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Articles 1 - 8 of 8
Full-Text Articles in Hematology
Evaluating The Therapeutic Potential Of Geranylgeranyl Diphosphate Synthase Inhibitor, Ram2061, In Myeloma Bone Disease, Molly Muehlebach
Evaluating The Therapeutic Potential Of Geranylgeranyl Diphosphate Synthase Inhibitor, Ram2061, In Myeloma Bone Disease, Molly Muehlebach
Theses & Dissertations
Multiple myeloma (MM) is a hematological malignancy of the plasma cells which often results in lytic bone disease. Myeloma bone disease (MBD), characterized by diffuse osteopenia, bone lesions, or pathological fracture, results from MM mediated promotion of osteoclast resorption and dual inhibition of bone formation, drastically reducing bone strength and integrity. Development of MBD is known to significantly impact patient quality of life and increase risk of mortality. Considering that up to 80-95% of MM patients are expected to develop bone disease post-initial MM diagnosis, there is a significant need within this population for therapeutics which address both MM disease …
Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou
Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou
Theses & Dissertations
Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …
The Link Between Fat Soluble Vitamin Deficiencies, Decreased Microbiota Diversity And Severity In Children With Sickle Cell Disease Followed In A Clinic In Omaha Nebraska, Chinenye R. Dike
Theses & Dissertations
Fat soluble vitamin (FSV) deficiencies are associated with worse pain in individuals with sickle cell disease (SCD). Data on the dietary and pancreatic function influence on fat soluble vitamin levels are limited. Additionally, individuals with SCD have gut dysbiosis but there are gaps in knowledge on the impact of this on severity. This thesis attempted to evaluate FSV prevalence and gut microbial profile in our cohort of children with SCD and compare this with matched healthy children and to ascertain if diet or pancreatic function affects these levels and see if these affects sickle cell severity.
Apixaban To Prevent Thrombosis In Adult Patients Treated With Asparaginase, Krishna Gundabolu
Apixaban To Prevent Thrombosis In Adult Patients Treated With Asparaginase, Krishna Gundabolu
Theses & Dissertations
The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved dramatically after intensification of the multi-agent chemotherapy backbone over a period of time starting from 1960’s, and asparaginase (ASP) is an important part of this success story. Adoption of such strategy in adult ALL and other high grade lymphoid neoplasms had been difficult due to higher anticipated toxicities including thrombosis. Many thrombosis prevention strategies including antithrombin (AT) replacement, Enoxaparin, unfractionated heparin (UFH) was studied but there is no firmly established evidence-based approach yet. We report the safety and efficacy of thrombosis prophylaxis with apixaban 2.5 mg orally twice daily for …
Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt
Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt
Theses & Dissertations
Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …
Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch
Dnmt3a Haploinsufficiency Provokes Hematologic Malignancy Of B-Lymphoid, T-Lymphoid, And Myeloid Lineage In Mice, Garland Michael Upchurch
Theses & Dissertations
DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3aΔ/Δ) and Dnmt3a heterozygous (Dnmt3a+/–) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220+CD19+CD5+; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ+CD3+CD8+CD4—; 40% penetrance (17/42)). …
Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang
Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang
Theses & Dissertations
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of generally aggressive lymphoid malignancies, accounting for 10-15% of all non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) represents approximately 20% of all PTCLs and is recognized as a distinct entity. Accurate diagnosis and classification of PTCL remain challenging. With the exception of ALK+ ALCL, patients with PTCL generally have a poor prognosis with standard chemotherapy and even with the availability of many novel drugs, including HDAC inhibitor (romidepsin and belinostat), gemcitabine, and bortezomib. Therefore, deciphering the pathogenesis of this group of diseases is needed to identify novel treatable targets for better therapeutic intervention. …
Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr
Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr
Theses & Dissertations
Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …