tbuckley/cabot-search huggingface dataset:
Phase II trial of the c-Met inhibitor tepotinib in advanced lung adenocarcinoma with <i>MET</i> exon 14 skipping mutations.
Authors: Paul K. Paik, Enriqueta Felip, Remi Veillon, Jürgen Scheele, Rolf Bruns
Journal: Journal of Clinical Oncology (2017)

e20541 Background: Approximately 3-4% of lung adenocarcinomas express a truncated form of c-Met (c-Met ex14 ) due to mutation-induced exon 14 skipping. c-Met ex14 accumulates on the cell surface and is constitutively active with the ability to drive NSCLC. Data suggest that lung adenocarcinomas harboring c-MET ex14 are sensitive to c-Met kinase inhibitors. The highly selective c-Met inhibitor tepotinib is well tolerated and active at an oral dose of 500 mg QD. This single-arm phase II trial (NCT02864992) is investigating the efficacy and safety of tepotinib in patients (pts) with advanced lung adenocarcinoma harboring MET ex14 . Methods: Adults with stage IIIB/IV lung adenocarcinoma who have failed 1 or 2 lines of systemic therapy, including a platinum doublet-containing regimen, are eligible. Tumors must harbor mutations that are known to cause exon 14 skipping, confirmed by a central laboratory, but not activating EGFR mutations or ALK rearrangements. Pts receive tepotinib 500 mg QD until disease progression, intolerable toxicity, or withdrawal from treatment for other reasons. The primary endpoint is objective response rate. Secondary endpoints include progression-free and overall survival, safety, pharmacokinetics, and quality of life. Recruitment of 60 patients in Europe, USA, and Japan is planned. Results: Four pts (age 64–77 years; 3 stage IV, 1 stage IIIB, all Caucasian males) have been enrolled. All had received two prior chemotherapy regimens including a platinum doublet. Pts have currently completed 1–5 cycles of tepotinib therapy. The majority of adverse events observed to date have been grade 1/2 in severity; grade 3 disease-related dyspnea, pulmonary embolism, and pleural effusion were observed in one patient and grade 3 tepotinib-related elevated serum amylase in another. Of the 3 pts with post-baseline tumor evaluations, two have had an unconfirmed partial response and the third (with only one post-baseline assessment) stable disease. Conclusions: These initial data suggest that the efficacy of tepotinib 500 mg QD is comparable to that of less selective c-Met inhibitors in pts with c-MET ex14 NSCLC (ORR &gt; 40%). Tepotinib is also well tolerated. Recruitment to the trial is ongoing. Clinical trial information: NCT02864992.
The Spot on My Wrist
Authors: Joseph Gascho
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
OP0100 Overall cancer risk in patients with rheumatoid arthritis treated with tnf inhibitors, tocilizumab, abatacept, or rituximab
Authors: H Wadström, T Frisell, J Askling
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Immune incompetence may lower host surveillance against incipient tumours. Conversely, immune therapies have emerged as a promising therapeutic approach to cancer. Malignancies thus constitute an important aspect of the safety of biologics as used in Rheumatology, including agents targeting TNF, CD20 and IL6, and immunomodulation using CTLA4. Whereas previous reports concerning TNF inhibitors (TNFi) and risk of malignancies in rheumatoid arthritis (RA) have mostly been reassuring, risks with other biological disease modifying anti-rheumatic drugs (bDMARDs) are less studied. <h3>Objectives</h3> To assess the risk of malignancies in patients with RA treated with bDMARDs. <h3>Methods</h3> Through linkages of Swedish national and population-based registers we assembled cohorts of patients with RA initiating (Jan 2006 through Dec 2014) a first ever treatment of tocilizumab, abatacept, rituximab, or a TNFi, one cohort of patients initiating a second TNFi, one cohort of biologics-naïve csDMARD treated RA. Through linkage with the Swedish Cancer Register information on incident cancers was collected. Outcomes were defined as a first ever solid or hematologic malignancy excluding non-melanoma skin cancer (NMSC) during follow-up. Patients with a previous malignancy were excluded. Patients were followed from treatment start until death, emigration, outcome or end of follow up (Dec 2014). Hazard ratios were calculated using Cox-regression adjusted for age, sex, educational level, comorbidities, sero-positivity, number of hospitalizations and days spent in inpatient care, use of prednisolone at baseline, use of non-steroidal anti-inflammatory drugs (NSAIDs) at baseline, number of prescription drugs at baseline, and sick leave and disability (yes/no) the year before cohort entry. <h3>Results</h3> Adjusted for age, sex, disease- and treatment characteristics (see above), and educational level, there were no statistically significant differences in risk of a first solid or hematologic malignancy between initiators of tocilizumab, abatacept, rituximab, or a first- or second TNFi, and RA patients treated with csDMARDs. <h3>Conclusions</h3> The overall risk of malignancies among RA patients initiating, tocilizumab, abatacept, rituximab, or a first- or second TNFi in clinical practice did not differ substantially from that of RA patients treated with csDMARDs. Increased risk of tumours at specific sites, or with longer latency, cannot be excluded. <h3>Disclosure of Interest</h3> None declared
An NF-κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function
Authors: Hyunju Oh, Yenkel Grinberg-Bleyer, Will Liao, Dillon Maloney, Pingzhang Wang, Zikai Wu, Jiguang Wang, Dev M. Bhatt, Nicole Heise, Roland M. Schmid, Matthew S. Hayden, Ulf Klein, Raul Rabadan, Sankar Ghosh
Journal: Immunity (2017)
生きた動物の2光子励起時間分解イメージングのためのナノプローブ:ナノキャリアの腫瘍標的化動力学のその場解析【Powered by NICT】
Authors: Yang Wen, Fu Li-Min, Wen Xue, Liu Ying, Tian Ye, Liu Yu-Chen, Han Rong-Cheng, Gao Zhi-Yue, Wang Tian-En, Sha Yin-Lin, Jiang Yu-Qiang, Wang Yuan, Zhang Jian-Ping
Journal: Biomaterials (2016)
Endothelin a Receptor (ETRA) Blockade Inhibits Leukocyte Adhesion to the Vascular Endothelium in Sickle Cell Disease
Authors: Haiyan Xiao, Diana R. Gutsaeva, Zhen Zheng, Nianlan Yang, Carol Dickerson, James B Parkerson, Shobha Yerigenahally, Songwei Wu, Steffen E. Meiler
Journal: Blood (2016)
HHV6 Specific T-Cells Are Predictive Biomarker of Active HHV6 Infection after Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Study in 213 Patients
Authors: Raffaella Greco, Maddalena Noviello, Lara Crucitti, Sara Racca, Veronica Valtolina, Mara Morelli, Fabio Giglio, Daniele Mannina, Maria Chiara Barbanti, Alessandra Forcina, Mattia Pozzato, Serena Rolla, Andrea Angelo Assanelli, Matteo Giovanni Carrabba, Sarah Marktel, Massimo Bernardi, Consuelo Corti, Maria Teresa Lupo Stanghellini, Luca Vago, Jacopo Peccatori, Massimo Clementi, Fabio Ciceri, Chiara Bonini
Journal: Blood (2016)
Bioprinting: 3D Bioprinting Human Induced Pluripotent Stem Cell Constructs for In Situ Cell Proliferation and Successive Multilineage Differentiation (Adv. Healthcare Mater. 17/2017)
Authors: Qi Gu, Eva Tomaskovic‐Crook, Gordon G. Wallace, Jeremy M. Crook
Journal: Advanced Healthcare Materials (2017)

