Altered levels of plasma chemokines in breast cancer and their association with clinical and pathological characteristics.

Chemokines are a family of small, structurally related cytokines with chemoattractant and activation properties. In breast cancer, both epithelial cancer cells and cells within the microenvironment secrete chemokines with either tumor-promoting or anti-malignant potential. The equilibrium between these two chemokine activities plays a key role in the biology of the developing tumor, including its ability to metastasize. Here we evaluated the expression of chemokines in breast tumors and the plasma of breast cancer patients before treatment in order to identify a blood-based signature that could distinguish between malignant and non-malignant processes. We screened the mRNA expression of chemokine genes using cDNA microarray on homogenous, laser-capture microdissected breast cancer specimens. Further, using a protein array approach, we determined the levels of selected chemokines in the plasma of patients with breast cancer, benign breast tumors and healthy women. Finally, we analyzed the association between the levels of chemokines in breast and blood samples with the pathological characteristics of the disease. At mRNA level, 27 chemokines and 11 chemokine receptors were differentially expressed in cancers when compared with normal breast tissue. When compared to benign tumors, the only chemokine significantly upregulated in cancers was CXCL10. At protein level, with the exception of CXCL13, nine out of the ten selected chemokines (CCL2, CCL7, CCL18, CCL22, CXCL8, CXCL9, CXCL10, CXCL11 and osteoprotegerin) were significantly overexpressed in the plasma of breast cancers patients compared to healthy controls. After grouping, CXCL8, CXCL9 and CCL22 proved to be significant predictors for breast cancers as compared to healthy controls in a model of logistic regression. We found upregulation of CXCL8, CXCL11 and CXCL9 in triple negative carcinomas, CXCL9 in low proliferative carcinomas, and CXCL10, CCL7 and osteoprotegerin in poorly differentiated carcinomas. Furthermore, CXCL9 was overexpressed in lymph node negative tumors, whereas CXCL8 and CCL18 were higher in advanced stage carcinomas. We identified a panel of chemokines dysregulated in breast cancer that could be further investigated as prospective novel diagnostic markers or for therapeutic and prognostic applications.

Dietary patterns in young adults from Timis County.

UNLABELLED: Dietary patterns present at the age of the young adult have great probability to remain unchanged for the rest of the life and may contribute to eating disorders later in life. The aim of this study is the analysis of the intake patterns for fruits and vegetables in students from Timis County. MATERIAL AND METHODS: We conducted a cross sectional study using a stratified cluster sample design to produce a representative sample of students for the Timis County. The students' sample totalized 2076 students from the universities in Timis County. RESULTS: A large percent of the young people participating in the study (41.9%) does not consume fresh juices. For the consumption of fresh fruits, the present results back up the international di scoveries, only 32.8% of the young people consuming fruits daily, which is a smaller percent that the medium value reported by other countries. The frequency of consumption for fruits differs according to gender, being higher for girls. For salads, the percent of young people consuming this type of foods at least once a day is 17.0%, much lower compared to 32.8% of the young people consuming fresh fruits at least once a day. CONCLUSIONS: The examination of the dietary patterns related to the intake of fruits and vegetables helped us to determine priority areas for future interventions.

Expression of CCL18 and interleukin-6 in the plasma of breast cancer patients as compared with benign tumor patients and healthy controls.

A growing body of laboratory research has shown that pro-inflammatory cytokines can facilitate tumor growth and metastasis. Our goal was to quantify the expression of CCL18 and IL-6 in patients with breast cancer compared with benign breast tumors patients and healthy women, in order to evaluate if these cytokines could serve for breast cancer diagnosis and evaluation. We also correlated the cytokines level of expression with some clinical and pathological characteristics known as prognostic markers for breast cancer. Plasma samples were obtained before treatment from 58 breast cancers, 41 benign breast tumors and 30 healthy women. The quantitative dosage was performed using ELISA. Wilcoxon test was used to compare groups. IL-6 and CCL18 were dramatically upregulated in breast cancers in comparison with healthy controls, but in comparison with benign tumors only CCL18÷PARC was overexpressed at borderline significance in cancers (p=0.05). The plasma from benign breast tumor patients exhibited also significant higher levels of the two cytokines than normal controls. The cytokines profile was not linked to patient age, tumor size, histopathological type, lymph node status or histological grade. IL-6 was significantly upregulated in ER-positive and metastasized cancers. CCL18÷PARC presented a significantly higher expression in advanced stage and highly proliferative carcinomas. In summary, IL-6 and CCL18 could clearly distinguish between women with breast cancers and healthy controls. High expression of IL-6 seems to confer a poor prognosis for ER-positive cancers. CCL18 was associated with worse prognosis parameters like high Ki67.

