tbuckley/cabot-search huggingface dataset:
Досвід застосування психокорегуючої терапії в комплексному лікуванні хворих на гастроезофагеальну рефлюксну хворобу, поєднану з дисфункцією жовчовивідної системи
Authors: L.V. Demeshkina, L.M. Mosiychuk, O.P. Petishko, E.V. Zygalo, I.Yu. Zavyalova
Journal: GASTROENTEROLOGY (2016)

У сучасну епоху внаслідок бурхливого зростання числа стресорних факторів особливо велике значення мають психотерапія та психофармакотерапія в комплексному лікуванні хворих із захворюваннями шлунково-кишкового тракту. Психогенні нашарування відіграють провідну роль у клінічній картині захворювання та визначають зниження працездатності пацієнтів. Мета. Оцінити ефективність лікування із застосуванням психокорегуючого засобу у хворих на гастроезофагеальну рефлюксну хворобу (ГЕРХ), поєднану з дисфункцією жовчовивідної системи, при наявності у них депресивних і тривожних проявів. Матеріали та методи. Всі хворі були розподілені на дві групи: І групу становили 27 хворих, які отримували тільки комплексне базове лікування, ІІ групу — 25 пацієнтів, яким додатково до базисного лікування призначався тіоридазин, що є піперидиновим похідним фенотіазину та належить до групи нейролептиків. Обидві групи були репрезентативні за віком, тривалістю та перебігом захворювань. У всіх пацієнтів за допомогою шкали HADS були виявлені тривожно-депресивні прояви. Для аналізу якості життя був використаний опитувальник SF‑36. Ефективність терапії оцінювали через 14 діб. Результати. У результаті лікування в обох групах спостерігали покращення загального самопочуття на фоні зменшення больового та диспептичного синдромів. При додаванні психокорегуючого засобу (тіоридазину) до базисної терапії відзначалися більш виражені позитивні зміни за інтенсивністю тривожно-депресивних проявів. Розподіл пацієнтів за рівнем тривоги та депресії після лікування виявив, що відсутність цих показників частіше відзначалась хворими ІІ групи (в 2,6 та 1,5 раза відповідно). Проте в 4,6 та 3,7 раза більше встановлено випадків клінічно вираженої тривоги і депресії в групі пацієнтів, які не отримували тіоридазин. Різниця у балах між рівнем тривоги і депресії до та після лікування була в 4 рази більшою у хворих, які додатково отримували психокорекцію. Також у ІІ групі спостерігалося більш значне покращення показника якості життя при порівнянні балів до та після лікування. Висновок. Включення до основної терапії тіоридазину за наявності депресивних і тривожних порушень у хворих на ГЕРХ, поєднану з дисфункцією жовчовивідної системи, підвищує клінічну ефективність фармакотерапії даної коморбідної патології.
Multi-targeted inhibition of the epidermal growth factor (EGFR) and vascular endothelial growth factor receptor (VEGFR) pathways: A phase I study of cetuximab (C), erlotinib (E), and bevacizumab (B) in patients with solid tumors
Authors: G. G. Preston, E. Calvo, K. Papadopoulos, A. Patnaik, A. Mita, J. Sarantopoulos, M. Mita, P. O’Rourke, C. Takimoto, A. Tolcher
Journal: Journal of Clinical Oncology (2006)

3005 Background: Complex interrelationships exist between the EGFR and VEGFR pathways. EGFR activation elicits cell proliferation, and downstream effects increase expression of VEGF. In renal cell carcinoma, mutations increase hypoxia inducible factor-1alpha, stimulating VEGF and transforming growth factor expression. Moreover, there is additive tumor inhibition from combined EGFR targeting with C, and a tyrosine kinase inhibitor. To maximally inhibit EGFR, and then inhibit downstream VEGFR activity, this phase I study was initiated to determine the maximum tolerated dose (MTD) of E with a fixed dose of C, and then the MTD of B with combined E and C in patients with advanced malignancies. Methods: Patients with advanced malignancies likely to express EGFR were entered in part 1 to daily oral E (starting at 100mg, planned initially to increase to 150 mg), with fixed dose C (400 mg/m 2 loading and 250 mg/m 2 IV weekly). Once the MTD was determined for E in combination C, part 2 incorporated the addition of escalating doses of B (5 mg/kg IV every 2 weeks, to increase to 10 mg/kg) to the combination of E and C. Results: 27 patients were entered and received 84 courses over 3 dose levels. In part 1 grade 3 rash occurred in 2 patients at E at 100 mg daily, and the MTD of E for this combination was 50 mg daily with standard dose C (12 patients treated). Other adverse events included rash, diarrhea, hypomagnesemia, and nausea. Part 2: B at 5 mg/kg IV q14 days can be added to the MTD of E with C, with additional non-dose limiting toxicities of headache, proteinuria, and hypertension. Durable stable disease has been observed in 4 patients with metastatic disease for 7 (sqaumous cell); 10+, 12, and 12+ (renal cell) months. Conclusions: The MTD for E combined with standard C is 50 mg daily. B at 5mg/kg can be combined safely with this combination and dose escalation is ongoing. [Table: see text]
Prospective Pilot Study to Evaluate the Incremental Value of PET Information in Patients With Bladder Cancer Undergoing 18F-FDG Simultaneous PET/MRI
Authors: Andrew B. Rosenkrantz, Kent P. Friedman, Fabio Ponzo, Roy A. Raad, Kimberly Jackson, William C. Huang, Arjun V. Balar
Journal: Clinical Nuclear Medicine (2016)

