Tumor cell culture survival following glucose and glutamine deprivation at typical physiological concentrations

ObjectiveMost glucose (and glutamine)-deprivation studies of cancer cell cultures focus on total depletion, and are conducted over at least 24 h. It is difficult to extrapolate findings from such experiments to practical anti-glycolytic treatments, such as with insulin-inhibiting diets (with 10%–50% carbohydrate dietary restriction) or with isolated limb perfusion therapy (which usually lasts about 90 min). The aim of this study was to obtain experimental data on the effect of partial deprivation of d-glucose and l-glutamine (to typical physiological concentrations) during 0 to 6-h exposures of HeLa cells.MethodsHeLa cells were treated for 0 to 6 h with 6 mM d-glucose and 1 mM l-glutamine (normal in vivo conditions), 3 mM d-glucose and 0.5 mM l-glutamine (severe hypoglycemic conditions), and 0 mM d-glucose and 0 mM l-glutamine (“starvation”). Polarization-optical differential interference contrast and phase-contrast light microscopy were employed to investigate morphologic changes.ResultsReduction of glucose levels from 6 to 3 mM (and glutamine levels from 1 to 0.5 mM) brings about cancer cell survival of 73% after 2-h exposure and 63% after 4-h exposure. Reducing glucose levels from 6 to 0 mM (and glutamine levels from 1 to 0 mM) for 4 h resulted in 53% cell survival.ConclusionThese data reveal that glucose (and glutamine) deprivation to typical physiological concentrations result in significant cancer cell killing after as little as 2 h. This supports the possibility of combining anti-glycolytic treatment, such as a carbohydrate-restricted diet, with chemotherapeutics for enhanced cancer cell killing.     

Oral glutamine supplementation during preoperative radiochemotherapy in patients with rectal cancer: a randomised double blinded, placebo controlled pilot study

Background & aims

Enteral glutamine may have protective effects on gut function and reduce metabolic stress in patients receiving radiochemotherapy. The aim of our study was to evaluate its influence in patients with rectal cancer undergoing preoperative radiochemotherapy.

Methods

We performed a randomized double blind, placebo controlled pilot study in 33 patients. 30 g of glutamine, average dose 0.41 g/kg (SD = 0.07) g/kg/day was administered orally in three doses per day for five weeks during preoperative radiochemotherapy of rectal cancer. 30 g of maltodextrin was given as placebo. Body weight was measured and NRS 2002 screening was performed before and after treatment. Bowel function was evaluated by stool consistency and frequency. Plasma levels of inflammatory parameters and hormones were measured.

Results

There was no difference between groups in frequency and severity of diarrhoea during radiochemotherapy (p = 0.5 and p = 0.39 respectively), insulin levels significantly increased in both groups, IL-6 only in glutamine group.

Conclusion

Results of this small pilot study in rectal cancer patients receiving preoperative radiochemotherapy, showed that ingestion of larger quantities of glutamine given more often as previously reported did not diminish the incidence and severity of diarrhoea and did not affect inflammatory and metabolic activity compared to the placebo treatment with maltodextrin.     

Cell cycle:乳腺癌的致命伤

2011-12-01,Cell Cycle报道了美国杰佛逊大学(Thomas Jefferson University)Kimmel肿瘤中心题为Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ:Visualizing the therapeutic effects of metformin in tumor tissue的研究成果。该研究发现了乳腺癌细胞的致命伤——线粒体。这一发现为科学家开辟了寻找治疗乳腺癌及其他肿瘤新靶点的新路径。     

Acculturation does not necessarily lead to increased physical activity during leisure time: a cross-sectional study among Turkish young people in the Netherlands

Background  

Non-Western migrant populations living in Western countries are more likely to be physically inactive during leisure time than host populations. It is argued that this difference will disappear as they acculturate to the culture of the host country. We explored whether this is also true for migrants who experience contextual barriers such as having children, living in a less attractive neighbourhood, or having occupational physical activity.     

Effect of intermittent glutamine supplementation on skeletal muscle is not long-lasting in very old rats

Background and objective

Muscle is the major site for glutamine synthesis via glutamine synthetase (GS). This enzyme is increased 1.5–2 fold in 25–27-mo rats and may be a consequence of aging-induced stress. This stimulation is similar to the induction observed following a catabolic state such as glucocorticoid treatment (6 to 24 months). Although oral glutamine supply regulates the plasma glutamine level, nothing is known if this supplementation is interrupted before the experiment.

Design

Adult (8-mo) and very old (27-mo) female rats were exposed to intermittent glutamine supplementation for 50 % of their age lifetime. Treated rats received glutamine added to their drinking water and control rats water alone but the effect of glutamine supplementation was only studied 15 days after the last supplementation.

