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https://www.readbyqxmd.com/read/28446206/cooperation-of-neurotrophin-receptor-trkb-and-her2-in-breast-cancer-cells-facilitates-brain-metastases
#1
Cecilia Choy, Khairul I Ansari, Josh Neman, Sarah Hsu, Matthew J Duenas, Hubert Li, Nagarajan Vaidehi, Rahul Jandial
BACKGROUND: Patients with primary breast cancer that is positive for human epidermal growth factor receptor 2 (Her2+) have a high risk of developing metastases in the brain. Despite gains with systemic control of Her2+ disease using molecular therapies, brain metastases remain recalcitrant to therapeutic discovery. The clinical predilection of Her2+ breast cancer cells to colonize the brain likely relies on paracrine mechanisms. The neural niche poses unique selection pressures, and neoplastic cells that utilize the brain microenvironment may have a survival advantage...
April 26, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28443460/augmented-expression-of-runx1-deregulates-the-global-gene-expression-of-u87-glioblastoma-multiforme-cells-and-inhibits-tumor-growth-in-mice
#2
Yoel Bogoch, Gilgi Friedlander-Malik, Lior Lupu, Ekaterina Bondar, Nitzan Zohar, Sheila Langier, Zvi Ram, Ido Nachmany, Joseph M Klausner, Niv Pencovich
Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28439684/impact-of-altered-endogenous-igg-on-unspecific-mab-clearance
#3
Saskia Fuhrmann, Charlotte Kloft, Wilhelm Huisinga
Immunodeficient mice are crucial models to evaluate the efficacy of monoclonal antibodies (mAbs). When studying mAb pharmacokinetics (PK), protection from elimination by binding to the neonatal Fc receptor (FcRn) is known to be a major process influencing the unspecific clearance of endogenous and therapeutic IgG. The concentration of endogenous IgG in immunodeficient mice, however is reduced, and this effect on the FcRn protection mechanism and subsequently on unspecific mAb clearance is unknown, yet of great importance for the interpretation of mAb PK data...
April 24, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28438538/linking-newborn-severe-combined-immunodeficiency-screening-with-targeted-exome-sequencing-a-case-report
#4
Dipika R Patel, Hui Yu, Lee-Jun C Wong, James R Lupski, Filiz O Seeborg, Nicholas L Rider, Caridad A Martinez, Jordan S Orange, Celine Hanson
No abstract text is available yet for this article.
April 21, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28435246/cuprous-oxide-nanoparticle-inhibited-melanoma-progress-by-targeting-melanoma-stem-cells
#5
Bin Yu, Ye Wang, Xinlu Yu, Hongxia Zhang, Ji Zhu, Chen Wang, Fei Chen, Changcheng Liu, Jingqiang Wang, Haiying Zhu
Recent studies have shown that metal and metal oxide have a potential function in antitumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271(+/high) cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28426455/digoxin-attenuates-murine-experimental-colitis-by-downregulating-th17-related-cytokines
#6
Shinya Tani, Ryosuke Takano, Satoshi Tamura, Shinji Oishi, Moriya Iwaizumi, Yasushi Hamaya, Kosuke Takagaki, Toshi Nagata, Shintaro Seto, Toshinobu Horii, Isao Kosugi, Toshihide Iwashita, Satoshi Osawa, Takahisa Furuta, Hiroaki Miyajima, Ken Sugimoto
BACKGROUND: Digoxin, a cardiac glycoside used for the treatment of heart failure, was reported to inhibit the retinoid-related orphan receptor gamma t (RORγt) and attenuate the severity of experimental autoimmune encephalomyelitis and arthritis in mice. However, the effects of digoxin in a mice model of inflammatory bowel disease have not been elucidated. METHODS: Colitis was induced in severe combined immunodeficiency mice by adoptive transfer of CD45RB CD4 T cells...
May 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28423509/histone-lysine-methyltransferase-g9a-is-a-novel-epigenetic-target-for-the-treatment-of-hepatocellular-carcinoma
#7
Masayuki Yokoyama, Tetsuhiro Chiba, Yoh Zen, Motohiko Oshima, Yuko Kusakabe, Yoshiko Noguchi, Kaori Yuki, Shuhei Koide, Shiro Tara, Atsunori Saraya, Kazumasa Aoyama, Naoya Mimura, Satoru Miyagi, Masanori Inoue, Toru Wakamatsu, Tomoko Saito, Sadahisa Ogasawara, Eiichiro Suzuki, Yoshihiko Ooka, Akinobu Tawada, Masayuki Otsuka, Masaru Miyazaki, Osamu Yokosuka, Atsushi Iwama
Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone lysine methyltransferase G9a and is associated with the repression of transcription. However, both the role of G9a and the significance of H3K9me2 in hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted loss-of-function assay of G9a using short-hairpin RNA and pharmacological interference. Knockdown of G9a reduced H3K9me2 levels and impaired both HCC cell growth and sphere formation. However, transforming growth factor β1-induced epithelial mesenchymal transition (EMT) was not suppressed by G9a knockdown...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418539/ophthalmic-manifestations-of-congenital-zika-syndrome-in-colombia-and-venezuela
#8
Juan B Yepez, Felipe A Murati, Michele Pettito, Carlos F Peñaranda, Jazmin de Yepez, Gladys Maestre, J Fernando Arevalo
Importance: The ocular manifestations and sequelae of Zika virus infection are not well known. Recently, the World Health Organization changed the declaration of Zika as a public health emergency and designated the viral outbreak and related microcephaly clusters as a long-term program of work. This change indicates the urgent need to evaluate and document ophthalmic manifestations in patients for timely management of this disease. In addition, confirmation whether the public health problem in Brazil extends to other regions in South America is needed...
April 13, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/28416602/antigen-receptor-galaxy-a-user-friendly-web-based-tool-for-analysis-and-visualization-of-t-and-b-cell-receptor-repertoire-data
#9
Hanna IJspeert, Pauline A van Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Andrew P Stubbs, Mirjam van der Burg
Antigen Receptor Galaxy (ARGalaxy) is a Web-based tool for analyses and visualization of TCR and BCR sequencing data of 13 species. ARGalaxy consists of four parts: the demultiplex tool, the international ImMunoGeneTics information system (IMGT) concatenate tool, the immune repertoire pipeline, and the somatic hypermutation (SHM) and class switch recombination (CSR) pipeline. Together they allow the analysis of all different aspects of the immune repertoire. All pipelines can be run independently or combined, depending on the available data and the question of interest...
April 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28405609/preconditioned-mesenchymal-stem-cells-treat-myasthenia-gravis-in-a-humanized-preclinical-model
#10
Muriel Sudres, Marie Maurer, Marieke Robinet, Jacky Bismuth, Frédérique Truffault, Diane Girard, Nadine Dragin, Mohamed Attia, Elie Fadel, Nicola Santelmo, Camille Sicsic, Talma Brenner, Sonia Berrih-Aknin
Myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) Abs is an autoimmune disease characterized by severe defects in immune regulation and thymic inflammation. Because mesenchymal stem cells (MSCs) display immunomodulatory features, we investigated whether and how in vitro-preconditioned human MSCs (cMSCs) could treat MG disease. We developed a new humanized preclinical model by subcutaneously grafting thymic MG fragments into immunodeficient NSG mice (NSG-MG model). Ninety percent of the animals displayed human anti-AChR Abs in the serum, and 50% of the animals displayed MG-like symptoms that correlated with the loss of AChR at the muscle endplates...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28404888/ecto-5-nucleotidase-cd73-is-a-biomarker-for-clear-cell-renal-carcinoma-stem-like-cells
#11
Lei Song, Wenling Ye, Yong Cui, Jianzhong Lu, Yanan Zhang, Nan Ding, Wentao Hu, Hailong Pei, Zhongjin Yue, Guangming Zhou
Identification of a specific biomarker for cancer stem cells (CSCs) is of potential applications in the development of effective therapeutic strategies for renal cell carcinoma (RCC). In this study, both the RCC cell line 786-O and surgically removed clear cell RCC (ccRCC) tissues were implemented to grew as spheroids in serum-free medium supplemented with mitogens. This subpopulation possessed key characteristics defining CSCs. We also identified that surgically removed ccRCC tissues were heterogenic and there was a subpopulation of cells that was highly stained with rhodamine-123...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404538/haematopoietic-stem-cell-transplantation-in-primary-immunodeficiency-patients-in-the-black-sea-region-of-turkey
#12
Alişan Yıldıran, Mehmet Halil Çeliksoy, Stephan Borte, Şükrü Nail Güner, Murat Elli, Tunç Fışgın, Emel Özyürek, Recep Sancak, Gönül Oğur
OBJECTIVE: Haematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. MATERIALS AND METHODS: We retrospectively reviewed paediatric cases that were diagnosed with primary immunodeficiencies and scheduled for haematopoietic stem cell transplantation. RESULTS: We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received haematopoietic stem cell transplantation...
