tbuckley/cabot-search huggingface dataset:
Intensified Platinum Therapy Is an Ineffective Strategy for Improving Outcome in Pediatric Patients With Advanced Hepatoblastoma
Authors: Marcio H. Malogolowkin, Howard Katzenstein, Mark D. Krailo, Zhengjia Chen, Laura Bowman, Marleta Reynolds, Milton Finegold, Brian Greffe, Jon Rowland, Kurt Newman, Richard B. Womer, Wendy B. London, Robert P. Castleberry
Journal: Journal of Clinical Oncology (2006)

The INT-0098 Intergroup Liver Tumor Study demonstrated no statistically significant differences in event-free and overall survival between patients randomized to treatment with either cisplatin + fluorouracil + vincristine (C5V) or cisplatin + doxorubicin. Results from this and other therapeutic trials suggested that cisplatin was the most active agent against hepatoblastoma. To increase the platinum dose-intensity, a novel regimen was developed alternating carboplatin and cisplatin (CC) every 2 weeks. The P9645 study was designed to compare the risk of treatment failure for patients with stage III/IV hepatoblastoma randomized to either C5V or CC.C5V was given according to INT-0098 and CC consisted of carboplatin at 700 mg/m2 on day 0 (560 mg/m2 after two cycles) followed by cisplatin 100 mg/m2 on day 14. Granulocyte colony-stimulating factor was used after each CC cycle. All patients received four to six cycles of chemotherapy.From the time the study was opened until the time that random assignment was halted, 56 patients received CC and 53 patients received C5V. The 1-year event-free survival was 37% for patients receiving CC and 57% for those receiving C5V (P = .017). Patients randomly assigned to CC required more blood product support. As a result of a semiannual review by the Children's Oncology Group Data and Safety Monitoring Committee, random assignment was discontinued after 3 years of enrollment because the projected improvement in long-term outcome associated with CC was statistically excluded as a possible outcome of this trial.Intensification of therapy by alternating platinum analogs increased the risk of adverse outcome in children with unresectable or metastatic hepatoblastoma.
Clustering of genes into regulons using integrated modeling-COGRIM
Authors: Guang Chen, Shane T Jensen, Christian J Stoeckert
Journal: Genome biology (2007)

Abstract We present a Bayesian hierarchical model and Gibbs Sampling implementation that integrates gene expression, ChIP binding, and transcription factor motif data in a principled and robust fashion. COGRIM was applied to both unicellular and mammalian organisms under different scenarios of available data. In these applications, we demonstrate the ability to predict gene-transcription factor interactions with reduced numbers of false-positive findings and to make predictions beyond what is obtained when single types of data are considered.
Autoreactive, Cytotoxic T Lymphocytes Specific for Peptides Derived from Normal B-Cell Differentiation Antigens in Healthy Individuals and Patients with B-Cell Malignancies
Authors: Matthias Grube, Katayoun Rezvani, Adrian Wiestner, Hiroshi Fujiwara, Giuseppe Sconocchia, Jan J. Melenhorst, Nancy Hensel, Gerald E. Marti, Larry W. Kwak, Wyndham Wilson, John A. Barrett
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To investigate potential immunotherapeutic strategies in B lymphocytic malignancies we looked for CTLs recognizing CD19 and CD20 epitopes. Experimental Design: Three CD19 and CD20 peptides binding to HLA-A*0201 were identified and used to detect peptide specific CTLs by a quantitative real-time PCR to measure IFN-γ mRNA expression in 23 healthy individuals and 28 patients (18 chronic lymphocytic leukemia (CLL), 7 follicular lymphoma, 2 acute lymphocytic leukemia, and 1 large cell lymphoma). Peptide-specific CTLs were expanded in culture with CD40-activated B cells to test lytic activity in three patients. Results: In healthy individuals, CD8+ T-cell responses were detected in one to CD1974–82, in three to CD20127–135, and three to CD20188–196. Seven of 27 patients (6 with CLL) had CD8+ T cells recognizing CD1974–82. Seven patients responded to CD20127–135 and three to CD20188–196. All were CLL patients. CD1974–82-specific CTLs from three patients were expanded over 4 weeks. These cells were HLA-A*0201 specific and lytic for peptide-loaded antigen-presenting cells but not to malignant or unpulsed B cells. Conclusions: CTLs that recognize CD19 and CD20 epitopes exist in healthy individuals and may be increased in CLL patients. They are of low avidity and require high doses of peptide for activation. Strategies to increase T-cell avidity would be necessary for T-cell immunotherapeutic approaches using the peptides studied.
Dependence of Paclitaxel Sensitivity on a Functional Spindle Assembly Checkpoint
Authors: Tamotsu Sudo, Masayuki Nitta, Hideyuki Saya, Naoto T. Ueno
Journal: Cancer Research (2004)

