tbuckley/cabot-search huggingface dataset:
Verification of the Newly Proposed T Category (Seventh Edition of the Tumor, Node, and Metastasis Classification) from a Clinicopathological Viewpoint in Non-small Cell Lung Cancer—Special Reference to Tumor Size
Authors: Tokujiro Yano, Yosuke Morodomi, Kensaku Ito, Tsukihisa Yoshida, Akira Haro, Fumihiro Shoji, Takaomi Koga, Yoshihiko Maehara
Journal: Journal of Thoracic Oncology (2010)
Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome
Authors: Evanthia Diamanti-Kandarakis, Asimina Mitrakou, Magda M.I. Hennes, Dimitris Platanissiotis, Nicholas Kaklas, Jovanna Spina, Elli Georgiadou, Raymond G. Hoffmann, Ahmed H. Kissebah, Sotos Raptis
Journal: Metabolism (1995)
Abstract 4672: Tumor dihydropyrimide dehydrogenase (DPYD) expression is associated with survival in patients with metastatic colorectal cancer treated with gefitinib, 5-fluorouracil, leucovorin, and oxaliplatin (IFOX)
Authors: Edgar B. Francisco, James T. Link, Meghan Ramsey, Andy H. Beck, Erich Schwartz, Robert Rouse, George A. Fisher, Branimir I. Sikic
Journal: Cancer Research (2010)

Abstract New drugs that target the EGFR signaling pathways suggest that EGFR inhibition exerts a chemosensitizing effect in colorectal cancer. We have previously reported that the combination of gefitinib, leucovorin, 5-flourouracil, and oxaliplatin (IFOX) resulted in higher response rates than those reported with FOLFOX-4 alone in patients with metastatic colorectal cancer. The aim of the present study was to examine genomic factors that might be associated with response or survival in the IFOX regimen. Patients and Methods: Seventy-two patients had stage IV colorectal adenocarcinoma and were either untreated or previously treated prior to receiving the IFOX regimen. Formalin-fixed, paraffin-embedded tissues (FFPE; n=63) were obtained, and 4-um sections were cut, placed on slides, and deparaffinized in xylene, followed by laser capture microdissection (LCM; n=42) to enrich for tumor cells. Using real-time quantitative RT-PCR, thirty-five samples had good-quality actin RNA readings following LCM, and the expression levels of dihydropyrimidine dehydrogenase (DPYD), epidermal growth factor receptor (EGFR), excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), thymidylate synthase (TYMS), and thymidine phosphorylase (TYMP) were separately quantified. To detect mutations in KRAS, DNA was extracted from fifty-eight patient samples and analyzed using the KRAS Mutector II kit (TrimGen, Sparks, MD). Results: For the 33 patients available for RT-PCR analysis, expression levels of DPYD, EGFR, ERCC1, TYMP, or TYMS did not correlate significantly with response. However, in terms of survival, the overall survival rate was significantly worse in patients with a high DPYD expression level compared to patients with a low DPYD expression level (p&amp;lt;0.05), and in a multivariate analysis, patients with both a high DPYD expression and a low EGFR expression had the worst survival compared to all other patients with differing expression levels of these two genes (p&amp;lt;0.01). KRAS mutations were identified in 24 out of 58 patients (41%), but KRAS mutational status did not correlate with either response or survival. Conclusion: Dihydropyrimidine dehydrogenase mRNA expression was a significant independent prognostic factor for overall survival in colorectal cancer patients treated with FOLFOX-4 along with EGFR inhibition by gefitinib. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4672.
11beta-Hydroxysteroid dehydrogenase type 1 inhibitors: novel agents for the treatment of metabolic syndrome and obesity-related disorders?
Authors: Panagiotis Anagnostis, Niki Katsiki, Fotini Adamidou, Vasilios G. Athyros, Asterios Karagiannis, Marina Kita, Dimitri P. Mikhailidis
Journal: Metabolism (2012)
Activation of Flk-1/KDR mediates angiogenesis but not hypotension
Authors: B Malavaud
Journal: Cardiovascular Research (1997)

