The role of ASXL1 mutations and ASXL1 CircRNAs in cancer.

BACKGROUND: Mutations in the Additional Sex Combs Like 1 (ASXL1) gene were first reported in myelodysplastic syndromes. Recent studies have clarified the relationship between ASXL1 mutations and the development of cancers. OBJECTIVE: This study aims to review the roles of ASXL1 and ASXL1 CircRNAs, such as epigenetic regulation, chromatin modification, and transcription factor function in malignancies. METHOD: This study is a review of articles related to the role of ASXL1 and ASXL1 CircRNAs in malignancies, retrieved from PubMed and Scopus. RESULTS: ASXL1 plays a role in malignancies and is also related to poor overall survival and cancer metastasis. ASXL1 encodes conserved and abundant Circular RNAs (circRNAs) that act as post-transcriptional regulators, regulating tumorigenesis and progression in cancer. ASXL1 circRNA was identified in the top 10% of differentially expressed circRNAs in clinically relevant tissues. Additionally, the role of ASXL1 gene circRNAs in cancer development is reviewed in this study. CONCLUSION: ASXL1 and ASXL1circRNA have dual functions in combination with different proteins, being involved in both transcriptional activation and repression in a context-dependent manner. Moreover, studies indicate these genes play an important role in epithelial-mesenchymal transition (EMT) and metastasis. Ongoing research is aimed at determining this gene family's function in biological events.

Vitamin D and breast cancer risk: A systematic review and meta-analysis in Iranian patients.

•BsmI and TaqI have association with breast cancer risk in Iranian women.•No significant associations were identified between the FokI and ApaI and breast cancer risk in Iranian women.•No association was detected between Vitamin D level and breast cancer in Iranian women.

Expression of SCUBE2 and BCL2 Predicts Favorable Response in ERα Positive Breast Cancer.

BACKGROUND: The study aimed at evaluating steroid biomarker genes (ERα, PGR, ERß) and determining the expression level of estrogen-regulated genes (SCUB2 and BCL2) and growth factors receptors (HER2 and IGFR1) in cancer tissue samples obtained from Iranian patients with breast cancer. Moreover, relationships with clinicopathologic aspects of tumor and response to treatment were studied. METHODS: The current study was conducted on 246 breast tissue samples. The expression levels of these genes and their relationships with clinicopathologic aspects and treatment response were evaluated. RESULTS: Based on immunohistochemistry (IHC) results, 12% of the ER negative patients expressed ERα. Comparing the effects of ERα and coexpression of BCL2 and SCUBE2 on the survival of the patients demonstrated remarkably poorer survival in ERα positive, SCUBE2, and BCL2 negative groups in comparison with other patients, which was statistically significant in the log-rank analysis (P = 0.01). Evaluation of the effects of coexpression of HER2 and IGFR1 on patients' survival demonstrated a worse survival rate in patients with positive expression of both receptors, which was insignificant. CONCLUSION: Many studies suggest that PGR alone is not enough for the functional evaluation of ERα. Evaluation of the progesterone receptor expression as well as other genes such as BLC2, SCUBE2, and IGFR1, seems necessary to evaluate functionality.

Mesenchymal Stem Cells Pretreatment With Stromal-Derived Factor-1 Alpha Augments Cardiac Function and Angiogenesis in Infarcted Myocardium.

BACKGROUND: Stem cell therapy is among the novel approaches for the treatment of post-myocardial infarction cardiomyopathy. This study aims to compare the effect of stromal-derived factor 1 α (SDF1α), mesenchymal stem cells (MSCs) in combination with the lentiviral production of vascular endothelial growth factor (VEGF) on infarct area, vascularization and eventually cardiac function in a rat model of myocardial infarction (MI). METHODS: The influence of SDf1α on MSCs survival was investigated. MSCs were transduced via a lentiviral vector containing VEGF. After that, the effect of mesenchymal stem cell transfection of VEGF-A165 and SDf1α preconditioning on cardiac function and scar size was investigated in five groups of MI rat models. The MSC survival, cardiac function, scar size, angiogenesis, and lymphocyte count were assessed 72 hours and 6 weeks after cell transplantation. RESULTS: SDF1α decreased the lactate dehydrogenase release in MSCs significantly. Also, the number of viable cells in the SDF1α-pretreated group was meaningfully more than the control. The left ventricular systolic function significantly enhanced in groups with p240MSC, SDF1αMSC, and VEGF-A165MSC in comparison to the control group. CONCLUSIONS: These findings suggest that SDF1α pretreatment and overexpressing VEGF in MSCs could augment the MSCs' survival in the infarcted myocardium, reduce the scar size, and improve the cardiac systolic function.

