tbuckley/cabot-search huggingface dataset:
Safety and immunogenicity of immunotherapy with Bet v 1–derived contiguous overlapping peptides
Authors: François Spertini, Yannick Perrin, Régine Audran, Céline Pellaton, Caroline Boudousquié, Nathalie Barbier, Anne-Christine Thierry, Vincent Charlon, Christophe Reymond
Journal: Journal of Allergy and Clinical Immunology (2014)
Tumor Necrosis Factor-α Promotes Malignant Pleural Effusion
Authors: Georgios T. Stathopoulos, Androniki Kollintza, Charalampos Moschos, Ioannis Psallidas, Taylor P. Sherrill, Emmanuel N. Pitsinos, Spyridoula Vassiliou, Marilena Karatza, Spyros A. Papiris, Daniel Graf, Dora Orphanidou, Richard W. Light, Charis Roussos, Timothy S. Blackwell, Ioannis Kalomenidis
Journal: Cancer Research (2007)

Abstract Tumor necrosis factor (TNF)-α is present in the microenvironment of human tumors, including malignant pleural effusion (MPE). Although the cytokine is produced in the pleural cavity by both tumor and host cells, its effects on MPE formation are unknown. In these studies, we sought to determine the role of TNF-α in the pathogenesis of MPE and to assess the therapeutic effects of its neutralization in a preclinical model. For this, MPEs were generated in immunocompetent mice using intrapleural injection of mouse lung adenocarcinoma cells. The roles of tumor- and host-derived TNF-α were assessed using combined experimentation with TNF-α gene–deficient mice and in vivo TNF-α neutralization. To expand the scope of preclinical data, TNF-α and vascular endothelial growth factor (VEGF) expression were determined in human cancer cell lines and human MPE. In the MPE model, TNF-α of host and tumor origin was present. TNF-α neutralization significantly limited tumor dissemination, effusion formation, vascular hyperpermeability, TNF-α and VEGF expression, and angiogenesis, thereby improving survival. In contrast, these variables were not different between TNF-α gene–sufficient and TNF-α gene–deficient mice. In mouse cancer cells, TNF-α functioned via nuclear factor-κB– and neutral sphingomyelinase–dependent pathways to induce TNF-α and VEGF, respectively. These results were recapitulated in human cancer cells, and a correlation was detected between TNF-α and VEGF content of human MPE. We conclude that tumor-derived TNF-α is important in the development of MPE in mice, and provide preclinical evidence supporting the efficacy of TNF-α blockade against malignant pleural disease. [Cancer Res 2007;67(20):9825–34]
Angiotensin Receptor Blockade and Risk of Cancer in Type 2 Diabetes Mellitus: A Nationwide Case-Control Study
Authors: Chia-Hsuin Chang, Jou-Wei Lin, Li-Chiu Wu, Mei-Shu Lai
Journal: Journal of Clinical Oncology (2011)

The objective of this case-control study was to evaluate the risk of malignancy in diabetic patients who received angiotensin receptor blockers (ARBs).A total of 21,750 new diabetic patients who started antihypertensive treatment were identified from the Taiwan National Health Insurance claims database during the period from July 1, 2000, to December 31, 2000. As of December 31, 2007, patients with incident cancer were included as cases and up to four age- and sex-matched controls were selected by risk-set sampling. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% CIs between ARB use and cancer incidence, adjusted for other types of antihypertensive drugs, insulin, oral hypoglycemic agents, statins, and underlying diseases.Among the 1,281 patients with incident cancer and 5,104 controls, 333 (26.0%) and 1,341 (26.3%), respectively, received ARBs (OR, 0.98; 95% CI, 0.85 to 1.14). There was no statistically significant association between the effect of ARBs as a class and cancer incidence after adjustment for covariates (OR, 0.94; 95% CI, 0.80 to 1.10). Among the individual ARBs, losartan decreased the risk (OR, 0.78; 95% CI, 0.63 to 0.97) and candesartan (OR, 1.79; 95% CI, 1.05 to 3.06) and telmisartan (OR, 1.54; 95% CI, 0.97 to 2.43) possibly increased the risk of occurrence of malignancy.The results did not show an effect of ARBs as a class on increasing cancer incidence in patients with diabetes. However, there was a negative association of losartan but a positive one of candesartan and telmisartan with the overall occurrence of cancer. The underlying mechanism certainly requires further investigation.
SPECTRUM OF EPSTEIN-BARR VIRUS–ASSOCIATED DISEASES
Authors: J.L. Kutok, F. Wang
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

