Background
AZD7762 is a checkpoint kinase 1 (Chk 1) inhibitor, which has been reported to sensitize many tumor cells to DNA damage. However, whether AZD7762 could sensitize osteosarcoma cells to chemotherapy cisplatin has not been defined.
Methods
We used a variety of methods such as cell viability assays, flow cytometry, western blotting, and immunohistochemistry analysis to determine AZD7762 enhancing cisplatin-induced apoptosis on osteosarcoma cell lines in vitro and in vivo.
Results
In the present study, we demonstrated that AZD7762 could enhance cisplatin-mediated apoptosis and mitotic catastrophe of osteosarcoma cells in vitro, and promote the inhibition of xenograft growth induced by cisplatin in vivo. The mechanistic study indicated that AZD7762 enhance the effect of cisplatin through abrogating cisplatin-mediated G2/M arrest and inhibiting the cisplatin damage repair as demonstrated by increasing cisplatin-induced γH2AX expression.
Conclusion
These results suggest that AZD7762 could effectively promote cisplatin-induced apoptosis and mitotic catastrophe in osteosarcoma cells. The clinical application of AZD7762 as an adjuvant in the chemotherapy of osteosarcoma should be further explored.
Electronic supplementary material
The online version of this article (10.1186/s12935-019-0896-9) contains supplementary material, which is available to authorized users.
Objective
Retrospective study on the safety and efficacy of anlotinib in the treatment of advanced leiomyosarcoma in real-world.
Methods
Clinical data were collected from patients suffered from advanced leiomyosarcoma who received anlotinib treatment in Cancer Hospital of the University of Chinese Academy of Sciences from January 2018 to December 2020. Objective response rate (ORR) and disease control rate (DCR) were analyzed according to the RECIST 1.1 criteria. The progression free survival (PFS), overall survival (OS) and adverse reactions were recorded and calculated.
Results
A total of 19 patients (14 female, 5 male) were enrolled, 3 (15.8%) achieved partial response (PR), 11 (57.9%) achieved stable disease (SD), with an ORR of 15.8%, a DCR of 73.7%, a median PFS of 4.1 months (95% CI: 3.0~5.2) and a median OS of 23.5 months (95% CI: 14.2~32.7). The majority of adverse events were grade 1/2, the most common grade 3/4 adverse events were hand-foot syndrome (12.5%), hypertension (5.3%) and oral ulcer (5.3%).
Conclusion
Our results forecast that anlotinib is effective, safe and alternative in treatment of advanced leiomyosarcoma in real-world, combined with immunotherapy may become a potential treatment option. Further, more prospective randomized controlled trials are needed to confirm these findings.
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