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1.
Arch Dermatol Res ; 313(5): 373-380, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32772162

RESUMO

Cytokines involved in inflammatory and immune response have been associated with risk for development of basal cell carcinoma (BCC). In this study, three functional DNA polymorphisms affecting gene expression were investigated in 54 BCC patients and 111 healthy controls: interleukin-1b (IL-1b) +3953C/T, interleukin-10 (IL-10) - 1082G/A and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Significant increase of the variant alleles was observed in IL-10 - 1082G (P = 0.019) and in ACE D (P = 0.003) in BCC patients in comparison to controls. Multivariate logistic regression models evaluated the contribution of homozygous and heterozygous variant polymorphisms to the risk for BCC development. The studied polymorphisms influencing the expression of IL-10 and ACE genes were recognized as potential predictive factors for BCC. These findings suggest a possible molecular mechanism leading to BCC development that is likely to involve the activation of angiotensin receptors in combination with increased plasma levels of IL-10 in patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Basocelular/genética , Interleucina-10/genética , Peptidil Dipeptidase A/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Angiotensinas/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Basocelular/sangue , Carcinoma Basocelular/diagnóstico , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Voluntários Saudáveis , Humanos , Interleucina-10/sangue , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/metabolismo , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/diagnóstico , Adulto Jovem
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 ; 35(4): 1881-916, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25862842

RESUMO

AIM: to identify biological interactions between proliferating fibroblasts and HeLa cells in vitro. MATERIALS AND METHODS: Fibroblasts were isolated from both normal and tumour human tissues. Coverslip co-cultures of HeLa and fibroblasts in various ratios with medium replacement every 48 h were studied using fixed cell staining with dyes such as Giemsa and silver staining, with immunochemistry for Ki-67 and E-cadherin, with dihydrofolate reductase (DHFR) enzyme reaction, as well as live cell staining for non-specific esterases and lipids. Other techniques included carmine cell labeling, autoradiography and apoptosis assessment. RESULTS: Under conditions of feeding and cell: cell ratios allowing parallel growth of human fibroblasts and HeLa cells, co-cultured for up to 20 days, a series of phenomena occur consecutively: profound affinity between the two cell types and exchange of small molecules; encircling of the HeLa colonies by the fibroblasts and enhanced growth of both cell types at their contact areas; expression of carbonic anhydrase in both cell types and high expression of non-specific esterases and cytoplasmic argyrophilia in the surrounding fibroblasts; intense production and secretion of lipid droplets by the surrounding fibroblasts; development of a complex net of argyrophilic projections of the fibroblasts; E-cadherin expression in the HeLa cells; from the 10th day onwards, an increasing detachment of batches of HeLa cells at the peripheries of colonies and appearance of areas with many multi-nucleated and apoptotic HeLa cells, and small HeLa fragments; from the 17th day, appearance of fibroblasts blocked at the G2-M phase. Co-cultures at approximately 17-20 days display a cell-cell fight with foci of (a) sparse growth of both cell types, (b) overgrowth of the fibroblasts and (c) regrowth of HeLa in small colonies. These results indicate that during their interaction with HeLa cells in vitro, proliferating fibroblasts can be activated against HeLa. This type of activation is not observed if fibroblast proliferation is blocked by contact inhibition of growth at confluency, or by omitting replacement of the nutrient medium. CONCLUSION: The present observations show that: (a) interaction between proliferating fibroblasts and HeLa cells in vitro drastically influences each other's protein expression, growth pattern, chromatin features and survival; (b) these functions depend on the fibroblast/HeLa ratio, cell topology (cell-cell contact and the architectural pattern developed during co-culture) and frequent medium change, as prerequisites for fibroblast proliferation; (c) this co-culture model is useful in the study of the complex processes within the tumour microenvironment, as well as the in vitro reproduction and display of several phenomena conventionally seen in tumour cytological sections, such as desmoplasia, apoptosis, nuclear abnormalities; and (d) overgrown fibroblasts adhering to the boundaries of HeLa colonies produce and secrete lipid droplets.


