Prof. Dr. Haitham A . Badr | Zagazig University (original) (raw)

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Papers by Prof. Dr. Haitham A . Badr

Research paper thumbnail of Live cell integrated surface plasmon resonance biosensing approach to mimic the regulation of angiogenic switch upon anti-cancer drug exposure

Analytical chemistry, Jan 5, 2014

In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platfo... more In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platform to measure and compare the binding affinity of vascular endothelial growth factor (VEGF) to vascular endothelial growth factor receptor (VEGFR) and VEGF to bevacizumab. Results have shown that bevacizumab binds VEGF with a higher association rate and affinity compared to VEGFR. Further, this platform has been employed to mimic the in vivo condition of the VEGF-VEGFR angiogenic switch. Competitive binding to VEGF between VEGFR and bevacizumab was monitored in real-time using this platform. Results demonstrated a significant blockage of VEGF-VEGFR binding by bevacizumab. From the results, it is evident that the proposed strategy is simple and highly sensitive for the direct and real-time measurements of bevacizumab drug efficacy to the VEGF-VEGFR angiogenic switch in living SKOV-3 cells.

Research paper thumbnail of Cancer cell death induced by nanomagnetolectin

European journal of cell biology, Jan 10, 2017

Magnetic nanoparticles represent a new paradigm for molecular targeting therapy in cancer. Howeve... more Magnetic nanoparticles represent a new paradigm for molecular targeting therapy in cancer. However, the transformative targeting potential of magnetic nanoparticles has been stymied by a key obstacle-safe delivery to specified target cells in vivo. As cancer cells grow under nutrient deprivation and hypoxic conditions and decorate cell surface with excessive sialoglycans, sialic acid binding lectins might be suitable for targeting cancer cells in vivo. Here we explore the potential of magnetic nanoparticles functionalized with wheat germ lectin (WGA) conjugate, so-called nanomagnetolectin, as apoptotic targetable agents for prostate cancer. In the presence of magnetic field (magnetofection) for 15min, 2.46nM nanomagnetolectin significantly promoted apoptosis (∼12-fold, p value <0.01) of prostate cancer cells (LNCaP, PC-3, DU-145) compared to normal prostate epithelial cells (PrEC, PNT2, PZ-HPV-7), when supplemented with 10mM sialic acid under nutrient deprived condition. Nanomagn...

Research paper thumbnail of Harnessing cancer cell metabolism for theranostic applications using metabolic glycoengineering of sialic acid in breast cancer as a pioneering example

Abnormal cell surface display of sialic acids e a family of unusual 9-carbon sugars-is widely rec... more Abnormal cell surface display of sialic acids e a family of unusual 9-carbon sugars-is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation. We then describe how cancer cells experience nutrient deprivation during oncogenesis and discuss how the resulting metabolic reprogramming, which endows breast cancer cells with the ability to obtain nutrients during scarcity, constitutes an " Achilles' heel " that we believe can be exploited by metabolic glycoengineering (MGE) strategies to develop new diagnostic methods and therapeutic approaches. In particular, we hypothesize that adaptations made by breast cancer cells that allow them to efficiently scavenge sialic acid during times of nutrient deprivation renders them vulnerable to MGE, which refers to the use of exogenously-supplied, non-natural mono-saccharide analogues to modulate targeted aspects of glycosylation in living cells and animals. In specific, once non-natural sialosides are incorporated into the cancer " sialome " they can be exploited as epitopes for immunotherapy or as chemical tags for targeted delivery of imaging or therapeutic agents selectively to tumors.

