Rebeca Garcia-Roman - Academia.edu (original) (raw)

Papers by Rebeca Garcia-Roman

Research paper thumbnail of Enfermedades crónico degenerativas del estado de Veracruz: el ambiente oxidativo como un enfoque causal

Altepepaktli Salud De La Comunidad, 2009

El gran problema de salud publica del siglo veinte ha sido sin lugar a dudas la obesidad, a la cu... more El gran problema de salud publica del siglo veinte ha sido sin lugar a dudas la obesidad, a la cual se le relacionan muchas enfermedades como las cronico degenerativas (ECD). Las tres ECDs que se mantienen en los primeros lugares de mortalidad mundial y en el estado de Veracruz son las enfermedades cardiovasculares, la diabetes mellitus y el cancer. Evidencia experimental sobre el origen comun de estas tres patologias hacen suponer que el ambiente oxidativo juega un papel crucial en su genesis. El estres oxidativo causado por un aumento de las Especies Reactivas de Oxigeno (ERO) esta involucrado en el dano a las principales biomoleculas de la celula, lo que genera una inestabilidad biologica de todo el organismo. De las fuentes endogenas y exogenas de ERO, las ultimas son consideradas como las principales inductoras de la perdida de la homeostasis oxidoreduccion (redox). Estas ERO exogenas provienen del medio ambiente y del estilo de vida, por ejemplo: la radiacion ionizante (luz ultravioleta solar), el humo del cigarrillo, la ingesta excesiva de acidos grasos. Por ende, el uso de antioxidantes como terapia alternativa en la prevencion de las ECDs disminuiria la morbilidad de estas patologias. Esta revision tiene como objetivos exponer un panorama general de la relacion entre las principales ECD de nuestro estado y su origen comun generado por un ambiente pro-oxidante, asi como sugerir que la alimentacion con antioxidantes y adoptar un estilo de vida saludable, el cual incluya una dieta rica en vegetales y frutas, la abstinencia del consumo de tabaco, bebidas alcoholicas y eliminacion del sedentarismo, disminuirian la aparicion de las ECD e incrementarian la expectativa de vida

Research paper thumbnail of Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico

Viruses, 2012

Human rhinovirus (HRV) is a leading cause of acute respiratory infection (ARI) in young children ... more Human rhinovirus (HRV) is a leading cause of acute respiratory infection (ARI) in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR) of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not

Research paper thumbnail of Increased expression of prostaglandin reductase 1 in hepatocellular carcinomas from clinical cases and experimental tumors in rats

The International Journal of Biochemistry & Cell Biology, 2014

To identify novel tumor-associated proteins, we analyzed the protein expression patterns from exp... more To identify novel tumor-associated proteins, we analyzed the protein expression patterns from experimental hepatocellular carcinoma (HCC) that were induced using hepatocarcinogenesis models in rats. Rats were subjected to two previously described protocols of hepatocarcinogenesis using diethylnitrosamine as a carcinogen: the alternative Solt-Farber (aS&F) protocol, which induces HCC within 9 months, and Schiffer's model, which induces cirrhosis and multifocal HCC within 18 weeks. The patterns of protein expression from tumors and normal liver tissue were examined by SDS-PAGE and the bands identified at 33-34 kDa were analyzed by mass spectrometry. The prostaglandin reductase 1 (PTGR1) showed the highest number of peptides, with a confidence of level >99%. The increased expression of PTGR1 in tumors was confirmed in these two models by Western blotting and by increase in alkenal/one oxidoreductase activity (25-fold higher than normal liver). In addition, the gene expression level of Ptgr1, as measured by qRT-PCR, was increased during cancer development in a time-dependent manner (200fold higher than normal liver). Furthermore, PTGR1 was detected in the cytoplasm of neoplastic cells in rat tumors and in 12 human HCC cases by immunohistochemistry. These analyses were performed by comparing the expression of PTGR1 to that of two well-known markers of hepatocarcinoma, Glutathione S-transferase pi 1 (GSTP1) in rats and glypican-3 in humans. The increased expression and activity of PTGR1 in liver carcinogenesis encourage further research aimed at understanding the metabolic role of PTGR1 in HCC and its potential application for human cancer diagnosis and treatment.

