tbuckley/cabot-search huggingface dataset:
Detection of epithelial tumour RNA in the plasma of colon cancer patients is associated with advanced stages and circulating tumour cells
Authors: J M Silva
Journal: Gut (2002)

Background: Although circulating tumour DNA has been detected in patients with different types of cancer, little is known of free RNA in cancer patients. Aims: We investigated the presence of RNA from epithelial tumours in plasma from patients with colorectal carcinomas, and its correlation with tumour characteristics and circulating tumour cells. Methods: β-actin mRNA was analysed to assess the viability of plasma RNA in samples from 53 patients with colonic cancer and 25 controls. Subsequently, nested primers were used to detect the presence of cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) RNA in the same samples. Nine clinicopathological parameters were studied to correlate the molecular and clinical parameters. Additionally, we investigated for micrometastases in blood in 18 of these patients and in 10 of the controls samples. Results: All samples had detectable quantities of β-actin RNA. In the controls, one case (4%) was positive for CEA and five (20%) for CK19 RNA; of the 53 patients, 17 cases (32%) were positive for CEA and 39 (73.6%) for CK19 RNA. This was statistically significant (p=0.000001). Advanced stages (p=0.03) and soluble CEA status (p=0.03) were associated with the presence of CEA, CK19, or both RNAs in plasma. Lymph node metastases (p=0.06) and vascular invasion (p=0.07) were almost significant. On the basis of these results, we examined the possible presence of micrometastases in blood in several of these patients. The presence of plasma tumour RNA was found to be associated with circulating tumour cells in blood (p=0.04). Conclusions: Epithelial tumour RNA is detectable in plasma from colon cancer patients. This molecular event is associated with advanced stages and circulating tumour cells. Our results could offer new approaches in the diagnosis and monitoring of colon cancer.
Evidence for Oxidative Activation of c-Myc–Dependent Nuclear Signaling in Human Coronary Smooth Muscle Cells and in Early Lesions of Watanabe Heritable Hyperlipidemic Rabbits
Authors: Filomena de Nigris, Tammam Youssef, SilviaAnna Ciafré, Flavia Franconi, Vittorio Anania, GianLuigi Condorelli, Wulf Palinski, Claudio Napoli
Journal: Circulation (2000)

Background —Oxidized LDL (oxLDL) promotes atherogenesis, and antioxidants reduce lesions in experimental models. OxLDL-mediated effects on c-Myc are poorly characterized, and those on c-Myc nuclear pathways are completely unknown. c-Myc stimulates smooth muscle cell (SMC) proliferation and could be involved in atherosclerosis. We investigated the early effects of oxLDL and α-tocopherol on c-Myc, its binding partner Max, and the carboxy-terminal domain–binding factors activator protein-2 and elongation 2 factor in human coronary SMCs. We also investigated whether 9-week treatment of Watanabe heritable hyperlipidemic (WHHL) rabbits with diet-enriched α-tocopherol reduces c-Myc expression and oxLDL in the left coronary artery. Methods and Results —OxLDL enhanced c-Myc/Max expression and transcription by cotransfection assay and the nuclear activities of E2F and activator protein-2 by binding shift and supershift in coronary SMCs. α-Tocopherol significantly reduced these molecular events. Furthermore, α-tocopherol reduced early lesions, SMC density, and the immunohistochemical presence of c-Myc, which colocalized with oxLDL/foam cells in the coronaries of WHHL rabbits. Conclusions —We provide the first evidence that oxLDL and α-tocopherol may influence c-Myc activation and several c-Myc–dependent signaling pathways in human coronary SMCs. The observation that in vivo, an antioxidant reduces both c-Myc and oxLDL in early coronary lesions of rabbits is consistent with, but does not prove, the hypothesis that c-Myc–dependent factors activated by oxidative processes contribute to atherogenesis and coronary heart disease.
Milking the Evidence: Diet Does Matter
Authors: Donald I. Abrams
Journal: Journal of Clinical Oncology (2014)

