Kanji Mori

INSERM, GIP CYCERON, Caen, Basse-Normandie, France

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Publications (29)58.81 Total impact

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    Article: Molecular alterations associated with osteosarcoma development.
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    ABSTRACT: Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases which is the main cause of death. Unfortunately, the conventional chemotherapy is not fully effective on osteosarcoma metastases. The progression of a primary tumor to metastasis requires multiple processes, which are neovascularization, proliferation, invasion, survival in the bloodstream, apoptosis resistance, arrest at a distant organ, and outgrowth in secondary sites. Consequently, recent studies have revealed new insights into the molecular mechanisms of metastasis development. The understanding of the mechanism of molecular alterations can provide the identification of novel therapeutic targets and/or prognostic markers for osteosarcoma treatment to improve the clinical outcome.
    Sarcoma 01/2012; 2012:523432.
  • Article: Spinal glioblastoma multiforme of the conus medullaris with holocordal and intracranial spread in a child: a case report and review of the literature.
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    ABSTRACT: Spinal glioblastoma multiforme (GBM) is a rare clinical entity. According to our review of the literature, only 15 cases of spinal GBM originating from the conus medullaris (CM) have been reported. Furthermore, there has been no case of spinal GBM originating from the CM with holocordal and intracranial involvements, which were already present at the time of initial diagnosis. Despite a variety of treatments, the previous studies have uniformly reported poor results of this lethal condition. The present report illustrates a 10-year-old girl with spinal GBM with rare involvement pattern, that is, the tumor originating from the CM with the holocordal and intracranial involvements, undergoing a novel chemotherapy regimen. A case report and review of literature. Magnetic resonance (MR) imaging with gadolinium enhancement clearly revealed holocordal and intracranial lesions, which were otherwise unidentifiable by plane MR imaging. Open biopsy was performed. After histologic diagnosis, novel chemotherapy regimen, that is, simultaneous high-dose chemotherapy (cyclophosphamide, cisplatin, vincristine, and etoposide) combined with autologous peripheral blood stem cell transplantation (auto-PBSCT), intrathecal injections of both methotrexate and dexamethasone, and radiotherapy, which respected the tolerance threshold of the spinal cord, were performed. Novel chemotherapy regimen achieved marked tumor regression until the 12th month of treatment. The patient became ambulatory with T-shaped canes and has returned to the school life. Unfortunately, the patient died because of the relapse of the tumor 14 months after the initial diagnosis; however, this strategy has achieved longer survival than previously reported mean survival (12 months). The authors advocate enhanced MR imaging of the whole central nervous system for the potential spreading of this disease. This is the first report of simultaneous high-dose chemotherapy combined with auto-PBSCT, intrathecal injections of antineoplastic agents, and radiotherapy for the treatment of spinal GBM, which achieved marked tumor regression. We believe that accumulated experiences in the treatment of this lethal condition might contribute well to improve its therapeutic outcome.
    The spine journal: official journal of the North American Spine Society 12/2011; 12(1):e1-6. · 2.90 Impact Factor
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    Chapter: RANK/RANKL Axis in Melanoma
    06/2011; , ISBN: 978-953-307-291-3
  • Article: Spatiotemporal control of proliferation and differentiation of bone marrow-derived mesenchymal stem cells recruited using collagen hydrogel for repair of articular cartilage defects.
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    ABSTRACT: Articular cartilage has a poor healing capacity, and cartilage regeneration is not always warranted to achieve healing. On the other hand, collagen scaffolds have been shown to support regeneration of articular cartilage defects in animal models, whereas bone morphogenetic protein-2 (BMP-2) is known to cause chondrogenic differentiation of marrow-derived mesenchymal stem cells (MSCs). The purpose of this study was to evaluate the effectiveness of intra-articular administration of BMP-2 into bone marrow-derived MSCs recruited to defects using original collagen hydrogel in rabbits at various time points. Full-thickness defects were created in both knees, then collagen hydrogels were transplanted, and BMP-2 was supplied for 1-week periods, as follows. BMP-2 was administered immediately after the operation for 1 week (BMP0-1 group), and BMP-2 was administered between weeks 1 and 2 after the operation (BMP1-2 group). BMP2 was administered between weeks 2 and 3 (BMP2-3 group). Specimens were then obtained, and bromodeoxyuridine (BrdU)-positive cells were enumerated and histologic grading was also performed. In addition, the gene expression analysis was performed using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Enumeration of BrdU-positive cells showed a significant increase in the BMP0-1 group compared with the other groups. Similarly, histologic scores in the BMP0-1 group were superior for up to 8 weeks. Finally, RT-PCR findings revealed that immediate BMP-2 administration enhanced chondrogenic differentiation.
