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https://www.readbyqxmd.com/read/28430034/um-chor1-establishment-and-characterization-of-the-first-validated-clival-chordoma-cell-line
#1
John Henry Owen, Christine M Komarck, Anthony C Wang, Waleed M Abuzeid, Richard F Keep, Erin L McKean, Stephen Sullivan, Xing Fan, Mark E P Prince
OBJECTIVE Chordomas are rare malignant tumors thought to arise from remnants of the notochord. They can be located anywhere along the axial skeleton but are most commonly found in the clival and sacrococcygeal regions, where the notochord regresses during fetal development. Chordomas are resistant to many current therapies, leaving surgery as the primary method of treatment. Cancer cell lines have been useful for developing new cancer treatments in a laboratory setting that can then be transferred to the clinic, but there are only 4 validated chordoma cell lines available...
April 21, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28425238/depression-and-parkinson-disease-prevalence-temporal-relationship-and-determinants
#2
Hale Yapici Eser, Hatice Ayşe Bora, Aslı Kuruoğlu
BACKGROUND/AIM: Comorbidity of depression in Parkinson disease (PD) is a major factor that changes patients' quality of life. However, the neurobiological and sociodemographic risk factors for this comorbidity are not well studied. In this study, we aimed to define the prevalence, temporal relationship, and psychosocial and clinical determinants of depression comorbid with PD. MATERIALS AND METHODS: Fifty-five PD patients were evaluated with SCID, a data form that assessed sociodemographic and PD-related variables, UPDRS III, HAM-D, HAM-A, MMSE, and the Apathy Evaluation Scale...
April 18, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/28424681/the-spontaneous-autoimmune-neuromyopathy-in-icosl-nod-mice-is-cd4-t-cell-and-interferon-%C3%AE-dependent
#3
Claire Briet, Gwladys Bourdenet, Ute C Rogner, Chantal Becourt, Isabelle Tardivel, Laurent Drouot, Christophe Arnoult, Jean-Claude do Rego, Nicolas Prevot, Charbel Massaad, Olivier Boyer, Christian Boitard
Abrogation of ICOS/ICOS ligand (ICOSL) costimulation prevents the onset of diabetes in the non-obese diabetic (NOD) mouse but, remarkably, yields to the development of a spontaneous autoimmune neuromyopathy. At the pathological level, ICOSL(-/-) NOD mice show stronger protection from insulitis than their ICOS(-/-) counterparts. Also, the ICOSL(-/-) NOD model carries a limited C57BL/6 region containing the Icosl nul mutation, but, in contrast to ICOS(-/-) NOD mice, no gene variant previously reported as associated to NOD diabetes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28421882/inhibition-of-her3-activation-and-tumor-growth-with-a-human-antibody-binding-to-a-conserved-epitope-formed-by-domain-iii-and-iv
#4
Lisa C Schmitt, Alexander Rau, Oliver Seifert, Jonas Honer, Meike Hutt, Simone Schmid, Jonas Zantow, Michael Hust, Stefan Dübel, Monilola A Olayioye, Roland E Kontermann
Human epidermal growth factor receptor 3 (HER3, also known as ErbB3) has emerged as relevant target for antibody-mediated tumor therapy. Here, we describe a novel human antibody, IgG 3-43, recognizing a unique epitope formed by domain III and parts of domain IV of the extracellular region of HER3, conserved between HER3 and mouse ErbB3. An affinity of 11 nM was determined for the monovalent interaction. In the IgG format, the antibody bound recombinant bivalent HER3 with subnanomolar affinity (KD = 220 pM) and HER3-expressing tumor cells with EC50 values in the low picomolar range (27 - 83 pM)...
April 19, 2017: MAbs
https://www.readbyqxmd.com/read/28421616/the-validity-of-the-montgomery-asberg-depression-rating-scale-in-an-inpatient-sample-with-alcohol-dependence
#5
Breanne Hobden, Melanie L Schwandt, Mariko Carey, Mary R Lee, Mehdi Farokhnia, Sofia Bouhlal, Christopher Oldmeadow, Lorenzo Leggio
BACKGROUND: The Montgomery-Asberg Depression Rating Scale (MADRS) is commonly used to examine depressive symptoms in clinical settings, including facilities treating patients for alcohol addiction. No studies have examined the validity of the MADRS compared to an established clinical diagnostic tool of depression in this population. This study aimed to examine: 1) the validity of the MADRS compared to a clinical diagnosis of a depressive disorder (using the Structured Clinical Interview for DSM-IV (SCID)) in patients seeking treatment for alcohol dependence (AD); 2) whether the validity of the MADRS differs by type of SCID-based diagnosis of depression; and 3) which items contribute to the optimal predictive model of the MADRS compared to a SCID diagnosis of a depressive disorder...
