High-grade Malignant Bone Tumor Research Articles

Periosteal preservation: a new technique in resection of bone high-grade malignant tumors in children—about eleven cases

ObjectiveThe purpose of this study was to describe a surgical technique of bone resection with periosteal preservation and reconstruction in patients with high-grade bone malignant tumors and to determine its effect on local recurrences, and time and quality of bone union in bone autografting reconstruction.Patients and methodsWe retrospectively reviewed 11 cases of high-grade malignant bone tumors in children aged 4 to 16 years, who were treated with chemotherapy and tumor resection while preserving partially the adjacent periosteum. Tumors were located in the lower limb in eight cases; three tumors were in the humerus. The mean length of the bone defect after resection was 15.8 cm (range, 6–34.5 cm). Reconstruction was provided by non-vascularized autograft in eight cases (lower limb) and polymethyl methacrylate spacer in three cases (upper limb). Patients were followed up for a mean of 71 months.ResultsAt the last follow-up, no patients had local recurrence. Three patients were dead because of metastasis. Bone union was good in time and quality in all children who had bone autografting. In cases of PMMA reconstruction, there was periosteal bone formation around the spacer. According to the MSTS functional score, patients with lower limb localizations had a mean score of 27.75 points and patients with upper limb localizations had a score of 24/30.ConclusionPreservation of the periosteum in bone resection for malignant tumors could be a good adjuvant alternative for bone reconstruction, without increasing the risk of local recurrence. However, patients must be carefully selected.

MiR-877-3p inhibits tumor growth and angiogenesis of osteosarcoma through fibroblast growth factor 2 signaling

ABSTRACT Osteosarcoma (OS) is the most common high-grade malignant bone tumor in teenagers. MicroRNAs can function as posttranscriptional regulators of gene expression, playing critical roles in cancer dev-877-3p in OS. Quantitative real-time RT-PCR was carried out for detecting miR-877-3p expression in OS. The effects of miR-877-3p on proliferation was analyzed via MTT, colony formation, and flow cytometry assays. Angiogenesis of endothelial cells were investigated by wound healing and tube formation assay. Gene profiling based on PCR array and luciferase reporter assay were conducted to determine target genes of miR-877-3p. In-vivo study was used to determine the effects of miR-877-3p on the tumor growth. The expression of miR-877-3p was markedly downregulated in OS tissues and cell lines. Low expression of miR-877-3p predicts poor prognosis of OS patients. miR-877-3p overexpression was found to inhibit the proliferation of OS cell lines. The angiogenesis assays showed that miR-877-3p attenuated the angiogenesis. Further mechanism studies showed that miR-877-3p can reduce (Fibroblast Growth Factor 2) FGF2 expression in OS cells by binding to the 3’UTR end of FGF2. Moreover, increased expression of miR-877-3p was responsible for the inhibition of tumor growth and angiogenesis. Taken together, our findings indicated that miR-877-3p might exhibit tumor suppressive role by targeting FGF2 signaling, which may serve as potential target for OS.

MULTIMODALITY THERAPY FOR OSTEOSARCOMA OF THE STERNUM WITH RECONSTRUCTION OF COMPLEX CHEST WALL DEFECTS

Background. Osteosarcoma is a high-grade malignant bone tumor that accounts for up to 6 % of all bone neoplasms. There are only a few published cases of primary sternal osteosarcomas, reflecting the rarity of these tumors. Recently, there has been a growing interest in performing radical excisions of chest wall tumors followed by combined single-stage reconstruction of the rib cage with implants made of biologically compatible materials. Material and methods. We present the case of a 49-year-old woman diagnosed with osteosarcoma of the sternum. The patient received a combined modality treatment including chemotherapy, radiotherapy and surgery. Titanium nickelid implants were used for the reconstruction of chest wall defects. Results. The multimodality treatment with reconstruction of postoperative chest wall defects allowed the achievement of the optimal quality of life for 21 months in the patient with very poor prognosis. Conclusion. The chest wall reconstruction using biocompatible materials from titanium nickelid appeared to be an effective and safe technique for the treatment of chest wall tumors.

Evaluation of Clinical Results and Complications of Structural Allograft Reconstruction after Bone Tumor Surgery.

