tbuckley/cabot-search huggingface dataset:
Anti-Inflammatory Effect of Hepatocyte Growth Factor in Chronic Kidney Disease
Authors: Rujun Gong, Abdalla Rifai, Lance D. Dworkin
Journal: Journal of the American Society of Nephrology (2006)

Recent studies show that hepatocyte growth factor (HGF) has potent anti-inflammatory effects in multiple animal models of disease in various organ systems, including the kidney, suggesting that HGF may suppress a common proinflammatory process. The aim of this study was to examine the molecular mechanism of HGF's anti-inflammatory actions in a model of chronic kidney disease. Beginning 2 wk after subtotal nephrectomy, rats received a continuous infusion of recombinant HGF, neutralization of endogenous HGF by daily injection of an anti-HGF antibody, or preimmune IgG for an additional 2 wk. The effects on inflammation and injury were examined. HGF administration ameliorated whereas neutralizing endogenous HGF worsened renal inflammation in remnant kidneys. This was accompanied by parallel alterations in endothelial activation and inflammation, marked respectively by de novo E-selectin expression in renal vascular endothelium and leukocyte adhesion to endothelium. In vitro, HGF abrogated monocyte adhesion to TNF-alpha-activated endothelial monolayers and suppressed endothelial expression of E-selectin, which depended on NF-kappaB signaling. In addition, HGF suppressed NF-kappaB reporter gene activity that was induced by TNF-alpha and counteracted TNF-alpha-elicited NF-kappaB interaction with kappaB elements at the E-selectin gene level. Dissection of the NF-kappaB signaling cascade revealed that suppression of NF-kappaB depended on HGF's inhibitory action on NF-kappaB and IkappaB phosphorylation and IkappaB degradation. In vivo, continuous infusion of exogenous HGF markedly diminished sequestration of circulating fluorescence-labeled macrophages in the remnant kidney, mimicking the action of an E-selectin blocking antibody. These findings suggest that HGF has potent and direct anti-inflammatory effects on the basis of suppression of NF-kappaB activation and downstream endothelial inflammation.
Adjuvant Exemestane with Ovarian Suppression in Premenopausal Breast Cancer
Authors: Olivia Pagani, Meredith M. Regan, Barbara A. Walley, Gini F. Fleming, Marco Colleoni, István Láng, Henry L. Gomez, Carlo Tondini, Harold J. Burstein, Edith A. Perez, Eva Ciruelos, Vered Stearns, Hervé R. Bonnefoi, Silvana Martino, Charles E. Geyer, Graziella Pinotti, Fabio Puglisi, Diana Crivellari, Thomas Ruhstaller, Eric P. Winer, Manuela Rabaglio-Poretti, Rudolf Maibach, Barbara Ruepp, Anita Giobbie-Hurder, Karen N. Price, Jürg Bernhard, Weixiu Luo, Karin Ribi, Giuseppe Viale, Alan S. Coates, Richard D. Gelber, Aron Goldhirsch, Prudence A. Francis
Journal: New England Journal of Medicine (2014)

Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer.In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials.After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women.In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).
Outcome of nicotine replacement therapy in patients admitted to intensive care unit: A randomized case-control double blinded prospective pilot study
Authors: Vikas Pathak, Iliana Samara Hurtado Rendon, Roxana Lupu, Nancy Tactuk, Toyosi Olutade, Vijay Vegesna, Richard Stumacher
Journal: European Respiratory Journal (2011)

