-
European Review For Medical and... Feb 2022Osteosarcoma is a common bone sarcoma that often occurs in childhood and adolescence. In recent years, the efficacy of osteosarcoma treatments has been improved by... (Review)
Review
OBJECTIVE
Osteosarcoma is a common bone sarcoma that often occurs in childhood and adolescence. In recent years, the efficacy of osteosarcoma treatments has been improved by adjuvant chemotherapies and surgical approaches. However, poor prognosis often occurs among osteosarcoma patients due to recurrence, metastasis, or drug resistance problems. Cancer stem cells (CSCs), a specific type of tumor malignant cells with stem cell-like properties, have been reported to be responsible for tumor origination, aggression, metastasis, recurrence, and drug resistance. CSCs have been identified in osteosarcomas treatment, which exhibits self-renewal, multi-potency, and enhanced drug resistance. Therefore, in the present narrative review, we intend to summarize the role of lncRNAs in regulating CSCs and their effectiveness in the treatment of osteosarcoma.
MATERIALS AND METHODS
The databases PubMed (Medline), Web of Science, Embase, Scopus, and Cochrane Library, were used for the presented study. The keywords we used to complete our search are 'lncRNA', 'Stem cell', and 'osteosarcoma'. A total of over 800 relevant articles, with a time limit from 2010 to 2021, were identified according to search strategy. Duplicate records and review articles were excluded by their titles and abstracts. Finally, we found about 80 articles matching our inclusion criteria, which included about 13 relevant studies focusing on both the mechanism and effectiveness of osteosarcomas treatment among osteosarcoma patients.
RESULTS
CD133, CD117, ALDH, and Stro-1 are validated as the stem cell biomarkers in osteosarcoma CSCs. Accumulating evidence has revealed that lncRNAs, containing HIF2PUT, SOX2-OT, MALAT1, THOR, B4GALT1-AS1, H19, PVT1, FER1L4, LINK-A, DANCR, and DLX6-AS1, play a potential role in regulating CSCs in osteosarcoma. The drug resistance, inhibition of the relapse, and metastasis in osteosarcoma could be avoided via regulating lncRNAs of targeting CSCs.
CONCLUSIONS
Multiple lncRNAs regulate CSCs in osteosarcoma via various molecular mechanisms. This review demonstrated that the method of eliminating CSCs by targeting these lncRNAs is a safe, effective, and a well-tolerated way for osteosarcoma patients, which shows a broad research prospect in tumor diagnoses and therapies. However, this method should be further demonstrated by better animal models and more clinical experiments.
Topics: Animals; Bone Neoplasms; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Osteosarcoma; RNA, Long Noncoding
PubMed: 35179763
DOI: 10.26355/eurrev_202202_28006 -
Journal of B.U.ON. : Official Journal... 2021To detect the plasma levels of PLAC1 in osteosarcoma patients, and its regulatory effect on cell proliferation and apoptosis of osteosarcoma.
PURPOSE
To detect the plasma levels of PLAC1 in osteosarcoma patients, and its regulatory effect on cell proliferation and apoptosis of osteosarcoma.
METHODS
Plasma levels of PLAC1 in osteosarcoma patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Receiver operating characteristics (ROC) and Kaplan-Meier curves were performed for assessing the diagnostic and prognostic potentials of PLAC1 in osteosarcoma, respectively. Moreover, the regulatory effects of PLAC1 on proliferative and apoptotic rates of osteosarcoma cells were determined through cell counting kit-8 (CCK-8) and flow cytometry, respectively.
RESULTS
PLAC1 was highly expressed in plasma of osteosarcoma patients showing diagnostic and prognostic potentials. Overexpression of PLAC1 in U2-OS cells increased the proliferative rate but decreased the apoptotic rate, while knockdown of PLAC1 yielded the opposite results.
CONCLUSIONS
PLAC1 is upregulated in the plasma of osteosarcoma patients, serving as a diagnostic biomarker, and is unfavorable to the prognosis if this disease. PLAC1 promotes the development of osteosarcoma by stimulating cell proliferation and inhibiting apoptosis.
Topics: Adolescent; Biomarkers, Tumor; Humans; Osteosarcoma; Pregnancy Proteins
PubMed: 34077010
DOI: No ID Found -
International Journal of Molecular... Nov 2022Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause... (Review)
Review
Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations.
Topics: Child; Adolescent; Young Adult; Humans; Middle Aged; Osteosarcoma; Bone Neoplasms; Incidence
PubMed: 36499267
DOI: 10.3390/ijms232314939 -
Cancer Medicine May 2024Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14-19. This aggressive form of cancer often leads to... (Review)
Review
Osteosarcoma (OS) is a prevalent bone solid malignancy that primarily affects adolescents, particularly boys aged 14-19. This aggressive form of cancer often leads to deadly lung cancer due to its high migration ability. Experimental evidence suggests that programmed cell death (PCD) plays a crucial role in the development of osteosarcoma. Various forms of PCD, including apoptosis, ferroptosis, autophagy, necroptosis, and pyroptosis, contribute significantly to the progression of osteosarcoma. Additionally, different signaling pathways such as STAT3/c-Myc signal pathway, JNK signl pathway, PI3k/AKT/mTOR signal pathway, WNT/β-catenin signal pathway, and RhoA signal pathway can influence the development of osteosarcoma by regulating PCD in osteosarcoma cell. Therefore, targeting PCD and the associated signaling pathways could offer a promising therapeutic approach for treating osteosarcoma.
Topics: Osteosarcoma; Humans; Bone Neoplasms; Apoptosis; Signal Transduction; Autophagy; Ferroptosis; Necroptosis; Animals
PubMed: 38800967
DOI: 10.1002/cam4.7303 -
Acta Veterinaria Scandinavica Oct 2017Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with... (Comparative Study)
Comparative Study Review
Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is relatively poor, with 5 year OSA survival rates in people not having improved in decades. For dogs, 1 year survival rates are only around ~ 45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human OSA. Finally, the current position of canine OSA genetic research is discussed and areas for additional work within the canine population are identified.
Topics: Animals; Dog Diseases; Dogs; Genetic Predisposition to Disease; Humans; Osteosarcoma; Prognosis
PubMed: 29065898
DOI: 10.1186/s13028-017-0341-9 -
Journal of Orthopaedic Surgery and... Apr 2019Osteosarcoma was locally aggressive and frequently metastasizes to the lung. However, the etiology of osteosarcoma was unknown. Thus, exploring the mechanisms behind the...
BACKGROUND
Osteosarcoma was locally aggressive and frequently metastasizes to the lung. However, the etiology of osteosarcoma was unknown. Thus, exploring the mechanisms behind the occurrence of osteosarcoma was important for its prediction and prevention. To investigate the usefulness of mammalian Eps15 homology domain 1 (EHD1) as a prognostic marker for osteosarcoma, the expression of EHD1 in 57 osteosarcoma patients was measured using immunohistochemistry techniques and correlated with the clinicopathological features of patients.
METHODS
Correlations of EHD1 expression levels with clinicopathological features of patients were assessed using the Pearson χ test for categorical variables and the Student t test for continuous variables. Cumulative disease-free survival (DFS) curves and overall survival (OS) curves were plotted using the Kaplan-Meier method, and the relationship between each of the variables and survival was assessed by log-rank tests using univariate analysis. Subsequently, the parameters were tested using the multivariate Cox proportional hazards model, which was used to identify independent variables for predicting survival. EHD1 expression [P = 0.020; HR, 5.582; 95% confidence intervals (CI), 1.314-23.72] was an independent prognostic indicator of DFS in osteosarcoma patients; tumor size and EHD1 expression of osteosarcomas were independent prognostic indicators of OS in osteosarcoma patients.
RESULTS
EHD1 protein expression was a positive expression in examined tumor tissues. The median OS time of patients with high expression of EHD1 was 46.8 months (95% CI, 29.8-63.8 months), and the median OS time of patients with low expression of EHD1 was 58.8 months (95% CI, 31.6-86.0 months). The prognosis for patients with low expression of EHD1 in osteosarcomas was significantly better than that for patients with high expression of EHD1 (log-rank test, P = 0.019).
CONCLUSION
The expression of EHD1 was negatively correlated with DFS and OS of osteosarcoma patients; therefore, the expression of EHD1 is a prognostic marker for prediction and prevention of osteosarcomas.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Disease-Free Survival; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Osteosarcoma; Survival Rate; Vesicular Transport Proteins; Young Adult
PubMed: 30975166
DOI: 10.1186/s13018-019-1137-6 -
Discovery Medicine Jun 2014Osteosarcoma is an aggressive cancer in skeletal system with unknown molecular mechanisms of etiology and pathogenesis, therefore it remains a challenge for current... (Review)
Review
Osteosarcoma is an aggressive cancer in skeletal system with unknown molecular mechanisms of etiology and pathogenesis, therefore it remains a challenge for current therapeutic strategies to effectively treat osteosarcoma. The aim of this review is to give an overview of the molecular and mechanistic changes identified in recent years which might be new targets for the treatment of osteosarcoma. These molecules play important roles in different biological and pathological programs of osteosarcoma, including the altered oncogenes and tumor suppressor genes, molecules involved in tumor cell migration and invasion, angiogenesis, apoptosis and proliferation, miRNAs, and molecules involved in osteoclast function and multidrug resistance. Further research on these molecules in osteosarcoma will provide new insights into the target therapy for osteosarcoma.
Topics: Animals; Clinical Trials as Topic; Drug Resistance, Neoplasm; Humans; MicroRNAs; Molecular Targeted Therapy; Osteoclasts; Osteosarcoma
PubMed: 24979249
DOI: No ID Found -
Journal of the American Veterinary... Dec 2021To evaluate the metastasis rate, survival time, and prognostic factors associated with appendicular or scapular osteosarcoma treated by limb amputation in cats.
OBJECTIVE
To evaluate the metastasis rate, survival time, and prognostic factors associated with appendicular or scapular osteosarcoma treated by limb amputation in cats.
ANIMALS
67 cats with histologically confirmed appendicular or scapular osteosarcoma treated by limb amputation.
PROCEDURES
This retrospective cohort study included cats with histologically confirmed appendicular or scapular osteosarcoma between January 1997 and December 2018. A questionnaire survey was conducted at veterinary clinics where limb amputation was performed. Distant metastasis, local recurrence, and lymph node metastasis rates and survival time were determined. Factors associated with distant metastasis and survival were investigated.
RESULTS
The distant metastasis rate after limb amputation was 41.9% (26/62). The overall distant metastasis rate was 46.3% (31/67), including 5 cats with distant metastasis at the time of amputation. Osteosarcoma of the humerus resulted in distant metastasis in 6 of 7 cases. Osteosarcoma of the humerus was significantly associated with distant metastasis in univariate and multivariate analyses (adjusted OR, 9.56). The rate of lymph node metastasis after limb amputation was 3.0% (2/66), and the local recurrence rate was 9.0% (6/67). The median survival time was 527 days. Age and tumor location were not significantly associated with survival time.
CLINICAL RELEVANCE
Distant metastasis occurs in approximately 40% of cats with appendicular or scapular osteosarcoma after limb amputation. In addition, osteosarcoma of the humerus has a particularly high incidence of distant metastasis. Detailed follow-up is therefore necessary, even after limb amputation, especially in cases of osteosarcoma of the humerus.
Topics: Amputation, Surgical; Animals; Bone Neoplasms; Cat Diseases; Cats; Humans; Osteosarcoma; Retrospective Studies
PubMed: 34914624
DOI: 10.2460/javma.21.04.0213 -
Bioscience Reports Jun 2022In the last couple of decades, biomarkers have been on the rise for diagnostic and predictive value. There has been a rush to identify new markers using new technologies...