The aim of this study was to conduct a prospective pilot study comparing the diagnostic performance of MRI alone and F-FDG simultaneous PET/MRI using a diuresis protocol in bladder cancer patients.Twenty-two bladder cancer patients underwent F-FDG PET/MRI, using intravenous furosemide and oral hydration for bladder clearance. A radiologist scored probability of tumor in 3 locations (urinary bladder, pelvic lymph nodes, nonnodal pelvis) using 1- to 3-point scale (1 = negative, 2 = equivocal, 3 = definite tumor). A nuclear medicine physician reviewed fused PET/MRI images, after which scores were reassigned based on combined findings. Follow-up pathologic and imaging data served as reference. Performances of MRI alone and PET/MRI were compared.Of these patients, 82%, 38%, and 18% were positive for bladder, pelvic nodal, and nonnodal pelvic tumor, respectively. At a score of 3, PET/MRI exhibited greater accuracy for detection of bladder tumor (86% vs 77%), metastatic pelvic lymph nodes (95% vs 76%), and nonnodal pelvic malignancy (100% vs 91%). In the bladder, PET changed the level of suspicion in 36% of patients (50% increased suspicion, 50% decreased suspicion), with 75% of these changes deemed correct based on reference standard. For pelvic lymph nodes, PET changed suspicion in 52% (36% increase, 64% decrease), with 95% of changes deemed correct. For nonnodal pelvis, PET changed suspicion in 9% (100% increase), with 100% deemed correct.Additional PET information helped to appropriately determine level of suspicion in multiple anatomic sites for otherwise equivocal findings on MRI alone. Although requiring larger studies, findings suggest a possible role for simultaneous PET/MRI to assist bladder cancer management.
The Quality of Outpatient Care Delivered to Adults in the United States, 2002 to 2013
Authors: David M. Levine, Jeffrey A. Linder, Bruce E. Landon
Journal: JAMA Internal Medicine (2016)

Widespread deficits in the quality of US health care were described over a decade ago. Since then, local, regional, and national efforts have sought to improve quality and patient experience, but there is incomplete information about whether such efforts have been successful.To measure changes in outpatient quality and patient experience in the United States from 2002 to 2013.We analyzed temporal trends from 2002 to 2013 using quality measures constructed from the Medical Expenditure Panel Survey (MEPS), a nationally representative annual survey of the US population that collects data from individual respondents as well as respondents' clinicians, hospitals, pharmacies, and employers. Participants were noninstitutionalized US adults 18 years or older (range, 20 679-26 509 individuals each year).Outpatient quality measures were compiled through a structured review of prior studies and measures endorsed by national organizations. Nine clinical quality composites (5 "underuse" composites, eg, recommended medical treatment; 4 "overuse" composites, eg, avoidance of inappropriate imaging) based on 39 quality measures; an overall patient experience rating; and 2 patient experience composites (physician communication and access) based on 6 measures.From 2002 to 2013 (MEPS sample size, 20 679-26 509), 4 clinical quality composites improved: recommended medical treatment (from 36% to 42%; P < .01), recommended counseling (from 43% to 50%; P < .01), recommended cancer screening (from 73% to 75%; P < .01), and avoidance of inappropriate cancer screening (from 47% to 51%; P = .02). Two clinical quality composites worsened: avoidance of inappropriate medical treatments (from 92% to 89%) and avoidance of inappropriate antibiotic use (from 50% to 44%; P < .01 for both comparisons). Three clinical quality measures were unchanged: recommended diagnostic and preventive testing (76%), recommended diabetes care (68%), and inappropriate imaging avoidance (90%). The proportion of participants highly rating their care experience improved for overall care (from 72% to 77%), physician communication (from 55% to 63%), and access to care (from 48% to 58%; P < .01 for all comparisons).Despite more than a decade of efforts, the clinical quality of outpatient care delivered to American adults has not consistently improved. Patient experience has improved. Deficits in care continue to pose serious hazards to the health of the American public.
Late Cytomegalovirus Disease after Hematopoietic Cell Transplantation (HCT) in the Preemptive Therapy Era: Characteristics, Efficacy of PCR-Based Surveillance, and Impact on Mortality
Authors: Sezen Özkök, Hu Xie, Zach Stednick, Sachiko Seo, Michael Boeckh, Margaret L Green
Journal: Blood (2014)
A phase II trial of capecitabine (C) in combination with the farnesyltransferase (FT) inhibitor (FTI), tipifarnib (T), in patients (pt) with metastatic breast cancer (MBC): ECOG trial 1103
Authors: M. Wang, W. J. Gradishar, J. A. Sparano, E. A. Perez, G. Sledge
Journal: Journal of Clinical Oncology (2007)

