tbuckley/cabot-search huggingface dataset:
BMA temporarily suspends strike action
Authors: Abi Rimmer
Journal: BMJ (2015)

The BMA has temporarily suspended industrial action and agreed to enter negotiations with the government on the junior doctors’ contract.

The government has agreed to temporarily suspend plans to impose a new contract on juniors in England in August 2016, after conciliatory talks facilitated by the Advisory, Conciliation and Arbitration Service (Acas).

In a statement, Acas said that NHS Employers, which negotiates doctors’ contracts on the government’s behalf, had agreed to extend the time frame for the BMA to commence any industrial action by four weeks to 13 January 2016, to allow negotiations to …
Disabled homolog 2 controls macrophage phenotypic polarization and adipose tissue inflammation
Authors: Samantha E. Adamson, Rachael Griffiths, Radim Moravec, Subramanian Senthivinayagam, Garren Montgomery, Wenshu Chen, Jenny Han, Poonam R. Sharma, Garrett R. Mullins, Stacey A. Gorski, Jonathan A. Cooper, Alexandra Kadl, Kyle Enfield, Thomas J. Braciale, Thurl E. Harris, Norbert Leitinger
Journal: Journal of Clinical Investigation (2016)

Acute and chronic tissue injury results in the generation of a myriad of environmental cues that macrophages respond to by changing their phenotype and function. This phenotypic regulation is critical for controlling tissue inflammation and resolution. Here, we have identified the adaptor protein disabled homolog 2 (DAB2) as a regulator of phenotypic switching in macrophages. Dab2 expression was upregulated in M2 macrophages and suppressed in M1 macrophages isolated from both mice and humans, and genetic deletion of Dab2 predisposed macrophages to adopt a proinflammatory M1 phenotype. In mice with myeloid cell-specific deletion of Dab2 (Dab2fl/fl Lysm-Cre), treatment with sublethal doses of LPS resulted in increased proinflammatory gene expression and macrophage activation. Moreover, chronic high-fat feeding exacerbated adipose tissue inflammation, M1 polarization of adipose tissue macrophages, and the development of insulin resistance in DAB2-deficient animals compared with controls. Mutational analyses revealed that DAB2 interacts with TNF receptor-associated factor 6 (TRAF6) and attenuates IκB kinase β-dependent (IKKβ-dependent) phosphorylation of Ser536 in the transactivation domain of NF-κB p65. Together, these findings reveal that DAB2 is critical for controlling inflammatory signaling during phenotypic polarization of macrophages and suggest that manipulation of DAB2 expression and function may hold therapeutic potential for the treatment of acute and chronic inflammatory disorders.
Comparison Of Different Pretransplant Predictive Scores In Patients With Refractory Acute Myeloid Leukemia After Allogeneic Stem Cell Transplantation Including Highdose Melphalan: Results Of a Double-Center Observational Study
Authors: Nina Kristin Steckel, Markus Ditschkowski, Christoph Groth, Gerda Silling, U. Krug, Rudolf Trenschel, Hellmut Ottinger, Wolfgang E Berdel, Michael Koldehoff, Ahmet H. Elmaagacli, Dietrich Beelen, Matthias Stelljes
Journal: Blood (2013)
METGastric: A phase III study of onartuzumab plus mFOLFOX6 in patients with metastatic HER2-negative (HER2-) and MET-positive (MET+) adenocarcinoma of the stomach or gastroesophageal junction (GEC).
Authors: Manish A. Shah, Yung-Jue Bang, Florian Lordick, Josep Tabernero, Meng Chen, Stephen Paul Hack, See-Chun Phan, David S. Shames, David Cunningham
Journal: Journal of Clinical Oncology (2015)