Introduction:  The effects of nicotine withdrawal in smokers admitted to ICUs are not well understood and therefore the role of Nicotine Replacement Therapy (NRT) in patients admitted to ICUs is controversial.   Aims:  To prove that NRT in ICU patients decreases the use of sedatives and analgesics, the number of days on ventilator, and the total ICU stay.   Methods:  The study was performed in the 20 bed ICU. Forty patients meeting inclusion and exclusion criteria were randomized into either an interventional or control group. Patients in the interventional group received a 21mg nicotine patch every day until the patient was discharged from the ICU, transferred to the general medical floor, or until 10 weeks. Patients in the control arm received fake patch.The use of sedatives and analgesics during ICU stay, and use and duration of invasive mechanical ventilator were noted. The length of ICU stay was also compared in both the groups.   Results:  Twenty-seven patients were male,13 were female. The mean age of the interventional group patients was 57.4 years and 52.5 years in the control group.The mean APACHE II score was 14.3 in the interventional group vs. 13.8 in the control group.The mean length of ICU stay in the interventional group was 4.5 days while in the control group mean length of ICU stay was 7 days. The mean number of days on ventilator in interventional group was 1.9 days vs. 3.5 days in the control group. The number of days on sedation and analgesia was also less in the interventional group compared to the control group.   Conclusion:  The length of ICU stay and the number of days on ventilator decreases in the patients receiving NRT.
FGFR1 mRNA and Protein Expression, not Gene Copy Number, Predict FGFR TKI Sensitivity across All Lung Cancer Histologies
Authors: Murry W. Wynes, Trista K. Hinz, Dexiang Gao, Michael Martini, Lindsay A. Marek, Kathryn E. Ware, Michael G. Edwards, Diana Böhm, Sven Perner, Barbara A. Helfrich, Rafal Dziadziuszko, Jacek Jassem, Szymon Wojtylak, Aleksandra Sejda, Joseph M. Gozgit, Paul A. Bunn, D. Ross Camidge, Aik-Choon Tan, Fred R. Hirsch, Lynn E. Heasley
Journal: Clinical Cancer Research (2014)

FGFR1 gene copy number (GCN) is being evaluated as a biomarker for FGFR tyrosine kinase inhibitor (TKI) response in squamous cell lung cancers (SCC). The exclusive use of FGFR1 GCN for predicting FGFR TKI sensitivity assumes increased GCN is the only mechanism for biologically relevant increases in FGFR1 signaling. Herein, we tested whether FGFR1 mRNA and protein expression may serve as better biomarkers of FGFR TKI sensitivity in lung cancer.Histologically diverse lung cancer cell lines were submitted to assays for ponatinib sensitivity, a potent FGFR TKI. A tissue microarray composed of resected lung tumors was submitted to FGFR1 GCN, and mRNA analyses and the results were validated with The Cancer Genome Atlas (TCGA) lung cancer data.Among 58 cell lines, 14 exhibited ponatinib sensitivity (IC50 values ≤ 50 nmol/L) that correlated with FGFR1 mRNA and protein expression, but not with FGFR1 GCN or histology. Moreover, ponatinib sensitivity associated with mRNA expression of the ligands, FGF2 and FGF9. In resected tumors, 22% of adenocarcinomas and 28% of SCCs expressed high FGFR1 mRNA. Importantly, only 46% of SCCs with increased FGFR1 GCN expressed high mRNA. Lung cancer TCGA data validated these findings and unveiled overlap of FGFR1 mRNA positivity with KRAS and PIK3CA mutations.FGFR1 dependency is frequent across various lung cancer histologies, and FGFR1 mRNA may serve as a better biomarker of FGFR TKI response in lung cancer than FGFR1 GCN. The study provides important and timely insight into clinical testing of FGFR TKIs in lung cancer and other solid tumor types.
Less Yin, More Yang: Confronting the Barriers to Cancer Immunotherapy
Authors: Gregory Lizée, Mayra A. Cantu, Patrick Hwu
Journal: Clinical Cancer Research (2007)

