tbuckley/cabot-search huggingface dataset:
Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension
Authors: F. Perros, P. Dorfmüller, R. Souza, I. Durand-Gasselin, V. Godot, F. Capel, S. Adnot, S. Eddahibi, M. Mazmanian, E. Fadel, P. Hervé, G. Simonneau, D. Emilie, M. Humbert
Journal: European Respiratory Journal (2006)

Pulmonary hypertension is characterised by a progressive increase in pulmonary arterial resistance due to endothelial and smooth muscle cell proliferation resulting in chronic obstruction of small pulmonary arteries. There is evidence that inflammatory mechanisms may contribute to the pathogenesis of human and experimental pulmonary hypertension. The aim of the study was to address the role of fractalkine (CX3CL1) in the inflammatory responses and pulmonary vascular remodelling of a monocrotaline-induced pulmonary hypertension model. The expression of CX3CL1 and its receptor CX3CR1 was studied in monocrotaline-induced pulmonary hypertension by means of immunohistochemistry and quantitative reverse-transcription PCR on laser-captured microdissected pulmonary arteries. It was demonstrated that CX3CL1 was expressed by inflammatory cells surrounding pulmonary arterial lesions and that smooth muscle cells from these vessels had increased CX3CR1 expression. It was then shown that cultured rat pulmonary artery smooth muscle cells expressed CX3CR1 and that CX3CL1 induced proliferation but not migration of these cells. In conclusion, the current authors proposed that fractalkine may act as a growth factor for pulmonary artery smooth muscle cells. Chemokines may thus play a role in pulmonary artery remodelling.
The Molecular and Behavioral Pharmacology of the Orphanin FQ/Nociceptin Peptide and Receptor Family
Authors: Jeffrey S. Mogil, Gavril W. Pasternak
Journal: Pharmacological Reviews (2001)

The isolation of an opioid receptor-related clone soon led to the isolation and characterization of a new neuropeptide, termed orphanin FQ or nociceptin (OFQ/N). This heptadecapeptide binds to the NOP(1) (previously termed ORL1) receptor with exceedingly high affinity, but does not interact directly with classical opioid receptors. Functionally, the actions of OFQ/N are diverse and intriguing. Most work has focused upon pain mechanisms, where OFQ/N has potent anti-analgesic actions supraspinally and analgesic actions spinally. Other OFQ/N activities are less clear. The diversity of responses might reflect NOP(1) receptor heterogeneity, but this remains to be established. The actions of this neurochemical system may also be uniquely dependent on contextual factors, both genetic and environmental. This review will address the molecular biology and behavioral pharmacology of OFQ/N and its receptor.
The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapy
Authors: Moritz Stolla, Lucia Stefanini, R. Claire Roden, Massiel Chavez, Jessica Hirsch, Teshell Greene, Timothy D. Ouellette, Sean F. Maloney, Scott L. Diamond, Mortimer Poncz, Donna S. Woulfe, Wolfgang Bergmeier
Journal: Blood (2010)
Smad3 Is Overexpressed in Advanced Human Prostate Cancer and Necessary for Progressive Growth of Prostate Cancer Cells in Nude Mice
Authors: Shan Lu, Juwon Lee, Monica Revelo, Xiaohong Wang, Shan Lu, Zhongyun Dong
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The purpose of this study was to investigate the potential role of Smad3, a key mediator of transforming growth factor-β signaling, in progression of prostate cancer. Experimental Design: Expression of Smad proteins was determined in human prostate cancer tissue array and cell lines. Growth and metastasis of cells overexpressing dominant-negative Smad3 (Smad3D) were studied to determine its role in tumor progression in mice. Cell growth, apoptosis, and expression of angiogenic molecules in tumor lesions were studied to determine potential pathways that Smad3 promotes tumor progression. Results: Smad3 was overexpressed in human prostate cancer, which correlated with Gleason score and expression of proliferating cell nuclear antigen. Androgen-independent PC-3MM2 and DU145 cells expressed much higher levels of Smad3 than did androgen-dependent LNCaP, 22Rv1, and LAPC-4 cells. Overexpression of Smad3D in PC-3MM2 cells (PC-3MM2-Smad3D) had minimal direct effects on cell growth but attenuated effects of transforming growth factor-β1 on gene expression and cell growth. Overexpression of Smad3D did not significantly alter tumor incidence but reduced tumor growth rate and metastasis incidence. Most cells in the control tumors, but not PC-3MM2-Smad3D tumors, were positively stained by an antibody to proliferating cell nuclear antigen. Microvessels and expression of angiogenic molecule interleukin-8 were significantly reduced in tumors from PC-3MM2-Smad3D cells. PC-3MM2-Smad3D tumors also expressed lower levels of vascular endothelial growth factor and platelet-derived growth factor. Conclusions: These data suggest that Smad3, through regulating angiogenic molecule expression in tumor cells, is critical for progression of human prostate cancer.
Digital transcriptome profiling of normal and glioblastoma-derived neural stem cells identifies genes associated with patient survival
Authors: Pär G Engström, Diva Tommei, Stefan H Stricker, Christine Ender, Steven M Pollard, Paul Bertone
Journal: Genome Medicine (2012)

