tbuckley/cabot-search huggingface dataset:
HAVCR2 mutations are associated with severe hemophagocytic syndrome in subcutaneous panniculitis-like T-cell lymphoma
Authors: Gabrielle Sonigo, Maxime Battistella, Marie Beylot-Barry, Saskia Ingen-Housz-Oro, Nathalie Franck, Stéphane Barete, Serge Boulinguez, Olivier Dereure, Nathalie Bonnet, Gerard Socié, Pauline Brice, Olivia Boccara, Shristine ChB Bodemer, Henri Adamski, Michel D'Incan, Nicolas Ortonne, Sylvie Fraitag, Florence Brunet-Possenti, Stephane Dalle, Felipe Suarez, Ambroise Marcais, François Skowron, Dima Haidar, Eve Maubec, Gerome Bohelay, Liliane Laroche, Antoine Mahé, Elodie Birckel, Jean-David Bouaziz, Isabelle Brocheriou, Romain Dubois, Sarah Faiz, Jehane Fadlallah, Caroline Ram-wolff, Agnes Carlotti, Guido Bens, Brigitte Balme, Beatrice Vergier, Sara Laurent-Roussel, Lydia Deschamps, Olivier Carpentier, Philippe Moguelet, Genevieve Herve, François Comoz, François Le Gall, Guy Leverger, Antoine Finon, Olivier Augereau, Claire Bléchet, Remy Kerdraon, Laurence Lamant, Emilie Tournier, Frédéric Franck, Valérie Costes-Martineau, Vanessa Szablewski, Sebastien Taix, Isabelle Beschet, Frédéric Guerin, Fernando E Sepulveda, Martine Bagot, Genevieve de Saint Basile, David Michonneau, Adele de Masson
Journal: Blood (2020)
Increase in oxidative stress via glutathione reductase inhibition as a novel approach to enhance cancer sensitivity to doxorubicin
Authors: Teresa Seefeldt, Yong Zhao, Wei Chen, Laura Carlson, Adam Stoebner, Sarah Hanson, Ryan Foll, Xiangming Guan
Journal: Cancer Research (2007)

2357  Cancer drug resistance is a major cause of cancer treatment failure, and developing novel approaches to increase cancer sensitivity to chemotherapy is an ongoing research effort. Several anticancer agents, including doxorubicin, induce the production of damaging reactive oxygen species as part of their mechanism of action. Drug resistance to these medications can develop through increased levels of the intracellular antioxidant glutathione. Mechanisms of increasing the state of oxidative stress could enhance the sensitivity of cancer cells toward these chemotherapeutic agents. Modulation of intracellular oxidative stress via glutathione reductase inhibition is a novel approach to improve the activity of cancer chemotherapy. The objective of this project was to evaluate the effect of glutathione reductase inhibition on doxorubicin activity in a human ovarian cancer cell line. A novel irreversible glutathione reductase inhibitor, 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethyl-sulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (G0026), was used in this study. OVCAR-3 cells were treated with G0026 for 2 hours or 24 hours followed by treatment with doxorubicin. In order to determine the effect of the combination of G0026 and doxorubicin on glutathione and oxidative stress, the cellular content of glutathione, glutathione disulfide, total thiols, and total disulfides was determined. G0026 significantly increased the sensitivity of OVCAR-3 cells to doxorubicin; the best synergistic response was observed with a two hour pretreatment with G0026 25 μM. In addition, the combination of the glutathione reductase inhibitor and doxorubicin showed higher intracellular oxidative stress than doxorubicin alone. These findings indicate that an increase in oxidative stress produced via glutathione reductase inhibition can increase cancer response to chemotherapy.
Single-Cell Proteomic Profiling Identifies Combined AXL and JAK1 Inhibition as a Novel Therapeutic Strategy for Lung Cancer
Authors: Josephine A. Taverna, Chia-Nung Hung, Daniel T. DeArmond, Meizhen Chen, Chun-Lin Lin, Pawel A. Osmulski, Maria E. Gaczynska, Chiou-Miin Wang, Nicholas D. Lucio, Chih-Wei Chou, Chun-Liang Chen, Alia Nazarullah, Shellye R. Lampkin, Lianqun Qiu, David J. Bearss, Steven Warner, Clifford J. Whatcott, Lars Mouritsen, Mark Wade, Steven Weitman, Ruben A. Mesa, Nameer B. Kirma, Wei-Ting Chao, Tim H.-M. Huang
Journal: Cancer Research (2020)

