Submission ID 91661
| Poster Code | HR-P-97 |
|---|---|
| Title of Abstract | Radio-selective effects of a muscle-derived dipeptide in an external beam treated non-small cell lung cancer (NSCLC) mouse model |
| Abstract Submission | Combining radio-sensitizing agents with External Beam Radiotherapy (RT) improves radiation-mediated tumor cell killing. The ideal radio-sensitizer should improve RT-mediated tumour cell inactivation by affecting cancer cells only. The dipeptide L-Carnosine (CAR) shows promise, having radio-sensitizing and anti-neoplastic properties in vitro, and is clinically safe. We seek to validate CAR as an in vivo radio-sensitizer which improves radiation-mediated cancer cell inactivation while reducing radiation-mediated healthy tissue damage. Clonogenic assays were conducted to determine the effect of combining varying radiation doses and CAR concentrations in vitro. To evaluate in vivo effects, nude athymic mice were surgically implanted with H1299 in an orthotopic lung tumour model. When tumors reached 5-10 mm3 animals were randomly divided into four groups: Control, RT-only, CAR-only and CAR+RT. Control and RT-only received 8-days of intraperitoneal vehicle, while CAR-only and CAR+RT received 8-days of daily 500 uL of intraperitoneal 1 M CAR. After 4-days of injections, RT treatment delivering a single 20 Gy dose were planned and delivered for RT-only and CAR+RT animals. Bi-weekly computed tomography imaging was conducted for 30-days post-RT to track tumour progression. Animals were sacrificed after 30-days or when they reached the humane endpoint. Lungs were collected and processed for analysis. Pre-treatment of H1299 with 30 mM CAR (CAR+RT) in vitro significantly reduced the surviving fraction by 30% when compared to RT-only, with the reduction increasing beyond a dose of 2.5 Gy. CAR+RT treated animals had significantly smaller tumors by 86% after 11-days post-RT and showed significantly reduced expression of the proliferation marker ki67. CAR+RT animals survived longer compared to all groups. Lung tissue surrounding the tumor showed reduced macrophage numbers for CAR+RT treated animals, when compared to CAR-only or RT-only. CAR could be an effective radio-sensitizer, as it reduced the proliferation of tumor cells and tumor size, in CAR+RT treated animals improving tumor control. |
| Please indicate who nominated you | McGill University, Faculty of Medicine and Health Sciences |
| What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? | Cancer Research |
| What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? | Biomedical |
| PDF of abstract | ICAMAbstract.pdf 2023-01-24 at 11:02:06 |
| Presenter and Author(s) | Li Ming Wang Li Ming Wang Monica Serban Osvaldo Arias Yirui Ren Jan Seuntjens Norma Ybarra |
