tbuckley/cabot-search huggingface dataset:
Adjuvant high-dose IFN-alfa2b real life treatment outcome in the patients with malignant melanoma.
Authors: Z. Hlavata, T. Salek, J. Dolinsky, S. Porsok, J. Rajec, J. Mardiak
Journal: Journal of Clinical Oncology (2010)

e19037 Background: Kirkwood's studies found that adjuvant HD IFNa reduced 24%-38% relapse rate of malignant melanoma. This study findings want to confirm safety of HD regimen in terms of keeping the dose and time period in the induction and maintenance phase respectively. Methods: From May 2003 till November 2009 85 patients with completely wide local excision removed malignant melanoma were enrolled in our observational study. Median age was 49.9 yrs (range 20.5-64.5 yrs), female/male ratio was 37/48. The most common locality of incident was trunk in 49.4%. The median tumor thickness was 4.1 mm (Breslow) and the most common level of invasion was Clark IV (38.8%). T4N0M0 stadium (29%) was the most often indication to the treatment, ulceration had 30.5% of patients. SNB was performed in 63 (74.1%) patients. Results: We observed the reccurence of melanoma in 36 (42.4%) patients. There were 26 (33%) patients prematurely terminated the treatment, 17 because of progression, 7 because of toxicity, 2 because of noncompliance. We evaluated the data of toxicity from the induction phase and maintenance separately. The mean count of treatment days during induction was 35. The mean real IFNa dose, for patients with ≥ 28 days of treatment was 16.3 MIU/m2. The patients had, on average, 83.0% of calculated dose. Only 28 (33%) patients received 100% of calculated dose. The most common toxicity in the induction was flu-like syndrome (74.1% patients in the first week, 32.9% in second week and 27.1% in third and fourth week). Leucopenia G2 was the most common and fifth day was the most common day of toxicity as well as G3 (9.4%). We observed only G3 hepatotoxicity to 10% and fifth day was the most common day of presence. The mean real dose of IFNa for patients in maintenance phase was 5.9 MIU/m2. The patients had, on average, 60.7% of calculated dose. The most common toxicity was hepatotoxicity, leucopenia, weakness and myalgia. 7 patients presented neuropsychiatric symptoms. Conclusions: The toxicity of HD IFN-alfa2b is manageable and treatment regimen is safe. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough
Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer
Authors: Jenny L. Donovan, Freddie C. Hamdy, J. Athene Lane, Malcolm Mason, Chris Metcalfe, Eleanor Walsh, Jane M. Blazeby, Tim J. Peters, Peter Holding, Susan Bonnington, Teresa Lennon, Lynne Bradshaw, Deborah Cooper, Phillipa Herbert, Joanne Howson, Amanda Jones, Norma Lyons, Elizabeth Salter, Pauline Thompson, Sarah Tidball, Jan Blaikie, Catherine Gray, Prasad Bollina, James Catto, Andrew Doble, Alan Doherty, David Gillatt, Roger Kockelbergh, Howard Kynaston, Alan Paul, Philip Powell, Stephen Prescott, Derek J. Rosario, Edward Rowe, Michael Davis, Emma L. Turner, Richard M. Martin, David E. Neal
Journal: New England Journal of Medicine (2016)

Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes.
Characterization of Biomarkers of Tumorigenic and Chemoresistant Cancer Stem Cells in Human Gastric Carcinoma
Authors: Phu Hung Nguyen, Julie Giraud, Lucie Chambonnier, Pierre Dubus, Linda Wittkop, Geneviève Belleannée, Denis Collet, Isabelle Soubeyran, Serge Evrard, Benoit Rousseau, Nathalie Senant-Dugot, Francis Mégraud, Frédéric Mazurier, Christine Varon
Journal: Clinical Cancer Research (2016)

Purpose: Gastric carcinomas are heterogeneous, and the current therapy remains essentially based on surgery with conventional chemotherapy and radiotherapy. This study aimed to characterize biomarkers allowing the detection of cancer stem cells (CSC) in human gastric carcinoma of different histologic types.Experimental Design: The primary tumors from 37 patients with intestinal- or diffuse-type noncardia gastric carcinoma were studied, and patient-derived tumor xenograft (PDX) models in immunodeficient mice were developed. The expressions of 10 putative cell surface markers of CSCs, as well as aldehyde dehydrogenase (ALDH) activity, were studied, and the tumorigenic properties of cells were evaluated by in vitro tumorsphere assays and in vivo xenografts by limiting dilution assays.Results: We found that a subpopulation of gastric carcinoma cells expressing EPCAM, CD133, CD166, CD44, and a high ALDH activity presented the properties to generate new heterogeneous tumorspheres in vitro and tumors in vivo CD44 and CD166 were coexpressed, representing 6.1% to 37.5% of the cells; ALDH activity was detected in 1.6% to 15.4% of the cells; and the ALDH+ cells represented a core within the CD44+/CD166+ subpopulation that contained the highest frequency of tumorigenic CSCs in vivo The ALDH+ cells possessed drug efflux properties and were more resistant to standard chemotherapy than the ALDH- cells, a process that was partially reversed by verapamil treatment.Conclusions: CD44 and ALDH are the most specific biomarkers to detect and isolate tumorigenic and chemoresistant gastric CSCs in noncardia gastric carcinomas independently of the histologic classification of the tumor. Clin Cancer Res; 23(6); 1586-97. ©2016 AACR.
Phenomenology of Schizophrenia and the Representativeness of Modern Diagnostic Criteria
Authors: Kenneth S. Kendler
Journal: JAMA Psychiatry (2016)

<h3>Importance</h3> This article aims to determine the degree to which modern operationalized diagnostic criteria for schizophrenia reflect the main clinical features of the disorder as described historically by diagnostic experts. <h3>Observations</h3> Amazon.com, the National Library of Medicine, and Forgottenbooks.com were searched for articles written or translated into English from 1900 to 1960. Clinical descriptions of<i>schizophrenia</i>or<i>dementia praecox</i>appearing in 16 textbooks or review articles published between 1899 and 1956 were reviewed and compared with the criteria for schizophrenia from 6 modern US operationalized diagnostic systems. Twenty prominent symptoms and signs were reported by 5 or more authors. A strong association was seen between the frequency with which the symptoms/signs were reported and the likelihood of their presence in modern diagnostic systems. Of these 20 symptoms/signs, 3 (thought disorder, delusions, and hallucinations) were included in all diagnostic systems and were among the 4 most frequently reported. Three symptoms/signs were added then kept in subsequent criteria: emotional blunting, changes in volition, and changes in social life. Three symptoms/signs were added but then dropped: bizarre delusions, passivity symptoms, and mood incongruity. Eleven symptoms/signs were never included in any diagnostic system. Compared with historical authors, modern criteria favored symptoms over signs. Odd movements and postures, noted by 16 of 18 historical authors, were absent from all modern criteria.<i>DSM-5</i>criteria contain 6 of the 20 historically noted symptoms/signs. <h3>Conclusions and Relevance</h3> Although modern operationalized criteria for schizophrenia reflect symptoms and signs commonly reported by historical experts, many clinical features emphasized by these experts are absent from modern criteria. This is not necessarily problematic as diagnostic criteria are meant to index rather than thoroughly describe syndromes. However, the lack of correspondence in schizophrenia between historically important symptoms/signs and current diagnostic systems highlights the limitations of clinical evaluations and research studies that restrict the diagnostic assessments to current diagnostic criteria. We should not confuse our<i>DSM</i>diagnostic criteria with the disorders that they were designed to index.
Statistical controversies in clinical research: prognostic gene signatures are not (yet) useful in clinical practice
Authors: S. Michiels, N. Ternès, F. Rotolo
Journal: Annals of Oncology (2016)

