Tight junctions (TJs) that act as paracellular permeability barriers play an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. In this study, we investigated the correlation between the tightening of TJs, permeability and the invasive activity of genistein - a bioactive isoflavone of soybeans - in human breast carcinoma MCF-7 and MDA-MB-231 cells. The inhibitory effects of genistein on cell proliferation, motility and invasiveness were found to be associated with the increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance and a decrease in paracellular permeability. Additionally, the immunoblotting results indicated that genistein repressed the levels of the proteins that comprise the major components of TJ, claudin-3 and claudin-4, which play a key role in the control and selectivity of paracellular transport. Furthermore, genistein decreased the metastasis-related gene expressions of insulin like growth factor-1 receptor and snail, while concurrently increasing that of thrombospondin-1 and E-cadherin. In addition, we demonstrated that claudins play an important role in the anti-motility and invasiveness of genistein using claudin-3 small interfering RNA. Taken together, our results indicate a possible role for genistein as an inhibitor of cancer cell invasion through the tightening of TJs, which may counteract the up-regulation of claudins. In addition, our results indicate that this may be beneficial for the inhibition of tumor metastasis.
Purpose: The purpose of this study was to analyze the need for child hospice care programs in families of children with cancer. Methods: The survey of 104 families who were taking care of children with cancer was conducted. This survey was conducted from February 2004 to July 2004 at two general hospitals in Seoul. The data were collected through a self-reporting questionnaire of 22 items. The items were classified into five areas by factor analysis to identify the construct validity. The reliability of the tool was established by Cronbach's alpha as .94 and the data collected were analyzed by descriptive statistics, t-test and ANOVA. Results: 1) The degree of need for hospice care of the subjects showed a high average of 3.40 (${\pm}3.8$). The need for 'emotional care of children' showed the highest mean (M=3.55), 'management of terminal physical symptoms'(M=3.49), 'control of secondary physical problems' (M=3.41), 'acceptance of the family's difficulty' (M=3.20), 'spiritual care for preparing for death'(M=3.17), respectively. 2) With respect to the demographic characteristics of the subjects, there were statistically significant differences in hospice care needs, according to the child's mother's age (F==4.980, P=.009), whether or not there were cancer patients among their siblings or relatives (t=2.423, P=.017). Conclusion: The family of children with cancer have a heavy burden of ambivalence, especially in relieving the anxiety and fear of their children, communicating about death, and managing physical symptoms. Child hospice care must be provided considering the needs of families of children with cancer. Thus popular needs as well as hospice nurses' higher concern and support for hospice care of children require further education and program development to meet the current demands.
Genistein, a predominant isoflavone, has been shown to inhibit the growth of various cancer cells in vitro and in vivo without toxicity to normal cells. In the present study, we investigated the effects of genistein on the activity and the expression of matrix metalloproteinases (MMPs) in MCF-7 and MDA-MB-231 human breast adenocarcinoma cells. Our findings showed that MMP-9 and -2 activation was significantly increased in response to 12-O-tetradecanoyl phorbol-13-acetate (TPA). However, the increased activities of MMP-9 and -2 in TPA-treated cells were concentration-dependently inhibited by treatment with genistein, and this was also correlated with a decrease in the expression of their mRNA and proteins. In addition, a matrigel invasion assay showed that genistein reduced TPA-induced invasion of MCF-7 and MDA-MB-231 cells. Although further in vivo studies are needed, these results suggest that genistein treatment may inhibit tumor cell invasion and, therefore, act as a dietary source to decrease the risk of cancer metastasis.
In this study, we investigated the effects of ethyl alcohol extracts of Hizikia fusiforme (EHF) on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human gastric adenocarcinoma AGS cells. Inhibitory effects of EHF on cell proliferation, motility, and invasiveness were found to be associated with increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)-2 and -9 in AGS cells were dose-dependently inhibited by treatment with EHF, and this was also correlated with a decrease in expression of their mRNA and proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA levels were increased. Additionally, immunoblotting results indicated that EHF repressed the levels of claudin proteins (claudin-1, -3, and -4), major components of TJs that play key roles in control and selectivity of paracellular transport. Furthermore, EHF decreased expression of insulin such as growth factor-1 receptor proteins, while concurrently increasing that of thrombospondin-1 and E-cadherin. In conclusion, these results suggest that EHF treatment may inhibit tumor cell motility and invasion, and therefore act as a dietary source to decrease the risk of cancer metastasis.
People with obesity or over-weight need nutritional intervention to reduce their weight, because weight loss reduces the incidence rate of chronic diseases such as hypertension, type II diabetes, cardiovascular diseases and cancer in obese people. This study was to develop a system for individualized weight control program available both for wired and wireless internet users. This system is especially useful to users carrying wireless internet mobile device. If they input their physical information (height, weight and waist circumference) and mineral levels measured by hair tissue mineral analysis, the system provides evaluation of their health status and metabolic related functions such as endocrine and carbohydrate tolerance. Based on these evaluations, food menus are then offered to them to manage their health status and to improve their metabolic related physiological functions in a personalized way. The system also provides more information for recommended foods, such as nutritional information, food ingredients, recipes, and videos related to cooking. Bibimbap was selected as an example dish for customized contents for mobile web. Bibimbap is one of the most well-known Korean traditional dishes prepared with various kinds of ingredients including several different kinds of vegetables, meat, and egg so that it is a low calorie dish as well as a well-balanced diet. Therefore, this system developed in this study allows the mobile users to access web site through wired wireless internet everywhere and provides a customized content to the users to manage their weight and finally to achieve a desirable weight.
Objectives : Kyeongok-go has the effect of antioxidant, anti-cancer, improving fatigue, and hyperlipidemia, but it is not easy to use in clinical practice becausee of the complicated manufacturing process of heat control and moisture control. The aim of this study was to explore the lipid improvement effect of new manufacturing methods prodeced Kyeongok-go in hyperlipidemia rats. Methods : The SD rats were divided randomly into 8 groups of six animals each : Normal rats (Nor), hyperlipidemia rats (Con), hyperlipidemia rats treated with Spirulina 60 mg/kg(SP60), hyperlipidemia rats treated with Commercial Kyeongok-go 1 g/kg (K0), hyperlipidemia rats treated with Kyeongok-go manufactured by heating mantle 1 g/kg (K1), hyperlipidemia rats treated with ginseng fermentation Kyeongok-go 1 g/kg (KF), hyperlipidemia rats treated with Kyeongok-go with black ginseng 1 g/kg (BK), hyperlipidemia rats treated with black ginseng fermentation Kyeongok-go 1 g/kg (BKF). The experimental group induced hyperlipidemia by eating high cholesterol diet for 8 weeks. Also, we compared Kyeongok-go manufacturing method using the new method compared with traditional method. Results : As a result, the improvement effect of hyperlipemia using the new method showed the similar or better improvement effect compared with the conventional method, and it is considered that the Kyeongok-go manufacturing method using the new method can be substituted for the traditional Kyeongok-go manufacturing method. Conclusion : In conclusion, these results suggest that new manufacturing methods prodeced Kyeongok-go has the potential as a anti-hyperlipidemia material which possess lipid improvement activities.
In this study, we attempted to investigate the needs and problems of the terminal cancer patients and their family caregivers to provide them with nursing information to improve their quality of life and prepare for a peaceful death. Data was collected from August 1, 1995 to July 31, 1996 at the internal medicine unit of S hospital in Seoul area with the two groups of participants who were family members of terminal cancer patients seventy four of them were in-patients and 34 were out-patients who were discharged from the same hospital for home care. The research tool used in this study has been developed by selecting the questionnaires from various references, modifying them for our purpose and refining them based on the results of preliminary study. While general background information about the patients was obtained by reviewing their medical records, all other information was collected by interviewing the primary family caregivers of the patients using the questionnaire. The data collected were analyzed with the SPSS PC/sup +/ program. The results of this study are summarized as follows ; 1) Most frequently complained symptoms of the terminal cancer patients were in the order of pain(87%), weakness(86.1%), anorexia(83.3%) and fatigue (80.6%). 2) Main therapies for the terminal cancer patients were pain control (58.3%), hyperalimentation(47.2%) and antibiotics(21.3%). 3) Special medical devices that terminal cancer patients used most were oxygen device (11.1%), and feeding tube(5.6%). Other devices were used by less than 5% of the patients. 4) The mobility of 70.4% of the patients was worse than ECOG 3 level, they had to stay in bed more than 50% of a day. 5) Patients wanted their medical staffs to help relieve pain(45.4%), various physical symptoms(29.6%), and problems associated with their emotion(11.1%). 6) 16.7% of the family caregivers hoped for full recovery of the patients, refusing to admit the status of the patients. Also, 37% wished for the extension of the patient's life at least for 6 months. 7) Only 38.9% of the family members was preparing for the patient's funeral. 