Osteoblasts and bone lining cells form a near continuous layer covering the bone surface and inte... more Osteoblasts and bone lining cells form a near continuous layer covering the bone surface and interactions between these cells and the organic matrix of bone are important determinants of osteoblast proliferation and differentiation. In addition, cells of the osteoblast-lineage form functional communications with each other, with the extra-cellular matrix and with osteocytes through cytoplasmic processes extending through canaliculi in the bone. Together, these cells form a network of putative importance in the regulation of skeletal homeostasis. Cell-cell and cell-matrix interactions are mediated by members of several families of cell adhesion molecules, and knowledge of their interactions will be of fundamental importance in understanding the role of osteoblast in skeletal turnover. Here, the expression pattern of members of the major families of cell adhesion molecules by cells of the osteoblast lineage is reviewed. Special emphasis has been placed on human tissues. In addition, t...
Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the s... more Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the suppression was observed with members among HTLV-I-infected T cell lines independent of IL-2 for growth. In this study, we examined the molecular mechanism of IL-2-induced growth suppression with two HTLV-I-infected T cell lines; TL-OmI expressing endogenously three subunits, i.e. alpha, beta and gamma chains, of the IL-2 receptor, and an MT-1 transfectant expressing the endogenous alpha and gamma chains and exogenous beta chain. Our analysis revealed that IL-2 induced apoptosis in both T cell lines. Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1 beta-converting enzyme) was not involved in apoptosis induced by IL-2. Other MT-1 sublines introduced with mutant beta chains demonstrated that IL-2-induced apoptosis required signals from both the serine-rich (S) region and acidic (A) region of the IL-2 receptor beta chain, which are essential but not critical for IL-2-mediated cell growth respectively. Collectively, IL-2 functions not only on growth promotion and prevention of apoptosis but also on induction of apoptosis, which may be implicated in physiological regulation of immune reactions by controlling growth and activation of T cells.
This work reports the in vitro characterization and evaluation of three other com m nly used mAbs... more This work reports the in vitro characterization and evaluation of three other com m nly used mAbs (J415, J533, and J591) that bind the extracellular domain of Prostate-specific membrane antigen (PSMAext). Briefly, murine mAbs J415, J533, J591, and 7E11 were radiolabeled with I and evaluated in competitive and saturation binding studies with substrates derived from LNCaP cells. J415 and J591 were conjugated to 1,4,7,10-tetraazacyclododecaneN,N′,N′′,N′′′-tetraacetic acid labeled with In. The uptake and cellular processing of these antibodies w re evaluated in viable LNCaP cells. Competition assays revealed that J415 and J591 compete for bind ing to PSMAext antigen. J533 bound to a region close to the J591 binding epitope, but J533 did not inter fer with J415 binding to PSMA. 7E11 mAb did not inhibit the binding of J415, J533, or J591 (or vice versa) whereas 7E11 binds the intracellular domain of PSMA. Saturation binding studies demonstrated that J415 and J591 bound with a similar affi...
Prostate-specific membrane antigen (PSMA) has been successfully targeted in vivo with 111In-label... more Prostate-specific membrane antigen (PSMA) has been successfully targeted in vivo with 111In-labeled 7E11 monoclonal antibody, which binds to an intracellular epitope of PSMA. This work reports the in vitro characterization and evaluation of three other commonly used mAbs (J415, J533, and J591) that bind the extracellular epitope of PSMA (PSMAext). Briefly, murine mAbs J415, J533, J591, and 7E11 were radiolabeled with 131I and evaluated in competitive and saturation binding studies with substrates derived from LNCaP cells. J415 and J591 were conjugated to 1, 4, 7, 10- tetraazacyclododecane-N, N ′ , N″ , N-tetraacetic acid labeled with 111In. The uptake and cellular processing of these antibodies were evaluated in viable LNCaP cells. Competition assays revealed that J415 and J591 compete for binding to PSMAext antigen. J533 bound to a region close to the J591 binding epitope, but J533 did not interfere with J415 binding to PSMA. 7E11 mAb did not inhibit the binding of J415, J533, or ...
Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the s... more Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the suppression was observed with members among HTLV-I-infected T cell lines independent of IL-2 for growth. In this study, we examined the molecular mechanism of IL-2-induced growth suppression with two HTLV-I-infected T cell lines; TL-OmI expressing endogenously three subunits, i.e. α, β and γ chains, of the IL-2 receptor, and an MT-1 transfectant expressing the endogenous α and γ chains and exogenous β chain. Our analysis revealed that IL-2 induced apoptosis in both T cell lines. Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1β-converting enzyme) was not involved in apoptosis induced by IL-2. Other MT-1 sublines introduced with mutant β chains demonstrated that IL-2-induced apoptosis required signals from both the serine-rich (S) region and acidic (A) region of the IL-2 receptor β chain, which are essential but not critical for IL...
