摘要:

AbstractMRS defines the molecular state of water, the chemical environment of cells and tissues and the qualitative and quantitative state of intermediary metabolism. Because cancer has disordered physiology, obvious differences in MR spectra can be observed. However, the detailed understanding of the biochemistry of cancer will also emerge from careful, quantitative multinuclear MR. The intermediary metabolism of ATP, the Krebs cycle, creatine, cholines and lipids, is discussed. Finally, the biochemical challenge posed by oncogenes may be amenable to MR analyses.

ISSN:0952-3480    

DOI:10.1002/nbm.1940050504

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractIt is generally accepted that tumour microcirculation, blood flow, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status—factors which are usually closely linked and which define the so‐called metabolic microenvironment—can markedly influence the therapeutic response of malignant tumours to conventional irradiation, chemotherapy, other non‐surgical treatment modalities, and the cell proliferation activity within the tumours. Currently available information on the parameters defining the metabolic micromilieu in human tumours is presented in this paper. According to these data, significant variations in these relevant factors are likely to occur between different locations within a tumour, and between tumours of the same grading and clinical staging. Therefore, evaluation of the metabolic microenvironment in individual tumours before therapy and a corresponding ‘fine‐tuning’ of treatment protocols for individual patients may result in an improved tumour response

ISSN:0952-3480    

DOI:10.1002/nbm.1940050505

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractNMR methods are being applied to study phospholipid metabolism of cancer cells by monitoring the resonances which appear in the31P spectrum. This review, aside from considering the applicability of NMR to this specific pathway, raises the question of whether the phospholipid metabolite peaks observed by MR are indicators of cancer cell function or tumor response to treatment. After assessing the results from many investigations, it is concluded that there is no clear correlation and that a combination of techniques, includingin vitroand extract studies, will be necessary for a more comprehensive evaluation of thein vivodata.

ISSN:0952-3480    

DOI:10.1002/nbm.1940050506

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe technologies available for assessing the size and physiological status of malignant tumours are becoming more and more sophisticated. Some of these detect phenotypic biochemical alterations resulting from the genetic changes associated with malignant transformation. Many, however, monitor the abnormal relationship between the tumour mass and the host, detecting pathophysiological changes which result from the host/tumour interaction. The most important of these involve the microregional heterogeneities of nutrients resulting from diffusion patterns around abnormal, newly‐formed vascular networks, or inflammatory or immune responses of the host to the tumour. In order to validate new technologies for introduction to clinical medicine they are usually extensively tested in experimental models for cancer. The relevance of these models (whetherin vitrocell cultures or experimental tumours) must be considered carefully at the outset, with the factors that influence the parameter being measured, e.g., oxygen or energy status, being given special attention. The genetic similarity of tumour and host, the site of tumour growth, the size of the tumour, the burden it imposes and the immunocompetence of the host are all important features of the experimental model. Inappropriate models may give totally misleading information which cannot be extrapolated to human cancer

ISSN:0952-3480    

DOI:10.1002/nbm.1940050507

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractMethods of spectral localization are briefly reviewed and divided into two classes: those using phase encoding and those using frequency selective RF pulses in a constant gradient. A potentially troubling artifact in the latter case is the spatial misregistration of different compounds which causes serious errors in31P spectra from smaller regions. Chemical shift imaging (CSI) is presented as a typical example of phase encoding techniques. An analytical expression for the relationship of the signal observed to the true signal (the point spread function) is derived. Examples of CSI in one, two, and three dimensions are used to illustrate the principles of this type of localization.

ISSN:0952-3480    

DOI:10.1002/nbm.1940050508

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractFactors affecting the selection and application of localization methods for measuring tumours by NMR spectroscopy are considered, with particular regard to the S/N ratio and to contaminating signal from outside the volume of interest. Methods of assessing the performance of localization techniques are considered, and their importance for quantitative measurements and comparative studies is discussed.

ISSN:0952-3480    

DOI:10.1002/nbm.1940050509

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractLocalized proton NMR spectroscopyin vivoallows focal studies of cerebral metabolites in both man and laboratory animals from image‐defined regions as small as 1 mL or 64 μL, respectively. Although brain tumours lead to remarkable spectral alterations relative to normal brain, a number of problems may compromise the interpretation of the results. Potential complications arise from the chosen experimental conditions (method,TE, size and location of volume of interest), from regional metabolic heterogeneity in and around tumours, from differences between human tumours and animal models, and from discrepancies betweenin vivoandin vitrofindings. Strategies and pitfalls are illustrated with use of selected examples from primary brain tumours, a rat tumour model and perchloric acid extracts of resected specime

ISSN:0952-3480    

DOI:10.1002/nbm.1940050510

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe regional distribution of ATP, glucose, lactate and tissue pH was studied by bioluminescence and fluoroscopic imaging of intact cryostat sections of implantation tumors of cat. In tumors, marked heterogeneity of metabolites and pH was present: in solid parts ATP was similar to normal brain but glucose tended to decrease with an increase in lactate and pH to above normal; in necrobiotic regions ATP declined and pH became acidic. In peritumoral edema, ATP was consistently decreased whereas glucose, lactate and pH increased above normal. Correlation of ATP with water revealed an inverse relationship both in tumor and peritumoral edema but correlation of water with pH was direct in edema and inverse in tumors. The associations and dissociations of lactate, ATP and pH are interpreted in terms of aerobic and anaerobic glycolysis, as well as in respect to the extracellular localization of tumor edema. The findings are of relevance for the interpretation of volume selective NMR spectra and stress the importance of precise volume localization for differentiating between edema and tumor‐mediated metabolic alteration

ISSN:0952-3480    

DOI:10.1002/nbm.1940050511

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractAs positron emission tomography (PET) is outside of the main theme of this conference, it is necessary to outline what it offers as a method for assessing tissue functionin vivo.This is followed by illustrations of how PET has and is being used to study the physiology and biochemistry of tumours and pharmacokinetics and pharmacology of anticancer agents. Strategies are offered as to how PET may be used for the development of new chemotherapeutic agents.

ISSN:0952-3480    

DOI:10.1002/nbm.1940050512

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractIn the rational development of anticancer drugs it is important to employ all the available pharmacological information. Early clinical trials provide an opportunity for hypothesis testing. MRS techniques have the potential to provide valuable data on the preclinical and clinical pharmacokinetics and pharmacodynamics of drugs non‐invasively. Here we illustrate advantages and pitfalls of MRS using studies of two fluorine‐containing cancer drugs: a β,β‐difluoro analogue of the alkylating agent chlorambucil and a fluorinated derivative of the nitroimidazole misonidazole, Ro 07–0741. Limitations include signal quenching via protein binding and inadequate sensitivity for more potent drugs like β,β‐difluorochlorambucil; but fluoromisonidazole was shown to accumulate in tumours and shows promise as a chemical probe for tumour hypoxia, detecta

ISSN:0952-3480    

DOI:10.1002/nbm.1940050513

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY