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ABSTRACT: Histone deacetylase inhibitors (HDACi) have been extensively studied as potential candidates for treatment of various malignancies, including leukemia, since they not only induce growth inhibition, cell cycle arrest and apoptosis of cancer cells, but can also increase the sensitivity of cancer cells to chemotherapeutic drugs. The aim of this study was to investigate the effect of two HDACi, trichostatin A (TSA) and valproic acid (VPA), on etoposide-induced apoptosis in human leukemia cell lines.
Viability, apoptosis rate, caspase activity, mitochondrial membrane potential and expression of BCL2 mRNA were assessed in HL60 and U937 cell lines treated with 250 nM TSA or 1.25 mM VPA alone or followed by 5 μM etoposide.
Preincubation of HL60 cells with TSA or VPA significantly potentiated etoposide-induced cytotoxicity and apoptosis, which was associated with activation of caspases and loss of mitochondrial membrane potential. Similar effects were not observed in U937 cells. Expression of BCL2 mRNA was strongly down-regulated after treatment of cells with HDACi alone but did not show additive effect with etoposide.
Combination of HDACi with etoposide can have a synergistic effect on increased apoptosis in leukemia cells but this effect depends on the cancer cell type and other factors such as the concentration of drugs and the administration schedule.
Anticancer research 07/2012; 32(7):2791-9. · 1.73 Impact Factor
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ABSTRACT: LN-5 monoclonal antibody against human macrophages was found to selectively stain human sebaceous glands in formalin-fixed, paraffin-embedded skin samples. Undifferentiated sebocyte progenitors were negative, and only sebocytes from the onset of their differentiation revealed positive cytoplasmic immunofluorescence. Since there are very few selective and easy-to-use markers of sebaceous glands, LN-5 antibody can offer a simple and relatively specific way to detect human sebocytes from the onset of their differentiation in routinely processed material, both freshly prepared and archival.
Folia Histochemica et Cytobiologica 01/2012; 50(2):319-21. · 0.81 Impact Factor
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ABSTRACT: Cyclins play a fundamental role in the cell cycle. Recent studies have focused on their role in the development of various malignancies. The objective of this study was to evaluate and compare the expression of cyclins A and E in common nevi, dysplastic nevi and malignant melanomas, and to investigate the relationship between cyclin expression and some pathological parameters such as tumor thickness, ulceration, regression, and mitotic rate, as well as several clinical and phenotypic parameters such as skin phototype, hair and eye color, number of nevi, personal or family melanoma history, and personal history of nonmelanoma skin cancer (NMSC). A total of 102 melanocytic skin lesions, including 30 common nevi, 38 dysplastic nevi and 34 melanomas, were examined. Expression of cyclins was detected by immunohistochemistry and quantified as a percentage of immunostained cell nuclei in each sample. Significant differences in expression of both cyclins were found between all lesion types: the median percentage of cyclin A-positive nuclei was 8.2% in melanomas, 3.4% in dysplastic nevi, and 0.95% in common nevi (p < 0.001). The corresponding percentages for cyclin E were 9.5%, 4.25% and 1.44% (p < 0.001). Expression of both cyclins was significantly higher among patients with a personal history of NMSC. Cyclin A was also significantly overexpressed in patients with a high total nevus count (TNC) compared to moderate and low TNC. Expression of cyclins did not significantly correlate with the other clinicopathologic features investigated. These findings indicate the possible involvement of cyclins A and E in the pathogenesis of malignant melanoma. Our results also show a potential diagnostic significance of these cyclins as markers allowing discrimination between dysplastic nevi and melanoma.
Folia Histochemica et Cytobiologica 01/2012; 50(2):263-9. · 0.81 Impact Factor
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ABSTRACT: Cyclins, cyclin-dependent kinases, as well as proteins cooperating with them are responsible for cell cycle regulation which is crucial for normal development, injury repair, and tumorigenesis. D-type cyclins regulate G1 cell cycle progression by enhancing the activities of cyclin-dependent kinases, and their expression is frequently altered in tumors. Disturbances in cyclin expression were also reported in melanocytic skin lesions. The objective of the study was to evaluate the expression of cyclins D1 and D3 in common, dysplastic, and malignant melanocytic skin lesions. Forty-eight melanocytic skin lesions including common nevi (10), dysplastic nevi (24), and melanomas (14) were diagnosed by dermoscopy and excised. Expression of cyclin D1 and D3 was detected by immunohistochemistry and quantified as percentage of immunostained cell nuclei in each sample. In normal skin, expression of cyclins D1 and D3 was not detected. The mean percentage of cyclin D1-positive nuclei was 7.75% for melanoma samples, 5% for dysplastic nevi samples, and 0.34% for common nevi samples. For cyclin D3, the respective values were 17.8, 6.4, and 1.8%. Statistically significant differences in cyclin D1 expression were observed between melanomas and common nevi as well as between dysplastic and common nevi (p = 0.0001), but not between melanomas and dysplastic nevi. Cyclin D3 expression revealed significant differences between all investigated lesion types (p = 0.0000). The mean cyclin D1 and D3 scores of melanomas with Breslow thickness <1 mm and >1 mm were not significantly different. G1/S abnormalities are crucial for the progression of malignant melanoma, and enhanced cyclin D1 and D3 expression leading to increased melanocyte proliferation is observed in both melanoma and dysplastic nevi. In histopathologically ambiguous cases, lower cyclin D3 expression in dysplastic nevi can be a diagnostic marker for that lesion type.
