A. Cimpeanu - Academia.edu (original) (raw)

Papers by A. Cimpeanu

Chloride Intracellular Channel Protein 1 (CLIC1) Ιs Over-expressed in Muscle Invasive Urinary Bladder Cancer

AntiCancer Research, 2020

Background/Aim: Invasive bladder cancer mortality remains high despite progresses made in early d... more Background/Aim: Invasive bladder cancer mortality remains high despite progresses made in early diagnosis and surgical procedures. Thus, there is a need to define new markers for bladder cancer. CLIC1 has not been previously studied in bladder cancer and thus, we aimed to assess its immunohistochemical expression in relation to different stages of bladder cancer development. Materials and Methods: Immunohistochemistry for CLIC1 was applied in 50 cases of muscle invasive bladder cancer. Results: CLIC1 was not expressed in the normal urothelium, but a strong reaction was observed in dysplastic urothelium, carcinoma in situ and in 94% of the cases with invasive urothelial carcinoma; however, it was not expressed in squamous cell carcinoma cases. No correlation was found between the immunohistochemical expression of CLIC1 and the stage and grade of the tumour. Conclusion: CLIC1 was overexpressed in urinary bladder dysplastic epithelium, carcinoma in situ and invasive carcinoma. CLIC1 co...

Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide with a high mortalit... more Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide with a high mortality. Immunohistochemical overexpression of the p53 protein was correlated with a poor prognosis in various human malignancies, including HCC. In our study, 45 resected HCCs were examined to evaluate the expression of p53 and its correlation with clinicopathological parameters. Immunohistochemical detection of p53 with monoclonal human antibody, revealed its overexpression in 20 tumors (44%), including diffuse positive in 7 cases (35%), heterogeneous in 5 (25%), and focal in 8 (40%). We considered a positive reaction only in the presence of immunostained nuclei in brown shades in more than 5% of the tumor nuclei. To elucidate the significance of p53 in HCC, we correlated its protein expression with major clinicopathological features. We did not observe significant correlation with sex, age, presence of cirrhosis, chronic hepatitis status, tumoral necrosis and tumor size. The density and int...

Effects of antibodies to EG-VEGF on angiogenesis in the chick embryo chorioallantoic membrane

In vivo (Athens, Greece)

Endocrine gland-related vascular endothelial growth factor (EG-VEGF), is an angiogenic factor spe... more Endocrine gland-related vascular endothelial growth factor (EG-VEGF), is an angiogenic factor specifically targeting endothelial cells derived from endocrine tissues. The inhibition of the EG-VEGF/prokineticin receptor pathway could represent a selective antiangiogenic and anticancer strategy. to evaluate the impact of an antibody to EG-VEGF on the rapidly growing capillary plexus of the chick embryo chorioallantoic membrane (CAM). The in ovo CAM assay was performed for the humanized EG-VEGF antibody. Hemorrhagic damage was induced in the capillaries, which led to early death of the embryos. Upon morphological staining, there was evidence of vascular disruption and extravasation of red blood cells in the chorion. Signs of vacuolization of the covering epithelium were also observed. Blocking endogenous EG-VEGF might represent a valuable approach of impairing or inhibiting angiogenesis in steroidogenic-derived embryonic tissues.

Crosstalk between tumor blood vessels heterogeneity and hormonal profile of pituitary adenomas: evidence and controversies

Anticancer research, 2014

Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous cl... more Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous clinical behaviour. Angiogenesis and tumor blood vessels' role in pathogenesis, remain one of the great pituitary tumor mysteries. No connection between tumor vessel heterogeneity, hormonal profile and biological behaviour has been reported. We aimed to study pituitary adenomas blood vessels concerning their immature, intermediate or mature phenotype and microvessel density, correlated with immunohistochemical hormonal profile and hormone values in serum and cerebrospinal fluid. We classified pituitary adenomas according to hormone profile and we applied a double immunostaining highlighting both endothelial and perivascular cells for a more accurate assessment of blood vessel types. Overall microvessel density was found to be highest in growth hormone-secreting adenomas (48.51 ± 12.15) and lowest in prolactinomas (29.15 ± 18.78). When we differentially counted tumor blood vessels we ob...

Oncology Letters, 2012

Despite advances in treatment, the prognosis for lung cancer patients remains poor. Angiogenesis ... more Despite advances in treatment, the prognosis for lung cancer patients remains poor. Angiogenesis appears to be a promising target for lung cancer therapy; however, the clinical significance of vascular changes are not completely understood. The aim of this study was to evaluate the types and morphology of blood vessels in various lung carcinomas. Using double immunostaining, we investigated 39 biopsies from patients admitted with various histological types of lung carcinoma. Tumor blood vessels were quantified separately for CD34/smooth muscle actin and described as either immature, intermediate or mature. Double immunostaining evaluation of the type of blood vessels in lung carcinomas revealed a marked heterogeneity. The immature and intermediate type of vessels were more common in adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) of the lung. Small cell lung carcinomas revealed a significant correlation between pathological and immature types of blood vessels. Therefore, quantifying the types of tumor vessels in lung carcinomas may be an important element to improve the results of anti-vascular therapy.

International Journal of Experimental Pathology, 2011

The thymus is crucial for the normal development of the immune system, and its peculiar microenvi... more The thymus is crucial for the normal development of the immune system, and its peculiar microenvironment consisting of epithelial cells, connective tissue and blood vessels contributes to T cell differentiation . Much data have been accumulated in the past decades concerning the differentiation and maturation of T cells, including the contribution of the thymic stroma . Prenatal and postnatal human thymuses have been little investigated in terms of normal histological variants ) and of the presence of multipotent mesenchymal stromal cells in foetal and adult human thymus . Little data is available about the molecular mechanisms of the human thymus development and the role of different growth factors and their receptors in the normal organogenesis of this gland and its malignant transformation. Vascular endothelial growth factor (VEGF), VEGF receptors 1 and 2 (VEGFR-1 and -2), and fibroblast growth factor-2 (FGF-2) expression have been studied in the embryonic thymus . reported that nerve growth factor (NGF) and its receptors are involved in the formation of the thymus stroma and proliferation of epithelial cells. These data were supported by , which suggested that tropic

Cases Journal, 2008

Paraganglioma-like dermal melanocytic tumor is a rare subtype of benign dermal melanocytic tumors... more Paraganglioma-like dermal melanocytic tumor is a rare subtype of benign dermal melanocytic tumors. Its histopathologic features resemble those of paraganglioma, but the immunostaining characteristics are those of melanocytic lesions. We report a case of a 60-year-old male with a paraganglioma-like dermal melanocytic tumor of his left cheek and briefly review the English literature.

Archives of Biological Sciences, 2013

The aspect of reticular fibers is not considered in the current classifications of lung fibrosis.... more The aspect of reticular fibers is not considered in the current classifications of lung fibrosis. The aim of our study was to evaluate the distribution and the architecture of the reticular fibers for potential use as a tissue marker of fibrosis severity. We included in our study 25 pulmonary samples obtained by video-assisted thoracoscopy surgery (VATS) from a number of 20 cases. The cases were subdivided according to four criteria into: degree II, III and IV. We noticed no significant changes in the reticular network from interalveolar septa to the cases scored with 0, an accumulation of reticular fibers in the interalveolar septa (stage II), the condensation and thick bundles with network disorganization in all areas affected by fibrosis (stage III), partial to full depletion of reticular fibers (stage IV). Depletion of reticular fibers was constantly associated with advanced fibrosis stages.

The present study described for the first time a high heterogeneity of blood vessels in non-Hodgk... more The present study described for the first time a high heterogeneity of blood vessels in non-Hodgkin lymphomas (nHL). The tumor blood vessels were highlighted with CD105/smooth muscle actin (SMA) and CD34/SMA double immunostaining. For both follicular and diffuse types of lymphomas, more than 85% of CD34/SMA positive vessels were of immature and intermediate type. A percent of 96.54 from CD105/SMA assessed blood vessels were of activated and mature activated types with high expression of CD105 on endothelial cells of newly formed blood vessels. Our results suggest that these types of vessels are potential therapeutic targets for antivascular therapy.

Anti-Angiogenic and Anti-Cancer Evaluation of Betulin Nanoemulsion in Chicken Chorioallantoic Membrane and Skin Carcinoma in Balb/c Mice

Betulin (Bet), the main component of birch tree bark, has been recently reported to exert antican... more Betulin (Bet), the main component of birch tree bark, has been recently reported to exert anticancer activity in several cell lines; however the underlying mechanisms are only partially elucidated. The aims of the present work were to assess the in vivo effects of betulin administered as nanoemulsion (NE) in two experimental models: (i) the chicken embryo chorioallantoic membrane (CAM) assay for the study of anti-angiogenic effects and (ii) the two-stage model of skin carcinoma induced in mice for the study of anti-tumor and anti-inflammatory effects, respectively. On the CAM of the chicken betulin in nanoemulsion (BetNE) shows a good penetrability at extra-embryonic tissue level, affecting both the chorioallantoic membrane as well as the yolk sac by reducing the capillary density. In the animal model, the potential impact of local application of betulin on the respiratory function of isolated liver mitochondria was further assessed. Topical application of betulin nanoemulsion for 12 weeks together with DMBA (7,12-dimethylbenz[a]anthracene) and TPA (12-O-tetradecanoylphorbol 13-acetate), as tumor initiator and promoter, enhanced the active respiration of isolated liver mitochondria. Betulin also inhibit skin tumor apparition and promotion, proved by histological results and VEGF (vascular endothelial growth factor) expression correlated to non-invasive measurements. Betulin is active in nanoemulsion formulation as a potential inhibitory on the angiogenic process in CAM assay. BetNE can develop a potent anti-inflammatory and anti-carcinogenic activity with a low toxicity at skin level. It can also influence the penetration of carcinogens and reduce damage in main organs (e.g., liver).

International Journal of Molecular Sciences

Microscopic and molecular events related to alveolar ridge augmentation are less known because of... more Microscopic and molecular events related to alveolar ridge augmentation are less known because of the lack of experimental models and limited molecular markers used to evaluate this process. We propose here the chick embryo chorioallantoic membrane (CAM) as an in vivo model to study the interaction between CAM and bone substitutes (B) combined with hyaluronic acid (BH), saline solution (BHS and BS, respectively), or both, aiming to point out the microscopic and molecular events assessed by Runt-related transcription factor 2 (RUNX 2), osteonectin (SPARC), and Bone Morphogenic Protein 4 (BMP4). The BH complex induced osteoprogenitor and osteoblastic differentiation of CAM mesenchymal cells, certified by the RUNX2 +, BMP4 +, and SPARC + phenotypes capable of bone matrix synthesis and mineralization. A strong angiogenic response without inflammation was detected on microscopic specimens of the BH combination compared with an inflammatory induced angiogenesis for the BS and BHS combinat...

Journal of Breast Cancer, 2016

Recent studies have shown that normal breast tissue is composed of epithelial and nonepithelial c... more Recent studies have shown that normal breast tissue is composed of epithelial and nonepithelial cells with different profiles reflecting their maturation and differentiation [1]. In addition, cells of normal mammary tissue are known to yield abnormal clones that may contribute to the development of both preneoplastic and tumor lesions [2-4]. It appears that epithelial cells of the normal breast exhibit a heterogeneous profile depending on their differentiation stage. Considering these facts, several reports have referred to the existence of two luminal phenotypes and two basal phenotypes, based on differential immunohistochemical profiles [1]. These cells are known to express CD24, CD49f, and the epithelial cell adhesion molecule Epithelial cell adhesion molecule (EpCAM) [1]. Luminal progenitor cells, of normal breast tissue, express both CD49f and EpCAM while their mature variants do not express CD49f [1]. Myoepithelial cells, along with basal progenitor cells, lack EpCAM expression [1]. Both mature luminal cells and progenitor cells express CD44 and CD24 [1]. Based on cytokeratin (CK) 14 and CK19 expression in normal breast tissue, it appears that the normal mammary gland contains multipotent cells. These cells are located in the ducts,

In Vivo, May 1, 2013

Aim: Intranodal palisaded myofibroblastoma (IPM) is a rare benign mesenchymal tumor restricted to... more Aim: Intranodal palisaded myofibroblastoma (IPM) is a rare benign mesenchymal tumor restricted to the lymph nodes. Here, we report the case of a 44-year-old male patient with an IPM confined to the left laterocervical area. Case Report: After an accurate microscopic evaluation of morphological and histochemical stains, immunohistochemistry was performed for vimentin, smooth muscle actin vascular markers, S100 protein, D2-40, Ki67, lymphoid and melanoma markers, keratin and desmin on sections obtained from a paraffin-embedded surgical biopsy. Results: Spindle cell proliferation was positive for vimentin, smooth muscle cell actin and D2-40 and negative for the other markers. Low proliferative index, assessed by Ki67, was found. Based on morphological and immunohistochemical findings we diagnosed this case as intranodal palisaded myofibroblastoma and we highlighted a D2-40 expression in the tumor spindle cells. The presence of mast cells and their particular distribution inside the tumor are also, together with D2-40 expression, original findings of this study. No therapy was recommended after surgical and histopathological evaluation. The evolution of the patient was favorable with no other relapse following surgical removal of the lymphadenopathy. He has a normal life and no other changes of clinical and biological parameters were registered. Conclusion: To the best of our knolwedge, this is the first report regarding a D2-40-positive reaction in the spindle cells of intranodal palisaded myofibroblastoma. Thus, D2-40 could be added to the panel of antibodies used for immunohistochemical diagnosis of such types of tumors.