Assuntos
Proliferação de Células/genética , Técnicas In Vitro , Microambiente Tumoral/genética , Comunicação Celular/genética , Sobrevivência Celular/genética , Cromatina/genética , Técnicas de Cocultura , Fibroblastos/metabolismo , Fibroblastos/patologia , Células HeLa , Humanos , Células Estromais/patologia
4.
In Vivo ; 28(5): 851-61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25189899

RESUMO

BACKGROUND/AIM: Aberrant microRNA (miRNA) expression in blood of cancer patients is a common finding. The present study aimed at evaluating the differences in miRNA expression in whole blood samples of oral squamous cell carcinoma (OSCC) patients compared to healthy controls. MATERIALS AND METHODS: Microarray based miRNA profiling was performed on whole blood samples of 20 OSCC patients and 20 healthy volunteers and the differences in expression patterns between the two groups were evaluated. The results were validated by Reverse Transcription quantitative-Polymerase Chain Reaction (RT-qPCR) in 50 OSCC patients and 35 volunteers. RESULTS: 21 miRNAs were identified to be significantly differentially expressed in whole blood of OSCC patients compared to healthy controls. The impact of miR-186 (p=0.002), miR-494 (p=0.001) and miR-3651 (p=0.0001) could be validated by RT-qPCR. CONCLUSION: The aberrant expressions of miR-186, miR-494 and miR-3651 in whole blood of OSCC patients may serve as the basis for establishing minimally-invasive screening methods for OSCC based on miRNAs as biomarkers.


Assuntos
Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Bucais/genética , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Análise por Conglomerados , Feminino , Humanos , Metástase Linfática , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Neoplasias Bucais/patologia , Gradação de Tumores , Estadiamento de Neoplasias , Curva ROC , Carga Tumoral
5.
Oncol Rep ; 31(3): 1429-36, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24452363

RESUMO

microRNAs (miRNAs) are aberrantly expressed in the whole blood of patients suffering from different types of cancer. Collection of whole blood samples is a minimally invasive procedure. To date, little is known concerning the altered miRNA expression in patients suffering from oral squamous cell carcinoma (OSCC). The present study aimed to evaluate the difference in miRNA expression in whole blood samples in OSCC patients as compared to healthy volunteers who served as controls. In 20 blood samples from patients and healthy volunteers, the expression patterns of 1,205 human miRNAs were examined by miRNA microarray in order to identify those with the most pronounced differential expression. The results were verified by quantitative RT-PCR (RT-qPCR) for miR-186, miR-3651 and miR-494 using 57 samples of patients and 33 samples of healthy volunteers. Receiver operating characteristic (ROC) curves and the highest Youden index were calculated in order to assess cut-off points (COPs) that allowed the distinguishing of blood samples of OSCC patients from those of healthy volunteers. Significantly different expression rates were found for miR-186 (p=0.01), miR-3651 (p=0.0001) and miR-494 (p=0.004) between the OSCC patients and healthy controls. In the OSCC patients, there was a 2-fold upregulation for miR-494 and miR-3651 and a 2-fold downregulation for miR-186. Based on the determined COPs, significant correlations between miR-3651 overexpression and lymph node status (p=0.04), tumor grade (p=0.02) and clinical stage (p=0.04) were indicated. Aberrant expression levels of miR-186, miR-494 and miR-3651 in whole blood samples of OSCC patients may provide the possibility to establish a minimally invasive screening method for OSCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , MicroRNAs/sangue , Neoplasias Bucais/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Proteínas dos Microfilamentos , Pessoa de Meia-Idade , Proteínas de Ligação a RNA , Curva ROC
6.
Anticancer Res ; 33(9): 4033-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24023347

