tbuckley/cabot-search huggingface dataset:
Concerns About Sexuality of Young Women with Breast Cancer and Their Partners
Authors: L. Vanlemmens, C. Duprez, A. Lesur, F. Ait Kaci, A. Congard, P. Antoine, C. Loustalot, C. Guillemet, M. Leclercq, C. Levy, V. Christophe
Journal: Annals of Oncology (2014)
UBC9-Mediated Sumoylation Favorably Impacts Cardiac Function in Compromised Hearts
Authors: Manish K. Gupta, Patrick M. McLendon, James Gulick, Jeanne James, Kamel Khalili, Jeffrey Robbins
Journal: Circulation Research (2016)

SUMOylation plays an important role in cardiac function and can be protective against cardiac stress. Recent studies show that SUMOylation is an integral part of the ubiquitin proteasome system, and expression of the small ubiquitin-like modifier (SUMO) E2 enzyme UBC9 improves cardiac protein quality control. However, the precise role of SUMOylation on other protein degradation pathways, particularly autophagy, remains undefined in the heart.To determine whether SUMOylation affects cardiac autophagy and whether this effect is protective in a mouse model of proteotoxic cardiac stress.We modulated expression of UBC9, a SUMO E2 ligase, using gain- and loss-of-function in neonatal rat ventricular cardiomyocytes. UBC9 expression seemed to directly alter autophagic flux. To confirm this effect in vivo, we generated transgenic mice overexpressing UBC9 in cardiomyocytes. These mice have an increased level of SUMOylation at baseline and, in confirmation of the data obtained from neonatal rat ventricular cardiomyocytes, demonstrated increased autophagy, suggesting that increased UBC9-mediated SUMOylation is sufficient to upregulate cardiac autophagy. Finally, we tested the protective role of SUMOylation-mediated autophagy by expressing UBC9 in a model of cardiac proteotoxicity, induced by cardiomyocyte-specific expression of a mutant α-B-crystallin, mutant CryAB (CryAB(R120G)), which shows impaired autophagy. UBC9 overexpression reduced aggregate formation, decreased fibrosis, reduced hypertrophy, and improved cardiac function and survival.The data showed that increased UBC9-mediated SUMOylation is sufficient to induce relatively high levels of autophagy and may represent a novel strategy for increasing autophagic flux and ameliorating morbidity in proteotoxic cardiac disease.
The Role of Environmental Toxins in Amyotrophic Lateral Sclerosis Risk
Authors: Jacquelyn J. Cragg, Merit E. Cudkowicz, Marc G. Weisskopf
Journal: JAMA Neurology (2016)

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Residential Road Traffic Noise and High Depressive Symptoms after Five Years of Follow-up: Results from the Heinz Nixdorf Recall Study
Authors: Ester Orban, Kelsey McDonald, Robynne Sutcliffe, Barbara Hoffmann, Kateryna B. Fuks, Nico Dragano, Anja Viehmann, Raimund Erbel, Karl-Heinz Jöckel, Noreen Pundt, Susanne Moebus
Journal: Environmental Health Perspectives (2015)

Traffic noise affects a large number of people, particularly in urbanized areas. Noise causes stress and annoyance, but less is known about the relationship between noise and depression.We investigated the association of residential road traffic noise with depressive symptoms using 5-year follow-up data from a German population-based study.We analyzed data from 3,300 participants in the Heinz Nixdorf Recall study who were between 45 and 75 years old and were without depressive symptoms at baseline (2000-2003). Depressive symptoms were defined based on the Center for Epidemiologic Studies Depression scale (CES-D) 15-item questionnaire (total score ≥ 17) and antidepressant medication intake. Road traffic noise was modeled according to European Parliament/Council Directive 2002/49/EC. High noise exposure was defined as annual mean 24-hr noise levels > 55 A-weighted decibels [dB(A)]. Poisson regression with robust variance was used to estimate relative risks (RRs) a) adjusting for the potential confounders age, sex, socioeconomic status (SES), neighborhood-level SES, and traffic proximity; b) additionally adjusting for body mass index and smoking; and c) additionally adjusting for the potential confounders/intermediates comorbidities and insomnia.Overall, 35.7% of the participants were exposed to high residential road traffic noise levels. At follow-up (mean = 5.1 years after baseline), 302 participants were classified as having high depressive symptoms, corresponding to an adjusted RR of 1.29 (95% CI: 1.03, 1.62; Model 1) for exposure to > 55 versus ≤ 55 dB(A). Adjustment for potential confounders/intermediates did not substantially alter the results. Associations were stronger among those who reported insomnia at baseline (RR = 1.62; 95% CI: 1.10, 2.59 vs. RR = 1.21; 95% CI: 0.94, 1.57) and appeared to be limited to those with ≤ 13 years of education (RR = 1.43; 95% CI: 1.10, 1.85 vs. 0.92; 95% CI: 0.56, 1.53 for > 13 years).Our results suggest that exposure to residential road traffic noise increases the risk of depressive symptoms.Orban E, McDonald K, Sutcliffe R, Hoffmann B, Fuks KB, Dragano N, Viehmann A, Erbel R, Jöckel KH, Pundt N, Moebus S. 2016. Residential road traffic noise and high depressive symptoms after five years of follow-up: results from the Heinz Nixdorf Recall Study. Environ Health Perspect 124:578-585; http://dx.doi.org/10.1289/ehp.1409400.
Cold Shock Proteins Mediate GN with Mesangioproliferation
Authors: Cheng Zhu, Eva Sauter, Anja Schreiter, Claudia R.C. van Roeyen, Tammo Ostendorf, Jürgen Floege, Florian Gembardt, Christian P. Hugo, Berend Isermann, Jonathan A. Lindquist, Peter R. Mertens
Journal: Journal of the American Society of Nephrology (2016)

DNA binding protein A (DbpA) is a member of the human cold shock domain-containing protein superfamily, with known functions in cell proliferation, differentiation, and stress responses. DbpA mediates tight junction-associated activities in tubular epithelial cells, but the function of DbpA in mesangial cells is unknown. Here, we found DbpA protein expression restricted to vascular smooth muscle cells in healthy human kidney tissue but profound induction of DbpA protein expression within the glomerular mesangial compartment in mesangioproliferative nephritis. In vitro, depletion or overexpression of DbpA using lentiviral constructs led to inhibition or promotion, respectively, of mesangial cell proliferation. Because platelet-derived growth factor B (PDGF-B) signaling has a pivotal role in mesangial cell proliferation, we examined the regulatory effect of PDGF-B on DbpA. In vitro studies of human and rat mesangial cells confirmed a stimulatory effect of PDGF-B on DbpA transcript numbers and protein levels. Additional in vivo investigations showed DbpA upregulation in experimental rat anti-Thy1.1 nephritis and murine mesangioproliferative nephritis models. To interfere with PDGF-B signaling, we injected nephritic rats with PDGF-B neutralizing aptamers or the MEK/ERK inhibitor U0126. Both interventions markedly decreased DbpA protein expression. Conversely, continuous PDGF-B infusion in healthy rats induced DbpA expression predominantly within the mesangial compartment. Taken together, these results indicate that DbpA is a novel target of PDGF-B signaling and a key mediator of mesangial cell proliferation.
Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer
Authors: Philip D. Dunne, Darragh G. McArt, Conor A. Bradley, Paul G. O'Reilly, Helen L. Barrett, Robert Cummins, Tony O'Grady, Ken Arthur, Maurice B. Loughrey, Wendy L. Allen, Simon S. McDade, David J. Waugh, Peter W. Hamilton, Daniel B. Longley, Elaine W. Kay, Patrick G. Johnston, Mark Lawler, Manuel Salto-Tellez, Sandra Van Schaeybroeck
Journal: Clinical Cancer Research (2016)