Cytometry by time-of-flight (CyTOF) simultaneously measures multiple cellular proteins at the single-cell level and is used to assess intertumor and intratumor heterogeneity. This approach may be used to investigate the variability of individual tumor responses to treatments. Herein, we stratified lung tumor subpopulations based on AXL signaling as a potential targeting strategy. Integrative transcriptome analyses were used to investigate how TP-0903, an AXL kinase inhibitor, influences redundant oncogenic pathways in metastatic lung cancer cells. CyTOF profiling revealed that AXL inhibition suppressed SMAD4/TGFβ signaling and induced JAK1-STAT3 signaling to compensate for the loss of AXL. Interestingly, high JAK1-STAT3 was associated with increased levels of AXL in treatment-naïve tumors. Tumors with high AXL, TGFβ, and JAK1 signaling concomitantly displayed CD133-mediated cancer stemness and hybrid epithelial-to-mesenchymal transition features in advanced-stage patients, suggesting greater potential for distant dissemination. Diffusion pseudotime analysis revealed cell-fate trajectories among four different categories that were linked to clinicopathologic features for each patient. Patient-derived organoids (PDO) obtained from tumors with high AXL and JAK1 were sensitive to TP-0903 and ruxolitinib (JAK inhibitor) treatments, supporting the CyTOF findings. This study shows that single-cell proteomic profiling of treatment-naïve lung tumors, coupled with
Clinical significance of TP53, BIRC3, ATM and MAPK-ERK genes in chronic lymphocytic leukaemia: data from the randomised UK LRF CLL4 trial
Authors: Stuart J. Blakemore, Ruth Clifford, Helen Parker, Pavlos Antoniou, Ewa Stec-Dziedzic, Marta Larrayoz, Zadie Davis, Latha Kadalyayil, Andrew Colins, Pauline Robbe, Dimitris Vavoulis, Jade Forster, Louise Carr, Ricardo Morilla, Monica Else, Dean Bryant, Helen McCarthy, Renata J. Walewska, Andrew J. Steele, Jacqueline Chan, Graham Speight, Tanja Stankovic, Mark S. Cragg, Daniel Catovsky, David G. Oscier, Matthew J. J. Rose-Zerilli, Anna Schuh, Jonathan C. Strefford
Journal: Leukemia (2020)

Abstract Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with chemotherapy trials representing an invaluable resource to explore disease-related/genetic features contributing to long-term outcomes. In 499 LRF CLL4 cases, a trial with &gt;12 years follow-up, we employed targeted resequencing of 22 genes, identifying 623 mutations. After background mutation rate correction, 11/22 genes were recurrently mutated at frequencies between 3.6% ( NFKBIE ) and 24% ( SF3B1 ). Mutations beyond Sanger resolution (&lt;12% VAF) were observed in all genes, with KRAS mutations principally composed of these low VAF variants. Firstly, employing orthogonal approaches to confirm &lt;12% VAF TP53 mutations, we assessed the clinical impact of TP53 clonal architecture. Whilst ≥ 12% VAF TP53 mut cases were associated with reduced PFS and OS, we could not demonstrate a difference between &lt;12% VAF TP53 mutations and either wild type or ≥12% VAF TP53 mut cases. Secondly, we identified biallelic BIRC3 lesions (mutation and deletion) as an independent marker of inferior PFS and OS. Finally, we observed that mutated MAPK-ERK genes were independent markers of poor OS in multivariate survival analysis. In conclusion, our study supports using targeted resequencing of expanded gene panels to elucidate the prognostic impact of gene mutations.
Monitoring innate immune cell dynamics in the glioma microenvironment by magnetic resonance imaging and multiphoton microscopy (MR-MPM)
Authors: Kianush Karimian-Jazi, Philipp Münch, Allen Alexander, Manuel Fischer, Kira Pfleiderer, Manuel Piechutta, Matthia A. Karreman, Gergely M. Solecki, Anna S. Berghoff, Mirco Friedrich, Katrin Deumelandt, Felix T. Kurz, Wolfgang Wick, Sabine Heiland, Martin Bendszus, Frank Winkler, Michael Platten, Michael O. Breckwoldt
Journal: Theranostics (2020)

