tbuckley/cabot-search huggingface dataset:
The expression of EPS8 in oral cancer
Authors: Lee-Fah Yap, Max Robinson, Suzy Huntley, Ian Paterson
Journal: Cancer Research (2006)

914   The genetic changes underlying oral carcinogenesis are starting to be elucidated, but there is still limited information on the precise nature of those genes that specifically promote the development and progression of oral squamous cell carcinoma (OSCC). We have used Affymetrix high-density oligonucleotide microarrays to identify those genes which are differentially expressed between human OSCC-derived cell lines (n=8) and normal oral keratinocytes (n=3). One gene, epidermal growth factor receptor pathway substrate, EPS8, was shown to be up-regulated (approximately 5-fold) in the OSCC-derived cell lines relative to normal keratinocytes. EPS8 has been shown previously to enhance EGF-dependent mitogenic signals and to participate in both EGFR signaling through RAC and EGFR trafficking through RAB5. With respect to cancer biology, EPS8 is thought to be oncogenic and to enhance cancer cell motility and invasiveness, possibly via its ability to regulate actin polymerization. The up-regulation of EPS8 was confirmed in the OSCC cell lines by RT-PCR and by Western blotting, and in tissue samples of primary OSCC (5 of 7) by real-time quantitative PCR (RT-QPCR). Further, the expression of EPS8 was examined in a panel of 38 primary OSCCs by immunohistochemistry. EPS8 expression was detected in a one third of the tumors examined (13 of 38) and ranged from weak and focal to strong and diffuse. Normal oral epithelium and epithelium adjacent to the tumor was consistently negative, whereas salivary duct epithelium was always positive. Work is ongoing to examine EPS8 expression in the context of clinico-pathological parameters and to determine the functional significance of elevated EPS8 on tumor cell behavior  in vitro . The results of the present study have shown that EPS8 is expressed in a subset of OSCCs, but is not expressed in normal surface epithelium. These data suggest that EPS8 may function as an oncogene in the pathogenesis of OSCC.
Soluble Vascular Endothelial Growth Factor (sVEGF) and the Risk of Venous Thromboembolism in Patients with Cancer: Results from the Vienna Cancer and Thrombosis Study (CATS)
Authors: Florian Posch, Johannes Thaler, Gerhard-Johann Zlabinger, Oliver Königsbrügge, Silvia Koder, Christoph Zielinski, Ingrid Pabinger, Cihan Ay
Journal: Clinical Cancer Research (2015)

Cancer patients are at an increased risk of venous thromboembolism (VTE). VEGF promotes the growth of highly thrombogenic tumor vessels. Here, we explored the utility of soluble plasma VEGF-A (sVEGF) as a biomarker for the prediction of VTE in patients with cancer.Eight hundred four patients with newly diagnosed cancer or progression after remission were prospectively followed for 2 years until the occurrence of VTE or death [tumor sites: brain (n = 87), breast (n = 137), lung (n = 120), gastrointestinal (n = 143), pancreas (n = 53), prostate (n = 95), kidney (n = 22), myeloma and lymphoma (n = 99), and others (n = 48)]. Primary endpoint was symptomatic or fatal VTE. sVEGF was measured by immunoassay in baseline plasma.Fifty-five patients developed VTE (6.8%) and 364 patients (45.3%) died. Five-hundred and forty-two (68.3%) participants had sVEGF levels above the detection limit of 0.5 pg/mL. The median sVEGF level (25th-75th percentile) was 8.1 pg/mL (0-17.7). The cumulative 2-year incidence of VTE was 10.2% [95% confidence interval (CI), 6.4-14.9] in patients with sVEGF greater than the 75th percentile of the sVEGF distribution (Q3, cutoff: 17.7 pg/mL), and 5.9% (95% CI, 4.2-7.9) in patients with lower levels (P = 0.03). The corresponding 2-year risk of death was 52.8% (95% CI, 46.0-60.0) and 43.9% (95% CI, 40.0-48.0), respectively (P = 0.02). In univariable time-to-VTE regression, elevated sVEGF was associated with VTE [subhazard ratio (SHR) per 10 pg/mL increase, 1.04; 95% CI,1.00-1.09; P = 0.04)]. The association between sVEGF and risk of VTE prevailed after multivariable adjustment for high-risk tumor sites, age, gender, factor VIII, thrombin generation potential, and soluble P-Selectin (adjusted SHR, 1.04; 95% CI, 1.00-1.09, P = 0.05).Elevated sVEGF is associated with an increased risk of VTE in patients with cancer.
BODY BUILD IN INFANTS
Authors: Harry Bakwin, Ruth Morris Bakwin
Journal: Journal of Clinical Investigation (1931)

