tbuckley/cabot-search huggingface dataset:
Defining the contribution of neuroinflammation to Parkinson’s disease in humanized immune system mice
Authors: Gunjan Dhawan Manocha, Angela Marie Floden, Kendra Lynn Puig, Kumi Nagamoto-Combs, Clemens R. Scherzer, Colin Kelly Combs
Journal: Molecular Neurodegeneration (2017)

Reactive microglia have been associated with the histological changes that occur in Parkinson’s disease brains and mouse models of the disease. Multiple studies from autopsy brains have verified the presence of microgliosis in several brain regions including substantia nigra, striatum, hippocampus and various cortical areas. MPTP injections in rodents have also shown striato-nigral microgliosis correlating with the loss of dopaminergic neurons. However, consistent data with respect to cytokine and immune cell changes during Parkinson’s disease have not been fully defined. In order to improve understanding of the role of neuroinflammation in Parkinson’s disease, we employed the MPTP injection model using humanized CD34+ mice along with age-matched C57BL/6 mice. NSG mice engrafted with hu-CD34+ hematopoietic stem cells were injected with MPTP to quantify cytokine changes, neuron loss, gliosis, and behavioral dysfunction. The mice were also treated with or without the calcineurin/NFAT inhibitor, FK506, to determine whether modulating the immune response could attenuate disease. MPTP injections produced impairment of motor performance, increased microgliosis, elevated brain cytokine levels, and reduced tyrosine hydroxylase immunoreactivity in the substantia nigra and striatum of both humanized CD34+ mice and C57BL/6 mice with a strikingly different profile of human versus mouse cytokine elevations observed in each. Interestingly, FK506 injections significantly attenuated the MPTP-induced effects in the humanized CD34+ mice compared the C57BL/6 mice. In addition, analyses of human plasma from Parkinson’s disease donors compared to age-matched, healthy controls demonstrated an increase in a number of pro-inflammatory cytokines in female patients similar to that observed in MPTP-injected female CD34+ mice. This study demonstrates for the first time, induction of Parkinson’s disease-like symptoms in female humanized CD34+ mice using MPTP. The profile of cytokine changes in the serum and brains of the humanized CD34+ mice following MPTP injection differed significantly from that occurring in the more commonly used C57BL/6 strain of mice. Moreover, several cytokine elevations observed in the MPTP injected humanized CD34+ mice were similarly increased in plasma of PD patients suggesting that these mice offer the more relevant model for the inflammatory aspects of human disease. Consistent with this, the effects of MPTP on loss of tyrosine hydroxylase immunoreactivity, loss of motor strength, and increase in proinflammatory cytokines were attenuated using an immunosuppressant drug, FK506, in the humanized CD34+ but not the C57BL/6 mice. Collectively, these findings suggest that MPTP injected, humanized CD34+ mice represent a more accurate model for assessing inflammatory changes in PD.
