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II. Grape Seeds and Skins
Grape is a woody vines of the genus Vitis, belong to the family Vitaceae, native to southern Turkey.
D. By Foods to prevent and treat cancers
1. Brain and Spinal Cord Cancer
Resveratrol is a type of natural phenol found abundantly in Grapes, red wine, berries and peanuts of the group of Stilbenoids, produced naturally by many plants when under attack by bacteria or fungi. It has been studied by many researchers for it health benefits in treating chronic diaereses, including cancer, diabetes, heart disease, etc. Resveratrol is known to have antioxidant, anti-inflammatory and antiproliferative effects on a variety of cancer cells in vitro and in various animal models. However, the effect(s) of resveratrol in vivo on humans are still controversial. This study discusses current knowledge with regard to the effects of resveratrol in relation to its potential as a chemopreventive and/or chemotherapeutic molecule against human gliomas(1).
2. Esophageal cancer
Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol found in the skin of the grape and red wine, has been found to have chemopreventitive effects in some carcinogenic models. In the observation to evaluate the effects of resveratrol on the transition from reflux esophagitis to Barrett's metaplasia to dysplasia toesophageal adenocarcinoma in an established rat model. Male Sprague-Dawley rats underwent esophagoduodenal anastomosis as per institutional approved protocol, showed that morphological characteristics consistent with decreased esophagitis and incidences of metaplasia and esophageal adenocarcinoma were seen on histopathology in the resveratrol group. Resveratrol resulted in a small diminution of the carcinogenic effects and progression to metaplasia, and further human studies are designed to explore the potential anticarcinogenic mechanism(2).
3. Cervical Cancer
Resveratrol, a polyphenol found a abundantly in skins of grapes and red wine has been shown to significantly alter the cellular physiology of tumor cells, as well as block the process of initiation and progression, some studies found that tumor cells may exhibit changes in the cellular response to IR following exposure toresveratrol, a naturally occurring compound that inhibits cyclooxygenase-1 (COX-1) activity. Thus, clonogenic cell survival assays were performed using irradiated HeLa and SiHa cells pretreated with resveratrol prior to IR exposure, and resulted in enhanced tumor cell killing by IR in a dose-dependent manner(3).
4. Breast cancer
In study of red wine intake and its beneficial health effects on the proliferation of hormone-dependent breast cancer cells found that the estrogenic activity of PIC(piceatannol) and MYR(myricetin) might be considered at least as a potential factor in the association of red wine intake and breast tumors, particularly in postmenopausal women, according to "The red wine phenolics piceatannol andmyricetin act as agonists for estrogen receptor alpha in human breast cancercells" by Maggiolini M, Recchia AG, Bonofiglio D, Catalano S, Vivacqua A, Carpino A, Rago V, Rossi R, Andò S.(4)
5. Hodgkin's lymphoma
In the study to explore the effect of resveratrol on B-cell leukemia/lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) expression in rats with oxygen-induced retinopathy of prematurity (ROP), found that Resveratrol can significantly inhibit expression of Bcl-2 and VEGF in the retina of neonatal rats with oxygen-induced ROP. It may provide a protective effect on retinal neovascular diseases, including ROP(5).
6. Renal cell carcinoma (Kidney cancer/renal cells)
Resveratrol (Res) is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc. has potential to be used in treating kidney cancer. In the study to investigated the effects of Res on the expression of the vascular endothelial growth factor (VEGF) gene and on cell proliferation in human renal cancer (786-0) cells, suggested that Res inhibited the expression of the VEGF gene, and its inhibitory effect increased according to the concentration and treatment time. These results indicate that Res significantly inhibits the proliferation of 786-0 cells and exerts an antitumor effect by suppressing the expression of the VEGF gene(6).
7. Ovarian cancer
Myricetin is a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, etc.. In the research of inverse associations with certain flavonoids or flavonoid subclasses (myricetin, kaempferol, quercetin, luteolin, and apigenin) and ovarian cancer risk, found that In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest vs. lowest quintile = 0.79, 95% CI = 0.59-1.06; p-trend = 0.26), and this association was significant after adjustment for intake of the other 4 individual flavonoids (comparable RR = 0.72, 95% CI = 0.53-0.98; p-trend = 0.09), according to "Flavonoid intake and ovarian cancer risk in a population-based case-control study" by Gates MA, Vitonis AF, Tworoger SS, Rosner B, Titus-Ernstoff L, Hankinson SE, Cramer DW.(7)
8. Skin cancer
in the study to evaluate the chemopreventive effects of resveratrol against UVB radiation-mediated skin tumorigenesis in the SKH-1 hairless mouse model, suggests that resveratrol enhanced apoptosis in UVB-exposure-mediated skintumors. Our study, for the first time, demonstrated that 1) resveratrol imparts strong chemopreventive effects against UVB exposure-mediated skincarcinogenesis (relevant to human skin cancers), and 2) the chemopreventive effects of resveratrol may, at least in part, be mediated via modulations in Survivin and other associated events. On the basis of our work, it is conceivable to designresveratrol-containing emollient or patch, as well as sunscreen and skin-care products for prevention of skin cancer and other conditions, which are believed to be caused by UV radiation(8).
9. Prostate cancers
Myricetin, a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, fruits, etc has been used as antioxidant to lower cholesterol, treat certain types of cancer, etc.
In the selection of several potential uPA inhibitors (antipain, leupeptin, folic acid, rosmarinic acid, lavendustin A, fisetin, myricetin, tolfenamic acid) and examination of theirs effects in prostate cancer found that a proper diet rich in uPA-inhibiting nutraceuticals might support the prevention of prostrate cancer and be a supportive tool in prostate cancer treatment, according to "Nutraceutical inhibitors of urokinase: potential applications in prostate cancer prevention and treatment" by Jankun J, Selman SH, Aniola J, Skrzypczak-Jankun E.(9)
10. Pancreatic cancer
Myricetin, a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, etc. has been used as antioxidant to lower cholesterol, treat certain types of cancer, etc. In the observation of the flavonoid myricetin and its effect on metastatic pancreatic cancer cell lines, found that myricetin resulted in tumor regression and decreased metastatic spread. Importantly, myricetin was non-toxic, both in vitro and in vivo, underscoring its use as a therapeutic agent against pancreatic cancer, according to the study of "Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway" by Phillips PA, Sangwan V, Borja-Cacho D, Dudeja V, Vickers SM, Saluja AK.(10)
11. Multiple myeloma (Myeloma)
In the study to investigate the effect of Resveratrol trans-3, 4', 5,-trihydroxystilbene, insuppressing the multiple myeloma (MM), found thatResveratrol activated IRE1α as evidenced by XBP1 messenger RNA splicing and phosphorylation of both IRE1α and its downstream kinase c-Jun N-terminal kinase in MM cells. These responses were associated with resveratrol-induced cytotoxicity of MM cells. Resveratrol selectively suppressed the transcriptional activity of XBP1s while it stimulated gene expression of the molecules that are regulated by the non-IRE1/XBP1 axis of the ER stress response. Luciferase assays indicated that resveratrol suppressed the transcriptional activity of XBP1s through sirtuin 1, a downstream molecular target of resveratrol. Chromatin immunoprecipitation studies revealed that resveratrol decreased the DNA binding capacity of XBP1 and increased the enrichment of sirtuin 1 at the XBP1 binding region in the XBP1 promoter(11).
12. Oral cancer
Resveratrol and quercetin are polyphenols which have been found in abundantly in significant amounts in green vegetables, citrus fruits and red grape wines. Quercetin exhibited a biphasic effect, stimulation at 1 and 10 microM, and minimal inhibition at 100 microM in cell growth and DNA synthesis. Combining 50 microM of resveratrol with 10, 25 and 50 microM of quercetin resulted in a gradual and significant increase in the inhibitory effect of quercetin on cell growth and DNA synthesis(12).
13. Melanoma skin cancer
In the examined the effect of grape seed proanthocyanidins (GSPs) on melanomacancer cell migration and the molecular mechanisms underlying these effects using highly metastasis-specific human melanoma cell lines, A375 and Hs294t, indicated that GSPs have the ability to inhibit melanoma cell invasion/migration by targeting the endogenous expression of COX-2 and reversing the process of epithelial-to-mesenchymal transition(13).
