmann, Jochem Potenberg, Ralf Lorenz, Guelten Oskay-Oezcelik, Marcus Schmidt, Petra Krabisch, Hans-Joachim Lueck, Rolf Richter, Elena Ioana Braicu, Andreas du Bois, Jalid Sehouli, Werner Lichtenegger, Isil Yalcinkaya, Marion Kittner, Ellen Konwert, Maren Keller, Alexander Mustea, Dominique Koensgen-Mustea, Klaus Pietzner, Oumar Camara, Pauline Wimberger, Gabriele Elser, Sandra Polleis
Journal: The Lancet Oncology (2018)
Effects of Ovariectomy on Experimental Atherosclerosis in Rabbits
Authors: Giuseppemininni, Stephencontro, Carlochecchia
Journal: Circulation Research (1955)

The effect of previous ovariectomy on the development of cholesterol-induced atherogenesis in the rabbit was investigated. It was found that an ovariectomized group of animals had a significantly greater degree of hypercholesterolemia, but that the control group with intact ovaries developed slightly more aortic and coronary atheromatosis. The implications of these findings are discussed.
Superiority of Nitrate-Enhanced 201Tl Over Conventional Redistribution 201Tl Imaging for Prognostic Evaluation After Myocardial Infarction and Thrombolysis
Authors: SumitBasu, RoxySenior, UshaRaval, AvijitLahiri
Journal: Circulation (1997)

Background 201Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201Tl imaging, such as reinjection and nitrate-enhanced rest 201Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium. Methods and Results We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest 201Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initia...
AB0973 The efficacy of electromyographic biofeedback on pain, function and maximal thickness of vastus medialis oblique muscle in patients with knee oa; a randomised clinical trial
Authors: L. Sedighipour, S.A. Raeissadat, S.M. Rayegani, Z. Bossaghzadeh, M.H. Abdollahzadeh, F. Malayi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Isometric exercises play important role in treatment of Knee OA and are easy to do by the growing elderly population. Electromyographic (EMG) biofeedback devices are designed to enhance patient's participation in these exercises by giving them feedback signals of visual or auditory nature, so that it can affect the subject's voluntary activity. <h3>Objectives</h3> The aim of this survey was to study the effect of EMG biofeedback on pain, function, thickness of the vastus medialis oblique muscle and maximal electrical activity of this muscle in isometric contraction, in patients with knee OA. <h3>Methods</h3> In this single-blinded clinical trial, 46 patients aged between 45 to 70, referring to Shohadaye Tajrish and Shahid Modarres hospitals with diagnosis of knee OA, were recruited. Patients were randomlyassigned to two groups of case (23 patients), with EMG biofeedback associatedexercise, and control (23 patients), with sham biofeedback associatedexercise. The exercise program includes 12 sessions of 15 min isometric quadriceps exercise. Data were gathered via VAS score, the Persian version of WOMAC and Lequesne questionnaires, ultrasonography of VMO muscle and surface electromyography of this muscleat baseline and at the end of 2 months period of this study. Variables compared before and after exercises program in each group and between the two groups. <h3>Results</h3> At the end of the study, there were no significant differences between the two groups regarding VAS score, VMO muscle electrical activity, maximal VMO muscle thickness, WOMAC and Lequesne questionnaires scores including overall scores and scores in each subcategories. Although all assessed parameters, except for VMO muscle thickness, were found to be improved significantly in each group, the changes were not more significant in case group except for the VAS score. VMO muscle thickness didn't change significantly after 12 sessions of exercise in either of the groups. <h3>Conclusions</h3> Isometric exercises accompanied by EMGBF and the same exercises with sham biofeedback for 2 months both lead to significant improvements in pain, and function of patients with knee OA. Real EMG biofeedback was not superior to sham biofeedback. The only parameter found to be improved to a greater extent in the EMGBF group was the subjective measure of VAS score. <h3>Disclosure of Interest</h3> None declared
Abstract 2098: Quantitative modeling as a systematic approach for drug combination evaluation in immuno-oncology (IO)
Authors: Gabriel Helmlinger, Yuri Kosinsky, Lulu Chu, Kirill Peskov, Veronika Voronova, Alexandra Borodovsky, Richard Woessner, Kris Sachsenmeier, Nidal Al-huniti
Journal: Cancer Research (2018)

Abstract Objectives: Multiple strategies for eliciting and enhancing antitumor immunity are currently being evaluated. However, a more systematic approach is needed, to analyze and translate such results into clinic practice, while rationally designing combination therapies based on mechanistic understanding of potential synergistic effects (1). The objective of this study was to provide predictive simulations, via a quantitative systems pharmacology (QSP) model, capable of categorizing the types of synergistic effects that may arise from IO agent combinations, across realistic baseline conditions prevailing in the tumor microenvironment (TME). Methods: The QSP model was developed and qualified using in vivo mouse data published in the literature and from internal research. The following pharmacologic modalities were calibrated: PD-L1/PD-1, CTLA-4, CXCR2, A2AR inhibition, and OX40 agonism. Various combination scenarios were simulated for these modalities, at four baseline conditions prevailing in different syngeneic murine models. Results: Simulated efficacy results were highly dependent on the baseline conditions. Several combinations and monotherapies were effective only within a specific baseline TME phenotype. These findings were in agreement with experimental data (2). At baselines with higher levels of MDSC, best results were obtained for a PD-L1 mAb combined with either an OX40 agonist or a CXCR2 inhibitor, with 90% of complete responders. Anti (PD-L1 + CTLA-4) combinations showed high efficacy in Treg prevalence, but only moderate efficacy (22% complete responders), under baseline conditions of a dual (Treg + MDSC) immunosuppressive TME. Conclusion: This work provides a quantitative modeling framework to comparatively predict responses to IO combinations, based on realistic baseline conditions prevailing in the TME, while revealing mechanistic interactions underlying such responses in IO combinations. References: 1. Melero I et al. Nat Rev Cancer 2015;15:457-72. 2. Mosely S et al. Cancer Immunol Res 2016;5:29-41. Citation Format: Gabriel Helmlinger, Yuri Kosinsky, Lulu Chu, Kirill Peskov, Veronika Voronova, Alexandra Borodovsky, Richard Woessner, Kris Sachsenmeier, Nidal Al-huniti. Quantitative modeling as a systematic approach for drug combination evaluation in immuno-oncology (IO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2098.
Factors Affecting Vaccination in Children and Their Siblings After Autism Spectrum Disorder Diagnosis—Reply
Authors: Ousseny Zerbo, Nicola P. Klein
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
The Pulmonary Vessels in Incipient Left Ventricular Decompensation
Authors: Morrissimon
Journal: Circulation (1961)

Dilatation of the pulmonary vessels of the upper zones and constriction of the vessels of the lower zones characterizes left ventricular decompensation. These changes may precede the onset of clinical symptoms providing a useful warning sign of impending danger. A hypothesis is suggested to account for the non-uniform vessel pattern. An exception is noted in patients with severe emphysema or bronchitis in whom generalized dilatation may occur.
Biochemical Studies in Full-Blooded Navajo Indians
Authors: Reubenstraus, Jarveygilbert, Moseswurm
Journal: Circulation (1959)

The Navajo Indians, who have a low incidence of coronary artery disease and a high fat intake, have also been shown to have significant elevation of serum gamma globulins. In this electrophoretic study of patterns of serum proteins it was found that adult Indians had elevated gamma globulins but that Indian children had electrophoretic patterns similar to white children. These observations indicate that the gamma globulin elevation is not an inherited characteristic in this Indian race and is probably not related to the low frequency of coronary disease.