Xeni Provatopoulou

International Institute of Anticancer Research, Αθίκια, Peloponnese, Greece

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Publications (27)63.14 Total impact

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    ABSTRACT: The physiological and pathological development of the breast is strongly affected by the hormonal milieu consisting of steroid hormones. Mass spectrometry (MS) technologies of high sensitivity and specificity enable the quantification of androgens and consequently the characterization of the hormonal status. The aim of this study is the assessment of plasma androgens and androgen glucuronides, in the par excellence hormone-sensitive tissue of the breast, through the application of liquid chromatography-mass spectrometry (LC-MS). A simple and efficient fit-for-purpose method for the simultaneous identification and quantification of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4), androsterone glucuronide (ADTG) and androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) in human plasma was developed and validated. The presented method permits omission of derivatization, requires a single solid-phase extraction procedure and the chromatographic separation can be achieved on a single C18 analytical column, for all four analytes. The validated method was successfully applied for the analysis of 191 human plasma samples from postmenopausal women with benign breast disease (BBD), lobular neoplasia (LN), ductal carcinoma in situ and invasive ductal carcinoma (IDC). DHEAS plasma levels exhibited significant differences between LN, IDC and BBD patients (P < 0.05). Additionally, ADTG levels were significantly higher in patients with LN compared with those with BBD (P < 0.05).
    No preview · Article · Jan 2016 · Journal of chromatographic science
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    ABSTRACT: Background Irisin is a recently discovered myokine, involved in the browning of white adipose tissue. To date, its function has been mainly associated with energy homeostasis and metabolism, and it has been proposed as a promising therapeutic target for obesity and metabolic diseases. This is the first study investigating the role of irisin in human breast cancer. Methods Participants included one hundred and one (101) female patients with invasive ductal breast cancer and fifty one (51) healthy women. Serum levels of irisin, leptin, adiponectin and resistin were quantified in duplicates by ELISA. Serum levels of CEA, CA 15–3 and Her-2/neu were measured on an immunology analyzer. The association between irisin and breast cancer was examined by logistic regression analysis. The feasibility of serum irisin in discriminating breast cancer patients was assessed by ROC curve analysis. Potential correlations with demographic, anthropometric and clinical parameters, with markers of adiposity and with breast tumor characteristics were also investigated. Results Serum levels of irisin were significantly lower in breast cancer patients compared to controls (2.47 ± 0.57 and 3.24 ± 0.66 μg/ml, respectively, p < 0.001). A significant independent association between irisin and breast cancer was observed by univariate and multivariate analysis (p < 0.001). It was estimated that a 1 unit increase in irisin levels leads to a reduction in the probability of breast cancer by almost 90 %. Irisin could effectively discriminate breast cancer patients at a cut-off point of 3.21 μg/ml, with 62.7 % sensitivity and 91.1 % specificity. A positive association with tumor stage and marginal associations with tumor size and lymph node metastasis were observed (p < 0.05, p < 0.01, p < 0.01, respectively). Conclusions Our novel findings implicate irisin in breast cancer and suggest its potential application as a new diagnostic indicator of the presence of disease.
    Preview · Article · Nov 2015 · BMC Cancer
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    ABSTRACT: Thyroid disorders, including thyroid cancer and autoimmune thyroid diseases, have been closely associated with inflammation. This study aims to investigate the role of inflammation in thyroid disease by assessing serum cytokine levels in patients with malignant and benign thyroid conditions. Serum levels of ten interleukins (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 and IL-13) were quantitatively determined in 20 patients with thyroid cancer, 38 patients with benign thyroid disease and 50 healthy controls by multiplex technology. Serum IL-1β, IL-2, IL-4, IL-5 and IL-6 levels were strongly associated with each other. IL-10 and IL-12 correlated with IL-1β, IL-5, IL-6, and with each other. Age was inversely correlated with serum levels of IL-2, IL-4 and IL-13. A positive correlation between T3 and IL-13 levels was also observed. Significantly higher levels of IL-6, IL-7, IL-10 and IL-13, as well as significantly lower levels of IL-8 were observed in patients with benign and malignant thyroid disease compared to controls. The combination of IL-13 and IL-8 in a two-marker panel was highly efficient in discriminating thyroid disorders (AUC 0.90). Malignant and benign thyroid conditions are associated with altered expression levels of interleukins, supporting the association between thyroid disease and underlying inflammatory processes.
    No preview · Article · May 2014 · Agents and Actions
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    ABSTRACT: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is one of the most frequently mutated human tumor suppressor genes, implicated in cell growth and survival and suppressing tumor formation. Loss of PTEN activity, either at the protein or genomic level, has been related to many primary and metastatic malignancies including breast cancer. The present study investigates the heterozygosity, mutation spectrum and protein expression of PTEN in 43 patients with breast cancer or precursor lesions of the breast and 10 healthy individuals. Microsatellite analysis at the PTEN locus using D10S215, D10S541 and D10S579 markers indicated that the observed heterozygosity (Ho) is lower than the expected heterozygosity (Hs) in benign and malignant breast disease. Mutational analysis in exons 1, 5, 7 and 9 of the PTEN gene revealed several mutations, most of which cause truncation of the PTEN protein and consequently loss of activity. Increased circulating levels of PTEN and phosphorylated PTEN protein were also observed by immunostaining in patients with breast cancer and precursor breast lesions. In support, increased PTEN protein expression was detected in corresponding tissue specimens. Our data suggest an association between breast cancer and PTEN mutations, resulting in the production of truncated forms of the corresponding protein, thus indicating that breast carcinogenesis is potentially related to PTEN loss of activity rather than loss of expression. Peripheral blood sampling may provide an advantageous application for the determination of PTEN gene mutations and its protein expression in human cancer.
    No preview · Article · Mar 2014 · Anticancer research
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    Preview · Article · Dec 2013 · Life Sciences
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    ABSTRACT: Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC-MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC-MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.
    No preview · Article · Sep 2013 · Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

