tbuckley/cabot-search huggingface dataset:
TCF7L2 Polymorphism Associates with New-Onset Diabetes after Transplantation
Authors: Lidia Ghisdal, Christophe Baron, Yannick Le Meur, Arnaud Lionet, Jean-Michel Halimi, Jean-Philippe Rerolle, François Glowacki, Yvon Lebranchu, Mireille Drouet, Christian Noël, Hakim El Housni, Pascale Cochaux, Karl Martin Wissing, Daniel Abramowicz, Marc Abramowicz
Journal: Journal of the American Society of Nephrology (2009)

New-onset diabetes after transplantation (NODAT) is a serious and frequent complication in transplant recipients. Whether NODAT shares the same susceptibility genes as type 2 diabetes is unknown. In this multicenter study, we genotyped 1076 white patients without diabetes at transplantation for 11 polymorphisms that associate with type 2 diabetes. We defined NODAT as a fasting plasma glucose ≥126 mg/dl on at least two occasions or de novo hypoglycemic therapy. We compared clinical and genetic factors between patients who developed NODAT within 6 mo of transplantation (n = 118; incidence 11%) and patients without diabetes (n = 958). In multivariate analysis, NODAT significantly associated with the following characteristics: TCF7L2 polymorphism (odds ratio [OR] 1.60 per each T allele; P = 0.002), age (OR 1.03 per year; P < 0.001), body mass index at transplantation (OR 1.09 per unit; P < 0.001), tacrolimus use (OR 2.26; P < 0.001), and the occurrence of a corticoid-treated acute rejection episode (OR 2.78; P < 0.001). In summary, our data show that the TCF7L2 rs7903146 polymorphism, a known risk factor for type 2 diabetes in the general population, also associates with NODAT.
Dendritic Cell Vaccination in Medullary Thyroid Carcinoma
Authors: Anton Stift, Monika Sachet, Rubina Yagubian, Clemens Bittermann, Peter Dubsky, Christine Brostjan, Roswitha Pfragner, Bruno Niederle, Raimund Jakesz, Michael Gnant, Josef Friedl
Journal: Clinical Cancer Research (2004)

Prognosis and treatment effectiveness for medullary thyroid carcinoma (MTC) are strictly related to tumor stage. Palliative treatment options show no significant benefit. A promising treatment approach for human cancer is based on the vaccination of autologous dendritic cells (DCs).The objective of this study was to evaluate the effectiveness of DC vaccines in MTC patients. Therefore, we generated autologous tumor lysate-pulsed DCs from 10 patients suffering from advanced MTC for repeated vaccination. Mature DCs were derived from peripheral blood monocytes by using CD14 magnetic bead selection and subsequent culture in the presence of granulocyte macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor alpha with or without addition of IFN-gamma. DCs were loaded with tumor lysate and further injected into a groin lymph node. Toxicity, tumor marker profile, immune response, and clinical response were determined.Vaccination was well tolerated and induced a positive immunological response in all of the tested patients as evaluated by in vivo delayed-type hypersensitivity reactivity or in vitro intracytoplasmic IFN-gamma detection assay. Three patients had a partial response, 1 patient presented a minor response, and 2 patients showed stable disease. The remaining 4 patients had progressive disease.These data provide strong evidence that vaccination with tumor-lysate pulsed DCs results in the induction of a specific immune response in patients suffering from MTC. Objective clinical responses could be observed even for far-advanced disease. Therefore, we suggest that MTC is particularly suited for DC-based immunotherapy.
Tobacco Smoke Induces Polycomb-Mediated Repression of Dickkopf-1 in Lung Cancer Cells
Authors: Mustafa Hussain, Mahadev Rao, Ashley E. Humphries, Julie A. Hong, Fang Liu, Maocheng Yang, Diana Caragacianu, David S. Schrump
Journal: Cancer Research (2009)

