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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.
Anticancer Res ; 36(11): 6093-6096, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27793937

RESUMO

AIM: To study if the angiotensin receptor blocker olmesartan reduces levels of plasminogen activator inhibitor 1 (PAI1), a risk factor for oral cancer, in a mouse model and therefore whether it could be used in the treatment of this malignancy. MATERIALS AND METHODS: Twelve transgenic PAI1 mice aged 16-20 weeks were divided in two groups each containing six animals. One group was given olmesartan every day for 30 days in drinking water in an amount corresponding to their weight, 0.005 mg/g, while the second group did not receive any medication (control group). Blood samples were obtained from animals of both groups, before and after one month of olmesartan administration and plasma PAI1 levels were measured using enzyme-linked immunosorbent assay. RESULTS: In the olmesartan-treated group, a significant decrease of PAI1 level was found after 1 month of treatment (11.9±8.6 vs. 21.7±7.2 ng/ml, respectively; p=0.028). However, no statistically significant difference was observed in PAI1 levels between the olmesartan-treated and control groups after one month, (p=0.177). CONCLUSION: Olmesartan did not significantly affect PAI1 levels in this mouse model.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Imidazóis/farmacologia , Neoplasias Bucais/prevenção & controle , Inibidor 1 de Ativador de Plasminogênio/sangue , Tetrazóis/farmacologia , Animais , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Fatores de Risco
3.
Anticancer Res ; 29(6): 2379-86, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19528505

RESUMO

BACKGROUND: In light of the recently found contribution of inflammation-related factors to oral oncogenesis, the possible correlation of tumor necrosis factor alpha and beta genes (TNF-alpha and TNF-beta) with risk of oral cancer was investigated. MATERIALS AND METHODS: DNA samples of 160 German and Greek patients with oral squamous cell carcinoma and 153 healthy controls of equivalent age, gender and ethnicity were studied. The functional polymorphisms TNF-alpha (-308 G/A) and TNF-beta (252 G/A), which affect gene expression, were investigated by restriction fragment length polymorphism analysis. RESULTS: The frequencies of high expression A2 (-308A) TNF-alpha allele and high expression B1 (252G) TNF-beta allele were significantly increased in cancer patients compared to controls (respectively: 62.2% versus 14.7%, p<0.0001; OR 8.65, 95% CI 5.74-13.04 and 66.9% versus 15.7%, p<0.0001; OR 10.92, 95% CI 7.4-16.2). Three combined TNF-alpha/TNF-beta genotypes (A2A2/B1B1, A1A2/B1B2, A1A2/B1B1) were over-represented in cancer patients (p<0.001). No significant differences in allele frequencies were detected among most subgroups of patients divided in regard to cancer stage, family history for cancer or thrombosis, smoking or heavy alcohol consumption habits. CONCLUSION: This study showed a strong association of TNF-alpha and TNF-beta high expression alleles with increased risk of oral cancer. These findings are in accordance with previously observed high TNF-alpha levels in serum of patients with oral cancer in comparison to healthy controls.


Assuntos
Carcinoma de Células Escamosas/genética , Linfotoxina-alfa/genética , Neoplasias Bucais/genética , Polimorfismo Genético/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Fumar/genética
4.
In Vivo ; 22(5): 621-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18853758

RESUMO

BACKGROUND: H-ras and c-fos oncogenes interact in signalling pathways but their level and time course of expression during oral cancer development are unclear. The present study used an animal model for the simultaneous investigation of H-Ras and c-Fos expression in sequential stages of oral oncogenesis. MATERIALS AND METHODS: Three experimental groups of Syrian golden hamsters (A, B and C; 10 animals each) and one control group (7 animals) were used. The buccal pouches of hamsters in groups A, B and C were treated with 0.5% of the carcinogen 9,10-dimethyl-1,2-benzanthracene and were excised at 10, 14 and 19 weeks, respectively. The biopsies, which included tissue stages ranging from normal oral mucosa to moderately differentiated carcinoma, were studied immunohistochemically. RESULTS: A reduction in both H-Ras and c-Fos expression was observed from group A to B and from hyperplasias to early tumour stages, while a simultaneous increase was noted from group B to C and from well-differentiated to moderately-differentiated carcinomas. The H-ras/c-fos expression ratio had a value of approximately (1.09 +/- 0.21) in five out of seven studied tissue stages. CONCLUSION: H-Ras and c-Fos exhibit a similar expression pattern throughout most stages of oral carcinogenesis, an observation supported by the known molecular pathway connecting H-ras signalling with subsequent c-fos gene transcription.


Assuntos
Carcinoma/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Genes fos , Genes ras , Neoplasias Bucais/genética , Animais , Carcinógenos/toxicidade , Carcinoma/induzido quimicamente , Carcinoma/patologia , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/patologia , Cricetinae , Imuno-Histoquímica , Masculino , Mesocricetus , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/patologia
5.
Anticancer Res ; 28(3A): 1675-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18630525

RESUMO

BACKGROUND: In light of the recently found contribution of angiogenic and inflammation-related factors to malignancies, this study investigated the possible association of the angiotensinogen gene (AGT) with increased risk of oral cancer. MATERIALS AND METHODS: The M235T polymorphism, which influences AGT gene expression, was evaluated by restriction fragment length polymorphism analysis in the DNA samples of 163 German and Greek patients with oral squamous cell carcinoma (OSCC) and 124 healthy controls of equivalent gender, ethnicity and age. RESULTS: No significant difference of the mutant (235T) allele, which results in higher AGT gene expression, was observed in the whole patient group in comparison with the normal controls. Similarly, compared to the controls no significant difference of either allele or carrier frequency was detected in almost every subgroup of patients. Only in the subgroup of patients with a positive family history of cancer was a significant increase of mutant T allele and carrier frequencies observed, compared to the controls (50% vs. 36.7% and 79.3% vs. 61.3%, respectively, p < 0.05 in both cases). In this particular subgroup of patients the odds ratio for OSCC of TT homozygotes was 3.57 (CI 95% 1.2-10.62), while for the MT heterozygotes it was 2.41 (CI 95% 1.06-5.49). CONCLUSION: This study did not reveal an association of the AGT M235T polymorphism with oral oncogenesis, but certainly suggested a possible association of this specific polymorphism with other types of cancer. The present findings support a previous suggestion that the pathway of oral oncogenesis is probably based on angiotensin-converting enzyme and bradykinin interaction and not on AGT and angiotensin peptides.


Assuntos
Angiotensinogênio/genética , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Angiotensinogênio/biossíntese , Carcinoma de Células Escamosas/metabolismo , DNA de Neoplasias/genética , Expressão Gênica , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição
6.
Anticancer Res ; 28(1A): 271-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18383856

RESUMO

BACKGROUND: Stromal derived factor-1 (SDF-1), a protein related to angiogenesis and inflammation, has been correlated with the progression of a number of malignancies, but not with oral squamous cell carcinoma. In light of the known contribution to the development of oral cancer of other gene polymorphisms for proteins responsible for angiogenesis, inflammation and thrombosis, this study investigated whether the G801A polymorphism in the SDF-1 gene is associated with this malignancy. PATIENTS AND METHODS: The G801A polymorphism was examined by restriction fragment length polymorphism analysis in DNA samples from 159 patients with oral squamous cell carcinoma and 101 matched healthy controls. RESULTS: The detected allele frequency of the "high production related" A allele in the control group was 25.3%. There was a slight decrease in allele frequency in patients (18.6%), but it was not statistically significant. The same pattern was observed in subgroups of patients in regard to smoking habits and family history of cancer or thrombosis. Interestingly, in comparison to controls, the A allele frequency was significantly lower in patients with advanced cancer stages III and IV (12.5%, p=0.005) and in patients with alcohol abuse (12.5%, p=0.02). CONCLUSION: The G801A polymorphism of the SDF-1 gene is associated with advanced stages of oral cancer, especially in alcohol abusers.


Assuntos
Carcinoma de Células Escamosas/genética , Quimiocina CXCL12/genética , Neoplasias Bucais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Estudos de Coortes , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Polimorfismo Genético
7.
Anticancer Res ; 28(1A): 309-14, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18383862

RESUMO

BACKGROUND: Increased levels of interleukin-10 (IL-10) have been observed in patients with oral cancer, possibly as a result of suppression of the immune response. Based on this, the -1082A/G polymorphism, which influences IL-10 gene expression level, was investigated in regard to its possible association with risk for oral cancer. PATIENTS AND METHODS: The polymorphism was examined in DNA samples of 144 patients with oral squamous cell carcinoma and 141 healthy controls of equivalent gender, age and ethnicity. RESULTS: The detected allele frequencies for the high expression G allele were significantly higher in patients compared to controls (34.7% versus 21.3%, respectively, p=0.0004), as well as in patients that were smokers but not those that were heavy alcohol consumers. This highly significant difference in G allele frequency was mainly due to the increase of AG heterozygotes in patients compared to controls (OR 3.05, 95% CI 1.84-5.05). CONCLUSION: These findings suggest that the high expression G allele of the -1082A/G polymorphism of the inflammation and angiogenesis-related IL-10 is strongly associated with increased risk for oral cancer.


Assuntos
Carcinoma de Células Escamosas/genética , Interleucina-10/genética , Neoplasias Bucais/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
8.
J Cancer Res Clin Oncol ; 134(8): 821-32, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18273643

RESUMO

PURPOSE: Functional DNA polymorphisms affecting gene expression and serum or saliva levels of interleukins IL-1 beta,-4,-6,-8,-10 and tumor necrosis factors TNF-alpha,-beta have been associated with increased risk for the development of oral squamous cell carcinoma (OSCC). The present retrospective case-control study examines possible interactions between seven cytokine genotype polymorphisms and their combinatory effect in predicting the occurrence of OSCC in Caucasians. METHODS: Three hundred and thirty Greeks and Germans were studied, consisting of 162 OSCC cases and 168 healthy controls of comparable age, gender, and ethnicity. A series of multivariate logistic regression models, adjusted for age and gender, was constructed in order to assess the contribution of homozygous or heterozygous variant genotypes of polymorphisms IL-1 beta (+3953C/T), IL-4 (-590C/T), IL-6 (-174G/C), IL-8 (-251A/T), IL-10 (-1082A/G), TNF-alpha (-308G/A) and TNF-beta (+252G/A) upon overall, early and advanced stages of OSCC development. RESULTS: The contribution of TNF-alpha and IL-6 was consistent and robust in almost all models constructed. Furthermore, when the mode of inheritance of each variant allele was taken into account in a "biological" multivariate logistic regression model, four polymorphisms emerged as primary predictors for overall stages of OSCC: TNF-alpha (OR = 15.27; 95% CI = 7.30-31.96), IL-6 (OR = 8.33; 95% CI = 3.95-17.58), IL-8 (OR = 3.54; 95% CI = 1.69-7.43) and IL-10 (OR = 2.65; 95% CI = 1.28-5.46). Finally, IL-1 beta, IL-4 and TNF-beta polymorphisms were not primary predictors of OSCC development in all constructed models. CONCLUSIONS: This study revealed the highly significant contributions of two out of seven studied cytokines (IL-6 and TNF-alpha) in the occurrence of OSCC. Based on these findings and previous reports, possible stoichiometrical interactions of cytokines leading to OSCC development are discussed.


Assuntos
Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Interleucinas/genética , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Interleucina-1/genética , Interleucina-10/genética , Interleucina-1beta/genética , Interleucina-4/genética , Interleucina-6/genética , Interleucina-8/genética , Linfotoxina-alfa/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Análise de Regressão , Estudos Retrospectivos
9.
Oncol Rep ; 18(6): 1537-43, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17982641