Evaluation of exposure of regorafenib (REG) and its metabolites in pediatric patients by modeling, simulation, and clinical study
Authors: B. Ploeger, J. Grevel, M. Frede, M. Block, K. Schnizler, M. Gerisch, F.-T. Hafner, Z.J. Trnkova, A.C. Agostinho, I. Sturm, A. Cleton
Journal: Annals of Oncology (2016)
MPTH-50. AUTOMATED QUANTITATIVE ANALYSIS (AQUA) AS A RELIABLE METHOD TO ASSESS MGMT PROTEIN EXPRESSION IN GLIOBLASTOMAS
Authors: Aline Paixao Becker, Erica H. Bell, Joseph P. McElroy, Tiantian Cui, Marjolein Geurts, Jessica Fleming, Arup Chakraborty, Ziyan Liu, Pierre Robe, Arnab Chakravarti
Journal: Neuro-Oncology (2016)

MGMT methylation in glioblastomas is associated with better response to temozolomide + radiation therapy (Stupp protocol). While MGMT protein expression cut-off values using traditional immunohistochemistry (T-IHC) were previously reported, fluorescence-based IHC, Automated Quantitative Analysis (AQUA), still lacks standardization to be used as an alternative to assess MGMT protein expression. Our aim was to describe the results of MGMT expression by AQUA analysis and to evaluate for the first time its correlation with methylation and T-IHC results. We evaluated 533 GBMs FFPE samples (primary and recurrent tumors) arranged in 10 tissue microarrays. MGMT nuclear expression in tumor cells was adequately assessed in 501/533 samples. The results were compared with T-IHC (n=493) and methylation (n=227) data both for primary and recurrent tumors. Statistical analyses were performed with SPSS. AQUA values in primary tumors ranged from 12.87 – 815.29 (median=180.56) and appeared to follow a continuous unimodal distribution. Those values were significantly related to MGMT methylation status and loss of expression in T-IHC (p<0.0001 for both) in one-way ANOVA. AQUA values in first recurrence (n=32) were significantly higher (79.35 – 596.49, median= 195.91; p=0.013 on t-test) than in primary tumors. Our results showed that AQUA has excellent correlation with gene methylation and protein expression assessed by T-IHC. The lower cost and availability of semi-quantitative IHC makes it a worldwide accessible and cost-effective method to evaluate MGMT in a general Neuropathology practice. Cutoff values for AQUA to determine loss of expression and relationship with overall survival are to be determined in future studies. R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).
NIMG-49. DIFFERENTIATION OF OLIGODENDROGLIAL TUMORS FROM NON-OLIGODENDROGLIAL ASTROCYTOMAS BY MULTIPARAMETRIC HISTOGRAM ANALYSIS OF DSC AND DCE MRI
Authors: Kookjin Ahn
Journal: Neuro-Oncology (2016)

Differential diagnosis of oligodendroglial tumors (OT) from non-oligodendroglial astrocytomas (NOA) has become increasingly important with the recognition that OT are uniquely sensitive to chemotherapy and have better prognosis. The purpose of this study was to assess whether there are imaging parameters to differentiate OT from NOA, by using multiparametric histogram analysis of dynamic susceptibility contrast (DSC) and dynamic contrast (DCE) MRI. We retrospectively reviewed preoperative DCE and DSC perfusion MR in 85 patients (39 males and 46 females, mean age = 49.91 years, range = 16-82 years) with histologically confirmed OT (n=29) and NOS (n=56). After drawing the ROI in the anatomical images and co-registered parametric maps, a histogram analysis was performed to determine the mean, 90th and 98th percentile values of each parameter. We compared the values between the two groups. The receiver operating characteristic curve analysis and multivariate logistic regression analysis were used to distinguish OT from NOA. The normalized cerebral blood volume from DSC MRI was not significantly different between the two groups. However, the mean and 90th percentile values of DCE-derived parameters were significantly higher in NOA than OT except for Kep. The ROC curve analysis showed the highest area under the curve of mean ktrans and Ve. Multivariate logistic regression analysis showed that the mean and 90th percentile values of ktrans and Ve were significant predictors of the differentiation of OT from NOA. Permeability-related parameters, including ktrans and Ve, could be helpful in the differentiation of OT from NOA.
Phase II Study of Tegafur/Uracil and Leucovorin plus Bevacizumab for Elderly Patients with Advanced Colorectal Cancer
Authors: Kohei Murata, Tsunekazu Mizushima, Koji Tamagawa, Chu Matsuda, Mutsumi Fukunaga, Taishi Hata, Riichiro Nezu, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
Journal: Annals of Oncology (2016)
Correction: Corrigendum: Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge.
