tbuckley/cabot-search huggingface dataset:
Time to Activate Lung Cancer Clinical Trials and Patient Enrollment: A Representative Comparison Study Between Two Academic Centers Across the Atlantic
Authors: Andrea Wang-Gillam, Kristina Williams, Silvia Novello, Feng Gao, Giorgio V. Scagliotti, Ramaswamy Govindan
Journal: Journal of Clinical Oncology (2010)

Activation of clinical trials is a lengthy process. We studied the procedures and time required to activate lung cancer clinical trials in a US academic center compared with a European center.A retrospective review was performed of all thoracic oncology therapeutic trials submitted for regulatory review between 2001 and 2008 at Washington University School of Medicine (WUSM; St Louis, MO) and the University of Torino (UT; Torino, Italy). A process map was drafted by both institutions to establish the order of required events.We reviewed 137 therapeutic thoracic oncology trials from WUSM (n = 83) and UT (n = 54). The median times from submission to opening a trial were 163 days for WUSM and 112.5 days for UT (P = .048). The median times for regulatory approval were 75 days for WUSM and 31 days for UT (P < .001). The difference is more pronounced in a homogeneous subset of phase II, industrial-sponsored trials for the median calendar time from submission to opening a trial (239.5 days for WUSM v 112.5 days for UT; P < .001) and time for regulatory approval (99 days for WUSM v 13.5 days for UT; P < .001). The median number of patients accrued at WUSM was 7.4 patients per study compared with an average of 37 patients per study at UT. The proportion of trials that enrolled 20 patients or more represented 22.2% of trials at UT but only 1.1% of trials at WUSM.It takes additional steps and significantly longer time to activate a therapeutic thoracic clinical trial at a representative US site (WUSM) compared with a European site (UT).
Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-α production
Authors: Friederike Meyer-Wentrup, Daniel Benitez-Ribas, Paul J. Tacken, Cornelis J. A. Punt, Carl G. Figdor, I. Jolanda M. de Vries, Gosse J. Adema
Journal: Blood (2008)
Diagnosis of pulmonary embolism in hospitalised patients: retrospective survey of an institutional standard
Authors: S. Jouveshomme, I. Bohn, A. Cazaban
Journal: European Respiratory Journal (2007)

The aim of the present study was to assess the safety and implementation of a diagnostic strategy in hospitalised patients with suspected acute pulmonary embolism (PE). A diagnostic strategy was established and implemented in a general hospital. A retrospective cohort study, including 400 consecutive in-patients, was performed in order to assess the appropriateness of the diagnostic management and the incidence of symptomatic venous thromboembolic events (VTE) during follow-up. PE was confirmed in 116 (29%) patients. The incremental value of adding compression ultrasonography (CUS) to multidetector-row computed tomography (MDCT) for the diagnosis of PE was 8.6%. PE was appropriately excluded in 169 (42%) patients due to a normal lung scan (n = 34), a negative MDCT providing an alternative diagnosis (n = 94), and a negative MDCT and CUS (n = 41). During follow-up, VTE occurred in 3.5% patients. The almost unique cause of inappropriate management was the absence of further work-up after a MDCT-negative result for PE providing no alternative diagnosis (n = 115). Inappropriate management was associated with a nonsignificant increased risk of VTE (7.2%). A frontline diagnostic work-up based on pulmonary multidetector-row computed tomography associated with a compression ultrasonography of the leg veins is effective and more sensitive than pulmonary multidetector-row computed tomography alone in ruling out pulmonary embolism.
Occurrence of antibody to salivary duct epithelium in Sjogren's disease, rheumatoid arthritis, and other arthritides. A clinical and laboratory study.
Authors: R N MacSween, R B Goudie, J R Anderson, E Armstrong, M A Murray, D K Mason, M K Jasani, J A Boyle, W W Buchanan, J Williamson
Journal: Annals of the Rheumatic Diseases (1967)

Sj0gren's disease, first described in 1933 (Sj0gren, 1933), consists of chronic inflammation of the lacrimal and salivary glands leading to dryness of the eyes (keratoconjunctivitis sicca) and dryness of the mouth (xerostomia); in a proportion of patients lacrimal and salivary gland enlargement may also be present (Bloch, Buchanan, Wohl, and Bunim, 1965;Talal, 1966).In 50 to 60 per cent. of patients the disease may be associated with a connective tissue disorder, usually rheumatoid arthritis, but occasionally also with polymyositis, polyarteritis nodosa, progressive systemic sclerosis (scleroderma), and systemic lupus erythematosus.The term "sicca syndrome" or "sicca complex" is applied to those cases of Sj0gren's disease not associated with rheumatoid arthritis or other connective tissue disorders.In Sj0gren's disease, even in the absence of rheumatoid arthritis or other connective tissue disease (i.e. the sicca syndrome), there is hyper- gammaglobulinaemia and a high incidence of abnormal immunological reactions, such as antinuclear factors, rheumatoid factors, precipitating antibodies to tissue constituents, autoimmune complement-fixation tests, and passive cutaneous anaphylaxis in guinea-pigs (Jones, 1958;Stoltze,
Refractory coeliac disease: one step closer to the origin of aberrant lymphocytes
Authors: Victor F Zevallos, Detlef Schuppan
Journal: Gut (2012)

Aberrant intraepithelial lymphocytes (IELs) are the key feature of refractory coeliac disease type II (RCDII), but the cellular origin of these aberrant IELs remains unclear. In a recent paper Schmitz et al 1 further explored previously characterised aberrant IEL cell lines from four patients with RCDII by using a broad spectrum of cell specific markers, RNA array and immunological techniques, to compare these cell lines to IELs from the fetal intestine, the intestine of children and adults and the thymus.

IELs are a heterogeneous population of lymphocytes with innate and adaptive features that inhabit the small and large intestine. IELs are important for the maintenance of tolerance to common food antigens versus defence against pathogens. The development and expansion of IELs is influenced by nutritional factors, mainly vitamins and their active metabolites such as retinoic acid, and phytochemicals such as ligands of the aryl hydrocarbon receptor from cruciferous vegetables.2 However, uncontrolled activation and expansion of IELs leading to mucosal damage and potentially malignancy, is part of pathological response of chronic inflammatory conditions, especially of coeliac disease (CD).

Up to 5% of CD patients, particularly those diagnosed over the age of 50, fail to recover from clinical symptoms and villous atrophy despite strict avoidance of dietary gluten.3 After exclusion of dietary transgression and other potential underlying diseases,4 patients can be diagnosed with RCD which is classically classified as type I or type II, based on the histological coexpression of CD3 and CD8 (RCDI) or absence of such coexpression (RCDII), respectively.5 Moreover, in RCDII CD3 is largely expressed intracellularly (icCD3). Additional tools to diagnose RCDII include enhanced …
How do contemporary imaging techniques contribute to basic and clinical rheumatology?
Authors: Masaru Ishii
Journal: Annals of the Rheumatic Diseases (2012)

Recent major advances in biomedical imaging techniques have allowed us to visualise a variety of previously unseen biological phenomena. In particular, advanced fluorescent microscopy and radioimaging have enabled us to visualise cellular and molecular dynamics in living animals and humans. These new technologies have identified novel therapeutic targets against a wide array of diseases and have provided novel diagnostic tools for the evaluation of several disease conditions. In this brief review, the author outlines the contemporary imaging techniques used in the fields of immunology and rheumatology, with special focus on intravital fluorescent microscopy, and discusses how these cutting-edge methodologies contribute to clinical practice for patients with rheumatism.
A Study to Determine the Effects of Food and Multiple Dosing on the Pharmacokinetics of Vorinostat Given Orally to Patients with Advanced Cancer
Authors: Eric H. Rubin, Nancy G.B. Agrawal, Evan J. Friedman, Pamela Scott, Kathryn E. Mazina, Linda Sun, Lihong Du, Justin L. Ricker, Stanley R. Frankel, Keith M. Gottesdiener, John A. Wagner, Marian Iwamoto
Journal: Clinical Cancer Research (2006)

