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Histone Deacetylase Inhibitors as a Therapeutic Strategy to Eliminate Neoplastic "Stromal" Cells from Giant Cell Tumors of Bone.

The neoplastic "stromal" cells in giant cell tumor of bone (GCTB) harbor a mutation in the H3F3A gene, which causes alterations in the epigenome. Current systemic targeted therapies, such as denosumab, do not affect the neoplastic cells, resulting in relapse upon treatment discontinuation. Therefore, this study examined whether targeting the epigenome could eliminate the neoplastic cells from GCTB. We established four novel cell lines of neoplastic "stromal" cells that expressed the H3F3A p.G34W mutation. These cell lines were used to perform an epigenetics compound screen (n = 128), which ide

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… The affected glycine residue (p.G34W and, to a lesser extent, p.G34L mutations) is highly specific for GCTB, and helps to discriminate GCTB from chondroblastoma (characterized by p.K36M mutations in H3F3A and H3F3B ) and other giant cell-rich tumor types [ 9 , 10 ]. … Distinct H3F3A and H3F3B Driver Mutations Define Chondroblastoma and Giant Cell Tumor of Bone Nat. Genet. 2013 45 1479 1482 10.1038/ng.2814 24162739 PMC3839851 9. Cleven A.H.G. Höcker S. Briaire-De Bruijn I. Szuhai K. Cleton-Jansen A.M. Bovée J.V.M.G. …

Proximal Femur Megaprostheses in Orthopedic Oncology: Evaluation of a Standardized Post-operative Rehabilitation Protocol.

BackgroundReconstructions of the proximal femur after massive resections represent one of the main challenges in orthopedic oncology. Among the possible treatments, megaprostheses represent one of the most used and reliable reconstructive approaches. Although literature about their outcomes has flourished through the last decades, a consensus rehabilitative treatment is still far from being established.Materials and methodsWe evaluated the functional results of all our oncologic cases treated between 2016 and 2022 that could follow our standardized post-operative rehabilitative approach, consi

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… Among our twenty-two cases, nine suffered from primary bone tumors: four cases were diagnosed with a chondrosarcoma, two cases had giant cell bone tumors of the bone, one had an Ewing sarcoma, another case suffered from a synovial sarcoma, and the remaining patient had a chondroblastoma associated with … ABC Aneurysmal Bone Cyst * Excluding those complications that represented exclusion criteria and issues of grade I or II according to the Clavien–Dindo classification Diagnosis | 4 Chondrosarcoma 1 Synovial Sarcoma 1 Ewing Sarcoma 2 Giant Cell Tumor of the Bone 1 Chondroblastoma + ABC 1 Multiple Myeloma …

Interventional Radiology in the Management of Metastases and Bone Tumors.

Interventional Radiology (IR) has experienced an exponential growth in recent years. Technological advances of the last decades have made it possible to use new treatments on a larger scale, with good results in terms of safety and effectiveness. In musculoskeletal field, painful bone metastases are the most common target of IR palliative treatments; however, in selected cases of bone metastases, IR may play a curative role, also in combination with other techniques (surgery, radiation and oncology therapies, etc.). Primary malignant bone tumors are extremely rare compared with secondary bone

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… Indications: Benign: Extra-abdominal desmoid tumors, OO, OB, Aneurismal Bone Cists, primary bone tumors, neuroma and arteriovenous malformations (AVMs) and chondroblastoma. … Percutaneous curative treatment of primary bone tumors is feasible for benign lesions such as OO, OB, and chondroblastoma. OO was the first tumor to be successfully treated with RFA at any site. RFA is curative in most patients, usually after a single treatment. …

Primary Spinal Intradural Extramedullary Ewing's Sarcoma/Peripheral Neuroectodermal Tumour Masquerading Clinically as a Neurogenic Tumour: A Case Report and Review of Literature.

Ewing's Sarcomas (ES)/Peripheral neuroectodermal tumour (pPNET) are heterogenous group of rare, highly malignant, undifferentiated primitive round-cell neoplasms of neuroectodermal origin. pPNETs are seldom observed to involve the spine of which Spinal Intradural Extramedullary Extraosseous Primary ES/pPNET are extremely rare. We report a case of a 23-year-old male with complaints of low backache and hip pain radiating to the left inguinal region for four months. Radiology findings were suggestive of a neurogenic tumour. Cytomorphology, histomorphology and immunohistochemistry evaluation were

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… Schwannoma | Schwannoma | Myxopapillary Ependymoma | Metastasis | Epidural lipomatosis Chondroma | | Paraganglioma | Paraganglioma | Ganglioma | | Lymphoma Chondrosarcoma | | Intradural metastasis | Intradural metastasis | Paraganglioma | | Osteochondroma | | Lymphoma | Lymphoma | Subependymoma | | Chondroblastoma …

Osteoclasts in Tumor Biology: Metastasis and Epithelial-Mesenchymal-Myeloid Transition.

Osteoclast is a specialized cell that originates from monocytic lineage, communicates closely with osteoblasts under physiological conditions, participates in bone modeling and re-modeling, contributes to calcium homeostasis and osteoimmunity. In pathological conditions, it is involved in many tumors such as giant cell bone tumor (osteoclastoma), aneurysmal bone cyst, osteosarcoma, and metastatic cancers, and it usually causes local spread and progression of the tumor, working against the host. Since osteoclasts play an active role in primary bone tumors and bone metastases, the use of anti-os

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… Osteoclasts in Giant Cell Tumor of the Bone OCLs are associated with many tumors of the bone, such as GCTB, osteosarcoma, aneurysmal bone cyst, metaphyseal fibrous defect, and chondroblastoma, and possibly contribute to the lytic features of these tumors. … Behjati S Tarpey PS Presneau N Scheipl S Pillay N Van Loo P Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone . Nat Genet ( 2013 ) 45 : 1479 – 82 . 10.1038/ng.2814 24162739 PMC3839851 52. Salerno M Avnet S Alberghini M Giunti A Baldini N . …

Safety and Feasibility of Steerable Radiofrequency Ablation in Combination with Cementoplasty for the Treatment of Large Extraspinal Bone Metastases.

Background: Radiofrequency ablation (RFA) and cementoplasty, individually and in concert, has been adopted as palliative interventional strategies to reduce pain caused by bone metastases and prevent skeletal related events. We aim to evaluate the feasibility and safety of a steerable RFA device with an articulating bipolar extensible electrode for the treatment of extraspinal bone metastases. Methods: All data were retrospectively reviewed. All the ablation procedures were performed using a steerable RFA device (STAR, Merit Medical Systems, Inc., South Jordan, UT, USA). The pain was assessed

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… Chondroblastoma: Radiofrequency ablation—Alternative to surgical resection in selected cases. Radiology. 2009;251:599–604. doi: 10.1148/radiol.2512080500. 15. Callstrom M.R., Charboneau J.W., Goetz M.P., Rubin J., Atwell T.D., Farrell M.A., Welch T.J., Maus T.P. …

Knowledge of Dental Students and Practitioners About Medication-Related Osteonecrosis of the Jaw in the Central Region of Saudi Arabia.

BACKGROUND: Bisphosphonates (BPs) are often used in treating benign and malignant disorders. Medication-related osteonecrosis of the jaw (MRONJ) is a significant problem that arises from the long-term use of BPs. OBJECTIVE: In this study, we assessed the knowledge of students and dentists about MRONJ in the central region of Saudi Arabia. METHODS: A cross-sectional study was conducted to collect information from dental students and practitioners from the central region of Saudi Arabia. A valid, reliable, and structured questionnaire was used to gather data using a non-probability convenient

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… Bone metastases | 21.9% (25) | 14% (19) | 0.552 Chondroblastoma | 2.6% (3) | 1.5% (2) Hypercalcemia of malignancy | 2.6% (3) | 2.2% (3) Multiple myeloma | 7% (8) | 8.1% (11) Osteogenesis imperfecta | 5.3% (6) | 4.4% (6) Osteomyelitis | 13.2% (15) | 14% (19) Osteopenia and osteoporosis | 14.9% (17) | …

Recent topics in diagnosis and treatment of malignant spinal tumors.

