tbuckley/cabot-search huggingface dataset:
Overcoming gefitinib resistance in NSCLC via inactivation of the PI3K/AKT signaling pathway by a combination of FUS1 nanoparticles and EGFR inhibitors.
Authors: Hiroyuki Kawashima, Gitanjali Jayachandran, Wuguo Deng, Kai Xu, John D. Minna, Jack A. Roth, Lin Ji
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5426 

Gefitinib (Iressa) is an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that has been shown to be clinically effective in a subpopulation of non small cell lung cancer (NSCLC) patients. Despite initial responses to gefitinib in some NSCLC patients, cancer eventually progresses by unknown mechanisms of acquired resistance. We explored the use of the novel tumor suppressor FUS1 to enhance the chemotherapeutic potency of gefitinib and overcome gefitinib resistance in NSCLC. We found that reactivation of wild-type FUS1 by FUS1 nanoparticle-mediated gene transfer into FUS1-deficient and gefitinib-resistant NSCLC H1299, H322, H358, and H460 cells significantly ( P < 0.001) sensitized their response to gefitinib treatment and synergistically induced apoptosis in vitro and in an H322 orthotopic lung cancer mouse model. To understand the mechanism of gefitinib-induced resistance, we established a gefitinib-resistant HCC827GR NSCLC cell line (IC50 = 16 μM) by selecting against gefitinib from the parental HCC827 cells that contain an activating deletion mutation of the EGFR gene and are extremely sensitive to gefitinib treatment (IC50 = 0.016 μM). We found no secondary mutations in the EGFR gene in the HCC827GR cells, but these cells registered a significantly elevated level of phosphorylated AKT protein. Combination treatment with FUS1 nanoparticles and gefitinib at a dose level of IC10 significantly re-sensitized the cells to gefitinib, as demonstrated by synergistically enhanced growth inhibition and apoptosis. FUS1 nanoparticle treatment alone or with gefitinib markedly inactivated EGFR and AKT, as demonstrated by decreased phosphorylation levels of both proteins on Western blots, compared with either agent alone. Cleavage of caspase-3, caspase-9, and PARP was also significantly induced by the combination of FUS1 and gefitinib in HCC872GR and other gefitinib-resistant NSCLC cells. Our results suggest that a combination treatment of FUS1 nanoparticles and gefitinib could overcome drug-induced resistance by simultaneously inactivating EGFR and the AKT signaling pathway and by facilitating apoptosis. This abstract is supported by grants from NCI (SPORE P50CA70907) and DOD (TARGET, DAMD17002-1-0706).
Comparative Anatomy of the Domesticated Animals.
Authors: Auguste Chauveau, Saturnin Arloing, George Fleming
Journal: JAMA (1891)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Allocating the WHO's resources rationally
Authors: G. Bevan
Journal: BMJ (1998)

News p 1408 

Next week the World Health Assembly will consider a recommendation from the executive board of the World Health Organisation that will radically change the way that budgets are allocated to the WHO's regions.1 Until now regular budgets to regions have been based not on objective criteria but on previous practice, so each region's share has remained largely unchanged since the WHO's inception. The recommendation is for a new system to be implemented gradually over three bienniums from 2000-1. This system is based on the United Nation Development Programme's human development index, possibly adjusted for immunisation coverage, which incorporates population statistics of countries calculated according to “commonly accepted methods such as ‘logarithmic smoothing.’” These recommendations follow from the report of a special group2 charged with reviewing regional allocations. This group agreed that more transparent and objective criteria based on needs at country level should be established for these allocations.

The diagnosis of inadequacies in the WHO's budget setting and the proposed solution of a weighted …
The role of hen’s egg‐specific IgE, IgG and IgG4 in the diagnostic procedure of hen’s egg allergy
Authors: B. Ahrens, L. C. Lopes de Oliveira, G. Schulz, M. P. Borres, B. Niggemann, U. Wahn, K. Beyer
Journal: Allergy (2010)

To cite this article: Ahrens B, Lopes de Oliveira LC, Schulz G, Borres MP, Niggemann B, Wahn U, Beyer K. The role of hen’s egg‐specific IgE, IgG and IgG4 in the diagnostic procedure of hen’s egg allergy. Allergy 2010; 65 : 1554–1557. Abstract Background: Hen’s egg (HE) allergy is a common disease in childhood. HE‐specific serum IgE has been correlated with the outcome of oral food challenge tests, and diagnostic decision points have been described as helpful but still not sufficient to reduce the requirement for oral food challenges. The aim of the study was to correlate HE‐specific IgE, IgG and IgG4 levels with the outcome of double‐blind, placebo‐controlled food challenges (DBPCFC) in patients with suspected HE allergy to improve diagnostic procedures. Methods: HE‐specific IgE, IgG, and IgG4 levels were compared between 150 children with suspected HE allergy based on sensitization and/or patient’s history who underwent DBPCFC. Sixty‐six patients were HE‐allergic (HE‐sensitized with a positive DBPCFC), 48 HE‐sensitized but tolerant (negative DBPCFC), and 36 patients were nonsensitized and tolerant (negative DBPCFC). Prior to food challenge HE‐specific serum IgE, IgG, and IgG4 were measured with the Phadia CAP‐system. Results: HE‐specific IgE was significantly higher in HE‐allergic patients than in clinically tolerant ones. However, there was no difference in HE‐specific IgG and IgG4 concentrations between the patient groups. Conclusion: A proposed cut‐off level of 12 kU/l IgE would identify children above this level correctly as HE‐allergic. The level of HE‐specific IgG or IgG4 in serum of children with suspected HE allergy does not add any additional information in the diagnostic procedure of HE allergy. For diagnostic purposes, specific IgG or IgG4 should not routinely be tested.
Genetics for Medical Students
Authors: E. B. Ford
Journal: JAMA (1942)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Induction of tolerance in solar urticaria by ultraviolet A ‘rush hardening’: is this true desensitization?
Authors: R.S. Dawe
Journal: British Journal of Dermatology (2012)

Journal Article Induction of tolerance in solar urticaria by ultraviolet A 'rush hardening': is this true desensitization? Get access R.S. Dawe R.S. Dawe Department of Dermatology, Ninewells Hospital & Medical School, University of Dundee, Dundee, Tayside DD1 9SY, U.K. E‐mail: rdawe@nhs.net Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 167, Issue 1, 1 July 2012, Pages 4–5, https://doi.org/10.1111/j.1365-2133.2012.11030.x Published: 01 July 2012
p27kip1 functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes
Authors: Vassiliki A. Boussiotis, Gordon J. Freeman, Patricia A. Taylor, Alla Berezovskaya, Isabelle Grass, Bruce R. Blazar, Lee M. Nadler
Journal: Nature Medicine (2000)
Role of mir23a and PGC-1 alpha in pulmonary hypertension
Authors: Irene Sarrrión, Gustavo Juan, Mercedes Ramón, Julio Cortijo, Manuel Mata
Journal: European Respiratory Journal (2013)

Background: Human pulmonary arterial hypertension (PAH) is a disease largely restricted to small pulmonary arteries. PAH is characterized by vascular remodelling that leads to an increase in vascular resistance with devastating effects. Recently the role of miRNAs have been associated with hypoxia mechanisms events implicated in the remodelling of small arteries that occurs in HAP. We have analyzed differences in expression profiles of miRNA isolated from HAP diagnosed patients compared to healthy donors. We have also used a cellular model of small vascular endothelial and smooth muscle cells exposed to ET-1 and TGF-beta to analyze the role of mir23a modulating cell events implicated in EnMT and proliferation.  Methods:RNAs were isolated form peripheral blood extracted from 16 primary PAH diagnosed patients and 12 healthy donors. Blood peripheral miRNAs were analyzed using Affymetrix microarrays. Endothelial and smooth muscle cells were exposed to ET-1 an TFG for up to 72 hours. Gene expression were measured by RT-PCR.  Results: We have observed consistent changes in miRNAs which have been previously associated wit HAP, including miR-17 and miR-92, miR-22and miR-21 and miR-23a (implicated in cardiac damage and in inhibiting the expression of PGC-1alpha). siRNA experiment induced an increase in the expression of PGC-1alpha, while PPAR gamma agonist ciglitazone inhibited the molecular changes induced by endothelin and TGF in both endothelial and smooth muscular cells.  Conclusion: Our data supports the implication of miRNAs in the progression of HAP and the involvement of miRNA 23 in the control of PGC-1alpha which may by implicated in mitigate remodeling processes associated with changes in small vasculature.
Abstract P062: The Effect of Food Pricing on Dietary Behaviors and Adiposity: a Systematic Review and Meta-analysis
Authors: Ashkan Afshin, Liana Del Gobbo, Jose Silva, Melody Michaelson, Dariush Mozaffarian
Journal: Circulation (2014)

Background: While food pricing is a promising strategy to improve diet and reduce cardiometabolic disease, most prior evidence comes from cross-sectional price elasticity estimates. The prospective impact of food pricing on dietary behaviors and obesity has not been systematically evaluated. Objective: To systematically investigate and quantify the effect of price change on dietary intake and on adiposity, as well as whether other underlying factors alter these effects. Methods: Using MOOSE and PRISMA guidelines, we systematically searched PubMed, Embase, EconLit, OVID, Cochrane library, Web of Knowledge, and CINHAL for prospective observational or interventional studies of price differences and diet (foods, drinks, energy) or adiposity. Studies were excluded if cross-sectional; price data collected before 1990; or reporting only crude risk estimates. Data were extracted independently and in duplicate. Findings were pooled using inverse-variance meta-analysis Results: From 2,299 identified abstracts, 21 met inclusions. These included 6 randomized trials and 7 quasi-experimental studies in different settings (supermarket, school/workplace cafeteria, restaurant) in 3 countries (US, New Zealand, Netherland); and 8 observational studies mostly using nationally representative US data. Studies evaluated effects of increase (n=10, 1-35% increase) in price (fast food, energy dense snacks, soda) and decrease (n=11, 10-50% decrease) in price (fruits, vegetables, low fat/calorie products) among adults (n=13) and children (n=8). Studies consistently showed that price increases led to decreased consumption; effects of price decreases on consumption and price increases/decreases on BMI were less consistent. A mean $0.43/serving (12 oz) increase in price of soda was associated with 2.77 servings/wk lower consumption (95% CI: 1.58. 3.96, n=4 studies). A mean %30/serving decrease in price of fruits and vegetables was not significantly associated with consumption (+536 g/d, 95% CI: -427, 1500, n=2 studies). High between study heterogeneity was evident for price increase and soda intake and price discount and fruit intake. Conclusions: These prospective results support taxation to reduce soda intake. More evidence from prospective studies and trials is needed on food pricing and other dietary outcomes and adiposity.
Carnosine as a Possible Factor in Shock
Authors: Edward C. Mason, Sam Binkley
Journal: Annals of Internal Medicine (1931)

Article1 April 1931Carnosine as a Possible Factor in ShockEDWARD C. MASON, M. D., Ph. D., SAM BINKLEY, B. S., A. B.EDWARD C. MASON, M. D., Ph. D.Search for more papers by this author, SAM BINKLEY, B. S., A. B.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-10-1319 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe investigations of Gulewitsch and Amiradzibi1 led to the discovery of carnosine in beef muscle extract. Von Furth and Schwarz2 found that carnosine accounted for 30 to 44 per cent of the total extractive nitrogen of the skeletal muscle of the horse and dog. Applying similar methods, Guglia and Constantino3, also Von Winiwarter4, concluded that about one-third of the extractive nitrogen contained in skeletal muscle was in the form of carnosine.Carnosine has the following properties:5"100 grams water at 24.9-25 degrees dissolve 31 grams carnosine. It is precipitated from water by alcohol. The nitrate melts at 222 degrees. Colorless...References1 GULEWITSCHAMIRADZIBI WS: Zentrabl. f. Physiol. Chem., 1900-02, XXX, 565., Ber. Chem. Ges., 1900, XXXIII, 1902. CrossrefGoogle Scholar2 VON FURTHSCHWARZ OC: Biochem. Zeitschr., 1911, XXX, 413. Google Scholar3 BUGLIACONSTANTINO GA: Zentrabl. f. Physiol. Chem., 1912, XXVI, 120. CrossrefGoogle Scholar4 VON WINIWARTER A: Arch. Gynäk., 1913, C., 530. CrossrefGoogle Scholar5 MATHEWS AP: Physiol. Chem., 3rd Edition, 610. Google Scholar6 MASONDAVIDSONMATTHEWRASTELLO ECECCWPB: J. Lab. and Clin. Med., 1925, X, 622-630. Google Scholar7 MASONDAVIDSONRASTELLO ECECPB: J. Lab. and Clin. Med., 1925, X, 906-913. Google Scholar8 MASONDAVIDSONMATTHEW ECECCW: J. Lab. and Clin. Med., 1925, X, 997-999. Google Scholar9 DAVIDSON EC: Surg., Gynec. and Obst., 1925, XLI, 202-221. Google Scholar10 HUNTER G: Biochem. Jour., 1921, XV, 689. CrossrefGoogle Scholar11 MASONLEMON ECCW: Auto-intoxication and Shock, (in press). Google Scholar12 SCHWARZGOLDSCHMIDT CE: Pflüger's Arch. f. Physiol., 1924, CCII, 435-443. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Oklahoma City, Oklahoma*From the Department of Physiology, University of Oklahoma School of Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byVasodilatory actions of the dietary peptide carnosineAnalysis of an H 1 receptor-mediated, zinc-potentiated vasoconstrictor action of the histidyl dipeptide carnosine in rabbit saphenous veinCarnosine: Its properties, functions and potential therapeutic applicationsÜBER DIE CHEMISCHEN EIGENSCHAFTEN DES HOMO-CARNOSINS UND SEIN VORKOMMEN IM MUSKEL UND HIRN DES SCHWEINSCarnosine and anserineCarnosine and anserine 1 April 1931Volume 4, Issue 10Page: 1319-1327KeywordsAlcoholsMusclesNitratesShockSkeletal muscles ePublished: 1 December 2008 Issue Published: 1 April 1931 PDF downloadLoading ...
Detection of mitochondrial DNA mutations in head and neck cancers
Authors: Shaoyu Zhou, Keyaunoosh Kassauei, Maria L. Poeta, David J. Cutler, Wayne Koch, David Sidransky, Anirban Maitra, Joseph Califano
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4474 

The potential role of mitochondrial DNA (mtDNA) mutations in head and neck tumor development is not well defined. In the present study, we investigated the frequency and distribution of mitochondrial DNA mutations in head and neck tumors and examined relationship between mtDNA mutations and p53 status. Among the 83 samples sequenced, 52 (62.6%) were found to contain somatic mtDNA mutations. MtDNA mutations were identified in both non-coding (D-loop) and coding regions. Further analysis revealed that the mtDNA mutation frequency was different among individual mitochondrial genes. Most mutations were found in D-loop region, and 30 out of the 52 tumors with mutations carried D-loop mutations. All 13 coding genes were found to contain the mtDNA mutations, however, most mutations were detected in ND2 gene (20 out of 52 tumors), a mitochondrial complex I subunit, followed by ND4, and ND5. Since the mitochondrial complex I is a major source of reactive oxygen species, mutations in these subunits of the complex I may significantly change the status of mitochondrial reactive oxygen species, thus contribute to the tumor development. In addition, 16 tumors were found to carry mutations in ATP6. examination of p53 status showed that mtDNA mutations correlated positively with p53 mutations (p < 0.05). Given that the p53 mutations are frequently present in head and neck cancers, dissection of the causal relationship between p53 and mtDNA mutations may unravel new insights into the mechanism of human cancer development. Taken together, these results clearly demonstrate that mtDNA mutations selectively accumulate in certain mitochondrial genes, which may play an important role in the formation and development of head and neck cancers.
Abstract #5677: High throughput siRNA screening identifies NF-kB as a target for combination therapy in neuroblastoma
Authors: Patricia Tsang, Adam Cheuk, Qing-Rong Chen, Javed Khan
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Topotecan is a topoisomerase I inhibitor that is currently used for treating patients with neuroblastoma. Despite aggressive therapy, patients with high-risk neuroblastoma (metastatic, over the age of 18 months and/or with MYCN amplification) remain incurable. The aim of this study was to identify synergistic therapeutic strategies to use with Topotecan for treating these patients. We performed an in vitro , high-throughput siRNA screening on SKNAS, a neuroblastoma cell line, using a set of 418 apoptotic genes (Qiagen Apoptosis Set V.1). A wet reverse transfection protocol with Dharmafect 1 transfection agent (Dharmacon) was used to deliver siRNAs into cells. Topotecan at different concentrations was added 24 hours post transfection and cell number was measured. In the primary screen, 118 genes alone without Topotecan caused more than two fold suppression of cell growth. 63 genes showed synergy to Topotecan and 178 genes inhibited the action of Topotecan. Positive hits were selected for secondary screening with two new siRNAs sequences per gene and 33 genes continued to show synergy to Topotecan. Pathway analysis of these genes identified NF-kB to be significantly overrepresented amongst these synergistic genes. We next investigated if synergy was observed when Topotecan was used in combination with Fenretinide and Bortezomib which are known inhibitors of the NF-kB pathway. Both of the latter drugs have been extensively tested in the Phase 1/2 setting in pediatrics. We found that both Fenretinide and Bortezomib potentiated the effect of Topotecan in vitro in 3 neuroblastoma cell lines. Preliminary in vivo data using a minimal residual disease xenograft model in SCID BEIGE mice showed that tumor formation was significantly delayed in mice treated with drug combinations compared to single drug alone. Once validated these findings could be rapidly translated to the clinic for combination therapy in patients with high risk neuroblastoma.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5677.
Effect of Ketoconazole on the plasma pharmacokinetics of Axitinib (AG-013736) in healthy volunteers
Authors: Yazdi K. Pithavala, Karen J. Klamerus, May Garrett, Brian Hee, Janessa Mount, Paulina Selaru, Nenad Sarapa
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

