tbuckley/cabot-search huggingface dataset:
Оценка факторов риска развития поражений печени у больных хронической лимфоцитарной лейкемией в динамике химиотерапии
Authors: G.S. Maslova, I.M. Skrypnyk
Journal: GASTROENTEROLOGY (2019)

Актуальность. Лечение В-клеточной хронической лимфоцитарной лейкемии (В-ХЛЛ) сопровождается риском развития поражений печени, что связано с факторами, которые зависят от особенностей пациента, опухоли, и химио­терапией (ХТ). Цель — оценить риск развития и характер нарушений печеночных тестов у больных В-ХЛЛ в динамике ХТ. Материалы и методы. Обследовано 76 больных В-ХЛЛ, из них 44 (57,9 %) мужчины и 32 (42,1 %) женщины. Средний возраст — (66,81 ± 12,50) года. Стадию В-ХЛЛ определяли по классификациям К. Rai (1975, 1987) и J. Binet (1981, 2006). Назначали ХТ по схеме FC (флударабин, циклофосфан). Обследование проводили перед ХТ и после двух курсов FC. Учитывали гиперпластический синдром, гиперлейкоцитоз. Оценивали показатели биохимического анализа крови. Использовали критерии Common Terminology Criteria for Adverse Events (CTCAE), Version 4.02. Результаты. Поздние стадии В-ХЛЛ, ІV по Rai и С по Binet, у больных В-ХЛЛ ассоциируются с ростом риска не получить ответы на ХТ (отношение рисков (RR) 0,53; 95% доверительный интервал (ДИ) 0,31–0,90; р &lt; 0,05). Наличие гиперпластического синдрома сопровождается достоверным риском не достичь ответа на ХТ (RR 0,23; 95% ДИ 0,07–0,80; р &lt; 0,05). Поражение печени чаще регистрируют у больных В-ХЛЛ в III стадии (RR 1,96; 95% ДИ 1,33–2,88; р &lt; 0,05) и IV стадии (RR 2,13; 95% ДИ 1,47–3,08; р &lt; 0,05) по сравнению со ІІ стадией по Rai. У больных В-ХЛЛ риск развития гепатотоксических реакций ассоциируется с низкой эффективностью ХТ, а именно достижением частичного ответа (RR 3,18; 95% ДI 1,93–5,22; р &lt; 0,05) и отсутствием ответа на ХТ (RR 3,71; 95% ДI 2,37–5,81; р &lt; 0,05). Выводы. Риск возникновения поражений печени возрастает у больных В-ХЛЛ IV (С) стадии и ассоциируется с низкой эффективностью ХТ.
Safe Deep Sedation with Midazolam and Propofol for Cerebral MRI in Young Children with Sickle Cell Disease Is Safe: A Single Center Experience in Belgium
Authors: Cécile Callewaert, Laurence Dedeken, Françoise De Groote, Laurence Rozen, Phu-Quoc Lê, Sophie Huybrechts, Safiatou Diallo, Christine Devalck, Catherine Heijmans, Andrée De Ville, Alina Ferster
Journal: Blood (2016)
Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD
Authors: Mark Y. Fang, Sebastian Markmiller, Anthony Q. Vu, Ashkan Javaherian, William E. Dowdle, Philippe Jolivet, Paul J. Bushway, Nicholas A. Castello, Ashmita Baral, Michelle Y. Chan, Jeremy W. Linsley, Drew Linsley, Mark Mercola, Steven Finkbeiner, Eric Lecuyer, Joseph W. Lewcock, Gene W. Yeo
Journal: Neuron (2019)
Abstract 1961: Middle Cerebral Artery Stenting for Acute Ischemic Stroke after Merci Retriever Failure
Authors: Eric Sauvageau, Alison M Jeziorski, Ricky A Mehta, Elad I Levy, L. N Hopkins
Journal: Circulation (2006)

Background and Purpose: At our institution, intracranial stenting has been used in the treatment of ischemic stroke caused by acute intracranial vessel occlusion after Merci retriever failure. We d...
Abstract 3982: Isolation, culture &amp; characterization ofthe circulating tumor cells from breast cancer patients’ peripheral blood <i>in vitro</i>
Authors: Pan Zhao, Huirong Zhang, Chang Liu, Jianhong Wang, Wenbin Zhou, Chang Zou
Journal: Cancer Research (2019)

Abstract Background: Circulating tumor cells (CTCs) are rare tumor cells in peripheral blood. As a few studies showed CTCs would be a kind of intriguing drug targets and more beneficial for cancer patients if there genomic and proteomic information could be deciphered dynamically. However, the rarity, challenging isolation as well as the primary culture procedures limited the analysis of CTCs insightfully. Methods: The method of density gradient centrifugation was used to obtain PBMCs. Cells adherent and suspension culture for collecting the CTCs. Results: There was a cell cluster which named CTC-3 came out in the plate. CTC-3 steadily formed clones, displayed epithelial phenotype and showed stem-cell like properties. Immunofluorescence identification of CTC-3 were DAPI-positive, Cytokeratin-positive, and CD45-negative. The karyotyping results indicated that chromosomes were aneuploidthe, the chromosome number of CTC-3 varied from 56 to 60. CTC-3 had larger nuclear/cytoplasmic ratio and limitless replicative potential. Comparing with the MCF-7, CTC-3 grew more faster than MCF-7 from the fifth day. Furthermore, the sphere formation ability of CTC-3 was significantly higher than MCF-7 in vitro. Besides, the tumorigenesis of CTC-3 cells was almost the same as MCF-7 in vivo by the analysis of xenografting in immunodeficient mice. For drug resistance, CTC-3 cells were more resistant to anti-tumor drugs after 3D culture compared with 2D, survive rates of 3D CTC-3 cells after treatment were more than 80%. Finally, the RT-PCR results shows the expression of Vimentin, E-cadherin and CD44 were significantly higher in CTC-3. Conclusion: We have successfully isolated and expanted a new breast cancer cell line from the breast cancer patient, which could provide more drug sensitivity information of the patient and open up novel avenues towards the understanding of breast cancer. Keywords: Circulating tumor cell; Breast cancer Citation Format: Pan Zhao, Huirong Zhang, Chang Liu, Jianhong Wang, Wenbin Zhou, Chang Zou. Isolation, culture &amp; characterization ofthe circulating tumor cells from breast cancer patients’ peripheral blood in vitro [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 3982.
Acanthosis Nigricans Maligna
Authors: Margarida Moura Valejo Coelho, Joanna Prokop, Cândida Fernandes
Journal: JAMA Dermatology (2019)

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Cancer Clinical Investigators Should Converge with Pharmacometricians
Authors: Michael L. Maitland, Roisin E. O'Cearbhaill, Jogarao Gobburu
Journal: Clinical Cancer Research (2019)

The applied quantitative science pharmacometrics has significantly enhanced cancer therapeutics development. Pharmacometrics is now improving our understanding of complex diagnostics. Through the concept of convergence and methods of quantitative and systems pharmacology, pharmacometrics is poised to interconnect mathematical models of disease and therapy to advance cancer care.See related article by Colomban et al., p. 5342.
Abstract 2912A: Intratumoral heterogeneity and immune checkpoint inhibitor response in the KPC pancreatic cancer model
Authors: Sarah Martinez Roth
Journal: Cancer Research (2019)

Abstract Cancer cells are subjected to evolutionary selection and adaptation of clonal populations by changes in the tumor and metastatic microenvironment as well as their response to drug treatment. We wished to evaluate how this tumor heterogeneity impacts the efficacy and responses to immune checkpoint blockade. To understand the contribution of clonal subpopulations to the malignant progression and to the response to drugs, we established a model of tumor heterogeneity from six syngeneic, clonal primary cancer cells isolated from a p48-CRE X LSLmutKras X LSLmutP53 mouse pancreatic cancer (KPC). The clonal cell lines were characterized for genomic mutations, gene expression and tumor allografts reconstituted in syngeneic host mice from mixes of the clonal cell lines. Each of the clonal cells formed invasive and metastatic lesions when grafted into hosts. The original tumor and clonal cell lines harbored common mutations in 99 genes demonstrating their common ancestry. Additional unique mutations in the clonal lines were used to identify and quantitate clones in heterogeneous cell pools. The clones showed different levels of MAP kinase signaling, unique morphologies, different growth rates in vitro and tumor growth rates in immune competent mice. Moreover, the sensitivity to ~200 anticancer drugs revealed an up to 25-fold varying in vitro sensitivity of the clones to signal transduction inhibitors and cytotoxic drugs. Drug sensitivity of individual clones when included in a heterogeneous cell population was strikingly different from their drug sensitivity when growing on their own including the sensitivity of different clones to MEK or PI3K inhibition. Furthermore, the sensitivity of clones to an anti-PD1 checkpoint inhibitor was distinct across the clonal cells growing in the heterogeneous mixture: Some clones were resistant and others highly sensitive to the checkpoint blockade. We will discuss pathways and drivers of resistance as well as sensitivity in the different subpopulations. We conclude that malignant progression and selection of checkpoint inhibitor sensitive cancer cell subpopulations is impacted by the crosstalk between clonal cell populations present in heterogeneous tumors and the host environment. Citation Format: Sarah Martinez Roth. Intratumoral heterogeneity and immune checkpoint inhibitor response in the KPC pancreatic cancer model [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 2912A.
Abstract 127: CYP4A11 overexpression increases aggressiveness in glioblastoma and breast cancer
Authors: Thaiz F. Borin, Sehar Ali, Kartik Angara, Mohammad Rashid, Stephanie Myers, Divya Chawla, Roxan Ara, Iryna Lebedyeva, Bhagelu R. Achyut, Ali S. Arbab
Journal: Cancer Research (2019)

Abstract Metastatic breast cancer (BC) and glioblastoma (GBM) are two highly invasive forms of cancer that contribute greatly to patient mortality. Due to the complex mechanisms underlying cancer growth and metastasis, novel therapeutic targets must be found to increase patient survival. One such target is the cytochrome P450 4 (CYP4) metabolic pathway leading to the production of 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE is a lipid signaling molecule that promotes invasion, growth, and neovascularization in tumors by inducing the proliferation and migration of both, the endothelial cells and the tumor cells, therefore promoting BC and GBM tumor survival. N-hydroxy-N’-(4-butyl-2 methyl phenyl) formamidine (HET0016) is a selective inhibitor of 20-HETE synthesis and thus impairs tumor growth and neovascularization. In this study, we investigate the functional and phenotypic changes in BC (MDAMB231 and MCF7) and GBM (U251 and U87) cells overexpressing CYP4A11, a human CYP4 enzyme, with and without HET0016 treatment. Cells that overexpressed CYP4A11 were produced using lentivirus infection and confirmed via western blot. Tumor cell aggressiveness was assessed in vitro using migration and proliferation assays and in vivo by ascertaining the Ki67 levels and incidence of lung metastases foci. Tumor growth with and without CYP4A11 overexpression was followed for 21 days in vivo in athymic nude mice for all groups of cells and the acquisition of stem cell and angiogenic phenotypes by the tumor cells were determined by flow cytometry. The results demonstrated that cells overexpressing CYP4A11 showed protein levels 3-6 times higher than the non-modified cells. CYP4A11-overexpressing MDAMB231 and U87 cells demonstrated increased proliferation capacity, motility and significantly increased tumor growth. Interestingly, MCF7 and U251 cells overexpressing CYP4A11 did not show significant alterations in tumor growth compared to non-modified cells. Additionally, all cells treated with HET0016 showed decreased migration after 24 hours. U87 tumors showed increased stem cell and angiogenic phenotypes compared to non-modified U87 tumors. In conclusion, overexpression of CYP4A11 in Triple Negative BC and U87 GBM cells increased tumor aggressiveness proving that this pathway is an important target for therapeutic inhibition to control tumor growth and invasion. Citation Format: Thaiz F. Borin, Sehar Ali, Kartik Angara, Mohammad Rashid, Stephanie Myers, Divya Chawla, Roxan Ara, Iryna Lebedyeva, Bhagelu R. Achyut, Ali S. Arbab. CYP4A11 overexpression increases aggressiveness in glioblastoma and breast 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 127.
Comparable efficacy and safety of brodalumab in obese and nonobese patients with psoriasis: analysis of two randomized controlled trials
Authors: S. Hsu, L.J. Green, M.G. Lebwohl, J.J. Wu, A. Blauvelt, A.A. Jacobson
Journal: British Journal of Dermatology (2019)

Obesity is associated with psoriasis and negatively affects response to therapy. To evaluate the efficacy and safety of brodalumab in nonobese vs. obese patients with psoriasis. This is a post hoc analysis of the prospective, phase III, multicentre, randomized, placebo‐ and active‐comparator‐controlled AMAGINE‐2 and AMAGINE‐3 trials, in which patients were randomized to treatment with brodalumab 210 mg every 2 weeks, ustekinumab or placebo for a 12‐week induction phase. At week 12, patients who received brodalumab 210 mg every 2 weeks continued brodalumab, those treated with ustekinumab continued ustekinumab, and those who received placebo switched to brodalumab 210 mg every 2 weeks. Patients were categorized by body mass index (BMI) category (< 30 or ≥ 30 kg m−2) and efficacy was evaluated using the physician‐rated Psoriasis Area and Severity Index and static Physician's Global Assessment instruments. In total, 281 of 687 patients (40·9%) were obese. Skin clearance was comparable across BMI subgroups in brodalumab‐treated patients. Psoriasis Area and Severity Index 100% improvement rates in nonobese and obese patients at week 12 were 54·1% and 49·5%, respectively, and at week 52 they were 72·6% and 64·8%, respectively. Week 12 ustekinumab responses were lower than brodalumab responses and were 6–17% lower in obese than in nonobese patients. No appreciable differences in overall safety were observed between nonobese and obese patients. The efficacy and safety of brodalumab did not differ between patients with moderate‐to‐severe psoriasis who had a BMI < 30 kg m−2 or a BMI ≥ 30 kg m−2.
Abstract 3539: Impact of formalin time on targeted NGS performance in FFPE tissue
Authors: Thomas M. Blomquist, Erin Crawford, James Willey, Joshua Xu
Journal: Cancer Research (2019)

Abstract Targeted next generation sequencing (NGS) panel testing is now a standard of care for management of advanced stage cancer. At present, most targeted NGS oncology testing occurs with formalin fixed paraffin embedded (FFPE) tissue. This is due to the established utility and prevalence of FFPE in routine histologic classification, grading, staging, and ancillary testing. In addition, FFPE materials are an optimally suited medium for determining adequacy of the specimen prior to downstream NGS targeted panel testing. For these reasons, as well as a growing trend of minimally invasive procedures, clinical specimens are increasingly prioritized for FFPE to meet the bulk of standard oncology care. Currently, formalin fixation time guidelines do exist for specific immunohistochemical and in-situ hybridization oncology tests. However, specific FFPE processing guidelines have yet to be established that would optimize targeted NGS panel testing performance. In this study, our aim was to develop contrived FFPE materials using the FDA-led Sequencing Quality Control Phase II (SEQC2) consortium working group 2 (WG2) cell line materials. The overarching goal was to use these FFPE materials to identify an upper limit of formalin time associated with minimal impact on somatic variant calling performance in targeted NGS oncology panels. The SEQC2 - WG2 normal lymphoblast cell line was selected as a well-characterized test material to undergo systematic alteration in formalin fixation time (1, 2, 6 and 24 hours) prior to “routine” tissue processing and embedding (FFPE). These FFPE cell-block materials, derived from a single sample source (with both extracted FFPE DNA as well as shaved sections), were distributed to multiple labs running various targeted NGS amplicon and hybridization oncology panels. The expected outcome of these studies is to provide general guidance to the community on how formalin time in FFPE specimens impacts targeted NGS oncology panel testing performance. In addition, we hope to identify genomic regions (internal control regions) that serve as markers for the full range of formalin time FFPE-effect. This information will assist in improving the lower limit of detection for variant calling (&amp;lt;5% variant allele frequency). Citation Format: Thomas M. Blomquist, Erin Crawford, James Willey, Joshua Xu, Onco-panel Working Group of the Sequencing Quality Control Phase 2 (SEQC2) Consortium. Impact of formalin time on targeted NGS performance in FFPE tissue [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 3539.
Abstract 20353: HIV and Rapid Change in Atherosclerotic Coronary Plaque Volume: Novel Insights From Proteomics Discovery
Authors: Christopher deFilippi, Janet Lo, Lee Hang, Lauren Stone, Mable Toribio, Steven Grinspoon
Journal: Circulation (2017)

