tbuckley/cabot-search huggingface dataset:
Abstract #4630: EZN-3920, an LNA antisense oligonucleotide RNA antagonist, down modulates HER3 expression and PI3K/Akt signaling pathway and enhances antiproliferative effect of Gefitinib in tumor cells
Authors: Baisong Liao, Yixian Zhang, Jolanta Kosek, Wenzhe Liu, Stephen Castaneda, Peifang Zhu, Qinghong Dai, Timothy Qu, Puja Sapra, Lee Greenberger, Ivan Horak
Journal: Cancer Research (2009)

Introduction: The ErbB family consists of four tyrosine kinase receptors designated as ErbB1 (EGFR), HER2, HER3 and HER4. Inhibition of HER3 is likely to have antitumor effects since HER3 (1) heterodimerizes with HER2 and EGFR, (2) is a key link to the PI3K pro-survival signaling pathway, and (3) is activated in cells resistant to EGFR or HER2 targeting therapeutics. This study aimed at evaluating the activities of EZN3920, an HER3 locked nucleic acid (LNA) antisense oligonucleotide (ON), in various tumor cells. The regulation on downstream PI3K/Akt pathway and combination with EGFR inhibitor were also explored. Experimental Procedures: In vitro: the target knockdown, phospho-Akt inhibition, growth inhibition, apoptosis induction effects of EZN-3920 (Santaris Pharma) were evaluated by qRT-PCR, western blot analysis, MTS assay, caspase3/7 activity assay, respectively, in 14 cancer (prostate, liver, lung, colon, stomach, ovarian, breast, and epidermoid) cell lines two days after transfection with lipofectamine-2000. The combined antiproliferative effects of EZN3920 with gefitinib (EGFR inhibitor) were also examined in 8 ErbB inhibitor-sensitive and -insensitive tumor cell lines. In vivo: HER3 knockdown efficacy in liver and human tumors from 15PC-3 (prostate), A549 (lung) and N87 (gastric) nude mice xenograft models were examined after intravenous administration. Phospho-Akt (p-Akt) level was also monitored following the treatment. Scrambled LNA-ASONs and Molt-4 leukemia cell line served as negative controls. Results:In vitro, EZN3920 potently inhibited HER3 mRNA and protein levels in various tumor cells (IC50   Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4630.
Allergen nomenclature*
Authors: D. G. Marsh, L. Goodfriend, T. P. King, H. Løwenstein, T. A. E. Platts‐Mills
Journal: Allergy (1988)

This article presents a nomenclature system for allergens which has been officially recommended by the International Union of Immunological Societies (IUIS). The nomenclature is based on proposals of the IUIS Sub‐Committee for Allergen Nomenclature and is applicable to highly purified well‐characterized allergens and to non‐purified or partially purified allergenic extracts.
Early Administration of Low-Dose IL-2 Intensify Graft-Versus-Leukemia Effect without Worsening GVHD through Sequential Enhancement of Effector T Cell and CD62L+ Regulatory T Cell Subset
Authors: Yusuke Meguri, Ken-ichi Matsuoka, Shuntaro Ikegawa, Hiroyuki Sugiura, Makoto Nakamura, Yasuhisa Sando, Iwamoto Miki, Takanori Yoshioka, Takeru Asano, Yoshinobu Maeda
Journal: Blood (2017)
Chemotherapy-Induced Peripheral Neurotoxicity in Cancer Survivors: Predictors of Long-Term Patient Outcomes
Authors: Eva Battaglini, David Goldstein, Peter Grimison, Susan McCullough, Phil Mendoza-Jones, Susanna B. Park
Journal: Journal of the National Comprehensive Cancer Network (2021)

