Project description:This SuperSeries is composed of the following subset Series:; GSE9712: Detection of genes differentially expressed in radioresistant tumors; GSE9713: Detection of genes differentially expressed in radioresistant and radiosensitive tumors before and after irradiation; GSE9714: Interferon response of radioresistant and radiosensitive human head&neck tumor cell lines Experiment Overall Design: Refer to individual Series
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors were profiled using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway Keywords: Pair-wise comparison of radiosensitive vs radioresistant tumors; time course of irradation response
Project description:Prostate cancer cell lines DU145 and LNCaP were purchased from the American Type Culture Collection. Radioresistant (RR) sublines were generated form these original parental radiosensitive (RS) cell lines. Gene expression profiles of radiosensitive (RS) and radioresistant (RR) prostate cancer cell lines were measured.
Project description:Prostate cancer cell lines DU145 and LNCaP were purchased from the American Type Culture Collection. Radioresistant (RR) sublines were generated form these original parental radiosensitive (RS) cell lines. aCGH profiles of radiosensitive (RS) and radioresistant (RR) prostate cancer cell lines were measured and compared to normal DNA.
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors were profiled using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway Keywords: Pair-wise comparison of radiosensitive vs radioresistant tumors
Project description:Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here we report a novel role for statin-based treatment of HNSCCs as an actionable and safe adjuvant to radiotherapy. Proteomic profiling and comparison of radiosensitive and radioresistant HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin (and other related statins) sensitized SQ20B cells to ionizing radiation (IR) and reduced their clonogenic potential. In an effort to uncover the mechanism behind this statin-mediated sensitization, we analyzed prenylation of several important cellular targets upon combined IR-statin treatment. Overall, this study reinforces the view that the mevalonate pathway is a promsing novel therapeutic target in radioresistant HSNCCs.
2019-06-25 | PXD007188 | Pride
Project description:Radioresistant and radiosensitive tumors and cell lines
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors xenografts were profiled in two independent experiments using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway. In these experiments we detected genes responding to IFN alpha, beta and gamma in nu61 and SCC61 Keywords: Pair-wise comparison of un-treated and treated tumor cell lines
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors xenografts were profiled in two independent experiments using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway. In these experiments we detected genes responding to IFN alpha, beta and gamma in nu61 and SCC61 Experiment Overall Design: Cell lines derived from nu61 and SCC61 were grown in vitro and treated by the mixture of IFNalpha, IFNbeta and IFN gamma (100,100 and 5ng/ml respectively). 5 hours after administration of IFNs cells were lysed, RNA collected and used for hybridization with U133A chips to detect genes responding to IFN treatment in nu61 and SCC61
Project description:The clinical management of locally advanced oesophageal adenocarcinoma (OAC) commonly involves neoadjuvant chemoradiotherapy (CRT), but complete pathological response to CRT only occurs in 20-30% of patients, as radioresistance remains a major clinical challenge. In this study we used an established isogenic cell line model of radioresistant OAC to detect proteomic signatures of radioresistance in order to identify novel potential molecular and cellular targets of radioresistance in OAC. Intracellular proteins obtained from radiosensitive (OE33P) and radioresistant (OE33R) cells were subjected to LC-MS/MS analysis. We identified 5785 proteins of which 251 were significantly modulated in OE33R cells, when compared to OE33P. Gene ontology and pathway analysis of the significantly modulated proteins demonstrated altered metabolism in radioresistant cells accompanied by an inhibition of apoptosis in OE33R cells. In addition, radioresistant cells were predicted to have an activation of inflammatory and angiogenic pathways when compared to the radiosensitive cells. For the first time, we performed a comprehensive proteomic profiling of our established isogenic cell line model of radioresistant OAC, providing insights into the molecular and cellular pathways which regulates radioresistance in OAC, and we provided pathway specific signatures of radioresistance that will aid further studies on the development of targeted therapies and personalised approaches to radiotherapy, with the ultimate goal of improving response to radiotherapy in cancer patients.
