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Cellular Therapy

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https://www.readbyqxmd.com/read/28938558/human-menstrual-blood-derived-mesenchymal-stem-cells-as-a-cellular-vehicle-for-malignant-glioma-gene-therapy
#1
Xiao-Jun Wang, Bing-Yu Xiang, Ya-Hui Ding, Lu Chen, Hai Zou, Xiao-Zhou Mou, Charlie Xiang
Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938245/gallic-acid-induces-g1-phase-arrest-and-apoptosis-of-triple-negative-breast-cancer-cell-mda-mb-231-via-p38-mitogen-activated-protein-kinase-p21-p27-axis
#2
Hsiang-Lin Lee, Chun-Shiang Lin, Shao-Hsuan Kao, Ming-Chih Chou
Gallic acid (GA) possesses potential antitumoral activity on different types of malignancies. In this study, we aimed to explore the antitumoral effects of GA on triple-negative breast cancer (TNBC) cells, the breast cancer cells showing resistance to hormonal therapy or HER2 receptor targeting therapy. We observed that GA treatment significantly decreased the cell viability of human TNBC cell line MDA-MB-231 and HS578T in a dose-dependent manner. In addition, GA exerted a relative lower cytotoxicity on noncancer breast fibroblast MCF-10F...
September 21, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28937684/strategies-for-the-etiological-therapy-of-cystic-fibrosis
#3
REVIEW
Luigi Maiuri, Valeria Raia, Guido Kroemer
Etiological therapies aim at repairing the underlying cause of cystic fibrosis (CF), which is the functional defect of the cystic fibrosis transmembrane conductance regulator (CFTR) protein owing to mutations in the CFTR gene. Among these, the F508del CFTR mutation accounts for more than two thirds of CF cases worldwide. Two somehow antinomic schools of thought conceive CFTR repair in a different manner. According to one vision, drugs should directly target the mutated CFTR protein to increase its plasma membrane expression (correctors) or improve its ion transport function (potentiators)...
September 22, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28937214/injectable-thermoresponsive-hydrogel-formed-by-alginate-g-poly-n-isopropylacrylamide-releasing-doxorubicin-encapsulated-micelles-as-smart-drug-delivery-system
#4
Min Liu, Xia Song, Yuting Wen, Jing-Ling Zhu, Jun Li
In this work, we have synthesized a thermoresponsive copolymer, alginate-g-poly(N-isopropylacrylamide) (alginate-g-PNIPAAm), by conjugating PNIPAAm to alginate, where PNIPAAm with different molecular weight and narrow molecular weight distribution was synthesized by atomic transfer radical polymerization (ATRP). The copolymer dissolved in water or PBS buffer solution at room temperature, and formed self-assembled micelles with low critical micellization concentrations when temperature increased to above their critical micellization temperatures...
September 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28937091/obstruction-of-braf-v600e-transcription-by-complementary-pna-oligomers-as-a-means-to-inhibit-braf-mutant-melanoma-growth
#5
J H Rothman, O Surriga, E de Stanchina, S D Vasudeva, G K Schwartz
Peptide nucleic acid (PNA) oligomers are DNA mimics, which are capable of binding gene sequences 1000-fold more avidly than complementary native DNA by strand invasion and effectively obstruct transcription. Irreversibly obstructing the transcription or replication of a gene sequence, such as BRAF(V600E), offers a potential route to specifically target the cancer cell itself. We have employed PNA oligomers to target BRAF(V600E) in a sequence-specific complementary manner. These PNAs have been modified by appending configurationally stabilizing cationic peptides in order to improve their cellular delivery and target avidity...
September 22, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28937044/priming-of-the-cells-hypoxic-preconditioning-for-stem-cell-therapy
#6
REVIEW
Zheng Z Wei, Yan-Bing Zhu, James Y Zhang, Myles R McCrary, Song Wang, Yong-Bo Zhang, Shan-Ping Yu, Ling Wei
OBJECTIVE: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues...
October 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28936741/exosomes-derived-from-embryonic-stem-cells-as-potential-treatment-for-cardiovascular-diseases
#7
Yao-Hua Song, Lianbo Shao, Yu Zhang, Jin Zhou, Bin Liu, Xiangbin Pan, Yong-Jian Geng, Xi-Yong Yu, Yangxin Li
Cardiovascular diseases resulting from ischemic heart diseases remain to be the main causes of heart failure and death despite significant advances in medical treatment. The development of new therapies for heart failure is thus required to improve the outcome in these patients, and this has led to the development of cell-based therapies. Animal studies showed interesting results using various cell types. Some stem cell based therapies have been tested in clinical trials. Although the results were encouraging, challenges remain...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28936734/exosomes-as-new-intercellular-mediators-in-development-and-therapeutics-of-cardiomyocyte-hypertrophy
#8
Qi Huang, Benzhi Cai
Myocardial hypertrophy is a common cardiac condition in response to hemodynamic and neurohormonal alterations. Pathological hypertrophic growth in hearts caused the decline of cardiac functions, and finally developed into congestive heart failure. The exosomes are small membrane vesicles which are secreted by various cells and play important roles in cellular communication, migration, proliferation and differentiation. Recent studies uncovered that the exosomes from cardiac fibroblasts and other tissues participates in the development of myocardial hypertrophy...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28936464/innate-immune-responses-to-cryptococcus
#9
Lena J Heung
Cryptococcus species are encapsulated fungi found in the environment that predominantly cause disease in immunocompromised hosts after inhalation into the lungs. Even with contemporary antifungal regimens, patients with cryptococcosis continue to have high morbidity and mortality rates. The development of more effective therapies may depend on our understanding of the cellular and molecular mechanisms by which the host promotes sterilizing immunity against the fungus. This review will highlight our current knowledge of how Cryptococcus, primarily the species C...
September 2017: Journal of Fungi (Basel, Switzerland)
https://www.readbyqxmd.com/read/28936210/novel-mutations-of-the-tetratricopeptide-repeat-domain-7a-gene-and-phenotype-genotype-comparison
#10
Reyin Lien, Yung-Feng Lin, Min-Wei Lai, Hui-Ying Weng, Ren-Chin Wu, Tang-Her Jaing, Jing-Long Huang, Shih-Feng Tsai, Wen-I Lee
The gastrointestinal tract contains the largest lymphoid organ to react with pathogenic microorganisms and suppress excess inflammation. Patients with primary immunodeficiency diseases (PIDs) can suffer from refractory diarrhea. In this study, we present two siblings who began to suffer from refractory diarrhea with a poor response to aggressive antibiotic and immunosuppressive treatment after surgical release of neonatal intestinal obstruction. Their lymphocyte proliferation was low, but superoxide production and IL-10 signaling were normal...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28935918/host-directed-therapies-for-bacterial-and-viral-infections
#11
REVIEW
Stefan H E Kaufmann, Anca Dorhoi, Richard S Hotchkiss, Ralf Bartenschlager
Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology...
September 22, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28935694/cellular-kinetics-of-ctl019-in-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia-and-chronic-lymphocytic-leukemia
#12
Karen Thudium Mueller, Shannon L Maude, David L Porter, Noelle Frey, Patricia Wood, Xia Han, Edward Waldron, Abhijit Chakraborty, Rakesh Awasthi, Bruce L Levine, J Joseph Melenhorst, Stephan A Grupp, Carl H June, Simon F Lacey
Tisagenlecleucel (CTL019) is an investigational immunotherapy that involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor to identify and eliminate CD19-expressing cells. We previously reported that CTL019 achieved impressive clinical efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), including the expansion and persistence of CTL019 cells, which correlates with response to therapy. Here, we performed formal cellular kinetic analyses of CTL019 in a larger cohort of 103 patients treated with CTL019 in 2 different diseases (ALL and CLL)...
September 21, 2017: Blood
https://www.readbyqxmd.com/read/28935344/tailoring-natural-killer-cell-immunotherapy-to-the-tumour-microenvironment
#13
REVIEW
Alexander David Barrow, Marco Colonna
Natural killer (NK) cells are cytotoxic and cytokine-secreting cells that can mediate potent anti-tumour activity. Accumulating evidence indicates that NK cell functions are severely compromised within the confines of the tumour microenvironment thus impairing the efficacy and development of NK cell-based therapies. Here we review the various cellular and molecular pathways that tumours have supplanted to evade NK cell surveillance. We highlight novel strategies designed to alleviate or circumvent the immunosuppressive conditions of the tumour microenvironment in order to emancipate NK cell function and stifle the inexorable growth and metastasis of malignant cells...
September 18, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28935190/a-roadmap-for-cost-of-goods-planning-to-guide-economic-production-of-cell-therapy-products
#14
REVIEW
Yonatan Y Lipsitz, William D Milligan, Ian Fitzpatrick, Evelien Stalmeijer, Suzanne S Farid, Kah Yong Tan, David Smith, Robert Perry, Jessica Carmen, Allen Chen, Charles Mooney, John Fink
Cell therapy products are frequently developed and produced without incorporating cost considerations into process development, contributing to prohibitively costly products. Herein we contextualize individual process development decisions within a broad framework for cost-efficient therapeutic manufacturing. This roadmap guides the analysis of cost of goods (COG) arising from tissue procurement, material acquisition, facility operation, production, and storage. We present the specific COG considerations related to each of these elements as identified through a 2013 International Society for Cellular Therapy COG survey, highlighting the differences between autologous and allogeneic products...