The cover artwork for article number 1700175 represents novel tissue engineering by 3D bioprinting human induced pluripotent stem cells to create cell-laden constructs with the capacity to form ectodermal, endodermal and mesodermal tissues (exemplified by neuronal, lung and muscle cells) and therefore all tissues of the body. This method is introduced by Gordon G. Wallace, Jeremy M. Crook, and co-workers.
OAsis: An international phase I trial of obinutuzumab, venetoclax plus ibrutinib in relapsed/refractory mantle cell lymphoma.
Authors: Steven Le Gouill, Andrew Davies, Kamal Bouabdallah, David Chiron, Simon Rule
Journal: Journal of Clinical Oncology (2016)

TPS7583 Background: Mantle Cell Lymphoma (MCL) remains an incurable disease. MCL drug resistance are highly dependent on B-cell-receptor signaling, Bcl-2 and the microenvironment. Ibrutinibis a first-in-class Bruton’s tyrosine kinase (BTK) inhibitor approved in the US and EU for previously-treated MCL. It inhibits both tumor cell proliferation and binding to the microenvironment. Mechanisms of resistance to ibrutinib are unknown but BTK or BCR signaling cascade mutations have been described. (Chiron, Cancer Discovery). Venetoclax is a Bcl-2 inhibitor. The BCL-2 family proteins Mcl-1 and BCLXL are hypothesized to confer resistance to venetoclax. These proteins are upregulated by the tumor microenvironment but downregulated by Ibrutinib (Dasmahapatra, 2013, Touzeau, 2011, Chiron, 2015). Our preclinical investigations show that microenvironment-dependent long-term expansion and drug resistance to venetoclax are counteracted by obinutuzumab (type II glycoengineered humanized anti-CD20 antibody) and the obinutuzumab/venetoclax/ibrutinib combination is highly active against primary MCL cells. (Chiron et al submitted) The OAsIs trial (NCT02558816) has been designed to assess the safety, tolerability and efficacy of this combination. Methods: Oasis is a multicenter, non-randomised, phase I study for relapsed/refractory MCL and incorporates 2 steps. Step A evaluates the safety of obinutuzumab (1000mg IV C1D1, 8,15, C2-6 D1 and every 2 months until C24) plus ibrutinib (560mg/d until progression)(n = 9). Step B primary objective is to determine the MTD of obinutuzumab/venetoclax/ibrutinib. Venetoclax is administered from C2 (C2W1 100mg/d, C2W2 200mg/d, C2W3 400mg/d and C2W4-C6: 400, 600 or 800mg/d) (n = 24). Statistical design. A continual reassessment method (CRM) is used to allocate venetoclax doses at least (3 patients per dose-level). CRM estimation uses a hyperbolic tangent model that determines the dose administered. If no toxicity is observed, the dose is increased. The process is repeated until inclusion of 24 patients. The target dose-limiting toxicity is fixed at 33%. Enrolment started in November 2015. The first cohort of 3 patients in step A has been completed.
Host Factors in Human Carcinogenesis&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: John J. Mulvihill, M.D.
Journal: JNCI Journal of the National Cancer Institute (1982)

Journal Article Host Factors in Human Carcinogenesis Get access John J. Mulvihill, M.D. John J. Mulvihill, M.D. Clinical Epidemiology Branch Division of Cancer Cause and Prevention National Cancer Institute National Institutes of Health Public Health Service U.S. Department of Health and Human Services Bethesda, Maryland 20205 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 68, Issue 1, January 1982, Pages 173–174, https://doi.org/10.1093/jnci/68.1.173 Published: 01 January 1982
Reduction of Total Lipid-Protein Nitrogen Ratio of Mouse Epidermis by a Single Application of Methylcholanthrene&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: L. F. Wicks, V. Suntzeff
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Reduction of Total Lipid-Protein Nitrogen Ratio of Mouse Epidermis by a Single Application of Methylcholanthrene Get access L. F. Wicks, L. F. Wicks research fellow Search for other works by this author on: Oxford Academic PubMed Google Scholar V. Suntzeff V. Suntzeff research associate Barnard Free Skin and Cancer Hospital, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 2, October 1942, Pages 221–226, https://doi.org/10.1093/jnci/3.2.221 Published: 01 October 1942
Vitamin D Supplementation and Cardiovascular Disease Risk—Reply
Authors: Robert Scragg, Carlos A. Camargo
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis
Authors: N.L. Plantinga, A.M.G.A. de Smet, E.A.N. Oostdijk, E. de Jonge, C. Camus, W.A. Krueger, D. Bergmans, J.B. Reitsma, M.J.M. Bonten
Journal: Clinical Microbiology and Infection (2017)

Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) improved intensive care unit (ICU), hospital and 28-day survival in ICUs with low levels of antibiotic resistance. Yet it is unclear whether the effect differs between medical and surgical ICU patients.In an individual patient data meta-analysis, we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects.Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16 528 hospital admissions and 17 884 ICU admissions for complete case analysis. Compared to standard care or placebo, the pooled adjusted odds ratios for hospital mortality was 0.82 (95% confidence interval (CI) 0.72-0.93) for SDD and 0.84 (95% CI 0.73-0.97) for SOD. Compared to SOD, the adjusted odds ratio for hospital mortality was 0.90 (95% CI 0.82-0.97) for SDD. The effects on hospital mortality were not modified by type of ICU admission (p values for interaction terms were 0.66 for SDD and control, 0.87 for SOD and control and 0.47 for SDD and SOD). Similar results were found for ICU mortality.In ICUs with low levels of antibiotic resistance, the effectiveness of SDD and SOD was not modified by type of ICU admission. SDD and SOD improved hospital and ICU survival compared to standard care in both patient populations, with SDD being more effective than SOD.
Using hyperpolarized <sup>129</sup>Xe MRI to quantify regional gas transfer in idiopathic pulmonary fibrosis
Authors: Jennifer M Wang, Scott H Robertson, Ziyi Wang, Mu He, Rohan S Virgincar, Geoffry M Schrank, Rose Marie Smigla, Thomas G O’Riordan, John Sundy, Lukas Ebner, Craig R Rackley, Page McAdams, Bastiaan Driehuys
Journal: Thorax (2017)

Assessing functional impairment, therapeutic response and disease progression in patients with idiopathic pulmonary fibrosis (IPF) continues to be challenging. Hyperpolarized
Abstract 15068: Atenolol versus Losartan in Marfan Syndrome: A Meta-Analysis of Randomized Controlled Trials
Authors: Sharan Sharma, Khagendra Dahal
Journal: Circulation (2016)

Background: Aortic root dissection is the leading cause of death in Marfan syndrome. Beta-adrenergic blockers have been proposed as a preferred agent in Marfan syndrome to reduce aortic complicatio...
Dual activating FLT3-ITD/TKD mutations found in patients with AML induce resistance to FLT3 PTK inhibitors and daunorubicin by upregulation of Bcl-xL
Authors: Ksenia Bagrintseva, Stefanie Geisenhof, Ruth Schwab, Sabine Eichenlaub, Wolfgang Hiddemann, Karsten Spiekermann
Journal: Blood (2003)
Efficacy and safety of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel pamoate, and albendazole plus oxantel pamoate against hookworm and concomitant soil-transmitted helminth infections in Tanzania and Côte d'Ivoire: a randomised, controlled, single-blinded, non-inferiority trial
Authors: Wendelin Moser, Jean T Coulibaly, Said M Ali, Shaali M Ame, Amour K Amour, Richard B Yapi, Marco Albonico, Maxim Puchkov, Jörg Huwyler, Jan Hattendorf, Jennifer Keiser
Journal: The Lancet Infectious Diseases (2017)
Tissue-Specific Immunity at the Oral Mucosal Barrier
Authors: Niki M. Moutsopoulos, Joanne E. Konkel
Journal: Trends in Immunology (2017)

The oral mucosal barrier is constantly exposed to a plethora of triggers requiring immune control, including a diverse commensal microbiome, ongoing damage from mastication, and dietary and airborne antigens. However, how these tissue-specific cues participate in the training of immune responsiveness at this site is minimally understood. Moreover, the mechanisms mediating homeostatic immunity at this interface are not yet fully defined. Here we present basic aspects of the oral mucosal barrier and discuss local cues that may modulate and train local immune responsiveness. We particularly focus on the immune cell network mediating immune surveillance at a specific oral barrier, the gingiva - a constantly stimulated and dynamic environment where homeostasis is often disrupted, resulting in the common inflammatory disease periodontitis.
Assesment of EGFR somatic kinase domain mutant tumor response to erlotinib using FDG-PET imaging
Authors: Kendall Carey, Annie Ogasawara, Maria Romero, Jed Ross, Leanne McFarland, Simon Williams
Journal: Cancer Research (2006)

3466  Somatic mutations in the epidermal growth factor receptor (EGFR) have been identified in non-small lung cancer patients and are correlated with enhanced sensitivity to the tyrosine kinase domain inhibitor erlotinib (OSI-774, TarcevaR). Erlotinib is a selective, orally available competitive inhibitor for ATP binding to the EGFR tyrosine kinase domain and has been approved for use in the treatment of advanced non-small cell lung cancer for patients who have failed at least one prior chemotherapy regimen. To evaluate the biological role of EGFR somatic mutations and the influence of these mutations on erlotinib sensitivity, we have generated stable NR6 cell lines expressing equivalent levels of EGFR, and two clinically detected EGFR somatic mutations, EGFR-L858R and EGFR-Del(746-752). NR6 cells do not express EGFR or detectable levels of ErbB2, ErbB3, or ErbB4. Both the EGFR-L858R and EGFR-Del(746-752) mutations facilitate ligand-dependent anchorage-independent growth in soft agar, confer a higher proliferative rate, form tumors in immune compromised mice, and are differentially sensitive to erlotinib compared to wild-type EGFR both in vivo and in vitro. In this study, we have used positron emission tomography (PET) imaging of 2-fluoro-2-deoxy-D-glucose (FDG) uptake to evaluate the difference in metabolic activity of EGFR, EGFR-L858R, and EGFR-Del(746-750) expressing tumors in immune deficient mice. Tumors expressing wild-type and mutant EGFR have similar glucose uptake rates except after a period of overnight fasting where tumors expressing EGFR kinase domain mutations demonstrate a 2-fold increase in FDG uptake compared to wild-type EGFR tumors (p=0.001). 3H-FDG uptake in EGFR expressing cells is significantly higher compared to the NR6 parental cell line and erlotinib differentially inhibits glucose uptake in vitro for EGFR compared to EGFR-L858R and EGFR Del(746-752) (IC50=175nM, 85nM, and 9nM respectively). We find that FDG-PET is useful for evaluating the sensitivity of these mutations and the EGFR Del(746-752) and L858R mutations are significantly more sensitive to erlotinib compared to wild-type EGFR tumors. At the maximally effective dose of erlotinib (150mg/kg), the normalized glucose uptake decreased by 33% at 24 hours post-treatment and 57% at 48 hours in the tumors expressing EGFR-Del(746-752) compared with no significant decrease in the EGFR tumors. Our data indicate that EGFR somatic mutations influence EGFR signaling pathways that modulate glucose metabolism. These findings suggest FDG-PET is a sensitive method to evaluate the effects of small molecule kinase inhibitors and may be useful in evaluating clinical responders to erlotinib therapy.
Cystathionine β‐synthase is required for body iron homeostasis
Authors: Yu‐Fu Zhou, Xiao‐Mei Wu, Gan Zhou, Ming‐dao Mu, Fa‐Li Zhang, Fe‐Mi Li, Christopher Qian, Fang Du, Wing‐Ho Yung, Zhong‐Ming Qian, Ya Ke
Journal: Hepatology (2017)

Cystathionine β‐synthase (CBS) catalyzes the transsulfuration pathway and contributes, among other functions, to the generation of hydrogen sulfide. In view of the exceptionally high expression of CBS in the liver and the common interleukin‐6 pathway used in the regulatory systems of hydrogen sulfide and hepcidin, we speculate that CBS is involved in body iron homeostasis. We found that CBS knockout (CBS −/− ) mice exhibited anemia and a significant increase in iron content in the serum, liver, spleen, and heart, along with severe damage to the liver, displaying a hemochromatosis‐like phenotype. A high level of hepatic and serum hepcidin was also found. A major cause of the systemic iron overload is the reduced iron usage due to suppressed erythropoiesis, which is consistent with an increase in interleukin‐6 and reduced expression of erythropoietin. Importantly, in the liver, absence of CBS caused both a reduction in the transcriptional factor nuclear factor erythroid 2–related factor‐2 and an up‐regulation of hepcidin that led to a decrease in the iron export protein ferroportin 1. The resulting suppression of iron export exacerbates iron retention, causing damage to hepatocytes. Finally, administration of CBS‐overexpressing adenovirus into CBS mutant mice could partially reverse the iron‐related phenotype. Conclusion : Our findings point to a critical role of CBS in iron homeostasis of the body, and the liver in particular; it is likely that a hemochromatosis‐like phenotype in patients can be induced by aberration not only in the expression of key molecules in the hepcidin pathway but also of those related to CBS. (H epatology 2018;67:21‐35)