tbuckley/cabot-search huggingface dataset:
Persistence of natural killer cells with expansion of a hypofunctional CD56−CD16+KIR+NKG2C+ subset in a patient with atypical Janus kinase 3–deficient severe combined immunodeficiency
Authors: Laure Farnault, Hervé Chambost, Gérard Michel, Isabelle Thuret, Geneviève de Saint Basile, Alain Fischer, Capucine Picard, Christophe Picard, Florence Orlanducci, Catherine Farnarier, Alessandro Moretta, Daniel Olive
Journal: Journal of Allergy and Clinical Immunology (2012)
Multicenter phase II trial of dose-fractionated irinotecan in patients with advanced colorectal cancer failing oxaliplatin-based first-line combination chemotherapy
Authors: H Ulrich-Pur, G V Kornek, W Fiebiger, C Gedlicka, M Raderer, A Lenauer, D Depisch, F Lang, J Pidlich, W Scheithauer
Journal: Annals of Oncology (2001)
Distribution of Black Physicians in the United States, 1967
Authors: M. Alfred Haynes
Journal: JAMA (1969)

Only 2% of all physicians are black. Howard University College of Medicine and Meharry Medical College graduate about 83% of the black physicians. Of the predominantly white schools, the University of Illinois graduated the largest number of black physicians who are members of the National Medical Association. Black physicians are more highly concentrated in California, New York, and Washington, DC, than in other areas. They are less likely to practice in groups and more likely to be general practitioners. Internal medicine claims more specialists than any other specialty, but only 20% of these are board certified. Fifty-five percent of all NMA members are members of the American Medical Association.
Sport and exercise medicine in the undergraduate curriculum. Are we inspiring the next generation of sport and exercise medicine doctors and helping them overcome the barriers they face getting into the specialty?
Authors: Liam Richard West
Journal: British Journal of Sports Medicine (2013)

The BRIC universe, which includes Brazil, Russia, India, and China, represents one of the most promising emerging market equity composites. This study examines the existence of a leverage effect and time-varying risk parameters in relation to the BRIC countries’ stock market returns by employing GARCH, TGARCH-M, and EGARCH-M models. The period of study runs from July 2009 to June 2014 and assesses the existence of a leverage impact of a negative shock on the conditional variance, as compared to a positive shock in each of the BRIC countries. A global investor should discount and understand the volatility behavior as well as the business environment of the investee country as it changes over time. <b>TOPICS:</b>Security analysis and valuation, emerging, statistical methods, performance measurement
Increased Lung Metastasis in Transgenic NM23-Null/SV40 Mice with Hepatocellular Carcinoma
Authors: Mathieu Boissan, Dominique Wendum, Sandrine Arnaud-Dabernat, Annie Munier, Marcel Debray, Ioan Lascu, Jean-Yves Daniel, Marie-Lise Lacombe
Journal: JNCI Journal of the National Cancer Institute (2005)

