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W T Evanochko

Publications and source records attributed to W T Evanochko.

30 records · Page 2Linked to original sources
PubMed1984

NMR study of in vivo RIF-1 tumors. Analysis of perchloric acid extracts and identification of 1H, 31P and 13C resonances.

Perchloric acid extracts of radiation-induced fibrosarcoma (RIF-1) tumors grown in mice have been analyzed by multinuclear NMR spectroscopy and by various chromatographic methods. This analysis has permitted the unambiguous assignment of the 31P resonances observed in vivo to specific phosphorus-containing metabolites. The region of the in vivo spectra generally assigned to sugar phosphates has been found in RIF-1 tumors to contain primarily phosphorylethanolamine and phosphorylcholine rather than glycolytic intermediates. Phosphocreatine was observed in extracts of these tumor cells grown in culture as well as in the in vivo spectra, indicating that at least some of the phosphocreatine observed in vivo arises from the tumor itself and not from normal tissues. In the 31P-NMR spectra of the perchloric acid extract, resonances originating from purine and pyrimidine nucleoside di- and triphosphate were resolved. HPLC analyses of the nucleotide pool indicate that adenine derivatives were the most abundant components, but other nucleotides were present in significant amounts. The 1H and 13C resonance assignments of the majority of metabolites present in RIF-1 extracts have also been made. Of particular importance is the ability to observe lactate, the levels of which may provide a noninvasive measure of glycolysis in these cells in both the in vitro states. In addition, the aminosulfonic acid, taurine, was found in high levels in the tumor extracts.

Animals↗
PubMed1984

Application of in vivo NMR spectroscopy to cancer.

A critical review is presented of NMR spectroscopic studies of isolated tumor cells, excised tumors, and in vivo tumors. Although the majority of the studies examined deal with 31P NMR spectroscopy, the potential utility of multinuclear NMR investigations is emphasized. A major theme of this review is the evaluation of the potential applications of in vivo NMR spectroscopy to experimental tumor biology and to the clinical diagnosis and management of cancer. Data are presented demonstrating that this method may prove useful in distinguishing between relatively well vascularized aerobic tumors and poorly vascularized hypoxic tumors. This could provide a basis for identifying tumors responsive to X radiation or hyperthermia. Preliminary experiments point to the possibility that in vivo NMR spectroscopy will be capable of detecting tumor response to chemotherapy, X radiation, and hyperthermia and may also detect drug-induced toxicity to tissues vital to the survival of the host.

Animals↗
PubMed1984

Loss of high-energy phosphate following hyperthermia demonstrated by in vivo 31P-nuclear magnetic resonance spectroscopy.

We have used in vivo 31P-nuclear magnetic resonance spectroscopy to study the changes in high-energy phosphates following hyperthermia. Immediately after heating, there is a fall in adenosine triphosphate and apparent intracellular pH and an increase in inorganic phosphate. Following sublethal heating (40 degrees for 15 min), these changes were partial, and they resolved over the subsequent 45 hr. With tumors given severe hyperthermia (47 degrees for 15 min), there was complete disappearance of adenosine triphosphate, with no recovery by 24 hr posttreatment. Qualitatively similar effects were seen after heating of normal leg muscle. The degree of fall of the adenosine triphosphate/inorganic phosphate concentration ratio was directly proportional to the heat dose and to thermal cell kill. 31P-Nuclear magnetic resonance spectroscopy may be useful in thermal dosimetry and treatment evaluation following hyperthermia.

Animals↗
PubMed1983

Detection of antineoplastic agent induced cardiotoxicity by 31P NMR of perfused rat hearts.

Development of dose dependent chronic irreversible cardiotoxicity is a key problem encountered in chemotherapy with adriamycin. Here it has been demonstrated that infusion of this agent produced distinct and largely irreversible changes in levels of phosphate metabolites and substantial acidosis that are detected by 31P NMR of the Langendorf perfused heart. Administration of the antioxidant, butylated hydroxytoluene minimizes these spectral changes but does not substantially diminish the antineoplastic activity of adriamycin. Bisantrene (CL 216,942), a noncardiotoxic anthracene with antineoplastic activity, produces only minor perturbations of the 31P spectrum of the perfused rat heart. These studies demonstrate the potential utility of employing 31P NMR to monitor acute or chronic cardiotoxicity in the perfused rat heart and for developing noninvasive in vivo NMR techniques for monitoring cardiotoxicity in experimental animals and humans.

