BackgroundMore than 50% of all U.S. adults consume dietary supplements (DS) contributing to an es... more BackgroundMore than 50% of all U.S. adults consume dietary supplements (DS) contributing to an estimated $35 billion in sales in 2015. Among these are DS often recommended by oncology practitioners...
According to the National Cancer Institute more than 140,000 people will be diagnosed in the Unit... more According to the National Cancer Institute more than 140,000 people will be diagnosed in the United States with colorectal cancer this year alone. The adenomatus polyposis coli (APC) gene is frequently mutated in colorectal cancer, the APC-min mouse correspondingly is a widely used model for the study of this type of cancer. Studies indictate that the matricellular protein Thrombospondin 1 (TSP1) is lost during progression of colon cancer. To study the role of TSP1 in this disease we generated APC-min and TSP-/- APC-min mice. Our data indicates that expression of TSP1 in the APC-min mouse prevents the development of adenomas in the large intestine in mice fed a low fat diet. On the other hand lack of TSP1 increases tumor multiplicity in these mice, and up-regulates Ki67 in intestinal tissue. Moreover TSP-/- APC-min mice show 50% reduction in survival when compared to TSP+/+APC-min mice alone. Here we show that ADD1/SREBP1 a key transcription factor linking changes in nutritional status of certain genes that regulate systemic energy metabolism is upregulated only in the TSP null APC min/+ animals indicating and association with increased tumor aggressiveness. Together this data indicates that TSP1 regulates progression of colon carcinogenesis and define molecular targets of TSP1 in the prevention of colorectal cancer. Citation Format: David R. Soto Pantoja, Maria E. Torres, J. Michael Sipes, Nicole Morris, David D. Roberts, Nancy J. Emenaker. Thrombospondin-1 regulates carcinogenesis in an in vivo model of colorectal cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B18.
Clinical, epidemiological and experimental findings have provided evidence supporting a role of f... more Clinical, epidemiological and experimental findings have provided evidence supporting a role of free radicals in the etiology of cancer. Free radical production is enhanced in many disease states, by carcinogen exposure, and under conditions of stress contributing widely to cancer development in humans. We have established an experimental breast cancer model to examine the effects of all-trans-retinol (retinol/ vitamin A) on the production of free radicals in human breast epithelial cells induced by high linear energy transfer (LET)radiation in the presence of 17ß estradiol. The following cell lines were used in these studies: the MCF-10F cell line, a spontaneously immortalized human breast epithelial cell line. Alpha 5 derived from MCF-10F cells irradiated with two separated doses of 60 cGy • particles in the presence of estrogens (60E/60E). Tumor 2, from a tumor formed in nude mice after injection with the cell line Alpha 5. Tumor 3, from secondary tumor formed from injecting Tumor 2 cells into nude mice. Each of the cell types examined had significantly elevated H 2 O 2 production levels compared to MCF-10F control cells (p<0.001). Retinol (1 µl/ml) significantly (p<0.05) decreased H 2 O 2 production in all cell types examined. Retinol significantly decreased (p<0.05) invasive capabilities of cells across matrigel coated invasion chambers and significantly reduced (p<0.05) PCNA, Fra-1, mutant p53 and increased Rb protein expression levels in comparison to non-retinol-treated ones when assayed using immunofluorescent staining coupled with confocal microscopy. The reduced H 2 O 2 production, decrease in cell invasive capabilities and alterations in protein expression levels suggest that retinol can be used as a chemopreventive agent in human breast cancer.
