tbuckley/cabot-search huggingface dataset:
Surgery alone versus chemoradiotherapy followed by surgery for localized esophageal cancer: Analysis of a randomized controlled phase III trial FFCD 9901.
Authors: C. Mariette, J. F. Seitz, E. Maillard, F. Mornex, P. A. Thomas, J. Raoul, V. Boige, D. Pezet, C. Genet, L. Bedenne
Journal: Journal of Clinical Oncology (2010)

4005 Background: Resection remains the best treatment for carcinoma of the esophagus regarding local control but local recurrence, distant metastatis and poor survival remain an issue after surgery. Often investigated in locally advanced esophageal tumors, impact of neoadjuvant chemoradiotherapy in patients with small tumors is inknown. The aim of this randomised controlled phase III was to assess whether preoperative chemoradiotherapy improves outcomes for patients with localized (stages I or II) esophageal cancer. Methods: The primary endpoint was overall survival. Secondary endpoints were progression free survival, postoperative morbidity and mortality, R0 resection rate, prognostic factors identification. Analysis was done by intention to treat. To demonstrate an increase of overall survival from 35% (S group) to 50% (CRT group) with alpha 5% and 80% power, it was required to observe 182 deaths. 195 patients were randomized from 06/2000 to 06/2009 in 30 centers, 98 were assigned to surgery alone (S group) and 97 to neoadjuvant chemoradiotherapy group (CRT group; 45 Gy/25 F/5 weeks with 2 courses of concomitant chemotherapy 5-fluorouracil 800 mg/m2/day D1-D4 and cisplatin 75 mg/m2 D1 or D2). We report results of a planned interim analysis for primary endpoint. Results: Patient and tumor characteristics were similar between groups. Patients were preoperatively staged I in 18%, IIA in 49.7%, IIB in 31.8%, unknown in 0.5%. Postoperative morbidity and 30 day-mortality rates were 49.5% (S group) vs. 43.9% (CRT group) (p = 0.17) and 1.1% (S group) vs. 7.3% (CRT group) (p = 0.054), respectively. After a median follow-up of 5.7 years, 106 deaths were observed. Median survivals were 43.8 (S group) vs. 31.8 months (CRT group) (HR 0.92, 95% CI 0.63-1.34, p = 0.66). We could stop trial for futility. Conclusions: Neoadjuvant chemoradiotherapy with cisplatin and fluorouracil does not improve overall survival but enhances postoperative mortality rate for patients with stage I or II esophageal cancer compared with surgery alone. No significant financial relationships to disclose.
Non‐Hydrolysed and Hydrolysed Soy Protein
Authors: E. Taudorf, A. Bundgaard, S. Hancke, L. V. Hansen, P. Prahl, B. Weeke
Journal: Allergy (1984)

Daily consumption of soy protein has increased during recent years. Twelve healthy subjects and 12 atopic patients were given 30 g non‐hydrolysed soy protein (NHS) or 30 g hydrolysed soy protein (HS) daily during a 3‐month period. There were no changes in the following immunological parameters: IgE with specificity for NHS or HS. IgG with specificity for NHS, crossed radioimmunoelectrophoresis with NHS and skin prick test using NHS or HS. Hypertrophy of the pancreas in rats exposed to excessive peroral intake of soy flour has been reported. In out study the size of the pancreas was measured before dosing began and at the end of the study by means of ultrasound. No change in size was shown. Daily intake of 30 g NHS and 30 g HS gave rise to gastrointestinal discomfort, while 15 g of both soy protein preparations were usually accepted.
Metabolic tumor volume on interim PET is a better predictor of outcome in diffuse large B-cell lymphoma than semiquantitative methods
Authors: E Malek, A Sendilnathan, M Yellu, A Petersen, M Fernandez-Ulloa, J J Driscoll
Journal: Blood Cancer Journal (2015)

Metabolic tumor volume on interim PET is a better predictor of outcome in diffuse large B-cell lymphoma than semiquantitative methods
Bereavement after homicide: a synergism of trauma and loss
Authors: E K Rynearson, J M McCreery
Journal: American Journal of Psychiatry (1993)

