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Osteosarcoma adult

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https://www.readbyqxmd.com/read/28698375/bmtp-11-is-active-in-preclinical-models-of-human-osteosarcoma-and-a-candidate-targeted-drug-for-clinical-translation
#1
Valerae O Lewis, Eswaran Devarajan, Marina Cardó-Vila, Dafydd G Thomas, Eugenie S Kleinerman, Serena Marchiò, Richard L Sidman, Renata Pasqualini, Wadih Arap
Osteosarcoma occurs predominantly in children and young adults. High-grade tumors require multidisciplinary treatment consisting of chemotherapy in the neoadjuvant and adjuvant settings, along with surgical intervention. Despite this approach, death from respiratory failure secondary to the development and progression of pulmonary metastases remains a significant problem. Here, we identify the IL-11 receptor α subunit (IL-11Rα) as a cell surface marker of tumor progression that correlates with poor prognosis in patients with osteosarcoma...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28698141/epigenetic-silencing-of-the-wnt-antagonist-apcdd1-by-promoter-dna-hyper-methylation-contributes-to-osteosarcoma-cell-invasion-and-metastasis
#2
Weifeng Han, Junpeng Liu
Osteosarcoma (OS) is the most common type of bone tumor in children and adults. However, the molecular mechanism underlying OS tumorigenesis remains unclear. Here, we report that the expression of APCDD1, a Wnt antagonist, was reduced in OS tissues and cells compared to adjacent normal tissue and osteoblast cells, respectively. Mechanistically, this was due to increased levels of methylation in the promoter region of the APCDD1 gene. Consistently, the DNA methyltransferase inhibitor 5-AZA-dC, reduced DNA methylation in the APCDD1 promoter, and restored APCDD1 expression in OS tissue and cells...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28697168/pretreatment-neutrophil-to-lymphocyte-ratio-and-lymphocyte-recovery-independent-prognostic-factors-for-survival-in-pediatric-sarcomas
#3
Liliana Vasquez, Esmeralda León, Brady Beltran, Ivan Maza, Monica Oscanoa, Jenny Geronimo
BACKGROUND: Pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) recovery have been shown to be associated with prognosis in several types of cancer in adults. However, evidence in pediatric cancer is scarce. The aim of our study was to evaluate whether pretreatment NLR and lymphocyte recovery are prognostic factors in pediatric sarcomas. MATERIALS AND METHODS: Study participants were identified from a retrospective cohort of 100 children with osteosarcoma (n=55), rhabdomyosarcoma (n=22), and Ewing sarcoma (n=23)...
July 10, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28696044/practice-patterns-of-palliative-radiation-therapy-in-pediatric-oncology-patients-in-an-international-pediatric-research-consortium
#4
Avani Dholakia Rao, Qinyu Chen, Ralph P Ermoian, Sara R Alcorn, Maria Luisa S Figueiredo, Michael J Chen, Karin Dieckmann, Shannon M MacDonald, Matthew M Ladra, Daria Kobyzeva, Alexey V Nechesnyuk, Kristina Nilsson, Eric C Ford, Brian A Winey, Rosangela C Villar, Stephanie A Terezakis
BACKGROUND/OBJECTIVES: The practice of palliative radiation therapy (RT) is based on extrapolation from adult literature. We evaluated patterns of pediatric palliative RT to describe regimens used to identify opportunity for future pediatric-specific clinical trials. DESIGN/METHODS: Six international institutions with pediatric expertise completed a 122-item survey evaluating patterns of palliative RT for patients ≤21 years old from 2010 to 2015. Two institutions use proton RT...
July 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28673003/cucurbitacin-b-inhibits-cell-proliferation-and-induces-apoptosis-in-human-osteosarcoma-cells-via-modulation-of-the-jak2-stat3-and-mapk-pathways
#5
Zhi-Ren Zhang, Ming-Xia Gao, Kai Yang
Osteosarcoma (OS) is the most commonly diagnosed tumor of the bones in children and young adults. Even with conventional therapies the 5-year survival rate is ~65% in patients with OS. Considering the side effects and aggressiveness of malignant bone tumors, research is focussing on multi-targeted strategies in treatment. Cucurbitacin B, a triterpenoid compound has been demonstrated to induce apoptosis in various cancer cell types. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling cascades and mitogen activated protein kinases (MAPK) signalling cascades are critical regulators of tumorigenesis...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28671269/src-nuclear-localization-and-its-prognostic-relevance-in-human-osteosarcoma
#6
Enrica Urciuoli, Ilenia Coletta, Emanuele Rizzuto, Rita De Vito, Stefania Petrini, Valentina D'Oria, Marco Pezzullo, Giuseppe Maria Milano, Raffaele Cozza, Franco Locatelli, Barbara Peruzzi
Osteosarcoma is the most common malignant bone tumor in children and young adults. The identification of proteins which exhibit different subcellular localization in low- versus high-risk osteosarcoma can be instrumental to obtain prognostic information and to develop innovative therapeutic strategies. Beside the well-characterised membrane and cytoplasmic localization of Src protein, this study evaluated the prognostic relevance of its so-far unknown nuclear compartmentalization. We analyzed the subcellular distribution of total and activated (pY418) Src in a tissue microarray including 60 osteosarcoma samples...
July 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28643781/recurrent-mutation-of-igf-signalling-genes-and-distinct-patterns-of-genomic-rearrangement-in-osteosarcoma
#7
Sam Behjati, Patrick S Tarpey, Kerstin Haase, Hongtao Ye, Matthew D Young, Ludmil B Alexandrov, Sarah J Farndon, Grace Collord, David C Wedge, Inigo Martincorena, Susanna L Cooke, Helen Davies, William Mifsud, Mathias Lidgren, Sancha Martin, Calli Latimer, Mark Maddison, Adam P Butler, Jon W Teague, Nischalan Pillay, Adam Shlien, Ultan McDermott, P Andrew Futreal, Daniel Baumhoer, Olga Zaikova, Bodil Bjerkehagen, Ola Myklebost, M Fernanda Amary, Roberto Tirabosco, Peter Van Loo, Michael R Stratton, Adrienne M Flanagan, Peter J Campbell
Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28627672/inhibition-of-skp2-suppresses-the-proliferation-and-invasion-of-osteosarcoma-cells
#8
Lu Ding, Rong Li, Xiaoping Han, Yubo Zhou, Hua Zhang, Yong Cui, Wu Wang, Jingping Bai
Osteosarcoma (OS) is a common bone tumor that mainly affects children and young adults. S-phase kinase‑associated protein 2 (Skp2) has been characterized to play a critical oncogenic role in a variety of human malignancies. However, the biological function of Skp2 in OS remains largely obscure. In the present study, we elucidated the role of Skp2 in cell growth, cell cycle, apoptosis and migration in OS cells. We found that depletion of Skp2 inhibited cell growth in both MG-63 and SW 1353 cells. Moreover, we observed that depletion of Skp2 triggered cell apoptosis in two OS cell lines...
June 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28617714/perioperative-chemotherapy-with-and-without-high-dose-methotrexate-in-adult-osteosarcoma
#9
Marcelo Vailati Negrão, Lucila S da Silva Rocha, Daniel da Motta Girardi, Olavo Feher
Treatment of adult osteosarcoma (AOS) includes perioperative chemotherapy and surgery. Standard chemotherapy consists of cisplatin (CP) and doxorubicin (DOX). Although considered the standard of care for pediatric patients, high-dose methotrexate (HDM) remains controversial in adults. We aimed to evaluate the role of HDM in AOS treated with curative intent. This study included patients with AOS who received perioperative chemotherapy with DOX and CP (group 1; N=16) and DOX, CP, and HDM (group 2; N=10). The primary endpoint was grade 3 or superior toxicities...