  • No preview · Article · Mar 2013 · The Breast

  • No preview · Article · Mar 2013 · The Breast
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    Preview · Article · Mar 2013
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    ABSTRACT: Mammography is currently the standard breast cancer screening procedure, even though it is constrained by low specificity in the detection of malignancy and low sensitivity in women with dense breast tissue. Modern imaging modalities, such as magnetic resonance imaging (MRI), have been developed in an effort to replace or complement mammography, because the early detection of breast cancer is critical for efficient treatment and long-term survival of patients. Nuclear medicine imaging technology has been introduced in the field of oncology with the development of positron emission tomography (PET), positron emission tomography/computed tomography (PET/CT) and, ultimately, positron emission mammography (PEM). PET offers the advantage of precise diagnosis, by measuring metabolism with the use of a radiotracer and identifying changes at the cellular level. PET/CT imaging allows for a more accurate assessment by merging the anatomic localization to the functional image. However, both techniques have not yet been established as diagnostic tools in early breast cancer detection, primarily because of low sensitivity, especially for sub-centimeter and low-grade tumors. PEM, a breast-specific device with increased spatial resolution, has been developed in order to overcome these limitations. It has demonstrated higher detectability than PET/CT and comparable or better sensitivity than MRI. The ability to target the lesions visible in PEM with PEM-guided breast biopsy systems adds to its usability in the early diagnosis of breast cancer. The results from recent studies summarized in this review indicate that PEM may prove to be a useful first-line diagnostic tool, although further evaluation and improvement are required.
    No preview · Article · Dec 2012 · Breast Cancer
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    ABSTRACT: The aim of this study was to investigate the effect of breast cancer adjuvant therapies on the levels of circulating surfactant protein-D (SP-D), C-Reactive protein (CRP) and soluble receptor for advanced glycation end-products (sRAGE), as potential biomarkers of subclinical pulmonary inflammation. The soluble molecules were serially determined in 38 patients, prior to the initiation of radiation therapy (RT) and during adjuvant treatment, using immunoassays. Significantly higher levels of all three biomarkers were observed in patients prior to the initiation of RT compared to healthy controls (CRP: p<0.001, SP-D: p<0.05, sRAGE: p<0.05). SP-D levels exhibited a gradual increase after RT and during follow-up (p<0.005). Patients treated with a combination of RT and hormonal therapy presented a significant, but less pronounced, increase in SP-D and a significant decrease in CRP compared to those who did not receive hormonal therapy (p=0.0428 and p=0.0116, respectively). Patients treated with a combination of RT and trastuzumab presented a significant increase in SP-D levels (p=0.0310). The average rate of change in the levels of circulating SP-D and CRP during postoperative irradiation and adjuvant hormonal therapy suggests that the combined therapeutic regiment may potentially exert important anti-inflammatory effects on the lung. On the contrary, combined administration of RT and trastuzumab is likely to induce or provoke pulmonary inflammation.
    No preview · Article · Nov 2012 · Anticancer research
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    ABSTRACT: Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under investigation in various types of human cancer. ET-1 has been suggested to participate in breast cancer development and progression, while Big ET-1, its biological precursor, has also been found elevated in breast cancer patients. In the present study, we investigated plasma ET-1 and Big ET-1 levels in patients with suspicious mammographic lesions, in order to assess their potential application as diagnostic biomarkers in the early estimation of breast disease. The study consisted of 94 patients (Group A to 30 patients with invasive ductal carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit significant differences between patients and healthy controls (Group A to 0.92 fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86 fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with invasive or in situ carcinoma compared to healthy controls (Group A: 0.69 fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p < 0.01). Plasma Big ET-1 may provide a useful tool for the early detection of invasive or noninvasive ductal breast cancer. The utilization of such a diagnostic tool would greatly assist in the modern management of breast cancer.
    No preview · Article · Mar 2012 · Tumor Biology

  • No preview · Article · Mar 2012
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    ABSTRACT: Human leukocyte antigen-G (HLA-G) has been closely associated with diagnosis and prognosis in many types of human cancer. The current study aims to investigate soluble (s) HLA-G expression in patients with breast malignancy. sHLA-G plasma expression was determined in 120 patients with breast cancer and 40 healthy controls using enzyme-linked immunosorbent assay. Plasma sHLA-G levels were significantly higher in breast cancer patients compared to healthy controls (p<0.001), with an area under the receiver operating characteristic (ROC) curve of 0.735 (95% Confidence interval=0.630-0.841, p<0.001). Significantly increased sHLA-G expression was detected in patients with mixed type of coexisting ductal and lobular breast lesions, compared to patients with pure ductal carcinoma or pure lobular neoplasia (p<0.05). sHLA-G expression is closely associated with the histological type of breast cancer. Our findings support the application of sHLA-G as a potential biomarker in body fluids for preoperative breast cancer detection and diagnosis.
    No preview · Article · Mar 2012 · Anticancer research

  • No preview · Article · Mar 2012 · European Journal of Cancer
  • M. Piperi · E. Kalogera · X. Provatopoulou · G. Zografos · E. Athanasiou · A. Gounaris

    No preview · Article · May 2011 · Radiotherapy and Oncology
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    ABSTRACT: Electrochemotherapy is currently undergoing intensive investigation in the field of local control of cancer. In Greece, five medical centers have co-operated to perform ECT for the efficient management of growing, recurrent or newly emerging cutaneous and subcutaneous tumor nodules. ECT was applied alone or in combination with external beam radiation therapy, brachytherapy and surgery in 52 cancer patients, using bleomycin according to standard protocols. The treatment response for various tumors was 63.83% complete, 31.91% partial, and 95.74% overall of the treated nodules. Patients exerted neither systemic nor local side-effects. The results of ECT performance in Greece provided evidence that this new treatment strategy is safe and permits the effective control of tumors of various origins and histological types.
    No preview · Article · Mar 2011 · In vivo (Athens, Greece)
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    ABSTRACT: Heat-shock protein 90 (HSP90) is an abundant protein in mammalian cells. It interacts with a variety of proteins that play key roles in breast neoplasia. This is the first study to assess serum levels of HSP90 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and infiltrative lobular carcinoma (ILC). Serum concentrations of HSP90 in women with benign (n=34), ADH (n=26), DCIS (n=30), IDC (n=29), LN (n=20) and ILC (n=9) lesions were determined with immunoenzymatic assays. For the evaluation of serum concentrations along the transition from benign through precursor and preinvasive to invasive lesion, the severity of diagnosis was treated as an ordinal variable. No significant association was demonstrated between serum HSP90 levels and the severity of the lesion in ductal and lobular series. The post hoc comparison between the lobular and ductal precursor lesions (i.e. ADH vs. LN) did not yield a statistically significant difference. Similarly, the post hoc comparison between the lobular and ductal invasive carcinomas (i.e. IDC vs. ILC) did not point to a statistically significant difference. This is the first study evaluating HSP90 serum levels in both lobular and ductal lesions of the breast. Contrary to published pathological findings according to which HSP90 exhibits significant variability along both series, such a finding was not replicated for the level of serum HSP90 concentrations.
    No preview · Article · Mar 2011 · In vivo (Athens, Greece)
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    ABSTRACT: The involvement of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in breast cancer has been documented on palpable lesions. This study aims to assess serum MMP1, MMP-2, TIMP-1, and TIMP-2 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) specifically in non-palpable mammographic breast lesions. On women with benign (n=65), precursor [ADH (n=18) and LN (n=15)], preinvasive [DCIS (n=32)] and invasive [IDC (n=28)] lesions the serum concentrations of MMP-1, MMP-2, TIMP-1, TIMP-2, TPS, and TPA were determined with immunoenzymatic assays. All women had non-palpable mammographic breast lesions of less than 10mm in diameter, as estimated on the mammographic views. Statistical analysis followed. TIMP-2 serum concentrations were positively associated with the severity of the lesion. On the contrary, MMP-2 levels were marginally negatively associated with severity; as evident, the MMP-2/TIMP-2 ratio significantly decreased along with severity. Regarding TIMP-1, TPS, TPA, and TIMP-1/TIMP-2, no significant associations were demonstrated. MMP-2 and the MMP-2/TIMP-2 ratio were significantly higher in the LN subgroup versus the ADH subgroup. TIMP-2 and MMP-2/TIMP-2 ratio may exhibit meaningful changes along with progression of lesions. Extracellular cell matrix remodeling in ductal and lobular lesions may follow distinct patterns.
    No preview · Article · Mar 2011 · Clinica chimica acta; international journal of clinical chemistry
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    ABSTRACT: Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients. These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.
    Full-text · Article · Nov 2009 · BMC Cancer