tbuckley/cabot-search huggingface dataset:
Scavenger Receptor A1 Prevents Metastasis of Non–Small Cell Lung Cancer via Suppression of Macrophage Serum Amyloid A1
Authors: Yan Zhang, Yongyue Wei, Bin Jiang, Lili Chen, Hui Bai, Xudong Zhu, Xiaoyu Li, Hanwen Zhang, Qing Yang, Junqing Ma, Yong Xu, Jingjing Ben, David C. Christiani, Qi Chen
Journal: Cancer Research (2017)

Mechanisms of cross-talk between tumor cells and tumor-associated macrophages (TAM), which drive metastasis, are not fully understood. Scavenger receptor A1 (SR-A1) expressed primarily in macrophages has been associated with lung tumorigenesis. In this study, we used population genetics, transcriptomics, and functional analyses to uncover how SR-A1 is involved in lung cancer and its prognosis. SR-A1 genetic variants were investigated for possible association with survival of advanced stage NSCLC patients in the Harvard Lung Cancer Study cohort. Two SNPs (rs17484273, rs1484751) in SR-A1 were associated significantly with poor overall survival in this cohort. Data from The Cancer Genome Atlas showed considerable downregulation of SR-A1 in lung tumor tissues. The association of SR-A1 with prognosis was validated in animal models in the context of lung cancer metastasis. Macrophages derived from mice genetically deficient for SR-A1 exhibited accelerated metastasis in a model of lung cancer. On the other hand, tumor cell seeding, migration, and invasion, as well as macrophage accumulation in lung cancer tissue, were enhanced in SR-A1-deficient mice. SR-A1 deletion upregulated serum amyloid A1 (SAA1) in macrophages via MAPK/IκB/NFκB signaling. SAA1 promoted tumor cell invasion and macrophage migration in vitro and in vivo, but these effects were blocked by administration of an anti-SAA1 antibody. Overall, our findings show how SR-A1 suppresses lung cancer metastasis by downregulating SAA1 production in TAMs. Cancer Res; 77(7); 1586-98. ©2017 AACR.
Anti-tumor activity of PEGylated human IL-10 (AM0010) in renal cancer alone and in combination with anti-PD1
Authors: A. Naing, K.P. Papadopoulos, K.A. Autio, P.A. Ott, M.R. Patel, D.J. Wong, G. Falchook, S. Pant, M. Whiteside, D. Rasco, A. Patnaik, J.C. Bendell, T.M. Bauer, R.R. Colen, D. Hong, P. Van Vlasselaer, G.L. Brown, M. Oft, N. Tannir, J.R. Infante
Journal: Annals of Oncology (2016)
DREADDing proglucagon neurons: a fresh look at metabolic regulation by the brain
Authors: Jonathan E. Campbell, David A. D’Alessio
Journal: Journal of Clinical Investigation (2017)

Glucagon-like peptide 1 receptor (GLP-1R) signaling in the CNS has been linked to reduced food intake, lower body weight, improved glucose homeostasis, and activation of CNS stress axes. GLP-1 is produced by cells that express proglucagon (GCG); however, the stimuli that activate GCG+ neurons are not well known, which has made understanding the role of this neuronal population in the CNS a challenge. In this issue of the JCI, Gaykema et al. use designer receptors exclusively activated by designer drugs (DREADD) technology to specifically activate GCG+ neurons in mouse models. While activation of GCG+ neurons did reduce food intake, and variably decreased hepatic glucose production, other GLP-1-associated effects were not observed - e.g., activation of stress axes or stimulation of insulin secretion - in response to GCG+ neuron activation. The authors have provided a valuable model to study this set of neurons in vivo, and their results provide new insights into the function of GCG+ neural activity in the brain and raise questions that will move research on this clinically relevant neural system forward.
RTHP-03. GENE EXPRESSION LANDSCAPE INCLUDING miRNAs IN DELAYED RADIATION NECROSIS OF BRAIN
Authors: Shin-Ichi Miyatake, Taichirou Toho, Mitsugu Fujita, Motomasa Furuse, Shinji Kawabata, Toshihiko Kuroiwa, Naosuke Nonoguchi
Journal: Neuro-Oncology (2016)

Delayed brain radiation necrosis (DBRN) appears months to several years after radiotherapy for brain diseases, which may cause severe sequel especially for long-term survivors after radiotherapy. However, the treatment options are still limited to a few drugs, like as steroids, anticoagulants, and anti-VEGFA antibody. Therefore, further understanding of its pathophysiology is necessary for developing novel treatments for clinical DBRN. We had established a stable rodent DBRN model using single-dose X-ray irradiation to elucidate its pathophysiological mechanisms. Briefly, ~45 Gy irradiation didn’t develop DBRN at all. 65 Gy irradiation produced necrotic lesions in the cerebral white matter about 6 months after irradiation on MRI (Median: 179 d, 95%CI: 164-199 d), the pathology of which imitated a coagulative necrosis as seen in human DBRN. Meanwhile, >80 Gy irradiation developed a large melting necrosis 2 to 3 months following irradiation. In the present study, using the 65 Gy-irradiated DBRN model, we cyclopaedically analyzed the changes in gene expression over time in the 65 Gy-irradiated DBRN model using microarray analyses. At the peak phase (7M) of DBRN, 779 out of 36685 mRNAs tested, were significantly up- or down-regulated in comparison with at the early phase (2M) of DBRN. In the pathway analysis intended for these genes, 29 out of 20,717 gene pathways significantly altered; e.g. Chemokine signaling, Type-II interferon signaling, NF-kappa B signaling, mismatch repairing, renin-angiotensin signaling, HIF-1 signaling, EPO receptor signaling, VEGFR signaling etc. As for miRNAs, 135 out of 1218 miRNA expressions significantly altered through the development of DBRN; interestingly, some of them (Mir18a, Mir20a, Mir-92, Mir381, etc.) has been known to act in the direction of tumor promotion. This DBRN model would be useful for understanding the pathophysiological mechanisms and for searching therapeutic molecular targets or diagnostic biomarkers.
The Assessment of Estrogen Receptor Status and Its Intratumoral Heterogeneity in Patients With Breast Cancer by Using 18F-Fluoroestradiol PET/CT
Authors: Zhongyi Yang, Yifei Sun, Xiaoping Xu, Yongping Zhang, Jianping Zhang, Jing Xue, Mingwei Wang, Huiyu Yuan, Silong Hu, Wei Shi, Beiling Zhu, Yingjian Zhang
Journal: Clinical Nuclear Medicine (2017)

Aim The aim of this study was to investigate the clinical value of 18F-fluoroestradiol (18F-FES) PET/CT in the assessment of the estrogen receptor (ER) and its intratumoral heterogeneity in breast cancer patients. Methods Forty-six female patients (50 lesions) with histologically confirmed invasive breast cancer who underwent both 18F-FES and 18F-FDG PET/CT in our center were retrospectively included. All the patients enrolled were scheduled to undergo biopsy. The 18F-FES and FDG uptakes were compared with pathological features (tumor size, ER, progesterone receptor, human epidermal growth factor receptor 2, and Ki67%). The optimal threshold to discriminate ER-positive and ER-negative lesions was determined by receiver operating characteristic curve analysis. Furthermore, we observed the intratumoral heterogeneity by a heterogeneity index (SUVmax/SUVmean) and compared the results with the Chang-Gung Image Texture Analysis. Results There was good agreement between 18F-FES uptake and ER, progesterone receptor, and human epidermal growth factor receptor 2 expression (P < 0.001), and the use of SUVmean instead of SUVmax can provide a slightly better correlation. The optimal threshold for 18F-FES PET/CT to discriminate between ER-positive and ER-negative lesions, as determined by receiver operating characteristic curve analysis, was an SUVmax of 1.82 (sensitivity = 88.2% and specificity = 87.5%) and SUVmean of 1.21 (sensitivity = 85.3% and specificity = 93.7). Our simplified heterogeneity index–FES can easily observe ER heterogeneity. In addition, our results suggested that recurrent/metastatic patients and lesions located other than breast might have greater heterogeneity. Conclusions 18F-FES PET/CT is a feasible, noninvasive method for assessing ER expression in breast cancer patients. Because intratumoral heterogeneity exists, 18F-FES PET/CT might better reflect the ER expression, especially in metastatic patients after treatment, thus assisting in making individualized treatment decisions.
Stem Cell Mobilization Capacity Is Not a Predictor of Survival in Multiple Myeloma (MM) After Autologous Stem Cell Transplantation (ASCT).
Authors: Gloria Lim, Wei Xu, Trieu Young, Andrew Winter, Donna E. Reece, Suzanne Trudel, Vishal Kukreti, Peter Anglin, Christine Chen
Journal: Blood (2009)
Sorafenib plus long-acting octreotide in advanced hepatocellular carcinoma. Preliminary results of a multicenter ongoing study
Authors: S. Del Prete, L. Montella, R. Addeo, L. Maiorino, V. Montesarchio, G. Cennamo, G. Leo, G. Palmieri, M. Bianco, M. Caraglia
Journal: Journal of Clinical Oncology (2008)

15624 Background: Advanced hepatocellular carcinoma (HCC) not amenable to local therapies has limited chances of cure and has a poor prognosis. Sorafenib is a multikinase inhibitor with proven activity in advanced HCC. Octreotide is already used in this setting with conflicting but usually interesting results. Methods: In the present study an original schedule with sorafenib and long-acting octreotide is tested in advanced HCC enrolled from different Institutions. Criteria for inclusion are: pathologically confirmed HCC or alpha- fetoprotein more than 400 ng/dL plus radiological imaging; Performance Status 0–2 by ECOG; Child A or B; no other chances for standard cure; adequate liver, kidney, hematopoietic function and no heart disease being unstable. Sorafenib is administered at a dosage of 400 mg/daily for 28 days with a following week of rest. Ten days after starting sorafenib, long acting octreotide is administered at a dose of 40 mg with monthly scheduled administrations. Objectives of this study are the evaluation of activity and potential toxicity of the treatment. Additionally, a biological study is performed. Tumor response is assessed bimontly. Results: At the date of December 25th 30 patients were considered for study entry and 29 (sex: 25M/4F; age range: 57–79 years; HCV: 19 pts, HBV: 9 pts, HCV+HBV:1 pt; Child A/B: 18/11; pts naïve: 10) were enrolled. Eight patients were not evaluable because of premature treatment stopping. Three of them stopped treatment because of diarrhea grade 3. Among 11 evaluable patients at 2 months 2 minor responses, 6 stable disease and 3 disease progression are reported. Apart from diarrhea which caused premature stopping in 3 patients manageable toxicity is reported: skin toxicity grade 2 and grade 3 in 2 pts respectively, hypertension in 3 pts. Conclusions: The association of sorafenib and long acting octreotide appears feasible and promising in advanced hepatocellular carcinomas not susceptible of local therapies. Updated results will be presented at 2008 ASCO Meeting. No significant financial relationships to disclose.
HDAC11 Inhibits T-Cell Response to Alloantigens and Reduces Gvhd In Mice.
Authors: Dapeng Wang, Fengdong Cheng, Yu Yu, Kenrick Semple, Lirong Peng, Elphine Telles, Noreen Luetteke, Edward Seto, Claudio Anasetti, Eduardo M. Sotomayor, Xue-Zhong Yu
Journal: Blood (2010)
The efficacy of everolimus relies on a modulation of adaptative anti tumor T cell immunity
Authors: O. Adotévi, L. Mansi, L. Beziaud, P. Ravel, E. Lauret Marie-Joseph, C. Laheurte, L. Rangan, T. Maurina, G. Mouillet, T. Nguyen Tan Hon, E. Curtit, X. Pivot, Y. Godet, C. Borg, A. Thiery-Vuillemin
Journal: Annals of Oncology (2016)
High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells
Authors: Arun Sharma, Paul W. Burridge, Wesley L. McKeithan, Ricardo Serrano, Praveen Shukla, Nazish Sayed, Jared M. Churko, Tomoya Kitani, Haodi Wu, Alexandra Holmström, Elena Matsa, Yuan Zhang, Anusha Kumar, Alice C. Fan, Juan C. del Álamo, Sean M. Wu, Javid J. Moslehi, Mark Mercola, Joseph C. Wu
Journal: Science Translational Medicine (2017)

High-throughput screening of drugs with human induced pluripotent stem cell–derived cardiomyocytes reveals a “cardiac safety index.”
P03.03 Assessment of competence in patients affected by brain tumors
Authors: C. Zucchella
Journal: Neuro-Oncology (2016)

the activities were (a) considered to be IADL, (b) affected in glioma patients and (c) clearly formulated.Patients and their proxies only needed to answer the latter two questions.In step 2, the 6 HCPs and 6 other patient-proxy dyads were asked to generate relevant activities not covered by the A-IADL-Q.To do so, in-depth interviews were conducted.Predetermined decision rules defined which items to retain in step 1 and to add in step 2. Activities who met all three criteria (a, b & c) were retained.Activities that were considered IADL and affected, but unclearly formulated, were rephrased.Frequent newly generated activities were added to the existing list of items.In step 3, 6 new patient-proxy dyads vocalized their thoughts on the list of items constructed from the previous steps.Any residual ambiguities or repetitiveness identified during the cognitive debriefing would lead to item adjustments.RESULTS: In step 1, HCPs considered all 70 items as IADL if 3 items were to be rephrased slightly.However, HCPs considered only 63% of the activities as likely to be affected in glioma patients and just half (51%) as clearly formulated.According to the patient-proxy dyads, only 20-21% of the activities were affected in glioma patients, and 82-93% was considered clear.In accordance with the decision rules, a total of 28 items were retained.Fourteen new (including social and work related) items generated in step 2 were added.In step 3, the 42 items were presented to the patient-proxy dyads.Based on their input, several alterations were made resulting in a provisional list of 37 items.CONCLUSION: Evaluation of the dementia-specific A-IADL-Q suggests that this questionnaire is not appropriate for use in glioma patients; several items were not relevant and others missing.Glioma patients might have a unique set of IADL problems.Clearly, a new IADL questionnaire specifically for these patients is needed.Currently, this questionnaire is being developed at the EORTC QOL Group. P03.
Phase II Study of Rituximab and Cladribine (2-CDA) in Newly Diagnosed Mantle Cell Lymphoma (MCL) (N0189).
Authors: David James Inwards, David W. Hillman, Paul A. Fishkin, William L. White, Roscoe F. Morton, Shaker R. Dakhil, Daniel A. Nikcevich, Donald B. Wender, Tom R. Fitch, Paul J. Kurtin
Journal: Blood (2006)
Treatment of opioid-induced constipation with naldemedine in patients with cancer: onset of action in a randomized phase 3 trial
Authors: T. Murata, N. Katakami, T. Harada, K. Shinozaki, M. Tsutsumi, T. Yokota, M. Arai, Y. Suzuki, M. Narabayashi, N. Boku
Journal: Annals of Oncology (2016)
NIMG-25. RADIOMIC PROFILING MAPS AREAS OF PATHOLOGICALLY CONFIRMED TUMOR AND PREDICTS OVERALL SURVIVAL IN PRE-TREATMENT GLIOBLASTOMA
Authors: Sean McGarry, Sarah Hurrell, Amy Kaczmarowski, Elizabeth Cochran, Jennifer M. Connelly, Joseph Bovi, Scott Rand, Kathleen M. Schmainda, Peter S. LaViolette
Journal: Neuro-Oncology (2016)

Quantifying tumor heterogeneity in glioblastoma (GBM) plays a critical role in diagnosis as well as therapy design. Magnetic resonance imaging (MRI) can be used to identify and differentiate heterogeneous GBM characteristics such as hypercellularity, necrosis, and treatment effects. This study involves encoding four different types of MRI contrasts to produce a single radiomic image and quantify both inter and intra tumor heterogeneity. We hypothesized that patient prognosis can be predicted by the volume and location of specific radiomic profiles (RP) prior to therapy. Initial imaging data from 82 patients pre-treatment was retrospectively analyzed for this experiment. This included T1 (pre and post Gd contrast), apparent diffusion coefficient (ADC), and fluid attenuation inversion recovery (FLAIR) images. The volume of each RP was assessed on a patient by patient basis within the T1 enhancement and FLAIR hyperintensity. These values were normalized by tumor size to correct for known relationships between tumor size and prognosis. We first performed an exploratory analysis correlating RP volume to patient survival. A log-rank test with an iterative threshold was performed to determine what RP volume cutoff best predicted prognosis. The final pre-mortem imaging was analyzed similarly in three additional autopsied patients. Tissue samples were obtained from RPs that correlated with survival in the larger group. After correction for multiple comparisons, six RPs were significantly correlated with overall survival: three within contrast enhancement and three within FLAIR hyperintensity. Regions of pseudopalisading necrosis and hypercellular tumor were found in the areas indicated by these RPs. We present a pathologically-validated method for generating MRI-based radiomic profiles correlated with overall survival in patients with glioblastoma. These predictive profiles were generated prior to treatment, indicating potential as a precision medicine tool.
NCOG-01. PREOPERATIVE MAPPING OF CALCULATION FUNCTION BY rTMS IN PATIENTS WITH PARIETAL BRAIN TUMORS AND CORRELATION WITH POSTOPERATIVE OUTCOME
Authors: Sebastian Ille, Katrin Giglhuber, Stefanie Maurer, Nico Sollmann, Bernhard Meyer, Sandro M. Krieg
Journal: Neuro-Oncology (2016)

In order to resect brain tumors while preserving the patient’s brain functions, neurosurgeons apply intraoperative direct cortical stimulation (DCS) during awake surgery. Apart from language mapping, some highly specialized centers also map further higher cortical functions such as calculation function. Recently, the feasibility of mapping calculation function by repetitive navigated transcranial magnetic stimulation (rTMS) in healthy volunteers has been shown. To correlate the resection of calculation-positive sites in terms of rTMS with functional patient outcome of calculation performance. Nine patients with right- or left-sided (7 right-, 2 left-sided) parietal brain tumors (7 gliomas, 2 metastases) underwent preoperative rTMS calculation mapping. We stimulated 52 previously determined cortical sites over the whole tumor hemisphere while patients performed a calculation task with 80 simple arithmetic operations. Pre- and postoperatively, patients performed a standardized number processing and calculation test (NPCT). The overall error rate (ER = calculation errors per stimulations) for tumor hemispheres was 7.3%. The resection of calculation-positive sites in terms of rTMS worsened the postoperative NPCT result in 6 cases. In 2 cases no calculation-positive sites were resected and the postoperative NPCT result was similar or better than preoperatively. In one case the postoperative NPCT result was better than preoperatively although calculation-positive sites were resected. According to these results sensitivity and negative predictive value are 100%, specificity is 66.7%, and positive predictive value is 85.7%. The resection of calculation-positive sites in terms of rTMS correlated with postoperative NPCT results in 8 of 9 cases. Despite only presenting a low number of cases, rTMS might be a useful tool for preoperative mapping of calculation function. However, the reliability of the present results has to be evaluated in a larger series.
Genome-Wide Single Nucleotide Polymorphism Analysis in Juvenile Myelomonocytic Leukemia Uncovers Long-Range Uniparental Disomy Surrounding the NF1 Locus in Cases Associated with Type 1 Neurofibromatosis but Not in Cases with Mutant RAS or PTPN11.
Authors: Christian Flotho, Doris Steinemann, Gudrun Göhring, Charles Mullighan, Geoffrey Neale, Brigitte Schlegelberger, James Downing, Charlotte Marie Niemeyer
Journal: Blood (2006)
A meta-analysis of the complete remission ratio with replaced or refractory acute promyelocytic leukemia.
Authors: B. Jiang, Q. Gong, H. Watanabe, S. Zhu, J. Xie, Y. Ohashi
Journal: Journal of Clinical Oncology (2011)

6542 Background: There are many different treatment regimens for replaced or refractory Acute Promyelocytic Leukemia (APL) in clinical practice. Objective: To understand the efficacy of the treatment regimens on the replaced or refractory APL patients by using a meta-analysis. Methods: To estimate the complete remission (CR) ratio of the treatment regimens on the replaced or refractory APL patients, the Chinese databases of http://vip.fjinfo.gov.cn/index.asp, http://med.wanfangdata.com.cn/ and http://www.cnki.net/, the English database of MEDLINE, and Japanese database of JMEDPlus were searched based on the key words of: replaced, refractory or APL. Thirty-one literatures (20 in Chinese, 1 in Japanese, 10 in English) with over 20 subjects were selected in 1918 literatures (953 in Chinese, 30 in Japanese and 935 in English) from 1999 to October 2009. Thousand and sixty-three (1063) patients with CR evaluation were selected in the total 1437 replaced or refractory APL patients. Results: The CR rate in all treatment regimens was 75.2%±14.3%. The CR rates were higher in arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) (ATO + ATRA): 81.9% and ATO: 80.1% than those of the ATRA: 41.2% and chemotherapy: 55.8%. Additionally, this result was not changed with the adjustments of the other prognostic factors (pre-treatment, language of the paper and year of literature published and so on). Conclusions: The treatment regimen ATO (ATO + ATRA and ATO) was very effective for replaced or refractory APL.
Pathogenic and prognostic role of VEGF and VEGFR single nucleotide polymorphisms in gastroenteropancreatic neuroendocrine neoplasms
Authors: M. Torniai, F. Piva, S. Rinaldi, M. Santoni, S. Pagliaretta, S. Partelli, A. Savini, F. Morgese, M. Caramanti, M. Pistelli, A. Bittoni, R. Giampieri, A. Onofri, D. Pezzulla, G. Principato, M. Falconi, R. Berardi
Journal: Annals of Oncology (2016)
Early Switch to Nilotinib Does Not Overcome the Adverse Outcome for CML Patients Failing to Achieve Early Molecular Response On Imatinib, Despite Excellent Overall Outcomes in the TIDEL II Trial
Authors: David T Yeung, Michael Philip Osborn, Deborah L White, Susan Branford, Michael Kornhauser, Cassandra Slader, Samar Issa, Devendra K. Hiwase, Mark S. Hertzberg, Anthony P. Schwarer, Robin Filshie, Christopher K Arthur, Yiu Lam Kwan, Cecily J Forsyth, David Ross, Anthony K. Mills, Andrew Grigg, Timothy P. Hughes
Journal: Blood (2012)
Pharmacokinetic study of S-1, an oral fluorouracil antitumor agent in Japanese patients with impaired renal function
Authors: Keiko Goto, Yutaka Fujiwara, Takeshi Isobe, Yukari Tsubata, Takamasa Hotta, Naoko Chayahara, Naomi Kiyota, Toru Mukohara, Noboru Yamamoto, Hironobu Minami
Journal: Annals of Oncology (2016)
Inflammatory Disease Associated Gene Polymorphisms Detected in Patients with Chronic Graft-vs-Host Disease.
Authors: Masako Shimada, Makoto Onizuka, Taku Oba, Yosiaki Ogawa, Hiroshi Kawada, Koichi Miyamura, Tomomitsu Hotta, Yosihisa Kodera, Hidetoshi Inoko, Kiyoshi Ando
Journal: Blood (2006)
A Statement on Ethics From the HEART Group
Journal: Circulation (2008)

Over the past several years, the editors of leading international cardiovascular journals have met to form the HEART group and to discuss areas of growing, common interest. Recently, the HEART group has developed a document that addresses general ethical principles in the conduct of the scientific process with which all of the editors concur. Published essentially simultaneously in all of the participating journals, including this journal, this document presents the ethical tenets accepted by all of the undersigned editors that will (continue to) guide their decisions in the editorial process. These are the general principles on which the HEART Group is based and by which we, as a group, abide; however, please note that individual journal members and their respective societies may have their own rules and regulations that supersede the guidelines of the HEART Group.

### Acta Cardiologica

Hugo Ector, MD, PhD

Editor-in-Chief

Patrizio Lancellotti, MD

Editor-in-Chief …