Changes in apoptosis and Bcl-2 expression in human hyperglycemic, term placental trophoblast

Apoptosis and its associated regulatory mechanisms are physiological events crucial to the maintenance of placental homeostasis; imbalance of these processes, however, such as occurs under various pathological conditions, may compromise placenta function and, consequently, pregnancy success. Increased apoptosis occurs in the placentas of pregnant women with several developmental disabilities, while increased Bcl-2 expression is generally associated with pregnancy-associated tumors. Herein, we tested the hypothesis that apoptosis-associated disturbs might be involved in the placental physiopathology subjected to different maternal hyperglycemic conditions.Thus, in the present study we investigated and compared the incidence of apoptosis using TUNEL reaction and Bcl-2 expression, in term-placentas of normoglycemic, diabetic and daily hyperglycemic patients. Tissue samples were collected from 37 placentas, being 15 from healthy mothers with normally delivered healthy babies, and 22 from mothers with glucose disturbances. From these latter 22 patients, 10 showed maternal daily hyperglycemia and 12 were clinically diabetics. Both Bcl-2 expression and apoptotic DNA fragmentation were established and quantified in the trophoblasts of healthy mothers. Compared to these reference values, a higher apoptosis index and lower Bcl-2 expression were disclosed in the placentas of the diabetic women, while in the daily hyperglycemic group, values were intermediate between the diabetic and normoglycemic patients. The TUNEL/Bcl-2 index ratio in the placentas varied from 0.02 to 0.09 for pregnant normoglycemic and diabetic women, respectively, revealing a predominance of apoptosis in the diabetic group. Our findings suggest that hyperglycemia may be a key factor evoking apoptosis in the placental trophoblast, and therefore, is relevant to diabetic placenta function. (c) 2006 Elsevier B.V.. All rights reserved.

Human bcl-2 expression, cleaved caspase-3, and KSHV LANA-1 in Kaposi sarcoma lesions

We aimed to evaluate the frequency of Kaposi sarcoma (KS)-associated herpesvirus (KSHV) infection in KS lesions in patients from Brazil. In addition, expression of human bcl-2, cleaved caspase-3, and KSHV latency-associated nuclear antigen (LANA)-1 in tumors was evaluated using inummohistochemical analysis. We studied 64 KS cases, classified as follows: classical, 20 (31 %); iatrogenic, 2 (3 %); AIDS-associated, 25 (39%); and not otherwise specified (lack of information about HIV status), 17 (27%). KSHV was detected by polymerase chain reaction (PCR) in 61 cases (95%); 40 cases (63%) were KSHV+ by PCR and immunohistochemical analysis for LANA-L Immunoexpression of bcl-2 was detected in 47 cases (73%). Only a few cells in 15 cases (23%) of KS had demonstrable immunostaining for cleaved caspase-3. These results further support the association of KSHV with all KS forms. Cleaved caspase-3 in KS tumors was infrequent, which may reflect the inhibition of apoptosis owing to bcl-2 overexpression observed in the majority of KS tumors.

Avaliação da expressão da proteína bcl-2 no carcinoma de mama: estudo em punção aspirativa por agulha fina; correlação com grau histológico em espécimes cirúrgicos correspondentes

INTRODUÇÃO: O gene bcl-2 codifica uma proteína envolvida no processo de controle da apoptose. Inicialmente descrito em linfomas e posteriormente em tecidos epiteliais, sua expressão é freqüentemente encontrada em carcinomas de mama, associada a fatores de prognóstico favorável. Como a punção aspirativa por agulha fina (PAAF) tem sido utilizada como um método confiável na investigação de carcinomas de mama, acessamos a expressão de bcl-2 em material assim obtido e correlacionamos sua positividade com o grau histológico, avaliado em material cirúrgico correspondente, das respectivas pacientes, seguindo a classificação de SBR (Scarff, Bloom e Richardson). OBJETIVOS: Avaliar a expressão de bcl-2 em PAAF e correlacionar com grau histológico. METODOLOGIA: A positividade do bcl-2 foi analisada, por imunocitoquímica, em 118 casos consecutivos de PAAF e correlacionada com grau histológico em material cirúrgico correspondente, segundo classificação de SBR. RESULTADOS: A positividade para bcl-2 foi encontrada em 77 de 118 casos de PAAF (65,25%) e foi inversamente proporcional ao grau histológico (84,37%, p = 0,0022). CONCLUSÃO: A expressão de bcl-2 em PAAF correlaciona-se com fator de bom prognóstico. O índice de positividade encontrado, assim como a correlação inversa com grau histológico, está de acordo com dados publicados previamente. O fácil e rápido manejo do material obtido por PAAF permite a aplicação de técnicas complementares, de maneira confiável, como demonstra este estudo. A positividade do bcl-2 correlacionada com baixo grau histológico, assim como com outros fatores de bom prognóstico, pode, no futuro, proporcionar informação preditiva e prognóstica para pacientes candidatas a tratamento quimioterápico neo-adjuvante.