Massive bone allograft is an option in cases of limb preservation and reconstruction after massive benign and malignant bone tumor resection. The purpose of this study was to analyze the outcome of these procedures at Imam Reza Hospital, Mashhad University of Medical Sciences. In this study, 113 cases have been presented. Eleven cases were excluded (patients has a traumatic defect or they passed away before the completion of the study's two-year follow up period). Each patient completed a questionnaire, went through a physical examination and, if indicated, X-ray information was collected. The patients were divided into three groups: chemotherapy, chemotherapy plus radiation therapy, and no-adjuvant-therapy. Fifty-four cases were male and the mean age was 24.5±5.39. The number of cases and indications for surgery were: 33 cases of aggressive benign tumors or low grade malignant bone tumors (large bone defects) including 16 germ cell tumors, eight aneurysmal bone cysts, five low grade osteosarcomas, and four chondrosarcomas. Another 69 cases were high-grade malignant bone tumors including 42 osteosarcomas, 21 Ewing's sarcoma, and six other high grade osteosarcomas. Patients were divided into three groups: the first group received no adjuvant therapy, the second group received chemotherapy, and the third group received chemotherapy plus radiotherapy. The location of tumors were as follows: eight cases in the pelvic bone, 12 in the proximal femur, 18 in the femoral shaft, 36 in the distal femur, 12 in the proximal tibia, and 16 in the humeral bone. The 12 cases of proximal femoral defects were reconstructed by allograft composite prosthesis, 18 diaphyseal defects with intercalary allograft, and 36 distal femoral defects were reconstructed using osteoarticular allograft. The rate of deep infection was 7:8% (eight patients) and in this regard, we found a significant difference among the three groups, such that most cases of infection occurred in the adjuvant chemotherapy plus radiation therapy group. Allograft fracture occurred in six patients and prevalence was the same in all groups. Only in six cases of radio-chemotherapy nonunion occurred, so we used autogenous bone graft for union. Local recurrence was observed in six patients: three belonged to the adjuvant chemotherapy group and the other three were in the chemo-radiotherapy group; no significant difference was observed between these two groups. However, there was a significant difference between these two and the group that received no adjuvant therapy. Also, there were 11 cases of metastases and Restriction of knee joint motion occurred in 48 cases of osteo-cartilaginous grafts of the distal femur and proximal tibia. Although structural allograft is an appropriate choice in limb reconstruction after massive resection of involved tissues in malignant and invasive bone tumors, the risk of complications such as nonunion and infection in massive allograft increases in cases of adjuvant (chemotherapy and radiotherapy) modalities of treatment. Whereas the rate of tumor recurrence, metastasis, and restrictions in range of motion during a short term follow up after implantation showed no significant difference among the evaluated groups. Consequently, further attention and constant periodic visits of the patients and checking for local recurrence and distant metastasis should be done after surgery.

Triazine-modified dendrimer for efficient TRAIL gene therapy in osteosarcoma

Osteosarcoma is a high-grade malignant bone tumor that usually develops in the teenagers. Despite improvement in therapy, the five-year survival rate is poor for patients not responding to treatment or with metastases. Tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL) gene therapy is a new strategy in the treatment of cancers, however, the lack of efficient and low toxic vectors remains the major obstacle in TRAIL gene therapy. In this study, a triazine-modified dendrimer G5-DAT66 was synthesized and used as a vector for TRAIL gene therapy in vitro and in vivo. The material shows much higher transfection efficacy on osteosarcoma MG-63 cell line than commercial transfection reagents such as Lipofectamine 2000 and SuperFect. It effectively induces apoptosis in MG-63 cells and three-dimensional MG-63 cell cultures when delivering a TRAIL plasmid. In vivo studies further prove that G5-DAT66 efficiently transfects TRAIL plasmid in tumors and inhibits tumor growth in osteosarcoma-bearing mice. These results suggest that triazine-modified dendrimer has promising potential for TRAIL gene therapy in osteosarcoma.

Nuclear ING2 expression is reduced in osteosarcoma.

Osteosarcoma is a high-grade malignant bone tumor. Loss of inhibitor of growth2 (ING2) expression has been demonstrated in numerous types of cancers. However, no study has shown the relationship between ING2 expression and osteosarcoma. In the present study, we confirmed that the levels of ING2 mRNA and protein were lower in cancer tissues than these levels in normal tissues. Loss of nuclear ING2 protein was significantly associated with a decreased survival time of patients. Osteosarcoma cells were transfected with ING2 protein without a nuclear localization signal or intact ING2 protein to examine the effects of exogenous expression of ING2 invitro. Compared to the control cells, intact ING2-expressing cells exhibited increased apoptosis, G1 phase arrest and senescence. Taken together, these results suggest that ING2 acts as a tumor suppressor in osteosarcoma.