14. Non-Hodgkin's Lymphoma
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, etc. Resveratrol (trans-3,4,5-trihydroxystilbene) has received attention for its potential chemopreventive and antitumor effects in experimental systems. Dr. Jazirehi AR and Dr. Bonavida B. at the University of California at Los Angeles, in the study investigated whether resveratrol can sensitize NHL and MM cell lines to paclitaxel-mediated apoptosis and to delineate the underlying molecular mechanism of sensitization. Both resveratrol and paclitaxel negatively modulated tumor cell growth by arresting the cells at the G(2)-M phase of the cell cycle, suggested that Resveratrol selectively down-regulated the expression of antiapoptotic proteins Bcl-x(L) and myeloid cell differentiation factor-1 (Mcl-1) and up-regulated the expression of proapoptotic proteins Bax and apoptosis protease activating factor-1 (Apaf-1)(14).
15. Lung cancer
In the examination of study the mechanism of myricetin and its effect on the HepG-2 cell line found that Myricetin significantly inhibits the proliferation and induces the apoptosis of HepG-2 in a dose-dependent manner, which is accompanied with G2/M and S phase arrest. In addition, myricetin also increases the activation of caspase 3,9 and results in a depolarization and delta psi m collapse in a dose-dependent manner, according to "[Studies on mechanism ofmyricetin-induced apoptosis in human hepatocellular carcinoma HepG-2 cells].[Article in Chinese]" by Zhang X, Ling Y, Yu H, Ji Y.(15)
16. Larynx Cancer or Laryngeal Cancer
Flavonoids found abundantly in wine have exerted the potential effect in preventing and treating Laryngeal Cancer. Dr. Garavello W and the research team at the Istituto di Ricerche Farmacologiche Mario Negri, indicated that Significant inverse relations were found for the highest versus the lowest quintile of intake for flavan-3-ols (OR = 0.64), flavanones (OR = 0.60), flavonols (OR = 0.32) and total flavonoids (OR = 0.60), although the overall trends in risk were significant only forflavanones and flavonols. No consistent associations were observed for isoflavones, anthocyanidins and flavones. The estimates did not differ substantially across strata of alcohol drinking, tobacco smoking, body mass index and education, and tended to persist even after controlling for vegetable and fruit intake(16).
17. Etc.
Side Effects
1. Overdose may cause headache, itchy scalp, dizziness, and nausea, abdominal pain etc.
2. Do not take the herbs if you have high blood pressure
3. Grape seed extract may interact with other medication, such blood thinner, NSAID painkiller, etc.
4. Do not take the herb in children or if you are pregnant without approval of the related field specialist.
5. etc.
D. By Foods to prevent and treat cancers
1. Brain and Spinal Cord Cancer
Resveratrol is a type of natural phenol found abundantly in Grapes, red wine, berries and peanuts of the group of Stilbenoids, produced naturally by many plants when under attack by bacteria or fungi. It has been studied by many researchers for it health benefits in treating chronic diaereses, including cancer, diabetes, heart disease, etc. Resveratrol is known to have antioxidant, anti-inflammatory and antiproliferative effects on a variety of cancer cells in vitro and in various animal models. However, the effect(s) of resveratrol in vivo on humans are still controversial. This study discusses current knowledge with regard to the effects of resveratrol in relation to its potential as a chemopreventive and/or chemotherapeutic molecule against human gliomas(1).
2. Esophageal cancer
Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol found in the skin of the grape and red wine, has been found to have chemopreventitive effects in some carcinogenic models. In the observation to evaluate the effects of resveratrol on the transition from reflux esophagitis to Barrett's metaplasia to dysplasia toesophageal adenocarcinoma in an established rat model. Male Sprague-Dawley rats underwent esophagoduodenal anastomosis as per institutional approved protocol, showed that morphological characteristics consistent with decreased esophagitis and incidences of metaplasia and esophageal adenocarcinoma were seen on histopathology in the resveratrol group. Resveratrol resulted in a small diminution of the carcinogenic effects and progression to metaplasia, and further human studies are designed to explore the potential anticarcinogenic mechanism(2).
3. Cervical Cancer
Resveratrol, a polyphenol found a abundantly in skins of grapes and red wine has been shown to significantly alter the cellular physiology of tumor cells, as well as block the process of initiation and progression, some studies found that tumor cells may exhibit changes in the cellular response to IR following exposure toresveratrol, a naturally occurring compound that inhibits cyclooxygenase-1 (COX-1) activity. Thus, clonogenic cell survival assays were performed using irradiated HeLa and SiHa cells pretreated with resveratrol prior to IR exposure, and resulted in enhanced tumor cell killing by IR in a dose-dependent manner(3).
4. Breast cancer
In study of red wine intake and its beneficial health effects on the proliferation of hormone-dependent breast cancer cells found that the estrogenic activity of PIC(piceatannol) and MYR(myricetin) might be considered at least as a potential factor in the association of red wine intake and breast tumors, particularly in postmenopausal women, according to "The red wine phenolics piceatannol andmyricetin act as agonists for estrogen receptor alpha in human breast cancercells" by Maggiolini M, Recchia AG, Bonofiglio D, Catalano S, Vivacqua A, Carpino A, Rago V, Rossi R, Andò S.(4)
5. Hodgkin's lymphoma
In the study to explore the effect of resveratrol on B-cell leukemia/lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) expression in rats with oxygen-induced retinopathy of prematurity (ROP), found that Resveratrol can significantly inhibit expression of Bcl-2 and VEGF in the retina of neonatal rats with oxygen-induced ROP. It may provide a protective effect on retinal neovascular diseases, including ROP(5).
6. Renal cell carcinoma (Kidney cancer/renal cells)
Resveratrol (Res) is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc. has potential to be used in treating kidney cancer. In the study to investigated the effects of Res on the expression of the vascular endothelial growth factor (VEGF) gene and on cell proliferation in human renal cancer (786-0) cells, suggested that Res inhibited the expression of the VEGF gene, and its inhibitory effect increased according to the concentration and treatment time. These results indicate that Res significantly inhibits the proliferation of 786-0 cells and exerts an antitumor effect by suppressing the expression of the VEGF gene(6).
7. Ovarian cancer
Myricetin is a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, etc.. In the research of inverse associations with certain flavonoids or flavonoid subclasses (myricetin, kaempferol, quercetin, luteolin, and apigenin) and ovarian cancer risk, found that In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest vs. lowest quintile = 0.79, 95% CI = 0.59-1.06; p-trend = 0.26), and this association was significant after adjustment for intake of the other 4 individual flavonoids (comparable RR = 0.72, 95% CI = 0.53-0.98; p-trend = 0.09), according to "Flavonoid intake and ovarian cancer risk in a population-based case-control study" by Gates MA, Vitonis AF, Tworoger SS, Rosner B, Titus-Ernstoff L, Hankinson SE, Cramer DW.(7)
8. Skin cancer
in the study to evaluate the chemopreventive effects of resveratrol against UVB radiation-mediated skin tumorigenesis in the SKH-1 hairless mouse model, suggests that resveratrol enhanced apoptosis in UVB-exposure-mediated skintumors. Our study, for the first time, demonstrated that 1) resveratrol imparts strong chemopreventive effects against UVB exposure-mediated skincarcinogenesis (relevant to human skin cancers), and 2) the chemopreventive effects of resveratrol may, at least in part, be mediated via modulations in Survivin and other associated events. On the basis of our work, it is conceivable to designresveratrol-containing emollient or patch, as well as sunscreen and skin-care products for prevention of skin cancer and other conditions, which are believed to be caused by UV radiation(8).
9. Prostate cancers
Myricetin, a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, fruits, etc has been used as antioxidant to lower cholesterol, treat certain types of cancer, etc.
