ABSTRACT
Optimizing the colloidal state of polyamic acid (PAA) nanoparticles is essential for achieving a uniform and high-performance polyimide coating by electrophoretic deposition (EPD) on metal substrates of various shapes. In this paper, we report two important roles of the counterions in the formation of PAA colloids for EPD, which, to date, have not been recognized. First, when tertiary alkyl amines are used to neutralize PAA, the polarity of neutralizing counterions determines the size and stability of the PAA colloidal particles. The polarity can be finely tuned by using two different tertiary alkyl amines containing polar and nonpolar groups and adjusting the molar ratio. Depending on the polar/nonpolar ratio, various states of PAA colloids were obtained, including dissolved state, stable colloid, and aggregates. Second, we observed that the confined counterions inside PAA nanoparticles can act as an imidization catalyst during the thermal annealing process. It is revealed that some fraction of the counterion species, mostly having nonpolar groups, is not drawn toward the counter electrode and remains inside the PAA nanoparticles during the EPD process. Optimizing the polarity eventually allowed us to form uniform EPD coatings with high dielectric strengths.
ABSTRACT
PURPOSE: Preclinical data has demonstrated the potential of simvastatin to overcome cetuximab resistance in KRAS mutant CRC patients. Therefore, we designed a study using simvastatin/cetuximab/irinotecan for KRAS mutant CRC patients who are refractory to irinotecan and oxaliplatin-based chemotherapy. PATIENTS AND METHODS: In this phase II study, patients received 500 mg/m(2) cetuximab, 150-180 mg/m(2) (day 1), and 80 mg simvastatin (once daily, days 1-14, every 2 weeks). The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), the disease control rate (DCR), and safety. We also analyzed the relationship between the RAS gene expression signature score and treatment response to simvastatin/cetuximab/irinotecan. RESULTS: Fifty-two KRAS mutant CRC patients were enrolled. The ORR (complete response [CR], 0; partial response [PR], 1) was 1.9 % (95 % confidence interval [CI], -1.8-5.6). The DCR (CR, 0; PR, 1; stable disease, 33) was 65.4 % (95 % CI, 52.5-78.3). The median PFS and OS from the time of study drug administration were 7·6 months (95 % CI, 4.4-10.8) and 12.8 months (95 % CI, 9.5-16.2), respectively. The most common grade 3/4 adverse events were anemia (28.8 %), neutropenia (13.5 %), and diarrhea (7.7 %). The RAS signature score was significantly correlated with the maximal change in target lesions from baseline (r = 0.57, P = 0.014). CONCLUSION: The simvastatin/cetuximab/irinotecan regimen showed promising efficacy and safety in KRAS mutant CRC patients who failed irinotecan and oxaliplatin-based chemotherapy. The RAS signature may be a novel predictor of treatment response to cetuximab-combined chemotherapy in CRC patients.
