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https://www.readbyqxmd.com/read/28092670/neuropilin-1-is-upregulated-in-the-adaptive-response-of-prostate-tumors-to-androgen-targeted-therapies-and-is-prognostic-of-metastatic-progression-and-patient-mortality
#1
B W C Tse, M Volpert, E Ratther, N Stylianou, M Nouri, K McGowan, M L Lehman, S J McPherson, M Roshan-Moniri, M S Butler, J Caradec, C Y Gregory-Evans, J McGovern, R Das, M Takhar, N Erho, M Alshalafa, E Davicioni, E M Schaeffer, R B Jenkins, A E Ross, R J Karnes, R B Den, L Fazli, P A Gregory, M E Gleave, E D Williams, P S Rennie, R Buttyan, J H Gunter, L A Selth, P J Russell, C C Nelson, B G Hollier
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC)...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092656/influence-of-node-abundance-on-signaling-network-state-and-dynamics-analyzed-by-mass-cytometry
#2
Xiao-Kang Lun, Vito R T Zanotelli, James D Wade, Denis Schapiro, Marco Tognetti, Nadine Dobberstein, Bernd Bodenmiller
Signaling networks are key regulators of cellular function. Although the concentrations of signaling proteins are perturbed in disease states, such as cancer, and are modulated by drug therapies, our understanding of how such changes shape the properties of signaling networks is limited. Here we couple mass-cytometry-based single-cell analysis with overexpression of tagged signaling proteins to study the dependence of signaling relationships and dynamics on protein node abundance. Focusing on the epidermal growth factor receptor (EGFR) signaling network in HEK293T cells, we analyze 20 signaling proteins during a 1-h EGF stimulation time course using a panel of 35 antibodies...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28092486/use-of-polyclonal-monoclonal-antibody-therapies-in-transplantation
#3
Melissa Y Yeung, Steven Gabardi, Mohamed H Sayegh
For over thirty years, antibody (mAb)-based therapies have been a standard component of transplant immunosuppression, and yet much remains to be learned in order for us to truly harness their therapeutic capabilities. Current mAbs used in transplant directly target and destroy graft-destructive immune cells, interrupt cytokine and costimulation-dependent T and B cell activation, and prevent down-stream complement activation. Areas covered: This review summarizes our current approaches to using antibody-based therapies to prevent and treat allograft rejection...
January 16, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28092353/non-myeloablative-conditioning-for-second-hematopoietic-cell-transplantation-for-graft-failure-in-patients-with-non-malignant-disorders-a-prospective-study-and-review-of-the-literature
#4
K Mallhi, P J Orchard, W P Miller, Q Cao, J Tolar, T C Lund
Allogeneic hematopoietic cell transplantation (HCT) effectively treats several non-malignant disorders such as selected lysosomal disorders, cerebral adrenoleukodystrophy and hemoglobinopathies. However, rates of graft failure (GF) in non-malignant populations exceed those of patients with malignant indications for HCT. Salvage conditioning regimens and outcomes for second HCT for GF vary immensely in the literature. We report 17 consecutive pediatric patients with non-malignant disorders who underwent a second allogenic HCT for GF using a non-myeloablative, low-dose busulfan-based regimen...
January 16, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28092312/synchronous-presentation-of-renal-cell-carcinoma-and-hodgkin-lymphoma-in-an-adolescent
#5
Mohamed Y Elsaid, Kara G Gill, Ankush Gosain, Peter F Nichol, Charles M Leys, Darya Buehler, Catherine P Leith, Neha J Patel
BACKGROUND: Coincidence of renal cell carcinoma (RCC) and hematologic malignancies has been reported in adults but not in children. OBSERVATION: We report a case of a 16-year-old girl in whom RCC was incidentally discovered on the computed tomography scan that was performed to stage her underlying Hodgkin lymphoma. Analysis of constitutional cytogenetics for common genetic aberrations that predispose to RCC did not reveal any mutations or genetic variations. However, cytogenetics on the RCC tumor demonstrated a rare reciprocal translocation between chromosomes 6 and 11, t(6;11)(p21;q12)...
January 13, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28091965/deformability-of-human-mesenchymal-stem-cells-is-dependent-on-vimentin-intermediate-filaments
#6
Poonam Sharma, Zachary T Bolten, Diane R Wagner, Adam H Hsieh
Mesenchymal stem cells (MSCs) are being studied extensively due to their potential as a therapeutic cell source for many load-bearing tissues. Compression of tissues and the subsequent deformation of cells are just one type physical strain MSCs will need to withstand in vivo. Mechanotransduction by MSCs and their mechanical properties are partially controlled by the cytoskeleton, including vimentin intermediate filaments (IFs). Vimentin IF deficiency has been tied to changes in mechanosensing and mechanical properties of cells in some cell types...
January 13, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28091781/a-semifluorinated-alkane-f4h5-as-novel-carrier-for-cyclosporine-a-a-promising-therapeutic-and-prophylactic-option-for-topical-treatment-of-dry-eye
#7
Uta Gehlsen, Tobias Braun, Maria Notara, Sonja Krösser, Philipp Steven
PURPOSE: Cyclosporine A (Cs) has been used as effective topical therapy for inflammatory dry eye disease since more than a decade. However, due to its lipophilic character, Cs is formulated as emulsions or oily solutions for topical application. This experimental study aimed to test if the use of semifluorinated alkanes (SFAs) as a preservative-free, well-tolerated non-stinging or burning vehicle maintains or even improves the benefits of Cs in the topical therapy of dry-eye disease. METHODS: Desiccating stress was applied to C57BL/6 mice for 14 consecutive days to induce experimental dry-eye...
January 14, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28091566/efficient-generation-of-hpsc-derived-midbrain-dopaminergic-neurons-in-a-fully-defined-scalable-3d-biomaterial-platform
#8
Maroof M Adil, Gonçalo M C Rodrigues, Rishikesh U Kulkarni, Antara T Rao, Nicole E Chernavsky, Evan W Miller, David V Schaffer
Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson's Disease (PD) therapy; however, production of these cells typically involves undefined components and difficult to scale 2D culture formats. Here, we used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing mDA neurons after 25 days of differentiation (~40% tyrosine hydroxylase (TH) positive, maturing into 25% cells exhibiting mDA neuron-like spiking behavior)...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090796/impact-of-c-rel-inhibition-of-cord-blood-derived-b-t-and-nk-cells
#9
Shirin Fallahi, Seyede Momeneh Mohammadi, Hamid Tayefi Nasrabadi, Alireza Alihemmati, Naser Samadi, Sanaz Gholami, Dariush Shanehbandi, Hojjatollah Nozad Charoudeh
The c-Rel transcription factor is a unique member of the nuclear factor (NF)-κB family that has a role in curtailing the proliferation, differentiation, cytokine production, and overall activity of B- and T-cells. In addition, c-Rel is a key regulator of apoptosis in that it influences the expression of anti-apoptotic genes such as Bcl-2 and Bcl-xL; conversely, inhibition of c-Rel increases cell apoptosis. To better understand the relationship between c-Rel expression and effects on B- and T-cell expansion, the current study evaluated c-Rel expression in cord blood mononuclear cells...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28090321/gm-csf-signalling-blockade-and-chemotherapeutic-agents-act-in-concert-to-inhibit-the-function-of-myeloid-derived-suppressor-cells-in-vitro
#10
Tessa Gargett, Susan N Christo, Timothy R Hercus, Nazim Abbas, Nimit Singhal, Angel F Lopez, Michael P Brown
Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However tumours may evade the immune response and resist immune-targeted treatment by promoting an immune-suppressive environment and stimulating the differentiation or recruitment of immunosuppressive cells. Myeloid-derived suppressor cells (MDSC) have been identified in a range of cancers and are often associated with tumour progression and poor patient outcomes...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090089/transfer-of-minimally-manipulated-cmv-specific-t-cells-from-stem-cell-or-third-party-donors-to-treat-cmv-infection-after-allohsct
#11
M Neuenhahn, J Albrecht, M Odendahl, F Schlott, G Dössinger, M Schiemann, S Lakshmipathi, K Martin, D Bunjes, S Harsdorf, E M Weissinger, H Menzel, M Verbeek, L Uharek, N Kröger, E Wagner, G Kobbe, T Schroeder, M Schmitt, G Held, W Herr, L Germeroth, H Bonig, T Tonn, H Einsele, D H Busch, G U Grigoleit
Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively safety and efficacy of stem cell-donor- or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drug-refractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo MHC-Streptamer-isolated CMV epitope-specific donor T cells...
January 16, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28089834/recent-clinical-trials-utilizing-chimeric-antigen-receptor-t-cells-therapies-against-solid-tumors
#12
Shuanglin Han, Olivier Latchoumanin, Guang Wu, Gang Zhou, Lionel Hebbard, Jacob George, Liang Qiao
Chimeric antigen receptors (CARs) are a series of manufactured receptors that have the capacity of binding to specific antigens expressed on surface of tumor cells. A CAR normally has an extracellular antigen recognition domain derived from single variable chain of a monoclonal antibody, a transmembrane domain and an intracellular T cell activation domain. During the last decade, CAR-T cells were demonstrated to possess great therapeutic effects on hematological malignancies. However, strategies using CAR-T cells to treat solid tumors have been hindered by considerable obstacles including "on tissue off target" effects and cytokine storm syndrome...
