tbuckley/cabot-search huggingface dataset:
Epidermal Growth Factor Receptor Mutations in Patients with Non–Small Cell Lung Cancer
Authors: Bruce E. Johnson, Pasi A. Jänne
Journal: Cancer Research (2005)

Abstract A year has passed since mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) were discovered in patients with non–small cell lung cancer (NSCLC) who had dramatic clinical responses to treatment with gefitinib. Additional laboratory and clinical studies have provided further insight into the biological impact of EGFR mutations in cell culture experiments and in patients with NSCLC. In vitro characterizations of NSCLC cell lines and host cell lines transfected with these mutant and wild-type EGFR show that most cell lines with mutated EGFR are growth-inhibited by 10- to 100-fold lower concentrations of gefitinib and erlotinib compared with wild-type EGFR. NSCLC lines with mutations of the EGFR treated with concentrations of gefitinib and erlotinib that are achievable in the plasma undergo apoptosis rather than growth arrest. Retrospective studies of patients with NSCLC-treated gefitinib have reported a close association between EGFR mutations, increased chance of clinical response and longer survival. This review will provide information on the impact of EGFR mutations on gefitinib and erlotinib treatment by in vitro experiments, the outcome of NSCLC patients with these mutations when treated with gefitinib and erlotinib, and the subsets of patients with NSCLC in whom these mutations arise.
A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase
Authors: Bernardo Reina-San-Martín, Wim Degrave, Catherine Rougeot, Alain Cosson, Nathalie Chamond, Anabela Cordeiro-da-Silva, Mario Arala-Chaves, Antonio Coutinho, Paola Minoprio
Journal: Nature Medicine (2000)
736. Novel In Vitro and In Vivo Transcriptome Analysis Identifies New Adenovirus Responsive, Innate Gene Networks
Authors: Zachary Hartman, Anne Kiang, Ruth Everett, Joe Nevins, Esther Black, Andy Amalfiatano
Journal: Molecular Therapy (2005)

Ad (Ad) vector capsids, as well as genes transcribed from the Ad genome, are well understood to impact upon RNA levels of several cellular genes after Ad infection. In this study, we have critically quantitated the global innate cellular response to [E1-]Ad5 vectors at the transcriptome level, both in vitro and in vivo.
Gefitinib combined survival analysis of the mutation positives from the prospective phase II trials (I-CAMP)
Authors: S. Morita, T. Hirashima, K. Hagiwara, T. Hida, N. Sunaga, K. Sugio, A. Inoue, K. Yamazaki, T. Mitsudomi, T. Nukiwa
Journal: Journal of Clinical Oncology (2008)

8101 Background: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients (pts) with advanced non-small cell lung cancer (NSCLC). Several phase II trials of EGFR-TKIs in pts positive for such EGFR mutations have yielded a high response rate and good survival; however, the number of pts enrolled onto those trials was too small to draw any firm conclusion. Methods: We carried out a combined analysis of seven prospective trials conducted in Japan examining the efficacy and safety of gefitinib monotherapy for advanced NSCLC pts with EGFR mutations. In the present study we updated OS and PFS data for the combined survival analysis and examined prognostic factors for OS and PFS using a Cox regression model. Tumor response and gefitinib-related adverse events were also analyzed using the combined data set. Results: A total of 148 pts were combined from the seven trials. The mean age was 64 years (range: 33 to 89 years) and 69% of the patients were women. The patients had stage IIIb (13%), stage IV (60%), or recurrent (26%) disease, and 97% of them had adeno-carcinoma. The patients had a PS of 0 (37%), 1 (49%), 2 (9%), or 3–4 (5%), and 71% were non-smoker. 57% of the patients received gefitinib as their first line of therapy. It was found that median OS and PFS were 24.3 (95% C.I.: 19.8–28.2) months and 9.7months (95% C.I.: 8.2–11.1) months, respectively. Age (p=0.042), histology (p=0.002), and PS (p<0.001) were significantly related to OS. Age (p=0.050), PS (p=0.014), and the number of chemotherapeutic treatments (p=0.021) were significantly related to longer PFS. The combined response rate was 76.4% and only 6% of the patients had progressive disease. Grade 3/4 interstitial lung disease, skin, diarrhea, and liver adverse events were observed in 2.7%, 2.7%, 1.4%, and 8.1% of the pts, respectively. Conclusions: This is the largest analysis of pts with EGFR mutations and demonstrates that gefitinib produces significant antitumor activity and prolonged survival in this selected NSCLC population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Japan, Chugai Pharmaceuticals AstraZeneca Japan
Abstract 13035: Overexpressing Superoxide Dismutase 2 Induces Super-normal Cardiac Function by Enhancing Mitochondrial Function and Metabolic Dilation
Authors: Patrick T Kang, Vahagn Ohanyan, William M Chilian, Yeong-Renn Chen
Journal: Circulation (2014)

