phosphocreatine and Osteosarcoma

To study the characteristic changes of 31P-MR spectroscopy of bone and soft tissue tumors.. 41 patients were examined by phosphorus surface coil of 3 tesla MR machine, including 18 benign tumor foci and 28 malignant foci, and adjacent normal muscles. The areas under the peaks of various metabolites in the spectra were measured, including phosphomonoester (PME), inorganic phosphours (Pi), phosphodiester (PDE), phosphocreatine (Pcr), adenosine triphosphate (ATP) gamma, alpha, beta. The ratios of the metabolites to beta-ATP, NTP and Pcr were calculated. Intracellular pH was calculated according to the chemical shift change of Pi relative to Pcr.. The ratios of Pcr/PME and PME/NTP in benign and malignant tumor groups were significantly different from those of the normal group (P<0.05). Between benign and malignant tumor groups, the ratios of PME/beta-ATP and PME/NTP were significantly different (P<0.05).. Pcr/PME and PME/NTP are potential diagnostic indexes of bone and soft tissue tumors. PME/beta-ATP and PME/NTP are potential indexes of differential diagnosis of bone and soft tissue tumors.

Topics: Adenosine Triphosphate; Adolescent; Adult; Aged; Bone Neoplasms; Child; Diagnosis, Differential; Female; Fibroma; Giant Cell Tumors; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Organophosphates; Osteosarcoma; Phosphocreatine; Phosphorus; Phosphorus Isotopes; Sarcoma, Ewing; Soft Tissue Neoplasms; Young Adult

It has been hypothesized that the (31)Phosphorus ((31)P) nuclear magnetic resonance spectrum from certain tumors may provide prognostic information. The goal of the present study was to identify prognostic metabolic markers by using proton-decoupled phosphorus magnetic resonance spectroscopic imaging ((31)P MRSI). Twenty patients with bone [osteogenic (OS) and Ewing's (ES) and/or primitive neuroectodermal tumor (PNET)] sarcoma, treated with chemotherapy and surgery or with chemotherapy alone, underwent (31)P MRSI studies pre- and post-therapy. The studies were performed on a 1.5 Tesla General Electric (GE) clinical scanner equipped with a stand-alone proton decoupler and a dual (1)H/(31)P surface coil pair. The limited sensitivity of the (31)P nucleus required that a large soft tissue component of the disease be located within 10 cm (maximum distance) of the body surface and the use of a highly sensitive coil placed near the skin surface. Proton decoupling and nuclear Overhauser enhancement were used to improve the spectral resolution and signal:noise ratio. Baseline (31)P spectral features and metabolic changes with treatment were compared with treatment outcome. The patients were categorized depending on survival as event-free survivors or those who died. The pretreatment nucleoside triphosphate:inorganic phosphate (NTP:P(i)) ratio, an index of tumor bioenergetic status, was significant (P = 0.003) in differentiating event-free survivors versus those who died. The pretreatment NTP:P(i) was higher in patients who were destined to undergo a durable event-free survival compared with those who died. The results are promising, although a prospective study is necessary for confirmation. (31)P MRSI appears to be a useful tool for the prediction of survival before therapy in bone sarcomas.

Topics: Adolescent; Adult; Biomarkers, Tumor; Bone Neoplasms; Child; Ethanolamines; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Nucleotides; Osteosarcoma; Phosphocreatine; Phosphorus; Phosphorylcholine; Prognosis; Protons

To determine if changes in PCr/Pi and PME can be used to predict lack of tumor response to chemotherapy in a murine model of a chemotherapy-resistant human osteosarcoma.. Cisplatin-resistant sublines were grown from high-grade cisplatin-sensitive human osteosarcoma. Surface coil localized 31P NMR spectroscopy of implanted cisplatin-resistant and sensitive osteosarcoma tumors in nude mice was performed.. A cisplatin-resistant subline of a sensitive human osteosarcoma was developed that was five times more resistant to cisplatin than the parent cell line. Our NMR data shows a statistically significant difference in the change in the PCr/Pi ratio after treatment between sensitive and resistant osteosarcomas at the alpha = 0.05 level. Changes in PME were seen in the sensitive tumors but were not statistically significant.. Changes in PCr/Pi predict lack of tumor treatment response in human osteosarcoma implanted into nude mice with a specificity of 70% and a sensitivity of 54%. Monitoring of PCr/Pi in human osteosarcoma patients may allow detection of response to chemotherapy before conventional imaging techniques.

Topics: Animals; Antineoplastic Agents; Cisplatin; Humans; Magnetic Resonance Spectroscopy; Mice; Mice, Nude; Neoplasm Transplantation; Osteosarcoma; Phosphates; Phosphocreatine; Phosphorus; Sensitivity and Specificity; Transplantation, Heterologous; Tumor Cells, Cultured

Our objective was to determine whether changes in PME and PCr/Pi can be used to predict lack of tumor response to chemotherapy in a murine model of human osteosarcoma. A chemotherapy-sensitive human osteosarcoma cell line was implanted into the flank of 22 nude mice. Cisplatin was administered to 11 of the mice 9 days postimplantation. 31P MR spectroscopy was performed pre- and post-chemotherapy in both sets of mice. Statistically significant changes in PCr/Pi occur from post-chemotherapy in the treated mice, but not in the untreated mice during the same time. Change in PME parallels changes in tumor volume. Changes in PCr/Pi predict lack of chemotherapy treatment in human osteosarcoma implanted into nude mice with a specificity of 80% and a sensitivity of 63%. The change in PCr/Pi occurs prior to any changes in volume of the tumor [corrected].

Topics: Animals; Bone Neoplasms; Cisplatin; Humans; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Osteosarcoma; Phosphocreatine; Phosphorus; Sensitivity and Specificity

This study investigates the potential of in vivo 31P magnetic resonance spectroscopy (MRS) to characterize musculoskeletal tumors and to determine preoperative levels of histological necrosis, which is an important clinical indicator of patient response. Pretherapy MRS was performed on 28 patients with large musculoskeletal tumors: 13 with osteosarcoma, 3 with chondrosarcoma, 5 with malignant fibrous histiocytoma, 1 with desmoid tumor, 1 with Ewing's, 2 with hemangioendothelioma, 1 with myxoid liposarcoma, 1 with synovial cell sarcoma, and 1 with rhabdomyosarcoma. Fifteen patients had follow-up MRS examinations after commencement of chemotherapy (mean of five/patient), eight of whom have now had surgery. Elevated levels of PMEs (P < 0.01), P(i) (P < 0.01), and PDEs (P < 0.02) as well as elevated tumor pH (P < 0.05) were observed in all patients. The synovial cell sarcoma was characterized by high levels of PMEs (> 20%) and low pH (pH 6.76). This contrasted with the spectra obtained from the malignant fibrous histiocytomas which had high levels of PDEs (17 +/- 5%). Reductions in PDE levels postchemotherapy were associated with a high degree of necrosis (> 90%) at surgery, while an increase in PDE levels was associated with a low level of histological necrosis. Likewise, reductions in the ratios PDE/NTP and PDE/PCr and an increase in P(i)/PDE were also associated with a high level of necrosis.

Topics: Adult; Aged; Bone Neoplasms; Chemotherapy, Adjuvant; Ethanolamines; Female; Glycerylphosphorylcholine; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscular Diseases; Necrosis; Neoplasm Staging; Neoplasms; Osteosarcoma; Phosphatidylethanolamines; Phosphocreatine; Phosphorus; Phosphorylcholine; Preoperative Care

Cultured SK-OS-10 cells (human osteogenic sarcoma metastatic to lung) shed microvesicles (dia. 300-1000 nm) that contained procoagulant and proaggregatory activities inhibitable by hirudin, by anti-tissue factor antibody and by phospholipase A2. These results show that SK-OS-10 cells belong to a group including U87MG human glioblastoma and HL-60 promyelocytic leukemia in which these activities are due to a thrombin-dependent mechanism arising from the presence of tissue factor on the surface of the tumor cells and their shed microvesicles.

Topics: Antibodies; Blood Platelets; Cell Line; Creatine Kinase; Hirudins; Humans; Inclusion Bodies; Lung Neoplasms; Osteosarcoma; Phosphocreatine; Phospholipases; Platelet Activating Factor; Platelet Aggregation; Thromboplastin