Dietary risks now rank number one among 17 leading risk factors contributing to the number of deaths and percentage of disabilityadjusted–life-years for both sexes combined in the United States. 1 The aggregate of the 14 subcomponents of diet (ie, diet low in fruits, vegetables, whole grains, nuts and seeds, milk, fiber, calcium, seafood omega-3 fatty acids, polyunsaturated fatty acids; diet high in red meat, processed meats, sugar-sweetened beverages, trans-fatty acids, sodium 2 ) assessed by the US Burden of Disease Collaborators surpasses the impact of tobacco smoking on the nation’s morbidity and mortality and does not include high body mass index and physical inactivity (ranking fourth and fifth in contributing to overall deaths). It has been estimated that as many avoidable malignancies are related to diet as tobacco (30% to 35%), again not accounting for the significant addi
Interleukin 25 promotes the initiation of proallergic type 2 responses
Authors: Pornpimon Angkasekwinai, Heon Park, Yui-Hsi Wang, Yi-Hong Wang, Seon Hee Chang, David B. Corry, Yong-Jun Liu, Zhou Zhu, Chen Dong
Journal: The Journal of Experimental Medicine (2007)

The molecular mechanisms underlying the initiation of innate and adaptive proallergic type 2 responses are not understood. Interleukin (IL) 25, a member of the IL-17 cytokine family, was recently reported (Owyang, A.M., C. Zaph, E.H. Wilson, K.J. Guild, T. McClanahan, H.R. Miller, D.J. Cua, M. Goldschmidt, C.A. Hunter, R.A. Kastelein, and D. Artis. 2006. J. Exp. Med. 203:843-849; Fallon, P.G., S.J. Ballantyne, N.E. Mangan, J.L. Barlow, A. Dasvarma, D.R. Hewett, A. McIlgorm, H.E. Jolin, and A.N. McKenzie. 2006. J. Exp. Med. 203:1105-1116) to be important in Th2 cell-mediated immunity to parasitic infection. However, the cellular source and targets of IL-25 are not well understood. We show that mouse IL-25 is expressed by lung epithelial cells as a result of innate immune responses to allergens. Transgenic overexpression of IL-25 by these cells leads to mucus production and airway infiltration of macrophages and eosinophils, whereas blockade of IL-25 conversely reduces the airway inflammation and Th2 cytokine production in an allergen-induced asthma model. In addition, IL-25, with a receptor more highly expressed in Th2 than other effector T cells, promotes Th2 cell differentiation in an IL-4- and signal transducer and activator of transcription 6-dependent manner. During early T cell activation, IL-25 potentiates expression of the nuclear factor of activated T cells c1 and JunB transcription factors, which possibly results in increased levels of initial IL-4 production, up-regulation of GATA-3 expression, and enhanced Th2 cell differentiation. Thus, IL-25 is a critical factor regulating the initiation of innate and adaptive proallergic responses.
431 Co-inhibitory molecule B7-H1 may play an important role for chronicity of hepatitis C
Authors: Y.J. Lee, S.J. Park, S.R. Jee, S.H. Lee, S.Y. Seol, J.M. Chung, H.Y Jeong, S.K. Seo, S.G. Park, I.H. Cho
Journal: Journal of Hepatology (2006)
Inhibition of BET Bromodomain Targets Genetically Diverse Glioblastoma
Authors: Zhixiang Cheng, Yuanying Gong, Yufang Ma, Kaihua Lu, Xiang Lu, Larry A. Pierce, Reid C. Thompson, Susanne Muller, Stefan Knapp, Jialiang Wang
Journal: Clinical Cancer Research (2013)

