Bulletin Number Four 1985

epidemiology o f large-scale application. It offers almost unlimited research possibilities for scientists on campus and in Hong Kong and their overseas collaborators. As at present, requests for yuehchukene are plenty; WHO and the Biochemistry Department are carefully monitoring the situation as yuehchukene enters the course o f a new drug development. Studies of Energy Metabolism o f Cancer Cells —K.P. Fung It is a common phenomenon that cancer- bearing patients or experimental animals suffer from hypoglycaemia (low gl ucose in blood). Tumour cells depend primarily on the catabolic breakdown o f glucose for the provision o f energy. To maintain growth potential, it is essential that tumour cells should possess a highly efficient system for the transport o f glucose into the cell and to metabolize it. Based on this hypothesis, we began to study the glucose transport system o f cancer cells throughout proliferation and drug treatment. It is a common practice in medical science that before a drug is administered to human, pilo t tests on experimental animals or cell cultures should be performed. The animal model used in our studies is Ehrlich ascites tumour which grows in the abdomen o f mice and is one o f the commonest experimental animal models used in cancer research. The tissue cultures used in our research consisted o f various human, rat and mouse tumour cell lines. The first interesting observation we made was that the ability o f Ehrlich cells to take up glucose increased progressively during the course o f tumour development. Since the uptake o f glucose by cancer cells is mediated through a class o f molecules desig nated as ‘glucose carrier' on the membrane o f the cancer cells, we further studied the changes if any, in the number and characteristics o f the glucose carriers throughout tumour growth. We found that as the rate o f uptake o f glucose in tumour cells rose, the cell surface density o f these glucose carrier mol ecules also increased simultaneously. This enhance ment o f glucose uptake by cancer cells during tumour growth, through increases in the number o f glucose carriers, constitutes the primary cause o f hypo glycaemia seen in patients or experimental animals bearing cancer. We were also interested in knowing the mech anism underlying the increase in carrier density o f tumour cells during development. We hypothesized that a vicious circle might operate here. Tumour cells, in order to satisfy the hunger for glucose, elaborate a huge number o f carriers for its transport into the cell. This leads to a drop in the level o f blood glucose. And as the amount o f available glucose decreases, the tumour cell makes more glucose carrier molecules as a compensatory response. A series o f experiments showed that this is indeed the case. Furthermore, to our delight, when we studied the growth o f Ehrlich tumour cells in mice under fasting condition, we found that tumour regresses when the mice were starved. Of course, it is not a practice to starve a cancer patient in order to cure him o f cancer, but, fasting tumour-bearing mice provide a good experimental animal model for studying o f what makes a tumour cell tick. A logical question to ask at this point is how do anti-cancer agents fit into this scheme o f things? We studied a wide spectrum o f anti-cancer agents including garlic, methotrexate, N-(phosphonacetyl)- L-aspartate, interferon-inducers and tumour necrosis factor (TNF). O f particular interest is TNF. TNF is a protein produced by macrophages (large cells capable o f engulfing foreign particles and cells including bacteria) o f the host. It is special in that it is capable o f k illin g tumour cells while leaving normal cells untouched. It also exhibits no species-specificity, i.e. even TNF produced from mice can have an effect on human tumour cells. We developed a new method for the large-scale production o f TNF to facilitate our studies and observed that TNF, as expected, inhibits the proliferation o f tumour cells. As the growth rate decreased, the cellular uptake o f glucose (and the glucose carrier density on the cell surface) were found to be reduced simultaneously. We do not know yet how TNF does this but we plan to find out. Our ultimate goal is to find ways to k ill tumour cells effectively. TNF seems to be a candidate worthy o f pursuit. However, TNF has been shown to have but a short life span in circulation — it gets degraded easily. This severely curtails its effectiveness as a therapeutic agent. We are working to overcome this deficiency. By modifying its structure, by com plexing it w ith other molecular entities, we hope to increase the life span o f TNF w ithout diminishing its activity. The research project on the effect o f anti- tumour agents on the glucose transport system o f tumour cells was started in 1981 in the Department o f Biochemistry w ith financial support from World Health Foundation (H.K.). ( 3 ) Research e ffo rts o f the Physics Depa rtmen t Physics of Proteins —K .C. Cho Protein molecules are, in many respects, the most remarkable chemical substances in living organ isms. Functionally, they play two separate and distinct 24 RECENT DEVELOPMENTS