BACKGROUND: Withania somnifera (known as Ashwagandha) is a medicinal plant used in the ayurvedic medicines in India. Withaferin-A, a withanolide derived from the leaf extract of W. somnifera, has been reported to exhibit anti-tumor activity against various cancer cells, such as leukemia, breast cancer and colon cancer cells. METHODS: We investigated the anti-cancer effects of withaferin-A on the proliferation and migration of human colorectal cancer (HCT116) cells. And we evaluated the effects of withaferin-A on the transcriptional activity of STAT3 and the growth of HCT116 cells in xenograft mouse tumor model. RESULTS: In the present study, we found that withaferin-A inhibited the proliferation and migration of HCT116 cells in a concentration-dependent manner. Treatment of HCT116 cells with withaferin-A attenuated interleukin-6-induced activation of STAT3, which has been implicated in the development and progression of colon cancer. To examine the effect of withaferin-A on HCT116 cells proliferation in vivo, we generated HCT116 cells xenograft tumors in Balb/c nude mice and treated the tumor bearing mice with or without withaferin-A intraperitoneally. Treatment with withaferin-A exhibited significant decrease in the volume and weight of tumors as compared to untreated controls. CONCLUSIONS: The present study suggests that withaferin-A holds the potential to be developed as a small molecule inhibitor of STAT3 for the treatment of HCT116.
Animals ; Breast Neoplasms ; Colon* ; Colonic Neoplasms* ; Colorectal Neoplasms ; HCT116 Cells ; Heterografts ; Humans ; India ; Leukemia ; Mice ; Mice, Nude ; Plants, Medicinal ; STAT3 Transcription Factor ; Withania

Manganese (Mn) is an essential micronutrient for human and plays an important role as a cofactor for several enzymes involving fatty acid synthesis, hepatic gluconeogenesis, and oxidative stresses. Also, Mn intake status has been reported to have beneficial effects in reversing metabolic dysfunction including obesity and nonalcoholic steatosis which is linked to mitochondrial dysfunction and oxidative stresses, however, information on dietary Mn intake in Koreans are limited. Hence we investigated the relationship between dietary Mn intake and antioxidant defense factors in healthy and obese subjects. Total of 333 healthy subjects were recruited in the study and were assigned to one of three study groups: a normal group (18.5-22.9), a overweight group (23-24.9), and a obesity group (>25) according to their body mass index (BMI). We assessed Mn intakes (24-hr recall method) and several indicators for antioxidative defenses such as glutathione (GSH), glutathione peroxidase (GPx) and urinary malonaldehyde (MDA). Results showed that body weight and blood pressure of study subjects were increased in dependent of their BMI (p < 0.01). However dietary Mn intakes and oxidative stress biomarkers (GSH, GPx, and MDA) were not significantly different by groups defined by BMI. In correlation analysis adjusting for age, sex and energy intake, dietary Mn intake of the subjects in different BMI categories were not significantly correlated with GSH, GPx, MDA and showed a weak or no association with these oxidative stress markers. In conclusion dietary Mn intake at least in this study has a little or no influence on markers of oxidative status in both healthy and obese subjects.
Adult* ; Biomarkers* ; Blood Pressure ; Body Mass Index* ; Body Weight ; Energy Intake ; Gluconeogenesis ; Glutathione ; Glutathione Peroxidase ; Humans ; Malondialdehyde ; Manganese* ; Micronutrients ; Obesity ; Overweight ; Oxidative Stress*

No abstract available.
Aged* ; Humans ; Pneumonia*

No abstract available.
Aged* ; Humans ; Pneumonia*

BACKGROUND: Recent genome-wide sequencing studies have identified unexpected genetic alterations in cancer. In particular, missense mutations in isocitrate dehydrogenase-1 (IDH1) at arginine 132, mostly substituted into histidine (IDH1-R132H) were observed to frequently occur in glioma patients. METHODS: We have purified recombinant IDH1 and IDH1-R132H proteins and monitored their catalytic activities. In parallel experiments, we have attempted to find new selective IDH1-R132H chemical inhibitor(s) from a fragment-based chemical library. RESULTS: We have found that IDH1, but not IDH1-R132H, can catalyze the conversion of isocitrate into alpha-ketoglutarate (alpha-KG). In addition, we have observed that IDH1-R132H was more efficient than IDH1 in converting alpha-KG into (R)-2-hydroxyglutarate (R-2HG). Moreover, we have identified a new hit molecule, e.g., 2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one as a new selective IDH1-R132H inhibitor. CONCLUSIONS: We have observed an underlying biochemical mechanism explaining how a heterozygous IDH1 mutation contributes to the generation of R-2HG and increases cellular histone H3 trimethylation levels. We have also identified a novel selective IDH1-R132H chemical hit molecule, e.g., 2-(3-trifluoromethylphenyl)isothioazol-3(2H)-one, which could be used for a future lead development against IDH1-R132H.
Arginine ; Glioma ; Histidine ; Histones ; Humans ; Mutation, Missense

Several studies revealed that low calcium intake is related to high prevalence of cardiovascular diseases such as hypertension. The prevalence of hypertension is high in Koreans along with their low dietary calcium consumption. Thus, the aim of this study was to evaluate the status of calcium intake between the hypertension and normotension groups and to investigate the correlation between dietary calcium intake and blood pressure, blood lipid parameters, and blood/urine oxidative stress indices. A total of 166 adult subjects participated in this study and were assigned to one of two study groups: a hypertension group (n = 83) who had 140 mmHg or higher in systolic blood pressure (SBP) or 90 mmHg or higher in diastolic blood pressure (DBP), and an age- and sex-matched normotension group (n = 83, 120 mmHg or less SBP and 80 mmHg or less DBP). The hypertension group consumed 360.5 mg calcium per day, which was lower than that of the normotension group (429.9 mg) but not showing significant difference. In the hypertension group, DBP had a significant negative correlation with plant calcium (P < 0.01) after adjusting for age, gender, body mass index (BMI), and energy intake. In the normotension group, total calcium and animal calcium intake were significantly and positively correlated with serum triglycerides. No significant relationship was found between calcium intake and blood/urine oxidative stress indices in both groups. Overall, these data suggest reconsideration of food sources for calcium consumption in management of the blood pressure or blood lipid profiles in both hypertensive and normotensive subjects.
Adult ; Animals ; Biomarkers ; Blood Pressure ; Body Mass Index ; Calcium ; Calcium, Dietary ; Cardiovascular Diseases ; Energy Intake ; Humans ; Hypertension ; Oxidative Stress ; Plants ; Prevalence ; Triglycerides

OBJECTIVES: The purpose of this study was to investigate the eating behavior toward processed foods among college students who live in different types of residence. METHODS: This is a cross-sectional study targeting a total of 476 college students living at home with their family, living in a rental house with self-boarding, living in a lodging house, and living in a dormitory. Eating behaviors, including preference and the frequency of processed food intake were surveyed and compared according to the type of residence. RESULTS: The rate of skipping a meal was significantly higher among students who reported self-boarding than those living in other types of residences. The main reason for skipping meals was that they got up late. In the entire study population, the main reason for consuming processed food was easy-to-cook (33.8%) and the primary consideration for choosing processed food was the price (54.0%). The processed food the most favored by college students was the processed noodles; those living at home with their family or living in a dormitory preferred milk products; those living in a rental house with self-boarding or in a lodging house preferred confectionery, retort pouch, convenience food, and canned/bottled food. The frequency of processed food intake was significantly higher in the students who reported self-boarding than those living in other types of residences (p < 0.001). CONCLUSIONS: Students' preference toward processed foods differed according to their type of residence. The frequency of processed food intake was significantly higher in students who reported self-boarding indicating that the type of residence of student is associated with their choices and consumption of processed foods.
Cross-Sectional Studies ; Eating* ; Fast Foods ; Feeding Behavior ; Humans ; Korea ; Meals ; Milk

Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-kappaB signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-alpha (TNF-alpha)-induced NF-kappaB reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-kappaB activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.
Carcinogenesis ; Cell Line ; Cell Proliferation* ; Cytokines ; Humans* ; Inflammation ; NF-kappa B* ; Pancreatic Neoplasms ; Proteome

PURPOSE: In the last three decades liver transplantation (LT) has been established as a standard procedure for end-stage liver disease. However, the shortage of donor livers is the most significant factor inhibiting further application of clinical liver transplantation. In Korea, where B-hepatitis is endemic, most patients waiting for LT are adult with B-hepatitis associated end stage liver disease. Safe, in situ splitting of a cadaver donor liver for two separate adult recipients would be an attractive way to decrease the deaths of adult patients while waiting for organs. Split grafts weighing more than 1% of the recipient's body weight (Graft to Recipient Weight Ratio, GRWR>1%) should be transplanted in order to adequately meet postoperative metabolic needs. We investigated whether one cadaver liver can be split into two so that each graft has a GRWR>1%. METHODS: Between January 1999 and December 1999 at Guro medical center, we selected 47 patients diagnosed as early gastric cancer (EGC) or early stage colon cancer and reviewed their pre-operative abdominal CT films for use in our study. Pictures of CT films were taken with a digital camera and converted to TIF files in order to calculate the standard liver volumes which were then divided by the plane that represented two operative methods proposed in this study. First, we performed a Rt. lobectomy along the right side of the middle hepatic vein to increase the function of segment IV by preventing venous congestion. Second, we performed a Lt. lobectomy with hepatic IVC to save the volume of the caudate lobe (segment I). RESULTS: The body index of the 47 cases was distributed from -10% to 20%. The standard whole liver volume was 1266+/-299 ml (Mean+/-SD). Rt. lobe volume was 751+/-188 ml, and Lt. lobe volume was 515+/-154 ml. Each result was no less than 1% of 75 kg and 50 kg adult's body weight. CONCLUSION: On average, the GRWR of the Rt. lobe is more than 1% in a 75 kg adult by itself and that of the Lt. lobe can also be above 1% in a 50 kg adult by maximizing the function of segments I and IV using the surgical techniques mentioned above. Therefore, we would be able to successfully spilt a cadaver donor liver to a 75 kg and a 50 kg adult recipient, respectively.
Adult* ; Body Weight ; Cadaver ; Colonic Neoplasms ; End Stage Liver Disease ; Hepatic Veins ; Humans ; Hyperemia ; Korea ; Liver Diseases ; Liver Transplantation* ; Liver* ; Stomach Neoplasms ; Tissue Donors ; Tomography, X-Ray Computed ; Transplants

Sunitinib is a multi-targeted tyrosine-kinase inhibitor used for gastrointestinal stromal tumors and renal cell carcinoma (RCC). Several recent studies have reported sunitinib-induced hypothyroidism and thyroid dysfunction; however, the underlying mechanisms are not clear. Here, we report a patient with metastatic RCC, who developed destructive thyroidtis due to sunitinib treatment. The course followed in this case may be useful in understanding the clinical course of sunitinib-induced thyroiditis.
Carcinoma, Renal Cell ; Gastrointestinal Stromal Tumors ; Humans ; Hypothyroidism ; Indoles ; Pyrroles ; Thyroid Gland ; Thyroiditis