8) 45.4% of family caregivers prefer hospital as the place for the patient's death, 39.8% their own home, and 14.8% undetermined. 9) Caregivers of the patients were mostly close family members, i.e., spouse(62%), and sons and daughters or daughter-in-laws(21.3%). 10) 43.5% of the family caregivers were aware of hospice care. 46.8% of them learned about the hospice care from the mass media, 27.7% from health professionals, and the rest from books and other sources. 11) Caregivers were asked about the most difficult problems they encounter in home care, 41 of them pointed out the lack of health professionals they can contact, counsel and get help from in case of emergency, 17 identified the difficulty of finding appropriate transportation to hospital, and 13 stated the difficulty of admission in hospital as needed. 12) 93.6% of family caregivers demanded 24-hour hot line, 80% the visiting nurses and doctors, and 69.4% the volunteer's help. The above results indicate that terminal patients and their family caregivers demand help from qualified health professionals whenever necessary. Hospice care system led by well-trained medical and nursing staffs is one of the viable answers for such demands.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in many types of transformed cells; however, some human hepatocellular carcinoma cells are particularly resistant to the effects of TRAIL. Although genistein, a natural isoflavonoid phytoestrogen, has been shown to have pro-apoptotic activity against human cancer cell lines, little is known about the mechanism of genistein in terms of TRAIL-induced apoptosis. In the present study, it was investigated whether or not combined treatment with genistein and TRAIL synergistically induced apoptosis in Hep3B hepatocarcinoma cells. Results indicate that treatment with TRAIL in combination with nontoxic concentrations of genistein sensitized TRAIL-resistant Hep3B cells to TRAIL-induced apoptosis, which was associated with mitochondrial dysfunction. Further, the inhibition of p38 mitogen-activated protein kinase (MAPK) activation markedly decreased genistein and TRAIL-induced cell viability and apoptosis by enhanced truncation of Bid, increase of pro-apoptotic Bax, decrease of anti-apoptotic Bcl-2, and release of cytochrome c from mitochondria to cytoplasm. Activation of caspases and degradation of poly (ADP-ribose) polymerase induced by the combined treatment was also markedly increased by the inhibition of p38 MAPK, through the mitochondrial amplification step. In conclusion, our data suggest that genistein sensitizes TRAIL-induced-apoptosis via p38 MAPK-dependent pathway.
Park, Cheol;Jin, Cheng-Yun;Choi, Byung-Tae;Lee, Won-Ho;Choi, Yung-Hyun
Journal of Life Science
/
v.18
no.3
/
pp.336-343
/
2008
Histone deacetylases (HDACs) inhibitors have emerged as the accessory therapeutic agents for various human cancers, since they can block the activity of specific HDACs, restore the expression of some tumor suppressor genes and induce cell differentiation, cell cycle arrest and apoptosis in vitro and in vivo. In the present study, we investigated that the effect of trichostatin A (TSA), an HDAC inhibitor, on the cell growth and apoptosis, and its effect on the nuclear factor-kappaB $(NF-{\kappa}B)$ activity in 267B1 human prostate epithelial cells. Exposure of 267B1 cells to TSA resulted in growth inhibition and apoptosis induction in and dose-dependent manners as measured by fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. TSA treatment inhibited the levels of IAP family members such as c-IAP-1 and c-IAP-2 and induced the proteolytic activation of caspase-3, -8 and -9, which were associated with concomitant degradation of poly (ADP-ribose)-polymerase, ${\beta}-catenin$ and laminin B proteins. The increase in apoptosis by TSA was connected with the translocation of $NF-{\kappa}B$ from cytosol to nucleus, increase of the DNA binding as well as promoter activity of $NF-{\kappa}B$, and degradation of cytosolic inhibitor of KappaB $(I{\kappa}B)-{\alpha}$ protein. We therefore concluded that TSA demonstrated anti-proliferative and apoptosis-inducing effects on 267B1 cells in vitro, and that the activation of caspases and $NF-{\kappa}B$ may play important roles in its mechanism of action. Although further studies are needed, these findings provided important insights into the possible molecular mechanisms of the anti-cancer activity of TSA.
Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human canter cells, however its molecular mechanisms are poorly understood. In tile present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human hepatocarcinoma HepG2 cells. Treatment of HepG2 cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by DNA flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells suggesting that sulforaphane induced apoptosis. This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of ryclin A, cyclin 31 and Cdc2 protein. However, the levels of tumor suppressor p53 and Cdk inhibitor p21 mRNA and protein expression were significantly increased by sulforaphane treatment in a concentration-dependent manner. Although further studies are needed, the present work suggests that sulforaphane may be a potential rhemoprevetiveichemotherapeucc agent for the treatment of human cancer cells.
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