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Aim: Exploring the mechanisms of the combination therapy using VEGFR-TKI and immune checkpoint inhibitors might be useful to control the development of osteosarcoma. Materials & methods: The expression of PD-L1 and STAT3 in osteosarcoma were determined with western blot. Proliferation, migration and invasion were determined with CCK-8 and Transwell assays. Lung metastases, tumor growth, survival and immune cell populations were performed in tumor-bearing mice. Results: Sunitinib reduced the expression of PD-L1 by inhibiting the activation of STAT3 and suppressed the migration and invasion in osteosarcoma cells. Combination therapy reduced lung metastases, tumor growth, improved survival and reverse tumor microenvironment in tumor-bearing mice. Conclusion: Sunitinib inhibits PD-L1 expression by targeting STAT3 and remodels the immune system in tumor-bearing mice.

Osteosarcoma (OS) is a malignant disease with high morbidity and mortality rates in children and adolescents. Evidence has indicated that long non-coding RNAs (lncRNAs) may serve important roles in human cancer progression, including OS. In the present study, the role of lnc-double homeobox A pseudogene 8 (DUXAP8) in the development of OS was identified. The expression of lncRNA-DUXAP8 was determined by reverse transcription-quantitative polymerase chain reaction in OS tissues. Cell proliferation was evaluated using Cell Counting kit-8 and colony formation assays, and Transwell assays were conducted to measure cell invasion. Cell migration was evaluated using a wound healing assay. The binding site between lnc-DUXAP8 and miR-635 RNAs was investigated using a luciferase reporter assay. The expression of lnc-DUXAP8 was significantly upregulated in OS samples and OS cell lines compared with normal tissues. High expression of lncRNA DUXAP8 was associated with shorter overall survival times. Knockdown of lncRNA DUXAP8 inhibited proliferation, migration and invasion in OS cells. Notably, mechanistic investigation revealed that lncRNA DUXAP8 predominantly acted as a competing endogenous RNA in OS by regulating the miR-635/topoisomerase alpha 2 (TOP2A) axis. lncRNA DUXAP8 is upregulated in OS, and lncRNA DUXAP8-knockdown serves a vital antitumor role in OS cell progression through the miR-635/TOP2A axis. The results of the present study suggested that lncRNA DUXAP8 may be a novel, promising biomarker for the diagnosis and prognosis of OS.

Purpose: Osteosarcoma (OS) is a malignant tumor disease with high morbidity and mortality in children and adolescents. Evidence indicates that long non-coding RNAs (lncRNAs) may be important players in human cancer progression, including OS. In this study, we identified the role of lnc-DUXAP8 in the development of OS.Materials and Methods: Expression of lncRNA DUXAP8 was determined by real-time quantitative PCR and Western blotting in OS tissues. Cell proliferation was evaluated using CCK8 and colony formation assay; Transwell assay was conducted to measure cell invasion. Cell migration was evaluated using Wound Healing assay. The binding site between the lnc-DUXAP8 and miR-635 RNAs was evaluated using a luciferase reporter assay. Results: The expression of the lnc-DUXAP8 was significantly upregulated in OS samples and OS cell lines compared to normal tissue. High expression of lncRNA DUXAP8 was associated with shorter overall survival. Knockdown of lncRNA DUXAP8 inhibited proliferation and migration, and invasion in OS cells. More importantly, mechanism investigation revealed that lncRNA DUXAP8 was predominantly acted as a competing endogenous RNA (ceRNA) in OS by regulating miR-635/ TOP2A axis. Conclusion: LncRNA DUXAP8 is upregulated in OS, and LncRNA DUXAP8 knockdown plays a vital anti-tumor role in OS cell progression through a miR-635/ TOP2A axis. Our study suggests that LncRNA DUXAP8 may be a novel, promising biomarker for diagnosis and prognosis of OS.

Acute Myeloid Leukemia (AML) is a cancer of hematopoietic stem cells with a rapid progression. Recent studies indicated that endocrine disruptor chemicals (EDCs) are potential risk factors for AML progression. Our present data showed that an industrial endocrine disrupting chemical, Benzyl butyl phthalate (BBP), can promote the proliferation of AML cells and decrease their sensitivity to daunorubicin (DNR) and cytarabine (Ara-C) treatments. Further, BBP can increase the glucose consumption, lactate generation, and ATP levels of AML cells. Among the measured glycolysis-related genes, BBP can increase the expression of pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4), a mitochondrial protein that regulates the tricarboxylic acid cycle (TCA) cycle. The inhibitor of PDK4 or its specific siRNA can attenuate BBP-induced cell proliferation and ATP generation, which suggested the essential roles of PDK4 in BBP-induced glycolysis and proliferation. Further, BBP can increase the mRNA stability of PDK4, while had no effect on its transcription and protein stability. miR-15b-5p can bind with the 3'UTR of PDK4 to decrease its mRNA stability, while BBP can decrease the expression of miR-15b-5p in AML cells. Collectively, our data showed that BBP can trigger the malignancy of AML cells via regulation of miR-15b-5p/PDK4 signals.

This study was purposed to investigate the relationship between expression of the FANCG gene and adult sporadic acute myeloid leukemia (AML), real-time PCR with SYBR Green I technique was used for detecting FANCG gene expression level in bone marrow mononuclear cells of 54 newly diagnosed AML patients, 46 AML patients in complete remission (CR) and 36 control samples. β-actin gene was used as internal reference. Relative changes of FANCG gene expression level were detected by 2(-ΔΔCT) method in newly diagnosed AML patients and control samples, in newly diagnosed AML and patient in CR, as well as in AML patients in CR and control samples. The results showed that the relative expression level of FANCG mRNA was 0.56 ± 0.27 in newly diagnosed group, 0.75 ± 0.54 in AML CR group, and 0.85 ± 0.45 in control group. The expression level of FANCG mRNA in newly diagnosed group was significantly lower than that in control and AML CR groups (P0.05). There was no statistically significant deference in comparison of AML CR group with the control group (P0.05). It is concluded that the expression of FANCG gene decrease in the newly diagnosed AML patients. There is no significant difference between AML CR group and control group, which indicated that FANCG gene may be related with the onset and the prognosis of AML, and may provide a clinical value for evaluating effect of chemotherapy.