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Background: The essential oil of Pinus koraiensis (EOPK) is biologically active compound obtained from the leaves of P. koraiensis. The goal of this study was to investigate the anti-cancer mechanism of EOPK in HCT116 colorectal cancer cells. Methods: HCT116 cell proliferation was assessed by conducting crystal violet and BrdU assays. To assess the effects of EOPK on cell migration, we performed a wound-healing assay. Further, the contribution of PAK1 to EOPK-induced AKT and extracellular signal-regulated kinase (ERK) suppression was assessed by siRNA-mediated PAK1 knockdown. Changes to the expression and phosphorylation of PAK1 and its effectors were determined by western blotting, and changes to the actin cytoskeleton were determined by performing an immunofluorescence assay. Results: EOPK significantly decreased HCT116 cell proliferation and migration, and induced G1 arrest without affecting normal cells. Additionally, EOPK suppressed the expression of PAK1, and decreased ERK and AKT phosphorylation in HCT116 cells. Finally, EOPK suppressed β-catenin, cyclin D1, and CDK4/6 expression. Conclusions: Our studies indicate that EOPK significantly reduced proliferation and migration of colorectal cancer cells. Furthermore, EOPK suppressed PAK1 expression in a dose-dependent manner, and this suppression of PAK1 led to inhibition of ERK, AKT, and β-catenin activities. Our findings suggest that EOPK exerts its anticancer activity via the inhibition of PAK1 expression, suggesting it may be a potent chemotherapeutic agent for colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: S100A9 protein (myeloid-related protein MRP14, also referred to as calgranulin B) is a reliable marker of inflammation, an important proinflammatory factor of innate immunity and acts as an additional antimicrobial peptide in the innate immune system. Evidence indicates that S100A9 contributes to Alzheimer's disease (AD) pathology, although the precise mechanisms are not clear. Methods: We were interested to study the mechanisms of S100A9 release upon Aβ1-42 stimulation, the potential roles of extracellular S100A9 depletion in Aβ-induced cytotoxicity, and the interaction with innate immune response in THP-1 monocytic cells that have been challenged with mostly Aβ1-42 monomers instead of oligomers. We used protein preparation, Ca2+ influx fluorescence imaging, MTT assay, siRNA knockdown, colony forming units (CFUs) assay and western blotting techniques to perform our study. Results: Aβ1-42 monomers elicited a marked decrease of S100A9 release into the cell culture supernatant in a dose-dependent manner in human THP-1 monocytes. This reduction of S100A9 release was accompanied by an increase of intracellular Ca2+ level. Aβ1-42-mediated decrease of S100A9 release was not associated with Aβ1-42- induced cytotoxicity as measured by MTT reduction assay. This observation was confirmed with the recombinant S100A9, which had little effect on Aβ1-42-induced cytotoxicity. Moreover, depletion of S100A9 with siRNA did not significantly evoke the cell toxicity. On the other hand, Aβ1-42-induced extracellular S100A9 depletion resulted in decreased antimicrobial activity of the culture supernatant after Aβ1-42 stimulation. Immunodepletion of S100A9 with anti-S100A9 also decreased the antimicrobial peptide activity of the vehicle treated culture supernatant. Consistently, the recombinant S100A9 clearly elicited the antimicrobial peptide activity in vitro, confirming the observed antimicrobial activity of S100A9 in the culture supernatant. Conclusion: Collectively, our findings suggest that the mostly monomeric form of Aβ1-42 negatively regulates the innate immune system by down-regulating the secretion of S100A9, which is likely a main mediator of antimicrobial activity in the conditioned media of human THP-1 monocytes. [ABSTRACT FROM AUTHOR]

Though melatonin was known to regulate gap junctional intercellular communication (GJIC) in chick astrocytes and mouse hepatocytes, the underlying mechanism by melatonin was not elucidated in hydrogen peroxide- (H2O2-) treated HaCaT keratinocyte cells until now. In the current study, though melatonin at 2m M and hydrogen peroxide (H2O2) at 300 μ M showed weak cytotoxicity in HaCaT keratinocyte cells, melatonin significantly suppressed the formation of reactive oxygen species (ROS) in H2O2-treated HaCaT cells compared to untreated controls. Also, the scrape-loading dye-transfer assay revealed that melatonin enhances the intercellular communication by introducing Lucifer Yellow into H2O2-treated cells. Furthermore, melatonin significantly enhanced the expression of connexin 26 (Cx26) and connexin 43 (Cx43) at mRNA and protein levels, but not that of connexin 30 (Cx30) in H2O2-treated HaCaT cells. Of note, melatonin attenuated the phosphorylation of extracellular signal-regulated protein kinases (ERKs)more than p38 MAPK or JNK in H2O2-treated HaCaT cells. Conversely, ERK inhibitor PD98059 promoted the intercellular communication in H2O2-treated HaCaT cells. Furthermore, combined treatment of melatonin (200 μ M) and vitamin C (10 μg/mL) significantly reduced ROS production in H2O2-treated HaCaT cells. Overall, these findings support the scientific evidences that melatonin facilitates gap junctional intercellular communication in H2O2-treated HaCaT keratinocyte cells via inhibition of connexin 26/43 and ERK as a potent chemopreventive agent. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is one of important issues to cause the chemotherapy failure against cancers including gynecological malignancies. Despite some MDR reversal evidences of natural compounds including quinidine and cinchonine, there are no reports on MDR reversal activity of hydrocinchonine with its analogues quinidine and cinchonine especially in uterine sarcoma cells. Thus, in the current study, we comparatively investigated the potent efficacy of hydrocinchonine and its analogues quinidine and cinchonine as MDR-reversal agents for combined therapy with antitumor agent paclitaxel (TAX). Hydrocinchonine, cinchonine, and quinidine significantly increased the cytotoxicity of TAX in P-glycoprotein (gp)-positive MES-SA/DX5, but not in the P-gp-negative MES-SA cells at nontoxic concentrations by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Rhodamine assay also revealed that hydrocinchonine, cinchonine, and quinidine effectively enhanced the accumulation of a P-gp substrate, rhodamine in TAX-treated MES-SA/DX5 cells compared with TAX-treated control. In addition, hydrocinchonine, cinchonine, and quinidine effectively cleaved poly (ADP-ribose) polymerase (PARP), activated caspase-3, and downregulated P-gp expression as well as increased sub-G1 apoptotic portion in TAX-treated MES-SA/DX5 cells. Taken together, hydrocinchonine exerted MDR reversal activity and synergistic apoptotic effect with TAX in MES-SA/DX5 cells almost comparable with quinidine and cinchonine as a potent MDR-reversal and combined therapy agent with TAX. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2010) 112, 1477–1488. Published evidence has linked glutamate with the pathogenesis of Alzheimer’s disease (AD) and the up-regulation of a variety of chemokines, including monocyte chemotactic protein-1 (MCP-1)/chemokine ligand 2, with AD-associated pathological changes. In this study, we assessed the potential molecular basis for the role of glutamate in hippocampal inflammation by determining its effects on MCP-1 induction. We also attempted to identify the mechanism by which resveratrol (trans-3,5,4′-trihydroxystilbene), a polyphenolic phytostilbene, modulates the expression of MCP-1 in the glutamate-stimulated hippocampus. An ex vivo study using rat hippocampal slices demonstrated a time- and dose-dependent increase in MCP-1 release from glutamate-exposed hippocampus. This increase was accompanied by enhanced MCP-1 gene expression via the activation of the MEK/extracellular signal-regulated kinase (ERK) pathway and interleukin-1β (IL-1β) expression. The inhibition of the MEK/ERK pathway with SL327, which is capable of crossing the blood-brain barrier, nearly abolished the observed glutamate-induced effects. Furthermore, anti-IL-1β antibodies suppressed the glutamate-induced expression of MCP-1 mRNA and protein, whereas an isotype-matched antibody exerted only minimal effects. It is worthy of note that resveratrol, to a similar degree as SL327, down-regulated glutamate-induced IL-1β expression and reduced the expression of MCP-1 mRNA and protein release via the inactivation of ERK1/2. These results indicate that the activation of the MEK/ERK pathway and the consequent IL-1β expression are essential for glutamate-stimulated MCP-1 production in the hippocampus. Additionally, our data reveal an anti-inflammatory mechanism of resveratrol involving