Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 124
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Pathol Oncol Res ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32124227

RESUMO

Although the role of autophagy has been implicated in several forms of chronic hepatitis, it is still not fully understood. Active autophagy eliminates damaged molecules and organelles (such as mitochondria) by lysosomal degradation. In the present study, we aimed to examine and compare autophagy activity in chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) by detecting the expression of autophagy (LC3 and p62) and mitochondrium-related (TOMM20) proteins, as well as the levels of selected microRNAs (miR-101, -155, -204 and - 224) known to be involved in the regulation of autophagy. In addition, the expression levels were related to pathohistological parameters. Liver biopsy samples, including 45 CHC and 18 AIH cases, were immunohistochemically stained for LC3, p62 and TOMM20 and the expression of miRNAs was determined using real-time PCR. We found elevated LC3 and p62 in AIH samples as compared with CHC ones, indicating an activated autophagy that is impaired in AIH as no degradation of p62 seemed to occur. Moreover, p62 showed strong correlation with necroinflammatory grades in the AIH group. The observed elevated levels of TOMM20 and p62 suggest a less efficient elimination of damaged mitochondria in AIH as opposed to CHC, in which autophagy seems to have a more active function. The level of miR-101 was increased in case of CHC as compared with AIH, however, miR-155, -204 and 224 resulted in no expressional. Furthermore, miR-224 level correlated with steatosis and miR-155 expression with fibrosis stage in CHC. In conclusion, dissimilar autophagic activity was observed in CHC and AIH, suggesting a close association between impaired autophagy and severity of necroinflammation. This impairment may not be regulated by the analyzed miRNAs. Nevertheless, miR-224 and - 155 seem to be associated with CHC progression.

2.
Pediatr Blood Cancer ; 67(5): e28221, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32124532

RESUMO

BACKGROUND: Hepatoblastoma (HB) is the most common pediatric liver malignancy, occurring mainly during the first 4 years of life. Recent studies unraveled the frequent, coordinated activation of Wnt/ß-catenin and YAP/Hippo (where YAP is yes-associated protein) pathways in human HB samples. Furthermore, it was found that concomitant overexpression of activated forms of ß-catenin and YAP in the mouse liver triggers HB formation in YAP/ß-catenin mice. Cyclin-dependent kinases 9 (CDK9) is an elongating kinase, which has been shown to mediate YAP-driven tumorigenesis. The role of CDK9 in HB molecular pathogenesis has not been investigated to date. METHODS: CDK9 expression was determined in human HB lesions, HB cell lines, and YAP/ß-catenin mouse livers. CDK9 was silenced in human HB cell lines and the effects on growth rate and YAP targets were analyzed. Hydrodynamic transfection of YAPS127A and ∆N90-ß-catenin together with either shCdk9 or control shLuc (where Luc is luciferase) plasmids was employed to assess the requirement of Cdk9 for HB development in vivo. RESULTS: Nuclear immunoreactivity for CDK9 protein was more pronounced in human HB samples and YAP/ß-catenin mouse HB tumor tissues than in corresponding surrounding nontumorous liver tissues. CDK9 protein was also expressed in human HB cell lines. Silencing of CDK9 in human HB cell lines did not lead to consistent effects on HB cell growth or YAP target gene expression. Surprisingly, silencing of Cdk9 led to accelerated liver tumorigenesis in YAP/ß-catenin mice. CONCLUSION: CDK9 is not a major downstream mediator of YAP oncogenic function in HB development and progression.

3.
Helicobacter ; 25(1): e12670, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31701608

RESUMO

BACKGROUND: Clarithromycin (Cla) heteroresistance of Helicobacter pylori (H pylori) infections is commonly assessed by comparing the resistance status of antrum and corpus biopsy samples and by demonstrating the discrepancy between them (interniche heteroresistance). However, fluorescence in situ hybridization (FISH) technique is capable of showing the synchronous presence of susceptible and resistant bacteria (intraniche heteroresistance), enabling the detection of heteroresistant H pylori populations within one biopsy sample. MATERIALS AND METHODS: Antrum and corpus biopsy specimens of 305 H pylori-infected patients were investigated with an rRNA-targeted Cla-resistance FISH test. Anamnestic data were collected from the institutional electronic register. Prevalence rates of susceptible, homo- and heteroresistant cases were correlated with the anamnestic and clinicopathological data. RESULTS: Overall Cla-resistance rate was 23.9% (73 cases), consisting of 35 (11.5%) homoresistant and 38 (12.5%) heteroresistant cases. Thirty-five patients had at least one biopsy site where susceptible and resistant bacteria were present simultaneously. From this subset, 20 cases demonstrated intraniche heteroresistance on both sites. Prior Cla-based eradication attempts were more frequent in homoresistant than in susceptible and heteroresistant cases (P < .001, P < .001, respectively). Cla-containing therapy eradicated heteroresistant infections at a significantly lower rate in comparison with susceptible cases (P = .0112), but more effectively than homoresistants (P = .0393). CONCLUSIONS: The most frequent type of Cla-heteroresistance is the coexistence of susceptible and resistant H pylori bacteria in the same location (intraniche heteroresistance). A previous Cla-based eradication attempt predisposes patients to homoresistant infection. Heteroresistance is characterized by a non-eradication-related background and intermediate characteristics in many respects when compared to susceptible and homoresistant cases.

4.
Pathol Oncol Res ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705481

RESUMO

Acetaminophen (APAP) induced hepatotoxicity involves activation of c-Jun amino-terminal kinase (JNK), mitochondrial damage and ER stress. BGP-15, a hydroximic acid derivative, has been reported to have hepatoprotective effects in APAP overdose induced liver damage. Effect of BGP-15 was further investigated on mitochondria in APAP-overdose induced acute liver injury in mice. We found that BGP-15 efficiently preserved mitochondrial morphology, and it caused a marked decrease in the number of damaged mitochondria. Attenuation of mitochondrial damage by BGP-15 is supported by immunohistochemistry as the TOMM20 label and the co-localized autophagy markers detected in the livers of APAP-treated mice were markedly reduced upon BGP-15 administration. This effect, along with the observed prevention of JNK activation likely contribute to the mitochondrial protective action of BGP-15.

5.
Magy Onkol ; 63(2): 75-84, 2019 06 21.
Artigo em Húngaro | MEDLINE | ID: mdl-31225530

RESUMO

Cancer of Unknown Primary origin (CUP) is characterized by metastatic tumor spread without identifiable primary tumor. CUP cohort was selected from 6966 autopsy cases (2001-2014). Type-1 ("clinical") CUPs: primary site was not found clinically but identified by autopsy. Type-2 ("clinicopathological") CUPs: no primary site either clinically or by autopsy. Type-3 ("pathological") CUPs: no tumor was suspected clinically whereas autopsy revealed metastatic spread from unidentifiable source. 2160 malignant tumors were found including 80 CUPs (type-1/2/3: 42/29/9). Cumulative incidence declined with time (3.70%; 2001-2007: 4.51%; 2008-2014: 3.19%) due to decreasing incidence of type-1 and -3 CUPs. CUPs were mostly adenocarcinomas and type-1 CUPs usually originate from the lung or pancreas. As a conclusion, type-2 and -3 CUPs may originate from microscopic-sized metastasizing primary tumors. Based on the above classification, improvement of clinical diagnostics may contribute to decreased incidence of type-1 CUPs and transfer of type-3 CUPs into type-2 category.


