tbuckley/cabot-search huggingface dataset:
Abstract 4117: Novel bead-based multiplex assay for the quantification of human immune checkpoint biomarkers
Authors: Jason Lehmann, Priyanka Rughwani, Amy Zhao, Weiping Jiang, Shaoquan Ji, Binggang Sun
Journal: Cancer Research (2019)

Abstract Immune checkpoint molecules are important regulators of immune activation. This regulation is critical to maintaining immune homeostasis, and is driven by a complex interplay of both co-stimulatory and inhibitory signals. These checkpoints are key to preventing autoimmunity in healthy individuals; however, cancer cells often exploit this system by modulating the expression of these molecules in order to suppress anti-tumor responses during host immuno-editing. The ability to accurately quantify expression levels of checkpoint molecules is critical to ongoing biomedical research efforts exploring potential therapeutic interventions to overcome tumor-mediated immune-evasion. To further aid these ongoing research efforts, we have developed a new bead-based multiplex assay panel specifically designed to quantify several human oncology-related immune checkpoint biomarkers including sCD25 (IL-2Ra), GITR, 4-1BB, sCD27, B7.2 (CD86), free active TGF-β1, CTLA-4, PD-L1, PD-L2, PD-1, TIM-3, LAG-3, Galectin-9. The panel utilizes fluorescence-encoded microsphere technology and is designed for use on commonly available flow cytometers. The panel has been extensively validated for specificity, dilution linearity, cross-reactivity, and inter- and intra-assay precision. This multiplex panel is a robust tool for measuring the concentrations of several immune checkpoint mediators in human serum, plasma, and cell culture supernatant samples, and offers greater efficiency and broader dynamic ranges compared to conventional ELISA-based quantification methods. Citation Format: Jason Lehmann, Priyanka Rughwani, Amy Zhao, Weiping Jiang, Shaoquan Ji, Binggang Sun. Novel bead-based multiplex assay for the quantification of human immune checkpoint biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4117.
WHO draft guidelines on dietary saturated and trans fatty acids: time for a new approach?
Authors: Arne Astrup, Hanne CS Bertram, Jean-Philippe Bonjour, Lisette CP de Groot, Marcia C de Oliveira Otto, Emma L Feeney, Manohar L Garg, Ian Givens, Frans J Kok, Ronald M Krauss, Benoît Lamarche, Jean-Michel Lecerf, Philippe Legrand, Michelle McKinley, Renata Micha, Marie-Caroline Michalski, Dariush Mozaffarian, Sabita S Soedamah-Muthu
Journal: BMJ (2019)

The 2018 WHO draft guidelines on dietary saturated fatty acids and trans fatty acids recommend reducing total intake of saturated fat and replacing it with polyunsaturated and monounsaturated fatty acids
Abstract 13663: Cardiac Progenitor Cell Therapy Reduces Myocardial Fibrosis and Stiffness yo Improve Cardiac Function in Patients With Single Ventricle Physiology
Authors: Shuta Ishigami, Takuya Goto, Daiki Ousaka, Shingo Kasahara, Shinichi Ohtsuki, Shunji Sano, Hidemasa Oh
Journal: Circulation (2015)

