[Mn(PaPy2Q)(NO)]ClO4, a Near-Infrared Light activated release of Nitric Oxide drug as a nitric oxide donor for therapy of human prostate cancer cells in vitro and in vivo

This study was the first to investigate the synthesis of near-infrared light-sensitive NO prodrug [Mn(PaPy2Q)(NO)]ClO4, and detection the amount of NO released by the drug in different time and near infrared light (10 mW, 20 mW). It showed that with the increase of light power, the time required for the drug to release NO was shortened, and we selected 20 mW, 10 min as a follow-up study of light power and irradiation time while ensuring the near-infrared light did not affect tumor cells. The cells were irradiated with 20 mW of near-infrared light for 10 min at 6 h after treatment with the drug on PC-3, LNCaP and 22RV1 cells, and NO concentration and cell survival rate were tested at 12 h, 24 h and 48 h. Experiments showed that NO concentration remained stable within 48 h and [Mn(PaPy2Q)(NO)]ClO4 inhibited the proliferation of cells in a concentration and time-dependent manner. Then we also found that [Mn(PaPy2Q)(NO)]ClO4 increased the expression of apoptosis-related proteins (PARP, Bax, Caspase 3/9), inhibited the expression of BCl-2 and increased the activity level of Caspase 3/7, which showed [Mn(PaPy2Q)(NO)]ClO4 promoted prostate cancer cells apoptosis. Next, the results in xenograft mouse model showed that [Mn(PaPy2Q)(NO)]ClO4 also had anti-prostate cancer effects in vivo, and the NO concentration increased in the tumor after near-infrared light irradiation. After [Mn(PaPy2Q)(NO)]ClO4 treatment 6 weeks, tumor volume was significantly reduced, Ki67 and BrdU protein expression was significantly reduced. TUNEL assay results showed that [Mn(PaPy2Q)(NO)]ClO4 could promote the apoptosis of solid tumors in vivo and in a concentration-dependent manner

Table_2_Construction of a prognostic 6-gene signature for breast cancer based on multi-omics and single-cell data.csv

BackgroundBreast cancer (BC) is one of the females’ most common malignant tumors there are large individual differences in its prognosis. We intended to uncover novel useful genetic biomarkers and a risk signature for BC to aid determining clinical strategies.MethodsA combined significance (pcombined) was calculated for each gene by Fisher’s method based on the RNA-seq, CNV, and DNA methylation data from TCGA-BRCA. Genes with a pcombinedResultsThe RS signature consisted of C15orf52, C1orf228, CEL, FUZ, PAK6, and SIRPG showed good performance. It could distinguish the prognosis of patients well, even stratified by disease stages or subtypes and also showed a stronger predictive ability than traditional clinical indicators. The down-regulated expressions of many immune checkpoints, while the decreased sensitivity of many antitumor drugs was observed in TNBC patients with higher RS. The overall cells and lymphocytes composition differed between patients with different RS, which could facilitate a more personalized treatment.ConclusionThe six genes RS signature established based on multi-omics data exhibited well performance in predicting the prognosis of BC patients, regardless of disease stages or subtypes. Contributing to a more personalized treatment, our signature might benefit the outcome of BC patients.</p

DataSheet_1_Construction of a prognostic 6-gene signature for breast cancer based on multi-omics and single-cell data.docx

BackgroundBreast cancer (BC) is one of the females’ most common malignant tumors there are large individual differences in its prognosis. We intended to uncover novel useful genetic biomarkers and a risk signature for BC to aid determining clinical strategies.MethodsA combined significance (pcombined) was calculated for each gene by Fisher’s method based on the RNA-seq, CNV, and DNA methylation data from TCGA-BRCA. Genes with a pcombinedResultsThe RS signature consisted of C15orf52, C1orf228, CEL, FUZ, PAK6, and SIRPG showed good performance. It could distinguish the prognosis of patients well, even stratified by disease stages or subtypes and also showed a stronger predictive ability than traditional clinical indicators. The down-regulated expressions of many immune checkpoints, while the decreased sensitivity of many antitumor drugs was observed in TNBC patients with higher RS. The overall cells and lymphocytes composition differed between patients with different RS, which could facilitate a more personalized treatment.ConclusionThe six genes RS signature established based on multi-omics data exhibited well performance in predicting the prognosis of BC patients, regardless of disease stages or subtypes. Contributing to a more personalized treatment, our signature might benefit the outcome of BC patients.</p