232 

Introduction: Axitinib (AG-013736, AG), is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, 3. Pharmacokinetic (PK) studies have demonstrated that AG is predominantly metabolized by cytochrome P450 (CYP) 3A4 and by glucuronidation. The effect of single-dose AG administered with repeated doses of ketoconazole, a potent CYP3A4 inhibitor, on AG PK was assessed in healthy volunteers.     Methods : In a randomized, single-blind, 2-way crossover study, 35 healthy volunteers received AG 5 mg orally (PO) on day 1 after overnight fasting (treatment A), and ketoconazole (400 mg PO on days 1-7) plus AG 5 mg PO on day 4 (treatment B). Crossover treatments were separated by at least 14 days. Blood samples were collected up to 48 and 96 hours post AG dosing during treatment A and B respectively, to assess AG PK. Adverse events (AEs), electrocardiograms, pulse rate, blood pressure, and safety laboratory data were recorded to evaluate safety.    Results: Ketoconazole increased the AG geometric mean AUC0-∞ by approximately 2-fold (404.8 vs 196.7 ng•h/mL) and Cmax by 1.5 fold (76.7 vs 51.0 ng/mL) compared with AG alone. Peak concentrations were achieved after 1.5 hours (AG alone) or 2 hours (AG plus ketoconazole) after dosing. No major safety issues were reported and AEs were mostly mild. Eight subjects reported ≥1 treatment-related (AG or AG+ketoconazole) AE and the most frequently reported AEs were headache and nausea.    Conclusion: AG and ketoconazole co-administration increased AG plasma exposures and peak concentrations in healthy volunteers, thereby providing an upper bound for expected AG plasma concentrations in the presence of potent metabolic inhibition. AG, alone and in combination with ketoconazole, was well tolerated in this study.
Lymphoid Enhancer Binding Factor-1 (LEF1) Expression As a Prognostic Factor In Adult Acute Promyelocytic Leukemia
Authors: Francesco Albano, Luisa Anelli, Antonella Zagaria, Crescenzio Francesco Minervini, Paola Orsini, Luciana Impera, Paola Casieri, Angela Minervini, Giuseppina Tota, Domenico Pastore, Paola Carluccio, Angelo Cellamare, Claudia Brunetti, Nicoletta Coccaro, Giorgina Specchia
Journal: Blood (2013)