Assuntos
Neoplasias Primárias Desconhecidas/classificação , Neoplasias Primárias Desconhecidas/patologia , Adenocarcinoma/classificação , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Humanos , Incidência , Neoplasias Primárias Desconhecidas/epidemiologia
6.
Pathol Oncol Res ; 2019 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-30826971

RESUMO

Liver diseases such as liver cirrhosis, primary and metastatic liver cancers are still a major medical challenge. Syndecan-1 is one of the most important proteoglycans in the liver. Syndecan-1 is normally expressed on the surfaces of hepatocytes and cholangiocytes. Due to liver diseases the amount of syndecan-1 increases in the liver. Despite the emerging data of the biological function of syndecan-1, the clinical usefulness of this proteoglycan is still unknown. In our study we correlated syndecan-1 expression to clinico-pathological data. We found that syndecan-1 proved to be a good marker for hepatitis C virus based hepatocellular carcinoma and increased with liver dysfunction.

7.
Am J Pathol ; 189(5): 1077-1090, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30794805

RESUMO

Hepatoblastoma (HB) is the most common type of pediatric liver cancer. Activation of yes-associated protein (YAP) has been implicated in HB molecular pathogenesis. The transcriptional co-activator Yap regulates downstream gene expression through interaction with the TEA domain (TEAD) proteins. Nonetheless, YAP also displays functions that are independent of its transcriptional activity. The underlying molecular mechanisms by which Yap promotes HB development remain elusive. In the current study, we demonstrated that blocking TEAD function via the dominant-negative form of TEAD2 abolishes Yap-driven HB formation in mice and restrains human HB growth in vitro. When TEAD2 DNA-binding domain was fused with virus protein 16 transcriptional activation domain, it synergized with activated ß-catenin to promote HB formation in vivo. Among TEAD genes, silencing of TEAD4 consistently inhibited tumor growth and Yap target gene expression in HB cell lines. Furthermore, TEAD4 mRNA expression was significantly higher in human HB lesions when compared with corresponding nontumorous liver tissues. Human HB specimens also exhibited strong nuclear immunoreactivity for TEAD4. Altogether, data demonstrate that TEAD-mediated transcriptional activity is both sufficient and necessary for Yap-driven HB development. TEAD4 is the major TEAD isoform and Yap partner in human HB. Targeting TEAD4 may represent an effective treatment option for human HB.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Proteínas de Ligação a DNA/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/secundário , Proteínas Musculares/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Proteínas de Ligação a DNA/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Proteínas Musculares/genética , Prognóstico , Fatores de Transcrição/genética , Células Tumorais Cultivadas
8.
Pathol Oncol Res ; 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30734151

RESUMO

BPAP is a potent enhancer substance with catecholaminergic and serotoninergic activity in the brain. It was discovered that it is also effective against certain types of experimental cancers, showing the most promising results in case of lung cancer. That is why we tested its efficacy in two different doses in a newly developed EGFR wild type mouse lung adenocarcinoma xenograft model. Experiments were conducted on FVB/N and SCID mouse strains treated with low and high dose of BPAP. Body weight, survival, and tumor volumes were recorded. Furthermore, the activity of major signaling pathways of NSCLC such as MAPK and Akt/mTOR as well as cell cycle regulation were determined. Significant inhibition of tumor growth was exerted by both doses, but the mechanism of action was different. High dose directly inhibited, whereas low dose activated the main signaling pathways. Exposure to low dose BPAP resulted in elevated activity of the mTOR pathway together with p16INK-induced cell cycle arrest, a typical feature of geroconversion, a senescent state characterized by loss of cell proliferation. Finally the events culminated in cell cycle inhibition point in case of both doses mirrored by the decrease of cyclin D1, CDK4 and PCNA. In addition, BPAP treatment had a beneficial effect on bodyweight suggesting that the compound at least in part is able to compensate the cancer-related wasting. In view of the low toxicity and confirmed antitumor effect of BPAP against experimental lung adenocarcinoma, this novel compound deserves further attention.

9.
Pathol Oncol Res ; 25(2): 477-486, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29442221

RESUMO

Several biomarkers are in use to improve the sensitivity and specificity of cervical cancer screening. Previously, increased expression of tight junction protein claudin-1 (CLDN1) was detected in premalignant and malignant cervical lesions and applied for cytology screening. To improve the specificity, a double immunoreaction with CLDN1/Ki67 was developed in the recent study. Parallel p16/Ki67 (CINtec® PLUS) and CLDN1/Ki67 dual-stained cytology and histology were performed and compared. p16/Ki67 immunoreaction showed positivity in 317 out of 1596 smears with negativity in 1072 and unacceptable reactions in 207 samples. CLDN1/Ki67 dual staining was positive in 200 of 1358 samples, negative in 962, whereas 196 smears could not be evaluated due to technical reasons. Considering the high-grade squamous intraepithelial lesion cytology as gold standard, sensitivity of CLDN1/Ki67 reaction was 76%, specificity was 85.67%, while for p16/Ki67 sensitivity was 74% and specificity was 81.38%. Comparison of CLDN1/Ki67 and p16/Ki67 dual stainings showed the results of the two tests not to be significantly different. Analysing histological slides from 63 cases, the results of the two tests agreed perfectly. As conclusion the sensitivity and specificity proved to be similar using p16/Ki67 and CLDN1/Ki67 double immunoreactions both on LBC samples and on histological slides.


Assuntos
Biomarcadores Tumorais/análise , Claudina-1/biossíntese , Imuno-Histoquímica/métodos , Antígeno Ki-67/biossíntese , Neoplasias do Colo do Útero/diagnóstico , Adulto , Neoplasia Intraepitelial Cervical/diagnóstico , Citodiagnóstico/métodos , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Sensibilidade e Especificidade , Esfregaço Vaginal
10.
Pathol Oncol Res ; 25(3): 1103-1109, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30411298

RESUMO

The liver disease focal nodular hyperplasia (FNH) has several histological features that resemble hepatic cirrhosis. Since cirrhosis may develop further into hepatocellular carcinoma (HCC) contrary to FNH, the aim of the present study was to identify microRNAs (miRNA), which, by their altered expression levels, may be associated with the benign, tumor-like nature of FNH. Altogether 106 surgically removed formalin-fixed paraffin-embedded liver samples were selected, including 22 FNH, 45 cirrhosis, 24 HCC and 15 normal liver tissues. Etiology of the cases of cirrhosis and HCC includes hepatitis C and alcoholism and the HCC cases developed in cirrhotic livers. Relative expression levels of 14 miRNAs were determined using TaqMan MicroRNA Assays. In comparison to normal liver, the levels of miR-34a and miR-224 were elevated not only in FNH but also in cirrhosis and HCC, while the expression of miR-17-5p, miR-18a and miR-210 was decreased in FNH. Further, the levels of miR-21 and miR-222 were increased in cirrhosis and HCC but were decreased in FNH and the expression of miR-17-5p, miR-18a, miR-195 and miR-210 was decreased in FNH as compared with cirrhosis and/or HCC. In conclusion, the elevation of miR-34a and miR-224 may be associated with both benign and malignant proliferative processes, nevertheless the increased expression of oncomiRs miR-21 and miR-222 in cirrhosis and HCC but not in FNH may be related to malignant processes of the liver. The decreased levels of miR-18a, miR-195 and miR-210 may further differentiate FNH from cirrhosis, reflecting the different pathogenesis of these two entities contrary to some histologically similar features.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Hiperplasia Nodular Focal do Fígado/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Hiperplasia Nodular Focal do Fígado/patologia , Seguimentos , Humanos , Fígado/metabolismo , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
12.
Pathol Oncol Res ; 2018 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-30448973

RESUMO

Cholangiocarcinoma (CC) is the second most common tumor of the liver, originating from the biliary system with increasing incidence and mortality worldwide. Several new classifications review the significance of tumor localization, site of origin, proliferation and biomarkers in the intrahepatic, perihilar and distal forms of the lesion. Based on growth pattern mass-forming, periductal-infiltrating, intraductal, undefined and mixed types are differentiated. There are further subclassifications which are applied for the histological features, in particular for intrahepatic CC. Recognition of the precursors and early lesions of CC including biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile ducts (IPNB), biliary mucinous cystic neoplasm (MCNB) and the candidate precursors, such as bile duct adenoma and von Meyenburg complex is of increasing significance. In addition to the previously used biliary markers detected by immunohistochemistry, several new markers have been added to the differentiation of both the benign and malignant lesions, which can be used to aid in the subclassification in association with the outcome of CC. Major aspects of biliary carcinogenesis have been revealed, yet, the exact way of this diverse process is still unclear. The factors contributing to molecular cholangiocarcinogenesis include various risk factors, different anatomical localizations, multiple cellular origins, genetic and epigenetic alterations, tumor microenvironment, heterogeneity and clonal evolution. Driver mutations have been identified, implying that they are optimal candidates for targeted therapy. The most promising therapeutic candidates have entered clinical trials.

13.
Matrix Biol ; 68-69: 474-489, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29454902

RESUMO

Increased expression of syndecan-1 is a characteristic feature of human liver cirrhosis. However, no data are available on the significance of this alteration. To address this question we designed a transgenic mouse strain that driven by albumin promoter, expresses human syndecan-1 in the hepatocytes. Liver cirrhosis was induced by thioacetamide in wild type and hSDC1+/+ mice of the identical strain. The process of fibrogenesis, changes in signal transduction and proteoglycan expression were followed. In an in vitro experiment, the effect of syndecan-1 overexpression on the action of TGFß1 was determined. Human syndecan-1 and TGFß1 levels were measured by ELISA in the circulation. Without challenge, no morphological differences were observed between wild type and transgenic mice livers, although significant upregulation of phospho-Akt and FAK was observed in the latter. Fibrogenesis in the transgenic livers, characterized by picrosirius staining, collagen type I, and SMA levels, lagged behind that of control in the first and second months. Changes in signal transduction involved in the process of fibrogenesis, as SMAD, MAPK, Akt and GSK, pointed to the decreased effect of TGFß1, and this was corroborated by the decreased mRNA expression of TIEG and the growth factor itself. In vitro experiments exposing the LX2 hepatic stellate cell line to conditioned media of wild type and syndecan-1 transfected Hep3B cell lines proved that medium with high syndecan-1 content inhibits TGFß1-induced upregulation of SMA, TIEG, collagen type I and thrombospondin-1 expression. Detection of liver proteoglycans and heparan sulfate level revealed that their amounts are much higher in control transgenic liver, than that in the wild type. However, it decreases dramatically as a result of shedding after hepatic injury. Shedding is likely promoted by the upregulation of MMP14. As syndecan-1 can bind thrombospondin-1, and as our result demonstrated that the same is true for TGFß1, shed syndecan-1 can remove the growth factor and its activator together into the systemic circulation.Taking together, our results indicate that the effect of syndecan-1 is accomplished on two levels: a, the shedded syndecan can bind, inhibit and remove TGFß1; b, interferes with the activation of TGFß1 by downregulation and binding thrombospondin-1, the activator of the growth factor. However, by the end of the fourth month the protective effect was lost, which is explained by the considerable decrease of syndecan-1 and the almost complete loss of heparan sulfate from the surface of hepatocytes.


Assuntos
Cirrose Hepática Experimental/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Sindecana-1/genética , Sindecana-1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Linhagem Celular , Fatores de Transcrição de Resposta de Crescimento Precoce/genética , Humanos , Fatores de Transcrição Kruppel-Like/genética , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/genética , Camundongos , Camundongos Transgênicos , Fosforilação , Tioacetamida/efeitos adversos , Trombospondina 1/metabolismo , Ativação Transcricional , Fator de Crescimento Transformador beta1/genética , Regulação para Cima
14.
Oncotarget ; 8(43): 73433-73447, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088718

RESUMO

Hepatoblastoma (HB) is the most common type of liver malignancy in children. Recent studies suggest that activation of Yes-associated protein (YAP) is a major molecular event in HB development, as activated YAP synergizes with mutant ß-catenin to promote HB formation in mice (YAP/ß-catenin). However, how YAP regulates HB development remains poorly defined. Similarly, de-regulation of mammalian target of rapamycin complex 1 (mTORC1) signaling has been implicated in multiple tumor types, but its functional role in HB development is scarcely understood. In the present study, we found that mTORC1 is activated in human HB cells and YAP/ß-catenin-induced mouse HB tumor tissues. mTOR inhibitor MLN0128 significantly inhibits human HB cell growth in vitro. Furthermore, ablation of Raptor, the unique subunit of mTORC1, strongly delayed YAP/ß-catenin-induced HB development in mice. At the molecular level, we found that expression of the amino acid transporter SLC38A1 is induced in mouse HB tissues, and amino acid deprivation leads to mTORC1 suppression in HB cell lines. Silencing of YAP and/or its paralog, transcriptional co-activator with PDZ binding motif (TAZ), decreased SLC38A1 expression as well as mTORC1 activation in HB cells. Furthermore, a frequent and concomitant upregulation of mTORC1 and SLC38A1 was detected in a collection of human HB specimens. Altogether, our study demonstrates the key role of mTORC1 in HB development. YAP and TAZ promote HB development via inducing SLC38A1 expression, whose upregulation leads to mTORC1 activation. Targeting mTOR pathway or amino acid transporters may represent novel therapeutic strategies for the treatment of human HB.

15.
Helicobacter ; 22(4)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28402048

RESUMO

BACKGROUND: Conventional stainings (including H&E and special stains like Giemsa) are the most widely applied histopathologic detection methods of Helicobacter pylori (HP). MATERIALS AND METHODS: We aimed to compare the diagnostic performance of Giemsa staining with immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) on a monocentric cohort of 2896 gastric biopsies and relate results to histologic alterations in order to find such histopathologic subgroups in which these methods underperform. All cases were categorized regarding presence or absence of chronic gastritis, inflammatory activity, and mucosal structural alterations. RESULTS: Giemsa revealed 687 cases (23.7%), IHC 795 cases (27.5%), and FISH 788 cases (27.2%) as being HP positive. Giemsa showed significantly lower overall sensitivity (83.3%) compared to IHC (98.8%) and FISH (98.0%). Moreover, the sensitivity of Giemsa dramatically dropped to 33.6% in the nonactive cases. We found that sensitivity of Giemsa strongly depends on HP density and, accordingly, on the presence of activity. Structural alterations (intestinal metaplasia, atrophy, etc.) had only no or weak effect on sensitivity of the three stainings. Both IHC and FISH proved to be equally reliable HP detecting techniques whose diagnostic performance is minimally influenced by mucosal inflammatory and structural alterations contrary to conventional stainings. CONCLUSIONS: We highly recommend immunohistochemistry for clinically susceptible, nonactive chronic gastritis cases, if the conventional stain-based HP detection is negative. Moreover, we recommend to use IHC more widely as basic HP stain. Helicobacter pylori FISH technique is primarily recommended to determine bacterial clarithromycin resistance. Furthermore, it is another accurate diagnostic tool for HP.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Histocitoquímica/métodos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente/métodos , Adulto , Idoso , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Coloração e Rotulagem/métodos
16.
Pathol Oncol Res ; 23(2): 245-252, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27395057

RESUMO

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in supratentorial cases when compared to infratentorial tumors. Next we performed region-specific immunohistochemical analysis of the ependyma in neonatal and adult ependyma from the central canal of spinal cord to the choroid plexus of lateral ventricles for components of cell-cell junctions including cadherins, claudins and occludin. We found robust claudin-5 expression in the choroid plexus epithelia but not in other compartments of the ependyma. Ultrastructural studies demonstrated distinct regional differences in cell-cell junction organization. Surprisingly, we found that 9 out of 20 supratentorial but not infratentorial ependymomas expressed high levels of the brain endothelial tight junction component claudin-5 in tumor cells. Importantly, we observed an increased overall survival in claudin-5 expressing supratentorial ependymoma. Our data indicates that claudin-5 expressing ependymomas may follow a distinct course of disease. The assessment of claudin-5 expression in ependymoma has the potential to become a useful prognostic marker in this pediatric malignancy.


Assuntos
Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Claudina-5/metabolismo , Ependimoma/metabolismo , Ependimoma/patologia , Neoplasias Infratentoriais/metabolismo , Neoplasias Infratentoriais/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos
17.
Pathol Oncol Res ; 23(1): 151-156, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27687058

RESUMO

The aim of the study was to investigate the correlation between claudin (CLDN) protein expression and clinicopathological parameters as well as survival in histological subtypes of non-small cell lung cancer. Archived surgical resection specimens of 137 pathologic stage I primary bronchial cancers including 49 adenocarcinomas of non-lepidic variants (ADC), 46 adenocarcinomas of lepidic variants (L-ADC), and 42 squamous cell carcinomas (SCC) were examined. Immunohistochemistry (IHC) using antibodies against CLDN1,-2,-3,-4,-7 proteins as well as semiquantitative estimation (IHC scores 0-5) were performed. Claudin IHC scores of L-ADC differed significantly from ADC (CLDN1: p = 0.009, CLDN2: p = 0.005, CLDN3: p = 0.004, CLDN4: p = 0.001, CLDN7: p < 0.001, respectively) and SCC (CLDN1: p < 0.001, CLDN3: p < 0.001, CLDN7: p < 0.001, respectively). Highly significant CLDN3-CLDN4 parallel expression could be demonstrated in ADC and L-ADC (p < 0.001 in both), which was not observed in SCC (p = 0.131). ADC and SCC showed no correlation with smoking, whereas in case of L-ADC heavier smoking correlated with higher CLDN3 expression (p = 0.020). Regarding claudin expression and survival, in SCC significant correlation could be demonstrated between CLDN1 IHC positivity and better survival (p = 0.038). In NSCLC as a whole, high CLDN2 expression proved to be a better prognostic factor when compared with cases where CLDN2 IHC score was 0-1 vs. 2-5 (p = 0.009), however, when analyzed separately, none of the histological subgroups showed correlation between CLDN2 expression and overall survival. The claudin expression pattern was significantly different not only between the SCC-ADC and SCC-L-ADC but also between the L-ADC and ADC histological subgroups, which strongly underlines that L-ADC represents a distinct entity within the ADC group. CLDN1 overexpression is a good prognostic factor in NSCLC, but only in the SCC subgroup.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Claudina-1/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
Int J Cancer ; 140(5): 1119-1133, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27874187

RESUMO

The ongoing Triage and Risk Assessment of Cervical Precancer by Epigenetic Biomarker (TRACE) prospective, multicenter study aimed to provide a clinical evaluation of the CONFIDENCE™ assay, which comprises a human papillomavirus (HPV) DNA and a human epigenetic biomarker test. Between 2013 and 2015 over 6,000 women aged 18 or older were recruited in Hungary. Liquid-based cytology (LBC), high-risk HPV (hrHPV) DNA detection and single target host gene methylation test of the promoter sequence of the POU4F3 gene by quantitative methylation-specific polymerase chain reaction (PCR) were performed from the same liquid-based cytology sample. The current analysis is focused on the baseline cross-sectional clinical results of 5,384 LBC samples collected from subjects aged 25 years or older. The performance of the CONFIDENCE HPV™ test was found to be comparable to the cobas® HPV test with good agreement. When applying the CONFIDENCE Marker™ test alone in hrHPV positives, it showed significantly higher sensitivity with matching specificity compared to LBC-based triage. For CIN3+ histological endpoint in the age group of 25-65 and 30-65, the methylation test of POU4F3 achieved relative sensitivities of 1.74 (95% CI: 1.25-2.33) and 1.64 (95% CI: 1.08-2.27), respectively, after verification bias adjustment. On the basis of our findings, POU4F3 methylation as a triage test of hrHPV positives appears to be a noteworthy method. We can reasonably assume that its quantitative nature offers the potential for a more objective and discriminative risk assessment tool in the prevention and diagnostics of high-grade cervical intraepithelial neoplasia (CIN) lesions and cervical cancer.


