tbuckley/cabot-search huggingface dataset:
MET Signaling in Colon Cancer Stem-like Cells Blunts the Therapeutic Response to EGFR Inhibitors
Authors: Paolo Luraghi, Gigliola Reato, Elia Cipriano, Francesco Sassi, Francesca Orzan, Viola Bigatto, Francesca De Bacco, Elena Menietti, May Han, William M. Rideout, Timothy Perera, Andrea Bertotti, Livio Trusolino, Paolo M. Comoglio, Carla Boccaccio
Journal: Cancer Research (2014)

Metastatic colorectal cancer remains largely incurable, although in a subset of patients, survival is prolonged by new targeting agents such as anti-EGF receptor (anti-EGFR) antibodies. This disease is believed to be supported by a subpopulation of stem-like cells termed colon cancer-initiating cell (CCIC), which may also confer therapeutic resistance. However, how CCICs respond to EGFR inhibition has not been fully characterized. To explore this question, we systematically generated CCICs through spheroid cultures of patient-derived xenografts of metastatic colorectal cancer. These cultures, termed "xenospheres," were capable of long-term self-propagation in vitro and phenocopied the original patient tumors in vivo, thus operationally defining CCICs. Xenosphere CCICs retained the genetic determinants for EGFR therapeutic response in vitro and in xenografts; like the original tumors, xenospheres harboring a mutated KRAS gene were resistant to EGFR therapy, whereas those harboring wild-type RAS pathway genes (RAS(wt)) were sensitive. Notably, the effects of EGFR inhibition in sensitive CCICs could be counteracted by cytokines secreted by cancer-associated fibroblasts. In particular, we found that the MET receptor ligand hepatocyte growth factor (HGF) was especially active in supporting in vitro CCIC proliferation and resistance to EGFR inhibition. Ectopic production of human HGF in CCIC xenografts rendered the xenografts susceptible to MET inhibition, which sensitized the response to EGFR therapy. By showing that RAS(wt) CCICs rely on both EGFR and MET signaling, our results offer a strong preclinical proof-of-concept for concurrent targeting of these two pathways in the clinical setting.
Postoperative Mortality in Cancer Patients With Preexisting Diabetes
Authors: Bethany B. Barone, Hsin-Chieh Yeh, Claire F. Snyder, Kimberly S. Peairs, Kelly B. Stein, Rachel L. Derr, Antonio C. Wolff, Frederick L. Brancati
Journal: Diabetes Care (2010)

Diabetes appears to increase risk for some cancers, but the association between preexisting diabetes and postoperative mortality in cancer patients is less clear. Our objective was to systematically review postoperative mortality in cancer patients with and without preexisting diabetes and summarize results using meta-analysis. RSEARCH DESIGN AND METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE) for articles published on or before 1 July 2009, including references of qualifying articles. We included English language investigations of short-term postoperative mortality after initial cancer treatment. Titles, abstracts, and articles were reviewed by at least two independent readers. Study population and design, results, and quality components were abstracted with standard protocols by one reviewer and checked for accuracy by additional reviewers.Of 8,828 titles identified in our original search, 20 articles met inclusion criteria for qualitative systematic review. Of these, 15 reported sufficient information to be combined in meta-analysis. Preexisting diabetes was associated with increased odds of postoperative mortality across all cancer types (OR = 1.85 [95% CI 1.40-2.45]). The risk associated with preexisting diabetes was attenuated but remained significant when we restricted the meta-analysis to models that controlled for confounders (1.51 [1.13-2.02]) or when we accounted for publication bias using the trim and fill method (1.52 [1.13-2.04]).Compared with their nondiabetic counterparts, cancer patients with preexisting diabetes are approximately 50% more likely to die after surgery. Future research should investigate physiologic pathways to mortality risk and determine whether improvements in perioperative diabetes care can reduce postoperative mortality.
A Psychoendocrine Study of Pregnancy and Puerperium
Authors: C. RICHARD TREADWAY, FRANCIS J. KANE, ALI JARRAHI-ZADEH, MORRIS A. LIPTON
Journal: American Journal of Psychiatry (1969)

To investigate the relationship between hormonal changes associated with pregnancy and the increased incidence of psychiatric disturbances during the postpartum period, the authors conducted a controlled psychological and biochemical assessment of 21 women during pregnancy and the puerperium. On the basis of the findings reported here, they speculate that the increased incidence of clinically significant disorders among women in the postpartum period may be due to the increased environmental stresses of maternal responsibilities in association with lack of rebound from the biochemical changes of pregnancy.
652 MULTIPOLAR RADIOFREQUENCY ABLATION (MRFA) FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA (HCC) IN PATIENTS WITH CIRRHOSIS: PRELIMINARY EXPERIENCE IN 109 PATIENTS
Authors: O. Seror, G. Nkontchou, M. Aout, A. Mahmoudi, N. Ganne-Carrié, V. Grando, I. Baghad, P. Nahon, J.C. Trinchet, N. Sellier, D. Roulot, E. Vicaut, M. Beaugrand
Journal: Journal of Hepatology (2011)
Culture: The missing piece in theories of weak and strong reciprocity
Authors: Dwight Read
Journal: Behavioral and Brain Sciences (2012)

Guala does not go far enough in his critique of the assumption that human decisions about sharing made in the context of experimental game conditions accurately reflect decision-making under real conditions. Sharing of hunted animals is constrained by cultural rules and is not "spontaneous cooperation" as assumed in models of weak and strong reciprocity. Missing in these models is the cultural basis of sharing that makes it a group property rather than an individual one.
Relation of lung function, maximal inspiratory pressure, dyspnoea, and quality of life with exercise capacity in patients with chronic obstructive pulmonary disease.
Authors: P J Wijkstra, E M TenVergert, T W van der Mark, D S Postma, R Van Altena, J Kraan, G H Koeter
Journal: Thorax (1994)

BACKGROUND--Several studies have shown that both objective and subjective measurements are related to exercise capacity in patients with chronic obstructive pulmonary disease (COPD). In this study the relative contribution of lung function, maximal inspiratory pressure, dyspnoea, and quality of life to the performance in a walking distance test and a bicycle ergometer test was investigated. METHODS--Static lung volumes, forced expiratory volume in one second (FEV1), inspiratory slow vital capacity (IVC), transfer factor for carbon monoxide (TLCO) divided by the alveolar volume (TLCO/VA), static compliance (Cst), and maximal inspiratory peak pressure (PImaxPOES) were measured in 40 patients with COPD with severe airways obstruction (mean FEV1 44% predicted, mean FEV1/IVC 37% predicted). Quality of life was assessed by the Chronic Respiratory Questionnaire (CRQ) and dyspnoea by the Borg category scale. Exercise capacity was measured by both a six minute walking distance (test) and a maximal work load of the bicycle ergometer test (Wmax). RESULTS--Spirometric values and maximal inspiratory pressure were modestly correlated with both the six minute walking test and Wmax, r values ranging from 0.50 to 0.58. The TLCO was strongly correlated with the six minute walking test (r = 0.62) and with Wmax (r = 0.78). Quality of life showed no correlation with exercise capacity, while there was a correlation between dyspnoea and the six minute walking test (r = -0.41). Backward linear regression analysis selected TLCO and PImaxPOES as the most significant determinants for exercise performance. They explained 54% and 69% of the variance in the six minute walking test and Wmax, respectively. CONCLUSIONS--The results show that exercise capacity in patients with COPD with severe airways obstruction is more strongly related to inspiratory muscle strength and lung function than to dyspnoea and quality of life. The significant correlation between dyspnoea and the six minute walking test suggests that subjective variables are more strongly related to walking tests than to bicycle ergometer tests.
Infliximab treatment in a patient with rheumatoid arthritis and pulmonary fibrosis
Authors: E. Bargagli, M. Galeazzi, P. Rottoli
Journal: European Respiratory Journal (2004)

To the Editors: 

Infliximab is a chimeric human-mouse anti-tumour necrosis factor-α (anti-TNF-α) immunoglobulin G monoclonal antibody that binds the soluble and transmembrane forms of TNF-α. Its efficacy in the treatment of chronic inflammatory diseases, such as rheumatoid arthritis (RA) and Crohn's disease, is well documented 1, 2, and recent reports indicate a possible use in the treatment of psoriasis, giant cell arteritis, spondyloarthropaties and sarcoidosis 3–6.

As conventional treatments of idiopathic pulmonary fibrosis and lung fibrosis associated …
Early multimodal rehabilitation following lumbar disc surgery: a randomised clinical trial comparing the effects of two exercise programmes on clinical outcome and lumbar multifidus muscle function
Authors: Jeffrey J Hebert, Julie M Fritz, Anne Thackeray, Shane L Koppenhaver, Deydre Teyhen
Journal: British Journal of Sports Medicine (2013)

Background The optimal components of postoperative exercise programmes following single-level lumbar discectomy have not been identified. Facilitating lumbar multifidus (LM) function after discectomy may improve postoperative recovery. The aim of this study was to compare the clinical and muscle function outcomes of patients randomised to receive early multimodal rehabilitation following lumbar discectomy consisting of exercises targeting specific trunk muscles including the LM or general trunk exercises. Methods We included participants aged 18 to 60 years who were scheduled to undergo single-level lumbar discectomy. After two postoperative weeks, participants were randomly assigned to receive an 8-week multimodal exercise programme including either general or specific trunk exercises. The primary outcome was pain-related disability (Oswestry Index). Secondary outcomes included low back and leg pain intensity (0–10 numeric pain rating scale), global change, sciatica frequency, sciatica bothersomeness and LM function measured with real-time ultrasound imaging. Treatment effects 10 weeks and 6 months after surgery were estimated with linear mixed models. Results 61 participants were randomised to receive a general trunk (n=32) or specific (n=29) exercise programme. There were no between-group differences in clinical or muscle function outcomes. Participants in both groups experienced improvements in most outcome measures. Conclusions Following lumbar discectomy, multimodal rehabilitation programmes comprising specific or general trunk exercises have similar effects on clinical and muscle function outcomes. Local factors such as the individual patient characteristics identified by specific assessment findings, clinician expertise and patient preferences should direct therapy selection when considering the types of exercises tested in this trial for inclusion in rehabilitation programmes following lumbar disc surgery.
Making Genuine Progress Against Metastatic Breast Cancer
Authors: Gary H. Lyman, Harold J. Burstein, Aman U. Buzdar, Ralph D'Agostino, Paul A. Ellis
Journal: Journal of Clinical Oncology (2012)

Few drugs in oncology have generated as much discussion in both the medical literature and the popular and financial press as has bevacizumab for advanced breast cancer. The recent decision on the part of the US Food and Drug Administration (FDA) not to grant full approval for bevacizumab for first-line metastatic breast cancer (MBC) after granting accelerated approval 3 years earlier has sparked renewed debate about the oncology drug approval process and how best to measure clinical benefit in the setting of advanced cancer. Some have argued that the drug approval criteria are inconsistent and that regulatory standards are endangering progress in the treatment of MBC. Fortunately, that is not the case. Indeed, the experience with bevacizumab may illustrate how better to achieve rapid innovation and true progress in advanced breast cancer.
The role of oxygen termination of nanocrystalline diamond on immobilisation of BMP-2 and subsequent bone formation
Authors: Frank R. Kloss, Robert Gassner, Johannes Preiner, Andreas Ebner, Karin Larsson, Oliver Hächl, Tarkan Tuli, Michael Rasse, Doris Moser, Klaus Laimer, Eike A. Nickel, Gerhard Laschober, Regina Brunauer, Günther Klima, Peter Hinterdorfer, Doris Steinmüller-Nethl, Günter Lepperdinger
Journal: Biomaterials (2008)
Differential Cell Cycle–Regulatory Protein Expression in Biliary Tract Adenocarcinoma: Correlation With Anatomic Site, Pathologic Variables, and Clinical Outcome
Authors: William R. Jarnagin, David S. Klimstra, Michael Hezel, Mithat Gonen, Yuman Fong, Kevin Roggin, Karina Cymes, Ronald P. DeMatteo, Michael D'Angelica, Leslie H. Blumgart, Bhuvanesh Singh
Journal: Journal of Clinical Oncology (2006)

Biliary tract adenocarcinomas (BTAs), although anatomically related, arise through ill-defined and possibly different location-related pathogenetic pathways. This clinicopathologic study characterizes differences in cell cycle-regulatory protein expression across the spectrum of BTA.Tissue microarrays were prepared from paraffin-embedded surgical specimens with triplicate cores of BTA and benign tissue. Immunohistochemical expression of p53, cyclin D1, p21, Bcl2, p27, Mdm2, and Ki-67 was assessed, and the results were correlated with pathologic variables and survival. Hierarchical clustering was used to partition the data based on protein expression, and then the data were analyzed according to anatomic location.Tissue from 128 surgical patients (1992 to 2002) was obtained. Tumor sites of origin were intrahepatic cholangiocarcinoma (IH; n = 23), hilar cholangiocarcinoma (Hilar; n = 54), gallbladder (GB; n = 32), and distal bile duct (Distal; n = 19). p27 expression decreased progressively from proximal to distal in the biliary tree and correlated with location-related differences in outcome; cyclin D1 and Bcl2 overexpression also varied according to anatomic site. Aberrant p53 staining and cyclin D1 overexpression were lower in papillary tumors compared with the more common sclerosing tumors. The expression profiles of GB and Hilar were more similar to each other than either was to IH or Distal (86% clustering in the first partition). After an R0 resection, overexpression of Mdm2 (P = .0062) and absent p27 expression (P = .0165) independently predicted poor outcome.BTAs differentially express cell cycle-regulatory proteins based on tumor location and morphology. Prognostic roles were identified for Mdm2 and p27. Overlap in the pathogenesis of GB and Hilar tumors was suggested.
A population-based study on peanut, tree nut, fish, shellfish, and sesame allergy prevalence in Canada
Authors: Moshe Ben-Shoshan, Daniel W. Harrington, Lianne Soller, Joseph Fragapane, Lawrence Joseph, Yvan St Pierre, Samuel B. Godefroy, Susan J. Elliot, Ann E. Clarke
Journal: Journal of Allergy and Clinical Immunology (2010)