Abstract Purpose: This phase I study, conducted in advanced-stage cancer patients, assessed the safety and tolerability of oral vorinostat (suberoylanilide hydroxamic acid), single-dose and multiple-dose pharmacokinetics of vorinostat, and the effect of a high-fat meal on vorinostat pharmacokinetics. Experimental Design: Patients (n = 23) received single doses of 400 mg vorinostat on day 1 (fasted) and day 5 (fed) with 48 hours of pharmacokinetic sampling on both days. Patients received 400 mg vorinostat once daily on days 7 to 28. On day 28, vorinostat was given (fed) with pharmacokinetic sampling for 24 hours after dose. Results: The apparent t1/2 of vorinostat was short (∼1.5 hours). A high-fat meal was associated with a small increase in the extent of absorption and a modest decrease in the rate of absorption. A short lag time was observed before detectable levels of vorinostat were observed in the fed state, and Tmax was delayed. Vorinostat concentrations were qualitatively similar following single-dose and multiple-dose administration; the accumulation ratio based on area under the curve was 1.21. The elimination of vorinostat occurred primarily through metabolism, with &amp;lt;1% of the given dose recovered intact in urine. The most common vorinostat-related adverse experiences were mild to moderate nausea, anorexia, fatigue, increased blood creatinine, and vomiting. Conclusions: Vorinostat concentrations were qualitatively similar after single and multiple doses. A high-fat meal increased the extent and modestly decreased the rate of absorption of vorinostat; this effect is not anticipated to be clinically meaningful. Continued investigation of 400 mg vorinostat given once daily in phase II and III efficacy studies is warranted.
FAM83A confers EGFR-TKI resistance in breast cancer cells and in mice
Authors: Sun-Young Lee, Roland Meier, Saori Furuta, Marc E. Lenburg, Paraic A. Kenny, Ren Xu, Mina J. Bissell
Journal: Journal of Clinical Investigation (2012)

Breast cancers commonly become resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs); however, the mechanisms of this resistance remain largely unknown. We hypothesized that resistance may originate, at least in part, from molecular alterations that activate signaling downstream of EGFR. Using a screen to measure reversion of malignant cells into phenotypically nonmalignant cells in 3D gels, we identified FAM83A as a candidate cancer-associated gene capable of conferring resistance to EGFR-TKIs. FAM83A overexpression in cancer cells increased proliferation and invasion and imparted EGFR-TKI resistance both in cultured cells and in animals. Tumor cells that survived EGFR-TKI treatment in vivo had upregulated FAM83A levels. Additionally, FAM83A overexpression dramatically increased the number and size of transformed foci in cultured cells and anchorage-independent growth in soft agar. Conversely, FAM83A depletion in cancer cells caused reversion of the malignant phenotype, delayed tumor growth in mice, and rendered cells more sensitive to EGFR-TKI. Analyses of published clinical data revealed a correlation between high FAM83A expression and breast cancer patients' poor prognosis. We found that FAM83A interacted with and caused phosphorylation of c-RAF and PI3K p85, upstream of MAPK and downstream of EGFR. These data provide an additional mechanism by which tumor cells can become EGFR-TKI resistant.
Lymphocytes Stimulated With Recombinant Human Interleukin-2: Relationship Between Motility Into Protein Matrix and In Vivo Localization in Normal and Neoplastic Tissues of Mice
Authors: S. Ratner
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Lymphocytes Stimulated With Recombinant Human Interleukin-2: Relationship Between Motility Into Protein Matrix and In Vivo Localization in Normal and Neoplastic Tissues of Mice Get access Stuart Ratner Stuart Ratner E. Walter Albachten Department of Immunology, Michigan Cancer Foundation110 E. Warren Ave., Detroit, MI 48201 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 7, 4 April 1990, Pages 612–616, https://doi.org/10.1093/jnci/82.7.612 Published: 04 April 1990 Article history Received: 04 August 1989 Revision received: 06 December 1989 Accepted: 22 December 1989 Published: 04 April 1990
Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial
Authors: Henning Bliddal, Anthony R Leeds, Lise Stigsgaard, Arne Astrup, Robin Christensen
Journal: Annals of the Rheumatic Diseases (2011)

To evaluate 1-year symptomatic improvement in obese patients with knee osteoarthritis (OA) on an intensive low-energy diet (LED) maintained by frequent consultations with a dietician compared to minimal attention.The LED programme consisted of group therapy with dietary consultations and two periods of a low-calorie diet of 810 kcal/day during weeks 0-8 and weeks 32-36. The control group only received dietary instruction and attention for 2 h at baseline, and at weeks 8, 32, 36 and 52. The primary end point (total Western Ontario and McMaster Universities (WOMAC) index) was assessed as the mean group difference during and after 1 year.The study population consisted of 89 patients, 89% women, average age 63 years. After 1 year, mean weight loss in the LED group was -10.9 kg (11%) versus -3.6 kg (4%) in the control group (p<0.0001). There was no difference between the groups in total WOMAC index (p=0.11), although both groups improved. However, the LED intervention resulted in less WOMAC pain (7.7 mm), with a group mean difference of 7.2 mm (95% CI 1.0 to 13.4, p=0.022). After one year 14 (32.8%) responded to LED versus 7 (15.6%) to control, with an absolute benefit of 16.3% (-1.1& to 33.6%, p=0.066).Continuous reinforcement of a weight loss programme can be successful over a year in obese knee OA patients. Weight loss was statistically reflected only by a reduction in pain. However, the overall clinical benefits of the intervention on health should lead to a strong recommendation of weight loss in this group of patients.
What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK?
Authors: Emma L O'Dowd, Tricia M McKeever, David R Baldwin, Sadia Anwar, Helen A Powell, Jack E Gibson, Barbara Iyen-Omofoman, Richard B Hubbard
Journal: Thorax (2014)

<h3>Background</h3> The UK has poor lung cancer survival rates and high early mortality, compared to other countries. We aimed to identify factors associated with early death, and features of primary care that might contribute to late diagnosis. <h3>Methods</h3> All cases of lung cancer diagnosed between 2000 and 2013 were extracted from The Health Improvement Network database. Patients who died within 90 days of diagnosis were compared with those who survived longer. Standardised chest X-ray (CXR) and lung cancer rates were calculated for each practice. <h3>Results</h3> Of 20 142 people with lung cancer, those who died early consulted with primary care more frequently prediagnosis. Individual factors associated with early death were male sex (OR 1.17; 95% CI 1.10 to 1.24), current smoking (OR 1.43; 95% CI 1.28 to 1.61), increasing age (OR 1.80; 95% CI 1.62 to 1.99 for age ≥80 years compared to 65–69 years), social deprivation (OR 1.16; 95% CI 1.04 to 1.30 for Townsend quintile 5 vs 1) and rural versus urban residence (OR 1.22; 95% CI 1.06 to 1.41). CXR rates varied widely, and the odds of early death were highest in the practices which requested more CXRs. Lung cancer incidence at practice level did not affect early deaths. <h3>Conclusions</h3> Patients who die early from lung cancer are interacting with primary care prediagnosis, suggesting potentially missed opportunities to identify them earlier. A general increase in CXR requests may not improve survival; rather, a more timely and appropriate targeting of this investigation using risk assessment tools needs further assessment.
Orthopaedic surgery in patients with rheumatoid arthritis over 20 years: prevalence and predictive factors of large joint replacement
Authors: M C Kapetanovic, E Lindqvist, T Saxne, K Eberhardt
Journal: Annals of the Rheumatic Diseases (2008)

To study the prevalence of orthopaedic surgery and to evaluate possible predictive factors for large joint replacements in patients with early rheumatoid arthritis (RA).A cohort of 183 patients (116 (63.4%) female) with early RA was monitored for 16-20 years after recruitment during 1985-9. Mean (SD) age of patients 51.4 (12.4) years; mean (SD) duration of symptoms before inclusion 12 (7) months and mean (SD) duration of follow-up 16 (4) years. Occurrence of orthopaedic surgery was recorded continuously. A first prosthesis of a large joint (shoulder, elbow, wrist, hip, knee or ankle) was used as outcome variable in the predictive analyses.In total, 386 orthopaedic interventions were performed in 106/183 (58%) patients during follow-up and a large joint replacement was performed in 44/183 (24%) patients. Using a Cox regression model, it was shown that Health Assessment Questionnaire, C-reactive protein and erythrocyte sedimentation rate at inclusion, and radiographic changes in small joints after 1 year, were associated with an increased risk of receiving prosthesis of large joints.In this cohort of patients with RA monitored from early disease stage, orthopaedic surgical procedures were performed in more than half of the patients. This included first large joint replacements in 24% of the cases. Easily available measures were identified as predictors of such joint replacements. This study could serve as a reference for comparison with cohorts of patients with RA recruited today, in which new more efficacious treatments are used.
Characterization by Chromatofocusing of Estrogen Receptors From Rat Mammary Tumor MTW9
Authors: M. Platica, J. Doody, O. Platica, J. G. Cryan, V. P. Hollander
Journal: JNCI Journal of the National Cancer Institute (1989)

The estrogen receptor (ER) from rat mammary tumor MTW9-D, which is sensitive to ovariectomy, could be separated by chromatofocusing (CF) into two peaks specifically binding 3H-estradiol, focusing at pH 6.8 (peak A) and pH 6.0 (peak B). The ER from MTW9-MtT tumor, which is resistant to ovariectomy, presented only one peak, focusing at pH 6.0 (peak B). The peaks presented similar sedimentation coefficients (3.5s) with peak B being slightly larger than peak A. Regardless of the tumor sensitivity to hormonal manipulation, the two peaks presented similar molecular weights as shown by immunostaining of Western blots: a major duplex component of 70 kilodaltons (kd), and single bands at 48, 36, and 35 kd. The bands under 70 kd could be proteolytic products; however, the pattern could not be changed by addition of molybdate, leupeptin, or phenylmethylsulfonylfluoride. The pattern was reproducible in experiments done at different intervals of time or when rechromatofocusing. The peaks presented different isoelectric points: peak A, pH 6.8; peak B, pH 6.0. Also, they had different DNA binding abilities: peak A bound quantitatively to DNA, while peak B bound only 20%. Peak A was always present in tumors responsive to ovariectomy, a fact that suggests this ER component could be a marker for the responsiveness to hormonal therapy.
Unregulated use of clobetasol propionate
Authors: F.M. Keane, S.E. Munn, N.F. Taylor, A.W.P. Du Vivier
Journal: British Journal of Dermatology (2001)

SIR, Imported superpotent topical steroids are sold for use as skin‐lightening agents at certain street markets in London. We describe a patient who developed striae and adrenal suppression following the purchase and inappropriate use of clobetasol propionate. A 46‐year‐old Afro‐Caribbean woman had a 3‐month history of a hyperpigmented patch on her left forearm, and was prescribed topical beclomethasone dipropionate (Propaderm®; Glaxo Wellcome, Uxbridge, U.K.) by her general practitioner for presumed eczema. As the hyperpigmentation did not resolve, she purchased an ointment called Movate® at a local market selling unlicensed products, seemingly imported from Italy. The tube was labelled as 0·05% clobetasol propionate and the cream was described as ‘anti‐inflammatory, antiallergic, antipruritic’ and particularly indicated in the ‘treatment of the most resistant dermatoses’. She was not taking any other medications at that time. The patient applied in total 30 g Movate ointment to the plaque, and began to notice the development of striae in the axillae and inner upper arms, which were progressive. At presentation to our clinic, the initial plaque had cleared but there was residual skin atrophy and telangiectasia at this site. She was otherwise well, blood pressure was normal and she did not demonstrate any symptoms or signs of adrenal dysfunction.
Circulating Tumor Cell Counts Are Prognostic of Overall Survival in SWOG S0421: A Phase III Trial of Docetaxel With or Without Atrasentan for Metastatic Castration-Resistant Prostate Cancer
Authors: Amir Goldkorn, Benjamin Ely, David I. Quinn, Catherine M. Tangen, Louis M. Fink, Tong Xu, Przemyslaw Twardowski, Peter J. Van Veldhuizen, Neeraj Agarwal, Michael A. Carducci, J. Paul Monk, Ram H. Datar, Mark Garzotto, Philip C. Mack, Primo Lara, Celestia S. Higano, Maha Hussain, Ian Murchie Thompson, Richard J. Cote, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2014)

Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan.CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees.Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55).These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.