Abstract Clinical trials involving T cell–based immunotherapy for the treatment of human cancer have shown limited degrees of success. In cancer vaccine trials conducted at multiple centers worldwide, immunization has often resulted in the robust elicitation of T cells that specifically recognize antigens expressed on the surface of tumor cells. However, to date, objective clinical responses resulting from these approaches have remained relatively rare. By contrast, adoptive transfer of laboratory-expanded T cells into patients has had more success, producing impressive clinical regressions in a subset of advanced metastatic melanoma patients. The failure of activated T cells to consistently induce clinical responses in many other patients has pushed us toward a deeper understanding of natural immunoregulatory mechanisms that are directly responsible for diminishing tumor-specific T-cell activation, migration, and effector function in vivo. Such immunosuppressive factors likely evolved to prevent autoimmunity, but are frequently co-opted by tumors to evade tumor-specific immune responses. With this knowledge, it now becomes imperative to develop specific clinical interventions capable of eliminating tumor-specific immunosuppression, with the goal of shifting the balance to favor effector T-cell function and tumor cell killing.
Fibrocystin/Polyductin Modulates Renal Tubular Formation by Regulating Polycystin-2 Expression and Function
Authors: Ingyu Kim, Yulong Fu, Kwokyin Hui, Gilbert Moeckel, Weiyi Mai, Cunxi Li, Dan Liang, Ping Zhao, Jie Ma, Xing-Zhen Chen, Alfred L. George, Robert J. Coffey, Zhong-Ping Feng, Guanqing Wu
Journal: Journal of the American Society of Nephrology (2008)

Autosomal recessive polycystic kidney disease is caused by mutations in PKHD1, which encodes the membrane-associated receptor-like protein fibrocystin/polyductin (FPC). FPC associates with the primary cilia of epithelial cells and co-localizes with the Pkd2 gene product polycystin-2 (PC2), suggesting that these two proteins may function in a common molecular pathway. For investigation of this, a mouse model with a gene-targeted mutation in Pkhd1 that recapitulates phenotypic characteristics of human autosomal recessive polycystic kidney disease was produced. The absence of FPC is associated with aberrant ciliogenesis in the kidneys of Pkhd1-deficient mice. It was found that the COOH-terminus of FPC and the NH2-terminus of PC2 interact and that lack of FPC reduced PC2 expression but not vice versa, suggesting that PC2 may function immediately downstream of FPC in vivo. PC2-channel activities were dysregulated in cultured renal epithelial cells derived from Pkhd1 mutant mice, further supporting that both cystoproteins function in a common pathway. In addition, mice with mutations in both Pkhd1 and Pkd2 had a more severe renal cystic phenotype than mice with single mutations, suggesting that FPC acts as a genetic modifier for disease severity in autosomal dominant polycystic kidney disease that results from Pkd2 mutations. It is concluded that a functional and molecular interaction exists between FPC and PC2 in vivo.
Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer
Authors: G. Viale, A. Giobbie-Hurder, B.A. Gusterson, E. Maiorano, M.G. Mastropasqua, A. Sonzogni, E. Mallon, M. Colleoni, M. Castiglione-Gertsch, M.M. Regan, K.N. Price, R.W. Brown, R. Golouh, D. Crivellari, P. Karlsson, C. Öhlschlegel, R.D. Gelber, A. Goldhirsch, A.S. Coates
Journal: Annals of Oncology (2009)
Handbook of Gastroenterology
Authors: H FIDLER
Journal: Gut (1999)

Handbook of Gastroenterology . Edited by Yamada T, Alpers DH, Owyang C, et al . (Pp 726; $47.00/£29.38.) Philadelphia: Lippincott-Raven, 1998. ISBN 0-397- 51427-1.

I cannot think of anything more likely to produce dyspepsia in a editor than trying to produce a gastroenterology handbook “particularly suited to medical students, house officers and advanced trainees”. This large group are not known for buying textbooks unless highly relevant to their specific and disparate training needs. However, this is the wide audience that the editor of the phenomenally successful two-volume Textbook of Gastroenterology has targeted. Weighing in at over 800 grammes it is six times heavier than my stethoscope and so can only be used as a portable handbook on the wards for the more athletic trainee. It comprises 76 chapters …
SNPs and Haplotypes in <i>DPYD</i> and Outcome of Capecitabine–Letter
Authors: André B.P. van Kuilenburg, Carlo R. Largiadèr
Journal: Clinical Cancer Research (2011)

