Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522083 (Osteosarcoma)
 2,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma (OS), the most frequent bone tumor in children and adolescents, is highly malignant. Metastases are the major cause of death, and patients with relapse have a poor prognosis. Given the associations of S100A4 with OS and tumor metastasis, we explored its potential roles in OS metastasis. Among 32 OS (16 metastatic and 16 non- metastatic) specimens examined, we found a significant increase of S100A4 mRNA in metastatic tissues, and more importantly, expression of S100A4 and MMP-9 to be strongly correlated in patients who had lymph node or distant metastasis. We observed that siRNA mediated suppression of the S100A4 gene significantly reduced the proliferative and invasive capability of highly invasive OS cells, with a reduced rate of tumor growth and metastasis under in vivo conditions. Matrix metalloproteinase 9 (MMP-9) proved highly responsive to S100A4 gene suppression, demonstrating significant reduction in proteolytic activity, while overexpression of S100A4 increased the expression and proteolytic activity of MMP-9. Links of S100A4 with cell motility were confirmed by depletion which resulted in reduced cell migration. Moreover, loss of cell metastatic potential was completely rescued by overexpression of MMP-9. Collectively, our findings indicate that S100A4 contributes to OS metastasis by stimulating MMP-9 expression, suggesting potential as a novel diagnostic biomarker for OS progression as well as a therapeutic target.
Asian Pac J Cancer Prev 2011
PMID:Knockdown of S100A4 decreases tumorigenesis and metastasis in osteosarcoma cells by repression of matrix metalloproteinase-9. 2229 54

Osteosarcoma, the most common primary mesenchymal malignant tumor, usually has bad prognosis in man, with cancer stem-like cells (CSCs) considered to play a critical role in tumorigenesis and drug-resistance. It is known that phosphatidylinositol 3-kinase (PI3K) is involved in regulation of tumor cell fates, such as proliferation, cell cycling, survival and apoptosis. Whether and how PI3K and inhibitors might cooperate in human osteosarcoma CSCs is still unknown. We therefore evaluated the effects of LY294002, a PI3K inhibitor, on the cell cycle and apoptosis of osteosarcoma CSCs in vitro. LY294002 prevented phosphorylation of protein kinase B (PKB/Akt) by inhibition of PI3K phosphorylation activity, thereby inducing G0/G1 cell cycle arrest and apoptosis in osteosarcoma CSCs. Further studies also demonstrated that apoptosis induction by LY294002 is accompanied by activation of caspase-9, caspase-3 and PARP, which are involved in the mitochondrial apoptosis pathway. Therefore, our results indicate PI3K inhibitors may represent a potential strategy for managing human osteosarcoma via affecting CSCs.
Asian Pac J Cancer Prev 2012
PMID:LY294002 induces G0/G1 cell cycle arrest and apoptosis of cancer stem-like cells from human osteosarcoma via down-regulation of PI3K activity. 2299 17

Osteosarcoma is the most common primary bone malignancy in children and adolescents, and its clinical outcome is poor. We evaluated the influence of GSTP1, ERCC1 and ERCC2 polymorphisms on response to chemotherapy among osteosarcoma patients, and the significnace of these genes for prognosis. A total of 187 patients with osteosarcoma were administered methotrexate, cisplatin/adriamycin, actinomycin D, cyclophosphamide, or vincristine. GSTP1, ERCC1 and ERCC2 polymorphisms were genotyped by PCR-RFLP assay. The results showed the average survival time of 187 patients were 38.4 months. Some 97 patients showed response to neoadjuvant chemotherapy. The GSTP1 Val and ERCC2 A/A genotypes had significantly higher rates of response to chemotherapy, with adjusted OR (95% CI) of 2.19 (1.15-6.21) and 2.88 (1.14-13.3). Individuals with the ERCC2 A/A genotype were likely to have a lower risk of death from oseosarcoma, and the adjusted HR was 0.32 (0.13-0.95). Our study indicated that GSTP1 and ERCC2 Lys751Gln polymorphisms might be candidate pharmacogenomic factors to be explored in the future to identify osteosarcoma patients who might benefit from chemotherapy.
Asian Pac J Cancer Prev 2012
PMID:Glutathione S-transferase P1 and DNA polymorphisms influence response to chemotherapy and prognosis of bone tumors. 2331 81