The metastasis-suppressing role of the NM23 gene in the metastatic spread of solid tumors is still debated. We examined the role of NM23 in tumor development and metastatic dissemination by using transgenic mice that lack mouse NM23 (NM23-M1) in two mouse models of hepatocellular carcinoma (HCC) that recapitulate all steps of tumor progression.We induced HCC in mice that contained (NM23-M1(+/+)) or lacked (NM23-M1(-/-)) NM23-M1 by diethylnitrosamine injection or by a crossing scheme that transferred a transgene that leads to liver expression of simian virus 40 large T antigen (ASV mice). We used microscopic examination and immunohistochemistry to analyze tumor progression. Expression of Nm23 protein isoforms (Nm23-M1 and Nm23-M2) and several tumor markers was analyzed in the primary tumor and in metastases by Western blotting. The statistical significance of differences in the incidence of Nm23-M2 overexpression in null mice relative to that in wild-type mice was tested by a one-sided Fisher's exact test. The statistical significance of differences in the incidence of metastases was examined using one-sided chi-square tests. All other statistical tests were two-sided.In both models, Nm23-M1 and/or Nm23-M2 were overexpressed in the primary liver tumors compared with nontumor liver tissue; however, the lack of the NM23-M1 gene had no effect on primary tumor formation in either model. ASV mice developed pulmonary metastases that were positive for the Hep-Par 1 antibody, which recognizes a specific hepatocyte antigen, whereas the few pulmonary nodules that developed in diethylnitrosamine-injected mice were negative for this antigen. Statistically significantly more ASV/NM23-M1(-/-) mice than ASV/NM23-M1(+/+) mice developed lung metastases (69.2% versus 37.5%; difference = 31.7%, 95% confidence interval = 13.1% to 50.3%; P<.001). In ASV/NM23-M1(+/+) mice, immunohistochemical staining for Nm23-M1 was highly heterogeneous among the primary liver tumors, but weak or negative among lung metastases.The lack of NM23-M1 expression promotes metastasis in the SV40 animal model of liver carcinogenesis.
Overexpression of the Cell Adhesion Molecules DDR1, Claudin 3, and Ep-CAM in Metaplastic Ovarian Epithelium and Ovarian Cancer
Authors: Viola A. Heinzelmann-Schwarz, Margaret Gardiner-Garden, Susan M. Henshall, James Scurry, Richard A. Scolyer, Michael J. Davies, Matthias Heinzelmann, Larry H. Kalish, Anish Bali, James G. Kench, Lyndal S. Edwards, Patricia M. Vanden Bergh, Neville F. Hacker, Robert L. Sutherland, Philippa M. O’Brien
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A better understanding of the molecular pathways underlying the development of epithelial ovarian cancer (EOC) is critical to identify ovarian tumor markers for use in diagnostic or therapeutic applications. The aims of this study were to integrate the results from 14 transcript profiling studies of EOC to identify novel biomarkers and to examine their expression in early and late stages of the disease. Experimental Design: A database incorporating genes identified as being highly up-regulated in each study was constructed. Candidate tumor markers were selected from genes that overlapped between studies and by evidence of surface membrane or secreted expression. The expression patterns of three integral membrane proteins, discoidin domain receptor 1 (DDR1), claudin 3 (CLDN3), and epithelial cell adhesion molecule, all of which are involved in cell adhesion, were evaluated in a cohort of 158 primary EOC using immunohistochemistry. Results: We confirmed that these genes are highly overexpressed in all histological subtypes of EOC compared with normal ovarian surface epithelium, identifying DDR1 and CLDN3 as new biomarkers of EOC. Furthermore, we determined that these genes are also expressed in ovarian epithelial inclusion cysts, a site of metaplastic changes within the normal ovary, in borderline tumors and in low-grade and stage cancer. A trend toward an association between low CLDN3 expression and poor patient outcome was also observed. Conclusions: These results suggest that up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of EOC and have potential application in the early detection of disease.
Favorable Impact of the t(9;11) in Childhood Acute Myeloid Leukemia
Authors: Jeffrey E. Rubnitz, Susana C. Raimondi, Xin Tong, Deo Kumar Srivastava, Bassem I. Razzouk, Sheila A. Shurtleff, James R. Downing, Ching-Hon Pui, Raul C. Ribeiro, Frederick G. Behm
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine the impact of MLL rearrangements on the outcome of children with acute myeloid leukemia (AML). PATIENTS AND METHODS: We analyzed the clinical and biologic features of 298 infants and children with primary AML treated on four consecutive institutional clinical trials. The Kaplan-Meier method was used in survival analysis and the Cox proportional-hazards model was used to analyze the effect of potential prognostic factors on event-free survival (± 1 SE). RESULTS: Molecular studies of 152 cases detected 42 with MLL rearrangements. The karyotypes of these 42 revealed the t(9;11) (15 cases), abnormalities of chromosomes 10 and 11 (nine cases), the t(11;19) (four cases), other abnormalities of 11q23 (seven cases), and miscellaneous rearrangements (seven cases). Among these 42 patients, the 15 whose leukemic cells carried the t(9;11) had a better outcome (66% ± 15%) than the other 27 (25.9% ± 11.2%; P = .004). Cases with the t(9;11) were also characterized by M5 AML morphology (21 of 23 cases). Of the 63 patients with M5 AML, the 21 whose leukemic cells demonstrated the t(9;11) had a better outcome (71.1% ± 11%) than the other 42 (25.8% ± 7.9%; P = .0004). The only independent factors indicating a favorable prognosis were presenting leukocyte count less than 50 × 10 9 /L (relative risk of relapse, 0.73; 95% confidence interval, 0.55 to 0.97; P = .03) and the t(9;11) (relative risk of relapse, 0.32; 95% confidence interval, 0.16 to 0.64; P = .002). CONCLUSION: We conclude that the t(9;11) is the most favorable genetic factor for patients with AML treated at our institution.
Trp64Arg polymorphism in children with obstructive sleep apnea (OSAS) and controls
Authors: Afroditi Sakellaropoulou, Styliani Pappa, Maria Papageorgiou, Katerina Haidopoulou, Maria Emporiadou, Evaggelia Dosiadi, Maria Hatzistilianou
Journal: European Respiratory Journal (2013)

The b3-adrenergic receptor (ADRB3) plays a role in the regulation of metabolism. A point mutation at codon 64 of ADRB3 (Trp64Arg) is associated with obesity phenotypes. Its frequency varies considerably between the populations. Conflicting results have been reported about its role.

Our study aimed to evaluate the clinical and polysomnographic characteristics and the incidence of Trp64Arg polymorphism in a group of children with OSAS and controls.

The study group consisted of 42 children (2.5-14.5 years, 64.3% boys): 33.3% mild, 38.1% moderate and 28.6% severe OSAS. The control group comprised of 77 children with no history of OSA (59.74% girls).

Heterozygous for the polymorphism Trp64Arg were 6 children with OSAS (14.3%) and 3/77 (3.89%) controls. The frequencies of genotypes and alleles of the polymorphism of the Trp64Arg in both groups were in equilibrium (p=1.00, χ2=0.00).

Most of the patients with OSAS, carriers of the polymorphism Trp64Arg, were males (p = 0,049). No differences exist concerning the control group (p>0.05).

Patients with OSAS carrying the mutation compared with other patients with sleep apnea had higher: a) BMI z score (p= 0.215), b) Waist-Hip-Ratio (WHR), (p= 0.429), c) Waist to Hip Ratio (WHtR), (p= 0.228) and d) Conicity index (p= 0.172).

No correlation between the presence of the Trp64Arg polymorphism and the lipid profile was recorded in both groups (p>0.05). The presence of the Trp64Arg polymorphism does not affect the characteristics of the sleep study in patients with sleep apnea (p> 0.05).

The relationship between Trp64Arg polymorphism, sleep apnea and obesity is still unclear. Probably this polymorphism may be a marker for personalized weight loss in obese subjects.
IL-8 Signaling Plays a Critical Role in the Epithelial–Mesenchymal Transition of Human Carcinoma Cells
Authors: Romaine I. Fernando, Marianne D. Castillo, Mary Litzinger, Duane H. Hamilton, Claudia Palena
Journal: Cancer Research (2011)

The switch of tumor cells from an epithelial to a mesenchymal-like phenotype [designated as epithelial-to-mesenchymal transition (EMT)] is known to induce tumor cell motility and invasiveness, therefore promoting metastasis of solid carcinomas. Although multiple studies have focused on elucidating the signaling events that initiate this phenotypic switch, there has been so far no characterization of the pattern of soluble mediators released by tumor cells undergoing EMT, and the potential impact that this phenotypic switch could have on the remodeling of the tumor microenvironment. Here we show that induction of EMT in human carcinoma cells via overexpression of the transcription factor Brachyury is associated with enhanced secretion of multiple cytokines, chemokines, and angiogenic factors and, in particular, with the induction of the IL-8/IL-8R axis. Our results also indicate the essential role of interleukin 8 (IL-8) signaling for the acquisition and/or maintenance of the mesenchymal and invasive features of Brachyury-overexpressing tumor cells and show that IL-8 secreted by tumor cells undergoing EMT could potentiate tumor progression by inducing adjacent epithelial tumor cells into EMT. Altogether, our results emphasize the potential role of EMT in the modulation of the tumor microenvironment via secretion of multiple soluble mediators and suggest that IL-8 signaling blockade may provide a means of targeting mesenchymal-like, invasive tumor cells.
Differential expression profiling analyses identifies downregulation of 1p, 6q, and 14q genes and overexpression of 6p histone cluster 1 genes as markers of recurrence in meningiomas
Authors: Elisa Pérez-Magán, Ángel Rodríguez de Lope, Teresa Ribalta, Yolanda Ruano, Yolanda Campos-Martín, Gerardo Pérez-Bautista, Juan Fernando García, Ainoha García-Claver, Concepción Fiaño, José-Luis Hernández-Moneo, Manuela Mollejo, Bárbara Meléndez
Journal: Neuro-Oncology (2010)

