Construction of large scale boolean logic based pathways of colorectal cancer stem cells

Despite advances in the post-genomic era, which allowed for generation of an impressive amount of biological data, representing the whole network of biological interactions, gene regulating networks and signaling pathways in a unified temple and coherent way is still a challenging task. Here we performed analysis of upregulated molecular networks found in colorectal cancer stem cells (CCSC)

Small molecule targeting of the p38/Mk2 stress signaling pathways to improve cancer treatment

Purpose: Although a long-term goal of cancer therapy always has been the development of agents that selectively destroy cancer cells, more recent trends have been to seek secondary agents that sensitize cancer cells to existing treatment regimens. In this regard, the present study explored the possibility of using small molecule inhibitors of p38MAPK/MK2 stress signaling pathways as potential agents to enhance the sensitivity of cancer cells with abrogated G1 checkpoint to the DNA damaging agent etoposide by specifically targeting the DNA damage-induced G2 cell cycle checkpoint. Methods: We have applied CCK8 and FACS-based viability assays and cell cycle analysis to investigate the effect of small molecules SB203580 and MK2.III on the sensitivity of small cell lung cancer cells (SCLC) that lack the G1 checkpoint to the DNA damaging agent Etoposide when used in combination. We have also assessed the effectiveness of combination chemotherapy on tumor xenograft suppression with etoposide and MK2.III in immunosuppressed mice. In addition, additional CCK8 cell viability analysis of the MDA-MB-231 breast cancer cell line, and SW620, and SW480 colorectal cancer cell lines was performed. Results: Results suggest that etoposide produces a profound effect on the cell cycle profile of cells in a manner that is consistent with the degree of cell viability that is seen using the viable cell assay. Results of the co-treatment experiments revealed that the p38/MK2 kinase inhibitors SB203580 and MK2.III both enhanced the DNA-damaging effects of etoposide on NCI-H69 cell viability in vitro. Results revealed that in vivo MK2.III was able to act as a chemosensitizer when used in combination with etoposide making NCI-H69 lung cancer cells sensitive to chemotherapeutic drug by 45% compared to single usage of the drug. We also report that MK2.III sensitizes metastatic cell lines SW-620 and MDA-MB-231 to etoposide but does not increase the sensitivity of non-metastasizing SW-480 colorectal cells to DNA damaging agent in vitro. Conclusion: Findings reported in this study provide evidence that specific inhibitors of MK2 may indeed improve overall cancer therapy; however, their effectiveness depends on cell types

ENHANCING AN OXIDATIVE “TROJAN HORSE” ACTION OF VITAMIN C WITH ARSENIC TRIOXIDE FOR EFFECTIVE SUPPRESSION OF KRAS-MUTANT CANCERS: A PROMISING PATH AT THE BEDSIDE

The turn-on mutations of the KRAS gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Recently, the specific G12C mutant KRAS inhibitors have been developed but with a limited clinical outcome because they acquire drug resistance. Alternatively, exploiting a metabolic breach of KRAS-mutant cancer cells related to a glucose-dependent sensitivity to oxidative stress is becoming a promising indirect cancer targeting approach. Here, we discuss the use of a vitamin C (VC) acting in high dose as an oxidative “Trojan horse” agent for KRAS-mutant cancer cells that can be potentiated with another oxidizing drug arsenic trioxide (ATO) to obtain a potent and selective cytotoxic impact. Moreover, we outline the advantages of VC’s non-natural enantiomer, D-VC, because of its distinctive pharmacokinetics and lower toxicity. Thus, the D-VC and ATO combination shows a promising path to treat KRAS-mutant cancers in clinical settings

Rapid evaluation of DNA damage with comet assay in combination of high throughput microscopy

Comet assay is well known method for DNA damage evaluation. However, it also possesses some limitations related to the problem with manual entry of each comet for analysis that decreases the performance and measurement quality. Here we suggest the way for modification of this method based both on advances in microscopy and digital processing

Isolation and characterization of stem cells from mouse colon

In our experiments, we used Rat Mammary Tumor cell line as a supporting feeder cell layer and the media supplemented with several grows factors for mouse colon SC growing and expansion. The goal of our experiments was to identify potential markers that can be used for simple isolation of the SC from mouse colon using flow cytometry techniques

2 nd International conference "Personalized medicine and Global Health"

Preterm premature rupture of membranes (PPROM) is one of the leading causes of perinatal morbidity and mortality. Intrauterine continuous amnioinfusion via a subcutaneously implanted port system for PPROM is an attempt to improve the perinatal outcomes

La Rioja : diario político: Año II Número 291 - 1890 enero 3

Preterm premature rupture of membranes (PPROM) is one of the leading causes of perinatal morbidity and mortality. Intrauterine continuous amnioinfusion via a subcutaneously implanted port system for PPROM is an attempt to improve the perinatal outcomes

Genotoxic effect of unused and banned pesticides on the body of cattle kept on the territory of South Kazakhstan

On the territory of South Kazakhstan (Almaty region) there are old abandoned warehouses with prohibited and unused pesticides, the active substances and metabolites of which pollute natural water sources and pastures of farm animals located nearby. The analysis of blood samples of 50 heads of cattle from five monitoring points of the Almaty region was carried out for the presence of micronuclei in erythrocytes, genomic mutations and chromosomal aberrations in lymphocytes. Cell cultivation and preparation of prepa¬rations were carried out by standard cytogenetic methods. The frequency of erythrocytes with micronuclei in cattle kept in experimental plots was 3.3%, which is 4.7 times higher than in the control group. The incidence of genomic mutations in the blood system of experimental groups of animals exceeded that in the control group by an average of 1.6 times, and chromosomal aberrations—by 9.1 times. The proportion ofhypodiploid cells was 46% of the total number of genomic mutations. Polyploidy accounted for up to 17%, and hyperdip- loidy was found in 5% of cells. The analysis of individual indicators of general cytogenetic instability in the blood system of animals showed that hyperdiploidy and chromosomal aberrations are the main components of this indicator, which, on average for five monitoring sites, exceeded the control data by 7.9 times. Statistical data processing allows us to make a conclusion about the genotoxic effect of prohibited and unused pesticides on the body of cattle, which have clastogenic, aneogenous and mutagenic effects even after 30 years