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Petridou E.T.,National and Kapodistrian University of Athens | Sergentanis T.N.,National and Kapodistrian University of Athens | Antonopoulos C.N.,National and Kapodistrian University of Athens | Dessypris N.,National and Kapodistrian University of Athens | And 5 more authors.
Metabolism: Clinical and Experimental | Year: 2011

Insulin resistance is closely associated with numerous metabolic disorders. Although studies have supported the importance of insulin resistance in carcinogenesis, the existing data have not established its relevance in the context of lung cancer. The aim of the present case-control study was to evaluate the association between insulin resistance and lung cancer after adjusting for possible confounders. Homeostasis model assessment of insulin resistance (HOMA-IR) and serum leptin and adiponectin levels were determined in 81 lung cancer cases and 162 age- and sex-matched controls; anthropometric and lifestyle variables were recorded. Mean HOMA-IR in the cases was more than 2-fold higher compared with the mean value of controls (P <.001). Among controls, HOMA-IR correlated positively with serum leptin (r = 0.16; P =.04), body mass index (r = 0.43; P =.0001), and waist-to-hip ratio (r = 0.21; P =.01) but negatively with serum adiponectin (r = -0.29; P =.0002). As expected, smoking was associated with an approximately 10-fold increase in lung cancer risk in multiple logistic regression models. A positive association between HOMA-IR, treated as continuous variable, and lung cancer (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.16-1.99, P =.002, model 1) was demonstrated, which persisted after adjustment for somatometric and lifestyle variables (OR = 2.36, 95% CI: 1.00-5.55, P =.05, model 2). When serum adiponectin was also taken into account, the association seemed fairly robust (OR = 2.58, 95% CI: 1.11-6.01, P =.03, model 3); on the contrary, when serum leptin was added, the association remained positive, but lost its statistical significance (OR = 1.76, 95% CI: 0.78-3.98, P =.17, model 4). In the fully adjusted model, HOMA-IR was still positively, but only marginally, associated with lung cancer risk (OR = 2.02, 95% CI: 0.88-4.65, P =.10, model 5). Insulin resistance may represent a meaningful risk factor for lung cancer. © 2011 Elsevier Inc.


Nicolatou-Galitis O.,National and Kapodistrian University of Athens | Kouloulias V.,National and Kapodistrian University of Athens | Sotiropoulou-Lountou A.,Saint Savvas Anticancer Hospital | Dardoufas K.,Hygeia Hospital | And 4 more authors.
Open Cancer Journal | Year: 2011

Goal of work: This study compared the severity of oral mucositis, pain and xerostomia during and at the completion of radiotherapy in head and neck cancer patients who had received antifungal and antiviral treatment. Patients: The study included 135 patients. Mean total radiotherapy dose was 62.4 Gray. Chemotherapy was administered to 47% of patients. Methods: Oral mucositis was scored weekly, while patients self-evaluated their pain and xerostomia. Cytology smears for the assessment of herpetic infection complicating the ulcers of mucositis were taken from 46 patients. Systemic antifungals and antivirals were administered during radiotherapy, upon clinical, presumptive diagnosis of candidiasis and herpetic infection. Antifungals and antivirals were continued to the end of radiotherapy. Results: Radiotherapy was completed within the preplanned time in 117 patients (87%). During radiotherapy, the prevalence of severe mucositis, pain and xerostomia was 57%, 43% and 29% respectively, and was significantly reduced to 33%, (P<0.001), to 24%, (P<0.001), and to 18%, (P<0.05) at the end of radiotherapy. Antifungals and antivirals were utilized in 70% and 71% of patients, respectively. Viral cytology was positive in 14 of 46 (30.4%) patients. Conclusions: The significant reduction of severe oral mucositis, pain and xerostomia at time of completion of radiotherapy, as compared to during the course of radiotherapy, after the treatment and prevention of candidiasis and herpes, denotes an important role of these infections in radiation-induced mucositis. Limitations of the study are the practical issues of the lack of the verification of the fungal status before and after treatment and of the verification of the viral status in only 47.9% (46 of 96) of the patients with a clinical suspicion of herpetic infection. A controlled study is needed to investigate and further clarify the role of antifungal and antiviral prophylaxis relative to oral mucositis, pain and xerostomia during head and neck RT. © Nicolatou-Galitis et al.