The purpose of this study was to examine the intensity and relationship of trauma and responses to bereavement in family members after homicide.The authors established an outpatient clinic that offered evaluation and supportive psychotherapy after the homicide of a family member. A standardized evaluation protocol was followed with 18 adults in order to detail variables of previous trauma, bereavement, and psychiatric disorder. Standardized measures of bereavement (Texas Revised Inventory of Grief) and trauma (Impact of Event Scale and Dissociative Experiences Scale) were also administered.As a group, the 18 adults were characterized by a high frequency of antecedent psychiatric disorder (N = 12), the homicide of a child (N = 12), and an intensely idealized attachment to the decreased, whose image of violent dying recurred as a disorganizing flashback and dream. The measures of bereavement and trauma showed generally higher levels of intensity in the 18 subjects in the present study than in normal subjects and other cohorts of bereaved subjects.For those who have lost a family member through homicide, recognition of a relatively specific pattern of dysfunctional responses of grief and trauma would promote early identification and psychiatric referral.
Evaluation of a cefoxitin disk diffusion test for the routine detection of methicillin-resistant Staphylococcus aureus
Authors: I. Boutiba-Ben Boubaker, R. Ben Abbes, H. Ben Abdallah, K Mamlouk, F Mahjoubi, A Kammoun, A Hammami, S. Ben Redjeb
Journal: Clinical Microbiology and Infection (2004)
Satraplatin in patients with advanced hormone-refractory prostate cancer (HRPC): Overall survival (OS) results from the phase III satraplatin and prednisone against refractory cancer (SPARC) trial
Authors: A. O. Sartor, D. P. Petrylak, J. A. Witjes, W. R. Berry, G. S. Chatta, D. J. Vaughn, J. Ferrero, T. Demkow, J. C. Eymard, C. N. Sternberg
Journal: Journal of Clinical Oncology (2008)

5003 Background: Satraplatin is a novel oral platinum compound previously reported to reduce risk of disease progression among HRPC pts progressing after prior CT. Herein the impact of satraplatin on OS is reported. Methods: SPARC is a multinational, randomized, double blind, placebo-controlled trial comparing Satraplatin 80 mg/m2/day po x 5 q 5 weeks) + prednisone 5 mg po bid [S] vs placebo + prednisone [P] in patients with metastatic HRPC progressing after prior CT. Progression-free survival (PFS) and OS were co-primary endpoints. Secondary and exploratory endpoints included time to pain progression (TPP), pain response, duration of pain response, objective tumor response, and PSA response. Efficacy analyses were conducted on an intent-to-treat (ITT) basis. Results: 950 pts were randomized 2:1 to S (n=635) and P (n=315). Baseline characteristics were well-balanced across groups. Of all pts, 51% received prior docetaxel and 47% received post-SPARC CT. As reported, S was associated with statistically significant improvements in PFS; TPP; PSA response, objective tumor response, pain response, and duration of pain response. These improvements did not translate into an OS benefit: median OS was 61.3 weeks and 61.4 weeks in the S and P groups respectively (HR = 0.97; 95% CI: 0.83, 1.13). Trends for improved OS was observed in the subgroup of pts who received prior docetaxel (HR = 0.78; 95% CI: 0.61, 0.99; medians 66.1 vs. 62.9) as well as pts who reported a PPI score 2–5 at baseline (HR = 0.88; 95% CI: 0.67, 1.16; medians 45.7 vs. 43.0) when models were adjusted for baseline prognostic factors. In the S group; myelosuppression was the most common toxicity; grade 4 neutropenia was detected in 4% and only one patient experienced grade 4 thrombocytopenia. Grade 3/4 non- hematologic side effects in the S group included infection (4.5%), vomiting (1.6%) and diarrhea (1.9%). Conclusions: Satraplatin is well tolerated and reduces risk of disease progression for men with HRPC progressing after prior CT. Ongoing analyses are planned to define relationships between PFS, pain response, and OS, as well as to elucidate factors (including post-SPARC CT) that may have confounded the ITT survival analysis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GPC-Biotech GPC-Biotech GPC-Biotech
Brief Report: Endothelial Progenitor Cell Phenotype and Function Are Impaired in Childhood‐Onset Systemic Lupus Erythematosus
Authors: Smriti Mohan, Julie Barsalou, Timothy J. Bradley, Cameron Slorach, John A. Reynolds, Sarfaraz Hasni, Becky Thompson, Lawrence Ng, Deborah Levy, Earl Silverman, Mariana J. Kaplan
Journal: Arthritis & Rheumatology (2015)

