A. Diamond - Academia.edu (original) (raw)

Papers by A. Diamond

Research paper thumbnail of It takes 2 antioxidants to tango: the interaction between manganese superoxide dismutase and glutathione peroxidase-1

TURKISH JOURNAL OF BIOLOGY, 2014

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulati... more Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulation of ROS without an effective antioxidant response can lead to oxidative stress, resulting in macromolecular damage that is implicated in the etiology of various diseases including cancer. ROS detoxification is regulated by various antioxidant proteins, specifically manganese superoxide dismutase (MnSOD), which catalyzes the conversion of superoxide into H 2 O 2 , and the subsequent conversion of H 2 O 2 into water is catalyzed by glutathione peroxidase 1 (GPx-1). In vitro and in vivo evidence supports a conflicting role of MnSOD in tumor biology and indicates that an interaction between MnSOD and GPx-1 can modulate the impact of MnSOD on carcinogenesis. Additional support for this idea is provided by epidemiological data indicating that an association exists between polymorphisms in the MnSOD and GPx-1 genes and cancer risk, such that individuals who carry both at-risk polymorphisms are at a higher risk of several types of cancer. Future studies examining the impact of these 2 antioxidants on tumor biology need to consider the interplay between the 2 genes.

Research paper thumbnail of Evidence That Selenium Binding Protein 1 Is a Tumor Suppressor in Prostate Cancer

PLOS ONE, 2015

Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be a... more Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA) recurrence after prostatectomy and 202 matched control patients whose cancer did not recur. Samples were matched by age, ethnicity, pathological stage and Gleason grade, and images were quantified using the Vectra multispectral imaging system. Fluorescent labels were targeted for SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1 levels and the nuclear to cytoplasm ratio were inversely associated with tumor grade using linear regression analysis. Following classification of samples into quartiles based on the SBP1 levels among controls, tumors in the lowest quartile were more than twice as likely to recur compared to those in any other quartile. Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor cells to grow in soft agar, a measure of transformation, without affecting proliferation. Cells expressing SBP1 also demonstrated a robust induction in the phosphorylation of the p53 tumor suppressor at serine 15. These data indicate that loss of SBP1 may play an independent contributing role in prostate cancer progression and its levels might be useful in distinguishing indolent from aggressive disease.

Research paper thumbnail of The Isolation and Characterization of the Blym-1 Transforming Gene

Assessment of Risk from Low-Level Exposure to Radiation and Chemicals, 1985

There are a number of similarities between chicken bursal lymphomas and human Burkitt's l... more There are a number of similarities between chicken bursal lymphomas and human Burkitt's lymphomas. Both lymphomas are associated with viral infection, by LLV in bursal lymphomas and Epstein-Barr virus in Burkitt's lymphoma. Avian lymphoid leukosis virus integration is associated with enhanced c-myc expression, while the role EBV plays in tumorigenesis remains unclear. In Burkitt's lymphoma, however, c-myc activation does occur as a result of specific chromosomal translocations involving the human c-myc locus. Furthermore, the activated transforming genes detected by transfection of both bursal lymphoma and Burkitt's lymphoma DNAs are homologous members of the Blym family of genes. These similarities between chicken and human lymphomas provide evidence that viral involvement and oncogene activation are significant in tumor development and suggest they are involved in the multi-step progression to the neoplastic phenotype. The function of the Blym genes remains to be determined. Although the chicken and human Blym genes are only distantly related, they have maintained their homology to the amino-terminal regions of transferrins. This fact may reflect some functional constraint on the evolution of these genes. It is therefore possible that transforming genes such as Blym may function via a transferrin-related mechanism.

Research paper thumbnail of Natural allelic variations in glutathione peroxidase-1 affect its subcellular localization and function

Cancer research, Jan 15, 2014

Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases d... more Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases due to the association between specific allelic variations and cancer risk. The most common among these variations are the codon 198 polymorphism that results in either a leucine or proline and the number of alanine repeat codons in the coding sequence. The molecular and biologic consequences of these variations remain to be characterized. Toward achieving this goal, we have examined the cellular location of GPx-1 encoded by allelic variants by ectopically expressing these genes in MCF-7 human breast carcinoma cells that produce undetectable levels of GPx-1, thus achieving exclusive expression in the same cellular environment. A differential distribution between the cytoplasm and mitochondria was observed, with the allele expressing the leucine-198 polymorphism and 7 alanine repeats being more cytoplasmically located than the other alleles examined. To assess whether the distribution of G...