In the selection of several potential uPA inhibitors (antipain, leupeptin, folic acid, rosmarinic acid, lavendustin A, fisetin, myricetin, tolfenamic acid) and examination of theirs effects in prostate cancer found that a proper diet rich in uPA-inhibiting nutraceuticals might support the prevention of prostrate cancer and be a supportive tool in prostate cancer treatment, according to "Nutraceutical inhibitors of urokinase: potential applications in prostate cancer prevention and treatment" by Jankun J, Selman SH, Aniola J, Skrzypczak-Jankun E.(9)
10. Pancreatic cancer
Myricetin, a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, etc. has been used as antioxidant to lower cholesterol, treat certain types of cancer, etc. In the observation of the flavonoid myricetin and its effect on metastatic pancreatic cancer cell lines, found that myricetin resulted in tumor regression and decreased metastatic spread. Importantly, myricetin was non-toxic, both in vitro and in vivo, underscoring its use as a therapeutic agent against pancreatic cancer, according to the study of "Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway" by Phillips PA, Sangwan V, Borja-Cacho D, Dudeja V, Vickers SM, Saluja AK.(10)
11. Multiple myeloma (Myeloma)
In the study to investigate the effect of Resveratrol trans-3, 4', 5,-trihydroxystilbene, insuppressing the multiple myeloma (MM), found thatResveratrol activated IRE1α as evidenced by XBP1 messenger RNA splicing and phosphorylation of both IRE1α and its downstream kinase c-Jun N-terminal kinase in MM cells. These responses were associated with resveratrol-induced cytotoxicity of MM cells. Resveratrol selectively suppressed the transcriptional activity of XBP1s while it stimulated gene expression of the molecules that are regulated by the non-IRE1/XBP1 axis of the ER stress response. Luciferase assays indicated that resveratrol suppressed the transcriptional activity of XBP1s through sirtuin 1, a downstream molecular target of resveratrol. Chromatin immunoprecipitation studies revealed that resveratrol decreased the DNA binding capacity of XBP1 and increased the enrichment of sirtuin 1 at the XBP1 binding region in the XBP1 promoter(11).
12. Oral cancer
Resveratrol and quercetin are polyphenols which have been found in abundantly in significant amounts in green vegetables, citrus fruits and red grape wines. Quercetin exhibited a biphasic effect, stimulation at 1 and 10 microM, and minimal inhibition at 100 microM in cell growth and DNA synthesis. Combining 50 microM of resveratrol with 10, 25 and 50 microM of quercetin resulted in a gradual and significant increase in the inhibitory effect of quercetin on cell growth and DNA synthesis(12).
13. Melanoma skin cancer
In the examined the effect of grape seed proanthocyanidins (GSPs) on melanomacancer cell migration and the molecular mechanisms underlying these effects using highly metastasis-specific human melanoma cell lines, A375 and Hs294t, indicated that GSPs have the ability to inhibit melanoma cell invasion/migration by targeting the endogenous expression of COX-2 and reversing the process of epithelial-to-mesenchymal transition(13).
14. Non-Hodgkin's Lymphoma
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, etc. Resveratrol (trans-3,4,5-trihydroxystilbene) has received attention for its potential chemopreventive and antitumor effects in experimental systems. Dr. Jazirehi AR and Dr. Bonavida B. at the University of California at Los Angeles, in the study investigated whether resveratrol can sensitize NHL and MM cell lines to paclitaxel-mediated apoptosis and to delineate the underlying molecular mechanism of sensitization. Both resveratrol and paclitaxel negatively modulated tumor cell growth by arresting the cells at the G(2)-M phase of the cell cycle, suggested that Resveratrol selectively down-regulated the expression of antiapoptotic proteins Bcl-x(L) and myeloid cell differentiation factor-1 (Mcl-1) and up-regulated the expression of proapoptotic proteins Bax and apoptosis protease activating factor-1 (Apaf-1)(14).
