Cancer radioresistance is characterized by a differential lipid droplet content along the cell cycle.

BACKGROUND: Cancer radiation treatments have seen substantial advancements, yet the biomolecular mechanisms underlying cancer cell radioresistance continue to elude full understanding. The effectiveness of radiation on cancer is hindered by various factors, such as oxygen concentrations within tumors, cells' ability to repair DNA damage and metabolic changes. Moreover, the initial and radiation-induced cell cycle profiles can significantly influence radiotherapy responses as radiation sensitivity fluctuates across different cell cycle stages. Given this evidence and our prior studies establishing a correlation between cancer radiation resistance and an increased number of cytoplasmic Lipid Droplets (LDs), we investigated if LD accumulation was modulated along the cell cycle and if this correlated with differential radioresistance in lung and bladder cell lines. RESULTS: Our findings identified the S phase as the most radioresistant cell cycle phase being characterized by an increase in LDs. Analysis of the expression of perilipin genes (a family of proteins involved in the LD structure and functions) throughout the cell cycle also uncovered a unique gene cell cycle pattern. CONCLUSIONS: In summary, although these results require further molecular studies about the mechanisms of radioresistance, the findings presented here are the first evidence that LD accumulation could participate in cancer cells' ability to better survive X-Ray radiation when cells are in the S phase. LDs can represent new players in the radioresistance processes associated with cancer metabolism. This could open new therapeutic avenues in which the use of LD-interfering drugs might enhance cancer sensitivity to radiation.

Changes in Radical Levels as a Cause for the FLASH effect: Impact of beam structure parameters at ultra-high dose rates on oxygen depletion in water.

The influence of different average and bunch dose rates in electron beams on the FLASH effect was investigated. The present study measures O2 content in water at different beam pulse patterns and finds strong correlation with biological data, strengthening the hypothesis of radical-related mechanisms as a reason for the FLASH effect.

Does FLASH deplete oxygen? Experimental evaluation for photons, protons, and carbon ions.

PURPOSE: To investigate experimentally, if FLASH irradiation depletes oxygen within water for different radiation types such as photons, protons, and carbon ions. METHODS: This study presents measurements of the oxygen consumption in sealed, 3D-printed water phantoms during irradiation with x-rays, protons, and carbon ions at varying dose rates up to 340 Gy/s. The oxygen measurement was performed using an optical sensor allowing for noninvasive measurements. RESULTS: Oxygen consumption in water only depends on dose, dose rate, and linear energy transfer (LET) of the irradiation. The total amount of oxygen depleted per 10 Gy was found to be 0.04% atm - 0.18% atm for 225 kV photons, 0.04% atm - 0.25% atm for 224 MeV protons, and 0.09% atm - 0.17% atm for carbon ions. Consumption depends on dose rate by an inverse power law and saturates for higher dose rates because of self-interactions of radicals. Higher dose rates yield lower oxygen consumption. No total depletion of oxygen was found for clinical doses. CONCLUSIONS: FLASH irradiation does consume oxygen, but not enough to deplete all the oxygen present. For higher dose rates, less oxygen was consumed than at standard radiotherapy dose rates. No total depletion was found for any of the analyzed radiation types for 10 Gy dose delivery using FLASH.

First total synthesis of the neuronal cell protecting carbazole alkaloid carbazomadurin A by sequential transition metal-catalyzed reactions.

The highly oxygenated neuronal cell protecting carbazole alkaloid carbazomadurin A was synthesized in nine steps and 11% overall yield from isovanillic acid.