Research paper thumbnail of Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation

Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that maligna... more Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that malignant cells experience during various stages of tumor development. This study investigated the response of nutrient-deprived cancer cells and their non-malignant counterparts to sialic acid supplementation and found that cells utilize negligible amounts of this sugar for energy. Instead cells use sialic acid to maintain cell surface glycosylation through complementary mechanisms. First, levels of key metabolites (e.g., UDP-GlcNAc and CMP-Neu5Ac) required for glycan biosynthesis are maintained or enhanced upon Neu5Ac supplementation. In concert, sialyltransferase expression increased at both the mRNA and protein levels, which facilitated increased sialylation in biochemical assays that measure sialyltransferase activity as well as at the whole cell level. In the course of these experiments, several important differences emerged that differentiated the cancer cells from their normal counterparts including resistant to sialic acid-mediated energy depletion, consistently more robust sialic acid-mediated glycan display, and distinctive cell surface vs. internal vesicle display of newly-produced sialoglycans. Finally, the impact of sialic acid supplementation on specific markers implicated in cancer progression was demonstrated by measuring levels of expression and sialylation of EGFR1 and MUC1 as well as the corresponding function of sialic acid-supplemented cells in migration assays. These findings both provide fundamental insight into the biological basis of sialic acid supplementation of nutrient-deprived cancer cells and open the door to the development of diagnostic and prognostic tools.

Research paper thumbnail of Live Cell Integrated Surface Plasmon Resonance Biosensing Approach to Mimic the Regulation of Angiogenic Switch upon Anti-Cancer Drug Exposure

Analytical Chemistry 2014, 86, 7305−7310, Jul 9, 2014

In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platfo... more In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platform to measure and compare the binding affinity of vascular endothelial growth factor (VEGF) to vascular endothelial growth factor receptor (VEGFR) and VEGF to bevacizumab. Results have shown that bevacizumab binds VEGF with a higher association rate and affinity compared to VEGFR. Further, this platform has been employed to mimic the in vivo condition of the VEGF–VEGFR angiogenic switch. Competitive binding to VEGF between VEGFR and bevacizumab was monitored in real-time using this platform. Results demonstrated a significant blockage of VEGF–VEGFR binding by bevacizumab. From the results, it is evident that the proposed strategy is simple and highly sensitive for the direct and real-time measurements of bevacizumab drug efficacy to the VEGF–VEGFR angiogenic switch in living SKOV-3 cells.

Research paper thumbnail of Lectin approaches for glycoproteomics in FDA-approved cancer biomarkers

Expert Review of Proteomics, Vol. 11, No. 2 : Pages 227-236 , Apr 1, 2014

"The nine FDA-approved protein biomarkers for the diagnosis and management of cancer are approach... more "The nine FDA-approved protein biomarkers for the diagnosis and management of cancer are approaching maturity, but their different glycosylation compositions relevant to early diagnosis still remain practically unexplored at the sub-glycoproteome scale. Lectins generally exhibit strong binding to specific sub-glycoproteome components and this property has been quite poorly addressed as the basis for the early diagnosis methods. Here, we discuss some glycoproteome issues that make tackling the glycoproteome particularly challenging in the cancer biomarkers field and include a brief view for next generation technologies.
"

Research paper thumbnail of Preferential Lectin Binding of Cancer Cells upon Sialic Acid Treatment Under Nutrient Deprivation

Applied Biochemistry and Biotechnology Volume 171, Issue 4 , pp 963-974 , Oct 1, 2013

The terminal monosaccharide of glycoconjugates on a eukaryotic cell surface is typically a sialic... more The terminal monosaccharide of glycoconjugates on a eukaryotic cell surface is typically a sialic acid (Neu5Ac). Increased sialylation usually indicates progression and poor prognosis of most carcinomas. Here, we utilize two human mammary epithelial cell lines, HB4A (breast normal cells) and T47D (breast cancer cells), as a model system to demonstrate differential surface glycans when treated with sialic acid under nutrient deprivation. Under a starved condition, sialic acid treatment of both cells resulted in increased activities of α2→3/6 sialyltransferases as demonstrated by solid phase assay using lectin binding. However, a very strong Maackia amurensis agglutinin I (MAL-I) staining on the membrane of sialic acid-treated T47D cells was observed, indicating an increase of Neu5Acα2→3Gal on the cell surface. To our knowledge, this is a first report showing the utility of lectins, particularly MAL-I, as a means to discriminate between normal and cancer cells after sialic acid treatment under nutrient deprivation. This method is sensitive and allows selective detection of glycan sialylation on a cancer cell surface.

