Comparison of Adjunctive Naoxintong versus Clopidogrel in Volunteers with the CYP2C19*2 Gene Mutation Accompanied with Qi Deficiency and Blood Stasis Constitution

This study was to determine the impact of adjunctive Buchang Naoxintong Jiaonang (BNJ) to clopidogrel on volunteers with the CYP2C19*2 gene mutation accompanied with qi deficiency and blood stasis (QDBS) constitution. Eighteen males with QDBS constitution were selected, who were 6 CYP2C19*1/*1, 6 CYP2C19*1/*2, and 6 CYP2C19*2/*2, and signed informed consent. Results showed that the maximal platelet aggregation (Aggmax) and 5 min aggregation (Agglate) with 5-μmol/L ADP in three different CYP2C19*2 genotypes were significantly decreased after any drug therapy compared with corresponding baseline measurements (all values P < .05). But percent inhibitions of Aggmax and Agglate (IPAs) in CYP2C19*2/*2 genotype at 4 hours, 24 hours, 3 days, and 7 days after clopidogrel administration were all the lowest among three CYP2C19*2 genotypes (P < .01), and IPAs in CYP2C19*1/*2 genotype were between CYP2C19*1/*1 and CYP2C19*2/*2. IPAs had no significant difference among three different CYP2C19*2 genotypes after BNJ or adjunctive BNJ. In addition, changes of CD62P, PAC1, and sCD40L were similar to changes of ADP-induced platelet aggregation in three different CYP2C19*2 genotypes. Conclusion was that adjunctive BNJ to clopidogrel can enhance the antiplatelet effect in volunteers with the CYP2C19*2 gene mutation

Temozolomide and Pazopanib Combined with FOLFOX Regressed a Primary Colorectal Cancer in a Patient-derived Orthotopic Xenograft Mouse Model.

PurposeThe goal of the present study was to determine the efficacy of temozolomide (TEM) and pazopanib (PAZ) combined with FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) on a colorectal cancer patient-derived orthotopic xenograft (PDOX) mouse model.Materials and methodsA colorectal cancer tumor from a patient previously established in non-transgenic nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice in order to label the tumor stromal cells with GFP. Then labeled tumors were orthotopically implanted into the cecum of nude mice. Mice were randomized into four groups: Group 1, untreated control; group 2, TEM + PAZ; group 3, FOLFOX; group 4, TEM + PAZ plus FOLFOX. Tumor width, length, and mouse body weight were measured weekly. The Fluor Vivo imaging System was used to image the GFP-lableled tumor stromal cells in vivo. H&amp;E staining and immunohistochemical staining were used for histological analysis.ResultsAll three treatments inhibited tumor growth as compared to the untreated control group. The combination of TEM + PAZ + FOLFOX regressed tumor growth significantly more effectively than TEM + PAZ or FOLFOX. Only the combination of TEM + PAZ + FOLFOX group caused a decrease in body weight. PAZ suppressed lymph vessels density in the colorectal cancer PDOX mouse model suggesting inhibition of lymphangiogenesis.ConclusionOur results suggest that the combination of TEM + PAZ + FOLFOX has clinical potential for colorectal cancer patient