Rationale: Glioblastoma is the most frequent, primary brain tumor that is characterized by a highly immunosuppressive tumor microenvironment (TME). The TME plays a key role for tumor biology and the effectiveness of immunotherapies. Composition of the TME correlates with overall survival and governs therapy response. Non invasive assessment of the TME has been notoriously difficult. Methods: We have designed an in vivo imaging approach to non invasively visualize innate immune cell dynamics in the TME in a mouse glioma model by correlated MRI and multiphoton microscopy (MR-MPM) using a bimodal, fluorescently labeled iron oxide nanoparticle (NP). The introduction of Teflon cranial windows instead of conventional Titanium rings dramatically reduced susceptibility artifacts on MRI and allowed longitudinal MR-MPM imaging for innate immune cell tracking in the same animal. Results: We visualized tumor associated macrophage and microglia (TAM) dynamics in the TME and dissect the single steps of NP uptake by blood-born monocytes that give rise to tumor-associated macrophages. Next to peripheral NP-loading, we identified a second route of direct nanoparticle uptake via the disrupted blood-brain barrier to directly label tissue resident TAMs. Conclusion: Our approach allows innate immune cell tracking by MRI and multiphoton microscopy in the same animal to longitudinally investigate innate immune cell dynamics in the TME.
Abstract #41: Grape seed extract inhibits the growth of human head and neck carcinoma cells under both in vitro and in vivo conditions
Authors: Chapla Agarwal, Velmurugan Balaiya, Manjinder Kaur, Rajesh Agarwal
Journal: Cancer Research (2009)

Head and neck cancer accounts for nearly 40,000 cases of cancer diagnosed annually in the United States and has 5 year survival rate of ~50%. Despite considerable advancement in conventional therapeutic approaches to treat this malignancy, the survival rate of head and neck cancer patients remains almost same. Accumulating evidences suggest that consumption of diets rich in fruits and vegetables is associated with lower risk of cancer. Besides nutrients, fruits and vegetables contain non-nutritive phytochemicals, which have shown anti-cancer activity in many cancer models. Accordingly, in the present study, we evaluated the anti-cancer effects of grape seed extract (GSE), an excellent source of proanthocyanidins, against human head and neck cancer FaDu and UMSCC-22B cell lines. We observed that treatment with GSE (10- 40 µg/ml) for 24-72 h results in concentration- and time-dependent decrease in viability of both the cells lines. In case of FaDu cells, treatment with GSE for 24 h resulted in a decrease in the viability of these cells by 41-66% (P  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 41.
Cumulative Incidence and Predictors of CNS Metastasis for Patients With American Joint Committee on Cancer 8th Edition Stage III Melanoma
Authors: Lauren E. Haydu, Serigne N. Lo, Jennifer L. McQuade, Rodabe N. Amaria, Jennifer Wargo, Merrick I. Ross, Janice N. Cormier, Anthony Lucci, Jeffrey E. Lee, Sherise D. Ferguson, Robyn P.M. Saw, Andrew J. Spillane, Kerwin F. Shannon, Jonathan R. Stretch, Patrick Hwu, Sapna P. Patel, Adi Diab, Michael K.K. Wong, Isabella C. Glitza Oliva, Hussein Tawbi, Matteo S. Carlino, Alexander M. Menzies, Georgina V. Long, Alexander J. Lazar, Michael T. Tetzlaff, Richard A. Scolyer, Jeffrey E. Gershenwald, John F. Thompson, Michael A. Davies
Journal: Journal of Clinical Oncology (2020)