Limited information is available about epigenetic mechanisms by which cigarette smoke enhances the initiation and progression of lung cancer. To examine this issue, A549 and Calu-6 lung cancer cells were cultured in normal media with or without tobacco smoke condensate (TSC) under clinically relevant exposure conditions. Ten-day TSC exposure dramatically increased the tumorigenicity of lung cancer cells in nude mice. Microarray and quantitative reverse transcription-PCR (RT-PCR) experiments revealed that this phenomenon coincided with diminished expression of Dickkopf-1 (Dkk-1). Western blot, chromatin immunoprecipitation, methylation-specific PCR, and pyrosequencing experiments showed that repression of Dkk-1 coincided with decreased H4K16Ac, increased H3K27me3, and recruitment of SirT1, EZH2, SUZ12, and Bmi1 without DNA hypermethylation within the Dkk-1 promoter despite prolonged TSC exposures. Removal of TSC from culture media resulted in loss of promoter-associated polycomb repressor complexes and reexpression of Dkk-1. siRNA-mediated knockdown of EZH2 and SirT1 partially abrogated TSC-mediated inhibition of Dkk-1 expression. Western blot and quantitative RT-PCR array experiments showed that TSC exposure as well as knockdown of Dkk-1 activated Wnt signaling and significantly up-regulated Wnt5a in lung cancer cells. Knockdown of Dkk-1 recapitulated the dramatic protumorigenic effects of TSC exposure in Calu-6 cells. Despite the transient nature of Dkk-1 repression following TSC exposure in vitro, Dkk-1 remained silenced in tumor xenografts derived from TSC-treated Calu-6 cells. Collectively, these data provide evidence that cigarette smoke directly engages polycomb machinery to activate a signaling network implicated in maintenance of cancer stem cells.
Early prediction of response in patients with relapsed or refractory Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) treated with imatinib
Authors: Barbara Wassmann, Heike Pfeifer, Urban J. Scheuring, Anja Binckebanck, Nicola Gökbuget, Johannes Atta, Patrick Brück, Harald Rieder, Claudia Schoch, Lothar Leimer, Rainer Schwerdtfeger, Gerhard Ehninger, Thomas Lipp, Jolanta Perz, Matthias Stelljes, Harald Gschaidmeier, Dieter Hoelzer, Oliver G. Ottmann
Journal: Blood (2003)
Can brain MRI explain cognitive decline in COPD? A pilot study
Authors: Rebecca A. Charlton, James W. Dodd, Martin van den Broek, Franklyn A. Howe, Thomas R. Barrick, Paul W. Jones
Journal: European Respiratory Journal (2011)

Background: Cognitive deficits have been described in patients with COPD. We used MRI to investigate brain structure in COPD patients with and without evidence of cognitive decline and in healthy controls.

Methods: Participants (n=27) completed a full cognitive assessment and MRI scan. Two groups of COPD patients were selected; those who demonstrated evidence of cognitive decline (COPD-D; n=9) or who did not (COPD-ND; n=9). Age-matched healthy controls (HC; n=9) were studied. Volumes of grey matter (GMV), white matter (WMV), and white matter lesions (LV), were calculated. The presence of lesions in the brain stem (BSL) and external capsule (ECL) was noted.

Results: Groups did not differ on measures of GMV or WMV. LV was significantly greater in patients versus controls (t=-3.47, p=0.002); there was no difference between LV in COPD-ND and COPD-D (t=.342, p=.737). No significant group difference in the presence of BSL was observed (X2(df2)=3.0, p=0.223), but ECL was numerically more frequent in the COPD-D group (X2(df2)=5.64, p=0.060). See Table 1.

View this table:

Table 1. Demographics & MRI data





Conclusion: COPD-D and COPD-ND patients both have more white matter lesions than HC, possibly due to increased vascular risk. The significance of BSL and ECL requires further exploration. Future analysis will use methods that detect change in tissue microstructure, and associations between brain damage and cognition.
T cell abnormalities in NZB mice occur independently of autoantibody production.
Authors: J D Taurog, E S Raveche, P A Smathers, L H Glimcher, D P Huston, C T Hansen, A D Steinberg
Journal: The Journal of Experimental Medicine (1981)

By means of a series of crosses and backcrosses, ZB.CBA/N mice were prepared bearing largely NZB autosomal genes, but having X chromosomes derived only from CBA/N mice. The CBA/N X chromosome carries a gene, xid, that is associated with the lack of a B cell subset necessary for most of the spontaneous autoantibody production by NZB mice. These ZB.CBA/N mice failed to develop autoantibodies to T cells, erythrocytes, or DNA. The availability of mice that were mostly NZB, but which failed to make autoantibodies, especially anti-T cell antibodies, allowed us to study possible T cell regulatory defects in NZB mice in the absence of either antibodies reactive with such T cells or other autoantibodies. We found that such mice had derangements of T cell regulation as did the NZB mice. These observations strongly suggest that the t cell abnormalities of NZB mice are not caused by the B cell hyperactivity of these mice, but rather represent independent defects. Thus, NZB mice appear to have primary defects in both the B cell population and the T cell population. Whether or not these are separate, or derive from a common precursor cell abnormality, remains to be determined.
Late Cardiac Effects of Cancer Treatment
Authors: Daniel J. Lenihan, Daniela M. Cardinale
Journal: Journal of Clinical Oncology (2012)