RESUMO

It is well-known that there is an interplay between hemostasis, thrombosis and cancer. Functional DNA polymorphisms in genes encoding factors related to thrombosis have been associated with increased risk for oral squamous cell carcinoma (OSCC). The present study investigated the possible combinatory effect of 10 such polymorphisms as primary risk predictors for OSCC in a European population. Two groups including 160 patients with OSCC and 168 healthy controls of Greek and German origin were studied. The patient and control groups were comparable regarding ethnicity, age and gender. For all studied individuals, 10 genotypes of functional polymorphisms were investigated: 5,10-methylene tetrahydrofolate reductase (MTHFR) C677T, coagulation factor V (F5) Leiden, coagulation factor II (F2, also known as prothrombin) G20210A, coagulation factor XII (F12) C46T, coagulation factor XIII A1 subunit (F13A1) Val34Leu, serpine1 (SERPINE1, also known as plasminogen activator inhibitor-1) 4G/5G, protein Z (PROZ) -A13G, angiotensin I-converting enzyme (ACE) I/D, angiotensinogen (AGT) Met325Thr, and carboxypeptidase B2 (CPB2, also known as thrombin-activatable fibrinolysis inhibitor) C1040T. Multivariate logistic regression models were used in order to evaluate the relation and contribution of homozygous and heterozygous variant polymorphisms upon overall, early and advanced stages of OSCC. Five out of the studied polymorphisms, influencing the expression of SERPINE1 and ACE genes, as well as the activity of CPB2, F12 and F13 proteins, were recognized as significant predictive factors for OSCC. The 'mode of inheritance' regression model, in particular, revealed the low expression I allele of ACE to be a primary predictor in overall, early and advanced stages of oral cancer. Comparing the present findings with previous knowledge, possible interactions of these factors and their relation to the risk for OSCC development are discussed.


Assuntos
Carcinoma de Células Escamosas/genética , Predisposição Genética para Doença , Neoplasias Bucais/genética , Polimorfismo Genético , Trombose/genética , Carcinoma de Células Escamosas/complicações , Estudos de Casos e Controles , Genótipo , Humanos , Neoplasias Bucais/complicações , Análise de Regressão , Estudos Retrospectivos , Trombose/complicações
7.
Oncol Rep ; 30(3): 1149-56, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23784518

RESUMO

The present study evaluated the relevance of EGFR overexpression in prediction of malignant transformation of oral leukoplakia (OLP). The retrospective study comprised paraffin-embedded tissue samples of OLP that transformed into oral squamous cell carcinoma (OSCC) (n=53) and tissue samples of OLP that did not transform into OSCC (n=45) during a follow-up period of 5 years. EGFR overexpression was assessed immunohistochemically. A significantly different expression rate of EGFR was determined between transformed and non-transformed OLP (p=0.017). A statistically significant increase of EGFR expression for low dysplasia lesions in group I compared to group II was proven (D0, p=0.013; D1, p=0.049). By calculation of ROC curve and determination of highest Youden index the optimal threshold value [cut-off point (COP) = 44.96] for distinguishing the transformed from non-transformed lesions was estimated (critical expression rate of EGFR). Using the determined COP the correlation between high-risk lesions and the detection of increased expression rates were significant (p=0.001). In the future, the assessment of EGFR overexpression in OLP may allow identifying OLP lesions with an increased risk of malignant transformation that may have been regarded harmless when only the grade of dysplasia had been taken into account.


Assuntos
Biomarcadores Tumorais/metabolismo , Transformação Celular Neoplásica/patologia , Receptores ErbB/metabolismo , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Transformação Celular Neoplásica/metabolismo , Feminino , Seguimentos , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Técnicas Imunoenzimáticas , Leucoplasia Oral/metabolismo , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/metabolismo , Gradação de Tumores , Lesões Pré-Cancerosas/metabolismo , Prognóstico , Curva ROC , Estudos Retrospectivos
8.
Gynecol Oncol ; 129(2): 395-400, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23428459