Glioblastoma is refractory to conventional therapies. The bromodomain and extraterminal domain (BET) proteins are epigenetic readers that selectively bind to acetylated lysine residues on histone tails. These proteins recently emerged as important therapeutic targets in NUT midline carcinoma and several types of hematopoietic cancers. In this study, the therapeutic potential of a novel BET bromodomain inhibitor, JQ1, was assessed in a panel of genetically heterogeneous glioblastoma samples.
Rituximab as preventive therapy of a clinical relapse in TTP with ADAMTS13 inhibitor
Authors: N. Schleinitz, M. Ebbo, K. Mazodier, P. Poullin, E. Bernit, V. Veit, A. Veyradier, F. Fakhouri, G. Kaplanski, J.‐R. Harle
Journal: American Journal of Hematology (2007)
Orthotopic and heterotopic ovarian tissue transplantation
Authors: I. Demeestere, P. Simon, S. Emiliani, A. Delbaere, Y. Englert
Journal: Human Reproduction Update (2009)

conclusion: Additional evidence is required to define optimal conditions for ovarian tissue transplantation.Alternatives such as whole ovary or isolated follicles transplantations require further investigation but are likely to be successful in humans in the future.
Posttraumatic Stress Disorder and Identification in Disaster Workers
Authors: Robert J. Ursano, Carol S. Fullerton, Kelley Vance, Tzu-Cheg Kao
Journal: American Journal of Psychiatry (1999)

Disaster workers who work with deceased victims are at increased risk of posttraumatic stress disorder (PTSD). Identification with the deceased has been proposed as one of the mechanisms in this stress-illness relationship. To examine this hypothesis, this study investigated three types of identification with the dead in a group of disaster workers: identification with the deceased as oneself, identification with the deceased as a friend, and identification with the deceased as a family member.Fifty-four volunteer disaster workers who worked with the dead following an explosion on the USS Iowa naval ship were assessed 1, 4, and 13 months after the disaster. PTSD symptoms (measured with the DSMPTSD-IV scale), intrusive and avoidant disaster-related symptoms (measured with the Impact of Event Scale), somatization and general distress (measured with the SCL-90-R), and health care utilization were assessed.Disaster workers who reported identification with the deceased as a friend were more likely than those who did not to have PTSD, more intrusive and avoidant symptoms, and greater levels of other posttraumatic symptoms including somatization. Disaster workers who reported identification with the deceased as a family member had greater intrusive symptoms 1 month after the disaster than those who did not. There were no differences between those who did and did not identify with the deceased as self. Health care utilization was not associated with identification.Identification with the deceased is a risk factor for PTSD and posttraumatic symptoms in disaster workers exposed to the dead. Identification with the dead as a friend is specifically associated with higher risk for these workers.
Comparative Analysis of Normal versus CLL B-Lymphocytes Reveals Patient-Specific Variability in Signaling Mechanisms Controlling LFA-1 Activation by Chemokines
Authors: Alessio Montresor, Matteo Bolomini-Vittori, Scott I. Simon, Antonella Rigo, Fabrizio Vinante, Carlo Laudanna
Journal: Cancer Research (2009)

Abstract Activation of lymphocyte function–associated antigen-1 (LFA-1) by chemokines is fine-tuned by inside-out signaling mechanisms responsible for integrin-mediated adhesion modulation. In the present study, we investigated the possibility of qualitative variability of signaling mechanisms controlling LFA-1 activation in chronic lymphocytic leukemia (CLL) cells. We pursued a multiplexed comparative analysis of the role of the recently described chemokine-triggered rho-signaling module in human normal versus CLL B-lymphocytes. We found that the rho-module of LFA-1 affinity triggering is functionally conserved in normal B-lymphocytes. In contrast, in malignant B-lymphocytes isolated from patients with B-CLL, the role of the rho-module was not maintained, showing remarkable differences and variability. Specifically, RhoA and phospholipase D1 were crucially involved in LFA-1 affinity triggering by CXCL12 in all analyzed patients. In contrast, Rac1 and CDC42 involvement displayed a consistent patient-by-patient variability, with a group of patients showing LFA-1 affinity modulation totally independent of Rac1 and CDC42 signaling activity. Finally, phosphatidylinositol-4-phosphate 5-kinase isoform 1γ (PIP5KC) was found without any regulatory role in all patients. The data imply that the neoplastic progression may completely bypass the regulatory role of Rac1, CDC42, and PIP5KC, and show a profound divergence in the signaling mechanisms controlling integrin activation in normal versus neoplastic lymphocytes, suggesting that patients with CLL can be more accurately evaluated on the basis of the analysis of signaling mechanisms controlling integrin activation. Our findings could potentially affect the diagnosis, prognosis, and therapy of CLL disorders. [Cancer Res 2009;69(24):9281–90]
Prospects for the development of effective pharmacotherapy targeted at the skeletal muscles in chronic obstructive pulmonary disease: a translational review
Authors: Michael C Steiner, Ronenn Roubenoff, Ruth Tal-Singer, Michael I Polkey
Journal: Thorax (2012)

