Corina Cianga

Universitatea de Medicina si Farmacie Grigore T. Popa Iasi, Socola, Iaşi, Romania

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Publications (31)25.95 Total impact

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    ABSTRACT: Patients with end-stage renal disease (ESRD) have an increased risk of all-cause mortality. The prognostic value of the new cardiac biomarkers, cardiotrophin 1 (CT-1) and galectin 3 (GAL-3), has not yet been defined in hemodialysis (HD) patients. The aim of this study was to determine the use of these novel biomarkers for predicting mortality in HD patients. Plasma GAL-3 and CT-1 concentrations were determined (at baseline) in 88 HD patients followed for 22.2 ± 4.7 months. During the follow-up period, 21 (23.9%) deaths were recorded. According to Cox analysis, the cutoff point for GAL-3 as a predictor of mortality was 23.73 ng/mL, while the cutoff point for CT-1 as a predictor of mortality was 36 pg/mL. In univariate analysis, only GAL-3 >23.73 ng/mL was an independent predictor of mortality (hazard ratio 2.60; 95% confidence interval, 1.09-6.18). In a multivariable Cox proportional hazards model, GAL-3 levels above the cutoff value remained an independent predictor of all-cause mortality. Our data suggest that similar to the general population, GAL-3 is an independent predictor of mortality in HD patients.
    No preview · Article · Jan 2016 · Angiology
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    ABSTRACT: Most patients with MHC class I (MHC-I) deficiency carry genetic defects in transporter associated with antigen processing 1 (TAP1) or TAP2. The clinical presentation can vary, and about half of the patients have severe skin disease. Previously, one report described β2-microglobulin (β2m) deficiency as another monogenetic cause of MHC-I deficiency, but no further immunologic evaluation was performed. We sought to describe the molecular and immunologic features of β2m deficiency in 2 Turkish siblings with new diagnoses. Based on clinical and serologic findings, the genetic defect was detected by means of candidate gene analysis. The immunologic characterization comprises flow cytometry, ELISA, functional assays, and immunohistochemistry. Here we provide the first extensive clinical and immunologic description of β2m deficiency in 2 siblings. The sister had recurrent respiratory tract infections and severe skin disease, whereas the brother was fairly asymptomatic but had bronchiectasis. Not only polymorphic MHC-I but also the related CD1a, CD1b, CD1c, and neonatal Fc receptor molecules were absent from the surfaces of β2m-deficient cells. Absent neonatal Fc receptor surface expression led to low serum IgG and albumin levels in both siblings, whereas the heterozygous parents had normal results for all tested parameters except β2m mRNA (B2M) expression. Similar to TAP deficiency in the absence of a regular CD8 T-cell compartment, CD8(+) γδ T cells were strongly expanded. Natural killer cells were normal in number but not "licensed to kill." The clinical presentation of patients with β2m deficiency resembles that of patients with other forms of MHC-I deficiency, but because of the missing stabilizing effect of β2m on other members of the MHC-I family, the immunologic defect is more extensive than in patients with TAP deficiency. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Feb 2015 · Journal of Allergy and Clinical Immunology
  • Corina M. Cianga · Irina D. Florea · Petru Cianga
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    ABSTRACT: Background: Fas ligand (FasL) expression is one of the mechanisms responsible for the "immune privilege" of tissues such as testis and eye. Many solid tumors express FasL as an immune escape strategy, aiming to induce apoptosis in Fas-expressing leukocytes, and thus to prevent the accumulation of effector cells. Materials and Methods: We investigated by immunohistochemistry the FasL expression in human breast carcinomas vasculature (blood vessels versus lymphatics), endothelial activation status and markers associated with tumor aggressiveness. Results: We bring evidence of a heterogeneous FasL expression in the human breast carcinomas associated blood vessels, but not lymphatics. The endothelial FasL expression was significantly correlated with the tumor FasL expression, tumor size, the presence of rich vascular networks, and axillary lymph nodes metastases; however, it was not correlated with low tumor invading leukocytes density. Conclusion: Breast carcinomas are among tumors in which the tumor-host interaction is correlated with the clinical outcome, hence understanding the significance of endothelial FasL expression is of outmost importance.