Abstract Purpose: A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. Experimental Design: We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. Results: We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286–9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial–mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Conclusions: Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095–104. ©2016 AACR. See related commentary by Morris and Kopetz, p. 3989
Origin, fate and dynamics of macrophages at central nervous system interfaces
Authors: Tobias Goldmann, Peter Wieghofer, Marta Joana Costa Jordão, Fabiola Prutek, Nora Hagemeyer, Kathrin Frenzel, Lukas Amann, Ori Staszewski, Katrin Kierdorf, Martin Krueger, Giuseppe Locatelli, Hannah Hochgerner, Robert Zeiser, Slava Epelman, Frederic Geissmann, Josef Priller, Fabio M V Rossi, Ingo Bechmann, Martin Kerschensteiner, Sten Linnarsson, Steffen Jung, Marco Prinz
Journal: Nature Immunology (2016)
Development of a drug delivery system for efficient alveolar delivery of a neutralizing monoclonal antibody to treat pulmonary intoxication to ricin
Authors: Renaud Respaud, Denis Marchand, Thibaut Pelat, Kam-Meng Tchou-Wong, Chad J. Roy, Christelle Parent, Maria Cabrera, Joël Guillemain, Ronan Mac Loughlin, Eric Levacher, Alexandre Fontayne, Laurence Douziech-Eyrolles, Alexandra Junqua-Moullet, Laurent Guilleminault, Philippe Thullier, Emmanuelle Guillot-Combe, Laurent Vecellio, Nathalie Heuzé-Vourc'h
Journal: Journal of Controlled Release (2016)
Cocaine/"crack" dependence among psychiatric inpatients
Authors: G Bunt, M Galanter, H Lifshutz, R Castaneda
Journal: American Journal of Psychiatry (1990)

The authors studied 40 cocaine-dependent subjects admitted to psychiatric inpatient wards of a metropolitan hospital because of general psychiatric symptoms. The results indicate that the predominant form of cocaine administration (88%) was freebasing "crack." DSM-III-R cluster B personality disorders (N = 17) and schizophrenia (N = 13) constituted the diagnoses for 75% of the sample. Compared to the schizophrenic patients in this cohort, the patients with cluster B personality disorders used cocaine in greater quantities and more frequently and began abuse of the drug at an earlier age. The escalation in urban areas of psychiatric hospitalizations attributed to use of crack may be largely related to psychiatric symptoms in cocaine-dependent patients with personality disorders as well as cocaine-induced psychopathology in schizophrenic patients.
Modulation of P-glycoprotein and proinflammatory cytokines with HMG-CoA reductase inhibitor simvastatin (SV) in chronic myelogenous leukemia (CML) patients with imatinib mesylate (IM) resistance
Authors: E. McPherson, E. Hazel, P. Tassy, J. Kleinfeld
Journal: Journal of Clinical Oncology (2007)

17528 Background: Primarily monocyte-derived cytokines and soluble interleukin-2 receptor (sIL-2R) form a group of proinflammatory cytokines and mononuclear cell activaton respectively which are significantly elevated in patients with CML-chronic phase (CML-CP) or CML-blastic crisis (CML-BC).C-reactive protein (CRP) correlates with IL-6. IM is a tyrosine kinase inhibitor that specifically acts intracellularly by blocking the ATP-binding site of the kinase domain of Bcr/abl in CML. Acquired drug resistance in CML-CP patients treated with IM may occur by upregulation of P-glycoprotein (P-gp) drug efflux with P-gp+ leukemic cells and P-gp dependent decline of intracellular IM levels with retained phosphorylation Bcr/abl pattern and loss of IM effect on apoptosis and cellular proliferation. Modulation of P-gp with HMG-CoA reductase inhibitor (SV), a potent inhibitor of P-gp transport, readily overcame IM resistance. Methods: We present two cases of CML: CML-CP and CML-BC with evidence of IM resistance. After one year of IM therapy an 86 yo female with CML-CP stage II, developed reactivation of Bcr/abl signaling due to excretion of IM from the cell transmembrane transporters consistent with increased proinflammatory cytokines, sIL-2R, CRP, acute coronary syndrome but normal neopterin.Results: Modulation of proinflammatory cytokines with SV, IM dose adjustments, serial measurements of Bcr-abl/abl ratio didnot exceed 0.02% on three occasions or 0.05% on two occasions after changing from 0.001% to 0.003% and now after two years of IM plus SV, real-time Bcr-abl/abl ratio is 0.000 (a 5 log reduction).sIL-2R levels normalized from 31,709.55 pg/ml to 5,345.4 pg/ml (Normal 1770–9753 pg/ml). CRP decreased to 6.23 mg/dl from 16 mg/dl. Conclusions: IM an intracellular drug demonstrating high activity against Bcr/abl gene positive CML-CP or CML-BC patients may develop resistance and loss of cellular proliferation via upregulated P-gp-mediated drug efflux mechanism. Modulation of P-gp by HMG-CoA reductase (statins) inhibitor simvastatin, a potent inhibitor of P-gp, may allow intracellular levels of IM to restore its cytotoxicity and overcome resistance mechanism. No significant financial relationships to disclose.
Soundings: Privacy concerns
Authors: George Dunea
Journal: BMJ (2004)

