Harold Elias - Academia.edu (original) (raw)

Papers by Harold Elias

Research paper thumbnail of Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

Circulation research, Jun 28, 2016

The role of interleukin (IL)-6 in the pathogenesis of cardiomyocyte hypertrophy remains controver... more The role of interleukin (IL)-6 in the pathogenesis of cardiomyocyte hypertrophy remains controversial. To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Wild-type (WT) and IL-6 knockout (IL-6(-/-)) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6(-/-) mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6(-/-) hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiomyocytes from WT and IL-6(-/-) mic...

Research paper thumbnail of Analysis of a large single center cohort demonstrates poor prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in HIV infected patients (pts)

Journal of Clinical Oncology

e18077 Background: Even though HIV is associated with worse prognosis in many malignancies, the c... more e18077 Background: Even though HIV is associated with worse prognosis in many malignancies, the clinical course of MDS and AML in HIV+ pts has not been well studied. Determining the clinical presen...

Research paper thumbnail of Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-κB and osteosarcoma progression

Nature Communications, 2016

The ability of cancer cells to survive and grow in anchorage- and serum-independent conditions is... more The ability of cancer cells to survive and grow in anchorage- and serum-independent conditions is well correlated with their aggressiveness. Here, using a human whole-genome shRNA library, we identify TMIGD3 isoform1 (i1) as a factor that suppresses this ability in osteosarcoma (OS) cells, mainly by inhibiting NF-κB activity. Knockdown of TMIGD3 increases proliferation, tumour formation and metastasis of OS cells. Overexpression of TMIGD3 isoform1 (i1), but not isoform3 (i3) which shares a common C-terminal region, suppresses these malignant properties. Adenosine A3 receptor (A3AR) having an identical N-terminal region shows similar biological profiles to TMIGD3 i1. Protein expression of TMIGD3 and A3AR is lower in human OS tissues than normal tissues. Mechanistically, TMIGD3 i1 and A3AR commonly inhibit the PKA-Akt-NF-κB axis. However, TMIGD3 i1 only partially rescues phenotypes induced by A3AR knockdown, suggesting the presence of distinct pathways. Our findings reveal an unappreciated role for TMIGD3 i1 as a suppressor of NF-κB activity and OS progression.

Research paper thumbnail of Leucopenia in Acute Myeloid Leukemia Presenting as Myocardial Infarction: A Case Report

Journal of Bone Marrow Research, 2013

Research paper thumbnail of Activation of hypoxia signaling is marker of poor prognosis in myelodysplasia

Leukemia & Lymphoma, 2012

Research paper thumbnail of Role of endovascular stenting in radiation-induced stenosis of lower extremity veins

Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, Jan 25, 2014

Radiation-induced venous stenosis is rare with a few isolated cases reported in the medical liter... more Radiation-induced venous stenosis is rare with a few isolated cases reported in the medical literature involving the lower limb. Management options in such cases are thus not streamlined. We describe an unusual case of iliac vein stenosis in a patient with rectal carcinoma after combined chemoradiation therapy, managed with endovascular stenting. The possible mechanisms underlying the pathogenesis of venous stricture and their treatment options have been reviewed. © 2014 Wiley Periodicals, Inc.

Research paper thumbnail of Abstract 14804: Transplantation of Human Umbilical Cord Blood Mononuclear Cells Improves LV function and Remodeling After a reperfused Myocardial Infarction

Circulation, Nov 25, 2014

Research paper thumbnail of Aging, Nutrients, and Endogenous Stem Cell Populations

Research paper thumbnail of Abstract 18105: Genetic Deletion of IL-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Failure

Circulation, Nov 26, 2013

Research paper thumbnail of ONC2013520A

Research paper thumbnail of NF-KB Inhibition Protects Against Myocardial Ischemia/Reperfusion Injury via Activation of Antiapoptotic Signaling

Journal of the American College of Cardiology, 2015

Research paper thumbnail of Role of endovascular stenting in radiation-induced stenosis of lower extremity veins

Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, Jan 25, 2014

Radiation-induced venous stenosis is rare with a few isolated cases reported in the medical liter... more Radiation-induced venous stenosis is rare with a few isolated cases reported in the medical literature involving the lower limb. Management options in such cases are thus not streamlined. We describe an unusual case of iliac vein stenosis in a patient with rectal carcinoma after combined chemoradiation therapy, managed with endovascular stenting. The possible mechanisms underlying the pathogenesis of venous stricture and their treatment options have been reviewed. © 2014 Wiley Periodicals, Inc.

Research paper thumbnail of Influence of rituximab on CNS relapse in Diffuse Large B Cell Lymphoma and the role of prophylaxis - a systematic review of prospective studies

Clinical Lymphoma Myeloma and Leukemia, 2015

Introduction: Despite improvement in overall survival in DLBCL patients in the rituximab era, the... more Introduction: Despite improvement in overall survival in DLBCL patients in the rituximab era, the occurrence of CNS relapse heralds a very poor prognosis. There is conflicting evidence on the incidence and pattern of CNS relapse in the rituximab era, compared to the pre-rituximab era and on the role of CNS prophylaxis.

Research paper thumbnail of Genetic Deletion of IL-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Failure

Research paper thumbnail of A Murine Model of Cardiac Arrest by Exsanguination

Manual of Research Techniques in Cardiovascular Medicine, 2014

Research paper thumbnail of Aging, Nutrients, and Endogenous Stem Cell Populations

Nutritional and Therapeutic Interventions, 2013

Research paper thumbnail of Stem cell origin of myelodysplastic syndromes

Research paper thumbnail of Cardiac-Specific Transgenic Silencing of NF-KB Ameliorates Left Ventricular Dysfunction and Remodeling After Acute Myocardial Infarction

Journal of the American College of Cardiology, 2012

Research paper thumbnail of Do Patients Undergoing Elective Percutaneous Coronary Intervention Distinguish the Type of Stent They Receive? A Contemporary Perspective

Journal of the American College of Cardiology, 2012

Research paper thumbnail of Cardiac-Specific Transgenic Inhibition of NF-KB Activation Protects Against Myocardial Ischemia/Reperfusion Injury

Journal of the American College of Cardiology, 2012

ABSTRACT Background: Nuclear factor-kappaB (NF-kB), a stress-responsive transcription factor, has... more ABSTRACT Background: Nuclear factor-kappaB (NF-kB), a stress-responsive transcription factor, has been implicated in various cardiovascular pathologies.Although NF-kB is necessary for late preconditioning, its summative role in myocardial ischemia/reperfusion (I/R) injury remains unclear.Methods: Using mice with cardiac-specific inhibition of NF-kB activation via transgenic overexpression of a mutant IkBa protein, we examined the role of NF-kB in myocyte death in a mouse model of I/R injury. Considering the nonspecific actions of various pharmacological inhibitors of NF-kB, this genetic model offers the advantage of specifically ablating NF-kB activation in myocytes. Age-matched male wild-type (WT, C57BL/6, n=7), nontransgenic littermates (NTg, n=6) and IkBa transgenic (IkBa Tg, n=6) mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Mice were sacrificed and infarct size was determined by TTC staining. Results: The infarct size was similar in WT controls and NTg mice (Figure), indicating no untoward impact in NTg hearts. However, the infarct size was significantly smaller in IkBa Tg mice compared with both WT and NTg groups (Figure), indicating that myocardial NF-kB signaling plays a detrimental role during acute I/R injury.Conclusions: We conclude that NF-kB inhibition protects against acute myocardial I/R injury. These findings are relevant toward developing novel therapeutic strategies against myocardial infarction via modulation of NF-kB signaling in the heart.