During heightened cardiac work, O 2 consumption by the heart increases. This increase benefits energy production via mitochondrial e − transport, but some e − “leak” from respiratory chain and yields O 2 [[Unable to Display Character: &amp;#729;]] − , which is rapidly metabolized into H 2 O 2 by SOD2. To understand the potential systemic effects of the metabolic dilator, H 2 O 2 , we studied mice with cardiac specific SOD2 overexpression, which would increase H 2 O 2 produced by the cardiac mitochondria (by 1.9 fold vs WT). To determine if this enhanced production of H 2 O 2 enhances metabolic dilation, we first evaluated the effectiveness of SOD2 overexpression to effectively enhance mitochondrial function. Mitochondria of SOD2 transgenic mice had a decreased state 3 oxygen consumption rate, but maintained the same level of ATP production; thus indicating a higher P/O ratio and bioenergetics efficiency induced by overexpressing SOD2. Mitochondria of SOD2-tg (compared to WT) produced less • O 2 − , and had lower redox activity (by EPR) and lower GSSG concentration (decreased by 37.2±4.5%). EPR analysis of the isolated mitochondria showed significant decrease of semiquinone in the SOD2-tg at the Q i site (by 69.4±9.9%), and a diminished complex I-derived protein thiyl radical(s). These results support a more reductive physiological setting of the SOD2-tg heart. Cardiac mitochondria isolated from SOD2-tg exhibited no significant differences in the respiratory control index between WT and SOD2-tg. These results support that the SOD2 overexpression is effective and results in enhanced mitochondrial function. Contrast echocardiography was employed to evaluate hemodynamic effects. Mean arterial pressure (MAP) was lower in the SOD2-tg, but was normalized by intravenous injection of catalase suggesting “spill-over” of H 2 O 2 from the myocardium in sufficient amounts to produce a systemic effect. Increasing myocardial work (norepinephrine) caused a far greater increase myocardial blood flow (MBF) per level of work in SOD2-tg compared to WT. Echocardiography indicated SOD2-tg had a significant greater ejection fraction (90±1% vs 74±2%). In conclusion, SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to phenotype of super-normal cardiac function.
Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization
Authors: L. Tang, J.J. Wu, Q. Ma, T. Cui, F.M. Andreopoulos, J. Gil, J. Valdes, S.C. Davis, J. Li
Journal: British Journal of Dermatology (2010)

Journal Article Human lactoferrin stimulates skin keratinocyte function and wound re‐epithelialization Get access L. Tang, L. Tang Departments of Dermatology and Cutaneous Surgery, Search for other works by this author on: Oxford Academic Google Scholar J.J. Wu, J.J. Wu California Institute of Technology, Pasadena, CA 91125, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar Q. Ma, Q. Ma Departments of Dermatology and Cutaneous Surgery, Search for other works by this author on: Oxford Academic Google Scholar T. Cui, T. Cui Departments of Dermatology and Cutaneous Surgery, Search for other works by this author on: Oxford Academic Google Scholar F.M. Andreopoulos, F.M. Andreopoulos Biomedical Engineering and Surgery, and Search for other works by this author on: Oxford Academic Google Scholar J. Gil, J. Gil Departments of Dermatology and Cutaneous Surgery, Search for other works by this author on: Oxford Academic Google Scholar J. Valdes, J. Valdes Departments of Dermatology and Cutaneous Surgery, Search for other works by this author on: Oxford Academic Google Scholar S.C. Davis, S.C. Davis Departments of Dermatology and Cutaneous Surgery, Search for other works by this author on: Oxford Academic Google Scholar J. Li J. Li Departments of Dermatology and Cutaneous Surgery,Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL 33136, U.S.A. Jie Li. E‐mail: jli@med.miami.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 1, 1 July 2010, Pages 38–47, https://doi.org/10.1111/j.1365-2133.2010.09748.x Published: 01 July 2010
Inhibition of ongoing allergic reactions using a novel anti-IgE DARPin-Fc fusion protein
Authors: A. Eggel, P. Buschor, M. J. Baumann, P. Amstutz, B. M. Stadler, M. Vogel
Journal: Allergy (2011)

