Publicação
Optimization of Neoadjuvant Radiotherapy for zebrafish-avatars – towards personalized medicine
| Resumo: | Recently, Fior and colleagues developed zebrafish Patient-derived Xenografts (zPDX) for personalized medicine to quickly screen the recommended Adjuvant Chemotherapies for colorectal cancer (CRC). Now the Lab goal is to test if zPDX can also be used to screen patients for Neoadjuvant Radiotherapy (RT). In rectal cancer the Neoadjuvant RT comprises a short Fractionated RT regimen of 5x5Gy (FRT), used to shrink tumor before surgery. Preliminary results from the Lab showed to be possible to distinguish radiosensitive from radioresistant CRC zebrafish xenografts, using an adapted RT protocol Single-High Dose RT (SHD-RT, 1x25Gy). However this SHD-RT protocol was different from the one given in the clinic (FRT, 5x5Gy), raising the question whether this adaptation is a good proxy of tumor response. Thus, the main goal of this thesis was to compare both RT protocols and test if SHD-RT is suitable to determine tumor radiosensitivity/radioresistance. To address this aim, radiosensitive CRC zebrafish xenografts were generated and distributed into the different experimental conditions: Control (non-irradiated); FRT; and SHD-RT. Our results revealed that SHD-RT induces similar tumor responses to FRT, in 6 days, i.e. both protocols lead to a significant induction of apoptosis and reduction of tumor size, suggesting that SHD-RT is enough for a quick and feasible assay. However, we also investigated further the cumulative effect of radiation and whether “time matters” for the radiobiology of the tumors in this short assay. Indeed, our results showed that cumulative damage and time are crucial factors to reduce the overall tumor size. However, given the similar results in the 6dpi assay, the adapted SHD-RT protocol seemed a practical option for the zPDX assay. Nevertheless this study needs further confirmation with a radioresistant tumor. Moreover, CRC zebrafish avatars were tested for RT and its combination with Chemotherapy, suggesting an increase of apoptotic cells upon the treatment combination. |
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| Autores principais: | Ferreira, Susana Filipe |
| Assunto: | Colorectal cancer Radiotherapy SHD-RT FRT Zebrafish xenografts Radiosensitivity |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Recently, Fior and colleagues developed zebrafish Patient-derived Xenografts (zPDX) for personalized medicine to quickly screen the recommended Adjuvant Chemotherapies for colorectal cancer (CRC). Now the Lab goal is to test if zPDX can also be used to screen patients for Neoadjuvant Radiotherapy (RT). In rectal cancer the Neoadjuvant RT comprises a short Fractionated RT regimen of 5x5Gy (FRT), used to shrink tumor before surgery. Preliminary results from the Lab showed to be possible to distinguish radiosensitive from radioresistant CRC zebrafish xenografts, using an adapted RT protocol Single-High Dose RT (SHD-RT, 1x25Gy). However this SHD-RT protocol was different from the one given in the clinic (FRT, 5x5Gy), raising the question whether this adaptation is a good proxy of tumor response. Thus, the main goal of this thesis was to compare both RT protocols and test if SHD-RT is suitable to determine tumor radiosensitivity/radioresistance. To address this aim, radiosensitive CRC zebrafish xenografts were generated and distributed into the different experimental conditions: Control (non-irradiated); FRT; and SHD-RT. Our results revealed that SHD-RT induces similar tumor responses to FRT, in 6 days, i.e. both protocols lead to a significant induction of apoptosis and reduction of tumor size, suggesting that SHD-RT is enough for a quick and feasible assay. However, we also investigated further the cumulative effect of radiation and whether “time matters” for the radiobiology of the tumors in this short assay. Indeed, our results showed that cumulative damage and time are crucial factors to reduce the overall tumor size. However, given the similar results in the 6dpi assay, the adapted SHD-RT protocol seemed a practical option for the zPDX assay. Nevertheless this study needs further confirmation with a radioresistant tumor. Moreover, CRC zebrafish avatars were tested for RT and its combination with Chemotherapy, suggesting an increase of apoptotic cells upon the treatment combination. |
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