If you should become infected with gonococcus, Treponema pallidum, hepatitis B, or HIV, you may not wish this information published in the local newsletter, disseminated to your friends, or discussed in a loud voice by enthusiastic medical students before an interested audience in a crowded elevator. You may not want your medical records sent to every insurance company in the country. You would accordingly be pleased to hear that a comprehensive federal law—the 1996 Health Insurance Portability and Accountability Act (HIPAA)—contains provisions designed to protect the privacy of patients' medical information.

Unfortunately this law is now having distressing consequences. These seem to arise largely from uncertainties in understanding its complicated provisions, misinterpretations, and anxiety about breaking the law and incurring heavy penalties.

We read that some months ago a man jumped out a window because a hospital assumed that it was not allowed to inform the family that he had been treated for depression. People calling hospitals often cannot obtain information about the condition or even the location of their relatives. Police officers and firefighters are wary of notifying relatives after a road crash. Medical records departments have repeatedly refused to release vital patient information to inquiring doctors. And several doctors have been reluctant to release the results of tests on the phone and have insisted that patients come to the office to get them. In the clinic, patients have waited interminably or were never seen because the clerks were told not to make up a list of scheduled appointments. Chaplains and ministers have given up visiting patients in hospital because they often cannot find where they are.

This has also had an impact on research. Even simple studies, such as examining specimens collected for routine urinalysis, would require either signed consent forms from 1500 patients, or not using the clinical data at all and thus making the project useless. Data collection for disease registries has run into difficulties, and there has also been an impact on fundraising for charitable organisations.

None of this was intended in the original legislation. But things do not always turn out as planned.
Coproduction of Carcinoembryonic Antigen and Nonspecific Cross-Reacting Antigen by a Continuous Cell Line From a Human Pancreatic Tumor&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M Kuroki, S Ichiki, M Kuroki, Y Matsuoka
Journal: JNCI Journal of the National Cancer Institute (1982)

A simultaneous production of nonspecific cross-reacting antigen (NCA) and carcinoembryonic antigen (CEA) by the same individual cells of an established human pancreatic cell line (QGP-1) was demonstrated by the immunoperoxidase method. Kinetics of cell proliferation and production of CEA and NCA were analyzed, and active synthesis of both antigens was found to be accompanied with the active proliferation of cultured cells. Both antigens in culture medium were purified by immunoadsorption and gel filtration. Immunochemical studies confirmed that CEA and NCA produced by the QGP-1 cells had properties identical to those of authentic CEA derived from metastatic colorectal carcinoma and to those of NCA from normal lungs, respectively.
Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem–like Cells
Authors: Julie Giraud, Laura M. Failla, Jean-Marc Pascussi, Ebba L. Lagerqvist, Jérémy Ollier, Pascal Finetti, François Bertucci, Chu Ya, Imène Gasmi, Jean-François Bourgaux, Michel Prudhomme, Thibault Mazard, Imade Ait-Arsa, Leila Houhou, Daniel Birnbaum, André Pélegrin, Charles Vincent, James G. Ryall, Dominique Joubert, Julie Pannequin, Frédéric Hollande
Journal: Cancer Research (2016)

