tbuckley/cabot-search huggingface dataset:
Control of hepatocyte proliferation and survival by Fgf receptors is essential for liver regeneration in mice
Authors: Susagna Padrissa-Altés, Marc Bachofner, Roman L Bogorad, Lea Pohlmeier, Thomas Rossolini, Friederike Böhm, Gerhard Liebisch, Claus Hellerbrand, Victor Koteliansky, Tobias Speicher, Sabine Werner
Journal: Gut (2014)

<h3>Objective</h3> Fibroblast growth factors (Fgfs) are key orchestrators of development, and a role of Fgfs in tissue repair is emerging. Here we studied the consequences of inducible loss of Fgf receptor (Fgfr) 4, the major Fgf receptor (Fgfr) on hepatocytes, alone or in combination with Fgfr1 and Fgfr2, for liver regeneration after PH. <h3>Design</h3> We used siRNA delivered via nanoparticles combined with liver-specific gene knockout to study Fgfr function in liver regeneration. Liver or blood samples were analysed using histology, immunohistochemistry, real-time RT-PCR, western blotting and ELISA. <h3>Results</h3> siRNA-mediated knockdown of Fgfr4 severely affected liver regeneration due to impairment of hepatocyte proliferation combined with liver necrosis. Mechanistically, the proliferation defect resulted from inhibition of an Fgf15-Fgfr4-Stat3 signalling pathway, which is required for injury-induced expression of the Foxm1 transcription factor and subsequent cell cycle progression, while elevated levels of intrahepatic toxic bile acids were identified as the likely cause of the necrotic damage. Failure of liver mass restoration in <i>Fgfr4</i> knockdown mice was prevented at least in part by compensatory hypertrophy of hepatocytes. Most importantly, our data revealed partially redundant functions of Fgf receptors in the liver, since knockdown of Fgfr4 in mice lacking Fgfr1 and Fgfr2 in hepatocytes caused liver failure after PH due to severe liver necrosis and a defect in regeneration. <h3>Conclusions</h3> These results demonstrate that Fgfr signalling in hepatocytes is essential for liver regeneration and suggest activation of Fgfr signalling as a promising approach for the improvement of the liver9s regenerative capacity.
Glioblastoma-Derived Epidermal Growth Factor Receptor Carboxyl-Terminal Deletion Mutants Are Transforming and Are Sensitive to EGFR-Directed Therapies
Authors: Jeonghee Cho, Sandra Pastorino, Qing Zeng, Xiaoyin Xu, William Johnson, Scott Vandenberg, Roel Verhaak, Andrew D. Cherniack, Hideo Watanabe, Amit Dutt, Jihyun Kwon, Ying S. Chao, Robert C. Onofrio, Derek Chiang, Yuki Yuza, Santosh Kesari, Matthew Meyerson
Journal: Cancer Research (2011)

Genomic alterations of the epidermal growth factor receptor (EGFR) gene play a crucial role in pathogenesis of glioblastoma multiforme (GBM). By systematic analysis of GBM genomic data, we have identified and characterized a novel exon 27 deletion mutation occurring within the EGFR carboxyl-terminus domain (CTD), in addition to identifying additional examples of previously reported deletion mutations in this region. We show that the GBM-derived EGFR CTD deletion mutants are able to induce cellular transformation in vitro and in vivo in the absence of ligand and receptor autophosphorylation. Treatment with the EGFR-targeted monoclonal antibody, cetuximab, or the small molecule EGFR inhibitor, erlotinib, effectively impaired tumorigenicity of oncogenic EGFR CTD deletion mutants. Cetuximab in particular prolonged the survival of intracranially xenografted mice with oncogenic EGFR CTD deletion mutants, compared with untreated control mice. Therefore, we propose that erlotinib and, especially, cetuximab treatment may be a promising therapeutic strategy in GBM patients harboring EGFR CTD deletion mutants.
Expression of hepatitis C virus proteins does not interfere with major histocompatibility complex class I processing and presentation in vitro
Authors: Darius Moradpour, Benno Grabscheid, Andreas R. Kammer, Gunter Schmidtke, Marcus Groettrup, Hubert E. Blum, Andreas Cerny
Journal: Hepatology (2001)

