Osteosarcoma Causes, Risk Factors, and Prevention Risk Factors
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Infiltrating Myeloid Cells Drive Osteosarcoma Progression Via GRM4 Regulation of IL23
Published OnlineFirst September 16, 2019; DOI: 10.1158/2159-8290.CD-19-0154 RESEARCH BRIEF Infi ltrating Myeloid Cells Drive Osteosarcoma Progression via GRM4 Regulation of IL23 Maya Kansara 1 , 2 , Kristian Thomson 1 , Puiyi Pang 1 , Aurelie Dutour 3 , Lisa Mirabello 4 , Francine Acher5 , Jean-Philippe Pin 6 , Elizabeth G. Demicco 7 , Juming Yan 8 , Michele W.L. Teng 8 , Mark J. Smyth 9 , and David M. Thomas 1 , 2 ABSTRACT The glutamate metabotropic receptor 4 (GRM4 ) locus is linked to susceptibility to human osteosarcoma, through unknown mechanisms. We show that Grm4 − / − gene– targeted mice demonstrate accelerated radiation-induced tumor development to an extent comparable with Rb1 +/ − mice. GRM4 is expressed in myeloid cells, selectively regulating expression of IL23 and the related cytokine IL12. Osteosarcoma-conditioned media induce myeloid cell Il23 expression in a GRM4-dependent fashion, while suppressing the related cytokine Il12 . Both human and mouse osteosarcomas express an increased IL23:IL12 ratio, whereas higher IL23 expression is associated with worse survival in humans. Con- sistent with an oncogenic role, Il23−/− mice are strikingly resistant to osteosarcoma development. Agonists of GRM4 or a neutralizing antibody to IL23 suppressed osteosarcoma growth in mice. These fi ndings identify a novel, druggable myeloid suppressor pathway linking GRM4 to the proinfl ammatory IL23/IL12 axis. SIGNIFICANCE: Few novel systemic therapies targeting osteosarcoma have emerged in the last four decades. Using insights gained from a genome-wide association study and mouse modeling, we show that GRM4 plays a role in driving osteosarcoma via a non–cell-autonomous mechanism regulating IL23, opening new avenues for therapeutic intervention. -
Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Kidney: the MD Anderson Cancer Center Experience
cancers Article Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Kidney: The MD Anderson Cancer Center Experience Nidale Tarek 1,2,*, Rabih Said 3, Clark R. Andersen 4, Tina S. Suki 1, Jessica Foglesong 1,5 , Cynthia E. Herzog 1, Nizar M. Tannir 6, Shreyaskumar Patel 7, Ravin Ratan 7, Joseph A. Ludwig 7 and Najat C. Daw 1,* 1 Department of Pediatrics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] (T.S.S.); [email protected] (J.F.); [email protected] (C.E.H.) 2 Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut 1107, Lebanon 3 Department of Investigational Cancer Therapeutics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] 4 Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] 5 Division of Hematology, Oncology, Neuro-Oncology & Stem Cell Transplant, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USA 6 Department of Genitourinary Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] 7 Department of Sarcoma Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; [email protected] (S.P.); [email protected] (R.R.); [email protected] (J.A.L.) * Correspondence: [email protected] (N.T.); [email protected] (N.C.D.); Tel.: +1-713-792-6620 (N.C.D.) Received: 27 August 2020; Accepted: 5 October 2020; Published: 11 October 2020 Simple Summary: The Ewing sarcoma family of tumors (ESFT)s rarely originate in the kidneys and their treatment is significantly different from the other common kidney tumors. -
Advances in Immune Checkpoint Inhibitors for Bone Sarcoma Therapy T Pichaya Thanindratarna,B, Dylan C
Journal of Bone Oncology 15 (2019) 100221 Contents lists available at ScienceDirect Journal of Bone Oncology journal homepage: www.elsevier.com/locate/jbo Review Article Advances in immune checkpoint inhibitors for bone sarcoma therapy T Pichaya Thanindratarna,b, Dylan C. Deana, Scott D. Nelsonc, Francis J. Horniceka, ⁎ Zhenfeng Duana, a Department of Orthopedic Surgery, Sarcoma Biology Laboratory, David Geffen School of Medicine, University of California, 615 Charles E. Young. Dr. South, Los Angeles, CA 90095, USA b Department of Orthopedic Surgery, Chulabhorn hospital, HRH Princess Chulabhorn College of Medical Science, Bangkok, Thailand c Department of Pathology, University of California, Los Angeles, CA, USA ARTICLE INFO ABSTRACT Keywords: Bone sarcomas are a collection of sporadic malignancies of mesenchymal origin. The