RESUMO
OBJECTIVE: Recent studies have shown the role of autophagy in different types of cancer including lung cancer. MicroRNAs are considered as key factors in regulation of autophagy related genes. miR-30d, miR-204-5p and miR-20a are regulatory markers which can suppress the expression of beclin1, LC3, bcl2 and ULK1 as their target genes and they lead to decrement of autophagy in human cancer cells. Moreover, epigenetic modifications DNA methylation has been indicated in regulation of autophagy in different stages of cancer. METHODS: In this study, the expression levels of miR-30d, miR-204-5p and miR-20a as well as their target genes were analyzed in 30 non-small cell lung cancers (NSCLCs) patients sample and adjacent normal tissues by real-time qPCR. In addition, DNA methylation of beclin1, LC3, bcl2 and ULK1 genes were assessed by MS-HRM method. RESULTS: MiR-30d (p value= 0.01) and miR-204-5p (P=0.048) significantly down-regulated in tumor samples compared to normal adjacent tissues, while there was no significant change in expression level of miR-20a. On the other hand, target genes expression level was significantly increased in NSCLC tissues, however methylation pattern of the target gene promoters, did not show any significant alteration. CONCLUSION: These results indicate roles for miR-30d, miR-204-5p as tumor suppressor genes as well as target genes as oncogenes in NSCLC patients. Although these factors may have a significant role in NSCLC progression, further studies are necessary to investigate the implications of these findings for treatment of lung cancer.
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Assuntos
Adenocarcinoma de Pulmão/genética , Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Adenocarcinoma de Pulmão/patologia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Beclina-1/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Metilação de DNA , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/patologia , Masculino , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
BACKGROUND: Pregnancy loss affects 10%-15% of pregnancies and is caused by several factors, maternal and fetal. Most common cause is chromosomal aneuploidy and has traditionally been detected by karyotyping product of conception and/or fetal tissue. In recent years, array comparative genomic hybridization (a-CGH) has been used because of its higher detection and lower failure rates. METHODS: DNA was extracted from 1625 products of abortion or fetal tissue. In 1,104 cases both quantitative fluorescent-polymerase chain reaction (QF-PCR) and a-CGH, and in 521 cases only a-CGH, was performed. RESULTS: The detection rate using QF-PCR and a-CGH is 20% compared to 12.7%, overall, and 15.7%, excluding failed samples, by karyotypes in our center. QF-PCR and a-CGH failed in 1.9% of cases, while the failure rate for karyotypes was 20.1%. The difference of detection and failure rates is significant (p-value < 0.001 and p-value < 0.001 respectively). Unexpectedly we also found a significant difference in frequency of imbalances in related versus unrelated couples. (χ2 = 11.4926, p-value < 0.001). CONCLUSION: It is highly likely that the pregnancy loss in consanguineous couples is caused by other genetic and immune mechanisms. It is plausible that, through the same mechanism by which single gene disorders have a higher prevalence of manifesting disease in consanguineous couples, they can cause lethal genetic disorders leading to pregnancy loss and intra-uterine fetal death (IUFD) in these couples. Our findings suggest that this is a matter for further study as it will greatly influence the approach to counseling and managing consanguineous couples with pregnancy loss.
Assuntos
Aborto Espontâneo/genética , Aneuploidia , Consanguinidade , Feto Abortado/patologia , Aborto Espontâneo/patologia , Aborto Espontâneo/prevenção & controle , Hibridização Genômica Comparativa , Feminino , Aconselhamento Genético , Humanos , Irã (Geográfico) , Cariotipagem , GravidezRESUMO
MicroRNAs (miRNAs) exert a critical influence on physiological and pathological processes through posttranscriptional modification of their mRNA targets. They play important roles in tumorigenesis and are considered to be potential diagnostic and prognostic biomarkers with various cancers. MiR-200c and miR-9 are regulatory elements that can have dual impacts as oncogenes and/or tumor suppressor genes. MiR-200c regulates two transcription factors, ZEB1 and ZEB2, while miR-9 is a regulatory factor for the E-cadherin protein which has a critical function in cell-cell junctions and is inhibited by two transcription factors ZEB1 and ZEB2. In this study, expression levels of miR-200c and miR-9, ZEB-1, ZEB-2 and E-cadherin were assessed in 30 non-small cell lung cancers (NSCLCs) by real-time qPCR. MiR-9 was down-regulated significantly in tumor tissues compared to normal adjacent tissues, while there was no significant change in expression level of miR-200c. On the other hand, ZEB1 demonstrated significant increase and ZEB2a decrease at the mRNA level. These results indicate roles for miR-9 and ZEB1 in genesis of lung cancer, although clinico-pathological associations were not evident. Further studies are necessary to assess implications for treatment of lung cancer.
Assuntos
Antígenos CD/metabolismo , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Antígenos CD/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Caderinas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Estudos de Casos e Controles , Terapia Combinada , Feminino , Seguimentos , Humanos , Irã (Geográfico) , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genéticaRESUMO
Despite all advantages for using high-energy photons for radiotherapy, high-energy photon beams (≥10 MV) induce photonuclear and neutron capture interactions, which result in producing radionuclide byproducts inside the Linac head and bunker, exposing radiation therapy technologists (RTTs) and patients to excessive dose. By the use of higher photon energy, greater number of monitor unit, greater field size and adding treatment accessories, induced dose rate become greater in the isocenter mainly due to activation of high-Z materials inside the Linac head. Activated radionuclides disintegrate with γ, ß+ and ß- rays with half-lives between 2 min up to more than 5 years. Several researches estimated additional exposure to an RTT depend on treatment strategies, beam energy, and delay time before entrance to the treatment room between 0.1 and 4.9 mSv/y and proposed at least 2 min delay before entrance to the treatment room after treatments with high-energy photon beams.