Late Recurrence of Osteosarcoma: A Report of Two Cases

Igarashi, Kentaro; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hiroyuki; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Kimura, Hiroaki; Takeuchi, Akihiko; Miwa, Shinji; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Tsuchiya, Hiroyuki

doi:10.1177/230949901402200329

Cited by 3 publications

(4 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[5][6][7] Current treatment of OS, a combination of surgery and chemotherapy (doxorubicin, methotrexate, and cisplatin), has improved outcomes significantly, although this regime is still only successful in 90% of patients. 8 The precise underlying mechanism of OS remains obscure in most individuals; however, the risk of developing OS is influenced by bone turnover, age, environment (drug or radiation therapy), other bone diseases (such as Paget's disease), genetic alterations and hormonal regulation of puberty (such as growth hormone). [9][10][11][12][13] RNA sequencing (RNA-Seq) technology is a powerful tool to analyze the transcriptome of a cell.…”

Section: Introductionmentioning

confidence: 99%

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

Rothzerg

et al. 2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Alternative splicing of RNA is an essential mechanism that increases proteomic diversity in eukaryotic cells. Aberrant alternative splicing is often associated with various human diseases, including cancer. We conducted whole-transcriptome analysis of 18 osteosarcoma bone samples (paired normal—tumor biopsies). Using RNA-seq, we identified statistically significant (FDR <0.05) 26 differentially expressed transcript variants of leptin receptor overlapping transcript ( LEPROT) gene. Some of the transcripts were overexpressed in normal cells, whereas others were overexpressed in tumor cells. The function of LEPROT is not completely understood. Herein, we highlight a possible association between OS and aberrant alternative splicing events and its interaction with the expression of LEPROT. We also discuss the role of LEPROT in regulating growth hormone and its receptor, and the relationship with initiation and progression of OS. This research study may help to understand the association of alternative splicing mechanism in OS and in tumorigenesis more generally. Further, LEPROT gene can also be considered as a potential biomarker of osteosarcoma. Impact statement Osteosarcoma (OS, also known as osteogenic sarcoma) is the most common primary malignancy of bone in children and adolescents. The molecular mechanisms of OS are extremely complicated and its molecular mediators remain to be elucidated. We sequenced total RNA from 18 OS bone samples (paired normal—tumor biopsies). We found statistically significant (FDR <0.05) 26 differentially expressed transcript variants of LEPROT gene with different expressions in normal and tumor samples. These findings contribute to the understanding of molecular mechanisms of OS development and provide encouragement to pursue further research.

show abstract

Section: Introductionmentioning

confidence: 99%

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

Rothzerg

et al. 2020

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…The median time to the appearance of HO was shorter than the median time to the appearance of LR (8 months [3][4][5][6][7][8][9][10][11][12][13] versus 16 months [11][12][13][14][15][16][17][18][19][20][21]; p < 0.001). The median time to the initial LR of osteosarcoma was reported to be 14 months in an earlier study [20].…”

Section: Features That Allow the Surgeon To Differentiate Ho From Loc...mentioning

confidence: 99%

“…Hence, the presence or absence of pain may also be useful for differentiating HO from LR. Pain in the affected extremity is the most common symptom of primary or recurrent bone tumors [8,24]. According to the evidence, almost 85% of patients with osteosarcoma and 64% of patients with Ewing sarcoma present with symptoms of pain [24].…”

Section: Features That Allow the Surgeon To Differentiate Ho From Loc...mentioning

confidence: 99%

How Can We Differentiate Local Recurrence From Heterotopic Ossification After Resection and Implantation of an Oncologic Knee Prosthesis in Patients with a Bone Sarcoma?

