"In conclusion, the newly identified PARP1-CTF18-Polϵ #exonuclease axis and HDR act independently to prevent fork collapse at single-ended double-strand breaks. #Olaparib inhibits this axis, explaining the pronounced #cytotoxic effects of olaparib on HDR-deficient cells."

https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkad999/7369941

#polymerase #DNA #replication #mutations #cancer #oncology #cellBiology #genetics

Why Does COVID-19 Cause Severe Illness in Some Patients but Not Others?

Factors linked to disease outcomes included viral load, frequencies of certain cell types such as #cytotoxic #natural #killer (#NK) cells, various #inflammatory #states, and markers of #myocardial #damage.

In participants who died of the infection, #viral #loads persisted and even started to rise over time. By contrast, viral loads steadily declined in those with milder infections.

The activation of cell types such as cytotoxic NK cells increased in the milder cases as participants’ immune systems ramped up in response to the infection, while these cells decreased in the more severe groups.

Furthermore, participants who were sickest had higher levels of inflammatory markers upon hospitalization that increased over time, while patients in the milder groups showed an opposite pattern

< Yale School of Medicine

https://medicine.yale.edu/news-article/why-does-covid-19-cause-severe-illness-in-some-patients-but-not-others/

What if we could trace #cytotoxic #Tcells throughout the human body before and during #cancer #immunotherapy?

Researchers at the University of Groningen have used a CD8-specific positron emission tomography (#PET) tracer in a phase 1/2 clinical trial. Patients with solid tumors were imaged before and ~30 days after starting treatment with #antibodies against PD-L1, PD-1, and/or CTLA-4.

Article in Nature Medicine: https://www.nature.com/articles/s41591-022-02084-8

#checkpointinhibitor #solidtumor #clinicaltrial