Objective: The concept of therapeutic angiogenesis with vascular endothelial growth factor (VEGF) has been validated in peripheral arterial disease. Its use in myocardial ischemia may be delayed as the result of the description in a porcine model of peripheral vasodilation after intraluminal injections of VEGF resulting in a 50% fatality rate by hypotension. We carried out this study to test whether VEGF-induced hypotension (1) is species specific, (2) is mediated by the receptor mediating angiogenesis, (3) is prevented by inhibition of nitric oxide synthase. Methods: In the rabbit corneal pocket assay we tested whether a previously published anti-idiotypic antibody (AIA) agonist of the VEGF receptor Flk-1/KDR could elicit angiogenesis. Various doses of recombinant VEGF or AIA were injected into anesthetized normotensive Wistar–Kyoto rats and the mean arterial blood pressure (MABP) was recorded. To test the implication of nitric oxide in VEGF-induced hypotension we treated the animals with a competitive inhibitor of nitric oxide synthase prior to the injection of VEGF. Results: Both VEGF and AIA induce angiogenesis but only intravenous injections of VEGF induced a rapid, transient and dose-dependent decrease in MABP. The ED50 was 0.5 μg. The interval between two VEGF injections required to lead to a decrease of MABP was 40 minutes. Nitric oxide synthesis inhibitor prevented, in a reversible fashion, the effect of VEGF. Conclusion: VEGF-induced hypotension is not species specific. It is prevented by nitric oxide inhibition. VEGF-induced angiogenesis and hypotension are not mediated in vivo by the same VEGF receptor
A double‐blind, single‐dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine‐induced wheal and flare response for 24 h in healthy male subjects
Authors: Ja Grant, L Danielson, J‐p Rihoux, C DeVos
Journal: Allergy (1999)

Background: New H 1 ‐antagonists have become available, but there has been no comparison of their potency for inhibiting histamine in the skin. Methods: Cetirizine 10 mg, ebastine 10 mg, epinastine 20 mg, fexofenadine 60 mg, terfenadine 60 mg, loratadine 10 mg, or placebo was given to 14 healthy male volunteers in a double‐blind, crossover randomized manner. Inhibition of the wheal and flare response to epicutaneous histamine phosphate (100 mg/ml) challenge was measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after doses. Results: Epinastine inhibited the wheal and flare after 30 min. Cetirizine commenced acting at 1 h and was superior to other treatments. Ebastine was no better than placebo until 4 h, but was efficacious thereafter until 24 h. Terfenadine induced potent inhibition after 1 h and was superior to its metabolite fexofenadine. Loratadine was the least potent inhibitor. Inhibition of the flare response paralleled the patterns seen for wheals. The rank order for area under the curve (0–24 h) was cetirizine, epinastine, terfenadine, ebastine, fexofenadine, loratadine, and placebo. Conclusions: The inhibition of histamine effects in the skin may be useful in predicting the clinical utility of newly introduced antihistamines in treating allergic disorders.
A second locus for Marfan syndrome maps to chromosome 3p24.2–p25
Authors: Gwenaëlle Collod, Marie-Claude Babron, Guillaume Jondeau, Monique Coulon, Jean Weissenbach, Olivier Dubourg, Jean-Pierre Bourdarias, Catherine Bonaïti-Pellié, Claudine Junien, Catherine Boileau
Journal: Nature Genetics (1994)
Azathioprine therapy in the management of persistent erythema multiforme
Authors: R.RUSSELL JONES
Journal: British Journal of Dermatology (1981)

SUMMARY Two cases of recurrent erythema multiforme of unknown aetiology are reported. The term ‘persistent’ is appropriate as the lesions recurred whenever steroid therapy was discontinued. Both patients were eventually controlled with azathioprine alone, and one patient required treatment for 3 years.
Abstract 3157: An Rgnef (p190RhoGEF/Arhgef28) signaling axis regulates ovarian cancer progression
Authors: Nichol L. G. Miller, Isabelle Tancioni, Sean Uryu, Elizabeth G. Kleinschmidt, Denise C. Connolly, David D. Schlaepfer
Journal: Cancer Research (2014)

