RESUMO
Herein, we designed a DNA framework-based intelligent nanorobot using toehold-mediated strand displacement reaction-based molecular programming and logic gate operation for the selective and synchronous detection of miR21 and miR125b, which are known as significant cancer biomarkers. Moreover, to investigate the applicability of our design, DNA nanorobots were implemented as capping agents onto the pores of MSNs. These agents can develop a logic-responsive hybrid nanostructure capable of specific drug release in the presence of both targets. The prosperous synthesis steps were verified by FTIR, XRD, BET, UV-visible, FESEM-EDX mapping, and HRTEM analyses. Finally, the proper release of the drug in the presence of both target microRNAs was studied. This Hybrid DNA Nanostructure was designed with the possibility to respond to any target oligonucleotides with 22 nucleotides length.
Assuntos
MicroRNAs , Nanoestruturas , Neoplasias , Humanos , MicroRNAs/análise , MicroRNAs/genética , Biomarcadores Tumorais/genética , Neoplasias/genética , DNA/química , Nanoestruturas/químicaRESUMO
MAIN PURPOSE: This study aimed to determine any association of KRAS and BRAF mutations in colorectal cancer with clinicopathological features and overall survival (OS) of Southeast Iranian colorectal cancer (CRC) patients. METHODS: Overall, KRAS and BRAF status were assessed in 100 Iranian CRC subjects. A hundred consecutive stages I-IV CRC patients, who underwent surgical tumor resection from February 2012 to August 2015, were prospectively attained from three centers and were enrolled in the research. Direct sequencing and real-time PCR methods were used to the detection of KRAS and BRAF mutations, respectively. Logistic regression models were used to detect associations of KRAS and BRAF mutations with clinical/clinicopathological features. Kaplan-Meier model was used to estimate overall survival. RESULTS: In total, KRAS and BRAF mutations were detected in 29 (29%) and 7 (7%) of 100 CRC patients, respectively. BRAF mutations that all comprised V600E and KRAS mutations were found in codon 12, 13, and 61 (72.4%, 20.7 and 6.9%), respectively. In a multivariate analysis, older age (≥ 60) was significantly associated with higher KRAS mutations rate and high BRAF mutation rate was significantly associated with older age (≥ 60) and poorly differentiated tumors. KRAS and BRAF mutant vs. wild type of KRAS and BRAF, 5-year OS was 62.1% vs. 71.8% (p value > 0.05) and 57.1% vs. 67.7% (p value > 0.05), respectively. CONCLUSION: Mutations were found in both KRAS and BRAF genes in Iranian colorectal cancers patients and were associated with clinical/clinicopathologic features. Our data emphasizes the importance of these molecular features in Iranian CRC patients.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular/genética , Colo/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Análise Mutacional de DNA , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Prospectivos , Reto/patologia , Medição de Risco/métodos , Fatores de Risco , Adulto JovemRESUMO
Cancer stem cells (CSCs), a subgroup of cancer cells, have self-renewal capacity and differentiation potential and drive tumor growth. CSCs are highly-resistant to conventional chemo-radio therapy. Phytochemicals were shown to be able to eliminate CSCs. Phytol is a diterpene alcohol with demonstrated anticancer effects. The current study compared the effect of phytol with retinoic acid (RA) as a well-known inducers of CSC differentiation and cisplatin, a common chemotherapy drug, on CSC markers in human embryonic carcinoma NCCIT cells. NCCIT cells were exposed to 10 mM RA for 14 day to induce differentiation. Moreover, NCCIT cells were treated with IC50 dose of cisplatin (12 µM) and phytol (40 µM) for 7 day. Real-time PCR showed that phytol was more effective that RA and cisplatin in down-regulating the CSC markers OCT4, NANOG, SOX2, ALDH1, ABCB1, CD44 and CD133. Percentage of SP (13%) and ABCB1+ (0.34%) in NCCIT cells decreased to 7% and 0.1% respectively after treatment with phytol. A very small proportion of NCCIT cells were positive for CD44 (0.2%) and CD133 (0.48%) and this fraction did not change significantly after treatment with three agents. In conclusion, phytol has the greatest inhibitory effect on CSC population and markers than RA and cisplatin.