tbuckley/cabot-search huggingface dataset:
AB0525 Safety and Efficiency of Low-Dose Interleukin-2 Treatment in Systemic Lupus Erythematosus
Authors: J. He, X. Zhang, D. Yu, Z.-G. Li
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nuclear self-antigens, production of pathogenic autoantibodies and damage to multiple organs. While corticosteroids and immunosuppressive agents have improved the outcome of patients, there remains a significant unmet need for safe and more effective treatments. Low-dose Interleukin-2 (IL-2) therapy has recently been shown effective to treat autoimmune disease. <h3>Objectives</h3> To assess the safety and efficacy of low-dose IL-2 therapy in active SLE. <h3>Methods</h3> We conducted a clinical trail on active SLE patients (NCT02084238). A total of 40 patients were enrolled. Patients with SLE Disease Activity Index (SLEDAI) scores ≥8 received three courses of low dose recombinant human IL-2 (1 million IU every second day for 2 weeks followed by a 2-week hiatus). The primary end point was the response rate at week 10. Both the safety and efficiency of IL-2 therapy were evaluated. <h3>Results</h3> Total 36 patients (36/40, 90%) achieved an SLE Responder Index (SRI) improvement at week 6. No patients demonstrated high grad adverse events; mild injection-site reaction was observed in 5 patients (5/40, 12.5%). Better response was seen in patients with skin involvement (erythema, photo sensibility, Rdynolds, vasculitis), hematologic abnormities (leukopenia, Thrombocytopenia and anemia) and disease-related fever. Patients showed the improvement of major laboratory indicators, including reduced anti-dsDNA autoantibody titres and 24-hour proteinuria, and increased levels of the complement proteins C3 and C4. Immunological analysis showed significant increase of Treg cells and decrease of effector helper T cells after the therapy. <h3>Conclusions</h3> Our results showed that low-dose IL-2 therapy in active SLE were safe and achieved satisfactory efficacy with increasing Treg and decreasing effector helper T cells. <h3>References</h3> Jing He, Louis M. Tsai, Yew Ann Leong, Xin Hu, Cindy S. Ma, Nina Chevalier, Xiaolin Sun, Kirsten Vandenberg, Steve Rockman, Yan Ding, Lei Zhu, Wei Wei, Changqi Wang, Alexander Karnowski, Gabrielle T. Belz, Joanna R. Ghali, Matthew C. Cook, D. Sean Riminton, André Veillette, Pamela L. Schwartzberg, Fabienne Mackay, Robert Brink, Stuart G. Tangye, Carola G. Vinuesa, Charles R. Mackay, Zhanguo Li,* and Di Yu,* Circulating Precursor CCR7loPD-1hi CXCR5+ CD4+ T Cells Indicate Tfh Cell Activity and Promote Antibody Responses upon Antigen Reexposure. Immunity, 2013, 39(4),770-781 <h3>Disclosure of Interest</h3> None declared
Phase III study of immediate versus delayed docetaxel after induction therapy with gemcitabine plus carboplatin in advanced non-small cell lung cancer: Updated report with survival
Authors: P. Fidias, S. Dakhil, A. Lyss, D. Loesch, D. Waterhouse, J. Cunneen, R. Chen, J. Treat, C. Obasaju, J. Schiller
Journal: Journal of Clinical Oncology (2007)

