tbuckley/cabot-search huggingface dataset:
The current and future role of general practitioners in skin cancer care: an assessment of 268 general practitioners
Authors: M.C.J. van Rijsingen, B. van Bon, G.J. van der Wilt, A.L.M. Lagro-Janssen, M.J.P. Gerritsen
Journal: British Journal of Dermatology (2014)

Given the increase in skin cancer (SC) it seems inevitable that general practitioners (GPs) will play a larger role in SC care in the near future.To obtain insights into the opinion of GPs with respect to their role in SC care, and their SC knowledge and skills.A self-administered questionnaire was sent to GPs in the region of Nijmegen, the Netherlands.In total 268 GPs (49%) responded. An overwhelming majority were willing to extend their role in SC care. Furthermore, we noted the following results: (i) > 50% of GPs requested additional SC knowledge; (ii) GPs often treat actinic keratosis (AK) themselves, primarily with cryotherapy; (iii) > 50% would treat (low-risk) basal cell carcinoma (BCC) after additional training; (iv) only a few GPs are familiar with BCC guidelines; (v) the majority of patients with high-risk SC are referred to dermatologists; (vi) only a few GPs perform total body inspection and palpation of lymph nodes; and (vii) a large number of GPs inform their patients on risk factors in SC development.Most GPs are willing to extend their role in SC care; however, more training is requested and the usage of guidelines should be encouraged. Those willing to extend their role should focus on improving their clinical diagnosis of skin tumours, treatment of low-risk skin (pre)malignancies, including field-directed treatment of AK and noninvasive treatment of BCC, and on prevention.
<i>Staphylococcus aureus</i> synthesizes adenosine to escape host immune responses
Authors: Vilasack Thammavongsa, Justin W. Kern, Dominique M. Missiakas, Olaf Schneewind
Journal: The Journal of Experimental Medicine (2009)

Staphylococcus aureus infects hospitalized or healthy individuals and represents the most frequent cause of bacteremia, treatment of which is complicated by the emergence of methicillin-resistant S. aureus. We examined the ability of S. aureus to escape phagocytic clearance in blood and identified adenosine synthase A (AdsA), a cell wall-anchored enzyme that converts adenosine monophosphate to adenosine, as a critical virulence factor. Staphylococcal synthesis of adenosine in blood, escape from phagocytic clearance, and subsequent formation of organ abscesses were all dependent on adsA and could be rescued by an exogenous supply of adenosine. An AdsA homologue was identified in the anthrax pathogen, and adenosine synthesis also enabled escape of Bacillus anthracis from phagocytic clearance. Collectively, these results suggest that staphylococci and other bacterial pathogens exploit the immunomodulatory attributes of adenosine to escape host immune responses.
Platelet-activating factor (PAF) does not affect diastolic function in isolated rat hearts
Authors: H.R. Munoz, R.D. Evans, S.C.U. Marsch, P. Foex
Journal: Cardiovascular Research (1995)

Platelet-activating factor might be responsible for the alterations of diastolic function observed in different disease states and these potential effects have not been studied. The effect of incremental concentrations of platelet-activating factor (to a maximum of 200 nM) was therefore examined in isolated perfused rat heart. Platelet-activating factor decreased coronary flow rate and contractility in a dose-dependent manner. Although high-dose platelet-activating factor decreased peak -dP/dt compared to baseline, this was not significant when compared to vehicle-administered control. There were no changes in the time constant of left ventricular relaxation and the chamber stiffness constant. These results do not support a major direct role of platelet-activating factor in diastolic dysfunction.
Specific Occlusion of Murine and Human Tumor Vasculature by VCAM-1–Targeted Recombinant Fusion Proteins
Authors: Ariane Dienst, Andrea Grunow, Maike Unruh, Berit Rabausch, Jacques E. Nör, Jochen W. U. Fries, Claudia Gottstein
Journal: JNCI Journal of the National Cancer Institute (2005)

The tumor vasculature is increasingly recognized as a target for cancer therapy. We developed and evaluated recombinant fusion proteins targeting the coagulation-inducing protein soluble tissue factor (sTF) to the luminal tumor endothelial antigen vascular cell adhesion molecule 1 (VCAM-1, CD106).We generated fusion proteins consisting of sTF fused to antibody fragments directed against mouse or human VCAM-1 and characterized them in vitro by flow cytometry, surface plasmon resonance, and two-stage coagulation assays. Their therapeutic effects were tested in three human xenograft tumor models: L540rec Hodgkin lymphoma, Colo677 small-cell lung carcinoma, and Colo677/HDMEC small-cell lung carcinoma with human vasculature. Toxicity was analyzed by histologic examination of organs and determination of laboratory blood parameters.The fusion proteins bound VCAM-1 with nanomolar affinities and had the same coagulation activity as an sTF standard. Xenograft tumor-bearing mice treated with fusion protein (FP) alone or in combination with lipopolysaccharide (FP/L) or doxorubicin (FP/D) exhibited tumor-selective necrosis (L540rec tumors: 74% tumor necrosis [95% confidence interval {CI} = 55% to 93%] with FP/L versus 13% tumor necrosis [95% CI = 4% to 22%] with vehicle; Colo677 tumors: 26% [95% CI = 16% to 36%] with FP versus 8% [95% CI = 2% to 14%] with vehicle); tumor growth delay (Colo677/HDMEC: mean tumor weights after 3 days = 42 mg in FP-treated mice versus 71 mg in vehicle-treated mice, difference = 29 mg, 95% CI = 8 to 100, Mann-Whitney P = .008); and some tumor regressions (one of seven FP-treated Colo677 tumor-bearing mice and two of seven FP/D-treated mice). The fusion protein was well tolerated.Recombinant tissue factor-based fusion proteins directed against an intraluminal tumor endothelial cell marker induce tumor-selective intravascular coagulation, tumor tissue necrosis, and tumor growth delay.
Treatment of Chemotherapy-Resistant Human Ovarian Cancer Xenografts in C.B-17/SCID Mice by Intraperitoneal Administration of <i>Clostridium perfringens</i> Enterotoxin
Authors: Alessandro D. Santin, Stefania Cané, Stefania Bellone, Michela Palmieri, Eric R. Siegel, Maria Thomas, Juan J. Roman, Alexander Burnett, Martin J. Cannon, Sergio Pecorelli
Journal: Cancer Research (2005)

Abstract Ovarian cancer remains the most lethal gynecologic malignancy in the United States. Although many patients with advanced-stage disease initially respond to standard combinations of surgical and cytotoxic therapy, nearly 90% develop recurrence and inevitably die from the development of chemotherapy-resistant disease. The discovery of novel and effective therapy against chemotherapy-resistant/recurrent ovarian cancer remains a high priority. Using expression profiling, we and others have recently found claudin-3 and claudin-4 genes to be highly expressed in ovarian cancer. Because these tight junction proteins have been described as the low- and high-affinity receptors, respectively, for the cytotoxic Clostridium perfringens enterotoxin (CPE), in this study we investigated the level of expression of claudin-3 and/or claudin-4 in chemotherapy-naïve and chemotherapy-resistant primary human ovarian cancers as well as their sensitivity to CPE treatment in vitro. We report that 100% (17 of 17) of the primary ovarian tumors tested overexpress one or both CPE receptors by quantitative reverse transcription-PCR. All ovarian tumors showed a dose-dependent cytotoxic effect to CPE in vitro. Importantly, chemotherapy-resistant/recurrent ovarian tumors were found to express claudin-3 and claudin-4 genes at significantly higher levels when compared with chemotherapy-naïve ovarian cancers. All primary ovarian tumors tested, regardless of their resistance to chemotherapeutic agents, died within 24 hours to the exposure to 3.3 μg/mL CPE in vitro. In addition, we have studied the in vivo efficacy of i.p. CPE therapy in SCID mouse xenografts in a highly relevant clinical model of chemotherapy-resistant freshly explanted human ovarian cancer (i.e., OVA-1). Multiple i.p. administration of sublethal doses of CPE every 3 days significantly inhibited tumor growth in 100% of mice harboring 1 week established OVA-1. Repeated i.p. doses of CPE also had a significant inhibitory effect on tumor progression with extended survival of animals harboring large ovarian tumor burdens (i.e., 4-week established OVA-1). Our findings suggest that CPE may have potential as a novel treatment for chemotherapy-resistant/recurrent ovarian cancer.
Current clinical outcomes demand new treatment options for SCCHN
Authors: J.-L. Lefebvre
Journal: Annals of Oncology (2005)

Head and neck cancer can be a devastating disease. The mainstays of treatment for early stage disease are either radiotherapy or surgery. However, although disease responds well at this stage, the risk of a second primary cancer is high, with a development rate of about 4% per year. Advanced diseases are treated either by surgery with postoperative radiotherapy or by definitive radiotherapy, with surgery in reserve for salvage if necessary. Over the past two decades major advances have been made in surgery (reconstructive surgery, non-mutilating surgery). Either definitive or postoperative, radiotherapy is an integral part of the treatment for the majority of non-metastatic stages of disease and ways of improving the effects of radiotherapy are constantly being explored. Good activity has been reported for the use of altered radiation fractionation regimens, which allow the delivery of intensified radiation doses. In addition, in recent years randomized trials and meta-analyses have confirmed the survival benefit of adding chemotherapy to radiotherapy in a number of different settings. Cisplatin-based regimens have been identified as the most active and are now standard treatment choices. The survival benefits of chemotherapy appear to be limited to concomitant administration and do not extend to neoadjuvant administration, although this has demonstrated clinical utility in preserving organ function. Platinum-based combination chemotherapy is by many clinicians considered the standard approach to the treatment of recurrent/metastatic disease for patients who are able to tolerate such regimens, but the prognosis for these patients remains poor; this is particularly true for those whose disease progresses on such therapy. This paper discusses current approaches and recent advances in the treatment of head and neck cancer, specifically squamous cell carcinoma, and suggests future management aims for the different disease stages.
Innate Lymphoid Cells: Emerging Insights in Development, Lineage Relationships, and Function
Authors: Hergen Spits, Tom Cupedo
Journal: Annual Review of Immunology (2012)

Innate lymphoid cells (ILCs) are immune cells that lack a specific antigen receptor yet can produce an array of effector cytokines that in variety match that of T helper cell subsets. ILCs function in lymphoid organogenesis, tissue remodeling, antimicrobial immunity, and inflammation, particularly at barrier surfaces. Their ability to promptly respond to insults inflicted by stress-causing microbes strongly suggests that ILCs are critical in first-line immunological defenses. Here, we review current data on developmental requirements, lineage relationships, and effector functions of two families of ILCs: (a) Rorγt-expressing cells involved in lymphoid tissue formation, mucosal immunity, and inflammation and (b) type 2 ILCs that are important for helminth immunity. We also discuss the potential roles of ILCs in the pathology of immune-mediated inflammatory and infectious diseases including allergy.
Xylitol-induced increase in the plasma concentration and urinary excretion of uridine and purine bases
Authors: Tetsuya Yamamoto, Yuji Moriwaki, Sumio Takahashi, Zemta Tsutsumi, Jun-ichi Yamakita, Takashi Nakano, Keisai Hiroishi, Kazuya Higashino
Journal: Metabolism (1998)
Novel Mutation of BTK Gene in an XLA Patient with Late Manifestation of Chronic Arthritis, Encephalopathy and Pseudomonas Sepsis
Authors: W. Manuyakorn, W. Kamchaisatian, S. Benjaponpitak, D. Wattanasirichaigoon, C. Direkwattanachai
Journal: Journal of Allergy and Clinical Immunology (2006)
Talc-induced inflammation in the pleural cavity
Authors: MM van den Heuvel, HJ Smit, SB Barbierato, CE Havenith, RH Beelen, PE Postmus
Journal: European Respiratory Journal (1998)

Talc administration into the pleural cavity induces pleurodesis. To obtain further insight into the inflammatory process that causes pleurodesis, the cellular kinetics in the pleural space after the administration of talc was studied, along with its relation to chemokine concentrations in the pleural fluid. Thirteen consecutive patients with idiopathic spontaneous pneumothorax and eight patients with malignant pleural effusions received talc pleurodesis. The first group was treated with talc poudrage, whereas the second group was treated with talc slurry. Pleural fluids were isolated before talc administration as well as 3, 6, 24, 48 and 72 h afterwards. The talc induced a rapid polymorphonuclear neutrophil (PMN) influx followed by an accumulation of macrophages. In addition, increased production of interleukin (IL)-8 and monocyte chemotactic protein (MCP)-1 was observed. The talc-induced PMN influx reached its maximum after 3-24 h, and was related to the IL-8 concentration. In contrast, the MCP-1 was not related to the macrophage accumulation. Talc-induced inflammation in patients with idiopathic spontaneous pneumothorax and malignant pleural effusion is characterized by an influx of polymorphonuclear neutrophils related to interleukin-8, followed by an accumulation of monocytes.
Quit smoking with Champix: Parallel, randomised clinical trial of efficacy for the first time in Iran
Authors: Gholamreza Heydari, Saeid FallahTafti
Journal: European Respiratory Journal (2012)

Introduction:  Smoking cessation programs were first introduced in Iran in 1997 by the National Research Institute of Tuberculosis and Lung Diseases and up to now, various nicotine replacement therapies have been prescribed. The aim of this study was to evaluate effectiveness of Varenicline for tobacco cessation in this country and compare it with other measures.  Materials and Methods:  This was a randomized parallel clinical study during 2009-2010.  Participants were divided into three parallel groups randomly. The first group received brief counseling on cessation. The second group received nicotine patches 15 mg/daily for 8 weeks and the third group was prescribed Varenicline one 0.5 mg pill daily for the first 3 days, followed by 0.5 mg twice a day for 4 days and subsequently 1 mg twice daily for 8 weeks.  Results:  The study had 272 participants including 160 men (58.8%). Ninety one people were in the first group, 92 individuals in the second and 89 in the third group. At the end of the first month, 128 people from total (47.1%) succeeded in quitting; this included 17 individuals (18.7%) in the first group, 60 (65.2%) in the second group and 51 (57.3%) in the third group (P=0.000). Follow up at 6 month and a year showed 111 people of total (40.8%) and 58 individual (21.3%) remained smoke free which included 12 (13.2%) and 6 (6.6%) in the first group, 47 (51.1%) and 23 (25%) in the second group and 52 (58.4%) and 29(32.6%) in the third group respectively (P=0.000).  Conclusion:  Drug treatment can improve success in quitting several fold. Success with Varenicline is slightly better from nicotine replacement treatment.
Emergency department treatments and physiotherapy for acute whiplash: a pragmatic, two-step, randomised controlled trial
Authors: Sarah E Lamb, Simon Gates, Mark A Williams, Esther M Williamson, Shahrul Mt-Isa, Emma J Withers, Emanuela Castelnuovo, Jessica Smith, Deborah Ashby, Matthew W Cooke, Stavros Petrou, Martin R Underwood
Journal: The Lancet (2012)
Doxorubicin, mitomycin-C, and 5-fluorouracil (DMF) in the treatment of metastatic hormonal refractory adenocarcinoma of the prostate, with a note on the staging of metastatic prostate cancer.
Authors: C J Logothetis, M L Samuels, A C von Eschenbach, A Trindade, S Ogden, C Grant, D E Johnson
Journal: Journal of Clinical Oncology (1983)

Sixty-two patients with metastatic hormonal refractory adenocarcinoma of the prostate received a combination of doxorubicin, mitomycin-C, and 5-fluorouracil (DMF). Thirty (48%) of the patients achieved an objective response. Response criteria excluded disease "stabilization" as a manifestation of response. Four clinical prognostic categories were identified: osseous I (OI) had metastatic axial skeletal involvement (23 patients); osseous II (OII) had axial and extremity skeletaL involvement (18 patients); visceral I (VI) had pulmonary metastasis (9 patients); and visceral II (VII) had pulmonary metastasis and involvement of other viscera (12 patients). The 20 responding patients survived a median of 47.5 weeks, whereas the 32 nonresponding patients survived a median of 23.8 weeks (n = 0.002). Response rates were highest among patients with OI (52%) and VI (88%) disease; response rates were lower amont patients with OII (33%) and VII (33%) disease. Responding patients in each clinical category survived longer than nonresponding patients except for those patients with VII disease. The median duration of response for patients with OI disease was 11 months, for OII 9.5 months, for VI patients it was 6.5 months, and VII patients it was 5 months. DMF is an effective treatment of metastatic hormonal refractory prostate cancer, resulting in consistent objective responses. The staging system employed identifies four clinical categories of metastatic prostate cancer and allows for accurate comparison of diet and stratification of study populations.
Prevalence of airflow obstruction in smokers and never-smokers in Switzerland
Authors: P-O. Bridevaux, N.M. Probst-Hensch, C. Schindler, I. Curjuric, D. Felber Dietrich, O. Braendli, M. Brutsche, L. Burdet, M. Frey, M.W. Gerbase, U. Ackermann-Liebrich, M. Pons, J-M. Tschopp, T. Rochat, E.W. Russi
Journal: European Respiratory Journal (2010)

The aim of the present study was to measure age-specific prevalence of airflow obstruction in Switzerland in smokers and never-smokers using pulmonary function tests and respiratory symptoms from 6,126 subjects participating in the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults. The lower limit of normal of the forced expiratory volume in 1 s/forced vital capacity ratio was used to define airflow obstruction. Severity of airflow obstruction was graded according to the recommendations of the Global Initiative for Chronic Obstructive Lung Disease. Prevalence of airflow obstruction ranged from 2.5% in subjects aged 30–39 yrs to 8.0% in those aged ≥70 yrs. In multivariate analysis, age (OR 2.8, ≥70 yrs versus 30–39 yrs), smoking (OR 1.8) and asthma (OR 6.7) were associated with airflow obstruction. Never-smokers constituted 29.3% of subjects with airflow obstruction. Never-smokers with airflow obstruction were younger, more likely to be male and reported asthma more frequently than obstructive smokers. Obstructive smokers and never-smokers had similar level of symptoms and quality of life impairment. The prevalence of airflow obstruction in Switzerland is similar to other developed countries. Never-smokers account for a third of the prevalence, which is higher proportion than elsewhere. Airflow obstruction in never-smokers deserves attention because of its frequency and its similar health impact to that in smokers.
Sentinel lymph node biopsy in melanoma
Authors: Michael Bigby, Catalin Popescu
Journal: BMJ (2015)

Useful only to a small minority of patients who have the procedure

There are two diametrically opposed positions on the role of sentinel lymph node biopsy in the management of patients with melanoma. Either sentinel node biopsy affords patients with the best prognostic information and biopsy followed by complete lymph node dissection provides a survival advantage for patients with intermediate thickness melanomas, or the procedures are expensive and invasive, add little or no prognostic information, and have no survival advantage. The lack of consensus is reflected in the ambiguity of guidelines internationally.1 2 3 4 5

What additional prognostic information is provided by sentinel lymph node biopsy? Many studies indicate that compared with thickness, ulceration, inflammation, or mitotic rate, sentinel lymph node status is a stronger predictor of disease-free, disease specific, or overall survival,6 but we don’t know whether sentinel lymph node status alone is a better predictor of overall survival than a combination of known prognostic indicators.7 An important confounder is that knowledge of sentinel lymph node status affects patients’ subsequent treatment. People with negative results are …
Poly(ADP-Ribose) Polymerase Inhibition Synergizes with 5-Fluorodeoxyuridine but not 5-Fluorouracil in Ovarian Cancer Cells
Authors: Amelia M. Huehls, Jill M. Wagner, Catherine J. Huntoon, Liyi Geng, Charles Erlichman, Anand G. Patel, Scott H. Kaufmann, Larry M. Karnitz
Journal: Cancer Research (2011)

Abstract 5-Fluorouracil (5-FU) and 5-fluorodeoxyuridine (FdUrd, floxuridine) have activity in multiple tumors, and both agents undergo intracellular processing to active metabolites that disrupt RNA and DNA metabolism. These agents cause imbalances in deoxynucleotide triphosphate levels and the accumulation of uracil and 5-FU in the genome, events that activate the ATR- and ATM-dependent checkpoint signaling pathways and the base excision repair (BER) pathway. Here, we assessed which DNA damage response and repair processes influence 5-FU and FdUrd toxicity in ovarian cancer cells. These studies revealed that disabling the ATM, ATR, or BER pathways using small inhibitory RNAs did not affect 5-FU cytotoxicity. In stark contrast, ATR and a functional BER pathway protected FdUrd-treated cells. Consistent with a role for the BER pathway, the poly(ADP-ribose) polymerase (PARP) inhibitors ABT-888 (veliparib) and AZD2281 (olaparib) markedly synergized with FdUrd but not with 5-FU in ovarian cancer cell lines. Furthermore, ABT-888 synergized with FdUrd far more effectively than other agents commonly used to treat ovarian cancer. These findings underscore differences in the cytotoxic mechanisms of 5-FU and FdUrd and suggest that combining FdUrd and PARP inhibitors may be an innovative therapeutic strategy for ovarian tumors. Cancer Res; 71(14); 4944–54. ©2011 AACR.