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Pediatric osteosarcoma

Jorrit W van As, Henk van den Berg, Elvira C van Dalen
BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin or a combination of these, is used to treat a variety of paediatric malignancies. One of the most important adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different otoprotective medical interventions have been studied. This review is the second update of a previously published Cochrane review. OBJECTIVES: To assess the efficacy of medical interventions to prevent hearing loss and to determine possible effects of these interventions on anti-tumour efficacy, toxicities other than hearing loss and quality of life in children with cancer treated with platinum-based therapy...
September 27, 2016: Cochrane Database of Systematic Reviews
Leo Kager, Gevorg Tamamyan, Stefan Bielack
High-grade osteosarcomas are the most common primary malignant tumors of bone. With complete surgical resection and multi-agent chemotherapy up to 70% of patients with high-grade osteosarcomas and localized extremity tumors can become long-term survivors. The prognosis, however, is poor for patients with nonresectable, primary metastatic or relapsed disease. Outcome is essentially unchanged for three decades. Herein, we describe selected novel insights into the genomics, biology and immunology of the disease and discuss selected strategies, which hold promise to overcome the current stagnation in the therapeutic success in childhood osteosarcoma...
September 21, 2016: Future Oncology
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
Hernán Correa
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by a germline mutation of the TP53 gene on chromosome 17p13.1. It has an autosomal dominant pattern of inheritance with high penetrance. These patients have a very high lifetime cumulative risk of developing multiple malignancies and have a strong family history of early-onset malignancies. The protein p53, encoded by TP53, has a complex set of genome-preserving functions initiated during episodes of cellular stress and DNA damage. In LFS, TP53 gene mutations cause the loss of function of p53, leading to downstream events permissive for development of various malignancies throughout life...
June 2016: Journal of Pediatric Genetics
Christine M Heske, Arnulfo Mendoza, Leah D Edessa, Joshua T Baumgart, Sunmin Lee, Jane Trepel, David A Proia, Len Neckers, Lee J Helman
Long-term survival in patients with metastatic, relapsed, or recurrent Ewing sarcoma and rhabdomyosarcoma is dismal. Irinotecan, a topoisomerase 1 inhibitor, has activity in these sarcomas, but due to poor bioavailability of its active metabolite (SN-38) has had limited clinical efficacy. In this study we have evaluated the efficacy and toxicity of STA-8666, a novel drug conjugate which uses an HSP90 inhibitor to facilitate intracellular, tumor-targeted delivery of the topoisomerase 1 inhibitor SN-38, thus preferentially delivering and concentrating SN-38 within tumor tissue...
September 6, 2016: Oncotarget
Anant Ramaswamy, Bharat Rekhi, Sameer Bakhshi, Sachin Hingmire, Manish Agarwal
Bone sarcomas are rare tumors, approximating 0.2% of all cancers, with osteosarcoma (OGS), chondrosarcoma, and Ewing sarcoma being the most common cancers in this subset. The formation of disease management groups/clinics focused on sarcomas has resulted in better understanding and management of these uncommon tumors. Multiple large-scale retrospective data from Tata Memorial Hospital (TMH) and All India Institute of Medical Sciences have reported outcomes comparable to Western data in the field of OGS and Ewing sarcoma, with interesting prognostic factors identified for further evaluation...
July 2016: South Asian Journal of Cancer
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
Doralina L Anghelescu, Brenda D Steen, Huiyun Wu, Jianrong Wu, Najat C Daw, Bhaskar N Rao, Michael D Neel, Fariba Navid
BACKGROUND: Neuropathic pain (NP) after definitive surgery for extremity osteosarcoma (OS) has not been previously characterized. This study prospectively investigates the incidence, duration, and treatment of NP in limb sparing surgery and amputation groups. PROCEDURE: In patients treated for OS on a chemotherapy and definitive surgery (limb sparing vs. amputation) protocol (OS08), we prospectively collected the following data: (i) demographical data (age, sex, race); (ii) NP time of onset and duration; and (iii) dose (starting, maximum) and duration of gabapentin, amitriptyline, and methadone treatment...
August 30, 2016: Pediatric Blood & Cancer
Cheryl Stroud, Igor Dmitriev, Elena Kashentseva, Jeffrey N Bryan, David T Curiel, Hans Rindt, Carol Reinero, Carolyn J Henry, Philip J Bergman, Nicola J Mason, Josephine S Gnanandarajah, Julie B Engiles, Falon Gray, Danielle Laughlin, Anita Gaurnier-Hausser, Anu Wallecha, Margie Huebner, Yvonne Paterson, Daniel O'Connor, Laura S Treml, James P Stannard, James L Cook, Marc Jacobs, Gerald J Wyckoff, Lee Likins, Ubadah Sabbagh, Andrew Skaff, Amado S Guloy, Harlen D Hays, Amy K LeBlanc, Joan R Coates, Martin L Katz, Leslie A Lyons, Gayle C Johnson, Gary S Johnson, Dennis P O'Brien, Dongsheng Duan, James P Calvet, Barbara Gandolfi, David A Baron, Mark L Weiss, Debra A Webster, Francis N Karanu, Edward J Robb, Robert J Harman
A1 One health advances and successes in comparative medicine and translational researchCheryl StroudA2 Dendritic cell-targeted gorilla adenoviral vector for cancer vaccination for canine melanomaIgor Dmitriev, Elena Kashentseva, Jeffrey N. Bryan, David T. CurielA3 Viroimmunotherapy for malignant melanoma in the companion dog modelJeffrey N. Bryan, David Curiel, Igor Dmitriev, Elena Kashentseva, Hans Rindt, Carol Reinero, Carolyn J. HenryA4 Of mice and men (and dogs!): development of a commercially licensed xenogeneic DNA vaccine for companion animals with malignant melanomaPhilip J...
August 2016: Clinical and Translational Medicine
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
Peter Kaatsch, Jill Strothotte, Cornelia Becker, Stefan Bielack, Uta Dirksen, Maria Blettner
BACKGROUND: Malignant bone tumors are a rare group of childhood cancer. MATERIALS AND METHODS: This study describes incidence rates, survival probabilities, and time trends for 1831 children below 15 years of age with a bone tumor registered at the population-based German Childhood Cancer Registry between 1987 and 2011. RESULTS: Overall age-standardized annual incidence rate (ASR) was 5.5 per million. Osteosarcomas (ASR 2.8) and Ewing tumors (ASR 2...
August 23, 2016: Acta Oncologica
Adrienne H Long, Steven L Highfill, Yongzhi Cui, Jillian P Smith, Alec J Walker, Sneha Ramakrishna, Rana El-Etriby, Susana Galli, Maria G Tsokos, Rimas J Orentas, Crystal L Mackall
Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CAR) have shown impressive activity against B-cell malignancies, and preliminary results suggest that T cells expressing a first-generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies to treat pediatric sarcomas. We observed that 18 of 18 (100%) of osteosarcomas, 2 of 15 (13%) of rhabdomyosarcomas, and 7 of 35 (20%) of Ewing sarcomas expressed GD2...
October 2016: Cancer Immunology Research
Regan F Williams, Israel Fernandez-Pineda, Ankush Gosain
Pediatric sarcomas are a heterogeneous group of tumors accounting for approximately 10% of childhood solid tumors. Treatment is focused on multimodality therapy, which has improved the prognosis over the past two decades. Current regimens focus on decreasing treatment for low-risk patients to decrease the long-term side effects while maximizing therapy for patients with metastatic disease to improve survival. Pediatric sarcomas can be divided into soft tissue sarcomas and osseous tumors. Soft tissue sarcomas are further delineated into rhabdomyosarcomas, which affect young children and nonrhabdomyosarcomas, which are most common in adolescents...
