tbuckley/cabot-search huggingface dataset:
The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells
Authors: Marina Vilaseca, Héctor García‐Calderó, Erica Lafoz, Oihane García‐Irigoyen, Matías A. Avila, Joan Carles Reverter, Jaume Bosch, Virginia Hernández‐Gea, Jordi Gracia‐Sancho, Joan Carles García‐Pagán
Journal: Hepatology (2017)

In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension (PH) development. Hepatic stellate cells (HSCs) play a major role increasing IHVR because, when activated, they are contractile and promote fibrogenesis. Protease‐activated receptors (PARs) can activate HSCs through thrombin and factor Xa, which are known PAR agonists, and cause microthrombosis in liver microcirculation. This study investigates the effects of the oral anticoagulant, rivaroxaban (RVXB), a direct antifactor Xa, on HSC phenotype, liver fibrosis (LF), liver microthrombosis, and PH in cirrhotic rats. Hepatic and systemic hemodynamic, nitric oxide (NO) bioavailability, LF, HSC activation, and microthrombosis were evaluated in CCl 4 and thioacetamide‐cirrhotic rats treated with RVXB (20 mg/kg/day) or its vehicle for 2 weeks. RVXB significantly decreased portal pressure (PP) in both models of cirrhosis without changes in portal blood flow, suggesting a reduction in IHVR. RVXB reduced oxidative stress, improved NO bioavailability, and ameliorated endothelial dysfunction. Rivaroxaban deactivated HSC, with decreased alpha‐smooth muscle actin and mRNA expression of other HSC activation markers. Despite this marked improvement in HSC phenotype, no significant changes in LF were identified. RVXB markedly reduced fibrin deposition, suggesting reduced intrahepatic microthrombosis. Conclusion : RVXB decreases PP in two rat models of cirrhosis. This effect is mostly associated with decreased IHVR, enhanced NO bioavailability, HSC deactivation, and reduced intrahepatic microthrombosis. Our findings suggest that RVXB deserves further evaluation as a potential treatment for cirrhotic PH. (H epatology 2017;65:2031‐2044).
Fingolimod treatment abrogates chikungunya virus–induced arthralgia
Authors: Teck-Hui Teo, Yi-Hao Chan, Wendy W. L. Lee, Fok-Moon Lum, Siti Naqiah Amrun, Zhisheng Her, Ravisankar Rajarethinam, Andres Merits, Olaf Rötzschke, Laurent Rénia, Lisa F. P. Ng
Journal: Science Translational Medicine (2017)

Abrogation of pathogenic CD4 + T cells to the joints with fingolimod (FTY720) treatment prevents chikungunya virus–induced joint pathology.
Gene Expression for Chemokine Receptors Influences Survival of Non-Hodgkin Lymphoma Patients
Authors: Grzegorz Mazur, Emilia Jaskula, Ilona Kryczek, Dorota Dlubek, Tomasz Wrobel, Aleksandra Butrym, Andrzej Lange, Kazimierz Kuliczkowski
Journal: Blood (2010)
Frequency and Epitope Specificity of Anti-Factor VIII C1 Domain Antibodies in Acquired and Hereditary Hemophilia Inhibitor Patient Plasma
Authors: Joerg Kahle, Aleksander Orlowski, Anja Schmidt, Kerstin Brettschneider, Thomas Klingebiel, John F Healey, Ernest T Parker, John (Pete) S Lollar, Marc Jacquemin, Manuela Krause, Andreas Tiede, Dirk Schwabe, Christoph Königs
Journal: Blood (2015)
Multiple Fentanyl Overdoses — New Haven, Connecticut, June 23, 2016
Authors: Anthony J. Tomassoni, Kathryn F. Hawk, Karen Jubanyik, Daniel P. Nogee, Thomas Durant, Kara L. Lynch, Rushaben Patel, David Dinh, Andrew Ulrich, Gail D’Onofrio
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

On the evening of June 23, 2016, a white powder advertised as cocaine was purchased off the streets from multiple sources and used by an unknown number of persons in New Haven, Connecticut. During a period of less than 8 hours, 12 patients were brought to the emergency department (ED) at Yale New Haven Hospital, experiencing signs and symptoms consistent with opioid overdose. The route of intoxication was not known, but presumed to be insufflation ("snorting") in most cases. Some patients required doses of the opioid antidote naloxone exceeding 4 mg (usual initial dose = 0.1-0.2 mg intravenously), and several patients who were alert after receiving naloxone subsequently developed respiratory failure. Nine patients were admitted to the hospital, including four to the intensive care unit (ICU); three required endotracheal intubation, and one required continuous naloxone infusion. Three patients died. The white powder was determined to be fentanyl, a drug 50 times more potent than heroin, and it included trace amounts of cocaine. The episode triggered rapid notification of public health and law enforcement agencies, interviews of patients and their family members to trace and limit further use or distribution of the fentanyl, immediate naloxone resupply and augmentation for emergency medical services (EMS) crews, public health alerts, and plans to accelerate naloxone distribution to opioid users and their friends and families. Effective communication and timely, coordinated, collaborative actions of community partners reduced the harm caused by this event and prevented potential subsequent episodes.
ATPS-67MORPHOLOGIC HETEROGENEITY AT A PIXEL-LEVEL CAPTURED VIA ENTROPY OF GRADIENT ORIENTATIONS ON T1-POST CONTRAST MRI ENABLES DISCRIMINATION OF TUMOR RECURRENCE FROM CEREBRAL RADIATION NECROSIS
Authors: Prateek Prasanna, Archana Siddalingappa, Leo Wolansky, Lisa Rogers, Tai-Chung Lam, Victoria To, Anant Madabhushi, Pallavi Tiwari
Journal: Neuro-Oncology (2015)

OBJECTIVE: Radiation necrosis (RN) is a radiation injury due to high dose radiation, and is extremely challenging to differentiate from brain tumor recurrence (RT) on conventional MRI. Early identification of RN from RT has prognostic implications. While visually these two pathologies appear similar on MRI, morphologic differences at a per-pixel level between RT and RN may require more advanced computerized image analysis methods. In this work, we evaluate a new radiomic feature, CoLlAGe, to compare different grades of RT from RN on Gd-enhanced T1w-MRI. Mathematically, CoLlAGe captures the degree of disorder and in turn morphologic heterogeneity in gradient orientations on a per-voxel basis. The hypothesis is that, while there are known differences at cellular level between RN and RT, they are perhaps also reflected on MRI, and can be captured by computing localized gradient orientations on a per-pixel basis. METHOD AND MATERIALS: We computed CoLlAGe on every lesion on a unique cohort of 45 pathologically confirmed patients: (1) 14 ‘pure’ (100%) RN cases from nasopharyngeal carcinoma, (2) 10 ‘predominant’ RN (>80% RN, remainder RT), and 11 ‘predominant’ recurrence cases with >80% tumor (remainder RN) in radiated primary brain tumors, and (3) 10 cases on treatment-naive MRI (0% RN). RESULTS: CoLlAGe feature values were lowest for ‘pure’ RN with a mean and standard deviation of 0.74 +/- 0.11, 0.84 +/- 0.10 for ‘predominant’ RN, 0.91 +/- 0.06 for ‘predominant’ recurrence and 0.88 + /- .03 for treatment-naive GBMs respectively. At a normalized threshold of 0.8, 100% (21 of 21) tumor recurrence patients and 67% (16 of 24) RN patients were correctly identified using CoLlAGe values. CONCLUSION: The CoLlAGe values were found to be significantly different across RT and RN cohort with an overall accuracy of 82%. Timely identification of RN from RT could allow for personalized therapy options in brain tumor patients.
PD-1 blockade induces remissions in relapsed classical Hodgkin lymphoma following allogeneic hematopoietic stem cell transplantation
Authors: James Godfrey, Michael R. Bishop, Sahr Syed, Elizabeth Hyjek, Justin Kline
Journal: Journal for ImmunoTherapy of Cancer (2017)

Allogeneic hematopoietic stem cell transplantation and checkpoint blockade therapy are immune-based therapies that have activity in selected refractory hematologic malignancies. Interest has developed in combining these treatments for high-risk hematologic diseases. However, there is concern that checkpoint blockade could augment graft-versus-host disease, and very few studies have evaluated the safety of checkpoint blockade in the post-allogeneic setting. Here, we report the outcomes of three patients with relapsed classical Hodgkin's lymphoma following allogeneic transplant that were treated with the anti-PD-1 antibody, nivolumab.Three patients with Hodgkin's lymphoma relapsed following allogeneic transplant received nivolumab therapy at our institution. All patients were free of graft-versus-host disease and were off of all systemic immunosuppressive medications at the time of nivolumab treatment. Nivolumab was well-tolerated in two of the patients. However, nivolumab had to be discontinued in one patient due to development of immune-related polyarthritis requiring treatment with systemic corticosteroids and methotrexate. Objective responses were observed in all three patients.Our case series demonstrates that anti-PD-1 therapy with nivolumab can be highly effective following allogeneic transplant for Hodgkin's lymphoma, but serious immune-related adverse events can occur, requiring very close monitoring and interruption of therapy.
ATPS-32TUMOR-HOMING HUMAN INDUCED NEURAL STEM CELLS: TOWARDS PERSONALIZED CELL THERAPY FOR GLIOBLASTOMA
Authors: Juli Bago, Onyi Okolie, Raluca Dumitru, Matthew Ewend, Shawn Hingtgen
Journal: Neuro-Oncology (2015)

BACKGROUND: Engineered neural stem cells (NSC) are a promising new approach to treating glioblastoma (GBM). As NSC therapy for GBM enters clinical trials, the ideal NSC drug carrier should be easily isolated and autologous to avoid immune rejection. METHODS: As a new approach to personalized NSC therapy for cancer, we switched the fate of human fibroblasts in induced neural stem cells (h-iNSCs) using a new stem cell technology termed transdifferentiation (TD). The h-iNSCs were engineered to express optical reporters and either the pro-apoptotic agent TRAIL or prodrug/enzyme therapy thymidine kinase. The tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSCs were then assessed in human GBM cell models of solid and surgically resected disease in mice. RESULTS: To develop the first TD method capable of generating h-iNSCs fast enough for clinical GBM therapy, we discovered a new TD strategy that converted human skin fibroblasts into nestin+ h-iNSCs in only 4 days. Non-invasive optical imaging and immunostaining showed h-iNSCs survived in the brain of mice for 3 weeks and remained nestin+. Time-lapse motion analysis of 3-dimensional co-cultures showed h-iNSCs rapidly migrated to human GBMs cells and penetrated solid human GBM spheroids. Investigating h-iNSC therapy, h-iNSC secretion of TRAIL reduced solid GBM intracranial xenografts 250-fold in 3 weeks and prolonged median survival from 22 to 49 days. h-iNSC prodrug/enzyme therapy regressed human patient-derived GBM xenografts 20-fold and extended survival from 32 to 62 days. Mimicking clinical h-iNSC therapy, intra-cavity h-iNSC thymidine kinase/ganciclovir therapy delayed the regrowth of post-surgical GBMs 3-fold and prolonged survival in mice from 46 to 60 days. CONCLUSIONS: Transdifferentiating human skin into h-iNSCs is a new platform for creating tumor-homing cytotoxic cell therapies for cancer. Translating this approach has the potential to avoid carrier rejection and maximize treatment durability in patient trials.
Quantitative Assessment of Hematopoietic Chimerism after Allogeneic Nonmyeloablative Stem Cell Transplantation.
Authors: Bao-An Chen, Hui-Xia Xiong, Jia-Hua Ding, Chong Gao, Yun-Yu Sun, Jun Wang, Jian Cheng, Gang Zhao, Ning-Na Chen, Fei Fei
Journal: Blood (2006)
Imatinib Treated Chronic Myelogenous Leukemia Concomitant with Multiple Myeloma. Is There a Relationship?
Authors: Jose Mauro Kutner, Claudia Bley, Guilherme Fleury Perini, Fabio Santos, Morgani Rodrigues, Andreza Alice Feitosa Ribeiro, Nelson Hamerschlak
Journal: Blood (2010)
Minimal Residual Disease Monitoring in Patients with Newly Diagnosed Acute Promyelocytic Leukemia Treated with Arsenic Trioxide
Authors: Ezhilarasi Chendamarai, Poonkuzhali Balasubramanian, Kavitha Lakshmi, Auro Viswabandya, Biju George, Alok Srivastava, Mammen Chandy, Vikram Mathews
Journal: Blood (2008)
Glutamate and norepinephrine interaction: Relevance to higher cognitive operations and psychopathology
Authors: Chadi G. Abdallah, Lynnette A. Averill, John H. Krystal, Steven M. Southwick, Amy F. T. Arnsten
Journal: Behavioral and Brain Sciences (2016)

Abstract Mather and colleagues present an impressive interdisciplinary model of arousal-induced norepinephrine release and its role in selectively enhancing/inhibiting perception, attention, and memory consolidation. This model will require empirical investigation to test its validity and generalizability beyond classic norepinephrine circuits because it simplifies extremely complex and heterogeneous actions including norepinephrine mechanisms related to higher cognitive circuits and psychopathology.
FGF13 Selectively Regulates Heat Nociception by Interacting with Nav1.7
Authors: Liu Yang, Fei Dong, Qing Yang, Pai-Feng Yang, Ruiqi Wu, Qing-Feng Wu, Dan Wu, Chang-Lin Li, Yan-Qing Zhong, Ying-Jin Lu, Xiaoyang Cheng, Fu-Qiang Xu, Limin Chen, Lan Bao, Xu Zhang
Journal: Neuron (2017)
Strategies for improving the payload of small molecular drugs in polymeric micelles
Authors: Yu Zhang, Tianyang Ren, Jingxin Gou, Ling Zhang, Xiaoguang Tao, Bin Tian, Pengqian Tian, Dandan Yu, Jianbo Song, Xiaolin Liu, Yanhui Chao, Wei Xiao, Xing Tang
Journal: Journal of Controlled Release (2017)
Molecular Transfer of Human CD40 and OX40 Ligands to Leukemic Human B-CLL Cells Extensively Expands Tumor-Reactive Cytotoxic T-Lymphocytes.
Authors: Ettore Biagi, Giampietro Dotti, Eric Yvon, Raphael Rousseau, Edward Lee, Stephen Gotschalk, Malcolm Brenner
Journal: Blood (2004)
The Impact of Methylenetetrahydrofolate Reductase C677T Gene Polymorphism on Engraftment after Allogeneic Hematopoetic Cell Transplantation.
Authors: Ender A. Soydan, Pervin Topcuoglu, Muhit Ozcan, Onder Arslan, Gunhan Gurman, Meral Beksac, Mutlu Arat, Osman Ilhan
Journal: Blood (2005)
Corrections to “A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma”
Authors: A.M. Evens, K.R. Carson, J. Kolesar, C. Nabhan, I. Helenowski, N. Islam, B. Jovanovic, P.M. Barr, P.F. Caimi, S.A. Gregory, L.I. Gordon
Journal: Annals of Oncology (2014)
Altered Von Willebrand Factor Subunit Proteolysis and Multimer Processing Associated with the Cys1599(2362)Phe Mutation in the B2 Domain.
Authors: Luigi De Marco, Alessandra Casonato, Lisa Gallinaro, Marita Sztukowska, Mario Mazzucato, Monica Battiston, Antonio Pagnan, Zaverio M. Ruggeri
Journal: Blood (2006)
Both Expanded and Uncultured Mesenchymal Stem Cells from MDS Patients Are Genomically Abnormal, Showing a Specific Genetic Profile for the 5q- Syndrome.
Authors: Olga López Villar, Juan LuíS. García, Fermín. M Sánchez Guijo, Cristina Robledo, Pilar Hernandez Campo, Maria Diez Campelo, Sandra Muntion, Jose Antonio Pérez Simón, J.F. San Miguel, MaríA. Consuelo Del Cañizo
Journal: Blood (2008)
Competition elicits arousal and affect
Authors: R. Hans Phaf
Journal: Behavioral and Brain Sciences (2016)

The emotion-cognition integration in Mather et al. can be extended by specifying the relationship between competition and arousal in the reverse direction. According to affective monitoring, competition raises arousal, which, when sustained, results in negative affect, evoking theta oscillations, and when resolved, in positive affect, evoking gamma oscillations. Competition should be considered a core process in both cognition and emotion.
Phase 2 trial of talabostat in stage IV melanoma
Authors: B. G. Redman, M. S. Ernstoff, T. F. Gajewski, C. Cunningham, D. H. Lawson, L. Gregoire, E. Haltom, M. J. Uprichard
Journal: Journal of Clinical Oncology (2005)

7570 Background: Talabostat (T) is an oral inhibitor of dipeptidyl peptidases such as fibroblast activation protein found on the stroma of tumors and in melanomas. Administration of T stimulates cytokine and chemokine production in humans and animals resulting in specific T-cell immunity and T-cell independent activity. In xenograft models of melanoma (A375, A2058), T significantly reduced tumor size >60% in immunodeficient mice. A clinical trial was initiated to evaluate the activity of this oral agent in melanoma. Methods: Open-label, single-arm, Phase 2 study in up to 30 evaluable patients with Stage IV melanoma using the Simon 2-stage design. Treatment is administered as six 3-week cycles of T-300μg administered orally BID Days 1–14. Dose-escalation of T to 400μg BID allowed in subsequent cycles depending on tolerability. T can be continued past 6 cycles at the discretion of the investigator. Patients must have an ECOG PS 0–2 with expected survival ≥12 weeks, measureable disease per RECIST, no active CNS metastases, LDH, ALT, and AST <3X ULN, and no more than 1 prior bio- or chemotherapy regimen for Stage IV melanoma. Primary endpoint is disease response; secondary endpoints include survival, PFS, duration of response, and cytokine expression in serum and biopsy tissue. Results: Ten patients (7 men and 3 women) have enrolled to date. The median age is 64 (range 37 to 76). Six patients received prior treatment, and 4 are treatment-naive for Stage IV disease. One patient has SD after 6 cycles of treatment, 2 had PD after 2 cycles, and 6 are awaiting a post-Cycle 2 assessment. The most frequently reported AEs are edema (40%), and fatigue, nausea, and myalgia/arthralgia (all 20%). One patient experienced Grade 3 events of edema, hypotension, acute prerenal failure, hyperkalemia, nausea, and vomiting. The patient was hydrated and continued on study medication. One patient died due to PD in Cycle 1 prior to a post-baseline assessment. Conclusions: In the initial cohort of 10 patients, 1 patient has SD at 18 weeks, and 2 patients had PD after 6 weeks on treatment. Six patients are on treatment awaiting post-baseline evaluations. The most common AEs have been edema, fatigue, nausea, and myalgia/arthralgia. Updated results will be presented at the annual meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Point Therapeutics Point Therapeutics Point Therapeutics Point Therapeutics
Validation of Proposed European Leukemia Net Recommendations for Standardized Reporting and Classification of Cytogenetic Risk in AML Patients Treated with Stem Cell Transplantation
Authors: Claudia Ulrike Walter, Fahed Almhareb, Naeem A. Chaudhri, Wahiba Chebbo, Shad Ahmed, Fazal Hussain, Tusneem Elhassan, Hazzaa Al Zahrani, Said Mohamed, Walid Rasheed, Fahad Alsharif, Mahmoud Aljurf, Maher Albitar
Journal: Blood (2011)
New Targets in Cytometric Investigation of Acute Leukemia Selected From Gene Profiling Studies
Authors: Martina Vaskova, Ester Mejstrikova, Tomas Brdicka, Pavla Angelisova, Tomas Kalina, Veronika Kanderova, Daniela Cerna, Martin Kovac, Jan Trka, Fridtjof Lund-Johansen, Jan Stary, Ondrej Hrusak
Journal: Blood (2011)
Abstract B06: Cathepsin B expression in colorectal cancer in Middle East population: Potential value as a tumor biomarker for late stages
Authors: Maha Abdulla
Journal: Cancer Research (2017)