Bone–Prosthesis Composite with Rotating Hinged-Knee Prosthesis in Limb Salvage Surgery for High-Grade Sarcoma Around the Knee

Bone prosthesis composite (BPC) had been widely-used in reconstruction after wide excision of malignant tumors around the knee. However, implant selection for BPC remains a dilemma. Forty-one patients with high-grade malignant bone tumors around the knee who underwent excision and reconstruction with BPC and rotating hinged knee (RHK) prosthesis were included. The mean follow-up time was 54months (range, 31–78months). The average Musculoskeletal Tumor Society Rating score was 93.4% (range, 73–100%). The mean range of motion was 125°. Complications included 2 local recurrences, 2 nonunions, and 1 peri-prosthetic fracture. The reconstruction with BPC using the RHK prosthesis provided consistently good functional results with a low complication rate. The RHK prosthesis is a promising choice for BPC reconstruction.

Pterostilbene exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/STAT3 signaling pathway

Osteosarcoma is a high-grade malignant bone tumor. Pterostilbene (PTE) is a natural, dimethylated analog of resveratrol with higher bioavailability. While PTE has been shown to have potent antitumor activity against various types of cancer, the molecular mechanisms underlying the effects of PTE remain largely unknown. The Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling pathway plays a crucial role in tumorigenesis and immune development. In this study, we assessed the antitumor activity of PTE against human osteosarcoma cells and explored the role of JAK2/STAT3 and apoptosis-related signaling pathways on the activity of PTE. PTE treatment resulted in a dose- and time-dependent inhibition of osteosarcoma cell viability. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration and mitochondrial membrane potential (MMP) but also by increases in the apoptotic index, reactive oxygen species (ROS) and several biochemical parameters. Furthermore, PTE treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of STAT3. PTE also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. PTE, used in combination with a known JAK2/STAT3 inhibitor, AG490, further decreased the viability of osteosarcoma cells. Taken together, PTE is a potent inhibitor of osteosarcoma cell growth that targets the JAK2/STAT3 signaling pathway. These data suggest that inhibition of JAK2/STAT3 signaling is a novel mechanism of action for PTE during therapeutic intervention in osteosarcoma cancers.

Degraded Iota-Carrageenan Can Induce Apoptosis in Human Osteosarcoma Cells Via the Wnt/β-Catenin Signaling Pathway

Osteosarcoma (OS) is a high-grade malignant bone tumor. Therefore, using both in vitro and in vivo assays, the effects of degraded iota-Carrageenan (ι-CGN) on a human osteosarcoma cell line, HOS, were examined. Degraded ι-CGN was observed to induce apoptosis and G1 phase arrest in HOS cells. Moreover, degraded ι-CGN suppressed tumor growth in established xenograft tumor models. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumors treated with native ι-CGN or PBS. In addition, the formation of intratumoral microvessels was inhibited following treatment with degraded ι-CGN. In Western blot assays, degraded ι-CGN was found to inhibit the Wnt/β-catenin signaling pathway. Overall, these studies demonstrate the antitumor activity of degraded ι-CGN toward the OS cell line, HOS. Moreover, valuable insight into the mechanisms mediated by degraded ι-CGN was obtained, potentially leading to the identification of novel treatments for OS. However, additional studies are needed to confirm these results in other cell types, particularly in human umbilical vein endothelial cells.

Up-Regulation of Imp3 Confers In Vivo Tumorigenicity on Murine Osteosarcoma Cells

Osteosarcoma is a high-grade malignant bone tumor that manifests ingravescent clinical behavior. The intrinsic events that confer malignant properties on osteosarcoma cells have remained unclear, however. We previously established two lines of mouse osteosarcoma cells: AX cells, which are able to form tumors in syngeneic mice, and AXT cells, which were derived from such tumors and acquired an increased tumorigenic capacity during tumor development. We have now identified Igf2 mRNA-binding protein3 (Imp3) as a key molecule responsible for this increased tumorigenicity of AXT cells in vivo. Imp3 is consistently up-regulated in tumors formed by AX cells, and its expression in these cells was found to confer malignant properties such as anchorage-independent growth, loss of contact inhibition, and escape from anoikis in vitro. The expression level of Imp3 also appeared directly related to tumorigenic ability in vivo which is the critical determination for tumor-initiating cells. The effect of Imp3 on tumorigenicity of osteosarcoma cells did not appear to be mediated through Igf2-dependent mechanism. Our results implicate Imp3 as a key regulator of stem-like tumorigenic characteristics in osteosarcoma cells and as a potential therapeutic target for this malignancy.