Backgrounds: Patients with single ventricular physiology undergoing staged palliations may present myocardial fibrosis detected by late gadolinium enhancement (LGE) of cardiac MRI. Recent studies suggest that cardiosphere-derived cell (CDC) therapy may reduce substantial fibrosis to improve cardiac function. Purpose: The aim of this study is to investigate whether intracoronary CDC infusion may reverse the focal fibrotic area to functional myocardium. Methods: Thirty-three patients (age: 3.1±1.0 years) were evaluated by cMRI during enrollment and randomized to treat by Fontan palliation with or without intracoronary injection of CDCs 1 month after surgery. Eight out of 33 patients had LGE initial screening by cMRI (LGE+) and 25 patients were classified as LGE (-) group. Area of focal fibrosis was quantitated by standard deviation method. Echocardiography and cMRI were performed to evaluate ventricular strain before enrollment and during the 3 months of follow-up. Results- Baseline examination revealed that LGE (+) group showed reduced ejection fraction (P=0.01), increased cardiac volume (P=0.03), and reduced circumferential strain (base: P=0.02, mid: P=0.02, apex: P=0.0005) compared with LGE (-) group. These changes were associated with decreased ventricular elastance (P=0.02) and increased myocardial stiffness (P=0.03) approximated by catheter examination. When patients with LGE received CDC infusion, a significant reduction of scar mass (P=0.01), scar size (P=0.01), and scar volume (P=0.02) could be detected, while these parameters remained unchanged in patients received Fontan without CDC injection. In addition, CDC infusion significantly improved regional circumferential strain (P=0.0001) within the target segments with LGE. Conclusions: In patients with single ventricular physiology, LGE identified by cMRI before Fontan procedure may be associated with the pathogenesis of decreased cardiac elastance and increased myocardial stiffness, leading to the development of right ventricular dysfunction. Although latent heart failure could be predicted in these patients after palliations, CDC therapy may have a potential to reverse cardiac dysfunction by direct conversion of the extent and severity of myocardial fibrosis.
Abstract 753: In situ RNA expression profiling of 1600+ immuno-oncology targets in FFPE tissue using NanoString GeoMx™Digital Spatial Profiler
Authors: Margaret Hoang, Zoey Zhou, Michelle Kriner, Kristina Sorg, Zach Norgaard, Erin Piazza, Chris Merritt, Dae Kim, Joseph Beechem
Journal: Cancer Research (2019)

Abstract Clinical specimens including formalin-fixed, paraffin embedded (FFPE) tumor sections preserve spatial and molecular information of tumor cells and their surrounding microenvironment. This valuable spatial information is loss with bulk RNA-seq, the most prevalent method for gene expression profiling of archival FFPE samples. In contrast, the NanoString GeoMx™ Digital Spatial Profiler (DSP) is a high multiplexing assay that can profile thousands of RNAs from user selectable regions of interest (ROIs) in FFPE sections. Here we introduce a 1600+ gene panel of tumor, stroma, and immune cell-specific content derived from NanoString nCounter® PanCancer series. We compare RNA profiling using our 1600+ immune-oncology panel to the RNA-seq methodology in FFPE samples. DSP RNA in situ probes are photocleavable oligonucleotides tags coupled to hybridization sequences that bind to mRNA transcripts in the FFPE tissue section. We gridded 96 ROIs upon the FFPE section, photocleaved oligonucleotide tags from each ROI were collected and prepared into sequencing libraries with our NGS readout workflow. After sequencing, reads were charted back to each ROI in the tissue section, generating a map of transcript activity within the tissue. We found high concordance between “bulk” DSP RNA (counts from all 96 gridded ROIs) and RNA-seq from the same FFPE block. Individually, however, each ROI showed different expression patterns than bulk and ROI expression patterns clustered based on similar tissue morphology. We further profiled the tumor and microenvironment compartments from multiple FFPE cancer tissues, comparing our 1600+ RNA expression profile to RNA-seq. DSP was able to detect a higher number of genes with low expression within each spatial compartment compared to bulk RNA-seq. These data demonstrate that DSP offers unparalleled sensitivity for large-scale gene expression while preserving critical information about tissue architecture. GeoMx™ DSP technology is for Research Use Only and not for use in diagnostic procedures. Citation Format: Margaret Hoang, Zoey Zhou, Michelle Kriner, Kristina Sorg, Zach Norgaard, Erin Piazza, Chris Merritt, Dae Kim, Joseph Beechem. In situ RNA expression profiling of 1600+ immuno-oncology targets in FFPE tissue using NanoString GeoMx™Digital Spatial Profiler [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 753.
Protective effect of silibinin against ultraviolet B radiation-induced apoptosis in mouse epidermal JB6 cells involves prolonged p53 serine15 phosphorylation
Authors: Srirupa Roy and Rajesh Agarwal
Journal: Cancer Research (2006)

4786  Chronic exposure to solar ultraviolet radiation (UV) especially UVB (280-320 nm) is the major etiologic factor for non-melanoma skin cancers in humans. UVB exposure induces DNA lesions which are considered early biomarkers of tumor initiation as they are potentially mutagenic if allowed to persist in the genome. Recent studies by us in SKH1 hairless mice have shown that topical treatment of silibinin or its dietary feeding affords significant protection against a single UVB irradiation induced apoptosis as well as reduces the extent of DNA damage in skin keratinocytes. However, in cell culture studies, silibinin has shown dual efficacy against UVB-mediated apoptosis where it inhibits apoptosis induced by low to moderate doses of UVB but further enhances high doses of UVB-caused apoptosis in HaCaT and A431 cells. Based on these recent observations, the present study was designed to investigate the mechanism of the protective response of silibinin against UVB-induced cellular changes and apoptosis employing mouse epidermal JB6 cells, the most-extensively used model for UV molecular mechanistic studies. The cells were treated with silibinin and exposed to various doses of UVB, and as a function of time apoptosis was measured quantitatively by Annexin V/propidium iodide staining followed by FACS analysis. Silibinin pre-treatment of cells inhibited apoptosis induced by low doses (50 mJ/cm2) of UVB, and also partially reversed low dose UVB-induced S phase arrest. However, under identical treatment conditions, silibinin further increased UVB-caused apoptosis when UVB doses above 75 mJ/cm2 were used. Based on these observations, 30 and 50 mJ/cm2 doses of UVB were selected for further studies to investigate the mechanism of the protective effect of silibinin against UVB-caused cellular damages and apoptosis. The reduction in UVB-induced apoptosis by silibinin was accompanied by a further up-regulation of UVB-induced total as well as Ser15 phosphorylated forms of p53. In time-kinetics study, silibinin pre-treatment also showed a prolonged (up to 24 hrs after UVB irradiation) p53 phosphorylation at Ser15 as compared to UVB alone where no p53 Ser15 phosphorylation was evidenced after 12 hrs of exposure. In contrast to its effect on prolonged p53 Ser15 phosphorylation, silibinin pre-treatment of cells inhibited UVB-induced p21/Cip1 protein levels suggesting that silibinin might be down-regulating p21 independent of its effect on p53. Since ATR-Chk1 sensor pathway, activated by UVB-induced DNA damage, plays a key role in inducing p53 phosphorylation, we also investigated silibinin’s effect on Chk1 phosphorylation; however, silibinin pretreatment showed no effect on UVB-mediated Chk1 Ser317 phosphorylation. Taken together, these studies suggest a possible role of p53 in mediating silibinin’s protective response against UVB-caused apoptosis.
Abstract 4286: TGFβ induced SMAD4 dependent apoptosis proceeded by EMT in colorectal cancer
Authors: Pratheeshkumar Poyil, Abdul K. Siraj, Divya Sasidharan Padmaja, Sandeep Kumar Parvathareddy, Rong Bu, Tariq Masoodi, Yan Kong, Saravanan Thangavel, Saeeda Omer Ahmed, Nasser Al-Sanea, Luai H. Ashari, Alaa Abduljabbar, Samar Alhomoud, Fouad Al-Dayel, Khawla S. Al-Kuraya
Journal: Cancer Research (2019)

