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Ymittos Athens, Greece

Scorilas A.,National and Kapodistrian University of Athens | Ardavanis A.,Saint Savvas Cancer Hospital
Tumor Biology

Kallikrein-related peptidases (KLKs) are emerging novel new biomarkers for prognosis, diagnosis and therapeutic intervention of cancer. Kallikrein-related peptidase 6 (KLK6) has the highest expression in normal brain among other tissues. Although its expression has been extensively studied in many types of cancer and in neurodegenerative diseases, very little is known for its expression in intracranial tumors. In the present study, 73 intracranial tumor samples were examined for KLK6 messenger ribunucleic acid (mRNA) gene expression using quantitative real-time polymerase chain reaction. Statistical analysis revealed the significant association of KLK6 expression with clinical and pathological parameters. Follow-up information was available for a median time of 20 months (range 1-59 months). KLK6 is expressed more frequently in tumors of high malignancy like the glioblastomas (70.6 %) and less in tumors of low malignancy like the meningiomas (12.5 %). KLK6 positive expression is associated with tumor grade (p < 0.001), malignancy status (p < 0.001), and tumor histologic type (p = 0.001). Cox proportional hazard regression model using univariate analysis revealed for the first time that positive KLK6 expression is a significant factor for disease-free survival (DFS; p = 0.041) of patients suffering from intracranial tumors. Kaplan-Meier survival curves demonstrated that negative KLK6 expression is significantly associated with longer DFS (p = 0.032). KLK6 gene expression may have clinical utility as a marker of unfavorable prognosis for intracranial tumors, and consequently, it could be used as target for therapeutic intervention. © 2012 International Society of Oncology and BioMarkers (ISOBM). Source

Devetzi M.,University of Ioannina | Trangas T.,University of Ioannina | Scorilas A.,National and Kapodistrian University of Athens | Xynopoulos D.,Saint Savvas Cancer Hospital
Thrombosis and Haemostasis

Currently available colon cancer (CC) markers lack sensitivity and specificity. Kallikrein-related peptidases (KLKs) present a new class of biomarkers under investigation for diverse diseases, including cancer. KLKs are co-expressed in various tissues participating in proteolytic cascades. KLK7 in human tumours facilitates metastasis by degrading components of the extracellular matrix. KLK14 promotes tumourigenesis by activating proteinase-activated receptors. In the present study we examined the concomitant expression of KLK7 and KLK14 in 245 colonic tissue specimens from 175 patients; 70 were pairs of cancerous- normal tissues, 31 were cancerous tissues and 74 were colonic adenomas. We used quantitative real-time PCR and proved that both genes are up-regulated in CC at the mRNA level. Receiver-operating characteristic (ROC) analysis of our results showed that both genes have discriminatory value between CC and adenoma tissues, with KLK14 obtaining greater distinguishing power (area under the curve [AUC]=0.708 for KLK14; AUC=0.669 for KLK7). Current work showed that the two genes are fairly co-expressed in all three types of colon tissues examined (normal rs=0.667, p<0.001, adenomas rs=0.373, p=0.001, carcinomas rs=0.478, p<0.001). KLK14 is associated with shorter disease-free survival (DFS) and overall survival (OS) of patients (p=0.003, p=0.016 respectively), whereas KLK7 only with shorter DFS (p=0.004). KLK7 and KLK14 gene expression can be regarded as markers of poor prognosis for CC patients with discriminating power between CC and adenoma patients. © Schattauer 2013. Source

Scorilas A.,National and Kapodistrian University of Athens | Tsapralis N.,Saint Savvas Cancer Hospital | Missitzis I.,Saint Savvas Cancer Hospital | Ardavanis A.,Saint Savvas Cancer Hospital
Tumor Biology

Kallikrein-related peptidases (KLKs) are a group of 15 serine proteases, hormonally regulated, and localized on chromosome 19q13.4. Alternative splicing is a process that plays significant role in the development, physiology, and different diseases, like cancer. Kallikrein family numbers more than 82 alternative transcripts. Understanding the role that those gene transcripts play in various cancer types, could lead to the discovery of diagnostic markers or drug targets. The present study was designed to analyze the expression profile of the splice variants of kallikrein-related peptidase 12 (KLK12) in breast cancer patients and to evaluate their clinical significance. KLK12 splice variants (KLK12sv3 and KLK12sv1/KLK12sv2) were examined in 69 tissue samples of breast cancer using quantitative real-time PCR as well as semi-quantitative PCR. Relative quantitative expression of KLK12 was statistically associated to clinicopathological parameters. From the splice variants examined, statistical associations with clinicopathological parameters were obtained only from KLK12sv3 variant. KLK12sv3 is more frequently expressed in tumors of lower grade (p = 0.040), early patient TNM stage (p = 0.024), and smaller tumor size (p = 0.023). Positive KLK12sv3 expression is associated with longer patient disease-free survival (DFS) (p = 0.042) and higher progesterone receptor concentration (p = 0.008). KLK12sv1/KLK12sv2 expression is statistically associated with KLK12sv3 expression (p = 0.001). KLK12sv3 can be regarded as a marker of good prognosis in breast cancer. © 2012 International Society of Oncology and BioMarkers (ISOBM). Source

