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1.
Anticancer Res ; 39(10): 5525-5530, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570446

RESUMO

BACKGROUND/AIM: Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes. MATERIALS AND METHODS: DNA samples of 190 Greeks were studied, including 91 patients with BCC and 99 matched healthy controls. Molecular genotyping of patients and controls was performed for the polymorphisms AGT M235T, AGTR1 A1166C and AGTR2 G1675A. RESULTS: The mutant T allele that increases AGT gene expression was detected in two-fold increased frequency in BCC patients in comparison to healthy controls (p <0.001). On the contrary, no significant difference was observed in AGTR1 and AGTR2 variants between patients and controls. CONCLUSION: Increased expression of AGT may be associated with BCC.


Assuntos
Carcinoma Basocelular/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Angiotensinogênio/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/genética
2.
In Vivo ; 30(6): 927-930, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27815482

RESUMO

BACKGROUND: Thrombophilia-related mutations, such as coagulation factor V Leiden and factor II (G20210A), have been associated with female infertility due to spontaneous abortions during pregnancy. The possible role of mutations of these two factors in male infertility has not been studied to date. MATERIALS AND METHODS: A total of 208 unrelated Greek men were investigated, including 108 infertile men with idiopathic oligozoospermia, azoospermia, and oligozoospermia of various etiologies, as well as 100 fertile male controls. DNA extracted from participants' sperm or blood was analyzed for factor V Leiden and factor II G20210A mutations. RESULTS: There were no significant differences in factor V and factor II genotypes between infertile men and normal controls. CONCLUSION: An association of the two common thrombophilia-related mutations with male infertility was not observed in this preliminary study.


Assuntos
Fator V/genética , Infertilidade Masculina/genética , Mutação , Protrombina/genética , Alelos , Azoospermia/sangue , Azoospermia/genética , Frequência do Gene , Genótipo , Grécia , Humanos , Infertilidade Masculina/sangue , Masculino , Oligospermia/sangue , Oligospermia/genética
3.
In Vivo ; 29(3): 395-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25977387

RESUMO

BACKGROUND: Pathogenesis of cerebral aneurysms implicates several risk factors. Three common thrombophilia-predisposing mutations were studied in patients with cerebrovascular aneurysms. PATIENTS AND METHODS: A total of 186 Greeks (66 patients with intracranial aneurysm and 120 healthy controls) were studied. Fifteen patients had a family history of thrombophilia, while two of them had a first-degree relative with an aneurysm. Genetic analysis for thrombophilia-predisposing mutations factor V Leiden, factor II (prothrombin) G20210A and methylenetetrahydrofolate reductase C677T was performed in all subjects. RESULTS: Genotypic distributions and allelic frequencies were compatible with the Hardy-Weinberg equilibrium. There was no significant difference between healthy individuals and patients in mutant allelic frequencies of thrombophilia mutations. Nevertheless, the mutant allelic frequencies of factor V and II mutations were significantly increased in the sub-group of patients with a positive family history of thrombophilia compared to controls (p≤0.003). CONCLUSION: Certain thrombophilia-related mutations may contribute to pathogenesis of intracranial aneurysms in a subset of the general population.


Assuntos
Aneurisma Intracraniano/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Protrombina/genética , Trombofilia/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Risco , Fatores de Risco , Adulto Jovem
4.
Arch Dermatol Res ; 305(4): 333-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23299466