1036 Background: Approximately 30% of human cancers have mutated Ras genes that produce proteins that remain in an active state causing uncontrolled proliferative signals. Post-translational modification of Ras include farneyslation catalyzed by FT. Tipifarnib (R115777) is an oral FTI active against human tumor cell lines and exhibiting modest single agent activity in pts with previously treated MBC. A previous phase I trial reported that CT inhibited farneyslation in peripheral blood mononuclear cells without affecting the pharmacokinetics of either agent. Objective: To evaluate objective response rate (ORR) of CT in taxane refractory MBC and to secondarily evaluate associated toxicity and progression-free survival (PFS). Methods: Pt with measurable MBC, previously treated (rx) with an anthracycline and relapse on a taxane or within 30 days (d). Study rx: T- 300 mg, po BID × 14 d plus C- 1,000 mg/m 2 , po BID × 14 d, followed by 7 d rest. Tumor reassessment was repeated q 3 cycles. The study was designed to detect improvement in ORR from 25% with C alone to 40% for the CT combination (90.5% power; type I error rate of 9.9%; 21 responses in 64 eligible pt needed to be promising. Results: 66/71 pt are available for primary analysis. Median age 50 yrs. Performance status: 0–1, 100%. ORR: PR-4.8% (3/62) [95% CI 0.01, 0.13], SD - 21% (13/62) [ 95% CI 0.12, 0.33]. Median survival - 10.6 months. Toxicity (%): anemia - 8(G3/4), neutropenia - 30 (G3/4), thrombocytopenia - 8 (G3/4), HFS-8 (G3), nausea/vomiting - 11(G3), diarrhea - 8 (G3), sensory neuropathy - 5 (G3). Conclusion: CT in taxane -refractory MBC has low antitumor activity without excessive toxicity. More mature data, including PFS, will be presented. No significant financial relationships to disclose.
Infections Are a Major Cause of Prolongation of Hospital Stay in Hematopoietic Stem Cell Transplants in Tropical, Developing Countries: Profile of a Transplant Center in North India
Authors: Deepesh P Lad, Pankaj Malhotra, Alka Khadwal, Gaurav Prakash, Pallab Ray, Baijayantimala Mishra, Chakrabarti Aranoloke, Subhash Varma
Journal: Blood (2014)
Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation
Authors: J Kanda, Y Morishima, S Terakura, A Wake, N Uchida, S Takahashi, Y Ono, Y Onishi, H Kanamori, N Aotsuka, Y Ozawa, H Ogawa, T Sakura, K Ohashi, T Ichinohe, K Kato, Y Atsuta, T Teshima, M Murata
Journal: Leukemia (2016)
GW26-e2302 Non-vitamin K Antagonist Oral Anticoagulants (NOACs) in Patients with Atrial Fibrillation and Heart Failure: A Systemic Review and Meta-analysis of randomized trials
Authors: Qinmei Xiong, Yeecheng Lau, Keitaro Senoo, Kui Hong, Gregory YH Lip
Journal: Journal of the American College of Cardiology (2015)
Phase I Study of Vaccination with Dendritic Cell Myeloma Fusions.
Authors: David Avigan, Jacalyn Rosenblatt, Baldev Vasir, Zekui Wu, Adam Bissonnette, Claire MacNamara, Lynne Uhl, Corrinne Lenahan, Kenneth Miller, Robin Joyce, James D. Levine, Karen Lowe, Dilani Dombagoda, Paul Richardson, Kenneth Anderson, Nikhil Munshi, Donald Kufe
Journal: Blood (2007)
Variability of biomarkers in patients with chronic heart failure and healthy controls
Authors: Wouter C. Meijers, A. Rogier van der Velde, Anneke C. Muller Kobold, Janneke Dijck‐Brouwer, Alan H. Wu, Allan Jaffe, Rudolf A. de Boer
Journal: European Journal of Heart Failure (2016)