Authors: Scott G Hansen, Cassandra Vieville, Nathan Whizin, Lia Coyne-Johnson, Don C Siess, Derek D Drummond, Alfred W Legasse, Michael K Axthelm, Kelli Oswald, Charles M Trubey, Michael Piatak, Jeffrey D Lifson, Jay A Nelson, Michael A Jarvis, Louis J Picker
Journal: Nature Medicine (2009)
Prognostic impact of pre-treatment neutrophil-to-lymphocyte ratio in castration-resistant prostate cancer patients treated with first-line docetaxel
Authors: C. Buttigliero, M. Tucci, F. Vignani, C. Pisano, V. Bertaglia, D. Pignataro, P. Bironzo, P.F. Guglielmini, G.V. Scagliotti, M. Di Maio
Journal: Annals of Oncology (2016)
Prospective evaluation of BRAF, PI3K and PTEN as predictive and prognostic biomarkers in first-line advanced KRAS wild-type colorectal cancer treated with FOLFOX or FOLFIRI plus bi-weekly cetuximab. GEMCAD 10-02
Authors: V. Alonso, P. Escudero Emperador, M. Mendez Urena, J. Gallego, J.R. Rodriguez, J. Fernández, A. Salud, E. Falcó, H. Manzano, M. Zanui, M. Gil, U. Bohn Sarmiento, C. Fernández Martos, V. Calderero, A.I. Ferrer, M. Cuatrecasas, F. Rojo, J. Feliu, J. Maurel, X. García-Albéniz
Journal: Annals of Oncology (2016)
Aberrant Somatic Hypermutation in Primary Mediastinal Large B-Cell Lymphoma.
Authors: Davide Rossi, Michaela Cerri, Daniela Capello, Clara Deambrogi, Eva Berra, Silvia Franceschetti, Annarita Conconi, Chiara Vendramin, Marco Paulli, Pileri Stefano, Antonino Carbone, Gianluca Gaidano
Journal: Blood (2004)
Sustained Protection from Labile Plasma Iron (LPI) with the Once-Daily, Oral Iron Chelator Deferasirox (Exjade®, ICL670) in Iron-Overloaded β-Thalassemia Patients.
Authors: S. Daar, A. Taher, A. Pathare, H. Nick, U. Krahn, D. Hadler
Journal: Blood (2006)
Abstract 17: Exercise Capacity and Primary Prevention of Major Adverse Cardiac Events in Veterans: The ETHOS Study
Authors: Peter Kokkinos, Charles Faselis, Jonathan Myers, Puneet Narayan
Journal: Circulation (2016)

Introduction: Increased exercise capacity is associated with better health outcomes. However, less is known about the impact of increased fitness on the primary prevention of major adverse cardiovascular events (MACE) defined as fatal or non-fatal myocardial infarction, cardiac bypass surgery, heart failure or stroke, has not been determined. Hypothesis: We assessed the hypothesis that increased exercise capacity decreases the risk of primary MACE. Methods: We identified 21,062 veterans (mean age:58.4±11.4) who completed an exercise stress test to either assess fitness status or suspected ischemia at two VA Medical Centers (Washington DC and Palo Alto, Ca). None had documented cardiovascular disease or any evidence of ischemia during the test. We established five fitness categories based on age-stratified quintiles of peak metabolic equivalents (MET) achieved: Least-Fit (4.2±1.2 METs; n=4,035); Low-Fit (6.0±1.2; n=4,483); Moderate-Fit (7.9±1.0 METs; n=3,898); Fit (8.6±1.4 METs; n=5,115); and High-Fit (11.9±2.3 METs; n=3,531). Multivariable Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals [CI] for incidence of MACE across fitness categories. The models were adjusted for age, BMI, race, gender, cardiac risk factors, sleep apnea, alcohol dependence and medications. The Least-fit category was the referent. Results: During follow-up (median=11.3 yrs), 2,911 developed MACE. For every 1-MET increase in exercise capacity, the risk for MACE was 15% lower (HR=0.85, 95% CI: 0.84-0.87). When considering fitness categories, MACE risk was lower by: 28% in Low-Fit (HR=0.72; CI: 0.65-0.79); 36% in Moderate-Fit (HR=0.64; 95% CI, 0.57-0.71); 55% in Fit (HR, 0.45; 95% CI, 0.41-0.51); and 66% in High-Fit (HR, 0.34; 95% CI, 0.29-0.39) individuals. Similar trends were noted in each of the MACE components. Conclusions: Increased exercise capacity protects against primary MACE. The association is independent and graded.