most common subtypes Immune checkpoint include osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. Despite the use of aggressive treatment Immunotherapy protocols consisting of extensive surgical resection, chemotherapy, and radiotherapy, outcomes have not sig- Bone sarcoma nificantly improved over the past few decades for osteosarcoma or Ewing sarcoma patients. In addition, chon- Anti-PD-1/PD-L1 drosarcoma and chordoma are resistant to both chemotherapy and radiation therapy. There is, therefore, an Anti-CTLA-4 urgent need to elucidate which novel new therapies may affect bone sarcomas. Emerging checkpoint inhibitors have generated considerable attention for their clinical success in a variety of human cancers, which has led to works assessing their potential in bone sarcoma management. Here, we review the recent advances of anti-PD-1/ PD-L1 and anti-CTLA-4 blockade as well as other promising new immune checkpoint targets for their use in bone sarcoma therapy. -
Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies
Journal of Clinical Medicine Review Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies Richa Rathore 1 and Brian A. Van Tine 1,2,3,* 1 Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO 63110, USA; [email protected] 2 Division of Pediatric Hematology and Oncology, St. Louis Children’s Hospital, St. Louis, MO 63110, USA 3 Siteman Cancer Center, St. Louis, MO 63110, USA * Correspondence: [email protected] Abstract: Osteosarcoma is the most common primary malignant bone tumor in children and young adults. The standard-of-care curative treatment for osteosarcoma utilizes doxorubicin, cisplatin, and high-dose methotrexate, a standard that has not changed in more than 40 years. The development of patient-specific therapies requires an in-depth understanding of the unique genetics and biology of the tumor. Here, we discuss the role of normal bone biology in osteosarcomagenesis, highlighting the factors that drive normal osteoblast production, as well as abnormal osteosarcoma development. We then describe the pathology and current standard of care of osteosarcoma. Given the complex hetero- geneity of osteosarcoma tumors, we explore the development of novel therapeutics for osteosarcoma that encompass a series of molecular targets. This analysis of pathogenic mechanisms will shed light on promising avenues for future therapeutic research in osteosarcoma. Keywords: osteosarcoma; mesenchymal stem cell; osteoblast; sarcoma; methotrexate Citation: Rathore, R.; Van Tine, B.A. Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies. J. Clin. Med. 2021, 1. Introduction 10, 1182. https://doi.org/10.3390/ Osteosarcomas are the most common pediatric and adult bone tumor, with more than jcm10061182 1000 new cases every year in the United States alone. -
Malignant Bone Tumors (Other Than Ewing’S): Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up by Spanish Group for Research on Sarcomas (GEIS)
Cancer Chemother Pharmacol DOI 10.1007/s00280-017-3436-0 ORIGINAL ARTICLE Malignant bone tumors (other than Ewing’s): clinical practice guidelines for diagnosis, treatment and follow-up by Spanish Group for Research on Sarcomas (GEIS) Andrés Redondo1 · Silvia Bagué2 · Daniel Bernabeu1 · Eduardo Ortiz-Cruz1 · Claudia Valverde3 · Rosa Alvarez4 · Javier Martinez-Trufero5 · Jose A. Lopez-Martin6 · Raquel Correa7 · Josefina Cruz8 · Antonio Lopez-Pousa9 · Aurelio Santos10 · Xavier García del Muro11 · Javier Martin-Broto10 Received: 7 July 2017 / Accepted: 15 September 2017 © The Author(s) 2017. This article is an open access publication Abstract Primary malignant bone tumors are uncommon of a localized bone tumor, with various techniques available and heterogeneous malignancies. This document is a guide- depending on the histologic type, grade and location of the line developed by the Spanish Group for Research on Sar- tumor. Chemotherapy plays an important role in some che- coma with the participation of different specialists involved mosensitive subtypes (such as high-grade osteosarcoma). in the diagnosis and treatment of bone sarcomas. The aim is In other subtypes, historically considered chemoresistant to provide practical recommendations with the intention of (such as chordoma or giant cell tumor of bone), new targeted helping in the clinical decision-making process. The diag- therapies have emerged recently, with a very significant effi- nosis and treatment of bone tumors requires a multidiscipli- cacy in the case of denosumab. Radiation therapy is usually nary approach, involving as a minimum pathologists, radi- necessary in the treatment of chordoma and sometimes of ologists, surgeons, and radiation and medical oncologists. other bone tumors. Early referral to a specialist center could improve patients’ survival. -
A Rare Case of Peripheral Primitive Neuroectodermal Tumor in Palate
Surgery and Rehabilitation Case Report ISSN: 2514-5959 A rare case of peripheral primitive neuroectodermal tumor in palate Rajul Ranka1*, Anuj Jain2, Amol Gadbail3 and Minal Chaudhary1 1Oral Pathology and Microbiology, Sharad Pawar Dental College and Hospital, Sawangi(M), Wardha, India 2Department of Trauma and Emergency Medicine, All India Institute of Medical Sciences, Bhopal, India 3Department of Dentistry, Indira Gandhi Government Medical College, Nagpur, India Abstract Primitive Neuroectodermal Tumor (PNET) is an aggressive round cell malignant tumor which belongs to Ewing’s Sarcoma family. Peripheral PNET is rare in head and neck region and even rare in palate with handful of cases reported till date. A case of Peripheral PNET of palate in a 32-year-old female pa tient along with its clinico-pathologic, radiologic and immunohistologic features as well as its management is reported here. We emphasize the need of histopathology and immunohistochemistry (IHC) for early diagnosis of such aggressive tumors to improve the prognosis of patient by providing timely management. Introduction Case report A neuroectodermal tumor is a tumor of the central or peripheral A thirty-two years old female patient of Indian origin reported nervous system. They are divided into two categories viz. Group to the Out-Patient Department of our institute with a complaint of (I) tumors, such as the pituitary adenomas and carcinoid tumors, painful ulcer on her palate since five months. The ulcer was gradually represent tumors that show predominantly epithelial differenti ation. progressive but has now suddenly increased in size since few days. It Group (II) tumors, which incorporate malignant melanoma, olfactory was associated with dull aching, intermittent and localized pain which neuroblastoma, Ewing’s sar coma (EWS) and primitive neuroectodermal aggravated on mastication and relieved with time. -
Craniofacial Chondrosarcomas: Imaging Findings in 15 Untreated Cases
165 Craniofacial Chondrosarcomas: Imaging Findings in 15 Untreated Cases Ya-Yen Lee1 Radiographic findings of 15 untreated chondrosarcomas of the cranial and facial Pamela Van Tassel bones were reviewed. These tumors have a propensity to occur in the wall of a maxillary sinus, at the junction of sphenoid and ethmoid sinuses and vomer, and at the undersur face of the sphenoid bone. Because of its slow-growing nature, chondrosarcomas tend to be large, multi lobulated, and sharply demarcated when detected. Frequent bone changes are a combination of erosion and destruction, with sharp transitional zones and absent periosteal reaction. Tumor matrix calcifications, not necessarily chondroid, are almost always present. Both CT and MR may be necessary for thorough evaluation of tumor extent. Chondrosarcoma, a malignant but usually slow-growing cartilaginous tumor, constitutes approximately 11 % of malignant bone tumors [1] but rarely occurs in the craniofacial region . Because of its propensity to occur in the deep facial structures or base of the skull, the true extent and origin of the tumor may be overlooked if not properly evaluated radiographically. We review a relatively large series of craniofacial chondrosarcomas and discuss the differential diagnosis and choice of imaging technique. Materials and Methods This retrospective radiologic review was based on the pretreatment radiographic studies of 15 patients with craniofacial chondrosarcomas seen at our institution over a period of 40 years , excluding three intracranial dural chondrosarcomas, which are to be reported sepa rately. An attempt was also made to correlate the radiographic findings with the hi stologic grades of the tumors. The ages of the patients ranged from 10 to 73 years , with a mean of 40 years. -
Primary Bone Cancer a Guide for People Affected by Cancer
Cancer information fact sheet Understanding Primary Bone Cancer A guide for people affected by cancer This fact sheet has been prepared What is bone cancer? to help you understand more about Bone cancer can develop as either a primary or primary bone cancer, also known as secondary cancer. The two types are different and bone sarcoma. In this fact sheet we this fact sheet is only about primary bone cancer. use the term bone cancer, and include general information about how bone • Primary bone cancer – means that the cancer cancer is diagnosed and treated. starts in a bone. It may develop on the surface, in the outer layer or from the centre of the bone. As a tumour grows, cancer cells multiply and destroy The bones the bone. If left untreated, primary bone cancer A typical healthy person has over 200 bones, which: can spread to other parts of the body. • support and protect internal organs • are attached to muscles to allow movement • Secondary (metastatic) bone cancer – means • contain bone marrow, which produces that the cancer started in another part of the body and stores new blood cells (e.g. breast or lung) and has spread to the bones. • store proteins, minerals and nutrients, such See our fact sheet on secondary bone cancer. as calcium. Bones are made up of different parts, including How common is bone cancer? a hard outer layer (known as cortical or compact Bone cancer is rare. About 250 Australians are bone) and a spongy inner core (known as trabecular diagnosed with primary bone cancer each year.1 or cancellous bone). -
Immunological Status of Peripheral Blood Is Associated with Prognosis in Patients with Bone and Soft-Tissue Sarcoma
ONCOLOGY LETTERS 21: 212, 2021 Immunological status of peripheral blood is associated with prognosis in patients with bone and soft-tissue sarcoma YOUNGJI KIM1‑3, EISUKE KOBAYASHI1, YOSHIYUKI SUEHARA2, AYUMU ITO4, DAISUKE KUBOTA1,2, YOSHIKAZU TANZAWA1, MAKOTO ENDO1, FUMIHIKO NAKATANI1, TETSUYA NAKATSURA3, AKIRA KAWAI1, KAZUO KANEKO2 and SHIGEHISA KITANO3,5,6 1Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo 104‑0045; 2Department of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo 113‑8431; 3Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital, Tokyo 104‑0045; Departments of 4Hematopoietic Stem Cell Transplantation, and 5Experimental Therapeutics, National Cancer Center Hospital, Tokyo 104‑0045; 6Division of Cancer Immunotherapy Development, Advanced Medical Development Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135‑8550, Japan Received June 27, 2020; Accepted October 23, 2020 DOI: 10.3892/ol.2021.12473 Abstract. Immune‑checkpoint inhibitors have shown Multivariate Cox regression analysis demonstrated that the promising antitumor effects against certain types of cancer. number of Tim‑3+ CD8+ T cells was associated with lower However, specific immune‑checkpoint inhibitors for patients DFS time. A significant association was also found between with sarcoma have yet to be identified, whereas the immu‑ the number of M‑MDSCs and progression‑free survival (PFS) nological status of peripheral blood in patients with bone time in patients with metastasis. The results suggested the sarcoma and soft‑tissue sarcoma (STS) remains unknown. occurrence of immune surveillance, which indicated that the In addition, it is unclear whether the immunological status host immune reaction against cancer existed in patients with from the peripheral blood could be used as a prognostic bone sarcoma and STS. -
Conventional Chondrosarcoma James C
Conventional Chondrosarcoma James C. Wittig, MD SSSarcoma Surgeon Orthopedic Oncologist General Information Ma lignant mesenc hyma l tumor o f cart ilag inous different iat ion. Conventional Chondrosarcoma is the most common type of chondrosarcoma (malignant cartilage tumor) Neoplastic cells form hyaline type cartilage or chondroid type tissue (Chondroid Matrix) but not osteoid If lesion arises de novo, it is a primary chondrosarcoma If superimposed on a preexisting benign neoplasm, it is considered a secondary chondrosarcoma Central chondrosarcomas arise from an intramedullary location. They may grow, destroy the cortex and form a soft tissue component. Peripheral chondrosarcomas extend outward from the cortex of the bone and can invade the medullary cavity. Peripheral chondrosarcomas most commonly arise from preexisting osteochondromas. Juxtacortical chondrosarcomas arise from the inner layer of the periosteum on the surface of the bone. It is technically considered a peripheral chondrosarcoma. Chondrosarcoma Heterogeneous group of tumors with varying biological behavior depending on grade, size and location Cartilage tumors can have similar histology and behave differently depending on location. For instance a histologically benign appearing cartilage tumor in the pelvis will behave aggressively as a low grade chondrosarcoma. Likewise, a histologically more aggressive hypercellular cartilag e tumor localized in a p halanx of a dig it may behave in an indolent, non aggressive or benign manner. There are low (grade I), intermediate (grade II) and high grade (grade III) types of conventional chondrosarcoma. Low grade lesions are slow growing and rarely metastasize . Low grade chondrosarcomas can be difficult to differentiate from benign tumors histologically. Clinical features and radiographic studies are important to help differentiate. -
Bone & Soft Tissue
14A ANNUAL MEETING ABSTRACTS and testicular atrophy with aspermatogenia (negative OCT3/OCT4 stain). There was 47 Comparison of Autopsy Findings of 2009 Pandemic Influenza evidence of acute multifocal bronchopneumonia and congestive heart failure. He carried A (H1N1) with Seasonal Influenza in Four Pediatric Patients two heterozygous mutations in ALMS1: 11316_11319delAGAG; R3772fs in exon 16 B Xu, JJ Woytash, D Vertes. State University of New York at Buffalo, Buffalo, NY; Erie and 8164C>T ter; R2722X in exon 10. County Medical Examiner’s Office, Buffalo, NY. Conclusions: This report describes previously undefined cardiac abnormalities in this Background: The swine-origin influenza A (H1N1) virus that emerged in humans rare multisystem disorder. Myofibrillar disarray is probably directly linked to ALMS1 in early 2009 has reached pandemic proportions and cause over 120 pediatric deaths mutation, while fibrosis in multiple organs may be a secondary phenomenon to gene nationwide. Studies in animal models have shown that the 2009 H1N1 influenza virus alteration. Whether and how intracellular trafficking or related signals lead to cardiac is more pathogenic than seasonal A virus, with more extensive virus replication and dysfunction is a subject for further research. shedding occurring the respiratory tract. Design: We report four cases of influenza A-associated deaths (two pandemic and two 45 Sudden Cardiac Death in Young Adults: An Audit of Coronial seasonal) in persons less than fifteen years of age who had no underlying health issues. Autopsy Findings Autopsy finding on isolation of virus from various tissue specimen, cocurrent bacterial A Treacy, A Roy, R Margey, JC O’Keane, J Galvin, A Fabre. -
Spectrum of Bone Tumors in Chiang Mai University Hospital, Thailand According to WHO Classification 2002: a Study of 1,001 Cases
Spectrum of Bone Tumors in Chiang Mai University Hospital, Thailand According to WHO Classification 2002: A Study of 1,001 Cases Jongkolnee Settakorn MD*, Suree Lekawanvijit MD*, Olarn Arpornchayanon MD**, Samreung Rangdaeng MD*, Pramote Vanitanakom MD*, Sarawut Kongkarnka MD*, Ruangrong Cheepsattayakorn MD*, Charin Ya-In MD*, Paul S Thorner MD*** * Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai ** Department of Orthopedic Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai *** Department of Laboratory Medicine, Hospital for Sick Children and University of Toronto, Toronto, Canada Objective: The aim of the present study was to determine the spectrum, frequency and demographics of bone tumors. Material and Method: A retrospective study of the 1,001 bone tumor specimens from the files at the Pathology Department of the Chiang Mai University Hospital, Thailand from 2000 to 2004. Results: From the study, 41 were non-neoplastic mass lesions, and 960 were neoplastic, with 856 (89%) as primary and 104 (11%) as metastatic tumors. In the primary tumor group, 654 (76%) cases were of hemato- logic origin, and 202 (24%) were non-hematologic. The most common benign bone tumors were giant cell tumor (n = 37), osteochondroma (n = 25), and chondroma (n = 15). The most common malignant bone tumors were lymphoma-leukemia (n = 583), metastatic malignancy (n = 104), plasma cell myeloma (n = 71), and osteosarcoma (n = 58). Conclusion: The present study showed a higher frequency of osteosarcoma (68%), lower frequencies of chondrosarcoma (12%) and Ewing sarcoma (4%) among primary non-hematologic malignant bone tumors when compared with similar studies based on Western patients. Whether these differences reflect differences in the ethnic population or in practice patterns remains to be determined.