June 14, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28616573/yap-and-the-hippo-pathway-in-pediatric-cancer
#10
REVIEW
Atif A Ahmed, Abdalla D Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada
The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28611244/fdg-uptake-during-early-adjuvant-chemotherapy-predicts-histologic-response-in-pediatric-and-young-adult-patients-with-osteosarcoma
#11
James C Davis, Najat C Daw, Fariba Navid, Catherine A Billups, Jianrong Wu, Armita Bahrami, Jesse J Jenkins, Scott E Snyder, Wilburn E Reddick, Victor M Santana, M Beth McCarville, Junyu Guo, Barry L Shulkin
The purpose of this study was to determine the relationship of (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in the primary tumor at diagnosis, during therapy, and following therapy with histological response and event-free survival (EFS) in pediatric and young adult patients with osteosarcoma (OS). Methods: Serial (baseline, 5 and 10 weeks after start of therapy) (18)F-FDG positron emission tomography/computed tomography (PET/CT) imaging was obtained in patients with newly diagnosed OS treated uniformly on a therapeutic trial at a single institution...
June 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28599316/biomarker-significance-of-plasma-and-tumor-mir-21-mir-221-and-mir-106a-in-osteosarcoma
#12
Manjula Nakka, Wendy Allen-Rhoades, Yiting Li, Aaron J Kelly, Jianhe Shen, Aaron M Taylor, Donald A Barkauskas, Jason T Yustein, Irene L Andrulis, Jay S Wunder, Richard Gorlick, Paul S Meltzer, Ching C Lau, Tsz-Kwong Man
Osteosarcoma is the most common malignant bone tumor in children and young adults. Despite the use of surgery and multi-agent chemotherapy, osteosarcoma patients who have a poor response to chemotherapy or develop relapses have a dismal outcome. Identification of biomarkers for active disease may help to monitor tumor burden, detect early relapses, and predict prognosis in these patients. In this study, we examined whether circulating miRNAs can be used as biomarkers in osteosarcoma patients. We performed genome-wide miRNA profiling on a discovery cohort of osteosarcoma and control plasma samples...
May 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28561655/fertility-cardiac-and-orthopedic-challenges-in-survivors-of-adult-and-childhood-sarcoma
#13
Emma R Lipshultz, Ginger E Holt, Ranjith Ramasamy, Raphael Yechieli, Steven E Lipshultz
The combination of cisplatin, doxorubicin, and methotrexate was established as the standard backbone of contemporary osteosarcoma therapy in 1986. Since then, however, further improving the survival of patients with osteosarcoma has been challenging-30% to 40% of patients with osteosarcoma still die of this disease. In addition, these patients often experience loss of fertility at a young age, short- and long-term treatment-related cardiotoxicity, and adverse orthopedic effects from surgical resection of the tumor or endoprosthetic reconstructions...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28547952/mir-150-up-regulates-glut1-and-increases-glycolysis-in-osteosarcoma-cells
#14
Guangke Yuan, Yanqing Zhao, Dongjin Wu, Chunzheng Gao
Objective: Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Many studies have shown that microRNAs play a critical role in proliferation and metastasis with this tumour type. However, whether aberrant expression might contribute to a metabolism switch in osteosarcoma cases is not clearly understood. In this study, we explored expression and function of miR-150 in osteosarcoma cells. Materials and methods: Expression of miR-150 was assessed by real-time PCR in cell lines and human patient tissues...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28530214/-the-long-term-treatment-outcomes-of-adult-osteosarcoma
#15
Iwowa Ługowska, Andrzej Pieńkowski, Anna Szumera-Ciećkiewicz, Hanna Koseła-Paterczyk, Pawel Teterycz, Maciej Głogowski, Katarzyna Kozak, Anna Klimczak, Slawomir Falkowski, Piotr Rutkowski
Osteosarcoma is the most common primary bone tumor. Treatment of osteosarcoma patients is based on chemotherapy as well as surgical resection of primary tumor and distant metastases. Lung metastases are the primary cause of death in this group of patients. AIM: The aim of this study is to summarize the 20 years of osteosarcoma treatment outcomes in the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw. MATERIALS AND METHODS: Our analysis included clinical data of 299 osteosarcoma patients aged between 14 and 81 years (median 32) treated in Maria Sklodowska-Curie Memorial Cancer Center between 1998 and 2016...
April 21, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28521633/cd30-expression-in-pediatric-neoplasms-study-of-585-cases
#16
Jinjun Cheng, Haiqing Zhu, John Kim Choi
CD30 is a member of the tumor necrosis factor receptor superfamily, member 8 (TNFRSF8), and its normal expression is restricted to activated T and B cells. In tumor cells, CD30 expression is most commonly associated with lymphoid malignancies (Hodgkin and non-Hodgkin lymphomas) and is a therapeutic target using anti-CD30 antibody. CD30 expression has been reported also in mostly adult non-lymphoid malignancies, raising the possibility of CD30-targeted therapy for additional tumors. In this study, we examined the incidence of CD30 expression in 251 hematopoietic and 334 non-hematopoietic cases of pediatric tumors...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28455992/microrna-610-suppresses-osteosarcoma-oncogenicity-via-targeting-twist1-expression
#17
Chi Jin, Yongjian Feng, Yongjian Ni, Zhonglin Shan
Osteosarcoma is the most frequent primary bone tumor affects adolescents and young adults. Recently, microRNAs (miRNAs) are short, non-coding and endogenous RNAs that played as important roles in the initiation and progression of tumors. In this study, we try to explore the biological function and expression of miR-610 in the osteosarcoma. We showed that miR-610 expression was downregulated in the osteosarcoma tissues and cell lines. Elevated expression of miR-610 suppressed the osteosarcoma cell proliferation, cell cycle, invasion and EMT program...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454389/notch-signaling-is-important-for-epithelial-mesenchymal-transition-induced-by-low-concentrations-of-doxorubicin-in-osteosarcoma-cell-lines
#18
Jian Yang, Weichun Guo, Lu Wang, Ling Yu, Hongjun Mei, Shuo Fang, Anyuan Chen, Yang Liu, Kezhou Xia, Gaiwei Liu
Osteosarcoma is an aggressive pediatric tumor affecting growing bones that typically occurs in adolescents and young adults. Although advances in treatment have been made in recent years, a high proportion of patients relapse due to metastases, which are frequently resistant to chemotherapy and pose a significant threat to long-term survival. Previous studies have demonstrated that the epithelial-mesenchymal transition (EMT) is associated with cancer occurrence and metastasis, and our previous study demonstrated the occurrence of EMT in osteosarcoma...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28441368/skeletal-scintigraphy
#19
Jaime L Montilla-Soler, Rikesh Makanji
BACKGROUND: Skeletal scintigraphy remains a valuable tool in the initial and subsequent evaluation of the skeletal system in patients with a diagnosis of primary or metastatic neoplasms. METHODS: We discuss radiopharmaceuticals, nuclear medicine imaging techniques, and current as well as future oncological applications in the adult population. Pertinent literature was reviewed to describe the advantages and limitations of available technologies for the evaluation of skeletal metastatic disease...
April 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28435520/genetically-transforming-human-osteoblasts-to-sarcoma-development-of-an-osteosarcoma-model
#20
Yi Yang, Rui Yang, Michael Roth, Sajida Piperdi, Wendong Zhang, Howard Dorfman, Pulivarthi Rao, Amy Park, Sandeep Tripathi, Carrie Freeman, Yunjia Zhang, Rebecca Sowers, Jeremy Rosenblum, David Geller, Bang Hoang, Jonathan Gill, Richard Gorlick
Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras...
January 2017: Genes & Cancer
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