Archives for Dermatological Research 05/2010; 302(7):545-50. · 2.28 Impact Factor
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ABSTRACT: RAM11 is a mouse monoclonal anti-rabbit macrophage antibody recognizing connective tissue and vascular macrophages. Our previous report showed that RAM11 reacted with basal cells of stratified squamous epithelia of rabbit skin, oral mucosa and esophagus. The aim of the present study was to follow the appearance of RAM11 immunoreactivity in basal cells of regenerating oral epithelium in rabbits. No RAM11 immunostaining was observed in the regenerating epithelium examined on days 1 and 3 of wound healing. A weak immunofluorescence first appeared on day 7 in single basal cells and 32% of RAM11- positive basal cells were observed on day 14. These findings indicate that expression of the antigen recognized by RAM11 antibody is a transient event in the differentiation of oral keratinocytes which not always occurs during epithelial repair, although it is a constant feature of epithelial turnover in mature epithelium. Therefore this antigen can be regarded as basal cell marker only in mature stratified squamous epithelia.
Folia Histochemica et Cytobiologica 01/2010; 48(1):89-92. · 0.81 Impact Factor
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ABSTRACT: Two foci of mature lamellar bone with features of remodeling and with an adjacent hematopoietic compartment were revealed for the first time in an aortic valve homograft by hematoxylin and eosin staining and polarized light microscopy. The valve had been obtained originally from a 52-year-old non-beating-heart donor and implanted as 'fresh antibiotic-preserved' into the left ventricular outflow tract of a 21-year-old man, but was explanted after six years due to valvular insufficiency. The areas close to bone showed the presence of cells resembling osteoblasts, osteoclasts and degenerating chondrocytes. Von Kossa staining disclosed a small area of dystrophic calcification in the vicinity of one bone fragment, whereas the second fragment was accompanied by only weak, diffuse calcification. These findings shows that the formation of ectopic mature bone with secondary development of the hematopoietic compartment can occur in a relatively short time, and suggest that initiators of the process may be present in the grafted valve.
The Journal of heart valve disease 09/2009; 18(5):578-80. · 0.81 Impact Factor
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ABSTRACT: Schwannoma is a benign tumour originating from Schwann cells forming sheaths of peripheral nerves. Its location in the oral cavity, and particularly in the cheek, is very rare. A large tumour (5 cm) was surgically removed from the left cheek of a fifty-five-year-old man and pathological examination revealed schwannoma with Antoni A and B patterns. The tumour was investigated using immunofluorescence and histochemical stainings. It showed positive immunostaining for S-100, PGP 9.5, NSE, collagen IV, laminin, merosin and vimentin. No immunofluorescence for GFAP, NPY and CGRP was observed. Cells of the macrophage family (CD68-immunopositive) were scattered in the connective tissue. Neither B (CD20+) nor T (CD3+, CD8+) lymphocytes were found. The capillary network was revealed by CD34 immunostaining. SMA immunoreactivity was observed in walls of larger blood vessels but not in tumour cells. The tumour contained numerous mast cells visualized by thionin staining and an abundance of collagen fibres revealed by picrosirius red.
Polish journal of pathology: official journal of the Polish Society of Pathologists 04/2009; 60(1):52-6. · 0.35 Impact Factor
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ABSTRACT: Hamartomas are non-neoplastic lesions constituted by a mixture of tissues indigenous to the region. Respiratory epithelial adenomatoid hamartomas are characterised by glandular proliferation lined by ciliated airway epithelium. Their localisation in the nasal cavity is rare and most frequent cases described so far were associated with the posterior nasal septum.
A 9-year-old Caucasian boy presented with long-standing nasal obstruction. A large right nasal mass was evident on physical and CT examinations. It was surgically removed from the anterior nasal septum under general anaesthesia. Histologically, the diagnosis of REAH was established. The tumour lined by stratified squamous and ciliated respiratory epithelium was characterised by prominent glandular proliferation. By immunohistochemistry, the tumour was positive for cytokeratins, smooth muscle actin, vimentin, laminin, collagen type IV, CD8, and CD68. No S-100 immunoreactivity was observed. The patient has been asymptomatic for 12 months with completely healed lining of the nose.
Respiratory epithelial adenomatoid hamartoma, although rare, must be taken into consideration in differential diagnosis of nasal exophytic lesions.
Cases Journal 01/2009; 2:8151.
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ABSTRACT: Pituitary necrosis is mostly a result of pituitary haemorrhage or infarct. The frequency of pituitary necrosis in the Polish population has not yet been investigated. Hence, the aim of this study was to estimate the incidence of pituitary necrotic lesions in forensic autopsy material and to assess possible correlations of pituitary necrosis with sex, age, other pituitary pathologies, endocrine disorders and atherosclerosis. Serial sections of 100 human pituitary glands stained with hematoxylin-eosin were examined microscopically. Pituitary necrosis was found in 19 cases (19%), all of them in persons aged > 40 years. The majority of the lesions had relatively large size, occupying 10-50% of the gland. According to family interviews, none of the subjects manifested any clinical symptoms related to pituitary insufficiency, hence al the detected cases can be regarded as subclinical. There was no association of pituitary necrosis occurrence with sex, other pituitary pathologies found upon autopsy, endocrine diseases or cause of death. Only correlations with age and atherosclerosis were statistically significant. This study has shown that subclinical pituitary necrosis is a relatively frequent phenomenon in elderly persons, probably resulting from age-related deterioration in the vascular status.
Polish journal of pathology: official journal of the Polish Society of Pathologists 01/2008; 59(2):97-100. · 0.35 Impact Factor
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ABSTRACT: This paper presents a simple and reliable method of triple immunofluorescence staining that allows simultaneous detection of various cell types present in atherosclerotic plaque of apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice. We used combined direct and indirect procedures applying commercially available primary antibodies raised in different species to detect smooth muscle cells (Cy3-conjugated mouse anti-smooth muscle actin, SMA), macrophages (rat anti-CD68) and T lymphocytes (rabbit anti-CD3). Fixation of the material in acetone and modified incubation protocol employing nonfat dry milk in preincubation and incubation media significantly increased the intensity of labeling and effectively quenched the background. Our method offers an efficient way to detect qualitative as well as quantitative changes of macrophages, T lymphocytes and smooth muscle cells in atherosclerotic plaque of apoE/LDLR -/- mice during atherosclerosis development or in response to pharmacological treatment.
Folia Histochemica et Cytobiologica 01/2008; 46(2):143-6. · 0.81 Impact Factor
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ABSTRACT: RAM11 is a mouse monoclonal anti-rabbit macrophage antibody recognizing connective tissue and vascular (atheromatous tissue) macrophages. This study demonstrates a cross-reaction of RAM11 with an unknown antigen in rabbit normal epithelial cells. Formalin-fixed, paraffin sections of the New Zealand White rabbit normal skin, oral mucosa, esophagus, small intestine and lung were immunostained with RAM11 antibody followed by goat anti-mouse Cy-3-conjugated antiglobulin. RAM11-positive immunofluorescence was observed in basal layer cells of stratified squamous epithelia (skin, oral mucosa, esophagus). No RAM11 immunostaining was found in any cells of simple (intestinal, bronchial) epithelia. These findings show that basal cells of stratified squamous keratinized and non-keratinized epithelia of the rabbit express an antigenic epitope which is common with that of macrophage antigen recognized by RAM11 monoclonal antibody.
Folia Histochemica et Cytobiologica 02/2007; 45(3):229-32. · 0.81 Impact Factor
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ABSTRACT: Current data suggest an influence of the hypothalamic-pituitary-adrenal axis on suicidal behavior. The frequency of pituitary adenomas in suicide victims has not yet been investigated.
The aim of this study was to assess whether the incidence of pituitary adenomas is correlated with suicide.
Serial sections of 151 human pituitary glands obtained upon autopsy were examined microscopically. The glands were collected from 70 suicide victims and 81 subjects whose deaths were classified as unexpected or accidental (nonsuicidal group). The sections were stained with hematoxylin-eosin and the presence of adenoma was confirmed by immunostaining for collagen III.
