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Gold nanorod based delivery system could bring about superior therapy effect of Ramucirumab through direct cytotoxicity to cancer cell mediated by differential regulation of phagocytosis in gastric cancer cell

ABSTRACT: Gold nanorod based delivery system could bring about superior therapy effect of Ramucirumab through direct cytotoxicity to cancer cell mediated by differential regulation of phagocytosis in gastric cancer cell

PROVIDER: PRJNA751860 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15335100_1.fastq.gz	Fastqsanger.gz
	SRR15335100_2.fastq.gz	Fastqsanger.gz
	SRR15335101_1.fastq.gz	Fastqsanger.gz
	SRR15335101_2.fastq.gz	Fastqsanger.gz
	SRR15335102_1.fastq.gz	Fastqsanger.gz

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Gold nanorod based delivery system could bring about superior therapy effect of Ramucirumab through direct cytotoxicity to cancer cell mediated by differential regulation of phagocytosis in gastric cancer cell

2021-08-06 | GSE181369 | GEO

Project description:Gastric Cancer (GC) is one of the most serious cancers with high incidence and mortality all over the world. Chemotherapy hadn’t led to desirable effect and targeted therapy brings about a new stage to cancer treatment. Ramucirumab is the first FDA-approved single drug target therapy for advanced gastric cancer. It is well known that gold nanorod, a nontoxic biocompatible nanomaterial, is an especially promising candidate for cancer theranostic. In this study, Ramucirumab (Ab) were first modified by gold nanoparticles to enhance uptake efficiency. The simple Nano-delivery system had taken perfect aggregation effect in vivo even better than 5-fold Ab treatment. Gold nanomaterials, especially gold nanorod (AuNR), could induce direct cytotoxic effect to cancer cell in the presence of Ab, while Ab or gold nanoparticle themselves couldn’t lead to such direct killing effect even at an extremely high concentration. Proteomic and transcriptomic analyses revealed this direct cytotoxicity derived predominantly from Ab-mediated phagocytose, and the high affinity receptor for Fc gamma CD64 showed differential up-regulation only in gastric cancer cell treated by these nanodrugs compared with Ab, especially for AuNR group. This was the first time to discover that nanoparticle could induce regulation of immune related pathways and Fcγ receptor in the target cancer cell. Simplified and powerful designs of smart nanoparticles are highly desired for clinical. The dramatic enhancement of Ab accumulation with simple composition, combined with direct cytotoxic effect specific to cancer cells brought perfect therapeutic effects in vivo than Ab, which would promote further clinical application of gold nanorod in the diagnosis and therapeutics of gastric cancer.

2021-07-21 | PXD027484 |

An Anti-Cancer Gold(III)-Activated Porphyrin Scaffold that Covalently Modifies Protein Cysteine Thiols

Project description:Cysteine thiols of many cancer-associated proteins are attractive targets of anti-cancer agents. Herein, we unequivocally demonstrate a distinct thiol-targeting property of gold(III) mesoporphyrin IX dimethyl ester (AuMesoIX) and its anti-cancer activities. While the binding of cysteine thiols with metal complexes usually occurs via M–S bond formation, AuMesoIX is unique in that the meso-carbon atom of the porphyrin ring is activated by the gold(III) ion to undergo nucleophilic aromatic substitution with thiols. AuMesoIX was shown to modify reactive cysteine residues and inhibit the activities of anti-cancer protein targets including thioredoxin, peroxiredoxin, and deubiquitinases. Treatment of cancer cells with AuMesoIX resulted in the formation of gold-bound sulfur-rich protein aggregates, oxidative stress-mediated cytotoxicity, and accumulation of ubiquitinated proteins. Importantly, AuMesoIX exhibited effective anti-tumor activity in mice. Our study has uncovered a gold(III)-induced ligand scaffold reactivity for thiol targeting that can be exploited for anti-cancer applications.

2021-09-08 | PXD016875 | Pride

Gene expression profiling of macrophages: Implications for an immunosuppressive effect of dissolucytotic gold ions

Project description:Gold salts has been used in the treatment of rheumatoid arthritis but has been replaced by biologicals such as TNF-alpha inhibitors. The mechanisms behind the anti-inflammatory effect of metallic gold ions are still unknown, however, recent data showed that charged gold atoms are released from pure metallic gold implants by macrophages via a dissolucytosis membrane, and that gold ions are taken up by local macrophages, mast cells and to some extent fibroblasts. These current findings offer new treatment options for metallic gold and deeper understanding of the effect of metallic gold on key inflammatory cells as macrophages are essential. In the present study the impact of phagocytised gold ions on the global gene expression profile of the human monocytic cell line THP-1 was investigated, using microarray analysis comprising approximately 20,000 genes. The gene expression data was confirmed by measurement of three secreted proteins. A unique gene expression signature of dissolucytotic macrophages that had taken up gold ions was demonstrated. A large number of regulated genes were functionally related to immunomodulation/protection. Gold ion uptake into macrophages induced downregulation of central inflammatory cytokines as TNF-alpha, IL-32 and CD28. The data obtained in this study offer new insights into the mode of action of gold ions and suggest a future role of metallic gold as implants or topical applications in treating inflammation. To determine the effect of gold phagocytosis on global gene expression

2012-12-31 | E-GEOD-37814 | biostudies-arrayexpress

Understanding toxicity pathways of gold nanoparticles: RNA expression study on Caco-2 human colon carcinoma cells

Project description:A safer design and higher eficacy of nano-gold therapeutic formulations requires examination of cellular responses to gold nanoparticles (AuNPs). In this work we compared cellular uptake, cytotoxicity and RNA expression patterns induced in Caco-2 cells of citrate-stabilized Au NP of two different sizes (5 and 30 nm). The toxicity was measured with Colony Forming Efficiency (CFE) and Trypan Blue assays at 24 and 72 h after exposure to AuNPs in the 10 - 300 mM range. Toxicity was observed only in the CFE assay, at 200 and 300 mM exposure levels, and exclusively for smaller AuNPs size. Cellular internalization was dose and time-dependent for both AuNPs. The most pronounced changes in gene expression, evaluated with Agilent microarrays, were detected at 72 h (300 mM) for 5 nm AuNPs, with 103 up and 708 down regulated transcripts. For 30 nm AuNPs, only 4 gene transcripts were repressed under these conditions. The biological processes affected by 5 nm AuNPs were: RNA/zinc ion/transition metal ion binding (decreased), cadmium/copper ion binding and glutathione metabolism (increased). Some Nrf2 responsive genes (several metallothioneins, HMOX, G6PD, OSGIN1 and GPX2) were highly up regulated. Members of the selenoproteins (SELT, SELK, 15 kDa selenoprotein, SEPP1 and GPX2) were also differentially expressed. Our findings indicate that at high concentrations, smaller AuNPs can induce metal exposure and oxidative stress signaling pathways, and might influence selenium homeostasis. Therefore, some observed effects associated with nano-gold cytotoxicity can be further explored as potential enhancers of anti-cancer properties of already existing AuNPs based nanomedicin. Caco-2 cells were expoxed to spherical gold nanoparticles of two different sizes and concentrations (5 and 30 nm AuNPs, 100 and 300 microM). Cells were collected after 24 or 72 hours

2015-01-22 | E-GEOD-55349 | biostudies-arrayexpress

RNA SEQUENCING DATA OF NOVEL GOLD NANOPARTICLE TREATED PANCREATIC CANCER CELLS.

Project description:BxPC3 pancreatic cancer cell lines were treated with Gold Nanoparticles and RNA was isolated from untreated and treated cells, RNA was sequences by NGS method and data reported

2024-05-17 | GSE248677 | GEO

Gold nanoparticles enhance antibody effect through direct cancer cell cytotoxicity by differential regulation of phagocytosis.

Project description:Ramucirumab is the first FDA-approved monotherapy for advanced gastric cancer. In this study, Ramucirumab (Ab) is attached to gold nanoparticles to enhance uptake efficiency. Gold nanoparticles can induce direct cytotoxic effects to cancer cells in the presence of Ab, while individual Ab or gold nanoparticles don't have such an effective anticancer effect even at extremely high concentrations. Proteomic and transcriptomic analyses reveal this direct cytotoxicity is derived predominantly from Ab-mediated phagocytosis. High affinity immunoglobulin gamma Fc receptor I shows differential up-regulation in gastric cancer cells treated by these nanodrugs compared with Ab, especially for Ab with gold nanorods. Simplified and powerful designs of smart nanoparticles are highly desired for clinical application. The enhancement of Ab accumulation with a simple composition, combined with direct cytotoxic effects specific to cancer cells brought improved therapeutic effects in vivo compared with Ab, which can promote further clinical application of gold nanomaterials in the diagnosis and therapeutics of gastric cancer.

| S-EPMC8569206 | biostudies-literature

Understanding toxicity pathways of gold nanoparticles: RNA expression study on Caco-2 human colon carcinoma cells

2015-01-22 | GSE55349 | GEO

Gold Creek Plant Microbe Interactions

Project description:Gold Creek 52022

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RNA SEQUENCING DATA OF NOVEL GOLD NANOPARTICLE TREATED PANCREATIC CANCER CELLS.

Project description:RNA SEQUENCING DATA OF NOVEL GOLD NANOPARTICLE TREATED PANCREATIC CANCER CELLS.

| PRJNA1045572 | ENA