phosphocreatine and Skin-Neoplasms

In this study a human glioma-derived intracerebral tumor model was analyzed histologically and examined by image-guided 1H NMR spectroscopy. It was shown that histological characteristics such as cellular subpopulation and necrosis of the primary tumor were preserved in the implants. Usually circumscript tumor growth was present with tumor cells invading the surrounding brain parenchyma. It was demonstrated that tumor growth and tumor metabolism could be monitored by image-guided 1H NMR spectroscopy in a longitudinal study. One of the initial changes noticed was the rise of the lactate signal in the tumor region followed by an increase of the choline and a decrease of N-acetyl-aspartate and phosphocreatine signals. Even before tumor invasion in brain adjacent to the central tumor area could be demonstrated by NMR imaging increased lactate and moderately increased choline signals were measured in these regions. By histopathological examination these areas were shown to be infiltrated by single tumor cells. These observations indicate that image-guided 1H NMR spectroscopy could play an important role in the study of brain tumor biology, especially in the case of changing tumor metabolism during growth.

Topics: Animals; Aspartic Acid; Brain Neoplasms; Choline; Energy Metabolism; Glioblastoma; Humans; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Necrosis; Neoplasm Invasiveness; Neoplasm Transplantation; Phosphocreatine; Rats; Rats, Nude; Skin Neoplasms; Transplantation, Heterologous

We have used a rectangular surface coil and chemical shift imaging to conduct in vivo localized 31P NMR metabolic studies in a rat dorsal skin flap model. This approach permits regional comparisons without manipulation of either coil position or subject within the magnet bore. Both the PCr:Pi ratio (reflecting ischemia insult) and the PCr:ATP ratio (reflecting phosphagen reserves) decreased as functions of time and distance from the vascular pedicle. The maximum change was nearly 6-fold for the PCr:Pi ratio, and 3-fold for the PCr:ATP ratio. Signal contamination from subjacent muscle is constant and does not interfere with the metabolic evaluations of skin flaps. This technique may facilitate a better understanding of cutaneous metabolic derangements, such as burns and skin flaps used in reconstructive surgery, as well as studies of pharmacologic regimens developed for their treatment. It also holds potential for application in the study of congenital and neoplastic metabolic disorders of skin.

Topics: Adenosine Triphosphate; Animals; Burns; Energy Metabolism; Hempa; Ischemia; Magnetic Resonance Spectroscopy; Male; Models, Structural; Muscle, Skeletal; Phosphates; Phosphocreatine; Phosphorus Isotopes; Rats; Rats, Sprague-Dawley; Skin; Skin Diseases; Skin Neoplasms; Surgical Flaps; Time Factors

Phosphocreatine molecules (PCR) in skin regenerate adenosine triphosphate and help cutaneous tissue survive ischemia associated with skin flaps, grafts, and hair transplantation procedures. In addition, PCR concentration in psoriasis is elevated many times above normal, indicating either overproduction of PCR by mitochondrial creatine phosphokinase (CPK) enzymes or a defect in cytosol CPK enzymatic activity. Skin CPK isoenzymes, before this study, have not been identified. Herein, for the first time, cytosol CPK enzymatic activity was measured in normal and psoriatic, involved and uninvolved skin, skin tumors, and mouse skin and keratinocyte cell cultures. Creatine phosphokinase MM is the major isoenzyme in normal, uninvolved psoriatic and mouse skin. Total CPK enzymatic activity was increased in psoriasis and skin tumors. These data clearly indicate that increased PCR concentration in a psoriatic skin is not a result of decreased cytosol CPK enzymatic activity.

Topics: Adenosine Triphosphate; Animals; Cell Line; Creatine Kinase; Cytosol; Energy Metabolism; Humans; Isoenzymes; Keratinocytes; Male; Mice; Phosphocreatine; Psoriasis; Skin; Skin Diseases; Skin Neoplasms

Global blood flow (TBF), tumor vascular resistance, laser Doppler flow in superficial tumor areas, and mean arterial blood pressure were evaluated in rats bearing s.c. DS sarcomas. Measurements were performed before and after i.v. administration of rhTNF-alpha 2 or recombinant human lymphotoxin (rhLT) (1 mg/kg). Upon application of the cytokines a significant drop in TBF was found at t greater than or equal to 90 min with a stronger action following rhLT than rhTNF-alpha. At relatively constant mean arterial blood pressure values following the cytokine injection, the microcirculatory function in the tumor periphery was found to be impaired somewhat earlier than TBF, indicating that the cytokines do not preferentially act on the poorly perfused tumor center in the model chosen. This finding is inconsistent with previous histological studies on murine tumors. Acute flow changes encompassed only substantial reductions (i.e., hypoperfusion) rather than a complete ischemia. TBF was slightly increased during the first hour following rhLT whereas after rhTNF-alpha a continuous drop was observed. This differential response could not be observed during laser Doppler flowmetry. Tumor vascular resistance changes largely reflected alterations in TBF. 31P-Nuclear magnetic resonance spectroscopy on murine Meth-A fibrosarcomas revealed dose- and time-dependent decreases of ATP/Pi and phosphocreatine/Pi ratios following i.v. administration of rhTNF-alpha. From comparisons of dose-response curves rhLT appears to be more detrimental than rhTNF-alpha with respect to the bioenergetic status. The observed changes in tumor energy metabolism are similar to those described for TBF. It may therefore be concluded that most of the cytokine effects on the bioenergetic status are secondary to the inhibition of the microcirculatory function. As a major causative factor for the latter, an arterial hypotension can be excluded in the tumor model chosen.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Lasers; Lymphotoxin-alpha; Magnetic Resonance Spectroscopy; Methylcholanthrene; Mice; Mice, Nude; Phosphocreatine; Phosphorus; Rats; Rats, Inbred Strains; Regional Blood Flow; Sarcoma, Experimental; Skin Neoplasms; Tumor Necrosis Factor-alpha; Vascular Resistance

The metabolic response of the RIF-1 tumor to 5-fluorouracil (a single dose of 260 mg 5FU/kg, ip) was monitored in 10 mice using 19F and 31P MR spectroscopy. 19F MRS revealed a continuous drop in tumor 5FU level and an increase in the fluoronucleotide (Fnuc) signal to a plateau value of 50% of the initial 5FU level, during the first 2 h after chemotherapy. Although the 31P MR spectra of the tumors showed no significant initial changes, the total level of MR visible tumor phosphate decreased and tumor pH increased during the subsequent days. The changes in phosphate metabolism and tumor pH did not correlate with the detected fluorine levels or tumor response. However, the pretreatment Pi level, the plateau Fnuc level, and the 5FU induced decrease in tumor volume showed significant correlation. This indicates that both 19F and 31P MR spectroscopy have potential for predicting response to 5FU chemotherapy.

Topics: Animals; beta-Alanine; Female; Fibrosarcoma; Fluorine; Fluorouracil; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Phosphates; Phosphocreatine; Phosphorus; Regression Analysis; Remission Induction; Skin Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Energy Metabolism; Female; Humans; Magnetic Resonance Spectroscopy; Melanoma; Melphalan; Middle Aged; Neoplasm Recurrence, Local; Phosphates; Phosphocreatine; Skin Neoplasms