The association between Epstein-Barr virus (EBV) and a large number of benign and malignant diseases is unique among DNA viruses. Within infected tissues, proteins that are expressed during the normal lytic and latent viral life cycle lead to cellular alterations that contribute to these EBV-associated diseases. Although the early events of EBV infection are poorly understood, increasing knowledge of the viral processes that govern viral latency has shed light upon the potential mechanisms by which EBV infection can lead to cellular transformation. Our current understanding of the role of EBV in the development of Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and other EBV-associated diseases is discussed.
EXPLAINING FATIGUE IN CONGESTIVE HEART FAILURE
Authors: Helmut Drexler, M.D, Andrew J.S. Coats, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract Fatigue is a prominent symptom in patients with chronic heart failure, limiting physical activity and impairing quality of life. Although the underlying mechanisms are not clearly identified, alterations associated with peripheral adaptation in heart failure appear to play an important role, including a variably impaired peripheral perfusion during exercise, reduced oxidative capacity of skeletal muscle, impaired muscle strength, and possibly reflex mechanisms associated with alterations in the metabolism of skeletal muscle. Exercise training can, in part, reverse these peripheral alterations, improve exercise capacity, and alleviate fatigue.
Hormone-responsive Ca2+ entry in distal convoluted tubules.
Authors: P A Friedman, F A Gesek
Journal: Journal of the American Society of Nephrology (1994)

This editorial review focuses on recent observations regarding the mechanism and regulation of calcium transport in hormone-sensitive distal convoluted tubules. Parathyroid hormone (PTH) and calcitonin increase active calcium absorption by distal convoluted tubules. Occupancy of these peptide hormone receptors results in the activation of both protein kinase A and protein kinase C. The inhibition of either kinase blocks calcium transport. The time course of stimulation of calcium entry in distal convoluted tubules by PTH is slow compared with that by calcitonin. The latency associated with PTH action may be due to the induction of protein synthesis. PTH and calcitonin hyperpolarize membrane voltage, which in turn increases calcium entry. Calcium entry is mediated by calcium channels. These channels exhibit a low, single-channel conductance and are sensitive to dihydropyridine-type calcium channel blockers. Unlike L-type calcium channels, the channel open probability of distal convoluted tubule calcium entry channels is increased upon hyperpolarization. This novel combination of properties suggests that the underlying structure of these calcium entry channels may be unique.
Tracing of cells of the avian thymus through embryonic life in interspecific chimeras.
Authors: N M Le Douarin, F V Jotereau
Journal: The Journal of Experimental Medicine (1975)

Differences in the structure of the interphase nucleus between two species of birds, the Japanese quail (Coturnix coturnix japonica) and the chick (Gallus gallus) has been used to distinguish cells from different origins in interspecies combinations. This biological cell marking technique was applied to thymus histogenesis. Using various combinations between components of quail and chick thymic rudiments, the respective contribution of endodermal epithelium, mesenchyme, and blood-borne extrinsic elements to the histogenesis of thymus was analyzed. It was demonstrated that the whole lymphoid population of the thymus is derived from immigrant blood-borne stem cells which are chemically attracted by the endoderm of the 3rd and 4th pharyngeal pouch. The latter is determined to differentiate into thymic epithelial reticulum as soon as the 15-somite stage, and is able to attract blood stem cells even when transplanted in an heterotopic position such as the ventral body wall of the embryo. It was shown that the thymic mesenchyme originates from the neural crest mesectoderm which colonizes early the 3rd and 4th branchial arches. It participates in the formation of perivascular mesenchyme, but does not give rise to lymphocytes. From heterospecific transplantations of quail thymuses into chick embryo (and inversely) at various stages of development is appeared that the thymic rudiment becomes attractive for lymphoid stem cells at a precise stage of its evolution for each species. The attractivity period lasts about 24 h for the quail and 36 h for the chick. Then, the inflow of stem cells becomes very low until the end of the incubation period. At this time, a second wave of lymphocytoblasts invades the thymus and the primitive embryonic lymphoid population is completely renewed around the hatching time. Competent thymic stem cells are present in the blood before and after the period of physiological thymic attractivity. The identity of basophilic cells appearing in the thymus during its histogenesis and lymphoid stem cells has been demonstrated from the analysis of quail-chick chimeric thymuses.
Mandatory second opinion to reduce rates of unnecessary caesarean sections in Latin America: a cluster randomised controlled trial
Authors: Fernando Althabe, José M Belizán, José Villar, Sophie Alexander, Eduardo Bergel, Silvina Ramos, Mariana Romero, Allan Donner, Gunilla Lindmark, Ana Langer, Ubaldo Farnot, José G Cecatti, Guillermo Carroli, Edgar Kestler
Journal: The Lancet (2004)
Antro-pyloro-duodenal motor responses to gastric and duodenal nutrient in critically ill patients
Authors: M Chapman
Journal: Gut (2005)

<b>Background:</b> Gastric emptying is frequently delayed in critical illness which compromises the success of nasogastric nutrition. The underlying motor dysfunctions are poorly defined. <b>Aims:</b> To characterise antro-pyloro-duodenal motility during fasting, and in response to gastric and duodenal nutrient, as well as to evaluate the relationship between gastric emptying and motility, in the critically ill. <b>Subjects:</b> Fifteen mechanically ventilated patients from a mixed intensive care unit; 10 healthy volunteers. <b>Methods:</b> Antro-pyloro-duodenal pressures were recorded during fasting, after intragastric administration (100 ml; 100 kcal), and during small intestinal infusion of liquid nutrient (6 hours; 1 kcal/min). Gastric emptying was measured using a <sup>13</sup>C octanoate breath test. <b>Results:</b> In healthy subjects, neither gastric nor small intestinal nutrient affected antro-pyloro-duodenal pressures. In patients, duodenal nutrient infusion reduced antral activity compared with both fasting and healthy subjects (0.03 (0–2.47) waves/min <i>v</i> 0.14 (0–2.2) fasting (p = 0.016); and <i>v</i> 0.33 (0–2.57)/min in healthy subjects (p = 0.005)). Basal pyloric pressure and the frequency of phasic pyloric pressure waves were increased in patients during duodenal nutrient infusion (3.12 (1.06) mm Hg; 0.98 (0.13)/min) compared with healthy subjects (−0.44 (1.25) mm Hg; p&lt;0.02 after 120 minutes; 0.29 (0.15)/min; p = 0.0002) and with fasting (−0.06 (1.05) mm Hg; p&lt;0.03 after 160 minutes; 0.49 (0.13)/min; (p = 0.0001). Gastric emptying was delayed in patients (gastric emptying coefficient 2.99 (0.2) <i>v</i> 3.47 (0.1); p = 0.015) and inversely related to the number of pyloric pressure waves (<i>r</i> = −0.563, p = 0.029). <b>Conclusions:</b> Stimulation of pyloric and suppression of antral pressures by duodenal nutrient are enhanced in the critically ill and related to decreased gastric emptying.
Optimal arterial resistance for the maximal stroke work studied in isolated canine left ventricle.
Authors: K Sunagawa, W L Maughan, K Sagawa
Journal: Circulation Research (1985)