the inactivation of the ERK1/2 pathway in the hippocampus, which is linked principally to AD-associated cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: Individuals with osteoarthritis can experience difficulty walking and poor strength, possibly leading to falls and fractures. Exercise has been found to increase strength and bone mineral density. The purpose of this study was to determine the effects of 6 months of t'ai chi on knee muscle strength, bone mineral density, and fear of falling in older women with osteoarthritis. Methods: Eighty-two (82) women with osteoarthritis, recruited from outpatient clinics and community health centers, were randomly assigned to either a t'ai chi group and took part in a t'ai chi program, or a control group. Of these, 30 subjects (mean age = 63 years) in the t'ai chi group and 35 (mean age = 61 years) in the control group completed post-test measures at 6 months. Results: After the 6-month study period, subjects in the t'ai chi program had significantly greater knee extensor endurance (pre- to post-test mean increase = 36.4 W/kg, versus 1.1 W/kg for the controls), and significantly greater bone mineral density in the neck of the proximal femur (mean change = 0.09, versus −0.10 for the controls), Ward's triangle (mean change = 0.04, versus −0.04 for the controls), and trochanter (mean change = 0.07, versus −0.05 for the controls) than the controls. However, knee extensor and flexor strength did not differ significantly between the groups. The fear of falling during daily activities reduced significantly more in the t'ai chi group (mean change = −2.40, versus 0.66 for the controls). Conclusions: T'ai chi increased knee extensor muscle endurance and bone mineral density in older women with osteoarthritis, and decreased their fear of falling during daily activities. Further study with long-term follow-up is needed to substantiate the role of t'ai chi exercise in the prevention of fall and its related fracture. [ABSTRACT FROM AUTHOR]

Purpose/Objectives: To determine the feasibility of conducting a study of a tai chi self-help education program in Korean adults with gastric cancer and to describe the effects of a six-month tai chi self-help education program on depression, health-related quality of life (HRQOL), and immune markers.Design: One-group, pre- and post-test design.Setting: Outpatient clinics of two large hospitals in the Republic of Korea.Sample: Convenience sample of 33 Korean adults with gastric cancer diagnoses after gastrectomy.Methods: The Korean gastric cancer survivors participated in a 24-week tai chi self-help education program. The participants completed the Center for Epidemiologic Studies—Depression (Korean version) and the Functional Assessment of Cancer Therapy—General (Korean version) for HRQOL and provided blood samples for immune markers. All measurements were conducted at baseline and at one week following the 24-week intervention.Main Research Variables: Feasibility was determined as the percentage of participants completing the 24-week protocol. Preliminary data on depression, HRQOL, and immune markers were obtained.Findings: The dropout rate was 36.4%; 21 of 33 survivors participated in the tai chi self-help education program for 24 weeks. No complications or injuries occurred to the participants during the program. No significant differences were noted in depression, HRQOL, and immune markers before and after the intervention.Conclusions: Tai chi exercise, in combination with a self-help program, can be safe and feasible for Korean gastric cancer survivors. This feasibility study did not show that the tai chi self-help education program improves depression, HRQOL, and immune markers in Korean gastric cancer survivors.Implications for Nursing: Additional studies are needed to determine the long-term impact relative to usual care. [ABSTRACT FROM AUTHOR]

Purpose: This study was to examine the effects of adherence to a 6-month t'ai chi exercise program on glucose control, diabetic self-care activities, and quality of life among individuals with type 2 diabetes. Method: The data from a quasi-experimental study at multisite health-promotion centers in Korea with pretest and 3- and 6-month post-test measures were used. Ninety-nine (99) adults diagnosed with type 2 diabetes and HbA1c 6.0 or higher were included in the analysis. The t'ai chi intervention consisted of 19 movements from Yang and Sun styles provided twice a week for 6 months. Sixty-two (62) subjects completed both pretest and post-test measures. To achieve the desired outcomes, subjects needed to complete 80% of the sessions of the t'ai chi program, and 31 subjects who met this criteria were compared to those who did not ( n = 31). Outcome measures included glucose control (fasting blood sugar, HbA1c), diabetic self-care activities, and quality of life (36-Item Short Form Health Survey, version 2). Results: Using repeated measure analysis of variance for baseline, 3 months, and 6 months, the adherent group had greater decline in fasting glucose (interaction effect F = 5.60, df = 2, p < 0.05) and HbA1c (interaction effect F = 4.15, df = 2, p < 0.05) than the nonadherers. The adherent group performed significantly more diabetic self-care activities (interaction effect F = 5.13, df = 2, p < 0.05), and had better quality of life in mental component summary, social functioning, mental health, and vitality as compared to the nonadherent group. The significant differences in quality of life remained after adjusting for self-care activities except for mental health, which was no longer significant. Conclusion: For those with type 2 diabetes, t'ai chi could be an alternative exercise intervention to increase glucose control, diabetic self-care activities, and quality of life. Whether t'ai chi can reduce or prevent diabetic complications requires further study. [ABSTRACT FROM AUTHOR]

Cancer pain impairs the quality of life of cancer patients, but opioid analgesics can not only cause inhibition of respiratory function, and constipation, but also other significant side effects such as addiction and tolerance that further decrease quality of life. Thus, in the present study, the effects of electro-acupuncture treatment (EA) on mechanical allodynia were examined in cancer pain mouse model. In order to induce neuropathic cancer pain model, S-180 sarcoma cells were inoculated around the sciatic nerve of left legs of Balb/c mice. The mass of S-180 cancer cells embedded around sciatic nerve in a time course was confirmed by Magnetic Resonance Imaging (MRJ) scanning. Mechanical allodynia was most consistently induced in mouse sarcoma cell line S-180 (2 × 106 sarcoma cells) treated group among all groups. EA stimulation (2Hz) was daily given to ST36 (Zusanli) of S-180 bearing mice for 30 min for 9 days after S-180 inoculation. EA treatment significantly prolonged paw withdrawal latency from 5 days after inoculation as well as shortened cumulative lifting duration from 7 days after inoculation compared with tumor control. In addition, the overexpressions of pain peptide substance P in dorsal horn of spinal cord were significantly decreased in EA treated group compared with tumor control on Day 9 after inoculation. Furthermore, EA treatment effectively increased the concentration of beta endorphin in blood and brain of mice more than tumor control as well as normal group. The concentration of β-endorphin for EA treatment group increased by 51.457% in blood 12.6% in brain respectively, compared with tumor control group. These findings suggest that S-180 cancer pain model can be a consistent and short time animal model and also EA treatment can be an alternative therapeutic method for cancer pain via decreased substance P and increased beta endorphin. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a major health problem in Korea. To explore the effects of regular exercise on pain, fatigue, and disability, a descriptive study was conducted in 435 Korean patients with RA. Exercisers were defined as those who are currently exercising more than 3 times a week, for at least 20 minutes, and for more than 6-consecutive months after being diagnosed with RA. The primary finding was that exercisers had significantly less fatigue and disability compared with nonexercisers. Results suggest that regular exercise has advantages for patients with RA to decrease fatigue and disability. [ABSTRACT FROM AUTHOR]

Vitis amurensis Rupr. (Vitaceae) has long been used in Chinese/Oriental herbal medicine for the treatment of cancer, but its active compounds and mechanisms of action have not been well studied. To this end, we isolated from its root heyneanol A (HA), which is a tetramer of resveratrol (RES), and established the in vivo antitumor activity of HA using the mouse Lewis lung carcinoma (LLC) model. We administered HA and RES by daily intraperitonial injection to C57BL/6 mice that were subcutaneously inoculated with LLC cells. HA dose-dependently decreased tumor growth without any adverse effect on body weight and seemed more potent than RES. The tumor inhibitory effects were accompanied by a marked increase in tumor cell apoptosis detected by cleaved caspase-3 and TUNEL assays and decreased tumor cell proliferation index and tumor microvessel density, supporting the involvement of apoptotic and anti-angiogenic activities in the anticancer effects. We next investigated the cellular and molecular processes that mediate the apoptosis and anti-angiogenesis effects using cell culture models. Mechanistically, treatment of LLC cells in vitro with HA or RES significantly increased apoptotic cells. Both HA- and RES-induced cleavage of caspase-9 and caspase-3 and PARP were completely blocked by a pan caspase inhibitor, Z-VAD-FMK. In addition, HA and RES suppressed the basic fibroblast growth factor (bFGF)-induced proliferation and capillary differentiation of human umbilical vein endothelial cells, and inhibited the binding of bFGF to its receptor in a test tube assay and the bFGF-induced vascularization of Matrigel plugs in vivo. Remarkably, HA was fairly stable in cell culture medium and did not undergo intracellular conversion to RES. Therefore, HA is an active anticancer compound that induces caspase-mediated cancer cell apoptosis and inhibits angiogenesis rivaling the potency of RES and merits further evaluation for cancer chemoprevention. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) has anti-tumorigenic activity in vitro. In the present work, we evaluated the in vitro and in vivo antiangiogenic and antitumor activities of PGG and examined its molecular mechanisms. PGG significantly inhibited the proliferation and tube formation in basic fibroblast growth factor (bFGF)-treated human umbilical vein endothelial cells (HUVECs) at non-cytotoxic concentrations. PGG effectively disrupted the bFGF-induced neo-vascularization in chick chorioallantoic membrane (CAM) and in Matrigel plugs in the mice. When mice were intraperitoneally injected, PGG also significantly inhibited tumor angiogenesis induced by Lewis lung carcinoma (LLC) and the growth of LLC by 57 and 91% of control tumor weight at 4 and 20 mg/kg, respectively. Immunohistochemical analysis revealed decreased microvessel density, decreased expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF), reduced tumor cell proliferation and increased tumor cell apoptosis. Similarly, PGG significantly attenuated the expression of COX-2 and VEGF and reduced the secretion of VEGF and prostaglandin E2 in bFGF-treated HUVECs. Furthermore, the COX-2 inhibitor NS398 significantly inhibited tube formation and neo-vascularization in CAM, supporting the role of COX-2 in PGG inhibition of angiogenesis. PGG diminished the phosphorylation of extracellular signal regulated kinase 1/2, Jun NH2-terminal kinase and activated phospho-p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner in bFGF-treated HUVECs. In addition, p38 inhibitor SB203580 abolished the downregulation of COX-2, VEGF and the antiproliferative activity by PGG. Taken together, our data demonstrate that PGG exerts antitumor activity primarily via inhibition of angiogenesis through COX-2 and MAPK- dependent pathways. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore cultural meanings of breast cancer among Korean women in South Korea. A descriptive longitudinal study using methodological triangulation was conducted, and only qualitative findings are presented in this article. Ten Korean women who were newly diagnosed with a plan of surgery and subsequent chemotherapy, who did have severe fatigue at the time of recruitment, were recruited through Seoul National University Hospital. Data were collected using in-depth, 2-hour interviews and analyzed using thematic analysis. The themes emerged through the analysis process included: (a) "I did wrong," (b) "I cannot ask male physicians," (c) "I don't want to show the operation site to my husband," and (d) "I do household tasks by myself." The overriding theme was marginalization of the women within the context of their patriarchal culture. The findings suggest that culture is an important context circumscribing women's health/illness experience. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about family resilience, published in a 2004 issue.