In their recently published article in Clinical Cancer Research , Deenen and colleagues reported a number of single-nucleotide polymorphisms (SNP) and haplotypes in DPYD that were associated with toxicity of capecitabine ([1][1]). In particular, the silent c.1236G>A mutation was strongly associated
White-Light or Narrow-Band Imaging Colonoscopy in Surveillance of Ulcerative Colitis: A Prospective Multicenter Study
Authors: Ludger Leifeld, Gerhard Rogler, Andreas Stallmach, Carsten Schmidt, Ina Zuber-Jerger, Franz Hartmann, Mathias Plauth, Attyla Drabik, Ferdinand Hofstädter, Hans Peter Dienes, Wolfgang Kruis, Reinhard Büttner, Heike Löser, Uta Drebber, Axel Dignass, Birgit Terjung, Tilman Sauerbruch, Stefan Schreiber, Barbara Lanyi, Roland Pfuetzer, Julia Morgenstern, Stephan Böhm, Ulrich Böcker, Ann-Kathrin Rupf, Beate Appenroth, Erwin Biecker, Jens Walldorf
Journal: Clinical Gastroenterology and Hepatology (2015)
Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection.
Authors: N Kim, Y Vardi, H Padma-Nathan, J Daley, I Goldstein, I Saenz de Tejada
Journal: Journal of Clinical Investigation (1993)

Relaxation of the trabecular smooth muscle of the corpus cavernosum (the erectile tissue) of the penis is mediated by nitric oxide released by the nerves and endothelium. We have investigated the physiological role of oxygen tension in the regulation of trabecular smooth muscle tone. In human subjects, measurement of intracavernosal PO2 in blood drawn from corpus cavernosum in the flaccid state was comparable to that of venous blood (25-43 mmHg). Vasodilatation of the resistance arteries and trabecular smooth muscle relaxation by intracavernosal injection of papaverine and phentolamine caused oxygen tension to rise rapidly to arterial levels (PO2 approximately 100 mmHg). Isolated human and rabbit corpus cavernosum tissue strips in organ baths, exposed to arterial-like PO2 relaxed to the endothelium-dependent dilator acetylcholine and to electrical stimulation of the autonomic dilator nerves. These nitric oxide-mediated responses were progressively inhibited as a function of decreasing PO2 to levels measured in the flaccid penis. Reverting to normoxic conditions readily restored endothelium-dependent and neurogenic relaxation. Relaxation to exogenous nitric oxide was not impaired in low PO2. In rabbit corpus cavernosum, low PO2 reduced basal levels of cGMP and prevented cGMP accumulation induced by stimulation of dilator nerves. Furthermore, low PO2 inhibited nitric oxide synthase activity in corpus cavernosum cytosol. It is concluded that physiological concentrations of oxygen modulate penile erection by regulating nitric oxide synthesis in corpus cavernosum tissue.
Vascular remodeling of the vitelline artery initiates extravascular emergence of hematopoietic clusters
Authors: Ann C. Zovein, Kirsten A. Turlo, Ryan M. Ponec, Maureen R. Lynch, Kevin C. Chen, Jennifer J. Hofmann, Timothy C. Cox, Judith C. Gasson, M. Luisa Iruela-Arispe
Journal: Blood (2010)
Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis
Authors: Vincenzo Mazzaferro, Josep M Llovet, Rosalba Miceli, Sherrie Bhoori, Marcello Schiavo, Luigi Mariani, Tiziana Camerini, Sasan Roayaie, Myron E Schwartz, Gian Luca Grazi, René Adam, Peter Neuhaus, Mauro Salizzoni, Jordi Bruix, Alejandro Forner, Luciano De Carlis, Umberto Cillo, Andrew K Burroughs, Roberto Troisi, Massimo Rossi, Giorgio E Gerunda, Jan Lerut, Jacques Belghiti, Ilka Boin, Jean Gugenheim, Fedja Rochling, Bart Van Hoek, Pietro Majno
Journal: The Lancet Oncology (2008)
Vertebrate Membrane Proteins: Structure, Function, and Insights from Biophysical Approaches
Authors: Daniel J. Müller, Nan Wu, Krzysztof Palczewski
Journal: Pharmacological Reviews (2008)

