tbuckley/cabot-search huggingface dataset:
Impact on quality of life (QoL) of the addition of docetaxel (T) to neoadjuvant cisplatin plus 5-fluorouracil treatment in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN): EORTC study 24971
Authors: J. Bernier, C. Coens, E. Remenar, C. Van Herpen, J. Germa Lluch, S. Stewart, M. Degardin, C. Spirlet, J. B. Vermorken
Journal: Journal of Clinical Oncology (2006)

5522 Background: The EORTC 24971 trial compared the efficacy and safety of two neoadjuvant regimens in the treatment of stage III or IV, M0 SCCHN. Eligible patients (pts) with primary tumor sites in the oral cavity, oropharynx, hypopharynx, and larynx and WHO performance status (PS) ≤1) were randomized to 2–4 cycles of cisplatin (P) 100 mg/m 2 day 1, followed by a continuous infusion of 5-fluorouracil (F) 1000 mg/m 2 /day from days 1- 5 (PF), or T 75 mg/m 2 + P 75 mg/m 2 day 1 then F 750 mg/m 2 /day from days 1 - 5 (TPF), followed by locoregional radiation therapy (RT). The impact of the two regimens on QoL was a secondary endpoint. Methods: QoL was assessed at baseline, at cycles 2 and 4, and 6 and 9 months after RT using the EORTC QLQ-C30 questionnaire to obtain the Global Health Status/Quality of Life (GHS/QoL) score, and the Head and Neck Performance Status Scale (PSS-HN) to assesses the normality of diet, eating in public, and understandability of speech on a scale of 0 to 100. The EORTC QLQ-HN35 questionnaire was also administered at those time-points. Results: 358 pts were randomized to PF (181 pts) or TPF (177 pts). Baseline (BL) characteristics of the pts were well balanced between groups. TPF was superior to PF in terms of response rate, progression-free survival (primary endpoint), overall survival, and tolerability. Compliance with the QLQ-C30 questionnaire was good ranging from 96% at BL to 41% at 9 months post RT, and was similar between the treatment arms. GHS/QoL scores were comparable at BL between the two arms (p = 0.54) and improved in both arms on starting treatment. Over time this score remained stable with TPF, but decreased after RT with PF (treatment-time interaction: p = 0.009). Evolution of the PSS-H&amp;N score was better on TPF (normality of diet p= 0.0064; eating in public p = 0.0004; understandability of speech p = 0.0003). Moreover, TPF was associated with a 30% reduction in the risk of WHO PS deterioration (p = 0.0158) Conclusions: The use of docetaxel in neoadjuvant treatment of SCCHN improves efficacy without deleterious effects on QoL and functional outcomes. [Table: see text]
Abstract 17590: Diastolic Function Assessment Has an Independent and Incremental Value in Patients with Advanced Ischemic Cardiomyopathy - A Current Appraisal of an Old Question
Authors: Joao L Cavalcante, Nael Aldweib, Zoran B Popovic, Randall C Starling, Milind Y Desai, Scott D Flamm, Thomas H Marwick, Deborah H Kwon
Journal: Circulation (2012)
Utility of end consolidation bone marrow aspirates in childhood acute lymphoblastic leukemia [ALL]: A Pediatric Oncology Group study [POG]
Authors: K. J. Hull, B. B. Bell, A. R. Chauvenet, J. Kurtzberg, S. Sterikoff, M. Devidas, B. M. Camitta
Journal: Journal of Clinical Oncology (2004)

