Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.
Male ; Humans ; Glutamine/therapeutic use* ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

BACKGROUNDAssociations between glutamine (Gln) enriched nutrition support and surgical patients with gastrointestinal (GI) tumor remain controversy. The purpose of this meta-analysis was to assess the effect of Gln enriched nutrition support on surgical patients with GI tumor in term of relevant biochemical indices, immune indices, and clinical outcomes.

METHODSSix databases were systematically searched to find eligible randomized controlled trials (RCTs) from 1966 to May 2014. When estimated the analysis indexes, the relative risk (RR) was used as the effect size of the categorical variable, while the weighted mean difference (MD) was used as the effect size of a continuous variable. Meta-analysis was conducted with Rev Man 5.2.

RESULTSThirteen RCTs, involving 1034 patients, were included in the meta-analysis. The analysis showed that Gln enriched nutrition support was more effective in increasing serum albumin (MD: 0.10; 95% confidence interval [CI]: 0.02-0.18; P < 0.05), serum prealbumin (MD: 1.98; 95% CI: 1.40-2.55; P < 0.05) and serum transferring (MD: 0.35; 95% CI: 0.12-0.57; P < 0.05), concentration of IgG (MD: 1.26; 95% CI: 0.90-1.63; P < 0.05), IgM (MD: 0.18; 95% CI: 0.11-0.25; P < 0.05), IgA (MD: 0.22; 95% CI: 0.10-0.33; P < 0.05), CD3 + (MD: 3.71; 95% CI: 2.57-4.85; P < 0.05) and CD4/CD8 ratio (MD: 0.27; 95% CI: 0.12-0.42; P < 0.05). Meanwhile, it was more significant in decreasing the incidence of infectious complications (RR: 0.67; 95% CI: 0.50-0.90; P < 0.05) and shortening the length of hospital stay (MD: -1.72; 95% CI: -3.31--0.13; P < 0.05).

CONCLUSIONSGlutamine enriched nutrition support was superior in improving immune function, reducing the incidence of infectious complications and shortening the length of hospital stay, playing an important role in the rehabilitation of surgical GI cancer patients.

Enteral Nutrition ; Gastrointestinal Neoplasms ; surgery ; Glutamine ; therapeutic use ; Humans ; Parenteral Nutrition ; Postoperative Complications ; prevention & control ; Randomized Controlled Trials as Topic

OBJECTIVETo observe the effect of the couplet medicines (Astragalus Membranaceus and Jiaozhen) on intestinal barrier functions of postoperative colorectal cancer patients.

METHODSTotally 90 inpatients with confirmed colorectal cancer by pathological diagnosis were recruited as subjects in this study. They were assigned to the Chinese medicine group (CM, treated with Astragalus Membranaceus and Jiaozhen), the Western medicine group (WM, treated with glutamine), and the blank control group (treated with normal saline) according to random digit table, 30 in each group. The treatment course consisted of eight days. Levels of blood D-lactic acid, diamine oxidase (DAO), urinary lactulose/mannitol ratio (L/M), ET, TNF-alpha, and postoperative recovery time of bowel sound were observed before surgery and after surgery. The effect of the couplet medicines (Astragalus Membranaceus and Jiaozhen) on intestinal barrier functions of postoperative colorectal cancer patients were comprehensively assessed by taking blood D-lactic acid levels, DAO levels, urinary L/M as main potency indices; ET and TNF-alpha, recovery time of bowel sound as the secondary potency indices.

RESULTSCM showed similar effect with that of WM in improving blood D-lactic acid levels and DAO levels, and urinary L/M ratio, with no statistical difference between them (P > 0.05). But they showed better effect than that of the blank control group (P < 0.05). Levels of ET and TNF-alpha were decreased more in the CM group than in the WM group (P < 0.05). The recovery time of bowel sound was shorter in the CM group than in the WM group (P < 0.05, P < 0.01). Levels of ET and TNF-alpha were decreased more in the WM group than in the blank control group (P < 0.05). There was no statistical difference in the recovery time of bowel sound between the WM group and the blank control group (P > 0.05).

