tbuckley/cabot-search huggingface dataset:
Validation of a specific quality of life questionnaire for functional digestive disorders
Authors: O Chassany, P Marquis, B Scherrer, N W Read, T Finger, J F Bergmann, B Fraitag, J Geneve, C Caulin
Journal: Gut (1999)

BACKGROUND Dyspepsia and irritable bowel syndrome are suitable conditions for assessment of quality of life. Their similarities justify the elaboration of a single specific questionnaire for the two conditions. AIMS To examine the process leading to the validation of the psychometric properties of the functional digestive disorders quality of life questionnaire (FDDQL). METHODS Initially, the questionnaire was given to 154 patients, to assess its acceptability and reproducibility, analyse its content, and reduce the number of items. Its responsiveness was tested during two therapeutic trials which included 428 patients. The questionnaire has been translated into French, English, and German. The psychometric validation study was conducted in France, United Kingdom, and Germany by 187 practitioners. A total of 401 patients with dyspepsia or irritable bowel syndrome, defined by the Rome criteria, filled in the FDDQL and generic SF-36 questionnaires. RESULTS The structure of the FDDQL scales was checked by factorial analysis. Its reliability was expressed by a Cronbach’s α coefficient of 0.94. Assessment of its discriminant validity showed that the more severe the functional digestive disorders, the more impaired the quality of life (p&lt;0.05). Concurrent validity was supported by the correlation found between the FDDQL and SF-36 questionnaire scales. The final version of the questionnaire contains 43 items belonging to eight domains. CONCLUSIONS The properties of the FDDQL questionnaire, available in French, English, and German, make it appropriate for use in clinical trials designed to evaluate its responsiveness to treatment among patients with dyspepsia and irritable bowel syndrome.
Authors’ response to the eLetter by Moiseev<i>et al</i>
Authors: Sergio Prieto-González, Marina Depetris, Ana García-Martínez, Georgina Espígol-Frigolé, Itziar Tavera-Bahillo, Marc Corbera-Bellalta, Ester Planas-Rigol, Marco A Alba, José Hernández-Rodríguez, Josep M Grau, Franciso Lomeña, Maria C Cid
Journal: Annals of the Rheumatic Diseases (2014)

We thank Moiseev and colleagues for their interest in our manuscript addressing the sensitivity and specificity of positron emission tomography (PET)/CT with 18fluorodeoxyglucose (FDG) for detecting large-vessel inflammation in patients with giant-cell arteritis (GCA)1 and for sharing their own data.2 We totally agree with the authors that PET-CT may be a useful diagnostic tool for GCA although it may be still premature to state that PET/CT should be an independent diagnostic procedure. As mentioned in our article,1 one of the most important limitations in considering PET/CT as a routine diagnostic procedure is the lack of a precise definition of what is a positive or negative PET/CT. While cases with strong or no FDG uptake may …
34 PROSPECTIVE SCREENING OF INFECTION IN PATIENTS WITH SEVERE ALCOHOLIC HEPATITIS TREATED WITH STEROIDS: EARLY RESPONSE TO THERAPY IS THE KEY FACTOR
Authors: A. Louvet, S. Dharancy, J. Boitard, F. Wartel, V. Canva-Delcambre, P. Deltenre, P. Mathurin
Journal: Journal of Hepatology (2008)
BAFF and MyD88 signals promote a lupuslike disease independent of T cells
Authors: Joanna R. Groom, Carrie A. Fletcher, Stacey N. Walters, Shane T. Grey, Sally V. Watt, Mathew J. Sweet, Mark J. Smyth, Charles R. Mackay, Fabienne Mackay
Journal: The Journal of Experimental Medicine (2007)

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. However, the underlying cause of disease appears to relate to defects in T cell tolerance or T cell help to B cells. Transgenic (Tg) mice overexpressing the cytokine B cell–activating factor of the tumor necrosis factor family (BAFF) develop an autoimmune disorder similar to SLE and show impaired B cell tolerance and altered T cell differentiation. We generated BAFF Tg mice that were completely deficient in T cells, and, surprisingly, these mice developed an SLE-like disease indistinguishable from that of BAFF Tg mice. Autoimmunity in BAFF Tg mice did, however, require B cell–intrinsic signals through the Toll-like receptor (TLR)–associated signaling adaptor MyD88, which controlled the production of proinflammatory autoantibody isotypes. TLR7/9 activation strongly up-regulated expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), which is a receptor for BAFF involved in B cell responses to T cell–independent antigens. Moreover, BAFF enhanced TLR7/9 expression on B cells and TLR-mediated production of autoantibodies. Therefore, autoimmunity in BAFF Tg mice results from altered B cell tolerance, but requires TLR signaling and is independent of T cell help. It is possible that SLE patients with elevated levels of BAFF show a similar basis for disease.
Interleukin-2 and Histamine Dihydrochloride in Metastatic Melanoma
Authors: Sanjiv S. Agarwala, Kristoffer Hellstrand, Peter Naredi
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.99.302 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12177116 Interleukin-2 and Histamine Dihydrochloride in Metastatic Melanoma Sanjiv S. AgarwalaxSanjiv S. AgarwalaSearch for articles by this author , Kristoffer HellstrandxKristoffer HellstrandSearch for articles by this author , Peter NaredixPeter NarediSearch for articles by this author Show More Melanoma Center, University of Pittsburgh, Pittsburgh, PAUniversity of Göteborg, Göteborg, SwedenUniversity of Umeå, Umeå, Sweden https://doi.org/10.1200/JCO.2002.99.302 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Effect of Chemotherapeutic Agents on Natural Cell-Mediated Cytotoxicity in Mice2
Authors: Alberto Mantovani, Walter Luini, Giuseppe Peri, Annunciata Vecchi, Federic Spreafico
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Effect of Chemotherapeutic Agents on Natural Cell-Mediated Cytotoxicity in Mice Get access Alberto Mantovani, Alberto Mantovani 3Istituto di Ricerche Farmacologiche 'Mario Negri,' Via Eritrea, 62-20157 Milan, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter Luini, Walter Luini 3Istituto di Ricerche Farmacologiche 'Mario Negri,' Via Eritrea, 62-20157 Milan, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar Giuseppe Peri, Giuseppe Peri 3Istituto di Ricerche Farmacologiche 'Mario Negri,' Via Eritrea, 62-20157 Milan, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar Annunciata Vecchi, Annunciata Vecchi 3Istituto di Ricerche Farmacologiche 'Mario Negri,' Via Eritrea, 62-20157 Milan, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar Federic Spreafico Federic Spreafico 3Istituto di Ricerche Farmacologiche 'Mario Negri,' Via Eritrea, 62-20157 Milan, Italy. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 5, November 1978, Pages 1255–1261, https://doi.org/10.1093/jnci/61.5.1255 Published: 01 November 1978 Article history Received: 30 January 1978 Accepted: 08 May 1978 Published: 01 November 1978
Comparative efficacy of topical antipsoriatic treatments, systemic treatment and biologics: is severity assessment beyond Psoriasis Area and Severity Index a necessity?
Authors: P.C.M. van de Kerkhof, U. Mrowietz, S. Segaert, K. Kragballe
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, A retrospective analysis recently appeared in the International Journal of Dermatology summarizing data from six multicentre studies including 2452 patients on the efficacy and safety of the two‐compound product calcipotriol/betamethasone dipropionate ointment.1 In 54·1% of these patients with moderate to severe psoriasis a reduction of the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) was already reached after 4 weeks. When this result is compared with PASI 75 data of biologic treatments after 12 weeks, only infliximab was found to be as effective as the two‐compound topical product. This message challenges the common belief that the efficacy of a topical treatment is inferior to that of systemic treatments. However, we felt that some critical notes have to be made with respect to the design of comparative analyses between populations eligible for topical treatment, systemic treatment and biologics and, furthermore, with respect to the use of PASI as sole outcome criterion to assess severity of psoriasis symptoms at baseline and efficacy of treatments.
Randomized trial of 8-week versus 12-week VNCOP-B plusG-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin’s lymphoma patients
Authors: P.L. Zinzani, F. Gherlinzoni, S. Storti, A. Zaccaria, E. Pavone, L. Moretti, P. Gentilini, L. Guardigni, A. De Renzo, P.P. Fattori, B. Falini, V.M. Lauta, D. Mannina, F. Zaja, P. Mazza, E. Volpe, F. Lauria, E. Aitini, F. Ciccone, M. Tani, V. Stefoni, L. Alinari, M. Baccarani, S. Tura
Journal: Annals of Oncology (2002)
A Pilot Clinical Trial of Oral Sodium 4-Phenylbutyrate (Buphenyl) in Δ F508-Homozygous Cystic Fibrosis Patients
Authors: RONALD C. RUBENSTEIN, PAMELA L. ZEITLIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Sodium 4-phenylbutyrate (Buphenyl, 4PBA) is a new FDA approved drug for management of urea cycle disorders. We have previously presented data suggesting that 4PBA, at clinically achievable concentrations, induces CFTR channel function on the plasma membrane of Δ F508-expressing cystic fibrosis (CF) airway epithelial cells in vitro (Rubenstein, R. C., and P. L. Zeitlin, 1997. J. Clin. Invest. 100:2457– 2463). We hypothesized that 4PBA would induce epithelial CFTR function in vivo in individuals homozygous for Δ F508-CFTR. A randomized, double-blind, placebo-controlled trial in 18 Δ F508- homozygous patients with CF was performed with the maximum approved adult dose of 4PBA, 19 grams p.o. divided t.i.d., given for 1 wk. Nasal potential difference (NPD) response patterns and sweat chloride concentrations were determined before and after study drug treatment, and 4PBA and metabolites were assayed in plasma and urine at the end of study drug treatment. Subjects in the 4PBA group demonstrated small, but statistically significant improvements of the NPD response to perfusion of an isoproterenol/amiloride/chloride-free solution; this measure reflects epithelial CFTR function and is highly discriminatory between patients with and without CF. Subjects who had received 4PBA did not demonstrate significantly reduced sweat chloride concentrations or alterations in the amiloride-sensitive NPD. Side effects due to drug therapy were minimal and comparable in the two groups. These data are consistent with 4PBA therapy inducing CFTR function in the nasal epithelia of Δ F508-homozygous CF patients.
Abstract 4255: Rational targeting of the Androgen receptor interactome in prostate cancer
Authors: Preethi Ravindranathan, Wayne Tilley, Ganesh V. Raj
Journal: Cancer Research (2014)

Abstract Background: The Androgen receptor (AR) is the central driver of prostate cancer and AR signaling is intact across all stages of disease. The interaction of AR with protein cofactors is critical for its signaling: targeted disruption of these interactions may enable shutdown of AR signaling. Methods: Using known crystal structure, modeled structure and imputed structure based models, peptide agents were rationally designed to block the interface between AR and critical cofactors in its interactome and tested for physiologic activity using prostate cancer cell lines, xenografts and primary tumor explants. Results: Knowledge of the protein cofactors, their interacting motifs and structure of the interface are needed for optimal targeting of protein-protein interactions. Using an iterative rational design approach, we have been able to successfully disrupt three classes of the AR interactome: 1. Interactions where the protein cofactor, the motifs and the structure of the interface is known, (targeting AR-PELP1 interface through a helical LxxLL motif) 2. Interactions where the protein cofactor is known but the motifs and the structure of the interface is not known, (targeting AR-FoxA1 interaction) and 3. Interactions where the motif is known, but neither the protein cofactor nor the structure of the interface are known (only known is a critical motif on AR). The design of initial compounds targeting the interactions in Class 1 was based on crystal structures, while those for Class 2 and Class 3 were based on either predicted or imputed (motif in different context) structures. The interaction between AR and proteins in each of these classes is disrupted by a targeted agent as evidenced by co-immunoprecipitation of endogenous protein cofactors and AR. The functional utility of these agents blocking the AR interactome on AR driven gene expression and proliferation has been validated for agents in Class 1, but is being validated for agents in Classes 2 and 3. In each case, using significant structural modeling, active agents were synthesized with a minimal use of synthesis of analogues. Conclusions: The rational targeting of the AR interactome is feasible and may be a useful complement to traditional screening campaigns. We have demonstrated the utility of this approach to blocking the interface in three distinct classes of protein-protein interactions. Further validation/optimization of these drugs is needed prior to their clinical implementation. Citation Format: Preethi Ravindranathan, Wayne Tilley, Ganesh V. Raj. Rational targeting of the Androgen receptor interactome in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4255. doi:10.1158/1538-7445.AM2014-4255
Metastatic Progression with Resistance to Aromatase Inhibitors Is Driven by the Steroid Receptor Coactivator SRC-1
Authors: Jean McBryan, Sarah M. Theissen, Christopher Byrne, Eamon Hughes, Sinead Cocchiglia, Stephen Sande, Jane O'Hara, Paul Tibbitts, Arnold D.K. Hill, Leonie S. Young
Journal: Cancer Research (2011)

Aromatase inhibitors (AI) are a standard-of-care treatment for postmenopausal, estrogen receptor-positive breast cancers. Although tumor recurrence on AI therapy occurs, the mechanisms underlying acquired resistance to AIs remain unknown. In this study, we examined a cohort of endocrine-treated breast cancer patients and used a cell line model of resistance to the AI letrozole. In patients treated with a first-line AI, hormone receptor switching between primary and resistant tumors was a common feature of disease recurrence. Resistant cells exhibited a switch from steroid-responsive growth to growth factor-responsive and endocrine-independent growth, which was accompanied by the development of a more migratory and disorganized phenotype. Both the resistant cells and tumors from AI-resistant patients showed high expression of the steroid receptor coactivator SRC-1. Direct interactions between SRC-1 and the transcription factor Ets2 regulated Myc and MMP9. SRC-1 was required for the aggressive and motile phenotype of AI-resistant cells. Interestingly, SRC-1 expression in primary and/or recurrent tumors was associated with a reduction in disease-free survival in treated patients. Moreover, there was a significant association between SRC-1 and Ets2 in the recurrent tissue compared with the matched primary tumor. Together, our findings elucidate a mechanism of AI-specific metastatic progression in which interactions between SRC-1 and Ets2 promote dedifferentiation and migration in hormone-dependent breast cancer.
Electronic Cigarettes. A Position Statement of the Forum of International Respiratory Societies
Authors: Dean E. Schraufnagel, Francesco Blasi, M. Bradley Drummond, David C. L. Lam, Ehsan Latif, Mark J. Rosen, Raul Sansores, Richard Van Zyl-Smit
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<OverviewIntroductionAwareness and Prevalence ...SafetyHarm Reduction of Electro...Regulation and Legislativ...FIRS Positions on Electro...ConclusionsReferencesCITING ARTICLES
Microenvironmental effects limit efficacy of thymoquinone treatment in a mouse model of ovarian cancer
Authors: Andrew J. Wilson, Jeanette Saskowski, Whitney Barham, Dineo Khabele, Fiona Yull
Journal: Molecular Cancer (2015)

Ovarian cancer is the most lethal gynecologic malignancy, with limited treatment options for chemoresistant disease. An important link between inflammation and peritoneal spread of ovarian cancer is NF-κB signaling. Thymoquinone (TQ) exerts multiple anti-tumorigenic cellular effects, including NF-κB inhibition. We aimed to investigate the therapeutic potential of TQ in an established murine syngeneic model of ovarian cancer.ID8-NGL mouse ovarian cancer cells stably expressing an NF-κB reporter transgene were injected intra-peritoneally into C57BL/6 mice, and mice were treated with TQ or vehicle for 10 or 30 days. TQ was combined with the macrophage depleting drug, liposomal clodronate, in selected experiments. Effects on peritoneal tumor burden were measured by volume of ascites, number of peritoneal implants and mesenteric tumor mass. NF-κB reporter activity and markers of proliferation and apoptosis were measured in tumors and in confirmatory in vitro experiments. Protein or mRNA expression of M1 (anti-tumor) and M2 (pro-tumor) macrophage markers, and soluble cytokine profiles, were examined from harvested ascites fluid, peritoneal lavages and/or tumor sections. 2-tailed Mann-Whitney tests were used for measuring differences between groups in in vivo experiments.Consistent with its effects in vitro, TQ reduced proliferation and increased apoptosis in ID8-NGL tumors after 10 and 30 day treatment. Prolonged TQ treatment did not significantly alter tumor number or mass compared to vehicle, but rather exerted an overall deleterious effect by stimulating ascites formation. Increased ascites was accompanied by elevated NF-κB activity in tumors and macrophages, increased pro-tumor M2 macrophages and expression of pro-tumorigenic soluble factors such as VEGF in ascites fluid, and increased tumor infiltration of M2 macrophages. In contrast, a 10 day exposure to TQ produced no ascites, and reduced tumor NF-κB activity, M2 macrophages and soluble VEGF levels. Peritoneal macrophage depletion by clodronate significantly reduced tumor burden. However, TQ-stimulated ascites was further enhanced by co-treatment with clodronate, with macrophages present overwhelmingly of the M2 phenotype.Our findings show that pro-tumorigenic microenvironmental effects limited the efficacy of TQ in a syngeneic mouse model of ovarian cancer, and provide caution regarding its potential use in clinical trials in ovarian cancer patients.
Progressive encephalomyelitis with rigidity as refractory asthma
Authors: N Kikuchi
Journal: Thorax (2003)

<h3>Introduction</h3> Immune Checkpoint Inhibitors (CPI) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. <h3>Methods</h3> We conducted a multi-centre (six cancer centres), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with CTCAE grade 0 for diarrhoea at 12 weeks after IFX initiation. We also assessed cancer outcomes at one year using RECIST criteria. <h3>Results</h3> 127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhoea CTCAE grade &gt;2 and 115 (90.6%) required hospitalisation for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistical regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04-0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13-8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared to patients with IFX-responsive enterocolitis (37.5%; p=0.013). <h3>Conclusion</h3> This is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Utilizing pre-defined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI-therapy.
Blockade of a Chemokine, CCL2, Reduces Chronic Colitis-Associated Carcinogenesis in Mice
Authors: Boryana Konstantinova Popivanova, Feodora Ivanova Kostadinova, Kengo Furuichi, Mohamed M. Shamekh, Toshikazu Kondo, Takashi Wada, Kensuke Egashira, Naofumi Mukaida
Journal: Cancer Research (2009)

Accumulating evidence indicates the crucial contribution of chronic inflammation to various types of carcinogenesis, including colon carcinoma associated with ulcerative colitis and asbestosis-induced malignant mesothelioma. Ulcerative colitis-associated colon carcinogenesis can be recapitulated in mice by azoxymethane administration followed by repetitive dextran sulfate sodium ingestion. In the course of this carcinogenesis process, the expression of a macrophage-tropic chemokine, CCL2, was enhanced together with intracolonic massive infiltration of macrophages, which were a major source of cyclooxygenase (COX)-2, a crucial mediator of colon carcinogenesis. Mice deficient in CCL2-specific receptor, CCR2, exhibited less macrophage infiltration and lower tumor numbers with attenuated COX-2 expression. Moreover, CCL2 antagonists decreased intracolonic macrophage infiltration and COX-2 expression, attenuated neovascularization, and eventually reduced the numbers and size of colon tumors, even when given after multiple colon tumors have developed. These observations identify CCL2 as a crucial mediator of the initiation and progression of chronic colitis-associated colon carcinogenesis and suggest that targeting CCL2 may be useful in treating colon cancers, particularly those associated with chronic inflammation.
RADIOLABELLED ANTIBODY FOR LOCALISING METASTASES
Authors: P. Anderson, A.R. Bradwell, A.A. Keeling, P.W. Dykes, K.E. Britton, M. Granowska, S.J. Mather, R.M. Rainsbury, R.C. Coombes, J.H. Westwood, A.M. Neville, H. Haisma, J. Hilkens, W. Goedemans
Journal: The Lancet (1983)
Clonal distribution of HLA-restricted antigen-reactive T cells in man.
Authors: H Hirschberg, O J Bergh, E Thorsby
Journal: The Journal of Experimental Medicine (1979)

The [3H]thymidine suicide technique was used to test the hypothesis that the response of immune human T cells from HLA-D/DR heterozygous donors to the soluble protein antigen purified protein derivative (PPD) is clonally expressed and consists of the concurrent proliferation of at least two separable subpopulations of lymphocytes. The results showed that each of the two subpopulations react to one or the other of the HLA-D/DR antigens presented together with PPD by allogeneic monocytes. In addition, using in vitro priming techniques of in vivo sensitized lymphocytes from heterozygous donors, it was possible to generate specific memory cells capable of recognizing the priming soluble protein antigen together with the HLA-D/DR determinant present in the initial sensitizing culture.