April 13, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28402755/distribution-of-fcrn-across-species-and-tissues
#13
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/28388605/refining-strategies-to-translate-genome-editing-to-the-clinic
#14
REVIEW
Tatjana I Cornu, Claudio Mussolino, Toni Cathomen
Recent progress in developing programmable nucleases, such as zinc-finger nucleases, transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas nucleases, have paved the way for gene editing to enter clinical practice. This translation is a result of combining high nuclease activity with high specificity and successfully applying this technology in various preclinical disease models, including infectious disease, primary immunodeficiencies, hemoglobinopathies, hemophilia and muscular dystrophy...
April 3, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28383134/in-vitro-t-lymphocyte-proliferation-by-carboxyfluorescein-diacetate-succinimidyl-ester-method-is-helpful-in-diagnosing-and-managing-primary-immunodeficiencies
#15
Elif Azarsiz, Neslihan Karaca, Birgul Ergun, Mehmet Durmuscan, Necil Kutukculer, Guzide Aksu
BACKGROUND: Functional studies besides routine laboratory tests for the definitive diagnosis of T lymphocyte disorders with isolated T or combined T/B-cell immunodeficiencies are important. We hereby summarized our experience with a carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay for the assessment of mitogenic T-cell proliferation responses in primary immunodeficiency (PID) patients who have not been diagnosed yet or genetically analyzed, but classified as probably having T-cell defects...
April 6, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28366768/asgct-20-th-anniversary-special-issue-of-molecular-therapy-evolving-gene-therapy-in-primary-immunodeficiency
#16
REVIEW
Adrian J Thrasher, David A Williams
Prior to the first successful bone marrow transplant in 1968, patients born with severe combined immunodeficiency (SCID) invariably died. Today, with a widening availability of newborn screening, major improvements in the application of allogeneic procedures, and the emergence of successful hematopoietic stem and progenitor cell (HSC/P) gene therapy, the majority of these children can be identified and cured. Here, we trace key steps in the development of clinical gene therapy for SCID and other primary immunodeficiencies (PIDs), and review the prospects for adoption of new targets and technologies...
March 30, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28365567/use-of-p53-silenced-endothelial-progenitor-cells-to-treat-ischemia-in-diabetic-peripheral-vascular-disease
#17
Nabanita Kundu, Cleyton C Domingues, Cyril Chou, Neeki Ahmadi, Sara Houston, D Joseph Jerry, Sabyasachi Sen
BACKGROUND: Peripheral vascular disease is a major diabetes mellitus-related complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53- and p21-silenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53- and p21-silenced EPCs could improve collateral vessel formation and blood flow in diabetic vaso-occlusive peripheral vascular disease mouse models...
April 1, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28364370/recommendations-for-managing-drug-drug-interactions-with-statins-and-hiv-medications
#18
REVIEW
Barbara S Wiggins, Donald G Lamprecht, Robert L Page, Joseph J Saseen
The discovery of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) has enabled individuals to live longer. As a result, HIV is now often considered a chronic condition. However, as a result of the increase in longevity or the HIV treatment modalities themselves, individuals with HIV are at high risk for the development of atherosclerotic cardiovascular disease. Therefore, these patients should be optimized with pharmacologic therapy to lower their cardiovascular risk through the addition of statin therapy to their regimen...
April 1, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/28348607/epidemiology-and-outcomes-in-critically-ill-patients-with-human-immunodeficiency-virus-infection-in-the-era-of-combination-antiretroviral-therapy
#19
Shannon L Turvey, Sean M Bagshaw, Dean T Eurich, Wendy I Sligl
Purpose. The impact of critical illness on survival of HIV-infected patients in the era of antiretroviral therapy remains uncertain. We describe the epidemiology of critical illness in this population and identify predictors of mortality. Materials and Methods. Retrospective cohort of HIV-infected patients was admitted to intensive care from 2002 to 2014. Patient sociodemographics, comorbidities, case-mix, illness severity, and 30-day mortality were captured. Multivariable Cox regression analyses were performed to identify predictors of mortality...
2017: Canadian Journal of Infectious Diseases & Medical Microbiology
https://www.readbyqxmd.com/read/28345026/oncolytic-adenoviruses-armed-with-tumor-necrosis-factor-alpha-and-interleukin-2-enable-successful-adoptive-cell-therapy
#20
Riikka Havunen, Mikko Siurala, Suvi Sorsa, Susanna Grönberg-Vähä-Koskela, Michael Behr, Siri Tähtinen, João Manuel Santos, Pauliina Karell, Juuso Rusanen, Dirk M Nettelbeck, Anja Ehrhardt, Anna Kanerva, Akseli Hemminki
Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both...
March 17, 2017: Molecular Therapy Oncolytics
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