tbuckley/cabot-search huggingface dataset:
Thousands more patients with type 1 diabetes are getting flash glucose devices, data show
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The number of patients with type 1 diabetes who are receiving “flash” glucose monitoring devices on the NHS has increased markedly since NHS England told clinical commissioning groups to end the postcode lottery, show figures released to The BMJ .

Last year a BMJ investigation found that tens of thousands of patients were being denied the potential benefits of the devices because they were not being recommended in some areas.1

The national specialty adviser for diabetes, Partha Kar, said that The BMJ ’s investigation had influenced NHS England’s decision to issue new advice to CCGs in its NHS long term …
Ribociclib (RIB) plus letrozole (LET) in male patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC) from the CompLEEment-1 trial
Authors: M. Campone, M. De Laurentiis, C. Zamagni, I. Kudryavcev, M. Agterof, U. Brown-Glaberman, M. Palácová, S. Chatterjee, L. Menon-Singh, J. Wu, K. Zhou, M. Martin
Journal: Annals of Oncology (2019)
Enhancing functional abilities and cognitive integration of the lower limb prosthesis
Authors: Francesco Maria Petrini, Giacomo Valle, Marko Bumbasirevic, Federica Barberi, Dario Bortolotti, Paul Cvancara, Arthur Hiairrassary, Pavle Mijovic, Atli Örn Sverrisson, Alessandra Pedrocchi, Jean-Louis Divoux, Igor Popovic, Knut Lechler, Bogdan Mijovic, David Guiraud, Thomas Stieglitz, Asgeir Alexandersson, Silvestro Micera, Aleksandar Lesic, Stanisa Raspopovic
Journal: Science Translational Medicine (2019)

Recreated missing leg sensations, connected to the prosthesis sensors, restored leg functional abilities and promoted its cognitive integration.
IFN-γ drives inflammatory bowel disease pathogenesis through VE-cadherin–directed vascular barrier disruption
Authors: Victoria Langer, Eugenia Vivi, Daniela Regensburger, Thomas H. Winkler, Maximilian J. Waldner, Timo Rath, Benjamin Schmid, Lisa Skottke, Somin Lee, Noo Li Jeon, Thomas Wohlfahrt, Viktoria Kramer, Philipp Tripal, Michael Schumann, Stephan Kersting, Claudia Handtrack, Carol I. Geppert, Karina Suchowski, Ralf H. Adams, Christoph Becker, Andreas Ramming, Elisabeth Naschberger, Nathalie Britzen-Laurent, Michael Stürzl
Journal: Journal of Clinical Investigation (2019)

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with rising incidence. Diseased tissues are heavily vascularized. Surprisingly, the pathogenic impact of the vasculature in IBD and the underlying regulatory mechanisms remain largely unknown. IFN-γ is a major cytokine in IBD pathogenesis, but in the context of the disease, it is almost exclusively its immune-modulatory and epithelial cell–directed functions that have been considered. Recent studies by our group demonstrated that IFN-γ also exerts potent effects on blood vessels. Based on these considerations, we analyzed the vessel-directed pathogenic functions of IFN-γ and found that it drives IBD pathogenesis through vascular barrier disruption. Specifically, we show that inhibition of the IFN-γ response in vessels by endothelial-specific knockout of IFN-γ receptor 2 ameliorates experimentally induced colitis in mice. IFN-γ acts pathogenic by causing a breakdown of the vascular barrier through disruption of the adherens junction protein VE-cadherin. Notably, intestinal vascular barrier dysfunction was also confirmed in human IBD patients, supporting the clinical relevance of our findings. Treatment with imatinib restored VE-cadherin/adherens junctions, inhibited vascular permeability, and significantly reduced colonic inflammation in experimental colitis. Our findings inaugurate the pathogenic impact of IFN-γ–mediated intestinal vessel activation in IBD and open new avenues for vascular-directed treatment of this disease.
