Gilles Robichaud - Academia.edu (original) (raw)

Papers by Gilles Robichaud

Research paper thumbnail of Implication of mammaglobin 1 and lipophilin B in breast cancer

The FASEB Journal

ABSTRACT Mammaglobin 1 (MGB1) is a protein fairly specific to mammary tissues and is often over e... more ABSTRACT Mammaglobin 1 (MGB1) is a protein fairly specific to mammary tissues and is often over expressed in breast cancer. It belongs to the secretoglobin family and binds to another secretoglobin, lipophilin B (LPB), to form an active complex. The complete expression profiles of MGB1 and LPB have not been determined, however it seems certain that they are expressed in healthy mammary cells and overexpressed in cancerous mammary cells. The function of the MGB1/LPB complex is still unknown. Nonetheless, several recent studies have shed some light on one possible effect this complex could have on cancerous cells; it has been shown that the presence of MGB1 in primary breast tumors seems to reflect a less aggressive tumor phenotype and a better prognosis for this type of cancer. The objective of this study is to try to clarify the implications of the MGB1/LPB complex and its components, MGB1 and LPB individually, in breast cancer. More precisely, this study investigates the ability of the MGB1/LPB complex or the MGB1 and LPB proteins individually, to inverse or slow down the cancerous phenotype of mammary cells in terms of proliferation, apoptosis and extracellular matrix invasion. We will also investigate whether MGB1 can influence the expression levels of LPB and vice versa. Overall, the importance of the research is to deepen our knowledge on the MGB1/LPB complex, which seems to play an important role in the biological processes of mammary cells. Research support from New Brunswick Innovation Foundation, Canadian Institutes in Health Research and Atlantic Innovation Foundation.

Research paper thumbnail of Analysis of downstream events of human Pax‐5B signalling in B lymphocytes

The FASEB Journal

ABSTRACT The Pax-5 gene, which codes for a potent transcription factor named BSAP, plays an impor... more ABSTRACT The Pax-5 gene, which codes for a potent transcription factor named BSAP, plays an important role in B lymphocyte development and oncogenesis. Aberrant expression of Pax-5 has been associated with different cancer such as lymphomas, leukemia and testicular cancer. Under the control of two alternative promoters, Pax-5 can simultaneously express two different forms (i.e. Pax-5A and Pax-5B). Through the use of a ribozyme-based gene suppression system, we demonstrate that Pax-5B is an important factor in the regulation of intracellular signalling cascades and elements leading to modulation of biological processes such as cellular proliferation, survival and apoptosis. More specifically, this study characterizes the implication of the hPD-1 receptor, Bax/Bcl2 ratios and p53 in Pax-5B-mediated apoptosis. These findings bring new insight into autoimmune diseases and cancer processes in human B lymphocytes. Research support from New Brunswick Innovation Foundation and Canadian Institutes in Health Research and Atlantic Innovation Foundation.

Research paper thumbnail of Pax-5 Inhibits NF-κB Activity in Breast Cancer Cells Through IKKε and miRNA-155 Effectors

Journal of Mammary Gland Biology and Neoplasia

Research paper thumbnail of Antibiotic Mycotoxins from an Endophytic Fusarium acuminatum Isolated from the Medicinal Plant Geum macrophyllum

Natural Product Communications

An extract of the endophytic fungus Fusarium acuminatum (TC2-084) isolated from the Canadian medi... more An extract of the endophytic fungus Fusarium acuminatum (TC2-084) isolated from the Canadian medicinal plant Geum macrophyllum exhibited significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra when fermented in both malt extract and potato dextrose broths. However, significant differences observed in the NMR spectra of the respective extracts led us to further investigate both. Bioassay guided fractionation revealed that lateropyrone was solely responsible for the bioactivity observed when TC2-084 was fermented in malt extract broth, while the antimycobacterial activity of the extract derived from the isolate fermented in potato dextrose broth was augmented by the presence of enniatins B, B1, and B4 in addition to lateropyrone.

Research paper thumbnail of Pax-5 is a potent regulator of E-cadherin and breast cancer malignant processes

Oncotarget, Jan 5, 2017

Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the d... more Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the development and progression of lymphoid cancers and carcinoma. In contrast to B-cell cancer lesions, the specific expression signatures and roles of Pax-5 in breast cancer progression are relatively unknown. In the present study, we set out to profile Pax-5 expression in mammary tissues and elucidate the cellular and molecular roles of Pax-5 in breast cancer processes. Using immunohistology on mammary tissue arrays, Pax-5 was detected in a total of 298/306 (97.6%) samples tested. Interestingly, our studies reveal that Pax-5 inhibits aggressive features and confers anti-proliferative effects in breast carcinoma cells in contrast to its oncogenic properties in B cell cancers. More precisely, Pax-5 suppressed breast cancer cell migration, invasion and tumor spheroid formation while concomitantly promoting cell adhesion properties. We also observed that Pax-5 inhibited and reversed breast can...

Research paper thumbnail of Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways

Journal of Cancer, 2016

The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate th... more The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate the morbidity and mortality associated with this disease. One of these factors, Pax-5, modulates cancer aggressiveness through the regulation of various components of the epithelial to mesenchymal transitioning (EMT) process. We have previously reported that Pax-5 expression profiles in cancer tissues inversely correlate with those of the Focal Adhesion Kinase (FAK), a potent activator of breast cancer malignancy. In this study, we set out to elucidate the molecular and regulatory relationship between Pax-5 and FAK in breast cancer processes. Interestingly, we found that Pax-5 mediated suppression of breast cancer cell migration is dependent of FAK activity. Our mechanistic examination revealed that Pax-5 inhibits FAK expression and activation. We also demonstrate that Pax-5 is a potent modulator of FAK repressors (p53 and miR-135b) and activator (NFκB) which results in the overall suppression of FAK-mediated signaling cascades. Altogether, our findings bring more insight to the molecular triggers regulating phenotypic transitioning process and signaling cascades leading to breast cancer progression.

Research paper thumbnail of HIV Type 1 nef Gene Inhibits Tumor Necrosis Factor -Induced Apoptosis and Promotes Cell Proliferation through the Action of MAPK and JNK in Human Glial Cells

Aids Res Hum Retrovirus, 2000

In neurodegenerative diseases associated with AIDS, reactive astrocytosis plays a central role in... more In neurodegenerative diseases associated with AIDS, reactive astrocytosis plays a central role in the neurotoxicity of the brain parenchyma. Whereas the HIV-1 nef gene is overexpressed during restricted HIV-1 infection of human astrocytes, our previous results have demonstrated that nef expressed in human U251MG glial cells activates the sphingomyelin pathway triggered by TNF-alpha, increasing ceramide production. Since ceramide is an important regulatory molecule of programmed cell death induced by TNF-alpha, we examined whether nef could alter TNF-alpha-induced apoptosis in the U251MG human astrocytoma cell line. Transfection studies indicated that nef could both prevent apoptosis and promote cell proliferation in response to TNF-alpha stimulation. MAPK and JNK activities were further analyzed in order to elucidate signaling cascades subsequent to the upregulation of ceramide production. After TNF-alpha treatment, both kinases were shown to be preferentially activated in the presence of nef. These experiments strongly suggest that the HIV-1 Nef protein might modulate the sensitivity of astrocytes to inflammatory molecules, thus contributing to the development of neurodegenerative diseases associated with AIDS.

Research paper thumbnail of T Cell Activation and Regulation of HIV-1: Same Effectors with Distinct Outcomes

Canadian Journal of Infectious Diseases, 1999

The molecular mechanisms that regulate the function of the immune system and human immunodeficien... more The molecular mechanisms that regulate the function of the immune system and human immunodeficiency virus type-1 (HIV-1) gene expression are diverse and complicated. However, replication of HIV-1 is controlled by many of the same regulatory signals that play a crucial role in the transcriptional regulation of the immune system. For example, the viral promoter, as is the case for the immune system, is subject to complex regulation by combinations of cellular transcription factors that may quantitatively and/or qualitatively differ depending on cell types (eg, macrophages versus T lymphocytes) and cell states (eg, undifferentiated versus differentiated or quiescent versus activated). The present review discusses the regulation of HIV-1 gene expression by nuclear factor-kappa Band nuclear factor of activated T cells, and proposes that selective interference of these two cellular transcription factors may be a route to abrogate virus replication without disrupting normal cellular functi...