Pioglitazone delays proximal tubule dysfunction and improves cerebral vessel endothelial dysfunction in normoalbuminuric people with type 2 diabetes mellitus.

AIM: The renal and cerebral protective effects of pioglitazone were assessed in normoalbuminuric patients with type 2 diabetes mellitus (DM). METHODS: A total of 68 normoalbuminuric type 2 DM patients were enrolled in a one-year open-label randomized controlled trial: 34 patients (pioglitazone-metformin) vs. 34 patients (glimepiride-metformin). All patients were assessed concerning urinary albumin: creatinine ratio (UACR), urinary alpha1-microglobulin, urinary beta2-microglobulin, plasma asymmetric dymethyl-arginine (ADMA), GFR, hsC-reactive protein, fibrinogen, HbA1c; pulsatility index, resistance index in the internal carotid artery and middle cerebral artery, intima-media thickness in the common carotid artery; cerebrovascular reactivity was evaluated through the breath-holding test. RESULTS: At 1 year there were differences between groups regarding ADMA, urinary beta2-microglobulin, urinary alpha1-microglobulin, parameters of inflammation, serum creatinine, GFR, UACR, the cerebral haemodynamic indices. Significant correlations were found between alpha 1-microglobulin-UACR (R(2)=0.143; P=0.001) and GFR (R(2)=0.081; P=0.01); beta2-microglobulin-UACR (R(2)=0.241; P=0.0001) and GFR (R(2)=0.064; P=0.036); ADMA-GFR (R(2)=0.338; P=0.0001), parameters of inflammation, HbA1c, duration of DM, cerebral indices. There were no correlations between ADMA-UACR, urinary alpha1-microglobulin and beta2-microglobulin. CONCLUSION: Proximal tubule (PT) dysfunction precedes albuminuria and is dissociated from endothelial dysfunction in patients with type 2 DM. Pioglitazone delays PT dysfunction and improves cerebral vessels endothelial dysfunction in normoalbuminuric patients with type 2 DM.

Molecular profiling of ADAM12 gene in breast cancers.

ADAMs (a disintegrin and metalloproteinase) family have been associated with the process of proteolytic "shedding" of membrane-associated proteins ectodomain and hence the rapid modulation of key cell signaling pathways in tissues microenvironment. A variety of cytokines, chemokines and growth factors which are initially produced as transmembrane proforms are activated by these sheddase activities. ADAM12 is highly expressed in rapidly growing tissues such as placenta and malignant tumors and it was found as one of the Candidate Cancer Genes in a comprehensive mutational analysis of human breast cancers. Our aim was to determine the gene expression profile of ADAM12 in breast cancers in comparison with normal breast and to correlate their level of expression with the clinical and pathological characteristics of breast cancers. Gene expression of ADAM12 spliced variants (12L and 12S) was evaluated using quantitative reverse-transcription PCR in samples obtained by laser capture microdissection from 38 patients with breast cancers and compared with adjacent healthy breast tissues. Both ADAM12L and 12S expression were significantly up-regulated in breast cancers, while in the normal breast, we found a very low expression. ADAM12L expression was significantly correlated with the histopathological types and, although not statistically significant, ADAM12 both variants were up-regulated in high-grade, highly-proliferative and HER2÷neu positive tumors. From these preliminary results, we found that ADAM12 could be an interesting marker and eventually a therapeutic target for breast cancer.

Estrogen receptor alpha polymorphisms: correlation with clinicopathological parameters in breast cancer.

Polymorphisms in estrogen receptor alpha gene (ESR1) have been previously associated with breast cancer risk; however, the results were not fully consistent. Our purpose was to study interactions between common genotypes in ESR1, breast cancer risk and tumor phenotypes. 6 ESR1 single nucleotide polymorphisms (SNPs) were genotyped in 103 breast cancer patients and 90 controls using hybridization probes; the genotypes were correlated with known prognostic factors for breast cancer and 5 years-follow up data. To assess estrogen and progesterone receptors (ER, PR) and HER2/neu expressions, immunohistochemistry was performed. Our results showed that rs3798577 was significantly associated with the risk of breast cancer, the common allele C conferring susceptibility (p-trend=4 x 10(-5)); rs3798577 was also correlated with PR expression (p=0.01), but not with ER expression; rs2228480 (p=0.047) and rs1801132 (p=0.02) were associated with the age at diagnosis; rs1801132 was correlated with hypercholesterolemia (p=0.003) and increased BMI (body mass index) (p=0.01); rs2234693 showed a low significant association (p=0.042) with the tumor grade; rs3798577 was correlated with disease-free survival (p=0.05), allele C conferring increased risk for relapses, but it reached not statistical significance after adjustments. In conclusions, we identified four genotypes significantly correlated with either the risk or some tumor characteristics, suggesting that the main selection criteria of the investigated SNPs (frequency and the position in modulating domains of the gene) are pertinent instruments for establish correlations between the gene structure and the tumor phenotype.

Interaction between estrogens and androgen receptor genes microsatellites, prostate-specific antigen and androgen receptor expressions in breast cancer.

The role of estrogen and androgen receptors signaling in breast cancer is widely accepted, but the interrelations between them are not well understood. It was suggested that PSA could be a marker of endogenous balance between androgens and estrogens. In this context, we intended to investigate the potential of relationship between polymorphic tandem repeats (CAG, TA and CA) in AR (androgen receptor), ERalpha (estrogen receptor alpha) and ERbeta (estrogen receptor beta) genes and the immunoexpression of PSA and AR proteins. We assessed also the possible influences of CAG, TA, and CA variables and other available prognostic factors (ER, PR, AR, HER2/neu, PSA expression, and nodal status) on disease-free survival. We assessed the polymorphic tandem repeats lengths by genotyping, followed by high-resolution denaturing polyacrylamide gel electrophoresis in 163 breast cancers. Immunohistochemistry was performed to assess the expressions of AR, PSA, ER, PR and HER2/neu proteins. Our results showed that PSA was correlated with the length of CA repeats in the 3'-untranslated region of ERbeta, shorter CA repeats being correlated with PSA expression (p=0.03). AR immunoexpression was correlated with CAG repeats on AR gene, higher number of repeats being linked to a higher AR immunoexpression (p=0.04). Performing logistic regression to investigate relationships with prognosis, we observed that PSA immunoexpression (p=0.004), the nodal status (p-<0.001) and marginally, longer TA repeats (p=0.05) were correlated with increased disease-free survival. AR expression presented a low statistical value (p=0.054) in predicting evolution and was not entered into the multivariate regression analysis. Altogether, our findings supports the hypothesis that estrogens, through both alpha and beta-receptors variants are mediating the AR signaling pathway.

Eating habits in an adolescent population from Timis county.

UNLABELLED: Dietary patterns during adolescence may contribute to eating disorders and may increase the risk for several important chronic diseases later in life. OBJECTIVES: The aim of this study is to analyze eating behaviours among high school students residing in Timis county area. MATERIAL AND METHOD: We conducted a cross sectional study using a stratified cluster sample design to produce a representative sample of students for the Timis county. From 1083 primary sampling units (classes) 149 were randomly selected, stratified proportionally according to grades 9-12, high school profile (theoretical, industrial, vocational, and confessional), urban and rural environment. The study was carried out in 2004. RESULTS: The overall response rate of 74.6%. A total of 2908 students were included in the survey. The proportion of students consuming less than daily milk & diary products, green salad and fruits was: 58.3% for milk & dairy products, 71.2% for green salad and 59.1% for fruits. Based on multivariate analysis three common predictors for consuming fresh fruits, green salad and milk and diary products were identified: perceived weight, school performance and school grades. CONCLUSIONS: Through examination of prevalence rates of nutrition-related concerns we have identified priority areas to be targeted with future interventions.

[Food intake and colorectal cancers; an ecological study in Romania]. / Consumul de alimente in relatie cu cancerul colo-rectal. Studiu ecologic in România.

UNLABELLED: The aim of the present study performed in a Romanian population was to identify the food which can be either associated with or protect against colorectal carcinoma. MATERIAL AND METHOD: Correlation and regression analysis were used to examine the association between dietary intake and the rate of incidence for colon, rectum and anus cancers, in study groups from 7 regions of Romania. RESULTS: A strong and positive association was observed for colonic cancer and the intake of coffee, tea and cocoa (r = 0.77, p = 0.042) whereas statistical significance of borderline value was found for margarine (r = 0.73, p = 0.06) and sweets (r = 0.74, p = 0.066) intake. A potential protective effect can be attributed to wine consumption ( r = -0.75, p = 0.03). The malignancies of the rectum and anus showed both a strong positive correlation with the intake of red meat ( r = 0.76, p = 0.048), sausages ( r = 0.87, p = 0.012), margarine (r = 0.97, p = 0.0004), butter ( r = 0.76, p = 0.049), sweets ( r = 0.93, p = 0.003), beverages (r = 0.97, p = 0.0003), coffee, tea, cocoa ( r = 0.94, p = 0.002). Negative correlations were reported for the recto-anal cancer and the consumption of: fish (r = -0.8, p = 0.032), cheese (r = -0.9, p = 0.006), wine (r = -0.85, p = 0.015). CONCLUSION: The need for reducing the dietary intake of margarine, red meat, sausages and sweets while the beneficial effects of wine consumption have been also confirmed.

Role of multi-component functional foods in the complex treatment of patients with advanced breast cancer.

UNLABELLED: Cancer increases free radicals and that certain diets can influence oxidative stress. There is little evidence about the functional effect of multi-component functional foods on oxidative stress in breast cancer. MATERIAL AND METHODS: 34 female patients with histologically confirmed breast cancer, stages IIIB and IV were enrolled in a randomised controlled trial. All patients filled out the Quality of Life questionnaire FACT-B version 4, translated in Romanian and validated, obtained from Evanston North-Western Health Care, Illinois, USA. Seventeen patients, mean age 57.84 +/- 11.2, were put on a special diet consisting of 15 ml/day balsamic vinegar from apples and honey, with seabuckthorn berry rich in carotenoids, rosemary, sage and basil extracts, to be used in salads and vegetable soups, 150 g/day whole wheat bread with 2.5% of the nutraceutic mixture VITAPAN, 15 ml/day grape seed extract rich in polyphenols (gr. 1). Seventeen patients served as control (gr. 2). Parameters of the metabolic syndrome were measured: serum lipids, IR-HOMA insulin resistance index. Oxidative stress was measured by the FORT (free oxygen radical) test. Total hydro- and liposoluble antioxidants (ACW, ACL) in serum were measured by chemo-luminometry. All investigations were done at entry and after 3 months. RESULTS: Student's t test was applied to compare the means within group and between the 2 groups. The Physical well being subscale score of the QOL FACT-B version 4 questionnaire showed a significant difference between the 2 groups (p = 0.001). Also, functional well being subscale (p = 0.004), FACT-G (p = 0.003) and FACT-B (p = 0.002) showed significant differences on comparison. Breast Cancer Score (Additional Concerns) had a borderline significant difference (p = 0.057). Social/Family Well being subscale and Emotional well being subscale scores showed no significant difference. At inclusion, radical activity > 310 FORT units, relevant for increased oxidative stress were present in 95.1% cases. After 3 months radical activity > 310 FORT units were present in 52.8% cases in gr. 1. CONCLUSION: A proper design of foods enriched with bioactive compounds that can lead to significant effects on health represents a promising adjuvant treatment in patients with advanced breast cancer, due to its contribution in lowering the high oxidative stress present in these patients.

[Dermabrasion in two cases of tuberous sclerosis]. / Tratamentul prin dermabraziune a doua cazuri de scleroza tuberoasa Bourneville.

The authors made an attempt at treating tuberous sclerosis (Bourneville's disease) by means of dermabrasion. The technique and postoperative course are described. The immediate results were very encouraging, but in time returned to an appearance close to the initial one. In conclusion, dermabrasion is not an appropriate treatment for tuberous sclerosis.

[A study of risk factors and the epidemiology of accidents in the child population]. / Contributions á l'étude des facteurs de risque et l'épidémiologie des accidents chez la population infantile.

The medical social and economic consequences of motor vehicle accidents in the infant population represent a major problem in public health. The present study was conceived as a descriptive epidemiological survey carried out retrospectively over a six-year period on the basis of case records. Potential risk factors related to accidents were: sex, social origin, age group, calendar month, day of the week, circumstances of the accident, parental supervision, location of the injury. In order to get a clearer image of how injuries are produced in traffic accidents, the collision of vehicles and pedestrians was studied in terms of bio-mechanics with special emphasis on the specific impact forces affecting pedestrians.