Glioblastoma multiforme, the most common type of primary brain tumor in adults, is driven by cells with neural stem (NS) cell characteristics. Using derivation methods developed for NS cells, it is possible to expand tumorigenic stem cells continuously in vitro. Although these glioblastoma-derived neural stem (GNS) cells are highly similar to normal NS cells, they harbor mutations typical of gliomas and initiate authentic tumors following orthotopic xenotransplantation. Here, we analyzed GNS and NS cell transcriptomes to identify gene expression alterations underlying the disease phenotype.Sensitive measurements of gene expression were obtained by high-throughput sequencing of transcript tags (Tag-seq) on adherent GNS cell lines from three glioblastoma cases and two normal NS cell lines. Validation by quantitative real-time PCR was performed on 82 differentially expressed genes across a panel of 16 GNS and 6 NS cell lines. The molecular basis and prognostic relevance of expression differences were investigated by genetic characterization of GNS cells and comparison with public data for 867 glioma biopsies.Transcriptome analysis revealed major differences correlated with glioma histological grade, and identified misregulated genes of known significance in glioblastoma as well as novel candidates, including genes associated with other malignancies or glioma-related pathways. This analysis further detected several long non-coding RNAs with expression profiles similar to neighboring genes implicated in cancer. Quantitative PCR validation showed excellent agreement with Tag-seq data (median Pearson r = 0.91) and discerned a gene set robustly distinguishing GNS from NS cells across the 22 lines. These expression alterations include oncogene and tumor suppressor changes not detected by microarray profiling of tumor tissue samples, and facilitated the identification of a GNS expression signature strongly associated with patient survival (P = 1e-6, Cox model).These results support the utility of GNS cell cultures as a model system for studying the molecular processes driving glioblastoma and the use of NS cells as reference controls. The association between a GNS expression signature and survival is consistent with the hypothesis that a cancer stem cell component drives tumor growth. We anticipate that analysis of normal and malignant stem cells will be an important complement to large-scale profiling of primary tumors.
Nasogastric tube feeding is a cause of aspiration pneumonia in ventilated patients
Authors: S. Teramoto, T. Ishii, H. Yamamoto, Y. Yamaguchi, Y. Ouchi
Journal: European Respiratory Journal (2006)

<h3>Abstract</h3> Multi-wavelength analytical ultracentrifugation (MW-AUC) is a recent development made possible by new analytical ultracentrifuge optical systems. MW-AUC is suitable for a wide range of applications and biopolymer systems and is poised to become an essential tool to characterize macromolecular interactions. It adds an orthogonal spectral dimension to the traditional hydrodynamic characterization by exploiting unique chromophores in analyte mixtures that may or may not interact. Here we illustrate the utility of MW-AUC for representative classes of challenging biopolymer systems, including interactions between mixtures of different sized proteins with small molecules, mixtures of loaded and empty viral AAV capsids contaminated with free DNA, and mixtures of different proteins, where some have identical hydrodynamic properties, all of which are difficult to resolve with traditional AUC methods. We explain the improvement in resolution and information content obtained by this technique compared to traditional single- or dual-wavelength approaches. We discuss experimental design considerations and limitations of the method, and address the advantages and disadvantages of the two MW optical systems available today, and the differences in data analysis strategies between the two systems.
ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 Appropriate Use Criteria for Implantable Cardioverter-Defibrillators and Cardiac Resynchronization Therapy
Authors: Andrea M. Russo, Raymond F. Stainback, Steven R. Bailey, Andrew E. Epstein, Paul A. Heidenreich, Mariell Jessup, Suraj Kapa, Mark S. Kremers, Bruce D. Lindsay, Lynne Warner Stevenson, Michael B. Alexander, Ulrika Birgersdotter-Green, Alan S. Brown, Richard A. Grimm, Paul J. Hauptman, Sharon A. Hunt, Rachel Lampert, Joann Lindenfeld, David J. Malenka, Kartik Mani, Joseph E. Marine, Edward T. Martin, Richard L. Page, Michael W. Rich, Paul D. Varosy, Mary Norine Walsh, Michael J. Wolk, John U. Doherty, Pamela S. Douglas, Robert C. Hendel, Christopher M. Kramer, James K. Min, Manesh R. Patel, Leslee Shaw, Joseph M. Allen
Journal: Journal of the American College of Cardiology (2013)
A study of loss of heterozygosity at 70 loci in anaplastic astrocytoma and glioblastoma multiforme with implications for tumor evolution
Authors: Eric C. Wooten, Dan Fults, Ravindrannath Duggirala, Kenneth Williams, Athanassias P. Kyritsis, Melissa L. Bondy, Victor A. Levin, Peter O'Connell
Journal: Neuro-Oncology (1999)

Cancers that arise from astrocytes in the adult CNS present as either anaplastic astrocytomas (AAs) or as more aggressive glioblastomas multiforme (GBMs). GBMs either form de novo or progress from AAs. We proposed to examine the molecular genetic relationship between these CNS tumors by conducting a genome-wide allelic imbalance analysis that included 70 loci on examples of AA and GBM. We found significant loss of heterozygosity (LOH) at 13 discrete chromosomal loci in both AAs and GBMs. Loss was significant in both AAs and GBMs at 9 of these loci. AAs show the highest rates of LOH at chromosomes 1p, 4q, 6p, 9p, 11p, 11q, 13q, 14q, 15p, 17p, 17q, and 19q. GBMs showed the greatest losses at 1p, 6q, 8p, 9p, 10p, 10q, 11p, 13q, 17p, 17q, 18p, 18q, and 19q. GBMs also demonstrated significant amplification at the epidermal growth factor receptor locus (7p12). These data suggest that there are three classes of loci involved in glioma evolution. First are loci that are likely involved in early events in the evolution of both AAs and GBMs. The second class consists of AA-specific loci, typified by higher LOH frequency than observed in GBMs (4q, 6p, 17p, 17q, 19q). The third class consists of GBM-specific loci (6q, 8p, 10, 18q). Damage at these loci may either lead to de novo GBMs or permit existing AAs to progress to GBMs. Glioma-related LOH profiles may have prognostic implications that could lead to better diagnosis and treatment of brain cancer patients.
IMMUNOBIOLOGY AND PATHOGENESIS OF VIRAL HEPATITIS
Authors: Luca G. Guidotti, Francis V. Chisari
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Among the many viruses that are known to infect the human liver, hepatitis B virus (HBV) and hepatitis C virus (HCV) are unique because of their prodigious capacity to cause persistent infection, cirrhosis, and liver cancer. HBV and HCV are noncytopathic viruses and, thus, immunologically mediated events play an important role in the pathogenesis and outcome of these infections. The adaptive immune response mediates virtually all of the liver disease associated with viral hepatitis. However, it is becoming increasingly clear that antigen-nonspecific inflammatory cells exacerbate cytotoxic T lymphocyte (CTL)-induced immunopathology and that platelets enhance the accumulation of CTLs in the liver. Chronic hepatitis is characterized by an inefficient T cell response unable to completely clear HBV or HCV from the liver, which consequently sustains continuous cycles of low-level cell destruction. Over long periods of time, recurrent immune-mediated liver damage contributes to the development of cirrhosis and hepatocellular carcinoma.
Cost-effectiveness of ursodeoxycholic acid therapy in primary biliary cirrhosis
Authors: Tousif Pasha, Jenny Heathcote, Sherine Gabriel, Karen Cauch-Dudek, Roberta Jorgensen, Terry Therneau, Rolland E. Dickson, Keith D. Lindor
Journal: Hepatology (1999)

Ursodeoxycholic acid (UDCA) is a safe and effective treatment for patients with primary biliary cirrhosis (PBC), but the cost of this drug has raised concerns regarding cost–effectiveness. The aim of our study was to determine the cost–effectiveness of UDCA in PBC. We compared the costs and outcomes of managing PBC patients with and without UDCA. From two previously published trials, the effectiveness of UDCA was determined by comparing the annual reduction in the development of ascites, varices, variceal bleeding, encephalopathy, liver transplantation, and death between the treatment groups. Average annual costs for each of these events were estimated based on literature and institutional data. Approximately twice as many major events occurred in the placebo group compared with the UDCA group. The relative risk (RR) of liver transplantation (1.95; 95% CI: 1.14–3.68) and development of esophageal varices (3.11; 95% CI: 1.57–10.65) were significantly higher in the placebo group compared with the UDCA group. There were no significant increases in the RR of ascites, variceal bleeding, encephalopathy, or death between the two groups. Based on the estimated annual cost of managing these events and the annual costs of UDCA ($2,500), there was an annual cost savings per patient of $1,372. Compared with the placebo group, patients receiving UDCA had a lower incidence of major complications and lower medical care costs.
Is Physical Exercise a Core Therapeutical Element for Most Patients With Type 2 Diabetes?
Authors: Pierpaolo De Feo, Peter Schwarz
Journal: Diabetes Care (2013)

Over the last decade, growing scientific evidence has demonstrated that exercise is an effective therapeutic strategy for type 2 diabetes (1–12). According to position statements published by the American Diabetes Association, American College of Sports Medicine, and American Heart Association, exercise therapy should be part of a structured lifestyle intervention and include both aerobic and resistance training (13,14).

Physical activity is defined as any bodily movement produced by skeletal muscles that results in energy expenditure beyond resting expenditure. Exercise is a subset of physical activity that is planned, structured, repetitive, and purposeful in the sense that improvement or maintenance of physical fitness is the objective. As with pharmacological therapy, for aerobic or resistance exercise therapy it is necessary to prescribe the right dose (intensity, volume, and frequency) and to carefully consider the potential side effects and contraindications. The aim of this review is to discuss a correct approach to exercise therapy and to underline the beneficial effects, precautions, and limitations of the use of exercise in type 2 diabetic subjects. Another crucial point that merits discussion is the profound gap between the exercise therapy suggested by scientific guidelines and the applicability of it in the management of type 2 diabetes. Full compliance with an exercise regimen requires high motivation and capability, both in the diabetes team operators/facilitators and in their patients, and is based on a strong therapeutic alliance. There are several obstacles in this virtuous process: lack of time and lack of confidence in the behavioral and motivation strategies of physicians and other diabetic team operators, unhealthy lifestyles of physicians who should advise exercise, and reluctance of sedentary diabetic patients to change their lifestyle, mainly due to poor self-efficacy or lack of time (15). The “no” side of this debate will discuss the evidence …
Effects of Raf Kinase Inhibitor Protein Expression on Suppression of Prostate Cancer Metastasis
Authors: Z. Fu, P. C. Smith, L. Zhang, M. A. Rubin, R. L. Dunn, Z. Yao, E. T. Keller
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), is expressed at lower levels in human C4-2B metastatic prostate cancer cells than in the parental non-metastatic LNCaP prostate cancer cells from which they were derived. We examined whether RKIP functions as a suppressor of metastasis. Methods: Immunohistochemistry was used to detect RKIP expression in clinical samples of primary prostate cancer and prostate cancer metastases. LNCaP and C4-2B cells were stably transfected with plasmids that constitutively expressed antisense and sense RKIP cDNA, respectively, or with empty vector. Assays of cell proliferation, soft-agar colony formation, and in vitro cell invasion were used to examine the malignant phenotypes of the transfected cells. An orthotopic murine model was used to examine the effect of expressing RKIP in C4-2B cells on the development of spontaneous metastasis. Results: Clinical samples of primary prostate cancer had detectable RKIP expression, whereas clinical samples of prostate cancer metastases did not. There were no differences in the in vitro proliferation rate or colony-forming ability between the control vector-transfected and sense RKIP vector-transfected C4-2B cells or between the control vector-transfected and the antisense RKIP vector-transfected LNCaP cells. Overexpression of RKIP in C4-2B cells was associated with decreased in vitro cell invasion, decreased development of lung metastases in vivo, and decreased vascular invasion in the primary tumor but did not affect primary tumor growth in mice. Conclusions: RKIP does not influence the tumorigenic properties of human prostate cancer cells. It appears to be a novel and clinically relevant suppressor of metastasis that may function by decreasing vascular invasion.
Abstract A37: Ectopic claudin 6 and 18.2 expression as potential treatment target in non-small cell lung cancer.
Authors: Johanna SM Mattsson, Patrick Micke, Karolina Edlund, Miriam Lohr, Karin Jirström, Anders Berglund, Johan Botling, Jörg Rahnenfuehrer, Millaray Marincevic, Fredrik Pontén, Simon Ekman, Jan G. Hengstler, Stefan Wöll, Ugur Sahin, Özlem Türeci
Journal: Clinical Cancer Research (2014)

Abstract Claudins are central components of tight junctions that regulate epithelial cell barrier function and polarity. Altered claudin expression patterns have been demonstrated in numerous cancer types and lineage-specific claudins have been proposed as therapy targets. The objective of this study was to assess claudin 6 (CLDN6) and claudin 18 isoform 2 (CLDN18.2) expression in human non-small cell lung cancer (NSCLC). Transcript levels were evaluated based on gene expression microarray data from a fresh-frozen NSCLC tissue cohort (n=196). Protein expression levels of CLDN6 and CLDN18.2 were examined by immunohistochemistry on a tissue microarray (n=355), and analyzed with regard to frequency distribution and association with clinical parameters. High mRNA levels of CLDN6 and total CLDN18 were observed in subsets of non-squamous lung carcinomas. Correspondingly, distinct membranous positivity of CLDN6 (6.5%) and CLDN18.2 (3.7%) was displayed by virtually non-overlapping subgroups of adenocarcinomas and large cell carcinomas, while pneumocytes and bronchial epithelial cells were consistently negative. CLDN18.2 positive tumors were enriched among slowly proliferating, TTF1-negative adenocarcinomas, suggesting that isoform-specific claudin expression may delineate a specific subtype. Noteworthy, high CLDN6 mRNA as well as protein expression was associated with worse prognosis in lung adenocarcinoma. In conclusion, distinct CLDN6 and CLDN18.2 positivity was observed in minor subsets of non-squamous NSCLC, indicating that tumor-specific claudin expression may define molecular subtypes associated with clinical parameters. These findings encourage further clinical exploration of targeting ectopic claudin expression as a valuable treatment concept in NSCLC. Citation Format: Johanna SM Mattsson, Patrick Micke, Karolina Edlund, Miriam Lohr, Karin Jirström, Anders Berglund, Johan Botling, Jörg Rahnenfuehrer, Millaray Marincevic, Fredrik Pontén, Simon Ekman, Jan G. Hengstler, Stefan Wöll, Ugur Sahin, Özlem Türeci. Ectopic claudin 6 and 18.2 expression as potential treatment target in non-small cell lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A37.
Role of Breast Reconstructive Surgery in Physical and Emotional Outcomes Among Breast Cancer Survivors
Authors: J. H. Rowland
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Tissue-sparing approaches to primary treatment and reconstructive options provide improved cosmetic outcomes for women with breast cancer. Earlier research has suggested that conservation or restitution of the breast might mitigate the negative effects of breast cancer on women's sexual well-being. Few studies, however, have compared psychosocial outcomes of women who underwent lumpectomy, mastectomy alone, or mastectomy with reconstruction. To address some of these issues, we examined women's adaptation to surgery in two large cohorts of breast cancer survivors. Methods: A total of 1957 breast cancer survivors (1–5 years after diagnosis) from two major metropolitan areas were assessed in two waves with the use of a self-report questionnaire that included a number of standardized measures of health-related quality of life, body image, and physical and sexual functioning. All P values are two-sided. Results: More than one half (57%) of the women underwent lumpectomy, 26% had mastectomy alone, and 17% had mastectomy with reconstruction. As in earlier studies, women in the mastectomy with reconstruction group were younger than those in the lumpectomy or mastectomy-alone groups (mean ages = 50.3, 55.9, and 58.9, respectively; P = .0001); they were also more likely to have a partner and to be college educated, affluent, and white. Women in both mastectomy groups complained of more physical symptoms related to their surgeries than women in the lumpectomy group. However, the groups did not differ in emotional, social, or role function. Of interest, women in the mastectomy with reconstruction group were most likely to report that breast cancer had had a negative impact on their sex lives (45.4% versus 29.8% for lumpectomy and 41.3% for mastectomy alone; P = .0001). Conclusions: The psychosocial impact of type of primary surgery for breast cancer occurs largely in areas of body image and feelings of attractiveness, with women receiving lumpectomy experiencing the most positive outcome. Beyond the first year after diagnosis, a woman's quality of life is more likely influenced by her age or exposure to adjuvant therapy than by her breast surgery.