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Medicine Jun 2016Numerous original clinical studies have attempted to investigate the prognostic value of HER-2 overexpression in osteosarcoma, but the results of these studies are not... (Meta-Analysis)
Meta-Analysis Review
Numerous original clinical studies have attempted to investigate the prognostic value of HER-2 overexpression in osteosarcoma, but the results of these studies are not consistent. This meta-analysis and systematic review was performed to further assess the correlation between HER-2 expression and prognosis in patients with osteosarcoma. A detailed search of relevant publications was conducted using 7 electronic databases: PubMed, Embase, the Cochrane library, the Wanfang database, the China National Knowledge Internet (CNKI) database, the Chinese VIP database, and the Chinese Biological Medical (CBM) Database for publications through August 1, 2015, using the following keywords (HER-2 OR ErbB-2 OR C-erbB-2 OR neu) AND (osteosarcoma OR osteogenic tumor). The bibliographies of potentially relevant articles and identified articles were then searched by hand. Eligible studies were those that enrolled participants with osteosarcoma and provided survival outcome in HER-2 positive and negative groups. The hazard ratio (HR) and 95% confidence interval (CI) for each individual study was calculated and pooled to obtain integrated estimates, using random effects modeling. Sixteen studies involving 934 participants with osteosarcoma met our inclusion criteria. HER-2 overexpression was documented in 42.2% of patients with osteosarcoma. Compared with patients without HER-2 overexpression, those overexpressing HER-2 had decreased overall survival (HR = 2.03, 95% CI: 1.36-3.03, P < 0.001). Statistical associations between HER-2 overexpression and unfavorable overall survival (OS) were observed for both biopsy and surgical removal specimens (HR = 2.07, 95%CI: 1.16-3.72, P = 0.014; and HR = 2.02, 95%CI: 1.10-3.71, P = 0.024). Results for disease-free survival (DFS) were similar. Overexpression of HER-2 is significantly associated with poor outcome for patients with osteosarcoma and should be assessed at diagnosis and after surgery as a prognostic factor. However, larger-scale multicenter clinical studies are needed to further support these findings.
Topics: Biomarkers, Tumor; Biopsy; Bone Neoplasms; DNA, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Orthopedic Procedures; Osteosarcoma; Prognosis; Receptor, ErbB-2
PubMed: 27281068
DOI: 10.1097/MD.0000000000003661 -
Cureus Nov 2023Osteosarcoma (OS) is a debilitating cancer of the bone that commonly afflicts the young and old. This may be de novo or associated with tumorigenic syndromes. However,... (Review)
Review
Osteosarcoma (OS) is a debilitating cancer of the bone that commonly afflicts the young and old. This may be de novo or associated with tumorigenic syndromes. However, many molecular mechanisms are still being uncovered and may offer greater avenues for screening and therapy. Cadherins, including E-cadherin and N-cadherin/vimentin, are involved in epithelial-to-mesenchymal transmission (EMT), which is key for tumor invasion. A study reviewing the relationship between OS and cadherins might elucidate a potential target for therapy and screening. A robust literature review was conducted by searching PubMed with the keywords "osteosarcoma", "cadherin", "e-cadherin" and "n-cadherin". Of a preliminary 266 papers, 25 were included in the final review. Review articles and those without primary data were excluded. Loss of E-cadherin is noted in metastatic cell lines of osteosarcoma. Overexpression of E-cadherin or knockout of N-cadherin/vimentin results in loss of metastatic potential. There are several methods of gene knockout, including CRISPR-Cas9 gene editing, viral vector insertion with micro RNA complementary to long noncoding RNA within gene segments, or proteomic editing. Screening for EMT and genetic treatment of EMT is a possible avenue for the treatment of refractory osteosarcoma. Several studies were conducted ex vivo. Further testing involving in vitro therapy is necessary to validate these methods. Limitations of this study involve a lack of in vivo trials to validate methods.
PubMed: 38156135
DOI: 10.7759/cureus.49521 -
Medicine May 2023Pathogenesis of malignant tumors are often accompanied by aberrant expression of circular RNAs (circRNAs), indicating the potential diagnostic value of circRNAs in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pathogenesis of malignant tumors are often accompanied by aberrant expression of circular RNAs (circRNAs), indicating the potential diagnostic value of circRNAs in tumors. CircRNAs have been found to be enriched, stable and ubiquitous in serum and plasma exosomes. The study aims at evaluating the diagnostic performance of circulating (plasma and serum) exosomal circRNA in different types of cancer by synthesis of published data.
METHODS
A comprehensive literature search was conducted in PubMed, Embase, Medline and the Web of Science databases to identify potentially eligible studies published before April 2021. We conducted the meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.
RESULTS
Eleven articles comprising 21 studies were included, and a total of 1609 cases and 1498 controls were evaluated. Six types of cancer were involved in these studies, including lung cancer, hepatocellular carcinoma, colorectal cancer, gastric cancer, multiple myeloma and osteosarcoma. The pooled sensitivity and specificity were 0.72 (95% confidence interval [CI], 0.62-0.81) and 0.83 (95% CI, 0.78-0.88), respectively. Summary receiver operating characteristic curve was constructed and the pooled value of area under curve was 0.86 (95% CI, 0.83-0.89), indicating a favorable diagnostic efficacy of circulating exosomal circRNAs in malignancies.
CONCLUSIONS
In conclusion, our study evaluated the diagnostic power of circulating exosomal circRNAs in 6 types of cancer by synthesis of published data comprising 21 studies from eleven articles. The pooled analysis provided the evidence supporting circulating exosomal circRNAs as a promising noninvasive diagnostic biomarkers for malignancies.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Hepatocellular; Liver Neoplasms; RNA, Circular; Sensitivity and Specificity
PubMed: 37233410
DOI: 10.1097/MD.0000000000033872 -
Cancers Mar 2022Histone-lysine N-methyltransferase SETD7 regulates a variety of cancer-related processes, in a tissue-type and signalling context-dependent manner. To date, there is no... (Review)
Review
Histone-lysine N-methyltransferase SETD7 regulates a variety of cancer-related processes, in a tissue-type and signalling context-dependent manner. To date, there is no consensus regarding SETD7´s biological functions, or potential for cancer diagnostics and therapeutics. In this work, we summarised the literature on SETD7 expression and function in cancer, to identify the contexts where SETD7 expression and targeting can lead to improvements in cancer diagnosis and therapy. The most studied cancers were found to be lung and osteosarcoma followed by colorectal and breast cancers. SETD7 mRNA and/or protein expression in human cancer tissue was evaluated using public databases and/or in-house cohorts, but its prognostic significance remains inconclusive. The most studied cancer-related processes regulated by SETD7 were cell proliferation, apoptosis, epithelial-mesenchymal transition, migration and invasion with special relevance to the pRb/E2F-1 pathway. SETD7 consistently prevented epithelial to mesenchymal transition in different cancer types, and inhibition of its function appears to be associated with improved response to DNA-damaging agents in most of the analysed studies. Stabilising mutations in SETD7 target proteins prevent their methylation or promote other competing post-translational modifications that can override the SETD7 effect. This indicates that a clear discrimination of these mutations and competing signalling pathways must be considered in future functional studies.
PubMed: 35326563
DOI: 10.3390/cancers14061414 -
Photodiagnosis and Photodynamic Therapy Dec 2022Osteosarcoma (OS) is an aggressive malignant bone tumour with high mortality. A poor prognosis is noted in patients with distal metastases or multidrug resistance. As an... (Review)
Review
BACKGROUND
Osteosarcoma (OS) is an aggressive malignant bone tumour with high mortality. A poor prognosis is noted in patients with distal metastases or multidrug resistance. As an emerging antitumor strategy, photodynamic therapy (PDT) mediated by visible and near infrared light has attracted intensive attention given its target selectivity, remote controllability, minimal or non-invasive features. However, PDT also has obvious limitations. Specifically, due to the limited penetration of light, it is mainly used in the clinical treatment of superficial malignant tumours, such as musculoskeletal sarcomas and melanoma, but it has not been applied to the clinical treatment of deep malignant bone tumours except for a very small number of experiments on deep canine OS models.
MATERIALS AND METHODS
We searched for studies that focused on the effectiveness and safety of PDT for OS based on in vitro experiments and animal models in the last decade. A systematic search was conducted using electronic databases, including PubMed, ClinicalTrials.gov, and the Cochrane Library.
INCLUSION CRITERIA
(1) original research articles about PDT for OS; (2) articles in English; (3) in vitro or animal model research; and (4) detailed information, including cell name, fluence, irradiation wavelength, time of incubation with PS, duration between PS treatment and irradiation, and duration between irradiation and viability assays.
EXCLUSION CRITERIA
(1) study was a review/systemic review article, patent, letter, or conference abstract/paper; (2) articles were not published in English; (3) studies containing overlapping or insufficient data.
RESULTS
We identified 201 publications, and 44 articles met the inclusion criteria and were included in the synthesis. Unfortunately, there are no relevant clinical reports of the use of PDT in the treatment of human OS. In these studies, 8 studies only employed in vivo experiments to evaluate the efficiency of PDT in an OS animal model, 19 studies exclusively performed in vitro viability assays of cells treated with PDT under different conditions, and 17 studies included in vitro cell experiments and in vivo animal OS models to evaluate the effect of PDT on OS in vivo and in vitro. All studies have shown that PDT is cytotoxic to OS cells or can inhibit the growth of OS in heterologous or homologous animal OS models but exhibits minimal cytotoxicity at a certain range of dosages.
CONCLUSION
Based on this systematic review, PDT can eradicate OS cells in cell culture and there is some evidence for efficacy in animal models. However, the ability for PDT to control human OS is unclear, the animal and human reports do not show evidence of human OS control, they just do show feasibility. The major issues concerning the potential for treatment of osteosarcoma with PDT are that adequate light should be transmitted to tumor loci and if the disease is caught before metastasis and irradiation of tumor sites is feasible, curative potential is there. Otherwise, PDT may be mainly palliative. To determine whether PDT can safely and efficiently be used in the clinical treatment of OS, many preclinical orthotopic animal OS models and OS models of multiple systemic metastases must be performed and interstitial PDT or intraoperative PDT may be a good and potential candidate for human OS treatment. If these problems can be well solved, PDT may be a potentially effective strategy for the treatment of OS patients.
Topics: Humans; Animals; Dogs; Photochemotherapy; Photosensitizing Agents; Osteosarcoma; Bone Neoplasms; Models, Animal; Cell Line, Tumor
PubMed: 36031143
DOI: 10.1016/j.pdpdt.2022.103093 -
Cureus Sep 2021Osteosarcoma (OS) is the most common primary bone cancer affecting children and young adults, most often occurring at the metaphysis of long bones. At present, treatment... (Review)
Review
Osteosarcoma (OS) is the most common primary bone cancer affecting children and young adults, most often occurring at the metaphysis of long bones. At present, treatment with combinations of surgery and chemotherapy for the localized OS has only brought minuscule improvements in prognosis. In comparison, the advanced, metastatic, or recurrent forms of OS are often non-responsive to chemotherapy, adding to the dire need to develop new and efficient therapies. The question of interest investigated in this systematic review is whether immunotherapy can play a meaningful role in improving the clinical outcomes of children with OS. This article aims to summarize the preclinical and clinical research conducted thus far on potential therapeutic avenues for pediatric OS using immunotherapy, including methods like checkpoint inhibition, adoptive cellular therapy with T-cells, chimeric antigen receptor T (CAR-T), and natural killer (NK) cells. It also highlights the influence of the innate and adaptive immune system on the tumor microenvironment, allowing for OS progression and metastasis. This systematic review contains 27 articles and analyses of multiple clinical trials employing immunotherapeutic drugs to 785 osteosarcoma participants and over 243 pediatric patients. The articles were obtained through PubMed, PubMed Central, and ClinicalTrials.gov and individually assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist and the Cochrane risk-of-bias tool. The reviews reveal that immunotherapy's most significant impact on pediatric OS includes combining immune checkpoint blockers with traditional chemotherapy and surgery. However, due to the bimodal distribution of this aggressive malignancy, these studies cannot precisely estimate the overall effect and any potential life-threatening adverse events following therapy in children. Further research is required to fully assess the impact of these immunotherapies, including more extensive multinational clinical trials to focus on the pediatric population.
PubMed: 34725602
DOI: 10.7759/cureus.18349 -
Frontiers in Genetics 2023As a rare condition, osteosarcoma affects approximately 3% of all cancer patients. Its exact pathogenesis remains largely unclear. The role of p53 in up- and... (Review)
Review
As a rare condition, osteosarcoma affects approximately 3% of all cancer patients. Its exact pathogenesis remains largely unclear. The role of p53 in up- and down-regulating atypical and typical ferroptosis in osteosarcoma remains unclear. The primary objective of the present study is investigating the role of p53 in regulating typical and atypical ferroptosis in osteosarcoma. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Patient, Intervention, Comparison, Outcome, and Studies (PICOS) protocol were used in the initial search. The literature search was performed in six electronic databases, including EMBASE, Cochrane library of trials, Web of Science, PubMed, Google Scholar, and Scopus Review, using keywords connected by Boolean operators. We focused on studies that adequately defined patient profiles described by PICOS. We found that p53 played fundamental up- and down-regulatory roles in typical and atypical ferroptosis, resulting in either advancement or suppression of tumorigenesis, respectively. Direct and indirect activation or inactivation of p53 downregulated its regulatory roles in ferroptosis in osteosarcoma. Enhanced tumorigenesis was attributed to the expression of genes associated with osteosarcoma development. Modulation of target genes and protein interactions, especially SLC7A11, resulted in enhanced tumorigenesis. Typical and atypical ferroptosis in osteosarcoma were regulatory functions of p53. The activation of MDM2 inactivated p53, leading to the downregulation of atypical ferroptosis, whereas activation of p53 upregulated typical ferroptosis. Further studies should be performed on the regulatory roles of p53 to unmask its possible clinical applications in the management of osteosarcoma.
PubMed: 37065475
DOI: 10.3389/fgene.2023.1154299 -
Clinical Sarcoma Research 2020Osteosarcoma is a very aggressive primary bone tumour, affecting mainly young populations. Most cases diagnosed have distant macro- and micro-metastases at the time of... (Review)
Review
BACKGROUND
Osteosarcoma is a very aggressive primary bone tumour, affecting mainly young populations. Most cases diagnosed have distant macro- and micro-metastases at the time of diagnosis. Surgical resection with neoadjuvant and adjuvant therapies improves the overall and disease-free survival of patients. Doxycycline, a synthetic tetracycline, has been found to act either as an antibiotic drug or as a chemotherapeutic agent. Its anti-neoplastic role has been found to be significant, in vitro and in vivo laboratory trials, in various types of cancer, such as prostate, intestinal, central neural system cancers and osteosarcoma. Inhibition of metalloproteinases (MMPs) in different stages of tumour expansion is the most well-understood mechanism. MMPs are secreted molecules from various normal cells, such as fibroblasts, leucocytes and vascular smooth muscles, as well as from cells with high proliferative potential, such as tumour cells. In osteosarcoma, MMPs have been found to be overexpressed. MMPs help osteosarcoma cells survive, grow and produce metastases in distant sites, mainly in the lungs. Doxycycline blocks extracellular matrix and basic membrane degradation by suppressing MMP function. As a consequence, osteosarcoma cells lose their ability to invade and metastasize. Additionally, doxycycline eliminates the secretion of vascular endothelial growth factor (VEGF) and deprives the supply of circulating nutrients by its anti-angiogenesis action. The aim of this review is to evaluate doxycycline's action against osteosarcoma cells as an MMP-inhibitor and interpret its usage as a chemotherapeutic agent.
METHODS
We checked PubMed and Google Scholar for recently published data, on the tumour-supportive role of MMPs and VEGF in osteosarcoma cells. We further studied published experimental trials on the role of doxycycline as a tumour-suppressive agent via MMPs and VEGF inhibition.
RESULTS
MMPs and VEGF have been found to play a fundamental role in osteosarcoma cells survival and high aggressiveness by in vitro, in vivo and clinical trials. Nevertheless, doxycycline has proved its tumour-suppressive effect by in vivo experimental trials in various cancers but not yet in osteosarcoma.
CONCLUSION
Doxycycline remains a promising chemotherapeutic agent against osteosarcoma via MMP inhibition, showing the need for further in vivo and clinical trials to be carried out in the future.
PubMed: 32377334
DOI: 10.1186/s13569-020-00128-6 -
European Review For Medical and... Oct 2018The association between excision repair cross-complementation (ERCC) gene family (ERCC1 and ERCC2) and osteosarcoma risk was controversial. The aim of this study was to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The association between excision repair cross-complementation (ERCC) gene family (ERCC1 and ERCC2) and osteosarcoma risk was controversial. The aim of this study was to evaluate the association between ERCC1 or ERCC2 and osteosarcoma risk by systematic meta-analysis.
MATERIALS AND METHODS
Relative studies were retrieved from electronic databases without language restriction. The last search was updated on March 2017. Quality assessment was analyzed by the Newcastle-Ottawa Scale (NOS) score, which was recommended by the Agency for Healthcare Research and Quality (AHRQ). Meta-analysis was conducted by R language package (R 3.12).
RESULTS
This meta-analysis was performed based on 4 case-control studies that included 1208 cases and 2448 controls. The ERCC2-rs1799793 AA+AC > CC (OR=1.3428, 95% CI=1.0201; 1.7674) had an effect on the risk of osteosarcoma development, whereas, there were no significant associations among the other ERCC SNPs (ERCC1 rs3212986, ERCC1 rs11615, and ERCC2 rs13181) and osteosarcoma.
CONCLUSIONS
The ERCC2 rs1799793 polymorphism is related to the high risk of osteosarcoma development.
Topics: Bone Neoplasms; Case-Control Studies; DNA-Binding Proteins; Endonucleases; Genetic Predisposition to Disease; Humans; Osteosarcoma; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Xeroderma Pigmentosum Group D Protein
PubMed: 30402838
DOI: 10.26355/eurrev_201810_16142 -
Medicine Jul 2015There is no consensus on the optimal method of local control in Ewing's sarcoma (ES) of the mobile spine. Recent reports have suggested that en bloc resection may... (Review)
Review
There is no consensus on the optimal method of local control in Ewing's sarcoma (ES) of the mobile spine. Recent reports have suggested that en bloc resection may improve local control and survival. The authors therefore performed a systematic review to answer the following questions: (1) What is the outcome of en bloc resection for ES of the mobile spine with respect to local control and disease-free survival (DFS)? (2) How should residual ES of the mobile spine be treated?Inclusion criteria were articles published between the years 1960 and 2014 in English that contained more than five patients. This yielded 204 articles, from which 4 were selected for detailed analysis. The literature was graded for quality, summarized, and presented to a group of spinal oncology experts with consensus recommendations made.All 4 studies were retrospective case series graded as very low quality evidence. Local control strategies included radiotherapy (RT) alone, surgery and RT, or surgery alone. There was no standardized outcome reported across studies with respect to the type of surgical procedure, margins, and outcomes of interest such as local recurrence (LR) and DFS. When the en bloc procedures were pooled together, 2 of the 21 patients with available LR data developed LR (9.5%), and 5 of the 7 patients with available DFS data were disease free at a mean of 76 months. The remaining 2 died at 10 and 29 months, respectively. No studies were identified detailing the treatment of residual ES of the mobile spine.There is no consensus on the optimal method of local control for spinal ES or the treatment of residual disease. A weak recommendation supports that when the en bloc resection is technically possible, in combination with RT, this appears to provide superior local control than RT alone, or incomplete excision and RT. The effect on survival is indeterminate.
Topics: Disease-Free Survival; Humans; Orthopedic Procedures; Retrospective Studies; Sarcoma, Ewing; Spinal Neoplasms
PubMed: 26166072
DOI: 10.1097/MD.0000000000001019