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major adverse effect of cancer treatment. However, its impact remains poorly understood. This study aimed to investigate the impact associated with CIPN on the lives of cancer survivors.A volunteer sample of 986 individuals who had received neurotoxic chemotherapy completed an anonymous, cross-sectional survey. Outcomes assessed included CIPN symptoms, pain, neuropathic pain, quality of life (QoL), physical activity, and comorbid health conditions via the Self-Administered Comorbidity Questionnaire.Respondents had a mean age of 58 years (SD, 10.7), and 83.2% were female. Most were treated for breast (58.9%) or colorectal cancer (13.5%); had received docetaxel (32.7%), paclitaxel (31.6%), or oxaliplatin (12.5%); and had completed treatment 3.6 ± 3.5 years previously. We found that 76.5% of respondents reported current CIPN. Respondents reporting severe CIPN had poorer QoL, more comorbidities, and higher body mass index, and more often received multiple neurotoxic chemotherapies than those with mild CIPN. Respondents who completed the survey ≤1 year after completing chemotherapy did not differ in reported CIPN or pain compared with respondents who completed chemotherapy ≥6 years earlier. However, respondents who completed chemotherapy ≥6 years earlier reported better QoL. Multivariable linear regression analyses revealed predictors of CIPN severity as follows: F(7, 874) = 64.67; P<.001; R2 = 0.34, including pain (β = -0.36; P<.001), burning pain (β = 0.25; P<.001), sex (male sex associated with greater CIPN: β = 0.14; P<.001), years since completing chemotherapy (shorter time associated with greater CIPN; β = -0.10; P<.001), age (β = 0.80; P=.006), number of comorbid conditions (β = 0.07; P=.02), and body mass index (β = 0.07; P=.02).Respondents with a high CIPN symptom burden experienced poorer general health and QoL. Improvements in CIPN may be more likely soon after treatment. However, improvements in QoL may occur over time in those with chronic symptoms. CIPN seems to have lasting impacts on cancer survivors, and understanding risk factors is important to enable the design of further preventive and therapeutic management strategies.
Особливості лікувального харчування хворих на артеріальну гіпертензію
Authors: Yu.I Reshetilov, T.V. Bogoslav, L.Р. Kuznetsova
Journal: GASTROENTEROLOGY (2014)

Незважаючи на розробку превентивних і лікувальних заходів, стандартів ведення хворих, артеріальна гіпертензія залишається одним із найбільш поширених хронічних захворювань людини. За даними офіційної статистики Міністерства охорони здоров’я України на 1 січня 2011 року, 32,2 % дорослого населення країни страждають на артеріальну гіпертензію. За даними Всесвітньої організації охорони здоров’я, профілактика, спрямована на зміну способу життя, є універсальною «вакциною» проти артеріальної гіпертензії, а застосування немедикаментозних заходів сприяє зменшенню її нових випадків на 50 %. У статті викладені основні дієтологічні рекомендації для хворих на артеріальну гіпертензію, їх обґрунтованість з урахуванням патогенетичних аспектів формування артеріальної гіпертензії і розвитку атеросклеротичних змін з метою підвищення якості медикаментозного лікування, профілактики кардіоваскулярних ускладнень.
hiPSC Modeling of Lineage-Specific Smooth Muscle Cell Defects Caused by <i>TGFBR1</i> <sup> <i>A230T</i> </sup> Variant, and Its Therapeutic Implications for Loeys-Dietz Syndrome
Authors: Dong Zhou, Hao Feng, Ying Yang, Tingting Huang, Ping Qiu, Chengxin Zhang, Timothy R. Olsen, Jifeng Zhang, Y. Eugene Chen, Dogukan Mizrak, Bo Yang
Journal: Circulation (2021)