Stemness Phenotype in Tamoxifen Resistant Breast Cancer Cells May be Induced by Interactions Between Receptor Tyrosine Kinases and ERα-66.

BACKGROUND: Tamoxifen is widely administered for patients with estrogen receptor-positive breast cancer. Despite many patients benefiting from Tamoxifen as an effective anti-hormonal agent in adjuvant therapy, a noticeable number of patients tend to develop resistance. OBJECTIVE: The aim of this study was to shed light upon the molecular mechanisms associated with Tamoxifen resistance which can help improve current treatment strategies available for stimulating responsiveness and combating resistance. METHODS: Relevant articles were obtained from PubMed and google scholar, nearly all dated from 2010 to 2017. Articles were screened to select the ones meeting the objective. The molecular interactions in the resistant network were extracted from the appropriate articles. RESULTS: The mechanisms of developing Tamoxifen resistance were briefly outlined. Overactivation of Receptor Tyrosine Kinases (RTKs) pathways, commonly known as alternative growth cascades, is one of the main players in acquired cancer cell stemness, which can induce unrestricted proliferation in the presence of Tamoxifen. There are seven recent patents including 6291496B1 as an anti-HER2, 8143226B2 as an inhibitor of RTK phosphorylation, 9062308B2 as an anti-HOXB7, Lapatinib functioning as an anti-EGFR/HER2, Everolimus as an inhibitor of mTOR, Exemestane as an aromatase inhibitor and Perifosine as an AKT inhibitor. CONCLUSION: Altogether, it seems that tumor cells express a stemness phenotype which tends to override anti-hormonal adjuvant therapies. Since RTKs are overactivated and overexpressed in such cells, specialized targeted therapies suppressing RTKs would be a novel and effective way in restoring Tamoxifen sensitivity in resistant breast cancer tumor cells.

Exosomes in Cancer Liquid Biopsy: A Focus on Breast Cancer.

The important challenge about cancer is diagnosis in primary stages and proper treatment. Although classical clinico-pathological features of the tumor have major prognostic value, the advances in diagnosis and treatment are indebted to discovery of molecular biomarkers and control of cancer in the pre-invasive state. Moreover, the efficiency of available therapeutic options is highly diminished, and chemotherapy is still the main treatment due to lack of enough specific targets. Accordingly, finding the new noninvasive biomarkers for cancer is still an important clinical challenge that is not achieved yet. There are current technologies to screen, diagnose, prognose, and treat cancer, but the limitations of these implements and procedures are undeniable. Liquid biopsy as a noninvasive method has a promising future in the field of cancer, and exosomes as one of the recent areas have drawn much attention. In this review, the potential capability of exosomes is summarized in cancer with the special focus on breast cancer as the second cause of cancer mortality in women all around the world. It discusses reasons to choose exosomes for liquid biopsy and the studies related to different potential biomarkers found in the exosomes. Moreover, exosome studies on milk as a specific biofluid are also discussed. At last, because choosing the method for exosome studies is very challenging, a summary of different techniques is provided.

High expression of CEACAM19, a new member of carcinoembryonic antigen gene family, in patients with breast cancer.

Carcinoembryonic antigen (CEA) family members play important roles in malignancies and are introduced as biomarkers in different types of cancers. Among them CEACAM19 (CEAL1) gene, a new member of the CEA family, remains to be fully elucidated. The aim of this study was investigating the mRNA expression level of CEACAM19 in tumor samples of breast cancer patients compared to breast tissue of normal individuals. We evaluated the expression level of this gene in 75 breast tumors by using real-time quantitative PCR. Also, we studied the correlation between CEACAM19 expression and clinicopathological features and hormone receptors status, including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 of patients. Out of the enrolled patients, six of them (7.9%) showed low expression, ten (13.2%) showed normal expression and 59 (77.6%) showed high expression of CEACAM19. There was a significant correlation between high expression of CEACAM19 gene in tumor samples compared to normal tissues (P = 0.039). No significant correlation was seen between clinicopathological factors and disease-free survival with mRNA levels of CEACAM19 in tumor samples, while the difference between the expression of CEACAM19 in ER/PR-positive and ER/PR-negative breast cancer patients was statistically significant (P = 0.046). In conclusion, CEACAM19 showed high expression in tumor samples compared to normal mammary tissue. In addition, CEACAM19 may represent as a novel therapeutic target in certain subgroups of breast cancer patients such as ER/PR-negative. Critical roles of CEA proteins in tumor progression may nominate them as robust potential targets for therapeutic intervention in near future.