Hepatitis C virus (HCV) infection takes a chronic course in the majority of patients. The mechanisms underlying the evasion of the host immune response and viral persistence are poorly understood. In this context, we investigated interactions of HCV proteins with major histocompatibility complex (MHC) class I processing and presentation pathways using cell lines that allow the tetracycline-regulated expression of viral structural and nonstructural proteins. These well-characterized inducible cell lines were found to efficiently process and present endogenously synthesized HCV proteins via MHC class I. Functional MHC class I cell-surface expression and intracellular proteasome activity were not affected by the expression of HCV proteins. These results suggest that viral evasion of the host immune response does not involve interactions of HCV with MHC class I processing and presentation. Other mechanisms, such as interference with the interferon system, may be operative in HCV infection, leading to viral persistence.
Association between K469E allele of intercellular adhesion molecule 1 gene and inflammatory bowel disease in a Japanese population
Authors: J Matsuzawa
Journal: Gut (2002)

<b>Background and aims:</b> The genetic contribution to inflammatory bowel disease (IBD) is under investigation. Recent evidence indicates a significant linkage between a locus on chromosome 19p13 and IBD. We investigated the association between an intercellular adhesion molecule 1 gene (<i>ICAM-1</i>) polymorphism located on chromosome 19p13 and IBD in a Japanese population. <b>Methods:</b> We compared 207 Japanese patients who had IBD (79 with Crohn's disease (CD); 128 with ulcerative colitis (UC)) with 103 unrelated Japanese controls. We determined R241G and K469E polymorphisms of the <i>ICAM-1</i> gene using polymerase chain reaction (PCR) techniques. <b>Results:</b> Both frequency and carriage rate of the K469 allele were significantly higher in IBD patients than in controls (allelic frequency, p<sub>c</sub>=0.0026; carriage rate, p<sub>c</sub>=0.0034; odds ratio 2.59; 95% confidence interval 1.42–4.68). Furthermore, the frequency of the K469 allele was significantly increased in both CD and UC. Subgroup analysis demonstrated that both K469 allelic frequency and K469 carriage rate were significantly higher in patients with the small bowel and colon type of CD and entire colitis compared with healthy controls. <b>Conclusions:</b> We identified an overall association between IBD and ICAM-1 K469 in a Japanese population. Further studies of this chromosome region are required to elucidate the gene responsible for IBD.
Repression of BCL-6 is required for the formation of human memory B cells in vitro
Authors: Tracy C. Kuo, Arthur L. Shaffer, Joseph Haddad, Yong Sung Choi, Louis M. Staudt, Kathryn Calame
Journal: The Journal of Experimental Medicine (2007)

Memory B cells provide rapid protection to previously encountered antigens; however, how these cells develop from germinal center B cells is not well understood. A previously described in vitro culture system using human tonsillar germinal center B cells was used to study the transcriptional changes that occur during differentiation of human memory B cells. Kinetic studies monitoring the expression levels of several known late B cell transcription factors revealed that BCL-6 is not expressed in memory B cells generated in vitro, and gene expression profiling studies confirmed that BCL-6 is not expressed in these memory B cells. Furthermore, ectopic expression of BCL-6 in human B cell cultures resulted in formation of fewer memory B cells. In addition, the expression profile of in vitro memory B cells showed a unique pattern that includes expression of genes encoding multiple costimulatory molecules and cytokine receptors, antiapoptotic proteins, T cell chemokines, and transcription factors. These studies establish new molecular criteria for defining the memory B cell stage in human B cells.
The relationship between body fluid volume, sodium ion concentration, and sensitivity to pressor effect of angiotensin II in dogs.
Authors: A W Cowley, T E Lohmeier
Journal: Circulation Research (1978)

