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Aging Cell Jul 2023Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains... (Meta-Analysis)
Meta-Analysis Review
Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.
Topics: Humans; Mendelian Randomization Analysis; Arthritis, Rheumatoid; Glioma; Hypertension; Telomere; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37232505
DOI: 10.1111/acel.13874 -
Orthopedic Research and Reviews 2023Teriparatide is a recombinant human parathyroid hormone analog with anabolic mechanism of action utilized in the treatment of osteoporosis with well-established clinical... (Review)
Review
Teriparatide is a recombinant human parathyroid hormone analog with anabolic mechanism of action utilized in the treatment of osteoporosis with well-established clinical efficacy. Its use is significantly hindered due to label warnings resulting from pre-clinical rat studies demonstrating an increased risk of osteosarcoma. However, clinical trials and post-marketing surveillance studies did not demonstrate any increased risk of osteosarcoma, even after prolonged periods of surveillance reaching up to 15 years, with most of the identified cases of osteosarcomas being solitary and predominantly attributed to other factors. This systematic review provides a comprehensive overview of the currently available literature and provides the highest level of clinical evidence towards demonstrating the lack of any substantial evidence towards osteosarcoma development in patients utilizing TPTD.
PubMed: 37791038
DOI: 10.2147/ORR.S408718 -
International Journal of Medical... 2023The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5,... (Review)
Review
The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5, 6, 7) and δ (TMED 10), with a total of nine members, which are important regulators of intracellular protein transport and are involved in normal embryonic development, as well as in the pathogenic processes of many human diseases. Here we systematically review the composition, structure and function of TMED family members, and describe the progress of TMED family in human diseases, including malignancies (head and neck tumors, lung cancer, breast cancer, ovarian cancer, endometrial cancer, gastrointestinal tumors, urological tumors, osteosarcomas, etc.), immune responses, diabetes, neurodegenerative diseases, and nonalcoholic fatty liver disease, dilated cardiomyopathy, mucin 1 nephropathy (MKD), and desiccation syndrome (SS). Finally, we discuss and prospect the potential of TMED for disease prognosis prediction and therapeutic targeting, with a view to laying the foundation for therapeutic research based on TMED family causative genes.
Topics: Pregnancy; Female; Humans; Membrane Proteins; Protein Transport; Non-alcoholic Fatty Liver Disease; Vesicular Transport Proteins
PubMed: 37928880
DOI: 10.7150/ijms.87272 -
Non-coding RNA Research Jun 2024Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles... (Review)
Review
Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles published from January 2010 to September 2023 were searched across eight databases to compare circRNA expression profiles in osteosarcoma and control samples (human, animal and cell lines). Meta-analysis was conducted under a random effects model. Subgroup analysis of circRNAs in different samples and tissues was performed. Diagnostic value was evaluated using receiver operator characteristic curves. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis explored functions of circRNA host genes. A circRNA-miRNA-mRNA axis depicted the regulatory mechanism in osteosarcoma. Among 1356 circRNAs with differential expression were identified across 226 original studies, only 74 were reported in at least three published sub-studies. Meta-analysis identified 58 dysregulated circRNAs (52 upregulated and 6 downregulated). Eleven circRNAs consistently showed dysregulation in tissues and cell lines, with hsa_circ_0005721 showing potential as a circulating biomarker in osteosarcoma. Sensitivity analysis demonstrated 97 % consistency. The overall area under the curve was 0.87 (95 % CI, 0.83-0.89). GO and KEGG enrichment analyses revealed host gene involvement in cancer. The circRNA-miRNA-mRNA axis revealed the regulatory axis and interactions within osteosarcoma specifically. This study demonstrates circRNAs as potential diagnostic biomarkers for osteosarcoma. Consistently reported dysregulated circRNAs are potential biomarkers in osteosarcoma pathogenesis, with hsa_circ_0005721 as a potential circulating biomarker for diagnosis and treatment.
PubMed: 38505307
DOI: 10.1016/j.ncrna.2024.01.007 -
Cancer Treatment Reviews Nov 2023To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis. (Review)
Review
BACKGROUND/OBJECTIVE
To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis.
METHODS
A systematic review of trials registered on trial registries between 01/01/2017-14/02/2022. Comparison of 98 trials identified between 2003 and 2016. Publication search/analysis for both periods, last update on 01/12/2022.
RESULTS
Between 2017 and 2022, 71 phase-II trials met our selection criteria (19 osteosarcoma-specific trials, 14 solid tumor trials with and 38 trials without an osteosarcoma-specific stratum). The trial number increased over time: 13.9 versus 7 trials/year (p = 0.06). Monotherapy remained the predominant treatment (62% vs. 62%, p = 1). Targeted therapies were increasingly evaluated (66% vs. 41%, P = 0.001). Heterogeneity persisted in the trial characteristics. The inclusion criteria were measurable disease (75%), evaluable disease (14%), and surgical remission (11%). 82% of the trials included pediatric or adolescent patients. Biomarker-driven trials accounted for 25% of the total trials. The survival endpoint use (rather than response) slightly increased (40% versus 31%), but the study H/H hypotheses remained heterogeneous. Single-arm designs predominated over multiarm trials (n = 7). Available efficacy data on 1361 osteosarcoma patients in 58 trials remained disappointing, even though 21% of these trials were considered positive, predominantly those evaluating multi-targeted kinase inhibitors.
CONCLUSION
Despite observed changes in trial design and an increased number of trials investigating new therapies, high heterogeneity remained with respect to patient selection, study design, primary endpoints, and statistical hypotheses in recently registered phase II trials for osteosarcoma. Continued optimization of trial design informed by a deeper biological understanding should strengthen the development of new therapies.
PubMed: 37738712
DOI: 10.1016/j.ctrv.2023.102625 -
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 -
Cancer Treatment Reviews Mar 2024Patients with high-risk or metastatic Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) have a guarded prognosis. High-dose chemotherapy (HDT) with autologous stem cell... (Review)
Review
High-dose chemotherapy for Ewing sarcoma and Rhabdomyosarcoma: A systematic review by the Australia and New Zealand sarcoma association clinical practice guidelines working party.
INTRODUCTION
Patients with high-risk or metastatic Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) have a guarded prognosis. High-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) has been evaluated as a treatment option to improve outcomes. However, survival benefits remain unclear, and treatment is associated with severe toxicities.
METHODS
A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether utilization of HDT/ASCT impacts the outcome of patients with ES and RMS compared to standard chemotherapy alone, as part of first line treatment or in the relapse setting. Medline, Embase and Cochrane Central were queried for publications from 1990 to October 2022 that evaluated event-free survival (EFS), overall survival (OS), and toxicities. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed.
RESULTS
Of 1,172 unique studies screened, 41 studies were eligible for inclusion with 29 studies considering ES, 10 studies considering RMS and 2 studies considering both. In ES patients with high-risk localised disease who received HDT/ASCT after VIDE chemotherapy, consolidation with melphalan-based HDT/ASCT as first line therapy conveyed an EFS and OS benefit over standard chemotherapy consolidation. Efficacy of HDT/ASCT using a VDC/IE backbone, which is now standard care, has not been established. Survival benefits are not confirmed for ES patients with metastatic disease at initial diagnosis. For relapsed/refractory ES, four retrospective studies report improvement in outcomes with HDT/ASCT with the greatest evidence in patients who demonstrate a treatment response before HDT, and in patients under the age of 14. In RMS, there is no proven survival benefit of HDT/ASCT in primary localised, metastatic or relapsed disease.
CONCLUSION
Prospective randomised trials are required to determine the utility of HDT/ASCT in ES and RMS. Selected patients with relapsed ES could be considered for HDT/ASCT.
Topics: Humans; Sarcoma, Ewing; Combined Modality Therapy; Antineoplastic Combined Chemotherapy Protocols; Retrospective Studies; Prospective Studies; New Zealand; Neoplasm Recurrence, Local; Rhabdomyosarcoma; Transplantation, Autologous; Treatment Outcome; Hematopoietic Stem Cell Transplantation
PubMed: 38325070
DOI: 10.1016/j.ctrv.2024.102694 -
Journal of Pediatric Surgery Jul 2023Resection of pediatric chest wall tumors can result in large defects requiring reconstruction for function and cosmesis. Multiple reconstructive methods have been... (Review)
Review
BACKGROUND
Resection of pediatric chest wall tumors can result in large defects requiring reconstruction for function and cosmesis. Multiple reconstructive methods have been described. We performed a systematic review of the literature to describe commonly used approaches and outcomes.
METHODS
A systematic literature search was performed for English-language publications describing chest wall tumor resection and reconstruction using implantable materials in patients ≤21 years, excluding soft tissue resection only, sternal resection, and reconstruction by primary repair or muscle flaps alone. Data were collected on diagnoses, reconstructive method, and outcomes. Rigid chest wall reconstruction was compared to mesh reconstruction.
RESULTS
There were 55 articles with 188 patients included. The median age was 12 years. Most tumors were malignant (n = 172, 91.5%), most commonly Ewing's sarcoma (n = 65, 34.6%), followed by unspecified sarcomas (n = 34, 18.1%), Askin's tumor (n = 16, 8.5%; a subset of Ewing's sarcoma) and osteosarcoma (n = 16, 8.5%). A median of 3 ribs were resected (range 1-12). Non-rigid meshes were most common (n = 138, 73.4%), followed by rigid prostheses (n = 50, 26.6%). There were 19 post-operative complications (16.8%) and 22.2% of patients developed scoliosis. There were no significant differences in complications (20.5% rigid vs. 10.6% non-rigid, p = 0.18) or scoliosis (22.7% vs. 14.0%, p = 0.23) by reconstruction method, but complications after rigid reconstruction were more likely to require surgery (90.0% vs. 53.9%, p = 0.09). The median follow-up duration was 24 months.
CONCLUSIONS
In this review of the literature, there were no significant differences in overall post-operative complications or scoliosis development by reconstruction method, yet complications after rigid reconstruction were more likely to require surgical intervention.
LEVEL OF EVIDENCE
Level IV.
Topics: Humans; Child; Sarcoma, Ewing; Thoracic Wall; Scoliosis; Plastic Surgery Procedures; Bone Neoplasms; Thoracic Neoplasms; Postoperative Complications
PubMed: 36585305
DOI: 10.1016/j.jpedsurg.2022.11.008 -
Scientific Reports Feb 2024Osteosarcoma (OS) is the most common type of primary bone malignancy. Common genetic variants including single nucleotide polymorphisms (SNPs) have been associated with... (Meta-Analysis)
Meta-Analysis
Osteosarcoma (OS) is the most common type of primary bone malignancy. Common genetic variants including single nucleotide polymorphisms (SNPs) have been associated with osteosarcoma risk, however, the results of published studies are inconsistent. The aim of this study was to systematically review genetic association studies to identify SNPs associated with osteosarcoma risk and the effect of race on these associations. We searched the Medline, Embase, Scopus from inception to the end of 2019. Seventy-five articles were eligible for inclusion. These studies investigated the association of 190 SNPs across 79 genes with osteosarcoma, 18 SNPs were associated with the risk of osteosarcoma in the main analysis or in subgroup analysis. Subgroup analysis displayed conflicting effects between Asians and Caucasians. Our review comprehensively summarized the results of published studies investigating the association of genetic variants with osteosarcoma susceptibility, however, their potential value should be confirmed in larger cohorts in different ethnicities.
Topics: Humans; Bone Neoplasms; Genetic Predisposition to Disease; Osteosarcoma; Polymorphism, Single Nucleotide; Asian People; White People
PubMed: 38360742
DOI: 10.1038/s41598-024-53802-w -
Diagnostics (Basel, Switzerland) Apr 2024Pediatric sarcomas, rare malignancies of mesenchymal origin, pose diagnostic and therapeutic challenges. In this review, we explore the role of radiomics in reshaping... (Review)
Review
Advancing Pediatric Sarcomas through Radiomics: A Systematic Review and Prospective Assessment Using Radiomics Quality Score (RQS) and Methodological Radiomics Score (METRICS).
Pediatric sarcomas, rare malignancies of mesenchymal origin, pose diagnostic and therapeutic challenges. In this review, we explore the role of radiomics in reshaping our understanding of pediatric sarcomas, emphasizing methodological considerations and applications such as diagnostics and predictive modeling. A systematic review conducted up to November 2023 identified 72 papers on radiomics analysis in pediatric sarcoma from PubMed/MEDLINE, Web of Knowledge, and Scopus. Following inclusion and exclusion criteria, 10 reports were included in this review. The studies, predominantly retrospective, focus on Ewing sarcoma and osteosarcoma, utilizing diverse imaging modalities, including CT, MRI, PET/CT, and PET/MRI. Manual segmentation is common, with a median of 35 features extracted. Radiomics Quality Score (RQS) and Methodological Radiomics Score (METRICS) assessments reveal a consistent emphasis on non-radiomic features, validation criteria, and improved methodological rigor in recent publications. Diagnostic applications dominate, with innovative studies exploring prognostic and treatment response aspects. Challenges include feature heterogeneity and sample size variations. The evolving landscape underscores the need for standardized methodologies. Despite challenges, the diagnostic and predictive potential of radiomics in pediatric oncology is evident, paving the way for precision medicine advancements.
PubMed: 38667477
DOI: 10.3390/diagnostics14080832