Research paper thumbnail of Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction

Circulation research, Jun 28, 2016

The role of interleukin (IL)-6 in the pathogenesis of cardiomyocyte hypertrophy remains controver... more The role of interleukin (IL)-6 in the pathogenesis of cardiomyocyte hypertrophy remains controversial. To conclusively determine whether IL-6 signaling is essential for the development of pressure overload-induced left ventricular (LV) hypertrophy, and to elucidate the underlying molecular pathways. Wild-type (WT) and IL-6 knockout (IL-6(-/-)) mice underwent sham surgery or transverse aortic constriction (TAC) to induce pressure overload. Serial echocardiograms and terminal hemodynamic studies revealed attenuated LV hypertrophy and superior preservation of LV function in IL-6(-/-) mice after TAC. The extents of LV remodeling, fibrosis, and apoptosis were reduced in IL-6(-/-) hearts after TAC. Transcriptional and protein assays of myocardial tissue identified CaMKII and STAT3 activation as important underlying mechanisms during cardiac hypertrophy induced by TAC. The involvement of these pathways in myocyte hypertrophy was verified in isolated cardiomyocytes from WT and IL-6(-/-) mic...

Research paper thumbnail of Analysis of a large single center cohort demonstrates poor prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in HIV infected patients (pts)

Journal of Clinical Oncology

e18077 Background: Even though HIV is associated with worse prognosis in many malignancies, the c... more e18077 Background: Even though HIV is associated with worse prognosis in many malignancies, the clinical course of MDS and AML in HIV+ pts has not been well studied. Determining the clinical presen...

Research paper thumbnail of Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-κB and osteosarcoma progression

Nature Communications, 2016

The ability of cancer cells to survive and grow in anchorage- and serum-independent conditions is... more The ability of cancer cells to survive and grow in anchorage- and serum-independent conditions is well correlated with their aggressiveness. Here, using a human whole-genome shRNA library, we identify TMIGD3 isoform1 (i1) as a factor that suppresses this ability in osteosarcoma (OS) cells, mainly by inhibiting NF-κB activity. Knockdown of TMIGD3 increases proliferation, tumour formation and metastasis of OS cells. Overexpression of TMIGD3 isoform1 (i1), but not isoform3 (i3) which shares a common C-terminal region, suppresses these malignant properties. Adenosine A3 receptor (A3AR) having an identical N-terminal region shows similar biological profiles to TMIGD3 i1. Protein expression of TMIGD3 and A3AR is lower in human OS tissues than normal tissues. Mechanistically, TMIGD3 i1 and A3AR commonly inhibit the PKA-Akt-NF-κB axis. However, TMIGD3 i1 only partially rescues phenotypes induced by A3AR knockdown, suggesting the presence of distinct pathways. Our findings reveal an unappreciated role for TMIGD3 i1 as a suppressor of NF-κB activity and OS progression.

Research paper thumbnail of Leucopenia in Acute Myeloid Leukemia Presenting as Myocardial Infarction: A Case Report

Journal of Bone Marrow Research, 2013

Research paper thumbnail of Activation of hypoxia signaling is marker of poor prognosis in myelodysplasia

Leukemia & Lymphoma, 2012

Research paper thumbnail of Role of endovascular stenting in radiation-induced stenosis of lower extremity veins

Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, Jan 25, 2014

Radiation-induced venous stenosis is rare with a few isolated cases reported in the medical liter... more Radiation-induced venous stenosis is rare with a few isolated cases reported in the medical literature involving the lower limb. Management options in such cases are thus not streamlined. We describe an unusual case of iliac vein stenosis in a patient with rectal carcinoma after combined chemoradiation therapy, managed with endovascular stenting. The possible mechanisms underlying the pathogenesis of venous stricture and their treatment options have been reviewed. © 2014 Wiley Periodicals, Inc.