PD1 and PDL1 expression, tumoral microenvironment (TME) characterization and clinical implication in localized osteosarcoma
Authors: E. Palmerini, C. Agostinelli, P. Picci, S. Pileri, P. Lollini, K. Scotlandi, M.S. Benassi, S. Ferrari
Journal: Annals of Oncology (2016)
Donor’s NK Cells May Influence the Engraftment in Pediatrics Patients after T-Cell Depleted Haploidentical Stem Cell Transplant for Thalassemia
Authors: Antonella Isgro, Marco Marziali, Pietro Sodani, Javid Gaziev, Paola Polchi, Gioia De Angelis, Daniela Fraboni, Wilma Leti, Fernando Aiuti, Guido Lucarelli
Journal: Blood (2008)
Hyperthermic antiblastic perfusion for the treatment of soft tissue limb sarcoma
Authors: F. Di Filippo, D. Giannarelli, C. Botti, S. Carlini, F. Cavaliere, R. Garinei, M. Schiratti, V. Casaldi, M. Tedesco, R. Cavaliere
Journal: Annals of Oncology (1992)
Combined Assessment of WT1 and BAALC Expression Levels Improves Risk Stratification in Myelodysplastic Syndromes
Authors: Paola Minetto, Fabio Guolo, Marino Clavio, Laura Mitscheunig, Raffaella Grasso, Nicoletta Colombo, Enrico De Astis, Daniele Avenoso, Livia Giannoni, Giordana Pastori, Lisette Del Corso, Enrico Balleari, Filippo Ballerini, Roberto Lemoli, Marco Gobbi, Maurizio Miglino
Journal: Blood (2014)
Administration of Rituximab 375 Mg/m2 on Days +1 and +8 after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HCT) Regimens for Patients with Advanced CD20+ Lymphoid Malignancies
Authors: Mohamed A Kharfan-Dabaja, Cheryl Tate, Janelle Perkins, Teresa Field, Hugo F. Fernandez, Melissa Alsina, Ernesto Ayala, Jyotishankar Raychaudhuri, Lia Perez, J. Leonel Ochoa-Bayona, Linda Brand, Javier Pinilla-Ibarz, Eduardo Sotomayor, Dan Sullivan, Claudio Anasetti
Journal: Blood (2008)
Prognostic Impact of Kinase Mutations and Minimal Residual Disease in Core-Binding Factor Leukemia
Authors: David Sanford, Jorge E. Cortes, Farhad Ravandi, Wei Qiao, Keyur P. Patel, Thuyvan Hoang, Tapan Kadia, Hagop M. Kantarjian, Gautam Borthakur
Journal: Blood (2015)
The Complexities of Hypertension
Authors: Ann Marie Navar, Eric Peterson
Journal: JAMA Cardiology (2017)

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MYC Translocations and Expression Are Clinically Important in R-CHOP Treated Patients with De Novo DLBCL.