Research paper thumbnail of Mapping of the human Blym-1 transforming gene activated in Burkitt lymphomas to chromosome 1

Science, 1984

Blym-1, a transforming gene detected by transfection of NIH 3T3 cells with DNA from Burkitt lymph... more Blym-1, a transforming gene detected by transfection of NIH 3T3 cells with DNA from Burkitt lymphomas, was mapped to the short arm of chromosome 1 (1p32) by chromosomal in situ hybridization. The Blym-1 gene was not physically linked to the cellular myc oncogene or to any of the immunoglobulin gene loci implicated in the characteristic chromosomal translocations in Burkitt lymphoma.

Research paper thumbnail of Opal suppressor serine tRNAs from bovine liver form phosphoseryl-tRNA

Proceedings of the National Academy of Sciences, 1982

An unusual minor species of bovine liver serine tRNA has previously been isolated, sequenced, and... more An unusual minor species of bovine liver serine tRNA has previously been isolated, sequenced, and found to suppress the UGA termination codon in protein synthesis in vitro [Diamond, A., Dudock, B. & Hatfield, D. (1981) CeU25, 497-506].

Research paper thumbnail of Structure and properties of a bovine liver UGA suppressor serine tRNA with a tryptophan anticodon

Research paper thumbnail of Transforming Genes of Lymphoid Neoplasms

Research paper thumbnail of Natural allelic variations in glutathione peroxidase-1 affect its subcellular localization and function

Cancer research, Jan 15, 2014

Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases d... more Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases due to the association between specific allelic variations and cancer risk. The most common among these variations are the codon 198 polymorphism that results in either a leucine or proline and the number of alanine repeat codons in the coding sequence. The molecular and biologic consequences of these variations remain to be characterized. Toward achieving this goal, we have examined the cellular location of GPx-1 encoded by allelic variants by ectopically expressing these genes in MCF-7 human breast carcinoma cells that produce undetectable levels of GPx-1, thus achieving exclusive expression in the same cellular environment. A differential distribution between the cytoplasm and mitochondria was observed, with the allele expressing the leucine-198 polymorphism and 7 alanine repeats being more cytoplasmically located than the other alleles examined. To assess whether the distribution of G...

Research paper thumbnail of It takes 2 antioxidants to tango: the interaction between manganese superoxide dismutase and glutathione peroxidase-1

TURKISH JOURNAL OF BIOLOGY, 2014

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulati... more Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulation of ROS without an effective antioxidant response can lead to oxidative stress, resulting in macromolecular damage that is implicated in the etiology of various diseases including cancer. ROS detoxification is regulated by various antioxidant proteins, specifically manganese superoxide dismutase (MnSOD), which catalyzes the conversion of superoxide into H 2 O 2 , and the subsequent conversion of H 2 O 2 into water is catalyzed by glutathione peroxidase 1 (GPx-1). In vitro and in vivo evidence supports a conflicting role of MnSOD in tumor biology and indicates that an interaction between MnSOD and GPx-1 can modulate the impact of MnSOD on carcinogenesis. Additional support for this idea is provided by epidemiological data indicating that an association exists between polymorphisms in the MnSOD and GPx-1 genes and cancer risk, such that individuals who carry both at-risk polymorphisms are at a higher risk of several types of cancer. Future studies examining the impact of these 2 antioxidants on tumor biology need to consider the interplay between the 2 genes.

Research paper thumbnail of MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer

Nature Communications, 2015

Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the ty... more Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signalling. Here we demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H 2 O 2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics. Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD serves as a biomarker of cancer progression and acts as critical regulator of tumour cell metabolism.

