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Papers by Pierre Oliveira

Research paper thumbnail of The trouble with assimilation: Social dominance and the emergence of hostility against immigrants

International Journal of Intercultural Relations, 2010

Research paper thumbnail of Prejudice in the police: On the processes underlying the effects of selection and group socialisation

European Journal of Social Psychology, 2009

The principal aim of this study is to determine why police officers are generally found to be mor... more The principal aim of this study is to determine why police officers are generally found to be more prejudiced towards disadvantaged groups than are the standard population. Two independent processes were expected to account for this effect: Selection and group socialisation. Using a cross-sectional design (N = 170), firstly, we compared, newly recruited police officers with a control population (selection effect), and secondly, police officers with 1 year of training with the newly recruited ones (group socialisation effect). Results reveal a significant effect of both selection and group socialisation, the two being underlined by distinct processes; right-wing authoritarianism (RWA) in the case of the former and internalisation of a prejudice norm in the case of the latter. Finally, the results show that group identification moderates the change in internalisation of the prejudice norm. Copyright © 2009 John Wiley & Sons, Ltd.

Research paper thumbnail of Ad-IRF-1 Induces Apoptosis in Esophageal Adenocarcinoma

Neoplasia, 2006

The nuclear transcription factor interferon regulatory factor-1 (IRF-1) is a putative tumor suppr... more The nuclear transcription factor interferon regulatory factor-1 (IRF-1) is a putative tumor suppressor, but the expression and function of IRF-1 in esophageal adenocarcinoma (EA) remain unknown. We hypothesized that IRF-1 expression was reduced or lost in EA and that restoration of IRF-1 would result in the apoptosis of EA cells in vitro and the inhibition of tumor growth in vivo. Three EA cell lines were used to examine IRF-1 expression, IFN-; responsiveness, and the effects of IRF-1 overexpression using a recombinant adenoviral vector (Ad-IRF-1). All three EA cell lines produced IRF-1 protein following IFN-; stimulation, although IFN-; did not induce cell death. In contrast, Ad-IRF-1 infection resulted in high levels of IRF-1 protein and triggered apoptosis in all three EA cell lines. Potential mechanisms for the differential response to IFN-; versus Ad-IRF-1-such as modulation of c-Met or extracellular regulated kinase signaling, or altered expression of IRF-2, Fas, or survivin-were investigated, but none of these mechanisms can account for this observation. In vivo administration of IRF-1 in a murine model of EA modestly inhibited tumor growth, but did not lead to tumor regression. Strategies aimed at increasing or restoring IRF-1 expression may have therapeutic benefits in EA. Neoplasia (2006) 8, 31-37

Research paper thumbnail of Inhibition of c-Met as a Therapeutic Strategy for Esophageal Adenocarcinoma

Neoplasia, 2006

The hepatocyte growth factor (HGF) receptor c-Met is a tyrosine kinase receptor with established ... more The hepatocyte growth factor (HGF) receptor c-Met is a tyrosine kinase receptor with established oncogenic properties. We have previously shown that c-Met is usually overexpressed in esophageal adenocarcinoma (EA), yet the implications of c-Met inhibition in EA remain unknown. Three c-Met -overexpressing EA cell lines (Seg-1, Bic-1, and Flo-1) were used to examine the effects of a c-Met -specific small molecule inhibitor (PHA665752) on cell viability, apoptosis, motility, invasion, and downstream signaling pathways. PHA665752 demonstrated dose-dependent inhibition of constitutive and/or HGF-induced phosphorylation of c-Met, which correlated with reduced cell viability and inhibition of extracellular regulated kinase 1/2 phosphorylation in all three EA cell lines. In contrast, PHA665752 induced apoptosis and reduced motility and invasion in only one EA cell line, Flo-1. Interestingly, Flo-1 was the only cell line in which phosphatidylinositol 3-kinase (PI3K)/Akt was induced following HGF stimulation. The PI3K inhibitor LY294002 produced effects equivalent to those of PHA665752 in these cells. We conclude that inhibition of c-Met may be a useful therapeutic strategy for EA. Factors other than receptor overexpression, such as c-Met -dependent PI3K/Akt signaling, may be predictive of an individual tumor's response to c-Met inhibition. Neoplasia (2006) 8, 949 -955

Research paper thumbnail of Bile Salts Differentially Sensitize Esophageal Squamous Cells to CD95 (Fas/Apo1 Receptor) Mediated Apoptosis

Journal of Surgical Research, 2011

The role of non-acidic reflux contents on the pathophysiology of Barrett's Esophagus remains poor... more The role of non-acidic reflux contents on the pathophysiology of Barrett's Esophagus remains poorly understood. We hypothesized that esophageal squamous epithelium differs from Barrett's columnar epithelium in response to bile salts with respect to subsequent changes in the cell surface expression of CD95 (Fas/Apo-1) and sensitivity to CD95-mediated apoptosis.

Research paper thumbnail of Altered trafficking of Fas and subsequent resistance to Fas-mediated apoptosis occurs by a wild-type p53 independent mechanism in esophageal adenocarcinoma 1

Journal of Surgical Research, 2005

Background. Decreased cell-surface expression of Fas (CD95) results in resistance to Fas-mediated... more Background. Decreased cell-surface expression of Fas (CD95) results in resistance to Fas-mediated apoptosis in esophageal adenocarcinoma (EA). Because p53 is known to increase transcription of Fas and also may induce trafficking of the protein to the plasma membrane, we investigated whether the loss of wildtype (wt)-p53 function accounts for our previous findings.

Research paper thumbnail of The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma1

The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, ... more The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA) remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE), and normal esophagus (NE) using immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100%) EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2 -overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted. Neoplasia (2005) 7, 75 -84

Research paper thumbnail of The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma

Neoplasia, 2005

The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, ... more The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA) remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE), and normal esophagus (NE) using immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100%) EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2 -overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted. Neoplasia (2005) 7, 75 -84

Research paper thumbnail of Novel benzofuran inhibitors of human mitogen-activated protein kinase phosphatase-1

Bioorganic & Medicinal Chemistry, 2006

Protein tyrosine phosphatases have a central role in the maintenance of normal cellular functiona... more Protein tyrosine phosphatases have a central role in the maintenance of normal cellular functionality. For example, PTP1B has been implicated in insulin-resistance, obesity, and neoplasia. Mitogen-activated protein kinase phosphatase-1 (MKP-1 or DUSP1) dephosphorylates and inactivates mitogen-activated protein kinase (MAPK) substrates, such as p38, JNK, and Erk, and has been implicated in neoplasia. The lack of readily available selective small molecule inhibitors of MKP family members has severely limited interrogation of their biological role. Inspired by a previously identified inhibitor (NSC 357756) of MKP-3, we synthesized seven NSC 357756 congeners, which were evaluated for in vitro inhibition against several protein phosphatases. Remarkably, none displayed potent inhibition against MKP-3, including the desamino NSC 357756 analog NU-154. Interestingly, NU-154 inhibited human PTP1B in vitro with an IC 50 value of 24 ± 1 lM and showed little inhibition against Cdc25B, MKP-1, and VHR phosphatases. NU-126 [2-((E)-2-(5-cyanobenzofuran-2-yl)vinyl)-1H-indole-6-carbonitrile] inhibited MKP-1 and VHR in vitro but was less active against human MKP-3, Cdc25B, and PTP1B. The inhibition of MKP-1 by NU-126 was independent of redox processes. The benzofuran substructure represents a new potential scaffold for further analog development and provides encouragement that more selective and potent inhibitors of MKP family members may be achievable.

Research paper thumbnail of Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages

Nature Chemical Biology, 2009

The dual specificity phosphatase 6 (Dusp6) functions as a feedback regulator of fibroblast growth... more The dual specificity phosphatase 6 (Dusp6) functions as a feedback regulator of fibroblast growth factor (FGF) signaling to limit the activity of extracellular signal regulated kinase (ERK) 1 and 2. We have identified a small molecule inhibitor of Dusp6, (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), using a transgenic zebrafish chemical screen. BCI treatment blocked Dusp6 activity and enhanced FGF target gene expression in zebrafish embryos. Docking simulations predicted an allosteric binding site for BCI within the phosphatase domain. In vitro studies supported a model that BCI inhibits Dusp6 catalytic activation by ERK2 substrate binding. A temporal role for Dusp6 in restricting cardiac progenitors and controlling heart organ size was uncovered with BCI treatment at varying developmental stages. This study highlights the power of in vivo zebrafish chemical screens to identify novel compounds targeting Dusp6, a component of the FGF signaling pathway that has eluded traditional high-throughput in vitro screens.

