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https://www.readbyqxmd.com/read/28434148/advancing-chimeric-antigen-receptor-t-cell-therapy-with-crispr-cas9
#1
REVIEW
Jiangtao Ren, Yangbing Zhao
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28434147/increasing-the-safety-and-efficacy-of-chimeric-antigen-receptor-t-cell-therapy
#2
REVIEW
Hua Li, Yangbing Zhao
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28434112/dendritic-cell-based-vaccination-strategy-an-evolving-paradigm
#3
REVIEW
Anna C Filley, Mahua Dey
Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided only modest improvements in overall survival and remain limited by inevitable local recurrence, necessitating exploration of novel therapies. Among approaches being investigated, one of the leading contenders is immunotherapy, which aims to modulate immune pathways to stimulate the selective destruction of malignant cells. Dendritic cells (DCs) are potent initiators of adaptive immune responses and therefore crucial players in the development and success of immunotherapy...
April 22, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28434074/adipose-derived-stem-cells-ameliorate-experimental-murine-colitis-via-tsp-1-dependent-activation-of-latent-tgf-%C3%AE
#4
Hiroshi Takeyama, Tsunekazu Mizushima, Mamoru Uemura, Naotsugu Haraguchi, Junichi Nishimura, Taishi Hata, Chu Matsuda, Ichiro Takemasa, Masakazu Ikenaga, Kohei Murata, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
BACKGROUND: Adipose tissue-derived stem cells (ASCs) have been investigated as therapeutic tools for a variety of autoimmune diseases, including inflammatory diseases. However, the mechanisms underlying the immunomodulatory properties of ASCs are not well understood. Here, we investigated the mechanism of regulatory T cell (Treg) induction in ASC therapy in a murine model of inflammatory bowel disease. METHODS: Acute colitis was induced in mice using dextran sulfate sodium and ASCs administered intraperitoneally...
April 22, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28434032/diabetes-bone-and-glucose-lowering-agents-basic-biology
#5
REVIEW
Beata Lecka-Czernik
Skeletal fragility often accompanies diabetes and does not appear to correlate with low bone mass or trauma severity in individuals with diabetes. Instead (and in contrast to those with osteoporotic bone disease), bone remodelling and bone turnover are compromised in both type 1 and type 2 diabetes, contributing to defective bone material quality. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in this issue of Diabetologia by Ann Schwartz (DOI: 10...
April 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28434009/hypoxic-ischaemic-encephalopathy-and-the-blood-brain-barrier-in-neonates
#6
Wei Ling Amelia Lee, Adina T Michael-Titus, Divyen K Shah
This review aims to highlight a possible relationship between hypoxic-ischaemic encephalopathy (HIE) and the disruption of the blood-brain barrier (BBB). Inflammatory reactions perpetuate a large proportion of cerebral injury. The extent of injury noted in HIE is not only determined by the biochemical cascades that trigger the apoptosis-necrosis continuum of cell death in the brain parenchyma, but also by the breaching of the BBB by pro-inflammatory factors. We examine the changes that contribute to the breakdown of the BBB that occur during HIE at a macroscopic, cellular, and molecular level...
April 22, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28433998/interferon-%C3%AE-1a-modulates-expression-of-rage-but-not-s100a12-and-nuclear-factor-%C3%AE%C2%BAb-in-multiple-sclerosis-patients
#7
Gholamreza Asadikaram, Saam Noroozi, Hossein Ali Ebrahimi Meimand, Mojgan Sanjari, Nahid Zainodini, Hossein Khoramdelazad, Nader Shahrokhi, Mohammad Kazemi Arababadi
OBJECTIVES: Interferon-β 1a (IFN-β 1a) is a common strategy therapy for multiple sclerosis (MS) with unknown mechanisms. S100A12 (S100 calcium-binding protein A12) is a damage-associated molecular pattern molecule which binds to its receptor, RAGE (receptor for advanced glycation end products), and activates nuclear factor-κB (NF-κB). NF-κB is transcribed from proinflammatory molecules, which may participate in the pathogenesis of MS. Therefore, the aims of this study were to compare mRNA levels of S100A12, RAGE, and NF-κB in newly diagnosed MS patients with healthy controls and determine whether IFN-β 1a therapy affects the expression of the molecules...
April 22, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28433941/self-assembled-dual-responsive-micelles-stabilized-with-protein-for-co-delivery-of-drug-and-sirna-in-cancer-therapy
#8
M R Aji Alex, Chetan Nehate, Srivani Veeranarayanan, D Sakthi Kumar, Ritu Kulshreshtha, Veena Koul
Design of safe and efficient vehicles for the combinatorial delivery of drugs and genetic agents is an emerging requisite for achieving enhanced therapeutic effect in cancer. Even though several nanoplatforms have been explored for the co-delivery of drugs and genetic materials the translation of these systems to clinical phase is still a challenge, mainly due to tedious synthesis procedures, lack of serum stability, inefficient scalability etc. Here in, we report development of reduction and pH sensitive polymeric graft of low molecular weight poly (styrene -alt -maleic anhydride) and evaluation of its efficacy in co-delivering drug and siRNA...
April 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28433939/enhanced-proangiogenic-potential-of-mesenchymal-stem-cell-derived-exosomes-stimulated-by-a-nitric-oxide-releasing-polymer
#9
Wei Du, Kaiyue Zhang, Shuaiqiang Zhang, Ran Wang, Yan Nie, Hongyan Tao, Zhibo Han, Lu Liang, Di Wang, Jianfeng Liu, Na Liu, Zhongchao Han, Deling Kong, Qiang Zhao, Zongjin Li
Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for the treatment of degenerative diseases or injury and may provide an alternative to cell-based therapy. However, the compositions in MSC-derived exosomes are highly influenced by the microenvironment in which their original cells reside. Here, we hypothesized that a nitric oxide (NO)-releasing polymer can boost the proangiogenic compositions of exosomes and enhance their proangiogenic capacity. Our results demonstrated that exosomes, released from human placenta-derived MSCs (hP-MSCs) by NO stimulation, augment the angiogenic effects of human umbilical vein endothelial cells (HUVECs) in vitro...
April 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28433934/amino-acid-functionalized-gadofullerene-nanoparticles-with-superior-antitumor-activity-via-destruction-of-tumor-vasculature-in%C3%A2-vivo
#10
Yue Zhou, Ruijun Deng, Mingming Zhen, Jie Li, Mirong Guan, Wang Jia, Xue Li, Ying Zhang, Tong Yu, Toujun Zou, Zhigao Lu, Jun Guo, Lei Sun, Chunying Shu, Chunru Wang
Researchers have been puzzled of the therapy of malignant tumors and the current therapeutic strategies are always accompanied by toxicity or side effects. Developing efficient nanodrugs could reduce the dosage and greatly improve the therapeutic effects in cancer treatments. Here we initially reported a novel kind of gadofullerene nanoparticles functionalized with amino acid (β-alanine), which exhibited a superior antitumor activity in hepatoma H22 models via a novel therapeutic mechanism. The involvement of β-alanine improved the tumor inhibition rate up to 76...
April 14, 2017: Biomaterials
https://www.readbyqxmd.com/read/28433834/antimicrobial-and-anticancer-photodynamic-activity-of-a-phthalocyanine-photosensitizer-with-n-methyl-morpholiniumethoxy-substituents-in-non-peripheral-positions
#11
Jolanta Dlugaszewska, Wojciech Szczolko, Tomasz Koczorowski, Paulina Skupin-Mrugalska, Anna Teubert, Krystyna Konopka, Malgorzata Kucinska, Marek Murias, Nejat Düzgüneş, Jadwiga Mielcarek, Tomasz Goslinski
Photodynamic therapy involves the use of a photosensitizer that is irradiated with visible light in the presence of oxygen, resulting in the formation of reactive oxygen species. A novel phthalocyanine derivative, the quaternary iodide salt of magnesium(II) phthalocyanine with N-methyl morpholiniumethoxy substituents, was synthesized, and characterized. The techniques used included mass spectrometry (MALDI TOF), UV-vis, NMR spectroscopy, and photocytotoxicity against bacteria, fungi and cancer cells. The phthalocyanine derivative possessed typical characteristics of compounds of the phthalocyanine family but the effect of quaternization was observed on the optical properties, especially in terms of absorption efficiency...
April 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28433787/facile-encapsulation-of-hydroxycamptothecin-nanocrystals-into-zein-based-nanocomplexes-for-active-targeting-drug-delivery-and-cell-imaging
#12
Hongdi Wang, Wei Zhu, Yunna Huang, Zhixian Li, Yanbin Jiang, Qiuling Xie
Nano-drug delivery systems that integrate inorganic and organic or even bioactive components into a single nanoscale platform are playing a greatly important role in cancer treatment. Here, the fabrication of a versatile nanocarrier based on self-assembled structures of gold nanoparticles (AuNPs)-zein is reported, which displays high drug-loading efficiency for needle-shaped hydroxycamptothecin (HCPT) nanocrystals. The surface modification with folate-conjugated polydopamine (PFA) renders them stable and also facilitates their selective cellular internalization and enhancement of endocytosis...
April 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28433697/rab22a-enhances-cd147-recycling-and-is-required-for-lung-cancer-cell-migration-and-invasion
#13
Yang Zhou, Bo Wu, Jiang-Hua Li, Gang Nan, Jian-Li Jiang, Zhi-Nan Chen
Rab22a is a member of the Ras-related small GTPase family, which plays a key role in regulating the recycling of cargo proteins entering cells through clathrin-independent endocytosis (CIE). Rab22a is overexpressed in different cancer types, including liver cancer, malignant melanoma, ovarian cancer and osteosarcoma. However, its oncogenic role remains unknown. In this study, we found that silencing of Rab22a suppressed the migration and invasion of lung cancer cells. Furthermore, Rab22a interacts with CD147, and knockdown of Rab22a blocks CD147 recycling and promotes CD147 degradation...
April 19, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28433688/vitamin-d-downregulates-the-il-23-receptor-pathway-in-human-mucosal-ilc3
#14
Viktoria Konya, Paulo Czarnewski, Marianne Forkel, Anna Rao, Efthymia Kokkinou, Eduardo J Villablanca, Sven Almer, Ulrik Lindforss, Danielle Friberg, Charlotte Höög, Peter Bergman, Jenny Mjösberg
BACKGROUND: Vitamin D deficiency is a risk factor for inflammatory bowel disease (IBD). The IL-23-driven tissue-resident ILC3 play essential roles in intestinal immunity, and targeting IL-23/12 is a promising approach in IBD therapy. OBJECTIVE: We set out to define the role of 1α,25-dihydroxy vitamin D3 (1,25D) in regulating functional responses of human mucosal ILC3 to IL-23 plus IL-1β stimulation. METHODS: Transcriptomes of sorted tonsil ILC3 were assessed by microarray analysis...
April 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28433679/part-i-design-synthesis-and-biological-evaluation-of-novel-pyrazole-benzimidazole-conjugates-as-checkpoint-kinase-2-chk2-inhibitors-with-studying-their-activities-alone-and-in-combination-with-genotoxic-drugs
#15
Shadia A Galal, Ahmed S Abdelsamie, Samia A Shouman, Yasmin M Attia, Hamed I Ali, Ashraf Tabll, Reem El-Shenawy, Yasmine S El Abd, Mamdouh M Ali, Abeer E Mahmoud, Abeer H Abdel-Halim, Amal A Fyiad, Adel S Girgis, Hoda I El-Diwani
Activated checkpoint kinase 2 (Chk2) is a tumor suppressor as one of the main enzymes that affect the cell cycle. 2-Biarylbenzimidazoles are potent selective class of Chk2 inhibitors; the structure-based design was applied to synthesize a new series of this class with replacing the lateral aryl group by substituted pyrazoles. Ten pyrazole-benzimidazole conjugates from the best fifty candidates according to docking programs have been subjected to chemical synthesis in this study. The activities of the conjugates 5-14 as checkpoint kinase inhibitors and as antitumor alone and in combination with genotoxic drugs were evaluated...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28433662/iron-and-thiol-redox-signaling-in-cancer-an-exquisite-balance-to-escape-ferroptosis
#16
REVIEW
Shinya Toyokuni, Fumiya Ito, Kyoko Yamashita, Yasumasa Okazaki, Shinya Akatsuka
Epidemiological data indicate a constant worldwide increase in cancer mortality, although the age of onset is increasing. Recent accumulation of genomic data on human cancer via next-generation sequencing confirmed that cancer is a disease of genome alteration. In many cancers, the Nrf2 transcription system is activated via mutations either in Nrf2 or Keap1 ubiquitin ligase, leading to persistent activation of the genes with antioxidative functions. Furthermore, deep sequencing of passenger mutations is clarifying responsible cancer causative agent(s) in each case, including aging, APOBEC activation, smoking and UV...
