tbuckley/cabot-search huggingface dataset:
Analysis of a bone metastasis gene expression signature in patients with bone or non-bone metastases from solid tumors.
Authors: S. Casimiro, A. Fernandes, R. Pires, I. M. V. D. Luis, A. F. Francisco, J. Portela, L. Costa
Journal: Journal of Clinical Oncology (2011)

e21054 Background: Using human breast cancer (BC) cells in a mouse model, Kang et al. reported a bone metastasis (BM) gene signature. The BM-related genes encode secretory and cell surface proteins implicated in bone-homing (CXCR4), angiogenesis (CTGF and FGF5), invasion (MMP-1 and ADAMTS1), and osteoclast recruitment (IL-11). ADAMTS1, CTGF and IL-11 were found to be overexpressed in the primary of BC with BMs. We analyzed the expression of the six BM-related genes plus OPN, in patients with BC and bone or non-bone metastases (BCBMs and BCNBMs, respectively) and BMs from other solid tumors (OSTBMs), to assess its relevance in human clinical samples. Methods: Eleven BMs (BC: 3; OST: 8) and four BCNBMs (liver; lung; skin; lymph node) were analyzed. Areas with ≥80% tumor cells were dissected from cryosections. Gene expression was analyzed by RT-qPCR, and normalized for GADPH. The BC cell line MDA-MB-231 and the normal breast epithelium cell line MCF10A were used for experimental validation. Differences between groups were analyzed by Kruskal-Wallis test and Mann Whitney t-Test, and correlations between the expressions of gene pairs were analyzed by Spearman test. Results: The six genes selected from Kang's BM gene signature were overexpressed in MDA-MB-231 cells vs. MCF10A. These genes were also overexpressed in BCBMs, BCNBMs, and OSTBMs, without significant differences between groups. There was a significant correlation between the expressions of ADAMTS1 and CTGF in all metastases samples (P=0.0105), all BMs (P=0.0024), and BCBMs (P=0.0469), but not in BCNBMs (P=0.6). IL-11 and CXCR4 expressions correlated in BCBMs and BCNBMs (P<0.0001). Correlation between the expressions of ADAMTS1, CTGF, CXCR4, FGF5, and IL-11, was significant in BCBMs (P<0.0001), while between MMP-1 and OPN was only significant in BCNBMs (P<0.0001). Conclusions: The overexpression of the genes selected from Kang's BM signature was not restricted to BMs from BC. It was also observed in BMs from other solid tumors and BCNBMs. Our analysis suggests that the co-expression of MMP-1 and OPN can be more relevant in the non-bone setting, whereas ADAMTS1 and CTGF co-expression may be BM-related.
Clonal Evolution Revealed by Whole Genome Sequencing in a Case of Primary Myelofibrosis Transformed to Secondary Acute Myeloid Leukemia
Authors: Daniel A.C. Fisher, Christopher A. Miller, Michael D. McLellan, Robert S. Fulton, Katherine L. Martin, Charu Kaiwar, Deborah M. Moore, Timothy J. Ley, Stephen T. Oh
Journal: Blood (2012)
Cigarette Smoking Is An Independent Predictor of Chronic Pain In Sickle Cell Patients: Results From the Walk-PHaSST Study
Authors: Ruchika Goel, Kathryn Hassell, Oswaldo Castro, Robyn J. Barst, Erika Berman Rosenzweig, Vandana Sachdev, Roberto F. Machado, Simon Gibbs, Jane A Little, Dean E. Schraufnagel, Reda E. Girgis, Claudia R. Morris, David B. Badesch, Sophie Lanzkron, Jonathan C. Goldsmith, Victor R. Gordeuk, Gregory J. Kato, Mark Gladwin, Lakshmanan Krishnamurti
Journal: Blood (2010)
409. Novel Recombinant Coxsackievirus B3 Infection Elicits Robust Oncolytic Activity Against Human Non-Small Lung Cancer and Triple-Negative Breast Cancer
Authors: Miyako Sagara, Yuto Takishima, Shohei Miyamoto, Hiroyuki Shimizu, Yoichi Nakanishi, Kenzaburo Tani
Journal: Molecular Therapy (2016)

Oncolytic virotherapy using enteroviruses emerges as a promising anticancer strategy. As therapeutic advantages, enteroviruses immediately induce robust oncolytic activity and do not have oncogenes that may lead to tumorigenesis. We recently showed coxsackievirus B3 wild type (CVB3-WT) infection elicited remarkably oncolytic activity against human non-small cell lung cancer cells (NSCLC). However, CVB3-WT infection caused adverse events of weight loss, pancreatitis, and myocarditis in mice. To overcome these pathogenicity, we engineered CVB3-WT genome for the development of microRNA (miRNA)-regulated oncolytic virus. We focused on two miRNAs (miR-1 and miR-217) expressed mainly normal muscle or pancreas. We successfully genetically constructed a novel recombinant CVB3-miR-1&217T (CVB3-miRT) by inserting 4 tandem target sequences complementary to two miR-1 and two miR-217 into the 3'UTR of CVB3-WT genome. Recently, we investigated whether an infection with CVB3-miRT displays oncolytic activities against NSCLC. We found that CVB3-miRT infection induced potent oncolytic activity comparable to CVB3-WT in human NSCLC in vitro and in vivo. Here, we attempted to explore the oncolysis to triple-negative breast cancer (TNBC) because TNBC are highly aggressive and intractable tumors with dismal prognosis. We performed in vitro crystal violet staining to examine the effect of CVB3-miRT on TNBC. These results showed that CVB3-miRT had potent oncolytic activity against TNBC cell lines in a MOI-dependent manner. Furthermore, consecutive administrations of CVB3-miRT into subcutaneous xenografts of human TNBC pre-established in athymic nude mice significantly suppressed the tumor growth with a prolonged survival rate. The intratumoral CVB3-miRT administrations into human TNBC xenograft tumor mice model displayed dramatically decreased side effects of CVB3-WT-induced pathogenicity. Collectively, we showed that CVB3-miRT infection indicated marked oncolytic activity against human NSCLC and TNBC cells in vitro and in vivo as well as CVB3-WT. This approach could be a promising new therapeutic modality to improve survival in patients suffering from NSCLC and TNBC in advanced stage.
A Phase 2 Dose Regimen Optimization Study of Three Schedules of Voreloxin as Single Agent Therapy for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia.
Authors: Farhad Ravandi, Hagop M. Kantarjian, Larry D. Cripe, Michael Maris, Maureen Cooper, Shaker R. Dakhil, Richard M Stone, Francesco Turturro, Tianling Chen, Kristi Mahadocon, Judith Fox, Craig Berman, Glenn C Michelson, Robert K Stuart
Journal: Blood (2009)
Frequency and Clinical Correlates of JAK2 46/1 Haplotype in Comparison with JAK2V617F Variant in Myeloproliferative Neoplasms: Single Center Experience
Authors: Irina Panovska, Nadica Matevska, Martin Ivanovski, Sanja Trajkova, Dusko Dukovski, Lidija Cevreska, Aleksandar Dimovski
Journal: Blood (2011)
Down-Regulation of TfR1 Increases Erythroid Precursor Enucleation and Hepatocyte Hepcidin Expression in ß-Thalassemic Mice
Authors: Huihui Li, Tenzin Choesang, Weili Bao, Lionel Blanc, Huiyong Chen, Maria Feola, Jie Li, Guiyuan Li, Shuming Sun, Antonia Follenzi, Petra Pham, Xiuli An, Narla Mohandas, Robert E Fleming, Stefano Rivella, Yelena Ginzburg
Journal: Blood (2015)
Abstract POSTER-THER-1421: Epigenetic targeting of ovarian cancer stem cells
Authors: Yinu Wang, Horacio Cardenas, Fang Fang, Salvatore Condello, Pietro Taverna, Matthew Segar, Yunlong Liu, Daniela Matei, Kenneth P. Nephew
Journal: Clinical Cancer Research (2015)

Abstract In ovarian and other cancers, emerging data indicate that cancer stem cells contribute to chemoresistance and that their persistence alters clinical outcome. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may play a critical role in targeting this subpopulation. Epigenetic aberrations, especially DNA methylation, result in silencing of tumor suppressor and differentiation-associated genes and regulate ovarian cancer stem cell (OCSCs) survival. To test the hypothesis that DNA hypomethylating agents “reset” OCSCs towards differentiation, we investigated the effect of the new DNA methytransferase inhibitor SGI-110 on OCSCs, defined as aldehyde dehydrogenase 1 (ALDH)(+) cells. We demonstrated that ALDH(+) OC cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low dose SGI-110 reduced the stemness properties of ALDH(+) cells, including their tumor initiating capacity, resensitized these OCSCs to platinum, and induced re-expression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSCs, caused profound global tumor hypomethylation, and delayed tumor progression, supporting epigenomic targeting as a novel strategy after platinum-based therapy in OC. Collectively, our data suggest that a strategy targeting DNA methylation in OC exerts potent anti-tumor activity by allowing elimination of OCSCs enriched in residual, platinum resistant tumors. Our study provides the first evidence that epigenome targeting strategies delay tumor progression by targeting and reprogramming residual cancer stem cells, suggesting that SGI-110 in combination with platinum has the potential to prevent recurrent and chemoresistant OC. Citation Format: Yinu Wang, Horacio Cardenas, Fang Fang, Salvatore Condello, Pietro Taverna, Matthew Segar, Yunlong Liu, Daniela Matei, Kenneth P. Nephew. Epigenetic targeting of ovarian cancer stem cells [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1421.
NCO-08PARENT-REPORTED COGNITIVE FUNCTION COULD PREDICT LEUKOENCEPHALOPATHY GRADE OF CHILDREN WITH BRAIN TUMORS
Authors: Jin-Shei Lai, Corey Bregman, Cindy Nowinski, Stewart Goldman
Journal: Neuro-Oncology (2015)

