Mechanism of Ⅲ in the treatment of proteinuria in chronic kidney disease: a network pharmacology-based study / 南方医科大学学报

OBJECTIVE@#To identify the main active components in Ⅲ and their targets and explore the mechanism by which Ⅲ alleviates proteinuria in chronic kidney disease (CKD) based on network pharmacology.@*METHODS@#The active components of Ⅲ and their potential targets, along with the oral bioavailability and drug-like properties of each component were searched in the TCMSP database. The proteinuria-related targets were searched in the GeneCards database. The active component-target network was constructed using Cytoscape software, and the acquired information of the targets from ClueGO was used for enrichment analysis of the gene pathways.@*RESULTS@#A total of 102 active components were identified from Ⅲ. These active components acted on 126 targets, among which 69 were related to proteinuria. Enrichment analysis revealed fluid shear stress- and atherosclerosisrelated pathways as the highly significant pathways in proteinuria associated with CKD.@*CONCLUSIONS@#We preliminarily validated the prescription of Ⅲ and obtained scientific evidence that supported its use for treatment of proteinuria in CKD. The findings in this study provide a theoretical basis for further study of the mechanism of Ⅲ in the treatment of proteinuria in CKD.

Comparison of efficacy and safety of triple-drug treatment regimens for metastatic colorectal cancer / 中国肿瘤临床

Objective: To evaluate the preliminary efficacy and safety of the 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin (FOLF-OXIRI) and capecitabine, irinotecan, and oxaliplatin (CAPIRINOX) regimens as first-line therapy for unresectable advanced colorectal cancer. Methods: Between January 2013 and November 2018, 73 patients with metastatic colorectal cancer (mCRC) were analyzed. All patients received first-line chemotherapy. Of them, 45 patients were administered FOLFOXIRI, and the remaining 28 patients were ad-ministered CAPIRINOX. The clinical outcomes and safety profiles were evaluated according to the objective response rate (ORR), con-version resection rate, and adverse effects. Results: The ORR, median progression-free survival (mPFS), and R0 resection rate in the FOLFOXIRI group were not statistically different from those in the CAPIRINOX group (60% vs. 57.1%, 7.7 months vs. 9.6 months, 24.4% vs . 17.9% , respectively; P>0.05). No treatment-related deaths occurred. The major adverse events were leukopenia, neutropenia, fa-tigue, nausea, vomiting, diarrhea, alopecia, aspartate aminotransferase/alanine aminotransferase elevation, and neurotoxicity. The to-tal rate of grade 3/4 adverse events in the FOLFOXIRI group was 33.3% (15/45), while the total rate of grade 3/4 adverse events in the CAPIRINOX group was 46.4% (13/28). Toxicities between the two groups were not statistically significant (P=0.263). Conclusions: Both the FOLFOXIRI and CAPIRINOX regimens are effective as first-line treatment for metastatic colorectal cancer. The triple-agent chemo-therapy was associated with good efficacy and tolerable toxicity.

Trastuzumab combined with chemotherapy in patients with HER2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of trastuzumab combined with chemotherapy in the treatment for HER-2-positive chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma.</p><p><b>METHODS</b>Twenty consecutive cases of chemo-refractory advanced gastric or gastro-esophageal junction adenocarcinoma treated in Peking University Cancer Hospital between 2009 June and 2013 August were included in this study. The patients with adenocarcinoma were previously confirmed and were eligible if their tumor showed overexpression of HER-2+++ by immunohistochemistry or HER-2 gene amplification-positive by FISH, and if they failed to at least one previous chemotherapy. Response and toxicities were evaluated with RECIST 1.0 and CTC AE 3.0 criteria.</p><p><b>RESULTS</b>The twenty patients received trastuzumab plus second- or later-line chemotherapy, consisting of nine platinum with fluoropyrimidines, five paclitaxel with fluoropyrimidines, three fluoropyrimidines monotherapy, two irinotecan monotherapy, and one docetaxel monotherapy. In these 20 cases, 3 PR (15.0%) and 10 SD (50.0%) were achieved, with a disease control rate of 65.0%. The median PFS was 6.1 months (95%CI 3.0-9.2) and median OS was 11.1 months (95%CI 8.4-13.7). The median cycle number of Trastuzumab administration was 6.5. The patients treated with Trastuzumab ≥ 6 times had a median OS of 13.8 months, significantly longer than that of 9.5 months in the patients treated <6 times (P < 0.001). The patients treated with Trastuzumab ≥ 6 times had a median PFS of 7.8 months, significantly longer than that of 3.7 months in patients treated <6 times (P = 0.029). Among the 20 cases, loss of appetite (13 cases of grade 1-2), neutropenia (12 cases of grade 1-2 and 3 cases of grade 3-4) and fatigue (9 cases of grade 1-2 and 3 cases of grade 3-4) were the most frequent adverse events. No cardiac events including asymptomatic decreases in LVEF ≥ 10% and no treatment-related death were recorded.</p><p><b>CONCLUSIONS</b>Combination of trastuzumab with chemotherapy is effective and safe in patients with HER2-positive advanced chemo-refractory gastric or gastro-esophageal junction adenocarninoma. However, prospective studies are warranted to further confirm its efficacy and safety.</p>