4012 Background: Dysregulation of the MET/HGF pathway is associated with poor prognosis in GEC. Onartuzumab (O), a monovalent anti-MET antibody, inhibits the MET/HGF pathway. We investigated first-line mFOLFOX6 + O in metastatic, HER2-, MET+ GEC. Methods: This double-blind, placebo-controlled phase 3 study randomized patients (pts) 1:1 to mFOLFOX6 + placebo (P) or O (10 mg/kg; q2w). Eligibility criteria: no prior treatment for metastatic disease, age ≥ 18 yrs, ECOG PS 0–1, retained organ function, HER2-, MET+ (IHC 1+, 2+ or 3+) GEC. Co-primary endpoints: overall survival (OS) in ITT and MET 2+/3+ pts. Secondary endpoints: progression-free survival (PFS), overall response rate (ORR) and safety. The study was designed to enroll ~800 pts and powered to demonstrate improvement of median OS from 9 to 12.3 mo (ITT pts; HR 0.73) and 9 to 18 mo (MET 2+/3+ pts; HR 0.49). Enrollment stopped early due to negative final results from a phase 2 trial assessing mFOLFOX6 + O. Results: The ITT population comprised 562 pts (enrolled 19 Nov 2012–7 Mar 2014). The treatment arms were well balanced: median age (59 yrs O, 58 yrs P), male (67% O, 65% P), and MET 2+/3+ (38% O, 39% P). Serious adverse events (AEs) were slightly more frequent with O v P (35.8% v 32.5%). Grade ≥3 AEs more commonly seen with O included neutropenia (35.1% v 29.3%), thrombocytopenia (4.3% v 1.1%), peripheral edema (4.7% v 0.4%), and pulmonary embolism (6.1% v 3.6%). At data cutoff (25 Apr 2014), 26% of ITT pts in each arm had OS events. In the MET2+/3+ subgroup, 38% of P and 33% of O pts had OS events. See Table for efficacy data. Exploratory subgroup analyses showed improved OS for the O arm in non-Asian pts and pts with no prior gastrectomy regardless of MET status. Conclusions: The addition of onartuzumab to mFOLFOX6 was ineffective in ITT or MET 2+/3+ pts. Subgroup analysis suggests non-Asian pts and pts without prior gastrectomy may benefit. Further analyses may delineate the role of the MET pathway in GEC. NCT01662869. Clinical trial information: NCT01662869. ITT MET 2+/3+ P O P O Median OS, mo 11.3 11.0 9.7 11.0 HR, p value 0.82, 0.244 0.64, 0.062 Median PFS, mo 6.8 6.7 5.7 6.9 HR, p value 0.90, 0.429 0.79, 0.223 ORR, % 41 46 45 54 p value 0.253 0.228
Feline Oncornavirus-Associated Cell Membrane Antigen. I. Serologie Studies With Kittens Exposed to Cell-Free Materials From Various Feline Fibrosarcomas2
Authors: M. Essex, S. P. Snyder
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Feline Oncornavirus-Associated Cell Membrane Antigen. I. Serologie Studies With Kittens Exposed to Cell-Free Materials From Various Feline Fibrosarcomas Get access M. Essex, M. Essex Search for other works by this author on: Oxford Academic PubMed Google Scholar S. P. Snyder S. P. Snyder Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 1007–1012, https://doi.org/10.1093/jnci/51.3.1007 Published: 01 September 1973 Article history Received: 15 January 1973 Accepted: 09 May 1973 Published: 01 September 1973
Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy
Authors: Shari Pilon-Thomas, Krithika N. Kodumudi, Asmaa E. El-Kenawi, Shonagh Russell, Amy M. Weber, Kimberly Luddy, Mehdi Damaghi, Jonathan W. Wojtkowiak, James J. Mulé, Arig Ibrahim-Hashim, Robert J. Gillies
Journal: Cancer Research (2016)

