pyrophosphate and Osteosarcoma

N-BP, rapamycin and its derivatives have been originally developed respectively as anti-resorptive and anti-fungal agents. In fact, in vitro and in vivo experiments demonstrated that these compounds are multi-functional molecules exerting their effects on tumour cell growth and bone remodelling. The major challenge in treating cancer relates to mutations in key genes such as p53, Rb or proteins affecting caspase signalling carried by many tumour cells. Whether nitrogen containing bisphosphonates (N-BP) are potent bone inhibitors, they also inhibit tumour cell proliferation and increase atypical apoptosis of bone tumour cells regardless of the p53 and Rb status. N-BP may be then considered as effective therapeutic agents in clinical trials of bone tumours. Rapamycin and its derivatives inhibit mTOR dependent mRNA translation both in osteoclasts and tumour cells. Cellular physiological mechanisms regulated by mTOR integrate many environmental parameters including growth factors, hormones, cytokines, amino acids, energy availability and cellular stresses that are coupled with cell cycle progression and cell growth. Rapamycin and its derivatives as well as N-BP must be considered as bi-(multi) functional molecules affecting simultaneously bone and tumour metabolisms. The present survey describes these two molecular families and discusses their therapeutic interests for primary bone tumours and bone metastases.

Topics: Bone Neoplasms; Cell Division; Diphosphates; Diphosphonates; Humans; Osteosarcoma; Protein Kinases; Sirolimus; Structure-Activity Relationship; TOR Serine-Threonine Kinases

Osteonecrosis of the jaw (ONJ) is an emerging condition in patients undergoing long-term administration of bisphosphonates (BP) for the treatment of osteoporosis and hypercalcaemia associated with malignancy, multiple myeloma, and metastatic breast and prostate cancers. This is a follow-up study, its purpose was to examine the effects in-vitro of intravenous zoledronic acid (ZOL) and pamidronate (PAM) and oral alendronate (FOS) on the human oral cavity using gingival fibroblasts and osteoblasts cells and, in addition, osteogenic sarcoma cells (SaOS-2-cells).. Human gingival fibroblasts, osteoblasts and SaOS-2-cells were seeded on multiple 6-well plates at a density of 5 × 10(5)cells in a 4-week cell culture. Four different concentrations (1, 5, 10, 20 μM) of each BP (ZOL, PAM, FOS) and pyrophosphate were used in this study.. All BP decreased collagen production and lowered cell proliferation in-vitro. ZOL was the component with most inhibitory effect.. The findings in this study suggest that ZOL, PAM and FOS generally diminish cell proliferation and collagen production of human gingival fibroblasts, osteoblasts and SaOS-2-cells. The present follow-up study shows that not only ZOL and PAM but also FOS have a strong inhibitory effect on collagen production and cell survival in-vitro.

Topics: Alendronate; Alkaline Phosphatase; Bone Density Conservation Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cells, Cultured; Chromatography, High Pressure Liquid; Collagen Type I; Coloring Agents; Diphosphates; Diphosphonates; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Follow-Up Studies; Gingiva; Humans; Imidazoles; Osteoblasts; Osteocalcin; Osteosarcoma; Pamidronate; Tetrazolium Salts; Thiazoles; Zoledronic Acid

Topics: Bone Neoplasms; Diphosphates; Female; Humans; Middle Aged; Osteosarcoma; Radiography; Radionuclide Imaging; Talus; Technetium; Technetium Tc 99m Pyrophosphate

Fifty seven patients with histologically proven cyst-like lesions of the mandible are reviewed. The importance of combining radiographic with scintigraphic imaging is stressed. These two imaging modalities are complementary in demonstrating both the biological activity and the extent of the lesion. In osteomyelitis the bone scan, which is more sensitive than the radiograph, is also the method of choice in assessing the result of treatment.

Topics: Adolescent; Adult; Aged; Ameloblastoma; Carcinoma, Squamous Cell; Dentigerous Cyst; Diphosphates; Humans; Jaw Cysts; Mandibular Diseases; Mandibular Neoplasms; Middle Aged; Osteomyelitis; Osteosarcoma; Radicular Cyst; Radiography; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

The pathologic specimens of 18 osteosarcomas of long bones were examined to correlate histologic abnormalities with abnormalities seen on preoperative 99mTc pyrophosphate or methylene diphosphonate bone scans. Seven scans accurately represented the extent of the tumor. Eleven scans disclosed increased activity extending beyond the radiographic abnormalities. In eight of these, there was no occult tumor extension and in the other three, the scan activity did not accurately portray the skip metastases that were present. Therefore, these 11 scans demonstrated the falsely extended pattern of uptake beyond the true limits of the tumors. Pathologic slides were available for 10 of the 11 areas of bone that exhibited extended uptake. In two instances, there was no pathologic abnormality. In the other eight cases we found marrow hyperemia, medullary reactive bone, or periosteal new bone. This is the first description of these histologic abnormalities of medullary bone in areas of extended uptake on radionuclide bone scans.

Topics: Adolescent; Adult; Bone Neoplasms; Child; Child, Preschool; Diphosphates; Diphosphonates; Female; Femoral Neoplasms; Humans; Male; Osteosarcoma; Radionuclide Imaging; Retrospective Studies; Technetium; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate

Topics: Adult; Bone and Bones; Bone Neoplasms; Child; Chondroma; Chondrosarcoma; Diagnosis, Differential; Diphosphates; Diphosphonates; Female; Humans; Infant; Osteosarcoma; Radionuclide Imaging; Technetium; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate

The value of radioisotope bone scanning at the time of presentation and serially during follow-up has been evaluated in 55 patients with biopsy-proven osteogenic sarcoma. Many of the patients studied were treated with adjuvant chemotherapy. Bone metastases were detected at presentation in only one patient and in a second patient, proximal extension of the primary tumor not evident on radiographs was demonstrated by the radioisotope technique. During fellow-up, 20 patients experienced bone metastases and each had an abnormal bone scan. Eleven of these patients were asymptomatic for bone metastases at the time the scan became abnormal. Seven patients experienced bone metastases as their first site of tumor recurrence. The detection rate for soft tissue metastases was low, but the scan indicated stump recurrence in three patients. Although the yield is small, bone scanning is justified at presentation be cause the results may profoundly after the management. During follow-up, routine bone cans are indicated in all patients, whether they have symptoms or not.

Topics: Adolescent; Adult; Bone Neoplasms; Child; Diphosphates; Diphosphonates; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Prognosis; Radionuclide Imaging; Retrospective Studies; Technetium; Technetium Tc 99m Medronate; Technetium Tc 99m Pyrophosphate

Within 1 yr after localized irradiation of a hind limb with single (1756 rads) or fractionated (4650 rads in 3 wk) x-ray doses, radiation-induced osteosarcomas were observed in four of nine single-dose rabbits and two of 11 fractionated-dose rabbits. Tumors were observed in the proximal tibia in five cases and the distal femur in one case. In terms of production of osteoid or osseous tissue, three tumors were well differentiated, one slightly differentiated, and two (spindle-cell tumors) undifferentiated. This report summarizes the Tc-99m pyrophosphate (TcPPi) imaging and autoradiographic, radiographic, and histologic studies of these osteosarcomas. The four differentiated osteosarcomas were detected 1--2.5 mo earlier by TcPPi imaging than by radiography, whereas the two undifferentiated tumors were suspected 2 wk or 3.5 mo earlier radiographically. Autoradiograms showed TcPPi localization in bone produced by differentiated osteosarcomas, and in regions of reactive bone resorption and formation peripheral to tumors. The results support a recommendation for combined radiographic and scintigraphic techniques for the early detection of osteosarcomas.

Topics: Animals; Bone and Bones; Bone Neoplasms; Diphosphates; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Rabbits; Radiography; Radionuclide Imaging; Technetium

Topics: Abdomen; Adult; Diphosphates; Humans; Male; Neoplasm Metastasis; Osteosarcoma; Radionuclide Imaging; Technetium; Thorax