tbuckley/cabot-search huggingface dataset:
Na(+)-H+ exchange inhibitors decrease neointimal formation after rat carotid injury. Effects on smooth muscle cell migration and proliferation.
Authors: M Mitsuka, M Nagae, B C Berk
Journal: Circulation Research (1993)

The presence of multiple growth stimuli at the sites of vascular injury following angioplasty suggests that therapies targeted toward common growth pathways will be more effective than therapies that inhibit only a single growth factor. We tested this hypothesis using amiloride and ethyl isopropyl amiloride (EIPA), which are inhibitors of the Na(+)-H+ exchanger, whose activity is required in many cells for proliferation and migration. In the rat carotid injury model, EIPA (100 micrograms/h for 15 days) significantly decreased intimal area and the ratio of intimal to medial area, whereas amiloride (25 micrograms/h) showed an inhibitory trend that was similar to that observed for captopril (80 mg/kg per day) and heparin (25 U/h). EIPA and amiloride inhibited rat vascular smooth muscle cell DNA synthesis, with IC50 values of 8.8 and 82.2 microM, respectively. Using platelet-derived growth factor as a chemoattractant, EIPA caused a concentration-dependent inhibition of migration (IC50, approximately 60 microM). Because amiloride and EIPA have nonspecific effects on cellular function (especially inhibition of tyrosine kinases), we sought to characterize the specific role of the Na(+)-H+ exchanger in vascular smooth muscle cell proliferation and migration. We generated a Na(+)-H+ exchanger-deficient mutant cell line [RNHE(-)]. Studies with these cells suggested that the inhibitory effects of EIPA and amiloride were mediated only in part via Na(+)-H+ exchange because (1) RNHE(-) cells grew well at pH 6.8 to 7.5 in bicarbonate-containing medium, and (2) there was no difference in migration in response to platelet-derived growth factor in the RHNE(-) cells. In summary, these data indicate that amiloride and EIPA inhibit neointimal formation in the rat carotid after injury. However, the mechanism of inhibition is likely to involve cellular events other than Na(+)-H+ exchange, such as an effect on tyrosine kinases.
Fatty acid synthase is up-regulated during hepatitis C virus infection and regulates hepatitis C virus entry and production
Authors: Wei Yang, Brian L. Hood, Sara L. Chadwick, Shufeng Liu, Simon C. Watkins, Guangxiang Luo, Thomas P. Conrads, Tianyi Wang
Journal: Hepatology (2008)