Extracellular fluid volume, plasma electrolyes, and plasma angiotensin II (A II) were individually controlled to determine their influence on the acute pressor responsiveness to A II. Hemodialysis of nephrectomized dogs was used to simulate and control the changes of major variables which occur in the intact state during changes in sodium balance. A II dose-pressure response curves were determined in 11 dogs at three volume states with plasma [Na+] maintained constant and in five dogs at low, normal, and high plasma [Na+] with body fluid volume maintained constant. Parallel shifts of the log dose-response curves were obtained in the three volume states. The same rise in arterial pressure with identical doses of A II was obtained at normal, contracted, and expanded volume states, with the change of arterial pressure based on the uncompensated basal pressure level at each volume state. When the fall in pressure observed during volume depletion was returned to control levels with norepinephrine, there was no change in the A II dose-response relationship from the control state. No difference in the A II dose-pressure response relationship was obtained between states of 140, 146, and 156 mEq/liter plasma [Na+] with body fluid volume held constant. The studies indicate that short-term alterations in either sodium or water balance do not alter the "real" vascular sensitivity to A II. The "apparent" changes normally observed result from preexisting endogenous levels of circulating A II present at the time the dose-response curve is determined which probably alter the availability of receptor sites to A II.
“(Not) All (Dead) Things Share the Same Breath”: Identification of Cell Death Mechanisms in Anticancer Therapy
Authors: Santiago Rello-Varona, David Herrero-Martín, Roser López-Alemany, Cristina Muñoz-Pinedo, Oscar M. Tirado
Journal: Cancer Research (2015)

Abstract During the last decades, the knowledge of cell death mechanisms involved in anticancer therapy has grown exponentially. However, in many studies, cell death is still described in an incomplete manner. The frequent use of indirect proliferation assays, unspecific probes, or bulk analyses leads too often to misunderstandings regarding cell death events. There is a trend to focus on molecular or genetic regulations of cell demise without a proper characterization of the phenotype that is the object of this study. Sometimes, cancer researchers can feel overwhelmed or confused when faced with such a corpus of detailed insights, nomenclature rules, and debates about the accuracy of a particular probe or assay. On the basis of the information available, we propose a simple guide to distinguish forms of cell death in experimental settings using cancer cell lines. Cancer Res; 75(6); 913–7. ©2015 AACR.
Harnessing a Neural-immune Circuit to Control Inflammation and Shock
Authors: J. Edwin Blalock
Journal: The Journal of Experimental Medicine (2002)

That the mind can influence the body during health and disease is an ancient notion which, in part because of its origins in anecdotal observations, has been an often and sometimes hotly debated concept. Over 20 years ago, Dr. Robert A. Good formulated a concise and elegant description of the
Bayesian Hierarchical Changepoint Methods in Modeling the Tumor Growth Profiles in Xenograft Experiments
Authors: Lili Zhao, Meredith A. Morgan, Leslie A. Parsels, Jonathan Maybaum, Theodore S. Lawrence, Daniel Normolle
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The standard approach of using tumor doubling time to assess growth delay may not accurately represent tumor response, especially if the growth rates are not constant. Therefore, we developed a method to compare the antitumor activities of different treatments in xenograft experiments that uses the entire growth curve to estimate nonconstant growth rates. Experimental Design: A Bayesian hierarchical changepoint (BHC) method was used to model logarithmically transformed tumor volumes (TV). Each tumor was assumed to have a growth profile, represented by a prenadir regression rate, a regression period, a nadir volume, and a postnadir regrowth rate. Confidence intervals were calculated to compare these features between different treatments. We used data from a study assessing the effects of radiation, gemcitabine, and a Chk1/2 inhibitor on MiaPaCa-2 xenografts. Results: We found that the BHC model provided a good fit to the data and more descriptive features than the tumor doubling approach. This model detected significant tumor regression in the AZD7762 + 1 Gy and GEM + 1 Gy that was not detected when comparing the tumor doubling times. The BHC model also provided evidence that the growth inhibition resulted from a direct tumor effect rather than an indirect effect on the tumor bed, as evidenced by dramatic tumor regression in response to effective treatments and similar postnadir regrowth rates across all treatment groups. Conclusions: Compared with the tumor doubling time approach, the BHC model utilizes all data, providing more descriptive features that address mechanisms underlying tumor growth inhibition and maximize the biological information obtained from tumor xenografts studies. Clin Cancer Res; 17(5); 1057–64. ©2010 AACR.
Health and Economic Implications of HPV Vaccination in the United States
Authors: Jane J. Kim, Sue J. Goldie
Journal: New England Journal of Medicine (2008)