Research paper thumbnail of The differential NF-kB modulation by S-adenosyl-L-methionine, N-acetylcysteine and quercetin on the promotion stage of chemical hepatocarcinogenesis

Free Radical Research, 2008

S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect... more S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect. Likely this effect is mediated by counteracting, oxidative stress and NF-kB activation. To test this hypothesis F344 rats were subjected to hepatocarcinogenesis with or without antioxidants. NAC decreased foci in number and area, SAM and quercetin decreased area. Lipid-peroxidation was decreased by antioxidants, but only SAM increased glutathione. SAM, in its regulation from IKK downwards, abolished the NF-kB activation. NAC decreased IKK and IkB-a phosphorylation, and Rel-A/p65 and NF-kB binding, though the last two were affected with less intensity compared to the NF-kB inhibitor. Quercetin decreased Rel-A/p65, without modifying upstream signalling. Although all antioxidants inhibited oxidative stress as shown by reduction of lipid peroxidation, not all exerted the same effect on NF-kB signalling pathway and only SAM increased GSH. The mechanisms exerted by SAM in the reduction of foci makes this compound a potential liver cancer therapeutic agent.

Research paper thumbnail of Celecoxib activates Stat5 and restores or increases the expression of growth hormone-regulated genes in hepatocarcinogenesis

Anti-Cancer Drugs, 2010

Franç ois d and Saú l Villa-Treviñ o a We have previously evaluated the chemopreventive effect of... more Franç ois d and Saú l Villa-Treviñ o a We have previously evaluated the chemopreventive effect of celecoxib on preneoplastic lesions in rat liver. However, though the effects of celecoxib have been tested in a variety of carcinomas, there has not been a study on the modulation of gene expression in response to this drug. Here, we evaluated the effect of celecoxib on the gene expression profile associated with hepatocarcinogenesis. Male Sprague-Dawley rats underwent the modified resistant hepatocyte model and were fed a diet containing 1500 ppm of celecoxib. Gene expression profiles were evaluated using DNA microarrays and further validations were performed using quantitative PCR, western blotting and immunohistochemical staining. Celecoxib modulated the expression of 46 genes, and those regulated by growth hormone were selected for further analysis. Celecoxib significantly upregulated the expression of the Cyp2b1/2, Cyp3a1, and alpha2-urinary globulin (a2uG) genes and restored the expression of Cyp2b3 to normal. The protein expression of Cyp2b1/2 was increased, but the expressions of Cyp3a1 and a2uG were only restored to normal levels. The increased Cyp2b1/2 expression in response to celecoxib was mainly confined to preneoplastic lesions. A search for the upstream mediator of these genetic alterations found that carcinogenesis inactivated by 87% the signal transducer and activator of transcription 5 (Stat5), a transcription factor that is activated by growth hormone signaling, but celecoxib treatment restored its activation. In conclusion, these results suggest that celecoxib exerts anticancer effects on altered hepatic cells by restoring mRNA and the protein expression levels of specific genes, in part through the reactivation of Stat5. Anti-Cancer Drugs 21:411-422

Research paper thumbnail of Viral coinfection in acute respiratory infection in Mexican children treated by the emergency service: A cross-sectional study

