American Brachytherapy Society consensus statement for soft tissue sarcoma brachytherapy.

Metastasis is the major cause of cancer deaths, and cancer cells evolve to adapt to various tumor microenvironments, which hinders the treatment of tumor metastasis. Platelets play critical roles in tumor development, especially during metastasis. Here, we elucidate the role of platelet mitochondria in tumor metastasis. Cancer cells are reprogrammed to a metastatic state through the acquisition of platelet mitochondria via the PINK1/Parkin-Mfn2 pathway. Furthermore, platelet mitochondria regulate the GSH/GSSG ratio and reactive oxygen species (ROS) in cancer cells to promote lung metastasis of osteosarcoma. Impairing platelet mitochondrial function has proven to be an efficient approach to impair metastasis, providing a direction for osteosarcoma therapy. Our findings demonstrate mitochondrial transfer between platelets and cancer cells and suggest a role for platelet mitochondria in tumor metastasis. 

Cancer cells reprogram to metastatic state through the acquisition of platelet mitochondria

Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later, we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in the chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models of rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration. 

Rhabdomyosarcoma: Current Therapy, Challenges, and Future Approaches to Treatment Strategies

Abstract Canine osteosarcoma is increasingly recognized as an informative model for human osteosarcoma. Here we show in one of the largest clinically annotated canine osteosarcoma transcriptional datasets that two previously reported, as well as de novo gene signatures devised through single sample Gene Set Enrichment Analysis (ssGSEA), have prognostic utility in both human and canine patients. Shared molecular pathway alterations are seen in immune cell signaling and activation including TH1 and TH2 signaling, interferon signaling, and inflammatory responses. Virtual cell sorting to estimate immune cell populations within canine and human tumors showed similar trends, predominantly for macrophages and CD8+ T cells. Immunohistochemical staining verified the increased presence of immune cells in tumors exhibiting immune gene enrichment. Collectively these findings further validate naturally occurring osteosarcoma of the pet dog as a translationally relevant patient model for humans and improve our understanding of the immunologic and genomic landscape of the disease in both species. 

Transcriptional profiling of canine osteosarcoma identifies prognostic gene expression signatures with translational value for humans

Simple Summary Rhabdomyosarcoma (RMS) is a rare pediatric sarcoma affecting skeletal muscle in children and young adults. It is responsible for 3% of all childhood malignant tumors and is the third most prevalent pediatric extracranial solid tumor. Despite advances in diagnostic and treatment methods and clinical trials to improve pediatric RMS survival rates, children with high-risk RMS and recurrent disease have 5-year survival rates of less than 30% and 17%, respectively. The cure rate remains low and the current RMS therapies continue to pose potential life-threatening toxicities, which can lead to lifelong morbidity. The treatment strategies for RMS include multi-agent chemotherapies after surgical resection with or without radiotherapy. Here, we focus on chemotherapy strategies and discuss the impact of apoptosis, autophagy, and the UPR that are involved in the chemotherapy response. Then, to screen future therapeutic approaches and promote muscle regeneration, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models. Abstract Rhabdomyosarcoma is a rare cancer arising in skeletal muscle that typically impacts children and young adults. It is a worldwide challenge in child health as treatment outcomes for metastatic and recurrent disease still pose a major concern for both basic and clinical scientists. The treatment strategies for rhabdomyosarcoma include multi-agent chemotherapies after surgical resection with or without ionization radiotherapy. In this comprehensive review, we first provide a detailed clinical understanding of rhabdomyosarcoma including its classification and subtypes, diagnosis, and treatment strategies. Later, we focus on chemotherapy strategies for this childhood sarcoma and discuss the impact of three mechanisms that are involved in the chemotherapy response including apoptosis, macro-autophagy, and the unfolded protein response. Finally, we discuss in vivo mouse and zebrafish models and in vitro three-dimensional bioengineering models of rhabdomyosarcoma to screen future therapeutic approaches and promote muscle regeneration.

Osteosarcoma (OS) is the most common malignant bone tumor in children. Despite efforts to develop and implement new therapies, patient outcomes have not measurably improved since the 1980s. Metastasis continues to be the main source of patient mortality, with 30% of cases developing metastatic disease within 5 years of diagnosis. Research models are critical in the advancement of cancer research and include a variety of species. For example, xenograft and patient-derived xenograft (PDX) mouse models provide opportunities to study human tumor cells in vivo while transgenic models have offered significant insight into the molecular mechanisms underlying OS development. A growing recognition of naturally occurring cancers in companion species has led to new insights into how veterinary patients can contribute to studies of cancer biology and drug development. The study of canine cases, including the use of diagnostic tissue archives and clinical trials, offers a potential mechanism to further canine and human cancer research. Advancement in the field of OS research requires continued development and appropriate use of animal models. In this review, animal models of OS are described with a focus on the mouse and tumor-bearing pet dog as parallel and complementary models of human OS.

Canine and murine models of osteosarcoma

Rhabdomyosarcoma (RMS) is one of the most common primary orbital malignancies. However, orbital RMS is a very rare disease, especially in childhood, and the tumor has a high degree of malignancy and rapid development. The objective of the present study was to investigate the clinical treatment effects of radioactive 125I seeds interstitial brachytherapy on children with primary orbital RMS, which may provide a new method for treating RMS in clinical applications. Radioactive 125I seeds were used in the present study. Primary lesions from ten children with orbital RMS, including three male and seven female patients, were selected as the targeted areas. The activity, number and spatial location of the seeds were optimized and simulated by applying computer three-dimensional treatment planning system (TPS) software. The interstitial implantation of the radioactive 125I seeds was conducted on children under general anesthesia according to the TPS simulation results. Quality verifications of the operation were conducted by orbital computed tomography and X-ray plain film at the early stage after operation, and the children were followed up. The patients were followed up by October 2012 with an average follow-up time of 57 ± 17.43 months and a median follow-up time of 55 months. Nine cases achieved complete remission, and one case achieved partial remission, resulting in a total efficiency and survival rate of 100.0 % (10/10). Most patients recovered after treatment or had no radiotherapy side effect after the operations, though 20.0 % of the patients (2/10) experienced corneal opacity, eyeball movement disorder, or loss of sight. Radioactive 125I seeds interstitial brachytherapy was an effective treatment for children with primary orbital RMS. Results from this study may provide a new clinical approach for the treatment of child patients with primary orbital RMS.

https://link.springer.com/content/pdf/10.1007%2Fs12032-014-0415-8.pdf

Clinical research on the treatment effects of radioactive 125 I seeds interstitial brachytherapy on children with primary orbital rhabdomyosarcoma

DICER1-associated sarcoma of the aortic arch - a case report and literature review.

Background: Osteosarcoma (OS) is an aggressive pediatric cancer with unmet therapeutic needs. Glutaminase 1 (GLS1) inhibition, alone and in combination with metformin, disrupts the bioenergetic demands of tumor progression and metastasis, showing promise for clinical translation. Materials and Methods: Three positron emission tomography (PET) clinical imaging agents, [18F]fluoro-2-deoxy-2-D-glucose ([18F]FDG), 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT), and (2S, 4R)-4-[18F]fluoroglutamine ([18F]GLN), were evaluated, using the MG63.3 human OS xenograft mouse model, as companion imaging biomarkers after treatment for 7 d with a selective GLS1 inhibitor (CB-839, telaglenastat) and metformin, alone and in combination. Imaging and biodistribution data were collected before and after treatment from tumors and reference tissues. Results: Drug treatment altered tumor uptake of all three PET agents. Relative [18F]FDG uptake decreased significantly after telaglenastat treatment, but not within control and metformin-only groups. [18F]FLT tumor uptake appears to be negatively affected by tumor size. Evidence of a flare effect was seen with [18F]FLT imaging after treatment. Telaglenastat had a broad influence on [18F]GLN uptake in tumor and normal tissues. Conclusions: Image-based tumor volume quantification is recommended for this paratibial tumor model. The performance of [18F]FLT and [18F]GLN was affected by tumor size. [18F]FDG may be useful in detecting telaglenastat's impact on glycolysis. Exploration of kinetic tracer uptake protocols is needed to define clinically relevant patterns of [18F]GLN uptake in patients receiving telaglenastat.

Exploration of Imaging Biomarkers for Metabolically-Targeted Osteosarcoma Therapy in a Murine Xenograft Model.

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Canine and murine models of osteosarcoma

Clinical research on the treatment effects of radioactive 125 I seeds interstitial brachytherapy on children with primary orbital rhabdomyosarcoma

DICER1-associated sarcoma of the aortic arch - a case report and literature review.

Exploration of Imaging Biomarkers for Metabolically-Targeted Osteosarcoma Therapy in a Murine Xenograft Model.