8564 Background: There is little information on the value of bone marrow aspirates (BMA) as a guide to treatment in pediatric ALL. Although BMA morphology provides useful information at diagnosis, end of induction, and end of therapy, its value when performed at the end of consolidation is not known. During the conduct of several POG protocols, a decision was made to discontinue end of consolidation BMA. This provided an opportunity to study the value of BMA at that time point. Methods: We reviewed end of consolidation BMA morphology from four POG protocols, (POG 9201 Pilot for good-risk ALL; POG 9201, phase III study for good-risk ALL; and POG 9405/9605, phase III study for standard-risk ALL). Patients were stratified into low-, standard-, and high-risk groups according to NIH criteria (age, white count, CNS involvement), DNA index, and cytogenetics. POG 9201 Pilot, 9201, and 9605 defined the end of consolidation as week 25, and POG 9405 as week 28. 2086 study coordinator charts were reviewed: 697 [POG 9201 Pilot/9201], 301 [POG 9405], and 1088 [POG 9605]. Remission was defined as: M1: 0–5% blasts; M2: > 5–25%; M3: > 25%, with at least 200 cells counted. High-risk patients were not reviewed. Results: 776 patients (330/697, 66/301 and 380/1088) had complete information, including differential count, on the end of consolidation marrow (reflects study amendment to discontinue BMA). 773 of 776 (99.6%) of patients with end of consolidation BMA had M1 marrow. Two of 3 who had M2 marrow relapsed (28 and 45 months after achieving remission), and the third is continuously disease free (60 months). Conclusions: Routine BMA at the end of consolidation is not of prognostic or therapeutic value and should be restricted to protocols in which randomization to different treatments is after that time point. Traditional morphologic review will likely be supplanted by more sensitive measures of minimal residual disease, such as cytogenetics, flow cytometry, or molecular markers. No significant financial relationships to disclose.
Regulatory T cells (T<sub>Reg</sub>) in patients with colorectal carcinoma (CC)
Authors: M. Bueter, M. Gasser, N. Schramm, M. Grimm, C. Gerstlauer, A. Thalheimer, A. Thiede, H.-J. Gassel, D. Meyer, A. M. Waaga-Gasser
Journal: Journal of Clinical Oncology (2005)

9594 Background: In 3 years 18% of our patient cohort with CC (n=74) suffered tumor relapse after complete surgical resection. This may be caused by a modification of the anti-Tumor-Immune response through TReg. Demonstration of these cells and their increased IL-10 secretion could explain this phenomenon. Thus it was the aim of our study to investigate the tumor-specific immune response in CC patients UICC stage dependent and to characterize T cells in the blood and at the tumor site. The p53 protein was chosen as tumor associated antigen (TAA) as it is mutated and overexpressed in up to 60% of CC. Methods: 21% of 74 patients with CC were of UICC stage I, 26% of UICC II, 26% of UICC III and 27% of UICC stage IV. Peripheral blood lymphocytes (PBLs) from preoperative taken blood were stimulated with overlapping synthetic peptides encompassing the complete wildtype-p53 protein sequence and analyzed for cytokine secretion (IL-10, IFN-γ; ELISPOT, ELISA). PBL cytospin preparations and fresh tumor tissue were analyzed using immunohistochemistry (IHC) in single-, double- and triple-staining technique. P53 gene mutations and expression of TReg genes were analyzed by RTq-PCR. Results: After PBL stimulation with p53 peptides distinct residues were found inducing IFN-γ or IL-10 secretion. Thereby UICC stage played a crucial role for IL-10 secretion independent from specific p53 gene mutations: T cells from patients in UICC III and IV expressed significant more IL-10 than T cells from patients of UICC I and II. No correlation was observed between IFN-γ production and UICC stage. IHC showed more TReg (CD4+CD25+) and a stronger p53 accumulation for tumors of higher stages (UICC III/IV) than for lower UICC stages (p53: UICCI/II: 22,2%, UICC III/IV: 75,6%; CD4/CD25: UICC I/II: 33,3%, UICC III 66,7%, UICC IV 100% positive cells). TReg specific gene expression (CD4, CD25, Foxp3, GITR, GATA-3) also correlated with UICC stage. Conclusions: p53 induces both IFN-γ and IL-10 secretion. The predominance of the IL-10 production indicates that TReg directly participate in modulating an anti tumor immune response. IL-10 levels in the blood as well as expression of TReg-specific genes at the tumor site correlate with the UICC stages explaining poor prognosis and elevated relapse rate for CC. No significant financial relationships to disclose.
Androgen Deprivation Followed by Acute Androgen Stimulation Selectively Sensitizes AR-Positive Prostate Cancer Cells to Ionizing Radiation
Authors: Mohammad Hedayati, Michael C. Haffner, Jonathan B. Coulter, Raju R. Raval, Yonggang Zhang, Haoming Zhou, Omar Mian, Emma J. Knight, Nina Razavi, Susan Dalrymple, John T. Isaacs, Aileen Santos, Russell Hales, William G. Nelson, Srinivasan Yegnasubramanian, Theodore L. DeWeese
Journal: Clinical Cancer Research (2016)