CONCLUSIONSThe couplet medicines (Astragalus Membranaceus and Jiaozhen) had obvious protection for intestinal barrier dysfunction of postoperative colorectal cancer patients, showing similar efficacy to that of WM. It was even superior to glutamine in restoring bowel functions, reducing toxin absorption, and lowering levels of pro-inflammatory factors.

Amine Oxidase (Copper-Containing) ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; therapeutic use ; Astragalus membranaceus ; Chemotherapy, Adjuvant ; methods ; Colorectal Neoplasms ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Glutamine ; therapeutic use ; Humans ; Intestinal Mucosa ; drug effects ; Intestines ; Lactic Acid ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo observe the effects of glutamine combined with ulinastatin on inflammatory response of patients with severe burn injury.

METHODSSixty patients with severe burn injury admitted to our burn wards from January 2010 to December 2011 conforming to the study criteria were divided into control group (C, n = 20), glutamine group (G, n = 20), and glutamine combined with ulinastatin group (G + U, n = 20) according to the random number table. Another 10 healthy volunteers were chosen as normal control group (NC). Isonitrogenous and isocaloric nutrition supports were given to patients in groups C, G, and G + U from post burn day (PBD) 2. 0.3 g/kg protein in the form of glutamine dipeptide was given to patients in group G for 10 days. 0.3 g/kg protein was given to patients in group G + U for 10 days with the same amount of glutamine dipeptide as that in group G, followed by intravenous injection of 100 kU ulinastatin (once per 8 hours) for 7 days during 10 days. The nitrogen concentration of 24 h urine was determined with Kieldahl nitrogen determination method, and nitrogen balance was calculated one day before treatment and ten days after treatment. Meanwhile, the levels of D-lactate in serum was determined by colorimetric method, the levels of diamine oxidase (DAO), TNF-α, and IL-6 by enzyme-linked immunosorbent assay, and LPS level by kinetic turbidimetric assay with TAL. Above-mentioned indexes were also examined in group NC. The wound healing rate on PBD 30, total hospital stay days, and the incidence of burn sepsis of all burn patients were recorded. Data were processed with one-way analysis of variance, LSD test, t test, and chi-square test.

RESULTSCompared with that in group C [(-5.40 ± 1.67) g/d], nitrogen balance in group G was significantly increased ten days after treatment [(-1.35 ± 0.59) g/d, P < 0.01]. The serum levels of D-lactate, DAO, LPS, TNF-α, and IL-6 in group G ten days after treatment were significantly lower than those in group C (P < 0.05 or P < 0.01). No statistically significant difference was observed in nitrogen balance and the serum levels of D-lactate, DAO between group G + U and group G (P values all above 0.05). The serum levels of LPS, TNF-α, and IL-6 in group G + U ten days after treatment were respectively (0.167 ± 0.064) EU/mL, (43 ± 14) pg/mL, (139 ± 23) pg/mL, which were significantly lower than those in group G [(0.240 ± 0.079) EU/mL, (59 ± 8) pg/mL, (195 ± 31) pg/mL, respectively, P < 0.05 or P < 0.01]. The would healing rate on PBD 30 and total hospital stay days in group G were respectively higher and shorter than those in group C (P values all below 0.01), but no statistically significant difference in the incidence of burn sepsis was found between them (P > 0.05). The would healing rate on PBD 30 in group G+U [(96 ± 4)%] was enhanced, and total hospital stay days [(41 ± 4) d] were lowered than those in group G [(88 ± 7)%, (49 ± 5)d, P values all below 0.01]. The incidence of burn sepsis of patients in group G + U (5%) was significantly lower than that in group C (35%, χ(2) = 6.234, P < 0.05).