    Journal of Biomedical Materials Research Part B Applied Biomaterials 06/2011; 98B(2):360-8. · 2.15 Impact Factor
  • Article: Thoracoscopic en bloc extirpation for subperiosteal osteoid osteoma of thoracic vertebral body: a rare variety and its therapeutic consideration.
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    ABSTRACT: Osteoid osteoma is a rare benign osteoblastic tumor. Approximately 10% to 20% of osteoid osteomas occur in the spine with a high trend to involve the posterior components; in turn, vertebral body involvement is uncommon. Osteoid osteoma has been classified into cortical, cancellous, and subperiosteal subtypes according to the localization of the nidus. Subperiosteal osteoid osteoma is extremely rare and has been reported mainly in the femoral neck and small bones of the hands and feet. To the best of our knowledge, subperiosteal osteoid osteoma arising in spine has never been reported previously. To illustrate a rare case of a 23-year-old female with painful scoliosis because of subperiosteal osteoid osteoma of ninth thoracic vertebra that was treated by thoracoscopic intervention. A case report and review of literature. Magnetic resonance imaging revealed the inflammation/edema pattern intensity at right side of both 9th and 10th thoracic vertebrae. Computed tomography demonstrated the round radiolucency surrounded by reactive bone formation (nidus) at the right anterolateral aspect of ninth thoracic vertebra. Taken all findings including anatomical localization of the lesion into consideration, we decided to use thoracoscopic intervention. Improvement of scoliosis was achieved 2 months after surgery. At the time of final follow-up, the patient was free of symptom and there was no clinical and radiologic evidence of recurrence of the tumor 1.5 years postoperatively. Thoracoscopic intervention achieved en bloc extirpation of the nidus after partial removal of the 10th rib head. Thoracoscopic treatment has never been reported as a treatment modality of spinal osteoid osteoma. Within a few hours after the operation, the pain disappeared completely. Histopathological examination revealed that extracted lesion was compatible with osteoid osteoma. The lesion described here demonstrates an extremely rare variety of spinal osteoid osteoma, which was successfully treated by an unprecedented thoracoscopic intervention. This alternative surgical approach enabled en bloc extirpation and effective correction of scoliosis while achieving a cosmetic satisfaction.
    The spine journal: official journal of the North American Spine Society 05/2011; 11(5):e13-8. · 2.90 Impact Factor
  • Article: Mifamurtide for the treatment of nonmetastatic osteosarcoma.
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    ABSTRACT: INTRODUCTION: The standard treatment for osteosarcoma requires both macroscopic surgical wide resection and postoperative multi-drug chemotherapy in neoadjuvant and adjuvant settings. However, the 5-year event-free survival has remained at a plateau of 60-70% of patients with nonmetastatic osteosarcoma for more than 30 years. AREAS COVERED: Mifamurtide (liposomal muramyl tripeptide phosphatidylethanolamine; L-MTP-PE) is a new agent. L-MTP-PE is a nonspecific immunomodulator, which is a synthetic analog of a component of bacterial cell walls. L-MTP-PE activates macrophages and monocytes as a potent activator of immune response in addition to standard chemotherapy. It also improves the overall survival from 70 to 78% and results in a one-third reduction in the risk of death from osteosarcoma. This review summarizes the most recent findings about L-MTP-PE and its therapeutic application for nonmetastatic osteosarcoma. EXPERT OPINION: Recently, L-MTP-PE has been approved in Europe for the treatment of nonmetastatic osteosarcoma with chemotherapy. L-MTP-PE in combination with traditional treatment is expected to go mainstream and to be beneficial for patients with osteosarcoma. Information about potential benefit regarding mifamurtide use in the neoadjuvant setting (i.e., before surgery) and/or usefulness of L-MTP-PE in metastatic in relapsed and metastatic osteosarcoma requires analysis of expanded access and/or future clinical trials of L-MTP-PE in high-burden and low-burden situations.