Skeletal muscle dysfunction is a prevalent and clinically important systemic manifestation of chronic obstructive pulmonary disease (COPD) that predicts morbidity and mortality. Skeletal muscle retains its plasticity in response to anabolic stimuli such as exercise in COPD and is therefore a promising target for novel pharmacological therapies aimed at reducing disability and healthcare utilisation and improving mortality. In this article, we outline the steps the academic and pharmaceutical communities need to undertake for such therapeutic advances to be realised.
Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial
Authors: Kenneth R Chapman, Jonathan G W Burdon, Eeva Piitulainen, Robert A Sandhaus, Niels Seersholm, James M Stocks, Berend C Stoel, Liping Huang, Zhenling Yao, Jonathan M Edelman, Noel G McElvaney
Journal: The Lancet (2015)
Matrix metalloproteinase-9 is an important factor in hepatic regeneration after partial hepatectomy in mice
Authors: Eric W. Olle, Xiaodan Ren, Shannon D. McClintock, Roscoe L. Warner, Michael P. Deogracias, Kent J. Johnson, Lisa M. Colletti
Journal: Hepatology (2006)

Partial hepatectomy triggers hepatocyte proliferation, hepatic matrix remodeling, and hepatocyte apoptosis, all of which are important processes in the regenerating liver. Previous studies have shown an increase in the levels of matrix metalloproteinases gelatinase A (MMP-2) and gelatinase B (MMP-9) after partial hepatectomy. The goal of this study was to investigate the role of MMP-9 in liver regeneration after partial hepatectomy. A 70% hepatectomy or sham laparotomy was performed in wild-type or MMP-9–deficient (MMP-9−/−) mice. Hepatic regeneration was determined by liver weight/total body weight ratios and BrdU staining, which was used to a calculate mitotic index at several times postoperatively. Cytokine and growth factor expression was evaluated by Luminex™ bead–based ELISA and Western blots. Finally, the effect of MMP-9 on apoptosis was measured using TUNEL and caspase expression. The MMP-9−/− animals had a delayed hepatic regenerative response when compared with wild-type controls. The MMP-9–deficient animals expressed significantly less VEGF, HGF, and TNF-α between days 2 and 3 post-hepatectomy. Apoptosis, as measured by TUNEL staining and caspase expression, was decreased in the MMP-9−/−. In conclusion , MMP-9 plays an important role in liver regeneration after partial hepatectomy by affecting matrix remodeling, as well as cytokine, growth factor, and caspase expression. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
Hand-Foot Skin Reaction Increases with Cumulative Sorafenib Dose and with Combination Anti-Vascular Endothelial Growth Factor Therapy