Cardiac toxicities from cancer therapy can become evident many years after treatment, and these late cardiac effects can have a profound impact on cancer survivors. There are a myriad of potential cardiovascular complications from cancer therapy, but these can be grouped into three main categories. First, vascular conditions including atherosclerosis, thrombosis, and hypertension predominate. Second, cardiac structural problems, especially valvular degeneration, can have a dramatic impact long term. Lastly, and most importantly, cardiac dysfunction and heart failure are potentially common late cardiac effects and can certainly be prevented or detected early during active cancer therapy to result in optimal outcomes. Future research on late cardiac effects in cancer survivors needs to include advanced cardiac imaging techniques, novel cardiac biomarkers, and genetic determinants of response to cancer treatment.
Six1 Overexpression in Ovarian Carcinoma Causes Resistance to TRAIL-Mediated Apoptosis and Is Associated with Poor Survival
Authors: Kian Behbakht, Lubna Qamar, Carrie S. Aldridge, Ricardo D. Coletta, Susan A. Davidson, Andrew Thorburn, Heide L. Ford
Journal: Cancer Research (2007)

Abstract Tumorigenesis can arise from inappropriate activation of developmental genes in mature tissues. Here, we show that the developmental regulator Six1 is overexpressed in ovarian carcinoma cell lines (OCC) compared with normal ovarian surface epithelium. As observed in other cancers, Six1 overexpression in OCC leads to increased A-type cyclin expression and increased proliferation. In addition, Six1 overexpression renders OCC resistant to tumor necrosis factor–related apoptosis inducing ligand (TRAIL)–mediated apoptosis, and Six1 knockdown in the TRAIL-resistant SKOV3 ovarian carcinoma line dramatically sensitizes the cells to TRAIL. Because inactivation of the TRAIL response has been linked to metastasis, and because antibodies and recombinant ligand that activate the TRAIL pathway are currently in clinical trials against ovarian carcinoma, we screened normal ovarian and carcinoma specimens for Six1 mRNA. Six1 was overexpressed in 50% of the early-stage (stage I) and 63% of the late-stage (stages II, III, and IV) ovarian carcinomas examined, with late-stage carcinomas expressing ∼3-fold higher Six1 mRNA levels on average compared with early-stage tumors. Importantly, in patients with late-stage disease, high Six1 expression was associated with significantly shortened survival (P = 0.0015). These data suggest that Six1 may contribute to ovarian epithelial carcinogenesis by simultaneously increasing proliferation and decreasing TRAIL-mediated apoptosis and imply that Six1 may be an important determinant of TRAIL therapy response that should be considered in patient selection for TRAIL-related clinical trials. [Cancer Res 2007;67(7):3036–42]
NSAIDs Inhibit Tumorigenesis, but How?
Authors: Evrim Gurpinar, William E. Grizzle, Gary A. Piazza
Journal: Clinical Cancer Research (2013)

Numerous epidemiologic studies have reported that the long-term use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with a significant decrease in cancer incidence and delayed progression of malignant disease. The use of NSAIDs has also been linked with reduced risk from cancer-related mortality and distant metastasis. Certain prescription-strength NSAIDs, such as sulindac, have been shown to cause regression of precancerous lesions. Unfortunately, the extended use of NSAIDs for chemoprevention results in potentially fatal side effects related to their COX-inhibitory activity and suppression of prostaglandin synthesis. Although the basis for the tumor growth-inhibitory activity of NSAIDs likely involves multiple effects on tumor cells and their microenvironment, numerous investigators have concluded that the underlying mechanism is not completely explained by COX inhibition. It may therefore be possible to develop safer and more efficacious drugs by targeting such COX-independent mechanisms. NSAID derivatives or metabolites that lack COX-inhibitory activity, but retain or have improved anticancer activity, support this possibility. Experimental studies suggest that apoptosis induction and suppression of β-catenin-dependent transcription are important aspects of their antineoplastic activity. Studies show that the latter involves phosphodiesterase inhibition and the elevation of intracellular cyclic GMP levels. Here, we review the evidence for COX-independent mechanisms and discuss progress toward identifying alternative targets and developing NSAID derivatives that lack COX-inhibitory activity but have improved antineoplastic properties.
Oncogenes, Normal Cell Growth, and Connective Tissue Disease
Authors: W L Sibbitt
Journal: Annual Review of Medicine (1988)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
G-protein Inactivator RGS6 Mediates Myocardial Cell Apoptosis and Cardiomyopathy Caused By Doxorubicin
Authors: Jianqi Yang, Biswanath Maity, Jie Huang, Zhan Gao, Adele Stewart, Robert M. Weiss, Mark E. Anderson, Rory A. Fisher
Journal: Cancer Research (2013)