Unmet needs in oncology research related to radiological response evaluation: A multi-center survey in three European countries
Authors: S. Nisse Durgeat, H. Paynes, L. Saba, E. Calvo, I. Spoletini, A.L. Gomes, F. Bergaz, A. Balestrieri, M. Porcu
Journal: Annals of Oncology (2019)
Association of ABCG2 polymorphism with clinical efficacy of imatinib in patients with gastrointestinal stromal tumor.
Authors: Dong Hoe Koo, Min-Hee Ryu, Baek-Yeol Ryoo, Mo Youl Beck, Young-Soon Na, Jae-Gook Shin, Sang Seop Lee, Eun-Young Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2014)

10544 Background: Imatinib is a substrate of drug metabolizing enzymes, including those of the cytochrome P450 (CYP) system, and of several drug transporters. Differences in imatinib pharmacokinetics among individual patients may be influenced by genetic polymorphisms and be associated with clinical imatinib efficacy. This study evaluated the correlation of genetic polymorphisms with trough imatinib levels and clinical efficacy in GIST patients. Methods: A total of 209 patients with GIST who had received imatinib (400 mg daily) were genotyped for 6 single-nucleotide polymorphisms in 3 genes (CYP3A5 6986A>G; ABCB1 1236C>T, 2677G>A/T, and 3435C>T; and ABCG2 34G>A and 421C>A) via blood samples. Imatinib plasma trough levels and progression-free survival (PFS) were analyzed for association with each genotype. Results: With a median follow-up of 39.6 months (range, 16.7-97.5 months), the estimated 5-year PFS rate was 67.5% (95% CI, 59.9-75.1). Among the CYP3A5, ABCB1, and ABCG2 genotypes, there were no significant differences in imatinib plasma trough levels or PFS, while ABCG2 421C>A was associated with PFS. The 5-year PFS rate in patients with the AA variant of ABCG2 421C>A (92.3%; 95% CI, 77.8-100.0) was significantly superior to that of patients with CC/CA genotypes (65.0%; 95% CI, 56.9-73.1) (P = 0.047). Conclusions: The ABCG2 421C>A genetic variation could influence clinical efficacy in terms of PFS in patients with advanced GIST undergoing imatinib treatment.
Final results of a phase II study of induction chemotherapy (CT) with paclitaxel (PTX) and panitumumab (P) followed by radiotherapy (RT) and P in patients (pts) with locally advanced head and neck cancer (LAHNC) no candidates to platinum: Study PANTERA
Authors: J. Martinez Trufero, R. Mesia Nin, M.E. Ortega Izquierdo, A. Lozano, B. Cirauqui Cirauqui, J. Rubió Casadevall, M. Taberna Sanz, M. Pastor Borgoñon, J. Lambea Sorrosal, L. Iglesias, S. Vázquez, E. del Barco Morillo, P. Perez Segura, A. Lopez Pousa, J.M. Ponce, J.J. Cruz-Hernández
Journal: Annals of Oncology (2019)
P12.09 Multidimensional Personalized Response Assessment to Microglia Modulators in Gioblastoma Bioreactors
Authors: T Shekarian, A Wachnowicz, J Flammer, C Paganetti, T Martins, M Muraro, C Schürch, G Hutter
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Recently, strategies harnessing the non-neoplastic, immune tumor microenvironment (iTME) consisting of myeloid-derived macrophages and yolk sac derived microglia (termed TAMs) as well as adaptive immune components have been employed to treat glioblastoma (GBM). To evaluate the effect of TAM-modulating therapies in combination with T-cell checkpoint inhibitor approaches, we generated 3D GBM bioreactor cultures from patient-derived samples. Here, we report patient-tailored, tumor region specific response assessment to microglia modulators and T-cell checkpoint inhibitors using multidimensional fluorescent microscopy techniques MATERIAL AND METHODS GBM tissue fragments from the tumor center and periphery were placed into perfusion bioreactors shortly after resection and cultured for up to 3 weeks. Control conditions included non-perfused cultures of the same tissue. Cultures