    Expert Opinion on Pharmacotherapy 02/2011; 12(2):285-92. · 3.20 Impact Factor
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    Article: Balance Between S6K-S6 and 4E-BP1 Depends on ERK Activity in Developing Neurons
    Current Signal Transduction Therapy 01/2011; 6:82-87. · 0.50 Impact Factor
  • Article: Clinical output of the rheumatoid cervical spine in patients with mutilating-type joint involvement: for better activities of daily living and longer survival.
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    ABSTRACT: Retrospective study. To gain an insight for the final clinical output of surgically managed cervical lesions in seropositive rheumatoid arthritis (RA) patients with mutilating-type joint involvement (mutilating-RA patients), these patients was followed up until either death or complete bedridden. There has been no study reporting the final clinical output of surgically managed cervical lesion in mutilating-RA patients. In our previous study, we reported short- to middle-term result of such patient. The present study further traced those patients and reports the final clinical output. Seventeen seropositive mutilating-RA patients extracted from 504 RA patients were enrolled. Eleven patients underwent surgical treatments, whereas six patients did not. All patients, who underwent operation, have received occipitocervical or occipitocervicothoracic fusion. Neck pain, neurological symptoms and ADL score were completely followed up (i.e., follow-up period>10 years). The six patients of non-operated group worsened ADL score and resulted in either complete bedridden or death within 3 years. Contrary, 11 operated patients either improved or maintained ADL until their death. Survival rate in 6.2 years was 0% in non-operated group and 27% in operated group, respectively. The present study suggests that the seropositive mutilating-RA patients worsen cervical lesions once they become affected, and are likely to lose their ADL activity. Once seropositive mutilating-RA patients develop major spinal involvement(s), they are likely to undergo a life-threatening stage of the disease during the next 5-10 years. Surgical intervention is advocated not only to treat the neurological compromise but also to sustain their ADL levels during end stage of disease. The sustained ADL, in turn, may contribute to the longevity of these patients by preventing other major life-threatening events.
    Spine 06/2010; 35(13):1279-84. · 2.08 Impact Factor
  • Article: Chondroitin sulfate for the treatment of hip and knee osteoarthritis: current status and future trends.
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    ABSTRACT: Osteoarthritis (OA) is a common joint disorder and a major socio-economic burden. Chondroitin sulfate (CS), which has chondroprotective properties, is a promising candidate for the therapeutic treatment of OA. Here, we summarize current knowledge as well as future trends of CS for the treatment of hip and knee OA. We retrospectively reviewed pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of CS for the treatment of OA. The safety and tolerability of CS are confirmed. CS is effective, at least in part, for the treatment of OA, and its therapeutic benefits occur through three main mechanisms: 1) stimulation of extracellular matrix production by chondrocytes; 2) suppression of inflammatory mediators; and 3) inhibition of cartilage degeneration. CS is a safe and tolerable therapeutic agent for the management of OA. Its effects include benefits that are not achieved by current medicines and include chondroprotection and the prevention of joint space narrowing. Such positive effects of CS represent a breakthrough in the treatment of hip and knee OA.
    Life sciences 09/2009; 85(13-14):477-83. · 2.56 Impact Factor
  • Article: Serum IgA1 and IgA2 Subclass Antibodies against Collagens in Patients with Ankylosing Spondylitis
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    ABSTRACT: We measured IgAl and IgA2 subclass antibody levels against human type I, II, III and IV collagens in patients with ankylosing spondylitis (AS) by enzyme linked immunosorbent assay (ELISA). Significant elevations of IgAl antibodies against type II collagen (p<0.01) and IgA2 antibodies against type I (p<0.001), III (p<0.001), and IV (p<0.01) collagens were observed in AS patients compared with those of healthy controls. These findings suggest that serum IgA antibodies against type I, III and IV collagens were mainly produced in secretory lesions in AS patients.
    07/2009; 26(5):380-382.
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    Article: Conditioned media from mouse osteosarcoma cells promote MC3T3-E1 cell proliferation using JAKs and PI3-K/Akt signal crosstalk.
