3 dimensional Printable concentrated fluid metal amalgamated with high thermal conductivity
CBP/P300 inhibition promoted the regeneration of intestinal organoids invitro and of crypts invivo. Remarkably, the administration of CBP/P300 inhibitors to mice 24 hours after lethal irradiation promoted Lgr5
intestinal stem cell and crypt recovery, resulting in improved mouse survival. Moreover, our data show that CBP/P300 inhibitors rescued irradiated mice from RIGS by delaying intestinal epithelial cell cycle progression after radiation.
These data demonstrate that CBP/P300 inhibitors are effective medical countermeasures to mitigate gastrointestinal toxicity from radiation.
These data demonstrate that CBP/P300 inhibitors are effective medical countermeasures to mitigate gastrointestinal toxicity from radiation.
Autoimmune connective tissue disease (CTD) has historically represented a relative contraindication to breast conservation (BC) among patients with early-stage breast cancer. Controversy exists regarding the use of hypofractionated radiation therapy (RT) among patients with CTDs. We evaluated acute and late toxicity in patients with breast cancer and CTD treated with BC.
Of 1983 patients treated with BC from 2012 to 2016, we identified 91 patients with an autoimmune disease (AD). Each patient was matched to a control without AD based on age, RT field, and fractionation. RT toxicity and clinician-rated cosmesis were compared between cases and controls. Overall survival, disease-free survival, and local recurrence-free survival were estimated using the Kaplan-Meier method.
The median follow-up was 49.9 months for cases and 53.0 months for controls, and 67% of cases and controls were treated with hypofractionated RT. There was no difference in grade 2/3 acute toxicity between cases and controls (26.4% vs. late toxicity in the patients treated with hypofractionation.
In the largest matched case-control study of patients with CTD treated with conventional and hypofractionated RT, we demonstrate low rates of radiation toxicity, with good to excellent clinician-rated cosmesis. There was increased late toxicity in cases, especially in patients with active AD at time of RT. There was no increase in acute or late toxicity in the patients treated with hypofractionation.
Advances in germline genetic testing have led to a surge in identification of ATM variant carriers among breast cancer patients, raising numerous questions regarding use of breast radiotherapy (RT) in this population.
A literature search utilizing PubMed identified articles assessing association(s) between germline ATM variant status and risk of toxicity following breast RT. An expert panel of breast radiation oncologists, genetic counselors and basic scientists convened to review the association between ATM variants and radiation-induced toxicity or secondary malignancy risk and determine any impact on breast RT recommendations.
Carriers of pathogenic variants in ATM have a 2-4-fold increased risk for developing breast cancer. ATM variants do not consistently increase risk of toxicities following RT, except possibly among patients with the single nucleotide variant, c5557G>A (rs1801516) in whom a small increased risk for the development of both acute and late radiation effects has been identified. Itients younger than 45 years old with certain rare deleterious ATM variants who may be at higher risk for developing CBC. These latter patients should be counseled regarding this potential risk, and every effort should be made to minimize contralateral breast dose. However, the inconsistency of published data limits precise recommendations, magnifying the need for further prospective study and the development of a centralized database cataloging RT outcomes and genetic status.
The differential response of normal and tumor tissues to ultrahigh-dose-rate radiation (FLASH) has raised new hope for treating solid tumors but, to date, the mechanism remains elusive. One leading hypothesis is that FLASH radiochemically depletes oxygen from irradiated tissues faster than it is replenished through diffusion. The purpose of this study was to investigate these effects within hypoxic multicellular tumor spheroids through simulations and experiments.
Physicobiological equations were derived to model (1) the diffusion and metabolism of oxygen within spheroids; (2) its depletion through reactions involving radiation-induced radicals; and (3) the increase in radioresistance of spheroids, modeled according to the classical oxygen enhancement ratio and linear-quadratic response. These predictions were then tested experimentally in A549 spheroids exposed to electron irradiation at conventional (0.075 Gy/s) or FLASH (90 Gy/s) dose rates. Clonogenic survival, cell viability, and spheroid growth werexygen depletion and its slow replenishment are critical components of the FLASH effect.
Tumor spheroids can be used as a model to study FLASH irradiation in vitro. ML265 cell line The improved survival of tumor spheroids receiving FLASH radiation confirms that ultrafast radiochemical oxygen depletion and its slow replenishment are critical components of the FLASH effect.Natural language processing (NLP), which aims to convert human language into expressions that can be analyzed by computers, is one of the most rapidly developing and widely used technologies in the field of artificial intelligence. Natural language processing algorithms convert unstructured free text data into structured data that can be extracted and analyzed at scale. In medicine, this unlocking of the rich, expressive data within clinical free text in electronic medical records will help untap the full potential of big data for research and clinical purposes. Recent major NLP algorithmic advances have significantly improved the performance of these algorithms, leading to a surge in academic and industry interest in developing tools to automate information extraction and phenotyping from clinical texts. Thus, these technologies are poised to transform medical research and alter clinical practices in the future. Radiation oncology stands to benefit from NLP algorithms if they are appropriately developed and ncology research and clinics.