Infection of erythroid-lineage cells by human parvovirus B19 is characterized by a gradual cytoci... more Infection of erythroid-lineage cells by human parvovirus B19 is characterized by a gradual cytocidal effect. Accumulating evidence now implicates the nonstructural (NS1) protein of the virus in cytotoxicity, but the mechanism underlying the NS1-induced cell death is not known. Using a stringent regulatory system, we demonstrate that NS1 cytotoxicity is closely related to apoptosis, as evidenced by cell morphology, genomic DNA fragmentation, and cell cycle analysis with the human erythroleukemia cell line K562 and the erythropoietin-dependent megakaryocytic cell line UT-7/Epo. Apoptosis was significantly inhibited by an interleukin-1β (IL-1β)-converting enzyme (ICE)/CED-3 family protease inhibitor, Ac-DEVD-CHO (CPP32; caspase 3), whereas a similar inhibitor of ICE (caspase 1), Ac-YVAD-CHO, had no effect. Furthermore, stable expression of the human Bcl-2 proto-oncogene resulted in near-total protection from cell death in response to NS1 induction. Mutations engineered into the nucleos...
International journal of pharmaceutics, Jan 6, 2006
J591 monoclonal antibody (mAb) has high affinity for prostate specific membrane antigen (PSMA) on... more J591 monoclonal antibody (mAb) has high affinity for prostate specific membrane antigen (PSMA) on prostate cancer (PCA) cells. We coupled polyethylene glycol-J591 (PEGylated J591) to a salicyl hydroxamic acid (SHA)-derivatized polyethylenimine (PEI)/DNA-betagal vector to investigate the specificity and efficiency of targeting PSMA in PCA cells through encapsulation. Coupling was facilitated via the high affinity interaction between phenyl(di)boronic acid (PDBA) and SHA molecules yielding J591/PEG/PEI/DNA-betagal polyplex. After encapsulation with poly(d,l-lactic-co-glycolic acid)-b-polyethylene glycol-b-poly(d,l-lactic-co-glycolic acid) (PLGA-PEG-PLGA) tri-block copolymer, 8-10-fold increment of gene transfection levels were attained at the optimum concentration of 0.25% (w/v) using Pluronic F68 tri-block copolymer as a control. The enhanced transfection efficiency was attributed to increased internalization and uptake of the radiolabeled plasmid in the presence of PLGA-PEG-PLGA tri...
... Furthermore, through incubation of a range of silver and gold NP formulations with SK-BR-3 ce... more ... Furthermore, through incubation of a range of silver and gold NP formulations with SK-BR-3 cells overexpressing HER2, this study ... Soman and Giorgio developed anti-VEGF labeled QDs as an early diagnostic strategy and demonstrated the possibility to measure the ...
Osteoblasts and bone lining cells form a near continuous layer covering the bone surface and inte... more Osteoblasts and bone lining cells form a near continuous layer covering the bone surface and interactions between these cells and the organic matrix of bone are important determinants of osteoblast proliferation and differentiation. In addition, cells of the osteoblast-lineage form functional communications with each other, with the extra-cellular matrix and with osteocytes through cytoplasmic processes extending through canaliculi in the bone. Together, these cells form a network of putative importance in the regulation of skeletal homeostasis. Cell-cell and cell-matrix interactions are mediated by members of several families of cell adhesion molecules, and knowledge of their interactions will be of fundamental importance in understanding the role of osteoblast in skeletal turnover. Here, the expression pattern of members of the major families of cell adhesion molecules by cells of the osteoblast lineage is reviewed. Special emphasis has been placed on human tissues. In addition, t...
Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the s... more Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the suppression was observed with members among HTLV-I-infected T cell lines independent of IL-2 for growth. In this study, we examined the molecular mechanism of IL-2-induced growth suppression with two HTLV-I-infected T cell lines; TL-OmI expressing endogenously three subunits, i.e. alpha, beta and gamma chains, of the IL-2 receptor, and an MT-1 transfectant expressing the endogenous alpha and gamma chains and exogenous beta chain. Our analysis revealed that IL-2 induced apoptosis in both T cell lines. Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1 beta-converting enzyme) was not involved in apoptosis induced by IL-2. Other MT-1 sublines introduced with mutant beta chains demonstrated that IL-2-induced apoptosis required signals from both the serine-rich (S) region and acidic (A) region of the IL-2 receptor beta chain, which are essential but not critical for IL-2-mediated cell growth respectively. Collectively, IL-2 functions not only on growth promotion and prevention of apoptosis but also on induction of apoptosis, which may be implicated in physiological regulation of immune reactions by controlling growth and activation of T cells.
This work reports the in vitro characterization and evaluation of three other com m nly used mAbs... more This work reports the in vitro characterization and evaluation of three other com m nly used mAbs (J415, J533, and J591) that bind the extracellular domain of Prostate-specific membrane antigen (PSMAext). Briefly, murine mAbs J415, J533, J591, and 7E11 were radiolabeled with I and evaluated in competitive and saturation binding studies with substrates derived from LNCaP cells. J415 and J591 were conjugated to 1,4,7,10-tetraazacyclododecaneN,N′,N′′,N′′′-tetraacetic acid labeled with In. The uptake and cellular processing of these antibodies w re evaluated in viable LNCaP cells. Competition assays revealed that J415 and J591 compete for bind ing to PSMAext antigen. J533 bound to a region close to the J591 binding epitope, but J533 did not inter fer with J415 binding to PSMA. 7E11 mAb did not inhibit the binding of J415, J533, or J591 (or vice versa) whereas 7E11 binds the intracellular domain of PSMA. Saturation binding studies demonstrated that J415 and J591 bound with a similar affi...
