Abstract
Glutamine is an abundant and versatile nutrient that participates in energy formation, redox homeostasis, macromolecular synthesis, and signaling in cancer cells. These characteristics make glutamine metabolism an appealing target for new clinical strategies to detect, monitor, and treat cancer. Here we review the metabolic functions of glutamine as a super nutrient and the surprising roles of glutamine in supporting the biological
hallmarks of malignancy. We also review recent efforts in imaging and therapeutics to exploit tumor cell glutamine dependence, discuss some of the challenges in this arena, and suggest a disease-focused paradigm to deploy these emerging approaches.
Introduction
It has been nearly a century since the discovery that tumors display metabolic activities that distinguish them from differentiated, non-proliferating tissues and presumably contribute to their supraphysiological survival and growth (1). Interest in cancer metabolism was boosted by discoveries that oncogenes and tumor suppressors could regulate nutrient metabolism, and that mutations in some metabolic enzymes participate in the development of malignancy (2, 3). The persistent appeal of cancer metabolism as a line of investigation lies both in its ability to uncover fundamental aspects of malignancy and in the
Most cancers require treatments like radiotherapy and chemotherapy in the end. And radiotherapy and chemotherapy cause very great damage to our body especially mucosa cells damaged. If a patient has head or neck cancers, radiotherapy or chemotherapy might cause oral mucositis or diarrhea. Radiotherapy and chemotherapy can causes damage on the mucosa. If the patient has radiotherapy and chemotherapy on intestine and stomach, serious damage on intestinal mucosa might occur. Radiotherapy and chemotherapy may further cause diarrhea or intestinal bleeding. There was a lot of researches on those patients, given glutamine supplementation under these symptoms. The results was inconsistent. Some researches show that the improvement was not obvious, while some researches showed there is a significant improvement.
Nevertheless, glutamine is still the main energy source of the mucosal cell. Theoretically, supplying a huge amount of glutamine is helpful for mucosa cell in the reproduction, growth, and repair. Some researches do support this argument that after supplying the glutamine, the recovery of mucosa improved outstandingly.
This is an article about glutamine trial.
In this research, fierce debates were carried out: whether to supply patients with critical illness with glutamine. Why there are fierce debates? Because the result shows that glutamine supplementation had a negative impact on patients with critical illnesses. A lot of doctors suspended the supplement of glutamine to the patients with critical illness since then. This study was an international experiment and included data from 40 intensive care units from different nations. It is a very large-scale research. The research subjects were patients with critical illness and have to meet strict conditions. The conditions were patients with critical illnesses and multiorgan failure and were admitted to the intensive care unit, and rely on respirators to survive.
So, we could imagine that those patients who meet the condition of research were already in a severe situation. After admitted to the ICU within 24 hours, they will be supplemented with glutamine. Of course, control groups and tested groups are separated. Some groups were give glutamine and others were not. And some groups were given antioxidant nutrients instead of glutamine. In summary, researchers compared the impact on those patients with or without the supplement of glutamine. What was the outcome? They’ve found that group given with high dose of glutamine via intravenously or orally doesn’t gain much benefits from supplementation. On the contrary, the death rate of patients with multiple organ failure only increased.
In the previous chapter, we talked about the benefits of glutamine for post-surgery patients, infected patients or patients in an inflammatory condition. But the outcome of this study tells a whole different story, that supplementation of glutamine has no advantage on the patients with critical illness. Instead, glutamine supplementation increased the death rate of patients with multiple organ failure. The result of this research caused the doctors with great concerns on the application of glutamine. Because the supplementation of glutamine increased the death rate of the patients with critical illness. But the authors had also explained that the subjects from the experiments trials have different critical diseases and thus may have affect results. So, why glutamine supplementation had a negative result here?
Possible reason is that the research team subjected those patients with more than two organ failures. For those patients with multiple organ failures, their body might not able to cope with the absorption and application of the huge amount of glutamine given. Because glutamine is also an amino acid, after it enters into the body, we need to rely on our liver and kidney to have glutamine metabolized as well as excretion reaction. What if the patients had poor liver and kidney functions? These patients aren’t able to fully utilize the provided glutamine. And some patients may also have poor gut function that unable to absorb these glutamine. Although given with a high dosage of glutamine, patients’ body absorbability were still limited.
Abstract
Background: Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting.
Methods: In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance.
Results: There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).
Conclusions: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.).
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