tbuckley/cabot-search huggingface dataset:
Reduced Expression of miRNA-27a Modulates Cisplatin Resistance in Bladder Cancer by Targeting the Cystine/Glutamate Exchanger SLC7A11
Authors: Ross M. Drayton, Ewa Dudziec, Stefan Peter, Simone Bertz, Arndt Hartmann, Helen E. Bryant, James WF. Catto
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Resistance to cisplatin-based chemotherapy is a major obstacle to bladder cancer treatment. We aimed to identify microRNAs (miRNA) that are dysregulated in cisplatin-resistant disease, ascertain how these contribute to a drug-resistant phenotype, and how this resistance might be overcome. Experimental Design: miRNA expression in paired cisplatin-resistant and -sensitive cell lines was measured. Dysregulated miRNAs were further studied for their ability to mediate resistance. The nature of the cisplatin-resistant phenotype was established by measurement of cisplatin/DNA adducts and intracellular glutathione (GSH). Candidate miRNAs were examined for their ability to (i) mediate resistance and (ii) alter the expression of a candidate target protein (SLC7A11); direct regulation of SLC7A11 was confirmed using a luciferase assay. SLC7A11 protein and mRNA, and miRNA-27a were quantified in patient tumor material. Results: A panel of miRNAs were found to be dysregulated in cisplatin-resistant cells. miRNA-27a was found to target the cystine/glutamate exchanger SLC7A11 and to contribute to cisplatin resistance through modulation of GSH biosynthesis. In patients, SLC7A11 expression was inversely related to miRNA-27a expression, and those tumors with high mRNA expression or high membrane staining for SLC7A11 experienced poorer clinical outcomes. Resistant cell lines were resensitized by restoring miRNA-27a expression or reducing SLC7A11 activity with siRNA or with sulfasalazine. Conclusion: Our findings indicate that miRNA-27a negatively regulates SLC7A11 in cisplatin-resistant bladder cancer, and shows promise as a marker for patients likely to benefit from cisplatin-based chemotherapy. SLC7A11 inhibition with sulfasalazine may be a promising therapeutic approach to the treatment of cisplatin-resistant disease. Clin Cancer Res; 20(7); 1990–2000. ©2014 AACR.
Constancy of glucose and starch fermentations by two different human faecal microbial communities.
Authors: G A Weaver, J A Krause, T L Miller, M J Wolin
Journal: Gut (1989)

The fermentation of glucose and corn starch by faecal suspensions from two subjects was examined over a three and a half year period. The substrate specificity and products of the faecal fermentations of each subject were relatively stable during this period and were significantly different between subjects. The major soluble end products of fermentation of glucose or starch were acetate, propionate, and butyrate. Hydrogen temporarily accumulated and was subsequently used in fermentations by both subjects. Hydrogen was used without methane production in fermentations of subject 1, but was used for methane formation in fermentations of subject 2. Although the rates of glucose fermentation were similar between both subjects; subject 1 produced a significantly greater molar ratio of propionate than did subject 2. The rate of fermentation of starch by faecal suspensions from subject 1 was faster than that of subject 2. The molar ratio of butyrate was greater for starch fermentations by subject 2, while the molar ratio of propionate was greater with subject 1. Significant differences were found between subjects in molar ratios and concentration of acetate and propionate and concentrations of butyrate in faeces.
Preconditioning by Mitochondrial ATP-Sensitive Potassium Channel Openers : An Effective Approach for Improving the Preservation of Heart Transplants
Authors: E Kevelaitis, A Oubénaïssa, J Peynet, C Mouas, P Menasché
Journal: Circulation (1999)