The effects of polymorphisms in ERCC5, ERCC6, XPC, CCNH and MMS19L on osteosarcoma response to chemotherapy and the survival of the affected patients were assessed. Genotyping of ERCC5, ERCC6, XPC, CCNH and MMS19L was performed by PCR-RFLP assay. The median PFS was 12.8 months, and the median OS was 18.6 months. Individuals carrying homozygous genotypes of ERCC5 rs17655 and ERCC5 rs1047768 were more like to have good response to treatment, while those carrying homozygous genotypes of MMS19L rs29001322 showed poor response. Osteosarcoma patients carrying TT genotype of ERCC5 rs1047768 showed a significantly longer PFS (16.8 months) and OS (21.4 months) than CC genotype, with HRs(95% CI) of 0.31 (0.10-0.93) and 0.32 (0.06-0.97), respectively. Conversely, those with the TT genotype of MMS19L rs29001322 demonstrated shorter PFS and OS, the HRs (95% CI) being 2.23 (1.08-4.15) and 4.62 (1.45-16.08), respectively. Our findings showed polymorphisms in ERCC5 rs1047768 and MMS19L rs29001322 to be associated with clinical outcome of osteosarcoma patients undergoing chemotherapy.
Asian Pac J Cancer Prev 2013
PMID:Single nucleotide polymorphisms in the NER pathway and clinical outcome of patients with bone malignant tumors. 2367 17

Osteosarcoma is a common malignant tumor of bone, but mechanisms underlying its development are still unclear. At present, it is believed that the inhibition of normal apoptotic mechanisms is one of the reasons for the development of tumors, so specific stimulation of tumor cell apoptosis can be considered as an important therapeutic method. Livin, as a member of the newly discovered inhibitor of apoptosis proteins (IAPs) family, has specifically high expression in tumor tissues and can inhibit tumor cell apoptosis through multiple ways, which can become a new target for malignant tumor treatment (including osteosarcoma) and might of great significance in the clinical diagnosis of tumors and the screening of anti-tumor agents and carcinoma treatment.
Asian Pac J Cancer Prev 2014
PMID:Research progress on the livin gene and osteosarcomas. 2537 70

Osteosarcoma is the most common primary bone tumor in humans, especially in childhood. However, the genetic etiology for its pathogenesis remains elusive. It is known that microRNAs (miRNAs) are involved in the development of tumor progression. Here we show that microRNA-9 (miR-9) is a potential oncogene upregulated in osteosarcoma cells. Knockdown of miR-9 in osteosarcoma resulted in suppressed colony formation and cell proliferation. Further study identified GCIP, a Grap2 and cyclin D interacting protein, as a direct target of miR- 9. In addition, GCIP overexpression activated retinoblastoma 1 (Rb) and suppressed E2F transcriptional target expression in osteosarcoma cells. Moreover, GCIP depletion reversed miR-9 knockdown induced colony formation and cell proliferation suppression. In sum, these results highlight the importance of miR-9 as an oncogene in regulating the proliferation of osteosarcoma by directly targeting GCIP and may provide new insights into the pathogenesis of osteosarcoma.
Asian Pac J Cancer Prev 2015
PMID:miR-9 Modulates Osteosarcoma Cell Growth by Targeting the GCIP Tumor Suppressor. 2610 95