Biomarkers can be used for diagnosis, risk stratification, or management of patients with heart failure (HF). Knowledge about the biological variation is needed for proper interpretation of serial measurements. Therefore, we aimed to determine and compare the biological variation of a large panel of biomarkers in healthy subjects and in patients with chronic HF.The biological variability of established biomarkers [NT-proBNP and high-sensitivity troponin T (hsTnT)], novel biomarkers [galectin-3, suppression of tumorigenicity 2 (ST2), and growth differentiation factor 15 (GDF-15)], and renal/neurohormonal biomarkers (aldosterone, phosphate, parathyroid hormone, plasma renin concentration, and creatinine) was determined in 28 healthy subjects and 83 HF patients, over a period of 4 months and 6 weeks, respectively. The analytical (CVa ), intraindividual (CVi ), and interindividual (CVg ) variations were calculated, as well as the reference change value (RCV), which reflects the percentage of change that may indicate a 'relevant' change. All crude biomarker levels were significantly increased or decreased in HF patients compared with controls (all P < 0.01). Variation indices were comparable in healthy individuals and HF patients. CVi was not influenced by the individual levels of the biomarker itself. NT-proBNP and GDF-15 had relatively high CVi (21.8% and 16.6%) and RCV (61.7% and 64.3%), whereas ST2 (CVi , 15.0; RCV, 42.9%), hsTnT (CVi , 11.1; RCV, 31.4%), and galectin-3 (CVi , 8.1; RCV, 25.0%) had lower indices of variation.Biological variation indices are comparable between healthy subjects and HF patients for a broad spectrum of biomarkers. NT-proBNP and GDF-15 have substantial variation, with lower variation for ST2, hsTnT, and galectin-3. These data are instrumental in proper interpretation of biomarker levels in HF patients.
Validation of NAD(P)H quinone oxidoreductase (NQO1) expression as a predictive factor for adjuvant chemotherapy benefit in patients with early breast cancer.
Authors: Monica Arnedos, Aicha Goubar, Kam M. Sprott, Chunsheng Jiang, Jessica Suschak, David T. Weaver, Suzette Delaloge, Rosa Conforti, Fabrice Andre
Journal: Journal of Clinical Oncology (2012)

1091 Background: NAD(P)H:quinone oxidoreductase-1 (NQO1) has important antioxidant functions by stabilizing p53 from proteasomal degradation. NQO1 knockdown is associated with higher susceptibility to oxidative stress. Polymorphisms suppressing NQO1 are predictors of poor survival in patients with breast cancer (BC) treated with anthracyclines. BC cell lines with impaired NQO1 function showed resistance to epirubicin chemotherapy (CT) independently of p53 status suggesting NQO1 as predictive factor for anthracycline benefit. In this study we hypothesized that lack of NQO1 could predict resistance to anthracycline-containing CT in patients with early breast cancer (EBC). Methods: Patients were identified from two French multicentric trials that randomized patients with EBC to adjuvant anthracycline-based CT vs no CT between 1988 and 1995. NQO1 was determined in TMAs by automated quantitative assessment of immunofluorescence (On-Q-ity Inc, Waltham). Cut-off for positivity was the median value of NQO1 expression. Univariate and multivariate Cox regression models were performed. Treatment effect was assessed on long term overall survival (OS). Results: NQO1 expression was assessed in 600 patients. 75% were postmenopausal, had more often grade II (62%), LN-negative (58%) and ER-positive (67%) BC. Higher NQO1 expression was observed in postmenopausal (P=0.02) patients. No relation with other clinicopathological factors (grade, LN or ER) was observed. Effect of adjuvant CT on death rates was dependant on NQO1 level. Hazard ratio (HR) for treatment efficacy at the four quartiles of NQO1 were 1.07 (95%CI: 0.69-1.7), 0.87 (0.64-1.19), 0.66 (0.45-0.97), 0.46 (0.22-0.95) (interaction test: 0.1). Interaction test was statistically significant (0.02) when NQO1 expression was considered as binary variable with median value taken as cut-off. NQO1 remained predictive among ER+ patients only. HR for OS was 0.61 (0.36-1.02) and 1.25 (0.79-1.99) in patients with high and low NQO1 respectively. Conclusions: This study adds to the existing data suggesting NQO1 expression as an independent predictor of efficacy for adjuvant anthracycline-containing CT.
Abstract IA12: Stromal cells in the targeting and transport of tumor-penetrating peptides
Authors: Erkki Ruoslahti, Erkki Ruoslahti
Journal: Cancer Research (2016)