The diagnosis and treatment of malignant spinal tumors are complex and require an integrated approach known as Jaffe's triangle. This review discusses recent topics in the diagnosis and treatment of primary and metastatic malignant spinal tumors. Integrated diagnostic methods, including the development of a dumbbell scoring system for benign-malignant differentiation and the use of positron emission tomography and magnetic resonance imaging (PET-MRI), have improved diagnostic accuracy. Curative resection techniques such as vertebrectomy, sagittal resection, and posterior resection are crucial

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… Behjati S , Tarpey PS , Presneau N , et al Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone . Nature genet , 45 : 1479 - 1482 , 2013 . 24162739 10.1038/ng.2814 PMC3839851 22. …

Primary hyperhidrosis: an updated review.

BACKGROUND: Hyperhidrosis (HH) is a condition characterized by excessive sweating beyond the physiological needs of thermoregulation. HH can be classified as primary (idiopathic) hyperhidrosis (PHH) or secondary hyperhidrosis (SHH), which is associated with underlying medical conditions, medications or systemic disorders. This narrative review provides an updated overview of PHH, with a focus on epidemiology, aetiopathogenesis, clinical manifestations, diagnostic approaches and current management strategies, particularly highlighting pharmacological and procedural treatment options. METHODS:

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… acromegaly, diabetes, Vitamin D deficiency, obesity, pituitary adenoma, adrenal insufficiency, ovarian insufficiency, hyperpituitarism, polycystic ovary syndrome Malignancy | Lung cancer, renal cancer, melanoma, carcinoid tumours, pheochromocytomas, histiocytosis, systemic mastocytosis, metastatic chondroblastoma … Cutaneous metastases from a chondroblastoma initially presenting as unilateral palmar hyperhidrosis. J Am Acad Dermatol. 1999;40(2):325–327. doi: 10.1016/S0190-9622(99)70477-9. 43. Pranteda G, Carlesimo M, Pranteda G, et al. …

Denosumab induction and Zoledronic acid maintenance therapy for recurrent unresectable giant cell tumour of the distal tibia: A case report with sustained tumour control after drug withdrawal.

A 31-year-old woman was diagnosed with a recurrent and rapidly growing giant cell tumour of distal tibia with skin ulceration after intralesional curettage. The patient started on Denosumab 120 mg subcutaneously, once per month with additional loading doses on Days 8 and 15 attempting to avoid below-knee amputation. Twelve doses of Denosumab were administered in 9 months, resulting in resolution of pain, reduction of tumour size and calcification. Hence, the local surgical treatment was delayed and bisphosphonate maintenance therapy was initiated as skin healing was incomplete. The patient was

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… Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet. 2013 Dec;45(12):1479-82. doi: 10.1038/ng.2814. Epub 2013 Oct 27. Erratum in: Nat Genet. 2014 Mar;46(3):316. Goodie, Victoria [corrected to Goody, Victoria]. 5. …

Rechallenge of denosumab in jaw osteonecrosis of patients with unresectable giant cell tumour of bone: a case series analysis and literature review.

OBJECTIVES: Giant cell tumour of bone (GCTB) is a rare tumour, generally managed with surgery. Treatment of the very rare unresectable advanced/metastatic GCTB is challenging and denosumab is the only current available medical option, an anti-RANKL monoclonal antibody inhibiting osteolysis. An uncommon but severe and treatment-limiting adverse event of denosumab is the osteonecrosis of the jaw (ONJ). The clinical management of GCTB patients stopping denosumab for medication-related (MR)-ONJ and the possible reintroduction of denosumab after MR-ONJ resolution is matter of debate. We performed a

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… References 1 Behjati S , Tarpey PS , Presneau N , et al Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone . …

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

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… In addition, H3K36me3 is altered in various cancers, such as chondroblastoma, and colon, and head and neck cancer ( 110 , 111 ). These alterations in histone modifications and methylation enzymes contribute to changes in gene expression that may promote carcinogenesis. … Histone methyltransferase hSETD1A is a novel regulator of metastasis in breast cancer Mol Cancer Res 13 461 469 2015 10.1158/1541-7786.MCR-14-0389 25373480 110 Behjati S Tarpey PS Presneau N Scheipl S Pillay N Van Loo P Wedge DC Cooke SL Gundem G Davies H Distinct H3F3A and H3F3B driver mutations define chondroblastoma …

Комплексный номер копий с высоким разрешением и гистомолекулярный анализ диффузной глиомы в масштабах полушария, H3 G34-mutant обнаруживает общие аномалии TP53.

