How should the healthcare system support cancer survivors? Survivors' and health professionals' expectations and perception on comprehensive cancer survivorship care in Korea: a qualitative study.

BACKGROUND: Qualitative research on cancer survivors' need for comprehensive cancer survivorship care within the health care system is limited. Our study aimed to understand cancer survivors' and health professionals' expectations and perceptions for developing a comprehensive cancer survivorship care system in South Korea. METHODS: An exploratory qualitative study was conducted. A total of 16 subjects (11 cancer survivors and 5 health professionals) were purposively sampled from Regional Cancer Survivorship Centers or Cancer Survivor Clinics in Korea. In-depth semi-structured online or face-to-face interviews were conducted. Six steps of thematic analysis were used to analyze data. RESULTS: The following four primary themes emerged from the interviews: 1) introducing a customized follow-up care system to improve continuity of survivorship care, 2) implementing educational strategies for both survivors and health professionals to manage changed health, and 3) accepting cancer survivors as companions. These three themes included a total of nine subthemes. As a result, the comprehensive survivorship model identified needs in terms of 1) changes in the medical healthcare system and core services that can accommodate the cancer survivors' condition and 2) necessary care services and social support for cancer survivors. CONCLUSIONS: This study identified the existing gaps in Korea's current healthcare system regarding comprehensive cancer survivorship care for cancer survivors. Further research on eHealth-based counseling and educational support, the payment models of cancer survivorship care within universal health coverage, and changing social perceptions to strengthen the biopsychosocial needs of cancer survivors is needed.

Survival in untreated hepatocellular carcinoma: A national cohort study.

This study aimed to analyze the proportion, characteristics and prognosis of untreated hepatocellular carcinoma (HCC) patients in a large representative nationwide study. A cohort study was conducted using the National Health Insurance Service (NHIS) database in Korea. A total of 63,668 newly-diagnosed HCC patients between January 2008 and December 2013 were analyzed. Patients were categorized into treatment group and no treatment group using claim codes after HCC diagnosis. The proportion of untreated HCC patients was 27.6%, decreasing from 33.4% in 2008 to 24.8% in 2013. Compared to treated patients, untreated patients were more likely to be older (P < 0.001), female (P < 0.01), to have a distant SEER stage (P < 0.001), severe liver disease (P < 0.001), and lower income (P < 0.001). The fully-adjusted hazard ratio for all-cause mortality comparing untreated to treated patients was 3.11 (95% CI, 3.04-3.18). The risk of mortality was higher for untreated patients in all pre-defined subgroups, including those with distant SEER stage and those with severe liver disease. About one fourth of newly diagnosed HCC patients did not receive any HCC-specific treatment. Untreated patients showed higher risk of mortality compared to treated patients in all subgroups. Further studies are needed to identify obstacles for HCC treatment and to improve treatment rates.

Doxorubicin-induced heart failure in cancer patients: A cohort study based on the Korean National Health Insurance Database.

BACKGROUND: Doxorubicin is a typical anticancer drug that causes cardiomyopathy and heart failure (HF). The aim of our study was to investigate incidence, risk factors for doxorubicin-induced HF in Korean cancer patients and their survival rate, utilizing a nationwide population-based cohort. METHODS: We analyzed 58 541 cancer patients who received doxorubicin between 2003 and 2010. Descriptive analysis was performed in patients with breast cancer, hematologic malignancy, gynecological malignancy, and sarcoma. Risk factors associated with doxorubicin-induced HF were investigated using a Cox proportional hazards model. The survival rate of doxorubicin-induced HF patients was compared with that of patients without doxorubicin-induced HF. RESULTS: A total of 2324 (4%) were diagnosed with doxorubicin-induced HF. In patients with breast cancer, predictive risk factors for doxorubicin-induced HF included age over 65 years [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.05-1.72], hypertension [HR 2.45 (2.12- 2.84)], diabetes mellitus [HR 1.26 (1.05-1.51)], coronary artery disease [HR 2.08 (1.63-2.66)], advanced stage [HR 1.31 (1.13-1.50)], and trastuzumab administration [HR 2.94 (2.54-3.40)]. In patients with hematologic malignancy, predictive risk factors included age over 65 years [HR 1.75 (1.49-2.07)], hypertension [HR 1.62 (1.37-1.92)], and coronary artery disease [HR 2.28 (1.80-2.89)]. Five-year survival rates of patients with doxorubicin-induced HF were significantly lower relative to those of patients without HF in breast cancer and hematologic malignancy: 80% vs 84% and 69% vs 75%, respectively (P < 0.001). CONCLUSIONS: In cancer patients treated with doxorubicin, management of risk factors, early detection, and treatment for doxorubicin-induced HF might be critical for patient survival.

Anti-fatigue effect of Myelophil in a chronic forced exercise mouse model.

This study was performed to evaluate the anti-fatigue effects of Myelophil. ICR male mice (10 weeks old) were forced to run for 1 hour, 5 days/week for 4 weeks. Each running session was followed by administration of distilled water, Myelophil (50 or 100 mg/kg), or ascorbic acid (100 mg/kg) 1h later. Equal proportions of Astragali Radix and Salviae Miltiorrhizae Radix were extracted using 30% ethanol, and formulated into Myelophil. To evaluate the anti-fatigue effects of Myelophil, exercise tolerance and forced swimming tests were conducted. Underlying mechanisms, including oxidant-antioxidant balance, inflammatory response, and energy metabolism, were investigated by analyzing skeletal muscle tissues and/or sera. Myelophil significantly increased exercise ability and latency times, and decreased the number of electric shocks and immobility time on exercise tolerance and forced swimming tests compared with control group. Myelophil also significantly ameliorated fatigue-induced alterations in oxidative stress biomarkers, antioxidant enzymes and antioxidant capacity, as measured by multiple assays, including enzyme activity assays and western blotting, as well as alterations in pro- and anti-inflammatory cytokines in skeletal muscle. Furthermore, Myelophil normalized alterations in energy metabolic markers in sera. These findings suggest that Myelophil reduces the effects of chronic fatigue, likely by attenuating oxidative and inflammatory responses and normalizing energy metabolism. Consequently, this study provides evidence for the clinical relevance of Myelophil.

Ethanol extract of Astragali Radix and Salviae Miltiorrhizae Radix, Myelophil, exerts anti-amnesic effect in a mouse model of scopolamine-induced memory deficits.

ETHNOPHARMACOLOGICAL RELEVANCE: Myelophil, a combination of extracts taken from Astragali Radix and Salviae Miltiorrhizae Radix, is a traditional Chinese medicine used for the treatment of chronic fatigue-associated disorders. Here we examined the ability of Myelophil to alleviate memory impairment in a mouse model. We aimed to investigate whether Myelophil has the pharmacological effects on memory deficits associated with brain dysfunctions using an animal model. MATERIALS AND METHODS: Ten week-old male C57BL/6N mice were pretreated with Myelophil (50, 100, or 200 mg/kg), or tacrine (10 mg/kg) for 7 days, and then intraperitoneally injected with scopolamine (1 mg/kg). Memory-related behaviors were evaluated using the Morris water maze for 5 days. Levels of biomarkers of oxidative stress, antioxidant activity, acetylcholinesterase (AChE) activity, and extracellular signal-regulated kinase (ERK) were measured in brain tissues. RESULTS: Scopolamine treatment increased the escape latency time and shortened time spent in the target quadrant; these effects were ameliorated by pretreatment with Myelophil. Scopolamine-induced changes in reactive oxygen species (ROS), malondialehyde (MDA), and AChE activity were significantly attenuated in mice pretreated with Myelophil. Recovery of antioxidant capacities, including total glutathione (GSH) content, and the activities of GSH-reductase, GSH-S-transferase, and catalase was also evident in Myelophil-treated mice. The strongest effects were seen for ERK and muscarinic acetylcholine receptor 1 (mAChR1) at both the protein and gene expression levels, with significant amelioration of expression levels in the Myelophil pretreatment group. CONCLUSIONS: These results suggest that Myelophil confers anti-amnesic properties in a mouse model of memory impairment, driven in part by the modulation of cholinergic activity.

The economic burden of epilepsy in Korea, 2010.

