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P53 and liposomes

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https://www.readbyqxmd.com/read/28976121/strategies-used-in-the-clinical-trials-of-gene-therapy-for-cancer
#1
Thekkuttuparambil Ananthanarayanan Ajith
Advances in understanding and manipulating genes have set the stage for scientists to alter a person's genetic material to prevent or treat diseases. Over the past decade, somatic gene therapy has been increasingly applied in clinical trials where the genetic material (DNA and RNA) introduced into a person's cell. Mutation and inactivation of the tumor suppressor genes are the unified concept of the development of tumor in humans. Therefore, researchers have discovered potential of gene therapies in the treatment of cancer...
September 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/28932113/cationic-lipid-based-nanoparticles-mediate-functional-delivery-of-acetate-to-tumor-cells-in-vivo-leading-to-significant-anticancer-effects
#2
Leigh P Brody, Meliz Sahuri-Arisoylu, James R Parkinson, Harry G Parkes, Po Wah So, Nabil Hajji, E Louise Thomas, Gary S Frost, Andrew D Miller, Jimmy D Bell
Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system - liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28916339/d-amino-acid-mutation-of-pmi-as-potent-dual-peptide-inhibitors-of-p53-mdm2-mdmx-interactions
#3
Xiang Li, Chao Liu, Si Chen, Honggang Hu, Jiacan Su, Yan Zou
According to the previously reported potent dual l-peptide PMI of p53-MDM2/MDMX interactions, a series of d-amino acid mutational PMI analogues, PMI-1-4, with enhanced proteolytic resistence and in vitro tumor cell inhibitory activities were reported, of which Liposome-PMI-1 showed a stronger inhibitory activity against the U87 cell lines than Nutlin-3. This d-amino acid mutation strategy may give a hand for enhancing the potential of peptide drugs.
September 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28912139/a-combination-rnai-chemotherapy-layer-by-layer-nanoparticle-for-systemic-targeting-of-kras-p53-with-cisplatin-to-treat-non-small-cell-lung-cancer
#4
Li Gu, Jason Z Deng, Sweta Roy, Paula T Hammond
PURPOSE: Mutation of the Kirsten ras sarcoma viral oncogene homolog (KRAS) and loss of p53 function are commonly seen in non-small cell lung cancer (NSCLC). Combining therapeutics targeting these tumor defensive pathways with cisplatin in a single nanoparticle platform are rarely developed in clinic. EXPERIMENTAL DESIGN: Cisplatin was encapsulated in liposomes which multiple polyelectrolyte layers including siKRAS and miR-34a were built on to generate multifunctional layer-by-layer nanoparticle...
September 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28891579/sensitive-and-selective-detection-of-the-p53-gene-based-on-a-triple-helix-magnetic-probe-coupled-to-a-fluorescent-liposome-hybridization-assembly-via-rolling-circle-amplification
#5
Xia Li, Juan Song, Qingwang Xue, Haiyan Zhao, Min Liu, Baoli Chen, Yun Liu, Wei Jiang, Chen-Zhong Li
Developing a sensitive and selective sensing platform for the p53 gene and its mutation analysis is essential and may aid in early cancer screening and assessment of prognosis. Here, we developed a highly sensitive and selective p53 gene assay based on the coupling of a triple-helix magnetic probe (THMP) to a fluorescent liposome hybridization assembly, a process initiated by rolling circle amplification (RCA). In the presence of p53, the THMP unfolds and activates an enzymatic cleavage reaction, thus releasing the RCA primer and initiating the RCA product-assisted fluorescent liposome hybridization assembly...
October 7, 2017: Analyst
https://www.readbyqxmd.com/read/28735042/improved-selectivity-and-cytotoxic-effects-of-irinotecan-via-liposomal-delivery-a-comparative-study-on-hs68-and-hela-cells
#6
Ana Casadó, Margarita Mora, Maria Lluïsa Sagristá, Santi Rello-Varona, Pilar Acedo, Juan Carlos Stockert, Magdalena Cañete, Angeles Villanueva
Irinotecan (CPT-11) is an effective chemotherapeutic agent widely used to treat different cancers. Otherwise, the liposomal delivery of anti-tumor agents has been shown to be a promising strategy. The aim of this study has been to analyze the effect of liposomal CPT-11 (CPT-11lip) on two human cell lines (Hs68 and HeLa) to establish the suitability of this CPT-11 nanocarrier. We have demonstrated the highest uptake of CPT-11lip in comparison with that of CPT-11sol, in lactate buffer, and that CPT-11lip was internalized in the cells through an endocytic process whereas CPT-11sol does so by passive diffusion...