The cost-effectiveness of prophylactic vaccination against human papillomavirus types 16 (HPV-16) and 18 (HPV-18) is an important consideration for guidelines for immunization in the United States.We synthesized epidemiologic and demographic data using models of HPV-16 and HPV-18 transmission and cervical carcinogenesis to compare the health and economic outcomes of vaccinating preadolescent girls (at 12 years of age) and vaccinating older girls and women in catch-up programs (to 18, 21, or 26 years of age). We examined the health benefits of averting other HPV-16-related and HPV-18-related cancers, the prevention of HPV-6-related and HPV-11-related genital warts and juvenile-onset recurrent respiratory papillomatosis by means of the quadrivalent vaccine, the duration of immunity, and future screening practices.On the assumption that the vaccine provided lifelong immunity, the cost-effectiveness ratio of vaccination of 12-year-old girls was $43,600 per quality-adjusted life-year (QALY) gained, as compared with the current screening practice. Under baseline assumptions, the cost-effectiveness ratio for extending a temporary catch-up program for girls to 18 years of age was $97,300 per QALY; the cost of extending vaccination of girls and women to the age of 21 years was $120,400 per QALY, and the cost for extension to the age of 26 years was $152,700 per QALY. The results were sensitive to the duration of vaccine-induced immunity; if immunity waned after 10 years, the cost of vaccination of preadolescent girls exceeded $140,000 per QALY, and catch-up strategies were less cost-effective than screening alone. The cost-effectiveness ratios for vaccination strategies were more favorable if the benefits of averting other health conditions were included or if screening was delayed and performed at less frequent intervals and with more sensitive tests; they were less favorable if vaccinated girls were preferentially screened more frequently in adulthood.The cost-effectiveness of HPV vaccination will depend on the duration of vaccine immunity and will be optimized by achieving high coverage in preadolescent girls, targeting initial catch-up efforts to women up to 18 or 21 years of age, and revising screening policies.
Flexible and Stretchable Electronics for Biointegrated Devices
Authors: Dae-Hyeong Kim, Roozbeh Ghaffari, Nanshu Lu, John A. Rogers
Journal: Annual Review of Biomedical Engineering (2012)

Advances in materials, mechanics, and manufacturing now allow construction of high-quality electronics and optoelectronics in forms that can readily integrate with the soft, curvilinear, and time-dynamic surfaces of the human body. The resulting capabilities create new opportunities for studying disease states, improving surgical procedures, monitoring health/wellness, establishing human-machine interfaces, and performing other functions. This review summarizes these technologies and illustrates their use in forms integrated with the brain, the heart, and the skin.
Role of toll-like receptor 4 on the immune escape of human oral squamous cell carcinoma and resistance of cisplatin-induced apoptosis
Authors: Zujun Sun, Qingqiong Luo, Dongxia Ye, Wantao Chen, Fuxiang Chen
Journal: Molecular Cancer (2012)

Abstract Background Toll-like receptor 4 (TLR4) is expressed on immune cells as a sensor that recognizes lipopolysaccharide (LPS), a microbial conserved component. It has recently been determined that the expression of TLR4 is also found in various types of tumor cells. Cisplatin is a widely used chemotherapeutic agent for oral squamous cell carcinoma (OSCC) treatment. However, the mechanisms responsible for cisplatin resistance are not well understood. Results The present study was designed to elucidate the role of TLR4 expression in human OSCC regarding immune escape and apoptotic resistance to cisplatin. TLR4 and the myeloid differentiation primary response gene 88 (MyD88) were highly expressed in OSCC cell lines. Upon LPS stimulation both NF-κB and p38 MAPK pathways were activated in OSCC cell lines, followed by the production of large quantities of IL-6, IL-8 and VEGF compared with human immortalized oral epithelia cells (HIOECs). OSCC cell lines were found to be resistant to cisplatin-mediated apoptosis after pretreatment with LPS. Conclusions Our results suggested that TLR4 was functionally expressed in human OSCC cells and development of resistance to cisplatin in human OSCC might occur through the mechanism involving TLR4 and its signaling pathway. Suppression of TLR4 and its signaling pathway might thus elevate sensitivity to cisplatin and potentially help improve the prognosis of patients with OSCC.
Discussing Complementary Therapies With Cancer Patients: What Should We Be Talking About?
Authors: Harold J. Burstein
Journal: Journal of Clinical Oncology (2000)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.13.2501 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10893279 Discussing Complementary Therapies With Cancer Patients: What Should We Be Talking About? Harold J. Burstein, MD, PhDxHarold J. BursteinSearch for articles by this author Show More Dana-Farber Cancer Institute, Brigham & Women's Hospital, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2000.18.13.2501 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Itraconazole therapy is effective for pedal onychomycosis caused by some nondermatophyte molds and in mixed infection with dermatophytes and molds: A multicenter study with 36 patients
Authors: Piet R.G. De Doncker, Richard K. Scher, Robert L. Baran, J. Decroix, Hugo J. Degreef, Diane I. Roseeuw, V. Havu, Theodore Rosen, Aditya K. Gupta, Gerald E. Piérard
Journal: Journal of the American Academy of Dermatology (1997)
Preconditioning enhances cell survival and differentiation of stem cells during transplantation in infarcted myocardium
Authors: Z. Pasha, Y. Wang, R. Sheikh, D. Zhang, T. Zhao, M. Ashraf
Journal: Cardiovascular Research (2007)

