Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Here, we developed a novel oncolytic vaccinia virus (NOV) with the dual advantages of cancer selectivity and normal vessel reconstructive activity by replacing the viral thymidine kinase (vTk) and vaccinia growth factor (VGF) genes with genes encoding TNF-related apoptosis-inducing ligand (TRAIL) and angiopoietin 1 (Ang1), respectively. The pan-cancer-specific oncolytic potency of NOV was confirmed in various human and mouse cancer cell lines (colon, liver, pancreas, cholangiocarcinoma, cervical cancer, osteosarcoma, and melanoma). Vaccinia virus (VV) treatment directly induced early apoptosis in tumors within 24 h, and this effect was enhanced with further engineering; VGF and Tk deletion with Ang1 and TRAIL insertion. Meanwhile, treatment with the conventional anti-cancer drug cisplatin did not induce apoptosis. A virus-treated CT26 mouse colon cancer syngeneic model showed attenuated tumor growth, which was in accordance with the results of percent survival measurement, CD8 expression analysis, and TUNEL staining with advanced genetic engineering (vAng1 < vTRAIL < NOV). Taken together, our results indicate that NOV induces cancer tissue apoptosis and anti-tumor immunity and may constitute a highly advantageous therapeutic agent for next-generation solid tumor virotherapy with pan-cancer-specific oncolytic activity and high biosafety.
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PMID:Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity. 3234 3

The therapeutic strategies proposed currently for bone sarcomas are based on neo-adjuvant chemotherapy, delayed en-bloc wide resection, and adjuvant chemotherapy. Unfortunately, bone sarcomas are characterized by high rates of poor drug response, with a high risk of drug resistance, local recurrence and/or a high propensity for induced metastases. The pathogenesis of bone sarcomas is strongly associated with dysregulation of local bone remodeling and increased osteolysis that plays a part in tumor development. In this context, bisphosphonates (BPs) have been proposed as a single agent or in combination with conventional drugs to block bone resorption and the vicious cycle established between bone and sarcoma cells. Pre-clinical in vitro studies revealed the potential "anti-tumor" activities of nitrogen-bisphosphonates (N-BPs). In pre-clinical models, N-BPs reduced significantly primary tumor growth in osteosarcoma and Ewing sarcoma, and the installation of lung metastases. In chondrosarcoma, N-BPs reduced the recurrence of local tumors after intralesional curettage, and increased overall survival. In pediatric and adult osteosarcoma patients, N-BPs have been assessed in combination with conventional chemotherapy and surgery in randomized phase 3 studies with no improvement in clinical outcome. The lack of benefit may potentially be explained by the biological impact of N-BPs on macrophage differentiation/recruitment which may alter CD8+-T lymphocyte infiltration. Thanks to their considerable affinity for the mineralized extracellular matrix, BPs are an excellent platform for drug delivery in malignant bone sites with reduced systemic toxicity, which opens up new opportunities for their future use.
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PMID:Bisphosphonates in common pediatric and adult bone sarcomas. 3262 77

Recent data have suggested that PD-1 and PD-L1 are involved in osteosarcoma (OS) pathogenesis; however, their contributions are not well-established. Here, the PD-1/PD-L1 expression was evaluated in (OS) cases. Preoperative needle biopsy specimens were obtained from 16 patients with OS. Immunostaining for CD4, CD8, PD-1, and PD-L1 was performed on pathological specimens. Clinical parameters, including age, tumor size, preoperative alkaline phosphatase (ALP) level, standardized uptake value (SUV)-max level, and survival rate, were compared between PD-1/PD-L1-positive and -negative groups. CD4-, CD8-, PD-1-, and PD-L1-positive rates among all specimens were 75%, 75%, 18.7%, and 62.5%, respectively. The rates of co-expression of CD4 and CD8 with PD-L1 were 56.2% and 50%, respectively. Tumors were significantly larger in PD-L1-negative cases than in PD-L1-positive cases. Age, size and ALP and SUV-max levels did not differ significantly between PD-1/PD-L1-positive and -negative cases. The 3-year survival rates did not differ significantly between PD-1-positive and -negative cases or between PD-L1-positive and -negative cases. However, the occurrence of cancer-related events, including recurrence, metastasis, and death was associated with the PD-1-negative and PD-L1-positive status. The PD-1/PD-L1 checkpoint is likely involved in the immune microenvironment in OS and may be involved in the occurrence of cancer-related events.
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PMID:Characterization of PD-1/PD-L1 Immune Checkpoint Expression in Osteosarcoma. 3275 Nov 95


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