January 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28089609/de-immunized-and-functional-therapeutic-deft-versions-of-a-long-lasting-recombinant-alpha-interferon-for-antiviral-therapy
#13
Eduardo F Mufarrege, Sofía Giorgetti, Marina Etcheverrigaray, Frances Terry, William Martin, Anne S De Groot
Interferon α (IFN-α) exerts potent antiviral, immunomodulatory, and antiproliferative activity and have proven clinical utility in chronic hepatitis B and C virus infections. However, repeated IFN-α administration induces neutralizing antibodies (NAb) against the therapeutic in a significant number of patients. Associations between IFN-α immunogenicity and loss of efficacy have been described. So as to improve the invivo biological efficacy of IFN-α, a long lasting hyperglycosylated protein (4N-IFN) derived from IFN-α2b wild type (WT-IFN) was developed...
January 9, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28089377/phase-ii-trial-of-albumin-bound-paclitaxel-and-granulocyte-macrophage-colony-stimulating-factor-as-an-immune-modulator-in-recurrent-platinum-resistant-ovarian-cancer
#14
John B Liao, Ron E Swensen, Kelsie J Ovenell, Katie M Hitchcock-Bernhardt, Jessica L Reichow, Minjun C Apodaca, Leonard D'Amico, Jennifer S Childs, Doreen M Higgins, Barbara J Buening, Barbara A Goff, Mary L Disis
BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy. METHODS: Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m(2) days 1, 8, 15 followed by GM-CSF 250μg days 16-26 every 28days for 6 planned cycles...
January 12, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28088790/intraperitoneal-immunotherapy-with-t-cells-stably-and-transiently-expressing-anti-epcam-car-in-xenograft-models-of-peritoneal-carcinomatosis
#15
Wei Xia Ang, Zhendong Li, Zhixia Chi, Shou-Hui Du, Can Chen, Johan C K Tay, Han Chong Toh, John E Connolly, Xue Hu Xu, Shu Wang
The epithelial cell adhesion molecule (EpCAM) is overexpressed in a wide variety of tumor types, including peritoneal carcinomatosis (PC) from gastrointestinal and gynecological malignancies. To develop a chimeric antigen receptor T (CART) cell therapy approach to treat patients with end-stage PC, we constructed third generation CARs specific to EpCAM using the 4D5MOC-B single chain variable fragment. CART cells were generated with lentiviral transduction and exhibited specific in vitro killing activity against EpCAM-positive human ovarian and colorectal cancer cells...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088784/a-phase-i-clinical-study-of-autologous-dendritic-cell-therapy-in-patients-with-relapsed-or-refractory-multiple-myeloma
#16
Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Joon Haeng Rhee, Frank Emmrich, Je-Jung Lee
Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#17
REVIEW
Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype...
January 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28087278/prolyl-trna-synthetase-inhibition-promotes-cell-death-in-sk-mel-2%C3%A2-cells-through-gcn2-atf4-pathway-activation
#18
Takeo Arita, Megumi Morimoto, Yukiko Yamamoto, Hitoshi Miyashita, Satoshi Kitazawa, Takaharu Hirayama, Sou Sakamoto, Kazumasa Miyamoto, Ryutaro Adachi, Misa Iwatani, Takahito Hara
Protein translation is highly activated in cancer tissues through oncogenic mutations and amplifications, and this can support survival and aberrant proliferation. Therefore, blocking translation could be a promising way to block cancer progression. The process of charging a cognate amino acid to tRNA, a crucial step in protein synthesis, is mediated by tRNA synthetases such as prolyl tRNA synthetase (PRS). Interestingly, unlike pan-translation inhibitors, we demonstrated that a novel small molecule PRS inhibitor (T-3861174) induced cell death in several tumor cell lines including SK-MEL-2 without complete suppression of translation...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28087047/rational-design-of-low-immunogenic-anti-cd25-recombinant-immunotoxin-for-t-cell-malignancies-by-elimination-of-t-cell-epitopes-in-pe38
#19
Ronit Mazor, Gilad Kaplan, Dong Park, Youjin Jang, Fred Lee, Robert Kreitman, Ira Pastan
LMB-2, is a potent recombinant immunotoxin (RIT) that is composed of scFv antibody that targets CD25 (Tac) and a toxin fragment (PE38). It is used to treat T cell leukemias and lymphomas. To make LMB-2 less immunogenic, we introduced a large deletion in domain II and six point mutations in domain III that were previously shown to reduce T cell activation in other RITs. We found that unlike other RITs, deletion of domain II from LMB-2 severely compromised its activity. Rather than deletion, we identified T cell epitopes in domain II and used alanine substitutions to identify point mutations that diminished those epitopes...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28086758/toxoplasmosis-associated-iris-involving-the-cns-a-case-report-with-longitudinal-analysis-of-t-cell-subsets
#20
Rita Rb-Silva, Claudia Nobrega, Eugénia Reiriz, Soraia Almeida, Rui Sarmento-Castro, Margarida Correia-Neves, Ana Horta
BACKGROUND: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality...
January 13, 2017: BMC Infectious Diseases
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