Authors: Nathalie A. Johnson, Susanna Ben-Neriah, Kerry J. Savage, Tang Lee, Douglas E. Horsman, Joseph M. Connors, Wing C. Chan, Georg Lenz, George Wright, Lisa M. Rimsza, Rita M. Braziel, James R. Cook, Raymond R. Tubbs, Dennis D. Weisenburger, Elias Campo, Andreas Rosenwald, German Ott, Jan Delabie, Elaine S. Jaffe, Louis M. Staudt, Randy D. Gascoyne
Journal: Blood (2009)
Impact of tumor heregulin mRNA expression on outcome of patients with advanced/metastatic squamous NSCLC treated with lumretuzumab, a glycoengineered monoclonal antibody targeting HER3, in combination with erlotinib
Authors: D. Meulendijks, U. Lassen, A. Cervantes, J.-Y. Han, A. Calles, E. Felip, S.-W. Kim, J.H.M. Schellens, A. Taus, M. Sorensen, T. Fleitas, B. Bossenmaier, F. Michielin, C. Adessi, G. Meneses-Lorente, M. Ceppi, I. James, W. Jacob, M. Weisser, M. Martinez-Garcia
Journal: Annals of Oncology (2016)
Effects of Combination Therapy With Immunomodulators on Trough Levels and Antibodies Against Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease: A Meta-analysis
Authors: Yun Qiu, Ren Mao, Bai-li Chen, Sheng-hong Zhang, Jing Guo, Yao He, Zhi-rong Zeng, Shomron Ben-Horin, Min-hu Chen
Journal: Clinical Gastroenterology and Hepatology (2017)
RTHP-12. NON-OPERATIVE MANAGEMENT OF ACOUSTIC NEUROMA IN GERIATRIC PATIENTS: A NATIONWIDE CANCER DATABASE ANALYSIS
Authors: Shearwood McClelland, James D Murphy, Charles R Thomas
Journal: Neuro-Oncology (2016)

The in-hospital mortality rate of acoustic neuroma (AN) surgery is 0.5% and increases exponentially with age; consequently non-operative management has gained popularity (McClelland et al., 2011; Lau et al., 2012). Predominant non-operative AN management involves either radiation (fractionated stereotactic radiotherapy or stereotactic radiosurgery) or observation with serial imaging. The nationwide distribution of these two modalities in the geriatric (minimum age 65) AN population has not been examined. The National Cancer Data Base (NCDB) from 2004-2013 identified geriatric AN patients. Multivariable logistic regression characterized patients who received observation and radiation, including variables for patient age, race, sex, income, geographic region, primary payer for care, tumor size, and comorbidities. Of the 11,614 AN patients, 1,725 (14.9%) were geriatric (median 69;range=65-90); 54% were female. Most had Medicare (79%) or private insurance (15%); median tumor size was 2.1 cm. Solitary treatment was administered as radiation (225 patients; 13.0%), observation (147 patients; 8.5%), and surgery (1,285 patients; 74.5%). Patients with private insurance (OR=0.7;95%CI=0.5-1.0;p=0.005) and a Charlson/Deyo score of 1 or 2 (OR=0.5;95%CI=0.4-0.8;p=0.0005) were less likely to receive radiation, while men (OR=1.3;95%CI=1.0-1.7;p=0.03) and patients treated at a comprehensive cancer center (OR=1.4;95%CI=1.0-1.8;p=0.02) were more likely to receive radiation. African-American race (OR=1.5;95%CI=0.9-2.6;p=0.03) predicted increased observation, while a Charlson/Deyo score of 1 or 2 (OR=0.7;95%CI=0.5-1.0;p=0.03) predicted decreased observation. Fifteen percent of the AN population is at least age 65, with surgery by far the most commonly used treatment modality. Male gender and treatment at comprehensive cancer centers (by 40%) independently predicted receipt of radiation, while African-American race (by 50%) independently predicted receipt of observation. Given the proven impact of radiation therapy on local control in AN, and the relatively small proportion of geriatric patients receiving non-operative treatment, there is fertile ground for dissemination of radiation treatment for geriatric AN patients.
