Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan,
This study attempted to profile the tumor immune microenvironment (TIME) of non-small cell lung cancer (NSCLC) by multiplex immunofluorescence of 681 NSCLC cases. The number, density, and proportion of 26 types of immune cells in tumor nest and tumor stroma were evaluated, revealing some close interactions particularly between intrastromal neutrophils and intratumoral regulatory T cells (Treg) (r2 = 0.439, P < 0.001), intrastromal CD4+CD38+ T cells and CD20-positive B cells (r2 = 0.539, P < 0.001), and intratumoral CD8-positive T cells and M2 macrophages expressing PD-L1 (r2 = 0.339, P < 0.001). Three immune subtypes correlated with distinct immune characteristics were identified using the unsupervised consensus clustering approach. The immune-activated subtype had the longest disease-free survival (DFS) and demonstrated the highest infiltration of CD4-positive T cells, CD8-positive T cells, and CD20-positive B cells. The immune-defected subtype was rich in cancer stem cells and macrophages, and these patients had the worst prognosis. The immune-exempted subtype had the highest levels of neutrophils and Tregs. Intratumoral CD68-positive macrophages, M1 macrophages, and intrastromal CD4+ cells, CD4+FOXP3- cells, CD8+ cells, and PD-L1+ cells were further found to be the most robust prognostic biomarkers for DFS, which were used to construct and validate the immune-related risk score for risk stratification (high vs. median vs. low) and the prediction of 5-year DFS rates (23.2% vs. 37.9% vs. 43.1%, P < 0.001). In conclusion, the intricate and intrinsic structure of TIME in NSCLC was demonstrated, showing potency in subtyping and prognostication.
Reactive oxygen species (ROS) induction is an effective mechanism to kill cancer cells for many chemotherapeutics, while resettled redox homeostasis induced by the anticancer drugs will promote cancer chemoresistance. Natural
ent
-kaurane diterpenoids have been found to bind glutathione (GSH) and sulfhydryl group in antioxidant enzymes covalently, which leads to the destruction of intracellular redox homeostasis. Therefore, redox resetting destruction by
ent
-kaurane diterpenoids may emerge as a viable strategy for cancer therapy. In this study, we isolated 30
ent
-kaurane diterpenoids including 20 new samples from Chinese liverworts
Jungermannia tetragona
Lindenb and studied their specific targets and possible application in cancer drug resistance through redox resetting destruction. 11
β
-hydroxy-
ent
-16-kaurene-15-one (
23
) possessed strong inhibitory activity against several cancer cell lines. Moreover, compound
23
induced both apoptosis and ferroptosis through increasing cellular ROS levels in HepG2 cells. ROS accumulation induced by compound
23
was caused by inhibition of antioxidant systems through targeting peroxiredoxin I/II (Prdx I/II) and depletion of GSH. Furthermore, compound
23
sensitized cisplatin (CDDP)-resistant A549/CDDP cancer cells
in vitro
and
in vivo
by inducing apoptosis and ferroptosis. Thus, the
ent
-kaurane derivative showed potential application for sensitizing CDDP resistance by redox resetting destruction through dual inhibition of Prdx I/II and GSH in cancer chemotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.