Project description:Head and Neck Squamous Cell Carcinoma (HNSCC) is a common cause of cancer death. Despite enormous technical advances in surgery and radiotherapy in the recent decade, survival of HNSCC patients has not markedly improved, with only 30% of patients diagnosed with advanced HNSCC that will survive for 5 years. This highlights the need to look into molecular processes leading to mechanisms of HNSCC radioresistance in HNSCC and identify novel radiosensitizers. To identify the lncRNAs associated with radiotherapy resistance in HNSCC, we performed RNA-seq analysis of radiation resistant and sensitive HNSCC cells.
Project description:Expression profiling of nasopharyngeal carcinoma patients comparing radio-sensitive samples with radio-resistant samples. Two condition-experiments, radio-sensitive and radio-resistant nasopharyngeal carcinoma patients. Biological replicates: 8 radio-sensitive, 12 radio-resistant, different donors in the same hospital. One patient per array.
Project description:10 cell lines (five cetuximab sensitive and five cetuximab resistant) were selected for gene copy number array analysis on the Affymetrix SNP 6.0 platform. 39 protein coding genes were amplified in cetuximab resistant cells and normal in sensitive cells, all present on genomic regions 11q22.1 or 5p13-15. Five genes were selected for quantitative PCR verification, namely, YAP1 and TRPC6 (11q22.1) and PDCD6, TPPP, and PTGER4 (5p13-15). An extended panel of totally 10 cetuximab resistant and 10 sensitive cell lines verified that YAP1 amplified cells are cetuximab resistant. YAP1 gene amplification was highly correlated to the YAP1 mRNA expression, which was significantly higher in cetuximab resistant cells than in sensitive. YAP1 downregulation resulted in increased cetuximab sensitivity in one of two cetuximab resistant cell lines investigated and growth inhibition in another. We conclude that YAP1 is a marker for cetuximab resistance in head and neck cancer. head and neck cancer cell lines with established cetuximab response were selected. 5 cetuximab resistant cell lines and 5 cetuximab sensitive cell lines were selected for gene genome wide gene copy number analysis on the Affymetrix SNP6.0 array
Project description:10 cell lines (five cetuximab sensitive and five cetuximab resistant) were selected for gene copy number array analysis on the Affymetrix SNP 6.0 platform. 39 protein coding genes were amplified in cetuximab resistant cells and normal in sensitive cells, all present on genomic regions 11q22.1 or 5p13-15. Five genes were selected for quantitative PCR verification, namely, YAP1 and TRPC6 (11q22.1) and PDCD6, TPPP, and PTGER4 (5p13-15). An extended panel of totally 10 cetuximab resistant and 10 sensitive cell lines verified that YAP1 amplified cells are cetuximab resistant. YAP1 gene amplification was highly correlated to the YAP1 mRNA expression, which was significantly higher in cetuximab resistant cells than in sensitive. YAP1 downregulation resulted in increased cetuximab sensitivity in one of two cetuximab resistant cell lines investigated and growth inhibition in another. We conclude that YAP1 is a marker for cetuximab resistance in head and neck cancer.
Project description:The aim of the present study was to evaluate miRNAs as response predictors in FFPE head and neck samples from a phase II clinical trial designed to evaluate the feasibility of delivering cisplatin concurrent with radiotherapy after an induction chemotherapy (IC) regimen based on the combination of cisplatin plus paclitaxel in locally advanced head and neck squamous cell carcinoma (HNSCC) patients. For this purpose, we assessed the global miRNA expression profile of 15 HNSCC patients undergoing treatment, in order to identify miRNAs able to segregate resistant tumors from the sensitive ones, thus serving as markers to predict response. The results showed four miRNAs (miR-21, miR-494, miR-720 and miR-923) that were overexpressed in HNSCC FFPE samples.
Project description:We established panels of patient-derived culture of the cancer cells from small cell carcinoma of the cervix uteri (SCCC) by cancer tissue–originated spheroids (CTOS) method. Then we developed in vitro sensitivity assay for radiation using CTOSs to assess the intrinsic radio-sensitivity and mechanism of radio-resistance in individual SCCC patients. To find factors that affect to the radio-sensitivity we compared gene expression of radio-resistant CTOS (cerv-5) and radio-sensitive CTOS (cerv-9).
Project description:We established panels of patient-derived culture of the cancer cells from small cell carcinoma of the cervix uteri (SCCC) by cancer tissueM-bM-^@M-^Soriginated spheroids (CTOS) method. Then we developed in vitro sensitivity assay for radiation using CTOSs to assess the intrinsic radio-sensitivity and mechanism of radio-resistance in individual SCCC patients. To find factors that affect to the radio-sensitivity we compared gene expression of radio-resistant CTOS (cerv-5) and radio-sensitive CTOS (cerv-9). We compared gene expression of cerv5 and cerv9 CTOSs under the culture condition.