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International Journal of Molecular... Jan 2014To investigate the association of combined microRNA-340 (miR-340) and ROCK1 mRNA profiling with clinicopathologic features and prognosis in pediatric patients with...
To investigate the association of combined microRNA-340 (miR-340) and ROCK1 mRNA profiling with clinicopathologic features and prognosis in pediatric patients with osteosarcoma. Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect expression levels of miR-340 and ROCK1 mRNA in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. Compared with noncancerous bone tissues, the expression levels of miR-340 and ROCK1 mRNA were, respectively, downregulated and upregulated in osteosarcoma tissues (both p < 0.001), which was consistent with the results of in situ hybridization and immunohistochemistry analysis. The downregulation of miR-340 was negatively correlated with the upregulation of ROCK1 mRNA in osteosarcoma tissues (r = -0.78, p = 0.001). In addition, the combined miR-340 downregulation and ROCK1 upregulation (miR-340-low/ROCK1-high) occurred more frequently in osteosarcoma tissues with positive metastasis (p < 0.001) and poor response to pre-operative chemotherapy (p = 0.002). Moreover, miR-340-low/ROCK1-high expression was significantly associated with both shortest overall survival (p < 0.001) and progression-free survival (p < 0.001). Multivariate analysis further confirmed that miR-340-low/ROCK1-high expression was an independent prognostic factor of unfavorable survival in pediatric osteosarcoma (for overall survival: p = 0.006, for progression-free survival: p = 0.008). Our data offer convincing evidence, for the first time, that the combined miR-340 downregulation and ROCK1 upregulation may be linked to tumor progression and adverse prognosis in pediatric osteosarcoma.
Topics: Adolescent; Biomarkers, Tumor; Bone Neoplasms; Child; Child, Preschool; Disease Progression; Disease-Free Survival; Down-Regulation; Female; Humans; Immunohistochemistry; In Situ Hybridization; Male; MicroRNAs; Osteosarcoma; Prognosis; RNA, Messenger; Up-Regulation; Young Adult; rho-Associated Kinases
PubMed: 24398981
DOI: 10.3390/ijms15010560 -
In Vivo (Athens, Greece) 2022Little is known about the clinical characteristics in older patients of ≥75 years of age with primary osteosarcoma due to its rarity. We aimed to understand the... (Review)
Review
BACKGROUND/AIM
Little is known about the clinical characteristics in older patients of ≥75 years of age with primary osteosarcoma due to its rarity. We aimed to understand the clinical characteristics in these patients in order to make an appropriate diagnosis and provide treatment.
PATIENTS AND METHODS
The medical records of eight patients of ≥75 years of age with primary osteosarcoma were retrospectively reviewed. We investigated their clinical features, imaging findings, histopathological findings, treatment methods, and oncological outcomes.
RESULTS
There were two male and six female patients, with a mean age of 80 years. The mean follow-up period was 44 months. The initial symptom was pain in five, swelling in two, and a mass in one. The initial diagnosis was osteoarthritis in two, lumbar canal stenosis in two, benign bone tumor in four. The mean period from the first time the patient noticed symptoms to referral was 25 months. Two patients had a history of surgical curettage at their previous hospital for bone tumor that was considered benign. Lung metastasis was observed at presentation in three patients. The mean tumor size was 129 mm in its greatest dimension. Surgical treatment was performed on six patients, including frozen autograft reconstruction in one. Carbon-ion radiotherapy was conducted in one patient due to an unresectable pelvic lesion.
CONCLUSION
Diagnosis requires care because the radiological and histological findings of primary osteosarcoma in patients ≥75 years of age are often non-specific, in addition to their delayed consultation. Individualized treatment including surgical procedure and radiotherapy is essential for older patients to maintain a good quality of their lives.
Topics: Humans; Male; Female; Aged; Aged, 80 and over; Osteosarcoma; Retrospective Studies; Bone Neoplasms; Transplantation, Autologous; Radiography
PubMed: 36309390
DOI: 10.21873/invivo.13031 -
The Clinical Respiratory Journal Nov 2023About half of osteosarcomas occur near the knee joint, but other sites such as the humerus, upper femur, fibula, spine, and ilium can also occur. However, rib... (Review)
Review
About half of osteosarcomas occur near the knee joint, but other sites such as the humerus, upper femur, fibula, spine, and ilium can also occur. However, rib osteosarcoma is rarely reported. Here, we report the case of a 17-year-old female who was found to have a left dorsal mass on physical examination. Computed tomography (CT) revealed bone destruction in the seventh rib, leading to surgery for mass excision. Pathological results suggested chondroblastic osteosarcoma. After surgery, the patient was treated with chemotherapy and is doing well.
