In cancer radiotherapy, the lack of fixed DNA damage by oxygen in hypoxic microenvironment of solid tumors often leads to severe radioresistance. Nitric oxide (NO) is a potent radiosensitizer that acts in two ways. It can directly react with the radical DNA thus fixing the damage. It also normalizes the abnormal tumor vessels, thereby increasing blood perfusion and oxygen supply. To achieve these functions, the dosage and duration of NO treatment need to be carefully controlled, otherwise it will lead to the exact opposite outcomes. However, a delivery method that fulfills both requirements is still lacking. A NO depot is designed for the control of NO releasing both over quantity and duration for hypoxic tumor vessel normalization and radiosensitization. In B16‐tumor‐bearing mice, the depot can provide low dosage NO continuously and release large amount of NO immediately before irradiation for a short period of time. These two modes of treatment work in synergy to reverse the radioresistance of B16 tumors more efficiently than releasing at single dosage.

The P16 (CDKN2Aink4a) gene is an endogenous CDK4/6 inhibitor. Palbociclib (PD0332991) is an anti-CDK4/6 chemical for cancer treatment. P16 is most frequently inactivated by copy number deletion and DNA methylation in cancers. It is well known that cancer cells with P16 deletion are more sensitive to palbociclib than those without. However, whether P16 methylation is related to palbociclib sensitivity is not known. By analyzing public pharmacogenomic datasets, we found that the IC50 of palbociclib in cancer cell lines (n = 522) was positively correlated with both the P16 expression level and P16 gene copy number. Our experimental results further showed that cancer cell lines with P16 methylation were more sensitive to palbociclib than those without. To determine whether P16 methylation directly increased the sensitivity of cancer cells to palbociclib, we induced P16 methylation in the lung cancer cell lines H661 and HCC827 and the gastric cancer cell line BGC823 via an engineered P16-specific DNA methyltransferase (P16-Dnmt) and found that the sensitivity of these cells to palbociclib was significantly increased. The survival rate of P16-Dnmt cells was significantly lower than that of vector control cells 48 hrs post treatment with palbociclib (10 μM). Notably, palbociclib treatment also selectively inhibited the proliferation of the P16-methylated subpopulation of P16-Dnmt cells, further indicating that P16 methylation can increase the sensitivity of cells to this CDK4/6 inhibitor. These results were confirmed in an animal experiment. In conclusion, inactivation of the P16 gene by DNA methylation can increase the sensitivity of cancer cells to palbociclib.

BackgroundNucleotide-binding oligomerization domain-containing protein 2 (NOD2) may play an important role in the outcome of kidney cancer patients. To explore the relationship between NOD2 and the prognosis of kidney cancer patients, a databank-based reanalysis was conducted.Materials and MethodsData related to kidney cancer patients at least with survival information, was obtained mainly from The Cancer Genome Atlas (TCGA). Some clinical data, not available online, was collected by personal email to the author. Then, we reanalyzed all the data in order to make a conclusion about the relationship between NOD2 gene and the prognosis of kidney cancer patients.ResultsA total of 1953 samples with NOD2 information from four databanks of The Cancer Genome Atlas (TCGA) were enrolled in this study. The results of KIPAN showed the Kaplan-Meier curve for risk groups, concordance index, and p-value of the log-rank testing equality of survival curves ( Concordance Index = 56.57, Log−Rank Equal Curves p=0.0009006, R^2 = 0.036/0.953, Risk Groups Hazard Ratio = 1.61 (conf. int. 1.21 ~ 2.13), p = 0.001005) , while a box plot across risk groups, including the p-value testing for difference using t-test (or f-test for more than two groups) was shown. There was a statistical significance for the p value of the result (p < 0.01 ). The similar results could be seen in KIRC and the fourth data (including 468 samples).ConclusionsThe status of NOD2 gene maybe a biomarker for the survival of kidney cancer patients.

The risk of venous thrombosis and mortality associated with central catheter (PICC/CICC) for malignant tumor patients is not definite. So, we carried out a systematic review and meta-analysis to evaluate it. Among patients with comparing PICC with CICC, odds ratio (OR) or risk ratio (RR) was calculated with a random effect model meta-analysis. The result of the stratification analysis of 7 studies (PICC vs CICC) supported the theory that CICCs were associated with a decrease in the odds ratio of thrombosis compared with PICCs. 7 of 15 studies provided the information about the compared mortality rate of the patients. The result showed that CICCs were associated with a decrease in the odds ratio of thrombosis compared with PICCs (OR = 0.45, 95% CI:0.32–0.62, p < 0.0001, I2 = 0%,Tau2 = 0.00). Meta-analysis of 8 studies of 2639 patients showed that pharmacological deep vein thrombosis prophylaxis drugs could decrease the risk of mortality of malignant tumor patients with CICCs (RR = 0.58, 95% CI:0.48–0.71, Z = 5.32, p < 0.0001, I2 = 71%). We found that PICCs are associated with a raised risk of deep vein thrombosis, and pharmacological deep vein thrombosis prophylaxis drugs is a beneficial factor in decreasing the incidence of thrombosis, while warfarin may decrease the risk of mortality of malignant tumor patients with CICCs.

To explore the relationship between mouse double minute 2 binding protein (MTBP) and the prognosis of cancer patients, a databank-based reanalysis was conducted and a clinical observation about lung adenocarcinoma was taken to verify the result of data analysis.We reanalyzed all the downloaded data in order to make a conclusion about the relationship between MTBP and the prognosis of cancer patients. At last, we collected 112 lung cancer patients with MTBP information to verify the results of data analysis (GSE30219).The overall Kaplan-Meier curve results of 6 eligible data groups were shown in Fig. 1. The Kaplan-Meier curve result of GSE16011 was shown in Fig. 1A (concordance index = 59.48, Log-Rank Equal Curves [P = 5.942e-05], R = 0.045/1, risk groups hazard ratio = 1.69 [conf. int. 1.3-2.9], P = 7.344e-05), while the stratification results were displayed independently in Figs. 2 and 3. The similar results could be seen in other 5 data groups. The tissue sections of 112 patients with lung adenocarcinoma were collected and immunohistochemically stained. The hyper expression rate of MTBP in adenocarcinoma was 23.21% (26/112). The results showed that patients with hyper expression of MTBP had significantly worse prognosis than the control group, and the survival curves were clearly separated from each other (Fig. 4B, P = .000).Hyper expression of MTBP maybe an adverse event for the survival of some cancer patients, especially in glioblastoma, kidney cancer, and lung cancer patients, which has been verified in 112 lung cancer patients with MTBP status.