Abstract Objective: To investigate Cathepsin B (CTSB) expression in colorectal cancer (CRC) tissues and serum, the association of CTSB expression with tumor stages and metastasis and targeting CTSB by nanoparticles for potential CRC therapeutics. Methods: CTSB expression was determined in 100 pairs of CRC tumor and adjacent normal tissue using quantitative PCR for mRNA levels. Serum CTSB levels were evaluated in 95 patients and 20 healthy control using enzyme-linked immunosorbant assay (ELISA) technique. Detection of Cathepsin B protein expression in tissues was done using immunohistochemistry and western blotting. Cathepsin B protein expression was inhibited using cobalt oxide nanoparticles in human colorectal cancer cells. Results: Greater than 90% of tumors had detectable CTSB protein expression with significant increase staining in tumors compared with matched normal colon (p=0.006). The relative levels of CTSB mRNA in tumor samples and adjacent normal colorectal tissue were 0.04 ± 0.06 and 0.01 ± 0.02 respectively. The mRNA expression in early stage CRC compared to late stage CRC was 0.05 ± 0.04 and 0.02 ± 0.01, respectively. Increased mRNA expression was seen in the advanced stages with lymph node metastases compared to control P=0.002. CTSB was significantly higher in sera of patients with lymph node metastasis compared to early and late stage primary tumors. A subset of 40 paired tissue extracts were analyzed by western blotting. This also revealed consistent increase of CTSB protein level in tumor tissue. Treatment of human CRC cell HT-29 with increasing concentrations of cobalt oxide nanoparticles resulted in significant decrease of CTSB expression. Conclusion: These findings thus indicate that CTSB may be an important prognostic biomarker for early stage CRC and lymph node metastasis in Middle East populations. Monitoring serum CTSB in CRC patient may predict and diagnose lymph node metastasis. Furthermore CTSB may represent a potential target for nanoparticle-based drugs in the treatment of colorectal cancer. Citation Format: Maha Abdulla. Cathepsin B expression in colorectal cancer in Middle East population: Potential value as a tumor biomarker for late stages. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B06.
Prognostic value of extranodal extension and other lymph node parameters in patients with upper tract urothelial carcinoma.
Authors: Eugene K. Cha, Harun Fajkovic, Claudio Jeldres, Thomas F. Chromecki, Michael Rink, Vitaly Margulis, Giacomo Novara, Yair Lotan, Jay D. Raman, Wassim Kassouf, Karim Bensalah, Alon Z. Weizer, Marco Roscigno, Armin Pycha, Vincenzo Ficarra, Francesco Montorsi, Douglas Scherr, Shahrokh F. Shariat
Journal: Journal of Clinical Oncology (2012)

281 Background: The aim of the current study was to assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters in a large multicenter cohort of patients with LN metastasis (LNM) following radical nephroureterectomy (RNU). Methods: Retrospective analysis of 222 patients with LNM treated with RNU for upper tract urothelial carcinoma (UTUC) without neoadjuvant therapy. Microscopically, each LN metastasis was evaluated for presence of ENE. Results: The median number of LNs removed, number of positive LNs, and LN density were 4 (IQR: 8), 2 (IQR: 2), and 51.3% (IQR: 71.7%), respectively. Overall, 110 patients (49.5%) had ENE. Presence of ENE was associated with more advanced pT stage (p=0.026). In multivariable analyses, ENE was associated with disease recurrence (p=0.01) and cancer-specific mortality (p=0.013). LN density, when stratified by 30% cutoff, was associated with disease recurrence and cancer-specific mortality (p=0.048 and p=0.049) in univariable, but not in multivariable analyses. Addition of ENE to a multivariable model including pT stage and tumor architecture improved predictive accuracy for disease recurrence from 70.3% to 74.5% (p&lt;0.001). Addition of ENE to a multivariable model including age, pT stage, and tumor architecture improved predictive accuracy for cancer-specific mortality from 70.6% to 74.4% (p&lt;0.001). Conclusions: ENE is a powerful predictor of clinical outcomes in UTUC patients with LNM. While other LN parameters seem to have limited clinical value, ENE could help risk stratify UTUC patients with LNM for better counseling and clinical trial design.