    No preview · Article · Mar 2012 · Revista Romana de Medicina de Laborator
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    ABSTRACT: The neonatal Fc receptor (FcRn) was demonstrated to play a role both in the recycling and thus the protection of immunoglobulin G (IgG) from catabolism and in the maternal-fetal transfer of IgG. The expression of this particular receptor was evidenced in a variety of cell types, but the endothelial cell was considered the main cell able to perform both recycling and IgG catabolism. Based on preliminary data obtained in adult human mammary glands and skin, this study focused on a number of neonatal human tissues, targeting FcRn expression mainly in epithelial versus endothelial cells. Our results demonstrate that in most of the investigated tissues, the neonatal Fc receptor is not detectable in the endothelial cells lining the capillaries, whereas most epithelial cells are positive. We could also observe the receptor's expression in most macrophages, smooth muscle cells, and neurons. Taken together, these data suggest that the main sites of IgG catabolism might in fact be other than endothelial cells in human neonates.
    No preview · Article · Dec 2011 · Human immunology
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    Petru Cianga · Mihaela Zlei · Elena Rezus · Corina Cianga
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    ABSTRACT: Background: The detection of HLA-B27 expression is one of the most powerful diagnostic tools in ankylosing spondylitis and other spondylarthropaties, hence the importance of a reliable and accurate detection method. Flow cytometry is often used as an alternative HLA-B27 typing technique, mainly because it is a rapid test. However, even though it is based on various monoclonal antibodies, their ability to bind to cross-reactive HLA-B molecules was demonstrated by various groups. Materials and methods: The HLA-B27 typing was performed by flow cytometry using the BD TM HLA-B27 System, and by the HLA-SSP and HLA-SSO typing techniques. Results: We were able to confirm some of the known cross-reactivities and evidence some new ones, as HLA-B18 and B35, in the context of a characteristic flow cytometric labeling pattern. Conclusions: flow cytometry can offer clues indicating the presence of HLA-B27 cross-reactive molecules, but such situations will require HLA typing by molecular biology techniques.
    Preview · Article · Jun 2011 · Revista Romana de Medicina de Laborator
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    ABSTRACT: Endometrioid endometrial carcinoma developed from endometrial hyperplasia is associated with anomalies of proliferation, apoptosis, and matrix metalloproteinase (MMP) expression. Our study was designed to investigate steroid receptor (ER, PR) expression and its correlation with proliferative activity (PCNA), apoptosis (Fas, FasL, Bcl-2, Bax, and p53), gelatinases (MMP-2 and MMP-9) and their tissue specific inhibitor (TIMP-1 and TIMP-2) immunoexpression in endometrial carcinogenesis. A total of 38 cases were investigated, 10 non-neoplastic, 11 hyperplastic, and 17 carcinomatous endometria. Immunolabeling showed a higher expression of steroid receptors in hyperplasia and carcinoma than in non-neoplastic endometria and an ER/PR imbalance in carcinoma. The epithelial component of endometrial carcinomas had the highest proliferative index. Bcl-2 had a stronger expression in hyperplasia and carcinoma compared to non-neoplastic endometria and stromal tissue. The Bcl-2/Bax ratio was lower in endometrial carcinoma. Fas and FasL expression was stronger in hyperplasia and furthermore in carcinoma. p53 expression was progressively stronger along the sequence non-neoplastic endometrial to hyperplasia-carcinoma. Both types of investigated MMPs showed an increased expression in neoplastic endometria reaching a maximum level in carcinomas. MMP-9 immunostaining could be correlated to myometrial invasion. TIMP-1 decreased and TIMP-2 increased in expression from non-neoplastic endometria to hyperplastic and carcinomatous endometrial, respectively. Our study demonstrates that coordinated anomalies of steroid receptors, apoptosis and invasiveness factors are already present in hyperplasia as cumulative steps along the way to malignant transformation and that a complex MMP-2, MMP-9, TIMP-2/TIMP-1 imbalance seems to be responsible for the endometrial proliferation.
    No preview · Article · Feb 2011 · Annals of anatomy = Anatomischer Anzeiger: official organ of the Anatomische Gesellschaft
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    ABSTRACT: Analysis of protein phosphorylation within intracellular signaling pathways may clarify the functional status and biological responses of cells to various stimuli, reflecting an enhanced enzymatic activity. Phos-pho-specific antibody (p-Ab)-based detection methods that have been used to date, including flow cytometry, re-quire extensive optimization for the achievement of accuracy and rational specificity. Objective. We sought to op-timize a phospho-specific flow cytometry detection method, based on the premise that fixation is a critical step of such protocols. Materials and methods. We compared two different methods for phospho-detection in phorbol myristate acetate (PMA)-activated peripheral blood mononuclear cells (PBMCs) and assessed how they dis-tinctly impacted on cell viability, surface staining intensity and phospho-detection competence, aiming to develop an optimized protocol with balanced efficiency in surface and intracellular phospho-labeling. PMA-activated PBMCs were used for testing the detection efficiency of five p-Abs: pERK(T202/Y204), pp38MAPK(T180/Y182), pAKT(T308), pSTAT-3(S727), pSTAT-1(Y701) by flow cytometry. Results. 1. Fixation prior to surface staining led to an improved signal-to-noise ratio for all p-Abs evaluated; 2. cell suspension integrity was not affected by the fixation method used; 3. reduced efficiency of surface marker detection levels remained within acceptable ranges; 4. one freeze-thaw cycle did not significantly impair the cell suspension integrity or staining efficiency. Conclusion. These results provide a practical approach for phospho-detection in heterogeneous tissue samples. The clinical relevance of our technical approach appears substantial, as frequent dysfunctions within signaling pathways are linked to various diseases and consequently require proper identification methodology.
    Full-text · Article · Dec 2010 · Revista Romana de Medicina de Laborator
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    ABSTRACT: A 57-year-old woman, with left choroidal melanoma treated by laser photocoagulation and a history of repeated vitrectomies, checked for left eye acute pain and foreign body-like sensation, symptoms that occurred after three years since the primary tumor treatment. The left eyeball was enucleated and the tissues were investigated by immunohistochemistry for markers associated with cell differentiation, proliferation and adhesion, cell cycle regulation, apoptosis control, vascularization, invasiveness and local immune response. We identified, in fact, two independent tumors, with different localization and sharing some common features, markers of a highly aggressive potential: loss of cell differentiation markers and cell cycle regulators, ability to avoid death by suppressing Fas antigen expression and important invasive capacity by down regulation of E-cadherin expression. However, only in the posterior tumor, we found cells with high proliferation rate, Fas ligand molecule expression and MMP-9 secretion, acquisitions associated with a much more aggressive behavior. These particular phenotypes allowed the posterior cells to grow and to invade the surrounding tissues more rapidly than the anterior ones, leading to the development of a large size tumoral mass, responsible for the clinical symptoms. Photocoagulation, by destroying the tissues, makes impossible the evaluation of the primary tumor's biological features, important for the tumor evolution. The absence of these data stresses the importance of patient monitoring, eventually addressing a panel of soluble markers associated with recurrence or metastasis development.
    Preview · Article · Jan 2010 · Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie
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    ABSTRACT: Analysis of protein phosphorylation within intracellular signaling pathways may clarify the functional status and biological responses of cells to various stimuli, reflecting an enhanced enzymatic activity. Phospho- specific antibody (p-Ab)-based detection methods that have been used to date, including flow cytometry, require extensive optimization for the achievement of accuracy and rational specificity. Objective. We sought to optimize a phospho-specific flow cytometry detection method, based on the premise that fixation is a critical step of such protocols. Materials and methods. We compared two different methods for phospho-detection in phorbol myristate acetate (PMA)-activated peripheral blood mononuclear cells (PBMCs) and assessed how they distinctly impacted on cell viability, surface staining intensity and phospho-detection competence, aiming to develop an optimized protocol with balanced efficiency in surface and intracellular phospho-labeling. PMA-activated PBMCs were used for testing the detection efficiency of five p-Abs: pERK(T202/Y204), pp38MAPK(T180/Y182), pAKT(T308), pSTAT-3(S727), pSTAT-1(Y701) by flow cytometry. Results. 1. Fixation prior to surface staining led to an improved signal-to-noise ratio for all p-Abs evaluated; 2. cell suspension integrity was not affected by the fixation method used; 3. reduced efficiency of surface marker detection levels remained within acceptable ranges; 4. one freeze-thaw cycle did not significantly impair the cell suspension integrity or staining efficiency. Conclusion. These results provide a practical approach for phospho-detection in heterogeneous tissue samples. The clinical relevance of our technical approach appears substantial, as frequent dysfunctions within signaling pathways are linked to various diseases and consequently require proper identification methodology.
    No preview · Article · Jan 2010 · Revista Romana de Medicina de Laborator
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    ABSTRACT: To identify the types of the cells in a case of pilomatricoma and to evaluate the lesion's stage, the cells' proliferating rate and the associated inflammatory reaction. The paraffin-embedded tissue was investigated by histological examination and by immunohistochemistry for the expression of some markers such as: cytokeratins, CD3, CD20, CD68, PCNA, CD34 II. The lesion presented the characteristic epithelial cells of a classical pilomatricoma: bazaloid cells, ghost cells and transitional cells. 10-15% of the bazaloid cells were PCNA+. The MNF 116 antibody labeled only some of the transitional and of the ghost cells. We found no CD3-positive cells and few CD20-positive cells. A marked inflammatory reaction was noticed, dominated by giant multinucleated cells, positive for CD68 and PCNA and a rich network of blood vessels with a high vascular density. The histological pilomatricoma diagnosis was straightforward on the basis of the bazaloid and ghost cells presence. Immunohistochemistry brought additional data regarding the cells proliferation rate, the stage of the lesion and the intensity of the associated inflammation.
    No preview · Article · Jul 2009
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    ABSTRACT: Human gingival overgrowth may occur as a side effect of chronic administration of some therapeutic agents. The mechanisms responsible for the gingival tissues lesions, fibrosis and inflamation, involve an impaired balance between the production and the degradation of type I collagen. It has been demonstrated that CCN2/CTGF, a connective tissue growth factor, is highly expressed in the gingival tissues and positively correlated with the degree of fibrosis in the drug-induced gingival overgrowth. The aim of this study was to identify the presence and localization of CCN2/CTGF and CCN1/Cyr61, members of the same molecular family, in gingival tissues of cyclosporin A- and nifedipine-treated rats, by immunohistochemistry. Staining was evaluated with light microscope and the results show cellular and extracellular CTGF in nifedipin gingival overgrowth tissues with intensity of labeling higher compared to the CsA gingival overgrowth tissues or the controls. The staining for Cyr61 shows its intracellular localization with no diference of labeling intensity between drug-induced gingival overgrowth and normal tissues. Also, we were interested in the gingival TGF-â expression in those animals. We didn't find any commercial anti-rat TGF antibody and our anti-human antibody shows no cross-reactivity with rat tissues. The data from our study sustain the involvement of CTGF and Cyr61 as growth factors in the gingival tissues and the CTGF association with drug-induced gingival overgrowth.
    No preview · Article · Oct 2008
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    ABSTRACT: Endometrioid endometrial carcinoma is characterized by hyperestrogenism and high sensitivity to progestogens. Our study was designed in order to demonstrate the hormonal influences in neoplastic endometrium, by investigating steroid receptors expression and their correlation with proliferation activity, with matrix enzymes expression, and with susceptibility to apoptosis inducers, from hyperplasia to carcinoma. 13 cases were included in our study, 7 endometrial hyperplasias, and 6 endometrial carcinomas. Immunohistochemistry technique was performed, using antibodies against ER-á, PR, PCNA, MMP-2, MMP-9, Fas, and FasL molecules. Flow-cytometry was complementary used, for steroid receptors, PCNA and MMPs. Endometrial hyperplasias were positive for both hormonal receptors, in epithelial and stromal cells. An evident decrease of the percent of positive cells and of the staining intensity of both ER and PR was observed in poorly differentiated endometrial carcinomas. Endometrial hyperplasias presented a similar proliferative index with differentiated endometrioid endometrial carcinomas. Poorly differentiated endometrial carcinomas showed the highest PCNA index. Both types of investigated MMPs were evident, with similar aspect of localisation for both MMP-2 and MMP-9. The staining intensity for MMP-9 was higher than that of MMP-2, and was identified both in epithelial and in stromal cells. Fas and FasL expressions were identified in glandular epithelium of endometrial hyperplasias and carcinomas, although the staining intensity was reduced. Flow-cytometry showed a correlation between qualitative and quantitative data concerning hormonal receptors, PCNA and MMPs. Our study emphasises that neoplastic endometrial cells express several molecules correlated with malignant transformation and tumoral progression, by coordinated intervention of steroids, proliferating factors, gelatinases, in opposition with systems involved in apoptosis initiation.
    No preview · Article · Apr 2008
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    Full-text · Article · Nov 2007 · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin
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    ABSTRACT: We have identified by immunohistochemistry/ immunocytochemistry the expression of bcl-2 molecule in 55 primary breast carcinomas and in 30 corresponding axillary lymph nodes metastases, together with a set of molecules known as prognostic factors: estrogen receptors, progesterone receptors, and p53 protein. Our results demonstrated a significant correlation (p < 0.05) between bcl-2 and hormonal receptors expression in tumors, but not in axillary metastases (p < 0.1), a significant inverse correlation between bcl-2 and p53 expression in primary tumors (p < 0.02), but a significant direct correlation in axillary metastases (p < 0.02). The bcl-2+/p53- phenotype, associated with normal breast epithelium, is present in 79.17% primary tumors, but only in 15.38% axillary lymph nodes metastases. A larger number of lymph nodes metastases expressed a bcl-2+/ p53+ more aggressive phenotype compared with primary tumors (58.82% versus 48.39%). This shows that changes in the expression of bcl-2, p53, estrogen and progesterone receptors can lead to an increased cellular aggressiveness and thus to an increased tumoral invasive and metastasizing potential.
    No preview · Article · Jan 2005
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    ABSTRACT: We have investigated the cellular and serum CK18 in 26 non-treated primary ductal invasive breast carcinomas. The soluble CK18 (TPS) was detected by chemiluminescent assay, and the cellular CK18 and PCNA expression by immunocytochemistry. Flow-cytometry was used to estimate the amount of DNA in malignant cells. There was a significant correlation between soluble CK18 and the pre-menopausal status (p < 0.05), characterized in our group by a PCNA estimated low proliferation index. We have also found a significant correlation between soluble CK18 and the DNA index (p < 0.01). The intracellular CK18 has correlated with the PCNA expression (p < 0.05), while no correlation could be found between cellular and serum CK18. The values of soluble CK18 may offer information about the treatment-induced cell death, if monitored, while isolated measurements should be interpreted cautiously. Elevated levels of serum CK18 in non-treated carcinomas may rather reflect a high tumor turn-over or perhaps a more intensive tumor cell killing.
    No preview · Article · Jan 2005
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    ABSTRACT: The etiology and pathogenesis of acne vulgaris are not yet completely understood. Therefore we have investigated 5 patients with different clinical forms of disease, including the rare form of acne fulminans. Taking into consideration the four factors that are currently incriminated in the development of acne, sebaceous hypersecretion, hyperkeratosis of the pilosebaceous infundibulum, bacterial colonisation and perifollicular inflammation, we have focused our study on a set of cells involved in the chronic inflammatory process. We have evidenced by immunohistochemistry methods, using appropriate monoclonal antibodies, the presence of T lymphocytes and macrophages, while the B cells could be evidenced only in the severe forms. We were also interested to investigate the occurrence of new capillary formation, as an accompanying phenomenon of the inflammatory process. The presence and histological distribution of these cells highly supports the hypothesis that the mechanisms underlying the development of acne vulgaris belong to the Delayed Type Hypersensitivity.