CONCLUSIONSGlutamine combined with ulinastatin treatment can alleviate damage to intestine after severe burn injury, lower the serum level of inflammatory cytokines, promote wound healing, and reduce the incidence of burn sepsis.

Adolescent ; Adult ; Burns ; blood ; drug therapy ; Female ; Glutamine ; therapeutic use ; Glycoproteins ; therapeutic use ; Humans ; Interleukin-6 ; blood ; Lactic Acid ; blood ; Lipopolysaccharides ; blood ; Male ; Tumor Necrosis Factor-alpha ; blood ; Wound Healing ; Young Adult

OBJECTIVETo clarify the intestinal barrier function (IBF) state of patients with acute myocardial infarction-heart failure (AMI-HF), and to compare the therapeutic effects of rhubarb and Pantoprazole (proton pump inhibitor).

METHODSEnrolled were 107 AMI patients from ICU, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2008 to April 2010. Of them, 47 AMI patients without HF were recruited as the control group, while 60 AMI-HF patients were randomly assigned to the rhubarb group (30 cases, treated by rhubarb + Pantoprazole) or the Pantoprazole group (30 cases, treated by Pantoprazole + routine treatment). All patients were treated till the 14th day of the onset. The fecal occult blood (FOB) test was performed daily. The occurrence of the digestive tract hemorrhage on the 14th day after onset was compared. The N-terminal pro-brain natriuretic peptide (NT-proBNP), serum D-lactic acid, plasma glutamine (Gln), endotoxin and cytokines [high sensitive C reaction protein (hsCRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10)], and heart function were compared among the three groups before and after treatment.

RESULTSThere was no statistical difference in the case number of using aspirin, clopidogel, low molecular weight heparin, ACEI/ARB, statins, insulin, and antibiotics among the 3 groups. The case number of using beta-blocker was obviously lower in the two medication groups than in the control group (P < 0.05). The case number of using diuretics was obviously higher in the two medication groups than in the control group (P < 0.05). There was no statistical difference in the incidence of digestive tract hemorrhage (P = 0.413). Compared with the control group before treatment, Gln and ejection fraction (EF) were both lowered, NT-proBNP, D-lactic acid, endotoxin, hsCRP, TNF-alpha, and IL-10 increased in the two medication groups (P < 0.01). There was no statistical difference in each index between the two medication groups (P > 0.05). Compared with before treatment, NT-proBNP, D-lactic acid, endotoxin, hsCRP, TNF-alpha, and IL-10 decreased in the Pantoprazole group (P < 0.01), and no obvious change in Gin or EF was found (P > 0.05). Gin and EF increased in the rhubarb group after treatment, and they were higher than those of the control group. Blood NT-proBNP, D-lactic acid, endotoxin, hsCRP, TNF-alpha, and IL-10 decreased in the rhubarb group after treatment, showing statistical difference when compared with the control group (P < 0.01, P < 0.05).

CONCLUSIONSImpaired IBF and endotoxemia existed in AMI-HF patients. Rhubarb not only could prevent the digestive tract hemorrhage, but also could reduce endotoxemia, inhibit inflammatory reactions, and improve the heart function through ameliorating the IBF.

2-Pyridinylmethylsulfinylbenzimidazoles ; therapeutic use ; Aged ; Endotoxins ; blood ; Female ; Glutamine ; blood ; Heart Failure ; complications ; physiopathology ; therapy ; Humans ; Interleukin-10 ; blood ; Lactic Acid ; blood ; Male ; Middle Aged ; Myocardial Infarction ; complications ; physiopathology ; therapy ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Proton Pump Inhibitors ; therapeutic use ; Rheum ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the effects of microbiological and immunological enteral nutrition using composition of probiotics, glutamine, fish oil, and peptisorb on patients with gastrointestinal cancer complicated with diabetes mellitus.