Abstract Paclitaxel stabilizes microtubules, causing mitotic arrest and activating the spindle assembly checkpoint. We determined whether suppression of the checkpoint genes Mad2 and BubR1 affects paclitaxel resistance and whether overexpression of Mad2 protein in checkpoint-defective cells enhances paclitaxel sensitivity. Suppression of Mad2 and BubR1 in paclitaxel-treated cancer cells abolished checkpoint function, resulting in paclitaxel resistance that correlated with suppression of cyclin-dependent kinase-1 activity. In contrast, overexpression of Mad2 in cells with a checkpoint defect attributable to low Mad2 expression restored checkpoint function, resulting in enhanced paclitaxel sensitivity that correlated with enhanced cyclin-dependent kinase-1 activity. However, overexpression of Mad2 failed to enhance paclitaxel sensitivity via checkpoint activation in Mad2-independent checkpoint-defective and -intact cells. Thus, checkpoint function is required for paclitaxel sensitivity. These findings show that any molecules that could interfere with the spindle assembly checkpoint could generate paclitaxel resistance in any patient.
A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne
Authors: John S. Strauss, James J. Leyden, Anne W. Lucky, Donald P. Lookingbill, Lynn A. Drake, Jon M. Hanifin, Nicholas J. Lowe, Terry M. Jones, Daniel M. Stewart, Michael T. Jarratt, Irving Katz, David M. Pariser, Robert J. Pariser, Eduardo Tschen, Dan K. Chalker, Elyse S. Rafal, Ronald P. Savin, Harry L. Roth, Lawrence K. Chang, David J. Baginski, Steven Kempers, John McLane, Douglas Eberhardt, Eileen E. Leach, Graeme Bryce, Joseph Hong
Journal: Journal of the American Academy of Dermatology (2001)
Maternal inheritance of atopic IgE responsiveness on chromosome 11 q
Authors: W.O.C.M Cookson, R.P Young, A.J Sandford, M.F Moffatt, T Shirakawa, P.A Sharp, J.A Faux, P.N Le Souef, C Julier, G.M Lathrop, Y Nakumura, J.M Hopkin
Journal: The Lancet (1992)
Adhesion molecule expression on skin endothelia in atopic dermatitis: Effects of TNF-α and IL-4
Authors: I.Jolanda M. de Vries, Elisabeth G. Langeveld-Wildschut, Frank C. van Reijsen, Gerald R. Dubois, J.Annet van den Hoek, Ilse C. Bihari, Dick van Wichen, Roel A. de Weger, Edward F. Knol, Theo Thepen, Carla A.F.M. Bruijnzeel-Koomen
Journal: Journal of Allergy and Clinical Immunology (1998)
Psychodynamic Therapy and Cognitive-Behavioral Therapy in Social Anxiety Disorder: A Multicenter Randomized Controlled Trial
Authors: Falk Leichsenring, Simone Salzer, Manfred E. Beutel, Stephan Herpertz, Wolfgang Hiller, Juergen Hoyer, Johannes Huesing, Peter Joraschky, Bjoern Nolting, Karin Poehlmann, Viktoria Ritter, Ulrich Stangier, Bernhard Strauss, Nina Stuhldreher, Susan Tefikow, Tobias Teismann, Ulrike Willutzki, Joerg Wiltink, Eric Leibing
Journal: American Journal of Psychiatry (2013)

Objective Various approaches to cognitive-behavioral therapy (CBT) have been shown to be effective for social anxiety disorder. For psychodynamic therapy, evidence for efficacy in this disorder is scant. The authors tested the efficacy of psychodynamic therapy and CBT in social anxiety disorder in a multicenter randomized controlled trial. Method In an outpatient setting, 495 patients with social anxiety disorder were randomly assigned to manual-guided CBT (N=209), manual-guided psychodynamic therapy (N=207), or a waiting list condition (N=79). Assessments were made at baseline and at end of treatment. Primary outcome measures were rates of remission and response, based on the Liebowitz Social Anxiety Scale applied by raters blind to group assignment. Several secondary measures were assessed as well. Results Remission rates in the CBT, psychodynamic therapy, and waiting list groups were 36%, 26%, and 9%, respectively. Response rates were 60%, 52%, and 15%, respectively. CBT and psychodynamic therapy were significantly superior to waiting list for both remission and response. CBT was significantly superior to psychodynamic therapy for remission but not for response. Between-group effect sizes for remission and response were small. Secondary outcome measures showed significant differences in favor of CBT for measures of social phobia and interpersonal problems, but not for depression. Conclusions CBT and psychodynamic therapy were both efficacious in treating social anxiety disorder, but there were significant differences in favor of CBT. For CBT, the response rate was comparable to rates reported in Swedish and German studies in recent years. For psychodynamic therapy, the response rate was comparable to rates reported for pharmacotherapy and cognitive-behavioral group therapy.
Well controlled, double-blind, placebo-controlled trials of classical Ayurvedic treatment are possible in rheumatoid arthritis
Authors: D. E. Furst, M. M. Venkatraman, B. G. Krishna Swamy, M. McGann, C. Booth-LaForce, P. Ram Manohar, R. Sarin, A. Mahapatra, P. R. Krishna Kumar
Journal: Annals of the Rheumatic Diseases (2010)

The objective of this short communication is to demonstrate the feasibility and effectiveness of multiple placebos to individualise treatment when using classical Ayurveda for rheumatoid arthritis in well controlled, double-blind, placebo-controlled trials.

A total of 46 patients ≥18 years of age, with active rheumatoid arthritis as diagnosed using American College of Rheumatology criteria, were randomised to 1 of 3 outpatient treatment groups: methotrexate+placebo Ayurveda; Ayurveda+placebo methotrexate; and methotrexate+Ayurveda. The Ayurvedic doctor was free to choose from 148 formulations, which were in the form of 6 traditional dosage forms: decoctions, herbal powders, pills, herbal wines, herbal jams and herb-infused oils. Six placebos were also formulated, with each placebo representing a dosage form.

All appropriate institutional review board approvals were obtained. Formulations were …
Adult Xp11 Translocation Renal Cell Carcinoma Diagnosed by Cytogenetics and Immunohistochemistry
Authors: Yoshinobu Komai, Mutsunori Fujiwara, Yasuhisa Fujii, Hiroyuki Mukai, Junji Yonese, Satoru Kawakami, Shinya Yamamoto, Toshiro Migita, Yuichi Ishikawa, Morito Kurata, Takuro Nakamura, Iwao Fukui
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To determine the incidence of Xp11 translocation renal cell carcinoma (RCC) in adult patients using cytogenetics and immunohistochemstry. Experimental Design: Cytogenetic studies were prospectively done using tumor samples from 443 consecutive adult Japanese patients (ages 15-89 years) who underwent nephrectomy for RCC. TFE3 immunohistochemistry was done for cases in which cytogenetic results were not obtained. Clinicopathologic characteristics of Xp11 translocation RCC were examined. Results: Mitotic cells suitable for cytogenetic analysis were obtained in 244 tumor samples (55%); among these, we identified 4 cases (1.6%) of Xp11 translocation RCC. TFE3 immunohistochemistry identified 3 positive cases (1.5%) among the remaining 199 cases. The median age of the 7 patients was 41 years (range, 15-59 years), and 15% of RCC patients (4 of 26) who were younger than ages 45 years had this type of RCC. Of the four Xp11 translocation RCC patients whose karyotypes were determined, two had an ASPL-TFE3 gene fusion. Of these 2, 1 had pulmonary metastasis at presentation, and the other developed liver metastasis 12 months after nephrectomy and died of the disease. The remaining two patients had PRCC-TFE3 and PSF-TFE3 gene fusions, respectively. Both had nodal involvement but remained disease free for 3 and 5 years, respectively, after surgical resection of lymph node metastases. Of the 3 immunohistochemically diagnosed patients, 1 had nodal metastases at presentation and died 9 months after surgery. Conclusions: This is the first report to determine the incidence of Xp11 translocation RCC in adult patients. We found that this disease is relatively common in young adults.
The Role of Microsporidia in the Pathogenesis of HIV-Related Chronic Diarrhea
Authors: Linda Rabeneck, Ferenc Gyorkey, Robert M. Genta, Phyllis Gyorkey, Lorraine W. Foote, Jan M. H. Risser
Journal: Annals of Internal Medicine (1993)