Research paper thumbnail of Investigation of interaction between Pax5 isoforms and thioredoxin using de novo modelling methods

Isb, 2003

Pax-5 transcription factor plays a crucial role in B-cell development, activation and differentia... more Pax-5 transcription factor plays a crucial role in B-cell development, activation and differentiation. In murine B-cells four different isoforms of Pax-5 have been identified, and their role in the regulation of the activity of the wild-type protein was revealed although still not fully understood. Using theoretical methods, we investigated the properties of one region of the Pax-5e and Pax-5d isoforms (named UDE domain) and we present a possible theoretical model for the interaction of this domain with thioredoxin that have been previously postulated based on the experimental results. Domain UDE (MW 4.8 kDa) is characterised by an extremely high ratio of positively charged residues (8) in comparisons to negatively charged amino acids (3), as well as unusually large concentrations of prolines (11.6%) and cysteines (4.7%). This is indicative of its role in protein-protein interaction. The experimental 3D structure for either UDE domain or for any analogous sequence is not yet available, and therefore we resorted to various bioinformatics methods in order to predict the secondary and 3D structure from the primary sequence of UDE. Physicochemical properties of the predicted UDE structure gave more indication about possibilities for UDE-thioredoxin binding. In addition, UDE domain was shown to have both sequence and structure analogous to a segment of NAD-reducing hydrogenase HOXS a subunit which is believed to interact with thioredoxin. These studies showed that the UDE domain in Pax-5d and Pax-5e represents an ideal binding site for thioredoxin and we developed a model of UDE-TRX complex with two disulphide bridges. The active site of thioredoxin remained exposed after binding to UDE in this model and therefore binding of thioredoxin to Pax-5d could explain the unexpectedly high resistance of this isoform to oxidation. The complex between thioredoxin and Pax-5e can be a method for transportation of thioredoxin into the nucleus and also into the the vicinity of Pax-5a, explaining the observed activator role of Pax-5e.

Research paper thumbnail of Role of S100A8 and S100A9 proteins on breast cancer aggressivity

The Faseb Journal, Apr 1, 2009

Research paper thumbnail of Antimycobacterial Natural Products from Endophytes of the Medicinal Plant Aralia nudicaulis

Natural product communications, 2015

Antimycobacterial extracts of a Penicillium sp. (isolate HL4-159-41B) and a Coniothyrium sp. (iso... more Antimycobacterial extracts of a Penicillium sp. (isolate HL4-159-41B) and a Coniothyrium sp. (isolate HL6-097-027B) isolated from the rhizomes of the Canadian medicinal plant Aralia nudicaulis were found to contain palitantin (1) and botrallin (2), craterellin C (3), mycosporulone (4), spiromassaritone (5), and massarigenin D (6) respectively. Bioassays against Mycobacterium tuberculosis H37Ra revealed that 1 - 4 possess moderate antimycobacterial activity.

Research paper thumbnail of Isolation of Phomopsolide A and 6(E)-Phomopsolide A as Antimycobacterial Natural Products from an Unidentified Endophyte of the Canadian Medicinal Plant Heracleum maximum

Natural product communications, 2015

An extract of an unidentified endophyte from the Canadian medicinal plant Heracleum maximum exhib... more An extract of an unidentified endophyte from the Canadian medicinal plant Heracleum maximum exhibited a unique metabolomic profile and significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation of the extract led to the isolation of phomopsolide A (1) and 6(E)-phomopsolide A (2). This is the first report of antimycobacterial activity for 1 and 2.

Research paper thumbnail of Pax-5B predisposes B lymphocytes to a survival pathway

The Faseb Journal, Apr 1, 2009

Research paper thumbnail of Abstract 3094: MiRNAs 484 and 210 control Pax-5 expression and function in breast cancer

Research paper thumbnail of Abstract 3094: MiRNAs 484 and 210 control Pax-5 expression and function in breast cancer

Research paper thumbnail of Abstract P4-07-10: MiRNAs are important regulators of Pax-5 expression and function during breast cancer progression

Research paper thumbnail of Identification of variants of 5-lipoxygenase mRNA in human B lymphocytic cell lines

5-lipoxygenase (5-LO) catalyzes the initial reactions leading to the conversion of arachidonic ac... more 5-lipoxygenase (5-LO) catalyzes the initial reactions leading to the conversion of arachidonic acid into a number of biologically important mediators of inflammation. We seek to better understand the control of the biosynthesis of 5-LO products which is linked to inflammatory diseases such as asthma and atherosclerosis. In this study we used the human acute lymphocytic leukemia and Burkitt lymphoma cell lines REH and Raji, respectively, to investigate whether alternative variants of 5-LO mRNA are produced. Using reverse-transcription of extracted mRNA coupled with PCR, followed by molecular cloning and sequencing experiments, we have identified 4 different variants of 5-LO mRNA in these cell lines including the full length mRNA containing all 14 exons with the expected splicing sites. Amongst the alternative isoforms, one resulting from the exclusion of exon 13 was identified in both cell lines and was present in approximately 30% of the generated clones. This exclusion of exon 13 d...

Research paper thumbnail of Abstract 2266: The characterization of anti-breast cancer compounds isolated from the Juniperus communis

Research paper thumbnail of MicroRNAs and breast cancer malignancy: an overview of miRNA-regulated cancer processes leading to metastasis

Cancer biomarkers : section A of Disease markers, 2012

Cancer statistics show significant diagnosis numbers amongst men and women worldwide, where breas... more Cancer statistics show significant diagnosis numbers amongst men and women worldwide, where breast cancer is by far the most frequently diagnosed cancer in women. Multiple mechanisms and molecules have been shown to occupy major roles in cancer progression and aggressivity. Recently, small non-coding RNA molecules, called micro-RNAs, have become the subject of interest in many molecular pathways in relation to breast cancer, amongst many other pathologies. MiRNAs are capable of regulating gene expression in a sequence-specific manner and regulate diverse expression patterns which are dependent on the cell's state and identity. Studies have brought forward specific miRNAs that have the innate ability to govern unique gene expression profiles regulating cancer cell aggressivity. This review will outline recent findings of characterized miRNAs in relation to their molecular targets leading to cancer malignancy and progression. More specifically, we will focus on miRNAs associated w...

Research paper thumbnail of ChemInform Abstract: Synthesis and Structure-Activity Relationship of 1- and 2-Substituted 1,2,3-Triazole Letrozole-Based Analogues as Aromatase Inhibitors

Research paper thumbnail of Implication of mammaglobin 1 and lipophilin B in breast cancer

The FASEB Journal

ABSTRACT Mammaglobin 1 (MGB1) is a protein fairly specific to mammary tissues and is often over e... more ABSTRACT Mammaglobin 1 (MGB1) is a protein fairly specific to mammary tissues and is often over expressed in breast cancer. It belongs to the secretoglobin family and binds to another secretoglobin, lipophilin B (LPB), to form an active complex. The complete expression profiles of MGB1 and LPB have not been determined, however it seems certain that they are expressed in healthy mammary cells and overexpressed in cancerous mammary cells. The function of the MGB1/LPB complex is still unknown. Nonetheless, several recent studies have shed some light on one possible effect this complex could have on cancerous cells; it has been shown that the presence of MGB1 in primary breast tumors seems to reflect a less aggressive tumor phenotype and a better prognosis for this type of cancer. The objective of this study is to try to clarify the implications of the MGB1/LPB complex and its components, MGB1 and LPB individually, in breast cancer. More precisely, this study investigates the ability of the MGB1/LPB complex or the MGB1 and LPB proteins individually, to inverse or slow down the cancerous phenotype of mammary cells in terms of proliferation, apoptosis and extracellular matrix invasion. We will also investigate whether MGB1 can influence the expression levels of LPB and vice versa. Overall, the importance of the research is to deepen our knowledge on the MGB1/LPB complex, which seems to play an important role in the biological processes of mammary cells. Research support from New Brunswick Innovation Foundation, Canadian Institutes in Health Research and Atlantic Innovation Foundation.

Research paper thumbnail of Analysis of downstream events of human Pax‐5B signalling in B lymphocytes

The FASEB Journal

ABSTRACT The Pax-5 gene, which codes for a potent transcription factor named BSAP, plays an impor... more ABSTRACT The Pax-5 gene, which codes for a potent transcription factor named BSAP, plays an important role in B lymphocyte development and oncogenesis. Aberrant expression of Pax-5 has been associated with different cancer such as lymphomas, leukemia and testicular cancer. Under the control of two alternative promoters, Pax-5 can simultaneously express two different forms (i.e. Pax-5A and Pax-5B). Through the use of a ribozyme-based gene suppression system, we demonstrate that Pax-5B is an important factor in the regulation of intracellular signalling cascades and elements leading to modulation of biological processes such as cellular proliferation, survival and apoptosis. More specifically, this study characterizes the implication of the hPD-1 receptor, Bax/Bcl2 ratios and p53 in Pax-5B-mediated apoptosis. These findings bring new insight into autoimmune diseases and cancer processes in human B lymphocytes. Research support from New Brunswick Innovation Foundation and Canadian Institutes in Health Research and Atlantic Innovation Foundation.

Research paper thumbnail of Pax-5 Inhibits NF-κB Activity in Breast Cancer Cells Through IKKε and miRNA-155 Effectors

Journal of Mammary Gland Biology and Neoplasia

Research paper thumbnail of Antibiotic Mycotoxins from an Endophytic Fusarium acuminatum Isolated from the Medicinal Plant Geum macrophyllum

Natural Product Communications

An extract of the endophytic fungus Fusarium acuminatum (TC2-084) isolated from the Canadian medi... more An extract of the endophytic fungus Fusarium acuminatum (TC2-084) isolated from the Canadian medicinal plant Geum macrophyllum exhibited significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra when fermented in both malt extract and potato dextrose broths. However, significant differences observed in the NMR spectra of the respective extracts led us to further investigate both. Bioassay guided fractionation revealed that lateropyrone was solely responsible for the bioactivity observed when TC2-084 was fermented in malt extract broth, while the antimycobacterial activity of the extract derived from the isolate fermented in potato dextrose broth was augmented by the presence of enniatins B, B1, and B4 in addition to lateropyrone.

Research paper thumbnail of Pax-5 is a potent regulator of E-cadherin and breast cancer malignant processes

Oncotarget, Jan 5, 2017

Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the d... more Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the development and progression of lymphoid cancers and carcinoma. In contrast to B-cell cancer lesions, the specific expression signatures and roles of Pax-5 in breast cancer progression are relatively unknown. In the present study, we set out to profile Pax-5 expression in mammary tissues and elucidate the cellular and molecular roles of Pax-5 in breast cancer processes. Using immunohistology on mammary tissue arrays, Pax-5 was detected in a total of 298/306 (97.6%) samples tested. Interestingly, our studies reveal that Pax-5 inhibits aggressive features and confers anti-proliferative effects in breast carcinoma cells in contrast to its oncogenic properties in B cell cancers. More precisely, Pax-5 suppressed breast cancer cell migration, invasion and tumor spheroid formation while concomitantly promoting cell adhesion properties. We also observed that Pax-5 inhibited and reversed breast can...

Research paper thumbnail of Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways

Journal of Cancer, 2016

The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate th... more The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate the morbidity and mortality associated with this disease. One of these factors, Pax-5, modulates cancer aggressiveness through the regulation of various components of the epithelial to mesenchymal transitioning (EMT) process. We have previously reported that Pax-5 expression profiles in cancer tissues inversely correlate with those of the Focal Adhesion Kinase (FAK), a potent activator of breast cancer malignancy. In this study, we set out to elucidate the molecular and regulatory relationship between Pax-5 and FAK in breast cancer processes. Interestingly, we found that Pax-5 mediated suppression of breast cancer cell migration is dependent of FAK activity. Our mechanistic examination revealed that Pax-5 inhibits FAK expression and activation. We also demonstrate that Pax-5 is a potent modulator of FAK repressors (p53 and miR-135b) and activator (NFκB) which results in the overall suppression of FAK-mediated signaling cascades. Altogether, our findings bring more insight to the molecular triggers regulating phenotypic transitioning process and signaling cascades leading to breast cancer progression.

Research paper thumbnail of HIV Type 1 nef Gene Inhibits Tumor Necrosis Factor -Induced Apoptosis and Promotes Cell Proliferation through the Action of MAPK and JNK in Human Glial Cells

Aids Res Hum Retrovirus, 2000

In neurodegenerative diseases associated with AIDS, reactive astrocytosis plays a central role in... more In neurodegenerative diseases associated with AIDS, reactive astrocytosis plays a central role in the neurotoxicity of the brain parenchyma. Whereas the HIV-1 nef gene is overexpressed during restricted HIV-1 infection of human astrocytes, our previous results have demonstrated that nef expressed in human U251MG glial cells activates the sphingomyelin pathway triggered by TNF-alpha, increasing ceramide production. Since ceramide is an important regulatory molecule of programmed cell death induced by TNF-alpha, we examined whether nef could alter TNF-alpha-induced apoptosis in the U251MG human astrocytoma cell line. Transfection studies indicated that nef could both prevent apoptosis and promote cell proliferation in response to TNF-alpha stimulation. MAPK and JNK activities were further analyzed in order to elucidate signaling cascades subsequent to the upregulation of ceramide production. After TNF-alpha treatment, both kinases were shown to be preferentially activated in the presence of nef. These experiments strongly suggest that the HIV-1 Nef protein might modulate the sensitivity of astrocytes to inflammatory molecules, thus contributing to the development of neurodegenerative diseases associated with AIDS.

Research paper thumbnail of T Cell Activation and Regulation of HIV-1: Same Effectors with Distinct Outcomes

Canadian Journal of Infectious Diseases, 1999

The molecular mechanisms that regulate the function of the immune system and human immunodeficien... more The molecular mechanisms that regulate the function of the immune system and human immunodeficiency virus type-1 (HIV-1) gene expression are diverse and complicated. However, replication of HIV-1 is controlled by many of the same regulatory signals that play a crucial role in the transcriptional regulation of the immune system. For example, the viral promoter, as is the case for the immune system, is subject to complex regulation by combinations of cellular transcription factors that may quantitatively and/or qualitatively differ depending on cell types (eg, macrophages versus T lymphocytes) and cell states (eg, undifferentiated versus differentiated or quiescent versus activated). The present review discusses the regulation of HIV-1 gene expression by nuclear factor-kappa Band nuclear factor of activated T cells, and proposes that selective interference of these two cellular transcription factors may be a route to abrogate virus replication without disrupting normal cellular functi...

Research paper thumbnail of Investigation of interaction between Pax5 isoforms and thioredoxin using de novo modelling methods

Isb, 2003

Pax-5 transcription factor plays a crucial role in B-cell development, activation and differentia... more Pax-5 transcription factor plays a crucial role in B-cell development, activation and differentiation. In murine B-cells four different isoforms of Pax-5 have been identified, and their role in the regulation of the activity of the wild-type protein was revealed although still not fully understood. Using theoretical methods, we investigated the properties of one region of the Pax-5e and Pax-5d isoforms (named UDE domain) and we present a possible theoretical model for the interaction of this domain with thioredoxin that have been previously postulated based on the experimental results. Domain UDE (MW 4.8 kDa) is characterised by an extremely high ratio of positively charged residues (8) in comparisons to negatively charged amino acids (3), as well as unusually large concentrations of prolines (11.6%) and cysteines (4.7%). This is indicative of its role in protein-protein interaction. The experimental 3D structure for either UDE domain or for any analogous sequence is not yet available, and therefore we resorted to various bioinformatics methods in order to predict the secondary and 3D structure from the primary sequence of UDE. Physicochemical properties of the predicted UDE structure gave more indication about possibilities for UDE-thioredoxin binding. In addition, UDE domain was shown to have both sequence and structure analogous to a segment of NAD-reducing hydrogenase HOXS a subunit which is believed to interact with thioredoxin. These studies showed that the UDE domain in Pax-5d and Pax-5e represents an ideal binding site for thioredoxin and we developed a model of UDE-TRX complex with two disulphide bridges. The active site of thioredoxin remained exposed after binding to UDE in this model and therefore binding of thioredoxin to Pax-5d could explain the unexpectedly high resistance of this isoform to oxidation. The complex between thioredoxin and Pax-5e can be a method for transportation of thioredoxin into the nucleus and also into the the vicinity of Pax-5a, explaining the observed activator role of Pax-5e.

