Suppression of chronic inflammation with engineered nanomaterials delivering nuclear factor κB transcription factor decoy oligodeoxynucleotides

As a prototypical pro-inflammatory transcription factor, constitutive activation of NF-κB signaling pathway has been reported in several chronic inflammatory disorders including inflammatory bowel disease, cystic fibrosis, rheumatoid arthritis and cancer. Application of decoy oligodeoxynucleotides (ODNs) against NF-κB, as an effective molecular therapy approach, has brought about several promising outcomes in treatment of chronic inflammatory disorders. However, systematic administration of these genetic constructs is mostly hampered due to their instability, rapid degradation by nucleases and poor cellular uptake. Both chemical modification and application of delivery systems have shown to effectively overcome some of these limitations. Among different administered delivery systems, nanomaterials have gained much attention for delivering NF-κB decoy ODNs owing to their high loading capacity, targeted delivery and ease of synthesis. In this review, we highlight some of the most recently developed nanomaterial-based delivery systems for overcoming limitations associated with clinical application of these genetic constructs

Stimuli-Responsive Mesoporous Silica NPs as Non-viral Dual siRNA/Chemotherapy Carriers for Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer. It is associated with a very poor prognosis and intrinsically resistant to several conventional and targeted chemotherapy agents and has a 5-year survival rate of less than 25%. Because the treatment options for TNBC are very limited and not efficient enough for achieving minimum desired goals, shifting toward a new generation of anti-cancer agents appears to be very critical. Among recent alternative approaches being proposed, small interfering RNA (siRNA) gene therapy can potently suppress Bcl-2 proto-oncogene and p-glycoprotein gene expression, the most important chemotherapy resistance inducers in TNBC. When resensitized, primarily ineffective chemotherapy drugs turn back into valuable sources for further intensive chemotherapy. Regrettably, siRNA’s poor stability, rapid clearance in the circulatory system, and poor cellular uptake mostly hampers the beneficial outcomes of siRNA therapy. Considering these drawbacks, dual siRNA/chemotherapy drug encapsulation in targeted delivery vehicles, especially mesoporous silica nanoparticles (MSNs) appears to be the most reasonable solution. The literature is full of reports of successful treatments of multi-drug-resistant cancer cells by administration of dual drug/siRNA-loaded MSNs. Here we tried to answer the question of whether application of a similar approach with identical delivery devices in TNBC is rational

Comparing the Efficacy of High and Low Doses of Vitamin A in Prevention of Bronchopulmonary Dysplasia

Background Bronchopulmonary dysplasia (BPD) is one of the most common serious squeal of preterm infants. It involves approximately one quarter of infants with birth weight less than 1500 grams and 30% of less than 1000 grams. Vitamin A has been shown to reduce BPD rate. We compared efficacy of low and high doses of vitamin A for prevention of BPD in very low birth weight preterm infants. Materials and Methods In a randomized clinical trial, 120 preterm infants with gestation age 32 weeks or less and birth weight less than 1,500 grams were enrolled in the study. Group A (n=60) received 1,500 IU vitamin A intramuscularly three times per week and group B (n=60) received 5,000 IU vitamin A intramuscularly 3 times/week. Vitamin A was continued for 4 weeks in all patients. Oxygen dependency at age 28 days after birth and at 36 weeks’ postmenstrual age was determined in all studied infants. Results The mean gestation age and birth weight in group A was 29.2 ± 2.1 weeks and 1095 ± 211 gr and in group B 28.7 ± 2.1week and 1147 ± 218 grams (P>0.05). Moderate to severe bronchopulmonary dysplasia was detected in 6 (10%) neonates in group A and 13(21.6%) infants in group B, P= 0.09. Mortality rate was 4 (6.6%) infants in group A and 3 (5%) patients in group B (P>0.05). Conclusion In our study, high and low doses of vitamin A were similar with respect to the BPD, intra-ventricular hemorrhage, and retinopathy of prematurity and total number of days for hospital stay in very low birth weight preterm infants

PIWIL2 and PL2L60 (Cancer/Testis genes) Expression in Breast Cancer

Background: Cancer/testis antigens (CTAs) are members of a group of proteins which are normally expressed in testis germ cells and to a lesser extent in the ovaries. Because of recent reports about their aberrant and specific expression in some tumoral tissues, they may play a role as new candidates for targeted therapy. Therefore, the study of the expression pattern of these biomarkers and its relationship with clinical features of the patients is a subject of great interest. Methods: In this study, expression of PIWIL2 and genes was studied by multiplex RT-PCR in 65 breast tissue samples including 30 invasive ductal carcinomas (IDC), 30 normal adjacent tissue samples and five normal breast tissue samples and 2 normal testicular tissue samples as positive controls. beta actin was considered as internal control. Results: Results of gel electrophoresis analysis demonstrated no significant expression of target genes in any sample except testis. Simultaneously, beta actin was expressed in all the samples. Conclusions: The present study indicates lack of PIWIL2 and PL2L60 expression at mRNA level in breast cancer. Although cell lines can be used in cancer research, they are not representative of tumor tissues. More studies investigating the expression of these genes at protein level will help us decide whether to apply these candidate genes as tumor markers or not

The A-kinase anchoring proteins correlation with disease free survival in breast cancer

Background: Researchers are always trying to find specific markers which express specifically in cancer. These specific markers help to diagnose and treat cancer without affecting normal tissues. Cancer-testis antigens are among the new promising biomarkers, especially for targeted therapy. These markers are specially expressed in testis. Various studies have been reported individual expression of these proteins in some tumor tissues. Since testis is an immune privilege organ, abnormal expression of the above mentioned genes raises immune response and the serum antibody against them (CT antigene) can be detected as a marker of cancer. However, understanding their differential role in normal and cancer tissues may introduce them as new candidates of cancer biomarkers. The aim of this study was to evaluate AKAP3 gene expression in breast cancer and its correlation with clinicopathologic features of the disease. Methods: This study is a case-control study conducted at the Brest Cancer Research Center (BCRC)- Iran, between October 2014 to May 2016. AKAP3 gene expression was investigated with real-time PCR in breast samples including: 74 tumors, 73 normal adjacents and 15 normal tissues. On the other hand the correlation between gene expression, clinicopathologic features of the tumors and treatment regimen were evaluated. Results: Statistical analysis showed a significant correlation between lack of AKAP3 expression, tumor size (P=0.01) and stage (P=0.04). The association between poor prognosis and the absence of AKAP3 expression in normal adjacent tissues were observed. Kaplan Meier plot showed a significant better disease free survival in the normal adjacent patients group that are expressed AKAP3. Conclusion: It was observed that the better free survival in the normal adjacent group is because of the different AKAP3 expression, not treatment variations between two patient groups. As a result, AKAP3 can be a suitable candidate biomarker for breast cancer patients. Also, the study of gene expression in normal tissue of patients may be used to predict response to therapy

Unique CD44 intronic SNP is associated with tumor grade in breast cancer: a case control study and in silico analysis

Abstract Background CD44 encoded by a single gene is a cell surface transmembrane glycoprotein. Exon 2 is one of the important exons to bind CD44 protein to hyaluronan. Experimental evidences show that hyaluronan–CD44 interaction intensifies the proliferation, migration, and invasion of breast cancer cells. Therefore, the current study aimed at investigating the association between specific polymorphisms in exon 2 and its flanking region of CD44 with predisposition to breast cancer. Methods In the current study, 175 Iranian female patients with breast cancer and 175 age-matched healthy controls were recruited in biobank, Breast Cancer Research Center, Tehran, Iran. Single nucleotide polymorphisms of CD44 exon 2 and its flanking were analyzed via polymerase chain reaction and gene sequencing techniques. Association between the observed variation with breast cancer risk and clinico-pathological characteristics were studied. Subsequently, bioinformatics analysis was conducted to predict potential exonic splicing enhancer (ESE) motifs changed as the result of a mutation. Results A unique polymorphism of the gene encoding CD44 was identified at position 14 nucleotide upstream of exon 2 (A37692→G) by the sequencing method. The A > G polymorphism exhibited a significant association with higher-grades of breast cancer, although no significant relation was found between this polymorphism and breast cancer risk. Finally, computational analysis revealed that the intronic mutation generated a new consensus-binding motif for the splicing factor, SC35, within intron 1. Conclusions The current study results indicated that A > G polymorphism was associated with breast cancer development; in addition, in silico analysis with ESE finder prediction software showed that the change created a new SC35 binding site

Clinical significance of NDRG3 in patients with breast cancer

[Aim]: The expression level of NDRG3 gene is investigated among breast cancer (BC) patients.[Methods]: Real-time quantitative PCR was performed.[Results]: NDRG3 was downregulated in BC patients particularly in advanced stage of the disease. HER2 status was significantly correlated with the expression of NDRG3. Also, triple-negative BC patients showed low levels of NDRG3 expression in comparison to other subtypes. Lastly, the expression of NDRG3 had significant impact on survival, with NDRG3 downregulated patients having the worst event-free survival rate among others.[Conclusion]: We have presented that NDRG3 might be a tumor suppressor candidate. NDRG3 downregulation might be involved in the tumorigenesis and development of invasive BC in an advanced phase of the disease.Peer reviewe