To cite this article: Eggel A, Buschor P, Baumann MJ, Amstutz P, Stadler BM, Vogel M. Inhibition of ongoing allergic reactions using a novel anti-IgE DARPin-Fc fusion protein. Allergy 2011; 66: 961–968. Background: Aggregation of the high-affinity IgE receptor (FcεRI) with the low-affinity IgG receptor (FcγRIIb) on basophils or mast cells has been shown to inhibit allergen-induced cell degranulation. Molecules cross-linking these two receptors might therefore be of interest for the treatment of allergic disorders. Here, we demonstrate the generation of a novel bispecific fusion protein efficiently aggregating FcεRI-bound IgE with FcγRIIb on the surface of basophils to prevent pro-inflammatory mediator release. Methods: Alternative binding molecules recognizing receptor-bound human IgE were selected from DARPin (designed ankyrin repeat protein) libraries. One of the selected DARPins was linked to the Fc-part of a human IgG1 antibody for binding to FcγRIIb. Results: The resulting anti-IgE DARPin-Fc fusion protein was not anaphylactogenic and inhibited allergen-induced basophil activation in whole blood assays. Both binding moieties of the fusion protein, namely the anti-IgE DARPin as well as the IgG1 Fc-part, were required to achieve this inhibitory effect. Most importantly, inhibition was faster and more efficient than with Omalizumab, a humanized anti-IgE antibody currently used for the treatment of severe asthma. Conclusion: This novel anti-IgE DARPin-Fc fusion protein might represent a potential drug candidate for preventive or immediate treatment of allergic reactions.
Abstract 1788: 19-Substituted benzoquinone ansamycins. Hsp90 inhibitors with decreased off-target toxicity
Authors: Chuan-Hsin Chang, Derek A. Drechsel, Russell R.A. Kitson, David Siegel, Qiang You, Donald S. Backos, Cynthia Ju, Christopher J. Moody, David Ross
Journal: Cancer Research (2014)

Abstract Benzoquinone ansamycin (BQA) Hsp90 inhibitors such as 17-DMAG and 17-AAG have off-target toxicities in clinical trials including hepatotoxicity. Mechanisms underlying the toxicity of quinones are a function of their ability to redox cycle and/or arylate cellular nucleophiles at the unsubstituted 19-position of the molecule. Therefore, we designed 19-substituted BQAs to prevent glutathione conjugation and non-specific interactions with protein thiols as an approach to reduce the hepatotoxicity and minimize off-target effects of the BQA class of Hsp90 inhibitors. In this study, the results showed that 19-substituted BQAs did not react with glutathione at the 19-position, while marked reactivity was observed using parent BQAs. Importantly, while parent 17-DMAG induced cell death in primary and cultured mouse hepatocytes, 19-phenyl and 19-methyl 17-DMAG showed reduced toxicity, validating the overall approach. There was no significant difference between the redox cycling ability of either 19-phenyl or 19-methyl 17-DMAG with their parental BQAs in both mouse and human liver microsomes. Accordingly, this suggests that arylation reactions at the unsubstituted 19-position are predominantly responsible for hepatotoxicity. 19-substituted17-DMAG inhibited purified Hsp90 ATPase activity in an NQO1-dependent manner that demonstrated increased inhibitory efficacy of the hydroquinone ansamycin relative to its parent quinone. In human breast cancer cells, 19-phenyl BQAs induced growth inhibition in an NQO1-dependent manner with molecular signatures of Hsp90 inhibition, including decreases in client proteins and compensatory induction of Hsp70. These data indicate that 19-substituted BQAs may be useful Hsp90 inhibitors with decreased off target toxicity (Supported by NCI grant CA51210) Citation Format: Chuan-Hsin Chang, Derek A. Drechsel, Russell R.A. Kitson, David Siegel, Qiang You, Donald S. Backos, Cynthia Ju, Christopher J. Moody, David Ross. 19-Substituted benzoquinone ansamycins. Hsp90 inhibitors with decreased off-target toxicity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1788. doi:10.1158/1538-7445.AM2014-1788
Emergency Abdominal Surgery in Infancy, Childhood and Adult Life.
Authors: Peter F. Jones
Journal: Annals of Internal Medicine (1974)