Dimopoulos M.A.,National and Kapodistrian University of Athens | Kastritis E.,National and Kapodistrian University of Athens | Michalis E.,G Gennimatas Hospital | Tsatalas C.,Democritus University of Thrace | And 11 more authors.
Annals of Oncology | Year: 2012

Background: The International Staging System (ISS) is the most widely used staging system for patients with multiple myeloma (MM). However, serum β2-microglobulin increases in renal impairment (RI) and there have been concerns that ISS-3 stage may include 'up-staged' MM patients in whom elevated β2-microglobulin reflects the degree of renal dysfunction rather than tumor load. Patients and methods: In order to assess the impact of RI on the prognostic value of ISS, we analyzed 1516 patients with symptomatic MM and the degree of RI was classified according to the Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease (CKD) criteria. Results: Forty-eight percent patients had stages 3-5 CKD while 29% of patients had ISS-1, 38% had ISS-2 and 33% ISS-3. The frequency and severity of RI were more common in ISS-3 patients. RI was associated with inferior survival in univariate but not in multivariate analysis. When analyzed separately, ISS-1 and ISS-2 patients with RI had inferior survival in univariate but not in multivariate analysis. In ISS-3 MM patients, RI had no prognostic impact either in univariate or multivariate analysis. Results were similar, when we analyzed only patients with Bence-Jones >200 mg/day. Conclusions: ISS remains unaffected by the degree of RI, even in patients with ISS-3, which includes most patients with renal dysfunction. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Kontos C.K.,National and Kapodistrian University of Athens | Mavridis K.,National and Kapodistrian University of Athens | Talieri M.,Saint Savvas Anticancer Hospital | Scorilas A.,National and Kapodistrian University of Athens
Thrombosis and Haemostasis | Year: 2013

The human tissue kallikrein (KLK1) and kallikrein-related peptidases (KLKs) are secreted serine proteases with diverse expression patterns and physiological roles in different systems, including the digestive system. The aberrant expression of KLKs in gastrointestinal malignancies as well as their implication in carcinogenesis including cell growth regulation, angiogenesis, invasion, and metastasis, has prompted scientists to investigate their potential as cancer biomarkers. Expression of distinct KLKs is associated with various clinic-pathological parameters of patients with gastric, colorectal, pancreatic, hepatic, and esophageal cancer. Moreover, several KLKs possess significant favourable or unfavourable prognostic value in these human malignancies. Identification of novel diagnostic, prognostic and predictive biomarkers will contribute utmost to clinical decision-making, since early diagnosis of gastrointestinal cancer and early detection of recurrence following surgery are critical for the effective treatment of patients and for a positive clinical outcome. The current review provides a brief overview of the functional role of KLKs in gastric, colorectal, pancreatic, hepatic, and esophageal cancer, and describes the current status of KLKs as potential tumour biomarkers in these human malignancies. © Schattauer 2013.


PubMed | General Maternity District Hospital Helena Venizelou, Mhtera Maternity Hospital, National and Kapodistrian University of Athens and Saint Savvas Anticancer Hospital
Type: Journal Article | Journal: Diagnostic cytopathology | Year: 2016

There have been various attempts to assess endometrial lesions on cytological material obtained via direct endometrial sampling. The majority of efforts focus on the description of cytological criteria that lead to classification systems resembling histological reporting formats. These systems have low reproducibility, especially in cases of atypical hyperplasia and well differentiated carcinomas. Moreover, they are not linked to the implied risk of malignancy.The material was collected from women examined at the outpatient department of four participating hospitals. We analyzed 866 consecutive, histologically confirmed cases. The sample collection was performed using the EndoGyn device, and processed via Liquid Based Cytology, namely ThinPrep technique. The diagnostic categories and criteria were established by two cytopathologists experienced in endometrial cytology; performance of the proposed reporting format was assessed on the basis of histological outcome; moreover, the implied risk of malignancy was calculated.The proposed six diagnostic categories are as follows: (i) nondiagnostic or unsatisfactory; (ii) without evidence of hyperplasia or malignancy; (iii) atypical cells of endometrium of undetermined significance; (iv) atypical cells of endometrium of low probability for malignancy; (v) atypical cells of endometrium of high probability for malignancy; and (vi) malignant. The risk of malignancy was 1.42%0.98%, 44.44%32.46% (nine cases), 4.30%4.12%, 89.80%8.47%, and 97.81%2.45%, respectively.We propose a clinically oriented classification scheme consisting of diagnostic categories with well determined criteria. Each diagnostic category is linked with an implied risk of malignancy; thus, clinicians may decide on patient management and eventually reduce unnecessary interventional diagnostic procedures. Diagn. Cytopathol. 2016;44:888-901. 2016 Wiley Periodicals, Inc.


PubMed | National and Kapodistrian University of Athens and Saint Savvas Anticancer Hospital
Type: | Journal: International journal of endocrinology | Year: 2015

Objective. This study investigated whether thyroid hormone (TH) levels are correlated to cell proliferation (Ki67), in euthyroid breast cancer patients. Design and Methods. 86 newly diagnosed breast cancer patients with estrogen receptor (ER) positive tumors, who referred for surgery, were included in the study. Results. FT3, FT4, and TSH were within normal range. No correlation was seen between Ki67 and FT3 (r = -0.17, P = 0.15), FT4 (r = -0.13, P = 0.25), or TSH (r = -0.10, P = 0.39) in all patients studied. However, subgroup analysis showed that, in HER2(+) patients, a negative correlation existed between FT3 levels and Ki67 (r = -0.60 and P = 0.004) but not between Ki67 and FT4 (r = 0.04 and P = 0.85) or TSH (r = -0.23 and P = 0.30). In HER2(-) patients, there was no significant correlation between Ki67 and FT3 (r = -0.06, P = 0.67), FT4 (r = -0.15, P = 0.26), or TSH (r = -0.09, P = 0.49). Phospho-p44/total p44 ERK levels were found to be increased by 2-fold in HER2(+) versus HER2(-) tumors. No difference was detected in phospho-p42/total p42 ERK levels. Conclusions. TH profile is not altered in patients with newly diagnosed breast cancer. However, FT3 levels, even within normal range, are negatively correlated with cell proliferation in HER2(+) breast cancer tumors. This response may be due to the interaction between ERK and TH signaling.


Velaeti S.,Saint Savvas Anticancer Hospital | Dimitriadis E.,Saint Savvas Anticancer Hospital | Kontogianni-Katsarou K.,Evangelismos General Hospital | Savvani A.,Evangelismos General Hospital | And 6 more authors.
Tumor Biology | Year: 2014

The Ets-related gene fusions are among the most common molecular alterations in prostate cancer (PCa) and are detected in more than 50 % of PCas. Transmembrane protease serine 2 and Ets-related gene fusion (TMPRSS2-ERG) is the most frequently identified chimeric gene and has been associated with undifferentiated and invasive pheno-types. TMPRSS2-ERG has also been detected in prostate intraepithelial neoplasia (PIN) lesions and more rarely in benign prostatic hyperplasia (BPH) regions mainly in PCa-bearing glands. The possibility that the fusion TMPRSS2-ERG may be present in BPH samples in the absence of apparent PCa was addressed. Out of 115 BPH samples, three were found positive employing RT-PCR. The presence of the fusion gene was confirmed by FISH for these samples, and an additional four samples were found to carry the TMPRSS2-ERG fusion out of 43 tested by the later approach. The presence of the TMPRSS2-ERG fusion did not result in altered expression of 12 putative downstream targets. These findings indicate that TMPRSS2-ERG may or may not lead to PCa development. © International Society of Oncology and BioMarkers (ISOBM) 2014


