scholarly journals Molecular Alterations Associated with Osteosarcoma Development

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Kosei Ando ◽  
Kanji Mori ◽  
Franck Verrecchia ◽  
Baud’huin Marc ◽  
Françoise Rédini ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Lung Metastases ◽  
Apoptosis Resistance ◽  
Primary Bone Tumor ◽  
Molecular Alterations ◽  
Multiple Processes ◽  
Distant Organ ◽  
Metastasis Development ◽  
Primary Bone ◽  
Malignant Primary Bone Tumor

Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases which is the main cause of death. Unfortunately, the conventional chemotherapy is not fully effective on osteosarcoma metastases. The progression of a primary tumor to metastasis requires multiple processes, which are neovascularization, proliferation, invasion, survival in the bloodstream, apoptosis resistance, arrest at a distant organ, and outgrowth in secondary sites. Consequently, recent studies have revealed new insights into the molecular mechanisms of metastasis development. The understanding of the mechanism of molecular alterations can provide the identification of novel therapeutic targets and/or prognostic markers for osteosarcoma treatment to improve the clinical outcome.

Survival after second and subsequent recurrences in osteosarcoma: a retrospective multicenter analysis

2018 ◽  
Vol 104 (3) ◽  
pp. 202-206 ◽  
Author(s):  
Elisa Tirtei ◽  
Sebastian D. Asaftei ◽  
Rosaria Manicone ◽  
Marilena Cesari ◽  
Anna Paioli ◽  
...  
Keyword(s):  
Lung Disease ◽  
Lung Metastases ◽  
Surgical Removal ◽  
Disease Free Interval ◽  
Primary Bone Tumor ◽  
Multicenter Analysis ◽  
Primary Bone ◽  
Chemotherapeutic Treatment ◽  
First Recurrence ◽  
Multiple Recurrences

Purpose: Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. Methods: This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. Results: Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001) benefited patients without a third CSR. Conclusions: This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.

scholarly journals Macrophages in Osteosarcoma Immune Microenvironment: Implications for Immunotherapy

2020 ◽  
Vol 10 ◽  
Author(s):  
Zhong-Wei Luo ◽  
Pan-Pan Liu ◽  
Zhen-Xing Wang ◽  
Chun-Yuan Chen ◽  
Hui Xie
Keyword(s):  
Overall Survival ◽  
Tumor Microenvironment ◽  
Bone Tumor ◽  
Immune Cells ◽  
Therapeutic Approaches ◽  
Immune Microenvironment ◽  
Primary Bone Tumor ◽  
Promising Strategy ◽  
Primary Bone ◽  
Malignant Primary Bone Tumor

Osteosarcoma is a malignant primary bone tumor commonly occurring in children and adolescents. The treatment of local osteosarcoma is mainly based on surgical resection and chemotherapy, whereas the improvement of overall survival remains stagnant, especially in recurrent or metastatic cases. Tumor microenvironment (TME) is closely related to the occurrence and development of tumors, and macrophages are among the most abundant immune cells in the TME. Due to their vital roles in tumor progression, macrophages have gained increasing attention as the new target of tumor immunotherapy. In this review, we present a brief overview of macrophages in the TME and highlight the clinical significance of macrophages and their roles in the initiation and progression of osteosarcoma. Finally, we summarize the therapeutic approaches targeting macrophage, which represent a promising strategy in osteosarcoma therapies.

scholarly journals Mechanisms of Resistance to Conventional Therapies for Osteosarcoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 683
Author(s):  
Louise Marchandet ◽  
Morgane Lallier ◽  
Céline Charrier ◽  
Marc Baud’huin ◽  
Benjamin Ory ◽  
...  
Keyword(s):  
Survival Rate ◽  
Molecular Mechanisms ◽  
Tumor Resection ◽  
Mechanisms Of Resistance ◽  
Current Standard ◽  
Resistance Development ◽  
Primary Bone Tumor ◽  
Genes Expression ◽  
Primary Bone ◽  
New Strategies

Osteosarcoma (OS) is the most common primary bone tumor, mainly occurring in children and adolescents. Current standard therapy includes tumor resection associated with multidrug chemotherapy. However, patient survival has not evolved for the past decades. Since the 1970s, the 5-year survival rate is around 75% for patients with localized OS but dramatically drops to 20% for bad responders to chemotherapy or patients with metastases. Resistance is one of the biological processes at the origin of therapeutic failure. Therefore, it is necessary to better understand and decipher molecular mechanisms of resistance to conventional chemotherapy in order to develop new strategies and to adapt treatments for patients, thus improving the survival rate. This review will describe most of the molecular mechanisms involved in OS chemoresistance, such as a decrease in intracellular accumulation of drugs, inactivation of drugs, improved DNA repair, modulations of signaling pathways, resistance linked to autophagy, disruption in genes expression linked to the cell cycle, or even implication of the micro-environment. We will also give an overview of potential therapeutic strategies to circumvent resistance development.

scholarly journals Molecular Chaperones in Osteosarcoma: Diagnosis and Therapeutic Issues

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 754
Author(s):  
Morgane Lallier ◽  
Louise Marchandet ◽  
Brice Moukengue ◽  
Celine Charrier ◽  
Marc Baud’huin ◽  
...  
Keyword(s):  
Heat Shock ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Large Family ◽  
Poor Responders ◽  
Heat Shock Factor 1 ◽  
Primary Bone Tumor ◽  
Apoptosis Inhibition ◽  
Primary Bone ◽  
Shock Proteins

Osteosarcoma (OS) is the most common form of primary bone tumor affecting mainly children and young adults. Despite therapeutic progress, the 5-year survival rate is 70%, but it drops drastically to 30% for poor responders to therapies or for patients with metastases. Identifying new therapeutic targets is thus essential. Heat Shock Proteins (HSPs) are the main effectors of Heat Shock Response (HSR), the expression of which is induced by stressors. HSPs are a large family of proteins involved in the folding and maturation of other proteins in order to maintain proteostasis. HSP overexpression is observed in many cancers, including breast, prostate, colorectal, lung, and ovarian, as well as OS. In this article we reviewed the significant role played by HSPs in molecular mechanisms leading to OS development and progression. HSPs are directly involved in OS cell proliferation, apoptosis inhibition, migration, and drug resistance. We focused on HSP27, HSP60, HSP70 and HSP90 and summarized their potential clinical uses in OS as either biomarkers for diagnosis or therapeutic targets. Finally, based on different types of cancer, we consider the advantage of targeting heat shock factor 1 (HSF1), the major transcriptional regulator of HSPs in OS.

scholarly journals Wedding of Molecular Alterations and Immune Checkpoint Blockade: Genomics as a Matchmaker

2021 ◽  
Author(s):  
Elena Fountzilas ◽  
Razelle Kurzrock ◽  
Henry Hiep Vo ◽  
Apostolia-Maria Tsimberidou
Keyword(s):  
Molecular Mechanisms ◽  
Cell Receptor ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Beta Catenin ◽  
Molecular Alterations ◽  
Receptor Repertoire ◽  
Repair Deficiency ◽  
Tumor Mutational Burden

Abstract The development of checkpoint blockade immunotherapy has transformed the medical oncology armamentarium. But, despite its favorable impact on clinical outcomes, immunotherapy benefits only a subset of patients, and a substantial proportion of these individuals eventually manifest resistance. Serious immune-related adverse events and hyper-progression have also been reported. It is therefore essential to understand the molecular mechanisms and identify the drivers of therapeutic response and resistance. In this review, we provide an overview of the current and emerging clinically relevant genomic biomarkers implicated in checkpoint blockade outcome. U.S. Food and Drug Administration–approved molecular biomarkers of immunotherapy response include mismatch repair deficiency/microsatellite instability and tumor mutational burden ≥10 mutations/megabase. Investigational genomic-associated biomarkers for immunotherapy response include alterations of the following genes/associated pathways: chromatin remodeling (ARID1A, PBRM1, SMARCA4, SMARCB1, BAP1), major histocompatibility complex, specific (e.g., ultraviolet, APOBEC) mutational signatures, T-cell receptor repertoire, PDL1, POLE/POLD1, and neo-antigens produced by the mutanome; those potentially associated with resistance include β2-microglobulin, EGFR, Keap1, JAK1/JAK2/interferon-gamma signaling, MDM2, PTEN, STK11, and Wnt/Beta-catenin pathway alterations. Prospective clinical trials are needed to assess the role of a composite of these biomarkers in order to optimize the implementation of precision immunotherapy in patient care.

scholarly journals Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy

2021 ◽  
Vol 22 (6) ◽  
pp. 3007
Author(s):  
Isabel Lastres-Becker ◽  
Gracia Porras ◽  
Marina Arribas-Blázquez ◽  
Inés Maestro ◽  
Daniel Borrego-Hernández ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Autophagic Flux ◽  
Metabolic Disturbances ◽  
Molecular Alterations ◽  
Healthy Donors ◽  
Inflammatory Profile ◽  
Als Patients

Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition where motor neurons (MNs) degenerate. Most of the ALS cases are sporadic (sALS), whereas 10% are hereditarily transmitted (fALS), among which mutations are found in the gene that codes for the enzyme superoxide dismutase 1 (SOD1). A central question in ALS field is whether causative mutations display selective alterations not found in sALS patients, or they converge on shared molecular pathways. To identify specific and common mechanisms for designing appropriate therapeutic interventions, we focused on the SOD1-mutated (SOD1-ALS) versus sALS patients. Since ALS pathology involves different cell types other than MNs, we generated lymphoblastoid cell lines (LCLs) from sALS and SOD1-ALS patients and healthy donors and investigated whether they show changes in oxidative stress, mitochondrial dysfunction, metabolic disturbances, the antioxidant NRF2 pathway, inflammatory profile, and autophagic flux. Both oxidative phosphorylation and glycolysis appear to be upregulated in lymphoblasts from sALS and SOD1-ALS. Our results indicate significant differences in NRF2/ARE pathway between sALS and SOD1-ALS lymphoblasts. Furthermore, levels of inflammatory cytokines and autophagic flux discriminate between sALS and SOD1-ALS lymphoblasts. Overall, different molecular mechanisms are involved in sALS and SOD1-ALS patients and thus, personalized medicine should be developed for each case.

scholarly journals Chondroblastoma: An Update

2017 ◽  
Vol 141 (6) ◽  
pp. 867-871 ◽  
Author(s):  
Wenqian Chen ◽  
Lisa M. DiFrancesco
Keyword(s):  
Aneurysmal Bone Cyst ◽  
Bone Cyst ◽  
Cyst Formation ◽  
Giant Cells ◽  
Lytic Lesion ◽  
Primary Bone Tumor ◽  
Hemosiderin Deposition ◽  
Secondary Aneurysmal Bone Cyst ◽  
Primary Bone ◽  
Chondroblastic Osteosarcoma

Chondroblastoma is a rare primary bone tumor of young people that typically arises in the ends of the long bones. Radiologic investigations show a small, circumscribed, lytic lesion. The tumor is characterized histologically by the proliferation of chondroblasts along with areas of mature cartilage, giant cells, and occasionally, secondary aneurysmal bone cyst formation. Chondroblastoma, however, may also present with atypical features, such as prominent hemosiderin deposition, numerous giant cells, or the presence of a large aneurysmal bone cyst component. Malignant entities such as clear cell chondrosarcoma and chondroblastic osteosarcoma must also be considered. Recently, immunohistochemical stains such as DOG1 and SOX9 have been described in chondroblastoma, and K36M mutations in either the H3F3A or H3F3B genes have also been identified. While generally regarded as a benign entity, chondroblastoma manifests an intermediate type of behavior, given its ability to recur locally, and rarely, metastasize.

scholarly journals A retrospective analysis of computed tomography guided biopsy in the diagnosis of primary bone tumors