In a previous analysis of ventricular arterial interaction (Sunagawa et al., 1983), we represented the left ventricle as an elastic chamber which periodically increases its volume elastance to a value equal to the slope of the linear end-systolic pressure-volume relationship. Similarly, the arterial load property was represented by an effective elastance which is the slope of the arterial end-systolic pressure-stroke volume relationship. Since the maximal transfer of potential energy from one elastic chamber to another occurs when they have equal elastance, we hypothesized that the left ventricle would do maximal external work if the ventricular elastance and the effective arterial elastance were equal. We tested this hypothesis in 10 isolated canine left ventricles, ejecting into a simulated arterial impedance, by extensively altering arterial resistance and finding the optimal resistance that maximized left ventricular stroke work under various combinations of end-diastolic volume, contractility, heart rate, and arterial compliance. Each of these parameters was set at one of three levels while others were at control. The optimal resistance varied only slightly with arterial compliance, whereas it varied widely with contractility and heart rate. We thus determined that the ratio of the optimal effective arterial elastance to the given ventricular elastance remained nearly unity. This result supports the hypothesis that the left ventricle does maximal external work to the arterial load when the ventricular and arterial elastances are equalized.
Prospective Study of Serum γ-Glutamyltransferase and Risk of NIDDM
Authors: Ivan J Perry, S Goya Wannamethee, A Gerald Shaper
Journal: Diabetes Care (1998)