Kontou N.,Harokopio University | Psaltopoulou T.,National and Kapodistrian University of Athens | Soupos N.,National and Kapodistrian University of Athens | Polychronopoulos E.,Harokopio University | And 3 more authors.
Public Health Nutrition

Abstract Objective To investigate the association between dietary behaviours and colorectal cancer (CRC) in the context of the Mediterranean diet. Design Case-control study. Setting All patients (cases) were recruited from Saint Savvas Cancer Hospital and Alexandra General Hospital in Athens, Greece. Controls were voluntarily selected from the general population and matched to cases by age group (±10 years) and sex. Subjects Two hundred and fifty cases with newly diagnosed CRC (mean age 63 (sd 12) years, 59·6 % males) and 250 controls matched on age and sex were studied. A standardized questionnaire assessing sociodemographic, clinical, lifestyle, dietary characteristics and nutritional behaviours was applied. Multiple logistic regression analysis was used to evaluate the aforementioned factors in addition to the MedDietScore (an index that evaluates adherence to the Mediterranean diet) on CRC development. Results The higher the daily number of meals, the lower the likelihood of having CRC (OR = 0·74, 95 % CI 0·61, 0·89); coffee drinking was associated with higher likelihood of having CRC (OR = 3·27, 95 % CI 1·09, 9·8); the use of non-stick cookware was positively associated with CRC (OR = 1·57, 95 % CI 1·02, 2·4). However, these associations slightly lost their significance when adherence to the Mediterranean diet was taken into account. Moreover, a 1/75 increase in the modified-MedDietScore plus the aforementioned nutritional behaviours was associated with 13 % lower odds (95 % CI 0·83, 0·91, P < 0·001) of having CRC. Conclusions Nutritional behaviours in addition to dietary habits should be taken into account in detecting individuals prone to the development of CRC. Copyright © The Authors 2012. Source

Kontou N.,Harokopio University | Psaltopoulou T.,National and Kapodistrian University of Athens | Soupos N.,National and Kapodistrian University of Athens | Polychronopoulos E.,Harokopio University | And 3 more authors.
Diseases of the Colon and Rectum

BACKGROUND: Alcohol is considered to be a cocarcinogen or a tumor promoter, and various studies have shown a linear dose-dependent association between alcohol consumption and colorectal cancer. However, a few studies suggest that moderate alcohol consumption may have a protective effect, similar to that in cardiovascular disease. OBJECTIVE: The aim of this study was to evaluate the relationship of colorectal cancer to quantity and type of alcohol consumed. DESIGN: This was case-control study. SETTINGS: The study was conducted in the area of Attica, Greece. PARTICIPANTS: A total of 250 consecutive patients with a first diagnosis of colorectal cancer were matched for age group and sex with 250 controls recruited from the community. The mean age was 63 (SD, 12) years for the patient group (147 men, 59%; 103 women, 41%) and 55 (SD, 13) years for the control group (112 men; 44.8%; 138 women, 55.2%). MAIN OUTCOME MEASURES: Questionnaires were administered by trained interviewers to assess sociodemographic, clinical, and lifestyle characteristics, in addition to dietary habits and quantity and type of alcoholic beverages usually consumed during the preceding year. Adherence to the Mediterranean diet was evaluated with the MedDietScore (theoretical range, 0-55). RESULTS: With intake of less than 12 g of alcohol per day as the reference, moderate alcohol intake (12-35 g/day) was associated with a significantly decreased likelihood of colorectal cancer in men (OR, 0.35; 95% CI, 0.16-0.74) and in women (OR, 0.40; 95% CI, 0.18-0.91). High alcohol intake (more than 48 g/day) was associated with an increased likelihood, which was significant in men (OR, 3.45; 95% CI, 1.35-8.83) but not in women (OR, 3.40; 95% CI, 0.50-22.92). Drinking red wine was associated with reduced odds of colorectal cancer, significant in men (OR, 0.47; 95% CI, 0.23-0.96) but not in women (OR, 0.54; 95% CI, 0.23-1.30). None of the associations between other beverage types and colorectal cancer were significant. Adherence to the Mediterranean diet was independently associated with lower odds of colorectal cancer overall (p < 0.001), in men (OR, 0.90; 95% CI, 0.83-0.97), and in women (OR, 0.87; 95% CI, 0.80-0.94). LIMITATIONS: The major limitations of this study included the inability of a case-control design to determine causation and the potential for recall bias. CONCLUSIONS: The association between quantity of alcohol consumed and the presence of colorectal cancer followed a J-shaped curve. While demonstrating the detrimental effect of consuming large amounts of alcohol, the results of this study suggest that moderate alcohol consumption exerts a protective effect on colorectal cancer in both men and women, possibly related to the effects of red wine. © The ASCRS 2012. Source

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