were treated with combinations of TAM and T-cell modulating, FDA approved drugs including anti-PD1, anti-CTLA4 and anti-CD47 antibodies. Tissue was harvested for histology, RNA extraction, and supernatants were processed for multiplexed cytokine analysis. Multidimensional CODEX technology analysis using a customized TAM/microglia-centric 50 marker panel was implemented, and a map of individualized response criteria to specific immunotherapies developed. RESULTS We were able to cultivate viable GBM tissue with intact iTME. Tumor cell proliferation and invasion capacity were preserved for up to 3 weeks. Conventional immunohistochemistry confirmed the presence of TAMs and T cells. Treatment with immunomodulators resulted in a profound polarization shift of TAMs. Furthermore, cytokine analysis confirmed proinflammatory immune responses in most assessed samples. We present preliminary data of the CODEX analysis of our combinatorial immunotherapies in a series of 8 patient-specific explant samples. CONCLUSION GBM tissue could be incubated in the perfused 3D bioreactor model and kept viable for up to 21 days. The proposed model allows patient-tailored testing of immunomodulatory drugs by taking into account the patients individual iTME response. GBM tissue could be incubated in the perfused 3D bioreactor model and kept viable for up to 21 days. The proposed model allows patient-tailored testing of immunomodulatory drugs by taking into account the patients individual iTME response.
Pre-specified interim analysis of GALAHAD: A phase II study of niraparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and biallelic DNA-repair gene defects (DRD)
Authors: M.R. Smith, S.K. Sandhu, W.K. Kelly, H.I. Scher, E. Efstathiou, P.N. Lara, E.Y. Yu, D.J. George, K.N. Chi, F. Saad, J. Summa, J.M. Freedman, G.E. Mason, E. Zhu, D. Ricci, J.S. Simon, S. Cheng, K. Fizazi
Journal: Annals of Oncology (2019)
Outcomes of first-line FOLFIRINOX (FFX) versus gemcitabine and nab-paclitaxel (GN) in patients with advanced pancreatic cancer: Multi-Institutional Canadian sites experience
Authors: N. Papneja, S. Ahmed, P. Mondal, I. Barrera, A. Papneja, G. Batist, P. Kavan
Journal: Annals of Oncology (2019)
Safety profile of oral netupitant/palonosetron in hematopoietic stem cell transplantation recipients
Authors: M. Bosch-Damas, M. Rodriguez-Reyes, M. Cervera-Carbonell, N. Borràs-Maixenchs, E. Carcelero-San Martín, G. Riu-Viladoms, M. Valverde-Bosch, G. Gutierrez-Garcia
Journal: Annals of Oncology (2019)
CTONG 1509: Phase III study of bevacizumab with or without erlotinib in untreated Chinese patients with advanced EGFR-mutated NSCLC
Authors: Q. Zhou, Y.-L. Wu, Y. Cheng, Y. Liu, G. Chen, J. Cui, N. Yang, Y. Song, X.-L. Li, S. Lu, J. Zhou, Z. Ma, S.-Y. Yu, C. Huang, Y. Shu
Journal: Annals of Oncology (2019)

Abstract   Background  This study is an open-labeled, randomized, multicenter phase III study to investigate the efficacy and safety of bevacizumab (B) with or without erlotinib (E) in Chinese EGFR-mutated non-small cell lung cancer (NSCLC) patients (NCT02759614).    Methods  Patients with advanced non-squamous NSCLC harbouring EGFR-mutation were randomly (1:1) assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). Random assignment was stratified by sex (female/male), disease stage (stage IIIb vs. stage IV vs. recurrence), and EGFR gene mutation (exon 19 deletion vs. exon 21 L858R). The primary endpoint was Progression-free survival (PFS), as determined by an independent review committee (IRC). Secondary endpoints were PFS by investigator, tumor response (by IRC and investigator), overall survival (OS), time to failure (TTF), safety, patient-reported outcome (PRO) and exploratory biomarker analysis. Next-generation sequencing (NGS) of a 448-gene panel and transcriptome sequencing (RNA-Seq) was used for resistance biomarker analysis of paired frozen tissue samples.    