Assuntos
Carcinoma de Células Escamosas/química , Proteínas de Homeodomínio/análise , Infecções por Papillomavirus/metabolismo , Lesões Pré-Cancerosas/metabolismo , Fator de Transcrição Brn-3C/análise , Displasia do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/química , Adolescente , Adulto , Idoso , Biomarcadores , Biomarcadores Tumorais , Carcinoma de Células Escamosas/virologia , Neoplasia Intraepitelial Cervical/química , Neoplasia Intraepitelial Cervical/virologia , Metilação de DNA , Sondas de DNA de HPV , DNA Viral/análise , Feminino , Proteínas de Homeodomínio/genética , Humanos , Hungria/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/virologia , Regiões Promotoras Genéticas , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fator de Transcrição Brn-3C/genética , Triagem , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
19.
Orv Hetil ; 157(48): 1910-1918, 2016 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-27889974

RESUMO

INTRODUCTION: 1,25-Dihydroxy vitamin D3 mediates antitumor effects in hepatocellular carcinoma. AIM: We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D3-inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. METHODS: Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. RESULTS: Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (p<0.05). The majority of the HCC samples expressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. CONCLUSIONS: The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D3, providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Carcinoma Hepatocelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , RNA Mensageiro/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Colestanotriol 26-Mono-Oxigenase/metabolismo , Família 2 do Citocromo P450/metabolismo , Humanos , Neoplasias Hepáticas/genética , Vitamina D3 24-Hidroxilase/metabolismo
20.
Pathol Oncol Res ; 22(1): 179-88, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26463354

RESUMO

Several immunochemistry tests are used for triaging human papilloma virus (HPV) and cytology positive cases in cervical cancer screening and as an adjunct test to diagnose cervical cancer. Claudin-1 (CLDN1) protein is a major component of the tight junction, shown to have altered expression in cervical cancer. In this study, value of CLDN1 was analysed as a screening and triage immunochemistry test compared to cytology and HPV testing. A population of 352 women attending colposcopic referral visits resulting in cervical conisation and a second population of 150 women attending routine gynaecological visits with negative cervical cytology were enrolled in a multi-centre clinical study in Hungary. Cytology and HPV (Genoid Full Spectrum HPVAmplification and Detection System) testing were carried out along with immunocytochemistry for CLDN1, and as a reference, using CINtec p16 Cytology Kit. Three different evaluation protocols were used which assessed immunostaining characteristics with or without cytological readings. High correlation observable between p16INK4a and CLDN1 established CLDN1 as a competing marker in cervical cancer. Concordance of CLDN1 immunostaining of cervical intraepithelial neoplasia 2 and above (CIN2+) positives was 84.0 % (73.8­89.3); concordance of CIN2+ negatives was 69.0 % (59.6­75.8). In conclusion, CLDN1 has similar diagnostic potential as p16INK4a, our results established it as a histological and cytological biomarker with the potential to improve the clinical performance of cervical cytology and histology.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/patologia , Claudina-1/metabolismo , Citodiagnóstico , Neoplasias de Células Escamosas/patologia , Infecções por Papillomavirus/patologia , Neoplasias do Colo do Útero/patologia , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/metabolismo , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Hungria , Técnicas Imunoenzimáticas , Gradação de Tumores , Neoplasias de Células Escamosas/metabolismo , Neoplasias de Células Escamosas/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Prognóstico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA