tbuckley/cabot-search huggingface dataset:
Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis
Authors: Vidya Ganapathy, Rongrong Ge, Alison Grazioli, Wen Xie, Whitney Banach-Petrosky, Yibin Kang, Scott Lonning, John McPherson, Jonathan M Yingling, Swati Biswas, Gregory R Mundy, Michael Reiss
Journal: Molecular Cancer (2010)

Abstract Background Transforming Growth Factor β (TGF-β) plays an important role in tumor invasion and metastasis. We set out to investigate the possible clinical utility of TGF-β antagonists in a human metastatic basal-like breast cancer model. We examined the effects of two types of the TGF-β pathway antagonists (1D11, a mouse monoclonal pan-TGF-β neutralizing antibody and LY2109761, a chemical inhibitor of TGF-β type I and II receptor kinases) on sublines of basal cell-like MDA-MB-231 human breast carcinoma cells that preferentially metastasize to lungs (4175TR, 4173) or bones (SCP2TR, SCP25TR, 2860TR, 3847TR). Results Both 1D11 and LY2109761 effectively blocked TGF-β-induced phosphorylation of receptor-associated Smads in all MDA-MB-231 subclones in vitro . Moreover, both antagonists inhibited TGF-β stimulated in vitro migration and invasiveness of MDA-MB-231 subclones, indicating that these processes are partly driven by TGF-β. In addition, both antagonists significantly reduced the metastatic burden to either lungs or bones in vivo , seemingly independently of intrinsic differences between the individual tumor cell clones. Besides inhibiting metastasis in a tumor cell autonomous manner, the TGF-β antagonists inhibited angiogenesis associated with lung metastases and osteoclast number and activity associated with lytic bone metastases. In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer. Conclusions In aggregate, these studies support the notion that TGF-β plays an important role in both bone-and lung metastases of basal-like breast cancer, and that inhibiting TGF-β signaling results in a therapeutic effect independently of the tissue-tropism of the metastatic cells. Targeting the TGF-β pathway holds promise as a novel therapeutic approach for metastatic basal-like breast cancer.
Pulmonary arterial hypertension in patients treated with interferon
Authors: Maura Prella, Patrick Yerly, Laurent P. Nicod, John-David Aubert
Journal: European Respiratory Journal (2015)

We read with interest the article by Savale et al . [1] reporting pulmonary arterial hypertension (PAH) associated with treatment with interferon (IFN) in 53 patients from the French PAH registry. As noted by the authors, patients receiving IFN-α have confounding factors such as portal hypertension or HIV infection that may classify them in group 1.4.3 or 1.4.2, respectively, according to the 2013 updated pulmonary hypertension classification [2]. Therefore, "pure" cases, such as those treated with IFN-β for multiple sclerosis are important to identify in order to strengthen the causal relationship between the suspected drug and PAH. Suspected drug-induced PAH cases should be reported to pharmacovigilance networks and regulatory agencies <http://ow.ly/TthdY>
Soluble Fas Levels in Sera of Bone Marrow Transplantation Recipients Are Increased During Acute Graft-Versus-Host Disease But Not During Infections
Authors: Linda M. Liem, Thea van Lopik, Annemarie E.M. van Nieuwenhuijze, Hans C. van Houwelingen, Lucien Aarden, Els Goulmy
Journal: Blood (1998)
WITHDRAWN: Self-assembled docetaxel prodrug-based nanomedicine for cancer therapy: Synthesis, characterization and anticancer valuation in vitro and in vivo
Authors: Yongjun Wang, Guolian Ren, Dan Liu, Zhonggui He
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
No apparent transmission of transgenic α–synuclein into nigrostriatal dopaminergic neurons in multiple mouse models
Authors: Namratha Sastry, Wang Zheng, Guoxiang Liu, Helen Wang, Xi Chen, Michael Cai, Parth Contractor, Carmelo Sgobio, Lixin Sun, Chengsong Xie, Huaibin Cai
Journal: Translational Neurodegeneration (2015)