Abstract Cancer immunotherapies, such as immune checkpoint blockade or adoptive T-cell transfer, can lead to durable responses in the clinic, but response rates remain low due to undefined suppression mechanisms. Solid tumors are characterized by a highly acidic microenvironment that might blunt the effectiveness of antitumor immunity. In this study, we directly investigated the effects of tumor acidity on the efficacy of immunotherapy. An acidic pH environment blocked T-cell activation and limited glycolysis in vitro. IFNγ release blocked by acidic pH did not occur at the level of steady-state mRNA, implying that the effect of acidity was posttranslational. Acidification did not affect cytoplasmic pH, suggesting that signals transduced by external acidity were likely mediated by specific acid-sensing receptors, four of which are expressed by T cells. Notably, neutralizing tumor acidity with bicarbonate monotherapy impaired the growth of some cancer types in mice where it was associated with increased T-cell infiltration. Furthermore, combining bicarbonate therapy with anti-CTLA-4, anti-PD1, or adoptive T-cell transfer improved antitumor responses in multiple models, including cures in some subjects. Overall, our findings show how raising intratumoral pH through oral buffers therapy can improve responses to immunotherapy, with the potential for immediate clinical translation. Cancer Res; 76(6); 1381–90. ©2015 AACR.
Abstract 229: Hydrogen sulfide donor, the Organic Polysulfide Diallyl Trisulfide Augments Ischemia-induced Angiogenesis by Upregulation of VEGF-Akt-eNOS Pathway
Authors: Ryo Hayashida, Kazuhisa Kondo, Satoshi Shintani, Toyoaki Murohara
Journal: Circulation Research (2014)

Introduction: Hydrogen sulfide (H2S) upregulates anti-oxidant, anti-apoptosis, anti-inflammatory, and cell survival. H2S plays an extremely important role in the homeostasis of the cardiovascular system and in the pathogenesis of cardiovascular disease. The diallyl trisulfide (DATS) is a polysulfide constituent found in garlic oil, and known as H2S donor that is able to release H2S continuously. Peripheral artery disease (PAD) causes considerable morbidity and mortality. The aim of this study was investigate whether the DATS would augment ischemia-induced angiogenesis. Methods: The unilateral permanent femoral artery ligation was performed in C57BL/6J mice (8-10 weeks old, n=8-10/group) and eNOS KO mice (8-10 weeks old, n=5-8/group), and vehicle or DATS (500 μg/kg/day) was injected intra-peritonealy up to 1 week following the hind limb ischemia (HLI). We evaluated the blood flow recovery using the laser Doppler perfusion image and capillary density stained with CD31 at 3 weeks following HLI. We assessed VEGF level by qPCR analysis and activations of eNOS and Akt by western blot analysis in ischemic tissues. Moreover, we cultured HUVECs in a hypoxic chamber with serum starvation for 24 hour, and then evaluated apoptosis by tunnel staining and oxidative stress by DHE staining with or without DATS (50 μmol). We also evaluated activations of eNOS and Akt in cultured HUVECs with or without DATS. Results: DATS treatment significantly increased blood flow (0.45 vs 0.78,p&lt;0.05) and capillary density (1.57 vs 1.85,p&lt;0.05) at 3 weeks following HLI compared to vehicle. DATS also increased mRNA level of VEGF and activation of Akt and eNOS at 3 days following HLI. On the other hand, DATS treatment failed to increase blood flow and capillary density at 3 weeks following HLI in eNOS KO mice. The DATS treatment inhibited apoptosis and oxidative stress in cultured HUVECs via activation of Akt and eNOS pathway in vitro. Conclusions: Our results indicate that DATS treatment could augment ischemia-induced angiogenesis by upregulation of VEGF-Akt-eNOS pathway that leads to inhibitions of apoptosis and oxidative stress. These results suggest that administration of H2S releasing agents might be efficacious for the treatment of PAD.
A phase II trial of dose-escalated doxorubicin and ifosfamide/mesna in patients with malignant mesothelioma
Authors: L.Y. Dirix, J. van Meerbeeck, D. Schrijvers, B. Corthouts, A. Prové, E. van Marck, P. Vermeire, A.T. van Oosterom
Journal: Annals of Oncology (1994)
Modulation of Lung Tumor Colony Formation by a Subcutaneously Growing Tumor
Authors: Przemyslaw Janik, John S. Bertram, Bozena Szanlawska
Journal: JNCI Journal of the National Cancer Institute (1981)

When monodisperse tumor cell suspensions of the mouse sarcoma L1 were injected iv into inbred BALB/c mice bearing subcutaneous grafts of the same tumor, the number of tumor nodules developing in the lungs was highest in animals bearing the oldest primary tumor (28 days) and lowest in animals bearing the oldest primary tumor (28 days) and lowest in animals bearing 16-day-old primary tumors. The number of metastases developing in mice bearing 9-day-old subcutaneous tumors was the same as that in control animals without a subcutaneous tumor. This state of low and high susceptibility to lung metastases can be transferred from tumor-bearing mice to whole-body irradiated mice by means of spleen cells, and this transfer of susceptibility is stable for at least 3 weeks. The results indicate a) that a growing subcutaneous tumor can modulate the number of artificial metastases occurring in the lungs as a result of the iv injection of tumor cells, and b) that this modulation occurs by immune mechanisms. In the model presented here, the host is first protected and then made more susceptible to artificial lung metastases by the presence of a progressively growing subcutaneous tumor.
Recurrent Patterns Of Histone Methylation and Acetylation Regulating Protein Expression In Acute Myelogenous Leukemia (AML)
Authors: Steven M. Kornblau, Chenyu W Hu, Yihua Qiu, Suk Young Yoo, Nianxiang Zhang, Farhad Ravandi, Guillermo Garcia-Manero, Amina A Qutub, Kevin R. Coombes
Journal: Blood (2013)
Obstructive sleep apnoea and cardiovascular calcification
Authors: Magnus Bäck, Françoise Stanke-Labesque
Journal: Thorax (2015)

The increased cardiovascular risk associated with obstructive sleep apnoea (OSA) has been well established,1 but the mechanisms involved remain to be elucidated. The study by Lutsey et al ,2 published in this issue of Thorax adds another piece to the puzzle of the link between OSA and cardiovascular risk by showing significant associations between parameters of sleep-disordered breathing and coronary atherosclerotic calcification.

The initiation and progression of atherosclerosis is characterised by an accumulation of lipids and lipoproteins within the vascular wall, leading to immune activation and the recruitment of inflammatory cells.3 The resulting atherosclerotic plaques may remain silent for a long time before plaque destabilisation occurs, leading to plaque rupture, vessel occlusion and, if in a coronary artery, myocardial infarction. Prognostic markers are of particular interest to identify patients at risk of plaque rupture and who …
Rise in India’s health budget is “disappointing,” say experts
Authors: Ganapati Mudur
Journal: BMJ (2016)

Health experts have described increases to India’s health budget as “disappointing” despite new money for improved access to low cost generic medicines and higher, publicly funded health insurance cover for poor people.

In budget proposals announced on 29 February for the fiscal year starting 1 April 2016, the finance ministry allocated 370 billion rupees (£3.9bn; €5.0bn; $5.5bn) to healthcare services, a 19% increase on last year.

The ministry announced health insurance cover of up to Rs130 000 per household, a nationwide dialysis programme, and an increase in the number of government funded pharmacies that sell low cost generic medicines, up from fewer than 300 at present to more than 3000.

Members of the private healthcare sector welcomed the proposals, saying that they outlined fresh steps to protect families from health expenses. But several public health experts expressed concerns that the government was pulling away from public health facilities while encouraging the private sector.

