tbuckley/cabot-search huggingface dataset:
Renal cell carcinoma with a novel germ-line mutation in isocitrate dehydrogenase 1 (IDH1) and its functional study.
Authors: Tatsuya Takayama, Mitsuhiro Kitagawa, Naohisa Takaoka, Naoyuki Sugiyama, Kaori Igarashi, Miki Miyazaki, Takayuki Sugiyama, Fumitake Kai, Tomoyoshi Soga, Seiichiro Ozono
Journal: Journal of Clinical Oncology (2013)

e15568 Background: Recently, omics study such as metabolome analysis and whole genome sequencing has been applied to various disorders. We predicted the dysfunction of isocitrate dehydrogenase 1 (IDH1) in renal cell carcinoma (RCC) using metabolome analysis and identified a novel mutation of IDH1. In addition, we examined its function. Methods: We determined the global-scale metabolome profiling of human RCC by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), and compared the metabolite levels of tumors and paired normal tissues in 10 patients with RCC. We performed the genotyping of IDH1 and von Hippel-Lindau (VHL) gene. We also performed transfection experiments by using Lipofectamine and measured the enzymatic activity of IDH1 in RCC cell lines. All protocols were performed by the Institutional Review Board (IRB) of Hamamatsu University School of Medicine and Keio University. Informed consent was obtained from the patient in accordance with the IRB of Hamamatsu University School of Medicine. Results: The acceleration of glycolysis with low level of NADPH and citrate in one patient led to IDH1 dysfunction followed by identifying a novel missense mutation, V178I. In transfection experiment, the reductive activity of IDH1 variant (V178I) increased 2.5 times than that of IDH1 wild type while the oxidative activity of IDH1 variant oxidative activity was as well as that of IDH1 wild type. Furthermore, in the metabolome analysis using labeling glutamine, RCC cell lines deficient in the von Hippel-Lindau (VHL) protein preferentially use reductive glutamine metabolism. On the other hand, this patient with V178I mutation of IDH1 had no VHL mutation. Conclusions: Metabolome analysis led to the identification a novel IDH1 missense mutation in RCC. This mutation might be involved with acceleration of reductive reaction in tricarboxylic acid cycle. Metabolome analysis using CE-TOFMS could be a powerful tool for the global-scale exploration of disease-specific metabolism.
Changing to a New Donor for Second Hematopoietic Stem Cell Transplantation in Fanconi Anemia Seems to Improve Survival.
Authors: Korthof Elisabeth, Marlieke Ridder, Rosi Oneto, Andrea Bacigalupo, Johannes R Rischewski, Jakob R. Passweg, Gerard Socie, Carlo Dufour
Journal: Blood (2009)
Abstract 280: Protection of Oral Hydrogen Water as an Antioxidant on Pulmonary Hypertension
Authors: Bin He, Yufeng Zhang, Bo Kang, Jian Xiao, Bing Xie, Zhinong Wang
Journal: Circulation Research (2012)

Rationale: This study was to explore protection of hydrogen as an antioxidant on monocrotaline (MCT)-induced pulmonary hypertension (PH). Instead of hydrogen-rich saline, we made new modification by using oral hydrogen water (HW), which is more convenient, less costly and longer time to be released. Methods: Thirty-six SD rats were equally randomized to three groups: SHAM group, MCT group and MCT+HW group. The PH model was established by intraperitoneal injection of MCT (80 mg/kg body weight). The mean pulmonary arterial pressure (mPAP) was measured two weeks after establishment of the model, ensuring that mPAP in the modeled rats was higher than that in SHAM group. Animals in MCT group were administered with ordinary drinking water, and those in MCT+HW group were administered with HW. Two weeks later, the animals were sacrificed, and the heart and lung tissue were removed for measurement of the ventricular weight, left ventricular+septum weight, and right ventricle weight (RV). The right ventricular hypertrophy index (RVHI) was calculated. Changes in the degree of damage to the lung tissue was observed and scored by HE staining. Changes of 3-nitrityrosine (3-nt) and Intercellular Adhesion Molecule-1 (ICAM-1) in the lung tissue were observed by immunohistochemistry. Results: By the end of the experiment at day 28, mPAP, RV and RVHI in MCT group were 44.6±7.2 mmHg, 0.438±0.051 g and 0.59±0.065 respectively, which were significant higher than those in SHAM group ( P &lt; 0.05). mPAP, RV and RVHI in MCT+HW group were 31.4±6.5 mmHg, 0.346±0.041 g and 0.45±0.048 respectively, which were significantly lower than those in MCT group ( P &lt; 0.05). In addition, pulmonary inflammatory response, 3-nt and ICAM-1 were increased significantly in MCT group and decreased significantly in MCT+HW group as compared with SHAM group (both P &lt; 0.05). Conclusions: Oral hydrogen water has a significant protective effect on MCT-induced PH, which is more convenient to use than hydrogen-rich saline. And this effect is associated with the antioxidative ability of hydrogen and its action of reducing pulmonary inflammatory response.
PAIN AND AGITATION IN DEMENTIA Authors' reply to McShane and Regnard
Authors: Dag Aarsland, Bettina Husebo, Clive Ballard
Journal: BMJ (2011)

The absence of a placebo group is an obvious and acknowledged consideration in the interpretation of our results. Our point is that the effect size compared with the control condition of treatment as usual was within the magnitude reported by others with antipsychotic drugs, and thus analgesics may represent an alternative to antipsychotics for some patients. We also agree that identifying the specific symptoms that are most likely to benefit from analgesics, or from antipsychotics, is an important question. We are currently performing detailed secondary analyses, although we also emphasise the importance of not over-interpreting exploratory data. We agree with Regnard that careful assessment and a multi-modal approach to treating people with dementia is crucial. Indeed, in partnership with the Alzheimer’s Society and Department of Health in the UK we have developed a treatment pathway which considers pain as well as other multifactorial elements. We emphasise that most analgesia in our study was with paracetamol. Identifying painful medical conditions is a key part in evaluating people with dementia, and analgesia should be considered to be one of several potential management strategies for behavioural and psychiatric symptoms. Our results do suggest, however, that analgesia is potentially beneficial even in people without severe or overt pain and may be an additional potential treatment option even for them.
Coaggregation of DISC1 and mutant huntingtin dysregulates PDE4 in Huntington’s disease
Authors: Motomasa Tanaka, Koko Ishizuka, Yoko Nekooki-Machida, Ryo Endo, Noriko Takashima, Hideyuki Sasaki, Yusuke Komi, Amy Gathercole, Elaine Huston, Kazuhiro Ishii, Kelvin Kai-Wan Hui, Masaru Kurosawa, Sun-Hong Kim, Nobuyuki Nukina, Eiki Takimoto, Miles Douglas Houslay, Akira Sawa
Journal: Journal of Clinical Investigation (2017)
Prolonged Administration of the Telomerase Vaccine GRNVAC1 Is Well Tolerated and Appears to Be Associated with Favorable Outcomes In High-Risk Acute Myeloid Leukemia (AML)
Authors: H. Jean Khoury, Robert H. Collins, William Blum, Lori Maness, Patrick Stiff, Stephen M. Kelsey, Anita Reddy, Jennifer A. Smith, John F. DiPersio
Journal: Blood (2010)
The Burden of Early Phenotypes and the Influence of Wall Thickness in Hypertrophic Cardiomyopathy Mutation Carriers
Authors: Carolyn Y. Ho, Sharlene M. Day, Steven D. Colan, Mark W. Russell, Jeffrey A. Towbin, Mark V. Sherrid, Charles E. Canter, John L. Jefferies, Anne M. Murphy, Allison L. Cirino, Theodore P. Abraham, Matthew Taylor, Luisa Mestroni, David A. Bluemke, Petr Jarolim, Ling Shi, Lynn A. Sleeper, Christine E. Seidman, E. John Orav
Journal: JAMA Cardiology (2017)

Sarcomere mutations and left ventricular (LV) hypertrophy (LVH) are cardinal features of hypertrophic cardiomyopathy (HCM). However, little is known about the full spectrum of phenotypic manifestations or how LVH influences disease expression.
An Integer Weighted Genomic Mutation Scoring (IWGMS) Using the Trusight Myeloid Sequencing Panel (Illumina) Shows Higher Mortality in Patients with Intermediate Risk Acute Myeloid Leukemia- a Retrospective Study
Authors: Xinyu Nan, Michael Greenwood, Cesar Gentille Sanchez, Yan Xing, Arthur Zieske, Ibrahim Ibrahim, Kelty Baker, Lawrence Rice, Brian Merritt, Sai Ravi Pingali, Randall J Olsen, Swaminathan P. Iyer
Journal: Blood (2016)
PP18. DISCOVERY OF G PROTEIN-COUPLED RECEPTOR 158 AS A POTENTIAL GLIOMA BIOMARKER
Authors: Ms Ying Zhang, Dr Li Ningning, Prof Sebastian Brandner, Mr Kastytis Sidlauskas
Journal: Neuro-Oncology (2017)

INTRODUCTION: As reported previously, concomitant deletion of tumour suppressors p53 and Pten in mouse subventricular zone gives rise to glioma, while codeletion of p53 and Rb generates primitive neuroectodermal tumours (PNET). These experimental gliomas and PNETs exhibit significant differences in tumour proliferation and differentiation. Based on the two types of tumour, we aim to identify biomarkers for tumour malignance. In a later stage, biomarkers identified in mouse gliomas will be further analysed in human gliomas. METHODS: We performed gene exon and microRNA expression array of murine gliomas and PNETs. Differentially expressed candidates were further validated using quantitative PCR (qPCR). Direct binding of microRNA with its putative target RNAs was confirmed using a double pull-down assay, which hybrids Ago2 immunoprecipitation with biotin affinity pull-down. Human glioma RNA sequencing data (n=433) were downloaded from The Cancer Genome Atlas (TCGA), and human glioma tissue samples (n=78) were from our institution. RESULTS: The analysis of microRNA profiles identified a significant up-regulation of mir-449a in PNET. Among putative targets of mir-449a, G protein-coupled receptor 158 (GPR158) was identified as one of the key genes with a potential role in tumour malignance. Using double pull-down assay, we confirmed that GPR158 was a direct target of mir-449a. Subsequently, we analysed the expression of GPR158 in human gliomas, and found that patients with gliomas expressing higher levels of GPR158 survived longer. We then analysed GPR158 expression levels in glioma subtypes, which were stratified by a combination of molecular profile and histological features (integrated diagnosis). We found that GPR158 expression level was highest in central nervous system (CNS) and oligodendroglioma (IDH mutant and 1p/19q codeletion), followed by IDH mutant astrocytomas and it was lowest in primary glioblastomas in TCGA RNA-seq data and in glioma samples from our institution. Finally, as expected, the expression level of mir-449a and GPR158 was inversely correlated in human frozen glioma samples. CONCLUSION: In this study, we discovered the direct interaction between mir-449a and GPR158, and our data suggest that GPR158 is a potential diagnostic and prognostic marker in gliomas.
A Small Molecule Inhibitor Targeting CREB and CBP Inhibits Proliferation of AML Cells In Vitro and In Vivo,
Authors: Grace I Aldana-Masangkay, Bryan Mitton, Alan K Ikeda, Kazunari Yamada, Bingbing Li, Qiuhua Fan, Elliot Landaw, Xiangshu Xiao, Kathleen M Sakamoto
Journal: Blood (2011)
Abstract P6-07-31: Molecular mechanism of alcohol-associated breast cancer
Authors: S Zhong, Y Zhang, J Lei, W Li, Z Wu, G Shi
Journal: Cancer Research (2017)

Abstract Epidemiological studies have indicated that alcohol consumption is an established risk factor for breast cancer. The association of alcohol consumption and breast cancer is more pronounced in ER+ cases than in ER- cases. However, this molecular mechanism remains to be determined. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, increasing translational capacity to promote cell transformation and tumor formation. Our results reveal that alcohol increases Pol III gene transcription in both normal and cancer breast cell lines. The induction of Pol III genes by alcohol in ER+ breast cancer cells is significantly higher than in ER- normal breast cells and ER- breast cancer cells. E2 causes slight increase in Pol III gene transcription. The addition of ethanol to this system produces a marked increase. Alcohol increases ERa expression to enhance the cellular levels of Brf1 protein and mRNA. In addition, ethanol markedly stimulates phosphorylation of JNK1. Inhibition of JNK1 decreases ERE-Luc reporter activity and represses expression of ERa, Brf1 and Pol III genes. Reduction of ERa by its siRNA represses Brf1 and Pol III gene transcription. Ethanol with E2 produces larger and more numerous colonies. Repression of ERa or Brf1 inhibits alcohol-induced cell transformation. More interestingly, human biopsies studies show that Brf1 expression is significantly increased in nuclei of breast cancer cells, compared to tissue adjacent to the carcinoma. Together, these results support the idea that alcohol increases ERa expression through JNK1 pathway to elevate Brf1 expression and Pol III gene transcription, leading to greater phenotypic changes. ERa mediates Pol III gene transcription through Brf1, suggesting that ERa play a critical role in alcohol-induced deregulation of Pol III genes in ER+ breast cancer development. *: The project is supported by NIAAA/NIH grants: AA017288, AA021114 and AA02324 to S Zhong. Citation Format: Zhong S, Zhang Y, Lei J, Li W, Wu Z, Shi G. Molecular mechanism of alcohol-associated breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-31.
Monitoring and visualizing microRNA dynamics during live cell differentiation using microRNA-responsive non-viral reporter vectors
Authors: Hideyuki Nakanishi, Kenji Miki, Kaoru R. Komatsu, Masayuki Umeda, Megumi Mochizuki, Azusa Inagaki, Yoshinori Yoshida, Hirohide Saito
Journal: Biomaterials (2017)
A Proposed Steroid Mobilization Test to Separate Margination From Marrow Suppression and to Determine Drug Cessation for Safety in Lenalidomide-Induced Neutropenia in Non-Del(5q) MDS Low and INT-1 Patients
Authors: Philip A. Pancari, Emmanuel C. Besa, Jackie Quan, Amanda Padula, Erev E. Tubb, Raymond Vvacqua
Journal: Blood (2012)
心房中隔欠損症術後,部分肺静脈灌流異常残存,僧帽弁逸脱症の術前に感染性心内膜炎を発症した一例
Authors: 武寛, 楠瀬真奈, 佐原伸二, 尾原義和, 堀崎孝松, 伴場主一, 西本美香, 杉本和彦, 山本克人, 田邉佐和香, 大上賢祐, 鈴木友影, 金光真治, 宮川弘之, 三宅陽一郎, 岡部学
Journal: Circulation (2009)
Jab1/Csn5–Thioredoxin Signaling in Relapsed Acute Monocytic Leukemia under Oxidative Stress
Authors: Fuling Zhou, Yunbao Pan, Yongchang Wei, Ronghua Zhang, Gaigai Bai, Qiuju Shen, Shan Meng, Xiao-Feng Le, Michael Andreeff, Francois X. Claret
Journal: Clinical Cancer Research (2017)

Abstract Purpose: High levels of ROS and ineffective antioxidant systems contribute to oxidative stress, which affects the function of hematopoietic cells in acute myeloid leukemia (AML); however, the mechanisms by which ROS lead to malignant transformation in relapsed AML-M5 are not completely understood. We hypothesized that alterations in intracellular ROS would trigger AML-M5 relapse by activating the intrinsic pathway. Experimental Design: We studied ROS levels and conducted c-Jun activation domain–binding protein-1 (JAB1/COPS5) and thioredoxin (TRX) gene expression analyses with blood samples obtained from 60 matched AML-M5 patients at diagnosis and relapse and conducted mechanism studies of Jab1′s regulation of Trx in leukemia cell lines. Results: Our data showed that increased production of ROS and a low capacity of antioxidant enzymes were characteristics of AML-M5, both at diagnosis and at relapse. Consistently, increased gene expression levels of TRX and JAB1/COPS5 were associated with low overall survival rates in patients with AML-M5. In addition, stimulating AML-M5 cells with low concentrations of hydrogen peroxide led to increased Jab1 and Trx expression. Consistently, transfection of ectopic Jab1 into leukemia cells increased Trx expression, whereas silencing of Jab1 in leukemia cells reduced Trx expression. Mechanistically, Jab1 interacted with Trx and stabilized Trx protein. Moreover, Jab1 transcriptionally regulated Trx. Furthermore, depletion of Jab1 inhibited leukemia cell growth both in vitro and in vivo. Conclusions: We identified a novel Jab1–Trx axis that is a key cellular process in the pathobiologic characteristics of AML-M5. Targeting the ROS/Jab1/Trx pathway could be beneficial in the treatment of AML-M5. Clin Cancer Res; 23(15); 4450–61. ©2017 AACR.
Individualised risk in patients undergoing lung volume reduction surgery: the Glenfield BFG score
Authors: Neil J. Greening, Paul Vaughan, Inger Oey, Michael C. Steiner, Mike D. Morgan, Sridhar Rathinam, David A. Waller
Journal: European Respiratory Journal (2017)

