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Metastatic osteosarcoma

Claudia Maria Hattinger, Maria Pia Patrizio, Elisa Tavanti, Silvia Luppi, Federica Magagnoli, Piero Picci, Massimo Serra
Genetic characterization of osteosarcoma has evolved during the last decade thanks to the integrated application of conventional and new candidate-driven and genome-wide technologies. Areas covered: This review provides an overview of the state of art in genetic testing applied to osteosarcoma, with particular regard to novel candidate genetic biomarkers that can be analyzed in tumor tissue and blood samples, which might be used to predict toxicity and prognosis, detect disease relapse, and improve patients' selection criteria for tailoring treatment...
October 16, 2018: Expert Review of Molecular Diagnostics
Daniel G Fuja, Nino C Rainusso, Ryan L Shuck, Lyazat Kurenbekova, Lawrence A Donehower, Jason T Yustein
Osteosarcoma (OS) is a highly aggressive mesenchymal malignancy and the most common primary bone tumor in the pediatric population. OS frequently presents with or develops distal metastases. Patients with metastatic disease have extremely poor survival rates, thus necessitating improved molecular insights into OS metastatic biology. Utilizing our previously characterized genetically engineered mouse model (GEMM) of metastatic OS, we identified enhanced differential expression of Transglutaminase-2 (TGM2) in metastatic OS...
2018: American Journal of Cancer Research
Amy E Armstrong, David O Walterhouse, Patrick J Leavey, Jennifer Reichek, Amy L Walz
Outcome for patients with metastatic or recurrent/refractory osteosarcoma remains poor. Responses to sorafenib, a multikinase inhibitor, have been seen in recurrent/refractory osteosarcoma, although specific biomarkers of response have not been described. We report a partial response in a 7-year-old with refractory osteosarcoma treated with sorafenib 200 mg twice daily. Toxicities included Common Terminology Criteria for Adverse Events Grade 2 skin toxicities and growth suppression. After 51 months of therapy, he suffered a recurrence...
October 14, 2018: Pediatric Blood & Cancer
Anna Adamus, Katharina Peer, Iftikhar Ali, Jan Lisec, Abiodun Falodun, Marcus Frank, Guido Seitz, Nadja Engel
ETHNOPHARMACOLOGICAL RELEVANCE: Berberis orthobotrys (BORM) is a medical plant with a long history in traditional usage for the treatment of wounds, cancer, gastrointestinal malady and several other diseases. Our previous studies identified the endemic Pakistani plant Berberis orthobotrys Bien. ex Aitch. as promising source for the treatment of breast cancer and osteosarcoma. AIM OF THE STUDY: The present study was aimed to evaluate the anti-cancer properties of 26 plant derived extracts and compounds including the methanolic root extract of Berberis orthobotrys (BORM) on pediatric alveolar rhabdomyosarcoma (RMA), which is known to develop drug resistance, metastatic invasion and potential tumor progression...
October 10, 2018: Journal of Ethnopharmacology
Xiao-Jun Yu, Xin-Zhen Guo, Chao Li, Yang Chong, Tie-Nan Song, Jian-Feng Pang, Ming Shao
Osteosarcoma is the most common malignant bone cancer that mainly affects children and young adults. Recently, the NAD+ -dependent deacetylase, sirtuin 1 (SIRT1), has been reported to play a key role in the development of malignant tumors. The study aimed to investigate the role of SIRT1 in osteosarcoma and explore its underlying oncogenic mechanisms. The prognostic value of SIRT1 in osteosarcoma was assessed through detection of SIRT1 expression based on osteosarcoma biopsy tissue. Then, to further investigate the effect of SIRT1 in osteosarcoma, osteosarcoma cells were treated with small interfering RNA SIRT1 and overexpressed SIRT1 to detect the cell migration, invasion, and epithelial-mesenchymal transition (EMT)...
October 10, 2018: Journal of Cellular Biochemistry
Hee Won Cho, Ji Won Lee, Youngeun Ma, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo
Background: By estimating the survival rates and exploring prognostic factors in pediatric patients with relapsed or progressed solid tumors, our purpose was to generate background data for future studies. Methods: We reviewed the medical records of 258 patients with solid tumors who experienced relapse/progression and received subsequent salvage treatment between 1996 and 2016. Results: A total of 60 patients remained progression-free during first-line salvage treatment, while the remaining 198 patients experienced relapse/progression again; 149 underwent second-line salvage treatment...
October 8, 2018: Journal of Korean Medical Science
Chenyu Wang, Ming Ren, Xin Zhao, Ao Wang, Jincheng Wang
Osteosarcoma (OS) is a primary malignant bone tumor in early adolescence with high metastasis and death rates. Although the combination of polychemotherapy and surgical excision increased the survival rates up to 60%, the prognosis remains poor for most patients with metastatic or recurrent osteosarcoma. However, the exact pathogenic mechanism and pivotal elements regulating tumor invasion and metastasis are largely unknown. Circular RNAs (circRNAs) are novel endogenous non-coding RNA (ncRNA) molecules that generate the cyclic structure from back splicing...