Although the Indian health ministry is yet to provide …
Patients' expectations of therapeutic improvement and their outcomes
Authors: S Bloch, G Bond, B Qualls, I Yalom, E Zimmerman
Journal: American Journal of Psychiatry (1976)

The authors studied the relationship between patients' expectations of therapeutic improvement and their actual outcomes after 8 and 12 months of group psychotherapy. Using patients' self-evaluations and assessments by therapists and independent judges, they found a positive relationship between expectations and outcomes only when assessments were derived from patients. The authors discuss the possibility of a continuing expectational set in patients toward psychotherapy.
Efficient transduction of human hematopoietic repopulating cells generating stable engraftment of transgene-expressing cells in NOD/SCID mice
Authors: Jordi Barquinero, José Carlos Segovia, Manuel Ramı́rez, Ana Limón, Guillermo Güenechea, Teresa Puig, Javier Briones, Juan Garcı́a, Juan Antonio Bueren
Journal: Blood (2000)
Abstract 14643: Clinical and Electrocardiographic Characteristics are Insensitive Indicators of Acute Myocardial Infarction in Patients who Present with Chest Pain and Left Bundle Branch Block or Paced Rhythm
Authors: Melina Aguinaga-Meza, Joaquim Barboza, Rafael Cabrera, Moises Huaman, Henry Kim
Journal: Circulation (2012)

BACKGROUND Patients who present to the emergency department (ED) with chest pain and left bundle branch block (LBBB) or paced rhythm are a clinical dilemma. We aim to identify clinical and electroc...
A Markedly Disrupted Skeletal Network With Abnormally Distributed Intramembrane Particles in Complete Protein 4.1-Deficient Red Blood Cells (Allele 4.1 Madrid): Implications Regarding a Critical Role of Protein 4.1 in Maintenance of the Integrity of the Red Blood Cell Membrane
Authors: Ayumi Yawata, Akio Kanzaki, Florinda Gilsanz, Jean Delaunay, Yoshihito Yawata
Journal: Blood (1997)
Montelukast plus inhaled budesonide versus double dose inhaled budesonide in nonasthmatic eosinophilic bronchitis
Authors: Chuang Cai, Shu-Qing Zhong, Yan Tang, Nan-Shan Zhong
Journal: European Respiratory Journal (2011)

Background:  Montelukast added to inhaled corticosteroids (ICS) has been demonstrated to relieve asthma symptoms and control airway inflammation equal to double dose ICS. However, the clinical efficacy of montelukast as add-on therapy to ICS has not been reported in nonasthmatic eosinophilic bronchitis (NAEB).   Objectives:  Whether add-on therapy with montelukast to inhaled budesonide would equal double dose inhaled budesonide in alleviating cough and airway eosinophilia in adult patients with steroid-naive NAEB was studied, the primary endpoints were changes of cough visual analogue score (CVAS) and eosinophil ratio in induced sputum (EOS) during treatment.   Methods:  26 nonsmoking subjects were randomized to receive either montelukast 10mg qd plus budesonide turbuhalor 200 μg bid (MONT-BUD) or budesonide turbuhalor 400 μg bid (BUD) for 4 weeks. CVAS, EOS at baseline, 1 week, 2 week and 4 week after treatment were measured. Adverse reactions were monitored.   Results:  The two groups were comparable in age, median duration of cough and baseline CVAS. Median baseline EOS of MONT-BUD and BUD was 11.8% and 22.7%. Improvement of CVAS was more profound in MONT-BUD. In both groups EOS was normalized in both groups at end of therapy with similar EOS reduction at all time points. Both regimens were well tolerated.   Conclusions:  This study demonstrated that the addition of montelukast to inhaled budesonide was an effective and well tolerated alternative to inhaled budesonide with resolution of airway eosinophilia and more remarkable reduction of cough in NAEB.
An Epidermoid Carcinoma Cell Line Derived From Hamster 7,12- Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-Induced Buccal Pouch Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Onatolu Odukoya, B.D.S., M.Med.Sc., Joel Schwartz, D.M.D., D.M.Sc., Ralph Weichselbaum, M.D., Gerald Shklar
 5
Journal: JNCI Journal of the National Cancer Institute (1983)