Research paper thumbnail of Effects of Dietary Doum Palm Fruit Powder on Growth, Antioxidant Capacity, Immune Response, and Disease Resistance of African Catfish, Clarias gariepinus (B.)

Animals, 2020

Application of herbal immune-stimulants for modulation of fish growth and immune response has rec... more Application of herbal immune-stimulants for modulation of fish growth and immune response has received great interest during the past decades. With several pharmacological properties, Doum palm, Hyphaene thebaica (Mart.) is known to be a beneficial medicinal plant. The objective of this study was to investigate the effects of the dietary addition of doum palm fruit powder (DPFP) on growth performance, non-specific immune response, and antioxidant parameters of African catfish, Clarias gariepinus (B.). A total of 120 fish (average initial weight 60.50 ± 0.04 g) were randomly allocated to four groups (three replicates/group, 10 fish/aquarium); a basal diet without DPFP supplementation was used as a control, and three other diets were prepared by supplementing 5, 10, or 15 g kg−1 DPFP for a ten-week feeding period. Following ten weeks of feeding, the fish were challenged with Aeromonas hydrophila (as an immune challenge test), and mortalities were recorded. In comparison to the control...

Research paper thumbnail of The potential role of turmeric and black pepper powder diet supplements in reversing cadmium-induced growth retardation, ATP depletion, hepatorenal damage, and testicular toxicity in Clarias gariepinus

Aquaculture, 2019

Elhakim, et al., The potential role of turmeric and black pepper powder diet supplements in rever... more Elhakim, et al., The potential role of turmeric and black pepper powder diet supplements in reversing cadmium-induced growth retardation, ATP depletion, hepatorenal damage, and testicular toxicity in Clarias gariepinus, aquaculture,

Research paper thumbnail of Live cell integrated surface plasmon resonance biosensing approach to mimic the regulation of angiogenic switch upon anti-cancer drug exposure

Analytical chemistry, Jan 5, 2014

In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platfo... more In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platform to measure and compare the binding affinity of vascular endothelial growth factor (VEGF) to vascular endothelial growth factor receptor (VEGFR) and VEGF to bevacizumab. Results have shown that bevacizumab binds VEGF with a higher association rate and affinity compared to VEGFR. Further, this platform has been employed to mimic the in vivo condition of the VEGF-VEGFR angiogenic switch. Competitive binding to VEGF between VEGFR and bevacizumab was monitored in real-time using this platform. Results demonstrated a significant blockage of VEGF-VEGFR binding by bevacizumab. From the results, it is evident that the proposed strategy is simple and highly sensitive for the direct and real-time measurements of bevacizumab drug efficacy to the VEGF-VEGFR angiogenic switch in living SKOV-3 cells.

Research paper thumbnail of Cancer cell death induced by nanomagnetolectin

European journal of cell biology, Jan 10, 2017

Magnetic nanoparticles represent a new paradigm for molecular targeting therapy in cancer. Howeve... more Magnetic nanoparticles represent a new paradigm for molecular targeting therapy in cancer. However, the transformative targeting potential of magnetic nanoparticles has been stymied by a key obstacle-safe delivery to specified target cells in vivo. As cancer cells grow under nutrient deprivation and hypoxic conditions and decorate cell surface with excessive sialoglycans, sialic acid binding lectins might be suitable for targeting cancer cells in vivo. Here we explore the potential of magnetic nanoparticles functionalized with wheat germ lectin (WGA) conjugate, so-called nanomagnetolectin, as apoptotic targetable agents for prostate cancer. In the presence of magnetic field (magnetofection) for 15min, 2.46nM nanomagnetolectin significantly promoted apoptosis (∼12-fold, p value <0.01) of prostate cancer cells (LNCaP, PC-3, DU-145) compared to normal prostate epithelial cells (PrEC, PNT2, PZ-HPV-7), when supplemented with 10mM sialic acid under nutrient deprived condition. Nanomagn...

