Tumor necrosis factor alpha induced protein 3, interleukin 10, tumor necrosis factor alpha, and interleukin 17 F genes polymorphisms in Algerian patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation. Its pathogenesis involves immunological, genetic, and environmental factors. We investigate the association between Tumor Necrosis Factor α Protein 3 (TNFAIP3), Interleukin 10 (IL10), Tumor Necrosis Factor α (TNF α), and Interleukin 17 F (IL17F) polymorphisms with susceptibility to RA. METHODS AND RESULTS: 191 patients with RA diagnosed according to the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification and 190 healthy subjects were recruited. Rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and C-reactive protein (CRP) were measured. Genotyping of the polymorphisms was performed by real-time PCR. Analysis of the allelic frequencies of TNFAIP3 showed a positive association OR (95% CI) = 1.46 (1.01-2.09); p = 0.04, but failed to meet the criteria of significance after Bonferroni Correction. The genotypic and allelic distribution of the IL10, IL17F, and TNFα showed no significant difference when comparing the RA group with controls. Furthermore, the genotype codominant model shows a moderate positive association in the presence of ACPA (OR (95% CI) = 2.82 (1.22-6.24); p = 0.01. None of the polymorphisms studied was associated with RF and CRP production. CONCLUSION: Our results show that there is a tendency for the AG genotype of IL10-1082 to be associated with the production of ACPA in patients with RA. None of the variants studied were associated with RA susceptibility in Algerians.

Antibiotic photocatalysis and antimicrobial activity of low-cost multifunctional Fe3O4@HAp nanocomposites.

Water contamination by multiple pollutants is a serious environmental issue originating from the many diverse sources of pollution. It has worsened with the appearance of new contaminants, named emerging micropollutants, such as drug residues which are considered a potential threat to human health and/or ecosystems. These require prior treatment before release into the environment. Simultaneous adsorption and photocatalysis as well as solid-liquid separation are promising technologies for water treatment. In order to obtain low cost photoactive nanocomposites, porous and magnetic Fe3O4-hydroxyapatite (wFeHAp) nanocomposites were prepared by soft chemistry from the dissociation of natural phosphate into Ca2+ and H3PO4 precursors, further neutralized by ammonia in the presence of preformed Fe3O4 particles. The magnetic nanocomposites were characterized and examined as effective antibacterial agents. Fe3O4 association with apatite modifies the surface properties of the wFeHAp nanocomposite materials, yielding efficient antimicrobial activity for S. aureus, B. subtilis, E. coli and K. pneumoniae strains. The photocatalytic removal of ciprofloxacin (CPF) and oxytetracyclin (OXT) antibiotics in water was also evaluated. The wFeHAp nanocomposites adsorbed and degraded the selected antibiotics successfully. Toxicity evaluation of the treated water after photodegradation using the four strains demonstrates the absence of toxic by-products at the end of the reaction. Therefore, Fe3O4@HAp nanoparticles are valuable for antimicrobial and photocatalysis applications.

Transcriptome analysis reveals a complex response to the RGNNV/SJNNV reassortant Nervous Necrosis Virus strain in sea bream larvae.