Abstract This laboratory studies tissue-specific vascular markers, “vascular zip codes”, and their use in selective targeting of drugs to diseased tissues. Screening of phage libraries in live mice identifies peptides that direct phage homing to a specific target in the body. When the libraries are injected into the circulation, tissue-specific or tumor-specific differences in endothelial cells are primarily targeted. The endothelial target molecules are frequently also expressed by other tumor stromal cells and tumor cells, but not cells in normal tissues. Recently discovered tumor-penetrating peptides, through a complex mechanism that involves a proteolytic cleavage and binding to a second receptor, activate an endocytic transport pathway related to but distinct from macropinocytosis. This trans-tissue pathway, dubbed the CendR pathway, mediates the exit of payloads ranging from small molecule drugs to nanoparticles from the blood vessels and transport through extravascular tumor tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a drug, antibody, or nanoparticle payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Remarkably the payload does not have to be coupled to the peptide; the peptide activates a bulk transport system that sweeps along any compound that is present in the blood. Treatment studies in mice show improved anti-tumor efficacy and less damage to normal tissues. Citation Format: Erkki Ruoslahti, Erkki Ruoslahti. Stromal cells in the targeting and transport of tumor-penetrating peptides. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr IA12.
Abstract PR10: A glycoprotein-mediated mechanical switch promotes glioma aggression
Authors: J Matthew Barnes, Yekaterina A. Miroshnikova, Jason C. Tung, Russel O. Bainer, Valerie M. Weaver
Journal: Cancer Research (2016)

Abstract Glioblastoma multiforme (GBM) is a malignant brain tumor whose progression is associated with rampant extracellular matrix (ECM) remodeling. We recently found that ECM stiffness correlates with poor survival in human GBM specimens. Glycoproteins are the major constituent of normal brain ECM and many are overexpressed in brain tumors, yet the interplay between glycoproteins and mechanical signaling in GBM pathogenesis remains poorly understood. Here, we show that bulky glycoproteins and sugar-binding proteins are broadly upregulated in GBM relative to lower grade gliomas. Further, these genes are overexpressed in the mesenchymal (Mes) relative to the proneural (Pro) GBM subclass, the former of which is associated with treatment resistance and relapse. We took a specific interest in the hyaluronic acid (HA)-producing enzyme, HAS2, and the galactoside-binding lectin galectin-1 (Gal1) due to their ability to modulate tissue structure and rheology. Using mouse models of human GBM we showed that Mes tumors are enriched in HA and fibronectin, coincident with elevated ECM stiffness and mechanical signaling. These data suggest the possibility that aberrant glycoprotein expression drives GBM aggression through enhanced mechanical signaling resulting from tissue stiffening. Consistent with this hypothesis, by elevating mechanical signaling in Pro GBMs we induce a robust Mes-like transition and we see the opposite when reducing Gal1 expression or HA content in Mes tumors. Our data provides evidence of a feed-forward mechanism whereby mechanical signaling drives Gal1 and HA production which reinforce ECM stiffness, thus sustaining pro-tumorigenic mechanical signaling. This abstract is also presented as Poster A21. Citation Format: J Matthew Barnes, Yekaterina A. Miroshnikova, Jason C. Tung, Russel O. Bainer, Valerie M. Weaver. A glycoprotein-mediated mechanical switch promotes glioma aggression. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr PR10.
An Innovative High-Throughput Ex Vivo Drug Assay Incorporating the Native Microenvironment Reveals a Novel Mechanism of Action of Idelalisib in CLL
Authors: Joan Ballesteros, Lydia Scarfo, Mattias Mattsson, Aliki Xochelli, Pamela Ranghetti, Daniel Primo, Alicia Robles, Julian Gorrochategui, Joaquin Martinez-Lopez, Javier De la Serna, Marcos González, Veerendra Munugalavadla, Richard Rosenquist, Kostas Stamatopoulos, Christophe Quéva, Paolo Ghia
Journal: Blood (2015)