LBA7516 Background: Gemcitabine (G) plus carboplatin (C) therapy is active in patients with advanced non-small-cell lung cancer (NSCLC). For nonprogressing patients, optimal timing of second-line therapy with a non-cross-resistant agent is unclear. This Phase III, randomized trial assessed the efficacy and safety of docetaxel (D) administered either immediately after GC induction therapy or upon disease progression (PD). Methods: Patients having either Stage IIIB with pleural effusion or Stage IV NSCLC were enrolled. Prior chemotherapy for NSCLC was not permitted. For GC induction, G 1000 mg/m 2 was administered on Days 1, 8 followed by C AUC 5 on Day 1. After four 21-day cycles, nonprogressors were randomized to either the immediate D group (D 75 mg/m 2 administered on Day 1 every 21 days, for a maximum of 6 cycles) or the delayed D group (patients given best supportive care after randomization and the same D regimen after first evidence of PD) treatment arms. Primary endpoint was overall survival (OS). Additional analyses included response rates, toxicity and progression-free survival (PFS). Results: Results are summarized in the table below. OS was not statistically different (p=0.071) between the two D arms. However, 31 patients (20.1%) in the delayed D arm and 38 patients (24.8%) in the immediate D arm were censored for OS analysis. PFS analysis (from randomization to first evidence of PD or death) showed a statistically significant (p=&lt;0.0001) improvement in the immediate D arm. D given to NSCLS patients immediately after GC induction did not increase toxicity. Conclusions: Comparison of PFS for each D arm suggests a possible clinical benefit for immediate D therapy. However, even though OS trended in favor of immediate D therapy, the OS result did not reach statistical significance. The implications of these results will be discussed. [Table: see text] [Table: see text]
Continuous versus targeted medication in schizophrenic outpatients: outcome results [published erratum appears in Am J Psychiatry 1991 Jun;148(6):819]
Authors: W T Carpenter, T E Hanlon, D W Heinrichs, A T Summerfelt, B Kirkpatrick, J Levine, R W Buchanan
Journal: American Journal of Psychiatry (1990)

The authors report on the outcome of treatment of 116 outpatients with chronic schizophrenia who were assigned to a 2-year, single-blind course of treatment with either targeted or continuous medication. These patients were not restricted to those who were good candidates for a medication reduction strategy. Continuous medication was superior to targeted medication in preventing decompensations and hospitalizations and in extent of employment at 2 years. Other measures of psychopathology and functioning at 1 and 2 years did not differentiate the two groups of patients. The targeted approach achieved a substantial reduction in total medication through a reduction in the number of days of medication administration.
A case of advanced gastrointestinal stromal tumor (GIST)presenting with paraneoplastic syndrome
Authors: H. M. Guirgis, R. F. Holcombe
Journal: Journal of Clinical Oncology (2004)

4242 Background: Paraneoplastic syndromes are common manifestations of many malignancies but have not been reported with gastrointestinal stromal tumors (GIST). Methods: This is a case report of a 51 y/o white male with GIST. Results: The patient presented with dull persistent headache and diplopia. Eye examination revealed diffuse bilateral sixth nerve palsy. Routine laboratory tests and a spinal tap analysis were non-revealing. CT and MRI of the brain were normal. MRI of the orbits showed a mild, diffuse inflammation and thinckening of the extraocular muscles. The patient was treated with prednisone and improved. A few weeks later, the patient developed pleuritic pain and CT of the abdomen revealed a large paraduodenal mass and a second mass measuring 5x8 cm in the left lobe of the liver. The patien had complete resection of the paraduodenal mass and a left hepatic lobectomy. Pathology was consistent with GIST and the surgical margins were free of tumor involvement. The patient was followed without treatment with serial CT scans and also had open liver biopsies which were negative at the time of an incidental cholecystectomy. He remained symptom free for 6 years. Headache and diplopia returned and improved with prednisone. Restaging with CT and PET revealed a new mass in the right lobe of the liver. Biopsies revealed a c-kit positive tumor similar in morphology and immunohistochemical staining to the initial GIST. The patient responded to imatinib with resolution of the PET scan findings though CT continued to demonstrate a large mass. The headache and diplopia have not recurred following discontinuation of the prednisone. Conclusions: The temporal links between symptomatology and the original and recurrent tumors support the hypothesis that the headache and diplopia represent a paraneoplastic syndrome previously unreported for patients with GIST. No significant financial relationships to disclose.
Using impedance-based approaches for measuring cell-mediated cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC)
Authors: Brandon Lamarche, Yama Abassi
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The most common method for measuring cell-mediated cytotoxicity is the release assay. Effector cell-mediated disruption of the target cell membrane results in leakage of its cytoplasmic contents into the culture medium. Endogenous biomolecules (such as lactate dehydrogenase) or
Depressive illness among chemically dependent adolescents
Authors: E Y Deykin, S L Buka, T H Zeena
Journal: American Journal of Psychiatry (1992)

The purpose of this study was to investigate the prevalence and correlates of depression among adolescents being treated for chemical dependence.Using the National Institute of Mental Health Diagnostic Interview Schedule, the authors interviewed 223 adolescents, aged 15-19 years, who were in residential treatment for alcohol or drug dependence diagnosed according to DSM-III-R criteria. Data on sociodemographic characteristics, school and social performance, past history, family composition, familial alcohol and drug abuse, and previous victimization of the subjects were also gathered.Fifty-four (24.7%) of the subjects met the DSM-III-R criteria for depression. Very few of the traditional correlates of depression discriminated depressed from nondepressed subjects, suggesting that the presence of chemical dependence overrides other predictors of depression. Only female gender, paternal psychopathology, and victimization (physical abuse, sexual abuse) emerged as important variables associated with depression. However, subjects whose onset of depression preceded their chemical dependence had different characteristics from those whose depression began after their chemical dependence.The prevalence of depressive illness in these chemically dependent adolescents was approximately three times that reported for nonreferred groups of similar age. This high rate of depression reflects the contributions of two distinct groups--those with primary depression and those with depression subsequent to chemical dependence--whose characteristics differed, suggesting the possibility of two pathologic processes, similar in manifestation but with different associated features and possibly with distinct etiologies. Confirmation of these findings in further research could indicate that the two forms of depression may require different treatment approaches.
STUDIES ON X-RAY EFFECTS
Authors: Waro Nakahara, James B. Murphy
Journal: The Journal of Experimental Medicine (1921)

A relatively increased degree of resistance in mice to a certain strain of transplantable cancer was demonstrated after treatment of animals with small doses of x-rays capable of stimulating lymphoid tissue. The refractory state induced was determinable 3 to 7 days after the dose of x-rays was given.
A sense of urgency: Evaluating the link between clinical trial development time and the accrual performance of CTEP-sponsored studies
Authors: S. Cheng, M. Dietrich, S. Finnigan, A. Sandler, J. Crites, L. Ferranti, A. Wu, D. Dilts
Journal: Journal of Clinical Oncology (2009)

CRA6509 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. No significant financial relationships to disclose.
Ambulatory Blood Pressure Control and Subclinical Left Ventricular Dysfunction in Treated Hypertensive Subjects
Authors: Fusako Sera, Zhezhen Jin, Cesare Russo, Edward S. Lee, Joseph E. Schwartz, Tatjana Rundek, Mitchell S.V. Elkind, Shunichi Homma, Ralph L. Sacco, Marco R. Di Tullio
Journal: Journal of the American College of Cardiology (2015)
Predictors of toxicity for metastatic melanoma patients treated with ipilimumab
Authors: Sara Valpione, Sandro Pasquali, Luca Campana, Simone Mocellin, Luisa Piccin, Jacopo Pigozzo, Vanna Chiarion-Sileni
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Immunotherapy with ipilimumab, a monoclonal antibody anti-Cytotoxic T-Lymphocyte Antigen 4, demonstrated a survival advantage for metastatic melanoma patients, but the treatment is associated with immuno-related adverse events (irAEs) that may drive to severe comorbidities and
Continuous daily dosing (CDD) of sunitinib (SU) in pts with advanced GIST: Updated efficacy, safety, PK and pharmacodynamic analysis
Authors: S. George, J. Y. Blay, P. G. Casali, A. Le Cesne, S. E. DePrimo, C. S. Harmon, C. N. Law, V. Tassell, C. M. Baum, G. D. Demetri
Journal: Journal of Clinical Oncology (2008)

10554 Background: SU is an oral multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, FLT3, CSF-1R and RET, approved multinationally for the treatment of advanced imatinib (IM)-resistant/intolerant GIST on an intermittent dosing schedule comprising 4 wk on 50 mg/d followed by 2 wk off treatment. The safety and efficacy of SU 37.5 mg CDD in pts with GIST after IM failure were evaluated in this phase II study. Methods: In this open-label, multicenter trial, pts were randomized either to morning (AM) or evening SU dosing. The primary endpoint was clinical benefit rate (CBR; % of pts with RECIST-defined CR, PR or SD ≥24 wk). Secondary endpoints included PFS, OS, ORR, safety/tolerability, PK parameters and plasma concentrations of potential biomarkers. Results: 60/61 randomized pts (30/arm) received CDD of SU. As of Dec. 2007, pts had started a median of 11 28-d treatment cycles (range 1–24). 24 pts had completed 1 y of study treatment, and 37 had discontinued. To date, the overall CBR is 55%, including 7 pts (12%) with PRs. Median PFS overall is 32 wk (95% CI 25–48). With 60% of pts still alive, median OS is estimated to be 88 wk (95% CI 68-NA). The most common treatment-emergent (all- causality) non-hematologic Aes of any grade were diarrhea (45%), abdominal pain (42%) and asthenia (38%). Grade 3/4 hematologic laboratory abnormalities included reduced levels of neutrophils (12%), hemoglobin (12%) and platelets (3%). Dose reduction to 25 mg due to Aes occurred in 14 pts (23%). Sunitinib CDD achieved constant drug exposure with no unexpected accumulation. 23 pts on AM dosing had plasma samples taken at ≥2 timepoints during treatment. Analysis of VEGF, soluble (s)VEGFR-2, sVEGFR-3 and sKIT concentrations in these samples supported a persistent pharmacodynamic effect of SU with CDD, without the concentration rebound observed during off-treatment periods with intermittent dosing. Preliminary analyses suggested a correlation between OS and decreases in plasma sKIT after the first 3 cycles, and particularly after cycle 5 (n=17; P=0.007). Conclusions: CDD of SU appears to be a safe and potentially effective dosing strategy for pts with GIST after IM failure. CDD is associated with constant drug exposure and a persistent pharmacodynamic effect. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer GlaxoSmithKline, Infinity, MedImmune, Novartis, Pfizer, PharmaMar, Roche, sanofi-aventis Pfizer GlaxoSmithKline, Novartis, Pfizer, PharmaMar, Roche, SigmaTau Infinity, Janssen-Cilag, Novartis, Pfizer, SigmaTau Infinity, Novartis, Pfizer Novartis, PharmaMar
Autoimmunity, immunoglobulin adsorption and dilated cardiomyopathy: has the time come for randomized clinical trials?∗∗∗Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Douglas L Mann
Journal: Journal of the American College of Cardiology (2001)
A Novel HLA–DRB1*10:01–Restricted T Cell Epitope From Citrullinated Type II Collagen Relevant to Rheumatoid Arthritis
Authors: Karine Chemin, Sabrina Pollastro, Eddie James, Changrong Ge, Inka Albrecht, Jessica Herrath, Christina Gerstner, Karolina Tandre, Thais Sampaio Rizzi, Lars Rönnblom, Anca Catrina, Rikard Holmdahl, Lars Klareskog, Niek de Vries, Vivianne Malmström
Journal: Arthritis & Rheumatology (2015)

Antibodies against citrullinated type II collagen (Cit-CII) are common in the sera and synovial fluid of patients with rheumatoid arthritis (RA); however, the known T cell epitope of CII is not dependent on citrullination. The aim of this study was to identify and functionally characterize the Cit-CII-restricted T cell epitopes that are relevant to RA.Peripheral blood mononuclear cells (PBMCs) from HLA-DRB1*10:01-positive patients with RA and healthy donors were stimulated in vitro with candidate CII peptides. CD154 up-regulation was measured as a marker of antigen-specific activation, and anti-HLA-DR-blocking experiments confirmed HLA restriction. Cytokine production was measured using a Luminex technique. Direct peptide-binding assays using HLA-DRB1*10:01 and HLA-DRB1*04:01 monomeric proteins were performed. The T cell receptor (TCR) β-chain of CD154-enriched antigen-specific T cells was analyzed using high-throughput sequencing.A novel Cit-CII peptide was identified based on its ability to activate CD4+ T cells from HLA-DRB1*10:01-positive individuals. When stimulated in vitro, Cit-CII autoreactive T cells produced proinflammatory cytokines. Cit-CII(311-325) bound (with low affinity) to HLA-DRB1*10:01 but not to HLA-DRB1*04:01, while the native form was unable to bind either protein. In addition, highly expanded clones were identified in the TCRβ repertoire of Cit-CII(311-325) -stimulated PBMCs.These results illustrate the ability of the citrullination process to create T cell epitopes from CII, a cartilage-restricted protein that is relevant to RA pathogenesis. The exclusive binding of Cit-CII(311-325) to HLA-DRB1*10:01 suggests that recognition of citrullinated epitopes might vary between individuals carrying different RA-associated HLA-DR molecules.
Targeting the TGFβ pathway with galunisertib, a TGFβRI SMI, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint inhibition
Authors: David Schaer, Yanxia Li, Stephen Castaneda, Ivan Inigo, David Surguladze, Xiaohong Xu, Desiree Nugent, Mary Murphy, Gerald Hall, Karim Benhadji, Susan Guba, Yiwen Li, Michael Kalos, Kyla Driscoll
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts TGFβ signaling is known to play a central role in tumor biology, via inducing and/or enhancing tumor cell growth and differentiation, modulating the extracellular matrix in the stroma, inducing epithelial to mesenchymal transition, modulating angiogenesis, and inhibiting immune
Altered Cellular Responses As Biomarkers for Fluoranthene Exposure to the Bone Marrow-Mesenchymal Stem Cells: Implications for Stem Cell-Based in Vitro Models That Help Determine the Associated Hematotoxicity
Authors: Hwan-Young Kim, Ji-Eun Noh, Hee-Jo Baek, Jae-Dong Moon, Jong-Hee Shin, Soon-Pal Suh, Hoon Kook, Dong-Wook Ryang, Myung-Geun Shin
Journal: Blood (2014)
CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC).
Authors: Alan P. Venook, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Michelle R. Mahoney, Bert H. O'Neil, James Edward Shaw, Blase N. Polite, Howard S. Hochster, James Norman Atkins, Richard M. Goldberg, Robert J. Mayer, Richard L. Schilsky, Monica M. Bertagnolli, Charles David Blanke
Journal: Journal of Clinical Oncology (2014)

LBA3 Background: Irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6), combined with bevacizumab (BV) or cetuximab (CET), are first-line treatments for metastatic adenocarcinoma of the colon or rectum (MCRC). The optimal antibody combination is unknown. Methods: Patients (pts) with KRAS wild-type (wt)(codons 12 and 13) MCRC and performance status 0-1 received FOLFIRI or mFOLFOX6 (MD/pt choice at enrollment) and randomized to either CET 400 mg/m 2 X 1, then 250 mg/m 2 qw or BV 5 mg/kg q2w. The original study included unselected MCRC pts receiving FOLFIRI or mFOLFOX6 and randomized to CET, BV, or both. After 1,420 pts accrued the study amended as follows: only pts with KRAS wt tumors (codon 12 and 13) were included and the combination CET + BV arm was deleted. Rx continued until progression, death, unacceptable toxicity, curative surgery; treatment holidays of 4 wks permitted. Subsequent Rx not mandated. Accrual goal was 1,142 pts. One° endpoint was overall survival (OS). Results: Between November 2005 and March 2012, 3,058 unselected pts enrolled, 2,334 KRAS wt pts randomized; final N =1137 (333 pre-amend eligible retrospective KRAS test, 804 post-amend), median f/u = 24 mos; Median age – 59 y; 61% male. Chemo/BV – 559; chemo/CET – 578. FOLFIRI = 26.6%, mFOLFOX6 = 73.4%. OS analysis planned at 849 events; efficacy futility boundary crossed at 10 th interim analysis on 1/29/14. OS - chemo/BV v. chemo/CET = 29.04 (25.66 - 31.21) v. 29.93 (27.56 - 31.21) mos; HR = 0.92 (0.78, 1.09) (p value = 0.34). PFS (by investigator): chemo/BV v. chemo/CET: 10.84 (9.86 - 11.4) v. 10.45 (9.66 - 11.33) mos. There were 94 pts free of disease following surgery, median f/u 40 mos (range 8.0 - 86.0). Outcomes similar by gender. On-study toxicity and deaths as expected. Analyses underway: Expanded RAS, FOLFOX v. FOLFIRI, subsequent therapies, long-term survivors, correlates. Conclusions: Chemo/CET and chemo/BV equivalent in OS in pts KRAS wt (codons 12 + 13) MCRC; either is appropriate in first line. Overall OS of 29 + mos and 8% long-term survivors confirms progress in MCRC. The preference for FOLFOX limits chemotherapy comparison. Expanded RAS and other molecular and clinical analyses may identify subsets of pts who get more or less benefit from specific regimens. Clinical trial information: NCT00265850.