The anti-tumor role and mechanism of integrated and truncated PDCD5 proteins in osteosarcoma cells

Osteosarcoma (OS) is a high-grade malignant bone tumor. In these studies, the cell apoptosis-related gene, programmed cell death 5 gene (PDCD5), and various fragments of it, were overexpressed in the OS cell line, MG-63. The effects of PDCD5 on MG-63 cells both in vivo and in vitro were then identified. Our results indicate that PDCD5 can induce apoptosis and G2 phase arrest in MG-63 cells. Moreover, expression of PDCD5 in established xenografted tumors was associated with a decrease in tumor size and weight. Accordingly, the survival rate of these mice was significantly higher than that of mice bearing tumors that did not express PDCD5. To analyze the signaling pathway involved, western blotting was performed. In these assays, PDCD5 was found to inhibit the Ras/Raf/MEK/ERK signaling pathway, leading to inhibition of cyclin B and CDK1. In addition, down-regulation of ERK resulted in activation of caspase 3 and caspase 9. These results are consistent with the G2 phase arrest observed with overexpression of PDCD5. However, a G1 phase arrest was not observed. Therefore, proteins associated with the G1 phase of the cell cycle were overexpressed in combination with PDCD5 overexpression. Overall, these studies demonstrate the anti-tumor activity of PDCD5 in the OS cell line, MG-63, and provide insight into relevant mechanisms that may lead to novel treatments for OS.

Osteosarcoma in a Patient with Neurofibromatosis Type 1: A Case Report and Review of the Literature

Neurofibromatosis type 1 (NF1) or von Recklinghausen's disease is a genetic disease generally characterized by café-au-lait spots and neurofibromas. Malignant tumors of the nervous system, such as malignant schwannomas, gliomas, or astrocytomas, have been well known to coexist with neurofibromatosis. However, occurrence of malignant tumors unrelated to the nervous system is rare. We report an unusual case of a 29-year-old NF1 female suffering from malignant peripheral nerve sheath tumor (MPNST) that eventually developed osteosarcoma in the proximal femur. Osteosarcoma is the most common high-grade malignant bone tumor in which the neoplastic cells produce osteoid. At 23 and 24 years old, she underwent excision of MPNST in the left posterior thigh. No osteosarcomatous portion was identified in these specimens. The patient underwent postoperative chemotherapy. At 29, left proximal thigh pain and swelling appeared. Computed tomography demonstrated cortical bone destruction in the left proximal femur where MPNST occurred. Magnetic resonance imaging revealed extraskeletal growth of the tumor. Bone scintigraphy demonstrated increased uptake in the left proximal femur. Hip disarticulation was performed. The removed tumor was composed of highly anaplastic cells. Lace-like irregular osteoid formation was observed among the tumor cells. MPNST component was totally absent. The tumor was diagnosed as osteoblastic type osteosarcoma. Two months after disarticulation the patient died of bilateral pulmonary metastasis. The correlation between the histogenesis of osteosarcoma and the genetic abnormality in NF1 patients has not been elucidated, but the finding of osteosarcomatous transformation in this case suggests the divergent cellular differentiation to mesenchymal malignant tumors of neuroectodermal tissue in NF1 patients.

Rotationplasty--quality of life after 10 years in 22 patients.

We assessed the long-term results in 22 patients with rotationplasty after resection of high-grade malignant bone tumors. We used established methods (QLQ-C 30; FLZ) to evaluate the quality of life, diplomas, life-contentment, occupational situation and marriage status. After 10-year follow-up, we found no reduction in psychosocial adaptation, and life contentment was about the same as in healthy persons. We therefore recommend rotationplasty instead of amputation whenever conventional limb salvage is impossible.

Surgical treatment of pelvic sarcomas: oncologic and functional outcome.

The experiences in treating 93 consecutive patients (56 males, 37 females; mean age, 38.5 years; range, 4-69 years), including 76 patients with primary malignant bone tumors and 17 patients with soft tissue sarcomas involving the innominate bone, are reported. Oncologic and functional results were investigated in relation to the tumor stage, to the achieved surgical margin, and to the surgical procedure (hemipelvectomy, internal hemipelvectomy and endoprosthetic replacement, and continuity resection). The mean followup was 48 months (range, 8-222 months). The 5-year survival was 86% in patients with low-grade malignant bone tumors, 42% in patients with high-grade malignant bone tumors, and 25% in patients with high-grade soft tissue sarcomas. Survival was influenced by the grade of malignancy, the tumor stage, and the achieved surgical margins. Forty-six patients who survived were examined an average of 36 months after primary surgery. Excellent and good functional results were seen in 82% of patients who underwent continuity resection and in 55.5% of patients who underwent partial or total internal hemipelvectomy. All patients who survived hemipelvectomy had poor functional results. Surgical treatment of pelvic sarcomas is an extensive procedure with a considerable incidence of complications. It requires the knowledge of different techniques of resection and reconstruction of bone, joints, soft tissue, and intrapelvic organs.

Constrained Total Shoulder Arthroplasty for Patients with High Grade Malignant Bone Tumor of Humerus

Constrained Total Shoulder Arthroplasty for Patients with High Grade Malignant Bone Tumor of Humerus