Abstract Ovarian cancer is a leading cause of cancer death in women, is usually diagnosed in late stage, and currently has insufficient effective targeted therapies. The primary mode of metastasis is unique in that dissemination occurs via tumor cell shedding into the peritoneal cavity, survival and growth within ascites, and re-adhesion and proliferation of tumor cells at sites within the abdomen. Therefore, molecules and pathways involving cell adhesion and survival in non-adherent environments are of particular interest. Rgnef (p190RhoGEF/Arhgef28) is a Rho family guanine exchange factor that associates with focal adhesion kinase (FAK) and functions both as a downstream target of FAK tyrosine kinase activity and a regulator of FAK activity following integrin stimulation. FAK regulates cell adhesion, migration, and survival. Expression of FAK is associated with poor clinical outcome, its activity (as measured by FAK Y397 phosphorylation) is frequently increased in serous ovarian carcinomas, and it is currently under investigation as a therapeutic target in ongoing clinical trials. Immunohistochemical analysis of human tumor tissue arrays with antibodies specific for Rgnef and FAK pY397 reveal a positive correlation between Rgnef expression and FAK activation and increased stage/grade of serous-type ovarian cancer. Stable knockdown of Rgnef in human ovarian carcinoma cells grown as subcutaneous or intraperitoneal xenografts in mice suggest that Rgnef may play roles in both primary tumor growth and ascites-associated cell survival and spread. Here, we use a transgenic model of spontaneous ovarian cancer (MISIIR-T-Antigen) to test the role of Rgnef in ovarian cancer progression. Female Rgnef+/+;TAg+ and Rgnef-/-;TAg+ mice were monitored by ultrasound imaging from age 12 to 17 weeks before euthanasia. Rgnef-/-;TAg+ tumors were significantly smaller (p=0.0006) and contained fewer Ki67 positive cells than Rgnef+/+;TAg+ controls at 17 weeks. Tumors and ovarian carcinoma cells isolated from Rgnef-/-;TAg+ mouse ascites have reduced FAK pY397 and increased E-cadherin expression compared to controls, suggesting that loss of Rgnef results in a less aggressive tumor phenotype. These findings identify Rgnef as a component in signaling pathways promoting FAK activation and regulating ovarian tumor progression. Citation Format: Nichol L. G. Miller, Isabelle Tancioni, Sean Uryu, Elizabeth G. Kleinschmidt, Denise C. Connolly, David D. Schlaepfer. An Rgnef (p190RhoGEF/Arhgef28) signaling axis regulates ovarian cancer progression. [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 3157. doi:10.1158/1538-7445.AM2014-3157
907. Development of Recombinant Novel Adeno-Associated Viral (rAAV) Vectors Encoding Optimised Microdystrophin cDNAs for Duchenne Muscular Dystrophy (DMD)
Authors: Takis Athanasopoulos, Ian Graham, Capucine Trollet, Helen Foster, Norma Perez, Vanessa Hill, Phillippe Moullier, George Dickson
Journal: Molecular Therapy (2006)

Duchenne muscular dystrophy (DMD) is a lethal genetic muscle disorder affecting 1:3500 male individuals, caused by recessive mutations in the dystrophin gene. The size of the gene (2.4Mb) and mRNA (14kb) in addition to immunogenicity problems and inefficient transduction of mature myofibres by currently available vector systems are formidable obstacles to the development of gene therapy. AAV vectors overcome many of the problems associated with other vectors but accommodate limited transgene capacity (<5kb), allowing only truncated versions of dystrophin (microdystrophin) to be packaged. More than 9 AAV vector serotypes have been identified to date with certain serotypes(1, 5-9) displaying more favourable tropism in transducing muscle compared to the traditionally used AAV2. Human microdystrophin (mdys) cDNAs (<3.8 kb) rationally designed in our lab based on patient and preclinical data were packaged in AAV-based vector cassettes, under the control of CMV or Spc512 muscle synthetic promoter, effectively expressed mdys (CMV>Spc512), restored DAP complex and inhibited myofibre degeneration after local intramuscular administrations in nude/mdx and mdx mice. Expression of microdystrophins using e.g. an AAV1CMVhmdys vector was observed at high levels via i.m (>90%), i.p. (20-25%), but not via systemic i.v. route of administration. However, certain issues including systemic delivery, optimization of mdys cDNA constructs, AAV transduction efficiency, safety and immunogenicity while retaining species and tissue (muscle) specificity, still remain to be fully elucidated. Here we report on production of codon/sequence optimised, transcriptionally enhanced, species-specific (human, canine and murine) microdystrophin cDNA cassettes (based on Δ 3788 and Δ R4-23 published sequences) incorporating either constitutive or muscle-specific promoter elements. These cassettes offered 3-5 fold increase in expression in comparison to conventional configurations. Incorporation of Kozak/WPRE elements for transcriptional enhancement, packaging of the cassettes into recombinant AAV vectors of novel alternative serotypes (6, 7, 8 and 9) by pseudotyping and 'AAV-stealth' approaches have been envisaged. Resulting rAAV6 and rAAV8 pseudotyped vectors encoding species-specific comdys have been produced at titers>10E12 vg/mL and are currently screened utilising local and systemic routes of administration in preclinical models of the disease.
PGC-1 coactivators: inducible regulators of energy metabolism in health and disease
Authors: B. N. Finck
Journal: Journal of Clinical Investigation (2006)