Loeys-Dietz syndrome (LDS) is an inherited disorder predisposing individuals to thoracic aortic aneurysm and dissection. Currently, there are no medical treatments except surgical resection. Although the genetic basis of LDS is well-understood, molecular mechanisms underlying the disease remain elusive, impeding the development of a therapeutic strategy. In addition, aortic smooth muscle cells (SMCs) have heterogenous embryonic origins, depending on their spatial location, and lineage-specific effects of pathogenic variants on SMC function, likely causing regionally constrained LDS manifestations, have been unexplored.We identified an LDS family with a dominant pathogenic variant in the TGFBR1 gene (TGFBR1A230T) causing aortic root aneurysm and dissection. To accurately model the molecular defects caused by this mutation, we used human induced pluripotent stem cells from a subject with normal aorta to generate human induced pluripotent stem cells carrying TGFBR1A230T, and corrected the mutation in patient-derived human induced pluripotent stem cells using CRISPR-Cas9 gene editing. After their lineage-specific SMC differentiation through cardiovascular progenitor cell (CPC) and neural crest stem cell lineages, we used conventional molecular techniques and single-cell RNA sequencing to characterize the molecular defects. The resulting data led to subsequent molecular and functional rescue experiments using activin A and rapamycin.Our results indicate the TGFBR1A230T mutation impairs contractile transcript and protein levels, and function in CPC-SMC, but not in neural crest stem cell-SMC. Single-cell RNA sequencing results implicate defective differentiation even in TGFBR1A230T/+ CPC-SMC including disruption of SMC contraction and extracellular matrix formation. Comparison of patient-derived and mutation-corrected cells supported the contractile phenotype observed in the mutant CPC-SMC. TGFBR1A230T selectively disrupted SMAD3 (SMAD family member 3) and AKT (AKT serine/threonine kinase) activation in CPC-SMC, and led to increased cell proliferation. Consistently, single-cell RNA sequencing revealed molecular similarities between a loss-of-function SMAD3 mutation (SMAD3c.652delA/+) and TGFBR1A230T/+. Last, combination treatment with activin A and rapamycin during or after SMC differentiation significantly improved the mutant CPC-SMC contractile gene expression and function, and rescued the mechanical properties of mutant CPC-SMC tissue constructs.This study reveals that a pathogenic TGFBR1 variant causes lineage-specific SMC defects informing the etiology of LDS-associated aortic root aneurysm. As a potential pharmacological strategy, our results highlight a combination treatment with activin A and rapamycin that can rescue the SMC defects caused by the variant.
革新的なナノ医薬品を生産するためのミトコンドリアドラッグデリバリーシステムの力【JST・京大機械翻訳】
Authors: Yamada Yuma, Satrialdi, Hibino Mitsue, Sasaki Daisuke, Abe Jiro, Harashima Hideyoshi
Journal: Advanced Drug Delivery Reviews (2020)
Multi-Phase Ex Vivo Generation of Platelet-like Particles from CD34+ Cord Blood Cell-Derived Megakaryocytes
Authors: Jia J. Wu, Darryl A. Abbott, Meryem K. Terzioglu, Rajeev Ranjan, Dolores Mahmud, Hasan Issa, Neda Bagheri, Nadim Mahmud, William M. Miller
Journal: Blood (2017)
A practical strategy to subcutaneous administered in-situ gelling co-delivery system of arsenic and retinoic acid for the treatment of acute promyelocytic leukemia
Authors: Xiao Liu, Weiwei Yin, Andy Samuel Widjaya, Yueying Yang, Yunhu Liu, Yanyan Jiang
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Arsenic trioxide (ATO) combined with all trans retinoic acid (ATRA) is the first choice for the treatment of low and medium risk acute promyelocytic leukemia (APL). Clinical studies reported that the combination of ATO and ATRA could achieve a significant curative effect. However, the retinoic acid syndrome, serious drug resistance and the short half-life in vivo which lead to frequent and large dose administration limit the application of ATRA. In addition, the preparations of arsenic are conventional injections and tablets in clinic, which has poor patients' compliance caused by frequent long-term administration and serious side effects. In order to overcome the above limitations, a phospholipid phase separation gel (PPSG) loaded with ATO and ATRA was developed. ATO+ATRA-PPSG (AAP), as a biodegradable sustained-release delivery system, was the first achievement of co-delivery of hydrophilic ATO and lipophilic ATRA with high drug loading which is the main problem in the application of nano preparation. The prepared PPSG displayed high safety and biocompatibility. The drug in PPSG was released slowly and continuously in vivo and in vitro for up to 10 d, which could reduce the side effects caused by the fluctuation of blood drug concentration and solve the problem of the long treatment cycle and frequent administration. In vivo pharmacokinetics depicted that PPSG could improve the bioavailability, decrease the peak concentration, and prolong the t1/2 of ATO and ATRA. Particularly, AAP significantly inhibited the tumor volume, extended the survival period of tumor-bearing mice, and promoted the differentiation of APL cells into normal cells. Therefore, ATO+ATRA-PPSG not only could co-load hydrophilic ATO and lipophilic ATRA according to the clinical dosage, but also possessed the sustained-release and long-acting treatment effect which was expected to reduce administration time and ameliorate compliance of patients. Thus, it had great potential for clinical transformation and application.
SPA: A Quantitation Strategy for MS Data in Patient-Derived Xenograft Models
Authors: Xi Cheng, Lili Qian, Bo Wang, Minjia Tan, Jing Li
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract With the development of mass spectrometry (MS)-based proteomics technologies, patient-derived xenograft (PDX), which is generated from the primary tumor of a patient, is widely used for the proteome-wide analysis of cancer mechanism and biomarker identification of a drug. However, the proteomics data interpretation is still challenging due to complex data deconvolution from the PDX sample that is a cross-species mixture of human cancerous tissues and immunodeficient mouse tissues. In this study, by using the lab-assembled mixture of human and mouse cells with different mixing ratios as a benchmark, we developed and evaluated a new method, SPA (shared peptide allocation), for protein quantitation by considering the unique and shared peptides of both species. The results showed that SPA could provide more convenient and accurate protein quantitation in human–mouse mixed samples. Further validation on a pair of gastric PDX samples (one bearing FGFR2 amplification while the other one not) showed that our new method not only significantly improved the overall protein identification, but also detected the differential phosphorylation of FGFR2 and its downstream mediators (such as RAS and ERK) exclusively. The tool pdxSPA is freely available at https://github.com/Li-Lab-Proteomics/pdxSPA.
Abstract 15827: Pulmonary Vein Atresia: Transcatheter Interventions and Long-Term Outcomes
Authors: Varun Aggarwal, Gary E Stapleton, Henri Justino
Journal: Circulation (2019)

