Targeting ROS production through inhibition of NADPH oxidases.

NADPH oxidases (NOXs) are transmembrane enzymes that are devoted to the production of reactive oxygen species (ROS). In cancers, dysregulation of NOX enzymes affects ROS production, leading to redox unbalance and tumor progression. Consequently, NOXs are a drug target for cancer therapeutics, although current therapies have off-target effects: there is a need for isoenzyme-selective inhibitors.

Allosteric Regulation of Switch-II Domain Controls KRAS Oncogenicity.

Unlabelled: RAS proteins are GTPases that regulate a wide range of cellular processes. RAS activity is dependent on its nucleotide-binding status, which is modulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP). KRAS can be acetylated at lysine 104 (K104), and an acetylation-mimetic mutation of K104 to glutamine (K104Q) attenuates the in vitro-transforming capacity of oncogenic KRAS by interrupting GEF-induced nucleotide exchange.

Notch3 signaling-mediated melanoma-endothelial crosstalk regulates melanoma stem-like cell homeostasis and niche morphogenesis.

Melanoma is among the most virulent cancers, owing to its propensity to metastasize and its resistance to current therapies. The treatment failure is largely attributed to tumor heterogeneity, particularly subpopulations possessing stem cell-like properties, ie, melanoma stem-like cells (MSLCs). Evidence indicates that the MSLC phenotype is malleable and may be acquired by non-MSLCs through phenotypic switching upon appropriate stimuli, the so-called 'dynamic stemness'.

The associations between apolipoprotein B, A1, and the B/A1 ratio and nonalcoholic fatty liver disease in both normal-weight and overweight Korean population.

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with a higher risk of cardiovascular disease, but the relationship has not been established in nonobese populations. Higher apolipoprotein B (apo B) levels and the apo B/A1 ratio and lower apo A1 levels are associated with an elevated risk of cardiovascular disease. We investigated the associations between apo B, apo A1, and the apo B/A1 ratio and the presence of metabolic syndrome and NAFLD in both normal-weight and overweight Koreans.

The Prevalence of Toxocariasis and Diagnostic Value of Serologic Tests in Asymptomatic Korean Adults.

Purpose: Toxocariasis is the most common cause of peripheral blood eosinophilia in Korea and produces eosinophilic infiltration in various organs, including the lung. However, the prevalence of toxocariasis in the general population is rarely reported.

Methods: We investigated the seroprevalence of Toxocara larval antibody among asymptomatic people who attended Samsung Medical Center for a health checkup, including low-dose chest computed tomography (CT) between March 2012 and December 2013.

Induction of Vasculogenic Mimicry Overrides VEGF-A Silencing and Enriches Stem-like Cancer Cells in Melanoma.

The basis for resistance to VEGF inhibition is not fully understood despite its clinical importance. In this study, we examined the adaptive response to VEGF-A inhibition by a loss-of-function analysis using plasmid-based shRNA. Tumor xenografts that initially responded to VEGF-A inhibition underwent an adaptation in vivo, leading to acquired resistance.

KML001 enhances anticancer activity of gemcitabine against pancreatic cancer cells.

Background/aim: Gemcitabine is a drug commonly used to treat pancreatic cancer but chemoresistance to it is a common clinical issue. KML001 (sodium meta-arsenite) has demonstrated certain antitumor activity. The objective of the study was to evaluate the influence of KML001 on the anticancer activity of gemcitabine against pancreatic cancer cells.

KML001 inhibits cell proliferation and invasion in pancreatic cancer cells through suppression of NF-κB and VEGF-C.

Pancreatic cancer is an aggressive malignancy with poor prognosis and the efficacy of chemotherapy is limited. KML001 (sodium meta-arsenite) has been demonstrated to have anticancer activity against some solid cancer cells. The aim of the present study was to determine the effect of KML001 on cell proliferation, migration, and invasion of pancreatic cancer cells.

Association between markers of glucose metabolism and risk of colorectal adenoma.

Background & Aims: Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location.

CD133-targeted niche-dependent therapy in cancer: a multipronged approach.

Cancer treatment continues to be challenged by the development of therapeutic resistances and relapses in the clinical setting, which are largely attributed to tumor heterogeneity, particularly the existence of cancer stem cells (CSCs). Thus, targeting the CSC subpopulation may represent an effective therapeutic strategy. However, despite advances in identifying and characterizing CD133(+) CSCs in various human cancers, efforts to translate these experimental findings to clinical modalities have been slow in the making, especially in light of the growing awareness of CSC plasticity and the foreseeable pitfall of therapeutically targeting CSC base sorely on a surface marker.

The prevalence of colorectal adenomas in asymptomatic Korean men and women.

Background: Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans.

Methods: Cross-sectional study of 19,372 consecutive participants aged 20 to 79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009.

The association between cecal insertion time and colorectal neoplasm detection.

Background: Information on the impact of cecal insertion time on colorectal neoplasm detection is limited. Our objective was to determine the association between cecal insertion time and colorectal neoplasm detection rate in colonoscopy screening.

Methods: We performed a cross-sectional study of 12,679 consecutive subjects aged 40-79 years undergoing screening colonoscopy in routine health check-ups at the Center for Health Promotion of the Samsung Medical Center from December 2007 to June 2009.

HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS.

Unlabelled: Activating point mutations in K-RAS are extremely common in cancers of the lung, colon, and pancreas and are highly predictive of poor therapeutic response. One potential strategy for overcoming the deleterious effects of mutant K-RAS is to alter its posttranslational modification. Although therapies targeting farnesylation have been explored, and have ultimately failed, the therapeutic potential of targeting other modifications remains to be seen.

The association of serum lipids with colorectal adenomas.

Objectives: There is suggestive but sparse evidence that dyslipidemia is associated with colorectal neoplasms. We investigated the association of serum lipid and apolipoprotein concentrations with the prevalence of colorectal adenomas.

Methods: Cross-sectional study of 19,281 consecutive participants aged 40-79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009.

Differential Expression of PKD2-Associated Genes in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by formation of multiple fluid-filled cysts that expand over time and destroy renal architecture. The proteins encoded by the PKD1 and PKD2 genes, mutations in which account for nearly all cases of ADPKD, may help guard against cystogenesis. Previously developed mouse models of PKD1 and PKD2 demonstrated an embryonic lethal phenotype and massive cyst formation in the kidney, indicating that PKD1 and PKD2 probably play important roles during normal renal tubular development.

Regulation of RAS oncogenicity by acetylation.

Members of the RAS small GTPase family regulate cellular responses to extracellular stimuli by mediating the flux through downstream signal transduction cascades. RAS activity is strongly dependent on its subcellular localization and its nucleotide-binding status, both of which are modulated by posttranslational modification. We have determined that RAS is posttranslationally acetylated on lysine 104.

Guggulsterone enhances antitumor activity of gemcitabine in gallbladder cancer cells through suppression of NF-κB.

Purpose: Patients with gallbladder cancer usually have a poor prognosis, and effective standard chemotherapeutic regimens have not been established. The anticancer activities of guggulsterone have been demonstrated in various cancer cells. The aims of the study were to determine the effect of guggulsterone on gallbladder cancer cells and to investigate whether treatment with guggulsterone influences the antitumor activities of gemcitabine.

Do we need colonoscopy in patients with gastric adenomas? The risk of colorectal adenoma in patients with gastric adenomas.

Background: Gastric polyps are found frequently in various colonic polyposis syndromes. Genetic alterations of several genes occur in gastric adenomas and colorectal adenomas. However, it is unknown whether patients with gastric adenomas are at higher risk for colorectal adenomas.

Proteomic analysis of time-dependent difference of protein expression profile changes during neuronal differentiation of mouse embryonic stem cells.

The study of ES cell-mediated neuronal differentiation allows elucidating the mechanism of neuronal development in spite of the complexity and the difficult accessibility. During the differentiation of embryonic stem cells into neuronal cell, the expression profiles in the level of protein were extensively investigated by proteomic analysis. These cells were analyzed for charges in proteome during the differentiation of ES cells by 2-dimensional electrophoresis (2-DE) and MALDI-TOF MS.

Cyst formation in kidney via B-Raf signaling in the PKD2 transgenic mice.

The pathogenic mechanisms of human autosomal dominant polycystic kidney disease (ADPKD) have been well known to include the mutational inactivation of PKD2. Although haploinsufficiency and loss of heterozygosity at the Pkd2 locus can cause cyst formation in mice, polycystin-2 is frequently expressed in the renal cyst of human ADPKD, raising the possibility that deregulated activation of PKD2 may be associated with the cystogenesis of human ADPKD. To determine whether increased PKD2 expression is physiologically pathogenic, we generated PKD2-overexpressing transgenic mice.

NCAM as a cystogenesis marker gene of PKD2 overexpression.

ADPKD (Autosomal Dominant Polycystic Kidney Disease) is characterized by the progressive expansion of multiple cystic lesions in the kidneys. ADPKD is caused by mutations in Ed-pl. consider PKD1 and PKD2.