Abstract Colorectal cancer (CRC) is one of the leading cause of cancer-related deaths Worldwide. In Saudi Arabia, CRC is more aggressive and presents at younger age, warranting new treatment strategies. Role of TGFβ/Smad4 signaling pathway in initiation and progression of CRC is well documented. Current study examined the role of TGFβ/Smad4 signaling pathway in a large cohort of Saudi CRC, followed by in vitro analysis to dissect the dual role of TGFβ on inducing epithelial to mesenchymal transition (EMT) and apoptosis. In this study, we investigated Smad4 alterations and their association with clinicopathological outcomes in a large cohort of CRC samples using targeted capture sequencing, Fluorescent in-situ hybridisation and immunohistochemistry. Our study demonstrated high frequency of Smad4 alterations with low expression of Smad4 protein identifying a sub-group of aggressive CRC to be an independent marker for poor prognosis. Functional studies using CRC cells show that TGFβ induces Smad4 dependent EMT followed by apoptosis. Induction of mesenchymal transcriptional factors, Snail1 and Zeb1 was essential for TGFβ-induced apoptosis. Our results indicate that KLF5 acts as an oncogene in CRC cells regardless of Smad4 expression and inhibition of KLF5 is requisite for TGFβ-induced apoptosis. Furthermore, TGFβ/Smad4 signal inhibits the transcription of KLF5 that in turn switches Sox4 from tumor promoter to suppressor. A high incidence of Smad4 alterations were found in the Saudi CRC patients. Functional study results indicate that TGFβ induces Smad4 dependent EMT followed by apoptosis in CRC cells. Citation Format: Pratheeshkumar Poyil, Abdul K. Siraj, Divya Sasidharan Padmaja, Sandeep Kumar Parvathareddy, Rong Bu, Tariq Masoodi, Yan Kong, Saravanan Thangavel, Saeeda Omer Ahmed, Nasser Al-Sanea, Luai H. Ashari, Alaa Abduljabbar, Samar Alhomoud, Fouad Al-Dayel, Khawla S. Al-Kuraya. TGFβ induced SMAD4 dependent apoptosis proceeded by EMT in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4286.
Global burden of latent multidrug-resistant tuberculosis: trends and estimates based on mathematical modelling
Authors: Gwenan M Knight, C Finn McQuaid, Peter J Dodd, Rein M G J Houben
Journal: The Lancet Infectious Diseases (2019)

To end the global tuberculosis epidemic, latent tuberculosis infection needs to be addressed. All standard treatments for latent tuberculosis contain drugs to which multidrug-resistant (MDR) Mycobacterium tuberculosis is resistant. We aimed to estimate the global burden of multidrug-resistant latent tuberculosis infection to inform tuberculosis elimination policy.By fitting a flexible statistical model to tuberculosis drug resistance surveillance and survey data collated by WHO, we estimated national trends in the proportion of new tuberculosis cases that were caused by MDR strains. We used these data as a proxy for the proportion of new infections caused by MDR M tuberculosis and multiplied trends in annual risk of infection from previous estimates of the burden of latent tuberculosis to generate trends in the annual risk of infection with MDR M tuberculosis. These estimates were used in a cohort model to estimate changes in the global and national prevalence of latent infection with MDR M tuberculosis. We also estimated recent infection levels (ie, in 2013 and 2014) and made predictions for the future burden of MDR tuberculosis in 2035 and 2050.19·1 million (95% uncertainty interval [UI] 16·4 million-21·7 million) people were latently infected with MDR tuberculosis in 2014-a global prevalence of 0·3% (95% UI 0·2-0·3). MDR strains accounted for 1·2% (95% UI 1·0-1·4) of the total latent tuberculosis burden overall, but for 2·9% (95% UI 2·6-3·1) of the burden among children younger than 15 years (risk ratio for those younger than 15 years vs those aged 15 years or older 2·65 [95% UI 2·11-3·25]). Recent latent infection with MDR M tuberculosis meant that 1·9 million (95% UI 1·7 million-2·3 million) people globally were at high risk of active MDR tuberculosis in 2015.We estimate that three in every 1000 people globally carry latent MDR tuberculosis infection, and prevalence is around ten times higher among those younger than 15 years. If current trends continue, the proportion of latent tuberculosis caused by MDR strains will increase, which will pose serious challenges for management of latent tuberculosis-a cornerstone of tuberculosis elimination strategies.UK Medical Research Council, Bill & Melinda Gates Foundation, and European Research Council.
Abstract 18408: Paradoxical Muscle Stretch During Contraction Increases Regional ROS Generation and Arrhythmias in Rat Myocardium With Nonuniform Contraction
Authors: Masahito Miura, Taiki Hasegawa, Yui Takahashi, Ayana Matsumoto, Natsuki Morita, Haruka Sato
Journal: Circulation (2017)

