Saint Savvas Cancer Hospital

Athens, Greece

Saint Savvas Cancer Hospital

Athens, Greece
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Kontou N.,Harokopio University | Kontou N.,Saint Savvas Cancer Hospital | Psaltopoulou T.,National and Kapodistrian University of Athens | Soupos N.,National and Kapodistrian University of Athens | And 4 more authors.
Diseases of the Colon and Rectum | Year: 2012

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.

Talieri M.,Saint Savvas Cancer Hospital | Alexopoulou D.K.,Saint Savvas Cancer Hospital | Scorilas A.,National and Kapodistrian University of Athens | Kypraios D.,Saint Savvas Hospital | And 4 more authors.
Tumor Biology | Year: 2011

Kallikrein-related peptidases (KLKs) represent a serine protease family having 15 members. KLK10 is a secreted protease with a trypsin-like activity. The function of KLK10 is poorly understood, although it has been suggested that KLK10 may function as a tumor suppressor gene. In human cancer, KLK10 gene shows organ-specific up- or down-regulation. Since KLKs are promising tumor biomarkers, the examination of KLK10 mRNA expression and its association with colorectal cancer (CRC) progression was studied using semi-quantitative PCR. One hundred and nineteen primary CRC specimens were examined for which follow-up information was available for a median period of 29 months (range, 1-104 months). KLK10 expression was found to be significantly associated with TNM stage (p=0.028). Cox proportional hazard regression model using univariate analysis revealed for the first time that high status KLK10 expression is a significant factor for disease-free survival (DFS; p= 0.002) and overall survival (OS; p=0.026) of patients. Kaplan-Meier survival curves demonstrated that KLK10 expression of low status is significantly associated with longer DFS (p=0.001) as well as OS (p=0.021), suggesting that KLK10 gene expression may be used as a marker of unfavorable prognosis for CRC. As the epigenetics of cancer are unraveled, KLK10 may represent not only a novel biomarker, but also a promising future therapeutic target for the disease. © International Society of Oncology and BioMarkers (ISOBM) 2011.

Kontou N.,Harokopio University | Kontou N.,Saint Savvas Cancer Hospital | Psaltopoulou T.,National and Kapodistrian University of Athens | Soupos N.,National and Kapodistrian University of Athens | And 4 more authors.
Public Health Nutrition | Year: 2013

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.

Tsavaris N.,National and Kapodistrian University of Athens | Voutsas I.F.,Saint Savvas Cancer Hospital | Kosmas C.,Metaxa Cancer Hospital | Gritzapis A.D.,Saint Savvas Cancer Hospital | Baxevanis C.N.,Saint Savvas Cancer Hospital
Investigational New Drugs | Year: 2012

Background Bevacizumab, a monoclonal antibody (mAb) targeting vascular endothelial growth factor (VEGF), has produced promising results when combined with chemotherapy in the treatment of advanced colorectal cancer (CRC). The aim of the present study was to define the immunological profile of metastatic CRC patients at baseline and following chemotherapy with either irinotecan/5- fluorouracil/leucovorin (IFL) alone or IFL in combination with.bevacizumab (B-IFL). Methods Peripheral blood mononuclear cells (PBMCs) obtained from healthy donors (HD) (n=20) and patients (n=40) were tested for T-cell proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and cytokine production following stimulation with anti-CD3 mAb. Results,PBMCs obtained from CRC patients prior to treatment exhibited lower auto-MLR responses and low production of IL-2, IFN-γ, IL-12 and IL-18 cytokines, whereas IL-4 and IL-10 cytokines were increased as compared to HD (p<0.001, for all parameters) following in vitro stimulation with anti-CD3 mAb. During treatment, and in particular in week 12 of evaluation, IL-2 (p <0.001 for both IFL and B-IFL groups), IFN-γ (p<0.001 for IFL and p=0.001 for B-IFL), IL-12 (p<0.001 for both IFL and B-IFL) and IL-18 (p<0.001 for both IFL and B-IFL) production, as well as auto-MLR responses increased (p< 0.001 for both IFL and B-IFL), whereas IL-4 (p<0.001 for IFL and p=0.001 for B-IFL) and IL-10 [p<0.001 for IFL and p=0.067 (non-significant) for B-IFL] production decreased over baseline in the two treatment groups, yet their respective values never reached those of HD. Moreover, IL-2, IFN-γ production, and auto-MLR were higher in the B-IFL over the IFL treatment group (p<0.001, p<0.04, p<0.001, respectively). Conclusion Our study demonstrates that the abnormal immune parameters observed inmetastatic CRC patients at presentation can substantially improve during treatment with either IFL or B-IFL. The immune parameters examined can provide a sensitive and valuable tool for monitoring immune function in CRC patients, and could be applied as surrogate markers predicting treatment-related outcome. © Springer Science+Business Media, LLC 2010.