Hepatitis C virus (HCV) is a major human pathogen that causes serious illness, including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Using a mass spectrometry–based proteomics approach, we have identified 175 proteins from a cell culture supernatant fraction containing the HCV genotype 2a (JFH1) virus, among which fatty acid synthase (FASN), the multifunctional enzyme catalyzing the de novo synthesis of fatty acids, was confirmed to be highly enriched. Subsequent studies showed that FASN expression increased in the human hepatoma cell line, Huh7, or its derivative, upon HCV infection. Blocking FASN activity by C75, a pharmacological FASN inhibitor, led to decreased HCV production. Reduction of FASN by RNA interference suppressed viral replication in both replicon and infection systems. Remarkably, FASN appeared to be selectively required for the expression of claudin-1, a tight junction protein that was recently identified as an entry coreceptor for HCV, but not for the expression of another HCV coreceptor, CD81. The decrease in Claudin-1 expression resulting from FASN inhibition was accompanied by a decrease in transepithelial electric resistance of Huh7 cells, implying a reduction in the relative tightness of the cell monolayer. Consequently, the entry of human immunodeficiency virus–HCV pseudotypes was significantly inhibited in C75-treated Huh7 cells. Conclusion: As far as we know, this is the first line of evidence that demonstrates that HCV infection directly induces FASN expression, and thus suggests a possible mechanism by which HCV infection alters the cellular lipid profile and causes diseases such as steatosis. (HEPATOLOGY 2008.)
Fludarabine and epirubicin in the treatment of chronic lymphocytic leukaemia: A German multicenter phase II study
Authors: M.J. Rummel, G. Käfer, M. Pfreundschuh, E. Jäger, U. Reinhardt, P.S. Mitrou, D. Hoelzer, L. Bergmann
Journal: Annals of Oncology (1999)
Mortality From Second Tumors Among Long-Term Survivors of Retinoblastoma
Authors: C. Eng, F. P. Li, D. H. Abramson, R. M. Ellsworth, F. L. Wong, M. B. Goldman, J. Seddon, N. Tarbell, J. D. Boice
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Mortality From Second Tumors Among Long-Term Survivors of Retinoblastoma Get access Charis Eng, Charis Eng Divisions of Medical Oncology and Cancer Epidemiology and Control, Dana-Farber Cancer InstituteBoston, Mass.Harvard Medical SchoolBoston, Mass. Correspondence to: John D. Boice, Jr., Sc.D., Radiation Epidemiology Branch, National Cancer Institute, EPN 408, 6130 Executive Blvd, Rockville, MD 20852. Search for other works by this author on: Oxford Academic PubMed Google Scholar Frederick P. Li, Frederick P. Li Division of Cancer Epidemiology and Control, Dana-Farber Cancer Institute, and Harvard School of Public HealthBoston, Mass. Search for other works by this author on: Oxford Academic PubMed Google Scholar David H. Abramson, David H. Abramson Ophthalmic Oncology Center, New York Hospital-Cornell Medical CenterNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert M. Ellsworth, Robert M. Ellsworth Ophthalmic Oncology Center, New York Hospital-Cornell Medical CenterNew York, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar F. Lennie Wong, F. Lennie Wong Radiation Epidemiology Branch, National Cancer InstituteRockville, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marlene B. Goldman, Marlene B. Goldman Harvard School of Public Health Search for other works by this author on: Oxford Academic PubMed Google Scholar Johanna Seddon, Johanna Seddon Massachusetts Eye and Ear InfirmaryBoston, Mass.Harvard Medical School Search for other works by this author on: Oxford Academic PubMed Google Scholar Nancy Tarbell, Nancy Tarbell Joint Center for Radiation Therapy, Boston Children's HospitalBoston, Mass.Harvard Medical School Search for other works by this author on: Oxford Academic PubMed Google Scholar John D. Boice, Jr. John D. Boice, Jr. Radiation Epidemiology Branch, National Cancer InstituteRockville, Md. Correspondence to: John D. Boice, Jr., Sc.D., Radiation Epidemiology Branch, National Cancer Institute, EPN 408, 6130 Executive Blvd, Rockville, MD 20852. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 14, 21 July 1993, Pages 1121–1128, https://doi.org/10.1093/jnci/85.14.1121 Published: 21 July 1993 Article history Received: 22 September 1992 Revision received: 22 March 1993 Accepted: 06 May 1993 Published: 21 July 1993
Commentary: Sweden rolls out online access to medical records and is developing new e-health services to enable people to manage their care
Authors: M. Hagglund, S. Koch
Journal: BMJ (2015)

National e-health services in Sweden provide citizens with health information, contact details of providers, and interactive services where they can ask questions anonymously that are answered by healthcare professionals within seven days . The national portal My Healthcare Contacts lets citizens request, cancel, or reschedule healthcare appointments, renew prescriptions, and request contact with a specific clinician or hospital. Each healthcare centre or other local provider decides which e-services people can use to …
Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer
Authors: Joseph A. Sparano, Molin Wang, Silvana Martino, Vicky Jones, Edith A. Perez, Tom Saphner, Antonio C. Wolff, George W. Sledge, William C. Wood, Nancy E. Davidson
Journal: New England Journal of Medicine (2008)

We compared the efficacy of two different taxanes, docetaxel and paclitaxel, given either weekly or every 3 weeks, in the adjuvant treatment of breast cancer.
Part 14: Pediatric Advanced Life Support
Authors: Monica E. Kleinman, Leon Chameides, Stephen M. Schexnayder, Ricardo A. Samson, Mary Fran Hazinski, Dianne L. Atkins, Marc D. Berg, Allan R. de Caen, Ericka L. Fink, Eugene B. Freid, Robert W. Hickey, Bradley S. Marino, Vinay M. Nadkarni, Lester T. Proctor, Faiqa A. Qureshi, Kennith Sartorelli, Alexis Topjian, Elise W. van der Jagt, Arno L. Zaritsky
Journal: Circulation (2010)
Radiation Dose in the Selection of ^131I or Surgical Treatment for Toxic Thyroid Adenoma
Authors: COLUM A. GORMAN
Journal: Annals of Internal Medicine (1978)

Clinicians, by their patterns of referral to colleagues in nuclear medicine or surgery, may strongly influence the selection of 131I versus surgical treatment for patients with toxic thyroid adenoma. The information presented here is intended to aid them in making an informed choice. As nodule size of an adenoma increases from 2 cm to 6 cm, the amount of radioiodine administered to the patient to deliver the same dose (30 000 rads to the nodule center, assuming a 30% uptake) increases from 5.6 mCi to 135 mCi. Concurrently, the suppressed thyroid tissue receives a radiation dose as high as 2300 rads. Despite these potentially carcinogenic doses, few patients with radioiodine-induced thyroid tumors have been reported; we discuss possible reasons for this. For young patients with large nodules, surgery is preferred.
Quantitative Disease, Drug, and Trial Models
Authors: Jogarao V.S. Gobburu, Lawrence J. Lesko
Journal: The Annual Review of Pharmacology and Toxicology (2008)

Quantitative disease-drug-trial models allow learning from prior experience and summarize the knowledge in a ready to apply format. Employing these models to plan future development is proposed as a powerful solution to improve pharmaceutical R&amp;D productivity. The disease and trial models are, to a large extent, independent of the product, but the drug model is not. The goals are to apply the disease and trial models to future development and regulatory decisions, and publicly share them. We propose working definitions of these models, describe the various subcomponents, provide examples, and discuss the challenges and potential solutions for developing such models. Building useful disease-drug-trial models is a challenging task and cannot be achieved by any single organization. It requires a consorted effort by industry, academic, and regulatory scientists. We also describe the strategic goals of the FDA Pharmacometrics group.
Primary biliary cirrhosis: seeking the silent partner of autoimmunity
Authors: I Sutton
Journal: Gut (2002)

Primary biliary cirrhosis is a disorder characterised by an intense inflammatory response in the septal and interlobular bile ducts and is considered to be an autoimmune disease. Evidence to suggest that chronic viral infection could be a crucial element in the development of biliary epithelial cell damage and activation of the associated autoimmune response is reviewed
The events leading to the death of patients with pemphigus and pemphigoid
Authors: J. A. SAVIN
Journal: British Journal of Dermatology (1979)

This paper is based upon a study of all available records of patients certified as having died in hospital from pemphigus and pemphigoid in England and Wales from 1962 to 1969. The results differ from most published series in that many of the 210 patients died still with extensive skin lesions and with biochemical abnormalities, such as low serum albumin, sodium and chloride, which were secondary to this. Side-effects of treatment, such as diabetes, peptic ulceration, and infections, were also important but the commonest immediate causes of death were respiratory tract infections and pulmonary embolism.
Divergence of IL-1, IL-18, and cell death in NLRP3 inflammasomopathies
Authors: Susannah D. Brydges, Lori Broderick, Matthew D. McGeough, Carla A. Pena, James L. Mueller, Hal M. Hoffman
Journal: Journal of Clinical Investigation (2013)

The inflammasome is a cytoplasmic multiprotein complex that promotes proinflammatory cytokine maturation in response to host- and pathogen-derived signals. Missense mutations in cryopyrin (NLRP3) result in a hyperactive inflammasome that drives overproduction of the proinflammatory cytokines IL-1β and IL-18, leading to the cryopyrin-associated periodic syndromes (CAPS) disease spectrum. Mouse lines harboring CAPS-associated mutations in Nlrp3 have elevated levels of IL-1β and IL-18 and closely mimic human disease. To examine the role of inflammasome-driven IL-18 in murine CAPS, we bred Nlrp3 mutations onto an Il18r-null background. Deletion of Il18r resulted in partial phenotypic rescue that abolished skin and visceral disease in young mice and normalized serum cytokines to a greater extent than breeding to Il1r-null mice. Significant systemic inflammation developed in aging Nlrp3 mutant Il18r-null mice, indicating that IL-1 and IL-18 drive pathology at different stages of the disease process. Ongoing inflammation in double-cytokine knockout CAPS mice implicated a role for caspase-1-mediated pyroptosis and confirmed that CAPS is inflammasome dependent. Our results have important implications for patients with CAPS and residual disease, emphasizing the need to explore other NLRP3-mediated pathways and the potential for inflammasome-targeted therapy.
Genetic Dissection of the Cellular Pathways and Signaling Mechanisms in Modeled Tumor Necrosis Factor–induced Crohn's-like Inflammatory Bowel Disease
Authors: Dimitris Kontoyiannis, George Boulougouris, Menelaos Manoloukos, Maria Armaka, Maria Apostolaki, Theresa Pizarro, Alexey Kotlyarov, Irmgard Forster, Richard Flavell, Matthias Gaestel, Philip Tsichlis, Fabio Cominelli, George Kollias
Journal: The Journal of Experimental Medicine (2002)

Recent clinical evidence demonstrated the importance of tumor necrosis factor (TNF) in the development of Crohn's disease. A mouse model for this pathology has previously been established by engineering defects in the translational control of TNF mRNA (TnfΔAREmouse). Here, we show that development of intestinal pathology in this model depends on Th1-like cytokines such as interleukin 12 and interferon γ and requires the function of CD8+ T lymphocytes. Tissue-specific activation of the mutant TNF allele by Cre/loxP-mediated recombination indicated that either myeloid- or T cell–derived TNF can exhibit full pathogenic capacity. Moreover, reciprocal bone marrow transplantation experiments using TNF receptor–deficient mice revealed that TNF signals are equally pathogenic when directed independently to either bone marrow–derived or tissue stroma cell targets. Interestingly, TNF-mediated intestinal pathology was exacerbated in the absence of MAPKAP kinase 2, yet strongly attenuated in a Cot/Tpl2 or JNK2 kinase–deficient genetic background. Our data establish the existence of redundant cellular pathways operating downstream of TNF in inflammatory bowel disease, and demonstrate the therapeutic potential of selective kinase blockade in TNF-mediated intestinal pathology.
Review of Phase II Trial Designs Used in Studies of Molecular Targeted Agents: Outcomes and Predictors of Success in Phase III
Authors: Robert H. El-Maraghi, Elizabeth A. Eisenhauer
Journal: Journal of Clinical Oncology (2008)

Purpose Because the appropriate design and end points for phase II evaluation of targeted anticancer agents are unclear, we undertook a review of recent reports of phase II trials of targeted agents to determine the types of designs used, the planned end points, the outcomes, and the relationship between trial outcomes and regulatory approval. Methods We retrieved reports of single-agent phase II trials in six solid tumors for 19 targeted drugs. For each, we abstracted data regarding planned design and actual results. Response rates were examined for any relationship to eventual success of the agents, as determined by US Food and Drug Administration approval for at least one indication. Results Eighty-nine trials were identified. Objective response was the primary or coprimary end point in the majority of trials (61 of 89 trials). Fourteen reports were of randomized studies generally evaluating different doses of agents, not as controlled experiments. Enrichment for target expression was uncommon. Objective responses were seen in 38 trials; in 19 trials, response rates were more than 10%, and in eight, they were more than 20%. Agents with high response rates tended to have high nonprogression rates; renal cell carcinoma was the exception to this. Higher overall response rates were predictive of regulatory approval in the tumor types reviewed (P = .005). Conclusion In practice, phase II design for targeted agents is similar to that for cytotoxics. Objective response seems to be a useful end point for screening new targeted agents because, in our review, its observation predicted for eventual success. Improvements in design are recommended, as is more frequent inclusion of biological questions as part of phase II trials.
The pressure mounts on lung dendritic cells
Authors: B. N. Lambrecht, L. M. van den Toorn
Journal: European Respiratory Journal (2007)

A role for inflammatory processes in the pathogenesis of pulmonary arterial hypertension (PAH) has been proposed, since inflammatory infiltrates surrounding remodelled vessels in human and experimental PAH have been described by several groups [1,2].Increased levels and expression of cytokines, chemokines and lipid mediators have been found in the blood, lung parenchyma and affected pulmonary vessels.The higher prevalence of PAH in connective tissue disorders and the successful treatment with immunosuppressive therapy in some forms of PAH support the concept of inflammatory pathways in the development and/or modulation of the disease.Although data are scarce, the infiltrates found in plexiform lesions consist mainly of lymphocytes and macrophages, whereas neutrophilic inflammation has not traditionally been described.The presence of lymphocytes in the vessel wall suggests that these cells might control the disease process by secretion of pleiotropic cytokines, analogous to what has been described in other T-cell-mediated diseases, such as asthma, auto-immune disorders or transplant rejection.In these diseases, effector T-lymphocytes are activated locally by antigen-presenting dendritic cells (DCs) to mediate disease [3,4].A report by PERROS et al. [5] in the current issue of the European Respiratory Journal describes an increase in these DCs in plexiform lesions of idiopathic PAH (IPAH) patients and rats with monocrotaline-induced PAH.This strongly suggests that these DCs present some form of (auto-)antigen to T-cells that might initiate or perpetuate inflammation.
American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients
Authors: Stephanie J. Lee, Leslie R. Schover, Ann H. Partridge, Pasquale Patrizio, W. Hamish Wallace, Karen Hagerty, Lindsay N. Beck, Lawrence V. Brennan, Kutluk Oktay
Journal: Journal of Clinical Oncology (2006)