Research paper thumbnail of It takes 2 antioxidants to tango: the interaction between manganese superoxide dismutase and glutathione peroxidase-1

TURKISH JOURNAL OF BIOLOGY, 2014

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulati... more Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulation of ROS without an effective antioxidant response can lead to oxidative stress, resulting in macromolecular damage that is implicated in the etiology of various diseases including cancer. ROS detoxification is regulated by various antioxidant proteins, specifically manganese superoxide dismutase (MnSOD), which catalyzes the conversion of superoxide into H 2 O 2 , and the subsequent conversion of H 2 O 2 into water is catalyzed by glutathione peroxidase 1 (GPx-1). In vitro and in vivo evidence supports a conflicting role of MnSOD in tumor biology and indicates that an interaction between MnSOD and GPx-1 can modulate the impact of MnSOD on carcinogenesis. Additional support for this idea is provided by epidemiological data indicating that an association exists between polymorphisms in the MnSOD and GPx-1 genes and cancer risk, such that individuals who carry both at-risk polymorphisms are at a higher risk of several types of cancer. Future studies examining the impact of these 2 antioxidants on tumor biology need to consider the interplay between the 2 genes.

Research paper thumbnail of Evidence That Selenium Binding Protein 1 Is a Tumor Suppressor in Prostate Cancer

PLOS ONE, 2015

Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be a... more Selenium-Binding Protein 1 (SBP1, SELENBP1, hSP56) is a selenium-associated protein shown to be at lower levels in tumors, and its lower levels are frequently predictive of a poor clinical outcome. Distinguishing indolent from aggressive prostate cancer is a major challenge in disease management. Associations between SBP1 levels, tumor grade, and disease recurrence following prostatectomy were investigated by duplex immunofluorescence imaging using a tissue microarray containing tissue from 202 prostate cancer patients who experienced biochemical (PSA) recurrence after prostatectomy and 202 matched control patients whose cancer did not recur. Samples were matched by age, ethnicity, pathological stage and Gleason grade, and images were quantified using the Vectra multispectral imaging system. Fluorescent labels were targeted for SBP1 and cytokeratins 8/18 to restrict scoring to tumor cells, and cell-by-cell quantification of SBP1 in the nucleus and cytoplasm was performed. Nuclear SBP1 levels and the nuclear to cytoplasm ratio were inversely associated with tumor grade using linear regression analysis. Following classification of samples into quartiles based on the SBP1 levels among controls, tumors in the lowest quartile were more than twice as likely to recur compared to those in any other quartile. Inducible ectopic SBP1 expression reduced the ability of HCT-116 human tumor cells to grow in soft agar, a measure of transformation, without affecting proliferation. Cells expressing SBP1 also demonstrated a robust induction in the phosphorylation of the p53 tumor suppressor at serine 15. These data indicate that loss of SBP1 may play an independent contributing role in prostate cancer progression and its levels might be useful in distinguishing indolent from aggressive disease.

Research paper thumbnail of The Isolation and Characterization of the Blym-1 Transforming Gene

Assessment of Risk from Low-Level Exposure to Radiation and Chemicals, 1985

There are a number of similarities between chicken bursal lymphomas and human Burkitt's l... more There are a number of similarities between chicken bursal lymphomas and human Burkitt's lymphomas. Both lymphomas are associated with viral infection, by LLV in bursal lymphomas and Epstein-Barr virus in Burkitt's lymphoma. Avian lymphoid leukosis virus integration is associated with enhanced c-myc expression, while the role EBV plays in tumorigenesis remains unclear. In Burkitt's lymphoma, however, c-myc activation does occur as a result of specific chromosomal translocations involving the human c-myc locus. Furthermore, the activated transforming genes detected by transfection of both bursal lymphoma and Burkitt's lymphoma DNAs are homologous members of the Blym family of genes. These similarities between chicken and human lymphomas provide evidence that viral involvement and oncogene activation are significant in tumor development and suggest they are involved in the multi-step progression to the neoplastic phenotype. The function of the Blym genes remains to be determined. Although the chicken and human Blym genes are only distantly related, they have maintained their homology to the amino-terminal regions of transferrins. This fact may reflect some functional constraint on the evolution of these genes. It is therefore possible that transforming genes such as Blym may function via a transferrin-related mechanism.