RESUMO

The incidence of basal cell carcinoma (BCC) is significantly reduced in individuals treated with inhibitors of angiotensin I-converting enzyme (ACE) that produces angiotensin II. The objective of this study was to investigate the possible association of a functional polymorphism in the ACE gene, which affects its transcription, with risk for BCC. In DNA samples of 92 patients with BCC and 103 healthy controls of Greek origin and comparable age and gender, we studied the ACE gene insertion/deletion (I/D) polymorphism. Fisher's exact test was used for comparison of allele and genotype frequencies between the control and patients' groups. The detected low expression I allele frequency in the group of BCC patients was significantly decreased compared to controls (15.8 vs. 31.1 %, respectively; P = 0.001). ID heterozygotes exhibited 3.06 times lower BCC risk, compared with DD homozygotes (P = 0.001; OR = 0.327, 95 % CI = 0.174-0.615). The protective role of I allele was particularly prominent in women (P = 0.007, OR = 0.299, 95 % CI = 0.125-0.716), while for men it exhibited a marginal level (P = 0.041). These findings indicate that the low expression ACE I allele carriers have a decreased risk for BCC. The protective effect of the ID genotype against BCC may be explained by a possible underlying mechanism involving the effect of produced angiotensin II levels on its receptors due to putatively different binding affinity.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/genética , Deleção de Genes , Mutagênese Insercional/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
5.
In Vivo ; 26(6): 1001-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23160684

RESUMO

AIM: In an effort to assess the role of plasminogen activator inhibitor-1 (PAI-1) in oral squamous cancer development and progression, two different carcinogen treatment protocols were conducted. MATERIALS AND METHODS: Protocol I included mice from a PAI-1 transgenic (Tg) breed (n=56) and their wild-type (WT) counterparts (n=56), divided into one control group and two main experimental groups, treated with 7,12-dimethylbenz[a]anthracene (DMBA) for 8 and 16 weeks, respectively. Protocol II included the same number and types of animals and groups, which were similarly treated with 4-Nitroquinoline 1-oxide (4-NQO) in drinking water. Two drugs that affect plasma PAI-1 levels, enalapril and pravastatin, were administered to certain subgroups of animals in both protocols. RESULTS: None of the animals developed macroscopically-visible oral cancer lesions. Eleven animals under Protocol I and 52 animals under Protocol II died. Skin lesions were noted only in DMBA-treated animals (n=9). Almost all animals administered with 4-NQO developed alopecia and lost weight, while two of them developed stomach tumours, and one female mouse developed a large ovarian cyst. CONCLUSION: Transgenic mice may respond differently when used in well-established carcinogen models and oral carcinogenesis is hard to achieve in these rodents.


Assuntos
Transformação Celular Neoplásica , Neoplasias Bucais , Neoplasias de Células Escamosas , Serpina E2/genética , 4-Nitroquinolina-1-Óxido/toxicidade , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Carcinógenos/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Enalapril/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Transgênicos , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Neoplasias de Células Escamosas/induzido quimicamente , Neoplasias de Células Escamosas/genética , Neoplasias de Células Escamosas/patologia , Pravastatina/administração & dosagem , Serpina E2/sangue
6.
Anticancer Res ; 29(8): 3401-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19661364

RESUMO

BACKGROUND: Cervical cancer is the leading cause of mortality among women worldwide, despite existing prevention programs. In light of the recent development of anti-HPV vaccines, the aim of this study was to evaluate concurrently the efficacy of four methods for risk assessment (cytology, colposcopy, HPV molecular typing and detection of biomarkers in cervical biopsies) in an attempt to define the most efficient combination. PATIENTS AND METHODS: The studied group included 62 women with abnormal Pap tests and cervical lesions ranging from cervicitis and condylomas to intraepithelial neoplasias and invasive cancer. All women underwent full colposcopy assessment and colposcopically-taken biopsies were selected for histological examination, immunohistochemical identification of p16, p53, Bcl-2 biomarkers, as well as molecular detection and typing of HPV genomes. RESULTS: Cytology and colposcopy showed very high sensitivity in detecting CIN and cancer (91.7% and 94.4%, respectively), but low specificity (34.6% and 50%, respectively). The detection of the 3 biomarkers reached an impressive sensitivity (83.3%) and a moderate specificity (65.4%). HPV detection and typing achieved 77.8% sensitivity, and the highest specificity of 80.8% in detecting CIN and cancer cases. HPV DNA testing had the highest positive prognostic value (84.9%; confidence interval, CI: 67.4%- 94.3%) and cytology the lowest (66.0%; CI: 51.2%- 78.4%). Coupled HPV typing and colposcopy proved to be the most efficient combination, increasing sensitivity to 97.2% and negative prognostic value to 92.3%. The estimation of cervical neoplasia or cancer in women with high-risk HPV types increased approximately 15-fold (odds ratio, OR: 14.70; CI: 4.30-50.09, p<0.001), ~23-fold in the case of combined positive biomarkers (OR: 23.18; CI: 4.97- 104.23, p<0.001), and 35-fold in case of colposcopically detected cervical neoplasia (OR: 35.00; CI: 5.16- 225.07, p<0.001). CONCLUSION: The most efficient combination among all tested methodologies was found to be HPV typing with colposcopy.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , Colposcopia , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Neoplasia Intraepitelial Cervical/metabolismo , DNA Viral/genética , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/patologia , Prognóstico , Neoplasias do Colo do Útero/metabolismo , Esfregaço Vaginal , Adulto Jovem
7.
J Craniomaxillofac Surg ; 35(8): 382-7, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18023197