Authors: Nilofer S. Azad, Jeanny B. Aragon-Ching, William L. Dahut, Martin Gutierrez, William D. Figg, Lokesh Jain, Seth M. Steinberg, Maria L. Turner, Elise C. Kohn, Heidi H. Kong
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Sorafenib, a vascular endothelial growth factor (VEGF) receptor-2 and RAF kinase inhibitor, commonly causes skin toxicity. We retrospectively analyzed dermatologic toxicity in patients receiving combined antiangiogenic therapy involving sorafenib and bevacizumab. Experimental Design: Castration-resistant prostate cancer and metastatic non-small cell lung cancer patients were accrued to phase II studies, receiving sorafenib 400 mg twice daily. A phase I study explored sorafenib 200 to 400 mg twice daily with bevacizumab 5 to 10 mg/kg every 2 weeks in patients with advanced solid tumors. The probability of development of maximum grade of dermatologic toxicity as a function of the cumulative dose of sorafenib was determined. Additional analyses compared extent of toxicity, pharmacokinetics, and patient risk factors. Results: Ninety-six patients were enrolled: 54 received sorafenib and 42 received bevacizumab/sorafenib. Hand-foot skin reaction (HFSR) was observed in 50 of 96 (52%) patients. Grade 2 to 3 HFSR developed in 16 of 54 (30%) sorafenib patients and 24 of 42 (57%) bevacizumab/sorafenib patients (P = 0.012) and was associated with cumulative sorafenib exposure (P = 0.0008). Twenty-four of 42 phase I patients randomized to start with bevacizumab had increased risk of grade 2 to 3 HFSR than those starting with sorafenib (P = 0.013) after adjusting for association between HFSR risk and hypertension (P = 0.01), which was the only toxicity associated with HFSR. There was no association between HFSR and baseline history of neuropathy, prior taxane/platinum treatment, or systemic sorafenib levels. Conclusions: Sorafenib-related HFSR is associated with increasing cumulative sorafenib dose. HFSR is increased in patients treated with bevacizumab/sorafenib combination anti-VEGF therapy, and this finding is not explained by pharmacokinetic interaction between the two agents. Our results suggest that the pathophysiology of HFSR may be related to VEGF inhibition.
Immunoglobulin Changes using Different Dosing Regimens of Peanut Oral Immunotherapy (OIT) in Peanut Allergic Subjects
Authors: A. Thyagarajan, S.M. Jones, L. Pons, M. Kulis, P.B. Smith, P.H. Steele, J. Kamilaris, A.M. Scurlock, T.T. Perry, B. Vickery, A.W. Burks
Journal: Journal of Allergy and Clinical Immunology (2010)
Familial idiopathic myelofibrosis and multiple hemangiomas
Authors: Mariana Bonduel, Gabriela Sciuccati, Aurora Feliú Torres, Adrián Pierini, Guillermo Gallo
Journal: American Journal of Hematology (1998)

