tbuckley/cabot-search huggingface dataset:
Phase II Trial of Pemetrexed Plus Bevacizumab for Second-Line Therapy of Patients With Advanced Non–Small-Cell Lung Cancer: NCCTG and SWOG Study N0426
Authors: Alex A. Adjei, Sumithra J. Mandrekar, Grace K. Dy, Julian R. Molina, Araba A. Adjei, David R. Gandara, Katie L. Allen Ziegler, Philip J. Stella, Kendrith M. Rowland, Steven E. Schild, Ralph G. Zinner
Journal: Journal of Clinical Oncology (2009)

To evaluate the efficacy and toxicity of pemetrexed combined with bevacizumab as second-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) and to correlate allelic variants in pemetrexed-metabolizing genes with clinical outcome.Patients with previously treated NSCLC received pemetrexed (500 mg/m(2) intravenous) combined with bevacizumab (15 mg/kg intravenous) every 3 weeks. The primary end point, evaluated using a one-stage Fleming design for detecting a true success rate of at least 70%, was the proportion of patients who were progression free and on treatment at 3 months. Polymorphisms in genes responsible for pemetrexed transport (reduced folate carrier [SLC19A1]) and metabolism (folylpolyglutamate synthase [FPGS] and gamma-glutamyl hydrolase [GGH]) evaluated in germline DNA (blood) were correlated with treatment outcome.Forty-eight evaluable patients (14 females and 34 males) received a median of four cycles (range, one to 20 cycles). The most common grade 3 or 4 nonhematologic adverse events (AEs) were fatigue (13%), dyspnea (10%), and thrombosis (10%). Grade 3 or 4 hematologic AEs were neutropenia (19%) and lymphopenia (13%). Twenty-four (57%; 95% CI, 41% to 72%) of the first 42 patients met the success criteria. Median overall survival (OS) and progression-free survival (PFS) times were 8.6 and 4.0 months, respectively. The exon 6 (2522)C-->T polymorphism in SLC19A1 correlated with 3-month progression-free status (P = .01) and with PFS (P = .05). The IVS1(1307)C-->T polymorphism in GGH correlated with OS (P = .04).The study did not meet its primary end point. However, the median PFS time of 4 months is promising. Pharmacogenetic studies in larger cohorts are needed to definitively identify polymorphisms that predict for survival and toxicity of pemetrexed.
Brain indoles in human hepatic encephalopathy
Authors: Hanan Al Mardini, Emma J. Harrison, Paul G. Ince, Kim Bartlett, Christopher O. Record
Journal: Hepatology (1993)

The neurotransmitter serotonin has a profound effect on the control of sleep; thus excess serotonin activity in the brain could be responsible for impaired consciousness in hepatic encephalopathy. Furthermore, an increased brain level of 5-hydroxy-indoleacetic acid has been a consistent finding in various animal models of the condition. In this study, using high-performance liquid chromatography with fluorometric detection, we examined levels of brain serotonin (5-hydroxytryptamine) and its precursors and metabolites in 16 patients dying with hepatic encephalopathy complicating acute and chronic liver disease and 9 control subjects matched for age, sex, postmortem delay in brain retrieval and length of frozen tissue storage. In patients with chronic liver disease, serotonin level was significantly increased in thalamus (p < 0.02); levels of its metabolite 5-hydroxyindoleacetic acid were increased in frontal cortex (p < 0.05), globus pallidus (p < 0.05) and putamen (p < 0.01). Levels of the precursor amino acid tryptophan were increased in thalamus (p < 0.01) and globus pallidus (p < 0.01); in both patient groups levels of 5-hydroxytryptophan and the tryptamine metabolite indoleacetic acid were increased in all brain areas studied. 5-Hydroxytryptamine levels were also increased in thalamus, frontal cortex and globus pallidus in the three patients with fulminant liver failure. Our findings are consistent with disordered neurotransmission, especially in the thalamus, an area of particular importance in the regulation of consciousness, alertness and attention in human beings.
Codelivery of mTERT siRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression
Authors: Wei Wei, Pi-Ping Lv, Xiao-Ming Chen, Zhan-Guo Yue, Qiang Fu, Shi-Ying Liu, Hua Yue, Guang-Hui Ma
Journal: Biomaterials (2013)
Pancreatic islet cell tumour with watery diarrhoea and hypokalaemia
Authors: D. J. Stoker, V. Wynn
Journal: Gut (1970)

A further patient with watery diarrhoea and hypokalaemia in association with a non-beta islet cell tumour of the pancreas is reported. The mechanism by which fluid and electrolyte losses are produced is discussed and cases previously reported are reviewed.
Preclinical Evaluation of Drug-Eluting Stents for Peripheral Applications
Authors: Robert S. Schwartz, Elazer R. Edelman, Andrew Carter, Nicolas A. Chronos, Campbell Rogers, Keith A. Robinson, Ron Waksman, Lindsay Machan, Judah Weinberger, Robert L. Wilensky, Jennifer L. Goode, O.D. Hottenstein, Bram D. Zuckerman, Renu Virmani
Journal: Circulation (2004)

D rug-eluting stents implanted in the coronary arteries sub- stantially improve long-term outcomes for restenosis.The utility of the stents in peripheral atherosclerosis is under evaluation.Drug-eluting stent evaluation with coronary arteries appears to be an excellent method for evaluating human safety end points.Predicting clinical efficacy remains unclear, however.Because drug-eluting stents are undergoing development for human peripheral arteries, safety and efficacy questions arise in much the same context as they did for the coronary arteries.As they did with the coronary arteries, the clinical, scientific, regulatory, and commercial communities are seeking acceptable criteria for peripheral device evaluation.Substantial differences in stent requirements and biological effects for bare metal peripheral stents depend on implant site.Different anatomic locations under evaluation include femoral, renal, and neurologic arterial stents, and other peripheral applications such as outflow veins of dialysis arteriovenous fistulae are being evaluated.Peripheral in-stent restenosis is less of a problem in carotid and aortoiliac stents and in iliac veins and in the cavae.In general, the benefit:risk ratio for drug-eluting stents may be less for peripheral stents.It is for this reason that peripheral stent performance should be evaluated carefully.This document presents an integrated recommendation set for evaluating drug-eluting stents in peripheral vessels with preclinical models.The recommendations encompass study design, experimental performance, and histopathologic evaluations and emphasize the need to evaluate safety and efficacy at multiple points in time.The present document is a consensus of clinical, academic, and commercial groups-all experts in the evaluation of preclinical investigational or interventional devices.Because preclinical peripheral studies
Unusual Abdominal Tumors
Authors: Kwok C. Lam, Winnie Yeo, Janet F.Y. Lee, John Chow, Tony S.K. Mok
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.11.124 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12610203 Unusual Abdominal Tumors CASE 4. MULTIPLE LYMPHOMATOUS POLYPOSIS IN MANTLE CELL LYMPHOMA Kwok C. LamxKwok C. LamSearch for articles by this author , Winnie YeoxWinnie YeoSearch for articles by this author , Janet F.Y. LeexJanet F.Y. LeeSearch for articles by this author , John ChowxJohn ChowSearch for articles by this author , Tony S.K. MokxTony S.K. MokSearch for articles by this author Show More Departments of Clinical Oncology, Surgery and Anatomical and Cellular Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, People’s Republic of China https://doi.org/10.1200/JCO.2003.11.124 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein
Authors: Stephen Nabarro, Nourredine Himoudi, Antigoni Papanastasiou, Kimberly Gilmour, Sian Gibson, Neil Sebire, Adrian Thrasher, Michael P. Blundell, Mike Hubank, Glenda Canderan, John Anderson
Journal: The Journal of Experimental Medicine (2005)

Tumors have evolved elaborate mechanisms for evading immune detection, such as production of immunoinhibitory cytokines and down-regulation of major histocompatibility complex (MHC) expression. We have studied PAX3-FKHR as an example of an oncogenic fusion protein associated with an aggressive metastatic cancer. We show that PAX3-FKHR alters expression of genes that are normally regulated by Janus kinase/signal transducer and activator of transcription (STAT) signaling pathways. This occurs as a result of a specific interaction between PAX3-FKHR and the STAT3 transcription factor, which results in a dramatic reduction in tumor MHC expression, and an alteration in local cytokine concentrations to inhibit surrounding inflammatory cells and immune detection. Collectively, these data show that an oncogenic transcription factor can promote tumor growth and tissue invasion while inhibiting local inflammatory and immune responses. This is the first time that an immunomodulatory role has been described for an oncogenic fusion protein.
No seasonality in month of birth of inflammatory bowel disease cases: a prospective population based study of British under 20 year olds
Authors: T R Card
Journal: Gut (2002)