The current standard of care for patients with locally advanced prostate cancer is a combination of androgen deprivation and radiation therapy. Radiation is typically given with androgen suppression when testosterone levels are at their nadir. Recent reports have shown that androgen stimulation of androgen-deprived prostate cancer cells leads to formation of double-strand breaks (DSB). Here, we exploit this finding and investigate the extent and timing of androgen-induced DSBs and their effect on tumor growth following androgen stimulation in combination with ionizing radiation (IR).Androgen-induced DNA damage was assessed by comet assays and γH2A.X foci formation. Effects of androgen stimulation and radiation were determined in vitro and in vivo with xenograft models.We document that androgen treatment of androgen-deprived prostate cancer cell lines resulted in a dose- and time-dependent induction of widespread DSBs. Generation of these breaks was dependent on androgen receptor and topoisomerase II beta but not on cell-cycle progression. In vitro models demonstrated a synergistic interaction between IR and androgen stimulation when IR is given at a time point corresponding with high levels of androgen-induced DSB formation. Furthermore, in vivo studies showed a significant improvement in tumor growth delay when radiation was given shortly after androgen repletion in castrated mice.These results suggest a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. Clin Cancer Res; 22(13); 3310-9. ©2016 AACRSee related commentary by Chua and Bristow, p. 3124.
Early lung cancer detection: monoclonal antibody staining of exfoliated cells in sputum.
Authors: S D Bernal, A D Elias
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.11.1676 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2460593 Early lung cancer detection: monoclonal antibody staining of exfoliated cells in sputum. S D BernalxS D BernalSearch for articles by this author , A D EliasxA D EliasSearch for articles by this author Show More Dana-Farber Cancer Institute, Harvard Medical School, Boston. https://doi.org/10.1200/JCO.1988.6.11.1676 First Page PDF © 1988 by American Society of Clinical Oncology
Abstract 13596: Adenosine-Induced Pulmonary Vein Ectopy as a Predictor of Recurrent Atrial Fibrillation Following Pulmonary Vein Isolation
Authors: Jim W Cheung, Frank S Lin, James E Ip, Jeffrey H Chung, Steven M Markowitz, Christopher F Liu, George Thomas, Joseph M Lee, Seth J Lessner, Bruce B Lerman
Journal: Circulation (2012)

Background: Adenosine (ADO) has been used to unmask dormant conduction following pulmonary vein (PV) isolation. We have shown that ADO can induce ectopy in electrically silent PVs following PV isol...
Inter-tissue coexpression network analysis reveals DPP4 as an important gene in heart to blood communication
Authors: Quan Long, Carmen Argmann, Sander M. Houten, Tao Huang, Siwu Peng, Yong Zhao, Zhidong Tu, Jun Zhu
Journal: Genome Medicine (2016)

Inter-tissue molecular interactions are critical to the function and behavior of biological systems in multicellular organisms, but systematic studies of interactions between tissues are lacking. Also, existing studies of inter-tissue interactions are based on direct gene expression correlations, which can't distinguish correlations due to common genetic architectures versus biochemical or molecular signal exchange between tissues. We developed a novel strategy to study inter-tissue interaction by removing effects of genetic regulation of gene expression (genetic decorrelation). We applied our method to the comprehensive atlas of gene expression across nine human tissues in the Genotype-Tissue Expression (GTEx) project to generate novel genetically decorrelated inter-tissue networks. From this we derived modules of genes important in inter-tissue interactions that are likely driven by biological signal exchange instead of their common genetic basis. Importantly we highlighted communication between tissues and elucidated gene activities in one tissue inducing gene expression changes in others. We reveal global unidirectional inter-tissue coordination of specific biological pathways such as protein synthesis. Using our data, we highlighted a clinically relevant example whereby heart expression of DPP4 was coordinated with a gene expression signature characteristic for whole blood proliferation, potentially impacting peripheral stem cell mobilization. We also showed that expression of the poorly characterized FOCAD in heart correlated with protein biosynthetic processes in the lung. In summary, this is the first resource of human multi-tissue networks enabling the investigation of molecular inter-tissue interactions. With the networks in hand, we may systematically design combination therapies that simultaneously target multiple tissues or pinpoint potential side effects of a drug in other tissues.
Vitamin A-Induced Modification of Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene Metabolism in Syrian Hamster Cell Cultures
Authors: Ronald E. Rasmussen, Ph.D., Irene Y. Wang, Ph.D., T. Timothy Crocker, M.D.
Journal: JNCI Journal of the National Cancer Institute (1972)