OBJECTIVE Serum γ-glutamyltransferase (GGT) levels are raised inobese individuals, and a particularly strong association with central obesity has been described. We hypothesized that elevated GGT levels are a marker for visceral fat, and specifically for hepatic steatosis (fatty liver), and that hepatic steatosis leads to hepatic insulin resistance. To test this hypothesis, we examined the association between GGT levels and risk of NIDDM. RESEARCH DESIGN AND METHODS We carried out a prospective cohort study of incident cases of doctor-diagnosed NIDDM in a group of 7,458 nondiabetic men (aged 40–59 years) followed for a mean of 12.8 years (range 11.5–13.0). The men were randomly selected from general practice lists in 24 British towns. Cases of NIDDM were ascertained by repeated postal questionnaires to the men and by regular systematic review of primary care records. RESULTS A total of 194 men developed NIDDM during follow-up. Mean serum GGT at baseline (geometric mean [95% Cl]) was significantly higher in the NIDDM patients than in the rest of the cohort (20.9 [19.3–22.6] vs. 15.3 U/l [15.0–15.6], P &amp;lt; 0.0001). There was a smooth, graded increase in the age-adjusted risk of NIDDM with increasing GGT levels, with a relative risk in the top fifth of the distribution of 6.8 (3.5–12.9) relative to the bottom fifth (trend P &amp;lt; 0.0001). This association was independent of serum glucose and BMI and of other predictors of NIDDM with which GGT is associated, including alcohol intake and physical activity level (adjusted upper to lower fifth relative risk: 4.8 [2.0–11.8], trend P &amp;lt; 0.0001]). CONCLUSIONS These findings suggest that a raised serum GGT levelis an independent risk factor for NIDDM. Serum GGT level may be a simple andreliable marker of visceral and hepatic fat and, by inference, of hepatic insulin resistance.
Chimmitecan, a Novel 9-Substituted Camptothecin, with Improved Anticancer Pharmacologic Profiles <i>In vitro</i> and <i>In vivo</i>
Authors: Min Huang, Heyong Gao, Yi Chen, Hong Zhu, Yujun Cai, Xiongwen Zhang, Zehong Miao, Hualiang Jiang, Jian Zhang, Hongwu Shen, Liping Lin, Wei Lu, Jian Ding
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This study aimed to evaluate antitumor activities and pharmacologic profiles of chimmitecan, a novel 9-small-alkyl–substituted lipophilic camptothecin, in comparison with irinotecan (CPT-11) and topotecan. Experimental Design: The in vitro cytotoxities of chimmitecan in human tumor cell lines and multidrug resistance (MDR) cells were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and sulforhodamin B assays. DNA relaxation, cleavage assays, and cellular band depletion assay were combined to delineate its effects on topoisomerase I. DNA damage, cell cycle arrest, and apoptosis were assessed using comet assay, flow cytometry, and DNA ladder analysis, respectively. The in vivo antitumor activities were measured in nude mice bearing human tumor xenografts. Results: Chimmitecan displayed more potent cytotoxicity than SN38 and topotecan. Neither a cross-resistance to chimmitecan in MDR cells nor an influence of human serum albumin in its cytotoxity was observed. Chimmitecan exhibited comparable effects on topoisomerase I compared with the reference drugs, including inhibiting topoisomerase I catalytic activity and trapping and stabilizing covalent topoisomerase I-DNA complexes. Furthermore, nanomolar levels of chimmitecan caused impressive DNA damage, G2-M phase arrest, and apoptosis in human leukemia HL60 cells. I.v. administration of chimmitecan inhibited the growth of HCT-116, MDA-MB-435, BEL-7402, and A549 human carcinoma xenografts in nude mice, with greater potency than CPT-11 against the latter two tumors models. Chimmitecan presented potent efficacy in A549 tumor model when given orally. Conclusions: Chimmitecan is a potent inhibitor of topoisomerase I and displays outstanding activity in vitro and in vivo. The substitution at the 9-position benefits chimmitecan a salient anti-MDR activity, stability in human serum albumin, improved solubility, and oral availability, which might favorably promise its therapeutic potential in clinical settings.
Platinum-Etoposide Chemotherapy in Elderly Patients With Small-Cell Lung Cancer: Results of a Randomized Multicenter Phase II Study Assessing Attenuated-Dose or Full-Dose With Lenograstim Prophylaxis—A Forza Operativa Nazionale Italiana Carcinoma Polmonare and Gruppo Studio Tumori Polmonari Veneto (FONICAP-GSTPV) Study
Authors: Andrea Ardizzoni, Adolfo Favaretto, Luca Boni, Editta Baldini, Federico Castiglioni, Paola Antonelli, Franca Pari, Carmelo Tibaldi, Alfonso M. Altieri, Sante Barbera, Giancarlo Cacciani, Mario Raimondi, Lucia Tixi, Micaela Stefani, Silvio Monfardini, Antonio Antilli, Riccardo Rosso, Adriano Paccagnella
Journal: Journal of Clinical Oncology (2005)

Purpose Small-cell lung cancer (SCLC) is increasingly diagnosed in elderly patients, who are at higher risk of treatment-related morbidity and mortality. We conducted a randomized two-stage phase II study to assess the therapeutic index of two different platinum/etoposide regimens, attenuated-dose (AD) and full-dose (FD) plus prophylactic lenograstim. Patients and Methods SCLC patients older than 70 years were randomized to receive four courses of cisplatin 25 mg/m 2 on days 1 and 2, and etoposide 60 mg/m 2 on days 1, 2, and 3 every 3 weeks (AD); or cisplatin 40 mg/m 2 on days 1 and 2, and etoposide 100 mg/m 2 on days 1, 2, and 3 every 3 weeks, plus lenograstim 5 mg/kg days 5 through 12, every 3 weeks (FD). A combined primary end point named therapeutic success (TS), which took into account activity, toxicity, and compliance, was used. Results Ninety-five patients were enrolled. Seventy-five percent and 72% of the patients in the AD and FD arms, respectively, completed the treatment as per protocol. Response rate was 39% and 69% in the AD and FD arms, respectively, and 1-year survival probability was 18% and 39%, respectively. Treatment was well tolerated in both groups, with no grade 3 to 4 myelotoxicity in the AD arm, and 12% myelotoxicity in the FD arm. Overall, the observed TSs were 10 (36%) of 28 patients and 42 (63%) of 67 patients for AD and FD treatments, respectively. Conclusion In elderly patients with SCLC a full-dose cisplatin/etoposide regimen combined with prophylactic lenograstim is active and feasible, while attenuated doses of the same regimen are associated with a poor therapeutic outcome.
The Role of Wnt Signaling in Physiological and Pathological Angiogenesis
Authors: Elisabetta Dejana
Journal: Circulation Research (2010)