Research paper thumbnail of Bolo de Cenoura

Research paper thumbnail of The trouble with assimilation: Social dominance and the emergence of hostility against immigrants

International Journal of Intercultural Relations, 2010

Research paper thumbnail of Prejudice in the police: On the processes underlying the effects of selection and group socialisation

European Journal of Social Psychology, 2009

The principal aim of this study is to determine why police officers are generally found to be mor... more The principal aim of this study is to determine why police officers are generally found to be more prejudiced towards disadvantaged groups than are the standard population. Two independent processes were expected to account for this effect: Selection and group socialisation. Using a cross-sectional design (N = 170), firstly, we compared, newly recruited police officers with a control population (selection effect), and secondly, police officers with 1 year of training with the newly recruited ones (group socialisation effect). Results reveal a significant effect of both selection and group socialisation, the two being underlined by distinct processes; right-wing authoritarianism (RWA) in the case of the former and internalisation of a prejudice norm in the case of the latter. Finally, the results show that group identification moderates the change in internalisation of the prejudice norm. Copyright © 2009 John Wiley & Sons, Ltd.

Research paper thumbnail of Ad-IRF-1 Induces Apoptosis in Esophageal Adenocarcinoma

Neoplasia, 2006

The nuclear transcription factor interferon regulatory factor-1 (IRF-1) is a putative tumor suppr... more The nuclear transcription factor interferon regulatory factor-1 (IRF-1) is a putative tumor suppressor, but the expression and function of IRF-1 in esophageal adenocarcinoma (EA) remain unknown. We hypothesized that IRF-1 expression was reduced or lost in EA and that restoration of IRF-1 would result in the apoptosis of EA cells in vitro and the inhibition of tumor growth in vivo. Three EA cell lines were used to examine IRF-1 expression, IFN-; responsiveness, and the effects of IRF-1 overexpression using a recombinant adenoviral vector (Ad-IRF-1). All three EA cell lines produced IRF-1 protein following IFN-; stimulation, although IFN-; did not induce cell death. In contrast, Ad-IRF-1 infection resulted in high levels of IRF-1 protein and triggered apoptosis in all three EA cell lines. Potential mechanisms for the differential response to IFN-; versus Ad-IRF-1-such as modulation of c-Met or extracellular regulated kinase signaling, or altered expression of IRF-2, Fas, or survivin-were investigated, but none of these mechanisms can account for this observation. In vivo administration of IRF-1 in a murine model of EA modestly inhibited tumor growth, but did not lead to tumor regression. Strategies aimed at increasing or restoring IRF-1 expression may have therapeutic benefits in EA. Neoplasia (2006) 8, 31-37

Research paper thumbnail of Inhibition of c-Met as a Therapeutic Strategy for Esophageal Adenocarcinoma

Neoplasia, 2006

The hepatocyte growth factor (HGF) receptor c-Met is a tyrosine kinase receptor with established ... more The hepatocyte growth factor (HGF) receptor c-Met is a tyrosine kinase receptor with established oncogenic properties. We have previously shown that c-Met is usually overexpressed in esophageal adenocarcinoma (EA), yet the implications of c-Met inhibition in EA remain unknown. Three c-Met -overexpressing EA cell lines (Seg-1, Bic-1, and Flo-1) were used to examine the effects of a c-Met -specific small molecule inhibitor (PHA665752) on cell viability, apoptosis, motility, invasion, and downstream signaling pathways. PHA665752 demonstrated dose-dependent inhibition of constitutive and/or HGF-induced phosphorylation of c-Met, which correlated with reduced cell viability and inhibition of extracellular regulated kinase 1/2 phosphorylation in all three EA cell lines. In contrast, PHA665752 induced apoptosis and reduced motility and invasion in only one EA cell line, Flo-1. Interestingly, Flo-1 was the only cell line in which phosphatidylinositol 3-kinase (PI3K)/Akt was induced following HGF stimulation. The PI3K inhibitor LY294002 produced effects equivalent to those of PHA665752 in these cells. We conclude that inhibition of c-Met may be a useful therapeutic strategy for EA. Factors other than receptor overexpression, such as c-Met -dependent PI3K/Akt signaling, may be predictive of an individual tumor's response to c-Met inhibition. Neoplasia (2006) 8, 949 -955

Research paper thumbnail of Bile Salts Differentially Sensitize Esophageal Squamous Cells to CD95 (Fas/Apo1 Receptor) Mediated Apoptosis

Journal of Surgical Research, 2011

The role of non-acidic reflux contents on the pathophysiology of Barrett's Esophagus remains poor... more The role of non-acidic reflux contents on the pathophysiology of Barrett's Esophagus remains poorly understood. We hypothesized that esophageal squamous epithelium differs from Barrett's columnar epithelium in response to bile salts with respect to subsequent changes in the cell surface expression of CD95 (Fas/Apo-1) and sensitivity to CD95-mediated apoptosis.

