tbuckley/cabot-search huggingface dataset:
Interleukin-10: An Immune-Activating Cytokine in Cancer Immunotherapy
Authors: Hui Zhang, Yu Wang, E. Shelley Hwang, You-Wen He
Journal: Journal of Clinical Oncology (2016)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors. August 15, 2016 ARTICLE CITATION DOI: 10.1200/JCO.2016.69.6435 Journal of Clinical Oncology - published online before print August 29, 2016 PMID: 27573656 Interleukin-10: An Immune-Activating Cytokine in Cancer Immunotherapy Hui ZhangxHui ZhangSearch for articles by this author Yu WangxYu WangSearch for articles by this author E. Shelley HwangxE. Shelley HwangSearch for articles by this author You-Wen HexYou-Wen HeSearch for articles by this author Show More First Affiliated Hospital, China Medical University, Shenyang, People's Republic of ChinaDuke University Medical Center, Durham, NCDuke University Comprehensive Cancer Center, Durham, NCDuke University Medical Center, Durham, NC https://doi.org/10.1200/JCO.2016.69.6435 First Page Full Text PDF Figures and Tables © 2016 by American Society of Clinical Oncology Companion Safety, Antitumor Activity, and Immune Activation of Pegylated Recombinant Human Interleukin-10 (AM0010) in Patients With Advanced Solid Tumors
Systems Biology and Clinical Practice in Respiratory Medicine. The Twain Shall Meet
Authors: Cindy Thamrin, Urs Frey, David A. Kaminsky, Helen K. Reddel, Andrew J. E. Seely, Béla Suki, Peter J. Sterk
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Section:ChooseTop of pageAbstract <<How Does Complexity Arise...What Can Systems Biology ...Phenotypic Fingerprinting...Variability Analysis: Mon...Temporal Phenotyping: Ext...Variability Analysis: Mon...Conclusions and Implicati...ReferencesCITING ARTICLES
Icotinib versus vinorelbine/platinum as adjuvant therapy in stage II-IIIA non-small cell lung cancer with EGFR-mutations: A multicenter, randomized, positive-controlled, phase 3, indication-expanding study (EVIDENCE, CCTC-1501).
Authors: Jianxing He, Wenhua Liang, Shidong Xu, Shaofa Xu, Jianying Zhou, Weimin Mao, Qun Wang, Xiuyi Zhi, Fenlai Tan, Lieming Ding, Caicun Zhou
Journal: Journal of Clinical Oncology (2016)

TPS8570 Background: Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been recognized as the standard of care in patients with NSCLC harboring sensitive EGFR mutations in advanced stages, their benefits as adjuvant therapy after resection compared with standard platinum-based chemotherapy remained unclear. There is still not an EGFR-TKI that has been approved in adjuvant setting worldwide. Based on results from ICOGEN (NCT01040780) and a large real-world report (n > 6,000), icotinib (an EGFR-TKI developed in China) has been approved in front-line setting in advanced diseases. This trial is the first study that targeting at expanding the indication of EGFR-TKI to adjuvant setting, with an application for China Food and Drug Administration approval. Methods: This is a phase 3, multicenter, open labeled, and randomized controlled trial. Pathological stage II-IIIA NSCLC patients with sensitive EGFR mutations (deletion in exon 19 and L858R in exon 21) after complete resection were eligible. The primary endpoint is disease-free survival (DFS) and secondary endpoints are overall survival, tolerability and quality of life. The sample size was specified assuming a hazard ratio (HR) of 0.67, equating to an increase in median DFS from an expected 28 months for chemotherapy to 42 months for icotinib. To provide 85% power at a two-sided 5% significance level, and an estimated 10% dropout rate, a total of 320 patients are required. Eligible patients will be 1:1 randomly assigned to receive icotinib or platinum doublets. Experimental arm received icotinib 125 mg tid orally for up to 2 years while the active control arm received intravenously vinorelbine 25 mg/m2, day 1 and day 8 and cisplatin 75 mg/m2 day 1, 21 days/cycle for up to 4 cycles, until disease relapse or intolerable toxicity. Free icotinib will be provided to patients in the control arm upon relapse. Recruitment was started since June 1st, 2015 and is active in 17 out of 31 centers currently. The duration of recruitment will be 61 months (18 months of recruitment and 43 months of follow-up). Clinical trial information: NCT02448797.
Molecular Determinants of Mutant Phenotypes, Inferred from Saturation Mutagenesis Data
Authors: Arti Tripathi, Kritika Gupta, Shruti Khare, Pankaj C. Jain, Siddharth Patel, Prasanth Kumar, Ajai J. Pulianmackal, Nilesh Aghera, Raghavan Varadarajan
Journal: Molecular Biology and Evolution (2016)

