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https://www.readbyqxmd.com/read/29351902/targeting-the-sphk1-s1p-s1pr1-axis-that-links-obesity-chronic-inflammation-and-breast-cancer-metastasis
#1
Masayuki Nagahashi, Akimitsu Yamada, Eriko Katsuta, Tomoyoshi Aoyagi, Wei-Ching Huang, Krista P Terracina, Nitai C Hait, Jeremy C Allegood, Junko Tsuchida, Kizuki Yuza, Masato Nakajima, Manabu Abe, Kenji Sakimura, Sheldon Milstien, Toshifumi Wakai, Sarah Spiegel, Kazuaki Takabe
Although obesity with associated inflammation is now recognized as a risk factor for breast cancer and distant metastases, the functional basis for these connections remain poorly understood. Here we show that in breast cancer patients and in animal breast cancer models, obesity is a sufficient cause for increased expression of the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) which mediates cancer pathogenesis. A high fat diet was sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous breast tumors...
January 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29350874/diversification-of-human-nk-cells-lessons-from-deep-profiling
#2
REVIEW
Aaron J Wilk, Catherine A Blish
NK cells are innate lymphocytes with important roles in immunoregulation, immunosurveillance, and cytokine production. Originally defined on the functional basis of their "natural" ability to lyse tumor targets and thought to be a relatively homogeneous group of lymphocytes, NK cells possess a remarkable degree of phenotypic and functional diversity due to the combinatorial expression of an array of activating and inhibitory receptors. Diversification of NK cells is multifaceted: mechanisms of NK cell education that promote self-tolerance result in a heterogeneous repertoire that further diversifies upon encounters with viral pathogens...
January 19, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29348316/evaluation-of-next-generation-anti-cd20-antibodies-labeled-with-zirconium-89-in-human-lymphoma-xenografts
#3
Jason T Yoon, Mark S Longtine, Bernadette V Marquez-Nostra, Richard L Wahl
Radioimmunotherapies with monoclonal antibodies (mAbs) to the B-lymphocyte antigen 20 (CD20) are effective treatments for B-cell lymphomas, but United States Food and Drug Administration (FDA)-approved radioimmunotherapies exclusively use radiolabeled murine antibodies, potentially limiting re-dosing. The FDA recently approved two unlabeled anti-CD20 monoclonal antibodies, obinutizumab and ofatumumab, termed "next generation" as they are humanized (obinituzumab) or fully human (ofatumumab), thus potentially allowing a greater potential for re-dosing than with previous generation anti-CD20 antibodies, including rituximab (chimeric) and tositumumab (murine) which contain more murine peptide sequences...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29346131/toxicological-profile-and-safety-pharmacology-of-a-single-dose-of-fibroblast-activation-protein-%C3%AE-based-doxorubicin-prodrug-in-vitro-and-in-vivo-evaluation
#4
Sichao Huang, Yuchen Zhang, Jinsong Zhong, Ying Pan, Shaohui Cai, Jun Xu
Fibroblast activation protein-α (FAPα) is a promising tumor-associated target expressed by reactive stromal fibroblasts in tumor tissue. FAPα has a postprolyl peptidase activity and can specifically cleave N-terminal benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC. Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly limited by toxic adverse effects owing to poor tumor selectivity. Based on these facts, we previously designed a FAPα-targeting prodrug of doxorubicin (FTPD) which can be selectively hydrolyzed by FAPα...
January 17, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29344291/in-vivo-double-targeting-of-c26-colon-carcinoma-cells-and-microenvironmental-protumor-processes-using-liposomal-simvastatin
#5
Lavinia Luput, Emilia Licarete, Denise Minerva Drotar, Andras-Laszlo Nagy, Alina Sesarman, Laura Patras, Valentin Florian Rauca, Alina Porfire, Dana Muntean, Marcela Achim, Ioan Tomuta, Laurian Vlase, Cornel Catoi, Nicolae Dragos, Manuela Banciu
Purpose: Besides cholesterol lowering effects, simvastatin (SIM) at very high doses possesses antitumor actions. Moreover our previous studies demonstrated that tumor-targeted delivery of SIM by using long-circulating liposomes (LCL) improved the therapeutic index of this drug in murine melanoma-bearing mice. To evaluate whether this finding can be exploited for future therapy of colorectal cancer the antitumor activity and the underlying mechanisms of long-circulating liposomal simvastatin (LCL-SIM) efficacy for inhibition of C26 murine colon carcinoma growth in vivo were investigated...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344278/potent-peptide-conjugated-silicon-phthalocyanines-for-tumor-photodynamic-therapy
#6
Qian Liu, Mingpei Pang, Sihai Tan, Jin Wang, Qingle Chen, Kai Wang, Wenjie Wu, Zhangyong Hong
Phthalocyanines (Pcs) are a group of promising photosensitizers for use in photodynamic therapy (PDT). However, their extremely low solubility and their strong tendency to aggregate in aqueous solution greatly restrict their application. Conjugation of Pc macrocycles with peptide ligands could be a very useful strategy to optimize the physical properties of Pcs not only by increasing their water solubility and reducing their aggregation but also by endowing the conjugates with a tumor-targeting capability. To develop highly potent photosensitizers for tumor PDT, we prepared new peptide-conjugated photosensitizers using silicon Pc (SiPc), which has much higher photodynamic activity than zinc Pcs, as the light activation moiety and the cRGDfK peptide (or simply cRGD) as the peptide moiety...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29342352/chemically-defined-antibody-and-small-molecule-drug-conjugates-for-in-vivo-tumor-targeting-applications-a-comparative-analysis
#7
Samuele Cazzamalli, Alberto Dal Corso, Fontaine Widmayer, Dario Neri
We present the first direct comparative evaluation of an antibody-drug conjugate and of a small molecule-drug conjugate for cancer therapy, using chemically-defined products which bind with high-affinity to carbonic anhydrase IX, a marker of tumor hypoxia and of renal cell carcinoma.
January 17, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29340056/temozolomide-encapsulated-and-folic-acid-decorated-chitosan-nanoparticles-for-lung-tumor-targeting-improving-therapeutic-efficacy-both-in-vitro-and-in-vivo
#8
Kaidi Li, Naixin Liang, Huaxia Yang, Hongsheng Liu, Shanqing Li
Folic acid-conjugated temozolomide (TMZ)-loaded chitosan nanoparticles (CS-TMZ-FLA-NP) were developed to target lung cancer in the anticipation that folic acid would increase the affinity of nanoparticles for cancer cells. CS-TMZ-FLA-NP showed the highest anti-proliferative effect on the lung cancer cells in comparison to free TMZ and CS-TMZ-NP (nanoparticles without folic acid). A cellular uptake assay was performed on two different cell lines, L132 and A549. Cellular uptake efficiencies of CS-TMZ-NP and CS-TMZ-FLA-NP were found to be concentration-dependent in both cell lines...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339567/erythrocyte-membrane-coated-gold-nanocages-for-targeted-photothermal-and-chemical-cancer-therapy
#9
Dao-Ming Zhu, Wei Xie, Yu-Sha Xiao, Meng Suo, Ming-Hui Zan, Qing-Quan Liao, Xue-Jia Hu, Li-Ben Chen, Bei Chen, Wen-Tao Wu, Li-Wei Ji, Hui-Ming Huang, Shi-Shang Guo, Xing-Zhong Zhao, Quan-Yan Liu, Wei Liu
Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy...
January 17, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29339136/development-of-orally-applicable-combinatorial-drug-loaded-nanoparticles-for-the-treatment-of-fibrosarcoma
#10
Gulen Melike Demirbolat, Levent Altintas, Sukran Yilmaz, Ismail Tuncer Degim
Nanoparticulate systems have been receiving a significant attention especially for the treatment of cancer but one of the main hurdles is to produce these developed and high tech nanosystems in large quantities. Anticancer drug formulations are generally designed for parenteral administrations but oral administration is still the most convenient route. In this study, orally applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared using Nano Spray Dryer. It is possible to produce these NPs in large quantities by simply increasing the processing time using the machine without changing any parameter...
