PubMed Health⌕ Search

Biomedical subjects

R Benamouzig

Publications and source records attributed to R Benamouzig.

At least 19 recordsLinked to original sources

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature.

We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n = 957) for RFS and 18 for OS (n = 2383) and for VEGF in 17 studies, including nine studies for RFS (n = 1064) and 10 for OS (n = 1301). High MVD significantly predicted poor RFS (RR = 2.32 95% CI: 1.39-3.90; P < 0.001) and OS (RR = 1.44; 95% CI: 1.08-1.92; P = 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR = 2.84; 95% CI: 1.95-4.16) and OS (RR=1.65; 95% CI: 1.27-2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.

Adenocarcinoma↗

Impact of EGFR expression on colorectal cancer patient prognosis and survival.

BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.

Adult↗

[Chemoprevention of colorectal cancer].

A NEW CONCEPT: Chemoprevention of cancer consists in the administration of chemical agents to prevent or inhibit carcinogenesis. This strategy can be applied at any stage of carcinogenesis. ASSESSMENT: The development of such agents relies on classical bases: phases I, II and III. The approach consists in assessing the effect of the substance tested in patients with history of resected adenomas of the colon and at high risk of relapse and/or family risk of colon cancer. THE PRINCIPLE AGENTS UNDER ASSESSMENT: Are aspirin, type 2 cyclo-oxygenase inhibitors, calcium, folic acid, certain vitamins, hormone replacement therapy for menopausal women and difluoromethylornithine (DFMO).

Adenomatous Polyposis Coli↗

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Adolescent↗

Nutritional status after short-term dietary supplementation in hospitalized malnourished geriatric patients.

AIM: To examine the evolution of different parameters of the nutritional status after short-term oral protein-energy supplementation in moderately malnourished geriatric patients. METHODS: Seventeen hospitalized malnourished elderly patients and 12 healthy adults received dietary supplements for 10 days. A group of six malnourished elderly subjects served as controls. Spontaneous oral intakes, biological and biophysical markers of the nutritional status were measured. Fat-free mass (FFM) was assessed using Dual energy X-ray absorptiometry (DXA), bio-impedance analysis (BIA) and anthropometry. RESULTS: In elderly subjects, the supplementation significantly increased both dietary intake (energy +32%, protein +65%) and FFM (+1.3 kg, P<0.001) as assessed using DXA. BIA and anthropometric data correlated with DXA measurements in the elderly (BIA: r=0.68--0.80, anthropometry: r=0.80--0.89), but failed to reflect accurately the changes measured in FFM. Supplementation had no notable effect on biological markers in any of the groups. IGF-I and hand-grip strength were not significantly influenced by the supplementation despite trends towards an improvement. CONCLUSIONS: Monitoring short-term changes in nutritional status in malnourished elderly individuals is a problem in routine clinical management. Our data put in the limelight the changes in IGF-I values related to dietary supplementation, and, chiefly, suggest a prime role for the assessment of dietary intake and FFM, as assessed by DXA, as indicators of short-term efficacy of refeeding. Nevertheless larger studies are necessary to confirm the clinical and prognostic significance of the changes.

Absorptiometry, Photon↗

Guar gum does not impair the absorption and utilization of dietary nitrogen but affects early endogenous urea kinetics in humans.

BACKGROUND: Viscous gums enhance viscosity in the upper gastrointestinal lumen, quickly disturbing motility and promoting fluid secretion. OBJECTIVE: We sought to determine whether guar gum could acutely affect the absorption and utilization of dietary nitrogen and whether these luminal effects could also perturb the kinetics of urea. DESIGN: We studied the short-term effect of adding 1% of highly viscous guar gum to a (15)N-labeled protein meal (30 g soy protein isolate in 500 mL water) during the postprandial phase in humans. The effects on bioavailability were studied by using the [(13)C]glycine breath test (to assess gastric emptying) and (15)N enrichment in plasma amino acids (for systemic amino acid bioavailability). The kinetics of dietary and endogenous urea were assessed in plasma and urine. RESULTS: Guar gum modulated the gastric emptying kinetics of the liquid phase of the meal slightly (P < 0.05), but had no significant effect on either the systemic appearance of dietary amino acids or plasma and urinary dietary urea kinetics. Without significantly affecting plasma urea concentrations, guar gum reduced by approximately 40% the urinary excretion of endogenous urea for the first 2-h period after the meal (P < 0.01), although endogenous urinary excretion was similar at later stages. CONCLUSIONS: Guar gum did not significantly affect the bioavailability or utilization of dietary protein. We showed an early effect of guar gum on endogenous urea kinetics, which most probably arose from very early, short-term stimulation of the intestinal disposal of endogenous urea, at the expense of its urinary excretion.

Adult↗

The influence of the albumin fraction on the bioavailability and postprandial utilization of pea protein given selectively to humans.

Pulse seed proteins such as those found in peas (Pisum sativum) contain fractions of very dissimilar composition and properties, which may therefore be differently utilized by the human body. To analyze the nutritional value of the soluble protein fractions of pea seed, human volunteers ingested a mixed meal of 30 g of raw purified pea protein either as [15N]-globulins (G, n = 9) or as a mix of [15N]-globulins and [15N]-albumins (GA, n = 7) in their natural proportions (22:8). Dietary and endogenous nitrogen fluxes at the terminal ileum were assessed using a tube perfusion technique with an isotopic dilution method. Systemic dietary amino acid availability and the retention of dietary amino acids were determined using 15N enrichment in plasma amino acids and deamination products in blood and urine for 8 h postprandially. The results showed that the pea albumin fraction had the following effects: 1) significantly lowered the real ileal digestibility of pea protein (94 +/- 2.5% for G vs. 89.9 +/- 4% for GA), probably because of a direct effect of trypsin inhibitors; 2) did not promote acute intestinal losses of endogenous nitrogen; and 3) did not significantly improve the postprandial biological value of pea protein (76.5 +/- 3.9% for G vs. 78.7 +/- 3.6% for GA), despite the fact that it corrected the globulin deficiency in sulfur amino acids. We conclude that both G and GA are of good nutritional value for humans and show that cysteine-rich albumins have a far more modest effect on the efficiency of postprandial dietary protein utilization than would be expected from the amino acid scores.

Albumins↗

APACC, a French prospective study on aspirin efficacy in reducing colorectal adenoma recurrence: design and baseline findings.

UNLABELLED: Colorectal cancer is the second most frequent cause of death from cancer in western countries. Many lines of evidence suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may offer chemoprevention against colorectal cancer. A multicentre, double-blind, randomized, controlled trial is underway to determine the efficacy of regular aspirin intake (160 or 300 mg/day) in reducing colorectal adenoma recurrence. We now report the baseline characteristics of subjects enrolled into the trial. RESULTS: A total of 618 polyps were excised from 274 patients at the baseline colonoscopy. Men had on average (+/-SD) 2.5 +/- 1.8 polyps per subject and women had 1.7 +/- 1.2. Ninety-one (33.7%) had three or more adenomas and 183 (67.8%) had more than one adenoma measuring 10 mm or more in diameter. The mean (+/-SD) age of the subjects was 57.7 (+/- 9.4) years. Sixty-seven (24.9%) reported that they had previously had adenoma(s), 95 (35.2%) reported a family history of colorectal cancer and 41 (15.2%) a family history of colorectal adenomas. PERSPECTIVE: All subjects will undergo a one-year clearance colonoscopy by February 2001. Clinical, molecular biological and dietary data will enable us to investigate other factors influencing the recurrence of adenomas in this group of high-risk subjects.

Adenoma↗

Short-term protein and energy supplementation activates nitrogen kinetics and accretion in poorly nourished elderly subjects.