The gilthead sea bream (Sparus aurata) is a marine fish of great importance for Mediterranean aquaculture. This species has long been considered resistant to Nervous Necrosis Virus (NNV), an RNA virus that causes massive mortalities in several farmed fish animals. However, the recent appearance of RGNNV/SJNNV reassortant strains started to pose a serious threat to sea bream hatcheries, as it is able to infect larvae and juveniles of this species. While host response to NNV has been extensively studied in adult fish, little attention has been devoted to early life history stages, which are generally the most sensitive ones. Here we report for the first time a time-course RNA-seq analysis on 21-day old fish gilthead sea bream larvae experimentally infected with a RGNNV/SJNNV strain. NNV-infected and mock-infected samples were collected at four time points (6 h, 12 h, 24 h, and 48 h post infection). Four biological replicates, each consisting of five pooled larvae, were analysed for each time point and group. A large set of genes were found to be significantly regulated, especially at early time points (6 h and 12 h), with several heat shock protein encoding transcripts being up-regulated (e.g. hspa5, dnaj4, hspa9, hsc70), while many immune genes were down-regulated (e.g. myd88 and irf5 at T06, pik3r1, stat3, jak1, il12b and il6st at T12). A gene set enrichment analysis (GSEA) identified several altered pathways/processes. For instance, the formation of peroxisomes, which are important anti-viral components as well as essential for nervous system homeostasis, and the autophagy pathway were down-regulated at 6 h and 24 h post infection (hpi). Finally, two custom "reactomes" (i.e. significant gene sets observed in other studies) were defined and used. The first reactome integrated the transcriptomic response to NNV in different fish species, while the second one included all genes found to be stimulated either by interferon (IFN) or by IFN and Chikungunya virus in zebrafish. Genes in both reactomes showed predominant up-regulation at 6hpi and 12hpi and a general down-regulation at 24hpi. Such evidence suggest a certain degree of similarity between the response of sea bream and that of other fish species to NNV, while the observed down-regulation of IFN- and viral-stimulated pathways argues for a possible interference of NNV against the host response.

Clinical variables and ethnicity may influenced by polymorphism of CAT -262C/T and MnSOD 47C/T antioxidant enzymes in Algerian type1 diabetes without complications.

The latest studies in Algeria show that the frequency of type 1 diabetes (T1D) without complications is lower than that with complications and represents a significant burden in terms of cost and treatment. For this reason, we are interested in uncomplicated type1 diabetes and risk factors that are related to polymorphisms of antioxidant enzymes in order to prevent its complications. A total of 260 blood samples of young Algerian adults were examined. The genotypic analysis of Catalase gene (CAT -262C/T, rs1001179) and the superoxide dismutase gene (MnSOD 47C/T, rs4880) was performed by real-time PCR using TaqMan technology. The genotypic distribution of the CAT -262C/T promoter gene's polymorphism showed a significant difference between control and T1D patients for the CC genotype (p = 0.009; OR = 0.30) and for the T allele (p = 0.002; OR = 2.82). In addition, the genotypic distribution of the MnSOD 47C/T gene showed an association with T1D for the CT genotype (p = 0.040; OR = 2.37). Our results revealed that polymorphisms of CAT and MnSOD may be associated with physiopathology causing the onset of T1D. Our data, suggest that the genotypic frequencies of these SNPs appear to be influenced by clinical variables and by the Arab-Berber ethnic origin of the Algerian population.

NOD2/CARD15 and IL23R genetic variability in 204 Algerian Crohn's disease.

NOD2/CARD15 and IL23R gene variants play an important role in the susceptibility to Crohn's disease (CD). Studies of genotype-phenotype relationship suggest that these variants are associated with the development of the disease and specific phenotype. Preliminary reports analyzing the association between these variants have never been made on Algerian CD's. In a case-control design, 204 Algerian with CD diagnosed for at least 5years and 201 controls were included were genotyped for single nucleotide polymorphisms (SNP) in the NOD2/CARD15 gene R702W (SNP8, rs2066844), G908R (SNP12, rs2066845) and IL23R R381Q (rs11209026) gene variants were determined using the TaqMan SNP genotyping assays. NOD2/CARD15 908R was carried by 3% of the patients and none in control subjects (χ(2)=8.6, Pc=0.003, OR=13.20). NOD2/CARD15 702W was associated to CD outcome (χ(2)=17.2, Pc=0.00003, OR=12.5) and early onset of disease (group A1, χ(2)=19.3, Pc=1.10(-5), OR=14.05, PM-H=2.10(-6)). IL23R 381Q variants was more frequent in CD's patients than controls (χ(2)=8, Pc=0.005, OR=3.48), it was associated to earlier onset (group A1, χ(2)=7.1, Pc=0.007, OR=1.04, PM-H=0.002), extra-intestinal manifestations (EIM) outcome (χ(2)=10.6, Pc=0.001, OR=1.05, PM-H=0.002) and ileocolonic location (χ(2)=6.8, Pc=0.009, OR=1.05, PM-H=0.001). In this Algerian cohort, NOD2/CARD15 and IL23R variants were associated with CD's outcomes and linked to a particular clinical phenotype.

