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https://www.readbyqxmd.com/read/28088790/intraperitoneal-immunotherapy-with-t-cells-stably-and-transiently-expressing-anti-epcam-car-in-xenograft-models-of-peritoneal-carcinomatosis
#1
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
#2
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/28087488/cathepsin-k-targeted-sub-micron-particles-for-regenerative-repair-of-vascular-elastic-matrix
#3
Brenton Jennewine, Jonathan Fox, Anand Ramamurthi
: Abdominal Aortic Aneurysms (AAA) involve slow dilation and weakening of the aortic wall due to breakdown of structural matrix components, such as elastic fibers by chronically overexpressed matrix metalloproteinases (MMPs), primarily, MMPs-2 and -9. Auto-regenerative repair of disrupted elastic fibers by smooth muscle cells (SMCs) at the AAA site is intrinsically poor and together with chronic proteolysis prevents restoration of elastin homeostasis, necessary to enable AAA growth arrest or regression to a healthy state...
January 10, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28081462/in%C3%A2-vitro-evaluation-of-biodegradable-lignin-based-nanoparticles-for-drug-delivery-and-enhanced-antiproliferation-effect-in-cancer-cells
#4
Patrícia Figueiredo, Kalle Lintinen, Alexandros Kiriazis, Ville Hynninen, Zehua Liu, Tomás Bauleth-Ramos, Antti Rahikkala, Alexandra Correia, Tomáš Kohout, Bruno Sarmento, Jari Yli-Kauhaluoma, Jouni Hirvonen, Olli Ikkala, Mauri A Kostiainen, Hélder A Santos
Currently, nanosystems have been developed and applied as promising vehicles for different biomedical applications. We have developed three lignin nanoparticles (LNPs): pure lignin nanoparticles (pLNPs), iron(III)-complexed lignin nanoparticles (Fe-LNPs), and Fe3O4-infused lignin nanoparticles (Fe3O4-LNPs) with round shape, narrow size distribution, reduced polydispersity and good stability at pH 7.4. The LNPs showed low cytotoxicity in all the tested cell lines and hemolytic rates below 12% after 12 h of incubation...
January 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28081170/an-alpha-1a-adrenergic-receptor-agonist-prevents-acute-doxorubicin-cardiomyopathy-in-male-mice
#5
Megan D Montgomery, Trevor Chan, Philip M Swigart, Bat-Erdene Myagmar, Rajesh Dash, Paul C Simpson
Alpha-1 adrenergic receptors mediate adaptive effects in the heart and cardiac myocytes, and a myocyte survival pathway involving the alpha-1A receptor subtype and ERK activation exists in vitro. However, data in vivo are limited. Here we tested A61603 (N-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl]methanesulfonamide), a selective imidazoline agonist for the alpha-1A. A61603 was the most potent alpha-1-agonist in activating ERK in neonatal rat ventricular myocytes. A61603 activated ERK in adult mouse ventricular myocytes and protected the cells from death caused by the anthracycline doxorubicin...
2017: PloS One
https://www.readbyqxmd.com/read/28079265/chimeric-antigen-receptor-t-cells-in-hematologic-malignancies
#6
Brandon R Shank, Bryan Do, Adrienne Sevin, Sheree E Chen, Sattva S Neelapu, Sandra B Horowitz
Patients with B cell hematologic malignancies who progress through first or second line chemotherapy have a poor prognosis. Early clinical trials with autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin-2, and total body irradiation are often administered prior to infusion of CAR T cells, allowing for greater T cell expansion...