Results  From Mar 31, 2016 to Jul 26, 2017, 311 patients from 14 centers across China were randomized to receive BE (N = 157) or E (N = 154). Median follow-up time was 22 months for BE and 21.5 months for E. Baseline characteristics were well balanced in each arm. The median PFS by IRC was 18.0 months (95% CI 15.2-20.7) in BE and 11.3 months (95%CI 9.8-13.8) in E (p     Conclusions  As compared with E alone, B plus E showed superior efficacy with acceptable tolerability. This regimen could be a new standard first-line regimen in EGFR mutated NSCLC.    Clinical trial identification  NCT02759614.    Editorial acknowledgement  Li Zhang, from Shanghai Roche Pharmaceuticals Ltd.    Legal entity responsible for the study  Guangdong Association of Clinical Trials (GACT).    Funding  Shanghai Roche Pharmaceuticals Ltd.    Disclosure  Q. Zhou: Honoraria (self): AstraZeneca; Honoraria (self): Roche. Y. Wu: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Honoraria (self): Pierre Fabre; Honoraria (self): Pﬁzer; Honoraria (self): Sanoﬁ; Advisory / Consultancy: Merck; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Sex and the kidneys: current understanding and research opportunities
Authors: C. Noel Bairey Merz, Laura M. Dember, Julie R. Ingelfinger, Amanda Vinson, Joel Neugarten, Kathryn L. Sandberg, Jennifer C. Sullivan, Christine Maric-Bilkan, Tracy L. Rankin, Paul L. Kimmel, Robert A. Star
Journal: Nature Reviews Nephrology (2019)
Phase I study of low dose whole abdominal radiation therapy (LDWART) in combination with weekly paclitaxel (wP) for platinum resistant ovarian cancer (PROC)
Authors: N.Y.L. Ngoi, V.Y.M. Heong, N.B. Kumarakulasinghe, P.S. Phyu, E.Y. Peh, S.E. Lim, Y.W. Lim, J. Tang, B.A. Choo, V. Koh, A. Ilancheran, J. Low, J. Ng, Y.L. Thian, D.S. Tan
Journal: Annals of Oncology (2019)
Impact of second-line (2L) immune checkpoint inhibitors (ICIs) on the treatment (Tx) of advanced non-small cell lung cancer (NSCLC) in a UK centre: A REAL-oncology analysis from the I-O Optimise initiative
Authors: M. Snee, S. Cheeseman, M. Thompson, R. Bowman, L. Lacoin, W. Sopwith, C. Chaib, M. Daumont, J.R. Penrod, J.C. O’Donnell, G. Hall
Journal: Annals of Oncology (2019)
Efficacy of platinum-containing chemotherapy and prognosis of pancreatic cancer patients with homologous recombination deficiency: Meta-analysis of published clinical studies
Authors: E. Polyanskaya, I. Pokataev, M. Fedyanin, A. Popova, Y. Agafonova, A. Tryakin, S. Tjulandin
Journal: Annals of Oncology (2019)
GOSPEL: A Neuroprotective Protein that Binds to GAPDH upon S-Nitrosylation
Authors: Nilkantha Sen, Makoto R. Hara, Abdullah Shafique Ahmad, Matthew B. Cascio, Atsushi Kamiya, Jeffrey T. Ehmsen, Nishant Agrawal, Lynda Hester, Sylvain Doré, Solomon H. Snyder, Akira Sawa
Journal: Neuron (2009)
Treatment-related adverse events and tolerability in patients with advanced non-squamous non-small cell lung cancer treated with first-line checkpoint inhibitors in combination with chemotherapy
Authors: R. d’Cunha, P. D’Cunha, S. Swarup, A. Sultan, F. Mogollon-Duffo, N. Jahan, T. Win Htut, S. Wongsaengsak, N. Adhikari, A.M. Mon, P.P. Hlaing, A.M. Tun, N. D’Cunha, K.Z. Thein
Journal: Annals of Oncology (2019)
Clinical application of mutational analysis in breast cancer patients: The relevance of PIK3CA analysis for precision medicine
Authors: J.M. Cejalvo, S. Moragon, B. Ortega, C. Hernando, M. Martínez, V. Gambardella, N. Tarazona Llavero, D. Roda, O. Burgues, E. Alonso, S. Simón, J. Poveda, P. Rentero, S. Zuñiga, B. Bermejo, A. Lluch, A. Cervantes
Journal: Annals of Oncology (2019)
Predictive Value of Positron Emission Tomography/Computed Tomography After ABVD-Based Chemotherapy in Early-Stage Hodgkin Lymphoma
Authors: Carsten Kobe, Helen Goergen, Michael Fuchs, Horst Müller, Christan Baues, Andreas Engert, Markus Dietlein, Bastian von Tresckow, Peter Borchmann
Journal: Journal of Clinical Oncology (2019)
Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Authors: J.T. Matulay, M.T. Campbell, V.M. Narayan, M.A. Seif, A.H. Lim, A.Y. Shah, P. Msaouel, J. Gao, A.O. Siefker-Radtke, C.P.N. Dinney, A.M. Kamat, N. Navai
Journal: Annals of Oncology (2019)
Measuring financial toxicity of cancer in the Italian health care system: Initial results of the patient reported outcome for fighting financial toxicity of cancer project (proFFiT)
Authors: S. Riva, M Di Maio, F. Efficace, L. Frontini, C. Gallo, D. Giannarelli, V. Montesarchio, F. De Lorenzo, L. Del Campo, E. Iannelli, F. Traclò, L. Gitto, C. Jommi, C.M. Vaccaro, J.C. Bryce, A. Gimigliano, L. Sparavigna, F. Perrone
Journal: Annals of Oncology (2019)
Abstract 1808: The anti-estrogen endoxifen altered bone morphology and reduced muscle function in mice
Authors: Laura Wright, Khalid Mohammad, Theresa Guise
Journal: Cancer Research (2018)

Abstract Endoxifen, the predominant CYP2D6 metabolite of the selective estrogen receptor modulator (SERM) tamoxifen, is currently being developed as a novel anti-estrogen therapy for the treatment of estrogen receptor (ER)+ breast cancer. Genetic polymorphism of CYP2D6 is a predictor of response to tamoxifen in patients, implicating endoxifen as one of the most active and relevant tamoxifen metabolites. Breast cancer patients treated with adjuvant endocrine therapies including aromatase inhibitors (AIs) and SERMs often report unmanageable musculoskeletal toxicities that can result in treatment discontinuation. While ER binding affinity and anti-tumor effects have been established in preclinical models, the effects of endoxifen on the musculoskeletal system are not fully known. Twenty-week female C57BL/6 mice underwent sham surgery or ovariectomy (OVX) and were treated daily with vehicle, the AI letrozole, or the SERM endoxifen. Body composition was assessed prospectively by DXA. Bone indices and marrow adipose tissue volume were measured by μCT and muscle contractility of the extensor digitorum longus (EDL) was measured ex vivo. After eight weeks, trabecular bone volume fraction (BV/TV) decreased by 50% in OVX-vehicle and OVX-letrozole mice, whereas BV/TV increased threefold in endoxifen mice relative to sham-vehicle. Despite the presence of significantly more trabecular bone following endoxifen treatment, cortical bone analyses revealed impaired periosteal and endosteal expansion of bone, resulting in reduced polar moment of inertia, which is a measure of resistance to fracture. Uterine weight increased significantly in endoxifen-treated mice relative to all OVX groups, similar to what is observed with tamoxifen treatment. Peripheral body fat, bone marrow adipose tissue, and circulating leptin were reduced by endoxifen, suggesting that the drug may elicit positive systemic metabolic effects. At the termination of the study, muscle-specific force was reduced in OVX-endoxifen mice relative to sham-vehicle, OVX-vehicle, and OVX-AI mice, despite no change in muscle mass. While endoxifen shows promise as a potent anti-estrogen therapy for the treatment of ER+ breast cancer, it may be important to monitor patients for endometrial proliferation, morphological changes in bone that increase fracture risk, and for musculoskeletal side effects that could reduce drug compliance. Citation Format: Laura Wright, Khalid Mohammad, Theresa Guise. The anti-estrogen endoxifen altered bone morphology and reduced muscle function in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1808.