Results

Glutamine pretreatment discontinued 15 days before the experiment increased plasma glutamine to ～ 0.6 mM, a normal value in very old rats. However, it failed to decrease the up-regulated GS activity in skeletal muscle from very old rats.

Conclusion

Our results suggest that long-term treatment with glutamine started before advanced age but discontinued 15 days before rat sacrifice is effective in increasing plasma glutamine to recover basal adult value and in maintaining plasma glutamine in very old rats, but has no long-lasting effect on the GS activity of skeletal muscle with advanced age.     

Modulation of the nuclear factor-kappa B (NF-κB) signalling pathway by glutamine in peritoneal macrophages of a murine model of protein malnutrition

Background and aims

Protein malnutrition affects resistance to infection by impairing the inflammatory response, modifying the function of effector cells, such as macrophages. Recent studies have revealed that glutamine—a non-essential amino acid, which could become conditionally essential in some situations like trauma, infection, post-surgery and sepsis—is able to modulate the synthesis of cytokines. The aim of this study was to evaluate the effect of glutamine on the expression of proteins involved in the nuclear factor-kappa B (NF-κB) signalling pathway of peritoneal macrophages from malnourished mice.

Methods

Two-month-old male Balb/c mice were submitted to protein-energy malnutrition (n = 10) with a low-protein diet containing 2 % protein, whereas control mice (n = 10) were fed a 12 % protein-containing diet. The haemogram and analysis of plasma glutamine and corticosterone were evaluated. Peritoneal macrophages were pre-treated in vitro with glutamine (0, 0.6, 2 and 10 mmol/L) for 24 h and then stimulated with 1.25 μg LPS for 30 min, and the synthesis of TNF-α and IL-1α and the expression of proteins related to the NF-κB pathway were evaluated.

Results

Malnourished animals had anaemia, leucopoenia, lower plasma glutamine and increased corticosterone levels. TNF-α production of macrophages stimulated with LPS was significantly lower in cells from malnourished animals when cultivated in supraphysiological (2 and 10 mmol/L) concentrations of glutamine. Further, glutamine has a dose-dependent effect on the activation of macrophages, in both groups, when stimulated with LPS, inducing a decrease in TNF-α and IL-1α production and negatively modulating the NF-κB signalling pathway.

Conclusions

These data lead us to infer that the protein malnutrition state interferes with the activation of macrophages and that higher glutamine concentrations, in vitro, have the capacity to act negatively in the NF-κB signalling pathway.     

One step forward,one step sideways? Expanding research capacity for neglected diseases

Background  

There is general agreement, including from the pharmaceutical industry, that current market based methods of generating research into the development of pharmaceutical products that are relevant for developing countries do not work. This conclusion is relevant not just for the most neglected diseases such as leishmaniasis but even for global diseases such as cancer and cardiovascular disease.     

Effects of Kurozu concentrated liquid on adipocyte size in rats

Background  

Kurozu concentrated liquid (KCL) is used as a health-promoting supplement for the treatment of disorders such as cancer, hyperlipidemia, and hypertension in Japan. We investigated the possible anti-obesity effects of KCL in rats.     

Plasma lyso-phosphatidylcholine concentration is decreased in cancer patients with weight loss and activated inflammatory status

Background  

It has been observed that ras-transformed cell lines in culture have a higher phosphatidylcholine (PC) biosynthesis rate as well as higher PC-degradation rate (increased PC-turnover) than normal cells. In correspondence to these findings, the concentrations of the PC-degradation product lyso-phosphatidylcholine (LPC) in cancer patients were found to be decreased. Our objective was the systematic investigation of the relationship between LPC and inflammatory and nutritional parameters in cancer patients. Therefore, plasma LPC concentrations were assessed in 59 cancer patients and related to nutritional and inflammatory parameters. To determine LPC in blood plasma we developed and validated a HPTLC method.     

Glutamine attenuates nitric oxide synthase expression and mitochondria membrane potential decrease in interleukin-1β-activated rat hepatocytes

Background  

Mitochondrial dysfunction induced by nitric oxide (NO) overproduction is involved in the pathogenesis of organ failure during many severe diseases. Recently, several experiments have reported that glutamine (Gln) modifies inducible nitric oxide synthase (iNOS) gene expression which is thought to be responsible for its beneficial effects in critical illnesses.     

Membrane plasmalogen composition and cellular cholesterol regulation: a structure activity study

Background  

Disrupted cholesterol regulation leading to increased circulating and membrane cholesterol levels is implicated in many age-related chronic diseases such as cardiovascular disease (CVD), Alzheimer's disease (AD), and cancer. In vitro and ex vivo cellular plasmalogen deficiency models have been shown to exhibit impaired intra- and extra-cellular processing of cholesterol. Furthermore, depleted brain plasmalogens have been implicated in AD and serum plasmalogen deficiencies have been linked to AD, CVD, and cancer.     