The majority of meningiomas are probably benign but a number of tumors display considerable histological and/ or clinical aggressivity, sometimes with unexpectedly high recurrence rates after radical removal.Understanding the potential behavior of these tumors in individual patients is critical for rational therapeutic decision-making.This study aimed to identify gene expression profiles and candidate markers associated with original and recurrent meningiomas.Unsupervised hierarchical clustering of the samples confirmed 2 main groups of meningiomas with distinct clinical behaviors.The gene expression profiling study identified genes and pathways potentially associated with meningioma recurrence, revealing an overall lower level of gene expression.The differential gene expression profiling analyses of original and recurrent meningiomas identified 425 known genes and expressed sequence tags related to meningioma recurrence, with SFRP1 (8p12), TMEM30B (14q23), and CTGF (6q23) showing the most disparate expression.Most of the differentially expressed genes were located at 1p, 6q, and 14q and were underexpressed in recurrences.Loss of such chromosomal regions has previously been associated with a higher risk of meningioma recurrence or malignant progression.Thus, at these locations, we propose the existence of novel candidate genes that could be involved in meningioma recurrence.In addition, the overexpression of genes of histone cluster 1 (6p) in recurrent meningiomas is reported here for the first time.Finally, the altered genes related to meningioma recurrence are involved in pathways such as Notch, TGFb, and Wnt, as described previously, and in other pathways such as cell cycle, oxidative phosphorylation, PPAR, and PDGF, not related before to meningioma recurrence.
Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1
Authors: Robert Jan Lebbink, Talitha de Ruiter, Jelle Adelmeijer, Arjan B. Brenkman, Joop M. van Helvoort, Manuel Koch, Richard W. Farndale, Ton Lisman, Arnoud Sonnenberg, Peter J. Lenting, Linde Meyaard
Journal: The Journal of Experimental Medicine (2006)

Collagens are the most abundant proteins in the human body, important in maintenance of tissue structure and hemostasis. Here we report that collagens are high affinity ligands for the broadly expressed inhibitory leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). The interaction is dependent on the conserved Gly-Pro-Hyp collagen repeats. Antibody cross-linking of LAIR-1 is known to inhibit immune cell function in vitro. We now show that collagens are functional ligands for LAIR-1 and directly inhibit immune cell activation in vitro. Thus far, all documented ligands for immune inhibitory receptors are membrane molecules, implying a regulatory role in cell-cell interaction. Our data reveal a novel mechanism of peripheral immune regulation by inhibitory immune receptors binding to extracellular matrix collagens.
Lifetime Risk and Sex Difference of Hepatocellular Carcinoma Among Patients With Chronic Hepatitis B and C
Authors: Yen-Tsung Huang, Chin-Lan Jen, Hwai-I Yang, Mei-Hsuan Lee, Jun Su, Sheng-Nan Lu, Uchenna H. Iloeje, Chien-Jen Chen
Journal: Journal of Clinical Oncology (2011)

Purpose Both hepatitis B (HBV) and C viruses (HCV) are causes of hepatocellular carcinoma (HCC), but lifetime risk and sex difference remain unclear. This study aimed to assess the lifetime risk and sex difference of HCC among patients with chronic HBV and/or HCV. Methods A prospective cohort of 23,820 residents of Taiwan age 30 to 65 years were enrolled from 1991 to 1992, with 477 instances of HCC occurring subsequently. Serum samples collected at enrollment were tested for seromarkers and viral load of HBV and HCV. Newly developed HCC was ascertained through computerized data linkage with national cancer registry and death certification systems. Results The cumulative lifetime (age 30 to 75 years) incidences of HCC for men and women positive for both HBV surface antigen (HBsAg) and antibodies against HCV (anti-HCV) were 38.35% and 27.40%; for those positive for HBsAg only, 27.38% and 7.99%; for those positive for anti-HCV only, 23.73% and 16.71%; and for those positive for neither, 1.55% and 1.03%, respectively. There was a significant male predominance in incidence of HCC for chronic HBV carriers but not for chronic carriers of HCV or both. Multivariate adjusted hazard ratio of developing HCC decreased with age in HBsAg-seropositive men but increased with age in anti-HCV–seropositive women. Among dual-infected participants, there was an inverse association between HBV and HCV viral load. Risk of HCC increased significantly with increasing viral load of HBV and HCV. Conclusion There exists a suppressive effect of HCV on HBV viral load. Individual and combined effects of the two viruses on HCC vary with sex and age.
The Impact of Initial Gefitinib or Erlotinib versus Chemotherapy on Central Nervous System Progression in Advanced Non–Small Cell Lung Cancer with <i>EGFR</i> Mutations
Authors: Stephanie Heon, Beow Y. Yeap, Neal I. Lindeman, Victoria A. Joshi, Mohit Butaney, Gregory J. Britt, Daniel B. Costa, Michael S. Rabin, David M. Jackman, Bruce E. Johnson
Journal: Clinical Cancer Research (2012)

This retrospective study was undertaken to investigate the impact of initial gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) versus chemotherapy on the risk of central nervous system (CNS) progression in advanced non-small cell lung cancer (NSCLC) with EGFR mutations.Patients with stage IV or relapsed NSCLC with a sensitizing EGFR mutation initially treated with gefitinib, erlotinib, or chemotherapy were identified. The cumulative risk of CNS progression was calculated using death as a competing risk.One hundred and fifty-five patients were eligible (EGFR-TKI: 101, chemotherapy: 54). Twenty-four patients (24%) in the EGFR-TKI group and 12 patients (22%) in the chemotherapy group had brain metastases at the time of diagnosis of advanced NSCLC (P = 1.000); 32 of the 36 received CNS therapy before initiating systemic treatment. Thirty-three patients (33%) in the EGFR-TKI group and 26 patients (48%) in the chemotherapy group developed CNS progression after a median follow-up of 25 months. The 6-, 12-, and 24-month cumulative risk of CNS progression was 1%, 6%, and 21% in the EGFR-TKI group compared with corresponding rates of 7%, 19%, and 32% in the chemotherapy group (P = 0.026). The HR of CNS progression for upfront EGFR-TKI versus chemotherapy was 0.56 [95% confidence interval (CI), 0.34-0.94].Our data show lower rates of CNS progression in EGFR-mutant advanced NSCLC patients initially treated with an EGFR-TKI compared with upfront chemotherapy. If validated, our results suggest that gefitinib and erlotinib may have a role in the chemoprevention of CNS metastases from NSCLC.
RAP80 Responds to DNA Damage Induced by Both Ionizing Radiation and UV Irradiation and Is Phosphorylated at Ser205
Authors: Jun Yan, Xiao-Ping Yang, Yong-Sik Kim, Anton M. Jetten
Journal: Cancer Research (2008)

Abstract Receptor-associated protein (RAP80), a nuclear protein containing two ubiquitin-interacting motifs (UIM), was recently found to be associated with breast cancer-1 (BRCA1) and to translocate to ionizing radiation–induced foci (IRIF). In this study, we show that the BRCT mutant of BRCA1, R1699W, which is associated with increased risk of breast cancer, is unable to interact with RAP80. Previously, we showed that ataxia-telangiectasia mutated protein kinase (ATM) can phosphorylate RAP80 in vitro at Ser205, but whether this site is a target of ATM in whole cells was not established. To address this question, we generated an anti-RAP80Ser205P antibody that specifically recognizes RAP80 phosphorylated at Ser205. Our data show that RAP80 becomes phosphorylated at Ser205 in cells exposed to ionizing irradiation and that RAP80Ser205P translocates to IRIF. We show that this phosphorylation is mediated by ATM and does not require a functional BRCA1. The phosphorylation occurs within 5 minutes after irradiation, long before the translocation of RAP80 to IRIF. In addition, we show that UV irradiation induces translocation of RAP80 to DNA damage foci that colocalize with γ-H2AX. We further show that this translocation is also dependent on the UIMs of RAP80 and that the UV-induced phosphorylation of RAP80 at Ser205 is mediated by ATM- and RAD3-related kinase, not ATM. These findings suggest that RAP80 has a more general role in different types of DNA damage responses. [Cancer Res 2008;68(11):4269–76]