Introduction: Patients living with HIV (PLHIV) have increased atherosclerotic coronary vascular disease (ASCVD) compared to non-HIV infected controls; a process thought to be mediated through uniqu...
Abstract 9045: MRI of Autotransplantation of Bone Marrow-Derived Stem-Progenitor Cells: Toward Cell-Based Repair of Injured Arteries
Authors: Yanfeng Meng, Feng Zhang, Tiffany Blair, Huidong Gu, Hongqing Feng, Jinnan Wang, Chun Yuan, Zhaoqi Zhang, Bensheng Qiu, Xiaoming Yang
Journal: Circulation (2010)

Bone marrow (BM) derived stem-progenitor cells (SPCs) are capable of migrating to injured arteries for repairing and stabilizing vulnerable atherosclerotic plaques. The aim of this study was to val...
Abstract 2869: Zika virus is a potent oncolytic agent against aggressive human ependymoma
Authors: Carolini Kaid, Patrícia Semedo-Kuriki, Ernesto Goulart, Luiz Caires-Júnior, Renato Astray, Oswaldo Keith Okamoto, Mayana Zatz
Journal: Cancer Research (2019)

Abstract Ependymoma is a metastatic CNS tumor responsible for 10% of all pediatric brain tumors. Displaying a poor survival rate of only 32.5%, the conventional ependymoma treatment is surgery and radiation therapy associated to significant morbidity. Previous studies found significantly increased expression of NESTIN, a neural progenitor cell (NPC) marker, in aggressive ependymoma. Zika virus (ZIKV) has recently emerged as an oncolytic therapy against adult and pediatric CNS tumors due to its ability to infect NPCs and neural stem-like tumor cells. We showed for the first time that Brazilian Zika virus strain efficiently destroyed pediatric CNS tumor cells in vitro and in vivo, resulting in significantly mice longer survival and fewer metastasis. Once tumor cells overexpressing NPCs markers are more susceptible to ZIKV infection, here we evaluated the oncolytic properties of Brazilian ZIKV against human ependymoma. A patient-derived ependymoma cell line (USP21-EPE) has been established and found to abnormally express the pluripotency markers CD133, SOX2 and NESTIN. USP21-EPE monolayer culture showed massive cell death three days after ZIKV infection in four tested MOIs: 0.01, 0.1, 1 and 2. At MOI 0,1 50% of cell population decreased viability while at higher MOIs was observed 100% of cell death 72 hours post ZIKV infection. Moreover, ZIKV significantly disrupted CNS ependymoma tumorspheres reinforcing its oncolytic effect against the ependymoma tumor cells. Considering the poor effectiveness and severe side effects of available treatments for ependymoma and that most ZIKV infections are associated to very mild or no symptoms, our findings open new avenues for novel therapies against this aggressive pediatric tumor. Citation Format: Carolini Kaid, Patrícia Semedo-Kuriki, Ernesto Goulart, Luiz Caires-Júnior, Renato Astray, Oswaldo Keith Okamoto, Mayana Zatz. Zika virus is a potent oncolytic agent against aggressive human ependymoma [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 2869.
Clip-and-snare traction facilitates difficult biliary cannulation during ERCP
Authors: Xiao Hu, Yun-chao Yang, Xiao-gang Liu, Ren-yi Zhang, Sheng-xi Han, Liang-ping Li, Wei-hui Liu
Journal: Endoscopy (2019)

The adequate exposure of the ampullary orifice and reliable fixation of the duodenal papilla are always the basic principles of successful cannulation during endoscopic retrograde cholangiopancreatography (ERCP). In recent years, several traction strategies have proven to be effective in eversion of a hidden papilla within a large diverticulum, such as using a cannula [1], endobiliary forceps [2], or the SpyBite [3] to manipulate the papilla. However, with the above coaxial lifting strategies, it is not possible to optionally adjust the direction and intensity of traction because of interference with the duodenoscope. Therefore, here we report a novel clip-and-snare traction (CST) method to effectively accomplish successful biliary cannulation ([Video 1]), which had not been possible with guidewire-aided cannulation techniques.
Abstract 16874: Preoperative Skeletal Muscle Quality and Quantity by Chest Computed Tomography are Powerful Predictors of Mortality After Left Ventricular Assist Device Implantation
Authors: Rebecca Cogswell, Ranjit John, Adam Kuchnia, Cindy Martin, Carrie Earthman, Levi Teigen
Journal: Circulation (2017)

Introduction: Skeletal muscle (SM) mass decreases in end stage heart failure and is predictive of clinical outcomes in several disease states. Hypothesis: SM quantity and quality quantified by pre-...