OBJECTIVES: The purposes of this study were to evaluate the prevalence of epilepsy and to estimate the cost of epilepsy in Korea, 2010. METHODS: This study used a prevalence based approach to calculate the cost of epilepsy. Claims data from the Korean national health insurance and data from the Korea health panel, the Korea National Statistical Office's records of causes of death, and labor statistics were used to estimate the cost of epilepsy. Patients were defined as those who were hospitalized or visited an outpatient clinic during 2010 with a diagnosis of epilepsy (International Classification of Diseases 10th revision codes G40-G41). Total costs of epilepsy included direct medical costs, direct non-medical cost and indirect costs. RESULTS: The annual prevalence of treated epilepsy was 228 per 100 000 population, and higher in men. The age-specific prevalence was highest for teenagers. The total economic burden of epilepsy was 536 billion Korean won (KW). Indirect cost (304 billion KW) was 1.3 times greater than direct cost (232 billion KW). By gender, the male (347 billion KW) were more burdened than the female (189 billion KW). The estimated cost in young age younger than 20 years old was 24.5% of the total burden of epilepsy. CONCLUSIONS: A significant portion of the economic burden of epilepsy is borne by people in young age. To reduce the economic burden of epilepsy, effective prevention and treatment strategies are needed.

A strategy toward reconstructing the healthcare system of a unified Korea.

This road map aims to establish a stable and integrated healthcare system for the Korean Peninsula by improving health conditions and building a foundation for healthcare in North Korea through a series of effective healthcare programs. With a basic time frame extending from the present in stages towards unification, the roadmap is composed of four successive phases. The first and second phases, each expected to last five years, respectively, focus on disease treatment and nutritional treatment. These phases would thereby safeguard the health of the most vulnerable populations in North Korea, while fulfilling the basic health needs of other groups by modernizing existing medical facilities. Based on the gains of the first two phases, the third phase, for ten years, would prepare for unification of the Koreas by promoting the health of all the North Korean people and improving basic infrastructural elements such as health workforce capacity and medical institutions. The fourth phase, assuming that unification will take place, provides fundamental principles and directions for establishing an integrated healthcare system across the Korean Peninsula. We are hoping to increase the consistency of the program and overcome several existing concerns of the current program with this roadmap.

Web-based tailored education program for disease-free cancer survivors with cancer-related fatigue: a randomized controlled trial.

PURPOSE: To determine whether an Internet-based tailored education program is effective for disease-free cancer survivors with cancer-related fatigue (CRF). PATIENTS AND METHODS: We randomly assigned patients who had completed primary cancer treatment within the past 24 months in any of four Korean hospitals and had reported moderate to severe fatigue for at least 1 week to participate in a 12-week, Internet-based, individually tailored CRF education program or to receive routine care. We based the program on the CRF guidelines of the National Comprehensive Cancer Network (NCCN) and incorporated the transtheoretic model (TTM). At baseline and 12 weeks, we used the Brief Fatigue Inventory (BFI) and Fatigue Severity Scale (FSS) as primary outcomes and the Hospital Anxiety and Depression Scale (HADS) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) for secondary outcomes. RESULTS: We recruited 273 participants and randomly assigned 136 to the intervention group. Compared with the control group, the intervention group had an improvement in fatigue as shown by a significantly greater decrease in BFI global score (-0.66 points; 95% CI -1.04 to -0.27) and FSS total score (-0.49; 95% CI, -0.78 to -0.21). In secondary outcomes, the intervention group experienced a significantly greater decrease in HADS anxiety score (-0.90; 95% CI, -1.51 to -0.29) as well as global quality of life (5.22; 95% CI, 0.93 to 9.50) and several functioning scores of the EORTC QLQ-C30. CONCLUSION: An Internet-based education program based on NCCN guidelines and TTM may help patients manage CRF.

Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells.

Compelling evidence indicates that polyphenolic antioxidants protect against diabetic nephropathy. Pycnogenol is made up of flavonoids, mainly procyanidins and phenolic compounds, and is a known powerful antioxidant. Hyperglycemia is characteristic of diabetic nephropathy and induces renal tubular cell apoptosis. Thus, in this study, we used high glucose-treated renal tubular cells to investigate the protective action of pycnogenol against high glucose-induced apoptosis and diabetic nephropathy. We also sought to further delineate the underlying mechanisms elicited by oxidative stress and inflammation and suppressed by pycnogenol. Results show that pycnogenol significantly suppressed the high glucose-induced morphological changes and the reduction in cell viability associated with cytotoxicity. Bcl2/Bax protein levels indicated pycnogenol's anti-apoptotic effect against high glucose-induced apoptotic cell death. In addition, several key markers of oxidative stress and inflammation were measured for pycnogenol's beneficial effects. Results indicate pycnogenol's anti-oxidative and anti-inflammatory efficacy in suppressing lipid peroxidation, total reactive species (RS), superoxide ((·)O(2)), nitric oxide (NO(·)), peroxynitrite (ONOO(-)), pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) nuclear translocation. Based on these results, we conclude that pycnogenol's anti-oxidative and anti-inflammatory properties underlie its anti-apoptotic effects, suggesting further investigation of pycnogenol as a promising treatment against diabetic nephropathy.

Diallyl trisulfide-induced G2/M phase cell cycle arrest in DU145 cells is associated with delayed nuclear translocation of cyclin-dependent kinase 1.

PURPOSE: The present study was undertaken to gain insight into the molecular mechanism of G2/M phase cell cycle arrest resulting from treatment of DU145 cells with diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of garlic. METHODS: Cell cycle distribution was determined by flow cytometry. Immunoblotting was performed to determine protein expression. Overexpression of wild-type or mutant Cdc25C was achieved by transient transfection. Nuclear and cytoplasmic localization of cyclin B1 and cyclin-dependent kinase 1 (cdk1) was studied by immunoblotting. RESULTS: Exposure of DU145 human prostate cancer cells to DATS resulted in concentration- and time-dependent accumulation of G2/M phase cells, which correlated with down-regulation as well as increased S216 phosphorylation of Cdc25C. Ectopic expression of wild-type or redox-insensitive mutants (C330S and C330S/C377S) or S216A mutant of Cdc25C failed to confer protection against DATS-induced G2/M phase arrest. The DATS-mediated G2/M phase cell cycle arrest was also independent of reduced complex formation between cdk1 and cyclin B1, but correlated with delayed nuclear translocation of cdk1. CONCLUSION: The present study indicates that the DATS-mediated G2/M phase cell cycle arrest in DU145 cells results from differential kinetics of nuclear localization of cdk1 and cyclin B1.

Attenuation of oxidative stress and inflammation by gravinol in high glucose-exposed renal tubular epithelial cells.

Gravinol, a proanthocyanidin from grape seeds, has polyphenolic properties with powerful anti-oxidative effects. Although, increasing evidence strongly suggests that polyphenolic antioxidants suppress diabetic nephropathy that is causally associated with oxidative stress and inflammation, gravinol's protective action against diabetic nephropathy has not been fully explored to date. In the current study, we investigated the protective action of gravinol against oxidative stress and inflammation using the experimental diabetic nephropathy cell model, high glucose-exposed renal tubular epithelial cells. To elucidate the underlying actions of gravinol, several oxidative and inflammatory markers were estimated. Included are measurements of lipid peroxidation, total reactive species (RS), superoxide (O(2)), nitric oxide (NO), and peroxynitrite (ONOO(-)), as well as nuclear factor-kappa B (NF-kappaB) nuclear translocation. Results indicate that gravinol had a potent inhibitory action against lipid peroxidation, total RS, O(2), NO, ONOO(-), the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and more importantly, against NF-kappaB nuclear translocation. We propose that gravinol's strong protective effect against high glucose-induced renal tubular epithelial cell damage attenuates diabetic nephropathy by suppressing oxidative stress and inflammation.

Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells.

Garlic-derived organosulfur compounds (OSCs) are highly effective in affording protection against chemically induced pulmonary carcinogenesis in animal models. We now demonstrate that garlic constituent diallyl trisulfide (DATS) suppresses viability of cultured human lung cancer cell lines H358 (anon-small cell lung cancer cell line) and H460 (a large cell lung cancer cell line) by causing G2-M phase cell cycle arrest and apoptotic cell death. On the other hand, a normal human bronchial epithelial cell line BEAS-2B was significantly more resistant to growth inhibition and apoptosis induction by DATS compared with lung cancer cells. We also found that even a subtle change in the OSC structure could have a significant impact on its biological activity. For example, DATS was significantly more effective than either diallyl sulfide or diallyl disulfide against proliferation of lung cancer cells. The DATS-mediated G2-M phase cell cycle arrest was explained by down-regulation of cyclin-dependent kinase 1 (Cdk1) and cell division cycle 25C protein expression leading to accumulation of Tyr15 phosphorylated (inactive) Cdk1. The DATS-induced apoptosis correlated with induction of pro-apoptotic proteins Bax, Bak and BID, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL in lung cancer cells but not in BEAS-2B. Knockdown of Bax and Bak proteins conferred significant protection against DATS-induced apoptotic cytoplasmic histone-associated DNA fragmentation. On the other hand, BID protein was dispensable for DATS-induced apoptosis. In conclusion, the present study indicates that Bax and Bak proteins are critical targets of DATS-induced apoptosis in human lung cancer cells.

Paenibacillus ginsengihumi sp. nov., a bacterium isolated from soil in a ginseng field.

Strain DCY16T, a Gram-positive, spore-forming, rod-shaped, motile bacterium, was isolated from soil and characterized in order to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that strain DCY16T belonged to the genus Paenibacillus; highest sequence similarities were with Paenibacillus validus JCM 9077T (94.4 %), P. chinjuensis WN9T (94.4 %), P. naphthalenovorans DSM 14203T (94.2 %), P. ehimensis KCTC 3748T (92.8 %) and P. elgii KCTC 10016BP(T) (92.4 %). Chemotaxonomic data revealed that strain DCY16T possessed menaquinone MK-7 and the predominant fatty acids were C15 : 0 anteiso, C17 : 0 anteiso, C16 : 0 and C16 : 0 iso. The DNA G+C content of strain DCY16T was 50.9 mol%. Results of physiological and biochemical tests clearly demonstrated that strain DCY16T represents a distinct Paenibacillus species. Based on these data, DCY16T (=KCTC 13141T =JCM 14928T) should be classified as the type strain of a novel species, for which the name Paenibacillus ginsengihumi sp. nov. is proposed.

Parapedobacter soli sp. nov., isolated from soil of a ginseng field.

Strain DCY14(T), a Gram-negative, non-spore-forming, rod-shaped, non-motile bacterium, was isolated from soil from a ginseng field in Korea and was characterized in order to determine its taxonomic position. 16S rRNA gene sequence analysis revealed that strain DCY14(T) belongs to the family Sphingobacteriaceae, the highest degree of sequence similarity being found with respect to Parapedobacter koreensis Jip14(T) (95.8 %). Chemotaxonomic data revealed that strain DCY14(T) possesses MK-7 as the major menaquinone. The major fatty acids present were anteiso-C(13 : 0), iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 4 (C(16 : 1)omega7c/iso-C(15 : 0) 2-OH). The results of physiological and biochemical tests clearly demonstrated that strain DCY14(T) represents a distinct species. On the basis of these data, DCY14(T) represents a novel species of the genus Parapedobacter, for which the name Parapedobacter soli sp. nov. is proposed. The type strain is DCY14(T) (=KCTC 12984(T) =LMG 24069(T)).

Resveratrol inhibits nitric oxide and prostaglandin E2 production by lipopolysaccharide-activated C6 microglia.

Resveratrol, a natural polyphenolic antioxidant found in red wine and grapes, has been reported to exert a variety of important pharmacological effects, including anti-inflammatory, cardioprotective, and cancer chemopreventive properties. In the present study, we investigated the effect of resveratrol on the production of nitric oxide (NO) and prostaglandin (PG) E2 by lipopolysaccharide (LPS)-activated C6 microglia. Exposure of cultured rat C6 astroglioma cells to LPS increased their release of NO and PGE2 and their inducible expression of NO synthase and cyclooxygenase-2, all of which were significantly inhibited by resveratrol pretreatment. Further studies revealed that resveratrol suppressed LPS-induced nuclear translocation and activation of nuclear factor kappaB (NF-kappaB). These results demonstrate a potent suppressive effect of resveratrol on pro-inflammatory responses of microglia by modulation of NF-kappaB activity, suggesting a therapeutic potential for this compound in neurodegenerative diseases accompanied by microglial activation.

Protective effect of the Chinese prescription Kangen-karyu against high glucose-induced oxidative stress in LLC-PK1 cells.

We investigated the effects of Chinese prescription Kangen-karyu on high glucose-induced oxidative stress using LLC-PK(1) cells, renal tubular cells, which are the most vulnerable renal tissue to oxidative stress. High-concentration glucose (30mM) treatment induced LLC-PK(1) cell death, but Kangen-karyu, at a concentration of 5, 10 or 50 microg/ml, significantly inhibited high glucose-induced cytotoxicity. In addition, the intracellular reactive oxygen species level was increased by 30mM glucose treatment, but it was concentration-dependently inhibited by Kangen-karyu treatment. Moreover, 30mM glucose treatment induced high levels of superoxide anion, nitric oxide and peroxynitrite. However, Kangen-karyu treatment significantly reduced the radical overproduction induced by high glucose, suggesting Kangen-karyu has radical-scavenging activity that would protect against oxidative stress induced by high glucose. Kangen-karyu also reduced the overexpression of inducible nitric oxide synthase and cyclooxygenase-2 proteins induced by high glucose. Furthermore, treatment with Kangen-karyu, at a concentration of 50mug/ml, inhibited the nuclear translocation of nuclear factor-kappa B induced by 30mM glucose in LLC-PK(1) cells. These findings indicate that Kangen-karyu is a potential therapeutic agent that will reduce the damage caused by hyperglycemia-induced oxidative stress associated with diabetes.

Activity of wen-pi-tang, and purified constituents of rhei rhizoma and glycyrrhizae radix against glucose-mediated protein damage.

Wen-Pi-Tang, an Oriental medical prescription composed of Rhei Rhizoma, Ginseng Radix, Aconiti Tuber, Zingiberis Rhizoma and Glycyrrhizae Radix, is used clinically as a medicine to treat renal failure. This study was conducted to examine the inhibitory activity of the five crude drug components of Wen-Pi-Tang and several pure compounds isolated from Rhei Rhizoma and Glycyrrhizae Radix against the protein glycation reaction. Rhei Rhizoma exerted the most potent activity, Zingiberis Rhizoma and Glycyrrhizae Radix showed relatively moderate activity, whereas Aconiti Tuber and Ginseng Radix showed weak activity. On the other hand, of 20 compounds obtained from Rhei Rhizoma and Glycyrrhizae Radix, tannins, especially rhatannin, RG-tannin and procyanidin B-2 3,3'-di-O-gallate, showed significantly strong activities that were more effective than the positive control, aminoguanidine. Some flavones such as licochalcone A and licochalcone B, and anthraquinones such as emodin and aloe-emodin, also showed inhibitory activity. These findings may help to explain, at least in part, certain pharmacological activities of Wen-Pi-Tang, whose clinical efficacy against renal failure is already recognized.

The mechanisms underlying the anti-aging activity of the Chinese prescription Kangen-karyu in hydrogen peroxide-induced human fibroblasts.

Our previous study showed that Kangen-karyu extract protected against cellular senescence by reducing oxidative damage through the inhibition of reactive oxygen species generation and regulation of the antioxidative status. Although these findings suggest that Kangen-karyu could delay the aging process, the mechanisms responsible for protection against aging have rarely been elucidated. Therefore, this study was focussed on the mechanisms responsible for the anti-aging activity of Kangen-karyu extract using hydrogen peroxide (H(2)O(2))-induced human diploid fibroblasts, a well-established experimental model of cellular aging. Kangen-karyu extract exerted a protective effect against the morphological changes induced by H(2)O(2) treatment and inhibited senescence-associated beta-galactosidase activity. In addition, the beneficial effects of Kangen-karyu extract on cell viability and lifespan indicated that Kangen-karyu extract could delay the cellular aging process. The observation that Kangen-karyu extract prevented nuclear factor kappa B (NF-kappaB) translocation in response to oxidative stress suggested that Kangen-karyu exerted its anti-aging effect through NF-kappaB modulation and prevention of H(2)O(2)-induced overexpression of haem oxygenase-1 protein. Moreover, pretreatment with Kangen-karyu extract reduced overexpression of bax protein and prevented the mitochondrial membrane potential decline, suggesting that Kangen-karyu extract may protect mitochondria from mitochondrial oxidative stress and dysfunction. These findings indicate that Kangen-karyu is a promising potential anti-aging agent that may delay, or normalize, the aging process by virtue of its protective activity against oxidative stress-related conditions.

Resveratrol inhibits cell proliferation and induces apoptosis of human breast carcinoma MCF-7 cells.

Resveratrol, which is found in grapes and wine, has been reported to have a variety of important pharmacological effects including anti-inflammatory, anti-platelet, and anti-carcinogenetic properties. In this study, using the human breast cancer cell line MCF-7, we have analyzed a possible mechanism by which resveratrol could interfere with cell cycle control and induce cell death. Resveratrol treatment of MCF-7 cells resulted in a dose-dependent inhibition of the cell growth and the cells accumulated at the S phase transition of the cell cycle at low concentrations, but high concentrations do not induce S phase accumulation. The anti-proliferative effects of resveratrol were associated with a marked inhibition of cyclin D and cyclin-dependent kinase (Cdk) 4 proteins, and induction of p53 and Cdk inhibitor p21WAF1/CIP. Growth suppression by resveratrol was also due to apoptosis, as seen by the appearance of a sub-G1 fraction and chromatin condensation. In addition, the apoptotic process involves activation of caspase-9, a decrease of Bcl-2 as well as Bcl-XL levels, and an increase of Bax levels.