Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human osteosarcoma cell line, MG63, responds both to GM-CSF and to G-CSF in vitro. To assess the significance of these observations to tumor growth in vivo, MG63 cells were engineered by retroviral infection to produce human GM-CSF or G-CSF. These retrovirally infected cells become autostimulatory as measured by increased [3H]-thymidine incorporation (3- to 7-fold) and anchorage-independent colony formation (7- to 10-fold) as compared with uninfected MG63 cells or cells infected with control (neor) retrovirus. The increased proliferation induced by exogenous GM-CSF or G-CSF on uninfected MG63 cells in both assays could be completely inhibited by anti-GM-CSF or anti-G-CSF antibodies, while the same antibodies only partially abrogated proliferation by the growth-factor-producing cells. None of 34 nude or SCID mice developed tumors when injected s.c. with uninfected or neor-virus-infected cells. In contrast, all 30 mice injected with GM-CSF- or G-CSF-producing MG63 cells developed tumors which were G418-resistant and factor-producing. Tumor cell DNA showed a polyclonal retroviral integration pattern indistinguishable from that in the DNA of cells injected into mice. Tumors that formed following injection of a mixture of G418-resistant, GM-CSF-producing cells and cells infected with virus containing only the hygror gene contained hygromycin-resistant cells in the same proportion as was present in the original cell mixture. These data indicate that GM-CSF and G-CSF can support the growth of an osteosarcoma cell line both in vitro and in vivo whether the factor is supplied by autocrine production or from exogenous sources.
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PMID:The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro and in vivo. 750 89

Between January 1993 and December 1996, 21 children with advanced solid tumors were entered in a dose-escalating study of high-dose sequential chemotherapy followed by autologous stem cell transplantation. The diagnoses included neuroblastoma (NB) for 13 patients; Ewing's sarcoma (ES) for six patients and osteosarcoma for two patients. Nine patients received therapy as consolidation for primary metastatic disease, and 12 patients had had previous relapses. Treatment consisted of CY given i.v. at a dose of 7 g/m2 on day 1, followed by G-CSF until myeloid recovery. After 3 weeks of rest, all patients were given thiotepa i.v. on days 22-24. The total dose of thiotepa was 450 mg/m2 in three patients, 600 mg/m2 in six patients, and 750 mg/m2 in 12 patients. Melphalan was given i.v. at a dose of 180 mg/m2 i.v. on day 27 followed by stem cell infusion on day 28. Major toxic reactions included stomatitis, esophagitis, diarrhea and dermatitis. Three patients died of treatment-related complications. Twelve patients have had a relapse. Six patients (five with NB and one with ES) are alive in continuous remission 5-50 months (median 36) after transplantation. The results of this study show that it is feasible to administer high-dose sequential chemotherapy to children with advanced solid tumors.
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PMID:High-dose sequential chemotherapy and autologous stem cell reinfusion in advanced pediatric solid tumors. 946 76