METHODSFrom January 2007 to October 2010, 67 patients with gastrointestinal cancer complicated with diabetes mellitus were admitted to the Liaocheng People's Hospital of Shandong Province and were randomized into the treatment group(n=33, enteral nutrition with probiotics, glutamine, and fish oil) and the routine group(n=34, regular enteral nutrition). Fasting blood glucose(FBG), insulin(FINS), number of lymphocytes(including CD3(+)T cell, CD4(+)T cell, CD8(+)T cell, CD4(+)/CD8(+)) and natural killer (NK) cells of the two groups were detected on the day before surgery and postoperative day 3 and 7. Insulin resistance index (InHOMA-IR) was calculated by using the homeostasis model assessment(HOMA). The incidence of nosocomial infections and intestinal function recovery time, and length of hospital stay were collected.

RESULTSOn postoperative day 7, FINS[(8.4±3.7) mU/L vs. (13.7±5.4) mU/L, P<0.05] and InHOMA-IR(1.11±0.23 vs. 1.68±0.39, P<0.05) were lower in the treatment group than that in the routine group. The number of CD4(+)[(45.2±5.4)% vs. (38.1±2.9)%, P<0.05], CD4/CD8 (2.05±0.27 vs. 1.58±0.16, P<0.05), and NK cells [(19.5±6.6)% vs. (15.4±5.6)%, P<0.05] were higher in the treatment group. There were no significant differences in nosocomial infection [6.1%(2/33) vs. 17.6%(6/34), P>0.05] and intestinal function recovery time[(69.3±9.5) h vs. (70.1±11.6) h, P>0.05] between the two groups. However, the length of hospital stay [(17±3.8) d vs. (21±4.2) d, P<0.05] was significantly shorter in the treatment group.

CONCLUSIONFor patients with gastrointestinal cancer complicated with diabetes mellitus, microbiota enteral nutrition can reduce insulin resistance, improve the immune status, and promote postoperative recovery.

Adult ; Aged ; Diabetes Mellitus ; therapy ; Enteral Nutrition ; methods ; Female ; Fish Oils ; therapeutic use ; Gastrointestinal Neoplasms ; complications ; therapy ; Glutamine ; therapeutic use ; Humans ; Male ; Middle Aged ; Postoperative Care ; Probiotics ; therapeutic use

Special nutritional support containing glutamine, arginine, and omega-3 fatty acids has therapeutic and immunomodulatory effects, and can significantly reduce the incidence of postoperative infectious complications and length of hospital stay in surgical patients. This review provides a clinical update regarding the concept and the use of pharmaconutrition and immunonutrition in patients undergoing gastrointestinal surgery.
Arginine ; therapeutic use ; Digestive System Surgical Procedures ; Enteral Nutrition ; Fatty Acids, Omega-3 ; therapeutic use ; Glutamine ; therapeutic use ; Humans

INTRODUCTIONThe addition of glutamine to parenteral nutrition (PN) in neonates has not shown significant benefits as compared to adults thus far. This study aimed to determine the potential benefits of the addition of glutamine to neonatal PN in a tertiary hospital in a middle-income country.

METHODSThis was a double-blinded randomised controlled trial. Babies who were admitted to the neonatal intensive care unit (NICU) and who required PN were eligible for inclusion in the study. The subjects were randomised to receive either glutamine-added PN (intervention) or standard PN (control). The most important outcomes included time to full enteral nutrition, incidence of sepsis and necrotising enterocolitis (NEC), clinical or culture-proven sepsis.

RESULTSOut of 270 subjects, 132 were randomised to the intervention group and 138, to the control group. Baseline data were comparable in both groups. The median time taken to reach full enteral nutrition was similar for both intervention and control groups (six days in each group, p-value is 0.52). The incidences of NEC, clinical sepsis and culture-proven sepsis did not differ significantly in the intervention and control groups (5.8 vs. 7.1 percent, p-value is 0.68; 15.7 percent vs. 10.2 percent, p-value is 0.21 and 16.5 percent vs. 15.7 percent, p-value is 0.38, respectively). Other outcomes such as duration of ventilation, duration of NICU stay and a subgroup analysis for preterm and term babies also showed no statistically significant differences.

