Search results for " Osteosarcoma"

Different modulatory effect of the synthetic cannabinoid WIN55,212-2 on tumor cell migration.

2015

MicroRNAs are small non-coding regulatory molecules exerting pleiotropic action in different biological processes such as proliferation, differentiation, apoptosis, migration and metastasis. Deregulation of miRNA expression has been observed in various cancers, and accumulating data suggest that miRNAs can display an oncogenic, antioncogenic or an ambiguous behavior in relationship to tumor environment. In a previous research we showed that the synthetic cannabinoid WIN55,212-2 is able to reduce the migratory activity of osteosarcoma MG63 cells analyzed by means of wound healing assay. So we undertook a study to evaluate the biochemical mechanism through which WIN plays this action. To this…

The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells

2003

This study demonstrates that in human osteosarcoma cells treatment with 3-aminobenzamide (3-AB), a potent inhibitor of poly(ADP-ribose) polymerase (PARP), induces morphological and biochemical features of differentiation, the duration of which depends on whether or not the normal RB gene is expressed. In Saos-2 cells expressing a non-functional Rb protein, 3-AB treatment induced the formation of transient, short dendritic-like protrusions. In RB-transfected-Saos-2 cells (a clone previously generated in our laboratory that shows stable expression of wild-type Rb protein), 3-AB induced marked and prolonged changes with the formation of long dendritic-like protrusions and the appearance of ste…

Janus-Faced role of microRNA let-7d in osteosarcoma 3AB-OS cancer stem cells

2015

Osteosarcoma (OS) is the most common malignancy of bone in children and adolescent. It is a highly invasive and metastatic bone-malignancy because of which, despite therapeutic advances, 30%-50% of patients still die of pulmonary metastasis. As a consequence, there is an urgent need to identify new therapeutic strategies to improve the clinical outcome of the patients. Advances in OS treatment are inconceivable without better understanding of molecular mechanism of osteosarmagenesis and, especially, metastatic processes. Growing evidence suggests that cancer stem cells (CSCs), which have self-renewing and malignant potential, are at the root of tumor growth and relapse. Thus, a challenge fo…

Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation and loss of mitochondrial pool of heat shock protein 60 (hsp60)

2013

Osteosarcoma is one of the most malignant tumors of childhood and adolescence that is often resistant to standard chemo- and radio-therapy. Geldanamycin and geldanamycin analogs have been recently studied as potential anticancer agents for osteosarcoma treatment. Here, for the first time, we have presented novel anticancer mechanisms of geldanamycin biological activity. Moreover, we demonstrated an association between the effects of geldanamycin on the major heat shock proteins (HSPs) and the overall survival of highly metastatic human osteosarcoma 143B cells. We demonstrated that the treatment of 143B cells with geldanamycin caused a subsequent upregulation of cytoplasmic Hsp90 and Hsp70 w…

Cellule staminali di osteosarcoma umano 3AB-OS: un modello per analizzare le proprietà oncogeniche di p53 mutata.

2013

Alterazioni del gene TP53 si riscontrano in circa il 50% dei tumori umani (1). Negli ultimi anni è stato dimostrato che la proteina mutata p53 (mp53) acquisisce nuove proprietà oncogeniche, definite “gain of function” (GOF), che contribuiscono alla progressione tumorale (2). In questo studio è stato analizzato lo stato del gene TP53, della proteina da esso espressa e il loro ruolo nella promozione della proliferazione, invasività, resistenza all’apoptosi e staminalità delle cellule 3AB-OS, una linea tumorale staminale precedentemente isolata dalle cellule di osteosarcoma umano MG63 (3). Analisi comparative di RT-PCR, Methylation-Specific-PCR (MSP), Fluorescent-in situ-hybridization (FISH) e…

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells

2014

Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involv…

Human osteosarcoma 3AB-OS cancer stem cells is a model to study microRNA-29b-1 involvement in self-renewal and fate decisions of stem cells

2014

Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

2015

BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cance…

Occupational factors and risk of adult bone sarcomas:a multicentric case-control study in Europe

2006

International audience; We investigated the association between occupational factors and risk of bone sarcoma, a rare tumor with a largely unknown aetiology. A multicentric case-control study was conducted in 7 European countries in 1995-97. Ninety-six cases aged 35-69 years with a centrally reviewed diagnosis of bone sarcoma (68 chondrosarcomas and 28 osteosarcomas) were compared to 2,632 population (68%) or colon cancer (32%) controls. Subjects were interviewed to obtain information on occupational, medical and reproductive history, smoking and alcohol consumption and selected exposures including use of pesticides. Response proportions were 90% among cases and 66% among controls. Odds rat…

Modeling human osteosarcoma in mice through 3AB‐OS cancer stem cell xenografts

2012

Osteosarcoma is the second leading cause of cancer-related death for children and young adults. In this study, we have subcutaneously injected—with and without matrigel—athymic mice (Fox1nu/nu) with human osteosarcoma 3AB-OS pluripotent cancer stem cells (CSCs), which we previously isolated from human osteosarcoma MG63 cells. Engrafted 3AB-OS cells were highly tumorigenic and matrigel greatly accelerated both tumor engraftment and growth rate. 3AB-OS CSC xenografts lacked crucial regulators of beta-catenin levels (E-cadherin, APC, and GSK-3beta), and crucial factors to restrain proliferation, resulting therefore in a strong proliferation potential. During the first weeks of engraftment 3AB-…