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Source: Oncotarget

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Total 624 results found since Jan 2013.

Enhanced therapeutic effect of Adriamycin on multidrug resistant breast cancer by the ABCG2-siRNA loaded polymeric nanoparticles assisted with Ultrasound.
Authors: Bai M, Shen M, Teng Y, Sun Y, Li F, Zhang X, Xu Y, Duan Y, Du L Abstract The overexpression of the breast cancer resistance protein (ABCG2) confers resistance to Adriamycin (ADR) in breast cancer. The silencing of ABCG2 using small interfering RNA (siRNA) could be a promising approach to overcome multidrug resistance (MDR) in cancer cells. To deliver ABCG2-siRNA effectively into breast cancer cells, we used mPEG-PLGA-PLL (PEAL) nanoparticles (NPs) with ultrasound-targeted microbubble destruction (UTMD). PEAL NPs were prepared with an emulsion-solvent evaporation method. The NPs size was about 131.5 ± 6.5 ...
Source: Oncotarget - November 19, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Precision delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles.
Authors: Strand MS, Krasnick BA, Pan H, Zhang X, Bi Y, Brooks C, Wetzel C, Sankpal N, Fleming T, Goedegebuure SP, DeNardo DG, Gillanders WE, Hawkins WG, Wickline SA, Fields RC Abstract Over 95% of pancreatic adenocarcinomas (PDACs), as well as a large fraction of other tumor types, such as colorectal adenocarcinoma, are driven by KRAS activation. However, no direct RAS inhibitors exist for cancer therapy. Furthermore, the delivery of therapeutic agents of any kind to PDAC in particular has been hindered by the extensive desmoplasia and resultant drug delivery challenges that accompanies these tumors. Small interfer...
Source: Oncotarget - August 17, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

siRNA Knockdown of mitochondrial thymidine kinase 2 (TK2) sensitizes human tumor cells to gemcitabine.
Authors: Di Cresce C, Figueredo R, Rytelewski M, Vareki SM, Way C, Ferguson PJ, Vincent MD, Koropatnick J Abstract Nucleoside metabolism enzymes are determinants of chemotherapeutic drug activity. The nucleoside salvage enzyme deoxycytidine kinase (dCK) activates gemcitabine (2', 2'-difluoro-2'-deoxycytidine) and is negatively regulated by deoxycytidine triphosphate (dCTP). Reduction of dCTP in tumor cells could, therefore, enhance gemcitabine activity. Mitochondrial thymidine kinase 2 (TK2) phosphorylates deoxycytidine to generate dCTP. We hypothesized that: (1) TK2 modulates human tumor cell sensitivity to gemcit...
Source: Oncotarget - June 20, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Antibody targeting facilitates effective intratumoral siRNA nanoparticle delivery to HER2-overexpressing cancer cells.
Authors: Palanca-Wessels MC, Booth GC, Convertine AJ, Lundy BB, Berguig GY, Press MF, Stayton PS, Press OW Abstract The therapeutic potential of RNA interference (RNAi) has been limited by inefficient delivery of short interfering RNA (siRNA). Tumor-specific recognition can be effectively achieved by antibodies directed against highly expressed cancer cell surface receptors. We investigated the utility of linking an internalizing streptavidin-conjugated HER2 antibody to an endosome-disruptive biotinylated polymeric nanocarrier to improve the functional cytoplasmic delivery of siRNA in breast and ovarian cancer cell...
Source: Oncotarget - February 4, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model.
This study provides possible application of pRNA-3WJ RNP for specific delivery of therapeutics such as siRNA, microRNA and/or chemotherapeutic drugs into glioblastoma cells without inflicting collateral damage to healthy tissues. PMID: 25885522 [PubMed - as supplied by publisher]
Source: Oncotarget - April 19, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Therapeutic siRNA for drug-resistant HER2-positive breast cancer.
Authors: Gu S, Hu Z, Ngamcherdtrakul W, Castro DJ, Morry J, Reda MM, Gray JW, Yantasee W Abstract HER2 is overexpressed in about 20% of breast cancers and contributes to poor prognosis. Unfortunately, a large fraction of patients have primary or acquired resistance to the HER2-targeted therapy trastuzumab, thus a multi-drug combination is utilized in the clinic, putting significant burden on patients. We systematically identified an optimal HER2 siRNA from 76 potential sequences and demonstrated its utility in overcoming intrinsic and acquired resistance to trastuzumab and lapatinib in 18 HER2-positive cancer cell ...
Source: Oncotarget - February 21, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis.
Authors: Lv G, Zhu H, Li C, Wang J, Zhao D, Li S, Ma L, Sun G, Li F, Zhao Y, Gao Y Abstract Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS processes, its obvious secretion and expression has been initially characterized in hyperlipidemia patients' serum and AS mice's serum respectively. We then explored the possible role of TMEM98 in the pathogenesis of AS in vitro. IL-8,...
Source: Oncotarget - November 22, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Apoptosis induced by a HIPK2 full-length-specific siRNA is due to off-target effects rather than prevalence of HIPK2-Δe8 isoform.
Authors: Di Rocco G, Verdina A, Gatti V, Virdia I, Toietta G, Todaro M, Stassi G, Soddu S Abstract Small interfering RNAs (siRNAs) are widely used to study gene function and extensively exploited for their potential therapeutic applications. HIPK2 is an evolutionary conserved kinase that binds and phosphorylates several proteins directly or indirectly related to apoptosis. Recently, an alternatively spliced isoform skipping 81 nucleotides of exon 8 (Hipk2-Δe8) has been described. Selective depletion of Hipk2 full-length (Hipk2-FL) with a specific siRNA that spares the Hipk2-Δe8 isoform has been shown to strongly ...
Source: Oncotarget - December 5, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Antibody h-R3-dendrimer mediated siRNA has excellent endosomal escape and tumor targeted delivery ability, and represents efficient siPLK1 silencing and inhibition of cell proliferation, migration and invasion.
Authors: Li J, Liu J, Li S, Hao Y, Chen L, Zhang X Abstract The major obstacle to developing siRNA delivery is their extracellular and intracellular barriers. Herein, a humanized anti-EGFR monoclonal antibody h-R3 was developed to modify the self-assembled binary complexes (dendriplexes) of PAMAM and siRNA via electrostatic interactions, and two common ligands HSA and EGF were used as a control. Compared to dendriplexes, h-R3/EGF/HSA-dendriplexes showed increased particle size, decreased zeta potentials and lower cytotoxicity. Moreover, h-R3-dendriplexes presented greater cellular uptake and excellent endosomal esc...
Source: Oncotarget - February 19, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

HER2-siRNA delivered by EGFR-specific single chain antibody inhibits NSCLC cell proliferation and tumor growth.
Authors: Lu Y, Wang Y, Zhang M, Liu L, Li F, Zhang J, Ye M, Zhao H, Zhao J, Yan B, Yang A, Zhang R, Li X, Ren X Abstract Overexpression of human epidermal growth factor receptor type2 (HER2) is closely associated with aggressive progression and poor prognosis in non-small cell lung cancer (NSCLC). Here, we generated an EGFR-scFv-arginine nonamer peptide fusion protein (scFv-9R) as a cargo to deliver HER2 specific siRNA into HER2-positive NSCLC cells both in vitro and in vivo. HER2-siRNAs delivered by scFv-9R effeciently silenced HER2 expression in EGFR-positive NSCLC cells, and consequently resulted in G1 arrest an...
Source: Oncotarget - March 19, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Consequences of combining siRNA-mediated DNA methyltransferase 1 depletion with 5-aza-2'-deoxycytidine in human leukemic KG1 cells.
Authors: Vispé S, Deroide A, Davoine E, Desjobert C, Lestienne F, Fournier L, Novosad N, Bréand S, Besse J, Busato F, Tost J, De Vries L, Cussac D, Riond J, Arimondo PB Abstract 5-azacytidine and 5-aza-2'-deoxycytidine are clinically used to treat patients with blood neoplasia. Their antileukemic property is mediated by the trapping and the subsequent degradation of a family of proteins, the DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) leading to DNA demethylation, tumor suppressor gene re-expression and DNA damage. Here we studied the respective role of each DNMT in the human leukemia KG1 cell line using a...
Source: Oncotarget - May 9, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening.
Authors: Anania M, Gasparri F, Cetti E, Fraietta I, Todoerti K, Miranda C, Mazzoni M, Re C, Colombo R, Ukmar G, Camisasca S, Pagliardini S, Pierotti M, Neri A, Galvani A, Greco A Abstract The incidence of thyroid carcinoma is rapidly increasing. Although generally associated with good prognosis, a fraction of thyroid tumors are not cured by standard therapy and progress to aggressive forms for which no effective treatments are currently available. In order to identify novel therapeutic targets for thyroid carcinoma, we focused on the discovery of genes essential for sustaining the oncogenic phenotype of thyroid tum...
Source: Oncotarget - October 3, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy.
Authors: Liu T, Wu X, Wang Y, Zhang T, Wu T, Liu F, Wang W, Jiang G, Xie M Abstract The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial d...
Source: Oncotarget - June 5, 2016 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Charge reversible calcium phosphate lipid hybridnanoparticle for siRNA delivery.
Authors: Cai RQ, Liu DZ, Cui H, Cheng Y, Liu M, Zhang BL, Mei QB, Zhou SY Abstract Bcl-2 gene is an important target to treat lung cancer. The small interference RNA (siRNA) of Bcl-2 gene (siBcl-2) can specifically silence Bcl-2 gene. However, naked siBcl-2 is difficult to accumulate in the tumor tissue to exert its activity. In this paper, a calcium phosphate lipid hybrid nanoparticle that possessed charge reversible property was prepared to enhance the activity of siBcl-2 in vivo. The average diameter and zeta potential of siBcl-2 loaded calcium phosphate lipid hybrid nanoparticles (LNPS@siBcl-2) were 80 nm and -...
Source: Oncotarget - May 19, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

siRNA-mediated inactivation of HER3 improves the antitumour activity and sensitivity of gefitinib in gastric cancer cells.
Authors: Yuan HH, Yang YN, Zhou JH, Li YJ, Wang LY, Qin JW, Liu T, Li ZZ, Zhou QX, Wei XL, Zhang TT, Huang P, Zhang WJ, Liu L, Du XX, Han Y Abstract The human EGFR family consists of four type-1 transmembrane tyrosine kinase receptors: HER1 (EGFR, ErbB1), HER2 (Neu, ErbB2), HER3 (ErbB3), and HER4 (ErbB4). HER3 can dimerize with EGFR, HER2 and even c-Met and likely plays a central role in the response to EGFR-targeted therapy. Because HER3 lacks significant kinase activity and cannot be inhibited by tyrosine kinase inhibitors, neutralizing antibodies and alternative inhibitors of HER3 have been sought as cancer ther...
Source: Oncotarget - May 19, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research