Phase II study of third-line cetuximab rechallenge in patients with metastatic wild-type K-RAS colorectal cancer who achieved a clinical benefit in response to first-line cetuximab plus chemotherapy (JACCRO CC-08)
Authors: A. Tsuji, T. Eto, T. Masuishi, H. Satake, Y. Segawa, H. Tanioka, H. Hara, M. Kotaka, T. Sagawa, T. Watanabe, M. Nakamura, T. Takahashi, Y. Negoro, D. Manaka, H. Fujita, T. Suto, W. Ichikawa, M. Fujii, M. Takeuchi, T. Nakajima
Journal: Annals of Oncology (2016)
Multidisciplinary Evaluation Improves Efficacy and Safety of Iron Chelation Therapy with Deferasirox in MDS Elderly Patients
Authors: Lisette Del Corso, Elisa Molinari, Andrea Bellodi, Riccardo Ghio, Andrea Bacigalupo, Maria Teresa van Lint, Carmen Di Grazia, Marino Clavio, Gianluca Ubezio, Rodolfo Russo, Rodolfo Tassara, Marco Scudeletti, Tullio Calzamiglia, Rosa Filiberti, Massimiliano Brunofranco, Riccardo Goretti, Federico Simonetti, Martina Rousseau, Sara Galimberti, Matteo Schilardi, Lucia Biale, Eleonora Arboscello
Journal: Blood (2015)
A first-in-human (FIH) study of PF-04518600 (PF-8600) OX40 agonist in adult patients (pts) with select advanced malignancies
Authors: A. Diab, A. El-Khoueiry, F.A. Eskens, W. Ros, J.A. Thompson, C. Konto, C. Bermingham, T. Joh, K. Liao, B. Ganguly, O. Hamid
Journal: Annals of Oncology (2016)
Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells
Authors: Zhongming Tan, Qianghui Liu, Runqiu Jiang, Long Lv, Siamak S Shoto, Isabelle Maillet, Valerie Quesniaux, Junwei Tang, Wenjie Zhang, Beicheng Sun, Bernhard Ryffel
Journal: Cellular and Molecular Immunology (2017)
RIG‐I is a key antiviral interferon‐stimulated gene against hepatitis E virus regardless of interferon production
Authors: Lei Xu, Wenshi Wang, Yunlong Li, Xinying Zhou, Yuebang Yin, Yijin Wang, Robert A. de Man, Luc J.W. van der Laan, Fen Huang, Nassim Kamar, Maikel P. Peppelenbosch, Qiuwei Pan
Journal: Hepatology (2017)

Interferons (IFNs) are broad antiviral cytokines that exert their function by inducing the transcription of hundreds of IFN‐stimulated genes (ISGs). However, little is known about the antiviral potential of these cellular effectors on hepatitis E virus (HEV) infection, the leading cause of acute hepatitis globally. In this study, we profiled the antiviral potential of a panel of important human ISGs on HEV replication in cell culture models by overexpression of an individual ISG. The mechanism of action of the key anti‐HEV ISG was further studied. We identified retinoic acid–inducible gene I (RIG‐I), melanoma differentiation–associated protein 5, and IFN regulatory factor 1 (IRF1) as the key anti‐HEV ISGs. We found that basal expression of RIG‐I restricts HEV infection. Pharmacological activation of the RIG‐I pathway by its natural ligand 5′‐triphosphate RNA potently inhibits HEV replication. Overexpression of RIG‐I activates the transcription of a wide range of ISGs. RIG‐I also mediates but does not overlap with IFN‐α‐initiated ISG transcription. Although it is classically recognized that RIG‐I exerts antiviral activity through the induction of IFN production by IRF3 and IRF7, we reveal an IFN‐independent antiviral mechanism of RIG‐I in combating HEV infection. We found that activation of RIG‐I stimulates an antiviral response independent of IRF3 and IRF7 and regardless of IFN production. However, it is partially through activation of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) cascade of IFN signaling. RIG‐I activated two distinct categories of ISGs, one JAK‐STAT‐dependent and the other JAK‐STAT‐independent, which coordinately contribute to the anti‐HEV activity. Conclusion : We identified RIG‐I as an important anti‐HEV ISG that can be pharmacologically activated; activation of RIG‐I stimulates the cellular innate immunity against HEV regardless of IFN production but partially through the JAK‐STAT cascade of IFN signaling. (H epatology 2017;65:1823‐1839).
Accelerated Telomere Shortening Identifies a Subgroup of Patients with Myelodysplastic Syndrome and Isolated 5q Minus Deletion with a Higher Probability of Response to Lenalidomide Treatment
Authors: Fabian Beier, Ralph P Schneider, Guntram Buesche, Jens Panse, Ulrich Germing, Maria A Blasco, Tim H Brümmendorf
Journal: Blood (2012)