Recent studies have implicated mitochondrial ATP-sensitive potassium (K(ATP)) channels in the cardioprotective effects of ischemic preconditioning. The present study used a model of prolonged cold heart storage to assess whether the mitochondrial K(ATP) opener diazoxide could reproduce the protection conferred by ischemic preconditioning.Fifty-four isolated rat hearts were arrested with and stored in Celsior at 4 degrees C for 10 hours before a 2-hour reperfusion. They were divided into 5 groups. Group 1 hearts served as controls. In group 2, hearts were preconditioned by two 5-minute episodes of global ischemia, each separated by 5 minutes of reperfusion before arrest. In group 3, hearts received a 15-minute infusion of the mitochondrial K(ATP) opener diazoxide (30 micromol/L) followed by 5 minutes of washout before arrest. In groups 4 and 5, hearts underwent a protocol similar to that used in groups 2 and 3, respectively, except that the preconditioning was preceded by a 10-minute infusion of the mitochondrial K(ATP) blocker 5-hydroxydecanoate (5-HD, 100 micromol/L). Both ischemic and diazoxide preconditioning provided a similar degree of cardioprotection demonstrated by a significantly better preservation of left ventricular compliance, reduced leakage of creatine kinase, and smaller degree of myocardial edema compared with control hearts. These beneficial effects were abolished by 5-HD pretreatment. Postischemic left ventricular contractility and endothelium-dependent coronary response to 5-hydroxytryptamine and acetylcholine were not different among groups. However, the endothelium-independent vasodilatory postischemic response to papaverine was better preserved after ischemic and diazoxide preconditioning than in the other groups.These data support the concept that the cardioprotective effects of ischemic preconditioning can be duplicated by a mitochondrial K(ATP) opener and suggest that activation of these channels could be an effective means of improving the preservation of globally ischemic cold-stored hearts, as occurs during cardiac transplantation.
Flavopiridol downregulates hypoxia-mediated hypoxia-inducible factor-1α expression in human glioma cells by a proteasome-independent pathway: Implications for in vivo therapy
Authors: Elizabeth W Newcomb, M Aktar Ali, Tona Schnee, Li Lan, Yevgeniy Lukyanov, Mary Fowkes, Douglas C Miller, David Zagzag
Journal: Neuro-Oncology (2005)

Angiogenesis is a critical step required for sustained tumor growth and tumor progression. The stimulation of endothelial cells by cytokines secreted by tumor cells such as vascular endothelial growth factor (VEGF) induces their proliferation and migration. This is a prominent feature of high-grade gliomas. The secretion of VEGF is greatly upregulated under conditions of hypoxia because of the transcription factor hypoxiainducible factor (HIF)-1α, which controls the expression of many genes, allowing rapid adaptation of cells to their hypoxic microenvironment. Flavopiridol, a novel cyclin-dependent kinase inhibitor, has been attributed with antiangiogenic properties in some cancer cell lines by its ability to inhibit VEGF production. Here, we show that flavopiridol treatment of human U87MG and T98G glioma cell lines decreases hypoxia-mediated HIF-1α expression, VEGF secretion, and tumor cell migration. These in vitro results correlate with reduced vascularity of intracranial syngeneic GL261 gliomas from animals treated with flavopiridol. In addition, we show that flavopiridol downregulates HIF-1α expression in the presence of a proteasome inhibitor, an agent that normally results in the accumulation and overexpression of HIF-1α. The potential to downregulate HIF-1α expression with flavopiridol treatment in combination with a proteasome inhibitor makes this an extremely attractive anticancer treatment strategy for tumors with high angiogenic activity, such as gliomas.
Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region and that stimulate secondary allogenic proliferative and cytotoxic responses.
Authors: S Shaw, A H Johnson, G M Shearer
Journal: The Journal of Experimental Medicine (1980)

Five new histocompatibility antigens, designated secondary B cell or (SB) antigens, have been identified by secondary allogeneic proliferative and cytotoxic responses. The reagents used to define the SB antigents are lymphocytes primed between donors matched for all known HLA antigens. The SB antigens stimulate weak primary allogeneic proliferative responses (a mean relative response of 8%) but strong secondary proliferative responses. Strong secondary cell-mediated cytotoxicity is generated against target antigens that are distinguishable from the SB antigens defined by proliferation. Studies by direct lysis and by cold-target inhibition indicate that these target antigens are preferentially expressed on B cells relative to T cells. The SB antigens segregate with HLA, and the gene(s) encoding the SB1, 3, and 4 antigens maps centromeric to HLA-B. The SB antigens are major histocompatibility antigens not only because they are encoded by major histocompatibility complex (MHC) genes, but also by the functional criteria that the proliferative and cytotoxic responses to SB antigens are not restricted by HLA-DR or HLA-A,-B. Parallel studies of the SB antigens and the DR antigens with respect to: (a) their preferential expression on B cells, (b) their function in secondary allogeneic proliferative and cytotoxic respones, and (c) the location of their structural gene within the MHC. However, the SB antigens and the DR antigens are clearly distinct antigens, because population studies indicate that they can occur independently, and family studies indicate that specific SB antigens segregate with HLA haplotypes having different D and DR specificities. Our data are consistent with the hypotheses that the SB antigens are a new segregant series of B cell alloantigens, and that the SB gene and the DR gene derive from a duplicated ancestral gene.
Age-dependent susceptibility to a viral disease due to decreased natural killer cell numbers and trafficking
Authors: Min Fang, Felicia Roscoe, Luis J. Sigal
Journal: The Journal of Experimental Medicine (2010)

Although it is well known that aged hosts are generally more susceptible to viral diseases than the young, specific dysfunctions of the immune system directly responsible for this increased susceptibility have yet to be identified. We show that mice genetically resistant to mousepox (the mouse parallel of human smallpox) lose resistance at mid-age. Surprisingly, this loss of resistance is not a result of intrinsically defective T cell responses. Instead, the primary reason for the loss of resistance results from a decreased number of total and mature natural killer (NK) cells in the blood and an intrinsic impairment in their ability to migrate to the lymph node draining the site of infection, which is essential to curb systemic virus spread. Hence, our work links the age-dependent increase in susceptibility to a viral disease to a specific defect of NK cells, opening the possibility of exploring treatments to improve NK cell function in the aged with the goal of enhancing their resistance to viral diseases.
Endothelial targeting of semi-permeable polymer nanocarriers for enzyme therapies
Authors: Thomas D. Dziubla, Vladimir V. Shuvaev, Nan Kang Hong, Brian J. Hawkins, Muniswamy Madesh, Hajime Takano, Eric Simone, Marian T. Nakada, Aron Fisher, Steven M. Albelda, Vladimir R. Muzykantov
Journal: Biomaterials (2007)
Sex Differences in the Pathways to Major Depression: A Study of Opposite-Sex Twin Pairs
Authors: Kenneth S. Kendler, Charles O. Gardner
Journal: American Journal of Psychiatry (2014)

Personality and failures in interpersonal relationships play a stronger etiologic role in major depression for women, but childhood sexual abuse, externalizing psychopathology, prior depression, and acute financial, occupational, or legal stress were stronger etiologic pathways to depression for men. The sex differences in these pathways offer a road map for clinicians in addressing psychological issues important to their patients.
THE ROLE OF MAGNETIC RESONANCE IMAGING IN IDENTIFYING PATIENTS WITH CARDIAC SARCOIDOSIS AND PRESERVED LEFT VENTRICULAR FUNCTION IN PREDICTING FUTURE VENTRICULAR ARRHYTHMIAS
Authors: Thomas Crawford, Sinan Sarsam, Gisela Mueller, Sanjaya Gupta, Timir Baman, Karl Ilg, Diego Belardi, Mohamad Sinno, William Sauer, Khaled Abdul-Nour, Henry Kim, Mouaz AI-Mallah, Joseph Schuller, Fred Morady, Frank Bogun
Journal: Journal of the American College of Cardiology (2012)
Adverse Effects of Robotic-Assisted Laparoscopic Versus Open Retropubic Radical Prostatectomy Among a Nationwide Random Sample of Medicare-Age Men
Authors: Michael J. Barry, Patricia M. Gallagher, Jonathan S. Skinner, Floyd J. Fowler
Journal: Journal of Clinical Oncology (2012)

Purpose Robotic-assisted laparoscopic radical prostatectomy is eclipsing open radical prostatectomy among men with clinically localized prostate cancer. The objective of this study was to compare the risks of problems with continence and sexual function following these procedures among Medicare-age men. Patients and Methods A population-based random sample was drawn from the 20% Medicare claims files for August 1, 2008, through December 31, 2008. Participants had hospital and physician claims for radical prostatectomy and diagnostic codes for prostate cancer and reported undergoing either a robotic or open surgery. They received a mail survey that included self-ratings of problems with continence and sexual function a median of 14 months postoperatively. Results Completed surveys were obtained from 685 (86%) of 797 eligible participants, and 406 and 220 patients reported having had robotic or open surgery, respectively. Overall, 189 (31.1%; 95% CI, 27.5% to 34.8%) of 607 men reported having a moderate or big problem with continence, and 522 (88.0%; 95% CI, 85.4% to 90.6%) of 593 men reported having a moderate or big problem with sexual function. In logistic regression models predicting the log odds of a moderate or big problem with postoperative continence and adjusting for age and educational level, robotic prostatectomy was associated with a nonsignificant trend toward greater problems with continence (odds ratio [OR] 1.41; 95% CI, 0.97 to 2.05). Robotic prostatectomy was not associated with greater problems with sexual function (OR, 0.87; 95% CI, 0.51 to 1.49). Conclusion Risks of problems with continence and sexual function are high after both procedures. Medicare-age men should not expect fewer adverse effects following robotic prostatectomy.
Predictors for limb loss among patient with diabetic foot infections: an observational retrospective multicentric study in Turkey
Authors: N. Saltoglu, M. Yemisen, O. Ergonul, A. Kadanali, G. Karagoz, A. Batirel, O. Ak, H. Eraksoy, A. Cagatay, A. Vatan, G. Sengoz, F. Pehlivanoglu, T. Aslan, Y. Akkoyunlu, D. Engin, N. Ceran, B. Erturk, L. Mulazimoglu, O. Oncul, H. Ay, F. Sargin, N. Ozgunes, F. Simsek, T. Yildirmak, N. Tuna, O. Karabay, K. Yasar, N. Uzun, Y. Kucukardali, M. Sonmezoglu, F. Yilmaz, U. Tozalgan, S. Ozer, M. Ozyazar
Journal: Clinical Microbiology and Infection (2015)

We aimed to investigate the predictors for limb loss among patients with diabetes who have complicated skin/soft-tissue infections. In this observational study, consecutive patients with diabetic foot infection (DFI) from 17 centres in Turkey, between May 2011 and May 2013 were included. The Turkish DFI Working Group performed the study. Predictors of limb loss were investigated by multivariate analysis. In total, 455 patients with DFI were included. Median age was 61 years, 68% were male, 65% of the patients were hospitalized, 52% of the patients had used antibiotics within the last month, and 121 (27%) had osteomyelitis. Of the 208 microorganisms isolated, 92 (44.2%) were Gram-positive cocci and 114 (54.8%) were Gram-negative rods (GNR). The most common GNR was Pseudomonas; the second was Escherichia coli, with extended spectrum β-lactamase positivity of 33%. Methicillin-resistant Staphylococcus species were found in 14% (29/208). Amputations were performed in 126/455 (28%) patients, 44/126 (34%) of these were major amputations. In multivariate analysis, significant predictors for limb loss were, male gender (OR 1.75, 95% CI 1.04-2.96, p 0.034), duration of diabetes >20 years (OR 1.9, 95% CI 1.18-3.11, p 0.008), infected ulcer versus cellulitis (OR 1.9, 95% CI 1.11-3.18, p 0.019), history of peripheral vascular disease (OR 2, 95% CI 1.26-3.27, p 0.004), retinopathy (OR 2.25, 95% CI 1.19-4.25, p 0.012), erythrocyte sedimentation rate >70 mm/hr (OR 1.6, 95% CI 1.01-2.68, p 0.05), and infection with GNR (OR 1.8, 95% CI 1.08-3.02, p 0.02). Multivariate analysis revealed that, besides the known risk factors such as male gender, duration of diabetes >20 years, infected ulcers, history of peripheral vascular disease and retinopathy, detection of GNR was a significant predictor of limb loss.
Overcoming Antiangiogenic Resistance
Authors: James C. Yao, Alexandria Phan
Journal: Clinical Cancer Research (2011)

The success of drugs targeting angiogenesis is tempered by the transient duration of disease control and modest survival improvement. The very hypoxic stress produced by successful therapy may lead to upregulation of multiple pathways that promote angiogenesis and invasive behavior. Overcoming this evasive resistance may further improve outcome.
Expression of CD69 antigen on synovial fluid T cells in patients with rheumatoid arthritis and other chronic synovitis.
Authors: A Afeltra, M Galeazzi, G.M Ferri, A Amoroso, O De Pità, F Porzio, L Bonomo
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--The expression of the CD69 antigen on synovial fluid and peripheral blood lymphocytes was studied in 12 patients with rheumatoid arthritis (RA), five subjects with other forms of chronic synovitis, and on the peripheral blood lymphocytes of 15 patients with systemic lupus erythematosus (SLE) and immune vasculitis. METHODS--The CD69 antigen and other activation markers (HLA-DR, interleukin 2 receptor (IL-2R), transferrin receptor) were measured by cytometric analysis. In patients with RA soluble IL-2R was determined by enzyme linked immunosorbent assay (ELISA). RESULTS--The percentage of T cells bearing CD69 was significantly increased in synovial fluid from patients with RA (30.3 (13)%) and other chronic synovitis (18 (9)%). The expression of CD69 on peripheral blood lymphocytes of patients with RA, other chronic synovitis, and SLE and immune vasculitis was within the normal range 2.1 (1.2)%. According to previously published work, a high proportion of synovial fluid T cells are HLA-DR positive (64.2 (12.4)% in synovial fluid from patients with RA and 61 (1.2)% in synovial fluid from patients with other chronic synovitis). Transferrin receptor expression on synovial fluid was up-regulated compared with that on peripheral blood. The increase of IL-2R expression on synovial fluid lymphocytes v peripheral blood was not significant; the quantitative determination of soluble IL-2R levels gave a mean value of 921 (351) U/ml in synovial fluid of patients with RA, 672 (229) U/ml in the serum of the same patients, and 273 (100) U/ml in serum from normal subjects. CONCLUSIONS--Synovial fluid lymphocytes are in a different functional state than peripheral blood lymphocytes. CD69 antigen is an interesting cellular marker which should be studied in patients with chronic synovitis. The unusual expression of the activation antigens and the sequence of their appearance require further study.
Extraosseous Ewing's Sarcoma: 25 Years Later
Authors: Timothy M. Zagar, Timothy J. Triche, Timothy J. Kinsella
Journal: Journal of Clinical Oncology (2008)

Timothy M. Zagar, Department of Radiation Oncology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH Timothy J. Triche, Department of Pathology, Los Angeles Children’s Hospital, University of Southern California School of Medicine, Los Angeles, CA Timothy J. Kinsella, Department of Radiation Oncology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH
Effect of Procalcitonin-Based Guidelines vs Standard Guidelines on Antibiotic Use in Lower Respiratory Tract Infections
Authors: Philipp Schuetz, Mirjam Christ-Crain, Robert Thomann, Claudine Falconnier, Marcel Wolbers, Isabelle Widmer, Stefanie Neidert, Thomas Fricker, Claudine Blum, Ursula Schild, Katharina Regez, Ronald Schoenenberger, Christoph Henzen, Thomas Bregenzer, Claus Hoess, Martin Krause, Heiner C. Bucher, Werner Zimmerli, Beat Mueller, for the ProHOSP Study Group
Journal: JAMA (2009)

2][3] The most frequent indication for antibiotic prescriptions in the northwestern hemisphere is lower respiratory tract infections (LRTIs),which range in severity from self-limited acute bronchitis to severe acute exacerbation of chronic obstructive pulmonary disease (COPD), and to life-threatening bacte-rial community-acquired pneumonia (CAP). 46][7] As many as 75% of patients with LRTI are treated with antibiotics, despite the predominantly viral origin of their infection. 8 approach to estimate the probability of bacterial origin in LRTI is the measurement of serum procalcitonin (PCT).
Combination chemotherapy for locally advanced pancreatic cancer: equivalence to external beam irradiation and implication for future management.
Authors: F P Smith, D Stablein, S Korsmeyer, J Neefe, B K Chun, P V Woolley, P S Schein
Journal: Journal of Clinical Oncology (1983)

Chemotherapy with 5-fluorouracil, doxorubicin, and mitomycin-C was administered to 17 patients with locally advanced pancreatic cancer. The median survival for these patients was 8 months. With a multiaxial retrospective analysis, the overall survival of this study group appears to be least equivalent to that reported with 6,000 photon rad alone or of neutrons, and compares favorably to that achieved with combined 6,000 photo rad plus 5-fluorouracil. Of 15 relapses, only 4 had presented with evidence of disseminated disease. Based upon this analysis we recommend additional studies of combination chemotherapy with radiation therapy in future prospective randomized trials.
Post-Traumatic Stress Outcomes in Non-Hodgkin's Lymphoma Survivors
Authors: Sophia K. Smith, Sheryl Zimmerman, Christianna S. Williams, John S. Preisser, Elizabeth C. Clipp
Journal: Journal of Clinical Oncology (2008)

A large body of evidence suggests that being diagnosed with and treated for cancer adversely affects functioning and quality of life, yet less is known about longer term outcomes. Therefore, this study aims to estimate the prevalence of post-traumatic stress disorder (PTSD) symptoms in survivors of adult non-Hodgkin's lymphoma (NHL) who are at least 2 years postdiagnosis and identify the risk factors associated with PTSD symptoms, with a focus on those that are amenable for screening and modifiable.A total of 886 NHL survivors identified from the cancer registries of two hospitals in North Carolina participated, ranging in age from 25 to 92 years old and ranging from 2 to 44 years postdiagnosis. Survivors were mailed a survey that assessed PTSD symptoms and quality of life.Participants averaged 10.2 years postdiagnosis, and most (61%) reported no PTSD symptoms. The adjusted prevalence for full PTSD was 7.9%, with an additional 9.1% meeting criteria for partial PTSD. Modifiable risk factors that were independently associated with PTSD in multiple linear regression included less social support, negative appraisals of life threat and treatment intensity, and more employment and insurance issues. Additionally, several demographic characteristics (nonwhite race, less education, and younger age) and clinical or health-related factors (active disease, more recent diagnosis, and more comorbidity) were independently associated with PTSD.Although only 8% of survivors met PTSD diagnostic criteria, the impact of a cancer diagnosis and treatment persists for many survivors, as evidenced in 39% of this sample. Early identification of those at risk could enable treatment to minimize PTSD symptomatology.