Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, with highly aggressive behavior and early systemic metastasis. The survival rates for osteosarcoma remain unchanged over the past two decades. Studies aiming to find new or alternative therapies for patients with refractory osteosarcoma are urgently needed. Anlotinib, a novel multi-targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging clinical activity in NSLCC and soft tissue sarcoma, whereas its effect on osteosarcoma has not been studied. In our study, we investigated the anti-tumor activity and underlying mechanism of anlotinib in osteosarcoma. Various in vitro and in vivo models of human osteosarcoma were used to determine the anti-proliferative, anti-angiogenesis and anti-metastasis efficacy of anlotinib. Our results showed that anlotinib suppressed tumor growth and increased the chemo-sensitivity of osteosarcoma. In addition, anlotinib inhibited migration and invasion in osteosarcoma cells. Furthermore, in order to explore the anti-tumor mechanism of anlotinib, phospho-RTK antibody arrays were performed. These analyses confirmed that anlotinib suppressed the phosphorylation of MET, VEGFR2 and the downstream signaling pathway activation. Moreover, we demonstrated that anlotinib blocked hepatocyte growth factor (HGF)-induced cell migration, invasion and VEGF-induced angiogenesis. Notably, a 143B-Luc orthotopic osteosarcoma model further showed that anlotinib significantly inhibited growth and lung metastasis of implanted tumor cells. Our preclinical work indicates that anlotinib acts as a novel inhibitor of VEGFR2 and MET that blocks tumorigenesis in osteosarcoma, which could be translated into future clinical trials.
 ...
PMID:Anlotinib, a novel small molecular tyrosine kinase inhibitor, suppresses growth and metastasis via dual blockade of VEGFR2 and MET in osteosarcoma. 3071 15

Development of cisplatin (DDP)-resistance is a major challenge that largely limits the efficacy of chemotherapy for osteosarcoma. LncRNA Taurine up-regulated gene 1 (TUG1) is a recently identified oncogenic lncRNA that has been involved in chemo-resistance of various cancers. In this study, over-expression of TUG1 was found in two osteosarcoma cell lines resistant to DDP (Saos-2/DDP, MG-63/DDP). Knockdown of TUG1 inhibited the DDP-resistance and promoted the cytotoxicity and apoptosis induced by DDP in Saos-2/DDP and MG-63/DDP cells. TUG1 knockdown also markedly inhibited the expression level of MET and p-Akt. In conclusion, knockdown of TUG1 suppressed cell growth and increased apoptotic rate under DDP treatment possibly via regulating MET/Akt signalling pathway.
 ...
PMID:Anticancer potential of TUG1 knockdown in cisplatin-resistant osteosarcoma through inhibition of MET/Akt signalling. 3130 59

Cancer incidence has been increasing steadily and is the leading cause of mortality worldwide. Gastric cancer is still most common malignancy in Korea. Cancer initiation and progression are multistep processes involving various growth factors and their ligands. Among these growth factors, we have studied hepatocyte growth factor (HGF), which is associated with cell proliferation and invasion, leading to cancer and metastasis, especially in gastric cancer. We explored the intercellular communication between HGF and other surface membrane receptors in gastric cancer cell lines. Using complimentary deoxyribonucleic acid microarray technology, we found new genes associated with HGF in the stomach cancer cell lines, NUGC-3 and MKN-28, and identified their function within the HGF pathway. The HGF/N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) axis interacts with several molecules including E-cadherin, urokinase plasminogen activator, KiSS-1, Jun B, and lipocalin-2. This pathway may affect cell invasion and metastasis or cell apoptosis and is therefore associated with tumorigenesis and metastasis in gastric cancer.
 ...
PMID:Function of hepatocyte growth factor in gastric cancer proliferation and invasion. 3207 17

Recent clinical trials have shown several multi-target tyrosine kinase inhibitors (TKIs) to be effective in the treatment of osteosarcoma. However, these TKIs have a number of targets, and it is yet unclear which of these targets has a key role in osteosarcoma treatment. In this review, we first summarize the TKIs that were studied in clinical trials registered on ClinicalTrials.gov. Further, we compare and discuss the targets of these TKIs. We found that TKIs with promising therapeutic effect for osteosarcoma include apatinib, cabozantinib, lenvatinib, regorafenib, and sorafenib. The key targets for osteosarcoma treatment may include VEGFRs and RET. The receptor tyrosine kinases (RTKs) MET, IGF-1R, AXL, PDGFRs, KIT, and FGFRs might be relevant but unimportant targets for osteosarcoma treatment. Inhibition of one type of RTK for the treatment of osteosarcoma is not effective. It is necessary to inhibit several relevant RTKs simultaneously to achieve a breakthrough in osteosarcoma treatment. This review provides comprehensive information on TKI targets relevant in osteosarcoma treatment, and it will be useful for further research in this field.
 ...
PMID:Receptor Tyrosine Kinases in Osteosarcoma Treatment: Which Is the Key Target? 3298 34

Sarcomas are frequent in dogs and canine species are excellent animal models for studying the human counterpart. However, osteosarcomas are a rare form of sarcoma with high death rates in humans and dogs. miRNAs are small endogenous RNAs that regulate gene expression post-transcriptionally. The discovery of miRNAs could give a contribute in the diagnosis and prognosis of different types of tumors in animal species, as already in humans. The differentiated expression of miRNAs is a frequent finding in cancers and is related to their pathogenesis in many cases. Most canine and human sarcomas show similar miRNA aberrations. Lower levels of miR-1 and miR-133b in canine osteosarcoma tissues were found to increase tumorigenesis through a higher expression of their target genes MET and MCL1. The overexpression of miR-9 promotes a metastatic phenotype in canine osteosarcomas and its capacity as a prognostic biomarker for the disease is currently being evaluated. MicroRNAs at the 14q32 locus could be used as prognostic biomarkers, since their decreased expression has been associated with poor prognosis in canine and human osteosarcomas. Furthermore, a decreased expression of miR-34a in osteosarcoma tumour cells has been associated with shorter disease-free survival times and its reintroduction as a synthetic prodrug shows good potential as a novel therapeutic target to fight the disease. Circulating miR-214 and miR-126 are significantly increased in a broad-spectrum cancer and have the ability to successfully predict the prognosis of dogs. However, further studies are needed to make the use of miRNAs as biomarkers a common practice.
 ...
PMID:MicroRNAs as Biomarkers in Canine Osteosarcoma: A New Future? 3300 41


<< Previous 1 2 3 4