Pharmacogenetics of the Primary and Metastatic Osteosarcoma: Gene Expression Profile Associated with Outcome.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. In recent decades, OS treatment has reached a plateau and drug resistance is still a major challenge. Therefore, the present study aimed to analyze the expression of the genes related to pharmacogenetics in OS.

Quantitative expression evaluation of PRAME gene in osteosarcoma.

Background: In a previous study, our group observed that 68% of the osteosarcoma (OS) samples presented PRAME (Preferentially Expressed Antigen in Melanoma) gene expression. In this work, we propose to investigate quantitatively gene expression of PRAME in distinct patients groups.

Methods And Results: 61 osteosarcoma samples, from 3 distinct patients groups were selected for this study: (1) Patients younger than 10 years old at diagnosis, (2) Patients that had poor evolution of disease and (3) Patients that were in remission of disease and had treatment with no intercurrences) PRAME gene expression levels were obtained using quantitative Real-Time Polymerase Chain Reaction method (qRT-PCR).

Hepatoblastomas exhibit marked downregulation driven by promoter DNA hypermethylation.

Hepatoblastomas exhibit the lowest mutational burden among pediatric tumors. We previously showed that epigenetic disruption is crucial for hepatoblastoma carcinogenesis. Our data revealed hypermethylation of nicotinamide N-methyltransferase, a highly expressed gene in adipocytes and hepatocytes.

Genotypes Are Associated with Toxicity and Survival in Osteosarcoma Patients.

Osteosarcoma is the malignant bone tumor most common in children and adolescents. Many cytochrome P-450 (CYP) members detoxify anticancer drugs used in osteosarcoma treatment, and thus, the aim of the present study was to investigate polymorphisms in osteosarcoma patients. The present study investigated DNA from peripheral blood from 70 osteosarcoma patients treated with high doses of cisplatin, doxorubicin, and methotrexate.

Frequency of Pathogenic Germline Variants in Cancer-Susceptibility Genes in Patients With Osteosarcoma.

Importance: Osteosarcoma, the most common malignant bone tumor in children and adolescents, occurs in a high number of cancer predisposition syndromes that are defined by highly penetrant germline mutations. The germline genetic susceptibility to osteosarcoma outside of familial cancer syndromes remains unclear.

Objective: To investigate the germline genetic architecture of 1244 patients with osteosarcoma.

MAPK7 variants related to prognosis and chemotherapy response in osteosarcoma.

Osteosarcoma (OS) is a class of cancer originating from the bone, affecting mainly children and young adults. Our previous study showed that MAPK7 gene overexpression was significantly associated with tumor progression, poor treatment response, and worse overall survival, suggesting that MAPK7 could play an important role in OS tumorigenesis. We have investigated if MAPK7 overexpression was a result of any genomic changes in OS tumor specimens.

New therapeutic target for pediatric anaplastic ependymoma control: study of anti-tumor activity by a Kunitz-type molecule, Amblyomin-X.

EPNs comprise a heterogeneous group of neuroepithelial tumors, accounting for about 10% of all intracranial tumors in children and up to 30% of brain tumors in those younger than 3 years. Actually, the pattern therapy for low-grade EPNs includes complete surgical resection followed by radiation therapy. Total surgical excision is often not possible due to tumor location.

TET Upregulation Leads to 5-Hydroxymethylation Enrichment in Hepatoblastoma.

Hepatoblastoma is an embryonal liver tumor carrying few genetic alterations. We previously disclosed in hepatoblastomas a genome-wide methylation dysfunction, characterized by hypermethylation at specific CpG islands, in addition to a low-level hypomethylation pattern in non-repetitive intergenic sequences, in comparison to non-tumoral liver tissues, shedding light into a crucial role for epigenetic dysregulation in this type of cancer. To explore the underlying mechanisms possibly related to aberrant epigenetic modifications, we evaluated the expression profile of a set of genes engaged in the epigenetic machinery related to DNA methylation (, , , , , , , and ), as well as the 5-hydroxymethylcytosine (5hmC) global level.

Intravenous Grafts of Human Amniotic Fluid-Derived Stem Cells Reduce Behavioral Deficits in Experimental Ischemic Stroke.

Amniotic fluid has been investigated as new cell source for stem cells in the development of future cell-based transplantation. This study reports isolation of viable human amniotic fluid-derived stem cells, labeled with multimodal iron oxide nanoparticles, and its effect on focal cerebral ischemia-reperfusion injury in Wistar rats. Middle cerebral artery occlusion of 60 min followed by reperfusion for 1 h, 6 h, and 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in rats.

Tropism of mesenchymal stem cell toward CD133 stem cell of glioblastoma in vitro and promote tumor proliferation in vivo.

Background: Previous studies have demonstrated remarkable tropism of mesenchymal stem cells (MSCs) toward malignant gliomas, making these cells a potential vehicle for delivery of therapeutic agents to disseminated glioblastoma (GBM) cells. However, the potential contribution of MSCs to tumor progression is a matter of concern. It has been suggested that CD133 GBM stem cells secrete a variety of chemokines, including monocytes chemoattractant protein-1 (MCP-1/CCL2) and stromal cell-derived factor-1(SDF-1/CXCL12), which could act in this tropism.

Valproic acid treatment response in vitro is determined by TP53 status in medulloblastoma.

Purpose: Histone deacetylate inhibitors (HDACi), as valproic acid (VA), have been reported to enhance efficacy and to prevent drug resistance in some tumors, including medulloblastoma (MB). In the present study, we investigated VA role, combined to cisplatin (CDDP) in cell viability and gene expression of MB cell lines.

Methods: Dose-response curve determined IC values for each treatment: (1) VA single, (2) CDDP single, and (3) VA and CDDP combined.

DNA methylation landscape of hepatoblastomas reveals arrest at early stages of liver differentiation and cancer-related alterations.

Hepatoblastomas are uncommon embryonal liver tumors accounting for approximately 80% of childhood hepatic cancer. We hypothesized that epigenetic changes, including DNA methylation, could be relevant to hepatoblastoma onset. The methylomes of eight matched hepatoblastomas and non-tumoral liver tissues were characterized, and data were validated in an independent group (11 hepatoblastomas).

CYP genes in osteosarcoma: Their role in tumorigenesis, pulmonary metastatic microenvironment and treatment response.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The present study investigated the expression of Cytochrome P-450 (CYP) genes: CYP1A2, CYP3A4 and CYP3A5 by qRT-PCR in 135 specimens obtained from OS patients, including biopsy (pre-chemotherapy), tumor resected in surgery (post-chemotherapy), adjacent bone to tumor (nonmalignant tissue), pulmonary metastasis and adjacent lung to metastasis (nonmalignant tissue). Normal bone and normal lung tissues were used as control.

MAPK pathways regulation by DUSP1 in the development of osteosarcoma: Potential markers and therapeutic targets.

Osteosarcoma (OS) is the most frequent primary bone tumor that affect children and adolescents. This tumor is highly aggressive with high risk of metastasis and the implementation of new drugs has not been successful. The search for biomarkers or new therapeutic targets is urgently needed and can help in advances of OS treatment.

MAPK7 gene controls proliferation, migration and cell invasion in osteosarcoma.

Osteosarcomas (OS) are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. In our previous study, MAPK7 has been identified as a candidate oncogene, and a promising prognostic marker for OS. Sequential activation of protein kinases within the mitogen-activated protein kinase (MAPK) cascades is a common mechanism of signal transduction in many cellular processes.

GNAS mutations are not detected in parosteal and low-grade central osteosarcomas.

Parosteal osteosarcoma, low-grade central osteosarcoma, and fibrous dysplasia share similar histological features that may pose a diagnostic challenge. The detection of GNAS mutations in primary bone tumors has been useful in clinical practice for diagnosing fibrous dysplasia. However, the recent report of GNAS mutations being detected in a significant proportion of parosteal osteosarcoma challenges the specificity of this mutation.

A Genome-Wide Scan Identifies Variants in NFIB Associated with Metastasis in Patients with Osteosarcoma.

Unlabelled: Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in NFIB significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: P = 1.

Investigation of IGF2, Hedgehog and fusion gene expression profiles in pediatric sarcomas.

Unlabelled: The childhood sarcomas are malignant tumors with high mortality rates. They are divided into two genetic categories: a category without distinct pattern karyotypic changes and the other category showing unique translocations that originate gene rearrangements. This category includes rhabdomyosarcoma (RMS), Ewing's sarcoma (ES) and synovial sarcoma (SS).

Expression profiling using a cDNA array and immunohistochemistry for the extracellular matrix genes FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 in colorectal carcinoma progression and dissemination.

Colorectal cancer dissemination depends on extracellular matrix genes related to remodeling and degradation of the matrix structure. This investigation intended to evaluate the association between FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 gene and protein expression levels in tumor tissue with clinical and histopathological neoplastic parameters of cancer dissemination. The expression associations between ECM molecules and selected epithelial markers EGFR, VEGF, Bcl2, P53, and KI-67 have also been examined in 114 patients with colorectal cancer who underwent primary tumor resection.

SHH, WNT, and NOTCH pathways in medulloblastoma: when cancer stem cells maintain self-renewal and differentiation properties.

Purpose: Infant medulloblastoma (MB) is a malignant neuroepithelial embryonal tumor of the cerebellum, believed to derive from precursor granule cells with stem or progenitor cells appearance, and caused by a change in expression profile of genes related to the development. This work aims to study the expression profile of these genes in MB tumors, correlating with clinicopathological characteristics.

Methods: We quantified, by qPCR in 40 MB tumor samples, the expression of genes in HH (PTCH1, PTCH2, and GLI1), WNT (APC, CTNNB1, WIF1, and DKK2), and NOTCH pathways (NOTCH2 and HES1), which have a crucial role in development, and genes as MYCC, MYCN, and TERT, correlating this findings to patient's clinicopathological characteristics.