Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades

properly cited. Purpose. To investigate a frequency of antibody response to SEREX-identified medullary breast carcinoma autoantigens ZRF1 and KRR1 in sera of breast cancer patients taking into account clinical and molecular characteristics of tumors for opening of new perspectives in creation of minimally invasive immunological tests for cancer diagnostics. Methods. Enzyme-linked immunosorbent assay and bioinformatics analysis. Results. Increased frequency of antibody response was found in sera of breast cancer patients to ZRF and KRR1 antigens. The antibody response to these antigens was higher in sera of patients with invasive ductal carcinoma than in sera of patients with other histological types of breast tumors. Moreover, more frequent antibody response to ZRF antigen was found in sera of patients with less aggressive tumors. The sequence analysis of ZRF1 antigen SEREX clones obtained from cDNA libraries of different tumors demonstrates that they encode different protein isoforms. Conclusion. Tumor-associated antigens KRR1 and ZRF1 and their cognate autoantibodies could be considered as potential molecular markers of breast cancer which need to be further investigated

Cas9 Technique for Identification of Genes Regulating Oxaliplatin Resistance of Pancreatic Cancer Cell Line

© 2016, Springer Science+Business Media New York.Genome editing approach based on prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats) system is a simple and useful way to investigate gene functions on a genome-wide scale. It is especially important for cancer research because of genetic contribution to tumor development. We applied this technique in a high-throughput screening format to find genes that could be involved in chemotherapy resistance of pancreatic cancer. We used AsPC1 cell line expressing doxycycline-inducible Cas9 to screen two sgRNA lentiviral libraries: (1) cell cycle genes (CC, 983 genes, ∼12,000 sgRNA) and (2) genome-wide (GW, ∼90,000 sgRNA). These sets of cells with different gene knockouts were treated with oxaliplatin to identify knockouts which increase sensitivity to the drug. We have performed screening both in vitro and in vivo settings. For the in vivo arm of our experiments, peritoneal carcinomatosis model in severe combined immunodeficiency (SCID) mice was created by intraperitoneal injection of AsPC1/Cas9 cells infected with sgRNA library. Genomic DNA from cells and animal tumor material was analyzed using next generation sequencing (NGS) to obtain data about representation of sgRNA. Preliminary data allowed us to identify genes potentially modulating oxaliplatin sensitivity

Characterization of SLC34A2 as a Potential Prognostic Marker of Oncological Diseases

The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S/R/L, p.G257A/E/R, p.S318W, p.A396T, p.P410L/S/H, p.S461C, p.A473T/V, and p.Y503H/C/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers

Identification of New Regulators of Pancreatic Cancer Cell Sensitivity to Oxaliplatin and Cisplatin

The chemoresistance of tumor cells is one of the most urgent challenges in modern oncology and in pancreatic cancer, in which this problem is the most prominent. Therefore, the identification of new chemosensitizing co-targets may be a path toward increasing chemotherapy efficacy. In this work, we performed high-performance in vitro knockout CRISPR/Cas9 screening to find potential regulators of the sensitivity of pancreatic cancer. For this purpose, MIA PaCa-2 cells transduced with two sgRNA libraries (“cell cycle/nuclear proteins genes” and “genome-wide”) were screened by oxaliplatin and cisplatin. In total, 173 candidate genes were identified as potential regulators of pancreatic cancer cell sensitivity to oxaliplatin and/or cisplatin; among these, 25 genes have previously been reported, while 148 genes were identified for the first time as potential platinum drug sensitivity regulators. We found seven candidate genes involved in pancreatic cancer cell sensitivity to both cisplatin and oxaliplatin. Gene ontology enrichment analysis reveals the enrichment of single-stranded DNA binding, damaged DNA binding pathways, and four associated with NADH dehydrogenase activity. Further investigation and validation of the obtained results by in vitro, in vivo, and bioinformatics approaches, as well as literature analysis, will help to identify novel pancreatic cancer platinum sensitivity regulators

Le Petit Troyen : journal démocratique régional ["puis" journal quotidien de la démocratie de l'Est "puis" grand quotidien de la Champagne]

19 mai 19261926/05/19 (A48,N16705).Appartient à l’ensemble documentaire : ChArdenn