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Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme involved in nicotinamide adenine di- nucleotide (NAD) salvage pathway, is overexpressed in many human malignancies such as breast cancer. This enzyme plays a critical role in survival and growth of cancer cells. MicroRNAs (miRNAs) are among the most important regulators of gene expression, and serve as potential targets for diagnosis, prognosis, and therapy of breast cancer. Therefore, the aim of this study was to asse ss the effect of NAMPT inhibition by miR-381 on breast cancer cell survival. MCF-7 and MDA-MB-2 31 cancer cell lines were transfected with miR-381 mimic, inhibitor, and their corresponding negative controls (NCs). Subsequently, the level of NAMPT and NAD was assessed using real-time PCR, immuno-blotting, and enzymatic methods, resp ectively. In order to evalua te apoptosis, cells were labelled with Annexin V-FITC and propidium iodide and analyzed by flow cytometry. Bioinformatics analysis was performed to recognize whether NAMPT 3 ′ -untranslated region (UTR) is a direct target of miR-381 and the results were authenticated by the luciferase re porter assay using a vector containing the 3 ′ -UTR sequence of NAMPT. Our results revealed that the 3 ′ -UTR of NAMPT was a direct target of miR-381 and its up-regulation decreased NAMPT gene and protein expression, leading to a notable reduction in intracellular NAD and subse- quently cell survival and induction of apoptosis. It can be concluded that miR-381 has a vital role in tumor sup- pression by down-regulation of NAMPT, and it can be a promising candidate for breast cancer therapy., EXCLI Journal;Vol. 18 2019

Additional file 2: Figure S1. Protein–protein interaction (PPI) network analysis. PPI network explored the interactions between the 370 up-regulated genes with confidence ≥ 0.4. Five main clusters were obtained of the k-means algorithm that five colors were applied for indication gene clusters (each color indicates a cluster gene). Figure S2. Pathway analysis for the largest cluster covering 167 genes on Enrichr. Top ten results of pathway analysis that was performed based on BioPlanet, KEGG, WikiPathways, and Reactome libraries. Figure S3. Gene ontology analysis for the largest cluster covering 167 genes on Enrichr. Top ten results of gene ontology (GO) based on p-value. Results of GO analysis was contained cellular component (CC), biological process (BP), molecular function (MF) and Jensen diseases.

Additional file 1: Table S1. Search strategy and syntax in different databases based on the expression of cancer stem cell markers in gastric cancer.

One of the cutting edge techniques for treating cancer is the use of the patient's immune system to prevail cancerous disease. The versatility of the chimeric antigen receptor (CAR) T-cell approach in conjugation with promising treatments in haematological cancer has led to countless cases of research literature for the treatment of solid cancer. A systematic search of online databases as well as gray literature and reference lists of retrieved studies were carried out up to March 2019 to identify experimental animal studies that investigated the antigens targeted by CAR T-cell for pancreatic cancer treatment. Studies were evaluated for methodological quality using the SYstematic Review Center for Laboratory Animal Experimentation bias risk tool (SYRCLE's ROB tool). Pooled cytotoxicity ratio/percentage and 95% confidence intervals were calculated using the inverse-variance method while random-effects meta-analysis was used, taking into account conceptual heterogeneity. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I2 statistic using Stata 13.0. Of the 485 identified studies, 56 were reviewed in-depth with 16 preclinical animal studies eligible for inclusion in the systematic review and 11 studies included in our meta-analysis. CAR immunotherapy significantly increased the cytotoxicity assay (percentage: 65%; 95% CI: 46%, 82%). There were no evidence for significant heterogeneity across studies [P = 0.38 (Q statistics), I2 = 7.14%] and for publication bias. The quality assessment of included studies revealed that the evidence was moderate to low quality and none of studies was judged as having a low risk of bias across all domains. CAR T-cell therapy is effective for pancreatic cancer treatment in preclinical animal studies. Further high-quality studies are needed to confirm our finding and a standard approach of this type of studies is necessary according to our assessment.

Dynamin 2 is a GTPase protein that has been implicated in cancer progression through its various roles such as endocytosis, morphogenesis, epithelial-mesenchymal transition (EMT), cellular contractions, and focal adhesion maturation. The increased expression levels of this molecule have been demonstrated with the development of several cancers such as prostate, pancreas, and bladder. However, its clinical significance in breast cancer is unclear yet. In the present study, the membranous, cytoplasmic, and nuclear expression levels of dynamin 2 molecule were evaluated for the first time, using immunohistochemistry (IHC) on tissue microarray (TMA) slides in 113 invasive breast cancer tissues. Moreover, afterward, the association between the dynamin 2 expression and clinicopathological features was determined. Our finding showed that, a higher nuclear expression of dynamin 2 is significantly associated with an increase in tumor stage (P = 0.05), histological grade (P = 0.001), and age of the patients (P = 0.03). In addition, analysis of the cytoplasmic expression levels of this molecule revealed that, there was a statistically significant difference between the expression levels of dynamin 2 among the different breast cancer subtypes (P = 0.003). Moreover, a significant association was found between the increased expression of dynamin 2 membranous and vascular invasion (VI) (P = 0.02). We showed that dynamin 2 protein expression has an association with more aggressive tumor behavior and more advanced disease in the patients with breast cancer; therefore, dynamin 2 molecule could be considered as an indicator of disease progression and aggressiveness., EXCLI Journal; 19:Doc1423; ISSN 1611-2156

Additional file 1: Figure S1. MCF-7 & MDA-MB-231 cell lines transfected with FAM-labeled microRNAs. Fluorescence microscopy images of MCF-7 and MDA-MB-231 cells transfected with miR-154 mimic and miR inhibitor negative controls (NC) labeled with FAM. a) Evaluation of transfection efficiency under fluorescence and light microscope in MCF-7 cells transfected with FAM-labeled miR-154 mimic NC and miR-inhibitor NC. b) Evaluation of transfection efficiency, under fluorescence and light microscope, in MDA-MB-231 cells transfected with FAM-labeled miR-154 mimic NC and miR-inhibitor NC. The fluorescence microscopy images were obtained 24â h after transfection. Table S1. primer sequences for real-time PCR, and primer sequences used for amplification and cloning of NAMPT 3â ˛-UTR. The underlined sequences represent the restriction enzyme recognition sites (CTCGAG for XhoI and GCGGCCGC for NotI) added for cloning into psiCHECK-2.