To develop guidance to practicing oncologists about available fertility preservation methods and related issues in people treated for cancer.An expert panel and a writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature from 1987 to 2005 was performed, and included a search of online databases and consultation with content experts.The literature review found many cohort studies, case series, and case reports, but relatively few randomized or definitive trials examining the success and impact of fertility preservation methods in people with cancer. Fertility preservation methods are used infrequently in people with cancer.As part of education and informed consent before cancer therapy, oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists. Clinician judgment should be employed in the timing of raising this issue, but discussion at the earliest possible opportunity is encouraged. Sperm and embryo cryopreservation are considered standard practice and are widely available; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise.Fertility preservation is often possible in people undergoing treatment for cancer. To preserve the full range of options, fertility preservation approaches should be considered as early as possible during treatment planning.
Platelet-rich plasma and the biological complexity of tissue regeneration
Authors: Leon Creaney
Journal: British Journal of Sports Medicine (2011)

I congratulate the International Olympic Committee consensus panel1 on having produced as clear a summary of the current understanding of the basic and clinical science relating to platelet-rich plasma (PRP) as the body of published literature allows. While there was initially great hope in sports medicine circles that PRP would become the magic bullet for injuries, recent trials such as that of de Vos et al 2 have failed to provide the conclusive evidence so desired.

This is not surprising. The more we learn about tissue regeneration, the more apparent it becomes how complex a process it is. Tissue regeneration is not a passive phenomenon, instead it is a highly coordinated interplay of multiple cell lines at different stages of maturation. Different cellular and humoral components play their different roles.

The process can be likened to the repair of a collapsed building. Consider muscle injury. The initial cells on the scene, due to bleeding, are platelets, but they appear to …
Correlation of Computed Tomography and Positron Emission Tomography in Patients With Metastatic Gastrointestinal Stromal Tumor Treated at a Single Institution With Imatinib Mesylate: Proposal of New Computed Tomography Response Criteria
Authors: Haesun Choi, Chuslip Charnsangavej, Silvana C. Faria, Homer A. Macapinlac, Michael A. Burgess, Shreyaskumar R. Patel, Lei L. Chen, Donald A. Podoloff, Robert S. Benjamin
Journal: Journal of Clinical Oncology (2007)

Response Evaluation Criteria in Solid Tumors (RECIST) are insensitive in evaluating gastrointestinal stromal tumors (GISTs) treated with imatinib. This study evaluates whether computed tomography (CT) findings of GIST after imatinib treatment correlate with tumor responses by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and develops reliable, quantitative, CT response criteria.A total of 172 lesions selected by RECIST were evaluated in 40 patients with metastatic GISTs treated with imatinib. All patients had pretreatment and 2-month follow-up CTs and FDG-PETs. Multivariate analysis was performed using tumor size and density (Hounsfield unit [HU]) on CT and maximum standardized uptake value (SUVmax) on FDG-PET. Patients were observed up to 28 months.Mean baseline tumor size and density on CT were 5.3 cm and 72.8 HU, respectively, and mean baseline SUVmax on FDG-PET was 5.8. Thirty-three patients had good response on FDG-PET. A decrease in tumor size of more than 10% or a decrease in tumor density of more than 15% on CT had a sensitivity of 97% and a specificity of 100% in identifying PET responders versus 52% and 100% by RECIST. Good responders on CT at 2 months had significantly longer time to progression than those who did not respond (P = .01).Small changes in tumor size or density on CT are sensitive and specific methods of assessing the response of GISTs. If the prognostic value of our proposed CT response criteria can be confirmed prospectively, the criteria should be employed in future studies of patients with GIST.