October 4, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Ling Liu, Jun Pan, Huan Wang, Zhenni Ma, Jie Yin, Feng Yuan, Quanwen Yuan, Lu Zhou, Xiaofeng Liu, Yu Zhang, Zhaohua Bao, Huilin Yang, Jing Ling
BACKGROUND: Von Willebrand factor (vWF) is a major procoagulant molecule that was shown to differentiate between metastatic and primary osteosarcoma (OS) tissues and associated with increased metastasis. However, its functional role in OS progression has yet been unclear. METHODS: The expression profile of vWF and miR-24 in human OS tissues was characterized using immunofluorescence labelling and qRT-PCR analysis. The interaction between miR-24 and vWF was identified by dual luciferase reporter assay...
October 2, 2018: Bioscience Reports
Takahiro Shimizu, Yasushi Fuchimoto, Hajime Okita, Kazumasa Fukuda, Yuko Kitagawa, Shigeru Ueno, Tatsuo Kuroda
BACKGROUND/PURPOSE: This study aimed to assess the significance of tumor debulking surgery by using immune checkpoint inhibitors for advanced pediatric solid tumors in a murine model of advanced osteosarcoma. METHODS: In C3H mice, 5 × 106 LM8 (osteosarcoma cell line with a high metastatic potential in the lungs originating from the C3H mouse) cells were transplanted subcutaneously. Thereafter, the mice were divided into 4 groups as follows: the control group received no intervention (CG, n = 5), the surgery group underwent subcutaneous tumor resection (tumor debulking surgery) 11 days after transplantation (SG, n = 10), the immunotherapy group received a cocktail consisting of 200 μg each of three antibodies (anti-Tim-3, anti-PD-L1, and anti-OX-86) intraperitoneally on posttransplantation days 11, 14, 18, and 21 (IG, n = 10), and the combination therapy group, tumor debulking surgery on day 11 and the cocktail intraperitoneally on days 11, 14, 18, and 21 (COMBG, n = 10)...
September 2, 2018: Journal of Pediatric Surgery
Thierry Alcindor, Ali Al-Fakeeh, Krista Goulding, Susan Solymoss, Nathalie Ste-Marie, Robert Turcotte
BACKGROUND: Little has been published about the association of venous thromboembolism (VTE) and sarcoma. In this study, we sought to identify clinical features of patients with sarcoma presenting at least one VTE episode. METHODS: Our study was a retrospective case-control study of a single-institution database with univariate and multivariate analysis using chi-square and Student's t test. A p value less than .05 was considered significant. RESULTS: The overall incidence of VTE in patients with sarcoma was 7...
September 26, 2018: Oncologist
Holly L Spraker-Perlman, Donald A Barkauskas, Mark D Krailo, Paul A Meyers, Cindy L Schwartz, John Doski, Richard Gorlick, Katherine A Janeway, Michael S Isakoff
BACKGROUND: Despite drastic improvement in overall survival for pediatric patients with cancer, those with osteosarcoma have stable rates of survival since the 1980s. This project evaluates the effect of several variables on survival after first recurrence in patients with osteosarcoma. METHODS: Data from three prospective North American cooperative group trials for newly diagnosed osteosarcoma are included: INT-0133, POG-9754, and AOST0121. The analytic population for this study is all enrolled patients with first event-free survival (EFS) event of relapse...
September 25, 2018: Pediatric Blood & Cancer
Dinesh Chandra Doval, Juhi Tayal, Kumardeep Dutta Choudhary, Pankaj Goyal, Gurudutt Gupta, Sunil Pasricha
Extraosseous sarcoma of the breast occurs infrequently and is a harbinger of poor prognosis. The histogenesis of this tumor is ambiguous, and it can arise both in de novo and metastatic settings. Morphologically, it is indistinguishable from its skeletal counterpart, and clinically, it presents similarly to any other subtype of breast cancer. Tumor recurrence with a propensity for hematogenous rather than lymphatic spread plagues this malicious disease. The treatment guidelines are mainly derived from the those of other extraskeletal sarcomas as the literature is limited in this context...
September 13, 2018: Turkish Journal of Surgery
Yang Sun, Xiubo Jiang, Ying Lu, Jianwei Zhu, Lisha Yu, Bo Ma, Qi Zhang
Osteosarcoma is the most common primary bone tumor with highly invasive characteristic and low long-term survival. Recently, epithelial-mesenchymal transition (EMT) is reported as a key event in cancer invasion and metastasis. Oridonin, a bioactive diterpenoid, has been proved to possess anti-cancer effects. However, the effect of oridonin on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the underlying mechanism of oridonin on EMT and metastasis of osteosarcoma. We found that oridonin inhibited migration and invasion of MG-63 and 143B cells...
