RESUMO
INTRODUCTION: Xingu Indigenous Park (XIP) currently protects 16 ethnic Indigenous groups and is located in the central area of Brazil. XIP is the first and the largest Indigenous land to be recognized in the country. Community access is limited and restricted for the non-Indigenous population, and the Indigenous women are constantly dealing with shortages of medical care. High-risk human papillomavirus (HR-HPV) is the most common cause of cervical cancer and is detected in 99% of cervical precancers. HPV infections may be associated with bacterial agents such as Chlamydia trachomatis and Neisseria gonorrhoeae, which are also important causative agents of sexually transmitted infections and are responsible for the most frequent bacterial infections in the world. The present study evaluated the frequency and potential impact of Chlamydia trachomatis, Neisseria gonorrhoeae, and HR-HPV in the Indigenous women of XIP. METHODS: In this cross-sectional study, 992 cervical-vaginal samples were collected from Indigenous women, using a Cervex-Brush, and were immediately placed in a SurePath medium. All samples were submitted to the cobas® 4800 detection system for the identification of 14 different types of HR-HPV, and the multiplex Abbott RealTime CT/NG assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: HR-HPV was detected in 18.2% of women; 6% were positive for HPV16, 5% for HPV18, and 81% for other types of HR-HPV. Co-infections of HPV16 and other types was observed in 5% of women, and 3% had co-infections of HPV18 and other types. Moreover, 1.8% of women were positive for Chlamydia trachomatis, while Neisseria gonorrhoeae was not detected. In women with HR-HPV, 33% had Chlamydia trachomatis infections, 28% were positive for HR-HPV other than HPV16 or HPV18, and 5% had co-infections of HPV16 and the other types of HPV. Younger women were found to be more susceptible to HPV infections. CONCLUSION: The findings indicate a high frequency of HR-HPV and a considerable frequency of Chlamydia trachomatis in the Indigenous women of XIP. The detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and/or HR-HPV does not present evidence of a potential interrelationship for a combined pathogenic action in these women.
Assuntos
Infecções por Chlamydia , Coinfecção , Gonorreia , Infecções por Papillomavirus , Feminino , Humanos , Neisseria gonorrhoeae , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Chlamydia trachomatis , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Papillomavirus Humano , Estudos Transversais , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , GenitáliaRESUMO
Background: EGFR mutations are present in approximately 15−50% of non-small cell lung cancer (NSCLC), which are predictive of anti-EGFR therapies. At variance, NSCLC patients harboring KRAS mutations are resistant to those anti-EGFR approaches. Afatinib and allitinib are second-generation pan-EGFR drugs, yet no predictive biomarkers are known in the NSCLC context. In the present study, we evaluated the efficacy of pan-EGFR inhibitors in a panel of 15 lung cancer cell lines associated with the KRAS mutations phenotype. Methods: KRAS wild-type sensitive NCI-H292 cell line was further transfected with KRAS mutations (p.G12D and p.G12S). The pan-EGFR inhibitors' activity and biologic effect of KRAS mutations were evaluated by cytotoxicity, MAPK phospho-protein array, colony formation, migration, invasion, and adhesion. In addition, in vivo chicken chorioallantoic membrane assay was performed in KRAS mutant cell lines. The gene expression profile was evaluated by NanoString. Lastly, everolimus and pan-EGFR combinations were performed to determine the combination index. Results: The GI50 score classified two cell lines treated with afatinib and seven treated with allitinib as high-sensitive phenotypes. All KRAS mutant cell lines demonstrated a resistant profile for both therapies (GI50 < 30%). The protein array of KRAS edited cells indicated a significant increase in AKT, CREB, HSP27, JNK, and, importantly, mTOR protein levels compared with KRAS wild-type cells. The colony formation, migration, invasion, adhesion, tumor perimeter, and mesenchymal phenotype were increased in the H292 KRAS mutated cells. Gene expression analysis showed 18 dysregulated genes associated with the focal adhesion-PI3K-Akt-mTOR-signaling correlated in KRAS mutant cell lines. Moreover, mTOR overexpression in KRAS mutant H292 cells was inhibited after everolimus exposure, and sensitivity to afatinib and allitinib was restored. Conclusions: Our results indicate that allitinib was more effective than afatinib in NSCLC cell lines. KRAS mutations increased aggressive behavior through upregulation of the focal adhesion-PI3K-Akt-mTOR-signaling in NSCLC cells. Significantly, everolimus restored sensibility and improved cytotoxicity of EGFR inhibitors in the KRAS mutant NSCLC cell lines.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Afatinib/farmacologia , Afatinib/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Everolimo/farmacologia , Everolimo/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