[Susceptibility genes, HLA and diabetic retinopathy in the Algerian population]. / Gènes de susceptibilité HLA et rétinopathie diabétique chez la population algérienne.

BACKGROUND: Diabetic retinopathy (DR) is the most frequent microvascular complication of type I diabetes (T1D). Some well-controlled type I diabetics may develop DR, while other poorly-controlled diabetics do not develop DR. This might be explained by certain susceptibility genes or protective genes. The purpose of our study is to search for any association between the HLA class I and II markers and DR in the Algerian population. PATIENTS AND METHODS: This study was carried out in 52 T1D subjects with and without DR compared to 140 healthy controls. HLA typing was performed using the "microlymphocytotoxicity" technique. RESULTS: The frequency of HLA-A29 and HLA-DR9 antigens is higher in T1D with DR compared to T1D without DR and to controls with frequencies of HLA-A29 (59.26% vs. 0%, OR=∞, pc=4.6×10(-7)), (59.26% vs. 5.66%, OR=24.24, pc=7.6×10-10) and HLA-DR9 (29.63% vs. 0%, OR=∞, pc=1.310(-3)), (29.63% vs. 4.29%, OR=9.40, pc=7.010(-5)) respectively. However, the frequency of HLA-B49 antigen is significantly lower in T1D with DR than in T1D without DR (3.7% vs. 28%, OR=0.10, pc=8.8×10(-3)) and compared to controls (3.7% vs. 22.64%, OR=0.13, pc=0.011). CONCLUSION: HLA-A29 and HLA-DR9 antigens are probably markers of susceptibility for DR while HLA-B49 antigen is probably associated with a protective effect in the Algerian population.

Effective strategy for decreasing blood culture contamination rates: the experience of a Veterans Affairs Medical Centre.

Contaminated blood cultures constitute diagnostic challenges and place a burden on healthcare services. An observational retrospective study was undertaken to evaluate the effect of routine labelling of blood culture bottles with the initials of the healthcare worker who drew them, followed by individualized feedback, on blood culture contamination rates. The contamination rate of the entire facility was 2.6% before the procedural change, and this decreased significantly to 1.5% after the procedural change (P < 0.001) over the first 12 months of the intervention. Routine labelling of blood culture bottles with the initials of the healthcare worker who drew them, followed by individualized feedback, was effective in reducing blood culture contamination rates.

Association of interleukin-10 gene promoter polymorphisms with chronic and aggressive periodontitis.

OBJECTIVE: Interleukin-10 gene promoter polymorphisms have been associated with interleukin-10 decreased production, thereby playing a role in the pathogenesis of periodontitis. This study aimed to investigate whether interleukin-10 single nucleotide polymorphisms at positions -1087(G/A) and -597(C/A) are associated with generalised chronic periodontitis and localised aggressive periodontitis. METHODS: Genomic DNA samples were isolated from 276 unrelated Jordanian participants. Subjects were categorised into 86 periodontally healthy controls, 105 chronic periodontitis patients and 85 localised aggressive periodontitis patients. Genotype frequencies were calculated, and differences were determined using Pearson chi-squared test, and odds ratio and 95% confidence intervals were included. RESULTS: The frequencies of the -1087A and -597A alleles were significantly more common in chronic periodontitis patients than controls. The A-positive allele genotypes (GA, AA) at position -1087 and A-positive allele genotypes (CA, AA) at position -597 appeared to increase the risk of having chronic periodontitis. No significant differences were observed in the genotype frequencies between localised aggressive periodontitis patients and controls. CONCLUSIONS: These findings indicate the possible use of interleukin-10 single nucleotide polymorphisms as genetic markers in chronic periodontitis patients and further emphasise the molecular differences between chronic periodontitis and aggressive periodontitis.