Much is known about intestinal epithelial regulation by growth factors and nutrients but the intr... more Much is known about intestinal epithelial regulation by growth factors and nutrients but the intracellular signals governing cell phenotype are less well understood. In an initial attempt to evaluate the role of protein kinase C in these events, we studied the effects of protein kinase C modulation by the phorbol ester TPA upon the differentiation, motility, and doubling time of the human intestinal epithelial Caco-2 cell line, a common model for enterocytic brush border enzyme expression. We also compared the effects of TPA to those of 4 alpha-phorbol 12,13-didecanoate, which does not modulate protein kinase C activity. Differentiation was studied by quantitating brush order dipeptidyl peptidase (DPDD)-specific activity in protein-matched Caco-2 lysates via synthetic substrate digestion. Alkaline phosphatase (AP) was studied for comparison. Doubling time was assessed by log transformation of serial cell counts and motility by monolayer expansion across type I collagen. TPA (0.03-0.7 micrograms/ml) dose-dependently stimulated DPDD, with a maximal 455 +/- 26% increase at 0.7 micrograms/ml (P &lt; 0.01, n = 5). However, TPA dose-dependently inhibited AP to a maximal 91.6 +/- 0.3% decrease (P &lt; 0.01, n = 5). TPA also dose-dependently prolonged the cell doubling time from 26.5 +/- 0.4 to 64.5 +/- 8.8 hr (n = 20, P &lt; 0.01) with a maximal effect at 1.0 micrograms/ml and inhibited migration with essentially complete ablation of cell motility at 0.1 micrograms/ml (n = 10, P &lt; 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
... Vol. 10, No. 1-2, 2000 Article (PDF 429 KB) Original Paper. Alpha Integrin Subunits Regulate ... more ... Vol. 10, No. 1-2, 2000 Article (PDF 429 KB) Original Paper. Alpha Integrin Subunits Regulate Human (Caco-2) Intestinal Epithelial Proliferation and Phenotype Marc D. Basson, Nancy J. Emenaker, Matthew A. Sanders Depts. ... G. Schatz: A Matter of Wonder. ...
Fermentation of dietary fiber within the colonic lumen yields short chain fatty acids (SCFA) such... more Fermentation of dietary fiber within the colonic lumen yields short chain fatty acids (SCFA) such as butyrate, which may modulate colonic mucosal biology and inhibit the development of a malignant phenotype. However, different fibers yield varying proportions of various SCFA. We studied the effects of the three most common SCFA, acetate, butyrate, and propionate, on the proliferation, adhesion, and motility of the human intestinal Caco-2 cell line, as well as the effects of these SCFA on alkaline phosphatase and dipeptidyl dipeptidase specific activity (common laboratory markers of differentiation). In addition, we examined the modulation of c-myc protein and the tyrosine phosphorylation of cellular proteins by these SCFA in order to determine whether the variations in the potency of these three SCFA for phenotypic change extended to variations in effects on intracellular signaling and protooncogene expression. All three SCFA tended to slow proliferation, promote brush border enzyme activity, and inhibit both adhesion to and motility across a type I collagen matrix substrate. However, we observed substantial differences in the potency of these three SCFA with regard to these effects. In particular, butyrate was uniformly more potent than an equimolar concentration of acetate whereas equimolar propionate achieved comparable effects with regard to proliferation and brush border enzyme activity but was intermediate between butyrate and acetate with regard to modulation of cell-matrix interactions. Similarly, the SCFA downregulated c-myc protein levels and modulated the phosphorylation of several intracellular tyrosine phosphoproteins, but the effects of the three SCFA varied substantially for these parameters. These results suggest that the common short chain fatty acids are not equipotent in their effects on human Caco-2 colon cancer cell biology. Such differences in potency could contribute to the observed differences in effects of different dietary fibers in vivo.
We interrogated biochemical profiles in murine liver tissue from wild type, thrombospondin-1 (TSP... more We interrogated biochemical profiles in murine liver tissue from wild type, thrombospondin-1 (TSP) null, ApcMin/+ and ApcMin/+TSP-/-mice to identify metabolic changes accompanying tumorigenesis ari...