In the suicidal group, pituitary microadenomas were found in 32 cases (47.7%), while in the nonsuicidal group microadenomas were detected in 15 cases (18.3%). The observed difference was statistically significant (p = 0.0003). The relative risk ratio of suicide in persons with pituitary adenomas was estimated at 1.9. Logistic regression analysis in a model controlled for age and sex showed that microadenomas constituted a unique risk factor in this model. The immunohistochemical phenotyping revealed a higher percentage of immunopositive (secreting) microadenomas in the nonsuicidal group as compared to the suicidal group (80.0 vs. 59.38%) and a predominance of growth hormone-secreting microadenomas in both groups. However, these differences as well as differences in the hormonal profiles of microadenomas between the groups were not significant.
These results suggest that pituitary adenomas belong to suicide risk factors.
Neuropsychobiology 02/2007; 55(3-4):163-6. · 2.67 Impact Factor
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Grzegorz J Lis
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ABSTRACT: Pseudoexfoliation syndrome, known since nearly hundred years, is considered at present as generalized disorder of the extracellular substance metabolism, although its etiology and pathogenesis remain unclear. Its morphological manifestation includes accumulation of fibrillar material deposits in ocular tissues which may be a ground for various ocular pathologies, in particular the open-angle glaucoma for which the syndrome is the most common identifiable cause. In patients with ocular deposits aggregates of similar material were recently identified in the skin as well as in some internal organs (e.g. heart, lung, liver, kidney). However, their clinical significance is not clear--some evidences suggest their association with transient ischemic attacks or aortic aneurysm formation. Numerous recently presented epidemiological data and improvements in basic sciences brought a new insight into the syndrome, up to now regarded as a purely ophthalmologic matter. Histopathological features as well as actual knowledge on the pathogenesis of the pseudoexfoliation syndrome is described.
Przegla̧d lekarski 02/2006; 63(7):588-92.
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Acta cardiologica 05/2004; 59(2):212-3. · 0.61 Impact Factor
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ABSTRACT: This investigation was aimed at comparison of calcium content and calcium dispersion in allogenic aortic valve leaflets removed due to dysfunction, to establish the influence of both parameters on graft durability. Calcification was assessed histochemically (von Kossa) as well as physicochemically using atomic absorption spectroscopy (AAS). The morpho-metric data (leaflet area involved in the calcification process) were obtained by computer-assisted image analysis system. The dry weight content of leaflet calcium and phosphorus were assessed by atomic absorptive spectroscopy (AAS) and Ca/P ratio was calculated. Calcium dispersion coefficient (Dc) was established according to the formula: Dc = 1/Ca(c)/Ap, where Ca(c) = calcium dry weight concentration; Ap = percent of leaflet area involved in calcification. We found biphasic correlation between calcium concentration and area involved in calcification. The first one was characterized by rising dispersion of calcium deposits while for the second one saturation with hydroxyapatite of formerly calcified areas was predominant, negatively influencing graft durability. Allograft durability was correlated with calcium dispersion (Dc) (p<0.001), while no significant correlation was found with calcium concentration. Decreased Dc was characteristic for 93.8% of low durability grafts (<11.6 years). Our results suggest that lowered calcium dispersion decreasing allograft lifetime and is a better predictor of allograft durability than the total calcium content.
Przegla̧d lekarski 02/2004; 61(6):613-6.
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ABSTRACT: The study aim was to assess histological and mineralogical properties of leaflets in human, antibiotic-preserved aortic homograft valves (recovered during surgical replacement) in order to identify factors accounting for pathological changes leading to accelerated graft dysfunction. A comparison was made with aortic valves prepared for grafting, with a view to assessing morphological and mineralogical characteristics as a potential preimplantation risk factor.
Valve leaflets were examined with light and scanning electron microscopy. Mineralization was assessed histochemically, and also physicochemically by atomic absorption spectroscopy (AAS).
All explanted homograft valve leaflets revealed prominent degenerative changes seen as decreased surface area, fibrosis, mineralization and focal thrombosis. Substantial loss of endothelium and fibroblasts, reduced collagen bundles crimping, inflammation (81%) and disappearance of layered structure (59%) was identified. The elastic elements were relatively stable, though a gradual age-dependent loss was observed in both groups. Accelerated mineralization was seen in all explanted homografts; inorganic deposits were composed mainly of hydroxyapatite. Two types of mineralization were identified: large limited nodular structures, and diffuse mineral deposits. Homografts with moderately elevated mineralization, well-preserved layered structure and sporadic infective changes proved to have the greatest durability. Homograft durability was also affected by the difference in host and donor age.
Preimplantation factors affecting pathological changes determining homograft durability included morphological status of the graft itself and donor age; host-related factors included recipient age, endocarditis, native valve calcification, and host-donor matching (age difference between host and donor). A limited molecular mineralization may increase valvular durability, provided that no focal nodular calcifications exist that might adversely affect overall homograft integrity.
The Journal of heart valve disease 12/2003; 12(6):741-51. · 0.81 Impact Factor