Osteosarcoma is a common primary malignant bone tumor in children and adolescents. Recent worldwide average incidences of osteosarcoma in people aged 0 to 24 years were 4.3 and 3.4 per million, respectively, with a ratio of 1.4:1. However, data on the incidence of osteosarcoma in Thailand are limited. This study analyzed the incidence of osteosarcoma in the upper northern region of Thailand, with a population of 5.85 million people (8.9% of the total Thai population), using data for the years 1998 to 2012, obtained from the Chiang Mai Cancer Registry (CMCR) at Chiang Mai University Hospital and the Lampang Cancer Registry (LCR) at the Lampang Cancer Hospital, a total of 144 cases. The overall annual incidence of osteosarcoma was 1.67 per million with a male:female ratio of 1.36:1. Incidences by age group (male and female) at 0 to 24, 25 to 59 and over 60 years were 3.5 (3.9 and 3.0), 0.8 (0.9 and 0.6), and 0.7 (0.8 and 0.5), respectively. The peak incidence occurred at 15 to 19 years for males and at 10 to 14 years for females. The median survival time was 18 months with a 5year survival rate of 43%. Neither the age group nor the 5year interval period of treatment was significantly correlated with survival during the 15year period studied.
Asian Pac J Cancer Prev 2016
PMID:AgeStandardized Incidence Rates and Survival of Osteosarcoma in Northern Thailand. 2750 91

Osteosarcoma is one of the most common types of bone cancer in children. To gauge the extent of cancer treatment response in the patient after surgical resection, the H&E stained image slides are manually evaluated by pathologists to estimate the percentage of necrosis, a time consuming process prone to observer bias and inaccuracy. Digital image analysis is a potential method to automate this process, thus saving time and providing a more accurate evaluation. The slides are scanned in Aperio Scanscope, converted to digital Whole Slide Images (WSIs) and stored in SVS format. These are high resolution images, of the order of 109 pixels, allowing up to 40X magnification factor. This paper proposes an image segmentation and analysis technique for segmenting tumor and non-tumor regions in histopathological WSIs of osteosarcoma datasets. Our approach is a combination of pixel-based and object-based methods which utilize tumor properties such as nuclei cluster, density, and circularity to classify tumor regions as viable and non-viable. A K-Means clustering technique is used for tumor isolation using color normalization, followed by multi-threshold Otsu segmentation technique to further classify tumor region as viable and non-viable. Then a Flood-fill algorithm is applied to cluster similar pixels into cellular objects and compute cluster data for further analysis of regions under study. To the best of our knowledge this is the first comprehensive solution that is able to produce such a classification for Osteosarcoma cancer. The results are very conclusive in identifying viable and non-viable tumor regions. In our experiments, the accuracy of the discussed approach is 100% in viable tumor and coagulative necrosis identification while it is around 90% for fibrosis and acellular/hypocellular tumor osteoid, for all the sampled datasets used. We expect the developed software to lead to a significant increase in accuracy and decrease in inter-observer variability in assessment of necrosis by the pathologists and a reduction in the time spent by the pathologists in such assessments.
Pac Symp Biocomput 2017
PMID:COMPUTER AIDED IMAGE SEGMENTATION AND CLASSIFICATION FOR VIABLE AND NON-VIABLE TUMOR IDENTIFICATION IN OSTEOSARCOMA. 2789 75

Objective: Osteosarcoma (OS) is the most common malignant bone tumor in children and you
Asian Pac J Cancer Prev 2017 04 01
PMID:Mir-150 Up-Regulates Glut1 and Increases Glycolysis in Osteosarcoma Cells 2854 52

Osteosarcoma (OS) is one of the most common malignant bone tumors in children and adolescents, and the eighth leading form of childhood cancer. Matrix metalloproteinases (MMPs) are proteolytic enzymes implicated in certain cancers including OS. In this review, we discuss the mechanism of actions of MMPs in progression of OS, and the therapeutic use of MMPs inhibitors in the treatment of OS with subsequent clinical studies and future management. The expression of MMPs is upregulated in cancer cells by a variety of cytokines and growth factors, and upregulation of MMPs induces degradation of the extracellular matrix that contributes to cell proliferation by releasing growth factors. MMPs promote the detachment and migration of endothelial cells, cross the basement membrane as well as invade the surrounding lymphatic vessels and causes cancer metastasis. The use of selective MMP inhibitors with limited side effects might be promising therapeutic strategy in the treatment of OS. More clinical trials are necessary to evaluate the role of selective MMPs inhibitors in the prevention and treatment of OS along with their assessment of toxicity.
Asia Pac J Clin Oncol 2019 Aug
PMID:Pathological and therapeutic aspects of matrix metalloproteinases: Implications in osteosarcoma. 3111 66


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