Animal Models in Osteosarcoma

Guijarro, María V.; Ghivizzani, Steven C.; Gibbs, Charles P.

doi:10.3389/fonc.2014.00189

Cited by 65 publications

(69 citation statements)

References 76 publications

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“…It is characterized by high recurrence and metastasis of bone and soft tissue (Kager et al, 2003;Kim et al, 2004). Treatment includes multimodal approaches including surgery, radiotherapy and chemotherapy (Guijarro et al, 2014;Luetke et al, 2014). However, drug resistance and severe side effects associated with conventional therapeutics (Chou and Gorlick, 2006) have urged for novel and more effective therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells

Huang

et al. 2015

Bangladesh J Pharmacol

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Human osteosarcoma is the most prevalent primary malignant bone tumor with high frequency of invasion and metastasis. Strong resistance coupled with toxicity of the currently available chemotherapeutic drugs poses challenge in treatment. The study aimed to investigate if fisetin, a dietary flavonoid induced apoptosis in human osteosarcoma (U-2 OS) cells. Fisetin at 20-100 µM effectively reduced the viability of OS cells, and induced apoptosis by significantly inducing the expression of caspases (Caspases-3,-8 and -9) and proapoptotic proteins (Bax and Bad) with subsequent down-regulation of Bcl-xL and Bcl-2. While fisetin inhibited PI3K/Akt pathway and ERK1/2, it caused enhanced expressions of p-JNK, p-c-Jun and p-p38. Fisetin-induced ROS generation and decrease in mitochondrial membrane potential would have also contributed to rise in apoptotic cell counts. The observations suggest that fisetin was able to effectively induce apoptosis of U-2 OS cells through ROS generation and modulation of MAPK and PI3K/Akt signalling cascades. Article Info

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Section: Introductionmentioning

confidence: 99%

Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells

Huang

et al. 2015

Bangladesh J Pharmacol

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“…Approximately 11.0 % of these publications were related to the use of animal models for studying OS, mostly involving murine models (6.4 % or 373 publications) or canine models contributed (4.6 %; 265 publications). It is interesting to note that dogs are predisposed to OS, leading to their utility as spontaneous OS models [114]. Canine models of OS have been identified to present parallel genetic features to human OS [115], including similarly dysregulated p53, c-sis, and c-myc profiles [116].…”

Section: Primary Bone Malignancymentioning

confidence: 99%

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

Chong

Bao

et al. 2016

Curr Mol Bio Rep

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Xenografting involves the transplantation of human tissue or cells into animal models and is an important tool for regenerative medicine research. Implantation of engineered human bone tissues into animal models, for example, is performed in preclinical evaluations of product safety and efficacy. With the advent of improved experimental methodologies, these models are further being exploited to interrogate molecular mechanisms and physiological interactions in vivo. In parallel to these developments, patient-derived xenograft murine models of cancer are increasingly being studied for various applications in cancer research and therapy; it follows that xenograft models in tissue engineering may be adapted for such approaches. In this review, we first discuss the development of human bone xenograft models to recapitulate physiological states in regenerative medicine. Subsequently, we discuss the use of these techniques for applications in modeling pathological states in skeletal oncology, namely, hematopoietic malignancies, bone metastatic disease, and primary bone malignancy.

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“…6 These cells may undergo unwanted radiation exposure during radiotherapy sessions for cancer treatment and this may lead to secondary tumors such as osteosarcomas (OS) that is malignant form of bone cancer. 2,4,[7][8][9] For this reason we decided to study the effect of low and medium dose radiation on MSC biology. The choice of low and medium dose treatment aimed to mimic scatter radiation exposure to tissues surrounding target area, which receives instead high dose radiation.…”

Section: Introductionmentioning

confidence: 99%

“…We extended our analysis on MSCs with inactivated RB1 gene since 70% of OS cases show RB1 gene mutations. 7,10,11 The rationale was that this gene is implied in OS onset but also results in a significant risk of a secondary cancer for patients with hereditary retinoblastoma, which is enhanced by radiotherapy. 5 Retinoblastoma gene family has 2 other members (RB2/P130 and P107), besides RB1.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stromal cells having inactivated RB1 survive following low irradiation and accumulate damaged DNA: Hints for side effects following radiotherapy

et al. 2017

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Following radiotherapy, bone sarcomas account for a significant percentage of recurring tumors. This risk is further increased in patients with hereditary retinoblastoma that undergo radiotherapy. We analyzed the effect of low and medium dose radiation on mesenchymal stromal cells (MSCs) with inactivated RB1 gene to gain insights on the molecular mechanisms that can induce second malignant neoplasm in cancer survivors.MSC cultures contain subpopulations of mesenchymal stem cells and committed progenitors that can differentiate into mesodermal derivatives: adipocytes, chondrocytes, and osteocytes. These stem cells and committed osteoblast precursors are the cell of origin in osteosarcoma, and RB1 gene mutations have a strong role in its pathogenesis. Following 40 and 2000 mGy X-ray exposure, MSCs with inactivated RB1 do not proliferate and accumulate high levels of unrepaired DNA as detected by persistence of gamma-H2AX foci. In samples with inactivated RB1 the radiation treatment did not increase apoptosis, necrosis or senescence versus untreated cells. Following radiation, CFU analysis showed a discrete number of cells with clonogenic capacity in cultures with silenced RB1.We extended our analysis to the other members of retinoblastoma gene family: RB2/P130 and P107. Also in the MSCs with silenced RB2/P130 and P107 we detected the presence of cells with unrepaired DNA following X-ray irradiation. Cells with unrepaired DNA may represent a reservoir of cells that may undergo neoplastic transformation. Our study suggests that, following radiotherapy, cancer patients with mutations of retinoblastoma genes may be under strict controls to evaluate onset of secondary neoplasms following radiotherapy.

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Animal Models in Osteosarcoma

Cited by 65 publications

References 76 publications

Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells

Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

Mesenchymal stromal cells having inactivated RB1 survive following low irradiation and accumulate damaged DNA: Hints for side effects following radiotherapy

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