Endothelial Cell Proliferation and Vascular Endothelial Growth Factor Expression in Primary Colorectal Cancer Compared with Corresponding Liver Metastases

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a ... more Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC, and to determine whether these two markers correlate with conventional parameters of prognosis. Materials and Methods: Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal. The intensity of EGFR staining was scored on a scale of 0-3+: 0 no staining; 1+ when a weak membrane staining was observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense dark brown staining delineated the membrane. To determine the relationship between EGFR expression and p53, we performed double staining in the same HCC specimens. Results: By immunohistochemical staining, p53 protein was detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity of p53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked to histological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFR intensity (p=0.014). Conclusions: Our results suggest that overexpression of p53 and EGFR plays an important role in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuable predictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies.

Background: Scattered studies report on controversial results concerning evaluation of primary br... more Background: Scattered studies report on controversial results concerning evaluation of primary breast tumors and their matched lymph node metastases. Aim. To investigate the molecular profile of primary breast tumors and corresponding lymph node metastases (LNM) based on estrogen receptor (ER), progesterone receptor (PR) and human epiderma growth factor receptor-2 (HER2 protein). Materials and Methods: Sixty-six primary tumors and corresponding axillary lymph node metastases were evaluated by immunohistochemistry for ER, PR and HER2 protein. According to these markers, cases were stratified as Luminal A, B, HER2 subtypes and triple-negative. Results. Thirteen out of 66 cases (19.7%) exhibited different tumor cell phenotypes in nodal metastases compared to primary breast tumors. All cases with hybrid phenotype had metastases with a pure HER2 phenotype. The most frequent switching was observed from luminal A to luminal B phenotype. Conclusion: The high rate of discrepancy between primary tumor and nodal metastasis phenotype imposes the need for a comparative assessment of both primary tumor and nodal metastasis before any therapeutic decision, in order to avoid recurrence and to improve patient prognosis and overall survival.

Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie

E-cadherins are epithelial morphological stabilizers, performing complex functions as receptors, ... more E-cadherins are epithelial morphological stabilizers, performing complex functions as receptors, providers of cellular and tissular structural integrity, and functional interactive mediators. Structural and functional unbalance initiated due to E-cadherin expression loss results in direct effects on carcinogenesis specific biological processes, as cellular invasion and proliferation. We investigated the E-cadherin expression aiming (i) to identify the differences in the molecular subtypes of breast cancer, (ii) to analyze the correlations between E-cadherin and specific clinicopathological and molecular characteristics. The study included 42 cases that were investigated immunohistochemically using a panel of antibodies (ER, PR, Her2÷neu, CK5÷6, EGFR), which permitted a diagnostic in compliance with the molecular classification, followed by the E-cadherin evaluation. The semi-quantitative assessment of E-cadherin was performed using a scoring system based on the positive cells percen...

Archives of Biological Sciences, 2014

Mast cell (MC) active mediators promote inflammation through changes induced in the connective ti... more Mast cell (MC) active mediators promote inflammation through changes induced in the connective tissue components of human gingiva. The aim of this study was to evaluate the distribution, mast cell density and their relationship with the degree of inflammatory infiltrate in gingiva from patients with periodontal disease. Thirty-nine cases with periodontal disease and 12 cases without significant changes to the gingival mucosa were investigated. MCs were identified on paraffin-embedded specimens by immunohistochemistry using anti-mast cell tryptase. The inflammatory infiltrate was scored from 0 to 3, and the MCs were counted using the hotspot method. Intraepithelial MCs were scored from 0 to 2. We found a significant increase of mast cell density in cases with mild and moderate inflammatory changes, and a slight decrease in patients with severe periodontal disease. We noticed a higher degranulation rate in patients with periodontal disease compared to those with healthy mucosa. Intrae...

Archives of Biological Sciences, 2013

There is little information about the exact trigger mechanisms of vascular endothelial growth fac... more There is little information about the exact trigger mechanisms of vascular endothelial growth factor (VEGF) expression in hematolymphoid malignancies. The aim of this study was to investigate the expression of VEGF in malignant non-Hodgkin lymphoma (NHL), in terms of its immunohistochemical distribution and clinicopathological significance. We evaluated the distribution in tumor cells, macrophages and in non-tumoral cells. VEGF immunoreactivity was estimated according to this score: 0 (0% positive cells); 1 (<10%); 2 (10-30%); 3 (>30%). Histopathological evaluation revealed 18 cases of diffuse type lymphoma and 3 cases of follicular type lymphoma. VEGF was positive in 95.23% of cases and in one case, VEGF was negative in all cell types. We noticed a significant correlation in VEGF expression between tumor cells and macrophages (p=0,001), tumor cells and non-tumoral cells (p=0,002). In non-Hodgkin lymphoma, the main mechanism of angiogenesis seems to be dependent on the VEGF pathway and its expression particularly by stromal cells.

Chloride Intracellular Channel Protein 1 (CLIC1) Ιs Over-expressed in Muscle Invasive Urinary Bladder Cancer

AntiCancer Research, 2020

Background/Aim: Invasive bladder cancer mortality remains high despite progresses made in early d... more Background/Aim: Invasive bladder cancer mortality remains high despite progresses made in early diagnosis and surgical procedures. Thus, there is a need to define new markers for bladder cancer. CLIC1 has not been previously studied in bladder cancer and thus, we aimed to assess its immunohistochemical expression in relation to different stages of bladder cancer development. Materials and Methods: Immunohistochemistry for CLIC1 was applied in 50 cases of muscle invasive bladder cancer. Results: CLIC1 was not expressed in the normal urothelium, but a strong reaction was observed in dysplastic urothelium, carcinoma in situ and in 94% of the cases with invasive urothelial carcinoma; however, it was not expressed in squamous cell carcinoma cases. No correlation was found between the immunohistochemical expression of CLIC1 and the stage and grade of the tumour. Conclusion: CLIC1 was overexpressed in urinary bladder dysplastic epithelium, carcinoma in situ and invasive carcinoma. CLIC1 co...

Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide with a high mortalit... more Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide with a high mortality. Immunohistochemical overexpression of the p53 protein was correlated with a poor prognosis in various human malignancies, including HCC. In our study, 45 resected HCCs were examined to evaluate the expression of p53 and its correlation with clinicopathological parameters. Immunohistochemical detection of p53 with monoclonal human antibody, revealed its overexpression in 20 tumors (44%), including diffuse positive in 7 cases (35%), heterogeneous in 5 (25%), and focal in 8 (40%). We considered a positive reaction only in the presence of immunostained nuclei in brown shades in more than 5% of the tumor nuclei. To elucidate the significance of p53 in HCC, we correlated its protein expression with major clinicopathological features. We did not observe significant correlation with sex, age, presence of cirrhosis, chronic hepatitis status, tumoral necrosis and tumor size. The density and int...

Effects of antibodies to EG-VEGF on angiogenesis in the chick embryo chorioallantoic membrane

In vivo (Athens, Greece)

Endocrine gland-related vascular endothelial growth factor (EG-VEGF), is an angiogenic factor spe... more Endocrine gland-related vascular endothelial growth factor (EG-VEGF), is an angiogenic factor specifically targeting endothelial cells derived from endocrine tissues. The inhibition of the EG-VEGF/prokineticin receptor pathway could represent a selective antiangiogenic and anticancer strategy. to evaluate the impact of an antibody to EG-VEGF on the rapidly growing capillary plexus of the chick embryo chorioallantoic membrane (CAM). The in ovo CAM assay was performed for the humanized EG-VEGF antibody. Hemorrhagic damage was induced in the capillaries, which led to early death of the embryos. Upon morphological staining, there was evidence of vascular disruption and extravasation of red blood cells in the chorion. Signs of vacuolization of the covering epithelium were also observed. Blocking endogenous EG-VEGF might represent a valuable approach of impairing or inhibiting angiogenesis in steroidogenic-derived embryonic tissues.

Crosstalk between tumor blood vessels heterogeneity and hormonal profile of pituitary adenomas: evidence and controversies

Anticancer research, 2014

Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous cl... more Pituitary adenomas are intracranial tumors with controversial histopathology and heterogeneous clinical behaviour. Angiogenesis and tumor blood vessels' role in pathogenesis, remain one of the great pituitary tumor mysteries. No connection between tumor vessel heterogeneity, hormonal profile and biological behaviour has been reported. We aimed to study pituitary adenomas blood vessels concerning their immature, intermediate or mature phenotype and microvessel density, correlated with immunohistochemical hormonal profile and hormone values in serum and cerebrospinal fluid. We classified pituitary adenomas according to hormone profile and we applied a double immunostaining highlighting both endothelial and perivascular cells for a more accurate assessment of blood vessel types. Overall microvessel density was found to be highest in growth hormone-secreting adenomas (48.51 ± 12.15) and lowest in prolactinomas (29.15 ± 18.78). When we differentially counted tumor blood vessels we ob...

Oncology Letters, 2012

Despite advances in treatment, the prognosis for lung cancer patients remains poor. Angiogenesis ... more Despite advances in treatment, the prognosis for lung cancer patients remains poor. Angiogenesis appears to be a promising target for lung cancer therapy; however, the clinical significance of vascular changes are not completely understood. The aim of this study was to evaluate the types and morphology of blood vessels in various lung carcinomas. Using double immunostaining, we investigated 39 biopsies from patients admitted with various histological types of lung carcinoma. Tumor blood vessels were quantified separately for CD34/smooth muscle actin and described as either immature, intermediate or mature. Double immunostaining evaluation of the type of blood vessels in lung carcinomas revealed a marked heterogeneity. The immature and intermediate type of vessels were more common in adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) of the lung. Small cell lung carcinomas revealed a significant correlation between pathological and immature types of blood vessels. Therefore, quantifying the types of tumor vessels in lung carcinomas may be an important element to improve the results of anti-vascular therapy.

