Therkildsencrawford3856

Colorectal cancer (CRC) is the third most common cancer and the second cause of cancer-related deaths worldwide. Despite early diagnosis and treatment improvement, the majority of patients will still suffer from metastatic disease (mCRC), which has a poor prognosis. Molecular diversity of CRC requires personalized targeted approach for improving patient outcomes. Antiangiogenic agents proved to be beneficial in the continuum of mCRC treatment. For efficient epidermal growth factor receptor (EGFR) directed therapy, subtle molecular selection and better strategies to overcome resistance are needed. BRAF mutant and HER-2 positive mCRC will soon be provided with approved targeted treatments and check-point inhibitors demonstrated effectiveness in microsatellite instability (MSI) - high mCRC. Moreover, numeorous promising agents are entering clinical trial arena. This review summarizes actual and possible targets and current and promising agents for mCRC treatment. With broader accessibility of liquid biopsy we could track molecular evolution of CRC and target genetic alterations as they emerge.PURPOSE To evaluate the efficacy of first-line and not-conventional antineoplastic drug combinations in colorectal adenocarcinoma primary cultures (CRAC PCs). METHODS The efficacy and safety of 21 drug combinations (DCs) were evaluated using a simplified adenosine triphosphate-based chemotherapy response assay (sATP-CRA). The efficacy of each DC was reported as the percentage of cell death (PCD) produced on each of 12 CRAC-PCs, and the safety of each DC was evaluated as a safety window (SW). The SW was calculated as the quotient of PCD-CRAC PC/PCD-hMSC-TA (human mesenchymal stem cells derived from adipose tissue). Nine DCs contained 5-fluorouracil and oxaliplatin, and 1-3 non-front line drugs (NFLDs [carboplatin, doxorubicin, cisplatin, aspirin, or 3,3' diindolylmethane]). The other 11 DCs only contained 2-4 NFLDs. RESULTS The efficacy and safety each DC were highly variable and depended on each CRAC PC and DC. The usefulness of DCs was considered as a combination of PCD >20 and an SW >0.6 13 /21 DCs (62%) met the requirements of efficacy and safety on 7/12 CRAC PCs (58.3%). CONCLUSIONS The resistance to 5-fluorouracil/oxaliplatin of CRAC PCs and the usefulness of seven new DCs strongly suggest the convenience of performing ex vivo individualized assays to evaluate DCs, and implement new and more useful treatments, instead of submitting patients to standardized chemotherapies in a blinded manner. Approaches such as this and properly evaluated in clinical assays could increase the life expectancy of patients with cancer and improve their quality of life.PURPOSE To uncover the potential function of long non-coding RNA (lncRNA) ZEB2-AS1 in the progression of colorectal cancer (CRC), and its underlying mechanism. METHODS Relative level of ZEB2-AS1 in CRC tissues and matched normal ones was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between ZEB2-AS1 level and survival of CRC patients was analyzed by Kaplan-Meier method. Regulatory effects of ZEB2-AS1 on cellular behaviors of CRC cells were evaluated. The interactions between ZEB2-AS1 with LSD1 and EZH2 were explored by RNA immunoprecipitation (RIP) assay. 5-Ethynyl-2'- deoxyuridine (EdU) assay was performed to elucidate the roles of ZEB2-AS1, LSD1 and EZH2 on the proliferative ability of CRC cells. Finally, Spearman's correlation analysis was performed to analyze the relationship between ZEB2-AS1 level and expressions of proliferation- and invasion-related genes. RESULTS ZEB2-AS1 was upregulated in CRC tissues relative to matched controls. Its level remained higher in CRC patients with ≥6 cm in tumor size, nodal metastasis and stage III-IV. Fetuin price CRC patients with low-level ZEB2-AS1 presented worse survival compared with those with high-level ZEB2-AS1. QRT-PCR data showed higher abundance of ZEB2-AS1 in CRC cell lines than colonic epithelial cell line. Knockdown of ZEB2-AS1 attenuated the proliferative, migratory and invasive abilities, but induced apoptosis of DLD1 and SW620 cells. RIP assay demonstrated the interaction between ZEB2-AS1 and LSD1, EZH2. Moreover, EdU assay revealed that transfection of sh-ZEB2-AS1 attenuated the proliferative ability, which was further reduced after co-transfection of sh-LSD1 or sh-EZH2. Finally, correlation analysis showed that mRNA level of ZEB2-AS1 was positively correlated to those of LSD1, EZH2, MMP9, MMP12 and KRAS, but negatively correlated to KLF2. CONCLUSIONS LncRNA ZEB2-AS1 is upregulated in CRC. It accelerates CRC cells to proliferate via interacting with EZH2 and LSD1, thus promoting the progression of CRC.PURPOSE The main aim of the current study was to investigate the anticancer properties of naturally occurring triterpene - glycyrrhizin - against human colorectal carcinoma cells along with evaluation of its effects on cells apoptosis, autophagy and cell migration and invasion. METHODS Cell viability was evaluated by CellTiter95® Aqueous One Solution cell viability assay, while the effects on cell apoptosis were observed by fluorescence microscopy using DAPI staining. Effects on autophagy were detected by transmission electron microscopy (TEM) along with western blot method. Transwell assay was performed to monitor the effects on cell migration and invasion. RESULTS Glycyrrhizin induced selective and dose-dependent inhibition of cell growth in SW48 human colorectal carcinoma cells with lesser cytotoxicity in normal colon cells (CCD-18Co). Glycyrrhizin also led to cell apoptotic effects manifested by chromatin condensation and nuclear fragmentation as evidenced by brighter fluorescence. Apoptosis was confirmed by western blot which showed increase in Bax expression and decrease in Bcl-2 expression. TEM analysis showed that glycyrrhizin-treated cells at 12 μM showed autophagosomes indicating onset of autophagy. Western blot assay confirmed the autophagy results which showed glycyrrhizin-treated cells indicated increased expression of Beclin-1, LC3B-I and LC3B-II in a dose-dependent manner. Glycyrrhizin treatment also led to inhibition of both cell migration and invasion. CONCLUSION The results of this study reveal that glycyrrhizin can be developed as a potent anticancer agent against colorectal cancer provided further studied are performed, especially on its toxicity to humans.