tbuckley/cabot-search huggingface dataset:
A Personalized Preclinical Model to Evaluate the Metastatic Potential of Patient-Derived Colon Cancer Initiating Cells
Authors: Isabel Puig, Irene Chicote, Stephan P. Tenbaum, Oriol Arqués, José Raúl Herance, Juan D. Gispert, José Jimenez, Stefania Landolfi, Karina Caci, Helena Allende, Leire Mendizabal, Debora Moreno, Ramón Charco, Eloy Espín, Aleix Prat, Maria Elena Elez, Guillem Argilés, Ana Vivancos, Josep Tabernero, Santiago Rojas, Héctor G. Palmer
Journal: Clinical Cancer Research (2013)

Within the aim of advancing precision oncology, we have generated a collection of patient-derived xenografts (PDX) characterized at the molecular level, and a preclinical model of colon cancer metastasis to evaluate drug-response and tumor progression.We derived cells from 32 primary colorectal carcinomas and eight liver metastases and generated PDX annotated for their clinical data, gene expression, mutational, and histopathological traits. Six models were injected orthotopically into the cecum wall of NOD-SCID mice in order to evaluate metastasis. Three of them were treated with chemotherapy (oxaliplatin) and three with API2 to target AKT activity. Tumor growth and metastasis progression were analyzed by positron emission tomography (PET).Patient-derived cells generated tumor xenografts that recapitulated the same histopathological and genetic features as the original patients' carcinomas. We show an 87.5% tumor take rate that is one of the highest described for implanted cells derived from colorectal cancer patients. Cecal injection generated primary carcinomas and distant metastases. Oxaliplatin treatment prevented metastasis and API2 reduced tumor growth as evaluated by PET.Our improved protocol for cancer cell engraftment has allowed us to build a rapidly expanding collection of colorectal PDX, annotated for their clinical data, gene expression, mutational, and histopathological statuses. We have also established a mouse model for metastatic colon cancer with patient-derived cells in order to monitor tumor growth, metastasis evolution, and response to treatment by PET. Our PDX models could become the best preclinical approach through which to validate new biomarkers or investigate the metastatic potential and drug-response of individual patients.
Anti-CCP antibodies are a collection of ACPA that are cross-reactive to multiple citrullinated antigens
Authors: A Ioan-Facsinay, H el-Bannoudi, H U Scherer, D van der Woude, H A Menard, M Lora, L A Trouw, T W J Huizinga, R E M Toes
Journal: Annals of the Rheumatic Diseases (2010)

Anti-citrullinated protein/peptide antibodies (ACPA/anti-CCP) are a hallmark of rheumatoid arthritis and are believed to play a role in disease pathogenesis. These antibodies are typically detected in ELISA with citrullinated peptides (eg, CCP2) or -proteins as antigens. The absolute concentration of anti-CCP antibodies in serum is unknown. Although …
Relationship between estrogen receptor, progesterone receptor, HER-2 and Ki67 expression and efficacy of aromatase inhibitors in advanced breast cancer
Authors: H. Anderson, M. Hills, L. Zabaglo, R. A'Hern, A.F. Leary, B.P. Haynes, I.E. Smith, M. Dowsett
Journal: Annals of Oncology (2011)
Use of the paediatric bronchoscope, flexible and rigid, in 51 European centres
Authors: A Barbato, M Magarotto, M Crivellaro, A Novello, A Cracco, J de Blic, P Scheinmann, JO Warner, M Zach
Journal: European Respiratory Journal (1997)

We have undertaken a survey to establish current practices and differences in the use of bronchoscopes in children in European centres. A questionnaire was sent to all 220 members of the Paediatric Assembly of the European Respiratory Society (ERS). The questions concerned the following points: indications for bronchoscopy; site of bronchoscopy; type of sedation; any oxygen supplementation during the procedure; number of procedures performed in the previous 12 months; number of procedures performed in the neonatal intensive care unit; number of bronchoalveolar lavages (BALs); side-effects during and after the procedures; and diagnostic yield. Fifty one European centres (40.8% of the European centres contacted) took part in the study. A total of 7,446 bronchoscopies had been performed in the last 12 months: 4,587 using the flexible bronchoscope and 2,859 using the rigid bronchoscope. At centres using only the fibreoptic bronchoscope, the most frequent indication was "recurrent/persistent pneumonia" (17%); at centres using only the rigid bronchoscope, it was "foreign body inhalation" (36.7%); at centres using both methods, the most frequent indication was "other indications" (23.9%). In 12 months, 2,231 BALs were performed: 1,419 in immunocompetent children and 812 in immunocompromised patients. In centres using only the fibreoptic bronchoscope, the highest yield was for "stridor" (81%); in centres using only the rigid bronchoscope, the highest yield was for "persistent atelectasis" (68%); and in centres using both instruments, it was for "foreign body inhalation" (93%). The results of the study suggest that bronchoscopy in children is now a well-established procedure at several European centres, while others are just beginning to use this technique.
Predicting the spatial organization of chromosomes using epigenetic data
Authors: Raphaël Mourad, Olivier Cuvier
Journal: Genome biology (2015)

Chromosome folding can reinforce the demarcation between euchromatin and heterochromatin. Two new studies show how epigenetic data, including DNA methylation, can accurately predict chromosome folding in three dimensions. Such computational approaches reinforce the idea of a linkage between epigenetically marked chromatin domains and their segregation into distinct compartments at the megabase scale or topological domains at a higher resolution. Please see related articles: http://dx.doi.org/10.1186/s13059-015-0741-y and http://dx.doi.org/10.1186/s13059-015-0740-z
Performance Characteristics of the New Definition of Diabetes
Authors: Carlos Lorenzo, Steven M. Haffner
Journal: Diabetes Care (2009)

A1C > or =6.5% has been recently proposed as the defining criterion for diabetes. However, performance characteristics of this definition have not been described.In the Insulin Resistance Atherosclerosis Study, we compared new to previous definitions of diabetes: 1999 World Health Organization (DM(1999WHO)) and 2003 American Diabetes Association based on fasting glucose alone (DM(FPG126)).Participants with A1C > or =6.5%, DM(1999WHO), and DM(FPG126) were 44 (5.2%), 132 (15.4%), and 61 (7.1%), respectively. In individuals with DM(1999WHO), mean, median, and interquartile range of A1C were 6.3, 5.9, and 5.5-6.6%, respectively; in individuals with DM(FPG126), mean, median, and interquartile range of A1C were 7.0, 6.6, and 6.0-7.1%.A1C > or =6.5% identifies fewer individuals than DM(1999WHO) or DM(FPG126). Studies are needed to determine that A1C > or =6.5% compromises neither blood pressure and lipid management in early diabetes nor the implementation of lifestyle interventions for diabetes prevention.
Antibiotics for Acute and Chronic Respiratory Infection in Patients with Chronic Obstructive Pulmonary Disease
Authors: Marc Miravitlles, Antonio Anzueto
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Prevention and effective treatment of exacerbations are major objectives in the management of patients with chronic obstructive pulmonary disease (COPD). Antibiotics are mainstay treatment for patients with severe COPD with an acute exacerbation that includes increased sputum purulence and worsening shortness of breath. Although such treatment is associated with clinical benefit, treatment failure and relapse rates may be high, particularly in cases of inadequate antibiotic therapy through incomplete resolution of the initial exacerbation and persistent bacterial infection. These aspects have led to recommendations for a stratified approach to antibiotic therapy based on patient characteristics associated with increased risk factors for failure. Patients at greatest risk for poor outcome (i.e., those with severe COPD) are likely to derive greatest benefit from early treatment with antibiotics. Long-term or intermittent antibiotic treatment has been shown to prevent COPD exacerbations and hospitalizations. These effects may be achieved by reducing bacterial load in the airways in stable state and/or bronchial inflammation. Although systemic antibiotics are likely to remain the core treatment for patients with moderate to severe exacerbated COPD, inhaled antibiotics may represent a more optimal approach for the treatment and prevention of COPD exacerbations in the future. Regardless of the route of administration, further studies are required to evaluate the potential long-term adverse events of antibiotics and the development of bacterial resistance.
Exercise-induced homeostatic perturbations provoked by singles tennis match play with reference to development of fatigue
Authors: Alberto Mendez-Villanueva, Jaime Fernandez-Fernandez, David Bishop
Journal: British Journal of Sports Medicine (2007)

This review addresses metabolic, neural, mechanical and thermal alterations during tennis match play with special focus on associations with fatigue. Several studies have provided a link between fatigue and the impairment of tennis skills proficiency. A tennis player's ability to maintain skilled on-court performance and/or optimal muscle function during a demanding match can be compromised as a result of several homeostatic perturbations, for example hypoglycaemia, muscle damage and hyperthermia. Accordingly, an important physiological requirement to succeed at competitive level might be the player's ability to resist fatigue. However, research evidence on this topic is limited and it is unclear to what extent players experience fatigue during high-level tennis match play and what the physiological mechanisms are that are likely to contribute to the deterioration in performance.
Mind the Gap: Potential for Rebounds during Antiangiogenic Treatment Breaks
Authors: John M.L. Ebos, Roberto Pili
Journal: Clinical Cancer Research (2012)

VEGF pathway inhibitors have shown benefits in many cancers, yet many (often controversial) questions remain about whether vascular and tumor regrowth can occur when therapy is stopped. Marked increases in endothelial cell proliferation could play a role in putative rebounds, potentially influencing overall efficacy, dosing schedules, and presurgical intervention strategies.
Predictors of premature gonadal failure in patients with systemic lupus erythematosus. Results from LUMINA, a multiethnic US cohort (LUMINA LVIII)
Authors: L A Gonzalez, G McGwin, S Duran, G J Pons-Estel, M Apte, L M Vila, J D Reveille, G S Alarcon
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To examine the predictors of time to premature gonadal failure (PGF) in patients with systemic lupus erythematosus from LUMINA, a multiethnic US cohort. <h3>Methods:</h3> PGF was defined according to the SLICC Damage Index (SDI). Factors associated with time to PGF occurrence were examined by univariable and multivariable Cox proportional hazards regression analyses: three models according to cyclophosphamide use, at T0 (model 1), over time (model 2) and the total number of intravenous pulses (model 3). <h3>Results:</h3> Thirty-seven of 316 women (11.7%) developed PGF (19 Texan–Hispanics, 14 African–Americans, four Caucasians and no Puerto Rican–Hispanics). By multivariable analyses, older age at T0 (hazards ratio (HR) = 1.10–1.14; 95% CI 1.02–1.05 to 1.19–1.23) and disease activity (Systemic Lupus Activity Measure-Revised) in all models (HR = 1.22–1.24; 95% CI 1.10–1.12 to 1.35–1.37), Texan–Hispanic ethnicity in models 2 and 3 (HR = 4.06–5.07; 95% CI 1.03–1.25 to 15.94–20.47) and cyclophosphamide use in models 1 and 3 (1–6 pulses) (HR = 4.01–4.65; 95% CI 1.55–1.68 to 9.56–13.94) were predictors of a shorter time to PGF. <h3>Conclusions:</h3> Disease activity and Texan–Hispanic ethnicity emerged as predictors of a shorter time to PGF while the associations with cyclophosphamide use and older age were confirmed. Furthermore, cyclophosphamide induction therapy emerged as an important determinant of PGF.
Modulation of Reactive Oxygen Species in Pancreatic Cancer
Authors: Melissa L.T. Teoh, Wenqing Sun, Brian J. Smith, Larry W. Oberley, Joseph J. Cullen
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The aim of the present study was to compare the effects of the three different forms of the antioxidant enzyme superoxide dismutase [i.e., manganese superoxide dismutase (MnSOD), copper zinc superoxide dismutase (CuZnSOD), and extracellular superoxide dismutase (EcSOD)] on the malignant phenotype of human pancreatic cancer. Experimental Design: Human pancreatic cancer cell lines were infected with adenoviral vectors containing the cDNAs for three different forms of the antioxidant enzyme SOD. Intratumoral injections of the adenoviral vectors were used in nude mice with human tumor xenografts. Results: Increases in immunoreactive protein and enzymatic activity were seen after infections with the AdMnSOD, AdCuZnSOD, or AdEcSOD constructs. Increased SOD activity decreased superoxide levels and increased hydrogen peroxide levels. Increasing SOD levels correlated with increased doubling time. Cell growth and plating efficiency decreased with increasing amounts of the adenoviral constructs, with the AdCuZnSOD vector having the greatest effect in decreasing in vitro tumor growth. In contrast, inhibiting endogenous SOD with small interfering RNA increased superoxide levels and promoted tumor growth. Of the three SODs, tumors grew the slowest and survival was increased the greatest in nude mice injected with the AdEcSOD construct. Conclusions: Scavenging plasma membrane–generated superoxide may prove beneficial for suppression of pancreatic cancer growth.
Clinical Studies of Phenylbutazone (Butazolidin) and Butapyrin (Irgapyrin) in Rheumatoid Arthritis, Rheumatoid Spondylitis, and Gout
Authors: E. G. Kidd, K. C. Boyce, R. H. Freyberg
Journal: Annals of the Rheumatic Diseases (1953)

Clinical trials oftwodrugs newtotheAmerican continent, phenylbutazone (Butazolidin) andbutapyrin, werebegunwiththeassumption thatany beneficial effect fromtheminvarious rheumatic diseases wouldbechiefly that ofproducing analgesia. Asthestudies progressed itbecameapparent that thedrugs hadmorethanananalgesic action inacute goutyarthritis, thatstudies ofbutapyrin couldbe discontinued, andthattheinvestigation couldbe focused onphenylbutazone. Butazolidin isthetrade nameforphenylbutazone,a totally newcompoundoriginally usedin Europeasasolubilizing agent forvarious analgesics givenbyintramuscular injection, notably fordimethylamino-antipyrin (aminopyrin). Butapyrin (marketed insomecountries under thenameofIrgapyrin) isasimple mixture ofequal parts ofphenylbutazone anddimethylamino-antipyrin
Molecular Heterogeneity of Inflammatory Breast Cancer: A Hyperproliferative Phenotype
Authors: Dang M. Nguyen, Kathy Sam, Anna Tsimelzon, Xiaoxian Li, Helen Wong, Syed Mohsin, Gary M. Clark, Susan G. Hilsenbeck, Richard M. Elledge, D. Craig Allred, Peter O'Connell, Jenny C. Chang
Journal: Clinical Cancer Research (2006)

Inflammatory breast cancer (IBC) is associated with very poor prognosis. The aims of this study are (a) to prospectively identify differential gene expression patterns associated with IBC and (b) to confirm these pathways using tissue arrays.For gene expression analysis, IBC (n=14) was clinically defined as rapid-onset cancer associated with erythema and skin changes, whereas non-IBC patients (n=20) had stage III breast cancers, and cDNA analysis was carried out using the Affymetrix (Santa Clara, CA) HG-U133A microarrays. Tissue arrays were constructed from paraffin-embedded material, and the molecular phenotype of 75 IBC was compared with results from>2,000 non-IBC.Gene expression analyses indicated that IBC has higher expression of genes associated with increased metabolic rate, lipid signaling, and cell turnover relative to non-IBC tumors. Consistent with the expression analysis, IBC had statistically higher Ki-67 (93% versus 11%; P<0.001). BAX expression, reflecting increased apoptosis and cell turnover, was significantly uniformly higher in almost all IBC (98% versus 66%; P<0.05), whereas the expression of Bcl-2 was not significantly different. IBC tumors were more likely to be steroid hormone receptor negative (estrogen receptor, 49% versus 30%; P=0.002; progesterone receptor, 68% versus 42%; P=0.001). The expression of tyrosine kinases was not significantly different. E-cadherin was found to be expressed in 87% of IBC, whereas the expression p53 was not significantly different.This study is one of the largest molecular analyses of IBC. Both IBC and non-IBC are genetically heterogeneous with consistent differences in the molecular phenotype of IBC.
PTH-Related Peptide (PTHrP) in Hypercalcemia
Authors: Gregory R Mundy, James R Edwards
Journal: Journal of the American Society of Nephrology (2008)

It is now 20 years since the tumor-associated factor parathyroid hormone–related peptide was identified. Since then, there have been significant changes in the understanding of the hypercalcemic syndromes associated with malignancy and with the role of this peptide in normal physiology as well as this specialized pathologic setting. Parathyroid hormone–related peptide has become a useful diagnostic tool in the differential diagnosis of hypercalcemia, and approaches to inhibit its expression or its effects by malignant cells hold promise for treating the hypercalcemia and osteolysis associated with some cancers.
A Report of the Work CARRIED OUT AT THE RADIUM INSTITUTE, LONDON, IN 1914
Authors: A. E. H. Pinch
Journal: BMJ (1915)

TiIls report deals with, tlle cases which presented tlheni- selves at tlhe Radium Institute from January 1st, December 31st, 1914, inclusive.Thie cases treated were in no instance selected.The only cases refused liave thlose in wlhich the patients were practically moribund, or in w'hichl the disease was of a kiudfor whlichl radium tllerapy was manifestly unisuitable.No examples of malignant disease-rodent ulcer alone excepted-hlave been treated othier tlan tllose in wlichl operation lhad been declared to be unjustifiable, or in wlich operation lad been lutely declined by tile patient.Tle term apparent cure," used in relation to cases malignant disease, must be interpreted as representing condition in wlhiclh all trace of tlle original lesion or lhas disappeared, in whiielc there is no sign of any rence, and in wliiell tlle patienit is, so far as can determined by a tlhorough and careful examination, any indication or symptom of the disease.Casesllave been classed uuder the heading improved" only wlheni the result of treatment lhas been to produce definite and mnarked degree of benefit, eitlher in the direc- tion of retardation of tlhe progress of the disease.diminu- tion in tlhe size of a growtlh,healing of ulceration and arrest of haemorrhlaae and disclharge, or of suchl subjective symnptoms as itching, tenderness, clyspnoea, and dysplhagia.Tle chlaracter of tllis report is in many respects simiiilar to tllat of tile reports previously published in 1913 1914.-br.Siommary of -Cases.Examinied, but not treated 95)Recently trea%ted, anid results niot yet noted Received prophylactic irradiationi only Apparently cuired..... .
Free radical activity and pro-inflammatory effects of particulate air pollution (PM10) in vivo and in vitro.
Authors: X. Y. Li, P. S. Gilmour, K. Donaldson, W. MacNee
Journal: Thorax (1996)

BACKGROUND: Epidemiological evidence has implicated fine particulate air pollution, particularly particles less than 10 microns in diameter (PM10), in the development of exacerbations of asthma and chronic obstructive pulmonary disease (COPD) although the mechanism is unknown. The hypothesis that PM10 particles induce oxidant stress, causing inflammation and injury to airway epithelium, was tested. METHODS: The effects of intratracheal instillation of PM10 was assessed in rat lungs (three per group). Inflammatory cell influx was measured by bronchoalveolar lavage (BAL) and air space epithelial permeability was assessed as the total protein in BAL fluid in vivo. The oxidant properties of PM10 particles were determined by their ability to cause damage to plasmid DNA and by changes in reduced (GSH) and oxidised (GSSG) glutathione. The effects of PM10 particles were compared in some experiments with those of fine (CB) and ultrafine (ufCB) carbon black particles. RESULTS: Six hours after intratracheal instillation of PM10 there was an influx of neutrophils (up to 15% of total cells in BAL fluid) into the alveolar space, increased epithelial permeability, the mean (SE) total protein in the BAL fluid increasing from 0.39 (0.01) to 0.62 (0.01) mg/ml, and increased lactate dehydrogenase (LDH) concentrations in the BAL fluid. An even greater inflammatory response was seen following intratracheal instillation of ufCB but not following CB instillation. PM10 particles had free radical activity in vivo, as shown by a decrease in GSH levels in the BAL fluid from 0.36 (0.05) to 0.25 (0.01) nmol/ml following instillation. The free radical activity of PM10 was confirmed in vitro by its ability to deplete supercoiled plasmid DNA, an effect which could be reversed by mannitol, a specific hydroxyl radical scavenger. BAL fluid leucocytes from rats treated with PM10 produced greater amounts of nitric oxide (NO), measured as nitrite (control 3.07 (0.33), treated 4.45 (0.23) microM/1 x 10(6) cells), and tumour necrosis factor alpha (control 21.0 (3.1), treated 179.2 (29.4) units/l x 10(6) cells) in culture than those obtained from control animals. Since the PM10 preparation was contaminated with small amounts of filter fibres due to the extraction process, the effects of instillation of filter fibres alone was assessed. These studies showed that filter fibres did not account for the proinflammatory and injurious effects of the PM10 suspension. CONCLUSIONS: These findings provide evidence that PM10 has free radical activity and causes lung inflammation and epithelial injury. These data support the proposed hypothesis for the mechanism by which particulate air pollution causes adverse effects in patients with airways diseases.
Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms
Authors: Kiyoshi Sakai, Akihito Yamamoto, Kohki Matsubara, Shoko Nakamura, Mami Naruse, Mari Yamagata, Kazuma Sakamoto, Ryoji Tauchi, Norimitsu Wakao, Shiro Imagama, Hideharu Hibi, Kenji Kadomatsu, Naoki Ishiguro, Minoru Ueda
Journal: Journal of Clinical Investigation (2011)

Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.