α–synuclein (α–syn) is the main component of intracytoplasmic inclusions deposited in the brains of patients with Parkinson’s disease (PD) and certain other neurodegenerative disorders. Recent studies have explored the ability of α–syn to propagate between or across neighboring neurons and supposedly “infect” them with a prion–like mechanism. However, much of this research has used stereotaxic injections of heterologous α–syn fibrils to induce the spreading of inclusions in the rodent brains. Whether α–syn is able to transmit from the host cells to their neighboring cells in vivo is unclear. Using immunestaining, we examined the potential propagation of α–syn into nigrostriatal dopaminergic (DA) neurons in three lines of transgenic mice that overexpress human wild–type α–syn (hα–syn) in different neuron populations. After testing for three different routes by which hα–syn propagation might occur, we were unable to find any evidence that hα–syn behaved like a prion and could be transmitted overtime into the DA neurons initially lack of hα–syn expression. In transgenic mice hα–syn does not have the ability to propagate at pathologically significant levels between or across neurons. It must be noted that these observations do not disprove the studies that show its prion–like qualities, but rather that propagation is not detectable in transgenic models that do not use any injections of heterologous proteins or viral vectors to induce a spreading state.
Système Européen de Surveillance de la Résistance Antimicrobienne (EARSS) : objectifs et organisation
Authors: W. Goettsch
Journal: Eurosurveillance (1999)

Pour etre efficace, une surveillance europeenne doit beneficier de l’accord de tous les participants et de leur participation active  concluait la conference europeenne sur la necessite d’une surveillance des microorganismes resistants (the microbial threat ) qui s’est tenue au Danemark en septembre 1998 (1). Les profils de resistance aux antibiotiques sont tres variables d’un pays a l’autre au sein de l’Union Europeenne (2,3).
The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells
Authors: Jean Franciesco Vettorazzi, Rosane Aparecida Ribeiro, Patricia Cristine Borck, Renato Chaves Souto Branco, Sergi Soriano, Beatriz Merino, Antônio Carlos Boschero, Angel Nadal, Ivan Quesada, Everardo Magalhães Carneiro
Journal: Metabolism (2015)
A pilot study to assess the ability of an orally available selective thromboxane synthase inhibitor to improve renal function in cyclosporine-treated renal transplant recipients.
Authors: M R Weir, D K Klassen, J F Burdick
Journal: Journal of the American Society of Nephrology (1992)

Six cyclosporine (cyclosporine A [CsA])-treated renal transplant patients (4.3 +/- 0.6 months posttransplantation) were studied to see if selective urinary thromboxane (TX) inhibition with CGS 12970 (TX synthase inhibitor) would improve renal function and lessen CsA-induced decrements in RPF and GFR as measured by [99Tc]DTPA and [131I]hippuran clearances. The baseline trough CsA levels of the patients were 208 +/- 92 ng/mL. Before treatment with CGS 12970 (100 mg twice a day for 7 days), all drugs known to affect renal function or CsA pharmacokinetics were stopped. CGS 12970 therapy did not alter RPF (203 +/- 17 pre versus 200 +/- 15 mL/min post), GFR (38.5 +/- 3.2 pre versus 38.2 +/- 3.9 mL/min post), or serum creatinine (creat) (1.9 +/- .06 pre versus 1.8 +/- 0.18 mg/dL post), despite an average of 81% suppression of urine TX (65 +/- 14 pg/mg of creat pre versus 12 +/- 4 pg/mg of creat post); P less than 0.01), as measured by gas chromatography/mass spectrometry. CGS 12970 had no significant effect on urinary 6-keto-prostaglandin F1 alpha levels (63 +/- 4 pg/mg of creat pre versus 85 +/- 25 pg/mg of creat post). CGS 12970 did not alter CsA pharmacokinetics or drug levels, blood pressure, weight, or serum electrolytes of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Palbociclib (PD0332991)—a Selective and Potent Cyclin-Dependent Kinase Inhibitor
Authors: Amy S. Clark, Thomas B. Karasic, Angela DeMichele, David J. Vaughn, Mark O’Hara, Rodolfo Perini, Paul Zhang, Priti Lal, Michael Feldman, Maryann Gallagher, Peter J. O’Dwyer
Journal: JAMA Oncology (2015)