July 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28700899/pegylated-liposomal-formulation-of-doxorubicin-overcomes-drug-resistance-in-a-genetically-engineered-mouse-model-of-breast-cancer
#7
András Füredi, Kornélia Szebényi, Szilárd Tóth, Mihály Cserepes, Lilla Hámori, Veronika Nagy, Edina Karai, Péter Vajdovich, Tímea Imre, Pál Szabó, Dávid Szüts, József Tóvári, Gergely Szakács
Success of cancer treatment is often hampered by the emergence of multidrug resistance (MDR) mediated by P-glycoprotein (ABCB1/Pgp). Doxorubicin (DOX) is recognized by Pgp and therefore it can induce therapy resistance in breast cancer patients. In this study our aim was to evaluate the susceptibility of the pegylated liposomal formulation of doxorubicin (PLD/Doxil®/Caelyx®) to MDR. We show that cells selected to be resistant to DOX are cross-resistant to PLD and PLD is also ineffective in an allograft model of doxorubicin-resistant mouse B-cell leukemia...
September 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28627280/the-targeting-effect-of-hm2e8b-nctd-liposomes-on-b-lineage-leukemia-stem-cells-is-associated-with-the-hlf-slug-axis
#8
Jingying Zhang, Diyin Shen, Min Jia, Haizhao Zhao, Yongmin Tang
To identify an agent with specific activity against B-lineage leukemia stem cells (B-LSCs), we generated norcantharidin (NCTD)-encapsulated liposomes modified with a novel humanized anti-human CD19 monoclonal antibody, Hm2E8b (Hm2E8b-NCTD-liposomes). These liposomes were specially designed to recognize and kill B-LSCs in vitro, and to decrease non-specific cytotoxicity to untargeted cells. Hm2E8b-NCTD-liposomes selectively ablated B-LSCs through targeting hepatic leukemia factor (HLF), which is implicated in hematopoietic stem cell regulation and is overexpressed in LSCs...
June 19, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28624193/mir-375-and-doxorubicin-co-delivered-by-liposomes-for-combination-therapy-of-hepatocellular-carcinoma
#9
Yin-Ping Fan, Jia-Zhi Liao, Ya-Qi Lu, De-An Tian, Feng Ye, Peng-Xuan Zhao, Guang-Ya Xiang, Wang-Xian Tang, Xing-Xing He
Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28565974/pnc27-anticancer-peptide-as-targeting-ligand-significantly-improved-antitumor-efficacy-of-doxil-in-hdm2-expressing-cells
#10
Shahrzad Amiri Darban, Ali Badiee, Mahmoud Reza Jaafari
AIM: To investigate the potential of PNC27 peptide, 12-26 of p53 with high affinity for HDM2 protein, as targeting ligand for Doxil to improve its antitumor activity. MATERIALS & METHODS: Doxil postinserted with 25, 50, 100 and 200 PNC27 peptides per liposome. Flow cytometry and confocal analysis were performed on C26 colon carcinoma (HDM2 positive) and B16F0 melanoma (HDM2 negative) cells. In vivo studies were performed on BALB/c mice bearing C26 and C57BL/6 mice bearing B16F0 tumor models...
June 1, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28503689/effects-of-elemene-on-inhibiting-proliferation-of-vascular-smooth-muscle-cells-and-promoting-reendothelialization-at-the-stent-implantation-site
#11
Wenjie Sun, Yuhua Huang, Tieying Yin, Jingjing Wang, Ruolin Du, Juhui Qiu, Yuan Zhang, Yazhou Wang, Jinju Chen, Guixue Wang
Anticancer drugs are commonly used as inhibitors of vascular smooth muscle cell (VSMC) proliferation in clinical treatments. This study aims to investigate how elemene affects the proliferation of VSMCs, the restenosis, and the reendothelialization after implanting the elemene-coated stents. VSMCs derived from rat aorta were used to test the cell proliferation, cell cycle, migration, apoptosis, cytoskeletal protein F-actin, intracellular Ca(2+), IncRNA chip and gene expression of PCNA, P53, and Cx43 when cultured with elemene...
May 30, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28400564/a-novel-4-arm-dna-rna-nanoconstruct-triggering-rapid-apoptosis-of-triple-negative-breast-cancer-cells-within-24%C3%A2-hours
#12
Joline Tung, Lih Shin Tew, Yuan-Man Hsu, Yit Lung Khung
Measuring at ~30 nm, a fully customizable holliday junction DNA nanoconstruct, was designed to simultaneously carry three unmodified SiRNA strands for apoptosis gene knockout in cancer cells without any assistance from commercial transfection kits. In brief, a holliday junction structure was intelligently designed to present one arm with a cell targeting aptamer (AS1411) while the remaining three arms to carry different SiRNA strands by means of DNA/RNA duplex for inducing apoptosis in cancer cells. By carrying the three SiRNA strands (AKT, MDM2 and Survivin) into triple negative breast MDA-MB-231 cancer cells, cell number had reduced by up to ~82% within 24 hours solely from one single administration of 32 picomoles...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28351626/integrated-immunochromatographic-strip-with-glucometer-readout-for-rapid-quantification-of-phosphorylated-proteins
#13
Yuting Zhao, Xiao Chen, Sophie Lin, Dan Du, Yuehe Lin
A new technology to quantify phospho-p53(15) by converting its content to the amount of glucose which is detectable by a glucometer was developed. An immunochromatographic test strip (ITS) was used as a disposable platform, where primary antibody (Ab1)-modified Fe3O4 magnetic nanoparticles (Fe3O4-Ab1) were settled on the test zone to capture both the target phospho-p53(15) and the detection antibody (Ab2)-glucose encapsulating liposome (GEL) conjugate. The measurement was based on the release and subsequent detection of glucose from Ab2-GEL using a glucose meter (GM)...
April 29, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28338198/the-expression-of-sirt3-in-primary-hepatocellular-carcinoma-and-the-mechanism-of-its-tumor-suppressing-effects
#14
Y Liu, Y-L Liu, W Cheng, X-M Yin, B Jiang
OBJECTIVE: To observe the SIRT 3 expression in primary hepatocellular carcinoma (HCC), and then establish the eukaryotic expression vector of SIRT3 to observe the proliferation and apoptosis of pZsGreen-c1-SIRT3 HepG2 cells. Furthermore, we explored the mechanism of SIRT3 in inhibiting HCC. PATIENTS AND METHODS: Immunohistochemistry was used to detect the expression of SIRT3 in the tumor tissue and para-tumor tissue in 32 patients with HCC and the normal liver tissue in 10 patients...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28244731/tumor-microenvironment-activated-membrane-fusogenic-liposome-with-speedy-antibody-and-doxorubicin-delivery-for-synergistic-treatment-of-metastatic-tumors
#15
Hongzhang Deng, Kun Song, Xuefei Zhao, Yanan Li, Fei Wang, Jianhua Zhang, Anjie Dong, Zhihai Qin
Metastasis is the principal event leading to breast cancer death. Discovery of novel therapeutic approaches that are specific in targeting tumor metastasis factors while at the same time are an effective treatment of the tumor is urgently required. S100A4 protein is a key player in promoting metastasis and sequestrating the effect of tumor-suppressor protein p53. Here, a tumor microenvironment activated membrane fusogenic liposome was prepared to deliver rapidly anti-S100A4 antibody and doxorubicin into the cytoplasm directly in a fusion-dependent manner in order to bypass the cellular endocytosis to avoid the inefficient escape and degradation in the acidic endosome...
March 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27923599/the-role-of-the-atm-chk-p53-pathway-in-mediating-dna-damage-in-hand-foot-syndrome-induced-by-pld
#16
Jie Yang, Long Qiao, Zhen Zeng, Junnai Wang, Tao Zhu, Juncheng Wei, Mingfu Wu, Shuangmei Ye, Xiaoyuan Huang, Ding Ma, Ronghua Liu, Qinglei Gao
Pegylated liposomal doxorubicin (PLD) has been approved to treat patients with various types of cancers because it rarely caused side effects, such as cardiotoxicity, in comparison to doxorubicin, but it frequently results in hand-foot syndrome (HFS). This may affect the quality of life and require a reduction in the PLD dose. The pathophysiology of HFS was not well understood. This study was aimed at exploring the mechanism of HFS induced by PLD. We compared the effects of different doses of PLD on the proliferation inhibition and apoptosis in vitro in HaCaT cells and analyzed the skin changes and skin cell DNA damage in vivo using a zebrafish model...
January 4, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/27357628/safety-and-efficacy-in-advanced-solid-tumors-of-a-targeted-nanocomplex-carrying-the-p53-gene-used-in-combination-with-docetaxel-a-phase-1b-study
#17
Kathleen F Pirollo, John Nemunaitis, Po Ki Leung, Robert Nunan, Jana Adams, Esther H Chang
Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, occurs in most human cancers. SGT-53 is a liposomal nanocomplex designed for systemic, tumor-targeting delivery of the wt p53 gene. In this nanodelivery system, an anti-transferrin receptor single-chain antibody fragment serves as the targeting moiety. In an initial phase 1 trial in patients with advanced solid tumors, SGT-53 demonstrated tumor-specific targeting, was shown to be well tolerated, and was associated with an antitumor effect in several patients...
September 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27313702/liposome-mediated-transfection-of-wild-type-p53-dna-into-human-prostate-cancer-cells-is-improved-by-low-frequency-ultrasound-combined-with-microbubbles
#18
Wen-Kun Bai, Wei Zhang, Bing Hu, Tao Ying
Prostate cancer is a common type of cancer in elderly men. The aim of the present study was to evaluate the effects of ultrasound exposure in combination with SonoVue microbubbles on liposome-mediated transfection of wild-type P53 genes into human prostate cancer cells. PC-3 human prostate cancer cells were exposed to ultrasound; duty cycle was controlled at 20% (2 sec on, 8 sec off) for 5 min with and without SonoVue microbubble echo-contrast agent using a digital sonifier (frequency, 21 kHz; intensity, 46 mW/cm(2))...
June 2016: Oncology Letters
https://www.readbyqxmd.com/read/27220374/development-of-a-novel-microbubble-liposome-complex-conjugated-with-peptide-ligands-targeting-il4r-on-brain-tumor-cells
#19
See-Hyoung Park, Young Ii Yoon, Hyoungwon Moon, Ga-Hyun Lee, Byung-Heon Lee, Tae-Jong Yoon, Hak Jong Lee
Gas (SF6)-filled microbubbles (MBs) were prepared by emulsion and solvent-evaporation method. The prepared MBs were further conjugated with doxorubicin (Dox)-loaded nano-sized liposome and peptide ligands to interleukin-4 receptor (IL4R) for targeting brain tumor cells. The final MB-liposome (Dox)-IL4R targeting peptide ligand [MB-Lipo (Dox)-IL4RTP] had a spherical structure with the mean size of 1,500 nm. The MB-Lipo (Dox)‑IL4RTP exhibited cellular uptake in U87MG brain tumor cells (a brain tumor cell line expressing strongly IL4R) with frequency ultrasound energy suggesting that MB-Lipo (Dox)‑IL4RTP provided effective targeting ability for brain tumor cells...
July 2016: Oncology Reports
https://www.readbyqxmd.com/read/27179933/strong-synergy-with-apr-246-and-dna-damaging-drugs-in-primary-cancer-cells-from-patients-with-tp53-mutant-high-grade-serous-ovarian-cancer
#20
Åsa Fransson, Daria Glaessgen, Jessica Alfredsson, Klas G Wiman, Svetlana Bajalica-Lagercrantz, Nina Mohell
BACKGROUND: Mutation in the tumor suppressor gene TP53 is an early event in the development of high-grade serous (HGS) ovarian cancer and is identified in more than 96 % of HGS cancer patients. APR-246 (PRIMA-1(MET)) is the first clinical-stage compound that reactivates mutant p53 protein by refolding it to wild type conformation, thus inducing apoptosis. APR-246 has been tested as monotherapy in a Phase I/IIa clinical study in hematological malignancies and prostate cancer with promising results, and a Phase Ib/II study in combination with platinum-based therapy in ovarian cancer is ongoing...
May 14, 2016: Journal of Ovarian Research
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