Background: Outcomes for congenital or acquired pulmonary vein atresia (PVA) have historically been poor, often leading to progressive pulmonary hypertension, cardiac failure and death. Methods: Re...
心エコー検査における効率的な3D左心室セグメンテーションのためのディープアトラスネットワーク【JST・京大機械翻訳】
Authors: Dong Suyu, Luo Gongning, Tam Clara, Wang Wei, Wang Kuanquan, Cao Shaodong, Chen Bo, Zhang Henggui, Li Shuo
Journal: Medical Image Analysis (2020)
Learning From Technical Details With Effect on Postoperative Pancreatic Fistula—Reply
Authors: Suguru Yamada, Tsutomu Fujii, Hiroki Yamaue
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Harvesting, cryopreservation and re-implantation of autologous ovarian cortical strips (OCS) to reverse chemotherapy induced sterility in women treated for lymphoma and ALL
Authors: J Radford, B Lieberman, M Harris, J Varley, D Brison, S Howell, A Watson, R Gosden, S Shalet
Journal: Annals of Oncology (2000)
Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death
Authors: Xinping Kuai, Yuefei Zhu, Zheng Yuan, Shengyu Wang, Lin Lin, Xiaodan Ye, Yiping Lu, Yu Luo, Zhiqing Pang, Daoying Geng, Bo Yin
Journal: Acta Pharmaceutica Sinica B (2021)

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.
Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis
Authors: Jincheng Wang, Kaili Hu, Xuanyan Cai, Bo Yang, Qiaojun He, Jiajia Wang, Qinjie Weng
Journal: Acta Pharmaceutica Sinica B (2021)

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial pneumonia with unknown causes. The incidence rate increases year by year and the prognosis is poor without cure. Recently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT) signaling pathway can be considered as a master regulator for IPF. The contribution of the PI3K/AKT in fibrotic processes is increasingly prominent, with PI3K/AKT inhibitors currently under clinical evaluation in IPF. Therefore, PI3K/AKT represents a critical signaling node during fibrogenesis with potential implications for the development of novel anti-fibrotic strategies. This review epitomizes the progress that is being made in understanding the complex interpretation of the cause of IPF, and demonstrates that PI3K/AKT can directly participate to the greatest extent in the formation of IPF or cooperate with other pathways to promote the development of fibrosis. We further summarize promising PI3K/AKT inhibitors with IPF treatment benefits, including inhibitors in clinical trials and pre-clinical studies and natural products, and discuss how these inhibitors mitigate fibrotic progression to explore possible potential agents, which will help to develop effective treatment strategies for IPF in the near future.
Improving health equity and ending the HIV epidemic in the USA: a distributional cost-effectiveness analysis in six cities
Authors: Amanda My Linh Quan, Cassandra Mah, Emanuel Krebs, Xiao Zang, Siyuan Chen, Keri Althoff, Wendy Armstrong, Czarina Navos Behrends, Julia C Dombrowski, Eva Enns, Daniel J Feaster, Kelly A Gebo, William C Goedel, Matthew Golden, Brandon D L Marshall, Shruti H Mehta, Ankur Pandya, Bruce R Schackman, Steffanie A Strathdee, Patrick Sullivan, Hansel Tookes, Bohdan Nosyk
Journal: The Lancet HIV (2021)
Abstract 14211: STEMI and Ventricular Tachycardia: A Unique Presentation of Fabry Disease
Authors: Muhammad A Khan, Eric Czajkowski, Sheraz Hussain, Tareq Al Saadi, Fatima M Kazi, Melanie Gordon
Journal: Circulation (2019)