2017 ◽  
Vol 3 (3) ◽  
pp. 569
Author(s):  
Kuriakku Puthur Dominic ◽  
Davis Dijoe ◽  
Jacob Toms
Keyword(s):  
Computed Tomography ◽  
Bone Tumors ◽  
Diagnostic Efficiency ◽  
Ct Guided ◽  
Primary Bone Tumor ◽  
Primary Bone Tumors ◽  
Guided Biopsy ◽  
Ct Guided Biopsy ◽  
Significant Step ◽  
Primary Bone

<p><strong>Background:</strong> Primary bone tumors account for a small yet significant number in the total incidence of tumors. Computed tomography (CT) guided percutaneous core biopsy is a novel yet significant step in the approach towards the diagnosis of bone tumors and is increasingly performed by orthopaedic oncologists around the world. This study is aimed to evaluate the diagnostic accuracy of CT guided biopsy in the diagnosis of primary bone tumors. <strong></strong></p><p><strong>Methods:</strong> Patients who underwent CT guided biopsy and subsequent excision for primary bone tumors from January 2008 to July 2015 were analysed. CT guided biopsy results were compared with post-operative histopathological reports to evaluate its sensitivity and specificity.</p><p><strong>Results:</strong> A total of 161 patients were included in the retrospective study. Among them, 147 were true positives, 7 were false negatives, 6 were true negatives and one was false positive. The sensitivity of CT guided biopsy in the diagnosis of primary bone tumor was 95.4 % with specificity of 85.7% with a diagnostic efficiency of 90.5%. The complication rate was 4.3%.</p><p><strong>Conclusions:</strong> CT guided biopsy is a safe, simple and effective procedure to rule out and rule in the diagnosis of primary bone tumors.</p>

scholarly journals Onco-Multi-OMICS Approach: A New Frontier in Cancer Research

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Sajib Chakraborty ◽  
Md. Ismail Hosen ◽  
Musaddeque Ahmed ◽  
Hossain Uddin Shekhar
Keyword(s):  
Cancer Research ◽  
Systems Biology ◽  
Cancer Cells ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
The Cancer Genome Atlas ◽  
Resolving Power ◽  
Cancer Hallmarks ◽  
Molecular Alterations ◽  
Integrated Omics

The acquisition of cancer hallmarks requires molecular alterations at multiple levels including genome, epigenome, transcriptome, proteome, and metabolome. In the past decade, numerous attempts have been made to untangle the molecular mechanisms of carcinogenesis involving single OMICS approaches such as scanning the genome for cancer-specific mutations and identifying altered epigenetic-landscapes within cancer cells or by exploring the differential expression of mRNA and protein through transcriptomics and proteomics techniques, respectively. While these single-level OMICS approaches have contributed towards the identification of cancer-specific mutations, epigenetic alterations, and molecular subtyping of tumors based on gene/protein-expression, they lack the resolving-power to establish the casual relationship between molecular signatures and the phenotypic manifestation of cancer hallmarks. In contrast, the multi-OMICS approaches involving the interrogation of the cancer cells/tissues in multiple dimensions have the potential to uncover the intricate molecular mechanism underlying different phenotypic manifestations of cancer hallmarks such as metastasis and angiogenesis. Moreover, multi-OMICS approaches can be used to dissect the cellular response to chemo- or immunotherapy as well as discover molecular candidates with diagnostic/prognostic value. In this review, we focused on the applications of different multi-OMICS approaches in the field of cancer research and discussed how these approaches are shaping the field of personalized oncomedicine. We have highlighted pioneering studies from “The Cancer Genome Atlas (TCGA)” consortium encompassing integrated OMICS analysis of over 11,000 tumors from 33 most prevalent forms of cancer. Accumulation of huge cancer-specific multi-OMICS data in repositories like TCGA provides a unique opportunity for the systems biology approach to tackle the complexity of cancer cells through the unification of experimental data and computational/mathematical models. In future, systems biology based approach is likely to predict the phenotypic changes of cancer cells upon chemo-/immunotherapy treatment. This review is sought to encourage investigators to bring these different approaches together for interrogating cancer at molecular, cellular, and systems levels.

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