According to the National Cancer Institute more than 140,000 people will be diagnosed in the Unit... more According to the National Cancer Institute more than 140,000 people will be diagnosed in the United States with colorectal cancer this year alone. The adenomatus polyposis coli (APC) gene is frequently mutated in colorectal cancer, the APC‐min mouse correspondingly is a widely used model for the study of this type of cancer. Yet, intestinal tumors develop predominately in the small intestine reflecting familial adenomatous polyposis rather than colorectal cancer. Studies indicate that the matricellular protein Thrombospondin 1 (TSP1), a key component in modifying inflammatory processes, is lost during the development of colon cancer. To study the role of TSP1 during inflammation driven colorectal carcinogenesis we developed an APC‐min and TSP−/− APC‐min mouse model. A lack of TSP1 increases tumor size and multiplicity predominately in the large intestine of these mice. Our data indicate that expression of TSP1 in the APC‐min mouse prevents the development of adenomas in the large intestine in mice fed a low fat diet. Moreover, TSP−/− APC‐min mice show 50% reduction in survival when compared to TSP+/+APC‐min mice alone (P&lt;0.05). Our in vitro experiments indicate that this difference may be due to TSP1 regulation of pro‐inflammatory mechanisms. Together this data indicates TSP1 regulates progression of colon carcinogenesis and define cellular and molecular targets of TSP1 in the prevention of colorectal cancer.
The American Journal of Clinical Nutrition, Nov 1, 1996
Previous work has suggested that kidney hemocopper-based membranes suggested a tendency toward mo... more Previous work has suggested that kidney hemocopper-based membranes suggested a tendency toward moderate copper deficiency. However, this contention could not be confirmed by erythrocyte SOD activity or mononuclear cell copper measurements.
High intakes of dietary fiber or resistant starches have been associated with a lower incidence o... more High intakes of dietary fiber or resistant starches have been associated with a lower incidence of colon cancers. Because short-chain fatty acids (SCFA) such as butyrate are produced in the colonic lumen by the bacterial fermentation of dietary fibers and resistant starches, we hypothesized that SCFA may inhibit the development of invasive human colon cancers. To test this hypothesis, primary human invasive colonocytes were isolated from fresh surgical specimens and treated with 0.01 mol/L acetate, propionate or butyrate; cell invasion, cell adhesion, F-actin polymerization, urokinase plasminogen activator (uPA), tissue inhibitor matrix metalloproteinase (TIMP)-1, TIMP-2 and mutant p53, Bcl-2, Bax, p21 and proliferating cell nuclear antigen (PCNA) protein expression levels were examined. Although each of the SCFA tested significantly reduced primary cell invasion, butyrate was the most potent, inhibiting primary invasive human colon cancer invasion by 54% (P Ͻ 0.0001). The effects of SCFA on primary cell invasion appeared to be independent of cell adhesion and F-actin polymerization but dependent on the inhibition of uPA (P Ͻ 0.05) and the stimulation of TIMP-1 and TIMP-2 activities (P Ͻ 0.05). Protein expression levels of mutant p53, p21, Bax, Bcl-2 and PCNA were significantly altered by each of the SCFA tested (P Ͻ 0.05). These data indicate that SCFA inhibit invasive human colon cancer by modulating proteolytic uPA and antiproteolytic TIMP-1 and TIMP-2 activities, but their mechanisms of action on tumor suppression, apoptosis and growth arrest may differ. J. Nutr. 131: 3041S-3046S, 2001. KEY WORDS: • butyrate • invasive colon cancer • urokinase plasminogen activator • dietary fiber • gene-nutrient interactions
