Project description:Proton (PT) therapy represents an alternative to conventional X-ray therapy, and its clinical application for cancer treatment is on the rise due to associated dose deposit advantages. However, our knowledge of biological responses to PT, in comparison to X-ray, remains in its infancy. Identification of PT specific molecular signals is an important opportunity for the discovery of biomarkers and synergistic drugs. We have profiled the transcriptome regulation of lymphoma cells exposed to clinical sources of PT and X-ray radiation, respectively. Subsequent analysis demonstrated both common and radiation-specific deregulation of gene expression. Gene set enrichment discovered pathways unique to PT \ that contribute to the unfolded protein response (UPR) and mitochondrial transport.
Project description:The aim of the study is to disclose the distinct alteration of biological characteristics of gene expression features in pancreas cancer cell, MIAPaCa-2, irradiated by proton and x-ray. The survived MIAPaCa-2 cells after irradiation with proton and x-ray were isolated and gene expression profiles were analyzed.
Project description:The aim of the study is to disclose the distinct alteration of biological characteristics of gene expression features in pancreas cancer cell, MIAPaCa-2, irradiated by proton and x-ray. The survived MIAPaCa-2 cells after irradiation with proton and x-ray were isolated and gene expression profiles were analyzed.
Project description:The aim of the study is to disclose the distinct alteration of biological characteristics of gene expression features in pancreas cancer cell, MIAPaCa-2, irradiated by proton and x-ray. The survived MIAPaCa-2 cells after irradiation with proton and x-ray were isolated and gene expression profiles were analyzed.
Project description:The aim of the study is to disclose the distinct alteration of biological characteristics of gene expression features in pancreas cancer cell, MIAPaCa-2, irradiated by proton and x-ray. The survived MIAPaCa-2 cells after irradiation with proton and x-ray were isolated and gene expression profiles were analyzed.
Project description:Novel particle therapy was implemented into standard-of-care for cancer patients during the last years. However, experimental studies investigating cellular and molecular mechanisms are lacking although prognostic biomarker are urgently needed. The cancer stem cell (CSC)-related marker aldehyde dehydrogenase (ALDH) is known to impact on prostate cancer radiosensitivity through affecting defense against reactive oxygen species (ROS), reducing DNA damage repair and increasing cell survival. Surprisingly, we could show in a previous study that ionizing radiation itself enriches for ALDH-positive CSCs in a time- and dose-dependent manner through alteration in histone methylation. Within the present study, we investigated CSC marker dynamics upon proton beam irradiation and hypothesized that this novel particle therapy may have increased CSC targeting potential due to its increased ionization potential compared to conventional photon irradiation. However, we found that proton irradiation is affecting cellular dynamics and escape from cell death.
Project description:Novel particle therapy was implemented into standard-of-care for cancer patients during the last years. However, experimental studies investigating cellular and molecular mechanisms are lacking although prognostic biomarker are urgently needed. The cancer stem cell (CSC)-related marker aldehyde dehydrogenase (ALDH) is known to impact on prostate cancer radiosensitivity through affecting defense against reactive oxygen species (ROS), reducing DNA damage repair and increasing cell survival. Surprisingly, we could show in a previous study that ionizing radiation itself enriches for ALDH-positive CSCs in a time- and dose-dependent manner through alteration in histone methylation. Within the present study, we investigated CSC marker dynamics upon proton beam irradiation and hypothesized that this novel particle therapy may have increased CSC targeting potential due to its increased ionization potential compared to conventional photon irradiation. However, we found that proton irradiation is affecting cellular dynamics and escape from cell death.
Project description:Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume. These mice were then monitored for the remainder of their lifespan and a large number of T cell lymphomas were analysed, alongside those arising in mice exposed to equivalent doses of standard Cs137 gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikaros, Pten, Trp53 and Bcl11b genes we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. 32 unique tumours (12 gamma ray-induced, 20 carbon ion-induced) each with sex-matched reference DNA
Project description:Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume. These mice were then monitored for the remainder of their lifespan and a large number of T cell lymphomas were analysed, alongside those arising in mice exposed to equivalent doses of standard Cs137 gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikaros, Pten, Trp53 and Bcl11b genes we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed.
Project description:Proton irradiation is touted for its improved tumor targeting due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory have shown that, in addition to targeting advantages, proton irradiation can inhibit angiogenic and immune factors and thereby modulate tumor progression. High-energy protons also constitute a principal component of the galactic cosmic rays to which astronauts are exposed. Increased understanding of the biological effects of proton exposure would thus contribute to both improved cancer therapy and carcinogenesis risk assessment for space travel. In addition, age plays a major role in tumor incidence and is a critical consideration for estimating cancer risk. We investigated the effects of host age and proton exposure on tumor progression. Tumor lag time and growth dynamics were tracked following injection of murine Lewis lung carcinoma (LLC) cells into young (68 day) versus old (736 day) mice with or without coincident irradiation. Tumor progression was suppressed in old compared to young mice. Differences in progression were further modulated by proton irradiation (1GeV), with increased inhibition evident in old mice. Through global transcriptome analysis, TGFβ1 and TGFβ2 were determined to be key players that contributed to the tumor dynamics observed. These findings point to older hosts providing decreased systemic tumor support, which can be further inhibited by proton irradiation.