phosphocreatine and Lung-Neoplasms

In this Communication 1H MRI and MRS microscopy experiments of individual V79 lung tumor spheroids with diameters between 550 and 650 micrometer are reported. The results have been used to determine the T1, T2, and D values as well as the concentrations of water, total choline, creatine/phosphocreatine, and mobile lipids in the viable rims and in the necrotic centers.

Topics: Animals; Choline; Creatine; Cricetinae; Cricetulus; Lipids; Lung Neoplasms; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Microscopy; Phosphocreatine; Spheroids, Cellular; Tumor Cells, Cultured; Water

Two human small cell lung cancer tumor lines, maintained as solid tumor xenografts on nude mice and as in vitro cell cultures, were studied by in vivo 31P magnetic resonance spectroscopy and by biochemical analysis of extracts of solid tumors and cell cultures. The tumor lines CPH SCCL 54A and CPH SCCL 54B are subpopulations from the same tumor. In solid tumors (n = 125), the ATP/Pi ratio was greater in 54A than in 54B. This was due to a higher ATP level in 54A, whereas there was no difference in Pi, ADP, and AMP. A decrease in ATP/Pi during growth was caused by a decline in ATP, whereas Pi remained unchanged. Small amounts of phosphocreatine were found in the xenografts and in tumor extracts, but not in the cell extracts; correspondingly, there was a low creatine kinase activity in solid tumors and no activity in the cell cultures. Thus, the phosphocreatine content of the solid tumors originated from the stroma. A difference in ATP content between 54A and 54B was also found in cell cultures; hence, the metabolic difference is an intrinsic quality of the malignant cells and is not caused by the host system.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Carcinoma, Small Cell; Energy Metabolism; Humans; Lung Neoplasms; Magnetic Resonance Spectroscopy; Mice; Mice, Nude; Neoplasm Transplantation; Phosphocreatine; Phosphorus; Transplantation, Heterologous; Tumor Cells, Cultured

31P nuclear magnetic resonance (NMR) spectra of cells and of cell extract revealed high levels of phosphorylcholine (PC) and phosphocreatine (PCr) in an adriamycin-resistant human small cell lung carcinoma cell line (GLC4/ADR) and the adriamycin-sensitive parental cell line (GLC4). PCr levels in extracts of GLC4/ADR were increased compared to extracts of GLC4. We estimated that 11% of the total intracellular ATP is not bound to Mg2+ in both cell lines. This value corresponded to an intracellular free Mg2+ of 0.30 mM. The effects of different adriamycin concentrations, 0.05, 1 and 30 microM for GLC4 and 1, 30 and 200 microM for GLC4/ADR, on the phosphorus metabolite levels in continuously perfused cells were monitored. Significant differences between GLC4 and GLC4/ADR included: (a) a strong increase in the beta ATP level in the presence of 30 microM adriamycin in GLC4 only, followed by a fast decrease after 5 h of perfusion. (b) a less dramatic increase in the PC level in GLC4/ADR and an unchanged ATP level in the presence of increasing adriamycin concentrations. (c) an increased GPC level in GLC4/ADR in the presence of adriamycin. The changes in PC and GPC levels in the presence of adriamycin suggested that the phospholipid turnover was increased in GLC4/ADR and could be stimulated in the presence of adriamycin. In both cell lines, PCr levels decreased faster than the ATP levels after adriamycin treatment. Thus, biochemical markers for adriamycin resistance can be detected with NMR spectroscopy. However, more studies are necessary to obtain parameters to distinguish drug-sensitive from drug-resistant tumours in patients by NMR spectroscopy.

Topics: Adenosine Triphosphate; Carcinoma, Small Cell; Doxorubicin; Drug Resistance; Energy Metabolism; Humans; Lung Neoplasms; Magnesium; Magnetic Resonance Spectroscopy; Phosphocreatine; Phospholipids; Tumor Cells, Cultured

Human lung cancers are divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) based on established criteria. SCLC differs from NSCLC by the expression of biomarkers, including creatine kinase-BB isoenzyme (EC 2.7.3.2). Subtypes of SCLC are referred to as classic and variant, both of which have elevated levels of creatine kinase-BB isoenzyme. We, therefore, applied 31P nuclear magnetic resonance spectroscopy to cell lines of classic SCLC, variant SCLC, and NSCLC human tumors, using continuous perfusion to identify any differences in the detectable levels of intracellular high-energy phosphate compounds. The spectra indicate that only the variant SCLC cells maintain high levels of phosphocreatine. Additionally, the classic SCLC cells express elevated levels of a diphosphodiester. Neither phosphocreatine nor diphosphodiesters are found in the NSCLC cell spectra.

Topics: Adenosine Triphosphate; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Line; Creatine Kinase; Humans; Lung Neoplasms; Oncogenes; Phosphates; Phosphocreatine; Sugar Phosphates

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

Topics: Adenosine Triphosphate; Animals; Breast Neoplasms; Cell Line; Colonic Neoplasms; Female; Humans; Hydrogen-Ion Concentration; Lung Neoplasms; Magnetic Resonance Spectroscopy; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Phosphates; Phosphocreatine; Transplantation, Heterologous

Twenty-two patients undergoing thoracotomy for the diagnosis or treatment of a suspected pulmonary neoplasm had separate biopsies taken from their external and internal intercostal muscles at the time of surgery. Pulmonary function abnormalities ranged from none to moderate airway obstruction. Seventeen of the twenty-two patients had morphologic changes (targeting, variation in fiber size, splitting, and atrophy) in both respiratory muscles, but not in the control latissimus dorsi. Fiber atrophy was more marked in the internal intercostal muscle and was significantly related to the degree of airway obstruction, but not to age, malignancy, or weight loss. Biochemical analyses revealed decreased adenosine triphosphate (ATP) and phosphocreatine (PC) in 47 of 52 muscles, including the latissimus dorsi. The data suggested a relation between increasing airway obstruction and decreasing amounts of phosphocreatine in both intercostal muscles. This relationship may have been enhanced by the presence of malignancy or weight loss. There was a selective decrease in muscle glycogen found only in the external intercostal muscle that was not affected by airway obstruction, malignancy, or weight loss. Intercostal muscle abnormalities are common in patients with obstructive lung disease who undergo thoracotomy, and are probably multifactorial in origin. It is possible that these abnormalities affect the natural history of lung disease in some patients.

Topics: Adenosine Triphosphate; Aged; Humans; Intercostal Muscles; Lactates; Lung Diseases, Obstructive; Lung Neoplasms; Lung Volume Measurements; Middle Aged; Phosphocreatine

Topics: Alcoholism; Collagen Diseases; Creatine Kinase; Humans; Kidney Failure, Chronic; Lung Neoplasms; Muscular Dystrophies; Phosphocreatine