Comparative gene set enrichment analysis (GSEA) of the embryonic stem cell (ES) gene signatures in canine and human osteosarcoma

In this study, we sought to compare the expression profiles of embryonic stem cell (ES) gene signatures in canine and human OSA tissues and cell lines. The expression patterns of three major ES gene signatures (modules or gene sets)—namely Myc, Core, and PRC modules—were primarily analyzed through the gene set enrichment analysis method in three gene expression datasets. For verification of the primary results, an additional 13 ES gene sets which were categorized into four groups—nam ely NOS targets, ES expressed, Myc targets, and Polycomb targets—were evaluated in expression datasets. Additionally, the prognostic efficacy of the gene sets with a similar enrichment pattern in humans and dogs was evaluated using the Cox proportional hazard model. Our results revealed that there were similar ES module expression patterns in the human OSA tissue and cell line, where the MYC modules, Myc targets, ES exp1, and NOS target modules were upregulated and the Polycomb target modules were downregulated in both entities. The canine OSA cell line showed ES enrichment patterns more sim ilar to the patterns in its human counterpart, where we were able to detect the upregulation of the MYC modules, Myc targets, ES exp1, and NOS target modules and the downregulation of the Polycomb targets, including H3K27 bound and PRC2 targets. However, the canine OSA tissues presented a similar en richment pattern at a lower degree than the canine OSA cell line. Furthermore, survival...
Source: Comparative Clinical Pathology - Category: Pathology Source Type: research

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Osteosarcoma (OS) is the most common primary bone malignancy and is a leading cause of cancer-related death in children and young adults. Combination chemotherapy developed 3 decades ago significantly improved long-term survival compared to surgery alone. However, despite notable tumor cytoreduction and remission, the 5-year survival rate has remained static at ∼70% since, and the surviving patients have high chemoresistance with sustained risk of recurrent OS that has propensity to metastasize. After metastasis, the 5-year survival rate is abysmally low (∼10% to 20%). Emerging new evidence has revealed that within...
Source: Techniques in Orthopaedics - Category: Orthopaedics Tags: Symposium Source Type: research
Abstract Exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) promote osteosarcoma cell proliferation and migration, while the underlying mechanism remains unknown. Since the long non-coding RNA PVT1 has been reported to be upregulated in osteosarcoma cells and contributes to its growth and metastasis, we aim to investigate whether BMSC-derived exosomes promote osteosarcoma growth and metastasis via transporting PVT1 into osteosarcoma cells. The PVT1 expression in BMSC-derived exosomes was markedly higher than that in osteosarcoma cell-derived exosomes. The co-culturing of BMSC-derived exosomes and oste...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
TNF-α/miR-155 axis induces the transformation of osteosarcoma cancer stem cells independent of TP53INP1. Gene. 2019 Oct 26;:144224 Authors: Yao J, Lin J, He L, Huang J, Liu Q Abstract MicroRNA-155 (miR-155) has been identified to be overexpressed in various human cancers including osteosarcoma. However, whether the up-regulation of miR-155 is associated with osteosarcoma cancer stem cells (CSCs) is not well understood. In the present study, we showed that miR-155 induced the acquisition of stem-like features in U2OS osteosarcoma cells by increasing the expression of both CSCs surface markers (CD...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
Epigenomics, Ahead of Print.
Source: Future Medicine: Epigenomics - Category: Genetics & Stem Cells Authors: Source Type: research
This study aims to explore the anti ‐osteosarcoma effects of Bruceine D (BD), a natural compound derived fromBrucea javanica, and investigate its underlying mechanisms. Results demonstrated that BD could significantly inhibit cell proliferation and migration, induce cell cycle arrest, and promote apoptosis in osteosarcoma cells. Besides, BD could also suppress the sphere ‐forming and self‐renewal ability of OSCs. Mechanistically, the inhibitory role of BD on osteosarcoma cell growth and migration including OSC stemness was partially executed through the inhibition of STAT3 signaling pathway. More importantly, BD show...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Indian Hedgehog (IHH) signaling, a key regulator of skeletal development, is highly activated in cartilage and bone tumors. Yet deletion of Ptch1, encoding an inhibitor of IHH receptor Smoothened (SMO), in chondrocyte or osteoblasts does not cause tumorigenesis. Here, we show thatPtch1deletion in mice Prrx1+ mesenchymal stem/stromal cells (MSCs) promotes MSC proliferation and osteogenic and chondrogenic differentiation but inhibits adipogenic differentiation. Moreover,Ptch1 deletion led to development of osteoarthritis-like phenotypes, exostoses, enchondroma, and osteosarcoma in Smo-Gli1/2-dependent manners. The cartilage ...
Source: eLife - Category: Biomedical Science Tags: Cancer Biology Cell Biology Source Type: research
In this study, mesoporous bioactive glass (MBG) sub-micro particles were prepared through sol-gel synthesis and possessed a uniform and spherical structure with particle size of 302 ± 43 nm, a pore size of 4 nm and a high surface area of 354 m2 g−1. Alendronate (AL) is often used for the treatment of bone associated diseases, in particular osteosarcoma. However, due to the low bioavailability and high toxicity at increased doses, local and sustained release would be an ideal approach to AL delivery. Here, MBGs and aminated MBGs (AMBG) were applied as carriers for AL loading. High encapsulation effici...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
In this study, we reported that M2 macrophages were enriched in osteosarcoma tissues from patients, and M2-polarized TAMs enhanced cancer initiation and stemness of osteosarcoma cells, thereby establishing M2-polarized TAMs as a therapeutic target for blocking osteosarcoma formation. We also found that all-trans retinoic acid (ATRA) weakened TAM-induced osteosarcoma tumor formation by inhibiting M2 polarization of TAMs in vivo, and inhibited the colony formation, as well as sphere-formation capacity of osteosarcoma cells promoted by M2-type macrophages in vitro. Furthermore, M2-type macrophages enhanced cancer stem cells (...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
Bone primary tumors, such as osteosarcoma, are highly aggressive pediatric tumors that in 30% of the cases develop lung metastasis and are characterized by poor prognosis. Bone is also the third most common metastatic site in patients with advanced cancer and once tumor cells become homed to the skeleton, the disease is usually considered incurable, and treatment is only palliative. Bone sarcoma and bone metastasis share the same tissue microenvironment and niches. 3D cultures represent a new promising approach for the study of interactions between tumor cells and other cellular or acellular components of the tumor microen...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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