We hypothesized that preconditioning (PC) with stromal-derived factor 1 alpha (SDF-1) significantly enhances cell survival, proliferation, and engraftment of bone marrow-derived mesenchymal stem cells (MSCs) via SDF-1/CXCR4 signaling.MSCs were cultured and then incubated in medium for 60 min without SDF-1 (control group) or with SDF-1 0.05 microg/mL (SDF-1 group) or CXCR4-selective antagonist, AMD 3100 (AMD) (5 microg/mL, AMD group) or SDF-1 and AMD (0.05 microg/mL, 5 microg/mL, respectively, SDF-1+AMD group). MSCs were treated for 60 min, washed in normal medium, and then exposed to H2O2 (100 micromol/L) for 60 min to determine the effects of various treatments on cell injury, viability, and proliferation. For in vivo studies, rats were grouped (n = 6) after left anterior descending coronary artery ligation to receive 20 microL Dulbecco's modified Eagle's medium without cells or with 5 x 10(5) non-preconditioned MSCs (control group), SDF-1 preconditioned MSCs (SDF-1 group), AMD (AMD group), or MSCs treated with SDF-1 plus AMD (SDF-1+AMD group). Heart function, infarct size, fibrosis, and MSC proliferation and differentiation in infarcted myocardium were determined after 4 weeks. In vitro data showed a marked increase in cell viability and proliferation following SDF-1 PC. In vivo data in preconditioned group showed a robust cell proliferation, reduction in infarct size and fibrosis, and significant improvement in cardiac function. Effects of SDF-1 PC were abrogated by CXCR4 antagonist.We conclude that PC with the chemokine SDF-1 suppresses MSCs apoptosis, enhances their survival, engraftment, and vascular density, and improves myocardial function via SDF/CXCR4 signaling. Chemokine PC is a novel approach for enhancing stem cell survival and regeneration of infarcted myocardium.
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an under-recognised spectrum of disease
Authors: S. J Davies, J. R Gosney, D. M Hansell, A. U Wells, R. M du Bois, M. M Burke, M. N Sheppard, A. G Nicholson
Journal: Thorax (2006)

<b>Aims and Methods:</b> A review was undertaken of 19 patients diagnosed with diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) between 1992 and 2006. <b>Results:</b> Most patients were women (n = 15) and non-smokers (n = 16). Clinical presentation was either with symptomatic pulmonary disease (group 1; n = 9) or as an incidental finding during investigation for another disorder, most frequently malignant disease (group 2; n = 10). In group 1, cough and dyspnoea were the most frequent symptoms, with an average duration of 8.6 years before diagnosis. Both groups showed mainly stable disease without treatment, although one patient progressed to severe airflow obstruction and one was diagnosed at single lung transplantation. Mosaicism with nodule(s) was the typical pattern of DIPNECH on high-resolution computed tomography, but one case had normal imaging despite airflow obstruction. Lung function tests showed obstructive (n = 8), mixed (n = 3) or normal (n = 5, all group 2) physiology. Two patients underwent a bronchoalveolar lavage and showed a lymphocytosis (30%) with mild chronic bronchiolitis being seen in all biopsies. Tumourlets and associated typical carcinoids (n = 9) showed weak positivity for thyroid transcription factor-1. Three patients had atypical carcinoids, one with multiple endocrine neoplasia type 1 syndrome. <b>Conclusions:</b> DIPNECH is being increasingly recognised, probably because of an increase in the usage and accuracy of investigative imaging and increased awareness of the entity. Most cases remain stable over many years independent of the mode of presentation, although a few patients progress to severe airflow obstruction.