Topics: Female; Humans; Adolescent; Bone Neoplasms; Tomography, X-Ray Computed; Osteosarcoma; Ribs
PubMed: 37706233
DOI: 10.1111/crj.13686 -
Medicina (Kaunas, Lithuania) Feb 2021Osteosarcomas (OSs) are a group of neoplasms originating from bone cells, usually presenting in three specific age groups: children, young adults, and the elderly.... (Review)
Review
Osteosarcomas (OSs) are a group of neoplasms originating from bone cells, usually presenting in three specific age groups: children, young adults, and the elderly. High-grade OS is an extremely malignant tumor mainly due to evolution into metastatic disease, usually in the lungs. Survival of these patients has improved since the 1980s thanks to close cooperation between oncologists, oncological surgeons and orthopedic surgeons. Unfortunately, no progress has been made in the last 30 years and new, more effective drugs are needed. This article reviews the biological and pharmacological basis of the treatment of OS. Models of clinical pharmacology of the active drugs, toxic effects and reasons for primary and secondary resistance to old and new drugs are discussed.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Combined Modality Therapy; Humans; Osteosarcoma; Young Adult
PubMed: 33562455
DOI: 10.3390/medicina57020141 -
Clinical Orthopaedics and Related... Sep 2019MicroRNAs are small, noncoding RNAs that regulate the expression of posttranslational genes. The presence of some specific microRNAs has been associated with increased...
BACKGROUND
MicroRNAs are small, noncoding RNAs that regulate the expression of posttranslational genes. The presence of some specific microRNAs has been associated with increased risk of both local recurrence and metastasis and worse survival in patients with osteosarcoma. Pathologic fractures in osteosarcoma are considered to be more the manifestation of a neoplasm with a more aggressive biological behavior than the cause itself of worse prognosis. However, this has not been proved at the biological or molecular level. Currently, there has not been a microRNA profiling study of patients who have osteosarcoma with and without pathologic fractures that has described differences in terms of microRNA profiling between these two groups and their correlation with biologic behavior.
QUESTIONS/PURPOSES
(1) In patients with osteosarcoma of the extremities, how do the microRNA profiles of those with and without pathologic fractures compare? (2) What relationship do microRNAs have with local recurrence, risk of metastasis, disease-specific survival, and overall survival in osteosarcoma patients with pathologic fractures?
METHODS
Between 1994 and 2013, 217 patients were diagnosed and treated at our institution for osteosarcoma of the extremities. Patients were excluded if (1) they underwent oncologic resection of the osteosarcoma at an outside institution (two patients) or (2) they were diagnosed with an extraskeletal osteosarcoma (29 patients) or (3) they had less than 1 year of clinical follow-up and no oncologic outcome (local recurrence, metastasis, or death) (four patients). A total of 182 patients were eligible. Of those, 143 were high-grade osteosarcomas. After evaluation of tumor samples before chemotherapy treatment, a total of 80 consecutive samples were selected for sequencing. Demographic and clinical comparison between the sequenced and non-sequenced patients did not demonstrate any differences, confirming that both groups were comparable. Diagnostic samples from the extremities of 80 patients with high-grade extremity osteosarcomas who had not yet received chemotherapy underwent microRNA sequencing for an ongoing large-scale osteosarcoma genome profiling project at our institution. Six samples were removed after a second look by a musculoskeletal pathologist who verified cellularity and quality of samples to be sequenced, leaving a total of 74 patients. Of these, two samples were removed as they were confirmed to be pelvic tumors in a second check after sequencing. The final study sample was 72 patients (11 patients with pathologic fractures and 61 without). Sequencing data were correlated with fractures and local recurrence, risk of metastasis, disease-specific survival, and overall survival through Kaplan-Meier analyses.
RESULTS
Several microRNAs were expressed differently between the two groups. Among the markers with the highest differential expression (edgeR and DESeq algorithms), Hsa-mIR 656-3p, hsa-miR 493-5p, and hsa-miR 381-3p were upregulated in patients with pathologic fractures, whereas hsa-miR 363, hsa-miR 885-5p, and has-miR 20b-5p were downregulated. The highest differential expression fracture and nonfracture-associated microRNA markers also distinguished groups of patients with different metastasis risk, a well as different disease-specific and overall survival. Furthermore, the profile of pathologic fractures demonstrated a higher differential expression for microRNA markers that were previously associated with a higher risk of metastasis and lower survival rates in patients with osteosarcoma.