Lung volume reduction surgery (LVRS) has been shown to be beneficial in patients with chronic obstructive pulmonary disease, but there is low uptake, partly due to perceived concerns of high operative mortality. We aimed to develop an individualised risk score following LVRS.This was a cohort study of patients undergoing LVRS. Factors independently predicting 90-day mortality and a risk prediction score were identified. Reliability of the score was tested using area under the receiver operating characteristic curve (AUROC).237 LVRS procedures were performed. The multivariate analysis factors associated independently with death were: body mass index (BMI)<18.5 kg·m-2 (OR 2.83, p=0.059), forced expiratory volume in 1 s (FEV1)<0.71 L (OR 5.47, p=0.011) and transfer factor of the lung for carbon monoxide (TLCO) <20% (OR 5.56, p=0.031). A risk score was calculated and total score assigned. AUROC for the risk score was 0.80 and a better predictor than individual components (p<0.01). The score was stratified into three risk groups. Of the total patients, 46% were classified as low risk. Similar improvements in lung function and health status were seen in all groups. The score was introduced and tested in a further 71 patients. AUROC for 90-day mortality in this cohort was 0.84.It is possible to provide an individualised predictive risk score for LVRS, which may aid decision making for both clinicians and patients.
Pre-Transplant Rituximab Is Associated with a Greatly Reduced Risk of Epstein-Barr Virus Reactivation Following Allogeneic Stem Cell Transplantation
Authors: David Burns, Shabeeha Rana, Andrew Howman, Sandeep Nagra, Janice Ward, Husam Osman, Yusri Taha, Jenny Byrne, Emma Das-Gupta, Manoj Raghavan, Ram Malladi, Mark Cook, Prem Mahendra, Nigel H. Russell, Charles Craddock, Christopher Fox, Sridhar Chaganti
Journal: Blood (2012)
Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial
Authors: J. Guo, R.D. Carvajal, R. Dummer, A. Hauschild, A. Daud, B.C. Bastian, S.N. Markovic, P. Queirolo, A. Arance, C. Berking, V. Camargo, D. Herchenhorn, T.M. Petrella, D. Schadendorf, W. Sharfman, A. Testori, S. Novick, S. Hertle, C. Nourry, Q. Chen, F.S. Hodi
Journal: Annals of Oncology (2017)

The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment.Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors.ORR was 26.2% (n = 11/42; 95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR ≤10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib.Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations.ClinicalTrials.gov, NCT01028222.
Evaluation of Toxicity and Tissue Radiation Doses Obtained in Mice with An Anti-CD45 Monoclonal Antibody (mAb) Labeled with the Alpha-Emitting Radionuclides, Astatine-211 or Bismuth-213.
Authors: Hirohisa Nakamae, D. Scott Wilbur, Donald K Hamlin, Monica S Thakar, Erlinda B Santos, Darrell R Fisher, Amiee L Kenoyer, John M. Pagel, Oliver W. Press, Rainer F. Storb, Brenda M. Sandmaier
Journal: Blood (2008)
Somatic BRCA2 bi-allelic loss in the primary prostate cancer was associated to objective response to PARPi in a sporadic CRPC patient
Authors: N. Romero-Laorden, E. Piñeiro-Yañez, A. Gutierrez-Pecharroman, M.I. Pacheco, E. Calvo, F. Al-Shahrour, E. Castro, D. Olmos
Journal: Annals of Oncology (2017)
Successful Rescue of Childhood Acute Leukemia In Non-Remission by Non-T-Cell Depleted HLA-Haploidentical Hematopoietic Cell Transplantation.
Authors: Shogo Kobayashi, Atsushi Kikuta, Masaki Ito, Hideki Sano, Kazuhiro Mochizuki, Mitsuko Akaihata, Hitoshi Ohto, Mitsuaki Hosoya
Journal: Blood (2010)
Response to Endovascular Therapy for Acute Ischemic Stroke With Occlusion of the Middle Cerebral Artery M2 Segment—Reply
Authors: Amrou Sarraj, M. Shazam Hussain, Rishi Gupta
Journal: JAMA Neurology (2017)

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Hemophagocytic Syndrome (HPS) after Autologous Peripheral Stem Cell Tansplantation (APSCT) for Multiple Myeloma (MM)- Successful Treatment with High Dosages of Intravenous Immunoglobulin (IVIG).
Authors: Mauricio Ostronoff, Mariana Coutinho Domingues, Fabiana Ostronoff, Rodolfo Calixto, Rodrigo Florencio, Ana Patricia Souto, Alexandre Sucupira, Kleber Matias, Clemente Tagliari
Journal: Blood (2005)