tbuckley/cabot-search huggingface dataset:
Effect of nintedanib, a triple angiokinase inhibitor, on EGFR and HER2 in colorectal cancer (CRC) models, and rational for its combinations with the ErbB family blocker afatinib.
Authors: Annette K. Larsen, Aimery de Gramont, Aude Batistella, Arnaud Afchain, Paul Mésange, Virginie Poindessous
Journal: Journal of Clinical Oncology (2014)

485 Background: We have recently shown that combinations of afatinib, a pan-HER/ErbB blocker, and nintedanib, a triple angiokinase (VEGFR, FGFR, PDGFR) inhibitor show synergistic activity in CRC models (Poindessous et al., Clin Cancer Res. 17:6522, 2011). However, the mechanistic basis for the synergistic effects of the combination is incompletely understood. EGFR is activated following exposure to a wide variety of therapeutic modalities including ionizing irradiation and irinotecan. We speculated that nintedanib exposure could also activate EGFR signaling which might explain the synergistic activity of the combination. Methods: Mice with human CRC xenografts were treated with nintedanib and afatinib alone or in combination and the influence on tumor growth, viability and the presence of phosphorylated HER family members was determined. Different scheduling regimens were explored to identify an administration schedule which combined optimal antitumor activity with minimal toxic side effects. Results: We here show that nintedanib treatment results in activation of EGFR and HER2 in multiple CRC xenograft models in a dose-dependent manner. Among the different regimens tested, continuous nintedanib with administration of afatinib every second week proved almost as efficient as continuous administration of the two agents together and was less toxic. Finally, nintedanib plus afatinib was superior to nintedanib alone in three different tumor xenografts with mutant KRAS. Conclusions: We here report that prolonged exposure to nintedanib, a small molecule angiogenesis inhibitor, is accompanied by activation of EGFR and HER2. Accordingly, afatinib, an ErbB family blocker, was synergistic with nintedanib. We subsequently identified a novel regimen for optimizing the antitumor effects of the combination with limited toxic side effects and showed that this regimen is active in four different CRC tumor models including three with mutant KRAS. These findings provide a rationale for clinical trials of the two small molecules, even in patients with mutant KRAS.
Outcome of Patients with Multiple Myeloma (MM) After 1st Relapse Following Front-Line Treatment with Autologous Stem Cell Transplantation (ASCT): Impact of Early Reduced Intensity Allogeneic Transplantation (RICALLO)
Authors: Reza Tabrizi, Stephane Vigouroux, Gerald Marit, Arnaud Pigneux, Cyril Melot, Thibaut Leguay, Krimo Bouabdallah, Marie-Sarah Dilhuydy, Anna Schmitt, Noel Milpied
Journal: Blood (2011)
Phase I dose-finding study of biweekly oxaliplatin (E) in combination with gemcitabine (G), 5-fluorouracil (5-FU), leucovorin (LV) and irinotecan (G-FLIE) in patients with solid tumors
Authors: A. J. Olszewski, S. Malamud, M. L. Grossbard, T. Mirzoyev, M. Dietrich, A. Thurakal, T. Rodriguez, P. Kozuch
Journal: Journal of Clinical Oncology (2005)

4202 Background: This phase I dose-finding study of oxaliplatin in combination with fixed doses of gemcitabine, 5-FU/LV and irinotecan was initiated based on encouraging clinical data with G-FLIP (P = cisplatin) in the therapy of solid tumors, particularly pancreatic carcinoma. Patients and Methods: To date 12 patients have been enrolled with the following cancers: pancreatic (n=4), gastric (n=3), cholangio (n=2), head and neck carcinoma (n=1), and adenocarcinoma of unknown primary (CUP, n=2). Median patient age was 61 years (range 44–75) and median Karnofsky performance status was 80. Treatment consisted of biweekly cycles of sequential gemcitabine 500mg/m2, irinotecan 120 mg/m2, bolus 5-FU 400mg/m2 and LV 300mg on Day 1, a 24-hour 5-FU infusion 1500mg/m2, followed by oxaliplatin per dose escalation on Day 2. The oxaliplatin starting dose was 50 mg/m2, escalated by 10mg/m2 in cohorts of 3 pts until a maximum tolerated dose (MTD) not to exceed 85 mg/m2 was defined. Dose limiting toxicity (DLT) was defined as grade >3 non-hematologic toxicity or neutropenic fever. Results: To date patients have received a median of 4 cycles (range 1–11) at oxaliplatin dose levels 50 (n=6), 60(n=3), 70 mg/m2 (n=3). Of the 10 patients eligible for toxicity assessment, 3 experienced grade 3–4 adverse effects: stomatitis (n=1, dose level 0), anemia and neutropenia. Eight patients are evaluable for response per RECIST criteria: 1 SD (CUP), 5 PR (pancreatic, gastric (2), CUP, head and neck ca) were attained. Conclusion: G-FLIE is a novel outpatient chemotherapy regimen for treatment of solid tumors with acceptable toxicity at oxaliplatin doses up to of 70 mg/m2. Dose escalation as well as toxicity/efficacy evaluation continue. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Eli Lilly, Pfizer, Sanofi-Synthelabo Sanofi-Synthelabo
Association of Alzheimer Disease Susceptibility Variants and Gene Expression in the Human Brain
Authors: Qinghua Jiang, Yang Hu, Guiyou Liu
Journal: JAMA Neurology (2016)