Research paper thumbnail of Abstract 14804: Transplantation of Human Umbilical Cord Blood Mononuclear Cells Improves LV function and Remodeling After a reperfused Myocardial Infarction

Circulation, Nov 25, 2014

Research paper thumbnail of Aging, Nutrients, and Endogenous Stem Cell Populations

Research paper thumbnail of Abstract 18105: Genetic Deletion of IL-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Failure

Circulation, Nov 26, 2013

Research paper thumbnail of ONC2013520A

Research paper thumbnail of NF-KB Inhibition Protects Against Myocardial Ischemia/Reperfusion Injury via Activation of Antiapoptotic Signaling

Journal of the American College of Cardiology, 2015

Research paper thumbnail of Role of endovascular stenting in radiation-induced stenosis of lower extremity veins

Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions, Jan 25, 2014

Radiation-induced venous stenosis is rare with a few isolated cases reported in the medical liter... more Radiation-induced venous stenosis is rare with a few isolated cases reported in the medical literature involving the lower limb. Management options in such cases are thus not streamlined. We describe an unusual case of iliac vein stenosis in a patient with rectal carcinoma after combined chemoradiation therapy, managed with endovascular stenting. The possible mechanisms underlying the pathogenesis of venous stricture and their treatment options have been reviewed. © 2014 Wiley Periodicals, Inc.

Research paper thumbnail of Influence of rituximab on CNS relapse in Diffuse Large B Cell Lymphoma and the role of prophylaxis - a systematic review of prospective studies

Clinical Lymphoma Myeloma and Leukemia, 2015

Introduction: Despite improvement in overall survival in DLBCL patients in the rituximab era, the... more Introduction: Despite improvement in overall survival in DLBCL patients in the rituximab era, the occurrence of CNS relapse heralds a very poor prognosis. There is conflicting evidence on the incidence and pattern of CNS relapse in the rituximab era, compared to the pre-rituximab era and on the role of CNS prophylaxis.

Research paper thumbnail of Genetic Deletion of IL-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Failure

Research paper thumbnail of A Murine Model of Cardiac Arrest by Exsanguination

Manual of Research Techniques in Cardiovascular Medicine, 2014

Research paper thumbnail of Aging, Nutrients, and Endogenous Stem Cell Populations

Nutritional and Therapeutic Interventions, 2013

Research paper thumbnail of Stem cell origin of myelodysplastic syndromes

Research paper thumbnail of Cardiac-Specific Transgenic Silencing of NF-KB Ameliorates Left Ventricular Dysfunction and Remodeling After Acute Myocardial Infarction

Journal of the American College of Cardiology, 2012

Research paper thumbnail of Do Patients Undergoing Elective Percutaneous Coronary Intervention Distinguish the Type of Stent They Receive? A Contemporary Perspective

Journal of the American College of Cardiology, 2012

Research paper thumbnail of Cardiac-Specific Transgenic Inhibition of NF-KB Activation Protects Against Myocardial Ischemia/Reperfusion Injury

Journal of the American College of Cardiology, 2012

ABSTRACT Background: Nuclear factor-kappaB (NF-kB), a stress-responsive transcription factor, has... more ABSTRACT Background: Nuclear factor-kappaB (NF-kB), a stress-responsive transcription factor, has been implicated in various cardiovascular pathologies.Although NF-kB is necessary for late preconditioning, its summative role in myocardial ischemia/reperfusion (I/R) injury remains unclear.Methods: Using mice with cardiac-specific inhibition of NF-kB activation via transgenic overexpression of a mutant IkBa protein, we examined the role of NF-kB in myocyte death in a mouse model of I/R injury. Considering the nonspecific actions of various pharmacological inhibitors of NF-kB, this genetic model offers the advantage of specifically ablating NF-kB activation in myocytes. Age-matched male wild-type (WT, C57BL/6, n=7), nontransgenic littermates (NTg, n=6) and IkBa transgenic (IkBa Tg, n=6) mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Mice were sacrificed and infarct size was determined by TTC staining. Results: The infarct size was similar in WT controls and NTg mice (Figure), indicating no untoward impact in NTg hearts. However, the infarct size was significantly smaller in IkBa Tg mice compared with both WT and NTg groups (Figure), indicating that myocardial NF-kB signaling plays a detrimental role during acute I/R injury.Conclusions: We conclude that NF-kB inhibition protects against acute myocardial I/R injury. These findings are relevant toward developing novel therapeutic strategies against myocardial infarction via modulation of NF-kB signaling in the heart.