Understanding how mutations affect protein activity and organismal fitness is a major challenge. We used saturation mutagenesis combined with deep sequencing to determine mutational sensitivity scores for 1,664 single-site mutants of the 101 residue Escherichia coli cytotoxin, CcdB at seven different expression levels. Active-site residues could be distinguished from buried ones, based on their differential tolerance to aliphatic and charged amino acid substitutions. At nonactive-site positions, the average mutational tolerance correlated better with depth from the protein surface than with accessibility. Remarkably, similar results were observed for two other small proteins, PDZ domain (PSD95pdz3) and IgG-binding domain of protein G (GB1). Mutational sensitivity data obtained with CcdB were used to derive a procedure for predicting functional effects of mutations. Results compared favorably with those of two widely used computational predictors. In vitro characterization of 80 single, nonactive-site mutants of CcdB showed that activity in vivo correlates moderately with thermal stability and solubility. The inability to refold reversibly, as well as a decreased folding rate in vitro, is associated with decreased activity in vivo. Upon probing the effect of modulating expression of various proteases and chaperones on mutant phenotypes, most deleterious mutants showed an increased in vivo activity and solubility only upon over-expression of either Trigger factor or SecB ATP-independent chaperones. Collectively, these data suggest that folding kinetics rather than protein stability is the primary determinant of activity in vivo. This study enhances our understanding of how mutations affect phenotype, as well as the ability to predict fitness effects of point mutations.
Phase II study of the insulin-like growth factor-1 receptor (IGF-1R) antibody cixutumumab (C) in patients (pts) with thymoma (T) and thymic carcinoma (TC).
Authors: A. Rajan, A. W. Berman, R. J. Kelly, A. Lopez-Chavez, R. Dechowdhury, H. Chen, G. Giaccone
Journal: Journal of Clinical Oncology (2010)

e17525 Background: Platinum-based chemotherapy is the standard of care for advanced unresectable T and TC. New options for treatment are needed for pts with recurrent or refractory disease. We have demonstrated expression of IGF-1R by immunohistochemistry (IHC) in 132 resected tumor specimen from pts with T and TC. C is an anti-IGF-1R monoclonal antibody that has shown activity in pts with thymic malignancies. Methods: Eligibility: Pts with recurrent T or TC who have received ≥ 1 prior platinum-containing regimen; measurable disease; PS 0-2; normal organ function. C is dosed at 20 mg/kg IV on day 1 of a 21-day cycle. Primary objective: to determine the objective response rate (PR+CR). Statistical design: Simon's optimal two stage design with two independent cohorts for T and TC. Toxicity is assessed every cycle using CTCAE version 3.0 and tumor response is assessed every 6 weeks using RECIST 1.0. Blood samples are being collected for pharmacokinetic (PK) and pharmacodynamic (PD) analysis. Results: From 8/2009 to 12/2009, 13 pts (7 males, 6 females; 5 T, 8 TC) enrolled. Median age: 54 yrs (26-72). Mean number of prior systemic regimens: 4.5 (1-11). A median of 3 cycles (1-7) of C has been administered so far. Treatment has been well tolerated. 2 pts developed grade (G) 4 asymptomatic hyperuricemia post treatment (attributed to C). Uric acid levels normalized spontaneously and no treatment was required. G3 toxicities included 1 case of asymptomatic AST elevation and 1 lymphopenia. 1 pt with pleural metastases adjacent to the chest wall developed G2 pain and erythema locally after treatment on 2 different occasions. Pain did not respond to opioids but significant benefit was noted with non-steroidal anti-inflammatory agent (NSAID) use. This pt has shown a reduction in measurable disease by 15%. 3 other pts developed post treatment pain: 1 G2 and 2 G1. 13 pts are evaluable for response. Best response so far is stable disease in 8 pts (4T and 4 TC). 5 pts had disease progression. PK and PD analysis is ongoing. Conclusions: Treatment with C is well tolerated. No objective responses have been observed so far. 4 pts have experienced tumor pain after therapy. The study is open to accrual to both cohorts. No significant financial relationships to disclose.
From “sense of number” to “sense of magnitude”: The role of continuous magnitudes in numerical cognition
Authors: Tali Leibovich, Naama Katzin, Maayan Harel, Avishai Henik
Journal: Behavioral and Brain Sciences (2016)