Recent studies suggest an increased prevalence of food-induced allergy and an increased incidence of food-related anaphylaxis. However, prevalence estimates of food allergies vary considerably between studies.To determine the prevalence of peanut, tree nut, fish, shellfish, and sesame allergy in Canada.Using comparable methodology to Sicherer et al in the United States in 2002, we performed a cross-Canada, random telephone survey. Food allergy was defined as perceived (based on self-report), probable (based on convincing history or self-report of physician diagnosis), or confirmed (based on history and evidence of confirmatory tests).Of 10,596 households surveyed in 2008 and 2009, 3666 responded (34.6% participation rate), of which 3613 completed the entire interview, representing 9667 individuals. The prevalence of perceived peanut allergy was 1.00% (95% CI, 0.80%-1.20%); tree nut, 1.22% (95% CI, 1.00%-1.44%); fish, 0.51% (95% CI, 0.37%-0.65%); shellfish, 1.60% (95% CI, 1.35%-1.86%); and sesame, 0.10% (95% CI, 0.04%-0.17%). The prevalence of probable allergy was 0.93% (95% CI, 0.74%-1.12%); 1.14% (95% CI, 0.92%-1.35%); 0.48% (95% CI, 0.34%-0.61%); 1.42% (95% CI, 1.18%-1.66%); and 0.09% (95% CI, 0.03%-0.15%), respectively. Because of the infrequency of confirmatory tests and the difficulty in obtaining results if performed, the prevalence of confirmed allergy was much lower.This is the first nationwide Canadian study to determine the prevalence of severe food allergies. Our results indicate disparities between perceived and confirmed food allergy that might contribute to the wide range of published prevalence estimates.
Ten-Year Follow-Up of Radiation Therapy Oncology Group Protocol 92-02: A Phase III Trial of the Duration of Elective Androgen Deprivation in Locally Advanced Prostate Cancer
Authors: Eric M. Horwitz, Kyounghwa Bae, Gerald E. Hanks, Arthur Porter, David J. Grignon, Harmar D. Brereton, Varagur Venkatesan, Colleen A. Lawton, Seth A. Rosenthal, Howard M. Sandler, William U. Shipley
Journal: Journal of Clinical Oncology (2008)

To determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for patients electively treated with ADT before and during radiation therapy (RT).Prostate cancer patients with T2c-T4 prostate cancer with no extra pelvic lymph node involvement and prostate-specific antigen (PSA) less than 150 ng/mL were included. All patients received 4 months of goserelin and flutamide before and during RT. They were randomized to no further ADT (short-term ADT [STAD] + RT) or 24 months of goserelin (long-term ADT [LTAD] + RT). A total of 1,554 patients were entered. RT was 45 Gy to the pelvic nodes and 65 to 70 Gy to the prostate. Median follow-up of all survival patients is 11.31 and 11.27 years for the two arms.At 10 years, the LTAD + RT group showed significant improvement over the STAD + RT group for all end points except overall survival: disease-free survival (13.2% v 22.5%; P < .0001), disease-specific survival (83.9% v 88.7%; P = .0042), local progression (22.2% v 12.3%; P < .0001), distant metastasis (22.8% v 14.8%; P < .0001), biochemical failure (68.1% v 51.9%; P <or= .0001), and overall survival (51.6% v 53.9%, P = .36). One subgroup analyzed consisted of all cancers with a Gleason score of 8 to 10 cancers. An overall survival difference was observed (31.9% v 45.1%; P = .0061), as well as in all other end points herein.LTAD as delivered in this study for the treatment of locally advanced prostate cancer is superior to STAD for all end points except survival. A survival advantage for LTAD + RT in the treatment of locally advanced tumors with a Gleason score of 8 to 10 suggests that this should be the standard of treatment for these high-risk patients.
A Multigene Assay Is Prognostic of Survival in Patients with Early-Stage Lung Adenocarcinoma
Authors: Dan J. Raz, M. Roshni Ray, Jae Y. Kim, Biao He, Miquel Taron, Marcin Skrzypski, Mark Segal, David R. Gandara, Rafael Rosell, David M. Jablons
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Clinical staging does not adequately risk stratify patients with early stage non–small cell lung cancer. We sought to generate a real-time PCR (RT-PCR)–based prognostic model in patients with early stage lung adenocarcinoma, the dominant histology of lung cancer in the United States. Experimental Design: We studied gene expression of 61 candidate genes in 107 patients with completely surgically resected lung adenocarcinoma using RT-PCR. We used crossvalidation methods to select and validate a prognostic model based on the expression of a limited number of genes. A risk score was generated based on model coefficients, and survival of patients with high- and low-risk scores were analyzed. Results: We generated a four-gene model based on expression of WNT3a, ERBB3, LCK, and RND3. Risk score predicted mortality better than clinical stage or tumor size (adjusted hazard ratio, 6.7; 95% confidence interval, 1.6-28.9; P = 0.001). Among 70 patients with stage I disease, 5-year overall survival was 87% among patients with low-risk scores, and 38% among patients with high-risk scores (P = 0.0002). Among all patients, 5-year overall survival was 62% and 41%, respectively (P = 0.0054). Disease-free survival was also significantly different among low- and high-risk score patients. Conclusions: This multigene assay predicts overall and disease-free survival significantly better than clinical stage and tumor size in patients with early stage lung adenocarcinoma and performs especially well in patients with stage I disease. Prospective clinical trials are needed to determine whether high-risk patients with stage I disease benefit from adjuvant chemotherapy.
Swimming causes myosin adaptations in the rat cardiac isograft.
Authors: S V Advani, D Geenen, A Malhotra, S M Factor, J Scheuer
Journal: Circulation Research (1990)