April 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28433657/mir-938-promotes-colorectal-cancer-cell-proliferation-via-targeting-tumor-suppressor-phlpp2
#17
Chang-Feng Li, Yong-Chao Li, Jing-Peng Jin, Zhen-Kun Yan, Dan-Dan Li
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although the development of therapy approaches, the outcome of CRC patients still is poor, understanding the biological mechanism of CRC progression is critical to improve the treatment strategies. miRNAs regulate CRC progression, we found miR-938 was upregulated in CRC tissues and cells, MTT assay, colony formation assay and soft agar growth assay suggested miR-938 overexpression promoted CRC cell proliferation, miR-938 knockdown inhibited CRC cell proliferation...
April 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28433655/targeting-sarcoma-tumor-initiating-cells-through-differentiation-therapy
#18
Dan Han, Veronica Rodriguez-Bravo, Elizabeth Charytonowicz, Elizabeth Demicco, Josep Domingo-Domenech, Robert G Maki, Carlos Cordon-Cardo
Human leukocyte antigen class I (HLA-I) down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs) remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway...
April 13, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28433627/docosahexaenoic-acid-promotes-differentiation-of-photoreceptor-cells-in-three-dimensional-neural-retinas
#19
Eisuke Arai, Vipul M Parmar, Bhubanananda Sahu, Lindsay Perusek, Tanu Parmar, Akiko Maeda
Retinal tissues generated from human pluripotent stem cells can be an excellent tool for investigating pathogenesis of retinal diseases and developing new pharmacologic therapies. Moreover, patient derived retinal tissues could allow for retinal transplantation therapy for degenerative retinal diseases. However, obtaining retinal tissues with matured photoreceptor outer segments, which are essential for photoreceptor functions, is currently challenging. Here we investigated the effects of docosahexaenoic acid (DHA) for maturation of photoreceptor outer segments at the late stage and visual chromophore analog, 9-cis-retinal for the early stage of differentiation to three-dimensional (3D)-retinal tissues from human embryonic stem cells (hESCs), respectively...
April 19, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28433598/mir-590-5p-a-density-sensitive-microrna-inhibits-tumorigenesis-by-targeting-yap1-in-colorectal-cancer
#20
Chunlin Ou, Zhenqiang Sun, Xiayu Li, Xiaoling Li, Weiguo Ren, Zailong Qin, Xuemei Zhang, Weitang Yuan, Jia Wang, Wentao Yu, Shiwen Zhang, Qiu Peng, Qun Yan, Wei Xiong, Guiyuan Li, Jian Ma
YAP1, a transcription co-activator, mediates the biological functions of the Hippo pathway. YAP1 inactivation is involved in cell-cell contact inhibition. In various tumors, YAP1 is upregulated through multiple mechanisms, and it functions as an oncogene. Here, we provided evidence that YAP1 influenced multiple signaling pathways in colorectal cancer (CRC) cells. We reported that miR-590-5p directly targets YAP1 and inhibits tumorigenesis in CRC cells both in vitro and in vivo xenograft model. We analyzed different cell densities and found that increased density caused increased expression of miR-590-5p, and decreased expression of its precursors (pri- and pre-miR-590)...
April 19, 2017: Cancer Letters
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