Introduction: Fabry’s Disease (FD), an X linked recessive lysosomal storage disorder, is caused by deficiency of alpha-galactosidase A enzyme leading to cardiovascular, renal, gastrointestinal, neu...
Activation of γ-globin gene expression by GATA1 and NF-Y in hereditary persistence of fetal hemoglobin
Authors: Phillip A. Doerfler, Ruopeng Feng, Yichao Li, Lance E. Palmer, Shaina N. Porter, Henry W. Bell, Merlin Crossley, Shondra M. Pruett-Miller, Yong Cheng, Mitchell J. Weiss
Journal: Nature Genetics (2021)
Multimodal platform for assessing drug distribution and response in clinical trials
Authors: Begoña G C Lopez, Ishwar N Kohale, Ziming Du, Ilya Korsunsky, Walid M Abdelmoula, Yang Dai, Sylwia A Stopka, Giorgio Gaglia, Elizabeth C Randall, Michael S Regan, Sankha S Basu, Amanda R Clark, Bianca-Maria Marin, Ann C Mladek, Danielle M Burgenske, Jeffrey N Agar, Jeffrey G Supko, Stuart A Grossman, Louis B Nabors, Soumya Raychaudhuri, Keith L Ligon, Patrick Y Wen, Brian Alexander, Eudocia Q Lee, Sandro Santagata, Jann Sarkaria, Forest M White, Nathalie Y R Agar
Journal: Neuro-Oncology (2021)

Response to targeted therapy varies between patients for largely unknown reasons. Here, we developed and applied an integrative platform using mass spectrometry imaging (MSI), phosphoproteomics, and multiplexed tissue imaging for mapping drug distribution, target engagement, and adaptive response to gain insights into heterogeneous response to therapy.Patient-derived xenograft (PDX) lines of glioblastoma were treated with adavosertib, a Wee1 inhibitor, and tissue drug distribution was measured with MALDI-MSI. Phosphoproteomics was measured in the same tumors to identify biomarkers of drug target engagement and cellular adaptive response. Multiplexed tissue imaging was performed on sister sections to evaluate spatial co-localization of drug and cellular response. The integrated platform was then applied on clinical specimens from glioblastoma patients enrolled in the phase 1 clinical trial.PDX tumors exposed to different doses of adavosertib revealed intra- and inter-tumoral heterogeneity of drug distribution and integration of the heterogeneous drug distribution with phosphoproteomics and multiplexed tissue imaging revealed new markers of molecular response to adavosertib. Analysis of paired clinical specimens from patients enrolled in the phase 1 clinical trial informed the translational potential of the identified biomarkers in studying patient's response to adavosertib.The multimodal platform identified a signature of drug efficacy and patient-specific adaptive responses applicable to preclinical and clinical drug development. The information generated by the approach may inform mechanisms of success and failure in future early phase clinical trials, providing information for optimizing clinical trial design and guiding future application into clinical practice.
Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination — Kentucky, May–June 2021
Authors: Alyson M. Cavanaugh, Kevin B. Spicer, Douglas Thoroughman, Connor Glick, Kathleen Winter
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Although laboratory evidence suggests that antibody responses following COVID-19 vaccination provide better neutralization of some circulating variants than does natural infection (1,2), few real-world epidemiologic studies exist to support the benefit of vaccination for previously infected persons. This report details the findings of a case-control evaluation of the association between vaccination and SARS-CoV-2 reinfection in Kentucky during May-June 2021 among persons previously infected with SARS-CoV-2 in 2020. Kentucky residents who were not vaccinated had 2.34 times the odds of reinfection compared with those who were fully vaccinated (odds ratio [OR] = 2.34; 95% confidence interval [CI] = 1.58-3.47). These findings suggest that among persons with previous SARS-CoV-2 infection, full vaccination provides additional protection against reinfection. To reduce their risk of infection, all eligible persons should be offered vaccination, even if they have been previously infected with SARS-CoV-2.