Clinical use of the widely used chemotherapeutic agent doxorubicin is limited by life-threatening cardiotoxicity. The mechanisms underlying doxorubicin-induced cardiomyopathy and heart failure remain unclear but are thought to involve p53-mediated myocardial cell apoptosis. The tripartite G-protein inactivating protein RGS6 has been implicated in reactive oxygen species (ROS) generation, ATM/p53 activation, and apoptosis in doxorubicin-treated cells. Thus, we hypothesized that RGS6, the expression of which is enriched in cardiac tissue, might also be responsible for the pathologic effects of doxorubicin treatment in heart. In this study, we show that RGS6 expression is induced strongly by doxorubicin in the ventricles of mice and isolated ventricular myocytes via a posttranscriptional mechanism. While doxorubicin-treated wild-type (WT) mice manifested severe left ventricular dysfunction, loss of heart and body mass, along with decreased survival 5 days after doxorubicin administration, mice lacking RGS6 were completely protected against these pathogenic responses. Activation of ATM/p53 apoptosis signaling by doxorubicin in ventricles of WT mice was also absent in their RGS6(-/-) counterparts. Doxorubicin-induced ROS generation was dramatically impaired in both the ventricles and ventricular myocytes isolated from RGS6(-/-) mice, and the apoptotic response to doxorubicin in ventricular myocytes required RGS6-dependent ROS production. These results identify RGS6 as an essential mediator of the pathogenic responses to doxorubicin in heart, and they argue that RGS6 inhibition offers a rational means to circumvent doxorubicin cardiotoxicity in human patients with cancer.
Macrophage Migration Inhibitory Factor Limits Activation-Induced Apoptosis of Platelets via CXCR7-Dependent Akt Signaling
Authors: Madhumita Chatterjee, Oliver Borst, Britta Walker, Anna Fotinos, Sebastian Vogel, Peter Seizer, Andreas Mack, Setareh Alampour-Rajabi, Dominik Rath, Tobias Geisler, Florian Lang, Harald F. Langer, Jürgen Bernhagen, Meinrad Gawaz
Journal: Circulation Research (2014)

Rationale: Macrophage migration inhibitory factor (MIF) is released on platelet activation. Circulating MIF could potentially regulate platelets and thereby platelet-mediated inflammatory and regenerative mechanisms. However, the effect of MIF on platelets is unknown. Objective: The present study evaluated MIF in regulating platelet survival and thrombotic potential. Methods and Results: MIF interacted with CXCR4-CXCR7 on platelets, defining CXCR7 as a hitherto unrecognized receptor for MIF on platelets. MIF internalized CXCR4, but unlike CXCL12 (SDF-1α), it did not phosphorylate Erk1/2 after CXCR4 ligation because of the lack of CD74 and failed in subsequent CXCR7 externalization. MIF did not alter the activation status of platelets. However, MIF rescued platelets from activation and BH3 mimetic ABT-737–induced apoptosis in vitro via CXCR7 and enhanced circulating platelet survival when administered in vivo. The antiapoptotic effect of MIF was absent in Cxcr7 −/− murine embryonic cells but pronounced in CXCR7-transfected Madin–Darby canine kidney cells. This prosurvival effect was attributed to the MIF–CXCR7–initiated PI3K-Akt pathway. MIF induced CXCR7-Akt–dependent phosphorylation of BCL-2 antagonist of cell death (BAD) both in vitro and in vivo. Consequentially, MIF failed to rescue Akt −/− platelets from thrombin-induced apoptosis when challenged ex vivo, also in prolonging platelet survival and in inducing BAD phosphorylation among Akt −/− mice in vivo. MIF reduced thrombus formation under arterial flow conditions in vitro and retarded thrombotic occlusion after FeCl 3 -induced arterial injury in vivo, an effect mediated through CXCR7. Conclusion: MIF interaction with CXCR7 modulates platelet survival and thrombotic potential both in vitro and in vivo and thus could regulate thrombosis and inflammation.
THE TREATMENT OF INTRA-NASAL LUPUS BY SODIUM IODIDE AND PEROXIDE OF HYDROGEN (PFANNENSTIEL'S METHOD)
Authors: J. H. SEQUEIRA
Journal: British Journal of Dermatology (1911)