RESUMO

OBJECTIVE: Human papillomavirus (HPV) is strongly associated with cervical cancer and possibly with some oropharyngeal cancers. However, the relation between oral and cervical HPV infection is not fully understood. This study evaluates the prevalence rate and type-concordance of HPVs in these areas. METHODS: HPV DNA typing was performed in saliva and cervical specimens of 43 sexually active women, with the use of general consensus PCR and nested PCR (NPCR) tests. RESULTS: The prevalence rate of HPV DNA in cervical and saliva samples was 51.2% and 11.6% with general PCR, and 60.5% and 44.2% with NPCR, respectively. The probability of HPV DNA detection with general PCR in saliva was about 8 times lower compared to the cervix (P<0.001, OR: 0.13, 95% CI: 0.04-0.37), but showed no difference when the more sensitive NPCR method was applied (P=0.139, OR: 0.52, 95% CI: 0.22-1.21). The distribution of HPV variants according to their oncogenic potential revealed no statistically significant difference, regardless to the PCR method used for both sites. All general PCR HPV DNA positive saliva specimens belonged to women with cytology findings (n=5). These women had also 8.5 times higher risk for presenting with positive HPV detection in saliva with the NPCR method (P=0.009, OR=8.50, 95% CI: 1.74-39.70). CONCLUSIONS: Women with genital HPV infection are at higher risk for asymptomatic oral HPV infection. Prophylactic HPV-vaccination may reduce the burden of HPV-related diseases in both cervix and oropharynx.


Assuntos
Alphapapillomavirus/isolamento & purificação , Infecções Assintomáticas/epidemiologia , Testes de DNA para Papilomavírus Humano , Infecções por Papillomavirus/epidemiologia , Saliva/virologia , Esfregaço Vaginal , Adulto , Alphapapillomavirus/genética , Estudos de Coortes , DNA Viral , Feminino , Grécia/epidemiologia , Testes de DNA para Papilomavírus Humano/métodos , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase , Comportamento Sexual
9.
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
10.
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
11.
In Vivo ; 26(6): 1095-101, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23160700

RESUMO

Genetic association studies have revealed a correlation between DNA variations in genes encoding factors of the haemostatic system and thrombosis-related disease. This study investigated the prevalence of 13 such genetic risk factors in a sample (N=400 alleles) of the Hellenic population of Greece. Some of these polymorphisms [coagulation factor V (F5) Leiden, coagulation factor II (F2) G20210A, 5,10-methylene tetrahydrofolate reductase (MTHFR) C677T, coagulation factor XIII A1 subunit (F13A1) Val34Leu, serpine1 (SERPINE1) 4G/5G, angiotensin I-converting enzyme (ACE) I/D, angiotensinogen (AGT) Met325Thr, integrin A2 (ITGA2) C807T] have been previously studied in Hellenic populations of Greece and Cyprus, while others such as coagulation factor XII (F12) C46T, plasma carboxypeptidase B2 (CPB2) C1040T, platelet glycoprotein Ib α polypeptide (GP1BA) VNTR, thrombomodulin (THBD) -A33G and protein Z (PROZ) - A13G have not. Most of the allelic frequencies observed are similar to those reported for other Southern European populations. Knowledge of the prevalence of these variations in a given population may assist in the design of effective preventive measures against cardiovascular disease.


Assuntos
Biomarcadores/sangue , Estudos de Associação Genética , Predisposição Genética para Doença , Trombose , Chipre , Frequência do Gene , Genética Populacional , Grécia , Humanos , Polimorfismo de Nucleotídeo Único , Trombose/sangue , Trombose/genética , Trombose/patologia
12.
Anticancer Res ; 32(5): 1791-800, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22593463

RESUMO

Accumulating evidence has revealed the role of various components of the coagulatory system in different stages of carcinogenesis including precancerous and initial stages, tumor growth, angiogenesis, stroma generation, and metastasis of malignant cells. This comprehensive review discusses major points of evidence, in addition to recent findings on specific factors associated with the paradigm of oral squamous cell carcinoma. During carcinogenesis, angiogenesis is favored by local conditions of hypoxia, cell-to-cell interactions, and by expression of paracrine growth factors and inflammatory cytokines. In the oral region specifically, genetic association studies have revealed that constitutively high gene expression of certain inflammatory cytokines plays a major role in carcinogenesis. Tissue factor (TF) has a physiological role in hemostasis, but it also constitutes a notable procoagulant in many types of cancer, since it appears to be constitutively expressed by tumor cells. Furthermore, its pathway regulates mechanisms which involve plasmin and matrix metallo-proteinases, both of which seem to be critical in oral carcinogenesis. Thrombin has a central role in hemostasis but it may also promote angiogenesis through pathways independently of fibrin generation. Thrombomodulin may act through attenuation of the tumor-promoting properties of thrombin, but it also may function as a cell-to-cell adhesion molecule, independently of its anticoagulant action. The activation of fibrinogen by thrombin and its cleavage to fibrin monomers result in the rapid formation of fibrin matrix. Furthermore, it is well documented that fibrinogen and cross-linked fibrin reside inside the tumor stroma, facilitating its remodeling, angiogenesis, tumor growth and metastasis. In conclusion, the hemostatic system contributes to the development of the malignant phenotype acting on many different levels.