Environmental conditions and Puumala virus transmission in Belgium

Background  

Non-vector-borne zoonoses such as Puumala hantavirus (PUUV) can be transmitted directly, by physical contact between infected and susceptible hosts, or indirectly, with the environment as an intermediate. The objective of this study is to better understand the causal link between environmental features and PUUV prevalence in bank vole population in Belgium, and hence with transmission risk to humans. Our hypothesis was that environmental conditions controlling the direct and indirect transmission paths differ, such that the risk of transmission to humans is not only determined by host abundance. We explored the relationship between, on one hand, environmental variables and, on the other hand, host abundance, PUUV prevalence in the host, and human cases of nephropathia epidemica (NE). Statistical analyses were carried out on 17 field sites situated in Belgian broadleaf forests.     

Consistency and precision of cancer reporting in a multiwave national panel survey

Background  

Many epidemiological studies rely on self-reported information, the accuracy of which is critical for unbiased estimates of population health. Previously, accuracy has been analyzed by comparing self-reports to other sources, such as cancer registries. Cancer is believed to be a well-reported condition. This paper uses novel panel data to test the consistency of cancer reports for respondents with repeated self-reports.     

Out-of-home food outlets and area deprivation: case study in Glasgow,UK

Background  

There is a popular belief that out-of-home eating outlets, which typically serve energy dense food, may be more commonly found in more deprived areas and that this may contribute to higher rates of obesity and related diseases in such areas.     

Apple juice intervention modulates expression of ARE-dependent genes in rat colon and liver

Background  

The risk of cancer and other degenerative diseases is inversely correlated with consumption of fruits and vegetables. This beneficial effect is mainly attributed to secondary plant constituents such as polyphenols, supposed to play a major role in protection against ROS (reactive oxygen species)-associated toxicity.     

A systematic review of PET and PET/CT in oncology: A way to personalize cancer treatment in a cost-effective manner?

Background  

A number of diagnostic tests are required for the detection and management of cancer. Most imaging modalities such as computerized tomography (CT) are anatomical. However, positron emission tomography (PET) is a functional diagnostic imaging technique using compounds labelled with positron-emitting radioisotopes to measure cell metabolism. It has been a useful tool in studying soft tissues such as the brain, cardiovascular system, and cancer. The aim of this systematic review is to critically summarize the health economic evidence of oncologic PET in the literature.     

Rationales, design and recruitment of the Taizhou Longitudinal Study

Background  

Rapid economic growth in China in the past decades has been accompanied by dramatic changes in lifestyle and environmental exposures. The burdens of non-communicable diseases, such as cardiovascular diseases, diabetes and cancer, have also increased substantially.     

Effects of Mediterranean diets with low and high proportions of phytate-rich foods on the urinary phytate excretion

Background  

Important health benefits have been reported recently to phytate intake. This includes the prevention of pathological calcifications such as renal calculi, dental calculi and cardiovascular calcification, due its action as crystallization inhibitor of calcium salts, and as preventive of cancer.     

Tolerability of breast ductal lavage in women from families at high genetic risk of breast cancer

Background  

Ductal lavage (DL) has been proposed as a minimally-invasive, well-tolerated tool for obtaining breast epithelial cells for cytological evaluation of breast cancer risk. We report DL tolerability in BRCA1/2 mutation-positive and -negative women from an IRB-approved research study.     

Proteomic study of granulocytic differentiation induced by apigenin 7-glucoside in human promyelocytic leukemia HL-60 cells

Background

Nutritional factors is one of the most important regulators in the progression of cancer. Some dietary elements promote the growth of cancer but others, such as plant-derived compounds, may reverse this process.

Purpose

We tried to investigate yet another approach of cancer prevention through cancer cell differentiation, using a common non-mutagenic flavonoid apigenin 7-glucoside.

Methods

HL-60 cells were treated with or without apigenin 7-glucoside. Cell proliferation was measured by MTT assay, and the cell cycle distribution was estimated by propidium iodide staining of DNA. To determine cellular differentiation, cell surface differentiation markers CD11b and CD14 were used. Two-dimensional gel electrophoresis was then performed to identify proteins that may be important in HL-60 cell differentiation following apigenin 7-glucoside treatment.

Results

Apigenin 7-glucoside inhibited HL-60 cell growth, dose- and time-dependently, but did not cause apoptosis. The distribution of cells at different stages in the cell cycle indicated an accumulation of treated cells in G₂/M phase. Moreover, apigenin 7-glucoside induced granulocytic differentiation of HL-60 cells. Ten proteins that might play essential role in granulocytic differentiation were identified by proteomics.

Conclusions

A complete understanding of the preventive effects of plant-based diet on cancer depends on the mechanisms of action of different plant components on processes. We hope these findings may contribute to the understandings of the different approaches for chemoprevention of cancer.