Journal Article THE TREATMENT OF INTRA‐NASAL LUPUS BY SODIUM IODIDE AND PEROXIDE OF HYDROGEN (PFANNENSTIEL'S METHOD) Get access J. H. SEQUEIRA, M.D., F.R.C.P., F.R.C.S. J. H. SEQUEIRA, M.D., F.R.C.P., F.R.C.S. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 23, Issue 10, 1 October 1911, Pages 327–329, https://doi.org/10.1111/j.1365-2133.1911.tb16660.x Published: 01 October 1911
Reduced PDEF Expression Increases Invasion and Expression of Mesenchymal Genes in Prostate Cancer Cells
Authors: Xuesong Gu, Luiz F. Zerbini, Hasan H. Otu, Manoj Bhasin, Quanli Yang, Marie G. Joseph, Franck Grall, Tomi Onatunde, Ricardo G. Correa, Towia A. Libermann
Journal: Cancer Research (2007)

The epithelium-specific Ets transcription factor, PDEF, plays a role in prostate and breast cancer, although its precise function has not been established. In prostate cancer, PDEF is involved in regulating prostate-specific antigen expression via interaction with the androgen receptor and NKX3.1, and down-regulation of PDEF by antiproliferative agents has been associated with reduced PDEF expression. We now report that reduced expression of PDEF leads to a morphologic change, increased migration and invasiveness in prostate cancer cells, reminiscent of transforming growth factor beta (TGFbeta) function and epithelial-to-mesenchymal transition. Indeed, inhibition of PDEF expression triggers a transcriptional program of genes involved in the TGFbeta pathway, migration, invasion, adhesion, and epithelial dedifferentiation. Our results establish PDEF as a critical regulator of genes involved in cell motility, invasion, and adhesion of prostate cancer cells.
Diagnosis and Treatment of Obsessive Compulsive Disorder
Authors: Joseph De Veaugh-Geiss
Journal: Annual Review of Medicine (1993)

Obsessive compulsive disorder (OCD) is a common anxiety disorder that appears to be due to a disturbance in central serotonergic functioning. Drugs, such as clomipramine, that inhibit neuronal reuptake of serotonin are effective in treating OCD. Behavioral therapy techniques are also effective.
MENINGITIS IN MAN CAUSED BY A FILTERABLE VIRUS
Authors: Thomas M. Rivers, T. F. McNair Scott
Journal: The Journal of Experimental Medicine (1936)

Evidence was presented substantiating the idea that our active agent is a virus. The reactions produced in laboratory animals by the active agent were described, and a comparison of it with other viruses was made. The results of experiments indicating the immunological identity of our virus, Armstrong and Lillie's virus of lymphocytic choriomeningitis, and Traub's virus were given in detail. Finally, the evidence in regard to its natural host and its importance as a factor in diseases of human beings was presented and discussed.
Should Previous Responses Be Shown to Study Objects; A Comparison of Informed versus Blind Administration of the Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF)
Authors: J. van der Velde, B. Flokstra-de Blok, B. Vlieg-Boerstra, J. Oude Elberink, E. Duiverman, A. Dubois
Journal: Journal of Allergy and Clinical Immunology (2010)
Pre-natal exposure to dichlorodiphenyldichloroethylene and infant lower respiratory tract infections and wheeze
Authors: Mireia Gascon, Martine Vrijheid, David Martínez, Ferran Ballester, Mikel Basterrechea, Elizabeth Blarduni, Ana Esplugues, Esther Vizcaino, Joan O. Grimalt, Eva Morales, Jordi Sunyer
Journal: European Respiratory Journal (2011)

The aim of our study was to examine whether pre-natal exposure to dichlorodiphenyldichloroethylene (DDE) increases the risk of lower respiratory tract infections (LRTIs) and wheeze in infants. The study is based on a birth cohort of 1,455 mother–child pairs. Maternal serum concentrations of DDE, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) were measured during pregnancy. Parental reports on LRTI and wheeze were obtained when children were 12–14 months old. 35.4% of children developed at least one LRTI episode and 33.6% at least one wheezing episode during their first 12–14 months of life. Median DDE, PCBs and HCB concentrations were 116.3, 113.7 and 46.4 ng·g −1 lipid, respectively. DDE concentrations were associated with LRTI risk (relative risk (RR) per 10% increase 1.11, 95% CI 1.00–1.22), also after adjustment for PCBs and HCB. In all quartiles of DDE exposure, the risk of LRTI was increased compared with the lowest quartile, but the increase was statistically significant only in the third quartile (RR 1.33, 95% CI 1.08–1.62). No association was observed for PCBs and HCB. Results were similar for wheeze. This study suggests that pre-natal DDE exposure is associated with a higher risk of LRTI and wheeze in infants independently of exposure to other organochlorine compounds.