w cell line, HCPC I, was established from an epidermoid carcinoma of the Syrian golden hamster cheek pouch. The carcinoma was induced by applications three times a week of a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in heavy mineral oil. The HCPC I cell line has been maintained through 60 passages over 15 months. Electron microscopy of the cell line revealed tonofilaments and desmosomes, thereby confirming its epithelial nature. Presence of keratin in the HCPC I cells was demonstrated by both histochemical and indirect immunofluorescence studies. The population-doubling time of HCPC I, estimated from the exponential growth phase of the growth curve established for the cell line, was 12 hours. The plating efficiency of the cell line was estimated at 35%. When an inoculum size of HCPC I, numbering 2.4 X 10(7) cells, was transplanted to the cheek pouch of an immunosuppressed inbred hamster, a papillary tumor, measuring 5 X 1 mm and microscopically diagnosed as a well-differentiated epidermoid carcinoma, developed 1 week post transplantation. Further successful transplantation was achieved with 1.8 X 10(7) HCPC I cells inoculated into the cheek pouch of a nonimmunosuppressed inbred hamster. A raised plaquelike mass, microscopically diagnosed as invasive epidermoid carcinoma, developed in the hamster cheek pouch 5 weeks post transplantation. Furthermore, 5 nonimmunosuppressed hamsters that received 1 X 10(6) HCPC I cells on their cheek pouches developed tumors microscopically diagnosed as anaplastic carcinomas 14 weeks post transplantation. The largest of these tumors measured 2 cm in diameter.
Phase I study of the sequential administration of edatrexate and paclitaxel in patients with advanced solid tumors
Authors: J.R. Rigas, M.G. Kris, V.A. Miller, K.M.W. Pisters, R.T. Heelan, S.C. Grant, D.W. Fennelly, Ting-Chao Chou, F.M. Sirotnak
Journal: Annals of Oncology (1999)

Background:The antifolate edatrexate and the microtubulestabilizing agent paclitaxel have both demonstrated singleagent activity in lung and breast cancer.In vitro, the sequential combination of edatrexate followed by paclitaxel produced synergistic antitumor effects.This trial was designed to find the maximum tolerated doses of edatrexate and paclitaxel when given every two weeks utilizing this sequential schedule.Patients and methods: Thirty-four patients with solid tumors received edatrexate intravenously on days 1 and 15 and paclitaxel intravenously as a three-hour infusion on days 2 and 16 of each 28-day cycle.Edatrexate was escalated from 40 to 120 mg/m 2 and the paclitaxel dose fixed at 135 mg/m 2 .When the maximum-tolerated dose was not reached, edatrexate was fixed at 120 mg/m 2 and paclitaxel escalated to 175 and 210 mg/m 2 .Results: All 34 patients were assessable.The maximum tolerated doses were 120 mg/m 2 of edatrexate and 210 mg/m 2 of paclitaxel.Grade 3 myalgia, peripheral neuropathy, leukopenia, and an infusion-related reaction occurred.Eight patients with non-small-cell lung cancer and one with bladder cancer achieved major objective responses.Conclusions: The recommended phase II doses are 120 mg/m 2 of edatrexate days 1 and 15 and 175 mg/m 2 of paclitaxel as a three-hour infusion days 2 and 16 of a 28 day cycle.These results warrant phase II trials of the combination leading to phase III studies comparing the two drugs to a single agent to confirm the preclinical evidence of synergy.
Reply to Francesco Piva, Matteo Santoni, Marina Scarpelli, et al's Letter to the Editor re: Daniel M. Geynisman. Anti-programmed Cell Death Protein 1 (PD-1) Antibody Nivolumab Leads to a Dramatic and Rapid Response in Papillary Renal Cell Carcinoma with Sarcomatoid and Rhabdoid Features. Eur Urol 2015;68:912–4
Authors: Tim N. Beck, Erica A. Golemis, Daniel M. Geynisman
Journal: European Urology (2016)