Comparative analysis of the expression of proliferating cell nuclear antigen, p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma

Several epidermiologic studies have shown the malignant transformation potential of oral lichen planus; however, this potential is subject of much controversy. To evaluate the expression of proteins related to the cell proliferation and apoptosis processes in oral lichen planus, we compared oral lichen planus with oral squamous cell carcinoma. Twenty-four cases of each lesion were submitted according to streptavidin-biotin technique to evaluate the immunohistochemical expression of proliferating cell nuclear antigen, p53, bax, and bcl-2 proteins. X 2 test showed no statistically significant differences between the expression of p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma (P > .05). However, the expression of proliferating cell nuclear antigen was significantly lower in oral lichen planus than in oral squamous cell carcinoma (P < .05). No statistically significant differences between the expression of p53, bax, and bcl-2 in oral lichen planus and oral squamous cell carcinoma were observed, which may be an evidence of the potential of malignant transformation of oral lichen planus. (C) 2009 Elsevier B.V. All rights reserved.

Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide

4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the expression of bcl-2 and bax during tongue carcinogenesis induced by 4NQO. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Although no histological changes were induced in the epithelium after 4 weeks of carcinogen exposure, bcl-2 and bax were over-expressed (P < 0.01) in all layers of the 'normal' epithelium. The expression levels were the same in all layers of epithelium for both the antibodies used (bcl-2 or bax). In dysplastic lesions at 12 weeks following carcinogen administration, the levels of bcl-2 and bax expression did not increase when compared to negative control with the immunoreactivity for bcl-2 being restricted to the superficial layer of epithelium. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, bcl-2 was expressed in some cells of tumour islands. on the other hand, immunostaining for bax was widely observed at the tumour nests. The labelling index for bcl-2 and bax showed an increase (P < 0.05) after only 4 weeks of 4NQO administration. In conclusion, our results suggest that abnormalities in the apoptosis pathways are associated with the development of persistent clones of mutated-epithelial cells in the oral mucosa. Bcl-2 and bax expression appears to be associated with a risk factor in the progression of oral cancer.

Immunohistochemical expression of PCNA, p53, bax and bcl-2 in oral lichen planus and epithelial dysplasia.

The potential for malignant transformation of oral lichen planus is still controversial. The expression of proteins related to cell proliferation and apoptosis in oral lichen planus and epithelial dysplasia was analyzed to evaluate the true potential for malignant transformation of this disease. Twenty-four cases of each lesion were subjected to the streptoavidin-biotin technique for identifying the immunohistochemical expression of PCNA, p53, bax, and bcl-2 proteins. Of the 24 cases of oral lichen planus, 14 (58.33%) were positive for PCNA, 10 (41.67%) for p53, 4 (16.67%) for bcl-2 and 12 (50%) for bax, whereas of the 24 cases of epithelial dysplasia, 20 (83.33%) were positive for PCNA, 10 (41.67%) for p53, 6 (25%) for bcl-2, and 20 (83.33%) for bax. Chi-squared test showed no statistically significant differences between the expression of p53 and bcl-2 in oral lichen planus and epithelial dysplasia, regardless of the grade (P > 0.05). However, the expression of PCNA and bax was significantly increased in epithelial dysplasia (P < 0.05). The results of this study showed that alterations in expression of these proteins are observed in oral lichen planus and epithelial dysplasia, suggesting the potential for malignant transformation in both lesions.

Detecção de gene TP53 e expressão das proteínas p53, Bcl-2 e p63 no tumor venéreo transmissível canino

Pós-graduação em Ciência Animal - FMVA

Estudo da expressão da proteína BCL-2 em mulheres com carcinoma ductal invasivo de mama. Correlação anatomopatólogica e da sobrevida

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Avaliação de mutagenicidade, citotoxicidade e expressão de proteínas relacionadas a apoptose, Bak, BCL-2 e P53 fosforilado, em células tratadas com fuligem e particulado total de queima de cana-de-açúcar

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Influência da terapia fotodinâmica sobre a expressão dos genes BCL-2, BAX e HER-2 na carcinogênese mamária

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expressão dos genes MDR-1, TP53, BCL-2 e BAX em tumor venéreo transmissível canino e sua relação com a agressividade e resposta à terapia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Detection of the tumour suppressor gene TP53 and expression of p53, Bcl-2 and p63 proteins in canine transmissible venereal tumour

Canine transmissible venereal tumour (CTVT) is a neoplasm transmitted among healthy dogs by direct contact with injured skin and/or mucous tissue. This study aimed to identify the TP53 gene, messenger RNA (mRNA) as well as the expression of p53, Bcl-2 and p63 proteins in histological sections of 13 CTVT samples at different stages of evolution. The in situ hybridization (ISH) and in situ reverse transcriptase polymerase chain reaction (RT-PCR) assays were used, which showed the DNA homologous to TP53 and its respective mRNA in 92.3% of the samples. We detected p53, p63 and Bcl-2 proteins in most of the cell samples in different grades of intensity. In addition, 46% of the samples were in the progressive and 54% in the regression phase. This is the first description of these proteins and a detailed study of their role in CTVT cells needs to be addressed in or to verify how these cells undergo apoptosis.

Tumor venéreo transmissível canino: expressão dos genes MDR-1, TP53 e da família Bcl-2 e suas implicações no comportamento biológico e terapêutico

Transmissible venereal tumor (TVT) is a neoplasm of round cells with plasmocytoid or lymphocytoid appearance. The tumor presents several particularities, which have been the subject of numerous studies; however there still have investigations that need to be done. For example, a progressive increase of highly aggressive tumors with varying response to chemotherapy -including resistance- has been evidenced in recent years. There is scientific interest to understand these differences, allowing predicting possible clinical outcomes in affected dogs and increasingly searching adequate and individualized therapy. This review focuses on presenting possible implications of the expression of MDR-1 (P-glycoprotein), TP53, BCL-2, and BAX genes, regarding resistance to chemotherapy and/or the biologic behavior of TVT

Untersuchungen von intrazellulären Signalwegen bei neuraler Determinierung und Differenzierung in vitro: Einfluß von GAP-43 und Bcl-2

Die PCC7-Mz1-Zellinie stellt ein geeignetes Modell dar, um frühe neurale Determinierungs- und Differenzierungsprozesse unter kontrollierten Bedingungen in vitro zu untersuchen. Aus pluripotenten Stammzellen entwickelt sich nach Behandlung mit dem Morphogen Retinsäure (RA) ein stabiles Muster aus Neuronen, Fibroblasten und Astroglia-Zellen. Parallel stirbt ein reproduzierbarer Anteil der Kultur apoptotisch. Zur näheren Aufklärung der molekularen Vorgänge während der neuralen Entwicklung wurde der Einfluß von zwei Schlüsselmolekülen - dem Proteinkinase C Substrat (PKC) GAP-43 sowie dem antiapoptotischen Bcl-2 Protein - auf die neurale Differenzierung und die damit assoziierten Apoptoseereignisse der PCC7-Mz1-Zellen untersucht. Dazu wurden stabile Zellinien, die eine Überexpression von GAP-43 bzw. von Bcl-2 aufwiesen, hergestellt. GAP-43In PCC7-Mz1-Zellen wurde die Expression von GAP-43 sowohl auf mRNA- als auch auf Protein-Ebene innerhalb von 24 Stunden nach Zugabe von RA hochreguliert. GAP-43 war bereits in noch proliferierenden neuronalen Vorläuferzellen als Substrat für PKC und als Interaktionspartner von Calmodulin funktionell. Die Überexpression von GAP-43 in PCC7-Mz1-Zellen förderte die Ausprägung des neuronalen Phänotyps. Das Differenzierungspotential der Mz-GAP-43 Klone war eingeschränkt, da sich nach Induktion mit RA aus den Stammzellen nur noch Neurone, aber keine Fibroblasten und Astroglia-Zellen mehr entwickelten. Die Determinierung für das neuronale Entwicklungsschicksal war in den Mz-GAP-43 Klonen stärker fortgeschritten als in MzN-Klonen, die durch Subklonierung aus PCC7-Mz1-Zellen generiert wurden, da die GAP-43 überexprimierenden Zellen durch Wachstum auf Laminin nicht in den pluripotenten Phänotyp revertiert werden konnten. Aufgrund der Interaktion zwischen GAP-43 und Calmodulin in Stammzellen der Mz-GAP-43 Klone kann man vermuten, daß die neuronalen Determinierungsprozesse über Ca2+/Calmodulin-abhängige Signalwege verlaufen. Da das Gen für den Transkriptionsfaktor NCNF (

Prognostic relevance of Bcl-2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene

Overexpression of anti-apoptotic Bcl-2 plays a role in prostate cancer progression, particularly in transformation to androgen-independent disease. Androgen-independent prostate cancers have been shown to harbor Bcl-2 gene copy number gains frequently suggesting that this genetic alteration might play a role in Bcl-2 overexpression. The relation of Bcl-2 overexpression and copy number gains or translocation of the BCL-2 gene in prostate cancer under hormone-naïve conditions is unknown.