OBJECTIVE: Cognitive dysfunction is a major concern for children with brain tumors. A valid, user-friendly screening tool can facilitate prompt referral for comprehensive neuropsychological assessments facilitating early intervention. The pediatric perceived cognitive function item bank (pedsPCF) was developed to fill this need. The pedsPCF discriminated known groups of patients with brain tumor versus other cancer, and significantly correlated with neuropsychological testing scores. This study aims to evaluate the relationship between the pedsPCF and imaging data by evaluating whether pedsPCF could differentiate patients with different leukoencephalopathy grades. METHODS: Data from 59 children (mean age =12.3 yrs; 51.7% males) with brain tumors from Lurie Children's Hospital of Chicago were analyzed. Of them, 26.7% had a ganglioglioma and 23.3% had a medulloblastoma; 90% received chemotherapy, 60% radiation and 61.7% surgery. Average years since diagnosis were 5.4, and since last treatment were 3.5 years. Leukoencephalopathy grade was assessed using the Common Terminology Criteria for Adverse Events (CTCAE 4.0): 0 = no symptoms, 4 = life-threatening consequences. Parents of patients completed the pedsPCF and their scores were reported using the US general population based T-score matrix (mean = 50 and standard deviation = 10), in which higher scores mean better function. RESULTS: 17 patients had a leukoencephalopathy grade of 0; 19 with a grade = 1; 13 with a grade = 2 and 11 with a grade = 3 or 4. Averaged pedsPCF T-scores = 47.9 (SD = 7.9, range: 34.6-63.7). PedsPCF scores were significantly correlated with leukoencephalopathy grade, rho = -0.37 (p < 0.01), and significantly differentiated patients with different grades, F = 4.49, p = 0.016, and effect sizes ranged from 0.38 to 1.01. CONCLUSIONS: This pilot study indicated that the pedsPCF could differentiate patients with different leukoencephalopathy grades and has potential to serve as a screening tool for referral. The pedsPCF is a brief and user-friendly tool, which can be completed by using computerized adaptive testing or static short-forms.
Outbreak of <i>Salmonella</i> Oslo Infections Linked to Persian Cucumbers — United States, 2016
Authors: Lyndsay Bottichio, Carlota Medus, Alida Sorenson, Danielle Donovan, Reeti Sharma, Natasha Dowell, Ian Williams, Allison Wellman, Alikeh Jackson, Beth Tolar, Taylor Griswold, Colin Basler
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

In April 2016, PulseNet, the national molecular subtyping network for foodborne disease surveillance, detected a multistate cluster of Salmonella enterica serotype Oslo infections with an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern (XbaI PFGE pattern OSLX01.0090).* This PFGE pattern was new in the database; no previous infections or outbreaks have been identified. CDC, state and local health and agriculture departments and laboratories, and the Food and Drug Administration (FDA) conducted epidemiologic, traceback, and laboratory investigations to identify the source of this outbreak. A total of 14 patients in eight states were identified, with illness onsets occurring during March 21-April 9, 2016. Whole genome sequencing, a highly discriminating subtyping method, was used to further characterize PFGE pattern OSLX01.0090 isolates. Epidemiologic evidence indicates Persian cucumbers as the source of Salmonella Oslo infections in this outbreak. This is the fourth identified multistate outbreak of salmonellosis associated with cucumbers since 2013. Further research is needed to understand the mechanism and factors that contribute to contamination of cucumbers during growth, harvesting, and processing to prevent future outbreaks.
Abstract 4846: Long-Term Follow-Up in Patients with Tako-Tsubo Cardiomyopathy
Authors: Guido Parodi, Stefano Del Pace, Linda Zampini, Benedetta Bellandi, Claudia Salvadori, Nazario Carrabba, Gian Franco Gensini, David Antoniucci
Journal: Circulation (2008)