This book offers a comprehensive, detailed and accessible account of the whole field of emergency abdominal surgery. In this latest edition, each chapter has been thoroughly revised and updated by experienced surgeons qualified to offer extensive, practical, evidence-based guidance. They each provide an up-to-date review of the pathology, clinical presentation and diagnosis of their subject, before proposing tried-and-tested treatment options. Assessment is made of recent advances, consideration given to controversial options and attention drawn to areas of difficulty in the operative procedure, which is described and illustrated in detail. Finally, each chapter is fully indexed and cross-referenced.Of particular significance is the comprehensive coverage given to the acute abdomen in infants and children who present a number of distinctive conditions and requirements. Such discussion will become increasingly relevant in the context of treatment outside of specialist centres.
PhadiatopS in the diagnosis of respiratory allergy in children*1Allergy project ? PROAL, Brazil
Authors: C.K. Naspitz, D. Solé, B.A. Paes-Barreto, C.A.M. Jacob, E.C.S. Sarinho, F.J.P. Soares, L.S. Freitas, L.K.P. Arruda, M.C. Mallozi, M.L. Chavarria, M.M.S. Vilela, N.A. Rosário, N.F. Wandalsen, V.M. Dantas, W. Borges
Journal: Journal of Allergy and Clinical Immunology (2004)
Abstract 15903: “Out-Of Hospital Cardiac Arrest Clinical Trials, Relationship Between Clinical Trial Sample Size and the Odds Ratio of Treatment Effect 1978 to the Present"
Authors: Katelin M Engerer, James V Coleman, Luca F Valle, Matt Roginski, Norman A Paradis
Journal: Circulation (2014)

Introduction:  Randomized clinical trials (RCT) have been conducted in out of hospital cardiac arrest (OOHCA) since at least 19709s. Despite significant effort toward development of clinical trial expertise in resuscitation research, positive trials have been rare. It is well recognized that large treatment effects in early, relatively small clinical trials are often not replicated in later large Phase III trials.   Hypothesis:  There is a negative relationship between sample size (SS) and the odds ration (OR) of treatment effect in OOHCA randomized clinical trials (RCT’s).   Methods:  Comprehensive online search for RCTs in OOHCA with n > 100 (control group n>50), 1960 to present with extraction of demographic, clinical and outcome variable and regression analysis of SS and OR of treatment effect.   Results:  n=72 usable RCTS were identified, all since 1978. There was a significant negative relationship between OR and SS (p    Limitations:  Retrospective methodology and background regional differences limits significance and applicability, hypothesis generating only.   Conclusion:  Similar to other clinical entities, OOHCA RCT’s may have a relationship between the OR of treatment effect and the study SS. This effect should be considered in the evaluation and development of new therapies.
Abstract 4375: UVC irradiation in combination with fluorescence-guided surgery cures metastatic human pancreatic cancer in orthotopic mouse models
Authors: Yukihiko Hiroshima, Ali Maawy, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
Journal: Cancer Research (2014)