Kontou N.,Harokopio University | Kontou N.,Saint Savvas Cancer Hospital | Psaltopoulou T.,National and Kapodistrian University of Athens | Soupos N.,National and Kapodistrian University of Athens | And 4 more authors.
European Journal of Public Health | Year: 2013

Background: The protective role of Mediterranean diet (MD) and the detrimental effect of smoking on colorectal cancer (CRC) have already been shown. The aim of this work was to evaluate the potential mediating effect of MD on the association between the aforementioned factor (smoking) and CRC. Methods: It is a case-control study. Two hundred fifty consecutive patients with CRC (63 ± 12 years, 59% males) and 250 age-sex group-matched controls, both from the area of Attica, were studied. Various socio-demographic, clinical, lifestyle (including detailed smoking habits) and dietary characteristics were measured. Adherence to the MD was evaluated using the MedDietScore (theoretical range 0-55). Results: Each unit increase in the MedDietScore was associated with 13% lower likelihood of CRC (P < 0.001). Smoking habits were associated with 2.9-fold the likelihood of CRC among participants who were away from the MD (i.e. MedDietScore < 29) and with 2.1-fold the likelihood of CRC among those who were close to the MD (P < 0.05). Conclusions: Adherence to the MD was associated with a less detrimental association of smoking habits with CRC, suggesting indirect benefits of adherence to this dietary pattern with regards to CRC morbidity and mortality. © 2012 The Author 2012. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Talieri M.,Saint Savvas Cancer Hospital | Zoma M.,Saint Savvas Cancer Hospital | Devetzi M.,Saint Savvas Cancer Hospital | Scorilas A.,National and Kapodistrian University of Athens | Ardavanis A.,Saint Savvas Cancer Hospital
Tumor Biology | Year: 2012

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).

Devetzi M.,Saint Savvas Cancer Hospital | Devetzi M.,University of Ioannina | Trangas T.,University of Ioannina | Scorilas A.,National and Kapodistrian University of Athens | And 2 more authors.
Thrombosis and Haemostasis | Year: 2013

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.

Talieri M.,Saint Savvas Cancer Hospital
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2012

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.

Sakorafas G.H.,SAINT SAVVAS Cancer Hospital | Nasikas D.,SAINT SAVVAS Cancer Hospital | Thanos D.,SAINT SAVVAS Cancer Hospital | Gantzoulas S.,SAINT SAVVAS Cancer Hospital
Oncology Research and Treatment | Year: 2015

Incidental C cell hyperplasia (CCH) following thyroidectomy for other indications may rarely be encountered, which may raise concerns about its clinical significance and proper management. CCH can be classified as physiological (reactive) or neoplastic. Reactive CCH has no malignant potential and can be observed in association with many other thyroid diseases (including differentiated thyroid cancer); in contrast, neoplastic CCH should be considered as a preneoplastic stage in the spectrum of C cell disease, ultimately leading to the development of medullary thyroid cancer (MTC). Neoplastic CCH is commonly observed in patients with germ-line mutations in the RET oncogene (commonly in families with a history of hereditary MTC, i.e. familial MTC or multiple endocrine neoplasia type 2 (MEN2)). CCH should be considered in patients with hypercalcitoninemia without nodular thyroidopathy. Total thyroidectomy, which is commonly performed for the majority of thyroid diseases, is an adequate treatment and achieves cure, even in patients with neoplastic CCH. There is no role for cervical lymph node dissection in patients with pure CCH. In conclusion, reactive CCH has no malignant potential, in contrast to neoplastic CCH. Total thyroidectomy achieves cure of patients with CCH. © 2015 S. Karger GmbH, Freiburg.

PubMed | Saint Savvas Cancer Hospital
Type: Journal Article | Journal: Anticancer research | Year: 2016

Numerous studies have revealed a variety of pathways involved in the development of melanoma, however, the molecular and genetic divergence of underlying mechanisms remain vague. In a mouse model, we studied the expression pattern of insulin-like growth factor 2 mRNA-binding protein 1 (Igf2bp1) and target genes microphthalmia-associated transcription factor (Mitf), v-myc avian myelocytomatosis viral oncogene homolog (Myc), B-cell lymphoma 2 (Bcl2), prothymosin alpha (Ptma) and melan-A (Mlana) in relation to tumor-growth characteristics. The in vivo expression of the aforementioned genes was assessed by quantitative Real Time-Polymerase Chain Reaction (RT-PCR) in tumors established by B16-F1-derived clones. Gene expression was correlated with tumor growth characteristics. Simultaneous expression of elevated levels of Myc, Igf2bp1, Ptma and Mitf characterizes tumors with a more aggressive phenotype. Our findings introduce a tumor-specific molecular signature possibly associated with melanoma heterogeneity. The concomitant overexpression of key molecules such as IGF2BP1, PTMA, MYC and MITF could serve as prognostic or predictive marker.

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