CONCLUSIONAddition of glutamine to neonatal PN was not shown to improve outcome.

Double-Blind Method ; Enteral Nutrition ; Female ; Glutamine ; therapeutic use ; Humans ; Infant Nutritional Physiological Phenomena ; Infant, Newborn ; Intensive Care, Neonatal ; Malaysia ; Male ; Parenteral Nutrition ; Respiratory Tract Infections ; diagnosis ; Sepsis ; microbiology ; prevention & control ; Treatment Outcome

Cancer metabolism has emerged as an important area of research in recent years. Elucidation of the metabolic differences between cancer and normal cells and the underlying mechanisms will not only advance our understanding of fundamental cancer cell biology but also provide an important basis for the development of new therapeutic strategies and novel compounds to selectively eliminate cancer cells by targeting their unique metabolism. This article reviews several important metabolic alterations in cancer cells, with an emphasis on increased aerobic glycolysis (the Warburg effect) and glutamine addiction, and discusses the mechanisms that may contribute to such metabolic changes. In addition, metabolic alterations in cancer stem cells, mitochondrial metabolism and its influence on drug sensitivity, and potential therapeutic strategies and agents that target cancer metabolism are also discussed.
Antineoplastic Agents ; therapeutic use ; Drug Resistance, Neoplasm ; Genes, Tumor Suppressor ; physiology ; Glutamine ; metabolism ; Glycolysis ; drug effects ; physiology ; Humans ; Mitochondria ; genetics ; metabolism ; Mutation ; Neoplasms ; drug therapy ; metabolism ; pathology ; Neoplastic Stem Cells ; metabolism ; Oncogenes ; physiology ; Oxidative Phosphorylation

OBJECTIVETo investigate the effect of early enteral nutrition (EEN) supplemented with glutamine on postoperative intestinal mucosal barrier function of patients with gastric carcinoma.

METHODSEighty patients with gastric carcinoma who underwent intraoperative peritoneal hyperthermic chemotherapy(IPHC) were randomized into two groups: EEN+glutamine (EEN+Gln) group(n=40) and EEN group(n=40). Intestinal mucosal barrier function was evaluated by serum diamine oxidase (DAO), ratio of lactulose to mannitol(L/M), endotoxin lipopolysaccharides(LPS), and tumor necrosis factor-α(TNF-α) at 1 day before operation, 1 day, 7 days, 12 days after operation. Time to first flatus and tolerance to EEN were recorded as well.

RESULTSThere were no significant differences in the two groups in demographics(all P>0.05). Two cases(5%) in the EEN+Gln group and 1 case (2.5%) in the EEN group could not tolerate well(P>0.05). On postoperative day 1, there were no differences in serum DAO, L/M ratio, LPS, TNF-α between the two groups (P>0.05). On postoperative day 7, all the parameters for mucosal barrier function were significantly lower in the EEN+Gln group. On postoperative day 12, the urinary L/M and DAO, LPS, and TNF-α were still significantly lower in the EEN+Gln group, however, urinary L/M was comparable between the two groups. There were no differences between the two groups in the time to first flatus (P>0.05).

CONCLUSIONThe immunologic tolerance of enteral nutrition supplemented with glutamine is favorable, which provides protective effect on intestinal mucosal barrier in patients with gastric carcinoma undergoing IPHC.

Aged ; Enteral Nutrition ; methods ; Female ; Glutamine ; administration & dosage ; therapeutic use ; Humans ; Intestinal Mucosa ; drug effects ; physiopathology ; Male ; Middle Aged ; Postoperative Care ; Prospective Studies ; Stomach Neoplasms ; physiopathology ; therapy