LNT-229 human glioma cells 은 gastric adenocarcinoma 에 비해서 non-necrotic tumor 를 만든다.
Necrotic tumor 는 dietary restriction 에 훨씬 민감한데 이것은
necrotic areas 가 훨신더 제한된 nutrients와 oxygen 을 갖기 때문이다.
제한된 oxygen 하에선 자연히 glycolysis 를 통한 에너지 생산에 의존해야 살아갈수 있다. 결국
Hypoxic tumor cells 은 특히 더윽 glucose availability 에 의존하기 때문에
carbohydrates 의 제한은 이런 종양에 효과가 좋은 치료법일수 있다
그래서 gastric adenocarcinoma 는 dietary restriction 에 더욱 취약하다
참고자료 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199865/
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A reduction of tumor growth under conditions of caloric restriction and/or weight loss has repeatedly been shown in glioma models [17,18]. However, we rarely observe chemotherapy-associated (unintended) weight loss in brain tumor patients and a non-calorie-restricted ketogenic diet might be more easily realized than calorie restriction. We therefore performed an in vivo experiment using an unrestricted ketogenic diet. The diet was well accepted, and no significant differences developed in body weight between the two diet groups (Figure (Figure5A).5A). Further, glucose concentrations and IGF-1 levels did not differ substantially between the groups (Figure 5B,Table Table4).4). These results are consistent with prior analyses showing no decline in blood glucose concentrations when a ketogenic diet was administered in unrestricted amounts [18,31,69]. According to other studies [17,69,70], a reduction in circulating IGF-1 levels would have been expected only under conditions of caloric restriction. Thus, the stable values of body mass, glucose and IGF-1 help to distinguish between possible starvation-associated effects and other metabolism-specific effects of the ketogenic diet. Finally, the ketogenic diet alone did not influence tumor growth in the glioma model used (Figure (Figure6A);6A); tumor histopathology and metabolic mapping revealed no differences between mice fed the ketogenic diet and control animals (Figure (Figure7).7). Although these results are consistent with those obtained in other syngeneic (CT-2A) and xenogeneic (U87MG) glioma mouse models [18], they contrast with the findings of Otto et al. where a diet identical to the one used in our in vivo experiment significantly decreased the growth of subcutaneously implanted tumors of the gastric adenocarcinoma cell line 23132/87 [31]. The different results of the latter and our study most likely reflect intrinsic properties of the cell lines used. In contrast to the gastric adenocarcinoma cell line, LNT-229 human glioma cells usually form quite homogeneous non-necrotic tumors. Necrotic tumors might be more susceptible to dietary restriction, as the necrotic areas in those tumors reflect the already limited supply of nutrients and oxygen. Since hypoxic tumor cells particularly depend on glucose availability [37], limiting carbohydrates might be effective in these tumors. The downregulation of ketone body metabolizing enzymes under hypoxic conditions observed in our cell lines (Figure (Figure3A)3A) suggests an additional disadvantage of this hypoxic tumor fraction. Another possible explanation may be a differential energy supply of subcutaneous and intracranial tumors. The mouse brain cells could have adapted to metabolize ketone bodies, leaving enough glucose to meet the xenografts' energy requirements. Using a different unrestricted ketogenic diet and the GL261 syngeneic intracranial glioma mouse model, Stafford et al. found a reduced rate of tumor growth and prolonged survival [71]. Likewise, GL261 tumors display necrotic zones [72]. Obviously, the impact of ketosis and hence the results of such studies depend on the model applied.
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