Animals↗
PubMed1983

In vivo 31P NMR study of the metabolism of murine mammary 16/C adenocarcinoma and its response to chemotherapy, x-radiation, and hyperthermia.

(31)P NMR spectroscopy with surface coils has been used to monitor, in vivo, the phosphate metabolism of subcutaneously implanted mammary 16/C adenocarcinoma in C3H/He mice. This model tumor was studied during untreated tumor growth and after treatment with adriamycin, hyperthermia, and x-radiation. The mammary 16/C tumor exhibited a Gompertzian growth pattern. Levels of high-energy phosphate metabolites-phosphocreatine and ATP-decreased with increases in tumor mass. There was a concomitant increase in the level of P(i) and a decrease in the apparent pH of the tumor. These spectral changes appear to reflect changes in tumor vascularization that accompany tumor growth, the tumor becoming progressively more hypoxic. Partial response of this tumor to chemotherapy with adriamycin was reflected in a small but measurable increase in the phosphocreatine resonance, a decrease in P(i), and a return of the intra-tumor pH to neutral. Hyperthermia resulted in progressive conversion of the (31)P NMR spectrum to that of a dead tumor (high levels of P(i), small levels of residual sugar phosphates and pyridine dinucleotides, and acidic pH). X-irradiation (14.0 Gy) led to disappearance of the phosphocreatine peak within 15 min of treatment. Subsequently, this resonance grew back beyond its pretreatment level. As the tumor receded, its spectrum reflected the characteristics of aerobically metabolizing tissue (high levels of phosphocreatine and ATP and low levels of P(i) and sugar phosphates).

Adenocarcinoma↗
PubMed1982

Growth of Lactobacillus casei in deuterated media. Purification of deuterated thymidylate synthase and proton nuclear magnetic resonance studies.

The purification of thymidylate synthase from amethopterin-resistant Lactobacillus casei grown in a deuterated medium is described. The deuterated enzyme and the non-deuterated enzyme appear to be identical with respect to specific activity, pH optimum, electrophoretic mobility on polyacrylamide gels and ability to form ternary complexes with 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5,10-methylenetetrahydrofolate. The deuterated enzyme remained stable at 25 degrees C for 8 h during the acquisition of 400 MHz 1H-NMR spectra and was stored at 5 degrees C for 3 months without loss of catalytic activity. The incorporation of deuterium was essentially complete as demonstrated by a comparison of the NMR spectra of deuterated and non-deuterated enzyme. Proton NMR data obtained with deuterated thymidylate synthase and 1H-FdUMP are in agreement with the fluorine-19 NMR studies of Lewis et al. (Lewis, C.A., Jr., Ellis, P.D. and Dunlap, R.B. (1980) Biochemistry 19, 116-123) which support the formation of a binary complex where the enzyme is covalently linked to carbon 6 of 5-fluoro-5,6-dihydro-2'-deoxyuridylate.

Deuterium↗
PubMedDate not supplied

Potential approaches to evaluating the cardiovascular system using NMR.

The current status and some of the future possibilities for nuclear magnetic resonance imaging of the cardiovascular system have been described. With many of these possibilities there is overlap with existing techniques. For example, functional analysis of the left ventricle can be obtained using either echocardiography or radionuclide techniques. With current instrumentation and current costs, these conventional techniques could frequently provide a more cost-effective approach for morphologic and functional assessment of the cardiovascular system. Nevertheless, because of the excellent resolution, the inherent contrast, the sensitivity to blood motion, the three-dimensional nature, and the lack of ionizing radiation, the cardiovascular morphologic imaging capabilities of NMR may provide justification for such applications. However, for NMR to achieve its most important status as a cardiovascular imaging technique, some of its unique possibilities will need to be developed. These include the ability to reproducibly depict the proximal coronary arteries, to define regional myocardial blood flow distribution, to evaluate regional high energy phosphate or other metabolic activity; and to characterize myocardial disease using proton T1 and T2 alterations.

Animals↗