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 Neurology 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 Neurology journal
Mutation Of The Divalent Metal Transporter (Dmt1) Gene Results In Inefficient Induction Of The Erythroid Transcriptional Program Due To Latter Onset Of GATA-1 and Epor Expression
Authors: Nikola Curik, Pavel Burda, Tomas Zikmund, Filipp Savvulidi, Monika Horvathova, John Strouboulis, Vladimir Divoky, Tomas Stopka
Journal: Blood (2013)
Case 18-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Charles H. Weingarten, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

Presentation of Case First admission. A fifty-six-year-old man was admitted to the hospital because of difficulty in swallowing.He had been unable to swallow solid food for approximately six weeks before entry and had lost 50 pounds in weight. Exertional dyspnea had been present for one year.For forty years he had smoked 2 packages of cigarettes a day. There was no history of hypertension, diabetes or tuberculosis. He had worked as a photoengraver.On physical examination the patient was cachectic and dysarthric. The eyes were normal. There was a large ulcerating lesion involving the right posterior portion of . . .
Multidrug-resistant tuberculosis in children in northwest Russia: an observational cohort study
Authors: Polina A. Smirnova, Anna Turkova, Elena I. Nikishova, James A. Seddon, Elizabeth Chappell, Olga A. Zolotaya, Oxana M. Mironuk, Andrey O. Maryandyshev
Journal: European Respiratory Journal (2016)

Russia has the third highest absolute number of multidrug-resistant (MDR) tuberculosis (TB) cases in the world [1], yet little is known about the scale of childhood MDR-TB in the country; available publications are limited to small case series in older children [2, 3]. Successful treatment outcomes for children with MDR-TB vary widely in other settings, ranging from 53% to 97% [4]. High proportion of children with MDR-TB had favourable outcome (90%) with early diagnosis and treatment initiation <http://ow.ly/2eq5302gWmr> We thank all the staff of the Arkhangelsk Regional Tuberculosis Dispensary, and children and their parents who made this study possible.
CCL2 Produced by the Glioma Microenvironment Is Essential for the Recruitment of Regulatory T Cells and Myeloid-Derived Suppressor Cells
Authors: Alan L. Chang, Jason Miska, Derek A. Wainwright, Mahua Dey, Claudia V. Rivetta, Dou Yu, Deepak Kanojia, Katarzyna C. Pituch, Jian Qiao, Peter Pytel, Yu Han, Meijing Wu, Lingjiao Zhang, Craig M. Horbinski, Atique U. Ahmed, Maciej S. Lesniak
Journal: Cancer Research (2016)

In many aggressive cancers, such as glioblastoma multiforme, progression is enabled by local immunosuppression driven by the accumulation of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). However, the mechanistic details of how Tregs and MDSCs are recruited in various tumors are not yet well understood. Here we report that macrophages and microglia within the glioma microenvironment produce CCL2, a chemokine that is critical for recruiting both CCR4+ Treg and CCR2+Ly-6C+ monocytic MDSCs in this disease setting. In murine gliomas, we established novel roles for tumor-derived CCL20 and osteoprotegerin in inducing CCL2 production from macrophages and microglia. Tumors grown in CCL2-deficient mice failed to maximally accrue Tregs and monocytic MDSCs. In mixed-bone marrow chimera assays, we found that CCR4-deficient Treg and CCR2-deficient monocytic MDSCs were defective in glioma accumulation. Furthermore, administration of a small-molecule antagonist of CCR4 improved median survival in the model. In clinical specimens of glioblastoma multiforme, elevated levels of CCL2 expression correlated with reduced overall survival of patients. Finally, we found that CD163-positive infiltrating macrophages were a major source of CCL2 in glioblastoma multiforme patients. Collectively, our findings show how glioma cells influence the tumor microenvironment to recruit potent effectors of immunosuppression that drive progression. Cancer Res; 76(19); 5671-82. ©2016 AACR.
Prevalence of Differentiated Thyroid Cancer in Autopsy Studies Over Six Decades: A Meta-Analysis
Authors: Luis Furuya-Kanamori, Katy J.L. Bell, Justin Clark, Paul Glasziou, Suhail A.R. Doi
Journal: Journal of Clinical Oncology (2016)