Systemic lupus erythematosus (SLE) is characterized by increased cardiovascular risk in adult-onset and childhood-onset SLE. Type I interferons (IFNs) appear to play a prominent role in premature vascular damage in adult-onset SLE, at least in part, by inducing impairments in the phenotype and function of endothelial progenitor cells (EPCs), thereby hampering vascular repair. It is not clear whether EPC dysfunction is present in childhood-onset SLE in association with a type I IFN signature.The phenotype and numbers of EPCs were quantified in patients with childhood-onset SLE, patients with juvenile idiopathic arthritis (JIA), and matched healthy control subjects. In a separate cohort of patients with childhood-onset SLE, markers of subclinical atherosclerosis and endothelial dysfunction were quantified using standardized protocols and analyzed for associations with serum type I IFN activity.EPC numbers and function were significantly decreased in patients with childhood-onset SLE compared with patients with JIA and healthy control subjects. Serum from patients with childhood-onset SLE impaired differentiation of EPCs into mature endothelial cells in healthy controls, and this effect was blocked by inhibition of the type I IFN pathway. Type I IFN activity in serum was not significantly associated with subclinical atherosclerosis and endothelial function in patients with childhood-onset SLE.As in adult-onset SLE, childhood-onset SLE is characterized by phenotypic and functional EPC abnormalities, which are likely triggered by type I IFNs. Although cross-sectional analysis revealed no global association between type I IFN signatures and vascular measures of subclinical atherosclerosis, longitudinal assessments are needed to evaluate whether progression of vascular damage in patients with childhood-onset SLE is associated with type I IFNs, as observed in patients with adult-onset SLE.
Inhibition of Fucosylation Reshapes Inflammatory Macrophages and Suppresses Type II Collagen–Induced Arthritis
Authors: Jun Li, Hui‐Chen Hsu, Yana Ding, Hao Li, Qi Wu, PingAr Yang, Bao Luo, Amber L. Rowse, David M. Spalding, S. Louis Bridges, John D. Mountz
Journal: Arthritis & Rheumatology (2014)

Objective Fucosylation catalyzed by fucosyltransferases (FUTs) is an important posttranslational modification involved in a variety of biologic processes. This study was undertaken to determine the roles of fucosylation in rheumatoid arthritis (RA) and to assess the efficacy of reestablishing immune homeostasis with the use of 2‐deoxy‐ d ‐galactose (2‐ d ‐gal), a fucosylation inhibitor. Methods Quantitative polymerase chain reaction was performed to determine the expression of FUT genes in synovial tissue from RA and osteoarthritis (OA) patients and in fluorescence‐activated cell–sorted cells from RA synovial fluid. The in vivo inhibitory effect of 2‐ d ‐gal was evaluated in a murine collagen‐induced arthritis (CIA) model. The in vitro effects of 2‐ d ‐gal on differentiation of inflammatory macrophages, production of cytokines, and antigen uptake, processing, and presentation functions were analyzed. Results FUTs that are involved in terminal or subterminal fucosylation, but not those involved in core fucosylation or O ‐fucosylation, were up‐regulated in RA compared to OA synovial tissue. The expression of terminal FUTs was highly positively correlated with the expression of TNF (encoding for tumor necrosis factor α). Terminal FUTs were predominantly expressed in M1 macrophages. In vivo, 2‐ d ‐gal treatment of mice precluded the development of CIA by reducing inflammatory macrophages and Th17 cells in the draining lymph nodes and decreasing the levels of TNFα, interleukin‐6 (IL‐6), and antibodies to type II collagen in the serum. In vitro, treatment with 2‐ d ‐gal skewed the differentiation of M1 macrophages to IL‐10–producing M2 macrophages. Furthermore, 2‐ d ‐gal significantly inhibited the antigen‐presenting function of M1 macrophages. Conclusion Terminal fucosylation is a novel hallmark of inflammatory macrophages. Inhibition of terminal FUTs reshapes the differentiation and functions of M1 macrophages, leading to resolution of inflammation in arthritis.
Assay directed chemotherapy in advanced solid tumors: A phase II trial
Authors: J. B. Blitzer, D. Mc Connell, C. Cullinane, S. Grant, T. Asciuto, I. Shbeeb, B. Sommers, C. Jacobs, S. Davis, K. Byczynski, R. Nagourney
Journal: Journal of Clinical Oncology (2005)