Plasma copper, plasma ceruloplasmin activity, plasma ceruloplasmin concentration, erythrocyte Cu*... more Plasma copper, plasma ceruloplasmin activity, plasma ceruloplasmin concentration, erythrocyte Cu*Zn superoxidc dismutase, plasma interleukin-6, and mononuclear cell copper concentrations were investigated in hemodialysis (n=23), CAPD (n=26), and ageand gender-matched controls to study the impact o f dialysis techniques on copper status and acute phase response. Dialysis subjects were divided into four non-exclusive groups based on four clinical parameters thought to influence copper nutriture: antacid utilization, diabetes mellitus, cardiovascular disease, and gender. Compared to controls, hemodialysis subjects and CAPD subjects had significant reductions (p < 0.0S) in plasma copper, plasma ceruloplasmin activity, ceruloplasmin activity to ceruloplasmin concentration ratio, and significant elevations (p < 0.0S) in plasma interleukin-6 concentration. Plasma ceruloplasmin concentration was significantly elevated (p < 0.05) in only CAPD subjects, while erythrocyte Cu-Zn superoxide dismutase with extracted protein was significantly elevated (p < 0.05) in only hemodialysis subjects. Mononuclear cell copper concentrations o f hemodialysis and CAPD subjects were not significantly different from controls. When comparing hemodialysis subjects to CAPD subjects for indicators o f copper status, plasma copper and plasma ceruloplasmin concentrations were significantly elevated (p < 0.05) in CAPD subjects relative to hemodialysis subjects. ANOVA analyses suggested antacid utilization did not significantly impact indicators of copper status, while significantly elevated (p < 0.05) plasma ceruloplasmin concentrations occurred in diabetic hemodialysis and CAPD subjects compared to controls. Plasma ceruloplasmin concentration was significantly greater (p < 0.05) in diabetic CAPD subjects relative to diabetic hemodialysis subjects. Significantly elevated (p < 0.05) plasma ceruloplasmin concentrations occurred in hemodialysis subjects with cardiovascular disease, but was significantly reduced (p < 0.05) in CAPD subjects with cardiovascular disease. Plasma copper, plasma ceruloplasmin activity, and plasma ceruloplasmin concentration were impacted by gender. Plasma copper concentrations and plasma ceruloplasmin activity were significantly elevated (p < 0.05) in male hemodialysis subjects, but significantly reduced (p < 0.05) in males CAPD subjects compared to females receiving similar treatment. Plasma ceruloplasmin concentration was significantly elevated (p < 0.05) in male CAPD subjects compared to controls. Aberrations in copper status o f hemodialysis and CAPD subjects are prevalent despite technological advances in dialysis methodologies. Moreover, aberrations in copper status were found in hemodialysis and CAPD subjects with diabetes mellitus and/or cardiovascular disease. Gender differences in copper parameters in response to a particular dialysis treatment methodology suggests gender issues should be considered when prescribing a treatment regime.
BackgroundMore than 50% of all U.S. adults consume dietary supplements (DS) contributing to an es... more BackgroundMore than 50% of all U.S. adults consume dietary supplements (DS) contributing to an estimated $35 billion in sales in 2015. Among these are DS often recommended by oncology practitioners...
According to the National Cancer Institute more than 140,000 people will be diagnosed in the Unit... more According to the National Cancer Institute more than 140,000 people will be diagnosed in the United States with colorectal cancer this year alone. The adenomatus polyposis coli (APC) gene is frequently mutated in colorectal cancer, the APC-min mouse correspondingly is a widely used model for the study of this type of cancer. Studies indictate that the matricellular protein Thrombospondin 1 (TSP1) is lost during progression of colon cancer. To study the role of TSP1 in this disease we generated APC-min and TSP-/- APC-min mice. Our data indicates that expression of TSP1 in the APC-min mouse prevents the development of adenomas in the large intestine in mice fed a low fat diet. On the other hand lack of TSP1 increases tumor multiplicity in these mice, and up-regulates Ki67 in intestinal tissue. Moreover TSP-/- APC-min mice show 50% reduction in survival when compared to TSP+/+APC-min mice alone. Here we show that ADD1/SREBP1 a key transcription factor linking changes in nutritional status of certain genes that regulate systemic energy metabolism is upregulated only in the TSP null APC min/+ animals indicating and association with increased tumor aggressiveness. Together this data indicates that TSP1 regulates progression of colon carcinogenesis and define molecular targets of TSP1 in the prevention of colorectal cancer. Citation Format: David R. Soto Pantoja, Maria E. Torres, J. Michael Sipes, Nicole Morris, David D. Roberts, Nancy J. Emenaker. Thrombospondin-1 regulates carcinogenesis in an in vivo model of colorectal cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B18.
Clinical, epidemiological and experimental findings have provided evidence supporting a role of f... more Clinical, epidemiological and experimental findings have provided evidence supporting a role of free radicals in the etiology of cancer. Free radical production is enhanced in many disease states, by carcinogen exposure, and under conditions of stress contributing widely to cancer development in humans. We have established an experimental breast cancer model to examine the effects of all-trans-retinol (retinol/ vitamin A) on the production of free radicals in human breast epithelial cells induced by high linear energy transfer (LET)radiation in the presence of 17ß estradiol. The following cell lines were used in these studies: the MCF-10F cell line, a spontaneously immortalized human breast epithelial cell line. Alpha 5 derived from MCF-10F cells irradiated with two separated doses of 60 cGy • particles in the presence of estrogens (60E/60E). Tumor 2, from a tumor formed in nude mice after injection with the cell line Alpha 5. Tumor 3, from secondary tumor formed from injecting Tumor 2 cells into nude mice. Each of the cell types examined had significantly elevated H 2 O 2 production levels compared to MCF-10F control cells (p<0.001). Retinol (1 µl/ml) significantly (p<0.05) decreased H 2 O 2 production in all cell types examined. Retinol significantly decreased (p<0.05) invasive capabilities of cells across matrigel coated invasion chambers and significantly reduced (p<0.05) PCNA, Fra-1, mutant p53 and increased Rb protein expression levels in comparison to non-retinol-treated ones when assayed using immunofluorescent staining coupled with confocal microscopy. The reduced H 2 O 2 production, decrease in cell invasive capabilities and alterations in protein expression levels suggest that retinol can be used as a chemopreventive agent in human breast cancer.
Much is known about intestinal epithelial regulation by growth factors and nutrients but the intr... more Much is known about intestinal epithelial regulation by growth factors and nutrients but the intracellular signals governing cell phenotype are less well understood. In an initial attempt to evaluate the role of protein kinase C in these events, we studied the effects of protein kinase C modulation by the phorbol ester TPA upon the differentiation, motility, and doubling time of the human intestinal epithelial Caco-2 cell line, a common model for enterocytic brush border enzyme expression. We also compared the effects of TPA to those of 4 alpha-phorbol 12,13-didecanoate, which does not modulate protein kinase C activity. Differentiation was studied by quantitating brush order dipeptidyl peptidase (DPDD)-specific activity in protein-matched Caco-2 lysates via synthetic substrate digestion. Alkaline phosphatase (AP) was studied for comparison. Doubling time was assessed by log transformation of serial cell counts and motility by monolayer expansion across type I collagen. TPA (0.03-0.7 micrograms/ml) dose-dependently stimulated DPDD, with a maximal 455 +/- 26% increase at 0.7 micrograms/ml (P &lt; 0.01, n = 5). However, TPA dose-dependently inhibited AP to a maximal 91.6 +/- 0.3% decrease (P &lt; 0.01, n = 5). TPA also dose-dependently prolonged the cell doubling time from 26.5 +/- 0.4 to 64.5 +/- 8.8 hr (n = 20, P &lt; 0.01) with a maximal effect at 1.0 micrograms/ml and inhibited migration with essentially complete ablation of cell motility at 0.1 micrograms/ml (n = 10, P &lt; 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
... Vol. 10, No. 1-2, 2000 Article (PDF 429 KB) Original Paper. Alpha Integrin Subunits Regulate ... more ... Vol. 10, No. 1-2, 2000 Article (PDF 429 KB) Original Paper. Alpha Integrin Subunits Regulate Human (Caco-2) Intestinal Epithelial Proliferation and Phenotype Marc D. Basson, Nancy J. Emenaker, Matthew A. Sanders Depts. ... G. Schatz: A Matter of Wonder. ...