Early stages of vascular development include endothelial cell differentiation in a network of arteries, veins, and lymphatics. Subsequently, to respond to the specific needs of the organs, endothelial cells acquire specialized properties such as permeability control, expression of specific transcellular transport systems, membrane adhesive molecules, and others. Endothelial cell differentiation depends on communication between the surrounding tissues, which is mediated by growth and differentiation factors able to activate specific gene expression programs. Recent reports underline the important role of the Wnt system in vascular morphogenesis in the embryo and in organ-specific endothelial differentiation. Wnt signaling regulates fundamental aspects of development, including cell fate specification, proliferation, and survival, and may use different receptors and signaling pathways. Both loss- and gain-of-function experiments of members of the Wnt signaling pathway were found to cause marked alterations of vascular development and endothelial cell specification. Furthermore, altered Wnt signaling in the endothelium may contribute to pathological conditions such as retinopathies, pulmonary arterial hypertension, stroke, and others. Continued progress in this field holds the potential to identify novel therapeutics for the treatment of these diseases.
Neo-adjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase II study
Authors: C. Carlomagno, A. Farella, L. Bucci, F.P. D'Armiento, G. Pesce, S. Pepe, L. Cannella, R. Pacelli, A. De Stefano, R. Solla, M.R. D'Armiento, S. De Placido
Journal: Annals of Oncology (2009)
Value of prothrombin fragments F1+2 in the diagnosis of pulmonary embolism in patients hospitalized due to COPD exacerbation
Authors: Marinella Beckerman, Paltiel Weiner
Journal: European Respiratory Journal (2011)

Background:  One of four COPD patients who require hospitalization for an acute exacerbation may have pulmonary embolism. Normal D-dimer is now considered to be safe enough for ruling out thromboembolism in patients with a low pretest provability. However, 9% of patients with AECOPD with low clinical provability may still have PE, and D-dimer is normal only in minority of patients with AECOPD. The combining of D-Dimer testing with another markers of thrombosis may improve of the diagnostic efficiency.   Aim:  To assess the usefulness of F1+2 in the diagnosis of PE in hospitalized patients with exacerbation of COPD; and whether assay of F1+2 may have an additional value in the subgroup of patients with an abnormal D- dimer. To determine the sensitivity, specificity, NPV of F1+2 at various cut off values.   Methods:  Blood samples for F1+2 and D-dimer were obtained and CT pulmonary angiography was perfomed in 49 patients hospitalized due to AECOPD.   Results:  Prevalence of PE was 18.37%. Patients with proved pulmonary embolism had higher values of F1+2: 380 pmol/l (95% CI 235.5 - 523.7;) than in patients with high D-dimer level in whom PE was not confirmed: 204 pmol/l (95% CI 140.2 - 268.6; p- 0.0042).  At cutoff levels for F1+2 180 pmol/L or lower the sensitivity was 100%, and negative predicted value – 1,0. Taking a normal F1+2 level (cut-off 180) into account in the subgroup of patients with an abnormal D-dimer added significant clinical significance:11 of 29 patients (37.9%) could be withheld from additional imaging testing.   Conclusions:  Prothrombin fragment F1+2 assay may increase the proportion of patients in whom pulmonary embolism can be safely ruled out.