tbuckley/cabot-search huggingface dataset:
Abstract B36: Modeling genetic mechanisms of resistance in melanoma primary tumor xenografts
Authors: Alejandro Balbin, Angad Singh, Joshua Korn, Hui Gao, Darrin Stuart, John Green, Andrew Crenshaw, Scott Mahan, Nathan Houde, Alina Raza, Rebecca Leary, Derek Chiang, Michael Morrissey, Wendy Winckler, Sellers William
Journal: Clinical Cancer Research (2015)

Abstract Melanoma is the most lethal skin cancer and approximately 50% of the cases harbor mutations in the BRAF oncogene, with the mutation V600E representing 80-90% of all BRAF mutations in this indication. BRAF inhibitors as Vemurafenib and Dabrafenib have shown improved overall and progression free survival; however, the long term efficacy of these compounds is limited by the emergence of resistance. Several mechanisms of resistance to BRAF inhibitors have been already described, such as BRAF overexpression, increased ERBB3 signaling, expression of BRAF alternative isoforms, secondary mutations in BRAF or MEK1 and recently BRAF amplifications, among others. A fundamental aspect on devising optimal therapeutic regimes that overcome resistance is to develop preclinical models that resemble the genetic makeup of clinical patients who become resistance during the course of treatment to BRAF inhibitors. To this end, melanoma primary tumor xenografts (PTX) harboring BRAF V600E mutations were subject to treatment with BRAF inhibitors and response data was collected for a maximum of 180 days. Vehicle and treated samples were then sequenced using a targeted next generation sequencing approach in order to characterize their mutational landscape. Raw sequencing data was aligned to the human genome and potential mouse contamination was filter out before downstream analysis. Comparing SNV and copy number calls between treated and control samples revealed that focal amplifications of BRAF and de-novo mutations in the MEK1 gene were frequent genetic aberrations found in the PTX models that developed resistance. In summary, our results indicate that the genetic mechanisms of resistance observed in primary tumor xenograft models closely resemble what is observed in the clinical setting, making these models a valuable research tool for designing optimal therapeutic strategies. Citation Format: Alejandro Balbin, Angad Singh, Joshua Korn, Hui Gao, Darrin Stuart, John Green, Andrew Crenshaw, Scott Mahan, Nathan Houde, Alina Raza, Rebecca Leary, Derek Chiang, Michael Morrissey, Wendy Winckler, Sellers William. Modeling genetic mechanisms of resistance in melanoma primary tumor xenografts. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B36.
Allogeneic Stem Cell Transplantation for Agnogenic Myeloid Metaplasia: A European Group for Blood and Marrow Transplantation, Société Française de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study
Authors: P. Guardiola, J. Anderson, G. Bandini, F. Cervantes, V. Runde, W. Arcese, A. Bacigalupo, D. Przepiorka, M.R. O'Donnell, P. Polchi, A. Buzyn, L. Sutton, D. Cazals-Hatem, G. Sale, T.J.M. de Witte, H.J. Deeg, E. Gluckman
Journal: Blood (1999)
DNA Aptamer Selected against Pancreatic Ductal Adenocarcinoma for <i>in vivo</i> Imaging and Clinical Tissue Recognition
Authors: Xiaoqiu Wu, Zilong Zhao, Huarong Bai, Ting Fu, Chao Yang, Xiaoxiao Hu, Qiaoling Liu, Carole Champanhac, I-Ting Teng, Mao Ye, Weihong Tan
Journal: Theranostics (2015)

In this work, we have developed a truncated DNA aptamer, termed XQ-2d, with high affinity and specificity for pancreatic ductal adenocarcinoma (PDAC).Aptamer XQ-2d selectively binds to PL45 cells with a dissociation constant in the nanomolar range, as determined by its recognition of PL45 tumor cells in mice.Moreover, XQ-2d shows better recognition ratio for 40 tissue sections of clinical PDAC samples (82.5%) compared to the initial cell-SELEX selection library (5%).Therefore, XQ-2d can be considered a promising candidate as a tool for PDAC diagnosis and treatment.
Abstract 19355: Lower Heart Rates are Associated with Better Mid-term Outcomes in Fontan Patients
Authors: Clara Kurishima, Hideaki Senzaki, Tokuko Shinohara, Toshio Nakanishi
Journal: Circulation (2014)