A Next-Generation Fc-Bearing CD3-Engaging Bispecific DART® Platform with Extended Pharmacokinetic and Expanded Pharmacologic Window: Characterization As CD123 x CD3 and CD19 x CD3 DART Molecules
Authors: Ezio Bonvini, Ross La Motte-Mohs, Ling Huang, Chia-Ying Kao Lam, Thomas Kaufman, Liqin Liu, Ralph F. Alderson, Kurt Stahl, Jennifer G. Brown, Hua Li, Sharad Sharma, James Tamura, Syd Johnson, Paul Moore
Journal: Blood (2018)
Simultaneous Deletion of Endogenous TCRαβ for TCR Gene Therapy Creates an Improved and Safe Cellular Therapeutic
Authors: Laura T. Morton, Rogier M. Reijmers, Anne K. Wouters, Christiaan Kweekel, Dennis F.G. Remst, Cilia R. Pothast, J.H. Frederik Falkenburg, Mirjam H.M. Heemskerk
Journal: Molecular Therapy (2019)

Generation of an optimal T cell therapeutic expressing high frequencies of transgenic T cell receptor (tgTCR) is essential for improving TCR gene therapy. Upon TCR gene transfer, presence of endogenous TCRαβ reduces expression of tgTCR due to TCR mixed-dimer formation and competition for binding CD3. Knockout (KO) of endogenous TCRαβ was recently achieved using CRISPR/Cas9 editing of the TRAC or TRBC loci, resulting in increased expression and function of tgTCR. Here, we adopt this approach into current protocols for generating T cell populations expressing tgTCR to validate this strategy in the context of four clinically relevant TCRs. First, simultaneous editing of TRAC and TRBC loci was reproducible and resulted in high double KO efficiencies in bulk CD8 T cells. Next, tgTCR expression was significantly higher in double TRAC/BC KO conditions for all TCRs tested, including those that contained structural modifications to encourage preferential pairing. Finally, increased expression of tgTCR in edited T cell populations allowed for increased recognition of antigen expressing tumor targets and prolonged control of tumor outgrowth in a preclinical model of multiple myeloma. In conclusion, CRISPR/Cas9-mediated KO of both endogenous TCRαβ chains can be incorporated in current T cell production protocols and is preferential to ensure an improved and safe clinical therapeutic. Generation of an optimal T cell therapeutic expressing high frequencies of transgenic T cell receptor (tgTCR) is essential for improving TCR gene therapy. Upon TCR gene transfer, presence of endogenous TCRαβ reduces expression of tgTCR due to TCR mixed-dimer formation and competition for binding CD3. Knockout (KO) of endogenous TCRαβ was recently achieved using CRISPR/Cas9 editing of the TRAC or TRBC loci, resulting in increased expression and function of tgTCR. Here, we adopt this approach into current protocols for generating T cell populations expressing tgTCR to validate this strategy in the context of four clinically relevant TCRs. First, simultaneous editing of TRAC and TRBC loci was reproducible and resulted in high double KO efficiencies in bulk CD8 T cells. Next, tgTCR expression was significantly higher in double TRAC/BC KO conditions for all TCRs tested, including those that contained structural modifications to encourage preferential pairing. Finally, increased expression of tgTCR in edited T cell populations allowed for increased recognition of antigen expressing tumor targets and prolonged control of tumor outgrowth in a preclinical model of multiple myeloma. In conclusion, CRISPR/Cas9-mediated KO of both endogenous TCRαβ chains can be incorporated in current T cell production protocols and is preferential to ensure an improved and safe clinical therapeutic.