Objective: To determine whether infection with Microsporidia leads to diarrhea in patients with human immunodeficiency virus (HIV) infection. Design: Case-control study. Setting: Primary care outpatient HIV clinic at a Veterans Affairs medical center. Patients: One hundred six HIV-infected men, 55 with and 51 without chronic diarrhea. Measurements: Each patient underwent upper endoscopy and flexible sigmoidoscopy to obtain duodenal, rectal, and sigmoid colonic biopsy specimens. At the time of endoscopy, a fresh stool was obtained for culture, ova and parasite assessment, and Cryptosporidium examination. Biopsy tissue was examined using electron microscopy to detect Microsporidia. Results: The microsporidian parasite Enterocytozoon bieneusi was detected in the duodenal biopsy specimens of 31 of 106 men (29%); 24 of 106 men (23%) had other enteric pathogens. No significant difference was observed in the occurrence of microsporidiosis in patients with (18 of 55 [33%]) and without (13 of 51 [25%]) chronic diarrhea (odds ratio, 1.42; 95% CI, 0.61 to 3.31). A similar nonsignificant difference was observed after controlling for CD4 count and other enteric pathogens (odds ratio, 1.66; 95% CI, 0.68 to 4.06). Among patients with microsporidiosis, no difference was observed in the intensity of infection (defined by the presence of few, moderate, or abundant organisms) among cases and controls (P > 0.2). Conclusions: This is the first report to document the presence of E. bieneusi in HIV-positive patients without gastrointestinal symptoms. No significant difference was observed in the occurrence of E. bieneusi infection in HIV-infected patients with or without chronic diarrhea. Thus, the association between microsporidiosis and diarrhea, if one exists, may not be as strong as is currently believed.
Hepatic Steatosis in Hepatitis C: Comparison of Diabetic and Nondiabetic Patients in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial
Authors: Anna S.F. Lok, James E. Everhart, Raymond T. Chung, Latha Padmanabhan, Joel K. Greenson, Mitchell L. Shiffman, Gregory T. Everson, Karen L. Lindsay, Herbert L. Bonkovsky, Adrian M. Di Bisceglie, William M. Lee, Timothy R. Morgan, Marc G. Ghany, Chihiro Morishima
Journal: Clinical Gastroenterology and Hepatology (2007)
Origin of the Genetic Components of the Vomeronasal System in the Common Ancestor of all Extant Vertebrates
Authors: W. E. Grus, J. Zhang
Journal: Molecular Biology and Evolution (2008)

Comparative genomics provides a valuable tool for inferring the evolutionary history of physiological systems, particularly when this information is difficult to ascertain by morphological traits. One such example is the vomeronasal system (VNS), a vertebrate nasal chemosensory system that is responsible for detecting intraspecific pheromonal cues as well as environmental odorants. The morphological components of the VNS are found only in tetrapods, but the genetic components of the system have been found in teleost fish, in addition to tetrapods. To determine when the genetic components of the VNS originated, we searched for the VNS-specific genes in the genomes of two early diverging vertebrate lineages: the sea lamprey from jawless fishes and the elephant shark from cartilaginous fishes. Genes encoding vomeronasal type 1 receptors (V1Rs) and Trpc2, two components of the vomeronasal signaling pathway, are present in the sea lamprey genome, and both are expressed in the olfactory organ, revealing that the genetic components of the present-day VNS existed in the common ancestor of all extant vertebrates. Additionally, all three VNS genes, Trpc2, V1Rs, and vomeronasal type 2 receptors (V2Rs), are found in the elephant shark genome. Because V1Rs and V2Rs are related to two families of taste receptors, we also searched the early diverging vertebrate genomes for taste system genes and found them in the shark genome but not in the lamprey. Coupled with known distributions of the genetic components of the vertebrate main olfactory system, our results suggest staggered origins of vertebrate sensory systems. These findings are important for understanding the evolution of vertebrate sensory systems and illustrate the utility of the genome sequences of early diverging vertebrates for uncovering the evolution of vertebrate-specific traits.
Consequences of Radial Artery Harvest
Authors: William L. Holman, James E. Davies, Julia Y. Lin, Yajie Wang, Steven Goldman, Faisal G. Bakaeen, Rosemary Kelly, Stephen E. Fremes, Kelvin K. Lee, Todd H. Wagner, Gulshan K. Sethi
Journal: JAMA Surgery (2013)

To date, no study has defined the consequences of radial artery harvest based on a large number of patients in a prospective randomized trial.To compare pain at the harvest site and functional changes associated with harvesting the radial artery vs saphenous vein for coronary artery bypass grafting.This study compares the consequences of radial artery harvest with saphenous vein harvest in patients undergoing elective coronary artery bypass grafting procedures in Veterans Affairs hospitals.Eleven hospitals screened 6148 patients, of whom 751 were included in this trial. We analyzed 2 variables: pain at the harvest site as measured on a scale of 0 to 100 (least to most painful) and hand performance testing. Patients included in this analysis had radial artery only (n = 80) or saphenous vein only (n = 337) harvest. Pain score, grip strength, and dexterity were measured before surgery and at 3 and 12 months after surgery. We adjusted for pain scores of the nonharvested extremity, age, whether the patient underwent endoscopic vein harvesting, and comorbid health conditions (smoking history, type 2 diabetes mellitus, hypertension, and heart failure).There was a significant difference in change of pain score at 3 months from the preoperative baseline between radial artery and saphenous vein groups after adjusting for covariates (P < .001) but not at 12 months (P = .07). No significant changes occurred in grip strength or dexterity from preoperative baseline to 3 and 12 months after surgery (P > .05).The radial artery group reported significantly more pain than the saphenous vein group 3 months after surgery; however, similar levels of pain were observed in both groups at 12 months after surgery. Grip strength and manual dexterity were not changed by radial artery harvesting at 3 and 12 months.
Functional Plasminogen Activator Inhibitor-1 Gene Variants and Breast Cancer Survival
Authors: Xianglan Zhang, Xiao-Ou Shu, Qiuyin Cai, ZhiXian Ruan, Yu-Tang Gao, Wei Zheng
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Plasminogen activator inhibitor-1 (PAI-1) plays an important role in cancer invasion and metastasis. A common polymorphism (4G/5G) in the promoter region of the PAI-1 gene has been reported to influence transcription and plasma levels of PAI-1. We evaluated the association between PAI-1 4G/5G polymorphism and breast cancer survival in a population-based cohort of breast cancer patients. Experimental Design: Included in this analysis were 1,083 Chinese women diagnosed with stage 0 to III primary breast cancer at age 25 to 64 years who were recruited between 1996 and 1998 for the Shanghai Breast Cancer Study and followed for a median of 5.2 years. The Kaplan-Meier method and Cox model were used to evaluate the genotype and survival association. Results: After adjustment for known prognostic factors for breast cancer, patients homozygous for the 4G allele had significantly poorer disease-free survival [hazard ratio (HR), 1.7; 95% confidence interval (95% CI), 1.1-2.4] and overall survival (HR, 1.5; 95% CI, 1.0-2.3) than those homozygous for the 5G allele. The association was more evident in patients with advanced disease. The HRs (95% CI) were 3.5 (1.4-9.0) for disease-free survival and 3.1 (1.1-8.3) for overall survival in stage III patients. Conclusions: The PAI-1 4G/5G polymorphism may be a prognostic marker for young and middle-aged Chinese breast cancer patients.
Post-transcriptional regulation of tumour necrosis factor alpha production
Authors: P. Anderson
Journal: Annals of the Rheumatic Diseases (2000)

Tumour necrosis factor α (TNFα) is a proinflammatory cytokine produced by activated macrophages, lymphocytes and other cells.1-3 The production of TNFα is under transcriptional and post-transcriptional control.4-10Post-transcriptional control of TNFα expression is achieved by regulating translational initiation, mRNA stability, and polyadenylation.6 7 10 An adenine and uridine (AU)-rich element (ARE) in the 3' untranslated region (3' UTR) of TNFα transcripts11-13 is an important determinant of post-transcriptional control. Transfer of this element to heterologous reporter transcripts changes the expression of the reporter protein. Transacting factors that bind to the ARE and participate in post-transcriptional control have recently been identified. The ARE binding proteins expressed in a given cell are thought to determine the level of protein expression.

The 3' untranslated region of mRNAs encoding short lived immediate early genes (for example, fos, jun) as well as selected cytokines (for example, TNFα, GM-CSF) possess AU-rich elements that regulate protein expression. Class I AREs consist of one or more pentamer repeats (that is, AUUUA), whereas class II AREs consist of one or more nonamer repeats (that is, AUUUAUUUA). Whereas class I AREs are sufficient to promote the degradation of transcripts encoding immediate early proteins, both class I and class II AREs regulate the production of cytokines such as TNFα, GM-CSF, interleukin 3 (IL3) and interferon α (IFNα). The 3' untranslated region of TNFα transcripts contains both class I and class II AREs. Electrophoretic mobility shift assays have identified two distinct regulatory complexes that assemble on these adjacent cis elements in HeLa cells.14 15 The complex assembled on the class II ARE (designated complex 1) includes the related RNA binding proteins TIA-1 …