INTRODUCTION: Alternative methods of dry storage and transportation may be a viable alternative to the use of liquid storage medium for cervical samples, especially for screening programs in places with few resources. OBJECTIVE: The objective of this study is to verify the viability and efficacy of human papillomavirus DNA (HPV-DNA) detection in cervical cell samples collected and stored on a Flinders Technology Associates (FTA) card (Whatman Indicating FTA® Elute Micro Card) and subsequently recovered in ethanol-based liquid medium and to compare the results to those obtained using samples stored directly in ethanol-based liquid medium. STUDY DESIGN: Thirty-four women submitted to ETZ (excision of the transformation zone of the cervix) were included in this study. Before ETZ, 2 samples of exfoliated cervical cells were collected from each woman by a doctor and stored in ethanol-based liquid medium and on an FTA card. DNA recovery from FTA samples was performed using ethanol-based liquid medium. Detection of HPV-DNA in the samples was performed using the Cobas® 4800 HPV Test Platform. RESULTS AND CONCLUSIONS: The HPV-DNA detection positivity rates were 70.6% for the samples collected directly in liquid medium and 64.7% for the samples stored on the FTA card, with high detection accuracy in the DNA samples recovered from the FTA card (area under the curve = 0.958; 95% confidence interval = 0.890-1.000). The concordance between the results obtained using the 2 storage media was 94.1% (Kappa = 0.866). These preliminary results suggest that collection of cervical material on an FTA card may be an alternative to storage in liquid medium since the liquid medium has some limitations. In addition, DNA recovery from the card using ethanol-based liquid medium streamlines the workflow in the laboratory and reduces the cost associated with reagents, thereby facilitating access to the HPV test in places with few resources and potentially improving cervical cancer screening.
Assuntos
DNA Viral/isolamento & purificação , Etanol , Filtração/instrumentação , Testes de DNA para Papilomavírus Humano , Papel , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Manejo de Espécimes/instrumentação , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , DNA Viral/genética , Feminino , Humanos , Gradação de Tumores , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Projetos Piloto , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVES: The objective of this study was to evaluate the frequency of human papillomavirus (HPV) in the oral cavity of women with and without abnormal cervical cytology and to determine whether there is an association of oral HPV infection with infection of the cervix or with cervical cancer precursor lesions. METHODS: The present study was conducted among 406 women, aged 18-82 years, who attended the Prevention Department of Barretos Cancer Hospital (HCB), Brazil due to a previous altered cervical cytology result. Oral rinse, cervical cytology and biopsy were collected at the same day. The participants also answered a questionnaire about socioeconomic characteristics and risk factors for cervical cancer. Molecular screening for HPV16, HPV18 and 12 other high-risk HPV types was performed on cervical and oral rinse specimens using Cobas 4800 (Roche Molecular Systems, USA). RESULTS: HPV was detected in the oral rinse of 3.9% of participants. Infection of the oral cavity with a non-HPV16 or 18 type was most frequent (81.2%), followed by HPV16 (18.7%). Infection with HPV in the cervix and oral cavity was present in 11 (2.7%) of participants. There were no differences observed in the smoking status (p value 0.62), mean age of first sexual intercourse (p value 0.25), mean age of the first oral sex (p value 0.90) or mean lifetime number of sexual partners (p value 0.08) between the participants with oral HPV infection or not. CONCLUSION: The presence of HPV infection in the oral cavity was low in the group of women with abnormal cervical cancer screening findings and a high rate of cervical HPV infection.
Assuntos
Boca/virologia , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Comportamento Sexual/estatística & dados numéricos , Parceiros Sexuais , Fumar/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/virologiaRESUMO
Methylation levels in tumor-suppressor genes and repetitive sequences have previously been used to study the relationship between environmental air pollution and epigenetic changes related to cancer. In this study, we measured the methylation profiles of the promoter regions CDKN2A, MLH1 and APC and the repetitive sequence LINE-1 in 59 workers exposed to the construction environment and in 49 unexposed workers. We also evaluated the micronuclei frequency and levels of trace elements in the blood of all workers. We evaluated of levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) at the construction site to characterize the environmental exposure. Our findings demonstrated that exposed workers exhibited significantly higher average levels of promoter methylation of CDKN2A, APC, and MLH1 genes and increased hypomethylation of the LINE-1 in comparison to unexposed workers (all p < 0.05). A higher frequency of micronuclei was observed in the exposed group (2 ± 2) compared to the unexposed group (1 ± 1) with p < 0.001. High levels of particulate matter (51â»841 µg/m³) and some PAHs were found in samples from the construction environment. In summary, we provide evidence of increased DNA damage and altered DNA methylation of exposed workers, suggesting that genomic approaches to biomonitoring may be an effective way of estimating future cancer risk for construction workers.
Assuntos
Metilação de DNA , Testes para Micronúcleos , Exposição Ocupacional/análise , Adulto , Poluentes Atmosféricos , Estudos de Casos e Controles , Dano ao DNA , Humanos , Masculino , Hidrocarbonetos Policíclicos Aromáticos/análise , Regiões Promotoras GenéticasRESUMO
Cervical cancer is the third most commonly diagnosed tumor type and the fourth cause of cancer-related death in females. Therapeutic options for cervical cancer patients remain very limited. Annona crassiflora Mart. is used in traditional medicine as antimicrobial and antineoplastic agent. However, little is known about its antitumoral properties. In this study the antineoplastic effect of crude extract and derived partitions from A. crassiflora Mart in cervical cancer cell lines was evaluated. The crude extract significantly alters cell viability of cervical cancer cell lines as well as proliferation and migration, and induces cell death in SiHa cells. Yet, the combination of the crude extract with cisplatin leads to antagonistic effect. Importantly, the hexane partition derived from the crude extract presented cytotoxic effect both in vitro and in vivo, and initiates cell responses, such as DNA damage (H2AX activity), apoptosis via intrinsic pathway (cleavage of caspase-9, caspase-3, poly (ADP-ribose) polymerase (PARP) and mitochondrial membrane depolarization) and decreased p21 expression by ubiquitin proteasome pathway. Concluding, this work shows that hexane partition triggers several biological responses such as DNA damage and apoptosis, by intrinsic pathways, and was also able to promote a direct decrease in tumor perimeter in vivo providing a basis for further investigation on its antineoplastic activity on cervical cancer.
Assuntos
Annona , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Dano ao DNA , Feminino , Hexanos/química , Humanos , Neovascularização Patológica/tratamento farmacológico , Folhas de Planta , Solventes/química , Neoplasias do Colo do Útero/patologiaRESUMO
Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-α-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients.
Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Antimetabólitos/uso terapêutico , Antineoplásicos/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/análise , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/tratamento farmacológico , Acrilamidas/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/antagonistas & inibidores , Testes Diagnósticos de Rotina/métodos , Resistencia a Medicamentos Antineoplásicos , Feminino , Glucose/metabolismo , Humanos , Lapatinib , Quinazolinas/uso terapêutico , Nanomedicina Teranóstica/métodos , Usos TerapêuticosAssuntos
Aminoácidos , Cálcio , Leucina , Micronutrientes , Ciências da Nutrição , Proteínas , Vitamina DRESUMO
OBJECTIVE: Micronuclei (MN) are biomarkers that can be applied to buccal epithelial cells to assess populations occupationally exposed to potentially carcinogenic agents. Liquid-based cytology (LBC) is a way to improve and refine the results obtained by this test. STUDY DESIGN: Exfoliated buccal cells were collected from 40 subjects (20 construction workers from the Barretos Cancer Hospital and 20 administrative staff from the same institution). LBC and three stains (Feulgen/fast green, Papanicolaou and Giemsa) were used to prepare the slides. Student's t test was applied for statistical comparisons of the data. A p value of <0.05 was considered statistically significant. RESULTS: Regardless of the stain employed, the frequency of MN was greater in the case group (Feulgen/fast green: 5.15; Papanicolaou: 29; Giemsa: 26) than in the control group (Feulgen/fast green: 2.30; Papanicolaou: 17; Giemsa: 15). CONCLUSIONS: Using LBC to prepare slides and evaluate the frequency of MN potentially serves as a screening option for more comprehensive studies of cancer risk among populations occupationally exposed to potentially carcinogenic agents. In addition, the residual fluid enables the preparation of slides for DNA-specific stains that can be compared to those with Papanicolaou stain.
Assuntos
Carcinógenos Ambientais/efeitos adversos , Citodiagnóstico/métodos , Células Epiteliais/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Mucosa Bucal/efeitos dos fármacos , Manejo de Espécimes/métodos , Adulto , Corantes Azur , Brasil , Estudos de Casos e Controles , Corantes , Células Epiteliais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Teste de Papanicolaou , Valor Preditivo dos Testes , Fatores de Risco , Corantes de Rosanilina , Coloração e Rotulagem/métodos , Adulto JovemRESUMO
A cardiopatia congênita é a manifestação da alteração na estrutura cardiovascular normal ou da incapacidade da estrutura atingir desenvolvimento completo durante o período fetal, produ-zindo graus variáveis de disfunção circulatória, podendo afetar o crescimento e estado nutricional de crianças, sendo a desnutrição o fator de risco mais importante de morbimortalidade nesses pacientes. Objetivo: Descrever o perfil nutricional de crianças e adolescentes com cardiopatia em período pré-operatório sob regime de internação. Método: Estudo transversal com coleta de dados de crianças e adolescentes de ambos os gêneros internados na enfermaria pediátrica em um hospital de cardiologia de janeiro a março de 2012. Foram mensuradas as medidas de peso e estatura e calculados os escores-z de peso/idade, peso/estatura, estatura/idade, Índice de Massa Corporal (IMC)/idade segundo as curvas de crescimento da Organização Mundial da Saúde. A classificação do estado nutricional foi realizada de acordo com a recomendação do Sistema de Vigilância Alimentar e Nutricional - SISVAN. Resultados: Foram avaliados 60 pacientes. Segundo o índice peso/estatura, 54,3% crianças foram classificadas como eutróficas, 33,3% desnutridas e 11,9% apresentaram excesso de peso. De acordo com o IMC/idade, 51,7% dos pacientes eram eutróficos, 30% eram desnutridos e 21% com excesso de peso. Conclusão: Este grupo estudado apresentou elevada proporção de desnutrição segundo o índice peso/estatura e IMC/estatura, o que pode acarretar no aumento da morbidade e mortalidade desses pacientes. (AU)
Assuntos
Humanos , Avaliação Nutricional , Período Pré-Operatório , Cardiopatias CongênitasRESUMO
Os autores investigam através de atendimento clínico, a interferência do stress na disfunçäo da ATM (articulaçäo temporomandibular), e 48 pacientes atendidos pelo Centro de Disfunçäo Craniomandibular da UNIP. Observa-se que 89,6 por cento dos pacientes necessitam de atendimento psicológico, enquanto que 10,4 por cento dos pacientes näo necessitam de tal atendimento. Os autores acreditam que há interferência do stress na sintomatologia da disfunçäo da ATM