• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.7
• /
• pp.4033-4039
• /
• 2013

Links between cancer and metabolism have been suggested for a long time but compelling evidence for this hypothesis came from the recent molecular characterization of the LKB1/AMPK signaling pathway as a tumor suppressor axis. Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. In addition, AMPK plays a central role in the control of cell growth, proliferation and autophagy through the regulation of mTOR activity, which is consistently deregulated in cancer cells. Targeting of AMPK/mTOR is thus an attractive strategy in the development of therapeutic agents against non-small-cell lung cancer (NSCLC). In this review, the LKB1/AMPK/mTOR signaling pathway is described, highlighting its protective role, and opportunities for therapeutic intervention, and clinical trials in NSCLC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.12
• /
• pp.4853-4858
• /
• 2015

Background: Colorectal cancer is the most common gastrointestinal cancer in Oman with an increasing incidence. We here report the presenting features, treatment outcomes and survival in a University hospital in Oman and compare our data with regional and international studies. Materials and Methods: Medical records of patients with colorectal cancer were reviewed retrospectively between June 2000 and December 2013 and were followed until June 2014. Results: A total of 162 patients were diagnosed with colorectal cancer. The majority were males (58.6%), with a median age of 56 years. Rectum was involved in 29.6% of patients, followed by ascending and sigmoid colon. The majority of patients had stage III (42.6%) and stage IV (32.7%) disease at presentation. K-Ras status was checked for 79 patients, and 41 (51.9%) featured the wild type. Median relapse free survival was 22 months. Median overall survival for all patients was 43 months. Observed 5 year overall survival (OS) for stages I, II and III was 100%, 60% and 60% respectively. On Log rank univariate analysis, age, BMI, diabetes, hypertension, metformin use, stage, clinical nodal status for rectal cancer, pathological T and nodal status, site of metastasis, surgical intervention, chemotherapy, radiotherapy, chemotherapy regimen, no of cycles of chemotherapy, response, RFS, site of recurrence and administration of $2^{nd}$ line chemotherapy were significant factors affecting OS. On Cox regression multivariate analysis none of the factors independently affected the OS. Conclusions: The majority of patients present with advanced disease and at young age. The survival rates are comparable to the published regional and international literature.

• Journal of Nutrition and Health
• /
• v.31 no.6
• /
• pp.973-980
• /
• 1998

To investigate the effect of sea tangle on immune function in normal and diabetic states, 10-week old ICR mice were feed control(C) and sea tangle(5) diets containing 5%(w/w) cellulose and 13.6%(w/w) dry sea tangle for 4 weeks. After 4 weeks, three quarters of mice(CD and SD) were made diabetic by intramuscular injection of streptozotocin(150mg/kg bw). On the 4th day after diabetes was apparent by urinary glucose, one third of diabetic mire(CDG and SDG) were treated with glipizide(20mg/kg bw) and the other third(CDM and SDM) with metformin (500mg/kg bw) orally. Spleen weights of diabetic mice with no hypoglycemic drug treatment appeared to be higher in the sea tangle group(SD) than in control(CD), but were not different when drugs were administered. Data on splenocyte proliferation stimulated by lipopolysaccaride from Salmonella abortus equi(0.l$\mu\textrm{g}$/ml) showed that sea tangle increased mitogen response in normal mice(C group vs S group) and appeared to have the same effect in diabetic mice with or without drug treatment. Splenocyte proliferation induced by concanavalin A(0.1$\mu\textrm{g}$/ml) also showed similar results, although there were not statistically significant. Concentration of interleukin-2(IL-2) released from splenocytes of the S group seemed higher than from the C group, but the IL-2 concentrations were not different among six diabetic groups. Results of fatty acid compositions of splenocyte phospholipids showed that diabetes reduced arachidonic acid/linoleic acid ratios and that sea tangle intake and glipizide treatments increased contents of polyunsaturated fatty acids. It is concluded that dietary sea tangle has a positive effect on splenocyte proliferation under normal condition and could have the same effect under diabetic conditions. IL-2 appears to be one of factors mediating the effect but involvement of membrane fatty arid changes and other unknown factors needs lurker Investigation. (Korean J Nutrition 31(6) : 973-980, 1998)

