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1.
Mol Oncol ; 8(5): 1043-53, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24785097

RESUMO

Ral (Ras like) leads an important proto-oncogenic signaling pathway down-stream of Ras. In this work, RalA was found to be significantly overactivated in hepatocellular carcinoma (HCC) cells and tissues as compared to non-malignant samples. Other elements of RalA pathway such as RalBP1 and RalGDS were also expressed at higher levels in malignant samples. Inhibition of RalA by gene-specific silencing caused a robust decrease in the viability and invasiveness of HCC cells. Additionally, the use of geranyl-geranyl transferase inhibitor (GGTI, an inhibitor of Ral activation) and Aurora kinase inhibitor II resulted in a significant decrease in the proliferation of HCC cells. Furthermore, RalA activation was found to be at a higher level of activation in HCC stem cells that express CD133. Transgenic mouse model for HCC (FXR-Knockout) also revealed an elevated level of RalA-GTP in the liver tumors as compared to background animals. Finally, subcutaneous mouse model for HCC confirmed effectiveness of inhibition of aurora kinase/RalA pathway in reducing the tumorigenesis of HCC cells in vivo. In conclusion, RalA overactivation is an important determinant of malignant phenotype in differentiated and stem cells of HCC and can be considered as a target for therapeutic intervention.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas ral de Ligação ao GTP/antagonistas & inibidores , Proteínas ral de Ligação ao GTP/genética , Animais , Aurora Quinases/antagonistas & inibidores , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inativação Gênica , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Terapia de Alvo Molecular , Transdução de Sinais/efeitos dos fármacos
2.
Ann Thorac Surg ; 95(5): 1797-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23608267

RESUMO

Adrenocorticotropic hormone (ACTH) overproduction within the pituitary gland or ectopically leads to hypercortisolism. In this study a case of Cushing's syndrome caused by an ectopic ACTH-secreting carcinoid tumor in lung is discussed, as are the available diagnostic procedures. The patient was a 28-year-old woman with clinical features starting about 6 months previously. The results of her biochemical tests suggested ectopic Cushing's syndrome. Full-body computed tomography revealed a single nodule in the inferior lobe of the right lung. After removal of the nodule, the patient's symptoms subsided clinically, and laboratory tests confirmed remission of the hypercortisolism.


Assuntos
Síndrome de ACTH Ectópico/etiologia , Tumor Carcinoide/complicações , Síndrome de Cushing/etiologia , Neoplasias Pulmonares/complicações , Adulto , Feminino , Humanos
3.
Iran J Public Health ; 42(1): 79-85, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23514804

RESUMO

BACKGROUND: Human papilloma virus causes benign and malignant abnormalities in different part of the body. The link between high risk types of HPV and some anogenital and aerodigestive tract cancer is well established. Oral HPV infection plays a role in developing oropharyngeal squamous cell carcinoma. We studied the prevalence of oral HPV in healthy individuals and its relative risk factors. METHODS: Saliva samples of 114 healthy subjects were collected for HPV DNA analysis. Volunteers completed questionnaires and signed a written consent. For data analysis descriptive statistic, chi square test and odds ratio was used. RESULTS: The frequency of oral HPV in healthy individuals was 6.1 %(seven participant).The most frequent type was HPV-18 in five of them. HPV-6 and HPV-66 each was detected in one case. Relation of oral HPV positivity to demographic features and risk factors was not statistically significant. CONCLUSIONS: The prevalence of oral HPV infection in our community is the same as many other communities of developing countries, stressing that HPV-18 were the dominant type.

4.
Health Promot Perspect ; 1(1): 50-3, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-24688899

RESUMO

BACKGROUND: Leukemia is cancer of the blood or bone marrow, characterized by an unusual increase in white blood cells. It is the sixth most common malignancy in the country in both males and females. The aim of this study was to document some epidemiological features of leukemia in the Northwest of Iran. METHODS: The study subjects (n=669, including 377 males and 292 females) comprised all leukemia cases registered/notified to the clinical and pathology centers of Tabriz and Ardebil cities, from 2003 to 2006. All patients were classified using the ICD-10 based coding system (C91-C95, C77 and C42). Ninety-five percent confidence intervals were calculated to assess the statistical significance of the data. RESULTS: Annual incidence of leukemia was 3.7 [95% CI: 3.3-4.0] and 4.9 [95% CI: 4.2-5.6] per 100 000 population in Tabriz and Ardebil, respectively, with an overall case fatality rate of 13.5 percent [95% CI: 10.8-16.0]. The sex ratio (male/female) was 1.23. Myeloid leukemia (C92) and Hematopoetic and Reticuloendothelial system (C42) accounted proportionally for more than 47 percent of cases in the region. Over the study period, the annual occurrence of leukemia in the region increased from 3.9 [95% CI: 3.4-4.5] to 4.1 [95% CI: 3.5-4.6] per 100 000 population (P>0.1). CONCLUSIONS: The data from this cross-sectional study of leukemia in the North-West of Iran may be used as the baseline information to establish a population-based registry of hema-tologic disorders in the area for health care and research purposes. However, more investiga-tions are needed to develop effective strategies to control the relevant disorders in high-risk groups.

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