Differentiated thyroid cancer (DTC) incidence has been reported to have increased three- to 15-fold in the past few decades. It is unclear whether this represents overdiagnosis or a true increase in incidence. Therefore, the current study aimed to estimate the prevalence of incidental DTC in published autopsy series and determine whether this prevalence has been increasing over time.PubMed, Embase, and Web of Science were searched from inception to December 2015 for relevant studies. Two authors searched for all autopsy studies that had included patients with no known history of thyroid pathology and reported the prevalence of incidental DTC (iDTC). Two authors independently extracted the data, and discrepancies were resolved by another author. The pooled prevalence of iDTC was assessed using a fixed-effects meta-analysis model with robust error variance. The time effect was studied using an inverse-variance weighted logit-linear regression model with robust error variance and a time variable.Thirty-five studies, conducted between 1949 and 2007, met the inclusion criteria and contributed 42 data sets and 12,834 autopsies. The prevalence of iDTC among the partial and whole examination subgroups was 4.1% (95% CI, 3.0% to 5.4%) and 11.2% (95% CI, 6.7% to 16.1%), respectively. Once the intensiveness of thyroid examination was accounted for in the regression model, the prevalence odds ratio stabilized from 1970 onward, and no time effect was observed.The current study confirms that iDTC is common, but the observed increasing incidence is not mirrored by prevalence within autopsy studies and, therefore, is unlikely to reflect a true population-level increase in tumorigenesis. This strongly suggests that the current increasing incidence of iDTC most likely reflects diagnostic detection increasing over time.
Ganciclovir Suppresses Human T Lymphocyte Proliferation In Vitro.
Authors: Minoo Battiwalla, Yiyuan Wu, Ryotaro Nakamura, Marija Radovic, Rajinder P.S. Bajwa, Anjana Elefante, Brahm Segal, Nikolaos Almyroudis, Philip L. McCarthy
Journal: Blood (2005)
An evaluation of MIST 1 as an indicator of plasmacytic differentiation.
Authors: C. C. S. Yeung, J. Mills, J. Frater
Journal: Journal of Clinical Oncology (2011)

8084 Background: Currently available plasma cell markers include CD138 and CD38. However, CD38 is not specific to plasma cells and can be expressed by other hematopoietic cells, and rare CD138 negative plasma cell neoplasms may render their diagnoses exceedingly difficult. MIST 1 is a transcription factor expressed by mouse and human neoplastic and non-neoplastic plasma cells. Our goals were to compare MIST1 expression to CD38/ CD138 in neoplasms with plasmacytic differentiation, assess reactivity in normal samples and nonplasmacytic cell lineages, and to determine if MIST1 is expressed in CD138 negative plasma cell neoplasms. Methods: 26 neoplasms with plasma cell differentiation (marginal zone lymphoma, lymphoplasmacytic lymphoma, plasmablastic lymphoma, plasma cell neoplasm) and 2 non-neoplastic cases were tested with MIST1 immunohistochemistry. CD138 /38 expression for each case was compared to MIST1 staining. Results: MIST1 immunohistochemistry results are summarized in the Table. CD38 and/or CD138 were positive in all cases. Plasma cells were MIST1 positive in all cases. All other cell lineages were MIST1 negative, except MZL and LPL; in which MIST1 highlighted some of the lymphocytes, presumably the ones undergoing plasmacytic differentiation. Conclusions: MIST1 is a sensitive and specific marker of plasmacytic differentiation. There is nearly 100% concordance between CD138 and MIST1 expression; however, one plasmablastic lymphoma showed MIST1 positivity and no CD138 expression, suggesting MIST1 may be useful in certain CD138-negative cases. In MZL and LPL, MIST1 highlights some of the lymphocytes in lymphomas with plasmacytic differentiation. MIST 1 immunostaining characteristics. No. of cases MIST1 MZL 6 Strong nuclear stain in plasma cells and lymphocytes (3/6), strong nuclear stain in plasma cells (3/6) LPL 2 Strong nuclear stain in plasma cells and lymphocytes (2/2) PBL 2 One strong and one weak nuclear stain PCN 15 All plasma cells with strong nuclear stain CD138 neg PB 1 Weak nuclear stain in plasma cells Normal 2 Nuclear staining of scattered single plasma cells
High-dose chemotherapy followed by allogeneic stem cell transplantation in high-risk relapsed and refractory aggressive non-Hodgkin lymphoma: Results of a prospective study of the German high-grade non-Hodgkin lymphoma study group.
Authors: Bertram Glass, Justin Hasenkamp, Gerald Wulf, Peter Dreger, Michael Pfreundschuh, Martin Gramatzki, Gerda Silling, Christian Wilhelm, Matthias Zeis, Sebastian Pfeiffer, Lorenz Trümper, Norbert Schmitz
Journal: Journal of Clinical Oncology (2012)

8004 Background: The role of allogeneic stem cell transplantation (alloSCT) in high-risk aggressive NHL is poorly defined; the role of graft-versus-lymphoma effect is unclear. Reduced intensity conditioning has shown limited efficacy in patients with refractory disease. Methods: Patients with primary refractory disease, early relapse (&lt;12 months) or relapse after autologous SCT of aggressive B-cell (n=61) or T-cell (n=23) NHL were enrolled from June 2004 to March 2009. Myeloablative conditioning (fludarabine 125mg/m 2 , busulfan 12mg/kg, cyclophosphamide 120 mg/kg) was followed by alloSCT from related (n=24) or unrelated (n=60) donors. 57/84 patients received a 10 HLA-loci compatible graft. Results: Overall survival at 3 years was 42% (95% CI, 31% to 52%), progression-free survival (PFS) was 40% (95% CI 29% to 50%). Non-relapse mortality (NRM) was 12% at 100 days and 35% at one year. Graft-versus-host disease (GVHD) and infection were the predominant causes of NRM. Relapse rate was 30% with latest relapse at day +327. Patients with an HLA fully compatible donor (plus ATG with unrelated donors) (n=40) had the best outcome (NRM at 1y 10.4 vs 57.2%, PFS at 3y 64.7% vs 31.8%, p &lt; 0.0001). GVHD &gt; grade I correlated with improved PFS (HR 0.45, p=0.0088). Patients with refractory disease or early relapse (n=60) experienced PFS at 3y of 33%. Conclusions: Lymphoma-debulking (high-dose) chemotherapy followed by alloSCT shows excellent results in heavily pretreated patients with early relapse or primary refractory aggressive lymphoma. There was evidence of graft-versus-lymphoma activity in this setting. For patients with a fully matched (10/10) related or unrelated donor the results compare favorably to autoSCT or alloSCT following reduced-intensity conditioning.
SoxF Transcription Factors Are Positive Feedback Regulators of VEGF Signaling
Authors: Kangsan Kim, Il-Kug Kim, Jee Myung Yang, Eunhyeong Lee, Bong Ihn Koh, Sukhyun Song, Junseong Park, Sungsu Lee, Chulhee Choi, Jin Woo Kim, Yoshiaki Kubota, Gou Young Koh, Injune Kim
Journal: Circulation Research (2016)

Vascular endothelial growth factor (VEGF) signaling is a key pathway for angiogenesis and requires highly coordinated regulation. Although the Notch pathway-mediated suppression of excessive VEGF activity via negative feedback is well known, the positive feedback control for augmenting VEGF signaling remains poorly understood. Transcription factor Sox17 is indispensable for angiogenesis, but its association with VEGF signaling is largely unknown. The contribution of other Sox members to angiogenesis also remains to be determined.To reveal the genetic interaction of Sox7, another Sox member, with Sox17 in developmental angiogenesis and their functional relationship with VEGF signaling.Sox7 is expressed specifically in endothelial cells and its global and endothelial-specific deletion resulted in embryonic lethality with severely impaired angiogenesis in mice, substantially overlapping with Sox17 in both expression and function. Interestingly, compound heterozygosity for Sox7 and Sox17 phenocopied vascular defects of Sox7 or Sox17 homozygous knockout, indicating that the genetic cooperation of Sox7 and Sox17 is sensitive to their combined gene dosage. VEGF signaling upregulated both Sox7 and Sox17 expression in angiogenesis via mTOR pathway. Furthermore, Sox7 and Sox17 promoted VEGFR2 (VEGF receptor 2) expression in angiogenic vessels, suggesting a positive feedback loop between VEGF signaling and SoxF.Our findings demonstrate that SoxF transcription factors are indispensable players in developmental angiogenesis by acting as positive feedback regulators of VEGF signaling.
EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer
Authors: Philip Cornford, Joaquim Bellmunt, Michel Bolla, Erik Briers, Maria De Santis, Tobias Gross, Ann M. Henry, Steven Joniau, Thomas B. Lam, Malcolm D. Mason, Henk G. van der Poel, Theo H. van der Kwast, Olivier Rouvière, Thomas Wiegel, Nicolas Mottet
Journal: European Urology (2016)
298P A study of comparison of prognostic models in peripheral T cell lymphoma in a tertiary care centre in South India
Authors: M.S.U. Namratha, D. Lokanatha, K. Lakshmaiah, G. Babu, L.A. Jacob, S. Babu, K. Lokesh, S.C. Saldanha
Journal: Annals of Oncology (2015)
Helmet use and risk of head injuries in alpine skiers and snowboarders: changes after an interval of one decade
Authors: Steinar Sulheim, Arne Ekeland, Ingar Holme, Roald Bahr
Journal: British Journal of Sports Medicine (2016)