RESUMO

In light of recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of coagulation factors XII and XIII with increased risk for oral cancer. In DNA samples of patients with oral squamous cell carcinoma and healthy controls of comparable ethnicity, age and sex, we studied the C46T polymorphism in FXII gene which affects gene transcription and the V34L polymorphism in FXIII gene which affects enzyme activity resulting in alteration of the fibrin network structure. No significant differences were observed in genotype and mutant allele frequencies of the FXII C46T polymorphism between patients and healthy controls. On the contrary, the obtained data for FXIII V34L polymorphism revealed a significant frequency increase of the L allele, which results in thinner fibrin network, in the whole group of patients compared to controls (33.1 versus 22.2% respectively, Fischer value P=0.006). In addition, LL homozygotes had a 3-fold greater risk for developing oral cancer (OR 2.893, 95% CI 1.056-7.890), while in VL heterozygotes a 2-fold greater risk was observed (OR 1.868, 95% CI 1.126-3.101). Significantly increased frequency of L allele was also observed in sub-groups of patients without family history of thrombophilia or cancer, with and without tobacco abuse and with alcohol abuse (P<0.05). Interestingly, in comparison to controls only patients with early cancer stages I and II had significantly increased L alleles and not patients with advanced stages III and IV. These findings suggest that the presence of L allele is strongly associated with oral cancer generation but not with its progression and metastasis. In the presence of L allele, the fibrin network is composed of thinner fibers, is less porous and facilitates tumor stroma formation and therefore tumor cell proliferation. Nevertheless, this thinner and less porous fibrin network inhibits cell migration.


Assuntos
Fator XIII/genética , Fator XII/genética , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/genética , Substituição de Aminoácidos , Alemanha , Grécia , Humanos , Polimorfismo de Nucleotídeo Único , Prevalência , Mapeamento por Restrição , Fatores de Risco
10.
In Vivo ; 21(5): 745-50, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18019407

RESUMO

BACKGROUND: The tumor suppressor protein p16 plays a vital role in the regulation of the cell cycle. The expression of p16 was investigated in an experimental model of chemically induced carcinogenesis in normal and diabetic (type I) Sprague-Dawley rats. MATERIALS AND METHODS: Tissue sections ranging from normal oral mucosa to moderately differentiated oral squamous cell carcinoma (OSCC) were studied immunohistochemically. RESULTS: In normal rats p16 expression increased gradually during oral oncogenesis, but a significant increase was observed only in moderately differentiated OSCC (p=0.038). On the contrary, in diabetic rats the detected gradual increase was significant in hyperplasia, dysplasia, early invasion and well-differentiated OSCC (p<0.001). Nevertheless, there was no significant difference in p16 expression during oral oncogenesis between normal and diabetic animals. CONCLUSION: It seems that the expression of cell cycle regulator p16 is not affected by diabetes in the studied animal model of oral oncogenesis.


Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Animais , Diferenciação Celular , Transformação Celular Neoplásica/patologia , Feminino , Expressão Gênica , Imuno-Histoquímica , Invasividade Neoplásica , Ratos , Ratos Sprague-Dawley
11.
In Vivo ; 21(5): 901-4, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18019433

RESUMO

BACKGROUND: Inhibition of lung cell apoptosis in the bronchoalveolar lavage (BAL) of septic patients may have a prognostic value for the severity of sepsis. The present study evaluated apoptosis in the nasal and buccal mucosa of septic patients as an alternative and less invasive approach for studying the cells involved in bronchial inflammation. PATIENTS AND METHODS: A prospective study was designed. Nasal and buccal mucosa brushings were obtained from 20 consecutive septic patients who were admitted to two intensive care units. Twenty-four patients scheduled to undergo surgery for colorectal cancer or laparascopic cholocystectomy were the control group. Apoptosis was evaluated using a TUNEL assay, while BCL-2 and BAX expression were evaluated by immunohistochemistry. RESULTS: Significantly reduced apoptosis in the nasal mucosa of septic patients compared to the control group (p=0.043) was detected only by the TUNEL assay. CONCLUSION: Reduced apoptosis was found during sepsis in the nasal mucosa in accordance with the reduced apoptosis in the lungs of septic patients. In contrast to septic lungs the underlying mechanism leading to apoptosis in the nasal mucosa was unrelated to the expression of two apoptosis-related genes BCL-2 and BAX.


Assuntos
Apoptose , Nariz/patologia , Sepse/patologia , Idoso , Idoso de 80 Anos ou mais , Bochecha , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sepse/metabolismo
12.
Acta Oncol ; 46(8): 1097-102, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17851834

RESUMO

INTRODUCTION: In light to recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of angiotensin I- converting enzyme (ACE) with increased risk for oral cancer. MATERIALS AND METHODS: In DNA samples of 160 patients with oral squamous cell carcinoma and 153 healthy controls of comparable ethnicity, age and sex, we studied the insertion/deletion (I/D) polymorphism in the ACE gene, which affects its transcription. RESULTS: The I allele frequencies were significantly increased in patients compared to controls, 40.6% versus 27.5% (p < 0.001), respectively. The II homozygotes had a three-fold greater risk for developing oral cancer (odds ratio 3.17, 95% C.I. 1.32-7.61). A significant increase of I alleles was observed in patients regardless their smoking or alcohol consumption habits, early or advanced stage of cancer, presence or absence of a family history for cancer or thrombophilia (Fischer values p < 0.05). DISCUSSION: These findings suggest that the I/D polymorphism, by affecting the ACE gene expression, is associated with the progress of oral oncogenesis.


Assuntos
Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Mutação INDEL , Neoplasias Bucais/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Progressão da Doença , Feminino , Frequência do Gene , Genótipo , Alemanha , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Risco
13.
In Vivo ; 21(4): 623-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17708356

RESUMO

BACKGROUND: Increased expression of fibroblast growth factors and their receptors (FGFRs) has recently been described in oral squamous cell carcinoma. In addition, we have previously described a molecular basis for an association between oral cancer and diabetes. The expression of FGFR-2 and FGFR-3 investigated in an experimental model of chemically induced carcinogenesis in normal and diabetic (type I) rats. MATERIALS AND METHODS: Tissue sections ranging from normal mucosa to moderately-differentiated oral squamous cell carcinoma were studied using monoclonal antibodies against FGFR-2 and FGFR-3 proteins. RESULTS: A similar pattern of elevated FGFR-2 and FGFR-3 expression was observed in the initial stages of oncogenesis for both diabetic and non-diabetic animals. In the last stages of oral oncogenesis, the expression of both proteins remained relatively stable. CONCLUSION: It seems that diabetes does not affect the FGFR-2 and FGFR-3 pattern of expression throughout the various stages of oral oncogenesis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Neoplasias Bucais/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Animais , Anticorpos Monoclonais , Carcinoma de Células Escamosas/patologia , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Ratos , Ratos Sprague-Dawley , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/imunologia , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/imunologia
14.
Anticancer Res ; 27(4B): 2493-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17695544

RESUMO

BACKGROUND: In the light of the recently found contribution of matrix metalloproteinases (MMPs) to oral oncogenesis, the correlation of MMP-7 with risk for oral cancer was investigated. MATERIALS AND METHODS: The MMP-7 -181A/G polymorphism in 159 German and Greek patients with oral squamous cell carcinoma and 120 healthy controls of equivalent gender and ethnicity was studied. RESULTS: The detected carrier frequency of the high expression G allele was significantly higher in patients compared to controls (74.8% versus 61.7%, p = 0.0257). This significant difference was more pronounced in patients with early stages of cancer and absent in those with advanced stages. A/G heterozygotes have a double relative risk (OR 2.07, 95%, CI 1.17-3.67) of developing early stages of oral cancer than low expression A/A homozygotes. CONCLUSION: MMP-7 gene expression is associated with increased risk only for early stages of oral cancer, possibly due to the inhibitory effect of MMP-7 in angiogenesis.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Metaloproteinase 7 da Matriz/biossíntese , Neoplasias Bucais/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Metaloproteinase 7 da Matriz/genética , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único
15.
Am J Hematol ; 82(11): 1010-2, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17636471

RESUMO

No studies thus far have investigated the contribution of thrombin activatable fibrinolysis inhibitor (TAFI) to oral oncogenesis. We studied the activity-related 1040C/T polymorphism in 150 patients with oral cancer and 138 healthy controls matched by age, gender, and ethnicity. The increased-activity T allele frequency was significantly reduced in patients compared with controls (28.7% vs. 37.0%, P < 0.05). T/T homozygotes had about half the probability of developing oral cancer (O.R. 0.39, 95%C.I. 0.13-1.14), while no significant difference was observed in C/T heterozygotes. The observed prophylactic effect of increased TAFI activity might result from reduction of plasmin and inhibition of extracellular matrix dissolution.