Jamshidi

Bagherifard

Al-Baseesee

et al. 2020

Clin Orthop Relat Res

View full text Add to dashboard Cite

Background Heterotopic ossification (HO) is common after total joint arthroplasty and usually does not cause diagnostic problems. However, the occurrence of HO after oncologic prostheses implantation can be troublesome as it may mimic a locally recurrent tumor. Because this distinction could have a profound impact on the surgeon and patient, it is important to distinguish the two entities; to our knowledge, no study has evaluated this after oncologic endoprosthetic reconstruction around the knee after tumor resection. Questions/purposes (1) How common is the occurrence of HO compared with local recurrence (LR) after resection of bone sarcoma and the use of an oncologic knee prosthesis? (2) Are there any factors associated with the development of HO after limb salvage procedures with an endoprosthesis? (3) What features allow the surgeon to differentiate HO from a locally recurrent tumor in this setting? Methods Between 2002 and 2018, we performed 409 resections of primary bone tumors followed by reconstructions with oncologic endoprostheses. Of these, 17% (71 of 409) died before 2 years and did not have HO at that time, 2% (8 of 409) were lost to follow-up before 2 years, and another 2% (10 of 409) did not have radiographs available at a minimum of 2 years after surgery (and had not developed HO before then), and so could not be analyzed, leaving 320 patients for analysis in this retrospective study. Forty-two patients were excluded; 2% (5 of 320) for a history of failed allograft reconstruction, 3% (8 of 320) for pathologic fracture at presentation, 2% (6 of 320) for inadequate or complicated biopsy, 1% (2 of 320) for stem fractures, 2% (7 of 320) for stem loosening, and 4% (14 of 320) for extracortical bone bridging, leaving 278 patients for final evaluation. Two observers analyzed AP and lateral radiographs for signs of HO at a mean follow-up of 63 ± 33 months after surgery. We defined HO as extraskeletal bone formation in soft tissues. The primary study endpoint was survivorship free from HO, as ascertained by a competing-risks estimator. To identify factors associated with HO appearance, the demographic, radiographic, clinical, pathologic, and surgical characteristics were compared between patients with HO and those who had no lesion. Characteristic features were also compared between patients with HO and those with LR to help their differentiation. Univariate analysis was used for all statistical evaluations. Results HO developed in 8% (21 of 278) of patients in whom oncologic knee prosthesis was implanted. LR developed in 10% (28 of 278) of the patients. According to survivorship estimates, the HO-free survival rate was not different from the LR-free survival rate at 2 years after oncologic knee reconstruction (76 ± 5% [95% CI 63 to 87] versus 74 ± 5% [95% CI 62 to 88]; p = 0.19). History of infection was more common in patients with HO than in patients with no lesion (19% [4 of 21] versus 5% [12 of 229], Odds ratio [OR] 6 [95% CI 2 to 17]; p < 0.001). The male sex was more common in the HO group as well (76% [16 of 21] versus 55% [128 of 229], OR 2 [95% CI 1 to 5]; p = 0.03). The Modular Universal Tumor and Revision System prosthesis was more frequently used in patients with HO (67% [14 of 21]) compared to those with no lesions (40% [92 of 229]; OR 2 [95% CI 1 to 5]; p = 0.02). The lesion border in radiographs was ill-defined in 19% (4 of 21) of patients with HO and 100% (28 of 28) of patients with LR (OR 8 [95% CI 3 to 20]; p < 0.001). The median time to the appearance of HO was shorter than the time to LR (8 months [3 to 13] versus 16 months [11 to 21], [95% CI 10 to 13]; p < 0.001). Pain at presentation was more frequent in patients with LR than in those with HO (86% [24 of 28] versus 14% [3 of 21], OR 36 [95% CI 7 to 181]; p < 0.001). Conclusion HO may occur after the use of oncologic knee prostheses for reconstruction after tumor resection. In most patients, HO could be differentiated from local recurrence through identifying a well-defined border on radiographs. Otherwise, factors such as an earlier time of presentation and absence of pain could suggest an HO, rather than an LR. Level of Evidence Level III, therapeutic study.

show abstract

“…Current treatments of OS include neo-adjuvant chemotherapy with drugs such as doxorubicin, methotrexate, and cisplatin with the aim of reducing tumour size as well as eradicating micro-metastases. Ablative surgery is then followed by further chemotherapy determined by the cell death rate observed in the surgical specimens [7,8]. Current OS therapeutic agents are limited to cytotoxic drugs interfering with transcription and DNA replication [6].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

Rothzerg

et al. 2021

Genes

View full text Add to dashboard Cite

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (RUSC1-AS1, TBX2-AS1, PTOV1-AS1, UBE2D3-AS1, ERCC8-AS1, ZMIZ1-AS1, RNF144A-AS1, RDH10-AS1, TRG-AS1, GSN-AS1, HMGA2-AS1, ZNF528-AS1, OTUD6B-AS1, COX10-AS1 and SLC16A1-AS1) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.

show abstract

Late Recurrence of Osteosarcoma: A Report of Two Cases

Cited by 3 publications

References 26 publications

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma

How Can We Differentiate Local Recurrence From Heterotopic Ossification After Resection and Implantation of an Oncologic Knee Prosthesis in Patients with a Bone Sarcoma?

Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma

Contact Info

Product

Resources

About