With repeated passage, primary cultures of Syrian hamster embryo cells lost both the ability to convert benzo[a]pyrene (BP) to metabolic products and to bind BP to cellular components. Treatment of such late-passage cells with vitamin A, at levels of 1 µg/ml or less, restored their BP metabolizing activity. This effect was not immediate but required at least 2 days of exposure to vitamin A, suggesting that extensive subcellular changes were occurring. The restoration of BP metabolizing activity was observed as increased binding of 3H-BP to cell components as well as an increase in specific enzymatic activity of cell-free preparations from vitamin A-treated cells.
Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways
Authors: Stefania Crippa, Mohamed Nemir, Samir Ounzain, Mark Ibberson, Corinne Berthonneche, Alexandre Sarre, Gaëlle Boisset, Damien Maison, Keith Harshman, Ioannis Xenarios, Dario Diviani, Daniel Schorderet, Thierry Pedrazzini
Journal: Cardiovascular Research (2016)

The adult mammalian heart has poor regenerative capacity. In contrast, the zebrafish heart retains a robust capacity for regeneration into adulthood. These distinct responses are consequences of a differential utilization of evolutionary-conserved gene regulatory networks in the damaged heart. To systematically identify miRNA-dependent networks controlling cardiac repair following injury, we performed comparative gene and miRNA profiling of the cardiac transcriptome in adult mice and zebrafish.Using an integrated approach, we show that 45 miRNA-dependent networks, involved in critical biological pathways, are differentially modulated in the injured zebrafish vs. mouse hearts. We study, more particularly, the miR-26a-dependent response. Therefore, miR-26a is down-regulated in the fish heart after injury, whereas its expression remains constant in the mouse heart. Targets of miR-26a involve activators of the cell cycle and Ezh2, a component of the polycomb repressive complex 2 (PRC2). Importantly, PRC2 exerts repressive functions on negative regulators of the cell cycle. In cultured neonatal cardiomyocytes, inhibition of miR-26a stimulates, therefore, cardiomyocyte proliferation. Accordingly, miR-26a knockdown prolongs the proliferative window of cardiomyocytes in the post-natal mouse heart.This novel strategy identifies a series of miRNAs and associated pathways, in particular miR-26a, which represent attractive therapeutic targets for inducing repair in the injured heart.
Abstract 12235: The Incidence of Acute Myocardial Infarction is Decreasing but Out-of-Hospital Cardiac Arrest of Cardiac Origin is Increasing in the Completely Registered Data Out of 1,800,000 Prefectural Inhabitants in an Era of Aging Population
Authors: Sunao Kojima, Kunihiko Matsui, Hisao Ogawa
Journal: Circulation (2013)