9692 The lack of valid predictive assays for the selection of chemotherapy has impeded advances in cancer research. Recognizing that cancer represents dysregulated apoptosis, we developed assay methods based on cell-death as surrogate markers of drug induced apoptosis that have proven superior to older proliferation-based clonogenic (colony) & H3*-thymidine incorporation (EDR) techniques. To test the predictive validity, a phase II trial of assay directed therapy (ADT) in untreated NSCLC, colorectal (Col), gastric & pancreatic (Pan) cancers began accrual Nov. 2003. Drugs and combinations are selected from among FDA-approved agents for each diagnosis. The agents(s) with the lowest LC50 values define the Ex Vivo Best Regimen (EVBR). Patients with adequate performance (0,1) and measurable disease receive EVBR to progression or toxicity. Endpoints include response, time to progression, QOL and cost of care. Of the first 12 patients, 3 were found resistant to all standard cytotoxics with 1of them, a NSCLC, going on to achieve durable PR with 1st line Iressa. Eight patients are evaluable, 3 Col, 4 NSCLC & 1 Pan. Responses: NSCLC 1/4 PR; 3/4 SD ORR (25%); Col 2/3 PR, 1/3 CR ORR (100%), PAN 1/1 PD but with subsequent PR to 2nd line ADT therapy. Median time to progression is 6.2 months. One liver-metastatic Col patient has achieved pathologic CR confirmed at laparotomy. Toxicities are tolerable with no treatment related deaths. QOL and cost of care analyses are ongoing. In each disease, no single regimen or agent proved uniformly effective. Instead, highly individual profiles were observed supporting the concept of ADT to optimize drug selection. Though preliminary, the response rate of 50% (4/8), compares favorably with current results in these diagnoses. Accrual continues with additional patient results to be reported. Supported by a Research Grant from the Memorial Medical Center Foundation of Long Beach. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Malcolm C. Todd Cancer Institute, Rational Therapeutics
Patients' attitudes toward hallucinations
Authors: L J Miller, E O'Connor, T DiPasquale
Journal: American Journal of Psychiatry (1993)

This study examined patients' attitudes toward their hallucinations by assessing their beliefs about the purposes served by hallucinations and the adverse effects of hallucinations. It also investigated whether these attitudes were related to characteristics of the hallucinations or of the patients, whether the attitudes changed after treatment, and whether attitudes before treatment predicted the presence or absence of hallucinations after treatment.Fifty hallucinating psychiatric inpatients were given semistructured interviews shortly after admission to the hospital and again shortly before discharge. The interviews elicited detailed descriptions of 12 phenomenologic characteristics of hallucinations and 11 attitude variables.The majority of subjects reported some positive effects of hallucinations. The presence of olfactory hallucinations and the ability to predict hallucinations were significantly related to valuing hallucinations. Attitudes usually did not change with treatment; when they did change they usually became more positive. Subjects who valued hallucinations more before treatment were significantly more likely to be hallucinating after treatment.The findings are consistent with the idea that psychological factors contribute to the expression of hallucinations. Assessing adaptive functions of hallucinations may predict whether hallucinations will respond to treatment and identify fruitful areas for psychosocial intervention.
Jagged1 intracellular domain-mediated inhibition of Notch1 signalling regulates cardiac homeostasis in the postnatal heart
Authors: Mélanie Metrich, April Bezdek Pomey, Corinne Berthonneche, Alexandre Sarre, Mohamed Nemir, Thierry Pedrazzini
Journal: Cardiovascular Research (2015)

Notch1 signalling in the heart is mainly activated via expression of Jagged1 on the surface of cardiomyocytes. Notch controls cardiomyocyte proliferation and differentiation in the developing heart and regulates cardiac remodelling in the stressed adult heart. Besides canonical Notch receptor activation in signal-receiving cells, Notch ligands can also activate Notch receptor-independent responses in signal-sending cells via release of their intracellular domain. We evaluated therefore the importance of Jagged1 (J1) intracellular domain (ICD)-mediated pathways in the postnatal heart. In cardiomyocytes, Jagged1 releases J1ICD, which then translocates into the nucleus and down-regulates Notch transcriptional activity. To study the importance of J1ICD in cardiac homeostasis, we generated transgenic mice expressing a tamoxifen-inducible form of J1ICD, specifically in cardiomyocytes. Using this model, we demonstrate that J1ICD-mediated Notch inhibition diminishes proliferation in the neonatal cardiomyocyte population and promotes maturation. In the neonatal heart, a response via Wnt and Akt pathway activation is elicited as an attempt to compensate for the deficit in cardiomyocyte number resulting from J1ICD activation. In the stressed adult heart, J1ICD activation results in a dramatic reduction of the number of Notch signalling cardiomyocytes, blunts the hypertrophic response, and reduces the number of apoptotic cardiomyocytes. Consistently, this occurs concomitantly with a significant down-regulation of the phosphorylation of the Akt effectors ribosomal S6 protein (S6) and eukaryotic initiation factor 4E binding protein1 (4EBP1) controlling protein synthesis. Altogether, these data demonstrate the importance of J1ICD in the modulation of physiological and pathological hypertrophy, and reveal the existence of a novel pathway regulating cardiac homeostasis.
Mast cells influence the physiological functions of fibroblasts
Authors: Mariam Bagher, Oskar Hallgren, Gunilla Westergren-Thorsson, Leif Bjermer
Journal: European Respiratory Journal (2012)