Italian Journal of Pediatrics, 2015

Background: Acute respiratory infections (ARIs) cause illness. Children under five years of age a... more Background: Acute respiratory infections (ARIs) cause illness. Children under five years of age are highly vulnerable to these infections. Viral coinfection or multiple viral infection is a variable that can have a significant impact on the evolution of these diseases. Methods: This cross-sectional study was carried out in Mexican children (under five years of age) who had an ARI and who were treated by an emergency service in a hospital in Guadalajara, Jalisco, Mexico. The viral etiology, as well as the presence of multiple viral infections, was determined. A structured questionnaire was used to obtain demographic and clinical information. Odds ratio (OR) was calculated, and univariate and multivariate analyses using logistic regression were performed. Results: In the study population, metapneumovirus (hMPV) was the most frequent virus (22%), followed by adenovirus (hAD) (16%), respiratory syncytial virus (RSV) (14%), rhinovirus (hRV) (12%), bocavirus (hBoV) (9%), influenza virus (IF) (7%), and parainfluenza (PIF) (4%). The frequency of viral coinfections was 31.62%, and multiple logistic regression analysis revealed that hMPV, RSV, PIF, and hBoV were independently associated with multiple viral infection. No difference was found in the clinical manifestation of children with simple and multiple infections. Simple hMPV infection was associated with patients who presented with severe ARI. Using a multivariate analysis, we found that overcrowding is associated with coinfection when the viral etiology was hRV (OR = 2.56, 95% confidence interval (CI) 1.07 to 6.13), IF (OR = 2.56, 95% CI 1.07 to 6.13), PIF (OR = 2.96, 95% CI 1.15 to 7.65), hAD (OR = 2.56, 95% CI 1.07 to 6.13), and hBoV (OR = 2.9, 95% CI 1.14 to 7.34). Conclusions: Viral coinfections are frequent in children requiring treatment by an emergency service. However, the severity of ARI is similar to that of children with a simple infection. The hMPV is common and may confer a significant disease burden in the Mexican population. Finally, overcrowding is a housing characteristic that favors the development of coinfections.

Research paper thumbnail of Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

Research paper thumbnail of The transmembrane transporter ABCC3 participates in liver cancer progression and is a potential biomarker

Tumor Biology, 2015

The poor prognosis, few available treatment options, and multidrug resistance present in hepatoce... more The poor prognosis, few available treatment options, and multidrug resistance present in hepatocellular carcinoma are major problems, and new early biomarkers are needed to reduce the liver cancer death rate. ATP-binding cassette sub-family C member 3 (Abcc3) is overexpressed in different cancers and is associated with multidrug resistance and a carcinogenic stem cell phenotype. We present evidence for the first time that ABCC3 is a potential sanguine biomarker and anticancer target in hepatocellular carcinoma. Abcc3 mRNA expression was elevated in liver nodules and tumors in rat hepatocarcinogenesis model. Accordingly, the ABCC3 protein was preferentially overexpressed within the nodules and tumors during hepatocellular carcinoma progression and was secreted into the bloodstream of rat hepatocarcinogenesis model. The ABCC3 protein was expressed in human hepatoma cells and, importantly, was also present in HepG2- and Huh7-conditioned media. Furthermore, ABCC3 was overexpressed in human hepatocellular carcinoma. This report is the first to describe liver overexpression of Abcc3 during the cancer initiation, promotion, and progression periods in rat hepatocarcinogenesis model and in human hepatocellular carcinoma.

Research paper thumbnail of Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism

Free Radical Research, 2009

There is a correlation between oxidative stress generated by diethylnitrosamine (DEN) metabolism ... more There is a correlation between oxidative stress generated by diethylnitrosamine (DEN) metabolism and liver cancer development. Quercetin is a flavonoid with anti-carcinogenic and antioxidant properties. This study demonstrates the mechanism of action for the chemopreventive effect of quercetin. A 10 mg/kg dose of quercetin produced drastic effect, when it is administrated 2 h before DEN; at 24 days post-DEN, a 70.3% and 66.2% decrease in total area and number of preneoplastic lesions were observed, respectively. At 12 h post-DEN, quercetin inhibited levels of lipid peroxidation by 40%. Quercetin increased the levels of both GSH and of total glutathione, it increased the GSH/GSSG index and it caused a rapid and simultaneous elevation in the activities of superoxide dismutase, glutathione peroxidase and catalase. In conclusion, the quercetin mechanism of action is due to promote the enzymatic and non-enzymatic antioxidant defense system during the initiation of hepatocarcinogenesis.

Research paper thumbnail of The differential NF-kB modulation by S-adenosyl-L-methionine, N-acetylcysteine and quercetin on the promotion stage of chemical hepatocarcinogenesis

Free Radical Research, 2008

S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect... more S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect. Likely this effect is mediated by counteracting, oxidative stress and NF-kB activation. To test this hypothesis F344 rats were subjected to hepatocarcinogenesis with or without antioxidants. NAC decreased foci in number and area, SAM and quercetin decreased area. Lipid-peroxidation was decreased by antioxidants, but only SAM increased glutathione. SAM, in its regulation from IKK downwards, abolished the NF-kB activation. NAC decreased IKK and IkB-a phosphorylation, and Rel-A/p65 and NF-kB binding, though the last two were affected with less intensity compared to the NF-kB inhibitor. Quercetin decreased Rel-A/p65, without modifying upstream signalling. Although all antioxidants inhibited oxidative stress as shown by reduction of lipid peroxidation, not all exerted the same effect on NF-kB signalling pathway and only SAM increased GSH. The mechanisms exerted by SAM in the reduction of foci makes this compound a potential liver cancer therapeutic agent.

Research paper thumbnail of Chronic liver diseases and the potential use of S-adenosyl-L-methionine as a hepatoprotector

European Journal of Gastroenterology & Hepatology

Chronic liver diseases result in overall deterioration of health status and changes in metabolism... more Chronic liver diseases result in overall deterioration of health status and changes in metabolism. The search for strategies to control and combat these hepatic diseases has witnessed a great boom in the last decades. Nutritional therapy for controlling and managing liver diseases may be a positive influence as it improves the function of the liver. In this review, we focus mainly on describing liver conditions such as nonalcoholic fatty liver disease, and intrahepatic cholestasis as well as using S-adenosyl-L-methionine as a dietary supplement and its potential alternative therapeutic effect to correct the hepatic dysfunction associated with these conditions.

Research paper thumbnail of Enfermedades crónico degenerativas del estado de Veracruz: el ambiente oxidativo como un enfoque causal

Altepepaktli Salud De La Comunidad, 2009

El gran problema de salud publica del siglo veinte ha sido sin lugar a dudas la obesidad, a la cu... more El gran problema de salud publica del siglo veinte ha sido sin lugar a dudas la obesidad, a la cual se le relacionan muchas enfermedades como las cronico degenerativas (ECD). Las tres ECDs que se mantienen en los primeros lugares de mortalidad mundial y en el estado de Veracruz son las enfermedades cardiovasculares, la diabetes mellitus y el cancer. Evidencia experimental sobre el origen comun de estas tres patologias hacen suponer que el ambiente oxidativo juega un papel crucial en su genesis. El estres oxidativo causado por un aumento de las Especies Reactivas de Oxigeno (ERO) esta involucrado en el dano a las principales biomoleculas de la celula, lo que genera una inestabilidad biologica de todo el organismo. De las fuentes endogenas y exogenas de ERO, las ultimas son consideradas como las principales inductoras de la perdida de la homeostasis oxidoreduccion (redox). Estas ERO exogenas provienen del medio ambiente y del estilo de vida, por ejemplo: la radiacion ionizante (luz ultravioleta solar), el humo del cigarrillo, la ingesta excesiva de acidos grasos. Por ende, el uso de antioxidantes como terapia alternativa en la prevencion de las ECDs disminuiria la morbilidad de estas patologias. Esta revision tiene como objetivos exponer un panorama general de la relacion entre las principales ECD de nuestro estado y su origen comun generado por un ambiente pro-oxidante, asi como sugerir que la alimentacion con antioxidantes y adoptar un estilo de vida saludable, el cual incluya una dieta rica en vegetales y frutas, la abstinencia del consumo de tabaco, bebidas alcoholicas y eliminacion del sedentarismo, disminuirian la aparicion de las ECD e incrementarian la expectativa de vida

Research paper thumbnail of Clinical Characteristics and Genetic Variability of Human Rhinovirus in Mexico

Viruses, 2012

Human rhinovirus (HRV) is a leading cause of acute respiratory infection (ARI) in young children ... more Human rhinovirus (HRV) is a leading cause of acute respiratory infection (ARI) in young children and infants worldwide and has a high impact on morbidity and mortality in this population. Initially, HRV was classified into two species: HRV-A and HRV-B. Recently, a species called HRV-C and possibly another species, HRV-D, were identified. In Mexico, there is little information about the role of HRV as a cause of ARI, and the presence and importance of species such as HRV-C are not known. The aim of this study was to determine the clinical characteristics and genetic variability of HRV in Mexican children. Genetic characterization was carried out by phylogenetic analysis of the 5′-nontranslated region (5′-NTR) of the HRV genome. The results show that the newly identified HRV-C is circulating in Mexican children more frequently than HRV-B but not

Research paper thumbnail of Increased expression of prostaglandin reductase 1 in hepatocellular carcinomas from clinical cases and experimental tumors in rats

The International Journal of Biochemistry & Cell Biology, 2014

To identify novel tumor-associated proteins, we analyzed the protein expression patterns from exp... more To identify novel tumor-associated proteins, we analyzed the protein expression patterns from experimental hepatocellular carcinoma (HCC) that were induced using hepatocarcinogenesis models in rats. Rats were subjected to two previously described protocols of hepatocarcinogenesis using diethylnitrosamine as a carcinogen: the alternative Solt-Farber (aS&F) protocol, which induces HCC within 9 months, and Schiffer's model, which induces cirrhosis and multifocal HCC within 18 weeks. The patterns of protein expression from tumors and normal liver tissue were examined by SDS-PAGE and the bands identified at 33-34 kDa were analyzed by mass spectrometry. The prostaglandin reductase 1 (PTGR1) showed the highest number of peptides, with a confidence of level >99%. The increased expression of PTGR1 in tumors was confirmed in these two models by Western blotting and by increase in alkenal/one oxidoreductase activity (25-fold higher than normal liver). In addition, the gene expression level of Ptgr1, as measured by qRT-PCR, was increased during cancer development in a time-dependent manner (200fold higher than normal liver). Furthermore, PTGR1 was detected in the cytoplasm of neoplastic cells in rat tumors and in 12 human HCC cases by immunohistochemistry. These analyses were performed by comparing the expression of PTGR1 to that of two well-known markers of hepatocarcinoma, Glutathione S-transferase pi 1 (GSTP1) in rats and glypican-3 in humans. The increased expression and activity of PTGR1 in liver carcinogenesis encourage further research aimed at understanding the metabolic role of PTGR1 in HCC and its potential application for human cancer diagnosis and treatment.

Research paper thumbnail of The differential NF-kB modulation by S-adenosyl-L-methionine, N-acetylcysteine and quercetin on the promotion stage of chemical hepatocarcinogenesis

Free Radical Research, 2008

S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect... more S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect. Likely this effect is mediated by counteracting, oxidative stress and NF-kB activation. To test this hypothesis F344 rats were subjected to hepatocarcinogenesis with or without antioxidants. NAC decreased foci in number and area, SAM and quercetin decreased area. Lipid-peroxidation was decreased by antioxidants, but only SAM increased glutathione. SAM, in its regulation from IKK downwards, abolished the NF-kB activation. NAC decreased IKK and IkB-a phosphorylation, and Rel-A/p65 and NF-kB binding, though the last two were affected with less intensity compared to the NF-kB inhibitor. Quercetin decreased Rel-A/p65, without modifying upstream signalling. Although all antioxidants inhibited oxidative stress as shown by reduction of lipid peroxidation, not all exerted the same effect on NF-kB signalling pathway and only SAM increased GSH. The mechanisms exerted by SAM in the reduction of foci makes this compound a potential liver cancer therapeutic agent.

Research paper thumbnail of Celecoxib activates Stat5 and restores or increases the expression of growth hormone-regulated genes in hepatocarcinogenesis

Anti-Cancer Drugs, 2010

Franç ois d and Saú l Villa-Treviñ o a We have previously evaluated the chemopreventive effect of... more Franç ois d and Saú l Villa-Treviñ o a We have previously evaluated the chemopreventive effect of celecoxib on preneoplastic lesions in rat liver. However, though the effects of celecoxib have been tested in a variety of carcinomas, there has not been a study on the modulation of gene expression in response to this drug. Here, we evaluated the effect of celecoxib on the gene expression profile associated with hepatocarcinogenesis. Male Sprague-Dawley rats underwent the modified resistant hepatocyte model and were fed a diet containing 1500 ppm of celecoxib. Gene expression profiles were evaluated using DNA microarrays and further validations were performed using quantitative PCR, western blotting and immunohistochemical staining. Celecoxib modulated the expression of 46 genes, and those regulated by growth hormone were selected for further analysis. Celecoxib significantly upregulated the expression of the Cyp2b1/2, Cyp3a1, and alpha2-urinary globulin (a2uG) genes and restored the expression of Cyp2b3 to normal. The protein expression of Cyp2b1/2 was increased, but the expressions of Cyp3a1 and a2uG were only restored to normal levels. The increased Cyp2b1/2 expression in response to celecoxib was mainly confined to preneoplastic lesions. A search for the upstream mediator of these genetic alterations found that carcinogenesis inactivated by 87% the signal transducer and activator of transcription 5 (Stat5), a transcription factor that is activated by growth hormone signaling, but celecoxib treatment restored its activation. In conclusion, these results suggest that celecoxib exerts anticancer effects on altered hepatic cells by restoring mRNA and the protein expression levels of specific genes, in part through the reactivation of Stat5. Anti-Cancer Drugs 21:411-422

Research paper thumbnail of Viral coinfection in acute respiratory infection in Mexican children treated by the emergency service: A cross-sectional study

Italian Journal of Pediatrics, 2015

Background: Acute respiratory infections (ARIs) cause illness. Children under five years of age a... more Background: Acute respiratory infections (ARIs) cause illness. Children under five years of age are highly vulnerable to these infections. Viral coinfection or multiple viral infection is a variable that can have a significant impact on the evolution of these diseases. Methods: This cross-sectional study was carried out in Mexican children (under five years of age) who had an ARI and who were treated by an emergency service in a hospital in Guadalajara, Jalisco, Mexico. The viral etiology, as well as the presence of multiple viral infections, was determined. A structured questionnaire was used to obtain demographic and clinical information. Odds ratio (OR) was calculated, and univariate and multivariate analyses using logistic regression were performed. Results: In the study population, metapneumovirus (hMPV) was the most frequent virus (22%), followed by adenovirus (hAD) (16%), respiratory syncytial virus (RSV) (14%), rhinovirus (hRV) (12%), bocavirus (hBoV) (9%), influenza virus (IF) (7%), and parainfluenza (PIF) (4%). The frequency of viral coinfections was 31.62%, and multiple logistic regression analysis revealed that hMPV, RSV, PIF, and hBoV were independently associated with multiple viral infection. No difference was found in the clinical manifestation of children with simple and multiple infections. Simple hMPV infection was associated with patients who presented with severe ARI. Using a multivariate analysis, we found that overcrowding is associated with coinfection when the viral etiology was hRV (OR = 2.56, 95% confidence interval (CI) 1.07 to 6.13), IF (OR = 2.56, 95% CI 1.07 to 6.13), PIF (OR = 2.96, 95% CI 1.15 to 7.65), hAD (OR = 2.56, 95% CI 1.07 to 6.13), and hBoV (OR = 2.9, 95% CI 1.14 to 7.34). Conclusions: Viral coinfections are frequent in children requiring treatment by an emergency service. However, the severity of ARI is similar to that of children with a simple infection. The hMPV is common and may confer a significant disease burden in the Mexican population. Finally, overcrowding is a housing characteristic that favors the development of coinfections.

