Cancer human intervention studies

Phytochemicals have been the subject of many studies evaluating their effects in relation to common chronic human illnesses such as cancer and cardiovascular diseases. These studies encounter difficulties in using this information to influence the dietary patterns of consumers because in the past they have used models or experiments with animals. However, in the last decade, researchers have moved away from animal studies in favour of human cell models or human intervention studies. Scientists still need to determine the likely incidence of illness from exposure to known amounts of a given natural compound in the diet and specifically in relation to the complex matrices of whole foods. Therefore, it is inevitable that some animal studies have to be continued for toxicological studies. 

There has been some success with vitamin A and its derivatives for treatment of certain types of cancer (Niles, 2000). However, the use of P-carotene as a therapeutic agent suffered a setback when the results from two of three large human intervention studies indicated that high doses of P-carotene caused an increased risk of lung cancer in smokers and subjects exposed to asbestos. This increased risk is thought to be due to metabolites associated with high doses of p-carotene in the presence of smoke (Russell, 2004). 

Despite the epidemiological evidence for beneficial health effects of soy consumption, the safety of soy and its constituent isoflavones has been questioned. Concerns have mairrly arisen from animal and in vitro studies, but also a few human intervention studies relating to BC risk, which suggest that isoflavones may be involved in estrogen-sensitive cancer development, th5Toid dysfunction, and reduced fertility. 

With increasing interest in undertaking animal experimental and human clinical and intervention studies to evaluate the role of lycopene in cancer prevention, it is important that well-established molecular and clinical markers of cancer be used in these studies. In general, the main clinical end points used in animal and human experiments are the tumor burden and volume and survival rates. Now that our understanding of cancer pathology has advanced, several molecular events are beginning to be recognized and used in research to evaluate the outcomes from intervention studies. A brief overview of some of the more important molecular markers of cancer that can and should be used in future studies is presented in this section. 

Following this experimental design, approximately 700 plant materials have been evaluated and this has resulted in over 6,500 bioassay results. A number of active principles have been obtained that are active with the in vitro test systems, and several of the isolates have retained activity by preventing formation of preneoplastic lesions in mammary organ culture. Thus far, three lead compounds have been shown to mediate considerable cancer chemopreventive activity in full-term tumorigenesis models (28,34,45,46) and are being studied in more advanced test systems. We remain hopeful that one or more discoveries resulting from this project will be deemed worthy of human intervention trials. 

Human Intervention Trials In several human intervention trials, significant cancer-preventive effects of supplemental selenium have already been demonstrated, and several other studies are pres-... 

From the literature reviewed in the present chapter, it appears that lycopene is an important compound in coimection with the onset and the progression of cancer. Important epidemiological studies have traced the path that has been followed by the first clinical interventions and by the animal studies. Cellular mechanisms have appeared as well to show that the human and animal results are based on specific molecular events correlated with regulation of the cell cycle. An additional step in understanding the... 

To investigate the incorporation of CLA into membrane PL, we conducted an intervention study with 5 human volunteers in which the effects of two dietary levels of TFA on TFA and CLA contents in the PL classes of human erythrocytes was examined as an indicator of TFA desaturation to CLA in vivo (Hoffmann, K., et al., submitted for publication). The bioconversion of TFA to CLA is of interest as the current intake of CLA, estimated to be 350-430 mg/d (35), is lower than intakes associated with beneficial health effects in animal and human studies. Two recent studies proposed that the bioconversion of VA to CLA is as important for cancer prevention as the dietary supply of preformed CLA (36,37). 

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