Introduction: Muscle stretch increases the generation of reactive oxygen species (ROS) and the frequency of Ca2+ sparks. In diseased hearts, regional difference of contractile strength causes parad...
Abstract 4749: Acquired resistance to BET-PROTACs caused by genomic alterations in core components of E3 ligase complexes
Authors: Bridget Riley-Gillis, Lu Zhang, Priyanka Vijay, Yu Shen
Journal: Cancer Research (2019)

Abstract Proteolysis Targeting Chimeras (PROTACs) are bifunctional molecules that hijack endogenous E3 ubiquitin ligases to induce ubiquitination and subsequent degradation of protein of interest. Recently, it has been shown that PROTACs with robust in vitro and in vivo activities and, in some cases, drug-like pharmaceutical properties can be generated using small molecule ligands for the E3 ligases VHL and CRBN. These findings stoked tremendous enthusiasm on using PROTACs for therapeutics development. Innate and acquired drug resistance often underlies therapeutic failures, particularly for cancer therapy. With the PROTAC technology progressing rapidly towards therapeutic applications, it would be important to understand whether and how resistance to these novel agents may emerge. Using BET-PROTACs as a model system, we demonstrate that resistance to both VHL- and CRBN-based PROTACs can occur in cancer cells following chronic treatment. However, unlike what was often observed for many targeted therapeutics, resistance to BET-PROTACs did not result from secondary mutations that affect compound binding to the target. In contrast, acquired resistance to both VHL- and CRBN-based BET-PROTACs was primarily caused by genomic alterations that compromise core components of the relevant E3 ligase complexes. Citation Format: Bridget Riley-Gillis, Lu Zhang, Priyanka Vijay, Yu Shen. Acquired resistance to BET-PROTACs caused by genomic alterations in core components of E3 ligase complexes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4749.
Treatment of Fatty Liver Disease—Time to Implement Common Sense Measures
Authors: Elizabeth Adler, Danielle Brandman
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Abstract 2625: Identification of CTX-30916 as a novel antagonist of progesterone receptor signaling pathways
Authors: Deepak Lala, Tasir Haque
Journal: Cancer Research (2019)

Abstract Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer related death in women. Progesterone is a major mitogen in the adult human mammary epithelium that, in addition to estrogen, is a key driver of breast cancer cell proliferation. Activated PR signaling through MAPK-driven phosphorylation of the progesterone receptor (PR) is also an important driver of breast cancer stem cells. PR expression is associated with the presence of estrogen receptor-alpha (ESR1) mutations that are constitutively active and linked to resistance in the clinic in response to aromatase inhibitors, antiestrogens and CDK4/6 inhibitors. Thus, PR may play a role in tumor relapse and resistance in the clinic and blocking both estrogen and progesterone receptors would likely be an effective approach in 2L treatment for patients with advanced breast cancer. There is great interest in evaluating antiprogestins in the clinic in combination with antiestrogens or CDK4/6 inhibitors. Apristor®, an extended release formulation of onapristone, a full antagonist of PR, that has efficacy in multiple in vivo and in vitro models in combination with antiestrogestins and CDK4/6 inhibitors, is currently being evaluated in several human clinical trials. In this study we have examined the in vitro properties of CTX-30916, a novel mono-N-desmethyl analog of onapristone. CTX-30916 binds potently to PR and acts as an antagonist in cell-based transfection assays. CTX-30916 displays selectivity against other steroid receptors in binding assays and is also a potent inhibitor of T47D breast cancer cell proliferation. Interestingly, CTX-30916 leads to a unique co-regulator binding pattern in the Microarray Assay for Real-time Co-regulator-Nuclear receptor interaction (MARCoNI) assay compared with onapristone and mifepristone indicating that the co-regulator peptide-PR interaction landscape is different between the various antiprogestins. These data suggest that CTX-30916 binding to PR leads to a distinct receptor conformation and antagonizes PR signaling pathways in cancer through a unique mechanism of action compared to other antiprogestins. Citation Format: Deepak Lala, Tasir Haque. Identification of CTX-30916 as a novel antagonist of progesterone receptor signaling pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2625.