Research paper thumbnail of Occult HBV Infection: A Faceless Enemy in Liver Cancer Development

Research paper thumbnail of The transmembrane transporter ABCC3 participates in liver cancer progression and is a potential biomarker

Tumor Biology, 2015

The poor prognosis, few available treatment options, and multidrug resistance present in hepatoce... more The poor prognosis, few available treatment options, and multidrug resistance present in hepatocellular carcinoma are major problems, and new early biomarkers are needed to reduce the liver cancer death rate. ATP-binding cassette sub-family C member 3 (Abcc3) is overexpressed in different cancers and is associated with multidrug resistance and a carcinogenic stem cell phenotype. We present evidence for the first time that ABCC3 is a potential sanguine biomarker and anticancer target in hepatocellular carcinoma. Abcc3 mRNA expression was elevated in liver nodules and tumors in rat hepatocarcinogenesis model. Accordingly, the ABCC3 protein was preferentially overexpressed within the nodules and tumors during hepatocellular carcinoma progression and was secreted into the bloodstream of rat hepatocarcinogenesis model. The ABCC3 protein was expressed in human hepatoma cells and, importantly, was also present in HepG2- and Huh7-conditioned media. Furthermore, ABCC3 was overexpressed in human hepatocellular carcinoma. This report is the first to describe liver overexpression of Abcc3 during the cancer initiation, promotion, and progression periods in rat hepatocarcinogenesis model and in human hepatocellular carcinoma.

Research paper thumbnail of Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism

Free Radical Research, 2009

There is a correlation between oxidative stress generated by diethylnitrosamine (DEN) metabolism ... more There is a correlation between oxidative stress generated by diethylnitrosamine (DEN) metabolism and liver cancer development. Quercetin is a flavonoid with anti-carcinogenic and antioxidant properties. This study demonstrates the mechanism of action for the chemopreventive effect of quercetin. A 10 mg/kg dose of quercetin produced drastic effect, when it is administrated 2 h before DEN; at 24 days post-DEN, a 70.3% and 66.2% decrease in total area and number of preneoplastic lesions were observed, respectively. At 12 h post-DEN, quercetin inhibited levels of lipid peroxidation by 40%. Quercetin increased the levels of both GSH and of total glutathione, it increased the GSH/GSSG index and it caused a rapid and simultaneous elevation in the activities of superoxide dismutase, glutathione peroxidase and catalase. In conclusion, the quercetin mechanism of action is due to promote the enzymatic and non-enzymatic antioxidant defense system during the initiation of hepatocarcinogenesis.

Research paper thumbnail of The differential NF-kB modulation by S-adenosyl-L-methionine, N-acetylcysteine and quercetin on the promotion stage of chemical hepatocarcinogenesis

Free Radical Research, 2008

S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect... more S-adenosylmethionine (SAM), N-acetylcysteine (NAC) and quercetin exhibit a chemoprotective effect. Likely this effect is mediated by counteracting, oxidative stress and NF-kB activation. To test this hypothesis F344 rats were subjected to hepatocarcinogenesis with or without antioxidants. NAC decreased foci in number and area, SAM and quercetin decreased area. Lipid-peroxidation was decreased by antioxidants, but only SAM increased glutathione. SAM, in its regulation from IKK downwards, abolished the NF-kB activation. NAC decreased IKK and IkB-a phosphorylation, and Rel-A/p65 and NF-kB binding, though the last two were affected with less intensity compared to the NF-kB inhibitor. Quercetin decreased Rel-A/p65, without modifying upstream signalling. Although all antioxidants inhibited oxidative stress as shown by reduction of lipid peroxidation, not all exerted the same effect on NF-kB signalling pathway and only SAM increased GSH. The mechanisms exerted by SAM in the reduction of foci makes this compound a potential liver cancer therapeutic agent.

Research paper thumbnail of Chronic liver diseases and the potential use of S-adenosyl-L-methionine as a hepatoprotector

European Journal of Gastroenterology & Hepatology

Chronic liver diseases result in overall deterioration of health status and changes in metabolism... more Chronic liver diseases result in overall deterioration of health status and changes in metabolism. The search for strategies to control and combat these hepatic diseases has witnessed a great boom in the last decades. Nutritional therapy for controlling and managing liver diseases may be a positive influence as it improves the function of the liver. In this review, we focus mainly on describing liver conditions such as nonalcoholic fatty liver disease, and intrahepatic cholestasis as well as using S-adenosyl-L-methionine as a dietary supplement and its potential alternative therapeutic effect to correct the hepatic dysfunction associated with these conditions.