AIM:To introduce the concept of bridging study and its strategies in clinical trials for new drug application.METHODS:The concept of bridging study proposed in the ICH E5 guideline was introduced,with a case using bridging strategies in the new drug applications(NDAs)approved by the regulatory authority in Japan.The concrete mode and the development of bridging studies in Asia were summarized.RESULTS:With the application of the ICH E5,some countries and regions have successfully used the bridging strategy in the new drug applications.The bridging strategy is becoming a common and practical basis for the decision making of marketing approvals of new drugs in the Asia-pacific country.CONCLUSION:The currently bridging studies in Asia will play an important role in the extrapolation of foreign clinical data in new drug application.Using bridging study is very helpful in judging ethnic differences of drugs,reducing duplication of clinical trails,as well as shortening clinical development periods.

Objective To study the value of serum human epididymal protein 4 (HE4) ,cytokeratin 19 frag-ment (CYFRA21-1) ,neuron-specific enolase (NES) and gastrin release precursors (Pro-GRP) in the diagnosis of female lung cancer .Methods A total of 100 cases of female lung cancer patients in the hospital were select-ed as the research object ,100 cases of benign lung diseases and 100 female health examiners as the control ,the serum levels of HE4 ,CYFRA21-1 ,NES and Pro-GRP were measured ,and the related statistical analysis was carried out .Results The serum levels of HE4 ,CYFRA21-1 ,NES and Pro-GRP in patients with lung cancer were significantly higher than those of benign lung disease and healthy control group (P<0 .05) ,and there was no significant difference between the benign lung disease group and the healthy control group (P>0 .05) . There was no significant difference in serum HE4 expression in different stages and pathological types of lung cancer (P>0 .05) .The ROC curve analysis showed that the area (AUC) of HE4 ,CYFRA21-1 and NES/Pro-GRP w ere 0 .927 ,0 .758 ,0 .652 and 0 .799 respectively ,and the best critical values w ere 63 .38 ,2 .05 ,14 .05 and 58 .50 respectively ,and the sensitivity was 88 .0％ ,80 .0％ ,60 .0％ ,71 .0％ respectively ,and the speci-ficity was 96 .0％ ,73 .0％ ,87 .0％ and 89 .0％ respectively .HE4 was obviously better than the other 3 items . Combined detection of HE4 ,CYFRA21-1 ,NES and Pro-GRP could also improve the diagnostic sensitivity of lung cancer ,which was 89 .0％ ,but the specificity had decreased by 88 .0％ .Conclusion The level of serum HE4 in female patients with lung cancer is significantly higher ,which can be used as a candidate marker for differential diagnosis of pulmonary benign and malignant diseases .The combined detection of these 4 markers has a high sensitivity for the diagnosis of female lung cancer ,which is suitable for the survey of female lung cancer in clinical .

Marsdenia tenacissima injection, a standard Marsdenia tenacissima extract (MTE), has been approved as an adjuvant therapeutic agent for various cancers. Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer (PCa) cells. However, the underlying mechanisms and active ingredients of MTE against PCa were not completely understood. This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells. In addition, MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7, Cyt c, and Bax. In vivo, DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size. TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE. Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets, and 709 PCa-associated targets were retrieved, from which 149 overlapped targets were screened out. Pathway enrichment analysis showed that the HIF-1, PI3K-AKT, and ErbB signaling pathways were closely related to tumor apoptosis. Western blot results confirmed that MTE increased the expression of p-AKT^Ser473 and p-GSK3β^Ser9, and decreased the expression of p-STAT3^Tyr705in vitro and in vivo. A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLC-QTOF-MS/MS. Molecular docking analysis indicated that six compounds may interact with AKT, GSK3β, and STAT3. In conclusion, MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis, resulting in inhibition of PCa growth in vitro and in vivo.
Mice ; Animals ; Male ; Humans ; Mice, Inbred NOD ; Mice, SCID ; Marsdenia ; Proto-Oncogene Proteins c-akt ; Glycogen Synthase Kinase 3 beta ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Prostatic Neoplasms ; Apoptosis ; STAT3 Transcription Factor