Prenatal or perinatal environmental exposures have been postulated to change the risk of inflammatory bowel disease (IBD) later in life.1 One manifestation of this, perhaps because of early and seasonal infectious exposure, might be an association between the month of birth and risk of developing IBD later in life.2–4 Two recent publications, one from the UK,3 and the other from Denmark4 have examined cohorts of Crohn’s patients for such seasonality of birth. The findings of these two studies as well as their interpretations differ markedly. The British study was of adult patients diagnosed between 1972 and 1989 by four regional IBD registers in which a weak association was found between Crohn’s disease (CD) and birth in the first half of the year. The second (Danish) study examined national computerised hospital discharge records of children and young people aged less than 20 years coded between 1977 and 1992 for CD. This second study found an apparently stronger association with month of birth with the peak risk being for those born during August with a “sine wave” variation in risk between those born in different months of the year. The authors suggest that the differences compared with the British study might be explained by differences in age mix and nationality of the subjects, and further suggested that their findings give support to the importance of in utero and early childhood events in the aetiology of CD.

In view of these inconsistent findings, and the possibility that they may in part be explained by the differences in analytical technique as well as the age mix of the cases, we undertook an analysis of the national cohort of British IBD patients aged less than 20 years collected prospectively by the British Paediatric Surveillance Unit (BPSU) and the British Society of Gastroenterology Research Unit (BSGRU).5 We analysed this series using similar methods to those used by both the previous studies and in addition extended the statistical analysis to take into account possible shortcomings in them.
Oligomannurarate Sulfate, a Novel Heparanase Inhibitor Simultaneously Targeting Basic Fibroblast Growth Factor, Combats Tumor Angiogenesis and Metastasis
Authors: Huajun Zhao, Haiying Liu, Yi Chen, Xianliang Xin, Jing Li, Yongtai Hou, Zhonghua Zhang, Xiongwen Zhang, Chengying Xie, Meiyu Geng, Jian Ding
Journal: Cancer Research (2006)

Inhibitors of tumor angiogenesis and metastasis are increasingly emerging as promising agents for cancer therapy. Recently, heparanase inhibitors have offered a new avenue for such work because heparanase is thought to be critically involved in the metastatic and angiogenic potentials of tumor cells. Here, we report that oligomannurarate sulfate (JG3), a novel marine-derived oligosaccharide, acts as a heparanase inhibitor. Our results revealed that JG3 significantly inhibited tumor angiogenesis and metastasis, both in vitro and in vivo, by combating heparanase activity via binding to the KKDC and QPLK domains of the heparanase molecule. The JG3-heparanase interaction was competitively inhibited by low molecular weight heparin (4,000 Da) but not by other glycosaminoglycans. In addition, JG3 abolished heparanase-driven invasion, inhibited the release of heparan sulfate-sequestered basic fibroblast growth factor (bFGF) from the extracellular matrix, and repressed subsequent angiogenesis. Moreover, JG3 inactivated bFGF-induced bFGF receptor and extracellular signal-regulated kinase 1/2 phosphorylation and blocked bFGF-triggered angiogenic events by directly binding to bFGF. Thus, JG3 seems to inhibit both major heparanase activities by simultaneously acting as a substrate mimetic and as a competitive inhibitor of heparan sulfate. These findings suggest that JG3 should be considered as a promising candidate agent for cancer therapy.
Randomised comparison of initial triple DMARD therapy with methotrexate monotherapy in combination with low-dose glucocorticoid bridging therapy; 1-year data of the tREACH trial
Authors: P H de Jong, J M Hazes, H K Han, M Huisman, D van Zeben, P A van der Lubbe, A H Gerards, B van Schaeybroeck, P B de Sonnaville, M V van Krugten, J J Luime, A E Weel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To compare 1-year clinical efficacy of (1) initial triple disease-modifying antirheumatic drug therapy (iTDT) with initial methotrexate (MTX) monotherapy (iMM) and (2) different glucocorticoid (GC) bridging therapies: oral versus a single intramuscular injection in early rheumatoid arthritis. <h3>Methods</h3> In a single-blinded randomised clinical trial patients were randomised into three arms: (A) iTDT (methotrexate+sulfasalazine+hydroxychloroquine) with GCs intramuscularly; (B) iTDT with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. Primary outcomes were (1) area under the curve (AUC) of Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS) and (2) the proportion of patients with radiographic progression. <h3>Results</h3> 281 patients were randomly assigned to arms A (n=91), B (n=93) or C (n=97). The AUC DAS and HAQ were respectively −2.39 (95% CI −4.77 to −0.00) and −1.67 (95% CI −3.35 to 0.02) lower in patients receiving iTDT than in those receiving iMM. After 3 months, treatment failure occurred less often in the iTDT group, resulting in 40% fewer treatment intensifications. The difference in treatment intensifications between the arms required to maintain the predefined treatment goal remained over time. No differences were seen between the two GC bridging therapies. Respectively 21%, 24% and 23% of patients in arms A, B and C had radiographic progression after 1 year. Patients receiving iTDT had more adjustments of their medication owing to adverse events than those receiving iMM. <h3>Conclusions</h3> Treatment goals are attained more quickly and maintained with fewer treatment intensifications with iTDT than with iMM. However, no difference in radiographic progression is seen. Both GC bridging therapies are equally effective and, therefore, both can be used. <h3>Trial registration number</h3> ISRCTN26791028.
Analysis of an Ethylnitrosourea-generated Mouse Mutation Defines a Cell Intrinsic Role of Nuclear Factor κB2 in Regulating Circulating B Cell Numbers
Authors: Lisa A. Miosge, Julie Blasioli, Mathieu Blery, Christopher C. Goodnow
Journal: The Journal of Experimental Medicine (2002)

The number of circulating follicular B lymphocytes is normally kept within a precise range despite their dispersion through the body and daily overproduction of precursors in the bone marrow. By establishing a genome wide recessive mutation screen in C57BL/6 mice to identify critical components of immune system regulation, we identified a mutant strain with selective deficiency in recirculating B cells but not immature or peritoneal B1 cells. Analysis of mixed bone marrow chimeras established that the mutation affects a cell autonomous process within B cells that is required for their accumulation after emigrating to peripheral lymphoid organs. The defect is caused by a point mutation in the gene encoding transcription factor nuclear factor (NF)-κB2, terminating the encoded protein within the DNA-binding domain. These findings establish the feasibility of analyzing immune regulation by genome wide mutant screens and demonstrates an intrinsic requirement for NF-κB2 in regulating circulating follicular B cell numbers.
Fetal Diagnosis of Right Ventricular Aneurysm Associated With Supraventricular Tachycardia With Left Bundle-Branch Block Aberrancy
Authors: J. Blaine John, J. Timothy Bricker, Arnold L. Fenrich, G. Wesley Vick, Howaida G. El-Said, Nancy A. Ayres, Louis I. Bezold
Journal: Circulation (2002)
MELOE-1 is a new antigen overexpressed in melanomas and involved in adoptive T cell transfer efficiency
Authors: Yann Godet, Agnès Moreau-Aubry, Yannik Guilloux, Virginie Vignard, Amir Khammari, Brigitte Dreno, Francine Jotereau, Nathalie Labarriere
Journal: The Journal of Experimental Medicine (2008)

A cytotoxic T lymphocyte (CTL) clone was derived from a tumor-infiltrating lymphocyte (TIL) population infused to a melanoma patient who remained relapse free for 10 yr after this adoptive transfer. This clone recognized all melanoma cell lines tested and, to a lower extent, melanocytes, in the context of human histocompatibility leukocyte antigen A2 (HLA-A2), but it did not recognize other tumor cell types. The gene coding for the antigen recognized by this clone was identified by the screening of a melanoma complementary DNA expression library. This antigen is overexpressed in melanomas, compared with other cancer cell lines and healthy tissues, and was thus called melanoma-overexpressed antigen (meloe). Remarkably, the structure of meloe was unusual, with multiple short open reading frames (ORFs). The peptide recognized by the CTL clone was encoded by one of these ORFs, called MELOE-1. Using a specific HLA-A2/peptide tetramer, we showed a correlation between the infusion of TILs containing MELOE-1–specific T cells and relapse prevention in HLA-A2 patients. Indeed, 5 out of 9 patients who did not relapse were infused with TILs that contained MELOE-1–specific T cells, whereas 0 out of the 21 patients who relapsed was infused with such TIL-containing lymphocytes. Overall, our results suggest that this new antigen is involved in immunosurveillance and, thus, represents an attractive target for immunotherapy protocols of melanoma.
Differential expression of PHLDA1 (TDAG51) in basal cell carcinoma and trichoepithelioma
Authors: I. Yeh, T.H. McCalmont, P.E. LeBoit
Journal: British Journal of Dermatology (2012)

A recent small series demonstrated perfect sensitivity and specificity utilizing immunostaining for PHLDA1, a marker of follicular stem cells, in the distinction of desmoplastic trichoepithelioma and morphoeiform basal cell carcinoma (BCC) in small biopsy specimens.To assess this result more broadly.We performed immunoperoxidase staining of BCCs (superficial n = 16, nodular n = 15, micronodular n = 15, infiltrative n = 17, morphoeiform n = 16, infundibulocystic n = 14) and trichoepitheliomas (conventional n = 19, desmoplastic n = 16) with PHLDA1.Morphoeiform BCCs typically lacked PHLDA1 staining (88% demonstrated no staining and 12% of cases had staining in < 25% of the tumour), while in contrast 74% of classical and 88% of desmoplastic trichoepitheliomas demonstrated strong PHLDA1 staining in over half of the tumour. However, micronodular BCCs demonstrated focal to diffuse positive staining in a third of the cases.Based upon our staining results, we discuss the biological significance of PHLDA1 expression and the limits in its diagnostic utility.
A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2
Authors: Bart L Loeys, Junji Chen, Enid R Neptune, Daniel P Judge, Megan Podowski, Tammy Holm, Jennifer Meyers, Carmen C Leitch, Nicholas Katsanis, Neda Sharifi, F Lauren Xu, Loretha A Myers, Philip J Spevak, Duke E Cameron, Julie De Backer, Jan Hellemans, Yan Chen, Elaine C Davis, Catherine L Webb, Wolfram Kress, Paul Coucke, Daniel B Rifkin, Anne M De Paepe, Harry C Dietz
Journal: Nature Genetics (2005)
Iron-binding proteins in sputum of chronic bronchitis patients with Haemophilus influenzae infections
Authors: L Vogel, D Schoonbrood, F Geluk, F Hoek, P Bresser, T Out, H Jansen, J Dankert, L van Alphen
Journal: European Respiratory Journal (1997)

Airway inflammation during infection is associated with increased transudation of serum proteins and increased production of protein by the airway epithelium. We therefore, assessed whether Haemophilus influenzae infections in patients with chronic bronchitis are associated with increased levels of transferrin and lactoferrin in the sputum compared to uninfected patients. Sputum sol phase and serum samples from 14 infected and 13 uninfected patients with chronic bronchitis and from 12 bronchial asthma patients were included in the study. The median Q-values (the concentration in sputum sol phase/the concentration in serum) x 10(3) of transferrin appeared increased in chronic bronchitis patients with an H. influenzae infection (26.0, n=13) compared to uninfected controls (9.5, n=11) and bronchial asthma patients (4.5, n=6). The ratio of the Q(transferrin)/Q(albumin) was >1 in infected chronic bronchitis patients, indicating local production of transferrin. Growth of H. influenzae was stimulated more in sputum from infected and uninfected patients with chronic bronchitis than in sputum from patients with bronchial asthma. The concentrations of lactoferrin were not significantly different in infected (n=14) and uninfected (n=13) chronic bronchitis patients and bronchial asthma patients (n=12) (median 137.4, 84.6, 87.1 mg x L(-1), respectively). We conclude that in patients with chronic bronchitis with Haemophilus influenzae infections, the levels of transferrin are increased and the levels of lactoferrin are not associated with infections.
An audit of the completeness of non-melanoma skin cancer registration in Greater Glasgow
Authors: T.W. LUCKE, D.J. HOLE, R.M. MACKIE
Journal: British Journal of Dermatology (1997)

The incidence of basal cell carcinoma and squamous cell carcinoma (non-melanoma skin cancer) is increasing in the U.K., and the importance of this has been recognized in the 'Health of the Nation' target of halting the annual increase in the incidence of skin cancer by the year 2005. An accurate assessment of incidence is necessary both in meeting this target and in planning skin cancer services. We have examined the ways in which basal cell carcinoma and squamous cell carcinoma are diagnosed and treated in Greater Glasgow and have determined how many of these tumours are, recorded by the West of Scotland Cancer Registry. Our results show that there is under-registration of both basal cell carcinoma and squamous cell carcinoma. Overall, 39 of 127 basal cell carcinomas (31%; 95% confidence interval [CI] 23-39%) and 11 of 25 squamous cell carcinomas (44%; CI 26-63%) were not registered by the cancer registry. We also showed that dermatologists rarely treat clinically suspicious tumours without obtaining pathological proof of the diagnosis. Accurate data collection by selected representative cancer registries is suggested as a possible solution.