ABSTRACT: Through whole genome sequencing, this study will explore the mutational profiles and signatures within an angiosarcoma tumour from a patient with xeroderma pimentosum. Very little information is known about this tumour type and it has not previously been studied within the context of xerogerma pigmentosum.
Project description:Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, one of the taxanes (genotoxic drugs), although it has a limited effect due to chemoresistance for prolonged treatment. Here we examine a new angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We first find that the chemotherapeutic drugs, cisplatin and paclitaxel, efficiently induce cellular senescence of angiosarcoma cells. Subsequent treatment with a senolytic agent, ABT-263, eliminates senescent cells through the activation of the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype (SASP) genes are activated in senescent angiosarcoma cells and that ABT-263 treatment eliminates senescent cells expressing genes in the type-I interferon (IFN-I) pathway. Moreover, we show that cisplatin treatment alone requires a high dose to remove angiosarcoma cells, whereas a lower dose of cisplatin is sufficient to induce senescence, followed by the elimination of senescent cells by senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy.
Project description:Analysis of the effects of 4 hr and 24 hr propranolol treatment on gene expression of SVR mouse angiosarcoma cells. The hypothesis tested in the present study was that inhibiton of beta adrenergic receptor signaling could ablate the oncogenic properties of angiosarcoma cells. Results provide important information of the response of angiosarcoma cells to ablated beta adrenergic receptor signaling.
Project description:Analysis of the effects of 4 hr and 24 hr propranolol treatment on gene expression of SVR mouse angiosarcoma cells. The hypothesis tested in the present study was that inhibiton of beta adrenergic receptor signaling could ablate the oncogenic properties of angiosarcoma cells. Results provide important information of the response of angiosarcoma cells to ablated beta adrenergic receptor signaling. The total RNA was obtained from mouse angiosarcoma cells cultured in monolayer at 0, 4, and 24 hrs of 50 micromolar propranolol treatment. Illumina microarrays were performed to determine the whole genome expression changes following treatment.
Project description:We first use microRNA expression profiles to find miRNA expression signatures in 3 cases of human angiosarcoma and capillary hemangiomauman, then RT-PCR for large sample verification. Through the bioinformatics prediction of its target genes, we study its function and aim to find the new molecular markers and therapeutic targets.
Project description:A comparison of gene expression in OCT frozen human angiosarcoma compared with OCT frozen normal mesenchymal tissues RNA was isolated from 18 AS and normal human. RNA was isolated from 3 kidney and 2 skeletal muscle OCT frozen sections and 3 samples of frozen whole blood. Twenty-five nanograms of total RNA from each sample was used for amplification, and then was fluorescently labeled using Cy3 and hybridized onto Agilent whole human genome 8x60k gene expression microarrays (Agilent Technologies, Santa Clara, CA) according to Agilent standard procedures. After hybridization for 17 h at 65 oC and 10 rpm, the arrays were washed and scanned with the Agilent G3 high-resolution scanner. Probe features were extracted from the microarray scan data using Feature Extraction software v.10.7.3.1 (Agilent Technologies). Microarray data was read and processed with R/Bioconductor (version 2.15.1/2.16) statistical software environment using the limma package (version 3.12.1). The raw data was within array quantile normalized and probes that mapped to the same gene were combined by averaging.
Project description:We first use microRNA expression profiles to find miRNA expression signatures in 3 cases of human angiosarcoma and capillary hemangiomauman, then RT-PCR for large sample verification. Through the bioinformatics prediction of its target genes, we study its function and aim to find the new molecular markers and therapeutic targets. We identified the miRNA expression signatures in human angiosarcomas and capillary hemangiomas by using microRNA expression profiles