BACKGROUND: An increase in protein intake exerts a stimulating effect on protein kinetics in children, young adults, and healthy elderly persons. However, there are few data on the response to such dietary changes in malnourished elderly subjects, despite important medical implications in this population. OBJECTIVE: The objective of this study was to determine the metabolic response to short-term nutritional supplementation in moderately malnourished elderly subjects. DESIGN: The influence of 10 d of supplementation (1.67 MJ/d and 30 g protein/d) on body composition, resting energy expenditure, and whole-body protein kinetics was studied in 17 malnourished elderly patients and 12 healthy young adults. A control group of 6 malnourished elderly patients received no supplementation. RESULTS: Supplemented elderly subjects had a significantly greater fat-free mass gain than did unsupplemented elderly subjects (1.3 and 0.1 kg, respectively; age effect, P < 0.05; diet effect, P < 0.02) and a significantly greater increase in fasting rate of protein synthesis than did young supplemented subjects (0.6 and 0.2 g*kg FFM(-1)*11 h(-1); age effect, P < 0.05). The net protein balance in the supplemented elderly subjects in the fed state was positively correlated with protein intake (r(2) = 0.46) and in the fasted state was negatively correlated with protein intake (r(2) = 0.27). The sum of these regressions is a line with increasingly positive net diurnal protein balance produced by increasing protein intake. CONCLUSION: These data provide evidence of a short-term anabolic response of protein metabolism to dietary supplementation in malnourished elderly patients that is likely to improve muscle strength and functional status.

Absorptiometry, Photon↗

Postprandial modulation of dietary and whole-body nitrogen utilization by carbohydrates in humans.

BACKGROUND: Sucrose exerts a sparing effect on whole-body protein metabolism, mainly during the absorptive phase. OBJECTIVE: We aimed to characterize the acute postprandial effect of addition of sucrose on deamination of dietary and endogenous nitrogen, with particular consideration being given to the effects of bioavailability. DESIGN: Twenty-one subjects equipped with ileal tubes ingested (15)N-labeled soy protein combined with [(13)C]glycine, with (n = 10) or without (n = 11) sucrose. Dietary and endogenous ileal flow of nitrogen were determined from the ileal effluents. The kinetics of dietary amino acid transfer to the blood were characterized by (13)CO(2) enrichment in breath and (15)N enrichment in plasma amino acids. Deamination of dietary and endogenous amino acid was determined from body urea, urinary nitrogen, and (15)N enrichment. RESULTS: (13)CO(2) recovery in breath and (15)N plasma amino acid enrichments were highly correlated (R:(2) >/= 0.95, P: < 0.001, for both meals) and markedly delayed by sucrose (half-(13)CO(2) recovery: 274 min compared with 167 min), whereas exogenous and endogenous ileal nitrogen kinetics and balances remained unchanged. Addition of sucrose halved the early (0-2 h) deamination peak of dietary nitrogen and reduced endogenous nitrogen oxidation over the first 4 h. Both were reduced by 18-24% over the 8-h period after the meal. CONCLUSIONS: Without changing the nitrogen absorptive balance, sucrose markedly affected the bioavailability profile, which is governed by gastric emptying. Endogenous and dietary nitrogen were not spared in the same way and over the same periods, showing that the metabolism of endogenous and dietary nitrogen may be affected differently by nutritional modulation, even if the effects are of a similar magnitude over the entire postprandial period.

Adult↗

EAAT1 is involved in transport of L-glutamate during differentiation of the Caco-2 cell line.