Members of the PPARγ coactivator-1 (PGC-1) family of transcriptional coactivators serve as inducible coregulators of nuclear receptors in the control of cellular energy metabolic pathways. This Review focuses on the biologic and physiologic functions of the PGC-1 coactivators, with particular emphasis on striated muscle, liver, and other organ systems relevant to common diseases such as diabetes and heart failure.
Metastases Seen on SPECT Imaging Despite a Normal Planar Bone Scan
Authors: JAN ROLAND, DANIELLE VAN DEN WEYNGAERT, BRUNO KRUG, BOUDEWIJN BRANS, PIERRE SCALLIET, JOHAN VANDEVIVERE
Journal: Clinical Nuclear Medicine (1995)

Although bone scintigraphy is an extremely sensitive method for the detection of focal bone disease, small lesions below the resolution of planar imaging may be missed. This is a report of a patient with carcinoma of the breast who showed tumor progression 1 year after initial treatment. Complete evaluation was performed in order to detect the origin of increased level of a tumor marker. Although planar bone scintigraphy could not demonstrate any lesion in the spine, multiple metastases were detected in the lumbar and the thoracic spines on SPECT imaging. Only some of these lesions were seen with MRI. Repeat planar bone imaging 6 weeks later showed multiple bone lesions in the lumbar and thoracic areas.
Use of invasive neuroradiological investigations in patients with normal computerised tomography
Authors: G L V Tatler, I F Moseley
Journal: BMJ (1982)

A review of the results of neuroradiological investigation of patients in whom computed tomography had shown no intracranial abnormality showed that the use of invasive studies, particularly pneumoencephalography, has declined since installation of a computed tomography scanner, and indications for such studies have become firmer. Diagnostic yield from invasive procedures in patients presenting with epilepsy, dementia, headache (including facial pain), or loss of consciousness is negligible.
The Genetics of Dilated Cardiomyopathy — Emerging Clues to the Puzzle
Authors: Jeffrey M. Leiden
Journal: New England Journal of Medicine (1997)

Despite recent advances in both medical and surgical therapies, dilated cardiomyopathy remains a leading cause of cardiovascular morbidity and mortality. This syndrome consists of ventricular enlargement, abnormal systolic and diastolic left ventricular function, symptoms of congestive heart failure, and premature death due predominantly to heart failure and cardiac arrhythmias. Coronary artery disease, valvular heart disease, viral infection, toxins, autoimmunity, and primary genetic abnormalities can all cause dilated cardiomyopathy, but in many patients it is idiopathic. The remarkable similarities in the clinical course, histopathological findings, and hemodynamic abnormalities in patients with advanced dilated cardiomyopathy, whatever the cause, suggest that a common . . .
Late complications of reversed gastric tube oesophagoplasty.
Authors: A C Sitges, J M Sanchez-Ortega, A S Sitges
Journal: Thorax (1986)

This paper reports two late complications of oesophageal replacement using the reversed gastric tube described by Gavriliu. One patient developed obstruction of the gastric tube and the other a perforation of a diverticulum within the gastric tube, both occurring more than 10 years after the original operation. The occurrence of such complications should be made known to surgeons who are contemplating using this form of oesophageal replacement.
Patients with advanced lung cancer harboring oncogenic mutations should be admitted to intensive care units
Authors: Anne-Claire Toffart, Xavier Dhalluin, Nicolas Girard, Christos Chouaid, Clarisse Audigier-Valette, Michaël Duruisseaux, Bertrand Mennecier, Antoine Parrot, Pierre Fournel, Denis Moro-Sibilot, Jean-François Timsit
Journal: Intensive Care Medicine (2014)
Serve the People: Observations on Medicine in the People's Republic of China
Authors: Peter Kong-Ming New
Journal: JAMA (1974)

Since 1971, the Sidels have made a number of trips to the People's Republic of China, to study, observe, and understand the monumental changes that have taken place in China's health scene since 1949. Soon after they returned from their first trip, the Sidels, singly and jointly, have written and spoken widely in the United States and elsewhere on their experiences. Some of their observations are now rewritten and published in this volume. In this brief review, it is not possible to cover everything that the Sidels have seen and reported on. Basically, they corroborate many similar enthusiastic responses by Western observers who have been there recently. As far as medicine and public health were concerned, China had never previously used its manpower and health resources to the extent that Chairman Mao was able to harness in recent years. The Sidels report on some of the ways that the government
Vascular targeting of anti-CD40 antibodies and IL-2 into autochthonous tumors enhances immunotherapy in mice
Authors: Juliana Hamzah, Delia Nelson, Gerd Moldenhauer, Bernd Arnold, Günter J. Hämmerling, Ruth Ganss
Journal: Journal of Clinical Investigation (2008)

