Bulletin Autumn‧Winter 1997
HlGHLIGHTS OF RGC-FUNDED PROJECTS easily transmitted. Hypermotherapy can, however, be made more effective by being used in combination with radiotherapy and chemotherapy. What is the underlying mechanism of hyperthermia on tumour cells? Prof. C.Y. Lee and Prof. K.P. Fung of the Department of Biochemistry began investigating the issue in 1991. Their project, T h e Effect of Hyperthermia on Tumour Cells', received a grant of HK$350,000 from the Research Grants Council and was rated ‘excellent’ by the council in late 1996. Reaction of Tumour Cells to Hyperthermia Human cells thrive best at 37°C, the normal human body temperature. Results in recent studies indicate that normal cells continue to thrive under temperatures as high as 45°C and beyond. In contrast , the growth of many tumour cells is suppressed at 43°C. The t emp e r a t u re u s ed i n hyperthermia is, therefore, set at 43°C. It is not clear why normal cells have a greater tolerance for heat than tumour cells. But it is known that when treated with heat, normal cells produce high quantities of a class of protein k n own as 'heat shock proteins' which serve to protect the integrity of other proteins in the cell by maintaining their three-dimensional structures, and hence, their functions. The ability of tumour cells to produce 'heat shock proteins', however, is found to be greatly reduced under hyperthermia. Led by Profs. Lee and Fung, the research team investigated, from a biochemical angle, why tumour cells die at high temperatures, and the changes in cells produced by hyperthermia. The team studied the effect of hyperthermia at 4 l ° - 43°C on the cells of various tumours, including human breast tumour, glioma, leukaemia, and hepatoma, as well as Ehrlich ascites tumour and sarcoma in mice. Three main biochemical changes were observed. Investigators Prof. Lee Cheuk-yu received his Ph.D. from the University of British Columbia in Canada. He was postdoctoral fellow and later assistant professor at the New England Institute, USA, before joining the CUHK Department of Biochemistry as lectuer in 1972. He was promoted to professorship in January 1985. Prof. K.P. Fung received his Ph.D. in microbiology from the University of Hong Kong in 1978. He joined the Department of Biochemistry of The Chinese University of Hong Kong as assistant lecturer in 1978. He was promoted to lectureship in 1979, senior lectureship in 1987, and readership in 1995. Suppressed Glucose Transport in Tumour Cells Glucose is a major nutrient for living organisms, and tumour cells are especially dependent on glucose for growth and division. In normal cells, glucose is taken into the cell w i t h the aid of glucose transporters on the cell membrane. Once inside the cell, it is oxidized in the cytoplasm and mitochondria through a series of reactions to produce energy. In tumour cells, however, the number of mitochondria is relatively small, and the oxidation of glucose often cannot proceed to completion. The tumour cells thus try to compensate by making more glucose transporters to boost glucose intake. The researchers found that hyperthermia significantly suppresses glucose transport in tumour cells through reduced transporter synthesis. Faced with an insufficient energy supply, the tumour cells undergo a 'programmed cell death'. Increased Acidity in Tumour Cells The acidity of body fluids is rigidly controlled. The metabolic functions of human cells proceed optimally at pH 7.4. Small changes in this value by even 土 0.2 units to 7.2 or 7.6 can cause great physical A Heated Combat 21
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