What's new in proliferation and differentiation in malignant tumours?

The volume of a tumour is the difference between the integrals of cell production and cell loss. Cell production depends on mitosis. Cells are lost by detachment from external surface, loss into blood vessels and lymphatics and into body cavities. Immunological lysis, macrophagia and apoptosis take place, and there is necrosis due to hypoxia. Cell birth can be measured, cell loss must be calculated. Tumour cells differentiate and mature to varying degrees. An inverse relationship between maturation and proliferation exists. DNA synthesis inhibitors often also induce differentiation. Retrodifferentiation does not take place. Immature tumours are undifferentiated because of a population change, not because of retrodifferentiation. The oncogene theory assumes that proto-oncogenes are part of the normal genome. They can be activated to oncogenes by mutation or by loss of regulatory factors. Oncogenes code for important membrane proteins: growth factors or receptors. It has been proposed that anti-oncogenes also exist, coding for inhibitory growth factors like chalones. Much attention has hitherto been directed to attempts at arresting the birth rate of cells by cytostatic drugs. There is a trend in modern research to find substances that can force the cells into maturation. Lithium, DMSO, vitamin-analogues, human post-endotoxin serum, TPA, 4 NQO, hormones and acetamide have been shown to induce maturation in experimental systems. This area of research is presently gaining considerable impetus.