CONCLUSIONS
In patients who have osteosarcoma, the microRNA profiles of those with pathologic fractures are different than of patients without pathologic fractures. The highest differential expression mircroRNA molecules in patients with pathologic fractures predict also higher risk of metastatic disease as well as worse disease-specific survival and overall survival. Furthermore, we found higher differential expression of microRNAs in the pathologic fracture group previously associated with poor prognosis. The higher risk of metastasis and poorer overall survival in patients with pathologic fractures is inherent to tumor aggressive biologic behavior. It is plausible that the fracture itself is not the direct cause of worse prognosis but another manifestation of tumor biologic aggressiveness. Identification of these molecules through liquid biopsies may help to determine which patients may benefit from surgery before fractures occur. The same technology can be applied to identify patterns of response to conventional chemotherapy, assisting in more specific and accurate systemic therapy.
LEVEL OF EVIDENCE LEVEL
III, prognostic study.
Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Bone Neoplasms; Child; Female; Fractures, Spontaneous; Humans; Male; MicroRNAs; Middle Aged; Osteosarcoma; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 31389890
DOI: 10.1097/CORR.0000000000000867 -
Annals of Oncology : Official Journal... Aug 2013The aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine.
BACKGROUND
The aims of this analysis were to investigate features and outcome of high-grade osteosarcomas of the mobile spine.
PATIENTS AND METHODS
Since 1977, 20 Cooperative Osteosarcoma Study Group patients had a diagnosis of high-grade osteosarcomas of the mobile spine and were included in this retrospective analysis of patient-, tumor- and treatment-related variables and outcome.
RESULTS
The median age was 29 years (range 5-58). Most frequent tumor sites were thoracic and lumbar spine. All but three patients had nonmetastatic disease at diagnosis. Treatment included surgery and chemotherapy for all patients, 13 were also irradiated. Eight patients failed to achieve a macroscopically complete surgical remission (five local, one primary metastases, two both), six died, two are alive, both with radiotherapy. Of 12 patients with complete remission at all sites, three had a recurrence (two local, one metastases) and died. The median follow-up of the 11 survivors was 8.7 years (range 3.1-22.3), 5-year overall and event-free survival rates were 60% and 43%. Age <40 years, nonmetastatic disease at diagnosis and complete remission predicted for better overall survival (OS, P < 0.05).
CONCLUSIONS
Osteosarcomas of the mobile spine are rare. With complete resection (and potentially radiotherapy) and chemotherapy, prognosis may be comparable with that of appendicular osteosarcomas.
Topics: Adolescent; Adult; Child; Child, Preschool; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Osteosarcoma; Pain; Retrospective Studies; Spine; Survival Rate; Treatment Outcome; Young Adult
PubMed: 23613478
DOI: 10.1093/annonc/mdt154 -
European Review For Medical and... Oct 2014Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. Despite aggressive therapy, survival outcomes remain unsatisfactory,...
OBJECTIVE
Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. Despite aggressive therapy, survival outcomes remain unsatisfactory, especially for patients with metastatic disease or patients with a poor chemotherapy response. Previous study founds inosine 5'-monophosphate dehydrogenase type II (IMPDH2) was an independent prognostic factor and observed frequent IMPDH2 overexpression in osteosarcoma patients with poor response to chemotherapy. In the present work, we provide evidence for direct involvement of IMPDH2 in the development of radioresistance and chemoresistance.
MATERIALS AND METHODS
The expression of IMPDH2 was examined in OS cells. Stable cell lines overexpressing IMPDH2 and IMPDH2 knock-down cells were generated using the osteosarcoma cell line. The stable transfected cells, alone or in combination with cisplatin or γ-irradiation, was used to treat OS cells. The growth inhibitory and apoptotic effects of IMPDH2 in vitro and in vivo were examined.
RESULTS
Overexpression of IMPDH2 in IMPDH2 poor-expressed U2OS cells induced strong cisplatin chemoresistance and γ-irradiation radioresistance through inhibition of apoptosis in vitro and in vivo. Knockdown of IMPDH2 in IMPDH2 rich-expressed Saos-2 cells resulted in significant chemosensitivity and γ-irradiation radiosensitivity through inducing of apoptosis in vitro and in vivo.
