Heterogeneity in intratumoral cancers leads to discrepancies in drug responsiveness, due to diverse genomics profiles. Thus, prediction of drug responsiveness is critical in precision medicine. So far, in drug responsiveness prediction, drugs’ molecular “fingerprints”, along with mutation statuses, have not been considered. Here, we constructed a 1-dimensional convolution neural network model, DeepIC50, to predict three drug responsiveness classes, based on 27,756 features including mutation statuses and various drug molecular fingerprints. As a result, DeepIC50 showed better cell viability IC50 prediction accuracy in pan-cancer cell lines over two independent cancer cell line datasets. Gastric cancer (GC) is not only one of the lethal cancer types in East Asia, but also a heterogeneous cancer type. Currently approved targeted therapies in GC are only trastuzumab and ramucirumab. Responsive GC patients for the drugs are limited, and more drugs should be developed in GC. Due to the importance of GC, we applied DeepIC50 to a real GC patient dataset. Drug responsiveness prediction in the patient dataset by DeepIC50, when compared to the other models, were comparable to responsiveness observed in GC cell lines. DeepIC50 could possibly accurately predict drug responsiveness, to new compounds, in diverse cancer cell lines, in the drug discovery process.

The incidence of colorectal cancer (CRC) is increasing, with metastasis of newly diagnosed CRC reported in a large proportion of patients. However, the effect of Korean Red Ginseng extracts (KRGE) on epithelial to mesenchymal transition (EMT) in CRC is unknown. Therefore, we examined the mechanisms by which KRGE regulates EMT of CRC in hypoxic conditions. Human CRC cell lines HT29 and HCT116 were incubated under hypoxic (1% oxygen) and normoxic (21% oxygen) conditions. Western blot analysis and real-time PCR were used to evaluate the expression of EMT markers in the presence of KRGE. Furthermore, we performed scratched wound healing, transwell migration, and invasion assays to monitor whether KRGE affects migratory and invasive abilities of CRC cells under hypoxic conditions. KRGE-treated HT29 and HCT116 cells displayed attenuated vascular endothelial growth factor (VEGF) mRNA levels and hypoxia-inducible factor-1α (HIF-1α) protein expression under hypoxic conditions. KRGE repressed Snail, Slug, and Twist mRNA expression and integrin αVβ6 protein levels. Furthermore, hypoxia-repressed E-cadherin was restored in KRGE-treated cells; KRGE blocked the invasion and migration of colon cancer cells by repressing NF-κB and ERK1/2 pathways in hypoxia. KRGE inhibits hypoxia-induced EMT by repressing NF-κB and ERK1/2 pathways in colon cancer cells.

Tailored eradication strategy vs concomitant therapy for Helicobacter pylori eradication treatment in Korean patients

Kim JH, et al. J Korean Med Sci. 2016 Jun;31(6):873-878. https://doi.org/10.3346/jkms.2016.31.6.873

The aim of this study was to elucidate the predictive risk factors of synchronous multiple early gastric cancer regardless of the treatment modality. Patients who underwent early gastric cancer treatment between July 2005 and June 2015 were retrospectively reviewed. In total, 1529 patients who were treated for early gastric cancer were included. We analyzed the patient's data to find predictive factors of synchronous multiple early gastric cancer compared to solitary early gastric cancer. Further analysis was performed to verify the difference between endoscopic and surgical treatment groups. Among the 1529 patients, synchronous multiple early gastric cancer was diagnosed in 68 (4.4%) patients. Significant differences in sex (P = .004), gross appearance (P = .038), depth of invasion (P = .007), and lymphovascular invasion (P = .039) were found between patients with solitary early gastric cancer and synchronous multiple early gastric cancer by univariate analysis. In multivariate analysis, male sex (odds ratio, 2.475; P = .011) and submucosal invasion (odds ratio, 1.850; P = .033) were independent predictive risk factors of synchronous multiple early gastric cancer. In addition, in multivariate analysis, significant differences in age, tumor size, longitudinal location, depth of invasion, and histology were found between patients groups depending on the mode of treatment. Male sex and submucosal invasion were predictive risk factors of synchronous multiple early gastric cancer. Patients with these factors should undergo more meticulous endoscopic surveillance.

The incidence of colorectal cancer (CRC) is increasing worldwide. 8-hydroxy-2′-deoxyguanosine (8-OHdG), one of the most prevalent DNA alterations, is known to be upregulated in several carcinomas; however, 8-OHdG has not been used to predict the prognosis of patients with CRC. We aimed to determine 8-OHdG levels in patients with CRC using immunohistochemistry and conducted a survival analysis according to the pathological stage. The 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs) of the low 8-OHdG subgroup were 1.41 (95% confidence interval (CI): 1.01–1.98, p = 0.04) and 1.60 (95% CI: 1.12–2.28, p = 0.01), respectively. When tumor node metastasis (TNM) staging and 8-OHdG expression were combined, the 5-year EFS and DSS HRs of patients with CRC with low 8-OHdG expression cancer at the same TNM stage (stage Ⅲ/Ⅳ) were 1.51 (95% CI: 1.02–2.22, p = 0.04) and 1.64 (95% CI: 1.09–2.48, p = 0.02), respectively, compared to those with high 8-OHdG expression cancer, indicating a poor prognosis. Therefore, low 8-OHdG expression is a significant predictive factor for 5-year EFS and DSS in patients with CRC, and it can serve as an essential biomarker of CRC.