Assuntos
Carboxipeptidase B2/genética , Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Frequência do Gene , Alemanha , Grécia , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade
16.
Anticancer Res ; 27(3B): 1465-73, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17595763

RESUMO

BACKGROUND: The expression of tumour suppressor p53 and oncogene c-myc was investigated in an experimental model of chemically induced carcinogenesis in normal and diabetic (type I) Sprague-Dawley rats. MATERIALS AND METHODS: Tissue sections ranging from normal mucosa to moderately differentiated oral squamous cell carcinoma were studied using monoclonal antibodies against mutant p53 and c-myc proteins. RESULTS: From hyperplasia to later stages of oral oncogenesis, mutant p53 expression was at higher levels in diabetic rats in comparison to normal animals, although the pattern of expression was similar. In contrast, c-myc expression was significantly higher in diabetic than in normal rats only in normal mucosa and hyperplasia. CONCLUSION: It seems that diabetes contributed to increased accumulation of mutations in the p53 gene, contributing to increased proliferation of tumour cells during oral oncogenesis. Additionally, diabetes appeared to enhance c-myc expression only in the initial stages of oral oncogenesis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Transformação Celular Neoplásica/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Mucosa Bucal/metabolismo , Neoplasias Bucais/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/química , Transformação Celular Neoplásica/patologia , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Mucosa Bucal/química , Mucosa Bucal/patologia , Neoplasias Bucais/química , Neoplasias Bucais/patologia , Proteínas Proto-Oncogênicas c-myc/análise , Ratos , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/análise
17.
Anticancer Res ; 27(1A): 459-64, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17352267

RESUMO

BACKGROUND: The purpose of this study was to investigate the possible relation of matrix metalloproteinase-1 (MMP-1) to increased risk for oral cancer, in light of recently found contribution of angiogenesis and thrombosis-related factors to the development of malignancies. MATERIALS AND METHODS: The 1G/2G polymorphism in the MMP-1 gene, which influences its expression, was examined in 156 patients with oral squamous cell carcinoma and 141 healthy controls of comparable ethnicity (Greeks and Germans), gender and age. RESULTS: In comparison to controls, the detected 2G allele frequency was significantly lower in the patient group and in subgroups with early cancer stages, with positive family history of thrombophilia, with tobacco abuse and without alcohol abuse (p < 0.05). These findings were mainly due to a significant decrease in 2G/2G homozygotes despite a small increase in 1G/2G heterozygotes in the above groups. CONCLUSION: These findings suggest a significant involvement of the MMP-1 -1607 1G/2G polymorphism in the increasing risk for oral cancer in the 1G allele European carriers.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Metaloproteinase 1 da Matriz/genética , Neoplasias Bucais/enzimologia , Adulto , Idoso , Alelos , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Polimorfismo Genético
18.
Oncol Rep ; 17(4): 963-8, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17342343