In the last couple of decades, biomarkers have been on the rise for diagnostic and predictive value. There has been a rush to identify new markers using new technologies and drug repurposing approaches. SMARCB1 acronym arises from the SWI/SNF (SWItch/Sucrose Non-Fermentable)-related Matrix-associated Actin-dependent Regulator of Chromatin subfamily B member 1 (SMARCB1). It is a molecule, whose role is associated with the sucrose metabolism. SMARCB1 is also called INI1 (Integrase Interactor 1). The molecule was discovered in the mid-1990s. Its role as a loss-of-function marker for malignant rhabdoid tumors (MRT) of renal and extrarenal origin has enormously expanded the spectrum of involved neoplasms since that time. Several tumors have been characterized by genetic aberrations in the SMARCB1 gene. They include reduction in expression, loss of expression, and mosaic expression. Most of the tumors are sarcomas, but a variegated group of tumors with mixed phenotypes has also been delineated. It is well known that the outcome of patients harboring genetic aberrations in the SMARCB1 gene has been poor. Guo et al. reported that reduced SMARCB1 expression occurred in 70% of osteosarcomas. Their data significantly correlated with poor neoadjuvant response. These authors emphasize a shorter progression-free and overall survival of the patients demonstrating an altered expression of this gene. Interestingly, mRNA in silico analysis established that SMARCB1 expression correlates with the response to chemotherapy of osteosarcoma patients, but there was no reliable correlation between SMARCB1 expression level and metastasis, response to neoadjuvant therapy, overall survival, and progression-free survival. The study involved a tissue microarray (TMA) on bone tumors that may limit the full evaluation of the gene expression. Nevertheless, Guo et al.'s study is remarkable. It expands the list of the tumors harboring an altered SMARCB1 gene expression and suggests that this marker should be investigated in every pathology workup for potential predictive value. On the other side, much work needs to be done if we hope that we strive to provide additional therapeutic strategies for osteosarcoma patients with altered SMARCB1 gene expression.
Topics: Biomarkers, Tumor; Bone Neoplasms; Humans; Osteosarcoma; Prognosis; Rhabdoid Tumor; SMARCB1 Protein; Sucrose
PubMed: 35583077
DOI: 10.1042/BSR20220040 -
Oncology Reports Mar 2006Osteosarcoma is the most common primary bone tumor and represents a major therapeutic challenge in medical oncology. While the use of aggressive chemotherapy has... (Review)
Review
Osteosarcoma is the most common primary bone tumor and represents a major therapeutic challenge in medical oncology. While the use of aggressive chemotherapy has drastically improved the prognosis of the patients with non-metastatic osteosarcomas, the very poor prognosis of patients with metastasis have led to the exploration of new, more effective and less toxic treatments, such as immunotherapy for curing osteosarcoma. Compared to the numerous reports describing successful immunotherapy for other solid tumors, the number of reports concerning immunotherapy for osteosarcoma is low. However, this therapeutic strategy opens new areas for the treatment of osteosarcoma. In this review, the reasons for delay and all elements essential to develop immunotherapy concerning osteosarcoma are defined. Several pieces of evidence strongly support the potential capability of new therapies such as cellular therapy and gene therapy to eradicate osteosarcoma. Thus, clinical human trials using peptides, cytokines and dendritic cells have been performed. Tumor-infiltrating lymphocytes and some tumor antigens have been identified in osteosarcoma and resulted in an important breakthrough in cellular immunotherapy. Also, RANKL/RANK/OPG, the key regulator of bone metabolism, is a hot spot in this field as therapeutic tools. Immunotherapy for osteosarcomas has great potential, promising improvement in the survival rate and better quality of life for the patients.
Topics: Bone Neoplasms; Forecasting; Humans; Immunotherapy; Osteosarcoma
PubMed: 16465432
DOI: No ID Found