Subpopulations of cancer stem-like cells (CSC) are thought to drive tumor progression and posttreatment recurrence in multiple solid tumors. However, the mechanisms that maintain stable proportions of self-renewing CSC within heterogeneous tumors under homeostatic conditions remain poorly understood. Progastrin is a secreted peptide that exhibits tumor-forming potential in colorectal cancer, where it regulates pathways known to modulate colon CSC behaviors. In this study, we investigated the role of progastrin in regulating CSC phenotype in advanced colorectal cancer. Progastrin expression and secretion were highly enriched in colon CSC isolated from human colorectal cancer cell lines and colon tumor biopsies. Progastrin expression promoted CSC self-renewal and survival, whereas its depletion by RNA interference-mediated or antibody-mediated strategies altered the homeostatic proportions of CSC cells within heterogeneous colorectal cancer tumors. Progastrin downregulation also decreased the frequency of ALDH(high) cells, impairing their tumor-initiating potential, and inhibited the high glycolytic activity of ALDH(high) CSC to limit their self-renewal capability. Taken together, our results show how colorectal CSC maintain their tumor-initiating and self-renewal capabilities by secreting progastrin, thereby contributing to the tumor microenvironment to support malignancy. Cancer Res; 76(12); 3618-28. ©2016 AACR.
Suppression of the Avian Sarcoma Virus Genome in 8-Azaguanine-Resistant, Transformed, Hamster Cells1
Authors: M. Hladká, C. Altaner
Journal: JNCI Journal of the National Cancer Institute (1976)

The avian sarcoma virus genome (Schmidt-Ruppin strain) in transformed hamster cells resistant to 8-azaquanine [Ha(SR)AG-50] was strongly suppressed. The suppression was genetically stable and could not be overcome by attempts at induction with 5-iodo-2'-deoxyuridine. Fusion of hamster cells, which had suppressed virus genome, with chicken Rous-associated virus (RAV-1)-preinfected cells easily rescued the sarcoma virus. The rescued virus had envelope properties of RAV-1, as determined by viral interference, virus neutralization, and plating on genetically resistant chicken cells. By repeatedly cloning the rescued virus, we determined that virus recombined in the rescue experiment and that the recombinant virus had the envelope properties of helper virus used for its rescue. Cells with suppressed avian sarcoma virus genome were suitable for preparation of different recombinant viruses.
Which sequence prevents the heart from trastuzumab and anthracycline toxicity: Electron microscopy study in rats.
Authors: Sercan Aksoy, Neyran Kertmen, Aysegul Uner, Mustafa Sargon, Ozgur Ozkayar, Özge Keskin, Taner Babacan, Saim Furkan Sarici, Mehmet Ali Nahit Sendur, Zafer Arik, Serkan Akin, Kadri Altundag
Journal: Journal of Clinical Oncology (2014)

e11595 Background: Two effective cytotoxic agents, doxorubicin and trastuzumab, are associated with a potentially life-threatening cardiotoxicity. Currently, these agents are dose and duration limited to circumvent cardiac damage. The current study was designed to investigate the cardiotoxicity aggravated by the timing of administration of trastuzumab and doxorubicin in rats. Methods: A total of 24 mice were randomly assigned to one of four groups. Mice received one of the following treatment drug regimens administered via intraperitoneal injection: (1) 0.9% saline control (n = 6); (2) doxorubicin (5 mg/kg) day 1 then trastuzumab 10 mg/ kg day 15 ( n = 6); (3) trastuzumab 10 mg/ kg day 1 then doxorubicin (5 mg/kg) day 15 ( n = 6); (4) doxorubicin (5 mg/kg) day 1 and trastuzumab 10 mg/ kg day 1 ( n = 6). On the 30th day, all mice were euthanized and the hearts were removed and processed for pathological analysis by electron microscopy. Results: Electron microscopy showed the ultrastructurally normal heart tissue in the control group. In the transmission electron microscopic examination of the tissue samples in second group a mild degree of dilation was observed in the perinuclear cisternae of some heart muscle cells. No other ultrastructural pathologies were present. In the last group, a mild degree of dilation was observed in the perinuclear cisternae of some heart muscle cells. In this group; the myofibrils, mitochondria and intercalated discus were normal ultrastructurally. In the third group pathological changes were detected in some of mitochondrias. They were observed with their prominent cristae, which also showed a mild degree of ultrastructural pathology in mitochondria. Moreover prominent dilations were observed in the perinuclear cisternae of heart muscle cells. Conclusions: According to the electron microscopy findings; sequential administration of anthracycline first then trastuzumab is safer for cardiotoxicity and the most toxic schedule to the heart was trastuzumab first then anthracycline in rats.