Abstract In this review, we are pitting two theories against each other: the more accepted theory, the number sense theory , suggesting that a sense of number is innate and non-symbolic numerosity is being processed independently of continuous magnitudes (e.g., size, area, and density); and the newly emerging theory suggesting that (1) both numerosities and continuous magnitudes are processed holistically when comparing numerosities and (2) a sense of number might not be innate. In the first part of this review, we discuss the number sense theory. Against this background, we demonstrate how the natural correlation between numerosities and continuous magnitudes makes it nearly impossible to study non-symbolic numerosity processing in isolation from continuous magnitudes, and therefore, the results of behavioral and imaging studies with infants, adults, and animals can be explained, at least in part, by relying on continuous magnitudes. In the second part, we explain the sense of magnitude theory and review studies that directly demonstrate that continuous magnitudes are more automatic and basic than numerosities. Finally, we present outstanding questions. Our conclusion is that there is not enough convincing evidence to support the number sense theory anymore. Therefore, we encourage researchers not to assume that number sense is simply innate, but to put this hypothesis to the test and consider whether such an assumption is even testable in the light of the correlation of numerosity and continuous magnitudes.
Anticancer chemotherapy in teenagers and young adults: managing long term side effects
Authors: Saif S Ahmad, Marika AV Reinius, Helen M Hatcher, Thankamma V Ajithkumar
Journal: BMJ (2016)

Cancer is the leading cause of disease related death in teenagers and young adults (TYAs) in Western countries. 1 2In the UK, cancer in TYAs accounts for 9% and 15% of all male and female deaths respectively, and its incidence has risen by 19% since the mid-1990s, leading to 2300 new cases a year between 2011 and 2013. 1 In Japan it accounted for nearly 7000 deaths between 2000 and 2006. 3TYA cancer survivors are likely to live for many decades but are at risk of late effects of their treatment.This article provides information for generalists on late effects of anticancer chemotherapy (see infographic and supplementary table A) that may affect quality of life.Radiotherapy related effects are not discussed but are summarised elsewhere.
444P Overall survival (OS) by EGFR mutation status and subtypes (Deletion 19/L858R) for first-line therapies with maintenance regimens in advanced non-small-cell lung cancer (NSCLC): a Bayesian multiple treatment comparison (MTC) meta-analysis
Authors: P.S. Tan, G. Lopes, S. Aacharyya, M. Bilger, B. Haaland
Journal: Annals of Oncology (2015)
The Role Of PET Imaging For Predicting Treatment Failure In Primary Mediastinal B-Cell Lymphoma
Authors: Sarah J. Nagle, Elise A. Chong, Seble Chekol, Nirav N. Shah, Sunita D. Nasta, Eli Glatstein, John P. Plastaras, Drew Torigian, Stephen J. Schuster, Jakub Svoboda
Journal: Blood (2013)
Problematic Analysis and Inadequate Toxicity Data in Phase III Apatinib Trial in Gastric Cancer
Authors: Sheng Zhang
Journal: Journal of Clinical Oncology (2016)