Idiopathic myelofibrosis (MF) is a rare disease in childhood. The clinical spectrum is very variable. Familial idiopathic MF has been recorded exceptionally. In previous reports idiopathic MF in childhood has been described in association with congenital anomalies and with chromosome abnormalities, although neither of these features have been reported in a familial context. We report two sisters with idiopathic MF and multiple eruptive hemangiomas. Details of their clinical signs, laboratory findings, and histologic features are described. Am. J. Hematol. 59:175–177, 1998. © 1998 Wiley-Liss, Inc.
Day-to-Day Variation of Insulin Requirements of Patients With Type 2 Diabetes and End-Stage Renal Disease Undergoing Maintenance Hemodialysis
Authors: Eugene Sobngwi, Sostanie Enoru, Gloria Ashuntantang, Marcel Azabji-Kenfack, Mesmin Dehayem, Arnold Onana, Daniel Biwole, François Kaze, Jean-François Gautier, Jean-Claude Mbanya
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate day-to-day variations of insulin needs in type 2 diabetic patients with end-stage renal disease (ESRD) on maintenance hemodialysis. RESEARCH DESIGN AND METHODS We developed a 24-h euglycemic clamp in patients who received an average of 2,200 calories in a standardized three-meal and two-snack regimen per day, adjusted to body size and sex. Intravenous insulin was adjusted every 30 min to achieve 5.5 ± 1.1 mmol/l glycemia over 24 h prehemodialysis, during hemodialysis session, and 24 h posthemodialysis in 10 type 2 diabetic patients, aged 55.7 ± 8.7 years with 11.9 ± 4.5 years diabetes duration, undergoing maintenance hemodialysis for 2.3 ± 2.3 years. Insulin requirements were derived from the dose of insulin administered to maintain euglycemia per period of time and day-to-day comparisons performed. RESULTS Mean capillary glycemia was 5.5 ± 0.3 mmol/l prehemodialysis and 5.3 ± 0.2 mmol/l posthemodialysis (P = 0.39). Pre- and posthemodialysis areas under the glucose curve were comparable. This was achieved by infusing 23.6 ± 7.7 IU/24 h prehemodialysis vs. 19.9 ± 4.9 IU/24 h posthemodialysis, indicating a 15.3% decrease posthemodialysis (P = 0.09). Basal insulin needs decreased from 0.4 ± 0.1/h prehemodialysis to 0.3 ± 0.1/h posthemodialysis (P = 0.01). Total boluses were decreased by 2.2 ± 3.1 IU (P = 0.15). Changes in blood urea did not correlate with changes in insulin needs (r = 0.1, P = 0.79). CONCLUSIONS The present study has demonstrated a significant 25% reduction in basal insulin requirements the day after dialysis compared with the day before. No significant change in boluses was observed, and overall the reduction of total insulin requirements was −15% equivalent to −4 IU/day posthemodialysis of marginal statistical significance.
STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES
Authors: Gertrude Henle, Friedrich Deinhardt, Victor V. Bergs, Werner Henle
Journal: The Journal of Experimental Medicine (1958)

Inoculation of the MCN and Lung-To lines of human cells in continuous culture with Newcastle disease (NDV), mumps, or 6-6 viruses led to slight cytopathic effects (CPE) if the multiplicity of infection exceeded one. On second passage or with smaller initial inocula no CPE became apparent. The viruses multiplied, however, as determined by titrations in HeLa cultures or chick embryos. Indeed, persistently infected sublines of MCN and Lung-To were readily established without resort to special manipulations and some of these have been carried now for over 18 months on the same media and schedules as the uninfected parent strains. The viruses were found to be associated mainly with the cells and only 1, or at most 10 per cent of it was detectable in the media. The titers obtained were always low in relation to the available cell population. Reduction or even omission of the horse serum component in the media or ultraviolet irradiation of the cultures did not increase the yield of virus, and CPE became apparent only when similarly treated, uninfected cultures were, likewise, affected by the manipulations. The persistently infected cultures differed from their uninfected counterparts in that they exhibited (a) decreased cellular growth rates and ultimate yields; (b) increased aerobic glycolysis; and (c) a high degree of resistance to cytopathogenic viruses, influenza A (PR8), herpes simplex and, especially vesicular stomatitis (VSV) viruses. Prolonged treatment of persistently infected cultures by addition of specific antiviral immune sera to the media reduced significantly the amount of virus present and the degree of resistance to VSV. However, upon removal of the sera after as many as 187 days of treatment the viruses reappeared in all but one instance. The cured culture, on reinfection, became again persistently infected. No evidence was obtained to indicate genetic inhomogeneity of the cell populations. Of 50 cloned MCN lines none was destroyed by NDV and all became persistently infected. None were initially resistant to VSV but all after establishment of persistent NBV infection. All 39 cloned lines derived from MCN(NDV) cultures in the presence of anti-NDV serum, were free of virus and susceptible to VSV, and all acquired persistent infections and with it resistance to VSV following inoculation of NDV. NDV maintained in MCN cultures differed from the parent, chick embryo-adapted strain with respect to its plaque morphology. Whereas the former yielded only plaques on monolayers of chick embryo fibroblasts which were of pin-point size and hazy, those obtained with the latter were rarely of this type and mostly large and clear. This apparent selection of virus particles did not alter significantly their behavior with respect to cytopathogenicity for uninfected MCN cultures.