September 19, 2018: Chemico-biological Interactions
Jyoti Bajpai, Arun Chandrasekharan, Vijai Simha, Vikas Talreja, Ashay Karpe, Nikihil Pandey, Ashish Singh, Bharat Rekhi, Tushar Vora, Jaya Ghosh, Shripad Banavali, Sudeep Gupta
PURPOSE: Metastatic osteosarcoma is largely treated with high-dose methotrexate (HDMTX)-based therapy, especially in the pediatric population. This mandates complex pharmacokinetic monitoring in a costly inpatient setting to mitigate unpredictable serious toxicities. Hence, a non-HDMTX-based regimen is worth exploring, especially in India and low- and middle-income countries. MATERIALS AND METHODS: All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting of sequential doublets of doxorubicin, cisplatin, and ifosfamide...
September 2018: Journal of Global Oncology
Viviane Seba, Gabriel Silva, Mariana Bastos Dos Santos, Seung Joon Baek, Suzelei de Castro França, Ana Lúcia Fachin, Luis Octavio Regasini, Mozart Marins
Osteosarcoma (OS) is a primary malignant bone tumor that mainly affects children, adolescents, and young adults. The inhibition of metastasis is a main strategy of OS therapy since the development of metastatic disease due to drug resistance remains the most important cause of death from this cancer. Considering the severe side effects of current OS chemotherapy, the identification of anti-metastatic drugs with reduced toxicity is of great interest. Chalcones are polyphenols with a basic structure consisting of an α-, β-unsaturated carbonyl system linking two aryl rings...
September 19, 2018: International Journal of Molecular Sciences
Daisuke Kurita, Yasuji Mokuno, Hideo Matsubara, Hirokazu Kaneko, Mikihiro Shamoto, Akira Satou, Shinsuke Iyomasa
Hepatic carcinosarcoma (HCS) generally presents in advanced stages, demonstrates aggressive behavior, and has a poor prognosis. Other than curative primary resection, no effective treatment options exist. We present a case of resected HCS with four repeat resections for solitary lymph node recurrence followed by chemoradiotherapy with doxorubicin and ifosfamide. A 67-year-old Japanese man was admitted to our hospital for evaluation of an asymptomatic hepatic tumor. The patient underwent right hepatectomy with a presumptive preoperative diagnosis of atypical hepatocellular carcinoma...
August 2018: Nagoya Journal of Medical Science
E Canalis
Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role in cell differentiation and function. Notch receptors are activated following interactions with their ligands in neighboring cells. There are five classic ligands termed Jagged (Jag)1 and Jag2 and Delta-like (Dll)1, Dll3, and Dll4. Recent work has established Notch as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages and in skeletal development and bone remodeling...
September 7, 2018: Osteoporosis International
Dylan C Dean, Shen Shen, Francis J Hornicek, Zhenfeng Duan
Although the investigation into biomarkers specific for pulmonary metastasis within osteosarcoma (OS) has recently expanded, their usage within the clinic remains sparse. The current screening protocol after any OS diagnosis includes a chest CT scan; however, metastatic lung nodules frequently go undetected and remain the primary cause of death in OS. Recently, screening technologies such as liquid biopsy and next-generation sequencing have revealed a promising array of biomarkers with predictive and diagnostic value for the pulmonary metastasis associated with OS...
August 31, 2018: Cancer Metastasis Reviews
Jyoti Bajpai, Nehal Khanna, Tushar Vora, Ashish Gulia, Siddhartha Laskar, Ajay Puri, Bhanupriya Sanduptla, Girish Chinnaswamy, Prakash Nayak, Shashikant L Juvekar, Amit Janu, Subhash Desai, Jaya Ghosh, Nilendu Purandare, Mukta Ramadwar, Venkatesh Rangarajan, Bharat Rekhi
Introduction: Primary bone and soft tissue sarcomas are rare, but diagnostically and therapeutically challenging group of tumors, requiring multidisciplinary management. There are limited documented studies from multidisciplinary teams , in the form of comprehensive analysis of these tumors, from our country. This study is an analysis of cases of osteosarcomas, Ewing sarcomas (ESs), chondrosarcomas (CSs), and soft-tissue sarcomas (STSs), registered at our institution during 2012. Methods: Clinical details, including outcomes of cases of bone and STSs, during the year 2012, were retrieved from the medical records of our institution and were further analyzed...
January 2018: Indian Journal of Cancer
Yasunori Tome, Tasuku Kiyuna, Fuminari Uehara, Michael Bouvet, Hiroyuki Tsuchiya, Fuminori Kanaya, Robert M Hoffman
Human osteosarcoma 143B cells were previously stably transfected with an αv integrin green flourescent protein (GFP) vector. 143B cells expressing αv integrin-GFP were transplanted orthotopically in the tibia of transgenic nude mice ubiquitously expressing red fluorescent protein (RFP). The primary tumors acquired RFP-expressing stroma and were passaged orthotopically in the tibia in noncolored nude mice, which maintained the RFP stroma. The interaction of αv integrin-GFP expression in 143B cells with RFP-expressing host stromal cells was observed by confocal microscopy using the Olympus FV1000...
August 26, 2018: Journal of Cellular Biochemistry
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