15. Lung cancer
In the examination of study the mechanism of myricetin and its effect on the HepG-2 cell line found that Myricetin significantly inhibits the proliferation and induces the apoptosis of HepG-2 in a dose-dependent manner, which is accompanied with G2/M and S phase arrest. In addition, myricetin also increases the activation of caspase 3,9 and results in a depolarization and delta psi m collapse in a dose-dependent manner, according to "[Studies on mechanism ofmyricetin-induced apoptosis in human hepatocellular carcinoma HepG-2 cells].[Article in Chinese]" by Zhang X, Ling Y, Yu H, Ji Y.(15)
16. Larynx Cancer or Laryngeal Cancer
Flavonoids found abundantly in wine have exerted the potential effect in preventing and treating Laryngeal Cancer. Dr. Garavello W and the research team at the Istituto di Ricerche Farmacologiche Mario Negri, indicated that Significant inverse relations were found for the highest versus the lowest quintile of intake for flavan-3-ols (OR = 0.64), flavanones (OR = 0.60), flavonols (OR = 0.32) and total flavonoids (OR = 0.60), although the overall trends in risk were significant only forflavanones and flavonols. No consistent associations were observed for isoflavones, anthocyanidins and flavones. The estimates did not differ substantially across strata of alcohol drinking, tobacco smoking, body mass index and education, and tended to persist even after controlling for vegetable and fruit intake(16).
17. Etc.
Side Effects
1. Overdose may cause headache, itchy scalp, dizziness, and nausea, abdominal pain etc.
2. Do not take the herbs if you have high blood pressure
3. Grape seed extract may interact with other medication, such blood thinner, NSAID painkiller, etc.
4. Do not take the herb in children or if you are pregnant without approval of the related field specialist.
5. etc.
Chinese Food Therapy
The Best Way to prevent, treat your disease, including Obesity
and restore your health naturally with Chinese diet
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20010425
(2) http://www.ncbi.nlm.nih.gov/pubmed/19398904
(3) http://www.ncbi.nlm.nih.gov/pubmed/11741744
(4) http://www.ncbi.nlm.nih.gov/pubmed/16216908
(5) http://www.ncbi.nlm.nih.gov/pubmed/22148982
(6) http://www.ncbi.nlm.nih.gov/pubmed/21687947
(7) http://www.ncbi.nlm.nih.gov/pubmed/19117058
(8) http://www.ncbi.nlm.nih.gov/pubmed/22080352
(9) http://www.ncbi.nlm.nih.gov/pubmed/16820913
(10) http://www.ncbi.nlm.nih.gov/pubmed/21676539
(11) http://www.ncbi.nlm.nih.gov/pubmed/21723843
(12) http://www.ncbi.nlm.nih.gov/pubmed/10211549
(13) http://www.ncbi.nlm.nih.gov/pubmed/21738696
(14) http://www.ncbi.nlm.nih.gov/pubmed/14749477
(15) http://www.ncbi.nlm.nih.gov/pubmed/20617691
(16) http://www.ncbi.nlm.nih.gov/pubmed/17372161
The Best Way to prevent, treat your disease, including Obesity
and restore your health naturally with Chinese diet
Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
(1) http://www.ncbi.nlm.nih.gov/pubmed/20010425
(2) http://www.ncbi.nlm.nih.gov/pubmed/19398904
(3) http://www.ncbi.nlm.nih.gov/pubmed/11741744
(4) http://www.ncbi.nlm.nih.gov/pubmed/16216908
(5) http://www.ncbi.nlm.nih.gov/pubmed/22148982
(6) http://www.ncbi.nlm.nih.gov/pubmed/21687947
(7) http://www.ncbi.nlm.nih.gov/pubmed/19117058
(8) http://www.ncbi.nlm.nih.gov/pubmed/22080352
(9) http://www.ncbi.nlm.nih.gov/pubmed/16820913
(10) http://www.ncbi.nlm.nih.gov/pubmed/21676539
(11) http://www.ncbi.nlm.nih.gov/pubmed/21723843
(12) http://www.ncbi.nlm.nih.gov/pubmed/10211549
(13) http://www.ncbi.nlm.nih.gov/pubmed/21738696
(14) http://www.ncbi.nlm.nih.gov/pubmed/14749477
(15) http://www.ncbi.nlm.nih.gov/pubmed/20617691
(16) http://www.ncbi.nlm.nih.gov/pubmed/17372161
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