Strategies and developments of immunotherapies in osteosarcoma

Wan, Jia; Zhang, Xianghong; Liu, Tang; Zhang, Xiangsheng

doi:10.3892/ol.2015.3962

Cited by 41 publications

(43 citation statements)

References 118 publications

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“…Osteosarcoma has a high incidence of one to three per million every year in children and adolescents [3, 4]. Currently, the 5-year survival rate of osteosarcoma patients is quite low, especially in the patients insensitive to chemotherapy [4-6]. Although new targeting drugs have been developed in these years, side effects and poor response still disturb the osteosarcoma patients [7, 8].…”

Section: Introductionmentioning

confidence: 99%

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Jiang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteosarcoma, the most common primary bone malignancy, arises from primitive transformed cells of mesenchymal origin with the worldwide increasing morbidity and mortality. Previous studies found apoptosis of osteosarcoma cells was essential for an effective manner to improve the progress of osteosarcoma, and CXCR4 has been demonstrated to be relevant with various tumor progress and metastasis. Methods: The proliferation of cells transfected with CXCR4 shRNA and control shRNA were measured by BrdU assay. Apoptosis was detected by flow cytometry. Apoptotic protein expression levels were detected by Western blot. Caspase activity was detected by Colorimetric Assay Kits using microplate reader. Activation of NF-κβ signaling after CXCR4 down-regulation in osteosarcoma cells was examined by constructing NF-κβ promoter luciferase reporter plasmid. The expression and activation of NF-κβ Signaling relevant protein were analyzed to investigate the relationship between Akt and NF-κβ signaling after the down-regulation of CXCR4 in osteosarcoma cells. Results: Down-regulation of CXCR4 significantly reduced the cell proliferation, while remarkably increased the cell apoptosis and apoptotic protein expression levels in osteosarcoma cells. Furthermore, down-regulation of CXCR4 induced cell apoptosis was caspase dependent in osteosarcoma cells. This study also showed CXCR4 down-regulation induced apoptosis through inhibiting PI3K/Akt/NF-κβ signaling pathway. In addition, endoplasmic reticulum stress (ERS) activation was involved in cell apoptosis induced down-regulation of CXCR4. Knockdown of partial ERS relevant proteins followed down-regulation of CXCR4 significantly inhibited cell apoptosis and the apoptotic protein expression levels. Conclusions: Taken together, the results demonstrated that down-regulation of CXCR4 could induce apoptosis of human osteosarcoma cells through inhibiting PI3K/Akt/NF-κβ signaling pathway, indicating that CXCR4 could be vital for the clinical therapy of osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Jiang

et al. 2018

Cell Physiol Biochem

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“…Like in most other cancers, immunotherapy and the so-called targeted therapies are current hot topics 75– 78 . As exemplified in 29 patients with refractory/relapsed osteosarcomas registered between 2009 and 2013 within the French Sarcoma Group–Bone Tumor Study Group (GSF–GETO) who received 33 treatment lines of targeted therapies, off-label use is already quite common 79 .…”

Section: Future Outlookmentioning

confidence: 99%

Advances in the management of osteosarcoma

et al. 2016

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Osteosarcoma, a bone cancer most commonly seen in adolescents and young adults, is usually a high-grade malignancy characterized by a very high risk for the development of pulmonary metastases. High-grade osteosarcomas are usually treated by preoperative and postoperative chemotherapy and surgery, with a very limited number of active agents available. Rarer lower-grade variants such as parosteal and periosteal osteosarcoma or low-grade central osteosarcoma are treated by surgery only. Imaging to search for possible metastases focuses on the lung. Computed tomography is the most sensitive method but cannot reliably distinguish small metastases from benign lesions. Advances of local imaging and surgical reconstruction now allow the use of limb-salvage in an ever-increasing proportion of patients. While still troubled by complications, non-invasive endoprosthesis-lengthening mechanisms have led to an increased uptake of limb-salvage, even for young, skeletally immature patients. Radiotherapy is employed when osteosarcomas cannot be removed with clear margins, but very high doses are required, and both proton and carbon-ion radiotherapy are under investigation. Unfortunately, the past 30 years have witnessed few, if any, survival improvements. Novel agents have not led to universally accepted changes of treatment standards. In patients with operable high-grade osteosarcomas, the extent of histological response to preoperative chemotherapy is a significant predictive factor for both local and systemic control. Attempts to improve prognosis by adapting postoperative treatment to response, recently tested in a randomized, prospective setting by the European and American Osteosarcoma Study Group, have not been proven to be beneficial. Many agree that only increased knowledge about osteosarcoma biology will lead to novel, effective treatment approaches and will be able to move the field forward.

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“…These drugs may be used alone or in combination . Recently, immunologic checkpoint blockade and targeted therapy have emerged as potentially promising therapeutic tools . Moreover, the treatment with Listeria monocytogenes , an intracellular bacterium, expressing a chimeric human HER2/neu construct to induce HER2/neu‐specific immunity, suggests that immunotherapy associated with carboplatin chemotherapy reduces pulmonary metastatic disease and prolongs survival in dogs with HER2 + appendicular OSA …”

Section: Introductionmentioning

confidence: 99%

“…9,10 Recently, immunologic checkpoint blockade and targeted therapy have emerged as potentially promising therapeutic tools. 11 Moreover, the treatment with Listeria monocytogenes, an intracellular bacterium, expressing a chimeric human HER2/neu construct to induce HER2/neu-specific immunity, suggests that immunotherapy associated with carboplatin chemotherapy reduces pulmonary metastatic disease and prolongs survival in dogs with HER2 + appendicular OSA. 12 Canine appendicular OSA studies showed that animals which underwent amputation and received carboplatin had a higher survival rate than animals that received only surgical treatment.…”

Section: Introductionmentioning

confidence: 99%

Combination therapy of canine osteosarcoma with canine bone marrow stem cells, bone morphogenetic protein and carboplatin in an in vivo model

Rici

Will

Luna

et al. 2018

Vet Comparative Oncology

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Osteosarcoma (OSA) is the most common malignant bone cancer in children and dogs. The therapeutic protocols adopted for dogs and humans are very similar, involving surgical options such as amputation. Besides surgical options, radiotherapy and chemotherapy also are adopted. However, hematologic, gastrointestinal and renal toxicity may occur because of chemotherapy treatments. Recent study clearly showed that mesenchymal stem cells (MSCs) combined with recombinant human bone morphogenetic protein (rhBMP-2) may be associated with decreases of the tumorigenic potential of canine OSA. The aim of this study was to analyse the efficacy of chemotherapy with carboplatin and rhBMP-2 with MSCs in a canine OSA in vivo model. Canine OSA cells were implanted in mice Balb-c/nude with MSCs, rhBMP-2 and carboplatin. Flow cytometry and PCR for markers involved in tumour suppression pathways were analysed. Results showed that the combination of MSCs and rhBMP-2 reduced tumour mass and infiltration of neoplastic cells in tissues more efficiently than carboplatin alone. Thus it was demonstrated that the use of rhBMP-2 and MSCs, in combination with conventional antineoplastic, may be an efficient treatment strategy.

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Strategies and developments of immunotherapies in osteosarcoma

Cited by 41 publications

References 118 publications

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

Advances in the management of osteosarcoma

Combination therapy of canine osteosarcoma with canine bone marrow stem cells, bone morphogenetic protein and carboplatin in an in vivo model

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