Assuntos
Hemostasia , Neoplasias Bucais/etiologia , Coagulação Sanguínea , Plaquetas/fisiologia , Humanos , Lipoproteínas/fisiologia , Neoplasias Bucais/sangue , Neovascularização Fisiológica , Trombina/fisiologia , Trombomodulina/fisiologia , Tromboplastina/fisiologia
13.
In Vivo ; 26(1): 165-72, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22210734

RESUMO

BACKGROUND/AIM: Thrombophilia is a multifactorial predisposition for thromboembolism affecting about a tenth of any population. We investigated whether genetic counseling combined with molecular testing for two common dominant mutations (coagulation factor V Leiden and prothrombin G20210A) may increase prevention of venous thromboembolic incidents in individuals with a positive family history compared to the general population. PATIENTS AND METHODS: Mutation detection was carried out by Restriction Fragment Length Polymorphism analysis in DNA samples of 96 unrelated healthy Greeks (group A) who asked for genetic counseling for various reasons and had at least two relatives with thromboembolic incidents and 100 unrelated healthy Greeks (group B). RESULTS: In group A, both mutations were detected at five-fold higher frequencies (33.33% for Leiden and 19.79% for G20210A) compared to group B, which had frequencies typically found in the Greek population (6% and 4%, respectively). CONCLUSION: In populations with a high prevalence for these two common mutations, genetic counseling and molecular testing of at-risk individuals may significantly increase prevention of thromboembolic disease.


Assuntos
Aconselhamento Genético/métodos , Testes Genéticos/métodos , Mutação , Tromboembolia/genética , Tromboembolia/prevenção & controle , Trombofilia/genética , Adulto , Análise Mutacional de DNA , Fator V/genética , Saúde da Família , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Polimorfismo de Fragmento de Restrição , Protrombina/genética , Fatores de Risco , Tromboembolia/diagnóstico , Adulto Jovem
14.
Arch Facial Plast Surg ; 13(4): 271-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21768562

RESUMO

OBJECTIVE: To compare individually prefabricated computer-assisted designed/computer-assisted manufactured (CAD/CAM) glass-bioceramic implants with nonpreformed titanium meshes for orbital floor reconstruction in secondary correction of enophthalmos. METHODS: In a nonrandomized, comparative, prospective cohort study, 2 groups of 10 patients received secondary correction of enophthalmos with CAD/CAM implants in one group and titanium meshes in the other. Relative enophthalmometry and exophthalmometry data were assessed preoperatively, at the end of the operation, at day 90 postoperatively, and at day 365 postoperatively. RESULTS: In both groups, the globe position improved significantly at the end of the operation (P = .005 in both groups). At day 90, there was a significant tendency toward relapse of enophthalmos in both groups (P = .005 in the CAD/CAM group and P = .008 in the titanium mesh group). However, the globe position did not change significantly between postoperative days 90 and 365 in both groups (P = .57 in the CAD/CAM group and P = .35 in the titanium mesh group). CONCLUSIONS: Individually prefabricated CAD/CAM glass-bioceramic implants and nonpreformed titanium meshes produce similar results in secondary enophthalmos correction. Because of higher costs, the use of CAD/CAM implants should be confined to selected cases in secondary enophthalmos correction.