• Nutrition Research and Practice
• /
• v.6 no.5
• /
• pp.405-413
• /
• 2012

Rho iso-alpha acids-rich extract (RIAA) from Humulus lupulus (hops) and proanthocyanidins-rich extracts (PAC) from Acacia nilotica exert anti-inflammatory and anti-diabetic activity in vitro and in vivo. We hypothesized that a combination of these two extracts would exert enhanced effects in vitro on inflammatory markers and insulin signaling, and on nonfasting glucose and insulin in db/db mice. Over 49 tested combinations, RIAA:PAC at 5:1 ($6.25{\mu}g/mL$) exhibited the greatest reductions in $TNF{\alpha}$-stimulated lipolysis and IL-6 release in 3T3-L1 adipocytes, comparable to $5{\mu}g/mL$ troglitazone. Pretreatment of 3T3-L1 adipocytes with this combination ($5{\mu}g/mL$) also led to a 3-fold increase in insulin-stimulated glucose uptake that was comparable to $5{\mu}g/mL$ pioglitazone or $901{\mu}g/mL$ aspirin. Finally, db/db mice fed with RIAA:PAC at 5:1 (100 mg/kg) for 7 days resulted in 22% decrease in nonfasting glucose and 19% decrease in insulin that was comparable to 0.5 mg/kg rosiglitazone and better than 100 mg/kg metformin. RIAA:PAC mixture may have the potential to be an alternative when conventional therapy is undesirable or ineffective, and future research exploring its long-term clinical application is warranted.

• Journal of Pharmacopuncture
• /
• v.20 no.1
• /
• pp.45-51
• /
• 2017

Objectives: This study aimed to evaluate the hypoglycemic effects of an ethanol extract of Cassia abbreviata (ECA) bark and the possible mechanisms of its action in diabetic albino rats. Methods: ECA was prepared by soaking the powdered plant material in 70% ethanol. It was filtered and made solvent-free by evaporation on a rotary evaporator. Type 2 diabetes was induced in albino rats by injecting 35 mg/kg body weight (bw) of streptozotocin after having fed the rats a high-fat diet for 2 weeks. Diabetic rats were divided into ECA-150, ECA-300 and Metformin (MET)-180 groups, where the numbers are the doses in mg.kg.bw administered to the groups. Normal (NC) and diabetic (DC) controls were given distilled water. The animals had their fasting blood glucose levels and body weights determined every 7 days for 21 days. Oral glucose tolerance tests (OGTTs) were carried out in all animals at the beginning and the end of the experiment. Liver and kidney samples were harvested for glucose 6 phosphatase (G6Pase) and hexokinase activity analyses. Small intestines and diaphragms from normal rats were used for ${\alpha}-glucosidase$ and glucose uptake studies against the extract. Results: Two doses, 150 and 300 mg/kg bw, significantly reduced the fasting blood glucose levels in diabetic rats and helped them maintain normal body weights. The glucose level in DC rats significantly increased while their body weights decreased. The 150 mg/kg bw dose significantly increased hexokinase and decreased G6Pase activities in the liver and the kidneys. ECA inhibited ${\alpha}-glucosidase$ activity and promoted glucose uptake in the rats' hemi-diaphragms. Conclusion: This study revealed that ECA normalized blood glucose levels and body weights in type 2 diabetic rats. The normalization of the glucose levels may possibly be due to inhibition of ${\alpha}-glucosidase$, decreased G6Pase activity, increased hexokinase activity and improved glucose uptake by muscle tissues.

• The Journal of Korean Medicine
• /
• v.33 no.3
• /
• pp.33-45
• /
• 2012

Objectives: Recent data have revealed that the plasma concentration of inflammatory mediators is increased in the insulin-resistant states of obesity and type 2 diabetes. The purpose of this study was to investigate the antidiabetic and anti-obesity effect of Massa Medicata Fermentata on obese type 2 diabetes mice. Methods: In order to examine the effects of Massa Medicata Fermentata, obese type 2 diabetes mice induced by Surwit's high fat, high sucrose diet. Mice were divided into 4 groups of ND (normal diet), HFD (high fat and high sucrose diet), Met (high fat and high sucrose diet with metformin) and MMF (high fat and high sucrose diet with Massa Medicata Fermentata) and investigated over 8 weeks. Diabetic and obese clinical markers, including body weight, glucose level, lipid level, leptin concentration, epididymal fat pad and liver weights and adipose tissue macrophage (ATM) were determined. Results: Compared with the HFD group, body weight, fructosamine, triglyceride, epididymal fat pad weight and ATM were significantly reduced in the MMF group. Conclusions: From the above results, the intake of Massa Medicata Fermentata may be effective in anti-hyperglycemia and anti-obesity by the attenuation of glucose and lipid levels and also inflammation state. Massa Medicata Fermentata may be beneficial for controlling diabetes mellitus type 2 in humans.

• Journal of Ginseng Research
• /
• v.32 no.3
• /
• pp.187-193
• /
• 2008

The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.

• Journal of Veterinary Clinics
• /
• v.28 no.3
• /
• pp.280-286
• /
• 2011

The antiobese effects of Allium victorialis (AV) leaf methanol extract were evaluated in a high fat diet (HFD) supplied mice. The changes on the body weight, food consumption, leptin and adiponectin levels as well as the periovarian fat weights and histopathology of adipocytes were examined. The effects were compared with those of a group given 250 mg/kg of metformin. After 91 days of a continuous HFD supply, the mice were significantly showed obesity. However, the obesity induced by the HFD was inhibited by the AV extract treatment at the three different doses (62.5, 125 and 250 mg/kg) respectively. The results suggest that the AV methanol extract is beneficial for improving the diet-induced obesity in humans.

• The Journal of Korean Medicine
• /
• v.36 no.1
• /
• pp.75-85
• /
• 2015

Objectives: Type 2 diabetes mellitus is a metabolic disease characterized by insulin resistance and high blood glucose level from progressive insulin secretory defect. The rhizome of Atractylodes japonica Koidz. (AJ) has been used for treatment of retention of water in oriental medicine. The aim of this study is to examine the effects of AJ on type 2 diabetes rats. Methods: Type 2 diabetes was induced by 60% high fat diet and low dose streptozotocin. Rats were divided into 4 groups (n = 6); Nor (normal control group), Con (diabetic group treated with vehicle), Met (diabetic group treated with 200 mg/kg metformin) and AJ (diabetic group treated with 100 mg/kg AJ). The body weights and food intakes were measured during the treatment period. After 4 weeks treatment, blood glucose level, HOMA-IR, and protein expressions of IRS-1, p-IRS-1, PPAR-${\gamma}$, and GLUT4 were measured, and histopathological examination of beta cell was performed. Results: Compared with the control group, blood glucose level and HOMA-IR were reduced in rats treated with AJ. Impaired beta cells in pancreas of rats were recovered and phosphorylation of IRS-1 was increased in rats treated with AJ. And also, protein expressions of PPAR-${\gamma}$ and GLUT4 were increased by treatment of AJ. Conclusions: The results suggest that Atractylodes japonica Koidz. may have anti-diabetic effect on type 2 diabetic rats through regulation of blood glucose level and insulin resistance. Therefore Atractylodes japonica Koidz. may have positive effects on patients with type 2 diabetes.

• Korean Journal of Pharmacognosy
• /
• v.45 no.3
• /
• pp.194-199
• /
• 2014

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.