phosphocreatine and Pituitary-Neoplasms

Of primary central nervous system tumors treated each year, the majority are glioma, followed by meningioma and then pituitary adenoma. While the use of magnetic resonance (MR) and computed tomographic imaging is well established in the diagnosis and management of such tumors, these techniques have a limited role in determining the metabolic state, either prior to or following therapy. Multinuclear MR spectroscopy, on the other hand, provides information on tumor metabolism and the effect of therapy on tumor viability. This paper reviews MR spectroscopic studies performed on patients with central nervous system tumors and discusses the impact that such studies have had on tumor diagnosis and management.

Topics: Adenoma; Adenosine Triphosphate; Adolescent; Adult; Aged; Blood Chemical Analysis; Brain Chemistry; Brain Neoplasms; Child; Child, Preschool; Energy Metabolism; Female; Glioma; Humans; Hydrogen-Ion Concentration; Incidence; Infant; Magnetic Resonance Spectroscopy; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Phosphocreatine; Phospholipids; Pituitary Neoplasms

In a prospective study, proton (1H) and phosphorus (31P) nuclear magnetic resonance spectroscopy were used to search for effects of brain tumor radiotherapy on normal human central nervous system. Phosphorus spectroscopy data at 1.5 T seems to suggest that any radiation induced damage that may occur as a result of therapeutic brain irradiation, does not alter the relative concentrations of phosphorus metabolites or the intracellular pH beyond the limits of normal variation (approximately +/- 20%). Proton spectroscopy, on the other hand, detects post radiation changes in the ratios of certain nuclear magnetic resonance visible metabolites following radiotherapy, particularly choline/N-acetylaspartate, and especially in regions of brain receiving high doses of radiation. Such changes may be indicative of the release of membrane bound choline during radiation induced demyelination of brain. Of interest, we have found elevated metabolite ratios of 31P in normal central nervous system prior to radiotherapy, which persisted throughout the time span of the study in both the ipsilateral and contralateral cerebral hemispheres.

Topics: Adenoma; Adenosine Triphosphate; Brain; Brain Neoplasms; Energy Metabolism; Glioma; Humans; Hydrogen; Magnetic Resonance Spectroscopy; Oligodendroglioma; Phosphates; Phosphocreatine; Phosphorus; Pituitary Neoplasms; Prospective Studies; Reference Values

Magnetic resonance spectroscopy (MRS) uniquely provides noninvasive access to chemistry in vivo. 31P MRS can be used to monitor the high energy phosphates--phosphocreatine (PCr) and ATP, and their breakdown product--Pi, in situ in animals or patients. In several experimental tumor lines in animals it has been shown that the PCr/ATP and other related ratios steadily decline as the tumor increases in size, and that this effect is reversed when the tumor is treated with a therapeutic modality to which it responds. Acid extracts of freeze-clamped tumors at different stages of growth have confirmed these MRS observations and give additional information on related compounds such as creatine and ADP. Results show that, in the tumors studied, at least 80% of the ADP and about 40% of the Pi are bound and not in solution in the cytosol. Histological sections have indicated that the MRS response to endocrine therapy, in an NMU-induced estrogen-sensitive mammary tumor model, precedes any histological changes or any measurable regression. If these findings can be translated into a clinical setting, this may mean that MRS can be used in the clinic as an early predictor of tumor responsiveness to treatment. In untreated tumor growth, the cause of the decrease in PCr and ATP relative to Pi is probably due to the tumors outgrowing their blood supply and the cells becoming increasingly hypoxic. The PCr is lost more rapidly than ATP, indicating that the equilibrium in the creatine kinase reaction is maintained in these tumors. When the tumor is treated, cellular growth ceases and the requirement for oxygen and other nutrients is greatly reduced. This would allow the cellular energy reserves to be repleted and thus lead to the paradoxical improvement in the high energy phosphate status of a tumor that is about to regress.

Topics: Adenine Nucleotides; Adenocarcinoma; Animals; Cell Division; Creatine; Female; Magnetic Resonance Spectroscopy; Mammary Neoplasms, Experimental; Mice; Ovariectomy; Phosphates; Phosphocreatine; Phosphorus; Pituitary Neoplasms

31P-NMP, surface coil spectra of three subcutaneously implanted rat tumours (Morris hepatoma 7777, GH3 prolactinoma, Walker carcinosarcoma) and an N-methyl-N-nitrosourea induced rat mammary adenocarcinoma at different stages of growth were obtained and compared with histological sections taken immediately after NMR acquisitions. Metabolite ratios (phosphocreatine (PCr)/beta nucleoside triphosphate (beta NTP), PCr/Pi, beta NTP/Pi) calculated from the NMR spectra were compared with ratios obtained from acid extracts of tumours of similar size. Measurements of creatine and ADP were also made. Three of the tumours showed positive correlations between increasing tumour size and decreasing metabolite ratios measured both by NMR and in extracts, whereas the Walker carcinosarcoma showed no correlation between size and any parameters measured. Phosphorus metabolite ratios, measured in extracts of skin overlying the tumours, indicated a fall in high energy phosphate when there was histological evidence of skin invasion by the tumour. Surface coil 31P-NMR spectra of subcutaneously grown or induced tumours in the rat represent a slowly changing steady state as the tumour increases in size. We conclude that increasing numbers of hypoxic tumour cells, rather than large areas of necrotic tissue, contribute largely to the NMR spectrum.

Topics: Adenocarcinoma; Animals; Carcinoma 256, Walker; Cell Division; Creatine; Liver Neoplasms, Experimental; Magnetic Resonance Spectroscopy; Mammary Neoplasms, Experimental; Neoplasms, Experimental; Phosphocreatine; Pituitary Neoplasms; Prolactinoma; Rats

Prolactin (PRL)-secreting GH3 cells were grown, in vitro, with the creatine analogue beta-guanidinopropionic acid (GPA) added to the culture medium. After 5 days there was a small increase in basal and greatly increased thyrotropin-releasing hormone (TRH)-stimulated PRL secretion. The site of action of GPA is at the TRH-induced hydrolysis of phosphoinositides, since increased amounts of mono, bis and tris/tetrakis inositol phosphates were found in treated cells, while the PRL secretion induced by a phorbol ester or a calcium ionophore, treatments which mimic the second messages generated by inositol phospholipid hydrolysis, were not enhanced by GPA. The mechanism by which GPA increases phospholipase C activity has not been fully elucidated but may involve the activity of a controlling G protein.

Topics: Aminoquinolines; Animals; Calcimycin; Creatine; Dose-Response Relationship, Drug; Guanidines; Hydrolysis; Inositol Phosphates; Lactates; Lithium; Phosphatidylinositols; Phosphocreatine; Pituitary Neoplasms; Prolactin; Propionates; Rats; Tetradecanoylphorbol Acetate; Thyrotropin-Releasing Hormone; Tumor Cells, Cultured

Growth hormone has been synthesized in a cell-free system derived from Krebs II ascites cells, under the direction of RNA prepared from rat pituitary tumor (GC) cells. Growth hormone synthesized in the cell-free system was identified by precipitation with antiserum against growth hormone developed in baboon, followed by electrophoretic analysis of the dissolved precipitate on sodium dodecyl sulfate-polyacrylamide gels. RNA from both the membrane and the post-membrane fractions of the cytoplasm of GC cells stimulated protein synthesis in the cell-free system, but only RNA from the membrane fraction was found to direct the synthesis of growth hormone.

Topics: Animals; Carbon Radioisotopes; Carcinoma, Krebs 2; Cell-Free System; Electrophoresis, Polyacrylamide Gel; Growth Hormone; Immunoassay; Immunoelectrophoresis; Kinetics; Leucine; Methionine; Papio; Peptide Biosynthesis; Phosphocreatine; Phosphoenolpyruvate; Pituitary Neoplasms; Rats; RNA, Neoplasm; Sodium Dodecyl Sulfate; Sulfur Radioisotopes