Improved understanding of the incidence, risk factors, and timing of CNS metastasis is needed to inform surveillance strategies for patients with melanoma.
Caution When Continuing Benzodiazepines During rTMS: Response to Hunter and Leuchter
Authors: Tyler S. Kaster, Jonathan Downar, Fidel Vila-Rodriguez, Zafiris J. Daskalakis, Daniel M. Blumberger
Journal: American Journal of Psychiatry (2020)

Depression: A THREE-D Study," published in the May 2019 issue of the Journal (1), is the observed association between benzodiazepine use and poorer outcome to repetitive transcranial magnetic stimulation (rTMS).Benzodiazepine use emerged as the only modifiable clinical factor that was significantly associated with poorer response to rTMS treatment.This provocative finding from exploratory analyses of the THREE-D trial (2) is even more compelling in view of a contemporaneous report on concomitant medication use and rTMS treatment outcome in a large independent data set (3). Hunter and colleagues' exploratory analyses of 13 medication categories found benzodiazepine use as the only category that was associated with poorer outcome to an acute course of rTMS (3).Further similarities across the two studies are of note.First, neither study found any evidence of anxiety as an explanation of the effect.Second, both studies suggest that the benzodiazepine effect may be most pronounced in the first few weeks of rTMS treatment.In the Kaster et al. trajectory analyses, benzodiazepine users were underrepresented in the "rapid response" group (1), whereas in the Hunter et al. analyses of improvement in symptom severity at weeks 2, 4, and 6, the largest deficit in benzodiazepine users was seen at week 2. Given similar results across these two studies (1, 3) of 388 and 181 participants, respectively, it seems reasonable for clinicians to consider reductions in the clinical use of benzodiazepines during rTMS treatment.The high rates of benzodiazepine use reported in these cohorts (i.e., 40% [3] and 32% after excluding "high-dose" benzodiazepine use [1]) indicate that a substantial subgroup of patients may be at risk of poorer outcome.Prospective research is called for to elucidate the possible basis for a causal relationship between benzodiazepine use and poorer rTMS outcome, as well as to determine whether certain classes of medications may enhance rTMS treatment outcomes.Kaster et al. did not identify any antidepressant augmentation or combination that was associated with better response to treatment, whereas Hunter et al. found that the use of stimulants was associated with greater clinical improvement during rTMS.Overall, these two studies highlight the importance of the field of pharmacotherapy-TMS research in order to optimize treatment outcomes.
Adjuvant dabrafenib plus trametinib versus placebo in patients with resected, BRAFV600-mutant, stage III melanoma (COMBI-AD): exploratory biomarker analyses from a randomised, phase 3 trial
Authors: Reinhard Dummer, Jan C Brase, James Garrett, Catarina D Campbell, Eduard Gasal, Matthew Squires, Daniel Gusenleitner, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, Keith Flaherty, James Larkin, Caroline Robert, Richard Kefford, John M Kirkwood, Axel Hauschild, Dirk Schadendorf, Georgina V Long
Journal: The Lancet Oncology (2020)
Structural Analysis of Rabies Virus Glycoprotein Reveals pH-Dependent Conformational Changes and Interactions with a Neutralizing Antibody
Authors: Fanli Yang, Sheng Lin, Fei Ye, Jing Yang, Jianxun Qi, Zhujun Chen, Xi Lin, Jichao Wang, Dan Yue, Yanwei Cheng, Zimin Chen, Hua Chen, Yu You, Zhonglin Zhang, Yu Yang, Ming Yang, Honglu Sun, Yuhua Li, Yu Cao, Shengyong Yang, Yuquan Wei, George F. Gao, Guangwen Lu
Journal: Cell Host & Microbe (2020)
Coronavirus in China
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2020)