Rationale: Mast cells (MC) play a role in allergic disease and anaphylaxis, by releasing their granules containing pro-inflammatory and pro-fibrotic mediators. Recent studies, suggest that mast cells may have a role in non-allergic chronic lung diseases. Since tissue remodelling and fibrosis is a key feature in these diseases our hypothesis is that the mast cell-fibroblast interplay is altered.  Methods: MC isolated from human peripheral blood and fibroblasts (HFL-1 fibroblasts and primary fibroblasts from lungs) were used in the experiments. The effects of the MC proteases; chymase and tryptase on fibroblasts were analyzed with western blot and q-PCR. To investigate the impact of cell-cell interaction, co-cultures between MC and fibroblasts was established and differentiation and production of extracellular matrix proteins were investigated.  Results: Mast cell tryptase significantly increased HFL-1 cell migration while chymase had no effect. This effect was not due to increased cell proliferation as neither tryptase nor chymase influenced the cell number. Tryptase triggered increased expression of alpha-smooth muscle actin, a marker for myofibroblasts. This was accompanied by a change in the production of collagens and proteoglycans. MC adhered directly to HFL-1 and primary fibroblasts when using co-cultures. The cell-cell contact caused alterations in the fibroblast phenotype and in the extra cellular matrix production.  Conclusions: These data indicate that MC and their mediators influence fibroblast phenotype and the production of extra cellular matrix proteins. Our results suggest that mast cells may play an important role in tissue remodelling and fibrosis by modulating the physiological function of fibroblasts.
Gabapentin for the treatment of pain related to radiation-induced mucositis in patients with head and neck cancers treated with intensity modulated radiation therapy (IMRT)
Authors: V. Bar Ad, S. Both, P. Dutta, H. Quon
Journal: Journal of Clinical Oncology (2007)

16513 Background: Gabapentin has been reported to effectively treat multiple neuropathic pain syndromes. This retrospective study evaluates the efficacy of gabapentin for the treatment of pain related to radiation induced mucositis, in patients with head and neck cancers, treated with radiation therapy (RT). Methods: This retrospective study includes 30 pts with head and neck cancers, treated with RT, without concomitant or induction chemotherapy. IMRT planning was performed using a concomitant boost technique with a median dose of 54 Gy, 63 Gy, and 66 Gy delivered to the low risk clinical tumor volume (CTV), high risk CTV and boost target volume, respectively, using 30- 34 fractions. The dose of gabapentin was gradually increased starting on the second week of RT from 600 mg/day to the dose of 2700 mg/d over the course of one week. Narcotic pain medication (Roxicodone) was prescribed as needed. Results: 26 (86%) pts required no pain medication during the first two weeks of RT, despite the presence of grade 1 and/or 2 mucositis in 24 of them. During the third and fourth weeks of RT, 28 (93%) pts were treated with a median dose of 2700 mg/day of gabapentin, with only 3 (10%) pts requiring low dose narcotic pain medication, 15–30 mg/day of Roxicodone, added to gabapentin for adequate pain control, despite grade 2 or higher mucositis in 22 pts. During weeks 5 and 6, 28 (93%) pts continued to be treated with a median dose of 2700 mg/day of gabapentin with only 10 (35%) pts requiring 15–40 mg/day of Roxicodone, in addition to gabapentin for pain control, despite the presence of grade 2 or higher mucositis in 23 pts. Only 3% of the pts in this group had delay in RT delivery. Gabapentin was well tolerated with only 13% of pts experiencing mild side effects (somnolence, nausea, or vomiting), which were managed with reducing the dose or changing the dosing schedule. Conclusions: Gabapentin is effective and well-tolerated for the treatment of mucositis-induced pain related to radiation treatment in patients with head and neck cancers, treated with IMRT. We further demonstrate that the use of gabapentin at doses of 2700 mg per day can reduce or eliminate the need for narcotic pain medication. No significant financial relationships to disclose.