Palbociclib (PD0332991) is a newly developed drug that received breakthrough designation and recent US Food and Drug Administration approval in combination with endocrine therapy in the treatment of hormone receptor positive, ERBB2-negative (formerly HER2 or HER2/neu) breast cancer in the first-line metastatic setting.Herein we describe the preclinical and translational data and early- and late-phase clinical trials in which palbociclib has been investigated in a broad array of tumor types. We discuss the pharmacodynamics, pharmacokinetics, toxic effects, and clinical response rates.On March 1, 2015, we conducted a review of the literature describing the development of palbociclib. We used the PubMed search terms "PD0332991," "palbociclib," and "CDK4/6 inhibitor" to find all published articles of interest, without limitation as to publication date.Palbociclib is a potent and specific oral cyclin-dependent kinase (CDK) 4/6 inhibitor that has strong preclinical data to support its activity in retinoblastoma protein-expressing tumors. Phase 1 trials have demonstrated safety, and phase 2 trials have shown single-agent activity in mantle-cell lymphoma, breast cancer, liposarcoma, and teratoma with reversible neutropenia as the main toxic effect. Addition of palbociclib to endocrine therapy improves progression-free survival in endocrine therapy-naïve and endocrine therapy-resistant metastatic settings.Palbociclib is well tolerated and has therapeutic potential for multiple cancers, including breast cancer, where its efficacy has been demonstrated alone and in combination with endocrine therapy. Additional combinations of palbociclib with endocrine therapy, chemotherapy, and targeted therapy have potential in various tumors, and phase 3 trials are under way.
Withdrawn: Surface modification of hydrogel microcapsules by MPEG and improvement of protein repellency by controlling graft density
Authors: Jiani Zheng, Hongguo Xie, Weiting Yu, Weiyang Xie, Xiaojun Ma
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Renal Artery Stent Outcomes
Authors: Timothy P. Murphy, Christopher J. Cooper, Alan H. Matsumoto, Donald E. Cutlip, Karol M. Pencina, Kenneth Jamerson, Katherine R. Tuttle, Joseph I. Shapiro, Ralph D’Agostino, Joseph Massaro, William Henrich, Lance D. Dworkin
Journal: Journal of the American College of Cardiology (2015)
Risk groups and other target groups – preliminary ECDC guidance for developing influenza vaccination recommendations for the season 2010-11
Authors: H Nokleby, A Nicoll
Journal: Eurosurveillance (2010)

Providing guidance on risk and target groups for seasonal influenza immunisation is difficult for the 2010-11 season since there is no experience with the new influenza A(H1N1) virus in its seasonal form. Arguments exist for offering immunisation to people with chronic illness and older people, and also for other risk and target groups including pregnant women. A more rigorous approach is being developed to produce annual evidence-based guidance on risk and target groups for influenza vaccination.
Identification of a Novel Pathogenic Germline KDR Variant in Melanoma
Authors: Ines P. Silva, Amel Salhi, Keith M. Giles, Matjaz Vogelsang, Sung W. Han, Naima Ismaili, Kevin P. Lui, Eric M. Robinson, Melissa A. Wilson, Richard L. Shapiro, Anna Pavlick, Judy Zhong, Tomas Kirchhoff, Iman Osman
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The application of pan-cancer next-generation sequencing panels in the clinical setting has facilitated the identification of low frequency somatic mutations and the testing of new therapies in solid tumors using the "basket trial" scheme. However, little consideration has been given to the relevance of nonsynonymous germline variants, which are likely to be uncovered in tumors and germline and which may be relevant to prognostication and prediction of treatment response. Experimental Design: We analyzed matched tumor and normal DNA from 34 melanoma patients using an Ion Torrent cancer-associated gene panel. We elected to study the germline variant Q472H in the kinase insert domain receptor (KDR), which was identified in 35% of melanoma patients in both a pilot and an independent 1,223 patient cohort. Using patient-derived melanoma cell lines and human samples, we assessed proliferation, invasion, VEGF levels, and angiogenesis by analyzing tumor microvessel density (MVD) using anti-CD34 antibody. Results: Serum VEGF levels and tumor MVD were significantly higher in Q472H versus KDR wild-type (WD) patients. Primary cultures derived from melanomas harboring the KDR variant were more proliferative and invasive than KDR wild type. Finally, using a VEGFR2 antibody, we showed that KDR Q472H cells were sensitive to targeted inhibition of VEGFR2, an effect that was not observed in KDR WT cells. Conclusions: Our data support the integration of germline analysis into personalized treatment decision-making and suggest that patients with germline KDR variant might benefit from antiangiogenesis treatment. Clin Cancer Res; 22(10); 2377–85. ©2015 AACR.
Bleomycin in the Reticuloses
Journal: BMJ (1972)

Bleomycin alone was used in the treatment of 54 patients with Hodgkin9s disease in its later stages, 17 with generalized lymphosarcoma, 22 with reticulum cell sarcoma, and 7 with mycosis fungoides. The patients had had radiotherapy and full courses of conventional chemotherapy. Bleomycin was given in doses of 30 mg weekly to an average total dosage of 200 mg, though up to 800 mg could be given because of its marrow-sparing properties. Sixteen (29%) of the patients with Hodgkin9s disease remitted, most of them achieving only a partial remission, and similar results were obtained in the other three reticuloses. Bleomycin would seem to have some beneficial action in the late stages of Hodgkin9s disease, though it is less effective than some drug regimens recently introduced. Nevertheless it may be useful when there is diminished bone marrow reserve. It would be a suitable drug to use in combination therapy of these four reticuloses.
Syncope as a health risk for soldiers - influence of medical history and clinical findings on the sensitivity of head-up tilt table testing
Authors: Hans-Joachim Gilfrich, Lena Marie Heidelmann, Franziska Grube, Hagen Frickmann, Sven Andreas Jungblut
Journal: Military Medical Research (2015)