January 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28076709/phase-3-trial-of-177-lu-dotatate-for-midgut-neuroendocrine-tumors
#7
Jonathan Strosberg, Ghassan El-Haddad, Edward Wolin, Andrew Hendifar, James Yao, Beth Chasen, Erik Mittra, Pamela L Kunz, Matthew H Kulke, Heather Jacene, David Bushnell, Thomas M O'Dorisio, Richard P Baum, Harshad R Kulkarni, Martyn Caplin, Rachida Lebtahi, Timothy Hobday, Ebrahim Delpassand, Eric Van Cutsem, Al Benson, Rajaventhan Srirajaskanthan, Marianne Pavel, Jaime Mora, Jordan Berlin, Enrique Grande, Nicholas Reed, Ettore Seregni, Kjell Öberg, Maribel Lopera Sierra, Paola Santoro, Thomas Thevenet, Jack L Erion, Philippe Ruszniewski, Dik Kwekkeboom, Eric Krenning
Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ((177)Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either (177)Lu-Dotatate (116 patients) at a dose of 7...
12, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28076386/neutrophil-to-lymphocyte-ratio-for-predicting-loss-of-response-to-infliximab-in-ulcerative-colitis
#8
Yu Nishida, Shuhei Hosomi, Hirokazu Yamagami, Tomomi Yukawa, Koji Otani, Yasuaki Nagami, Fumio Tanaka, Koichi Taira, Noriko Kamata, Tetsuya Tanigawa, Masatsugu Shiba, Kenji Watanabe, Toshio Watanabe, Kazunari Tominaga, Yasuhiro Fujiwara
OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) has been used to determine the outcome in malignancies and coronary heart disease. Some reports considered the value of NLR as a predictor of response to infliximab in patients with Crohn's disease or rheumatoid arthritis; however, no similar studies have been reported for ulcerative colitis (UC). This study aimed to evaluate the clinical significance of the baseline NLR in patients with UC treated by infliximab. MATERIALS AND METHODS: Patients with moderate-to-severe active UC who received the first infliximab infusion in our hospital between 2010 and 2015, who showed clinical response during the induction period, were retrospectively evaluated for long-term outcomes and risk factors for loss of response (LOR) during infliximab maintenance therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28073042/rapid-infusions-of-human-normal-immunoglobulin-50g-l-are-safe-and-well-tolerated-in-immunodeficiencies-and-immune-thrombocytopenia
#9
Giuseppe Spadaro, Alessandra Vultaggio, A Alberto Bosi, Dietmar Reichert, Jan Janssen, Donatella Lamacchia, Liliana Nappi, Antonio Pecoraro, Cinzia Milito, Andrea Ferraro, Andrea Matucci, Francesca Bacchiarri, Valentina Carrai, Azra Hibbeler, Elisabet Speckman, Chiara Guarnieri, Serena Bongiovanni, Isabella Quinti
Intravenous immunoglobulin (IVIg) is accepted as an effective and well-tolerated treatment for primary and secondary immunodeficiencies (ID) and immune thrombocytopenia (ITP). Adverse reactions of IVIg are usually mild, comprising transient flu-like symptoms, change in blood pressure and tachycardia. However IVIg therapy can be burdensome for both patients and healthcare facilities, since the infusion may take up to 4h to administer. The objective of our multicentre, prospective, open-label phase III trial was to evaluate the tolerability and safety of human normal immunoglobulin 50g/l (Ig VENA) at high intravenous infusion rates in adult patients with ID and ITP who had previously tolerated IVIg treatment, by progressively increasing infusion rate up to 8ml/kg/hr...
January 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28070715/an-integrated-assessment-of-the-effects-of-immunogenicity-on-the-pharmacokinetics-safety-and-efficacy-of-elotuzumab
#10
Chaitali Passey, Johanna Mora, Robert Dodge, Leonid Gibiansky, Jennifer Sheng, Amit Roy, Akintunde Bello, Manish Gupta
Elotuzumab is a humanized, immunostimulatory anti-signaling lymphocytic activation molecule F7 (SLAMF7) IgG1 monoclonal antibody indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma (MM) who have received 1-3 prior therapies. We assessed the immunogenicity of elotuzumab as a monotherapy and in combination with bortezomib/dexamethasone and lenalidomide/dexamethasone in patients with MM in five clinical studies, including the pivotal ELOQUENT-2 trial (NCT01239797). Anti-drug antibody (ADA) prevalence was determined using a validated bridging assay...
January 9, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28069642/alpha-1-antitrypsin-enhances-islet-engraftment-by-suppression-of-instant-blood-mediated-inflammatory-reaction
#11
Jingjing Wang, Zhen Sun, Wenyu Gou, David B Adams, Wanxing Cui, Katherine A Morgan, Charlie Strange, Hongjun Wang
Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that alpha-1 antitrypsin (AAT, Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared to mice treated with saline...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28069570/anti-cd22-car-therapy-leads-to-all-remissions
#12
(no author information available yet)
In a first-in-human trial of an anti-CD22 chimeric antigen receptor T-cell therapy in children and young adults with relapsed and refractory acute lymphocytic leukemia, researchers found that the immunotherapeutic approach was not only feasible and safe, but also effective, leading to remissions in most patients. Infusions of higher numbers of T cells correlated with improved responses.
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28069044/effect-of-transcutaneous-electrical-acupoint-stimulation-combined-with-palonosetron-on-chemotherapy-induced-nausea-and-vomiting-a-single-blind-randomized-controlled-trial
#13
Jing Xie, Lei-Hua Chen, Zhou-Yu Ning, Chen-Yue Zhang, Hao Chen, Zhen Chen, Zhi-Qiang Meng, Xiao-Yan Zhu
BACKGROUND: Chemotherapy-induced nausea and vomiting adversely affects the quality of life of patients who receive chemotherapy via intravenous infusion or transcatheter arterial chemoembolization (TACE). This study aimed to investigate the clinical effects of transcutaneous electrical acupoint stimulation (TEAS) on nausea and vomiting after TACE. METHODS: A total of 142 patients who received TACE with cisplatin for primary or metastatic liver cancer were assigned to the active-acupuncture (n = 72) or placebo-acupuncture (n = 70) groups using a covariate-adaptive randomization at a ratio of 1:1...
January 10, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28068510/current-knowledge-and-priorities-for-future-research-in-late-effects-after-hematopoietic-stem-cell-transplantation-hct-for-severe-combined-immunodeficiency-patients-a-consensus-statement-from-the-second-pediatric-blood-and-marrow-transplant-consortium-international
#14
REVIEW
Jennifer Heimall, Jennifer Puck, Rebecca Buckley, Thomas A Fleisher, Andrew R Gennery, Benedicte Neven, Mary Slatter, Elie Haddad, Luigi D Notarangelo, K Scott Baker, Andrew C Dietz, Christine Duncan, Michael A Pulsipher, Mort J Cowan
Severe combined immunodeficiency (SCID) is 1 of the most common indications for pediatric hematopoietic cell transplantation (HCT) in patients with primary immunodeficiency. Historically, SCID was diagnosed in infants who presented with opportunistic infections within the first year of life. With newborn screening (NBS) for SCID in most of the United States, the majority of infants with SCID are now diagnosed and treated in the first 3.5 months of life; however, in the rest of the world, the lack of NBS means that most infants with SCID still present with infections...
January 6, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28067900/donor-cd19-car-t-cells-exert-potent-graft-versus-lymphoma-activity-with-diminished-graft-versus-host-activity
#15
Arnab Ghosh, Melody Smith, Scott E James, Marco L Davila, Enrico Velardi, Kimon V Argyropoulos, Gertrude Gunset, Fabiana Perna, Fabiana M Kreines, Emily R Levy, Sophie Lieberman, Hillary V Jay, Andrea Z Tuckett, Johannes L Zakrzewski, Lisa Tan, Lauren F Young, Kate Takvorian, Jarrod A Dudakov, Robert R Jenq, Alan M Hanash, Ana Carolina F Motta, George F Murphy, Chen Liu, Andrea Schietinger, Michel Sadelain, Marcel R M van den Brink
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28067704/intravenous-ketamine-infusions-for-neuropathic-pain-management-a-promising-therapy-in-need-of-optimization
#16
Dermot P Maher, Lucy Chen, Jianren Mao
Intravenous ketamine infusions have been used extensively to treat often-intractable neuropathic pain conditions. Because there are many widely divergent ketamine infusion protocols described in the literature, the variation in these protocols presents a challenge for direct comparison of one protocol with another and in discerning an optimal protocol. Careful examination of the published literature suggests that ketamine infusions can be useful to treat neuropathic pain and that certain characteristics of ketamine infusions may be associated with better clinical outcomes...
January 5, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28067165/gene-therapy-in-fanconi-anemia-a-matter-of-time-safety-and-gene-transfer-tool-efficiency
#17
Verhoeyen Els, Francisco José Román Rodríguez, François-Loïc Cosset, Camille Lévy, Paula Rio
Fanconi anemia (FA) is a rare genetic syndrome characterized by progressive marrow failure. Gene therapy by infusion of FA-corrected autologous hematopoietic stem cells (HSCs) may offer a potential cure since it is a monogenetic disease with mutations in the FANC genes, coding for DNA repair enzymes (See review[1]). However, the collection of hCD34 +-cells in FA patients implies particular challenges because of the reduced numbers of progenitor cells present in their bone marrow (BM)[2] or mobilized peripheral blood[3-5]...
January 9, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28063683/diphasic-dyskinesias-during-levodopa-carbidopa-intestinal-gel-lcig-infusion-in-parkinson-s-disease
#18
Meloni Mario, Solla Paolo, Mascia Mario Marcello, Marrosu Francesco, Cannas Antonino
OBJECTIVES: Levodopa-carbidopa intestinal gel infusion (LCIG) is indicated in patients with advanced levodopa-responsive Parkinson's disease (PD) for the treatment of motor fluctuations and dyskinesias. Here we describe 4 PD patients who developed disabling diphasic dyskinesias after LCIG initiation. METHODS: The clinical data of 33 PD patients consecutively treated with LCIG therapy were obtained through direct clinical observation and detailed review of medical records...
December 31, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28062334/intensity-of-vasopressor-therapy-for-septic-shock-and-the-risk-of-in-hospital-death
#19
Donald A Brand, Patricia A Patrick, Jeffrey T Berger, Mediha Ibrahim, Ajsza Matela, Shweta Upadhyay, Peter Spiegler
CONTEXT: Given the high mortality of 30-60% associated with septic shock, distinguishing which patients do or do not have a reasonable chance of surviving with aggressive treatment could help clinicians and families make informed decisions. OBJECTIVES: To determine if intensity of vasopressor therapy accurately predicts in-hospital death. METHODS: This observational cohort study analyzed in-hospital mortality as a function of intensity of vasopressor therapy in a consecutive series of adults with septic shock treated over a 4-year period...
January 3, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28059661/intravenous-infusion-of-mesenchymal-stem-cells-inhibits-intracranial-hemorrhage-after-recombinant-tissue-plasminogen-activator-therapy-for-transient-middle-cerebral-artery-occlusion-in-rats
#20
Masahito Nakazaki, Masanori Sasaki, Yuko Kataoka-Sasaki, Shinichi Oka, Takahiro Namioka, Ai Namioka, Rie Onodera, Junpei Suzuki, Yuichi Sasaki, Hiroshi Nagahama, Takeshi Mikami, Masahiko Wanibuchi, Jeffery D Kocsis, Osamu Honmou
OBJECTIVE Reperfusion therapy with intravenous recombinant tissue plasminogen activator (rtPA) is the standard of care for acute ischemic stroke. However, hemorrhagic complications can result. Intravenous infusion of mesenchymal stem cells (MSCs) reduces stroke volume and improves behavioral function in experimental stroke models. One suggested therapeutic mechanism is inhibition of vascular endothelial dysfunction. The objective of this study was to determine whether MSCs suppress hemorrhagic events after rtPA therapy in the acute phase of transient middle cerebral artery occlusion (tMCAO) in rats...
January 6, 2017: Journal of Neurosurgery
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