Review article epithelial to mesenchymal transition­associated microRNAs in breast cancer.

Despite major advances, breast cancer (BC) is the most commonly diagnosed carcinoma and remains a deadly disease among women worldwide. Many researchers point toward an important role of an epithelial to mesenchymal transition (EMT) in BC development and promoting metastasis. Here, will be discussed that how functional changes of transcription factors, signaling pathways, and microRNAs (miRNA) in BC promote EMT. A thorough understanding the EMT biology can be important to determine reversing the process and design treatment approaches. There are frequent debates as to whether EMT is really relevant to BC in vivo, in which due to the intrinsic heterogeneity and tumor microenvironment. Nevertheless, given the importance of EMT in cancer progression and metastasis, the implementation of therapies against cancer-associated EMT will continue to help us develop and test potential treatments.

Sensitization of A-549 lung cancer cells to Cisplatin by Quinacrine-loaded lipidic nanoparticles via suppressing Nrf2 mediated defense mechanism.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is believed to be responsible for the control mechanisms of cellular defense response and master regulator of antioxidant system by adjustment of endogenous antioxidants, phase II detoxifying enzymes and transporters, so inhibition of Nrf2 could be considered molecule target to overcome drug resistance and cancer progression. By harnessing liposome as an advanced nanoparticles transporter, we formulated Quinacrine known as nrf2 inhibitor into nano-carrier, and sensitized A-549 lung tumor cells to Cisplatin. The aim of this work was to prepare liposome nano-carriers to enhance the bioavailability of Quinacrine and to improve passive targeting in A549 cells. Quinacrine formulation into liposome exposed a mean particle size of 80±5 nm in passive targeting and 110±3 after decoration with chitosan oligosaccharides (COS), respectively. The highest amount of cell death (p<0.05) occurred with the co-incubation of the A549 cells with new formulation and Cisplatin. Additionally, Quinacrine-loaded liposomes declined Nrf2 expression more than Quinacrine alone (p<0.05). Correspondingly, the expression of Nrf2 downstream genes, MRP1, Trx, and bcl2 decreased significantly. Taking all the data into consideration, liposomes containing Quinacrine could ameliorate the effectiveness of Cisplatin by raising the permeability of cancer cells to the abovementioned chemical treatment and might be then given as a candidate to boost the therapeutic protocols in cancer patients.

Formulation of Stattic as STAT3 inhibitor in nanostructured lipid carriers (NLCs) enhances efficacy of doxorubicin in melanoma cancer cells.

Nowadays, nanoparticle-based combination therapy has been emerging as huge innovation in cancer treatment. Here, we studied the effect of Stattic (STAT3 inhibitor) loaded in nanostructured lipid carriers (NLCs) on enhancing the efficacy, cytotoxicity, and induction of apoptosis of doxorubicin in B16F10 mouse melanoma cancer cell. The evaluation of Stattic-loaded NLCs has been done in terms of zeta potential, particle size, scanning electron microscope (SEM), and cellular uptake. MTT assay was applied to evaluate the cell proliferation. Apoptotic cell death and identification of early and late apoptosis were assessed by DAPI staining and Annexin V/PI staining, respectively. Real-time RT-PCR was applied to measure the effects of doxorubicin and/or Stattic on key apoptotic genes such as Bad, Survivin, HIF1, and STAT3. The Stattic formulated into NLCs shown mean particle size of 56 ± 7 nm which was confirmed by SEM. The IC50 values for Stattic and doxorubicin were 2.95 ± 0.52 µM and 1.21 ± 0.36 µM, respectively. Stattic-loaded NLCs diminished percent of cell proliferation from 68 ± 6.8 to 54 ± 3.7% (p < 0.05). Combinational treatment of the cells with Stattic-loaded nanoparticles and doxorubicin give rise to a significant increase in the percentage of apoptosis (p < 0.05). The study of gene expression profile has shown a remarkable decrease in anti-apoptotic gene, Survivin, along with smooth decline in HIF1 as angiogenesis intermediator and increase in Bad mRNA levels. Our results recommend that NLCs as novel technology have potent strategy to augment efficacy of current chemotherapeutic agent in melanoma cancer cells.

Molecular analysis of interleukin-10 gene polymorphisms in patients with Behçet's disease.

BACKGROUND: Interleukin 10 (IL-10) is a cytokine with potent anti-inflammatory properties that play a fundamental role in restrictive host immune response to pathogens, by means of that is a crucial importance for chronic inflammatory disease studies. Therefore, the goal of this study was to measure the correlation of the IL-10 gene polymorphisms with the susceptibility to Behçet's disease compared with the control group in the Azeri population and to determine the expression of this gene in the two groups. Also, real-time PCR was performed for evaluate the IL-10 mRNA expression of the associated polymorphisms. METHODS: In this study, blood samples from 47 (1 missed) patients and 58 (3 missed) healthy control were taken, and then mononuclear cells isolated with ficoll protocol. The DNA and RNA were subsequently extracted. They were examined for -592A/C (rs1800872) of IL-10 gene single nucleotide polymorphism (SNP) using RFLP-PCR. Allele and genotype distributions were evaluated among groups using chi-square or Fisher's test. Following this, the extracted RNA was converted to cDNA using the RT-PCR method, after that expression of IL-10 evaluated by Real-time PCR. Serum levels of IL-10 were measured using Enzyme-linked immunosorbent assay (ELISA). RESULTS: Rates of the rs1800872 A allele was statistically lower in the control group compared with BD patients (p = 0.0315 and OR = 1.90 (1.05-3.42)). Also, as we expected, the expression level of the IL-10 gene was seen to significantly decrease in the patient group compared to the control. CONCLUSIONS: Our study showed that the rs1800872 A allele of the IL-10 gene may contribute to the genetic susceptibility of BD by regulating the expression of IL-10. Also as we expected, the expression level of this gene was seen to significantly decrease in the patient group compared to the control.