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46 Our observation of inconsistent autophagy dependency in patient-derived organoids (PDOs) under vertical RAS pathway inhibition may be due to the shorter time spans of 3D culture conditions (only 72 h compared with 2D assays with 714 days, allowing compensatory mechanisms to become more relevant) and/or the lower proliferative activity and more complex architecture of PDOs, including 3D cellcell interactions and oxygen/nutrient gradients, which may affect the regulation and necessity of autophagy differently than 2D cultures do

Neutrophils are the main sources of inflammatory mediators and can release the potent reactive oxygen species, which are cytotoxic and can promote tissue injury [37]

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