| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
Re-proliferation of radiation-resistant hypoxic cells has been considered to be the primary reason for many cases with the recurrence of tumors after radiotherapy. We attempted to quantify the amount of oxygen in tumor cells by perfusion imaging (^<31>P-MRS and MRI) and hypoxic cell imaging using a radio-labeled marker, with the objective of exploring a biologically optimum method of radiotherapy. The study was also designed to clarify the relationship between the presence of cancer-related gene mutations and tumor hypoxia. Particular attention was paid to examining how the presence of mutations of the p53 gene (a gene associated with apoptosis) might be affected by a low oxygen environment in the tumor.
Noninvasive evaluation of tumor hypoxia is expected to allow prediction of responses of tumors to treatment and estimation of the probability of distant metastasis. We, therefore, attempted various methods for evaluating the hypoxia in experimental tumors. It appeared that quantitative
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evaluation of tumor hypoxia using β-D-IAZGP (a marker of low-oxygen cells) was more useful than direct measurement of the oxygen levels within the tumor using electrodes, or the method using ^<31>P-MRS, because the adverse effects were less severe and evaluation of the tumor uptake of the marker was possible irrespective of the size of the tumor. In cases of cervical cancer, reduced tumor oxygen tension, as determined by our method, was found to be correlated with the tumor responses to treatment. HIF-1(hypoxia-inducible factor 1) overexpression in cervical cancer tissue was identified as a factor associated with poor prognosis, and significantly correlated with the presence of distant metastasis. Analysis of the expression of apoptosis-related factors (p53,p21,BAX,etc.) in addition to that of HIF-1 in patients with advanced esophageal cancer receiving chemoradiotherapy revealed that HIF-1 expression was more closely correlated with the initial therapeutic response than that of any other factors. These results suggest that analysis of hypoxic conditions in the tumor rather than analysis of p53-mediated apoptosis may allow better anticipation of the tumor responses to treatment. Less
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