    No preview · Article · Jan 2004
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    ABSTRACT: The major histocompatibility complex (MHC) class I related neonatal Fc receptor (FcRn) plays multiple roles, being involved in transporting immunoglobulin G (IgG) and protecting this antibody class from catabolism. The presence of this receptor was previously demonstrated in the lactating murine mammary gland. In the current study we have investigated FcRn expression in various histologic types of human breast carcinoma and lymph node metastases. We used immunohistochemical methods to demonstrate the presence of FcRn in epithelial cells, whereas this Fc receptor could not be detected in mammary gland endothelial cells. The presence of the receptor was also found in the metastasizing epithelial cells within the lymph nodes, and this provides a useful marker for their identification.
    Full-text · Article · Jan 2004 · Human Immunology
  • Corina Cianga · P Cianga · Laurette Cozma · C Diaconu · E Carasevici
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    ABSTRACT: Fas (CD95/APO-1) and its natural ligand, FasL, are molecules expressed on cellular membranes, being involved in the induction of programmed cells death or apoptosis. Recently, it has been shown that malignant cells originating from solid tumors tend to inhibit the expression of Fas, as an escape mechanism from the immune cells' attack and to express FasL, as a counterstrike mechanism against the immune effector cells. The purpose of this study was to investigate, by immunohistochemistry, the presence of Fas and FasL in 15 breast carcinomas and to establish possible associations between the expression of these molecules and the histological type and grading of the tumors. Our results showed that 7 breast tumors have lost the expression of Fas and 11 tumors were positive for the Fas-ligand expression, important arguments for the mechanisms of immune escape and tolerance induction. Furthermore, 7 of the 11 FasL+ tumors were poorly differentiated invasive ductal carcinomas, suggesting a possible association between FasL expression and tumor aggressivity.
    No preview · Article · Jan 2004
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    ABSTRACT: Malignant transformation is the result of genetic events, translated into sequential acquisitions of multiple abnormalities in the control of cellular growth and cell cycle regulation. We determined the expression of the estrogen receptor (ER), progesterone receptor (PR), c-erbB-2 and p53 gene products in a patient with mixed (ductal and lobular) invasive breast carcinoma bearing different coexisting lesions. The purpose of the study was to establish a possible correlation between the expression pattern for these molecules and the histological appearance of the breast tumor. Our results showed no positivity for ER. PR expression was restricted to normal epithelium, simple hyperplasia and in situ carcinoma. c-erbB-2 was detected in all lesions with the exception of normal epithelium and immunostaining for p53 was found positive only in in situ and invasive carcinoma. These findings support the hypothesis of tumorigenesis as a multistep process and as a sum of changes, each representing an advantageous acquisition for the malignant cells' behavior. The loss of hormone receptors' expression occurred as an early event in this case, while the p53 mutations were found only in more advanced neoplastic lesions.
    No preview · Article · Jul 2003 · Journal of B.U.ON.: official journal of the Balkan Union of Oncology
  • Corina Cianga · P Cianga · Laurette Cozma · C Diaconu · E Carasevici
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    ABSTRACT: Breast tumors growth is regulated by female sex steroid hormones. The level of the estrogen and progesterone receptors (ER and PR) expression by the malignant cells is important for the evaluation of the tumor prognostic and the benefit of a hormonal therapy. The aim of our study was to identify the expression of estrogen and progesterone receptors in primary breast tumors and in the corresponding axillary lymph nodes metastases, in 24 cases. The results showed that more than 30% of poorly differentiated breast carcinomas lost their expression of hormone receptors from the primary tumors to axillary metastases, an event which can be associated with an aggressive tumoral behaviour and resistance to hormonal therapy.
    No preview · Article · Jan 2003