International Journal of Experimental Pathology, 2011

The thymus is crucial for the normal development of the immune system, and its peculiar microenvi... more The thymus is crucial for the normal development of the immune system, and its peculiar microenvironment consisting of epithelial cells, connective tissue and blood vessels contributes to T cell differentiation . Much data have been accumulated in the past decades concerning the differentiation and maturation of T cells, including the contribution of the thymic stroma . Prenatal and postnatal human thymuses have been little investigated in terms of normal histological variants ) and of the presence of multipotent mesenchymal stromal cells in foetal and adult human thymus . Little data is available about the molecular mechanisms of the human thymus development and the role of different growth factors and their receptors in the normal organogenesis of this gland and its malignant transformation. Vascular endothelial growth factor (VEGF), VEGF receptors 1 and 2 (VEGFR-1 and -2), and fibroblast growth factor-2 (FGF-2) expression have been studied in the embryonic thymus . reported that nerve growth factor (NGF) and its receptors are involved in the formation of the thymus stroma and proliferation of epithelial cells. These data were supported by , which suggested that tropic

Cases Journal, 2008

Paraganglioma-like dermal melanocytic tumor is a rare subtype of benign dermal melanocytic tumors... more Paraganglioma-like dermal melanocytic tumor is a rare subtype of benign dermal melanocytic tumors. Its histopathologic features resemble those of paraganglioma, but the immunostaining characteristics are those of melanocytic lesions. We report a case of a 60-year-old male with a paraganglioma-like dermal melanocytic tumor of his left cheek and briefly review the English literature.

Archives of Biological Sciences, 2013

The aspect of reticular fibers is not considered in the current classifications of lung fibrosis.... more The aspect of reticular fibers is not considered in the current classifications of lung fibrosis. The aim of our study was to evaluate the distribution and the architecture of the reticular fibers for potential use as a tissue marker of fibrosis severity. We included in our study 25 pulmonary samples obtained by video-assisted thoracoscopy surgery (VATS) from a number of 20 cases. The cases were subdivided according to four criteria into: degree II, III and IV. We noticed no significant changes in the reticular network from interalveolar septa to the cases scored with 0, an accumulation of reticular fibers in the interalveolar septa (stage II), the condensation and thick bundles with network disorganization in all areas affected by fibrosis (stage III), partial to full depletion of reticular fibers (stage IV). Depletion of reticular fibers was constantly associated with advanced fibrosis stages.

The present study described for the first time a high heterogeneity of blood vessels in non-Hodgk... more The present study described for the first time a high heterogeneity of blood vessels in non-Hodgkin lymphomas (nHL). The tumor blood vessels were highlighted with CD105/smooth muscle actin (SMA) and CD34/SMA double immunostaining. For both follicular and diffuse types of lymphomas, more than 85% of CD34/SMA positive vessels were of immature and intermediate type. A percent of 96.54 from CD105/SMA assessed blood vessels were of activated and mature activated types with high expression of CD105 on endothelial cells of newly formed blood vessels. Our results suggest that these types of vessels are potential therapeutic targets for antivascular therapy.

Anti-Angiogenic and Anti-Cancer Evaluation of Betulin Nanoemulsion in Chicken Chorioallantoic Membrane and Skin Carcinoma in Balb/c Mice

Betulin (Bet), the main component of birch tree bark, has been recently reported to exert antican... more Betulin (Bet), the main component of birch tree bark, has been recently reported to exert anticancer activity in several cell lines; however the underlying mechanisms are only partially elucidated. The aims of the present work were to assess the in vivo effects of betulin administered as nanoemulsion (NE) in two experimental models: (i) the chicken embryo chorioallantoic membrane (CAM) assay for the study of anti-angiogenic effects and (ii) the two-stage model of skin carcinoma induced in mice for the study of anti-tumor and anti-inflammatory effects, respectively. On the CAM of the chicken betulin in nanoemulsion (BetNE) shows a good penetrability at extra-embryonic tissue level, affecting both the chorioallantoic membrane as well as the yolk sac by reducing the capillary density. In the animal model, the potential impact of local application of betulin on the respiratory function of isolated liver mitochondria was further assessed. Topical application of betulin nanoemulsion for 12 weeks together with DMBA (7,12-dimethylbenz[a]anthracene) and TPA (12-O-tetradecanoylphorbol 13-acetate), as tumor initiator and promoter, enhanced the active respiration of isolated liver mitochondria. Betulin also inhibit skin tumor apparition and promotion, proved by histological results and VEGF (vascular endothelial growth factor) expression correlated to non-invasive measurements. Betulin is active in nanoemulsion formulation as a potential inhibitory on the angiogenic process in CAM assay. BetNE can develop a potent anti-inflammatory and anti-carcinogenic activity with a low toxicity at skin level. It can also influence the penetration of carcinogens and reduce damage in main organs (e.g., liver).

