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Showing posts from March, 2023

Human Equivalent Dose: Limitations and Alternatives

Human equivalent dose (HED) is a widely used concept in drug development, but it has limitations in accurately predicting the appropriate dose for humans based on animal studies alone. In this article, we will explore the limitations of HED and some of the alternatives that researchers are using to better predict drug dosing in humans. Limitations of HED One of the main limitations of HED is the assumption that metabolic rate scales predictably with body weight across species. However, metabolic rate can vary between species and can be affected by factors such as age, gender, and disease state. This variability can make it difficult to accurately predict the appropriate dosage for humans based on animal studies alone. Another limitation of HED is the lack of consideration for other factors that can affect drug metabolism and response in humans, such as genetic differences and drug-drug interactions. HED calculations assume that all humans have the same metabolic rate and response to

Researchers Discover Key to T Cell Exhaustion in Cancer Treatment

Scientists have found the source of T cell exhaustion, a problem that reduces the effectiveness of CAR T-cell therapy, a treatment used to fight cancer. CAR T-cell therapy uses a patient's immune system T cells, modifies them to attack cancer cells, and then injects them back into the patient. However, these T cells often become exhausted and stop fighting cancer. Researchers from Dana-Farber Cancer Institute and NYU Grossman School of Medicine have discovered that mSWI/SNF protein complexes play a crucial role in both activating T cells and causing exhaustion. This finding, published in the journal Molecular Cell, suggests that targeting these complexes could reduce exhaustion and improve the ability of CAR T cells to fight cancer. The scientists found that the location of mSWI/SNF complexes on T cell DNA changes depending on certain proteins called transcription factors. By inhibiting specific genes related to these complexes, the T cells were able to continue fighting cancer