January 12, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29336140/synthesis-of-cisplatin-iv-prodrug-tethered-cufes2-nanoparticles-in-tumor-targeted-chemotherapy-and-photothermal-therapy
#11
Wubshet Mekonnen Girma, Shin-Hwa Tzing, Po-Jen Tseng, Chih-Ching Huang, Yong-Chien Ling, Jia-Yaw Chang
In this study, for the first time, CuFeS2 nanocrystals were successfully prepared through a facile noninjection-based synthetic strategy, by reacting Cu and Fe precursors with dodecanethiol in a 1-octadecene solvent. This one-pot noninjection strategy features easy handling, large-scale production, and high synthetic reproducibility. Following hyaluronic acid (HA) encapsulation, CuFeS2 nanocrystals coated with HA (CuFeS2@HA) not only readily dispersed in water and showed improved biocompatibility, but also possessed a tumor-specific targeting ability of cancer cells bearing the cluster determinant 44 (CD44) receptors...
January 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29334397/recombinant-phosphatidylserine-binding-nanobodies-for-targeting-of-extracellular-vesicles-to-tumor-cells-a-plug-and-play-approach
#12
Sander A A Kooijmans, Jerney J J M Gitz-Francois, Raymond M Schiffelers, Pieter Vader
Extracellular vesicles (EVs) are increasingly being recognized as candidate drug delivery systems due to their ability to functionally transfer biological cargo between cells. However, manipulation of targeting properties of EVs through engineering of the producer cells can be challenging and time-consuming. As a novel approach to confer tumor targeting properties to isolated EVs, we generated recombinant fusion proteins of nanobodies against the epidermal growth factor receptor (EGFR) fused to phosphatidylserine (PS)-binding domains of lactadherin (C1C2)...
January 15, 2018: Nanoscale
https://www.readbyqxmd.com/read/29334216/lysosome-independent-intracellular-drug-gene-co-delivery-by-lipoprotein-derived-nanovector-for-synergistic-apoptosis-inducing-cancer-targeted-therapy
#13
Wei Wang, Kerong Chen, Yujie Su, Jielei Zhang, Min Li, Jianping Zhou
In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein-derived nanovector, were constructed for co-delivery of paclitaxel (PTX) and wild type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53-rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they exhibited great serum stability and satisfactory sustained release characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR-BI) mediated lysosome-independent internalization and promoted the transfection of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser scanning microscopy analyses...
January 15, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29334184/ph-responsive-peg-doxorubicin-encapsulated-aza-bodipy-nanotheranostic-agent-for-imaging-guided-synergistic-cancer-therapy
#14
Dapeng Chen, Qianyun Tang, Jianhua Zou, Xiaoyan Yang, Wei Huang, Qi Zhang, Jinjun Shao, Xiaochen Dong
Synergistic cancer therapy is of great interest for multiple advantages, such as excellent targeting accuracy, low side effects, and enhanced therapeutic efficiency. Herein, a near-infrared photosensitizer aza-BODIPY (AB) with high singlet oxygen quantum yield (ΦΔ = 82%) is designed and synthesized. With Schiff's base obtained from condensation reaction between doxorubicin (DOX) and polyethylene glycol-benzaldehyde (PEG-CHO) as the polymer matrix, aza-BODIPY is encapsulated to afford hydrophilic nanoparticles (DAB NPs)...
January 15, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29333854/cucurbit-8-uril-based-giant-supramolecular-vesicles-highly-stable-versatile-carriers-for-photoresponsive-and-targeted-drug-delivery
#15
Cuihua Hu, Ningning Ma, Fei Li, Yu Fang, Yao Liu, Linlu Zhao, Shanpeng Qiao, Xiumei Li, Xiaojia Jiang, Tiezhu Li, Fangzhong Shen, Yibing Huang, Quan Luo, Junqiu Liu
Highly stable giant supramolecular vesicles were constructed by hierarchical self-assembly of cucurbit[8]uril (CB[8])-based supra-amphiphiles for photoresponsive and targeted intracellular drug delivery. These smart vesicles can encapsulate the model drugs with high loading efficiencies, and then release them by manipulating photoswitchable CB[8] heteroternary complexation to regulate the formation and dissociation of supra-amphiphiles that cause dramatic morphological changes of the assemblies to achieve remote optically-controlled drug delivery...