Membrane proteins are key targets for pharmacological intervention because they are vital for cellular function. Here, we analyze recent progress made in the understanding of the structure and function of membrane proteins with a focus on rhodopsin and development of atomic force microscopy techniques to study biological membranes. Membrane proteins are compartmentalized to carry out extra- and intracellular processes. Biological membranes are densely populated with membrane proteins that occupy approximately 50% of their volume. In most cases membranes contain lipid rafts, protein patches, or paracrystalline formations that lack the higher-order symmetry that would allow them to be characterized by diffraction methods. Despite many technical difficulties, several crystal structures of membrane proteins that illustrate their internal structural organization have been determined. Moreover, high-resolution atomic force microscopy, near-field scanning optical microscopy, and other lower resolution techniques have been used to investigate these structures. Single-molecule force spectroscopy tracks interactions that stabilize membrane proteins and those that switch their functional state; this spectroscopy can be applied to locate a ligand-binding site. Recent development of this technique also reveals the energy landscape of a membrane protein, defining its folding, reaction pathways, and kinetics. Future development and application of novel approaches during the coming years should provide even greater insights to the understanding of biological membrane organization and function.
Modifications of histone cores and tails in V(D)J recombination
Authors: Kathrin Muegge
Journal: Genome biology (2003)

The organization of chromatin and modifications to the tails of histone proteins are thought to be important in regulating the rearrangement of V, D and J gene segments, which encode immunoglobulins and T-cell receptors. A recent study shows that methylated lysine 79 in the core region of histone H3 also plays a role by providing a euchromatic 'mark' that may regulate access of the V(D)J recombinase.
Liver failure complicating segmental hepatic ischaemia induced by a PTFE-coated TIPS stent
Authors: F Vizzutti, U Arena, L Rega, M Zipoli, J G Abraldes, R G Romanelli, R Tarquini, G Laffi, M Pinzani
Journal: Gut (2009)

The use of polytetrafluoroethylene (PTFE)-covered prostheses improves trans-jugular intrahepatic porto-systemic shunt (TIPS) patency and decreases the incidence of clinical relapses and re-interventions. Therefore, the improvement provided by covered stents might expand the currently accepted recommendations for TIPS use. Stent-related occlusion of the hepatic vein with consequent ischaemia of the corresponding liver parenchyma emerges as a novel complication reported in at least 5% of patients implanted with coated stents. However, this complication was reported to be mild, without signs or symptoms of liver failure, and self-limiting. We report a case of segmental liver ischaemia following PTFE-covered stent placement resulting in a marked impairment in liver function in a patient with hepatitis C virus cirrhosis implanted because of refractory oesophageal bleeding, thus expanding the severity range of this new procedural complication. Moreover, we discuss the possible involvement of additional pathogenetic mechanisms other than out-flow obstruction in the onset of coated-stent induced congestive liver ischaemia.
Chemical Mediators Released by Primary–Cultured Human Hepatic Macrophages in Patients With and Without Cirrhosis: A Study in Tumor–Bearing Patients
Authors: N Funaki, S Arii, K Monden, H Higashitsuji, M Furutani, M Mise, J Tanaka, M Imamura
Journal: Hepatology (1996)

To elucidate the possible role of chemical mediators in modulating the host–defense activity of patients with cirrhosis, primary–cultured human hepatic macrophages (HHMΦ) were obtained from cirrhotic and noncirrhotic patients who received liver resections because of the presence of malignant liver tumors. The cirrhotic and noncirrhotic groups consisted of patients with similar malignancies: noncirrhotic patients had normal liver function and normal liver histology for nontumorous portions. The cultured HHMΦ were analyzed for their ability to release chemical mediators with specific activities in the host defense system. Dose–dependent increases in superoxide release, interleukin–1 (IL–1) release, and, within a relatively narrow range, prostaglandin–E2 (PGE2) release were observed in opsonized zymosan (oz)–stimulated HHMΦ derived from both cirrhotic and noncirrhotic patients. The release of O2– and PGE2 from HHMΦ derived from cirrhotic patients was significantly less than HHMΦ derived from noncirrhotic patients, whereas the release of IL–1 was significantly greater. Although, because of the limited sample availability, only tumor–bearing patients were studied, the mediator–releasing ability of HHMΦ derived from cirrhotic patients was significantly different from the ability of HHMΦ derived from noncirrhotic patients with similar malignancies. This phenomenon may be related to altered host defenses in patients with cirrhosis.