RESUMO

PURPOSE: The expression of oncogenic protein c-jun was investigated in an experimental model of chemically induced carcinogenesis in normal and diabetic (type I) Sprague-Dawley rats. MATERIAL AND METHODS: Thirteen diabetic and twelve normal rats developed cancer after 4-nitroquinoline-N-oxide treatment, while six diabetic and six normal animals were used as controls. The biopsies were classified pathologically from oral mucosal dysplasia to moderately differentiated oral squamous cell carcinoma (OSCC) and studied immunohistochemically using monoclonal antibody against c-jun protein. RESULTS: Higher c-jun levels were observed in non-cancerous and precancerous stages of normal rats compared with diabetic rats, while in different tumour stages, the expression of c-jun was practically identical for both groups. CONCLUSION: It seems that diabetes does not affect the c-jun N-terminal kinase (JNK)/c-jun pathway.


Assuntos
Diabetes Mellitus Experimental/complicações , Neoplasias Bucais/induzido quimicamente , Proteínas Proto-Oncogênicas c-jun/genética , 4-Nitroquinolina-1-Óxido/efeitos adversos , Animais , Biópsia , Carcinógenos , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Diabetes Mellitus Experimental/genética , Feminino , Regulação Enzimológica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Imuno-Histoquímica , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Risco
8.
Anticancer Res ; 27(6B): 4121-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18225582

RESUMO

BACKGROUND: We have previously found an association of platelet glycoprotein Ia polymorphism with increased risk for oral cancer. The purpose of this study was to investigate the possible relation of another platelet glycoprotein, Iba (GPIbalpha), with oral oncogenesis. PATIENTS AND METHODS: The variable number of tandem repeats (VNTR) polymorphism of the GPIbalpha gene, which affects the protein's structure and function, was examined in 162 Greek and German patients with oral squamous cell carcinoma and 225 healthy controls of equivalent age, gender and ethnicity. RESULTS: The B allele frequency detected, representing higher platelet activation, in the patient group and in the subgroups of patients without family history either of cancer or thrombophilia were significantly elevated in comparison with that of the control group (p = 0.03, p = 0.016 and p = 0.036, respectively). The D allele frequency (lower platelet activation) was significantly lower in comparison with controls only in patients with family history of thrombophilia. The frequency of B/B homozygotes was significantly increased in the total group of patients and the subgroup of patients with a family history of thrombophilia, in comparison with the control group (p = 0.042 and p = 0.043, respectively), while the frequency of heterozygotes for the C/B alleles was significantly lower in the subgroups of patients with a family history of cancer and thrombophilia (p = 0.036 and p = 0.027, respectively) compared to the control group. CONCLUSION: The VNTR polymorphism of the GPIbalpha gene, which affects the structure and function of this platelet glycoprotein, seems to be associated with risk for oral cancer, especially in patients without a family history of cancer.


Assuntos
Carcinoma de Células Escamosas/genética , Repetições Minissatélites , Neoplasias Bucais/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Plaquetas/metabolismo , Carcinoma de Células Escamosas/sangue , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/sangue
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