Variation of genetic diversity over time in local Italian chicken breeds undergoing in situ conservation.

The aim of this study was to analyze the variation of different genetic diversity measures in 5 Italian local chicken breeds over a 4-yr period of conservation. The local breeds were Ermellinata di Rovigo, Padovana, Pépoi, Robusta Lionata, and Robusta Maculata. A total of 368 samples were chosen for the analysis among the birds hatched in the years 2002 and 2006. Genetic variation over 30 microsatellite loci was analyzed. All 30 microsatellites were polymorphic, with a total number of alleles equal to 251, a mean (±SD) of 8.367 ± 3.378 across populations and 3.233 ± 1.338 within population. After 4 yr of conservation, a loss of alleles occurred for all the microsatellites, with the exception of 4 loci. The total number of alleles and expected heterozygosity estimates significantly decreased during the 4 yr of conservation, whereas no significant differences were detected for the microsatellites polymorphism information content or for the observed heterozygosity estimates. A decrease of the inbreeding coefficient occurred for all the breeds, with the exception of Padovana and Robusta Lionata. All populations showed evidence of a persistent significant deviation from Hardy-Weinberg equilibrium caused by an excess of homozygotes, except Robusta Maculata, which reached the equilibrium in 2006. For Pépoi, Padovana, Ermellinata di Rovigo, and Robusta Maculata, molecular coancestry increased significantly (P < 0.001) after the 4 yr of conservation. No evident genetic structures were detectable within breed, both for 2002 and for 2006 individuals. However, a slight increase in the proportion of membership for each breed had occurred in the year 2006 compared with the data obtained in the year 2002. As consequence, within breed, individuals in 2006 appear more homogeneous, producing clearer, more distinctive and separated groups. Molecular markers analysis helped us monitor the genetic variability of local breeds involved in a conservation scheme, enabling the planning of new strategies for the improvement of in situ conservation schemes.

Sarcomatoid squamous cell carcinoma: a long-standing case.

Sarcomatoid, or spindle cell squamous cell carcinoma (SCSC), is relatively uncommon, but may be encountered. It poses a challenge in differential diagnosis that includes other spindle cell neoplasms. We present a case where the lesion existed for 20 years and raised the potential of chronicity as a factor in inducing spindle cell morphology. Detailed immunohistochemical features are demonstrated, and discussion of the differential diagnosis is offered. The patient was an 89-year-old African-American female with an exophytic and polypoid mass of the right upper arm measuring 5.5 x 5.5 x 3.0 cm. The mass had been present for the last 20 years, and was gradually and very slowly increasing in size. After refusing surgery several times, she finally agreed to have an excision. The tumor proved to be SCSC.

Purification, preliminary characterization and immunohistochemical localization of POSVP21 in the sand rat (Psammomys obesus) seminal vesicles.

The sand rat Psammomys obesus is a mammalian species with male seasonal reproduction. Previously Gernigon et al. (1994) [Gernigon T, Berger M, Lecher P. Seasonal variations in the ultrastructure and production of androgen-dependent proteins in the seminal vesicles of a saharian rodent (Psammomys obesus). J Endocrinol 1994;142:37-46.] reported that the seminal vesicles of the adult sand rat contained a major secretory protein band (M.W. 21000) regulated by testosterone. This protein is synthesized in large amounts when the androgen level increases, and accounts for over 22% of soluble proteins from homogenate of seminal vesicles during the breeding season. When analyzed by NepHGE the protein band of 21kDa appeared to be composed of at least 3 visible spots with pHi values varying from 4 to 7. Its partially internal sequence was identified and exhibited five peptides. Polyclonal antibodies against POSVP21 were obtained in rabbits. They were also used to study immunohistochemical antigen localization by the means of an avidin-biotin peroxidase procedure. Observation showed that it is localized in the cytoplasm of epithelial cells and in secretory products in the lumen. The whole RNA of seminal vesicles was translated in a cell-free system derived from rabbit reticulocyte lysate and [35S]-methionine. Two major bands of 14.4 and 21kDa were visualized by means of denaturing gel electrophoresis. SDS-PAGE from medium incubation of seminal vesicle tissue with [35S]-methionine revealed one band with an apparent molecular weight of 21kDa. The results obtained indicate that seminal vesicle epithelium is the site of POSVP21 synthesis and the comparison of the partial amino acid composition of the internal sequence, indicated that POSVP21 constitute a family of most unusual proteins.

Constitutive nitric oxide synthase gene polymorphisms and house dust mite respiratory allergy in an Algerian patient group.

Genetic polymorphisms in neuronal nitric oxide synthase (NOS1) and calmodulin-dependent endothelial NOS (NOS3) genes are known to influence the course of allergic respiratory disorders. We investigated the role of NOS1 -84 G-->A and NOS3 -786 T-->C, 894 G-->T and 27 base pair (bp) repeat polymorphisms in 125 patients suffering from asthma and/or rhinitis and monosensitized against Dermatophagoides pteronyssinus (Dpter) and 111 controls from Algeria. We found a higher frequency of the -786 C NOS3 allele in patients than in controls [corrected P value (Pc) = 0.04], especially in female cases (Pc = 0.02) and that the 'ab' genotype of the 27-bp polymorphism was significantly associated with specific immunoglobulin E production against Dpter (P = 0.006). This study brings further support for the participation of NOS3 gene polymorphism in the pathogenesis of respiratory allergic disorders.

Fine needle aspiration cytology of lung lesions: a clinicopathological and cytopathological review of 150 cases with emphasis on the relation between the number of passes and the incidence of pneumothorax.

OBJECTIVE: The aim of this study was to review the lung fine needle aspirations (FNA) that were done in our hospital between January 1998 and April 2004. Interobserver agreement, sample adequacy and the relation between the number of passes and the occurrence of pneumothorax are presented. STUDY DESIGN: One hundred fifty cases of lung FNA from the department of pathology files were identified and the available specimens and patient charts were reviewed. The interobserver agreement was calculated. The relation between the number of passes and the subsequent development of pneumothorax was tested using Mann-Whitney U-test. RESULTS: The material of 132 patients (88%) out of 150 were retrieved and reviewed. There were 85 cases of non-small cell lung cancer (NSCLC) (64.4%), nine cases of small cell lung cancer (6.8%), five cases of metastatic cancer (3.8%) and 33 cases were reported negative for cancer (25%). The NSCLC included 36 cases of adenocarcinoma (27.3%), 32 cases of squamous cell carcinoma (24.2%), and 17 cases of large cell undifferentiated carcinoma (12.9%). The interobserver agreement k was 0.93, (95% CI 0.87-0.98). The majority of cases (95.5%) were considered adequate for interpretation. The charts of 138 patients (92%) were reviewed for postprocedure radiologically confirmed pneumothorax. Sixteen patients (11.6%) developed pneumothorax only three of whom (2%) required a chest tube for treatment. The number of passes was identified in 118 patients (85.5%). The number of passes did not have a statistically significant association with the development of a pneumothorax (P = 0.747). CONCLUSION: Fine needle aspirations to diagnose lung lesions is a safe procedure with a low incidence of pneumothorax. Its findings are reproducible with high interobserver agreement. Immediate adequacy evaluation and triage by a pathologist guarantees adequate sample in most instances. The number of passes was not associated with an increased incidence of pneumothorax.

Differential expression of HER-2/NEU receptor of invasive mammary carcinoma between Caucasian and African American patients in the Detroit metropolitan area. Correlation with overall survival and other prognostic factors.

GOALS: HER-2/neu overexpression in invasive mammary carcinoma is associated with more aggressive biologic behavior. Breast cancer in African American (AA) women has been associated with a shorter survival rate than that seen in Caucasians (C). This study evaluated the frequency of HER-2/neu overexpression in C compared to AA patients and the association of HER-2/neu expression with overall survival and other prognostic factors. METHODS: A retrospective review of the SEER data of Karmanos Cancer Institute for patients with invasive mammary carcinoma was conducted between 1998 and 2001. Pathology reports and pathology slides were obtained for those patients with missing data. Available data and material on 608 patients were found. The median follow-up interval was 35 months with a range of 1-91 months. 46.7% of the study population was C while 53.3% was AA. The differential of HER-2/neu expression in C and AA was evaluated. The association of HER-2/neu expression and other prognostic factors with overall survival was carried out by univariate and multivariable analyses using Cox's proportional hazards regression model. PRINCIPLE RESULTS: No statistically significant difference was found in HER-2/neu expression between C and AA patients. Overexpression of HER-2/neu did not correlate with decreased overall survival in this analysis. MAJOR CONCLUSIONS: Breast cancer HER-2/neu expression in AA patients is not statistically different from that of Caucasians. HER-2/neu expression is not associated with overall survival. Among the other prognostic factors analyzed, ER status and histologic grade were not statistically significant.

[Autoimmune chronic active hepatitis: anatomoclinic's study of 50 patients]. / Les Hépatites auto-immunes (HAI) chroniques de l'adulte: étude anatomoclinique d'une série de 50 patients.

PURPOSE: To analyse anatomoclinic and evolutive aspects of autoimmune hepatitis (AIH) through 50 observations collected in two Internal Medicine departments in Algiers from 1998 to 2002 and to make a review of the literature. METHODS: The study is prospective. The diagnosis of autoimmune hepatitis (AIH) is established according to the recommendations of the score of the International Autoimmune Hepatitis Group (1991) or/and hepatitic damage confirmed by histology. RESULTS: Fifty patients were studied: (32 women-18 men) and the mean age was 38 years (17 to 73). Autoimmune extra-hepatitic manifestations were associated in 26%. The AIH type 1 has been noted in 58%. AIH were type 2 in only 6%. In 22% of the cases AIH were sero-negative and the others AIH represented 14% were classed as overlap-syndrome (5 cases of primary biliary cirrhosis and 2 cases of primary sclerosing cholangitis hepatitis overlap syndrome). The first liver biopsy tissue showed strong necrotic-inflammatory activity in 56% and cirrhosis was identified in 19 patients (38%). The treatment (azathioprine and corticosteroid) was prescribed in 37 patients (74%) in active chronic hepatitis or in compensed cirrhosis. FOLLOW-UP: 28% of the patients died (9-36 months) because cirrhosis's complications or because complications of hepatocarcinoma (3 cases). CONCLUSION: The diagnosis of AIH must be established early for each patient with chronic liver disease particularly is those are supposed as a crypto genetic hepatitis. The prognosis is compromised by delayed diagnosis and the mortality in middle following up is high.

Role of glucose and ketone bodies in the metabolic control of experimental brain cancer.

Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and elevate ketone bodies in the CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice were fed either a standard diet unrestricted (SD-UR), a ketogenic diet unrestricted (KD-UR), the SD restricted to 40% (SD-R), or the KD restricted to 40% of the control standard diet (KD-R). Body weights, tumour weights, plasma glucose, beta-hydroxybutyrate (beta-OHB), and insulin-like growth factor 1 (IGF-1) were measured 13 days after tumour implantation. CT-2A growth was rapid in both the SD-UR and KD-UR groups, but was significantly reduced in both the SD-R and KD-R groups by about 80%. The results indicate that plasma glucose predicts CT-2A growth and that growth is dependent more on the amount than on the origin of dietary calories. Also, restriction of either diet significantly reduced the plasma levels of IGF-1, a biomarker for angiogenesis and tumour progression. Owing to a dependence on plasma glucose, IGF-1 was also predictive of CT-2A growth. Ketone bodies are proposed to reduce stromal inflammatory activities, while providing normal brain cells with a nonglycolytic high-energy substrate. Our results in a mouse astrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevate ketone bodies.

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model.

Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30-40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal x day(-1), respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers.