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Osteosarcoma adult

Ryan A Durfee, Maryam Mohammed, Hue H Luu
Osteosarcoma is the most common primary malignancy of bone in children and young adults. This tumor has a very heterogeneous genetic profile and lacks any consistent unifying event that leads to the pathogenesis of osteosarcoma. In this review, some of the important genetic events involved in osteosarcoma will be highlighted. Additionally, the clinical diagnosis of osteosarcoma will be discussed, as well as contemporary chemotherapeutic and surgical management of this tumor. Finally, the review will discuss some of the novel approaches to treating this disease...
October 19, 2016: Rheumatol Ther
Kirby Rickel, Fang Fang, Jianning Tao
Osteosarcoma is the predominant form of bone cancer, affecting mostly adolescents. Recent progress made in molecular genetic studies of osteosarcoma has changed our view on the cause of the disease and ongoing therapeutic approaches for patients. As we draw closer to gaining more complete catalogs of candidate cancer driver genes in common forms of cancer, the landscape of somatic mutations in osteosarcoma is emerging from its first phase. In this review, we summarize recent whole genome and/or whole exome genomic studies, and then put these findings in the context of genetic hallmarks of somatic mutations and mutational processes in human osteosarcoma...
October 16, 2016: Bone
Gaia Palmini, Roberto Zonefrati, Cecilia Romagnoli, Alessandra Aldinucci, Carmelo Mavilia, Gigliola Leoncini, Alessandro Franchi, Rodolfo Capanna, Maria Luisa Brandi
Osteosarcoma (OSA) is the most common primary malignant bone tumor, usually arising in the long bones of children and young adults. There are different subtypes of OSA, among which we find the conventional OS (also called medullary or central osteosarcoma) which has a high grade of malignancy and an incidence of 80%. There are different subtypes of high grade OS like chondroblastic, fibroblastic, osteoblastic, telangiectatic, and the small cell osteosarcoma (SCO). In this study, for the first time, we have isolated, established, and characterized a cell line of cancer stem cells (CSCs) from a human SCO...
2016: Stem Cells International
Richard Lock, Hernan Carol, John M Maris, E Anders Kolb, Richard Gorlick, C Patrick Reynolds, Min H Kang, Stephen T Keir, Jianrong Wu, Andrei Purmal, Andrei Gudkov, Dias Kurmashev, Raushan T Kurmasheva, Peter J Houghton, Malcolm A Smith
BACKGROUND: CBL0137 is a novel drug that modulates FAcilitates Chromatin Transcription (FACT), resulting in simultaneous nuclear factor-κB suppression, heat shock factor 1 suppression and p53 activation. CBL0137 has demonstrated antitumor effects in animal models of several adult cancers and neuroblastoma. PROCEDURES: CBL0137 was tested against the Pediatric Preclinical Testing Program (PPTP) in vitro cell line panel at concentrations ranging from 1.0 nM to 10...
September 21, 2016: Pediatric Blood & Cancer
Marie-Françoise Heymann, Hannah Brown, Dominique Heymann
INTRODUCTION: Osteosarcomas are the main malignant primary bone tumours found in children and young adults. Conventional treatment is based on diagnosis and resection surgery, combined with polychemotherapy. This is a protocol that was established in the 1970s. Unfortunately, this therapeutic approach has reached a plateau of efficacy and the patient survival rate has not improved in the last four decades. New therapeutic approaches are thus required to improve the prognosis for osteosarcoma patients...
September 15, 2016: Expert Opinion on Investigational Drugs
Christina K Lettieri, Nicole Appel, Nicole Labban, Danielle M Lussier, Joseph N Blattman, Pooja Hingorani
Survival outcomes for osteosarcoma have plateaued since the 1980s, and patients with relapsed or refractory disease have a particularly dismal outcome. Treatment options for these patients are limited primarily due to the paucity of effective therapeutics. Immune therapies such as tumor vaccines and traditional antigen-targeted monoclonal antibodies have had limited success in solid tumors. The recent discovery of novel immune checkpoint blockade strategies and their success in adult cancers has revitalized the use of immunotherapy strategies for the treatment of solid tumors...
October 2016: Immunotherapy
Andrea Ferrari, Uta Dirksen, Stefan Bielack
The definition of soft tissue and bone sarcomas include a large group of several heterogeneous subtypes of mesenchymal origin that may occur at any age. Among the different sarcomas, rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma and osteosarcoma are aggressive high-grade malignancies that often arise in adolescents and young adults. Managing these malignancies in patients in this age bracket poses various clinical problems, also because different therapeutic approaches are sometimes adopted by pediatric and adult oncologists, even though they are dealing with the same condition...
2016: Progress in Tumor Research
Robert J Canter
Since preoperative chemotherapy has been clearly shown to improve outcomes for patients with Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma, practitioners have attempted to extend the use of adjuvant/neoadjuvant chemotherapy to other types of adult soft tissue sarcoma. Given the high risk of distant recurrence and disease-specific death for patients with soft tissue sarcoma tumors larger than 10 cm, these patients should be considered candidates for neoadjuvant chemotherapy as well as investigational therapies...
October 2016: Surgical Oncology Clinics of North America
Karen M Chisholm, Robert S Ohgami, Brent Tan, Robert P Hasserjian, Olga K Weinberg
Primary lymphoma of bone (PLB) accounts for 3-7% of primary neoplasms of bone and must be distinguished from more common bone tumors in the pediatric population such as osteosarcoma, Ewing sarcoma, and other small round blue cell tumors. In this study, pathology databases from four institutions were queried for PLB in individuals 1-21 years old. A total of 54 cases of PLB were identified, including 41 diffuse large B cell lymphomas (DLBCL, 76%), 8 B lymphoblastic lymphomas (BLL, 15%), 3 anaplastic large cell lymphomas (ALCL, 6%), and 2 low grade follicular lymphomas (FL, 4%)...
August 20, 2016: Human Pathology
Alyaa Al-Ibraheemi, Carrie Y Inwards, Riyam T Zreik, Doris E Wenger, Sarah M Jenkins, Jodi M Carter, Jennifer M Boland, Peter S Rose, Long Jin, Andre M Oliveira, Karen J Fritchie
Although the majority of giant cell tumors (GCTs) of the bone occur in adult patients, occasionally they arise in the pediatric population. In this setting they may be mistaken for tumors more commonly seen in this age group, including osteosarcoma, aneurysmal bone cyst, and chondroblastoma. All cases of primary GCT of the bone arising in patients 18 years and below were retrieved from our institutional archives and examined with emphasis on the evaluation of various morphologic patterns. Clinical/radiologic records were reviewed when available...
August 11, 2016: American Journal of Surgical Pathology
Eline Boon, Winette T A van der Graaf, Hans Gelderblom, Margot E T Tesselaar, Robert J J van Es, Sjoukje F Oosting, Remco de Bree, Esther van Meerten, Ann Hoeben, Ludi E Smeele, Stefan M Willems, Max J H Witjes, Jan Buter, Robert J Baatenburg de Jong, Uta E Flucke, Petronella G M Peer, Judith V M G Bovée, Carla M L Van Herpen
BACKGROUND: There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. METHODS: All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. RESULTS: We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3...
August 10, 2016: Head & Neck
Camille Jacques, Lidia Rodriguez Calleja, Marc Baud'huin, Thibaut Quillard, Dominique Heymann, François Lamoureux, Benjamin Ory
Osteosarcoma and Ewing Sarcoma are the two most common types of Bone Sarcomas, principally localized at the long bones of the extremities and mainly affecting adolescents and young adults. Cisplatin is one of the current options in the therapeutic arsenal of drugs available to cure these aggressive cancers. Unfortunately, chemoresistance against this agent is still a major cause of patient relapse. Thus, a better understanding of the molecular pathways by which these drugs induce cancer cell death, together with a better delineation of the origins of chemoresistance are required to improve the success rate of current treatments...
July 29, 2016: Oncotarget
Suzanne McLaughlin, Christopher Terry, Fernando Barbosa, Bradley DeNardo
Approximately 1 in 285 children in the United States (US) will be diagnosed with cancer before the age of 20.1 More than 80% of children diagnosed with cancer will become long-term survivors.2 As of January, 2010, there are more than 380,000 adult survivors of childhood cancer in the US.3 More than two-thirds of survivors will develop chronic conditions.4 Professional organizations have advocated for specialized risk-based care of survivors.5 Locally and nationally, lack of transition services and insurance coverage are barriers to care of these adult survivors...
2016: Rhode Island Medical Journal
Christos Adamopoulos, Antonios N Gargalionis, Christina Piperi, Athanasios G Papavassiliou
Mechanotransduction is a key process by which cells perceive extracellular mechanical cues/intercellular physical interactions and transform them into intracellular biochemical signals. This physiological process is crucial during bone development and bone remodeling throughout childhood and adult life, whereas several aberrations during this process have emerged as a distinct pathogenic molecular entity in bone maladies and tumor formation. The present review focuses on recent advances regarding the mechanobiology of osteosarcoma, the most common type of bone cancer...