International Journal of Molecular Sciences

Microscopic and molecular events related to alveolar ridge augmentation are less known because of... more Microscopic and molecular events related to alveolar ridge augmentation are less known because of the lack of experimental models and limited molecular markers used to evaluate this process. We propose here the chick embryo chorioallantoic membrane (CAM) as an in vivo model to study the interaction between CAM and bone substitutes (B) combined with hyaluronic acid (BH), saline solution (BHS and BS, respectively), or both, aiming to point out the microscopic and molecular events assessed by Runt-related transcription factor 2 (RUNX 2), osteonectin (SPARC), and Bone Morphogenic Protein 4 (BMP4). The BH complex induced osteoprogenitor and osteoblastic differentiation of CAM mesenchymal cells, certified by the RUNX2 +, BMP4 +, and SPARC + phenotypes capable of bone matrix synthesis and mineralization. A strong angiogenic response without inflammation was detected on microscopic specimens of the BH combination compared with an inflammatory induced angiogenesis for the BS and BHS combinat...

Journal of Breast Cancer, 2016

Recent studies have shown that normal breast tissue is composed of epithelial and nonepithelial c... more Recent studies have shown that normal breast tissue is composed of epithelial and nonepithelial cells with different profiles reflecting their maturation and differentiation [1]. In addition, cells of normal mammary tissue are known to yield abnormal clones that may contribute to the development of both preneoplastic and tumor lesions [2-4]. It appears that epithelial cells of the normal breast exhibit a heterogeneous profile depending on their differentiation stage. Considering these facts, several reports have referred to the existence of two luminal phenotypes and two basal phenotypes, based on differential immunohistochemical profiles [1]. These cells are known to express CD24, CD49f, and the epithelial cell adhesion molecule Epithelial cell adhesion molecule (EpCAM) [1]. Luminal progenitor cells, of normal breast tissue, express both CD49f and EpCAM while their mature variants do not express CD49f [1]. Myoepithelial cells, along with basal progenitor cells, lack EpCAM expression [1]. Both mature luminal cells and progenitor cells express CD44 and CD24 [1]. Based on cytokeratin (CK) 14 and CK19 expression in normal breast tissue, it appears that the normal mammary gland contains multipotent cells. These cells are located in the ducts,

In Vivo, May 1, 2013

Aim: Intranodal palisaded myofibroblastoma (IPM) is a rare benign mesenchymal tumor restricted to... more Aim: Intranodal palisaded myofibroblastoma (IPM) is a rare benign mesenchymal tumor restricted to the lymph nodes. Here, we report the case of a 44-year-old male patient with an IPM confined to the left laterocervical area. Case Report: After an accurate microscopic evaluation of morphological and histochemical stains, immunohistochemistry was performed for vimentin, smooth muscle actin vascular markers, S100 protein, D2-40, Ki67, lymphoid and melanoma markers, keratin and desmin on sections obtained from a paraffin-embedded surgical biopsy. Results: Spindle cell proliferation was positive for vimentin, smooth muscle cell actin and D2-40 and negative for the other markers. Low proliferative index, assessed by Ki67, was found. Based on morphological and immunohistochemical findings we diagnosed this case as intranodal palisaded myofibroblastoma and we highlighted a D2-40 expression in the tumor spindle cells. The presence of mast cells and their particular distribution inside the tumor are also, together with D2-40 expression, original findings of this study. No therapy was recommended after surgical and histopathological evaluation. The evolution of the patient was favorable with no other relapse following surgical removal of the lymphadenopathy. He has a normal life and no other changes of clinical and biological parameters were registered. Conclusion: To the best of our knolwedge, this is the first report regarding a D2-40-positive reaction in the spindle cells of intranodal palisaded myofibroblastoma. Thus, D2-40 could be added to the panel of antibodies used for immunohistochemical diagnosis of such types of tumors.

Endothelial Cell Proliferation and Vascular Endothelial Growth Factor Expression in Primary Colorectal Cancer Compared with Corresponding Liver Metastases

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a ... more Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC, and to determine whether these two markers correlate with conventional parameters of prognosis. Materials and Methods: Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal. The intensity of EGFR staining was scored on a scale of 0-3+: 0 no staining; 1+ when a weak membrane staining was observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense dark brown staining delineated the membrane. To determine the relationship between EGFR expression and p53, we performed double staining in the same HCC specimens. Results: By immunohistochemical staining, p53 protein was detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity of p53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked to histological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFR intensity (p=0.014). Conclusions: Our results suggest that overexpression of p53 and EGFR plays an important role in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuable predictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies.

Background: Scattered studies report on controversial results concerning evaluation of primary br... more Background: Scattered studies report on controversial results concerning evaluation of primary breast tumors and their matched lymph node metastases. Aim. To investigate the molecular profile of primary breast tumors and corresponding lymph node metastases (LNM) based on estrogen receptor (ER), progesterone receptor (PR) and human epiderma growth factor receptor-2 (HER2 protein). Materials and Methods: Sixty-six primary tumors and corresponding axillary lymph node metastases were evaluated by immunohistochemistry for ER, PR and HER2 protein. According to these markers, cases were stratified as Luminal A, B, HER2 subtypes and triple-negative. Results. Thirteen out of 66 cases (19.7%) exhibited different tumor cell phenotypes in nodal metastases compared to primary breast tumors. All cases with hybrid phenotype had metastases with a pure HER2 phenotype. The most frequent switching was observed from luminal A to luminal B phenotype. Conclusion: The high rate of discrepancy between primary tumor and nodal metastasis phenotype imposes the need for a comparative assessment of both primary tumor and nodal metastasis before any therapeutic decision, in order to avoid recurrence and to improve patient prognosis and overall survival.

Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie

E-cadherins are epithelial morphological stabilizers, performing complex functions as receptors, ... more E-cadherins are epithelial morphological stabilizers, performing complex functions as receptors, providers of cellular and tissular structural integrity, and functional interactive mediators. Structural and functional unbalance initiated due to E-cadherin expression loss results in direct effects on carcinogenesis specific biological processes, as cellular invasion and proliferation. We investigated the E-cadherin expression aiming (i) to identify the differences in the molecular subtypes of breast cancer, (ii) to analyze the correlations between E-cadherin and specific clinicopathological and molecular characteristics. The study included 42 cases that were investigated immunohistochemically using a panel of antibodies (ER, PR, Her2÷neu, CK5÷6, EGFR), which permitted a diagnostic in compliance with the molecular classification, followed by the E-cadherin evaluation. The semi-quantitative assessment of E-cadherin was performed using a scoring system based on the positive cells percen...

Archives of Biological Sciences, 2014

Mast cell (MC) active mediators promote inflammation through changes induced in the connective ti... more Mast cell (MC) active mediators promote inflammation through changes induced in the connective tissue components of human gingiva. The aim of this study was to evaluate the distribution, mast cell density and their relationship with the degree of inflammatory infiltrate in gingiva from patients with periodontal disease. Thirty-nine cases with periodontal disease and 12 cases without significant changes to the gingival mucosa were investigated. MCs were identified on paraffin-embedded specimens by immunohistochemistry using anti-mast cell tryptase. The inflammatory infiltrate was scored from 0 to 3, and the MCs were counted using the hotspot method. Intraepithelial MCs were scored from 0 to 2. We found a significant increase of mast cell density in cases with mild and moderate inflammatory changes, and a slight decrease in patients with severe periodontal disease. We noticed a higher degranulation rate in patients with periodontal disease compared to those with healthy mucosa. Intrae...

Archives of Biological Sciences, 2013

There is little information about the exact trigger mechanisms of vascular endothelial growth fac... more There is little information about the exact trigger mechanisms of vascular endothelial growth factor (VEGF) expression in hematolymphoid malignancies. The aim of this study was to investigate the expression of VEGF in malignant non-Hodgkin lymphoma (NHL), in terms of its immunohistochemical distribution and clinicopathological significance. We evaluated the distribution in tumor cells, macrophages and in non-tumoral cells. VEGF immunoreactivity was estimated according to this score: 0 (0% positive cells); 1 (<10%); 2 (10-30%); 3 (>30%). Histopathological evaluation revealed 18 cases of diffuse type lymphoma and 3 cases of follicular type lymphoma. VEGF was positive in 95.23% of cases and in one case, VEGF was negative in all cell types. We noticed a significant correlation in VEGF expression between tumor cells and macrophages (p=0,001), tumor cells and non-tumoral cells (p=0,002). In non-Hodgkin lymphoma, the main mechanism of angiogenesis seems to be dependent on the VEGF pathway and its expression particularly by stromal cells.