Research paper thumbnail of Role of S100A8 and S100A9 proteins on breast cancer aggressivity

The Faseb Journal, Apr 1, 2009

Research paper thumbnail of Antimycobacterial Natural Products from Endophytes of the Medicinal Plant Aralia nudicaulis

Natural product communications, 2015

Antimycobacterial extracts of a Penicillium sp. (isolate HL4-159-41B) and a Coniothyrium sp. (iso... more Antimycobacterial extracts of a Penicillium sp. (isolate HL4-159-41B) and a Coniothyrium sp. (isolate HL6-097-027B) isolated from the rhizomes of the Canadian medicinal plant Aralia nudicaulis were found to contain palitantin (1) and botrallin (2), craterellin C (3), mycosporulone (4), spiromassaritone (5), and massarigenin D (6) respectively. Bioassays against Mycobacterium tuberculosis H37Ra revealed that 1 - 4 possess moderate antimycobacterial activity.

Research paper thumbnail of Isolation of Phomopsolide A and 6(E)-Phomopsolide A as Antimycobacterial Natural Products from an Unidentified Endophyte of the Canadian Medicinal Plant Heracleum maximum

Natural product communications, 2015

An extract of an unidentified endophyte from the Canadian medicinal plant Heracleum maximum exhib... more An extract of an unidentified endophyte from the Canadian medicinal plant Heracleum maximum exhibited a unique metabolomic profile and significant antimycobacterial activity against Mycobacterium tuberculosis H37Ra. Bioassay guided fractionation of the extract led to the isolation of phomopsolide A (1) and 6(E)-phomopsolide A (2). This is the first report of antimycobacterial activity for 1 and 2.

Research paper thumbnail of Pax-5B predisposes B lymphocytes to a survival pathway

The Faseb Journal, Apr 1, 2009

Research paper thumbnail of Abstract 3094: MiRNAs 484 and 210 control Pax-5 expression and function in breast cancer

Research paper thumbnail of Abstract 3094: MiRNAs 484 and 210 control Pax-5 expression and function in breast cancer

Research paper thumbnail of Abstract P4-07-10: MiRNAs are important regulators of Pax-5 expression and function during breast cancer progression

Research paper thumbnail of Identification of variants of 5-lipoxygenase mRNA in human B lymphocytic cell lines

5-lipoxygenase (5-LO) catalyzes the initial reactions leading to the conversion of arachidonic ac... more 5-lipoxygenase (5-LO) catalyzes the initial reactions leading to the conversion of arachidonic acid into a number of biologically important mediators of inflammation. We seek to better understand the control of the biosynthesis of 5-LO products which is linked to inflammatory diseases such as asthma and atherosclerosis. In this study we used the human acute lymphocytic leukemia and Burkitt lymphoma cell lines REH and Raji, respectively, to investigate whether alternative variants of 5-LO mRNA are produced. Using reverse-transcription of extracted mRNA coupled with PCR, followed by molecular cloning and sequencing experiments, we have identified 4 different variants of 5-LO mRNA in these cell lines including the full length mRNA containing all 14 exons with the expected splicing sites. Amongst the alternative isoforms, one resulting from the exclusion of exon 13 was identified in both cell lines and was present in approximately 30% of the generated clones. This exclusion of exon 13 d...

Research paper thumbnail of Abstract 2266: The characterization of anti-breast cancer compounds isolated from the Juniperus communis

Research paper thumbnail of MicroRNAs and breast cancer malignancy: an overview of miRNA-regulated cancer processes leading to metastasis

Cancer biomarkers : section A of Disease markers, 2012

Cancer statistics show significant diagnosis numbers amongst men and women worldwide, where breas... more Cancer statistics show significant diagnosis numbers amongst men and women worldwide, where breast cancer is by far the most frequently diagnosed cancer in women. Multiple mechanisms and molecules have been shown to occupy major roles in cancer progression and aggressivity. Recently, small non-coding RNA molecules, called micro-RNAs, have become the subject of interest in many molecular pathways in relation to breast cancer, amongst many other pathologies. MiRNAs are capable of regulating gene expression in a sequence-specific manner and regulate diverse expression patterns which are dependent on the cell's state and identity. Studies have brought forward specific miRNAs that have the innate ability to govern unique gene expression profiles regulating cancer cell aggressivity. This review will outline recent findings of characterized miRNAs in relation to their molecular targets leading to cancer malignancy and progression. More specifically, we will focus on miRNAs associated w...

Research paper thumbnail of ChemInform Abstract: Synthesis and Structure-Activity Relationship of 1- and 2-Substituted 1,2,3-Triazole Letrozole-Based Analogues as Aromatase Inhibitors