July 27, 2016: Journal of Cellular Biochemistry
Zhiguo Chen, Pengji Gao, Zongpeng Li
G protein-coupled receptor 56 (GPR56) is an atypical G protein-coupled receptor, with the long extracellular N-terminus. GPR56 can trigger various downstream signaling responsible for cell survival, proliferation, adhesion, and migration. Expression of GPR56 is associated with cell malignant transformation and tumor cell metastasis in several carcinomas such as melanoma and glioma. Osteosarcoma is the most common malignant bone tumor in adolescents and young adults with high metastasis tendency. The overall survival of osteosarcoma is unsatisfied, partially due to the lacking of predictive markers for metastasis and overall prognosis...
2016: Tohoku Journal of Experimental Medicine
Sophie Piperno-Neumann, Marie-Cécile Le Deley, Françoise Rédini, Hélène Pacquement, Perrine Marec-Bérard, Philippe Petit, Hervé Brisse, Cyril Lervat, Jean-Claude Gentet, Natacha Entz-Werlé, Antoine Italiano, Nadège Corradini, Emmanuelle Bompas, Nicolas Penel, Marie-Dominique Tabone, Anne Gomez-Brouchet, Jean-Marc Guinebretière, Eric Mascard, François Gouin, Aurélie Chevance, Naïma Bonnet, Jean-Yves Blay, Laurence Brugières
BACKGROUND: Based on preclinical data for the antitumour effect of zoledronate in osteosarcoma, we assessed whether zoledronate combined with chemotherapy and surgery improved event-free survival in children and adults with osteosarcoma. METHODS: In this randomised, multicentre, open-label, phase 3 trial (OS2006), patients aged between 5 years and 50 years with newly diagnosed high-grade osteosarcoma were randomly assigned to receive standard chemotherapy with or without ten zoledronate intravenous infusions (four preoperative and six postoperative)...
August 2016: Lancet Oncology
Q Zhang, Y Jin, C F Zhao, W J Wang, G Y Liu
Osteosarcoma (OS) is an aggressive cancer of the long bones, and usually affects children and young adults. The receptor for advanced glycation end-products (RAGE) has recently been recognized as an oncogenic receptor that binds to different ligands, and promotes the progression of various cancers. However, little is known about the association between RAGE and the pathogenesis of OS. In this study, we first examined the expression of RAGE in OS tissues using immunohistochemical staining, western blotting, and reverse transcription quantitative polymerase chain reaction...
2016: Genetics and Molecular Research: GMR
Konstantin Dobrenkov, Irina Ostrovnaya, Jessie Gu, Irene Y Cheung, Nai-Kong V Cheung
BACKGROUND: GD2 and GD3 are the tumor-associated glycolipid antigens found in a broad spectrum of human cancers. GD2-specific antibody is currently a standard of care for high-risk neuroblastoma therapy. In this study, the pattern of GD2 and GD3 expression among pediatric/adolescent or young adult tumors was determined, providing companion diagnostics for targeted therapy. METHODS: Ninety-two specimens of human osteosarcoma (OS), rhabdomyosarcoma (RMS), Ewing family of tumors, desmoplastic small round cell tumor (DSRCT), and melanoma were analyzed for GD2/GD3 expression by immunohistochemistry...
October 2016: Pediatric Blood & Cancer
Panfeng Wu, Jieyu Liang, Fang Yu, Zhengbing Zhou, Juyu Tang, Kanghua Li
Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. miR-145 is a microRNA highly expressed in vascularized tissues and has been widely studied in cancers. In this study, we explored the expression and function of miR-145 in OS. We found that miR-145 was consistently under-expressed in OS tissues and cell lines as compared to normal bone tissues and osteoblast cells. Ectopic expression of miR-145 in OS cells inhibited their proliferation and migration and induced apoptosis...
June 11, 2016: Oncotarget
C Y Chen, H Z Zhang, Z M Jiang, J Zhou, J Chen, L Liu
OBJECTIVE: To investigate the value of combined application of MDM2, CDK4 and SATB2 immunohistochemistry in pathological diagnosis of low-grade osteosarcoma. METHODS: Forty-seven cases of low grade osteosarcoma, including low grade central osteosarcoma (n=20) and parosteal osteosarcoma (n=27), were selected from Shanghai Jiaotong University Affiliated the Sixth People's Hospital. The clinical, radiography and histopathology were reviewed. The sensitivity and specificity of MDM2, CDK4 and SATB2 immunohistochemistry in the diagnosis of low-grade osteosarcoma were assessed along with an evaluation of their expressions in fibrous dysplasia, desmoplastic fibroma, low-grade fibrosarcoma and other fibrous tumors...
June 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
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