Fermentation of dietary fiber within the colonic lumen yields short chain fatty acids (SCFA) such... more Fermentation of dietary fiber within the colonic lumen yields short chain fatty acids (SCFA) such as butyrate, which may modulate colonic mucosal biology and inhibit the development of a malignant phenotype. However, different fibers yield varying proportions of various SCFA. We studied the effects of the three most common SCFA, acetate, butyrate, and propionate, on the proliferation, adhesion, and motility of the human intestinal Caco-2 cell line, as well as the effects of these SCFA on alkaline phosphatase and dipeptidyl dipeptidase specific activity (common laboratory markers of differentiation). In addition, we examined the modulation of c-myc protein and the tyrosine phosphorylation of cellular proteins by these SCFA in order to determine whether the variations in the potency of these three SCFA for phenotypic change extended to variations in effects on intracellular signaling and protooncogene expression. All three SCFA tended to slow proliferation, promote brush border enzyme activity, and inhibit both adhesion to and motility across a type I collagen matrix substrate. However, we observed substantial differences in the potency of these three SCFA with regard to these effects. In particular, butyrate was uniformly more potent than an equimolar concentration of acetate whereas equimolar propionate achieved comparable effects with regard to proliferation and brush border enzyme activity but was intermediate between butyrate and acetate with regard to modulation of cell-matrix interactions. Similarly, the SCFA downregulated c-myc protein levels and modulated the phosphorylation of several intracellular tyrosine phosphoproteins, but the effects of the three SCFA varied substantially for these parameters. These results suggest that the common short chain fatty acids are not equipotent in their effects on human Caco-2 colon cancer cell biology. Such differences in potency could contribute to the observed differences in effects of different dietary fibers in vivo.
We interrogated biochemical profiles in murine liver tissue from wild type, thrombospondin-1 (TSP... more We interrogated biochemical profiles in murine liver tissue from wild type, thrombospondin-1 (TSP) null, ApcMin/+ and ApcMin/+TSP-/-mice to identify metabolic changes accompanying tumorigenesis ari...
According to the National Cancer Institute more than 140,000 people will be diagnosed in the Unit... more According to the National Cancer Institute more than 140,000 people will be diagnosed in the United States with colorectal cancer this year alone. The adenomatus polyposis coli (APC) gene is frequently mutated in colorectal cancer, the APC‐min mouse correspondingly is a widely used model for the study of this type of cancer. Yet, intestinal tumors develop predominately in the small intestine reflecting familial adenomatous polyposis rather than colorectal cancer. Studies indicate that the matricellular protein Thrombospondin 1 (TSP1), a key component in modifying inflammatory processes, is lost during the development of colon cancer. To study the role of TSP1 during inflammation driven colorectal carcinogenesis we developed an APC‐min and TSP−/− APC‐min mouse model. A lack of TSP1 increases tumor size and multiplicity predominately in the large intestine of these mice. Our data indicate that expression of TSP1 in the APC‐min mouse prevents the development of adenomas in the large intestine in mice fed a low fat diet. Moreover, TSP−/− APC‐min mice show 50% reduction in survival when compared to TSP+/+APC‐min mice alone (P&lt;0.05). Our in vitro experiments indicate that this difference may be due to TSP1 regulation of pro‐inflammatory mechanisms. Together this data indicates TSP1 regulates progression of colon carcinogenesis and define cellular and molecular targets of TSP1 in the prevention of colorectal cancer.
The American Journal of Clinical Nutrition, Nov 1, 1996
Previous work has suggested that kidney hemocopper-based membranes suggested a tendency toward mo... more Previous work has suggested that kidney hemocopper-based membranes suggested a tendency toward moderate copper deficiency. However, this contention could not be confirmed by erythrocyte SOD activity or mononuclear cell copper measurements.
