Apurinic/apyrimidinic endonuclease 1 is associated with poor prognosis after curative resection followed by adjuvant chemotherapy in patients with stage III colon cancer.

Purpose: Apurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme involved in the base excision repair pathway. It also has redox activity and maintains various transcription factors in an active reduced state. APE1 may be associated with chemoresistance.

Honokiol induces apoptosis and suppresses migration and invasion of ovarian carcinoma cells via AMPK/mTOR signaling pathway.

Honokiol, a natural biphenolic compound, exerts anticancer effects through a variety of mechanisms on multiple types of cancer with relatively low toxicity. Adenosine 5'‑phosphate‑activated protein kinase (AMPK), an essential regulator of cellular homeostasis, may control cancer progression. The present study aimed to investigate whether the anticancer activities of honokiol in ovarian cancer cells were mediated through the activation of AMPK.

Combination of pristimerin and paclitaxel additively induces autophagy in human breast cancer cells via ERK1/2 regulation.

Pristimerin, a quinonemethide triterpenoid, has demonstrated anticancer activity against a number of types of cancer, including breast cancer. However, its mechanism of action remains unclear. The present study investigated the autophagy‑induced anticancer efficacy of pristimerin on MDA‑MB‑231 human breast cancer cells.

A natural ent‑kaurane diterpenoid induces antiproliferation in ovarian cancer cells via ERK1/2 regulation and inhibition of cellular migration and invasion.

Ovarian cancer is one of the most common causes of female mortalities from gynecological tumors. An ent‑kaurane diterpenoid compound CRT1 (ent‑18‑acetoxy‑7β‑hydroxy kaur‑15‑oxo‑16‑ene), mainly isolated from the Vietnamese herb Croton tonkinesis has been used in folk medicine in Vietnam for cancer treatment. However, the effect of this compound on human ovarian cancer cells has not yet been reported.

Corosolic acid reduces 5‑FU chemoresistance in human gastric cancer cells by activating AMPK.

5‑Fluorouracil (5‑FU) is one of the most commonly used chemotherapeutic agents for gastric cancer. Resistance to 5‑FU‑based chemotherapy remains the major obstacle in the treatment of gastric cancer. A growing body of evidence has suggested that adenosine monophosphate‑activated protein kinase (AMPK) is pivotal for chemoresistance.

Inhibitory effect of emodin on fatty acid synthase, colon cancer proliferation and apoptosis.

Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated.

Sonographic Differentiation Between Schwannomas and Neurofibromas in the Musculoskeletal System.

Objectives: The purpose of this study was to determine key features and define a strategy for differentiation between schwannomas and neurofibromas using sonography.

Methods: This retrospective study was approved by the Institutional Review Board at our hospital, and informed consent was waived. We reviewed sonograms of pathologically proven schwannomas and neurofibromas of the extremities and body wall.

Corosolic acid enhances 5-fluorouracil-induced apoptosis against SNU-620 human gastric carcinoma cells by inhibition of mammalian target of rapamycin.

5‑Fluorouracil (5‑FU), one of the oldest anticancer therapeutic agents, is increasingly being administered in cancer chemotherapy. In the present study, the anticancer effects of 5‑FU combined with corosolic acid (CRA) were determined in SNU‑620 human gastric carcinoma cells and the underlying mechanisms were examined. A combination treatment of 5‑FU and CRA inhibited the viability of cells additively.

Determination of major UDP-glucuronosyltransferase enzymes and their genotypes responsible for 20-HETE glucuronidation.

The compound 20-HETE is involved in numerous physiological functions, including blood pressure and platelet aggregation. Glucuronidation of 20-HETE by UDP-glucuronosyltransferases (UGTs) is thought to be a primary pathway of 20-HETE elimination in humans. The present study identified major UGT enzymes responsible for 20-HETE glucuronidation and investigated their genetic influence on the glucuronidation reaction using human livers (n = 44).

Development of a multiplex and cost-effective genotype test toward more personalized medicine for the antiplatelet drug clopidogrel.

There has been a wide range of inter-individual variations in platelet responses to clopidogrel. The variations in response to clopidogrel can be driven by genetic polymorphisms involved in the pathway of absorption, distribution, metabolism, excretion, and the target receptor P2Y12. A set of genetic variants known for causing variations in clopidogrel responses was selected, which included CYP2C19*2, *3, *17, CYP2B6*4, *6, *9, CYP3A4*18, CYP3A5*3, MDR1 2677G>T/A, 3435C>T, and P2Y12 H2 (742T>C).

Identification and characterization of novel alternative splice variants of human constitutive androstane receptor in liver samples of Koreans and Caucasians.

Human constitutive androstane receptor (hCAR, NR1I3) is a member of the orphan nuclear receptor family and regulates the transcription of many drug-metabolizing enzymes and drug transporters. Previous studies have shown that the hCAR gene produces a number of different kinds of mRNA splicing variants (SVs) in non-Asian ethnicities. In the present study, we identified 18 hCAR SVs (SV1-SV18), including four novel SVs in Korean human livers.

Anticancer activity of pristimerin in epidermal growth factor receptor 2-positive SKBR3 human breast cancer cells.

Pristimerin is a naturally occurring triterpenoid that causes cytotoxicity in several cancer cell lines. However, the mechanism of action for the cytotoxic effect of pristimerin has not been unexplored. The purpose of this study was to investigate the effect of pristimerin on cytotoxicity using the epidermal growth factor receptor 2 (HER2)-positive SKBR3 human breast cancer cell line.

An ent-kaurane diterpenoid from Croton tonkinensis induces apoptosis by regulating AMP-activated protein kinase in SK-HEP1 human hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality worldwide. Traditional chemotherapy for HCC is not widely accepted by clinical practitioners because of its toxic side effects. Thus, there is a need to identify chemotherapeutic drugs against HCC.

Magnolol-induced apoptosis in HCT-116 colon cancer cells is associated with the AMP-activated protein kinase signaling pathway.

Colon cancer is the third most common malignancy around the world. Surgery, chemotherapy, and radiotherapy are generally used to treat colon cancer, but no effective therapy for advanced colon carcinoma is available. Therefore, there is a need to identify other therapeutic agents against this disease.

Fatty acid synthase inhibition by amentoflavone suppresses HER2/neu (erbB2) oncogene in SKBR3 human breast cancer cells.

Fatty acid synthase (FASN) is a potential therapeutic target for treatment of cancer and obesity, and is highly elevated in 30% of HER2-overexpressing breast cancers. Considerable interest has developed in searching for novel FASN inhibitors as therapeutic agents in treatment of HER2-overexpressing breast cancers. Amentoflavone was found to be effective in suppressing FASN expression in HER2-positive SKBR3 cells.

Anticancer properties of pomolic acid-induced AMP-activated protein kinase activation in MCF7 human breast cancer cells.

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status found in all eukaryotes. Recent studies indicate that AMPK activation strongly suppresses cell proliferation in tumor cells, which requires high rates of protein synthesis and de novo fatty acid synthesis for their rapid growth. Pomolic acid (PA) has been previously described as being active in inhibiting the growth of cancer cells.

Chrysophanic acid blocks proliferation of colon cancer cells by inhibiting EGFR/mTOR pathway.

Inactivation of epidermal growth factor receptor (EGFR) is a prime method used in colon cancer therapy. Here it is shown that chrysophanic acid, a natural anthraquinone, has anticancer activity in EGFR-overexpressing SNU-C5 human colon cancer cells. Chrysophanic acid preferentially blocked proliferation in SNU-C5 cells but not in other cell lines (HT7, HT29, KM12C, SW480, HCT116 and SNU-C4) with low levels of EGFR expression.

A haplotype of CYP2C9 associated with warfarin sensitivity in mechanical heart valve replacement patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * CYP2C9 single nucleotide polymorphisms (SNPs) are important in safe and effective oral anticoagulation with warfarin use. * Although CYP2C9*2 and *3 are important genetic factors for the warfarin dose, one of the CYP2C9 SNPs, IVS-65G>C, has been suggested to be associated with warfarin sensitivity. However, as of yet, there has been no explanation about the possible mechanism and linkage analysis.

Activation of AMP-activated protein kinase on human gastric cancer cells by apoptosis induced by corosolic acid isolated from Weigela subsessilis.

Corosolic acid is one of the triterpenoids present in the leaves of Weigela subsessilis. The antidiabetic activity of corosolic acid has been reported previously, but to date, the anticancer effects on gastric cancer have been poorly studied. In this study, corosolic acid showed growth inhibition on SNU-601 human gastric cancer cells, with an IC₅₀ value of 16.

Down-regulation of human epidermal growth factor receptor 2/neu oncogene by corosolic acid induces cell cycle arrest and apoptosis in NCI-N87 human gastric cancer cells.

Overexpression/amplification of human epidermal growth factor receptor (HER)2/neu (erbB-2) oncogene plays a causal role in carcinogenesis and correlates with a poor clinical prognosis. However, little is known about HER2 in gastric cancer. In this study, we explored the pharmacological activities of natural triterpenoid corosolic acid (CRA) in HER2 signaling and its role in gastric cancer development and progression.

CT colonography after metallic stent placement for acute malignant colonic obstruction.

Purpose: To evaluate the feasibility of using computed tomographic (CT) colonography for preoperative examination of the proximal colon after metallic stent placement in patients with acute colon obstruction caused by colorectal cancer.

Materials And Methods: Institutional review board approval was obtained, and patient informed consent was waived. Fifty patients (mean age +/- standard deviation, 58.

Genetic polymorphism of hepatocyte nuclear factor-4alpha influences human cytochrome P450 2D6 activity.

Unlabelled: Hepatocyte nuclear factor-4 alpha (HNF4A) is an essential transcriptional regulator for many genes that are expressed preferentially in the liver. Among the important functions of the liver is drug metabolism in response to xenobiotic exposure. Recent studies have suggested that HNF4A regulates the expression of cytochrome P450 (CYP), including CYP2D6 and CYP3A4, which show large individual variations in their activities.

Ionizing radiation can induce GSK-3beta phosphorylation and NF-kappaB transcriptional transactivation in ATM-deficient fibroblasts.

DNA damage by ionizing radiation (IR) can induce activations of both NF-kappaB and p53 through the upstream kinase ataxia telangiectasia mutated (ATM). NF-kappaB activation could also be signaled through two distinct or overlapped pathways; IkappaB kinases (IKKs)-IkappaBalpha and Akt-glycogen synthase kinase-3 (GSK-3). In the present study, however, we show that activation of Akt1 and the subsequent phosphorylation and inactivation of GSK-3beta by IR could also occur in ATM-deficient AT5BIVA cells as well as in normal MRC5CV1 fibroblasts.

CYP2S1 gene polymorphisms in a Korean population.

Cytochrome P450 2S1 (CYP2S1) is a drug-metabolizing enzyme that shows interindividual variations in response to treatments for psoriasis and is regarded as a putative prognostic marker for colorectal cancer treatment. To gain insight into the genetic basis for the interindividual variations, CYP2S1 gene polymorphisms were analyzed in Korean subjects. Using direct sequencing of the CYP2S1 gene, 12 genetic variations, which included the two novel nonsynonymous mutations CYP2S1 S61N (0.

In vitro metabolism of a new cardioprotective agent, KR-32570, in human liver microsomes.

KR-32570 (5-(2-methoxy-5-chlorophenyl)furan-2-ylcarbonyl)guanidine) is a new reversible Na+/H+ exchanger inhibitor for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-32570 in human liver microsomes. Human liver microsomal incubation of KR-32570 in the presence of NADPH and UDPGA resulted in the formation of six metabolites, M1-M6.