Background In a previous study, we concluded that a safety helmet can reduce the risk for head injury by 60%. Other studies reported similar effects, resulting in a general recommendation to wear a helmet while skiing or snowboarding. Aim To determine the effect of the expected increased helmet wear on the risk of head injury one decade after the recommendation. Methods Ski patrols reported injury cases in major Norwegian alpine ski resorts. Injury type, helmet use and other risk factors were recorded. A multiple logistic regression analysis was used to assess the relation between individual risk factors and the risk of head injuries by comparing head injured skiers (cases) with skiers and snowboarders who reported other injuries (controls). Results Helmet use was associated with improved odds for head injuries (OR: 0.45, 95% CI 0.34 to 0.60; p&lt;0.001) in 2002; this effect was attenuated in 2010 (OR: 0.79, 95% CI 0.63 to 0.98; p=0.02), and not significant in 2011 (OR: 0.80, 95% CI 0.60 to 1.06; p=0.12). For potentially severe head injuries, the protective effect of using a helmet was better sustained over the observation period, from an OR of 0.44 (95% CI 0.28 to 0.68, p&lt;0.001) in 2002 to an OR of 0.74 (95% CI 0.57 to 0.97, p=0.02) in 2010 and 0.67 (95% CI 0.47 to 0.96; p=0.03) in 2011. Conclusions We observed an unexpected reduction in the protective effect of a skiing helmet. This may be due to new skiing trends in the alpine resorts.
Survey of diagnostic and typing capacity for Clostridium difficile infection in Europe, 2011 and 2014
Authors: Sofie M van Dorp, Daan W Notermans, Jeroen Alblas, Petra Gastmeier, Silja Mentula, Elisabeth Nagy, Patrizia Spigaglia, Katiusha Ivanova, Fidelma Fitzpatrick, Frédéric Barbut, Trefor Morris, Mark H Wilcox, Pete Kinross, Carl Suetens, Ed J Kuijper
Journal: Eurosurveillance (2016)

Suboptimal laboratory diagnostics for Clostridium difficile infection (CDI) impedes its surveillance and control across Europe. We evaluated changes in local laboratory CDI diagnostics and changes in national diagnostic and typing capacity for CDI during the European C. difficile Infection Surveillance Network (ECDIS-Net) project, through cross-sectional surveys in 33 European countries in 2011 and 2014. In 2011, 126 (61%) of a convenience sample of 206 laboratories in 31 countries completed a survey on local diagnostics. In 2014, 84 (67%) of these 126 laboratories in 26 countries completed a follow-up survey. Among laboratories that participated in both surveys, use of CDI diagnostics deemed 'optimal' or 'acceptable' increased from 19% to 46% and from 10% to 15%, respectively (p < 0.001). The survey of national capacity was completed by national coordinators of 31 and 32 countries in 2011 and 2014, respectively. Capacity for any C. difficile typing method increased from 22/31 countries in 2011 to 26/32 countries in 2014; for PCR ribotyping from 20/31 countries to 23/32 countries, and specifically for capillary PCR ribotyping from 7/31 countries to 16/32 countries. While our study indicates improved diagnostic capability and national capacity for capillary PCR ribotyping across European laboratories between 2011 and 2014, increased use of 'optimal' diagnostics should be promoted.
STAT1 Gain-of-Function in Patients with Chronic Mucocutaneous Candidiasis Can be Detected By the Excessive Phosphorylation of STAT1 in Peripheral Blood Monocytes
Authors: Yoko Mizoguchi, Miyuki Tsumura, Satoshi Okada, Osamu Hirata, Shizuko Minegishi, Nobuyuki Hyakuna, Jean-Laurent Casanova, Tomohiro Morio, Masao Kobayashi
Journal: Blood (2014)