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    ABSTRACT: The maintenance of bone mass requires a strict balance between bone formation by osteoblasts and bone resorption by osteoclasts. In tumoral bone environment, tumor cells frequently disturb this balance by interaction with bone cells to create a favorable site for tumor growth, and promote pathological bone changes. Thus, elucidation of the mechanisms underlying interaction between tumor cells and bone cells might eventually lead to a more rational strategy for therapeutic intervention for bone tumors and better understanding of bone biology. In the present study, the effects of mouse osteosarcoma cells on mouse preosteoblastic cells were determined by assessment of cell viability, osteoblastic differentiation and signal transduction pathways. MOS-J/POS-1 conditioned media (CM) significantly induced MC3T3-E1 cell proliferation in a dose-dependent manner and reduced both alkaline phosphatase activity and mineralized nodule formation. Piceatannol, AG490, LY294002 and rapamycin significantly abrogated this up-regulated cell proliferation; however, UO126 and STAT3 inhibitor peptide did not affect this up-regulated cell proliferation. MOS-J/POS-1 CM activated ERK 1/2, STAT3 and Akt signal transduction pathways; however, pro-proliferating signal induced by MOS-J/POS-1 CM was transmitted via Akt not ERK 1/2 and STAT3 pathways. Furthermore, Western blot analyses clearly revealed novel signal crosstalk between JAKs and PI3-K/Akt in osteoblastic cells. The specific factor(s) involved in MOS-J/POS-1 CM-induced MC3T3-E1 cell proliferation that use JAKs/PI3-K/Akt/mTOR pathway remain(s) to be determined. Determination of the specific factor(s) responsible for JAKs and PI3-K/Akt signal crosstalk that results in up-regulated preosteoblast proliferation will offer new insight into the pathology of osteosarcoma as well as other bone-related diseases.
    Cancer Science 11/2008; 99(11):2170-6. · 3.33 Impact Factor
  • Article: Oncostatin M induces bone loss and sensitizes rat osteosarcoma to the antitumor effect of Midostaurin in vivo.
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    ABSTRACT: In cultures, the cytokine oncostatin M (OSM) reduces the growth and induces differentiation of osteoblasts and osteosarcoma cells into glial/osteocytic cells. Moreover, OSM sensitizes these cells to apoptosis driven by various death inducers such as the kinase inhibitor staurosporine. Here, we asked whether OSM would have similar effects in vivo. Adenoviral gene transfer of OSM (AdOSM) was done in naive and osteosarcoma-bearing rats, alone or in combination with Midostaurin (PKC412), a derivative of staurosporine currently used in cancer clinical trials. Bone variables were analyzed by micro-computed tomography scanner, by histology, and by the levels of various serum bone markers. Osteosarcoma progression was analyzed by the development of the primary bone tumor, evolution of pulmonary metastasis, histology (necrosis and fibrosis), and animal survival. In naive rats, AdOSM reduced serum osteoblastic and osteoclastic markers in correlation with a reduced trabecular bone volume. In an osteosarcoma rat model, the combination of AdOSM with PKC412 reduced the progression of the primary bone tumor, pulmonary metastatic dissemination, and increased overall survival, whereas these agents alone had no antitumor effect. Increased tumor necrosis and tissue repair (fibrosis) were observed with this combination. These in vivo experiments confirm that systemic OSM overexpression alters osteoblast/osteosarcoma activity. Because OSM sensitizes rat osteosarcoma to apoptosis/necrosis, the use of kinase inhibitors such as Midostaurin in association with OSM could represent new adjuvant treatments for this aggressive malignancy.
    Clinical Cancer Research 10/2008; 14(17):5400-9. · 7.74 Impact Factor
  • Article: RANKL/RANK/OPG: key therapeutic target in bone oncology.
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    ABSTRACT: Cancer is one of the major leading causes of death all over the world. Primary and secondary bone tumors can significantly deteriorate the quality of life (QOL) and the activity of daily living (ADL) of the patients. These unwelcome diseases become a social and economic burden seriously. Thus, more effective therapies for both primary and secondary bone tumors are actually required. Bone homeostasis depends on the strictly balanced activities between bone formation by osteoblasts and bone resorption by osteoclasts. Imbalance of bone formation and resorption results in various bone diseases. Both primary and secondary bone tumors develop in the unique environment bone, it is therefore necessary to understand bone cell biology in tumoral bone environment. Recent findings strongly revealed the significant involvement of the receptor activator of nuclear factor kappaB ligand (RANKL)/RANK/osteoprotegerin (OPG) triad, the key regulators of bone remodeling in bone oncology. Indeed, RANKL/RANK blocking successfully prevented the development of bone metastases. Furthermore, some cancer cells express RANK which is involved in tumor cell migration. Thus, the regulation of this triad will be a rational, encouraged therapeutic hot spot in bone oncology. In this review, we summarize the accumulating knowledge of the RANKL/RANK/OPG triad and discuss about its therapeutic capability in primary and secondary bone tumors.
    Current Drug Discovery Technologies 09/2008; 5(3):263-8.
  • Article: Liposomal muramyl tripeptide phosphatidyl ethanolamine: a safe and effective agent against osteosarcoma pulmonary metastases.
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    ABSTRACT: Osteosarcoma is the most common form of primary malignant bone tumor. The use of chemotherapy drugs with many side effects, including high-dose methotrexate, doxorubicin, cisplatin and ifosfamide, has greatly improved osteosarcoma survival compared with surgery alone. However, for 20 years, overall survival remained at a plateau of 60-70% in nonmetastatic disease and 20-30% in metastatic osteosarcoma owing to lung metastases. Liposomal muramyl tripeptide phosphatidyl ethanolamine (L-MTP-PE) is a new agent that improves overall osteosarcoma survival (chemotherapy without L-MTP-PE 70% versus with L-MTP-PE 78%; p = 0.03). L-MTP-PE offers additional benefit for osteosarcoma treatment in combination with chemotherapy, particularly ifosfamide-containing regimens. Clinical experience indicates that side effects such as fever are temporary and controlled or prevented with ibuprofen and/or acetoaminophen premedication; severe side effects are rare. Although surgery will remain the main approach for osteosarcoma treatment of lung metastases, L-MTP-PE combined with other modalities, including chemotherapy, appears to be of benefit in these patients as well.
    Expert Review of Anti-infective Therapy 03/2008; 8(2):151-9. · 2.65 Impact Factor
  • Article: Association of the MSX2 gene polymorphisms with ankylosing spondylitis in Japanese.
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    ABSTRACT: Several genes have been implicated in the etiology of ankylosing spondylitis (AS); however, the significance of these genes except HLA-B27 remains to be elucidated. In this study, we examined the association of AS with novel candidate genes and previously reported genes other than HLA-B27. We examined a total of 45 single nucleotide polymorphisms (SNPs) in 15 genes by a sequential screening. We first genotyped 170 Japanese AS patients and 896 controls for the SNPs (first screen). Then, we genotyped eight SNPs with P < 0.05 in the first screen for 108 additional Japanese patients (second screen). We checked the replication of the association of the most significant SNP by genotyping 219 Taiwanese AS patients and 185 controls. When the first and second screens were combined, four SNPs showed nominal significance of P < 0.05. An intronic SNP (IVS1 + 996G > A) in MSX2, a novel candidate gene, showed the most significant association (P = 0.0030). The association was not replicated in our Taiwanese population; however, there was the same trend with the Japanese population in the allelic frequency distribution of the SNP. In the genes previously reported to have association with AS, only one synonymous SNP, c.963T > G in ANKH, showed a marginal association in the Japanese population (P = 0.045).
    Journal of Human Genetics 02/2008; 53(5):419-24. · 2.57 Impact Factor
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    Article: Receptor activator of nuclear factor-kappaB ligand (RANKL) directly modulates the gene expression profile of RANK-positive Saos-2 human osteosarcoma cells.
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    ABSTRACT: Receptor activator of nuclear factor kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) are the key regulators of bone metabolism. Recent findings demonstrated a crucial role of RANK in several bone-associated tumors. Indeed, we have recently demonstrated functional RANK expression both in a mouse and several human osteosarcoma cell lines. However, RANKL effects on osteosarcoma cells remain to be determined. In this study, we determined RANKL effects on RANK-positive Saos-2 human osteosarcoma cells. cDNA microarray and quantitative RT-PCR analyses clearly demonstrated that RANK-positive osteosarcoma cells were the target of RANKL as well as osteoclasts/osteoclast precursors. Thus, we present for the first time that RANKL can directly and significantly modulate gene expression of RANK-expressing Saos-2 cells. RANKL-modulated genes included genes that were implicated in protein metabolism, nucleic acid metabolism, intracellular transport, cytoskeleton organization and biogenesis, apoptosis and signaling cascade. Our results strengthen the involvement of the RANK/RANKL/OPG axis in osteosarcoma biology and capability to identify novel therapeutic approaches targeting RANK-positive osteosarcomas.
    Oncology Reports 01/2008; 18(6):1365-71. · 1.84 Impact Factor
  • Article: A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.
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    ABSTRACT: Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the chi (2) test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.
    Human Genetics 08/2006; 119(6):611-6. · 5.07 Impact Factor
  • Article: Osteosarcoma: current status of immunotherapy and future trends (Review).
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    ABSTRACT: 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.
    Oncology Reports 04/2006; 15(3):693-700. · 1.84 Impact Factor
  • Article: RANKL directly induces bone morphogenetic protein-2 expression in RANK-expressing POS-1 osteosarcoma cells.
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    ABSTRACT: The POS-1 murine model of osteolytic osteosarcoma was used to elucidate the molecular and cellular mechanisms involved in the development of primary bone tumors and associated lung metastasis. The POS-1 cell line is derived from an osteosarcoma tumor which develops spontaneously in C3H mice. The POS-1 cell line was characterized in vitro by mineralization capacity and expression of bone markers by semi-quantitative RT-PCR, compared to primary osteoblasts and bone marrow cells. POS-1 cells showed no mineralization capacity and exhibited an undifferentiated phenotype, expressing both osteoblastic and unexpected osteoclastic markers (TRAP, cathepsin K and RANK). Thereby, experiments were performed to determine whether RANK was functional, by studying the biological activity of murine RANKL through the receptor RANK expressed on POS-1 cells. Results revealed a RANKL-induced increase in ERK phosphorylation, as well as BMP-2 induction at the mRNA and protein levels, and a decrease of POS-1 cell proliferation in the presence of 10 ng/ml RANKL. BMP-2 induction is dependent on the ERK 1/2 signal transduction pathway, as its expression is abolished in the presence of UO126, a specific synthetic inhibitor of the ERK 1/2 pathway. Moreover, a 2-fold molar excess of soluble RANK blocks the RANKL-induced BMP-2 expression, demonstrating that the biological effects of RANKL observed in POS-1 cells are mediated by RANK. This is the first report describing a functional RANK expressed on osteosarcoma cells, as shown by its ability to induce signal transduction pathways and biological activity when stimulated by RANKL.
    International Journal of Oncology 02/2006; 28(1):261-9. · 2.40 Impact Factor
  • Article: Evaluation of standard nucleotomy for lumbar disc herniation using the Love method: results of follow-up studies after more than 10 years.
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    ABSTRACT: A retrospective analysis of long-term follow-up results more than 10 years after a standard nucleotomy for lumbar disc herniation with the Love method was done to determine the effectiveness of this procedure. Nucleotomy according to Love was the standard treatment for lumbar disc herniation before the various minimally invasive alternatives were recently introduced. Without long-term follow-up analysis of Love operations, evidence-based evaluation of those new methods is impossible. We believe that the standard nucleotomy procedure should now be evaluated precisely. In this study we present a comparison of 1-year follow-up results to the results more than 10 years after lumbar nucleotomy. Seventy-six consecutive patients who had undergone lumbar nucleotomy were identified. It was possible to assess 54 (71.1%) of the cases more than 10 years after surgery. The initial and final outcomes were assessed using the MacNab classification and the Japanese Orthopaedic Association (JOA) score. With the MacNab classification a successful outcome 1 year after surgery was achieved in 87.0% of the cases. At the final follow-up, this result was reduced to 74.1%. Seven patients required a second operation and patients under 21 years of age were at risk for reoperation. Patient overall satisfaction with the results of the standard nucleotomy was high. The disc height of the operation site significantly decreased after surgery; nevertheless, this did not affect the clinical outcome. A standard lumbar nucleotomy according to Love is a safe and reliable method of treating selected patients with lumbar disc herniations.
    European Spine Journal 12/2004; 13(7):626-30. · 1.97 Impact Factor