Syncope is a relevant health problem in military environments. Reliable diagnosis is challenging. Tilt table testing is an important tool for syncope diagnosis. The aim of this study was to determine whether signs such as prodromal symptoms, co-morbidity, frequency of syncopal events, body length, body mass index, and electrocardiography abnormalities can be used to predict the success of tilt table testing at diagnosing syncope. Data from 100 patients with histories of syncope or pre-syncope, who were diagnosed using head-up tilt table testing, were retrospectively analyzed in a cross-sectional analysis. The diagnostic procedure was based upon a modified version of the Westminster protocol without any pharmacological provocation. Patients showing pathological reaction patterns during tilt table testing suffered from prodromal symptoms, such as dizziness and sweating, significantly more often. The patients reported more injuries resulting from syncopal events and more previous syncopal events, and the prevalence of co-morbidity was greater among patients presenting negative findings during tilt testing. An asthenic-leptosomal physique was not confirmed as a risk factor for syncopal events as is the case for idiopathic arterial hypotension. However, patients with pathological reaction patterns during tilt table testing were significantly taller. This finding was detected for both females and males. No significant predictors were found in the electrocardiogram (ECG) patterns of patients showing syncope during tilt table testing. Frequency of prior syncope and prodromal symptoms, and increased body length with an otherwise good state of health influence the predictive value of tilt table testing for syncope diagnosis. In particular, if these factors are present, tilt table testing should be considered part of the diagnostic algorithm for soldiers with recurrent syncope.
Use of the ratio of time to progression following first- and second-line therapy to document the activity of the combination of oxaliplatin with 5-fluorouracil in the treatment of colorectal carcinoma
Authors: A Bonetti, M Zaninelli, R Leone, T Franceschi, A P Fraccon, F Pasini, R Sabbioni, G L Cetto, D Sich, S Brienza, S B Howell
Journal: Annals of Oncology (2001)
Genome Editing and Dialogic Responsibility: “What's in a Name?”
Authors: Alessandro Blasimme, Ignacio Anegon, Jean-Paul Concordet, John De Vos, Anne Dubart-Kupperschmitt, Marc Fellous, Pierre Fouchet, Nelly Frydman, Carine Giovannangeli, Pierre Jouannet, Jean-Loius Serre, Julie Steffann, Emmanuelle Rial-Sebbag, Mogens Thomsen, Anne Cambon-Thomsen
Journal: The American Journal of Bioethics (2015)
Elevation of CSF somatostatin concentrations in mania
Authors: R P Sharma, G Bissette, P G Janicak, J M Davis, C B Nemeroff
Journal: American Journal of Psychiatry (1995)

The aim of this study was to compare levels of CSF somatostatin (somatotropin release-inhibiting factor) in drug-free patients with different major psychiatric disorders.CSF somatostatin concentrations were measured in 66 drug-free inpatients with Research Diagnostic Criteria diagnoses of schizophrenia, major depressive disorder, manic disorder, or schizoaffective disorder.In comparison with both the patients with schizophrenia and the patients with schizoaffective disorder, the manic patients had markedly elevated CSF somatostatin concentrations. The depressed patients had significantly higher levels than the schizophrenic patients.Mania is associated with relatively higher CSF somatostatin concentrations.
World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010
Authors: Arie H. Havelaar, Martyn D. Kirk, Paul R. Torgerson, Herman J. Gibb, Tine Hald, Robin J. Lake, Nicolas Praet, David C. Bellinger, Nilanthi R. de Silva, Neyla Gargouri, Niko Speybroeck, Amy Cawthorne, Colin Mathers, Claudia Stein, Frederick J. Angulo, Brecht Devleesschauwer
Journal: PLoS Medicine (2015)