Диффузная глиома в масштабах полушария, Н3 G34-mutant (В тыс.DHG-H3 G34 характеризуется главным образом молекулярным профилированием метилирования и исследованиями последовательности. Мы описываем комплексную гистомолекулярную оценку, включая профили копий с высоким разрешением серии 60 DHG-H3 G34 для дальнейшего понимания спектра генетических изменений, связанных с этим типом опухолей. Случаи были подвергнуты клиническому тестированию с использованием: 187-gene мутация и синтез были нацелены на нейроонтологию следующего поколения (n = 60) и онкосканского хромосомного микроаррара (n = 26) одно

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… Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone. Nat Genet. 2013;45:1479–1482. 35. Nazem A, Lavezo J, Abdullaev Z, Aldape K, Quezado M, Cimino PJ, et al. …

Chronic Pain and Bone-Related Pathologies: A Narrative Review.

PurposePain related to bone may occur as a result of trauma, bone fracture, genetic disease, arthritis, benign or malignant primary bone tumors and bone cancer metastases. We discuss the pathophysiology of chronic bone-related pain, treatment options and therapeutic perspectives.MethodsUsing predefined terms, we searched PubMed, MEDLINE, and Google Scholar for meta-analyses, evidence-based reviews, and clinical practice guidelines. This narrative article reviews pathologies linked to chronic bone pain and discusses the preventive and therapeutic strategies for better bone pain management.Resul

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… Chronic pain is known to have a very negative impact on quality of life, and psychosocial factors are important determinants of pain severity. 20 Benign bone tumors (osteochondroma, giant cell tumor, osteoid osteoma, chondroblastoma) are non-cancerous masses characterized by significant osteoclastic …

Educational Case: Atypical presentation of primary hyperparathyroidism with brown tumor.

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… The most important clinical features are age and skeletal maturity as many lesions in the histologic differential occur only or almost always in children, adolescents or young adults and would not be seen in a patient this age such as the following: chondroblastoma, aneurysmal bone cyst, non-ossifying …

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients.

The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number >4 times in the dead compared with the alive group) were EWSR1, FLT3,

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… Mutation of these genes leads to some human cancers such as chondroblastoma, osteosarcoma, and epithelial ovarian cancer [ 37 ]. In addition, H3-3B up-regulation has been suggested as a marker for pre-metastatic colon cancer [ 38 ]. …

Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation

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… Benign chondroblastoma of bone: A reinterpretation of the so-called calcifying or chondromatous giant cell tumor Am. J. Pathol. 1942 18 969 19970672 PMC2032980 9. Singh S. Padhy S.K. Mohapatra S.S. Panda A. Shahi P. …

Nuances in the treatment of malignant tumors of the clival and petroclival region.

Introduction Malignancies of the clivus and petroclival region are mainly chordomas and chondrosarcomas. Although a spectrum of malignancies may present in this area, a finite group of commonly encountered malignant pathologies will be the focus of this review, as they are recognized to be formidable pathologies due to adjacent critical neurovascular structures and challenging surgical approaches. Objectives The objective is to review the literature regarding medical and surgical management of malignant tumors of the clival and petroclival region with a focus on clinical presentation, diagnost

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… The following are 5-year survival rates of tumor subtypes and their encountered frequencies: chondrosarcoma, otherwise not specified (70%); myxoid (71%); mesenchymal (48%); dedifferentiated (0%); juxtacortical (93%); chondroblastoma (85%); clear cell (100%). 26 Currently accepted treatment paradigms …

Rare Diseases of the Orbit.

This article provides an overview of rare orbital diseases. Congenital malformations, inflammatory diseases, benign and malignant neoplasias are described. Although it represents a relatively small area of the body the orbit contains multiple different tissues. Therefore, a great variety of diseases can be found within the orbital space. That is the reason, why both the completeness and the level of detail in the description of particular diseases must be somewhat limited. Nevertheless, clinical manifestations, important aspects of diagnosis, treatment strategies, and, when specific data are a

How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

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… Specifically, mutations in H3K27, G34 and K36 residues, located at or near histone modification sites, have been well studied and are associated with the development and progression of brain tumors, chondroblastoma, and squamous cell carcinomas of the head and neck 230 , 231 , 232 , 233 . …