Background: In adult heart failure, higher heart rates (HR) are known to be associated with increased risks of myocardial infarction and sudden cardiac death. Thus, HR modulation has been increasingly recognized as a potentially effective therapy for heart failure. HR may also be a useful therapeutic target in patients after the Fontan surgery, in which effective treatment to improve prognosis remains to be established. We hypothesized that lower HR is associated with better mid-term outcomes in Fontan patients. Methods: We retrospectively analyzed 24-hour Holter ECG in 56 consecutive patients in the chronic phase (at least 1 year) after the Fontan operation and in the sinus rhythm (mean age; 19 years, range; 9-49 years). Data for minimum, maximum, and average HR were extracted. We then examined the relationships between HR values and mid-term hemodynamic and clinical (6-min walk-distance) outcomes. Mid-term outcomes were assessed both at 1-3 years (mean 1.5 years) after the initial Holter recording (Group 1) and at more than 3 years (mean 4.9 years) after the initial Holter recording (Group 2). Results: Lower values of mean and minimum HR were significantly correlated with lower CVP in both groups (P&lt;0.05, for each). Mean and minimum HR were also significantly and negatively correlated with the 6-min walk-distance in Group 2 (P &lt;0.05 for each). The results were similar after controlling for age by multivariate analysis. Importantly, lower HR was not associated with decreased cardiac output. Conclusions: The present study demonstrated for the first time that lower HR can lead to better mid-term outcomes of hemodynamics and exercise capacity in Fontan patients. HR can be an important therapeutic target to improve the prognosis after the Fontan operation.
Hepatitis C virus replication in mice with chimeric human livers
Authors: David F. Mercer, Daniel E. Schiller, John F. Elliott, Donna N. Douglas, Chunhai Hao, Aline Rinfret, William R. Addison, Karl P. Fischer, Thomas A. Churchill, Jonathan R.T. Lakey, David L.J. Tyrrell, Norman M. Kneteman
Journal: Nature Medicine (2001)
685. Epithelium-Specific Gene Therapy Vector Protects Cftr Knockout Mice from Acute Lung Infection
Authors: David R. Koehler, Umadevi Sajjan, McKerlie Colin, Allan Coates, Keith Tanswell, Forstner F. Janet, Jim Hu
Journal: Molecular Therapy (2004)

Development of safe and effective vectors remains a major challenge for lung gene therapy. We developed a helper-dependent adenoviral vector for cystic fibrosis (CF) lung gene therapy, using epithelium-specific control elements to drive expression of the CF transmembrane conductance regulator (Cftr) gene. The vector expressed properly localized CFTR in human CF bronchial epithelial cells cultured at an air-liquid interface. Following a single intranasal dose, the vector expressed human CFTR specifically in the airway epithelium of mice, for up to 3 months. Acute inflammation was minimal to moderate. CFTR protein was also detected in the airway epithelium of 2 month-old mice that received one vector dose postnatally. Delivery of the vector to rabbit lung, in an aerosol containing surfactant, yielded strong gene expression (lacZ reporter) specifically in the airway epithelium, including trachea, bronchi, and bronchioles.
Immunization With a Lipid-Conjugated Membrane Antigen To Suppress Growth of a Fibrosarcoma Induced by Simian Virus 402
Authors: Robert L. Hunter, Faith Strickland
Journal: JNCI Journal of the National Cancer Institute (1975)

The covalent conjugation of fatty acid to a tumor cell membrane preparation transformed it from an antigen that enhanced tumor growth to one that suppressed it. A crude cell membrane preparation was made by sequential hypertonic and hypotonic salt extraction of tumor cells from a fibrosarcoma induced in hamsters by simian virus 40. The membranes were chemically conjugated with dodecanoic anhydride in 0.5 M carbonate buffer (pH 9.0). Injection of unmodified membranes 10 days before transplantation of live tumor cells produced clear-cut enhancement of the tumor growth rate. In contrast, injection of lipid-conjugated membranes in a similar dose and protocol suppressed tumor growth. The lymphoid proliferative reactions to the tumor cells as demonstrated by the histology of both the tumor and regional lymph nodes were consistent with the hypothesis that unmodified membranes stimulated the production of antibody which participated in the enhancement of tumor growth, and that lipid-conjugated membranes stimulated the production of cell-mediated immunity which suppressed this growth.
A Rapid Quantitative Hematocrit Method for Measuring Increase in Cell Population of Strain L (Earle) Cells Cultivated in Serum-Free Nutrient Solutions&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Charity Waymouth
Journal: JNCI Journal of the National Cancer Institute (1956)

A Rapid Quantitative Hematocrit Method for Measuring Increase in Cell Population of Strain L (Earle) Cells Cultivated in Serum-Free Nutrient Solutions Get access Charity Waymouth Charity Waymouth Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 17, Issue 3, September 1956, Pages 305–313, https://doi.org/10.1093/jnci/17.3.305 Published: 01 September 1956 Article history Received: 27 April 1956 Published: 01 September 1956
Clinical trials in primary care
Authors: R. Foy, J. Parry, B. McAvoy
Journal: BMJ (1998)

“Why is it every time that I mention the word reform' GPs reach nervously for their wallets?” These cynical words from Kenneth Clarke, former secretary of state for health, contain a grain of truth. Most British general practices are small businesses, understandably influenced by financial incentives and disincentives—or “the imagination, enterprise and investment assumptions of corner shopkeeping.”1What effect does this have on research in primary care? And would explicit financial incentives improve the amount and quality of primary care research?

Demand for high quality research in primary care is growing, particularly multicentre randomised controlled trials. But such studies are difficult to conduct, disruptive to routine practice, and may fail to recruit enough general practitioners or patients.2 The Mant report advocates expanding recruitment of multidisciplinary researchers and redistributing funds to support the required infrastructure.3 Such a long term strategy to build capability is essential but will not be sufficient on its own to improve rates of practice recruitment to clinical trials.

Several factors are known to influence general practitioners' participation in research. One is the level of personal interest in the research topic.4Concern has grown recently that “enquiry led research is becoming endangered with the growth in the …
TUBERCULOSIS AND CORONARY THROMBOSIS
Authors: J H ROGERS
Journal: Annals of Internal Medicine (1957)

Article1 July 1957TUBERCULOSIS AND CORONARY THROMBOSISJ. H. ROGERS, M.D.J. H. ROGERS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-47-1-78 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAttention has recently been called to the low incidence of coronary disease in various groups throughout the world. These groups include Orientals, some African tribes and American Indians, and possibly others. Attention has also been called to the low incidence of coronary disease which prevailed in countries of Western Europe during the war and immediate postwar period. In these countries, prior to the war (as now), coronary disease had presented a serious problem. These observations have been largely responsible for the present popularity of the dietary or metabolic concept of coronary disease, since a substandard diet, low in fat, has...Bibliography1. JonesBlackSparr RSTCHA: Incidence and significance of thromboembolism in pulmonary tuberculosis, Am. Rev. Tuberc. 61: 826 (June) 1950. MedlineGoogle Scholar2. FoxRobitzekBernsteinBobb TTEHIAL: Bed rest in thromboembolization in tuberculosis, Am. Rev. Tuberc. 57: 485, 1948. MedlineGoogle Scholar3. Coryllos PN: Surgical discussion, Quart. Bull., Sea View Hosp. 1: 132, 1935. Google Scholar4. PeckWillis WMHS: Bed rest in tuberculosis: its dangers and proprieties, Am. Rev. Tuberc. 52: 15, 1945. Google Scholar5. Zins EI: Concerning the location of pulmonary infarction, Am. Rev. Tuberc. 60: 206, 1949. MedlineGoogle Scholar6. ZahnPierce DWCT: Venous thrombosis and pulmonary embolism in tuberculosis, Am. J. Med. 5: 716, 1948. CrossrefMedlineGoogle Scholar7. Wintrobe MM: Clinical hematology, 4th Ed., 1956, Lea and Febiger, Philadelphia, p. 888. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Gadsden, Alabama*Received for publication March 16, 1957.Requests for reprints should be addressed to Joseph Handley Rogers, M.D., 3d floor American National Bank Building, Gadsden, Alabama. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byGame TheoryGame TheoryEpidemiologic Investigations in Relation to Diet in Groups Who Show Little Atherosclerosis and Are Almost Free of Coronary Ischemic Heart DiseaseNormal hemoglobin level and coronary heart diseaseCORONARY THROMBOSIS AND CONOVIDPROFESSIONS SUPPLEMENTARYIMMUNISATION FOR THROMBOSIS AND ARTERIOSCLEROSISCORONARY THROMBOSIS, CEREBRAL VASCULAR ACCIDENT AND PULMONARY EMBOLISM IN LEPROSY*JOSEPH H. ROGERS, M.D. 1 July 1957Volume 47, Issue 1Page: 78-80KeywordsCOVID-19DietFatsMetabolic disordersNative American peopleThrombosisTuberculosis ePublished: 1 December 2008 Issue Published: 1 July 1957 PDF downloadLoading ...
QRS Duration in Patients Hospitalized for Worsening Heart Failure
Authors: Abdul Hakeem, Sabha Bhatti, Zainab Samad
Journal: JAMA (2008)