April 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28420742/synergistic-internal-ribosome-entry-site-microrna-based-approach-for-flavivirus-attenuation-and-live-vaccine-development
#6
Konstantin A Tsetsarkin, Guangping Liu, Evgeniya Volkova, Alexander G Pletnev
The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Using another flavivirus (Langat virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we describe a dual strategy for virus attenuation which synergistically accesses the specificity of microRNA (miRNA) genome targeting and the effectiveness of internal ribosome entry site (IRES) insertion. To increase the stability and immunogenicity of bicistronic LGTVs, we developed a novel approach in which the capsid (C) protein gene was relocated into the 3' noncoding region (NCR) and expressed under translational control from an IRES...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28417956/establishment-and-characterization-of-an-orthotopic-patient-derived-group-3-medulloblastoma-model-for-preclinical-drug-evaluation
#7
Emma Sandén, Cecilia Dyberg, Cecilia Krona, Gabriel Gallo-Oller, Thale Kristin Olsen, Julio Enríquez Pérez, Malin Wickström, Atosa Estekizadeh, Marcel Kool, Edward Visse, Tomas J Ekström, Peter Siesjö, John Inge Johnsen, Anna Darabi
Medulloblastomas comprise a heterogeneous group of tumours and can be subdivided into four molecular subgroups (WNT, SHH, Group 3 and Group 4) with distinct prognosis, biological behaviour and implications for targeted therapies. Few experimental models exist of the aggressive and poorly characterized Group 3 tumours. In order to establish a reproducible transplantable Group 3 medulloblastoma model for preclinical therapeutic studies, we acquired a patient-derived tumour sphere culture and inoculated low-passage spheres into the cerebellums of NOD-scid mice...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416634/a-molecular-mechanism-to-switch-the-aryl-hydrocarbon-receptor-from-a-transcription-factor-to-an-e3-ubiquitin-ligase
#8
Sandra Luecke-Johansson, Michael Gralla, Helene Rundqvist, Jolene Caifeng Ho, Randall S Johnson, Katarina Gradin, Lorenz Poellinger
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is known as a mediator of toxic responses. Recently, it was shown that AhR has dual functions. Besides being a transcription factor it also possesses an intrinsic E3 ubiquitin ligase function that targets e.g. the steroids receptors for proteasomal degradation. The aim of the study was to identify the molecular switch that determines whether AhR acts as a transcription factor or an E3 ubiquitin ligase. To do that, we used the breast cancer cell line MCF7, which expresses a functional ERα signaling pathway...
April 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28414146/tissue-distribution-of-a-therapeutic-monoclonal-antibody-determined-by-large-pore-microdialysis
#9
Satyawan B Jadhav, Vipada Khaowroongrueng, Matthias Fueth, Michael B Otteneder, Wolfgang Richter, Hartmut Derendorf
Therapeutic monoclonal antibodies (mAbs) exhibit limited distribution to the target tissues. Determination of target tissue interstitial concentration of mAbs is an important aspect in the assessment of their pharmacokinetic/pharmacodynamics (PK/PD) relationship especially for mAbs targeting membrane bound receptors. The pharmacokinetics of R7072, a full length mAb (IgG) targeting human insulin like growth factor-1 receptor (IGF-1R) was evaluated following a single intravenous (IV) dose at 1, 6.25 and 25 mg/kg in healthy female SCID-beige mice...
April 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28413871/comparison-of-the-gene-expression-profiles-of-human-hematopoietic-stem-cells-between-humans-and-a-humanized-xenograft-model
#10
Hideyuki Matsuzawa, Hiromichi Matsushita, Takashi Yahata, Masayuki Tanaka, Kiyoshi Ando
The aim of this study is to evaluate the feasibility of NOD/Shi-scid-IL2Rγ(null)(NOG) mice transplanted with human CD34(+)/CD38(-)/Lin(-/low) hematopoietic cells from cord blood (CB) as an experimental model of the gene expression in human hematopoiesis. We compared the gene expressions of human CD34(+)/CD38(-)/Lin(-/low) cells from human bone marrow (BM) and in xenograft models. The microarray data revealed that 25 KEGG pathways were extracted from the comparison of human CD34(+)/CD38(-)/Lin(-/low) HSCs between CB and BM, and that 17 of them--which were mostly related to cellular survival, RNA metabolism and lymphoid development--were shared with the xenograft model...
April 20, 2017: Tokai Journal of Experimental and Clinical Medicine
https://www.readbyqxmd.com/read/28412732/small-molecule-inhibitor-screening-identifified-hsp90-inhibitor-17-aag-as-potential-therapeutic-agent-for-gallbladder-cancer
#11
Helga Weber, José R Valbuena, Mustafa A Barbhuiya, Stefan Stein, Hana Kunkel, Patricia García, Carolina Bizama, Ismael Riquelme, Jaime A Espinoza, Stephen E Kurtz, Jeffrey W Tyner, Juan Francisco Calderon, Alejandro H Corvalán, Manuel Grez, Akhilesh Pandey, Pamela Leal-Rojas, Juan C Roa
Gallbladder cancer (GBC) is a lethal cancer with poor prognosis associated with high invasiveness and poor response to chemotherapy and radiotherapy. New therapeutic approaches are urgently needed in order to improve survival and response rates of GBC patients. We screened 130 small molecule inhibitors on a panel of seven GBC cell lines and identified the HSP90 inhibitor 17-AAG as one of the most potent inhibitory drugs across the different lines. We tested the antitumor efficacy of 17-AAG and geldanamycin (GA) in vitro and in a subcutaneous preclinical tumor model NOD-SCID mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28409338/fluorine-18-labeling-of-the-her2-targeting-single-domain-antibody-2rs15d-using-a-residualizing-label-and-preclinical-evaluation
#12
Zhengyuan Zhou, Ganesan Vaidyanathan, Darryl McDougald, Choong Mo Kang, Irina Balyasnikova, Nick Devoogdt, Angeline N Ta, Brian R McNaughton, Michael R Zalutsky
PURPOSE: Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts...
April 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28409183/combination-of-il-10-and-il-2-induces-oligoclonal-human-cd4-t-cell-expansion-during-xenogeneic-and-allogeneic-gvhd-in-humanized-mice
#13
Sojan Abraham, Hua Guo, Jang-Gi Choi, Chunting Ye, Midhun Ben Thomas, Nora Ortega, Alok Dwivedi, N Manjunath, Guohua Yi, Premlata Shankar
IL-10 is a crucial anti-inflammatory cytokine which can also exert a seemingly divergent immunostimulatory effects under certain conditions. We found high levels of the cytokine in a xenogeneic GVHD model where NOD-scid IL2rγcnull (NSG) mice were transplanted with human PBMCs in presence of IL-2. Presence of exogenous IL-10 altered the kinetics of IL-2 induced human T cell reconstitution in vivo, showing an initial delay, followed by rapid expansion. Further, compared to IL-2 alone, treatment with IL-2 in combination with IL-10 increased survival in most animals and completely protected ∼20% of mice from GVHD...
April 2017: Heliyon
https://www.readbyqxmd.com/read/28408423/improving-transplantation-for-il2rg-jak3-scid
#14
Michael D Keller
No abstract text is available yet for this article.
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28407689/radioiodinated-indomethacin-amide-for-molecular-imaging-of-cyclooxygenase-2-expressing-tumors
#15
Agnieszka Morgenroth, Andreas T J Vogg, Bernd Neumaier, Felix M Mottaghy, Boris D Zlatopolskiy
Cyclooxygenase-2 (COX-2) is an important biomarker in several tumors. Available imaging probes display relatively low tumor to background ratios (smaller than 2:1). We evaluated newly developed indomethacin (Ind) derivatives for in vivo molecular imaging of COX-2 expressing carcinoma. Radioiodinated Ind derivatives Ind-NH-(CH2)4-NH-3-[I-125]I-Bz ([I-125]5), Ind-NH-(CH2)4-NH-5-[I-124/125]I-Nic ([I-124/125]6) and Ind-NH-(CH2)4-NH-5-[I-125]I-Iphth ([I-125]7) were prepared from the respective SnBu3-precursors (45-80% radiochemical yield; > 95% radiochemical purity)...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407688/npc-26-kills-human-colorectal-cancer-cells-via-activating-ampk-signaling
#16
Zhen Zhao, Li Feng, Jiqin Wang, Deshan Cheng, Mei Liu, Meirong Ling, Weiping Xu, Keyu Sun
NPC-26 is novel mitochondrion-interfering compound. The current study tested its potential effect against colorectal cancer (CRC) cells. We demonstrated that NPC-26 induced potent anti-proliferative and cytotoxic activities against CRC cell lines (HCT-116, DLD-1 and HT-29). Activation of AMP-activated protein kinase (AMPK) signaling mediated NPC-26-induced CRC cell death. AMPKα1 shRNA knockdown or dominant negative mutation abolished NPC-26-induced AMPK activation and subsequent CRC cell death. NPC-26 disrupted mitochondrial function, causing mitochondrial permeability transition pore (mPTP) opening and reactive oxygen species (ROS) production...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406754/spheroid-coculture-of-hematopoietic-stem-progenitor-cells-and-monolayer-expanded-mesenchymal-stem-stromal-cells-in-polydimethylsiloxane-microwells-modestly-improves-in-vitro-hematopoietic-stem-progenitor-cell-expansion
#17
Kathryn Futrega, Kerry Atkinson, William B Lott, Michael R Doran
While two-dimensional (2D) monolayers of mesenchymal stem/stromal cells (MSCs) have been shown to enhance hematopoietic stem/progenitor cell (HSPC) expansion in vitro, expanded cells do not engraft long term in human recipients. This outcome is attributed to the failure of 2D culture to recapitulate the bone marrow (BM) niche signal milieu. Herein, we evaluated the capacity of a novel three-dimensional (3D) coculture system to support HSPC expansion in vitro. A high-throughput polydimethylsiloxane (PDMS) microwell platform was used to manufacture thousands of uniform 3D multicellular coculture spheroids...
April 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28405526/anti-vegfr2-interferon-%C3%AE-2-regulates-the-tumor-microenvironment-and-exhibits-potent-antitumor-efficacy-against-colorectal-cancer
#18
Zhaoting Li, Yijia Zhu, Chenchen Li, Ryan Trinh, Xueyan Ren, Fumou Sun, Youfu Wang, Pengzhao Shang, Tong Wang, Min Wang, Sherie L Morrison, Juan Zhang
Interferon-α (IFNα) has multiple antitumor effects including direct antitumor toxicity and the ability to potently stimulate both innate and adaptive immunity. However, its clinical applications in the treatment of malignancies have been limited because of short half-life and serious adverse reactions when attempting to deliver therapeutically effective doses. To address these issues, we fused IFNα2a to the anti-vascular endothelial growth factor and receptor 2 (VEGFR2) antibody JZA00 with the goal of targeting it to the tumor microenvironment where it can stimulate the antitumor immune response...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28402755/distribution-of-fcrn-across-species-and-tissues
#19
Sari Latvala, Bjoern Jacobsen, Michael B Otteneder, Annika Herrmann, Sven Kronenberg
The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I type molecule that binds to, transports, and recycles immunoglobulin G (IgG) and albumin, thereby protecting them from lysosomal degradation. Therefore, besides the knowledge of FcRn affinity, FcRn protein expression is critical in understanding the pharmacokinetic behavior of Fc-containing biotherapeutics such as monoclonal antibodies. The goal of this investigation was to achieve for the first time a comparative assessment of FcRn distribution across a variety of tissues and species...
April 1, 2017: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/28400146/comparison-of-four-brief-depression-screening-instruments-in-ovarian-cancer-patients-diagnostic-accuracy-using-traditional-versus-alternative-cutpoints
#20
Eileen H Shinn, Alan Valentine, George Baum, Cindy Carmack, Kelly Kilgore, Diane Bodurka, Karen Basen-Engquist
OBJECTIVES: We compared the diagnostic accuracy of 4 depression screening scales, using traditional and alternative scoring methods, to the gold standard Structured Clinical Interview-DSM IV major depressive episode (MDE) in ovarian cancer patients on active treatment. METHODS: At the beginning of a new chemotherapy regimen, ovarian cancer patients completed the following surveys on the same day: the Center for Epidemiological Studies Depression Scale (CES-D), the Beck Depression Inventory Fast-Screen for Primary Care (BDI-FastScreen), the Patient Health Questionnaire-9 (PHQ-9), and a 1-item screener ("Are you depressed?")...
April 8, 2017: Gynecologic Oncology
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