Assuntos
Enoftalmia/cirurgia , Traumatismos Oculares/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/instrumentação , Procedimentos de Cirurgia Plástica/instrumentação , Próteses e Implantes , Telas Cirúrgicas , Adulto , Cerâmica , Desenho Assistido por Computador , Enoftalmia/etiologia , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Estudos Prospectivos , Titânio , Resultado do Tratamento
15.
Support Care Cancer ; 18(4): 449-60, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19609572

RESUMO

GOALS OF WORK: This is a prospective clinical study aimed at assessing the success rate of osteotomy and primary wound closure in patients with bisphosphonate-associated osteonecrosis of the jaw (BONJ). MATERIALS AND METHODS: Fifty patients who had received bisphosphonates intravenously and subsequently suffered from BONJ were included in the study. All patients underwent osteotomy of the affected jaw bone region and primary wound closure under general anaesthesia. They were followed up bimonthly for a period of 12 months. RESULTS: Macroscopically altered bone could be completely removed in all cases. In two patients with plasmocytoma, major bleeding occurred postoperatively that required monitoring in an intensive care unit. In two cases, recurrence of BONJ was diagnosed during the first 2 months. In three patients, recurrence appeared between the fourth and the sixth month. In these cases, an additional osteotomy had to be performed. Six patients died during the follow-up period. In the remaining 39 patients, no signs of recurrence could be detected during the follow-up of 12 months. The success rate of the surviving patients was 89% after 1 year. CONCLUSION: Due to the high success rate of osteotomy and primary wound closure, it should be checked for every patient suffering from BONJ if osteotomy is a viable treatment option.


Assuntos
Difosfonatos/efeitos adversos , Doenças Maxilomandibulares/cirurgia , Osteonecrose/cirurgia , Osteotomia/métodos , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Feminino , Seguimentos , Humanos , Doenças Maxilomandibulares/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Osteonecrose/induzido quimicamente , Plasmocitoma/complicações , Estudos Prospectivos , Recidiva , Reoperação , Técnicas de Sutura , Resultado do Tratamento
16.
Clin Oral Investig ; 14(3): 311-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19513765

RESUMO

It was the aim of the present study to find out which radiological imaging techniques allow assessing the extent of bisphosphonate-associated osteonecrosis of the jaw (BONJ) in an adequate way. Twenty-four patients suffering from BONJ were included in the study. Before surgery, each patient was examined with panoramic radiograph, contrast-enhanced magnetic resonance imaging (MRI) and non-enhanced computed tomography. The detectability of BONJ was assessed for the three imaging techniques. The extent of the jaw region affected by BONJ was determined in MRI and CT scans and compared to the intra-operative situation. The detectability of BONJ lesions was 54% for panoramic radiographs, 92% for MRI scans and 96% for computed tomography (CT) scans. The intra-operatively assessed extent of BONJ correlated significantly with the measurements on CT scans (p = 0.0004) but did not correlate significantly with the measurements in MRI scans (p = 0.241). The intra-operatively measured extent of BONJ differed significantly from the CT measurements (p = 0.00003) but not from the MRI data (p = 0.137). Although MRI as well as CT have a high detectability for BONJ lesions that exceeds that of panoramic radiographs by far, both techniques show problems with the exact assessment of the extent of BONJ lesions in the individual patients. Therefore, the relevance of MRI and CT for the preoperative assessment of the extent of BONJ lesions is limited. Future research should focus on the identification of imaging techniques that allow assessing the extent of BONJ lesions with a higher accuracy.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Doenças Maxilomandibulares/diagnóstico , Imageamento por Ressonância Magnética , Osteonecrose/diagnóstico , Radiografia Panorâmica , Tomografia Computadorizada por Raios X , Idoso , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Medula Óssea/cirurgia , Meios de Contraste , Feminino , Seguimentos , Gadolínio , Humanos , Imidazóis/efeitos adversos , Doenças Maxilomandibulares/diagnóstico por imagem , Doenças Maxilomandibulares/cirurgia , Masculino , Doenças Mandibulares/diagnóstico , Doenças Mandibulares/diagnóstico por imagem , Doenças Mandibulares/cirurgia , Doenças Maxilares/diagnóstico , Doenças Maxilares/diagnóstico por imagem , Doenças Maxilares/cirurgia , Compostos Organometálicos , Osteólise/diagnóstico , Osteólise/diagnóstico por imagem , Osteólise/cirurgia , Osteonecrose/diagnóstico por imagem , Osteonecrose/cirurgia , Pamidronato , Ácido Zoledrônico
17.
Dis Markers ; 27(2): 75-84, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19893202

RESUMO

OBJECTIVE: Melanoma associated antigens-A (MAGE-A) expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC). METHODS: Total of 70 OSSC and 20 normal oral mucosal (NOM) samples of otherwise healthy volunteers were examined for the expression of 10 different single antigens out of 12 different MAGE-A subtypes by highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) methods. The results were correlated to clinicopathological parameters of tumor samples. RESULTS: Expression of MAGE-A was restricted to OSCC. The expression frequency of single antigen was between 10% and 55%. However, expression rate was increased up to 93% by the elevated number of genes examined. A significant correlation was found between the expression of MAGE-A and malignancy (p = 0.0001). In addition, multiple MAGE-A detection has also correlated to the incidence of lymph node metastasis, grading and advanced clinical stages. CONCLUSIONS: Analysis of multiple MAGE-A expression is more sensitive than the analysis of a single MAGE-A for the diagnostic evaluation of OSCC. Multiple MAGE-A expression analysis may be a very sensitive method to be used for the diagnosis even in the early stage of OSCC.


Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
J Reconstr Microsurg ; 25(9): 545-53, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19697284

RESUMO

The aims of the present study were to check for metabolism of the bony segments of osteocutaneous free flaps that included lateral as well as medial scapular crests by 18F-fluoride positron emission tomography (PET)/computed tomography (CT) examinations and to assess donor site morbidity. Twenty patients were included in the study. In 10 patients, osteocutaneous free flaps were harvested that included lateral as well as medial scapular crests. Seven days after surgery, an 18F-fluoride PET/CT examination was performed to assess the metabolism and viability of the bony segments. In the additional 10 patients, flaps were harvested that only included the lateral scapular crest. All patients were asked to fill in the disabilities of the arm, shoulder, and hand (DASH) questionnaire 1 and 6 months after surgery. In the 10 free flaps that included lateral as well as medial scapular crests, 18F-fluoride PET/CT examinations revealed metabolism and viability of both bony segments. The DASH scores for the two patient groups did not differ significantly at 1 and 6 months after surgery (p(1 month) = 0.520, p(6 months) = 0.545). It seems that scapular osteocutaneous free flaps adopting lateral as well as medial scapular crests are a viable option for mandibular reconstruction and may be an alternative to the fibular double barrel.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Mandibulares/cirurgia , Neoplasias Bucais/cirurgia , Escápula/metabolismo , Escápula/transplante , Retalhos Cirúrgicos/irrigação sanguínea , Idoso , Avaliação da Deficiência , Feminino , Humanos , Masculino , Mandíbula/cirurgia , Pessoa de Meia-Idade , Esvaziamento Cervical , Tomografia por Emissão de Pósitrons , Procedimentos de Cirurgia Plástica , Escápula/irrigação sanguínea , Escápula/cirurgia , Retalhos Cirúrgicos/fisiologia , Sobrevivência de Tecidos/fisiologia , Tomografia Computadorizada por Raios X
20.
Anticancer Res ; 29(8): 3191-3, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19661334

RESUMO

BACKGROUND: The ataxia-telangiectasia-mutated gene (ATM) product is a well-characterized tumour suppressor that plays a key role in the maintenance of genomic stability. Given the fact that the loss of heterozygosity at the ATM locus is common in head and neck tumours, we investigated the possible association of 7636del9, which is the most frequent ATM deletion, with risk for oral cancer. PATIENTS AND METHODS: The 7636del9 9nt deletion was investigated in DNA samples of 67 German and Greek patients with oral cancer and 57 healthy controls of equivalent ethnicity, age and gender, by polymerase chain reaction (PCR) followed by electrophoretic analysis. RESULTS: The anticipated deleted sequence was not detected in any of the DNA samples of oral cancer patients or controls. CONCLUSION: The findings of the present study indicated no association of the most common mutation in the ATM gene with risk for oral cancer.


Assuntos
Ataxia Telangiectasia/genética , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Neoplasias Bucais/genética , Proteínas Serina-Treonina Quinases/genética , Deleção de Sequência , Proteínas Supressoras de Tumor/genética , Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma de Células Escamosas/secundário , Estudos de Casos e Controles , Humanos , Neoplasias Bucais/patologia
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