In these three papers the body build of infants during health and disease is described quantitatively. This is done by comparison of ratios of various external dimensions to the total body length. In the first paper the technique for measuring the external dimensions of the body in infants is described and various sources of error discussed. In the second paper general empirical formulae for the relationship between various external dimensions and total body length in healthy infants are developed. By comparing two groups of infants from different social environments, it is shown that environment may influence body build. In the third paper the results obtained in the second paper for healthy infants are used for comparison with sick infants. Various differences in the body build of infants with acute intestinal intoxication, tetany and eczema are described.
Radioimmunotherapy: recent results and future directions.
Authors: R B Wilder, G L DeNardo, S J DeNardo
Journal: Journal of Clinical Oncology (1996)

PURPOSE To review antibody structure, function, and production; suitable radioisotopes for radioimmunotherapy; challenges facing the field; recent clinical results; toxicity; and future directions. DESIGN The radioimmunotherapy literature was reviewed, with an emphasis on clinical results and future directions. RESULTS The highest complete response rates (overall, approximately 50%) have been achieved in patients with B-cell non-Hodgkin's lymphoma. Challenges that currently face radioimmunotherapy include circulating free antigen, binding of antibodies to nonspecific Fc receptors, insufficient tumor penetration, antigenic heterogeneity and insufficient antigen expression, antigenic modulation, and development of human antimouse antibodies. Possible approaches to these challenges, including high-dose radioimmunotherapy and chemotherapy followed by autologous bone marrow transplantation, the use of radionuclides such as yttrium 90 (90Y) and copper 67 (67Cu), and the development of humanized and bifunctional antibodies, are under investigation. CONCLUSION Although radioimmunotherapy is a relatively new field, substantial progress has been made. Additional research will ultimately resolve many of the challenges that currently face radioimmunotherapy and hopefully lead to the cure of some currently incurable malignancies.
The importance of pulmonary mineralogic analysis (PMA) in interstitial lung disease (ILD). A retrospective study of 226 samples from 2005 to 2011
Authors: Cécile Chemarin, Mikael Catinon, Brice Daverton, Anne Sophie Blanchet, Sylvie Blas Vuillemoz, Marie José Labalme, Eric Laennec, Cathrine Pouchelle, Michel Vincent
Journal: European Respiratory Journal (2013)

Rational  : PMA conducted on pulmonary biopsy (PB) and bronchioloalveolaire lavage (BAL) provide information about asbestosis bodies (AB) overload. Moreover, the development of a method of numerical image analysis in optical microscopy (Abramoff MD. Image processing with Image J. J Biophotonics Intern 2004;11:36-42) sometimes coupled with electronic microscopy (EM) facilitates the study of non fibrous particules (NFP).   Objective : Primary: collect positive cases for AB analysis among 226 samples addressed for ILD and, through a questionnaire sent to pulmonologists, determine final diagnosis, occupational disease recognition and/or indemnisation by French fund asbestos victims (FFAV). Secondary: evaluate NFP analysis contribution.   Results : between 2005 and 2011: 4/32 PB (12,5%) and 39/194 (20%) tested positive for AB level. 12 were admitted as occupational disease related to asbestos and 8 were compensated by FFAV. Concerning NFP analysis, the geometric mean in the BAL of 12 pneumoconiosis patients is 88.10 3 /ml BAL, and in 6 patients in whom the cause of ILD was identified as being unrelated to dust exposure, the geometric mean was 13.10 3 /ml without significant difference (Mann and Whitney test: p=0,061). Transmission electron microscope analysis of a sarcoidosis case revealed an aluminium overload.   Discussion : PMA with NFP quantification by numerical image analysis may be a novel method useful for detecting abnormal mineral overload associated with AB analysis. It may allow the reclassification, after further inquiry, of certain ILD as pneumoconiosis. Prospective studies are envisaged.
A cluster of person-to-person transmission cases caused by SFTS virus in Penglai, China
Authors: X.L. Jiang, S. Zhang, M. Jiang, Z.Q. Bi, M.F. Liang, S.J. Ding, S.W. Wang, J.Y. Liu, S.Q. Zhou, X.M. Zhang, D.X. Li, A.Q. Xu
Journal: Clinical Microbiology and Infection (2014)
Antigen Fluctuation and Virus Activation in EL 4 Cells Transplanted in Hybrid Mice or Cultured In Vitro 2
Authors: Maria I. Colnaghi, Marco A. Pierotti, Gabriella Della Torre, Silvia Miotti
Journal: JNCI Journal of the National Cancer Institute (1977)

Because normal C3Hf (C3) mouse serum was previously demonstrated to contain natural antilymphoma antibodies (NAA's) that reacted with EL 4 lymphoma cells grown in syngeneic C57BL/6J (B6) mice found devoid of NAA's, we investigated the in vivo interaction between NAA's and their cell membrane receptors by transferring the EL 4 lymphoma in the NAA-positive (B6 × C3)F1 or NAA-negative (B6 × BALB/c)F1 offspring. The amount of NAA receptors, studied by direct cytotoxicity assay, absorption, and immunoelectronmicroscopy, was found to decrease when the lymphoma was grown in the NAA-positive but not in the NAA-negative hybrids. A simultaneous decrease in H-2 antigens and an active production of C-type virus particles were observed. The phenomena were reversible: When the EL 4 cells were retransferred in the parental NAA-negative B6 strain, the expression of both NAA receptors and histocompatibility antigens was fully recovered and the virus production dropped to the original low level. EL 4 cells cultured in vitro showed a similar decrease in expression of NAA receptors and H-2 antigens and a concomitant increase in C-type virus production. The increased virus production, which took place in either immune responsive hybrids or in vitro-cultured cells, was thought to be responsible for the observed antigenic variations.
Evidence for a genetical contribution to non-smoking-related lung cancer
Authors: Shamus R Carr, Wallace Akerley, Mia Hashibe, Lisa A Cannon-Albright
Journal: Thorax (2015)

The majority of lung cancers are smoking-related, with environmental and genetical factors contributing. The interplay between environmental and genetical contributions in non-smoking-related lung cancers is less clear.We analysed a population-based computerised genealogy resource linked to a state-wide cancer registry of lung cancer cases (n=5544) for evidence of a genetical contribution to lung cancer predisposition in smoking (n=1747) and non-smoking cases (n=784). Statistical methods were used to test for significant excess relatedness of cases and estimate relative risk (RR) in close and distant relatives of lung cancer cases.Significant excess relatedness was observed for all lung cancer cases (p<0.001) and for the subsets of smoking-related (p<0.001) and non-smoking-related (p<0.001) cases when all pairwise relationships were considered. Only the non-smoking-related subset of cases showed significant excess relatedness when close relationships were ignored (p=0.020). First-degree, second-degree, and fourth-degree relatives of non-smoking-related lung cancer cases had significantly elevated RR. An even higher elevated RR was observed for first-degree, second-degree, third-degree and fourth-degree relatives of smoking-related lung cancer cases.Non-smoking-related lung cancer cases show significant excess relatedness for close and distant relationships, providing strong evidence for a genetical contribution as well as an environmental contribution. Significant excess relatedness for only close family relationships in all lung cancer cases and in only smoking-related lung cancer cases implies environmental contribution. Additionally, the highest RR for lung cancer was observed in the relatives of smoking-related lung cancer, suggesting predisposition gene carriers who smoke are at highest risk for lung cancer. Screening and gene identification should focus on high-risk pedigrees.
Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location
Authors: Farzana A. Faisal, Debasish Sundi, Jeffrey J. Tosoian, Voleak Choeurng, Mohammed Alshalalfa, Ashley E. Ross, Eric Klein, Robert Den, Adam Dicker, Nicholas Erho, Elai Davicioni, Tamara L. Lotan, Edward M. Schaeffer
Journal: European Urology (2015)
Novel Programs and Discoveries Aim to Combat Antibiotic Resistance
Authors: Tracy Hampton
Journal: JAMA (2015)