Current anticancer therapy is a delicate balance between elimination of malignant cells and harmful side effects for the host. In this study, we used a tumor-homing peptide to engineer anti-CD40 agonist antibodies and recombinant IL-2 such that they were selectively delivered into spontaneously arising tumors in a transgenic mouse model of islet cell carcinogenesis. Intravenous injection of these agents, either separately or together, led to accumulation in the vicinity of tumor neovessels without toxic side effects. Although both molecules are critical for adaptive immunity, the most profound effects were seen in endothelial cells. Combined, local anti-CD40 and IL-2 therapy reduced tumor vascularity and significantly delayed tumor growth in mice. Remarkably, tumor-bearing mice remained disease-free long-term when targeted anti-CD40 and IL-2 were combined with transfers of preactivated antitumor immune cells. In this therapeutic setting, triggering of CD40 on endothelial cells induced an inflammatory response of the vessel wall and facilitated effector cell accumulation in the tumor parenchyma while IL-2 promoted antigen-specific immune cell persistence. We believe this is a novel and highly effective anticancer approach, whereby tumor stroma is "conditioned" for enhanced immune cell entry and survival, facilitating immune-mediated tumor destruction and leading to a sustained antitumor response.
Ageing alongside and outside EU borders
Authors: P. Kowal, S. R. Williams, S. Chatterji
Journal: BMJ (2011)

The challenges and contributions of ageing populations extend beyond EU borders to low and middle income countries (LMICs), where most older people live.1 By 2031, those over 65 years will exceed one billion, with 71% in less developed countries.2 Ageing will become the next public health challenge globally, not just for the EU.

Keeping people …
Hyperhomocysteinemia in Hypothyroidism
Authors: Charles Faiman, Donald W. Jacobsen, Ralph Green
Journal: Annals of Internal Medicine (2000)

Letters18 April 2000Hyperhomocysteinemia in HypothyroidismCharles Faiman, MD, Donald W. Jacobsen, PhD, and Ralph Green, MDCharles Faiman, MDThe Cleveland Clinic Foundation; Cleveland, OH 44195 (Faiman)The Cleveland Clinic Foundation; Cleveland, OH 44195 (Jacobsen)University of California; Sacramento, CA 95817 (Green)Search for more papers by this author, Donald W. Jacobsen, PhDThe Cleveland Clinic Foundation; Cleveland, OH 44195 (Faiman)The Cleveland Clinic Foundation; Cleveland, OH 44195 (Jacobsen)University of California; Sacramento, CA 95817 (Green)Search for more papers by this author, and Ralph Green, MDThe Cleveland Clinic Foundation; Cleveland, OH 44195 (Faiman)The Cleveland Clinic Foundation; Cleveland, OH 44195 (Jacobsen)University of California; Sacramento, CA 95817 (Green)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-8-200004180-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Weiss for underscoring a potential renal mechanism by which l-thyroxine normalizes the hyperhomocysteinemia seen in hypothyroidism. To examine the relation between homocysteine and GFR, we retrospectively examined serum creatinine levels (as a surrogate for GFR) in 13 of the 14 patients for whom frozen specimens were still available from our study.We confirm the findings of Kreisman and Hennessey (1) indicating a decline in serum creatinine levels in hypothyroid persons after the attainment of euthyroidism with l-thyroxine replacement. The median serum creatinine values decreased significantly from the hypothyroid to the euthyroid state—from 1.0 mg/dL (range, ...Reference1. Kreisman SH, Hennessey JV. Consistent reversible elevations of serum creatinine levels in severe hypothyroidism. Arch Intern Med. 1999;159:79-82. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: The Cleveland Clinic Foundation; Cleveland, OH 44195 (Faiman)The Cleveland Clinic Foundation; Cleveland, OH 44195 (Jacobsen)University of California; Sacramento, CA 95817 (Green) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoNormalization of Hyperhomocysteinemia with l-thyroxine in Hypothyroidism Wiam I. Hussein , Ralph Green , Donald W. Jacobsen , and Charles Faiman Hyperhomocysteinemia in Hypothyroidism Daniel Weiss Metrics Cited byRisk Factors for Cardiovascular Disease in Women with Subclinical HypothyroidismCurrent Awareness 18 April 2000Volume 132, Issue 8Page: 677KeywordsBlood plasmaCreatinineHypothyroidismRetrospective studiesThyroxine Issue Published: 18 April 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...