Illness and death from diseases caused by contaminated food are a constant threat to public health and a significant impediment to socio-economic development worldwide. To measure the global and regional burden of foodborne disease (FBD), the World Health Organization (WHO) established the Foodborne Disease Burden Epidemiology Reference Group (FERG), which here reports their first estimates of the incidence, mortality, and disease burden due to 31 foodborne hazards. We find that the global burden of FBD is comparable to those of the major infectious diseases, HIV/AIDS, malaria and tuberculosis. The most frequent causes of foodborne illness were diarrheal disease agents, particularly norovirus and Campylobacter spp. Diarrheal disease agents, especially non-typhoidal Salmonella enterica, were also responsible for the majority of deaths due to FBD. Other major causes of FBD deaths were Salmonella Typhi, Taenia solium and hepatitis A virus. The global burden of FBD caused by the 31 hazards in 2010 was 33 million Disability Adjusted Life Years (DALYs); children under five years old bore 40% of this burden. The 14 subregions, defined on the basis of child and adult mortality, had considerably different burdens of FBD, with the greatest falling on the subregions in Africa, followed by the subregions in South-East Asia and the Eastern Mediterranean D subregion. Some hazards, such as non-typhoidal S. enterica, were important causes of FBD in all regions of the world, whereas others, such as certain parasitic helminths, were highly localised. Thus, the burden of FBD is borne particularly by children under five years old–although they represent only 9% of the global population–and people living in low-income regions of the world. These estimates are conservative, i.e., underestimates rather than overestimates; further studies are needed to address the data gaps and limitations of the study. Nevertheless, all stakeholders can contribute to improvements in food safety throughout the food chain by incorporating these estimates into policy development at national and international levels.
P-246 Feasibility study of sequential adjuvant chemotherapy with three months oxaliplatin-based regimen followed by three months capecitabine in patients with stage III and high risk stage II colorectal cancer: (JSWOG C2)
Authors: H. Tanioka, K. Yamashita, A. Tsuji, H. Okumura, Y. Oka, A. Tsuruta, M. Inukai, T. Yamakawa, T. Yamatsuji, M. Yoshimitsu, K. Toyota, T. Yamano, Y. Yamamoto, T. Nagasaka, M. Okajima
Journal: Annals of Oncology (2015)
Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria
Authors: K Borch-Johnsen, A Neil, B Balkau, S Larsen, A Nissinen, J Pekkanen, S Keinanen-Kiukaanniemi, L Hiltunen, S L Kivela, Jaakko Tuomilehto, P Jousilahti, J Lindstrom, M Pyorala, K Pyorala, E Eschwege, G Gallus, M P Garancini, A Schranz, R J Heine, J M Dekker, E Feskens, H Lithell, B Zethelius, M Peltonen, N Unwin, N Ahmad, K G M M Alberti, M M Alberti, J Eriksson, Q Qiao
Journal: The Lancet (1999)
Chronic amphotericin B nephrotoxicity in the rat
Authors: J P Tolins, L Raij
Journal: Journal of the American Society of Nephrology (1991)

Amphotericin B is used despite predictable nephrotoxicity because it remains the most efficacious agent currently available for systemic fungal infections. It has been previously shown that calcium channel blockade prevents renal vasoconstriction and blunts the fall in glomerular filtration rate during acute amphotericin B infusion in the rat. Therefore, the effect of cotreatment with diltiazem on nephrotoxicity during chronic daily amphotericin therapy in rats was studied. Rats were given diltiazem (45 mg/kg, 1 h before and 1 h after amphotericin) or vehicle by gastric tube; and amphotericin B (5 mg/kg/day i.p.) for 10 days. Control rats received corresponding vehicles by gastric tube and daily i.p. infection. Renal function was determined 24 h after the last dose of amphotericin or vehicle. Serum creatinine rose significantly in rats receiving amphotericin alone (initial versus final, 0.50 +/- 0.07 versus 1.09 +/- 0.20 mg/dL; P less than 0.05) but not with amphotericin plus diltiazem (0.54 +/- 0.11 versus 0.84 +/- 0.23 mg/dL; P was not significant). Amphotericin rats had a marked decrease in glomerular filtration rate (amphotericin versus control, 0.28 +/- 0.04 versus 1.23 +/- 0.08 mL/min/g kidney wt; P less than 0.05) and renal plasma flow (1.63 +/- 0.19 versus 3.50 +/- 0.40 mL/min/g kidney wt; P less than 0.05). These adverse renal hemodynamic effects were prevented by cotreatment with diltiazem (amphotericin plus diltiazem; glomerular filtration rate, 0.82 +/- 0.18 mL/min/g kidney wt; P less than 0.05 versus amphotericin; P was not significant versus control; renal plasma flow, 3.24 +/- 0.63 mL/min/g kidney wt; P less than 0.05 versus amphotericin; P was not significant versus control).(ABSTRACT TRUNCATED AT 250 WORDS)