High intakes of dietary fiber or resistant starches have been associated with a lower incidence o... more High intakes of dietary fiber or resistant starches have been associated with a lower incidence of colon cancers. Because short-chain fatty acids (SCFA) such as butyrate are produced in the colonic lumen by the bacterial fermentation of dietary fibers and resistant starches, we hypothesized that SCFA may inhibit the development of invasive human colon cancers. To test this hypothesis, primary human invasive colonocytes were isolated from fresh surgical specimens and treated with 0.01 mol/L acetate, propionate or butyrate; cell invasion, cell adhesion, F-actin polymerization, urokinase plasminogen activator (uPA), tissue inhibitor matrix metalloproteinase (TIMP)-1, TIMP-2 and mutant p53, Bcl-2, Bax, p21 and proliferating cell nuclear antigen (PCNA) protein expression levels were examined. Although each of the SCFA tested significantly reduced primary cell invasion, butyrate was the most potent, inhibiting primary invasive human colon cancer invasion by 54% (P Ͻ 0.0001). The effects of SCFA on primary cell invasion appeared to be independent of cell adhesion and F-actin polymerization but dependent on the inhibition of uPA (P Ͻ 0.05) and the stimulation of TIMP-1 and TIMP-2 activities (P Ͻ 0.05). Protein expression levels of mutant p53, p21, Bax, Bcl-2 and PCNA were significantly altered by each of the SCFA tested (P Ͻ 0.05). These data indicate that SCFA inhibit invasive human colon cancer by modulating proteolytic uPA and antiproteolytic TIMP-1 and TIMP-2 activities, but their mechanisms of action on tumor suppression, apoptosis and growth arrest may differ. J. Nutr. 131: 3041S-3046S, 2001. KEY WORDS: • butyrate • invasive colon cancer • urokinase plasminogen activator • dietary fiber • gene-nutrient interactions
Plasma copper, plasma ceruloplasmin activity, plasma ceruloplasmin concentration, erythrocyte Cu*... more Plasma copper, plasma ceruloplasmin activity, plasma ceruloplasmin concentration, erythrocyte Cu*Zn superoxidc dismutase, plasma interleukin-6, and mononuclear cell copper concentrations were investigated in hemodialysis (n=23), CAPD (n=26), and ageand gender-matched controls to study the impact o f dialysis techniques on copper status and acute phase response. Dialysis subjects were divided into four non-exclusive groups based on four clinical parameters thought to influence copper nutriture: antacid utilization, diabetes mellitus, cardiovascular disease, and gender. Compared to controls, hemodialysis subjects and CAPD subjects had significant reductions (p < 0.0S) in plasma copper, plasma ceruloplasmin activity, ceruloplasmin activity to ceruloplasmin concentration ratio, and significant elevations (p < 0.0S) in plasma interleukin-6 concentration. Plasma ceruloplasmin concentration was significantly elevated (p < 0.05) in only CAPD subjects, while erythrocyte Cu-Zn superoxide dismutase with extracted protein was significantly elevated (p < 0.05) in only hemodialysis subjects. Mononuclear cell copper concentrations o f hemodialysis and CAPD subjects were not significantly different from controls. When comparing hemodialysis subjects to CAPD subjects for indicators o f copper status, plasma copper and plasma ceruloplasmin concentrations were significantly elevated (p < 0.05) in CAPD subjects relative to hemodialysis subjects. ANOVA analyses suggested antacid utilization did not significantly impact indicators of copper status, while significantly elevated (p < 0.05) plasma ceruloplasmin concentrations occurred in diabetic hemodialysis and CAPD subjects compared to controls. Plasma ceruloplasmin concentration was significantly greater (p < 0.05) in diabetic CAPD subjects relative to diabetic hemodialysis subjects. Significantly elevated (p < 0.05) plasma ceruloplasmin concentrations occurred in hemodialysis subjects with cardiovascular disease, but was significantly reduced (p < 0.05) in CAPD subjects with cardiovascular disease. Plasma copper, plasma ceruloplasmin activity, and plasma ceruloplasmin concentration were impacted by gender. Plasma copper concentrations and plasma ceruloplasmin activity were significantly elevated (p < 0.05) in male hemodialysis subjects, but significantly reduced (p < 0.05) in males CAPD subjects compared to females receiving similar treatment. Plasma ceruloplasmin concentration was significantly elevated (p < 0.05) in male CAPD subjects compared to controls. Aberrations in copper status o f hemodialysis and CAPD subjects are prevalent despite technological advances in dialysis methodologies. Moreover, aberrations in copper status were found in hemodialysis and CAPD subjects with diabetes mellitus and/or cardiovascular disease. Gender differences in copper parameters in response to a particular dialysis treatment methodology suggests gender issues should be considered when prescribing a treatment regime.
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