Background:  A great number of registries on acute myocardial infarction (AMI) demonstrated that there was a steady trend of increasing incidence for AMI. However, a small number of AMI patients in the limited areas and hospitals where coronary intervention is aggressively performed are merely included. Moreover, patients with cardiac arrest probably due to AMI who were not transferred to a hospital are rarely counted. Kumamoto Acute Coronary Event (KACE) Study has been conducted since 2004 to explore the accurate trends for AMI and cardiac death in an era of an aging population.   Methods and Results:  Kumamoto prefecture is located in southwestern Japan and has a stable population over the last 10 years (1,852,135 in 2004 and 1,805,000 in 2011). A total of 8,131 AMI patients in 2004-2011 and 6,064 patients with out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin in 2005-2011 in Kumamoto prefecture were entirely registered. The age-adjusted incidence (/100,000 persons/year) of AMI decreased from 32.8 in 2004 to 24.5 in 2011 (P=0.005). However, the proportion of AMI patients >80 years in 2010-2011 were higher than those in 2004-2005 (30 vs 26%, P=0.010). Moreover, the rate of non-cardiac death (e.g. sepsis, multiple organ failure, pneumonia, adult respiratory distress syndrome) evidently increased from 10% in 2004-2005 to 20% in 2010-2011 (P=0.049). Whereas, overall age-adjusted incidence of OHCA gradually increased from 18.4 in 2005 to 24.6 in 2011 (P=0.006). Especially, the incidence of OHCA patients >85 years in 2011 was 1.8 times as much as those in 2005 (Figure).   Conclusions:  Decreasing incidence of AMI is recently equal to increasing incidence of OHCA of cardiac origin. Non-cardiac death due to complications accompanied by medical treatments is highlighted rather than cardiac death in senior AMI patients. Urgent measures against cardiovascular emergency care indispensable to patients of advanced age should be taken in an era of an aging population in Japan.
Change in quantitative FDG-PET was significantly more accurate than change in size at predicting histopathologic response to neoadjuvant therapy in high grade soft tissue sarcomas
Authors: V. Evilevitch, W. A. Weber, W. D. Tap, K. Chow, M. Allen-Auerbach, S. D. Nelson, F. R. Eilber, J. J. Eckardt, J. Czernin, F. C. Eilber
Journal: Journal of Clinical Oncology (2007)

10017 Background: Change in size by RECIST (Response Evaluation Criteria in Solid Tumors) has been the standard to assess response to therapy in non-GIST soft tissue sarcomas (STS). Although recent studies have demonstrated that Positron Emission Tomography with F18-fluorodeoxyglucose (FDG-PET) may be used to assess response, there has not been a direct comparison between these modalities. The aim of this study was to prospectively evaluate whether a change in quantitative FDG-PET or a change in size [computed tomography(CT)] was more accurate at predicting histopathologic response to neoadjuvant therapy in patients with high grade STS using a combined FDG-PET/CT scan. Methods: From 1/05 - 12/06 58 patients with resectable biopsy proven high grade STS scheduled to undergo neoadjuvant chemotherapy were prospectively enrolled in this study. Patients underwent FDG-PET/CT prior to and after neoadjuvant treatment (prior to surgery). Tumor FDG-uptake was quantified by standardized uptake values (SUV). Changes in tumor size were quantified according to RECIST. Following tumor resection, response was assessed histopathologically. Patients with = 10% viable tumor cells were classified as responders. To date, 36 patients have completed the study and are the subject of this analysis. Results: In histopathologic responders (n=10, 28%), reduction of tumor FDG-uptake was significantly greater (-64%) than in histopathologic non-responders (-37%), (p=0.005). Using a 50% decrease in tumor SUV as a threshold value resulted in a sensitivity of 90% and a specificity of 58% for assessment of histopathologic response (p=0.01). Response assessment per RECIST showed no significant correlation with histopathologic response (sensitivity 20%, specificity 89%, p=0.4). There was no correlation between changes in tumor size and histopathologic response (area under the ROC curve = 0.6, p=0.1). Conclusions: In patients with high grade STS, quantitative FDG-PET was significantly more accurate than size based criteria for assessment of histopathologic response to neoadjuvant therapy. FDG-PET should be considered as a modality to monitor treatment response is patients with high grade STS. No significant financial relationships to disclose.
Vitamin A Content of Foods and Feeds.
Journal: JAMA (1933)

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Abstract 15652: Comparison of the Novel Peroxisome Proliferator-Activated Receptor Alpha Agonist K-877 and Fenofibrate on High-Density Lipoprotein Subclass Distribution Determined by High-Performance Liquid Chromatography in Patients With Dyslipidemia
Authors: Shizuya Yamashita, Shun Ishibashi, Hidenori Arai, Eiichi Araki, Koutaro Yokote, Tatsuhiko Kodama
Journal: Circulation (2013)

Introduction: HDL is a class of structurally and functionally heterogeneous particles. Among the HDL particles, small HDL (HDL3) are more functional than large HDL (HDL2) in reverse cholesterol tra...