October 2016: Surgical Clinics of North America
Ricardo J Flores, Aaron J Kelly, Yiting Li, Manjula Nakka, Donald A Barkauskas, Mark Krailo, Lisa L Wang, Laszlo Perlaky, Ching C Lau, M John Hicks, Tsz-Kwong Man
BACKGROUND: Osteosarcoma (OS) is the most common malignant pediatric bone tumor. The identification of novel biomarkers for early prognostication will facilitate risk-based stratification and therapy. This study investigated the significance of circulating cytokines/chemokines for predicting the prognosis at the initial diagnosis. METHODS: Luminex assays were used to measure cytokine/chemokine concentrations in blood samples from a discovery cohort of OS patients from Texas Children's Hospital (n = 37) and an independent validation cohort obtained from the Children's Oncology Group (n = 233)...
August 16, 2016: Cancer
Sarah A Hansen, Marcia L Hart, Susheel Busi, Taybor Parker, Angela Goerndt, Kevin Jones, James M Amos-Landgraf, Elizabeth C Bryda
Somatic mutations in the Tp53 tumor suppressor gene are the most commonly seen genetic alterations in cancer, and germline mutations in Tp53 predispose individuals to a variety of early-onset cancers. Development of appropriate translational animal models that carry mutations in Tp53 and recapitulate human disease are important for drug discovery, biomarker development and disease modeling. Current Tp53 mouse and rat models have significant phenotypic and genetic limitations, and often do not recapitulate certain aspects of human disease...
October 1, 2016: Disease Models & Mechanisms
Upal Basu-Roy, Eugenia Han, Kirk Rattanakorn, Abhilash Gadi, Narendra Verma, Giulia Maurizi, Preethi H Gunaratne, Cristian Coarfa, Oran D Kennedy, Michael J Garabedian, Claudio Basilico, Alka Mansukhani
Osteosarcoma (OS) is a highly aggressive pediatric bone cancer in which most tumor cells remain immature and fail to differentiate into bone-forming osteoblasts. However, OS cells readily respond to adipogenic stimuli suggesting they retain mesenchymal stem cell-like properties. Here we demonstrate that nuclear receptor PPARγ agonists such as the anti-diabetic, thiazolidinedione (TZD) drugs induce growth arrest and cause adipogenic differentiation in human, mouse and canine OS cells as well as in tumors in mice...
August 12, 2016: Oncotarget
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
Nerea Bilbao-Aldaiturriaga, Ziortza Askaiturrieta, Itsasne Granado-Tajada, Katja Goričar, Vita Dolžan, For The Slovenian Osteosarcoma Study Group, Purificación Garcia-Miguel, Nagore Garcia de Andoin, Idoia Martin-Guerrero, Africa Garcia-Orad
Two polymorphisms in the murine double minute 2 (MDM2) gene (rs1690916 and rs2279744) have been associated with the risk of osteosarcoma (OS). When we analyzed these two polymorphisms in two new independents cohorts (Spanish and Slovenian), we found no association. In order to clarify this, we conducted a meta-analysis including six populations, with a total of 246 OS patients and 1,760 controls for rs1690916; and 433 OS patients and 1,959 controls for rs2279744. Pooled odds ratio risks and corresponding 95% CI were estimated to assess the possible associations...
October 2016: Pediatric Research
Joanne P Lagmay, Mark D Krailo, Ha Dang, AeRang Kim, Douglas S Hawkins, Orren Beaty, Brigitte C Widemann, Theodore Zwerdling, Lisa Bomgaars, Anne-Marie Langevin, Holcombe E Grier, Brenda Weigel, Susan M Blaney, Richard Gorlick, Katherine A Janeway
PURPOSE: The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. PATIENTS AND METHODS: We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007...
September 1, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Jia-Li Zhao, Feng-Li Chen, Quan Zhou, Wei Pan, Xin-Hong Wang, Jin Xu, Shao-Xian Zhang, L I Ni, Hui-Lin Yang
Osteosarcoma is an aggressive type of bone tumor that commonly occurs in pediatric age groups. The complete molecular mechanisms behind osteosarcoma formation and progression require elucidation. B7-H3 is a protein of the B7 family that acts as a co-stimulatory molecule with a significant role in adaptive immune responses. The link between B7-H3 expression and its role in different types of cancer remains unclear. B7-H3 protein exhibits different functional roles in in vivo and in vitro conditions that remain controversial...
July 2016: Oncology Letters
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