RESUMO

The present study was performed in order to investigate the possible association of the -418 G/C polymorphism in the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene, which affects its expression, with the risk of developing oral cancer. PCR-based restriction analysis was performed in DNA samples from 158 patients with oral squamous cell carcinoma (OSCC) and 168 healthy controls of equivalent sex, age and ethnicity (Greeks and Germans). Statistical analyses were performed with Fisher's exact test and the calculation of odds ratios with a 95% confidence interval (CI). The frequency of the low C allele expression was ten times greater in the patients than the controls (31% vs 2.7%, respectively; P<0.001). The C/C and G/C genotypes were associated with an increased risk of developing OSCC (P<0.001, OR=40.88, 95% CI=2.24-744.40, and P<0.001, OR=21.31, 95%=9.82-46.21, respectively). The same pattern of significant differences with the controls was also observed in the subgroups of patients in regard to the initial or advanced stages of oral cancer, family history of any type of cancer or thrombosis, and smoking habits or alcohol abuse. These findings are consistent with the reduced levels of TIMP-2 in the presence of the low expression C allele, which are insufficient to inhibit the matrix metalloproteinase-driven degradation of the extracellular matrix (leading to cancer invasion) and mitogen-driven neoangiogenesis (leading to tumor growth and metastasis). In conclusion, the studied TIMP-2 polymorphism is strongly associated with an increased risk of OSCC in Europeans carrying the low C allele expression. These results indicate that this polymorphism could serve as a genetic marker for the susceptibility of cancer in the oral cavity.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Polimorfismo Genético , Inibidor Tecidual de Metaloproteinase-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Risco
19.
Anticancer Res ; 27(6B): 3981-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18225559

RESUMO

BACKGROUND: Elevated serum levels of interleukin-1 beta (IL-1beta) have been previously observed in patients with oral cancer. Considering the demonstrated effect of other interleukins to the development of oral cancer, this study investigated whether the +3953 C/Tpolymorphism in the IL-1beta gene is associated with this malignancy. PATIENTS AND METHODS: The +3953 C/T polymorphism was examined in DNA samples of 108 patients with oral squamous cell carcinoma and 156 healthy controls. RESULTS: The detected allele and carrier frequencies of the high expression T allele in the control group were 28.8% and 48.1%, respectively. In the patient group there was a slight decrease both in allele and carrier frequencies (24.1% and 38.9%, respectively), but these findings were not statistically significant. The same pattern was observed in subgroups of patients regarding cancer stage, family history of cancer or thrombosis, as well as smoking or heavy drinking habits. CONCLUSION: The +3953 C/T polymorphism, was not found to be associated with risk for oral cancer. It seems that IL-1beta does not play a primary role in oral oncogenesis, since other interleukins, already associated with this malignancy, appear to exert a more prominent effect.


Assuntos
Carcinoma de Células Escamosas/genética , Interleucina-1beta/genética , Neoplasias Bucais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Carcinoma de Células Escamosas/imunologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/imunologia , Polimorfismo Genético
20.
Anticancer Res ; 27(6B): 4027-30, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18225566

RESUMO

BACKGROUND: Based on the known contribution of other metalloproteinases to the development of oral cancer, this study investigated the possible association of the -77A/G polymorphism in the matrix metalloproteinase-13 (MMP-13) gene with the risk of oral cancer. PATIENTS AND METHODS: The polymorphism -77A/G, which affects gene transcription, was examined in DNA samples of 161 patients with oral squamous cell carcinoma and 97 healthy controls of comparable ethnicity, age and gender. RESULTS: The detected allele and carrier frequency for the high expression A allele in the patient group were not significantly increased in comparison to that of the control group (70.8% versus 65.5%, and 95% versus 89.7%, respectively). The same pattern was observed between controls and patients or subgroups of patients in regard to family history of cancer, smoking and heavy alcohol consumption. Only in the subgroup of patients with advanced stages of cancer was the allele frequency for the high expression A allele significantly increased compared to controls (p = 0.038). In the same subgroup AA genotypes had a borderline significant difference from controls (p = 0.059). CONCLUSION: MMP-13 gene expression-related polymorphism is associated with risk for the highly aggressive form of oral cancer. The high expression A allele of the -77A/G polymorphism seems to be a prognostic factor for tumor progression.


Assuntos
Carcinoma de Células Escamosas/genética , Metaloproteinase 13 da Matriz/genética , Neoplasias Bucais/genética , Alelos , Carcinoma de Células Escamosas/enzimologia , Estudos de Casos e Controles , Expressão Gênica , Predisposição Genética para Doença , Genótipo , Humanos , Metaloproteinase 13 da Matriz/biossíntese , Neoplasias Bucais/enzimologia , Polimorfismo Genético
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