An Italian-Scandinavian treatment and research protocol with high-dose chemotherapy and double peripheral blood stem cell (PBSC) transplantation has been designed in an attempt to improve overall results of children with metastatic osteosarcoma (OST). Six patients, aged 12-17 years, underwent PBSC mobilization with CY 4 g/m2 and VP-16 600 mg/m2 followed by G-CSF (n = 4 with recurrent disease) or ifosfamide 15 g/m2 plus G-CSF (n = 2 with synchronous metastases). The target dose of CD34+ cells for two transplant procedures was 8 x 10(6)/kg or more; conditioning regimen for both the grafts consisted of carboplatin 375 mg/m2/day for 4 days and VP16 450 mg/m2/day for 4 days. The first transplant was planned 2-4 weeks after the mobilization, the second transplant 4-6 weeks after the first graft. In three patients a single course of CY-VP16 mobilised a total number of CD34+ sufficient for two transplants; in the patient who did not obtain the target dose of CD34+ cells a bone marrow harvest was added. In the two other children high-dose ifosfamide failed to achieve the required CD34+ number: one patient underwent a single transplant procedure, one patient was successfully mobilized with doxorubicin 90 mg/m2 plus G-CSF. Patients underwent a median of two collections (range 2-4). Leukapheresis resulted in the collection of a median of 8.9 CD34+ cells/kg (range 1.3-14.8). The median time to granulocyte count recovery to more than 0.5 x 10(9)/l was 10 days (range 9-14 days) after the first graft and 11 days (range 10-12 days) after the second graft, respectively. Platelets recovered to 50 x 10(9)/l at a median of 11 (range 10-30 days) and 13 days (range 10-28) respectively after the first and the second graft. Conditioning regimen was well tolerated in all patients with mild extra haematological toxicity, also following the second transplant. Two patients grafted with metastases at diagnosis are alive and disease free 3 and 7 months from the transplant. One of the four patients transplanted for recurrent disease developed pulmonary metastases 2 months after the procedure; one patient is alive with significant reduction of tumor mass 1 month after the first transplant, one patient is alive without evidence of disease 9 months from the second transplant and one after a complete metastasectomy (tumor necrosis >90%) which followed the second transplant. With the limits of the small number of cases and the short follow-up, these preliminary results show that this approach may be promising for the treatment of patients with metastatic OST who currently are not cured by conventional-dose regimens.
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PMID:Feasibility of high-dose chemotherapy and autologous peripheral blood stem cell transplantation in children with high grade osteosarcoma. 998 88

Permanent human osteosarcoma cell lines are important tools for the study of bone cancer. As representative of an osteoblastic phenotype, they partly reflect their normal osteoblastic counterparts and, thus, may represent appropriate models to investigate the mechanisms involved in bone remodelling and in haematopoietic differentiation. In the present work, we describe a new human cell line, CAL 72, obtained from an osteosarcoma of the knee of a 10-year-old boy. These cells grow in continuous culture, and karyotypic analysis has revealed clonal abnormalities in number and structure, especially loss of chromosome Y. These cells exhibit morphological, immuno-histochemical and molecular characteristics of the osteoblastic lineage. Using RT-PCR, we have shown that the CAL 72 cell line expresses high levels of mRNA coding for several cytokines, such as G-CSF, GM-CSF, IL-1beta and IL-6. In view of this expression profile, the CAL 72 phenotype appears to be closer to normal primary osteoblasts than other reported osteosarcomas. Moreover, these cells express mRNA for both HGF and its receptor c-MET, suggesting that this autocrine loop might contribute to the invasiveness of the tumour from which CAL 72 originated.
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PMID:Establishment, characterisation and partial cytokine expression profile of a new human osteosarcoma cell line (CAL 72). 1038 64

The introduction of aggressive chemotherapy in the treatment of osteosarcoma has improved the long-term outcome for these patients. With the increasing aggressiveness of chemotherapy protocols, hematopoietic growth factors have emerged as useful adjuncts involving, in some cases, rescue by peripheral blood stem cell (PBSC) infusion to assist faster recovery and maintain relative dose intensity. To evaluate the number of PBSCs needed, we analyzed the number of CD34+ cells and hematopoietic progenitor cells in the peripheral blood of 16 patients with osteoblastic, condroblastic and fibroblastic osteosarcoma enrolled in an Istituto Ortopedico Rizzoli-Scandinavian Sarcoma Group (IOR-SSG) pilot study, consisting of two cycles of preoperative high dose chemotherapy. The blood samples were studied at different times. The CD34+ cells were analyzed by flow cytometry and the hematopoietic progenitor cells were analyzed by tissue culture clonogenic assay. In comparing the two courses of chemotherapy, we observed that modification of the mean values of WBC, CD34+ and CFU-GM were very similar. The second course of chemotherapy seemed to induce greater hematological toxicity. All three parameters showed good correlation. The results demonstrated that the best time to collect PBSC by means of leukapheresis is post G-CSF used as rescue after ifosfamide treatment. We verified the ability of G-CSF to mobilize PBSCs in patients with osteosarcoma through cytofluorimetric analysis of CD34+ cells and their clonogenic capability. Moreover, during this preoperative treatment, we identified the best time to collect a sufficient number of PBSCs, that is after 9-10 days of G-CSF treatment following the first cycle of ifosfamide.
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PMID:Cd 34+ cells and clonogenicity of peripheral blood stem cells during chemotherapy treatment in association with granulocyte colony stimulating factor in osteosarcoma. 1046 32

In the present paper, we review the evidence for chemotherapy in patients with bone and soft part sarcoma and discuss the contributions and improvements made by chemotherapy to the treatment of patients with bone and soft part sarcoma. In the osteosarcoma and Ewing's sarcoma family, neoadjuvant and adjuvant chemotherapy have improved the 5-year disease-free survival to 60%, and limb-salvage operations have improved this to 70-80% in cases of non-metastatic malignant bone tumor. Several trials were conducted in order to overcome rate relapses and metastatic bone sarcoma. With osteosarcoma, thoracotomy improved the survival of lung metastatic patients, but CDDP-ADM branch switched according to the neoadjuvant chemotherapy and failed to elevate the continuous disease-free survival of patients. Dose intensive use of cytotoxic drugs with G-CSF or autologous bone marrow transplantation and multidrug programs were conducted in preliminary studies and achieved favorable results in a high risk factors group for tumors of the Ewing's sarcoma family. Surgical techniques have brought improvements in the treatment of soft tissue sarcoma, but there has been no impact by chemotherapy. Ifosfamide and adriamycin combination is being evaluated in the treatment of local advanced and metastatic soft part sarcoma by local control rate or survival from relapse.
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PMID:[Evidence-based chemotherapy for patients with bone and soft part sarcoma]. 1070 Aug 89

With the intention of starting an international protocol between Italy and Scandinavia on neoadjuvant treatment of extremity osteosarcoma using the four active drugs at maximum doses (doxorubicin 75 mg/m2 pre-operatively, and 90 mg/m2 post-operatively, cisplatin 120 mg/m2, methotrexate 12 g/m2, and ifosfamide 15 g/m2), a single center (the Rizzoli institute) performed a pilot study to closely monitor toxicity, safety, and tumor necrosis. Only 7 patients (10%) had a reduced number of the scheduled cycles. A total of 1,050 of the expected 1,076 cycles (98%) were administered. Delays and dose reduction were minimal, leading to a mean received dose intensity of 89%. Limb salvage surgery was performed in 59 cases (87%), with 6 amputations and 3 rotation plasties. Chemotherapy-induced necrosis higher than 95% was observed in 38 patients (56%). Eleven patients had total necrosis (16%). At a median follow-up of 60 months (range 50-65 months), 53 patients (73%) were continuously disease-free. Six of the relapsed patients were rescued with further treatments leading to an overall survival of 87%. Hematological toxicity was remarkable despite the use of G-CSF and hospitalization due to febrile neutropenia occurred in 25 patients (37%). Platelet transfusions were required in 77 of the 194 episodes of grade 4 thrombocytopenia, but no case of major bleeding was observed. Red blood cell transfusions were necessary in all patients (in 15 cases perioperatively only). Non-hematological toxicity comprised grade 1-2 nephrotoxicity in 3 cases, CNS toxicity in 2 cases, and dilata- tive cardiopathy leading to heart transplantation in 1 case. In conclusion, the pilot study was feasible in the vast majority of cases with toxicity not superior to that of the previous protocols where chemotherapy was given in lower doses. The rate of limb salvage procedures, event-free survival and overall survival seemed to be higher than in previous protocols. On the basis of this study, in March 1997 the Italian and Scandinavian Sarcoma Groups started a new protocol for osteosarcoma of the extremities.
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PMID:High dose ifosfamide in combination with high dose methotrexate, adriamycin and cisplatin in the neoadjuvant treatment of extremity osteosarcoma: preliminary results of an Italian Sarcoma Group/Scandinavian Sarcoma Group pilot study. 1201 78

A total number of 608 cycles of G-CSF and/or GM-CSF was applied in 280 patients aged from 6 months to 20 years during neutropaenia associated with chemotherapy of children's neoplasms (NHL-124, NBL-42, RMS-36, Nephroblastoma-18, Osteosarcoma-17, Ewing's Sarcoma-14, Hepatoblastoma-6, Neurofibrosarcoma-6, PNET-5, Medulloblastoma-3, Fibrohistiocytoma-3, Angiosarcoma-2, other - 4). G-CSF - Neupogen (Filgastrim, Hoffman La Roche - 492 cycles) and GM-CSF - Leucomax (Molgramostim, Shering Plough - 116 cycles) were administered 5 mg/kg/day s.c. Forty one children with malignancies (NHL -21 cases, solid tumours -17) treated before cytokines were in use served as a control group. Our study demonstrated that G-CSF and GM-CSF therapy, gives a shorter period of neutropaenia, reduction of the number of febrile days, decreased frequency of infection and shortened its duration.
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PMID:[G-CSF and GM-CSF in treatment of neutropaenia after chemotherapy in children with neoplasms]. 1202 71

Bone hybrids made of bioceramics seeded with mesenchymal or osteoblastic cells are very promising alternatives to autologous bone graft. Along this line, the development of in vitro models, dedicated to analyze the influence of these biomaterials on osteogenic cells, will help to improve the performance of these bone substitutes. In the present work we analyzed the effects of a macroporous biphasic calcium phosphate ceramic (BCP, Triosite) on three different human osteosarcoma cell lines and on human primary osteogenic cells and compared this culture substratum to traditional culture on plastic. We showed that all these osteoblastic cells adhere and proliferate on the trabecular BCP blocks, with a different spatial organization for osteosarcoma cells compared to normal osteogenic cells. We also demonstrated that osteoblastic marker genes such as Cbfa1, type I collagen, osteonectin, osteopontin, and osteocalcin were expressed at similar levels by these cells cultured on either substratum, suggesting that adhesion to BCP does maintain the osteoblastic phenotype of these cells. Next, we provided the first evidence of differences of cytokine expression profiles revealed on this Ca-P ceramic as compared to expression in classical culture. These modifications affected the expression of cytokines such as TGF-beta1, G-CSF, and IL-3 and were quantitatively different between osteosarcoma cells and normal osteogenic cells. Given the role of these cytokines in bone biology and in hematopoiesis, these results obtained in vitro suggest that the BCP ceramic studied here could stimulate osteogenesis in vivo by activating cellular processes during bone formation and healing. This study highlights the notion that the nature of the culture substratum must be taken into account when studying bone cell biology in vitro. Owing to the nature and spatial organization of the BCP, our hypothesis is that culture on BCP is closer to the physiological situation than culture on plastic.
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PMID:Modification of gene expression induced in human osteogenic and osteosarcoma cells by culture on a biphasic calcium phosphate bone substitute. 1281 Jan 67

When human blood monocytes were cocultured with stromal cells derived from human giant cell tumor of bone (GCTSC) and a Millipore filter (0.4 microm) was interposed between monocytes and GCTSC, multinucleated giant cell formation of monocytes was induced. The multinucleated giant cells have characters as osteoclast-like cells, indicating that a soluble osteoclast-inducing factor(s) is secreted from GCTSC expressing RANK, RANKL/ODF/OPGL and TACE mRNA. Furthermore, OCIF/OPG inhibited GCTSC-induced osteoclastogenesis, showing that the RANK-RANKL system is involved in GCTSC-induced osteoclastogenesis and that soluble form of ODF/RANKL induces osteoclasts from monocytes. GCTSC expressed the cytokine mRNAs such as M-CSF, GM-CSF, IL-3, IL-4, IL-6, and IFN-gamma mRNAs. None of IL-1ralpha, IL-1alpha, IL-1beta, IL-2, IL-4, IL-10, IL-18, TNF-alpha, G-CSF and IFN-gamma could be detected in all culture media. A significant amount of IL-6 could be detected in the culture media of all GCTSC. IL-8 was found in the culture media of two GCTSC and two osteosarcoma-derived cells. M-CSF was detected in all culture media. GCTSC express CaSR, and stimulation of GCTSC with either extracellular Ca(2+) or neomycin, agonist of CaSR, augmented the expression of RANKL. Some lines of GCTSC expressed alkaline phosphatase, osteocalcin and Cbfa1, suggesting that GCTSC are intimately related to osteoblastic lineage.
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PMID:Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclast formation of human blood monocytes without cell to cell contact. 1602 7


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