Research paper thumbnail of Harnessing cancer cell metabolism for theranostic applications using metabolic glycoengineering of sialic acid in breast cancer as a pioneering example

Abnormal cell surface display of sialic acids e a family of unusual 9-carbon sugars-is widely rec... more Abnormal cell surface display of sialic acids e a family of unusual 9-carbon sugars-is widely recognized as distinguishing feature of many types of cancer. Sialoglycans, however, typically cannot be identified with sufficiently high reproducibility and sensitivity to serve as clinically accepted biomarkers and similarly, almost all efforts to exploit cancer-specific differences in sialylation signatures for therapy remain in early stage development. In this report we provide an overview of important facets of glycosylation that contribute to cancer in general with a focus on breast cancer as an example of malignant disease characterized by aberrant sialylation. We then describe how cancer cells experience nutrient deprivation during oncogenesis and discuss how the resulting metabolic reprogramming, which endows breast cancer cells with the ability to obtain nutrients during scarcity, constitutes an " Achilles' heel " that we believe can be exploited by metabolic glycoengineering (MGE) strategies to develop new diagnostic methods and therapeutic approaches. In particular, we hypothesize that adaptations made by breast cancer cells that allow them to efficiently scavenge sialic acid during times of nutrient deprivation renders them vulnerable to MGE, which refers to the use of exogenously-supplied, non-natural mono-saccharide analogues to modulate targeted aspects of glycosylation in living cells and animals. In specific, once non-natural sialosides are incorporated into the cancer " sialome " they can be exploited as epitopes for immunotherapy or as chemical tags for targeted delivery of imaging or therapeutic agents selectively to tumors.

Research paper thumbnail of Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation

Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that maligna... more Cancer is characterized by abnormal energy metabolism shaped by nutrient deprivation that malignant cells experience during various stages of tumor development. This study investigated the response of nutrient-deprived cancer cells and their non-malignant counterparts to sialic acid supplementation and found that cells utilize negligible amounts of this sugar for energy. Instead cells use sialic acid to maintain cell surface glycosylation through complementary mechanisms. First, levels of key metabolites (e.g., UDP-GlcNAc and CMP-Neu5Ac) required for glycan biosynthesis are maintained or enhanced upon Neu5Ac supplementation. In concert, sialyltransferase expression increased at both the mRNA and protein levels, which facilitated increased sialylation in biochemical assays that measure sialyltransferase activity as well as at the whole cell level. In the course of these experiments, several important differences emerged that differentiated the cancer cells from their normal counterparts including resistant to sialic acid-mediated energy depletion, consistently more robust sialic acid-mediated glycan display, and distinctive cell surface vs. internal vesicle display of newly-produced sialoglycans. Finally, the impact of sialic acid supplementation on specific markers implicated in cancer progression was demonstrated by measuring levels of expression and sialylation of EGFR1 and MUC1 as well as the corresponding function of sialic acid-supplemented cells in migration assays. These findings both provide fundamental insight into the biological basis of sialic acid supplementation of nutrient-deprived cancer cells and open the door to the development of diagnostic and prognostic tools.

Research paper thumbnail of Live Cell Integrated Surface Plasmon Resonance Biosensing Approach to Mimic the Regulation of Angiogenic Switch upon Anti-Cancer Drug Exposure

Analytical Chemistry 2014, 86, 7305−7310, Jul 9, 2014

In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platfo... more In this work, we report a novel surface plasmon resonance (SPR) based live-cell biosensing platform to measure and compare the binding affinity of vascular endothelial growth factor (VEGF) to vascular endothelial growth factor receptor (VEGFR) and VEGF to bevacizumab. Results have shown that bevacizumab binds VEGF with a higher association rate and affinity compared to VEGFR. Further, this platform has been employed to mimic the in vivo condition of the VEGF–VEGFR angiogenic switch. Competitive binding to VEGF between VEGFR and bevacizumab was monitored in real-time using this platform. Results demonstrated a significant blockage of VEGF–VEGFR binding by bevacizumab. From the results, it is evident that the proposed strategy is simple and highly sensitive for the direct and real-time measurements of bevacizumab drug efficacy to the VEGF–VEGFR angiogenic switch in living SKOV-3 cells.