CONCLUSIONS
IMPDH2 is directly involved in the development of chemoresistance and radioresistance in osteosarcoma cells, suggesting that targeting of IMPDH2 by shRNA in combination with chemotherapy and γ-irradiation might be a promising means of overcoming chemoresistance and radioresistance in osteosarcomas with high IMPDH2 expression.
Topics: Animals; Apoptosis; Bone Neoplasms; Cell Line, Tumor; Cisplatin; Drug Resistance, Neoplasm; Female; Humans; IMP Dehydrogenase; Mice, Nude; Osteosarcoma
PubMed: 25392102
DOI: No ID Found -
FEBS Open Bio Jan 2023Osteosarcomas are prevalent in children and young adults and have a high recurrence rate. Cisplatin, doxorubicin, and methotrexate are common adjuvant chemotherapy drugs...
Osteosarcomas are prevalent in children and young adults and have a high recurrence rate. Cisplatin, doxorubicin, and methotrexate are common adjuvant chemotherapy drugs for treatment of osteosarcoma, but multidrug resistance is a growing problem. Therefore, understanding the molecular mechanisms of chemotherapy resistance in osteosarcoma cells is crucial for developing new therapeutic approaches and ultimately improving the prognosis of osteosarcoma patients. To identify genes associated with cisplatin resistance in osteosarcoma, we screened a large-scale mutant library generated by transfecting human osteosarcoma cells with a piggyBac (PB) transposon-based gene activation vector. Several candidate genes were identified by using Splinkerette-PCR paired with Next Generation Sequencing. We created a disease-free survival predictor model, which includes ZNF720, REEP3, CNNM2, and CGREF1, using TARGET (Therapeutically Applicable Research to Generate Effective Treatments) datasets. Additionally, the results of our enrichment analysis between the Four_genes_high group and Low_group suggested that these four genes may participate in cisplatin resistance in osteosarcoma through cross talk between various signaling pathways, especially the signaling pathway related to bone formation. These data may help guide future studies into chemotherapy for osteosarcoma.
Topics: Child; Humans; Young Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Doxorubicin; Osteosarcoma; Drug Resistance, Neoplasm
PubMed: 36408691
DOI: 10.1002/2211-5463.13524 -
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 -
Indian Journal of Cancer 2020Despite the advances in systemic treatment, about 30%-40% of the patients with extremity osteosarcomas relapse and more than 80% of these relapses localize in the lungs.... (Review)
Review
BACKGROUND
Despite the advances in systemic treatment, about 30%-40% of the patients with extremity osteosarcomas relapse and more than 80% of these relapses localize in the lungs. Our understanding of the management of pulmonary metastases from extremity osteosarcomas is largely based on retrospective data from single institutions or compiled from registries; hence, there is great degree of variability in the reported management of pulmonary metastasis in patients with osteosarcomas.
AIMS AND OBJECTIVES
To analyze the demographic profile, disease characteristics and survival outcomes of patients who had undergone potentially curative pulmonary metastasectomies from extremity osteosarcomas.
MATERIALS AND METHODS
Retrospective analysis of the 37 patients with resectable pulmonary metastasis (both synchronous and metachronous) from osteosarcoma of the extremity, treated from January 1, 2003 to December 31, 2017 at a tertiary regional cancer center in South India.
RESULTS
The median overall survival (OS) of our patient cohort was 38 ± 2.7 months. The 2-, 3-, and 5-year OS were 86 ± 5.8%, 60.8 ± 8.6%, and 20.7 ± 7.4%, respectively. A formal analysis of the various prognostic factors revealed disease-free interval >2 years, completion of the planned systemic chemotherapy, and absence of pulmonary recurrence post-metastasectomy to be significantly influencing the survival outcomes.
CONCLUSION
Our study reiterates the need for consideration of pulmonary metastasectomy in carefully selected patients of extremity osteosarcomas. There is a paucity of data on pulmonary metastasectomies from India and our cohort is possibly the largest series for pulmonary metastasectomies from an osteosarcoma primary. In routine clinical practice, we recommend that the final decision to proceed with pulmonary metastasectomy should ideally be taken by a multidisciplinary tumor board on a case-by-case basis.
Topics: Adult; Bone Neoplasms; Female; Humans; Lung Neoplasms; Male; Metastasectomy; Osteosarcoma; Prospective Studies; Retrospective Studies; Survival Analysis; Young Adult
PubMed: 32445321
DOI: 10.4103/ijc.IJC_497_18