Research paper thumbnail of Natural allelic variations in glutathione peroxidase-1 affect its subcellular localization and function

Cancer research, Jan 15, 2014

Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases d... more Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases due to the association between specific allelic variations and cancer risk. The most common among these variations are the codon 198 polymorphism that results in either a leucine or proline and the number of alanine repeat codons in the coding sequence. The molecular and biologic consequences of these variations remain to be characterized. Toward achieving this goal, we have examined the cellular location of GPx-1 encoded by allelic variants by ectopically expressing these genes in MCF-7 human breast carcinoma cells that produce undetectable levels of GPx-1, thus achieving exclusive expression in the same cellular environment. A differential distribution between the cytoplasm and mitochondria was observed, with the allele expressing the leucine-198 polymorphism and 7 alanine repeats being more cytoplasmically located than the other alleles examined. To assess whether the distribution of G...

Research paper thumbnail of Mapping of the human Blym-1 transforming gene activated in Burkitt lymphomas to chromosome 1

Science, 1984

Blym-1, a transforming gene detected by transfection of NIH 3T3 cells with DNA from Burkitt lymph... more Blym-1, a transforming gene detected by transfection of NIH 3T3 cells with DNA from Burkitt lymphomas, was mapped to the short arm of chromosome 1 (1p32) by chromosomal in situ hybridization. The Blym-1 gene was not physically linked to the cellular myc oncogene or to any of the immunoglobulin gene loci implicated in the characteristic chromosomal translocations in Burkitt lymphoma.

Research paper thumbnail of Opal suppressor serine tRNAs from bovine liver form phosphoseryl-tRNA

Proceedings of the National Academy of Sciences, 1982

An unusual minor species of bovine liver serine tRNA has previously been isolated, sequenced, and... more An unusual minor species of bovine liver serine tRNA has previously been isolated, sequenced, and found to suppress the UGA termination codon in protein synthesis in vitro [Diamond, A., Dudock, B. & Hatfield, D. (1981) CeU25, 497-506].

Research paper thumbnail of Structure and properties of a bovine liver UGA suppressor serine tRNA with a tryptophan anticodon

Research paper thumbnail of Transforming Genes of Lymphoid Neoplasms

Research paper thumbnail of Natural allelic variations in glutathione peroxidase-1 affect its subcellular localization and function

Cancer research, Jan 15, 2014

Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases d... more Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases due to the association between specific allelic variations and cancer risk. The most common among these variations are the codon 198 polymorphism that results in either a leucine or proline and the number of alanine repeat codons in the coding sequence. The molecular and biologic consequences of these variations remain to be characterized. Toward achieving this goal, we have examined the cellular location of GPx-1 encoded by allelic variants by ectopically expressing these genes in MCF-7 human breast carcinoma cells that produce undetectable levels of GPx-1, thus achieving exclusive expression in the same cellular environment. A differential distribution between the cytoplasm and mitochondria was observed, with the allele expressing the leucine-198 polymorphism and 7 alanine repeats being more cytoplasmically located than the other alleles examined. To assess whether the distribution of G...

Research paper thumbnail of It takes 2 antioxidants to tango: the interaction between manganese superoxide dismutase and glutathione peroxidase-1

TURKISH JOURNAL OF BIOLOGY, 2014

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulati... more Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulation of ROS without an effective antioxidant response can lead to oxidative stress, resulting in macromolecular damage that is implicated in the etiology of various diseases including cancer. ROS detoxification is regulated by various antioxidant proteins, specifically manganese superoxide dismutase (MnSOD), which catalyzes the conversion of superoxide into H 2 O 2 , and the subsequent conversion of H 2 O 2 into water is catalyzed by glutathione peroxidase 1 (GPx-1). In vitro and in vivo evidence supports a conflicting role of MnSOD in tumor biology and indicates that an interaction between MnSOD and GPx-1 can modulate the impact of MnSOD on carcinogenesis. Additional support for this idea is provided by epidemiological data indicating that an association exists between polymorphisms in the MnSOD and GPx-1 genes and cancer risk, such that individuals who carry both at-risk polymorphisms are at a higher risk of several types of cancer. Future studies examining the impact of these 2 antioxidants on tumor biology need to consider the interplay between the 2 genes.

Research paper thumbnail of MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer

Nature Communications, 2015

Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the ty... more Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signalling. Here we demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H 2 O 2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics. Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD serves as a biomarker of cancer progression and acts as critical regulator of tumour cell metabolism.