Research paper thumbnail of Lectin approaches for glycoproteomics in FDA-approved cancer biomarkers

Expert Review of Proteomics, Vol. 11, No. 2 : Pages 227-236 , Apr 1, 2014

"The nine FDA-approved protein biomarkers for the diagnosis and management of cancer are approach... more "The nine FDA-approved protein biomarkers for the diagnosis and management of cancer are approaching maturity, but their different glycosylation compositions relevant to early diagnosis still remain practically unexplored at the sub-glycoproteome scale. Lectins generally exhibit strong binding to specific sub-glycoproteome components and this property has been quite poorly addressed as the basis for the early diagnosis methods. Here, we discuss some glycoproteome issues that make tackling the glycoproteome particularly challenging in the cancer biomarkers field and include a brief view for next generation technologies.
"

Research paper thumbnail of Preferential Lectin Binding of Cancer Cells upon Sialic Acid Treatment Under Nutrient Deprivation

Applied Biochemistry and Biotechnology Volume 171, Issue 4 , pp 963-974 , Oct 1, 2013

The terminal monosaccharide of glycoconjugates on a eukaryotic cell surface is typically a sialic... more The terminal monosaccharide of glycoconjugates on a eukaryotic cell surface is typically a sialic acid (Neu5Ac). Increased sialylation usually indicates progression and poor prognosis of most carcinomas. Here, we utilize two human mammary epithelial cell lines, HB4A (breast normal cells) and T47D (breast cancer cells), as a model system to demonstrate differential surface glycans when treated with sialic acid under nutrient deprivation. Under a starved condition, sialic acid treatment of both cells resulted in increased activities of α2→3/6 sialyltransferases as demonstrated by solid phase assay using lectin binding. However, a very strong Maackia amurensis agglutinin I (MAL-I) staining on the membrane of sialic acid-treated T47D cells was observed, indicating an increase of Neu5Acα2→3Gal on the cell surface. To our knowledge, this is a first report showing the utility of lectins, particularly MAL-I, as a means to discriminate between normal and cancer cells after sialic acid treatment under nutrient deprivation. This method is sensitive and allows selective detection of glycan sialylation on a cancer cell surface.

Research paper thumbnail of Effects of Dietary Doum Palm Fruit Powder on Growth, Antioxidant Capacity, Immune Response, and Disease Resistance of African Catfish, Clarias gariepinus (B.)

Animals, 2020

Application of herbal immune-stimulants for modulation of fish growth and immune response has rec... more Application of herbal immune-stimulants for modulation of fish growth and immune response has received great interest during the past decades. With several pharmacological properties, Doum palm, Hyphaene thebaica (Mart.) is known to be a beneficial medicinal plant. The objective of this study was to investigate the effects of the dietary addition of doum palm fruit powder (DPFP) on growth performance, non-specific immune response, and antioxidant parameters of African catfish, Clarias gariepinus (B.). A total of 120 fish (average initial weight 60.50 ± 0.04 g) were randomly allocated to four groups (three replicates/group, 10 fish/aquarium); a basal diet without DPFP supplementation was used as a control, and three other diets were prepared by supplementing 5, 10, or 15 g kg−1 DPFP for a ten-week feeding period. Following ten weeks of feeding, the fish were challenged with Aeromonas hydrophila (as an immune challenge test), and mortalities were recorded. In comparison to the control...

Research paper thumbnail of The potential role of turmeric and black pepper powder diet supplements in reversing cadmium-induced growth retardation, ATP depletion, hepatorenal damage, and testicular toxicity in Clarias gariepinus

Aquaculture, 2019

Elhakim, et al., The potential role of turmeric and black pepper powder diet supplements in rever... more Elhakim, et al., The potential role of turmeric and black pepper powder diet supplements in reversing cadmium-induced growth retardation, ATP depletion, hepatorenal damage, and testicular toxicity in Clarias gariepinus, aquaculture,