Prostate-specific membrane antigen (PSMA) has been successfully targeted in vivo with 111In-label... more Prostate-specific membrane antigen (PSMA) has been successfully targeted in vivo with 111In-labeled 7E11 monoclonal antibody, which binds to an intracellular epitope of PSMA. This work reports the in vitro characterization and evaluation of three other commonly used mAbs (J415, J533, and J591) that bind the extracellular epitope of PSMA (PSMAext). Briefly, murine mAbs J415, J533, J591, and 7E11 were radiolabeled with 131I and evaluated in competitive and saturation binding studies with substrates derived from LNCaP cells. J415 and J591 were conjugated to 1, 4, 7, 10- tetraazacyclododecane-N, N ′ , N″ , N-tetraacetic acid labeled with 111In. The uptake and cellular processing of these antibodies were evaluated in viable LNCaP cells. Competition assays revealed that J415 and J591 compete for binding to PSMAext antigen. J533 bound to a region close to the J591 binding epitope, but J533 did not interfere with J415 binding to PSMA. 7E11 mAb did not inhibit the binding of J415, J533, or ...
Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the s... more Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the suppression was observed with members among HTLV-I-infected T cell lines independent of IL-2 for growth. In this study, we examined the molecular mechanism of IL-2-induced growth suppression with two HTLV-I-infected T cell lines; TL-OmI expressing endogenously three subunits, i.e. α, β and γ chains, of the IL-2 receptor, and an MT-1 transfectant expressing the endogenous α and γ chains and exogenous β chain. Our analysis revealed that IL-2 induced apoptosis in both T cell lines. Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1β-converting enzyme) was not involved in apoptosis induced by IL-2. Other MT-1 sublines introduced with mutant β chains demonstrated that IL-2-induced apoptosis required signals from both the serine-rich (S) region and acidic (A) region of the IL-2 receptor β chain, which are essential but not critical for IL...
Infection of erythroid-lineage cells by human parvovirus B19 is characterized by a gradual cytoci... more Infection of erythroid-lineage cells by human parvovirus B19 is characterized by a gradual cytocidal effect. Accumulating evidence now implicates the nonstructural (NS1) protein of the virus in cytotoxicity, but the mechanism underlying the NS1-induced cell death is not known. Using a stringent regulatory system, we demonstrate that NS1 cytotoxicity is closely related to apoptosis, as evidenced by cell morphology, genomic DNA fragmentation, and cell cycle analysis with the human erythroleukemia cell line K562 and the erythropoietin-dependent megakaryocytic cell line UT-7/Epo. Apoptosis was significantly inhibited by an interleukin-1β (IL-1β)-converting enzyme (ICE)/CED-3 family protease inhibitor, Ac-DEVD-CHO (CPP32; caspase 3), whereas a similar inhibitor of ICE (caspase 1), Ac-YVAD-CHO, had no effect. Furthermore, stable expression of the human Bcl-2 proto-oncogene resulted in near-total protection from cell death in response to NS1 induction. Mutations engineered into the nucleos...
International journal of pharmaceutics, Jan 6, 2006
J591 monoclonal antibody (mAb) has high affinity for prostate specific membrane antigen (PSMA) on... more J591 monoclonal antibody (mAb) has high affinity for prostate specific membrane antigen (PSMA) on prostate cancer (PCA) cells. We coupled polyethylene glycol-J591 (PEGylated J591) to a salicyl hydroxamic acid (SHA)-derivatized polyethylenimine (PEI)/DNA-betagal vector to investigate the specificity and efficiency of targeting PSMA in PCA cells through encapsulation. Coupling was facilitated via the high affinity interaction between phenyl(di)boronic acid (PDBA) and SHA molecules yielding J591/PEG/PEI/DNA-betagal polyplex. After encapsulation with poly(d,l-lactic-co-glycolic acid)-b-polyethylene glycol-b-poly(d,l-lactic-co-glycolic acid) (PLGA-PEG-PLGA) tri-block copolymer, 8-10-fold increment of gene transfection levels were attained at the optimum concentration of 0.25% (w/v) using Pluronic F68 tri-block copolymer as a control. The enhanced transfection efficiency was attributed to increased internalization and uptake of the radiolabeled plasmid in the presence of PLGA-PEG-PLGA tri...
... Furthermore, through incubation of a range of silver and gold NP formulations with SK-BR-3 ce... more ... Furthermore, through incubation of a range of silver and gold NP formulations with SK-BR-3 cells overexpressing HER2, this study ... Soman and Giorgio developed anti-VEGF labeled QDs as an early diagnostic strategy and demonstrated the possibility to measure the ...
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Papers by stanley moffatt