Withincreasing concerns over the continued development of bacterial resistance to antibiotic drugs, researchers and public health officials are conductingandsupportingnew initiatives to develop novel antibiotics and to discover the mechanisms involved with resistance in bacteria that cause urinary tract infections, pneumonia, bloodstream infections, and others. The need for these efforts will only continue to grow: antibiotic-resistant organisms are associated with approximately 23 000 deaths and 2 million infections in theUnited States each year (http://1 .usa.gov/1nDmtkJ). What’s more, an estimated 700 000 deaths per year worldwide are attributable to antimicrobial resistance (AMR), and experts estimate that 10 million people will die worldwide each year by 2050 due to increasing AMR, with some of the highest potential burdens in Asia and Africa (http://bit.ly/1yCt7re). Drug discovery efforts are not keeping pace; between 1983 and 1987, 16 new systemic antibacterial agents were approved by the US Food and Drug Administration (FDA), but this number has been decreasing steadily ever since, with only 2 new agents having been approved between 2008 and 2012 (Boucher HW et al. Clin Infect Dis. 2013;56[12]:1685-1694). The perception that the commercial potential of antibiotics is much lower than that of drugs used to treat conditions such as cancer, heart disease, or mental illness has historically stalled investments and advances in novel antibiotic development (Hwang TJ et al. Sci Transl Med. 2015; 7[276]:276fs9). However, the annual effect of antibiotic-resistant infections on the US economymay be as high as $20 billion in excess direct health care costs and as much as $35 billion in lost productivity fromhospitalizations and sick days (http://1 .usa.gov/1nDmtkJ). “Much of the true innovation in antibiotic development right now is based in academic medical centers and small pharmaceutical and biotech companies,” said Aaron Kesselheim, MD, JD, MPH, an associate professor of medicine at Harvard Medical School and the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital, in Boston. “We need to support this work with greater public investment and other tailored incentives that focus on antibiotics of high clinical need, but we also need systems in place to ensure rational use of the products once approved, or else we’ll never break the cycle we’re in now.”
Effects of Metformin on Metabolite Profiles and LDL Cholesterol in Patients With Type 2 Diabetes
Authors: Tao Xu, Stefan Brandmaier, Ana C. Messias, Christian Herder, Harmen H.M. Draisma, Ayse Demirkan, Zhonghao Yu, Janina S. Ried, Toomas Haller, Margit Heier, Monica Campillos, Gisela Fobo, Renee Stark, Christina Holzapfel, Jonathan Adam, Shen Chi, Markus Rotter, Tommaso Panni, Anne S. Quante, Ying He, Cornelia Prehn, Werner Roemisch-Margl, Gabi Kastenmüller, Gonneke Willemsen, René Pool, Katarina Kasa, Ko Willems van Dijk, Thomas Hankemeier, Christa Meisinger, Barbara Thorand, Andreas Ruepp, Martin Hrabé de Angelis, Yixue Li, H.-Erich Wichmann, Bernd Stratmann, Konstantin Strauch, Andres Metspalu, Christian Gieger, Karsten Suhre, Jerzy Adamski, Thomas Illig, Wolfgang Rathmann, Michael Roden, Annette Peters, Cornelia M. van Duijn, Dorret I. Boomsma, Thomas Meitinger, Rui Wang-Sattler
Journal: Diabetes Care (2015)

OBJECTIVE Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. RESEARCH DESIGN AND METHODS We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. RESULTS We found significantly lower (P &amp;lt; 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years’ follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. CONCLUSIONS Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease.
Validation of the surveillance system for new cases of tuberculosis in a province of northern Italy. Varese Tuberculosis Study Group
Authors: GB Migliori, A Spanevello, L Ballardini, M Neri, C Gambarini, ML Moro, L Trnka, MC Raviglione
Journal: European Respiratory Journal (1995)

In Italy tuberculosis (TB) surveillance is hampered by several problems (inconsistency of data and underreporting). A tuberculosis surveillance system was established in Varese Province (VSS) in 1992. The aim of the present study was, using VSS, to estimate: 1) coverage and validity of data collected by the national Compulsory Surveillance System (CSS); 2) validity of diagnosis and risk factors for tuberculosis; 3) tuberculosis incidence. A specifically designed form, including the same items as the CSS form and 10 more questions on risk factors and diagnostic issue, was completed in all the existing health facilities in the province for each new tuberculosis case diagnosed, collected by the study co-ordinator during monthly supervision after a review of clinical records, and stored in a database at the co-ordinating centre. Routine notifications collected at national level by CSS for the province were nominally linked with VSS data. To evaluate coverage and data validity, a comparison was made between VSS and CSS data after removal of duplicates. Quality of data, risk factors and incidence were evaluated on VSS data (gold standard). CSS coverage was 63% with a significant underreporting of extrapulmonary cases. Within CSS, 20% of data were missing (particularly diagnostic information: 42-72%). According to VSS, smear was performed on 88% of cases and culture on 66%. Half of the cases had no risk factors. The overall incidence of tuberculosis in Varese Province was 15 per 100,000. We estimated the coverage and validity of the data collected by CSS, validity of diagnosis, risk factors for and incidence of tuberculosis and proposed several suggestions to improve CSS nationwide.
Hypersensitivity to larvae of chironomids (non‐biting midges).
Authors: N. E. Eriksson, B. Ryden, P. Jonsson
Journal: Allergy (1989)

In 2,368 consecutive adult patients with asthma and/or rhinitis the incidence of positive skin prick test (SPT) with a chironomid extract (CHIR) (produced from “red feather mosquito larvae” used as fish food) was 14% (26% in atopics and 4% in non‐atopics). RAST with chironomid was positive in 4% of 110 consecutive sera (8% in atopic sera). Significant correlations were found between RAST and SPT results with chironomid and between SPT results with CHIR and with various crustaceans. Correlations were also found reciprocally among SPT results with different crustaceans and between some crustaceans and moluscs (clam and oyster) as well as among RAST results with chironomid, shrimp and crab. Inhibition experiments showed that chironomid extracts inhibited RAST with shrimp, and vice versa. It is concluded that Chironomidae might be allergens of clinical importance in asthma and rhinitis in Sweden, that cross‐allergy exists between chironomids and shrimp and that cross‐allergy also might occur among chironomids, crustaceans and molluscs.