January 15, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29331575/validation-of-mri-to-trus-registration-for-high-dose-rate-prostate-brachytherapy
#16
Eric Poulin, Karim Boudam, Csaba Pinter, Samuel Kadoury, Andras Lasso, Gabor Fichtinger, Cynthia Ménard
PURPOSE: The objective of this study was to develop and validate an open-source module for MRI to transrectal ultrasound (TRUS) registration to support tumor-targeted prostate brachytherapy. METHODS AND MATERIALS: In this study, 15 patients with prostate cancer lesions visible on multiparametric MRI were selected for the validation. T2-weighted images with 1-mm isotropic voxel size and diffusion weighted images were acquired on a 1.5T Siemens imager. Three-dimensional (3D) TRUS images with 0...
January 10, 2018: Brachytherapy
https://www.readbyqxmd.com/read/29330793/hypoxia-induced-metabolomic-alterations-in-pancreatic-cancer-cells
#17
Venugopal Gunda, Sushil Kumar, Aneesha Dasgupta, Pankaj K Singh
Hypoxic conditions in the pancreatic tumor microenvironment lead to the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which acts as the master regulator of cancer cell metabolism. HIF-1α-mediated metabolic reprogramming results in large-scale metabolite perturbations. Characterization of the metabolic intermediates and the corresponding metabolic pathways altered by HIF-1α would facilitate the identification of therapeutic targets for hypoxic microenvironments prevalent in pancreatic ductal adenocarcinoma and other solid tumors...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29326979/nanometer-precision-linear-sorting-with-synchronized-optofluidic-dual-barriers
#18
Yuzhi Shi, Sha Xiong, Lip Ket Chin, Jingbo Zhang, Wee Ser, Jiuhui Wu, Tianning Chen, Zhenchuan Yang, Yilong Hao, Bo Liedberg, Peng Huat Yap, Din Ping Tsai, Cheng-Wei Qiu, Ai Qun Liu
The past two decades have witnessed the revolutionary development of optical trapping of nanoparticles, most of which deal with trapping stiffness larger than 10-8 N/m. In this conventional regime, however, it remains a formidable challenge to sort out sub-50-nm nanoparticles with single-nanometer precision, isolating us from a rich flatland with advanced applications of micromanipulation. With an insightfully established roadmap of damping, the synchronization between optical force and flow drag force can be coordinated to attempt the loosely overdamped realm (stiffness, 10-10 to 10-8 N/m), which has been challenging...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29325469/current-update-of-a-thermosensitive-liposomes-composed-of-dppc-and-brij78
#19
Laurence Ho, Mehrdad Bokharaei, Shyh-Dar Li
Thermosensitive liposomes (TSLs) have been a prominent area of study in the discipline of tumor-targeted chemotherapeutics. The representative product of TSLs is ThermoDox® (DPPC/lyso-PC/PEG-lipid), which has advanced to Phase III clinical trials. Various groups have sought to develop a new TSL to improve upon the LTSL (lyso-lipid temperature sensitive liposomes) formulation that is used to prepare ThermoDOX®. This review focuses on the development and recent update of an innovative TSL formulation, HaT-liposomes composed of DPPC and Brij78...
January 11, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29317822/novel-functionalized-nanoparticles-for-tumor-targeting-co-delivery-of-doxorubicin-and-sirna-to-enhance-cancer-therapy
#20
Yu Xia, Tiantian Xu, Changbing Wang, Yinghua Li, Zhengfang Lin, Mingqi Zhao, Bing Zhu
Human homeobox protein (Nanog) is highly expressed in most cancer cells and has gradually emerged as an excellent target in cancer therapy, owing to its regulation of cancer cell proliferation, metastasis and apoptosis. In this study, we prepared tumor-targeting functionalized selenium nanoparticles (RGDfC-SeNPs) to load chemotherapeutic doxorubicin (DOX) and Nanog siRNA. Herein, RGDfC peptide was used as a tumor-targeting moiety which could specifically bind to αvβ3 integrins overexpressed on various cancer cells...
2018: International Journal of Nanomedicine
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