With the genomic revolution and the era of targeted therapy, prognostic and predictive gene signatures are becoming increasingly important in clinical research. They are expected to assist prognosis assessment and therapeutic decision making. Notwithstanding, an evidence-based approach is needed to bring gene signatures from the laboratory to clinical practice. In early breast cancer, multiple prognostic gene signatures are commercially available without having formally reached the highest levels of evidence-based criteria. We discuss specific concepts for developing and validating a prognostic signature and illustrate them with contemporary examples in breast cancer. When a prognostic signature has not been developed for predicting the magnitude of relative treatment benefit through an interaction effect, it may be wishful thinking to test its predictive value. We propose that new gene signatures be built specifically for predicting treatment effects for future patients and outline an approach for this using a cross-validation scheme in a standard phase III trial. Replication in an independent trial remains essential.
Glucagon-Like Peptide-1 and Its Class B G Protein–Coupled Receptors: A Long March to Therapeutic Successes
Authors: Chris de Graaf, Dan Donnelly, Denise Wootten, Jesper Lau, Patrick M. Sexton, Laurence J. Miller, Jung-Mo Ahn, Jiayu Liao, Madeleine M. Fletcher, Dehua Yang, Alastair J. H. Brown, Caihong Zhou, Jiejie Deng, Ming-Wei Wang
Journal: Pharmacological Reviews (2016)

The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein–coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, enteroendocrine L cells in the distal intestine, <i>α</i> cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity. Physiologic and biochemical studies with truncated, chimeric, and mutated peptides and GLP-1R variants, together with ligand-bound crystal structures of the extracellular domain and the first three-dimensional structures of the 7-helical transmembrane domain of class B GPCRs, have provided the basis for a two-domain–binding mechanism of GLP-1 with its cognate receptor. Although efforts in discovering therapeutically viable nonpeptidic GLP-1R agonists have been hampered, small-molecule modulators offer complementary chemical tools to peptide analogs to investigate ligand-directed biased cellular signaling of GLP-1R. The integrated pharmacological and structural information of different GLP-1 analogs and homologous receptors give new insights into the molecular determinants of GLP-1R ligand selectivity and functional activity, thereby providing novel opportunities in the design and development of more efficacious agents to treat metabolic disorders.
P1-251: Skin toxicities difference between erlotinib (E) and gefitinib (G) in the treatment of advanced non-small-cell lung cancer (NSCLC)
Authors: Francesco Grossi, Annalisa Brianti, Carlotta Defferrari, Maura Loprevite, Gianluca Catania, Maria Giovanna Dal Bello, Paolo Pronzato
Journal: Journal of Thoracic Oncology (2007)
P2-186: The incidence of histologic subtypes and b symptoms in long term survival of non surgically treated non small cell lung cancer
Authors: Ewan D. Johnson, Jan M. Hanneken, Suyu Liu, Javier Rojo, Sarah H. Taylor, David J. Stewart, Muriel C. Camarillo, Ignacio I. Wistuba, Scott M. Lippman, Daniel D. Karp
Journal: Journal of Thoracic Oncology (2007)
E-cigarettes help smokers quit, Cochrane review confirms
Authors: Anne Gulland
Journal: BMJ (2016)

Electronic cigarettes may help smokers quit, and no serious side effects are associated with their use, a review of the latest evidence has found.1

An updated Cochrane review found no new randomised controlled trials of e-cigarettes since its first review, published in December 2014.2 However, the updated review includes 11 observational studies, and those that measured side effects found no serious side effects from using e-cigarettes for as …
Clinical outcomes of patients with desmoid tumors treated with dacarbazine plus doxorubicin regimen.
Authors: L. A. Costa, A. A. da Costa, L. Cezana, F. N. Santos, U. R. Nicolau, A. A. Dettino, M. F. Fanelli, M. J. De Barros E Silva
Journal: Journal of Clinical Oncology (2010)

e20524 Background: Desmoids are a rare, slow growing, soft-tissue tumors with a locally agressive behavior. These tumors are often unresectable at diagnosis and there is no standard first line chemotherapy. Methods: We present a retrospective review of the outcomes of patients treated with the same regimen comprised by doxorubicin (DOX) 20mg/m2 daily plus dacarbazine (DTIC) 150 mg/m2 daily over four days of drip infusions at a single institution from June 2005 to December 2009. Results: A total of five patients were analyzed. All of them had a diagnosis of familial adenomatous polyposis (FAP). There were three men (60%) and the median age at diagnosis was 30 (range, 18 to 38 years). Four patients had intrabdominal tumors (80%) and were considered unresectable. The protocol DOX plus DTIC was the first line therapy for them. The remaining patient had tumor in abdominal wall and it was resected at diagnosis. This patient received tamoxifen to local relapse that occurred thirty-two months after surgery. In this case, the regimen DOX plus DTIC was used as second line therapy after tamoxifen progression. The median number of cycles was five (range, 3 to 6 cycles). All of the patients seemed to tolerate the chemotherapy well, and none patient showed severe treatment-related toxicity (grade 3 or 4). There were two partial responses and three stable disease. None complete response was observed. All except one were administered meloxicam (10 mg/m2) after chemotherapy. With a median follow-up time of 14,3 months (range, 8.5 to 54 months), only one progression disease occurred at 52 months. Conclusions: In our series of cases, doxorubicin plus dacarbazine was a safe and well tolerated regimen. Despite the low downstaging rates, it seems prolong substantially the time to disease progression in patients with desmoid tumours. No significant financial relationships to disclose.
Serum Vaccine Antibody Concentrations in Adolescents Exposed to Perfluorinated Compounds
Authors: Philippe Grandjean, Carsten Heilmann, Pal Weihe, Flemming Nielsen, Ulla B. Mogensen, Esben Budtz-Jørgensen
Journal: Environmental Health Perspectives (2016)

Postnatal exposure to perfluorinated alkylate substances (PFASs) is associated with lower serum concentrations of specific antibodies against certain childhood vaccines at 7 y.We prospectively followed a Faroese birth cohort to determine these associations at 13 y.In 516 subjects (79% of eligible cohort members) who were 13 years old, serum concentrations of PFASs and of antibodies against diphtheria and tetanus were measured and were compared with data from the previous examination at 7 y. Multiple regression analyses and structural equation models were applied to determine the association between postnatal PFAS exposures and antibody concentrations.Serum concentrations of PFASs and antibodies generally declined from 7 y to 13 y. However, 68 subjects had visited the emergency room and had likely received a vaccination booster, and a total of 202 children showed higher vaccine antibody concentrations at 13 y than at 7 y. Therefore, separate analyses were conducted after exclusion of these two subgroups. Diphtheria antibody concentrations decreased at elevated PFAS concentrations at 13 y and 7 y; the associations were statistically significant for perfluorodecanoate (PFDA) at 7 y and for perfluorooctanoate (PFOA) at 13 y, both suggesting a decrease by ∼25% for each doubling of exposure. Structural equation models showed that a doubling in PFAS exposure at 7 y was associated with losses in diphtheria antibody concentrations at 13 y of 10–30% for the five PFASs. Few associations were observed for anti-tetanus concentrations.These results are in accord with previous findings of PFAS immunotoxicity at current exposure levels. https://doi.org/10.1289/EHP275.
The REQUITE project: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side effects.
Authors: Tiziana Rancati, Christopher Talbot, David Azria, Antony Brookes, Tom Burr, Jenny Chang-Claude, Susan Davidson, Dirk De Ruysscher, Alison Dunning, Rebecca M. Elliot, Sara Gutierrez-Enríquez, Philippe Lambin, Barry Rosenstein, R. Paul Symonds, Hubert Thierens, Riccardo Valdagni, Ana Vega, Frederik Wenz, Martin Yuille, Catharine West
Journal: Journal of Clinical Oncology (2014)

276 Background: Recently the first replicated genetic associations for adverse reactions to radiotherapy (RT) have been reported. These will help to build predictive statistical models for optimising RT delivery or interventions to alleviate the side effects. It is now timely to start a project that aims to validate known predictors of adverse reactions and develop the statistical models to become clinically useful. REQUITE is a European Union funded FP7 project that aims to do this. Methods: REQUITE’s objectives: (1.) Perform a multi-centre, cohort study collecting: blood samples, epidemiology and treatment data, longitudinal side-effect and QOL data (before and after treatment, yrs 1 and 2). (2.) Produce a centralised biobank of DNA from 5,300 patients and a centralised data management system. (3.) Validate published biomarkers of radiosensitivity. (4.) Validate clinical predictors of RT toxicity in breast, prostate, and lung cancer and incorporate biomarker data. (5.) Design interventional trials to reduce long-term side effects. (6.) Provide a resource for dissemination and exploitation to the RT community. Results: REQUITE is funded for 60 mos and organised into 7 work packages. Overall management and scientific oversight is run by Manchester. The central activity of the project is a multi-centre, observational study. Enrolment will proceed for 2 yrs in 9 clinical centres, with 2 yrs follow-up. The primary endpoints are change in breast appearance; rectal bleeding (prostate); pneumonitis (lung). Blood samples will be collected before radiotherapy. Tracking, biobanking, DNA preparation and validation of biomarkers (genetic markers and apoptosis assays) as predictive factors will be carried out in WP3-4. Some clinical factors have suggested predictive value for RT side-effects, but there is no consensus. Validation of published models in existing cohorts will be performed, leading to replicated models that can be validated using the REQUITE cohorts. Conclusions: The predictive models will be used to design clinical interventional trials and produce protocols that seek to lower RT side-effects in those individuals at high risk of developing them without affecting tumour control. Dissemination will follow.
An acute lymphoblastic leukemia (ALL) cell line with stem cell phenotype derived by long term co-culture with bone marrow stromal cells
Authors: Lin Wang, Heather O’Leary, James Fortney, Laura F. Gibson
Journal: Cancer Research (2006)

1022  Accumulating evidence suggests that a sub-population of tumor cells that contribute to relapse of leukemia may be comprised of leukemic stem cells (LSC) characterized by their ability to self-renewal and differentiate to multiple lineages. Their significant proliferative potential emphasizes the need to understand the signals that regulate LSC survival during treatment, include cues provided by bone marrow stromal cells. This information is critical for the development of novel treatment strategies that target LSCs to reduce the potential contribution to relapse of disease. In the current study we sought to determine whether acute lymphoblastic leukemia cells with a LSC phenotype are protected by bone marrow stromal cells during chemotherapy. Further, we investigated the mechanisms underlying stromal cell protection of ALL LSCs. A LSC population with expression of markers consistent with that of a hemangioblast, VE-cadherin+Flk-1+CD31+CD34+CD38+CD19+, was isolated following long term co-culture of the ALL cell line Sup-B15 with murine bone marrow stromal cells. Sup-B15 cells that were maintained in culture with adherent stroma for greater than 2 months formed colonies morphologically comparable to human embryonic stem cell colonies grown on mouse embryonic feeder layers. Consistent with their morphological similarity to human embryonic stem cell derived colonies grown in our laboratory, the tumor cells expressed the stem cell markers SSEA-3, SSEA-4, Oct-4, Tra-1-60 and Tra-1-81. Microarray analysis indicated that Sup-B15 cells with the LSC phenotype had a gene expression profile that was clearly distinguishable from the parent population of Sup-B15 cells grown in media alone. Long term co-culture with stromal cells, as well as exposure to the stromal cell derived growth factor TGF-β up-regulated a variety of molecules involved in the Wnt signaling pathway including Wnt 10a and Wnt16. TGF-β1 treatment of Sup-B15 LSCs also resulted in elevated VE-cadherin expression and stabilization of nuclear beta-catenin, while TGF-β2 or TGF-β3 had no effect on cellular distribution of beta-catenin. These data demonstrate a subpopulation of ALL tumor cells, derived by sustained co-culture with bone marrow stromal cells, may be influenced by factors released from the bone marrow microenvironment. The availability of Sup-B15 sustained in media alone, which does not express stem cell markers, will allow unique comparisons between the “bulk” tumor population and a matched “tumor stem cell” with identical genetic make-up as we strive to understand regulation of the survival of each by the bone marrow microenvironment.
TNK-tissue plasminogen activator compared with front-loaded tissue plasminogen activator in acute myocardial infarction: primary results of the TIMI 10B trial
Authors: CP Cannon, CH McCabe, CM Gibson, AA Adgey, MJ Schweiger, RF Sequeira, MJ Frey, HS Mueller, E McCluskey, NL Fox, Frans Van de Werf, E Braunwald, WD Weaver
Journal: Circulation (1997)