Heterotypic cell-in-cell structures between cancer and NK cells are associated with enhanced anticancer drug resistance.

The heterotypic CIC structures formed of cancer and immune cells have been observed in tumor tissues. We aimed to assess the feasibility of using heterotypic CICs as a functional biomarker to predict NK susceptibility and drug resistance. The heterotypic CIC-forming cancer cells showed a lower response to NK cytotoxicity and higher proliferative ability than non-CIC cancer cells. After treatment with anticancer drugs, cancer cells that formed heterotypic CICs showed a higher resistance to anticancer drugs than non-CIC cancer cells. We also observed the formation of more CIC structures in cancer cells treated with anticancer drugs than in the non-treated group. Our results confirm the association between heterotypic CIC structures and anticancer drug resistance in CICs formed from NK and cancer cells. These results suggest a mechanism underlying immune evasion in heterotypic CIC cancer cells and provide insights into the anticancer drug resistance of cancer cells.

Comparative effect of angiotensin converting enzyme inhibitor versus angiotensin ii type i receptor blocker in acute myocardial infarction with non-obstructive coronary arteries; from the Korea Acute Myocardial Infarction Registry - National Institute of Health.

BACKGROUND: Selecting angiotensin converting enzyme inhibitor (ACEI) or angiotensin II type I receptor blocker (ARB) in patients diagnosed as acute myocardial infarction (AMI) with non-obstructive coronary arteries (MINOCA) is not established. The purpose of this study is to compare the clinical effect of ACEI vs. ARB in MINOCA patients. METHODS AND RESULTS: A total of 273 patients between November 2011 to June 2015, diagnosed with MINOCA who were registered in the Korea Acute Myocardial Infarction Registry - National Institute of Health were enrolled. Patients were divided into ACEI (n = 112) and ARB groups (n = 161). The primary endpoint was cumulative incidence of major adverse cardiac events (MACE) defined as cardiac death, recurrent MI, any new revascularization during 2 years clinical follow-up. Secondary endpoint was heart failure requiring re-hospitalization. Propensity score matching analysis was done. The incidence of primary endpoint was similar (10.4% vs. 15.6%, HR: 0.65; 95% CI: 0.29-1.47; p = 0.301) among both groups. However, the incidence of recurrent MI was significantly lower in ACEI group compared to ARB group (2.1% vs. 10.4%, HR: 0.18, 95% CI: 0.04-0.86; p = 0.031). CONCLUSIONS: In the present study, the risk and incidence of MACE was similar between ACEI and ARB therapy in MINOCA patients. However, ACEI significantly reduced the risk of recurrent MI. Further larger scale multi-center randomized clinical trials are needed to clarify the proper use of renin-angiotensin-aldosterone system blocker in these patients.

Optimal Revascularization Strategy in Non-ST-Segment-Elevation Myocardial Infarction With Multivessel Coronary Artery Disease: Culprit-Only Versus One-Stage Versus Multistage Revascularization.

Background Few studies have investigated optimal revascularization strategies in non-ST-segment-elevation myocardial infarction with multivessel disease. We investigated 3-year clinical outcomes according to revascularization strategy in patients with non-ST-segment-elevation myocardial infarction and multivessel disease. Methods and Results This retrospective, observational, multicenter study included patients with non-ST-segment-elevation myocardial infarction and multivessel disease without cardiogenic shock. Data were analyzed at 3 years according to the percutaneous coronary intervention strategy: culprit-only revascularization (COR), 1-stage multivessel revascularization (MVR), and multistage MVR. The primary outcome was major adverse cardiac events (MACE: a composite of all-cause death, nonfatal spontaneous myocardial infarction, or any repeat revascularization). The COR group had a higher risk of MACE than those involving other strategies (COR versus 1-stage MVR; hazard ratio, 0.65; 95% CI, 0.54-0.77; P<0.001; and COR versus multistage MVR; hazard ratio, 0.74; 95% CI, 0.57-0.97; P=0.027). There was no significant difference in the incidence of MACE between 1-stage and multistage MVR (hazard ratio, 1.14; 95% CI, 0.86-1.51; P=0.355). The results were consistent after multivariate regression, propensity score matching, inverse probability weighting, and Bayesian proportional hazards modeling. In subgroup analyses stratified by the Global Registry of Acute Coronary Events score, 1-stage MVR lowered the risk of MACE compared with multistage MVR in low-to-intermediate risk patients but not in patients at high risk. Conclusions MVR reduced 3-year MACE in patients with non-ST-segment-elevation myocardial infarction and multivessel disease compared with COR. However, 1-stage MVR was not superior to multistage MVR for reducing MACE except in low-to-intermediate risk patients.

Peroxisome-targeted Supramolecular Nanoprobes Assembled with Pyrene-labelled Peptide Amphiphiles.

Despite the versatile metabolic functions of peroxisomes such as lipid synthesis and fatty acid oxidation and their relevance to genetically inherited diseases, namely, peroxisome biogenesis disorders and peroxisomal enzyme deficiency, there is not much research on peroxisome-targeting therapeutics. Herein we present supramolecular nanostructured probes based on the self-assembly of peptide amphiphiles (PAs) having peroxisome-targeting ability in mammalian cells. The PA was designed to include the peroxisome-targeting tripeptide (SKL) and a fluorescent dye (pyrene). It was revealed that the presence of the SKL-appended carboxyl terminal group of PA, the extent of α-helical nature of the peptide block, and the fibrillar morphology of nano-assemblies affected the targeting efficiency of PA supramolecular nanoprobe. The simple modification of PAs by the peroxisome-targeting strength prediction showed an enhanced peroxisome specificity, as expected. This work provides important insights into designing subcellular organelle-targeting nanoparticles for next-generation nanomedicines.