European Journal of Cancer: Highlights of Issue 37:13

Do slowly proliferating gastric tumours have a worse prognosis than those that rapidly proliferate?

It was, until recently, a widely believed, and perhaps logical, concept that rapidly proliferating tumours are generally of a more aggressive nature and thereby associated with a worse prognosis. However, data from studies examining the relationship between proliferation kinetics and clinical outcome have been contradictory. Moreover, evidence is emerging in the field of cancer kinetics that the reverse may be case, at least for some tumours. Sendler and colleagues provide some preliminary data to support this hypothesis in a study of n=111 tumour samples from resected gastric cancer patients. The patients were given 200mg intravenously of Bromodeoxyuridine (BrdU) pre-operatively and tumour samples were analysed, using flow cytometry, for DNA ploidy, the proportion of cells in S phase, the BrdU labelling index (LI), the DNA synthesis time, the potential tumour doubling time (Tpot) and the proliferating cell nuclear antigen (PCNA) and Ki-67 LIs. In multivariate analysis, only Tpot and tumour stage were significantly associated with survival. Furthermore, in a classification and regression trees (CART) analysis for the stage I, II and IIIA tumours, a shorter Tpot (< and =3.8 days) was associated with a better survival (5-year survival of 93% compared with 49% for those with a Tpot >3.8 days; P=0.013). Further work is eagerly awaited on this interesting observation.

The drug or the vehicle-which is the culprit?

In the development of new anti-cancer drugs, one of the major problems that has to be overcome is obtaining an adequate drug solubility for agents that are poorly water-soluble. For this purpose, agents are often formulated with various vehicles. In this issue, Gelderblom and colleagues discuss this area with a particular emphasis on the use of Cremophor EL. This vehicle is a heterogenous non-ionic surfactant that is commonly used in the formulation of the anti-cancer agent paclitaxel. However, as the authors discuss, although previously thought to be inert, it is likely that Cremophor EL, rather than the anti-cancer agent itself, is responsible for some of the major side-effects, such as the hypersensitivity reactions, that are often observed following the use of paclitaxel-containing chemotherapy regimens. This review, therefore, clearly underlines the importance of understanding the biological and pharmacological effects of such vehicles during new drug development and points to the need to develop new formulation approaches.

Does decreased Bid expression protect HCC cells from apoptosis?

Bid is a member of the Bcl-2 family of proteins that are known to have both pro- and anti-apoptotic functions. Deregulation of members of this family is thought to be linked to the progression of many different cancers. In this issue, Chen and colleagues show that both the mRNA and protein expression levels of Bid, a pro-apoptotic member of the family, are reduced in hepatocellular carcinoma (HCC) tumour tissues when compared with the corresponding non-cancerous tissues. This leads the authors to speculate that by downregulating Bid, HCC cells are able to proliferate uncontrollably, possibly by bypassing the Fas-induced apoptotic pathway. Furthermore, although preliminary, transfection experiments suggest that the HBV x protein may be involved in this reduction of Bid expression, an interesting observation given that the virus is known to be associated with the development of HCC.

Back . . .