On Dec 31, 2019, China alerted WHO to several cases of pneumonia associated with an unknown virus. The cases were concentrated in Wuhan City, in Hubei Province in central China, home to 11 million people. By Jan 7, 2020, there was confirmation that a new type of coronavirus had emerged. It was temporarily named 2019-nCoV. It is the seventh identified coronavirus that can cause diseases of the respiratory tract in humans. On Jan 9, there was the first reported death from 2019-nCoV—a 61-year-old man who had visited the now-closed Huanan Seafood Wholesale Market, where the virus is thought to have originated.
13O_PR Translational Studies Within the Tamrad Randomized Gineco Trial: Evidence for Torc1 Activation Marker as a Predictive Factor for Everolimus Efficacy in Metastatic Breast Cancer (MBC)
Authors: T. Bachelot, J. Ferrero, C. Cropet, C. Bourgier, S. Abadie-Lacourtoisie, C. Levy, E. Legouffe, A. Lortholary, E. Pujade-Lauraine, I. Treilleux
Journal: Annals of Oncology (2012)
Forceps-assisted technique: a new technique for difficult cannulation
Authors: Mohamed Borahma, Imane Benelbarhdadi, Camellia Berhili, Nawal Lagdali, Fatima Zahra Ajana
Journal: Endoscopy (2020)

See also: The forceps-assisted technique for difficult cannulation has been in widespread use since 1996Endoscopy 2021; 53(04): 457-457DOI: 10.1055/a-1288-0801
CCBE1 promotes tumor lymphangiogenesis and is negatively regulated by TGFβ signaling in colorectal cancer
Authors: Jinglue Song, Wei Chen, Xuewei Cui, Zhenyu Huang, Dongpeng Wen, Yili Yang, Wei Yu, Long Cui, Chen-Ying Liu
Journal: Theranostics (2020)

Collagen and calcium-binding EGF domain-1 (CCBE1) is essential for lymphatic vascular development as it promotes vascular endothelial growth factor C (VEGFC) proteolysis. A recent study reported that CCBE1 was overexpressed in epithelial colorectal cancer (CRC) cells; however, the role of CCBE1 in tumor lymphangiogenesis and the mechanism underlying dysregulated CCBE1 expression in CRC remain undefined. Methods: The role of CCBE1 in tumor lymphangiogenesis and lymphatic metastasis was investigated using human lymphatic endothelial cells (HLECs) model in vitro, and a hindfoot lymphatic metastasis model in vivo. Immunochemistry analysis was performed to assess CCBE1 expression, prognostic value and correlation with clinicopathological characteristics in CRC. The biochemical function and transcriptional regulatory mechanism of CCBE1 were explored by western blot, qPCR, and chromatin immunoprecipitation. Results: Cancer cell-derived CCBE1 enhances VEGFC proteolysis in vitro, facilitates tube formation and migration of HLECs in vitro, and promotes tumor lymphangiogenesis and lymphatic metastasis in vivo. In addition to CRC cells, tumor stroma within CRC tissue shows high CCBE1 expression, which is associated with high lymphatic vessel density, increased lymph node metastasis and poor prognosis. Cancer-associated fibroblasts (CAFs) express and secret CCBE1, thereby contributing to VEGFC maturation and tumor lymphangiogenesis in CRC. Transforming growth factor beta (TGF-β) downregulates the transcription and lymphangiogenic function of CCBE1 in CAFs and CRC cells through direct binding of SMADs to CCBE1 gene locus. Inactivation of the TGF-β pathway correlates with increased CCBE1 expression in CRC. Conclusion: Our results demonstrate the protumorigenic role of CCBE1 in promoting lymphangiogenesis and lymphatic metastasis in CRC, revealing a new mechanism by which loss of TGF-β signaling promotes CRC metastasis.
A myelin-related transcriptomic profile is shared by Pitt–Hopkins syndrome models and human autism spectrum disorder
Authors: BaDoi N. Phan, Joseph F. Bohlen, Brittany A. Davis, Zengyou Ye, Huei-Ying Chen, Brent Mayfield, Srinidhi Rao Sripathy, Stephanie Cerceo Page, Morganne N. Campbell, Hannah L. Smith, Danisha Gallop, Hyojin Kim, Courtney L. Thaxton, Jeremy M. Simon, Emily E. Burke, Joo Heon Shin, Andrew J. Kennedy, J. David Sweatt, Benjamin D. Philpot, Andrew E. Jaffe, Brady J. Maher
Journal: Nature Neuroscience (2020)
Urinary Incontinence in Women
Authors: Camille P. Vaughan, Alayne D. Markland
Journal: Annals of Internal Medicine (2020)

Urinary incontinence (UI) is common among women and contributes to decreased quality of life. Several effective treatment options are available for the most common types of UI (stress, urge, and mixed), including lifestyle and behavioral therapy, drug therapy, and minimally invasive procedures. Most women improve with treatment, and UI is not an inevitable part of aging. To maximize the opportunity for successful treatment, it is critical to align the treatment approach with patient goals and expectations for care, including an assessment of patient-driven priorities regarding potential adverse effects, costs, and expected benefit of different treatment approaches.
Stapled peptide targeting the CDK4/Cyclin D interface combined with Abemaciclib inhibits KRAS mutant lung cancer growth
Authors: Celine Bouclier, Matthieu Simon, Guillaume Laconde, Morgan Pellerano, Sebastien Diot, Sylvie Lantuejoul, Benoit Busser, Laetitia Vanwonterghem, Julien Vollaire, Véronique Josserand, Baptiste Legrand, Jean-Luc Coll, Muriel Amblard, Amandine Hurbin, May C. Morris
Journal: Theranostics (2020)

et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Abstract 355: Effect of Poloxamer 188 on Rat Brain Isolated Mitochondria After Exposure to Hydrogen Peroxide
Authors: Johannes A Pille, Michele M Salzman, Anna A Sonju, Felicia P Lotze, Josephine E Hees, William J Cleveland, Claudius Balzer, Matthias L Riess
Journal: Circulation (2019)

Introduction: In a pig model of myocardial infarction (MI), intracoronary delivered Poloxamer (P) 188 significantly reduces ischemia/reperfusion (IR) injury when given immediately upon reperfusion, with improved mitochondrial function as a predominant effect. As mitochondria are heavily damaged during IR, a direct effect of P188 on mitochondria may lead to better therapy options during reperfusion. To show not only a similar reduction of IR injury by P188 in the brain, but also a direct P188 effect on mitochondria, we established an in-vitro model of IR that consists of damaging isolated rat brain mitochondria with hydrogen peroxide (H 2 O 2 ), one component of ischemia, then applying P188, and analyzing mitochondrial function. Methods: Male Sprague-Dawley rat brains were removed, and the mitochondria isolated by differential centrifugation and Percoll gradients, then kept on ice to slow their bioenergetics prior to any experimental treatments. Mitochondria were exposed to 200 μM H 2 O 2 for 10 min at room temperature with slight agitation; controls received no H 2 O 2 . Samples were then diluted ½ with buffer ± P188 (250 μM after dilution) to simulate reperfusion and treatment, and kept at room temperature for 10 further minutes. ATP synthesis was measured in a luminometer using a luciferase enzymatic assay. Oxygen consumption was measured by closed cell respirometry with an oxygen meter. In both assays, Complex I and Complex II were examined; Complex I substrates glutamate and malate, Complex II substrate succinate plus the Complex I inhibitor rotenone. Statistics: Data are expressed as mean ± SEM. One-Way ANOVA, SNK-Test; Kruskal-Wallis-Test; α=0.05, * vs control. Results: In both Complex I and II, mitochondrial function was significantly impaired by H 2 O 2 , with ATP synthesis affected more at Complex I and oxygen consumption affected more at Complex II. Addition of P188 did not provide any significant improvement in mitochondrial function. Conclusions: Although P188 significantly reduced IR injury when given during reperfusion in a pig model of MI, it does not appear to provide direct protection to mitochondria in this in-vitro model. Whether the exposure to H 2 O 2 causes the appropriate injury for P188 to become effective remains to be elucidated.
A Rapid Change in Pressure
Authors: Kristin D’Silva, Barbara Cockrill, William J. Anderson, Amy L. Miller, Joseph Loscalzo
Journal: New England Journal of Medicine (2020)

A 74-year-old woman presented with a 6-week history of progressive dyspnea on exertion. She also noted a nonproductive cough, fatigue, loss of appetite, and an unintentional weight loss of 9 kg over the previous 6 months.