ABSTRACT
The treatment and signaling pathway regulation effects of kidney- tonifying traditional Chinese medicine on osteoporosis have been widely studied, but without a systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicine on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedium, Drynariae Rhizoma, Cnidium, Eucommia, Psoralen and Dipsacus. Based on the existing findings, we concluded the following conclusions: (1) kidney-tonifying traditional Chinese medicine treats osteoporosis mainly through BMP-Smads, Wnt/β-catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/RANK, estrogen, CTSK signaling pathway to inhibit osteo?clasts of bone resorption. ① Epimedium, Drynariae Rhizoma, Cnidium and Psoralen up-regulate the key proteins and genes of BMP-Smads and Wnt/β-catenin signaling pathways to promote bone formation.② Epimedium, Drynariae Rhizoma, Cnidium, Eucommia, Psoralen, Dipsacusinhibit the bone resorption by mediating the OPG/RANKL/RANK signaling pathway. (2) Kidney-tonifying traditional Chinese medicine prevent and treat osteoporosis through a variety of ways: Icariin, Naringin, Osthol, Psoralen can regulate BMP-Smads, Wnt/β-catenin signaling pathway to promote bone formation, but also activate OPG/RANKL/RANK, CTSK and other signaling pathway to inhibit bone resorption. (3) The crosstalk of the signaling pathways and the animal experiments of the traditional Chinese medicine on the prevention and treatment of osteoporosis as well as their multi-target mechanism and comprehensive regulation need further clarification.
ABSTRACT
The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.