September 18, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28935149/molecular-aspects-of-cancer-chemopreventive-and-therapeutic-efficacies-of-tea-and-tea-polyphenols
#15
REVIEW
Subhayan Sur, Chinmay Kumar Panda
The natural dietary product tea (Camellia sinensis) and its bioactive polyphenols such as epigallocatechin gallate (EGCG) and theaflavin (TF) demonstrated potential anticancer effects in different preclinical and clinical studies. The aim of the present review was to understand the molecular mechanisms of the tea and tea polyphenol-mediated cancer prevention and therapy. In the setting of in vivo cancer prevention studies, administration of the tea and tea polyphenols at preinitiation stages only showed partial prevention, whereas continuous administration showed potential effect in restriction of carcinogenesis in the body's multiple organs at early premalignant stages throughout the experiment...
November 2017: Nutrition
https://www.readbyqxmd.com/read/28934149/oncolytic-reovirus-infection-is-facilitated-by-the-autophagic-machinery
#16
Vera Kemp, Iris J C Dautzenberg, Ronald W Limpens, Diana J M van den Wollenberg, Rob C Hoeben
Mammalian reovirus is a double-stranded RNA virus that selectively infects and lyses transformed cells, making it an attractive oncolytic agent. Despite clinical evidence for anti-tumor activity, its efficacy as a stand-alone therapy remains to be improved. The success of future trials can be greatly influenced by the identification and the regulation of the cellular pathways that are important for reovirus replication and oncolysis. Here, we demonstrate that reovirus induces autophagy in several cell lines, evident from the formation of Atg5-Atg12 complexes, microtubule-associated protein 1 light chain 3 (LC3) lipidation, p62 degradation, the appearance of acidic vesicular organelles, and LC3 puncta...
September 21, 2017: Viruses
https://www.readbyqxmd.com/read/28933600/a-novel-acetyltransferase-p300-inhibitor-ameliorates-hypertension-associated-cardio-renal-fibrosis
#17
Rahul Rai, Suresh K Verma, David Kim, Veronica Ramirez, Elizabeth Lux, Chengjin Li, Susmita Sahoo, Lisa D Wilsbacher, Douglas E Vaughan, Susan E Quaggin, Asish K Ghosh
Hypertension-associated end-organ damage commonly leads to cardiac and renal fibrosis. As no effective anti-fibrotic therapy currently exists, the unchecked progression of fibrogenesis manifests as cardio-renal failure and early death. We have previously shown that FATp300-p300 with intrinsic factor acetyltransferase activity-is an essential epigenetic regulator of fibrogenesis, and is elevated in several fibrotic tissues. In this report, we investigate the therapeutic efficacy of a novel FATp300 inhibitor, L002, in a murine model of hypertensive cardio-renal fibrosis...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28933554/rational-targeting-of-cellular-cholesterol-in-diffuse-large-b-cell-lymphoma-dlbcl-enabled-by-functional-lipoprotein-nanoparticles-a-therapeutic-strategy-dependent-on-cell-of-origin
#18
Jonathan S Rink, Shuo Yang, Osman Cen, Tim Taxter, Kaylin M McMahon, Sol Misener, Amir Behdad, Richard Longnecker, Leo I Gordon, C Shad Thaxton
Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1)...
September 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28933415/integrative-systems-biology-investigation-of-fabry-disease
#19
Marco Fernandes, Holger Husi
Fabry disease (FD) is a rare X-linked recessive genetic disorder caused by a deficient activity of the lysosomal enzyme alpha-galactosidase A (GLA) and is characterised by intra-lysosomal accumulation of globotriaosylceramide (Gb3). We performed a meta-analysis of peer-reviewed publications including high-throughput omics technologies including naïve patients and those undergoing enzyme replacement therapy (ERT). This study describes FD on a systems level using a systems biology approach, in which molecular data sourced from multi-omics studies is extracted from the literature and integrated as a whole in order to reveal the biochemical processes and molecular pathways potentially affected by the dysregulation of differentially expressed molecules...
November 15, 2016: Diseases (Basel)
https://www.readbyqxmd.com/read/28933212/impact-of-traumatic-brain-injury-on-dopaminergic-transmission
#20
Yuan-Hao Chen, Eagle Yi-Kung Huang, Tung-Tai Kuo, Jonathan Miller, Yung-Hsiao Chiang, Barry J Hoffer
Brain trauma is often associated with severe morbidity and is a major public health concern. Even when injury is mild and no obvious anatomic disruption is seen, many individuals suffer disabling neuropsychological impairments such as memory loss, mood dysfunction, substance abuse, and adjustment disorder. These changes may be related to subtle disruption of neural circuits as well as functional changes at the neurotransmitter level. In particular, there is considerable evidence that dopamine (DA) physiology in the nigrostriatal and mesocorticolimbic pathways might be impaired after traumatic brain injury (TBI)...
July 2017: Cell Transplantation
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