To investigate the contributions of humoral and hemodynamic factors to cardiac adaptations associated with chronic exercise, female Fischer 344 rats were subjected to chronic swimming, infrarenal cardiac transplantation, or both. Swimming resulted in hypertrophy (11-12%) of the in situ hearts in both the unoperated and operated animals compared with the matched sedentary controls. The cardiac isograft exhibited atrophy (32-35%), which was not attenuated by swimming. The cardiac isograft was also associated with a decrease in the percent of V1 myosin isoenzyme, which was attenuated by swimming (45 +/- 5% versus 66 +/- 6%). Swimming also increased the percent of this isomyosin in the in situ hearts of operated rats. These data suggest that hemodynamic load and/or neural innervation are necessary for hypertrophy associated with chronic conditioning by swimming, whereas myosin isoenzyme control is significantly mediated by humoral factors.
Lower Toenail Chromium in Men With Diabetes and Cardiovascular Disease Compared With Healthy Men
Authors: Swapnil Rajpathak, Eric B. Rimm, Tricia Li, J. Steven Morris, Meir J. Stampfer, Walter C. Willett, Frank B. Hu
Journal: Diabetes Care (2004)

Chromium may improve insulin sensitivity, which can modify the risk of diabetes and cardiovascular disease (CVD). Therefore, we evaluated the association between toenail chromium and CVD in diabetic men.We performed cross-sectional and nested case-control analyses among men aged 40-75 years within the Health Professionals Follow-up Study. The cross-sectional analysis compared men with diabetes only (n = 688), diabetes with prevalent CVD (n = 198), and healthy control subjects (n = 361). The nested case-control study included 202 men with baseline diabetes who developed incident CVD and 361 matched control subjects.Mean toenail chromium (microg/g) was 0.71 in healthy control subjects, 0.61 in diabetes-only subjects, and 0.52 in diabetic subjects with prevalent CVD (P for trend = 0.003). In the cross-sectional analysis, the multivariate odds ratio (OR) between extreme quartiles was 0.74 (95% CI 0.49-1.11; P for trend = 0.18), comparing diabetes only with healthy control subjects. A similar comparison between diabetic subjects with prevalent CVD and healthy control subjects yielded an OR of 0.45 (0.24-0.84; P for trend = 0.003). In the nested case-control study, comparing diabetic men with incident CVD with healthy control subjects, the multivariate OR was 0.65 (0.36-1.17; P for trend = 0.16) between extreme quartiles. When we combined prevalent and incident CVD cases among diabetic men and compared them with healthy control subjects, the OR was 0.62 (0.39-1.01; P for trend = 0.02) between extreme quartiles.Our results suggest that diabetic men with CVD have lower toenail chromium than healthy control subjects. However, this study could not distinguish between the effects of chromium on diabetes and those on CVD. Long-term clinical trials are needed to determine whether chromium supplementation is beneficial for preventing CVD among diabetic patients.