Saratsiotou I.,Saint Savvas Anticancer Hospital | Kordoni M.,Hygeia Hospital | Bakogiannis C.,Hygeia Hospital | Livadarou E.,Metropolitan Hospital | And 3 more authors.
Journal of Oncology Pharmacy Practice | Year: 2011

Purpose. The aim of this prospective observational study was to investigate the patterns of treatment adherence to orally administered chemotherapy of patients being treated for cancer.Methods. Patients were asked to participate in the survey during their visits to the study centers' pharmacists or doctors to obtain their oral medication from April 2008 until May 2009. The data were collected using a self-reported anonymous 7-page long questionnaire, which contained questions about their demographic profile, disease and treatment characteristics, and side-effects and adherence information, both intentional and nonintentional.Results. 99 Patients completed the questionnaire. Missing values ranged from 1% to 8%. Unintended nonadherence to therapy was reported by 19 patients. The most important factor correlating with unintended nonadherence was the patient's belief regarding treatment effectiveness since only 16.7% of the patients believing that their treatment is effective reported nonadherence as opposed to 62.5% for those that did not believe that treatment is effective (p=0.03). Intentional nonadherence was reported by 14 patients The most important factor correlating to intentional nonadherence was time since disease diagnosis, as nonadherence was reported by 33.3% of the patients having the disease less than 6 months, compared to 16.7% for those between 6 and 24 months and 8.3% for those between 2 and 5 years (p=0.01).Conclusion. Greek patients seem to have similar nonadherence pattern as in other countries. Confidence in treatment efficacy appeared as a significant adherence determinant. © 2011 The Author(s).


PubMed | Saint Savvas Anticancer Hospital
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2014

The Ets-related gene fusions are among the most common molecular alterations in prostate cancer (PCa) and are detected in more than 50 % of PCas. Transmembrane protease serine 2 and Ets-related gene fusion (TMPRSS2-ERG) is the most frequently identified chimeric gene and has been associated with undifferentiated and invasive phenotypes. TMPRSS2-ERG has also been detected in prostate intraepithelial neoplasia (PIN) lesions and more rarely in benign prostatic hyperplasia (BPH) regions mainly in PCa-bearing glands. The possibility that the fusion TMPRSS2-ERG may be present in BPH samples in the absence of apparent PCa was addressed. Out of 115 BPH samples, three were found positive employing RT-PCR. The presence of the fusion gene was confirmed by FISH for these samples, and an additional four samples were found to carry the TMPRSS2-ERG fusion out of 43 tested by the later approach. The presence of the TMPRSS2-ERG fusion did not result in altered expression of 12 putative downstream targets. These findings indicate that TMPRSS2-ERG may or may not lead to PCa development.


Fostira F.,National Diagnostics | Konstantopoulou I.,National Diagnostics | Mavroudis D.,University of Crete | Tryfonopoulos D.,Saint Savvas Anticancer Hospital | And 2 more authors.
Clinical Genetics | Year: 2015

Currently, hereditary breast cancer is being attributed to more than 20 genes of differing penetrance. Although BRCA1 and BRCA2 are still the genes of reference for breast cancer susceptibility, extreme breast cancer phenotypes may be the result of deleterious alleles of other genes. Here, we report three families with early-onset breast cancer that were initially referred for BRCA1/BRCA2 genetic testing. They were diagnosed with breast cancer at an extraordinarily early age. On the basis of their extensive family history, which included multiple cancer types, and their Her2 status, they were suspected for Li-Fraumeni syndrome. Indeed, all three probands were found to harbor TP53 tumor suppressor gene mutations. These included p.C275X, described here for the first time, as well as p.R213X and p.Y220C, which have been described in the past. Our conclusion is that decisions on genetic analysis for inherited early onset breast cancer should always be based on detailed pedigree information, combined with Her2 status. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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