In this study, a method of Bacillus subtilis spore inactivation under high pressure (P, 200 MPa) combined with moderate temperature (T, 80 °C) and the addition of antimicrobial peptide LK (102 μg/mL) was investigated. Spores presented cortex hydrolysis and inner membrane (IM) damage with an 8.16 log reduction in response to treatment with PT-LK, as observed by phase-contrast and inverted fluorescence microscopy and flow cytometry (FCM) analysis. Furthermore, a tandem mass tag (TMT) quantitative proteomics approach was utilized because Liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis data were used. After treatment with PT-LK, 17,017 polypeptides and 3166 proteins were detected from B. subtilis spores. Among them, 78 proteins showed significant differences in abundance between the PT-LK-treated and control groups, with 49 proteins being upregulated and 29 proteins being downregulated in the PT-LK-treated group. Genetic information processing, metabolism, cellular process, and environmental information processing were the main mechanisms of PT-LK-mediated spore inactivation.
Intensity-modulated radiation therapy (IMRT) has been used for high-accurate physical dose distribution sculpture and employed to modulate different dose levels into Gross Tumor Volume (GTV), Clinical Target Volume (CTV) and Planning Target Volume (PTV). GTV, CTV and PTV can be prescribed at different dose levels, however, there is an emphasis that their dose distributions need to be uniform, despite the fact that most types of tumour are heterogeneous. With traditional radiomics and artificial intelligence (AI) techniques, we can identify biological target volume from functional images against conventional GTV derived from anatomical imaging. Functional imaging, such as multi parameter MRI and PET can be used to implement dose painting, which allows us to achieve dose escalation by increasing doses in certain areas that are therapy-resistant in the GTV and reducing doses in less aggressive areas. In this review, we firstly discuss several quantitative functional imaging techniques including PET-CT and multi-parameter MRI. Furthermore, theoretical and experimental comparisons for dose painting by contours (DPBC) and dose painting by numbers (DPBN), along with outcome analysis after dose painting are provided. The state-of-the-art AI-based biomarker diagnosis techniques is reviewed. Finally, we conclude major challenges and future directions in AI-based biomarkers to improve cancer diagnosis and radiotherapy treatment.
Objectives: Glioblastoma (GBM) is the most common malignant primary brain tumor with local recurrence after radiotherapy (RT), the most common mode of failure. Standard RT practice applies the prescription dose uniformly across tumor volume disregarding radiological tumor heterogeneity. We present a novel strategy using diffusion-weighted (DW-) MRI to calculate the cellular density within the gross tumor volume (GTV) in order to facilitate dose escalation to a biological target volume (BTV) to improve tumor control probability (TCP). Methods: The pre-treatment apparent diffusion coefficient (ADC) maps derived from DW-MRI of ten GBM patients treated with radical chemoradiotherapy were used to calculate the local cellular density based on published data. Then, a TCP model was used to calculate TCP maps from the derived cell density values. The dose was escalated using a simultaneous integrated boost (SIB) to the BTV, defined as the voxels for which the expected pre-boost TCP was in the lowest quartile of the TCP range for each patient. The SIB dose was chosen so that the TCP in the BTV increased to match the average TCP of the whole tumor. Results: By applying a SIB of between 3.60 Gy and 16.80 Gy isotoxically to the BTV, the cohort’s calculated TCP increased by a mean of 8.44% (ranging from 7.19 to 16.84%). The radiation dose to organ at risk is still under their tolerance. Conclusions: Our findings indicate that TCPs of GBM patients could be increased by escalating radiation doses to intratumoral locations guided by the patient’s biology (i.e., cellularity), moreover offering the possibility for personalized RT GBM treatments. Advances in knowledge: A personalized and voxel level SIB radiotherapy method for GBM is proposed using DW-MRI, which can increase the tumor control probability and maintain organ at risk dose constraints.
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