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
The Antiinflammatory Properties of Medroxyprogesterone Acetate
Authors: Dominik Rachoń
Journal: Circulation (2002)

The Antiinflammatory Properties of Medroxyprogesterone AcetateTo the Editor:I have read the article by Wakatsuki et al 1 with considerable interest.The study showed that the continuous oral treatment of postmenopausal women for 3 months with conjugated equine estrogens (CEE) (0.625 mg/day) alone or with medroxyprogesterone acetate (MPA) at the dose of 2.5 mg/day, significantly increased serum C-reactive protein (CRP) and amyloid A protein (SAA) levels.This effect was attenuated by the concurrent administration of MPA at the dose of 5 mg/day.CEE alone significantly decreased the concentration of E-selectin, but the concentrations of intracellular adhesion molecule (ICAM-1) and vascular cellular adhesion molecule (VCAM-1) did not change significantly.Concentrations of ICAM-1, VCAM-1, and E-selectin were all significantly reduced among postmenopausal women treated with CEE plus MPA 5 mg/day.The authors conclude that because androgens have antiinflammatory properties, 2 androgenic progestins such as MPA (?) may attenuate proinflammatory effects of estrogens and may actually be responsible for the favorable effect of estrogen-progestogen combinations on inflammatory markers such as cellular adhesion molecules (ICAM-1, VCAM-1, E-selectin) and acute phase proteins (CRP and SAA) in postmenopausal women undergoing hormonal replacement therapy.MPA is a 17␣-hydroxyprogesterone derivative and it is structurally related to progesterone and not testosterone. 3In addition to binding to progesterone receptor, MPA may interact with the glucocorticoid receptor. 4Progesterone and its derivatives have antiinflammatory and immunosuppressive properties that are relevant for maintenance of pregnancy. 5Because MPA is not a 19nortestosterone derivative (androgenic progestin), its antiinflammatory properties can be attributed to its ability to interact with the progesterone and glucocorticoid receptors, not the androgen receptor.
Arylsulfatase A Overexpressing Human iPSC-derived Neural Cells Reduce CNS Sulfatide Storage in a Mouse Model of Metachromatic Leukodystrophy
Authors: Jonas Doerr, Annika Böckenhoff, Benjamin Ewald, Julia Ladewig, Matthias Eckhardt, Volkmar Gieselmann, Ulrich Matzner, Oliver Brüstle, Philipp Koch
Journal: Molecular Therapy (2015)

Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder resulting from a functional deficiency of arylsulfatase A (ARSA), an enzyme that catalyzes desulfation of 3-O-sulfogalactosylceramide (sulfatide). Lack of active ARSA leads to the accumulation of sulfatide in oligodendrocytes, Schwann cells and some neurons and triggers progressive demyelination, the neuropathological hallmark of MLD. Several therapeutic approaches have been explored, including enzyme replacement, autologous hematopoietic stem cell-based gene therapy, intracerebral gene therapy or cell-based gene delivery into the central nervous system (CNS). However, long-term treatment of the blood-brain-barrier protected CNS remains challenging. Here we used MLD patient-derived induced pluripotent stem cells (iPSCs) to generate long-term self-renewing neuroepithelial stem cells and astroglial progenitors for cell-based ARSA replacement. Following transplantation of ARSA-overexpressing precursors into ARSA-deficient mice we observed a significant reduction of sulfatide storage up to a distance of 300 µm from grafted cells. Our data indicate that neural precursors generated via reprogramming from MLD patients can be engineered to ameliorate sulfatide accumulation and may thus serve as autologous cell-based vehicle for continuous ARSA supply in MLD-affected brain tissue. Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disorder resulting from a functional deficiency of arylsulfatase A (ARSA), an enzyme that catalyzes desulfation of 3-O-sulfogalactosylceramide (sulfatide). Lack of active ARSA leads to the accumulation of sulfatide in oligodendrocytes, Schwann cells and some neurons and triggers progressive demyelination, the neuropathological hallmark of MLD. Several therapeutic approaches have been explored, including enzyme replacement, autologous hematopoietic stem cell-based gene therapy, intracerebral gene therapy or cell-based gene delivery into the central nervous system (CNS). However, long-term treatment of the blood-brain-barrier protected CNS remains challenging. Here we used MLD patient-derived induced pluripotent stem cells (iPSCs) to generate long-term self-renewing neuroepithelial stem cells and astroglial progenitors for cell-based ARSA replacement. Following transplantation of ARSA-overexpressing precursors into ARSA-deficient mice we observed a significant reduction of sulfatide storage up to a distance of 300 µm from grafted cells. Our data indicate that neural precursors generated via reprogramming from MLD patients can be engineered to ameliorate sulfatide accumulation and may thus serve as autologous cell-based vehicle for continuous ARSA supply in MLD-affected brain tissue.
Abstract 20295: Key Role of Integrin Alpha6/Beta4 in Endothelial Cell Barrier Regulation
Authors: Anne E Cress, Weiguo Chen, Yulia Epstein, Joseph B Mascarenhas, Ting Wang, Tong Zhou, Rick Kittles, Joe G Garcia, Jeffrey R Jacobson
Journal: Circulation (2014)

The dynamic regulation of lung endothelial cell (EC) barrier integrity is essential in the initiation and resolution of inflammation during acute lung injury (ALI) and ventilator-induced lung injury (VILI). In previous studies, we identified integrin beta β4 (ITGβ4) as a key focal adhesion (FA) component, involved in human lung EC barrier enhancement by simvastatin. The clear functional role and key contribution of ITGβ4 in endothelial barrier regulation vascular permeability is largely unknown. We demonstrated that reduced ITGβ4 expression (siRNA attenuated sphingosine-1-phosphate (S1P, 1 μM) or hepatocyte growth factor (HGF, 25 ng/ml) mediated endothelial barrier enhancement. At the same time, S1P receptor 1 (S1PR1) or HGF receptor cMet knockdown also attenuated S1P- or HGF-mediated endothelial barrier enhancement. Consistent with these findings, in situ proximity ligation assays revealed that ITGβ4, S1PR1, and cMet, translocated together to the cell periphery as co-localized proteins after HGF treatment. We further confirmed that the interaction of c-Met and S1PR1 with ITGβ4 was dependent upon ITGβ4 phosphorylation, which is essential for HGF-mediated barrier enhancement. The selective antibody targeting integrin α6 (ITGα6, 10 μg/ml), the only binding partner of ITGβ4, attenuates S1P-mediated endothelial barrier enhancement. Furthermore, this antibody retarded barrier recovery after thrombin (0.5 U/ml), an EC barrier disruptor. These findings highly suggest ITGβ4 is essential participant in EC barrier regulation and paracellular gap closure. We next exposed genetically-engineered mice expressing a mutant ITGβ4 that lacks the cytoplasmic tail to ventilator-induced lung injury (VILI). The absence of the cytoplasmic tail conferred significant attenuation of inflammatory lung injury compared to wild-type controls with reduced BAL protein and cell counts and lung inflammation. These data suggest that the ITGβ4 cytoplasmic domain is an important participant in both pro- and anti-inflammatory responses to the excessive mechanical stress produced by VILI. In summary, ITGβ4 is a central regulator of endothelial barrier function, and a novel therapeutic target for acute lung inflammation.