Abstract The aim of this study was to determine the efficacy of UVC irradiation in combination with fluorescence-guided surgery (FGS) in an orthotopic model of pancreatic cancer. Two weeks after orthotopic implantation of human MiaPaCa-2-GFP pancreatic cancer cells, bright-light surgery (BLS) was performed on all tumor-bearing mice (n=24). Postoperatively, the surgical resection bed was imaged with the OV100 variable magnification imaging system with a magnification of 0.56x to detect residual tumor. The mice which underwent BLS were randomized into 3 groups; BLS only (n=8) or FGS (n=8) or FGS-UVC (n=8). The residual tumors were resected with FGS using a portable, hand-held imaging system. After FGS, the surgical resection bed was imaged with the OV100 with a magnification of 0.89x, to detect minimal residual tumor and was irradiated with 2700 J/m2 UVC (emission peak 254 nm) from the bottom of a chamber using a Benchtop 3UV transilluminator (UVP, LLC, Upland, CA). The average residual tumor area after FGS was significantly smaller than BLS (0.135 ± 0.137 mm2 and 3.338 ± 2.929 mm2, respectively; p=0.007). Relapse-free survival (RFS) and overall survival (OS) were determined in 3 groups. Three-month RFS in the BLS, FGS and FGS-UVC were 0%, 50% and 100%, respectively. Five-month OS in BLS, FGS and FGS-UVC was 10%, 90% and 100%, respectively. FGS and FGS-UVC resulted in significantly increased survival compared to BLS for both RFS and OS. FGS-UVC showed significantly increased survival compared to the FGS for both RFS and OS (p=0.008 and p=0.025, respectively). These results suggests that UVC irradiation in combination with FGS could be a curative strategy for human pancreatic cancer. Citation Format: Yukihiko Hiroshima, Ali Maawy, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. UVC irradiation in combination with fluorescence-guided surgery cures metastatic human pancreatic cancer in orthotopic mouse models. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4375. doi:10.1158/1538-7445.AM2014-4375
ARTERIAL OXYGEN SATURATION IN CIRRHOSIS OF THE LIVER
Authors: Robert C. Darling
Journal: Annals of Internal Medicine (1940)

Article1 November 1940ARTERIAL OXYGEN SATURATION IN CIRRHOSIS OF THE LIVERROBERT C. DARLING, M.D.ROBERT C. DARLING, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-5-898 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe finding of a severe degree of oxygen unsaturation in the arterial blood of patients with cirrhosis of the liver has been reported by Snell.1 Later, Keyes and Snell2 studied a further series with oxygen dissociation curves, and found a small but significant shift in the curve from the accepted normal value. In this second series the oxygen unsaturation of the arterial blood was less marked than in the first series. From this work it was concluded that the hemoglobin in liver disease had properties somewhat different from normal.Since there are few objective tests for measuring the disturbances of...Bibliography1. SNELL AM: The effects of chronic disease of the liver on the composition and physicochemical properties of blood: changes in the serum proteins; reduction in the oxygen saturation of the arterial blood, ANN. INT. MED., 1935, ix, 690-711. Google Scholar2. KEYESSNELL AAM: Respiratory properties of the arterial blood in normal man and in patients with disease of the liver: position of the oxygen dissociation curve, Jr. Clin. Invest., 1938, xvii, 59-67. CrossrefGoogle Scholar3. DILLGRAYBIELHURTADOTAQUINI DBAAAC: Der Gasaustausch in den Lungen in Alter, Ztschr. f. Altersforsch., 1940, ii, 20-33. Google Scholar4. DILLEDWARDSCONSOLAZIO DBHTWV: Blood as a physicochemical system. XI. Man at rest, Jr. Biol. Chem., 1937, cxviii, 635-648. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication July 3, 1940.Research Service (Formerly Research Division for Chronic Diseases), First Division, Welfare Hospital, Department of Hospitals, New York City, and Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe oxyhemoglobin dissociation curve in health and diseaseClosing volume — A test of small airway function?Hypertrophic osteoarthropathy with arthritis and synovial calcification in a patient with alcoholic cirrhosisCirrhosis, cyanosis and polycythaemia: Multiple pulmonary arteriovenous anastomosesOxyhemoglobin Dissociation in Patients with Hepatic EncephalopathyArterial Changes in the Lungs in Cirrhosis of the Liver — Lung Spider NeviSystemic Circulatory Adjustments in Hepatic DiseaseVENOARTERIAL SHUNTS IN CIRRHOSIS OF THE LIVER 1 November 1940Volume 14, Issue 5Page: 898-902KeywordsBloodCirrhosisHemoglobinHospital medicineLiverLiver diseasesOxygenSurgeons Issue Published: 1 November 1940 PDF downloadLoading ...