This study sought to assess the long-term outcome of patients with Tako-tsubo Cardiomyopathy (TTC). TTC is a recently described acute cardiac syndrome of uncertain etiology and outcome. One-hundred and one consecutive patients (94 female; mean age 73±10 years; range: from 33 to 90 years) with a confirmed diagnosis of TTC by angiography were prospectively identified and included in the study. Primary end-points were: death, syndrome recurrence and hospitalization from any cause. Over a mean follow-up of 2.0±1.3 years, only 55 patients resulted free from symptoms or major events. Chest pain (n=7) and dyspnea (n=5) were also the more frequent reasons for the high rehospitalization rate (22%). Only one patient had a recurrence of TTC. During long-term follow-up, 11 patients died (7 from cardiovascular cause). The only independent predictor of death at Cox analysis was age (HR 1.159, 95% CI 1.047–1.283; p=0.005). The use of beta-blockers was associated with a trend towards lower mortality rate (8% vs 16%; p=0.098). However, chest pain recurrence (26% vs 6%; p=0.021) and hospitalization rate (34% versus 16%; p=0.06) were more frequent in patients with beta-blockers therapy than in those without. The recurrence of TTC is rare. While, recurrence of chest pain or dyspnea is common in TTC patients and frequently results in hospital admission. Mortality was mainly related to patient’s old age. The role of beta-blockers therapy in the long-term management of patients with TTC is still to be clearly defined.
Low molecular weight (LMW) orally bioavailable inhibitors of tumor vascular endothelial growth factor (VEGF) translation delay tumor growth in vivo: A new approach to inhibition of angiogenesis
Authors: M. Weetall, L. Cao, Y. C. Moon, T. Davis, S. Hirawat, J. Colacino, N. Almstead, J. Babiak, L. Miller, S. Peltz
Journal: Journal of Clinical Oncology (2004)

3123 Background: VEGF plays a critical role in the pathogenic angiogenesis associated with a number of diseases including cancer. Blockade of VEGF by a humanized monoclonal antibody or by inhibitors of the KDR VEGF receptor slows tumor growth in preclinical and clinical studies. However, antibodies must be injected and may have stochiometric limitations in the context of high local concentrations of VEGF at the tumor site. KDR inhibitors will not block flk-receptor mediated responses. Here, we (1) evaluate the pharmacokinetic properties of a series of orally administered LMW compounds that target the untranslated regions (UTRs) of the VEGF mRNA and inhibit its translation and (2) demonstrate the efficacy of these compounds in vivo. Methods: Human fibrosarcoma tumors were established in nude mice. Once tumors were 100 mm3, mice were treated with LMW UTR-specific inhibitors of VEGF translation or with vehicle by oral gavage. At the end of the study, tumors and plasma were collected. Drug concentrations were measured using LC-MS/MS. Intra-tumor human VEGF, human survivin, and human FGF-2 were measured using specific ELISA assays. Results: These compounds effectively inhibited tumor growth. A dose of 50 mg/kg of one of the more potent compounds extended the time for the tumor to reach 1 cm3 to 56 days, compared to 21 days with vehicle. These compounds inhibited intra-tumor VEGF production, but did not inhibit intra-tumor survivin or bFGF levels. Efficacy in these studies correlated with trough plasma drug levels at the end of the study that were at least 5-fold above the in vitro EC90 value. Conclusions: Orally bioavailable LMW compounds can specifically and potently inhibit translation of tumor VEFG, resulting in significant tumor growth delay. Pharmacodynamic efficacy correlates with drug exposure in vivo, suggesting the need for continuous inhibition of VEGF production for efficacy. Efficacy in vivo also correlates with the in vitro EC90 as opposed to the EC50, suggesting that VEGF production must be significantly inhibited to delay tumor growth. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PTC Therapeutics
Rheumatoid Arthritis and Risk of Malignant Lymphoma: Is the Risk Still Increased?
Authors: K. Hellgren, E. Baecklund, C. Backlin, C. Sundstrom, K. E. Smedby, J. Askling
Journal: Arthritis & Rheumatology (2016)

Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas with a strong correlation with RA disease severity. Given the changes in RA therapy over recent decades, this study was undertaken to assess whether lymphoma risk remains increased, and if so, to explore risk predictors and lymphoma subtypes.We identified 12,656 cases of incident RA in the Swedish Rheumatology Quality Register 1997-2012 and obtained information on therapy and inflammatory activity during the first year after diagnosis. Each patient was matched to 10 population comparator subjects. Through linkage to the Swedish Cancer Register, lymphomas, including subtypes, were identified. We assessed hazard ratios (HRs) using Cox regression.Overall, the HR for lymphoma was increased in RA, to 1.6 (95% confidence interval [95% CI] 1.2-2.1). Taking RA duration into account, risks did not appear to have declined over successive calendar years of RA diagnosis. Neither use of methotrexate the first year after RA diagnosis nor ever use of tumor necrosis factor inhibitors (TNFi) increased lymphoma risk (HR 0.9 [95% CI 0.4-1.9]). Use of oral corticosteroids the first year after RA diagnosis was associated with a reduced risk (HR 0.5 [95% CI 0.3-0.9]). Inflammatory activity during the first year after RA diagnosis did not predict future lymphoma risk. Chronic lymphocytic leukemia occurred less frequently, and Hodgkin's lymphoma occurred more frequently, in RA patients than in the general population.The average lymphoma risk in recently diagnosed RA is similar in magnitude to that reported in historical cohorts. Standard antirheumatic treatment including TNFi did not predict future lymphoma risk. Distribution of lymphoma subtypes warrants further investigation.
Factors Associated with Relapse-Free Survival in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated with Imatinib-Combined Chemotherapy.
Authors: Masamitsu Yanada, Jin Takeuchi, Isamu Sugiura, Hideki Akiyama, Noriko Usui, Fumiharu Yagasaki, Kazuhiro Nishii, Yasunori Ueda, Makoto Takeuchi, Shuichi Miyawaki, Atsuo Maruta, Hiroto Narimatsu, Yasushi Miyazaki, Shigeki Ohtake, Itsuro Jinnai, Keitaro Matsuo, Tomoki Naoe, Ryuzo Ohno
Journal: Blood (2007)
Clinical Efficacy and Cost Benefit of Low-Dose Granulocyte Colony-Stimulating Factor after Standard Chemotherapy in Patients with Non-Hodgkin’s Lymphoma.
Authors: Satoshi Hashino, Masanobu Morioka, Tatsuro Irie, Noriyuki Shiroshita, Tsugumichi Kawamura, Sachiko Suzuki, Hiroshi Iwasaki, Shintaro Umehara, Yasutaka Kakinoki, Mitsutoshi Kurosawa, Kaoru Kahata, Koh Izumiyama, Hajime Kobayashi, Masahiro Onozawa, Mutsumi Takahata, Fumie Fujisawa, Takeshi Kondo, Masahiro Asaka
Journal: Blood (2006)
Pharmacologic inhibition of Hsp90 to prevent GLT-1 degradation as an effective therapy for epilepsy
Authors: Longze Sha, Xueqin Wang, Jing Li, Xinze Shi, Liwen Wu, Yan Shen, Qi Xu
Journal: The Journal of Experimental Medicine (2016)

The glutamate transporter GLT-1 is critical for the maintenance of low interstitial glutamate concentrations. Loss of GLT-1 is commonly observed in neurological disorders, including temporal lobe epilepsy (TLE). Despite the hypothesis that targeting the mechanisms of GLT-1 deficiency may be a novel strategy for treating drug-resistant epilepsy, the underlying molecular cascade remains largely unknown. Here, we show that Hsp90β is up-regulated in reactive astrocytes of the epileptic hippocampus in patients with TLE and mouse models of epilepsy. Inhibition of Hsp90, but not Hsp70, increased GLT-1 levels. Mechanistically, Hsp90β recruits GLT-1 to the 20S proteasome, thereby promoting GLT-1 degradation. Hsp90 inhibitor prevents GLT-1 degradation by disrupting the association between Hsp90β and GLT-1. Using a model of TLE, we demonstrated that long-term systemic administration of 17AAG dramatically suppressed spontaneous recurrent seizures and ameliorated astrogliosis. Overall, these results suggest that up-regulation of GLT-1 by inhibiting Hsp90β in reactive astrocytes may be a potential therapeutic target for the treatment of epilepsy and excitotoxicity.
EFFECT OF EMPAGLIFLOZIN ON MORTALITY AND CAUSES OF DEATH IN PATIENTS WITH TYPE 2 DIABETES AT HIGH CARDIOVASCULAR RISK
Authors: David H. Fitchett, Silvio Inzucchi, John Lachin, Christoph Wanner, Michaela Mattheus, Odd Erik Johansen, Hans-Juergen Woerle, Uli C. Broedl, Bernard Zinman
Journal: Journal of the American College of Cardiology (2016)