Research paper thumbnail of Altered trafficking of Fas and subsequent resistance to Fas-mediated apoptosis occurs by a wild-type p53 independent mechanism in esophageal adenocarcinoma 1

Journal of Surgical Research, 2005

Background. Decreased cell-surface expression of Fas (CD95) results in resistance to Fas-mediated... more Background. Decreased cell-surface expression of Fas (CD95) results in resistance to Fas-mediated apoptosis in esophageal adenocarcinoma (EA). Because p53 is known to increase transcription of Fas and also may induce trafficking of the protein to the plasma membrane, we investigated whether the loss of wildtype (wt)-p53 function accounts for our previous findings.

Research paper thumbnail of The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma1

The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, ... more The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA) remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE), and normal esophagus (NE) using immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100%) EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2 -overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted. Neoplasia (2005) 7, 75 -84

Research paper thumbnail of The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma

Neoplasia, 2005

The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, ... more The hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA) remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE), and normal esophagus (NE) using immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100%) EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2 -overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted. Neoplasia (2005) 7, 75 -84

Research paper thumbnail of Novel benzofuran inhibitors of human mitogen-activated protein kinase phosphatase-1

Bioorganic & Medicinal Chemistry, 2006

Protein tyrosine phosphatases have a central role in the maintenance of normal cellular functiona... more Protein tyrosine phosphatases have a central role in the maintenance of normal cellular functionality. For example, PTP1B has been implicated in insulin-resistance, obesity, and neoplasia. Mitogen-activated protein kinase phosphatase-1 (MKP-1 or DUSP1) dephosphorylates and inactivates mitogen-activated protein kinase (MAPK) substrates, such as p38, JNK, and Erk, and has been implicated in neoplasia. The lack of readily available selective small molecule inhibitors of MKP family members has severely limited interrogation of their biological role. Inspired by a previously identified inhibitor (NSC 357756) of MKP-3, we synthesized seven NSC 357756 congeners, which were evaluated for in vitro inhibition against several protein phosphatases. Remarkably, none displayed potent inhibition against MKP-3, including the desamino NSC 357756 analog NU-154. Interestingly, NU-154 inhibited human PTP1B in vitro with an IC 50 value of 24 ± 1 lM and showed little inhibition against Cdc25B, MKP-1, and VHR phosphatases. NU-126 [2-((E)-2-(5-cyanobenzofuran-2-yl)vinyl)-1H-indole-6-carbonitrile] inhibited MKP-1 and VHR in vitro but was less active against human MKP-3, Cdc25B, and PTP1B. The inhibition of MKP-1 by NU-126 was independent of redox processes. The benzofuran substructure represents a new potential scaffold for further analog development and provides encouragement that more selective and potent inhibitors of MKP family members may be achievable.

Research paper thumbnail of Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages

Nature Chemical Biology, 2009

The dual specificity phosphatase 6 (Dusp6) functions as a feedback regulator of fibroblast growth... more The dual specificity phosphatase 6 (Dusp6) functions as a feedback regulator of fibroblast growth factor (FGF) signaling to limit the activity of extracellular signal regulated kinase (ERK) 1 and 2. We have identified a small molecule inhibitor of Dusp6, (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), using a transgenic zebrafish chemical screen. BCI treatment blocked Dusp6 activity and enhanced FGF target gene expression in zebrafish embryos. Docking simulations predicted an allosteric binding site for BCI within the phosphatase domain. In vitro studies supported a model that BCI inhibits Dusp6 catalytic activation by ERK2 substrate binding. A temporal role for Dusp6 in restricting cardiac progenitors and controlling heart organ size was uncovered with BCI treatment at varying developmental stages. This study highlights the power of in vivo zebrafish chemical screens to identify novel compounds targeting Dusp6, a component of the FGF signaling pathway that has eluded traditional high-throughput in vitro screens.

Research paper thumbnail of Bolo de Cenoura