Little is known concerning the expression of amino acid transporters during intestinal epithelial cell differentiation. The transport mechanism of L-glutamate and its regulation during the differentiation process were investigated using the human intestinal Caco-2 cell line. Kinetic studies demonstrated the presence of a single, high-affinity, D-aspartate-sensitive L-glutamate transport system in both confluent and fully differentiated Caco-2 cells. This transport was clearly Na(+) dependent, with a Hill coefficient of 2. 9 +/- 0.3, suggesting a 3 Na(+)-to-1 glutamate stoichiometry and corresponding to the well-characterized X(A,G)(-) system. The excitatory amino acid transporter (EAAT)1 transcript was consistently expressed in the Caco-2 cell line, whereas the epithelial and neuronal EAAT3 transporter was barely detected. In contrast with systems B(0) and y(+), which have previously been reported to be downregulated when Caco-2 cells stop proliferating, L-glutamate transport capacity was found to increase steadily between day 8 and day 17. This increase was correlated with the level of EAAT1 mRNA, which might reflect an increase in EAAT1 gene transcription and/or stabilization of the EAAT1 transcript.

ATP-Binding Cassette Transporters↗

[Standards, Options and Recommendations (SOR) for the use of appetite stimulants in oncology. Work group. Federation of the French Cancer Centres (FNCLCC)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the use of appetite stimulants in oncology. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 55 independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS: The main recommendations for the use of appetite stimulants in oncology are: 1) Corticosteroids and the synthetic progestogens (megestrol acetate and medroxyprogesterone acetate) are appetite stimulants. 2) They can be useful in managing anorexia and weight loss in cancer patients, especially in the palliative setting, despite the potential side-effects of these agents. 3) The most effective way of using these drugs is not known. Inclusion in clinical trials is recommended. 4) Cyproheptadine, metoclopramide, nandrolone and pentoxif line should not be used outside prospective clinical trials. 5) Hydrazine sulfate should not be used.

Adrenal Cortex Hormones↗

Systematic review of epidemiological studies on meat, dairy products and egg consumption and risk of colorectal adenomas.

In view of the direct contact between food residues and metabolites and the large bowel mucosa, it might be expected that food consumption patterns would affect the risk of colorectal carcinogenesis. Many lines of evidence support the adenoma-carcinoma sequence as the major mechanism of colorectal carcinogenesis. The present study aimed to investigate the role of foods of animal origin such as meat, dairy products and eggs in the early stages of colorectal carcinogenesis. Eleven case-control and two cohort studies on colorectal polyps and meat, dairy products and eggs were identified. A quantitative review of these studies and a meta-analysis were carried out. The combined odds ratios suggest a positive association between the risk of colorectal polyps and beef consumption and a negative association with fish or combined poultry/fish consumption. An increase in the ratio of the consumption of red meat to consumption of fish/chicken was associated with an increase in the colorectal polyp risk. Neither dairy product nor egg consumption had a substantial effect on the development of colorectal polyps. These results suggest that dietary factors associated with polyp development may be not the same as those associated with cancer.

Adenoma↗

Intraluminal immunoreactive caseinomacropeptide after milk protein ingestion in humans.

Caseinomacropeptide (CMP)is a 64 amino acids peptide which is the first product released after kappa-casein hydrolysis. The present work investigates the kinetics delivery of CMP in human jejunal lumen during the digestion of intrinsically [15N]-labelled casein, whey protein, yoghurt and pea flour meal. Effluents were collected through a nasointestinal tube and analysed for the enrichment in [15N] to evaluate the dietary nitrogen fraction. Detection and quantification of CMP was performed by an inhibition Elisa procedure. No trace of CMP was detected in the ileum of volunteers after the ingestion of the casein meal. The results showed that CMP appears in the jejunal effluents within the first 20 min after meal ingestion at a level varying from meal to meal. During digestion of whey protein, CMP appeared rapidly as a single peak and in high amounts, whereas it is discharged slowly in moderate proportions with the casein meal. These results demonstrate that CMP is emptied from the stomach in significant amounts during milk products digestion and support the hypothesis that food-born peptides could exert a physiological function. Moreover, in the present study a relation could be assumed between the amount of CMP in the meal and the stimulation of luminal endogenous nitrogen secretion. However, the specific physiological activity of CMP in humans, particularly on the digestion process, requires further studies.

Adult↗