Bcl-2 expression in cell lines breast cancer and death program.

Breast cancer is a hormone-dependence and heterogenic disease. Drug resistance is the main reason for the failure of breast cancer treatment. Combinatory medications are methods for treatment but they are not sufficient in action. However, new approaches like molecular therapy reveal a new insight into cancer treatment. Studies show that Bcl-2 gene family inhibitors and ER blockers cause the improvement of recovery. Interfering molecules such as antisense ones can inhibit the expression of Bcl-2 and push the cancer cells to apoptosis. Our team designed a new Antisense Oligonucleotide (ASO) based on Antisense oligo G3139. MCF-7 and MDA-MB-231 cell lines were used to evaluate cellular proliferation. Liposomes and cationic nano-complex (Niosome) are used to increase the cellular delivery of ASO and Tamoxifen. We also investigated the cytotoxicity and apoptotic effects of Tamoxifen, naked ASO and Nano-packed ASO. The results indicated significant down-regulation of the Bcl-2 gene and inhibition of MCF-7 and MDA-MB-231 cellular proliferation. Flow-cytometry showed early apoptosis in all cell groups. The newly designed ASO reduced the expression of the Bcl-2 gene. It also had a synergistic effect with the Tamoxifen. The cationic nano-complex (Niosome) was more efficient than the liposome in delivering designed oligo antisense Bcl-2 in the cancer cells.

An in silico comparative transcriptome analysis identifying hub lncRNAs and mRNAs in brain metastatic small cell lung cancer (SCLC).

Small cell lung cancer (SCLC) is a particularly lethal subtype of lung cancer. Metastatic lung tumours lead to most deaths from lung cancer. Predicting and preventing tumour metastasis is crucially essential for patient survivability. Hence, in the current study, we focused on a comprehensive analysis of lung cancer patients' differentially expressed genes (DEGs) on brain metastasis cell lines. DEGs are analysed through KEGG and GO databases for the most critical biological processes and pathways for enriched DEGs. Additionally, we performed protein-protein interaction (PPI), GeneMANIA, and Kaplan-Meier survival analyses on our DEGs. This article focused on mRNA and lncRNA DEGs for LC patients with brain metastasis and underlying molecular mechanisms. The expression data was gathered from the Gene Expression Omnibus database (GSE161968). We demonstrate that 30 distinct genes are up-expressed in brain metastatic SCLC patients, and 31 genes are down-expressed. All our analyses show that these genes are involved in metastatic SCLC. PPI analysis revealed two hub genes (CAT and APP). The results of this article present three lncRNAs, Including XLOC_l2_000941, LOC100507481, and XLOC_l2_007062, also notable mRNAs, have a close relation with brain metastasis in lung cancer and may have a role in the epithelial-mesenchymal transition (EMT) in tumour cells.

Diagnostic of Cytokeratin-19 Gene Expression in Iranian Breast Cancer Patients.

Sentinel lymph node (SLN) biopsy is currently the recommended procedure for axillary staging in clinically node-negative early breast cancer at diagnosis. The present study aimed to identify Cytokeratin-19 (CK19) gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor samples from breast cancer patients were analyzed for the expression of the CK19 gene using quantitative PCR. Also, normal breast tissues (N = 50) were taken from the same patients that had undergone partial or total mastectomy. This gene signature was confirmed based on tumor's stage, grade, and estrogen receptor (ER) status, using conditional logistic regression. Based on these findings, the negative reported lymph nodes for metastasis had micrometastasis in significant values. There was a significant difference between normal and cancer samples in  CK19 expression. In this sentinel node evaluation, the relationship of this gene with tumor characteristics needs to be established and discussed finding a clear role for this gene in tumor outcome.

Are Estrogen Receptor Genomic Aberrations Predictive of Hormone Therapy Response in Breast Cancer?

CONTEXT: Breast cancer is the most common cancer in women worldwide. Estrogen receptor (ER) positive breast cancer constitutes the majority of these cancers. Hormone therapy has significantly improved clinical outcomes for early- and late-stage hormone receptor positive breast cancer. Although most patients with early stage breast cancer are treated with curative intent, approximately 20% - 30% of patients eventually experience a recurrence. During the last two decades, there have been tremendous efforts to understand the biological mechanisms of hormone therapy resistance, with the ultimate goal of implementing new therapeutic strategies to improve the current treatments for ER positive breast cancer. Several mechanisms of hormone therapy resistance have been proposed, including genetic alterations that lead to altered ER expression or ERs with changed protein sequence. EVIDENCE ACQUISITION: A Pubmed search was performed utilizing various related terms. Articles over the past 20 years were analyzed and selected for review. RESULTS: On the basis of published studies, the frequencies of ESR1 (the gene encoding ER) mutations in ER positive metastatic breast cancer range from 11% to 55%. Future larger prospective studies with standardized mutation detection methods may be necessary to determine the true incidence of ESR1 mutations. ESR1 amplification in breast cancer remains a controversial issue, with numerous studies either confirmed or challenged the reports of ESR1 amplification. The combination of intra-tumor heterogeneity regarding ESR1 copy number alterations and low level ESR1 copy number increase may account for these discrepancies. CONCLUSIONS: While numerous unknown issues on the role of ESR1 mutations in advanced breast cancer remain, these new findings will certainly deepen current knowledge on molecular evolution of breast cancer and acquired resistance to hormone therapy.

The analysis of association between SNCA, HUSEYO and CSMD1 gene variants and Parkinson's disease in Iranian population.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. Both genetic and environmental factors are involved in the etiology of the disease. Many studies have revealed the susceptibility genes and variations for PD which need further confirmation. Here we evaluated the association of variations in SNCA, HUSEYO and CSMD1 genes with PD. A case-control study was conducted with 489 PD patients and 489 healthy controls. DNA was extracted from peripheral blood of all subjects and rs356220 and rs11931074 in SNCA, rs2338971 in HUSEYO and rs12681349 in CSMD1 were genotyped using PCR-RFLP method. The genotypes and allele frequencies were significantly different between case and control groups for rs356220, rs11931074 and rs2338971 but not for rs12681349. We provided further evidence that rs356220 is associated with increased risk of PD supporting previous studies in Caucasian-based and Japanese populations. The association of rs11931074 with decreased risk of PD was also significant. This study revealed the first evidence of the association of rs2338971 with increased risk of PD in the Iranian population. Nevertheless, these findings need further validation via more replication studies.