cancer. In superiority trials, intention-to-treat (ITT) analyses that include all patients according to the allocated treatment are standard. This can lead to a conservative estimate of effect size and avoid bias associated with nonrandom loss of participants; however, excluding patients who did not start treatment or who stopped treatment during the trial can lead to biased estimates. This ITT analysis has been required by CONSORT statement, and the pitfalls of not performing ITTanalysis have been documented previously. 2 In the current study, five patients in the experimental arm and one patient in the placebo arm were excluded from the ITTanalyses, which may exaggerate the modest survival benefi to bserved. 1 Toxicity is one crucial aspect of clinical trial reporting. In a previous phase II trial that used apatinib for treatment of 25 patients with breast cancer, the dose of 750 mg once per day resulted in substantial toxicities: a dose delay of at least one cycle with dose reduction occurred in 84% of patients. Almost all patients experienced grade $ 3 toxicity, and treatment-related death occurred in two patients. 3 Because of the heavy toxicity of apatinib, the dose was reduced to 500 mg once per day in further studies. In the current study, Li et al 1 concluded that a dose of 850 mg once per day is tolerable and acceptable. Reasons for this discrepancy are not clear; however, even in the current trial, of the 40 patients that discontinued apatinib treatment, 22 patients (55%) stopped treatment as a result of toxicity, and dose reduction occurred in 21% patients who finished apatinib treatment. 1 What is the total
Impact of Red Blood Cell and Platelet Transfusions at Early after Engraftment on Outcome of Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Kazuhiko Ikeda, Yumiko Mashimo, Hiroshi Ohkawara, Hiroshi Takahashi, Akiko Shichishima-Nakamura, Kayo Shirado Harada, Miki Furukawa, Hideyoshi Noji, Kazuei Ogawa, Hitoshi Ohto, Yasuchika Takeishi
Journal: Blood (2014)
Assessing the performance of Watson for oncology, a decision support system, using actual contemporary clinical cases.
Authors: Mark G. Kris, Ayca Gucalp, Andrew S. Epstein, Andrew David Seidman, Julia Fu, Jeffrey Keesing, Aryeh Caroline, Mark Megerian, Thomas Eggebraaten, Robert DeLima, Marie Setnes, Marjorie Glass Zauderer
Journal: Journal of Clinical Oncology (2015)

8023 Background: IBM Watson for Oncology (WFO), trained by Memorial Sloan Kettering (MSK), is a cognitive computing system designed to assist medical oncologists making treatment decisions for individual patients. Recommendations are consistent with established guidelines and published evidence, as reflected in MSK’s practice and historical cases. Treatment options are classified as Recommended (WFO-REC), For Consideration (WFO-FC), or Not Recommended (WFO-Not REC). Published evidence, medical logic, and drug information are presented for each treatment option. We sought to assess the current performance of WFO to benchmark accuracy and identify areas for development. Methods: 20 de-identified cases were selected from the practices of two MSK thoracic medical oncologists. Patients presented for initial consultation regarding first-line systemic therapy during 2014 and all necessary information to make a treatment decision was available at the time of initial consultation or within two weeks, including molecular pathology. Cases were entered into WFO using structured attributes. WFO recommendations were compared to those of the MSK thoracic medical oncologist (MSKMD-REC). Results: WFO-REC and MSKMD-REC matched 50% of the time. 25% of the MSKMD-RECs appeared in the WFO-FC category and 25% in WFO-Not REC. In the 16 cases with metastatic lung cancers, 88% of administered regimens were returned as WFO-REC or WFO-FC. All choices were within established guidelines. Cases where the MSKMD-REC appeared as WFO-Not REC involved elderly patients with co-morbidities not yet included in WFO. Conclusions: While WFO‘s choices today fall within evidence-based standards, WFO has the capacity to provide greater precision through iterative training and development. Elderly patients for whom care choices are heterogeneous based on co-morbid illnesses represent a challenge. Benchmarking against actual cases has helped us to prioritize development work to increase the number of attributes to include more co-morbid conditions and to incorporate patient preferences to improve precision.
Polycythemia Vera Among Participants of a Nuclear Weapons Test
Authors: Janet L. Sobell
Journal: JAMA (1987)

To the Editor.—  In August 1984,The Journalpublished a report by Caldwell et al 1 from the Centers for Disease Control pertaining to polycythemia vera among participants of the Smoky nuclear weapons test. Of 3217 nucleartest participants present at the detonation on Aug 31,1957, 95.5% were located and contacted to ascertain health status as of December 1981. For those who reported ill health, medical data were collected from the various physicians and hospitals involved in their care.  Using well-defined diagnostic criteria, two cases of definite polycythemia vera and two suspected cases were found. In contrast to the observed number of affected individuals, the authors report an expected number of 0.2 cases, derived by applying age-specific incidence rates reported by Modan 2 for metropolitan Baltimore. The standard mortality rate (SMR) for the two definite cases was 10 ( P =.02). When both the two definite and the two suspected cases of
Vasectomy and Increased Risk of Prostate Cancer
Authors: Stephen Sidney
Journal: JAMA (1993)

To the Editor.  —In their studies of the relationship of vasectomy to prostate cancer, Giovannucci et al 1,2 relied on self-report by cohort members or their wives to identify incident prostate cancers and confirmed as many of these cases as possible by request for and review of medical records. Self-report of prostate cancer may potentially result in significant underascertainment of cases. The Kaiser Permanente Study 3 of vasectomy and prostate cancer afforded an opportunity to assess the potential for underascertainment. In the Kaiser Permanente Study, incident prostate cases were identified in a cohort of multiphasic health checkup (MHC) examinees by linking the medical record number of the MHC examinee to computerized tumor registry and hospitalization records, a method that does not rely on self-report. Of the 38 MHC cohort members who had a second MHC after an incident prostate cancer, 17 (45%) did not report a history of any cancer
Curative radiation therapy for primary ocular lymphomas: Demonstration of dose response.
Authors: A. Turaka, T. Li, W. Lubbe, M. R. Smith, M. M. Millenson, R. J. Schilder, H. Borghaei, A. D. Cohen, T. I. Al-Saleem, N. Nicolaou
Journal: Journal of Clinical Oncology (2010)

e18503 Background: Orbital lymphomas (OL) are rare and account for less than 1% of all cases of non-Hodgkin lymphoma. Radiotherapy (RT) alone provides good local control rates (97-100%) for extranodal marginal zone lymphoma (MALT) of the orbit. We report the outcomes of OL patients treated at FCCC. Methods: Between 1991 and 2008, 23 patients (28 eyes, 5 bilateral, 20%) treated at FCCC with local radiation therapy for orbital lymphoma were reviewed. Treatment consisted of 24-36 Gy,1.5-2.5 Gy per fraction (median 30 Gy in 20 fractions) of RT to the orbit using 6 MV photons. Patient, tumor and treatment related factors including age, stage, histology, type of treatment, RT details and late side effects were analyzed for the local control rates (LC), relapse free and overall survival (OS) by number of patients and orbits independently. Results: The median follow-up was 27 months (range: 1-123 months). The median age was 72 years (range: 37-87), 11 were females, 12 males. Most common presenting symptom was proptosis (74%). 20 patients had tumor in orbit only, 2 in conjunctiva only and 1 in both conjunctiva + orbit. Histology was MALT in 13 patients, and other low grade B cell NHL in 10. The 5-year LC and OS rates were 95%, 63% by patients and 96%, 68% by orbits respectively. The 5-year LC rate at patient level for MALToma was 91% versus 100% for other NHL histologies (p=0.3) and 100% for RT dose ≥ 30 Gy versus 75% for < 30 Gy (p = 0.04). One patient had both systemic + orbital relapse and systemic relapse was seen in two. The median interval to first relapse was 25 months (0.99- 122.37). On univariate analysis including age (≤ 70 versus > 70 years), stage (IAE vs others), histology (MALT versus others), and location of tumor (orbit vs others), there was no difference in outcomes except for RT dose (≥ 30 Gy vs < 30 Gy) for LC (p = 0.04). 4/23 patients had three lines of improvement in Snellen's visual acuity after one year of treatment. Minimal dry eye was seen in 77% patients. Five patients developed cataracts. There were no late effects like corneal ulcer, papillopathy or secondary glaucoma. Conclusions: Radiation therapy alone is the extremely effective in the curative management of primary localized orbital lymphoma. RT dose of 30 Gy provides better LC rates. No significant financial relationships to disclose.
Potential for Zika virus introduction and transmission in resource-limited countries in Africa and the Asia-Pacific region: a modelling study
Authors: Isaac I Bogoch, Oliver J Brady, Moritz U G Kraemer, Matthew German, Maria I Creatore, Shannon Brent, Alexander G Watts, Simon I Hay, Manisha A Kulkarni, John S Brownstein, Kamran Khan
Journal: The Lancet Infectious Diseases (2016)
No Observation of Chromosomal Instability after Transplantation of RPS14- and TP53-Modified Human HSCs in NSG/NSGS Mice
Authors: Kathrin Thomay, Azam Salari, Beate Vajen, Andrea Schienke, Maike Hagedorn, Juliane Ebersold, Hans Heinrich Kreipe, Andreas Krueger, Axel Schambach, Brigitte Schlegelberger, Gudrun Göhring
Journal: Blood (2015)