Anti-NCL monoclonal antibody, clone 240DU54.9.6

Injectable implants with the ability to form in situ are one of the most promising carriers for the delivery of chemotherapeutic drugs to tumor sites. We have reported a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA), ethyl oleate, along with the sol-gel phase transition. The chemotherapeutic drug-loaded injectable NBCA ethyl oleate implant (INEI) exhibited excellent therapeutic efficacy for local chemotherapy. Herein, we utilize this INEI to carry N, N '-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide) (TE-C-5003), which is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor, to treat the lung cancer mice model. The in vitro experiment shows that TE-C-5003 has a good anti-tumor effect on lung cancer (IC50 = 0.7022 mu M for A549; IC50 = 0.6844 mu M for NCL-H1299) and breast cancer (IC50 = 0.4128 mu M for MCF-7; IC50 = 0.5965 mu M for MDA-MB-231). Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human lung cancer cells by the TE-C-5003-loaded INEI (40% NBCA) was 68.23%, which is far more than TC-E-5003 alone (31.76%). Our study further confirms that INEI is an effective technique to improve the anti-tumor effect. The druggability of small molecule compounds can be improved with the help of the mentioned technology. Also, TC-E-5003 may be developed as a broad spectrum anti-tumor drug.

Background-The nonculprit lesion (NCL) management in ST-segment-elevation myocardial infarction patients with multivessel disease is debated. We sought to assess whether quantitative flow ratio (QFR), a noninvasive tool to identify potentially flow-limiting lesions, may be reliable in this scenario. Methods and Results-The present proof-of-concept study is based on a 3-step process: (1) identification of the QFR reproducibility in NCLs assessment (cohort A, n= 31); (2) prospective validation of QFR diagnostic accuracy in respect to fractional flow reserve (cohort B, n= 45); and (3) investigation of long-term clinical outcomes of NCLs stratified according to QFR (cohort C, n= 110). A blinded core laboratory computed QFR values for all NCLs. Cohort A showed a good correlation and agreement between QFR values at index (acute) and at staged (subacute, 3-4 days later) procedures (r=0.98; 95% confidence interval, 0.96-0.99; mean difference, 0.004 [-0.027 to 0.34]). The inter-rater agreement was kappa=0.9. In cohort B, fractional flow reserve and QFR identified 16 (33%) and 17 (35%) NCLs potentially flow limiting. Sensitivity, specificity, negative, and positive predictive values were 88%, 97%, 94%, and 94%. The area under the receiver operating characteristics curve was 0.96 (95% confidence interval, 0.89-0.99). Finally, in cohort C, we identified 110 ST-segmentelevation myocardial infarction patients where at least 1 NCL was left untreated. Patients with NCLs showing a QFR value <= 0.80 were at higher risk of adverse events (hazard ratio, 2.3; 95% confidence interval, 1.2-4.5; P=0.01). Conclusions-In a limited and selected study population, our study showed that QFR computation may be a safe and reliable tool to guide coronary revascularization of NCLs in ST-segment-elevation myocardial infarction patients.