269 results match your criteria: "Aflac Cancer Center[Affiliation]"

Activated leukocyte cell adhesion molecule: a new paradox in cancer.

Transl Res

March 2008

Department of Pediatrics, Aflac Cancer Center and Blood Disorders Services, Emory University School of Medicine, Atlanta, Ga, USA.

The activated leukocyte cell adhesion molecule [ALCAM/CD166/melanoma metastasis clone D (MEMD)] is an immunoglobulin superfamily cell adhesion molecule. It is expressed developmentally in cells of all 3 embryonic lineages. The ALCAM expression is limited to subsets of cells in most adult tissues.

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The overall prognosis for patients with high-grade glioma remains dismal, despite advances in treatment modalities including neurosurgery, radiation therapy and conventional cytotoxic chemotherapy. In this article, we review literature that provides a rationale for the use of antiangiogenic therapy to improve the treatment of high-grade neoplasms in the CNS. In particular, we focus our discussion on the central role of the phosphatidylinositol 3-kinase-Akt- phosphatase and tensin homolog (PI3K-Akt-PTEN) axis as a potential molecular target for the control of angiogenesis in brain tumors via the coordinated control of cell division, tumor growth, angiogenesis, apoptosis, invasion and cellular metabolism in the tumor and stromal compartments.

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Melanoma in children and adolescents.

Surg Oncol

November 2007

Division of Pediatric Surgery and the Department of Hematology/Oncology/BMT, Aflac Cancer Center, Emory School of Medicine, Atlanta, GA, USA.

Melanoma is rarely described in the pediatric population. However, recent studies show that the incidence may be increasing. The diagnosis of melanoma presents unique challenges in this age group.

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The diversity of factor VIII (fVIII) C2 domain antibody epitopes was investigated by competition enzyme-linked immunosorbent assay (ELISA) using a panel of 56 antibodies. The overlap patterns produced 5 groups of monoclonal antibodies (MAbs), designated A, AB, B, BC, and C, and yielded a set of 18 distinct epitopes. Group-specific loss of antigenicity was associated with mutations at the Met2199/Phe2200 phospholipid binding beta-hairpin (group AB MAbs) and at Lys2227 (group BC MAbs), which allowed orientation of the epitope structure as a continuum that covers one face of the C2 beta-sandwich.

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Contribution of A1 subunit residue Q316 in thrombin-activated factor VIII to A2 subunit dissociation.

Biochemistry

August 2007

Aflac Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, and the Department of Pediatrics, Emory University, Atlanta, Georgia 30322, USA.

Blood coagulation factor VIII (fVIII) is activated by thrombin to form an A1/A2/A3-C1-C2 heterotrimer, which functions as a cofactor for factor IXa during intrinsic pathway factor X activation. Human thrombin-activated fVIII (fVIIIa) decays rapidly because of first-order dissociation of the A2 subunit, which may function to regulate the coagulation mechanism. The three fVIII A domains each consist of two cupredoxin-like subdomains.

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Inflammation enhances consumption and presentation of transfused RBC antigens by dendritic cells.

Blood

October 2007

Department of Pediatric Hematology/Oncology, Emory University School of Medicine, Children's Healthcare of Atlanta, AFLAC Cancer Center and Blood Disorders Service, Atlanta, GA 30322, USA.

Factors regulating which patients become alloimmunized to red blood cell (RBC) antigens are poorly understood. Using a murine model of transfusion, we recently reported that viral-like inflammation with polyinosinic polycytidylic acid [poly (I:C)] significantly enhances RBC alloimmunization. Herein, we tested the hypothesis that poly (I:C) exerts this effect, at least in part, at the level of antigen-presenting cells (APCs).

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Insufficient expression of factor VIII (fVIII) is a major hurdle in the development of successful nucleic acid treatments for hemophilia. However, we recently showed that under myeloablative and reduced-intensity total body irradiation (TBI) conditioning, transplantation of hematopoietic stem cells (HSCs) transduced with recombinant retroviruses containing B domain-deleted porcine fVIII (BDDpfVIII) sequences provides curative fVIII levels in a hemophilia A mouse model. In the current study, we tested BDDpfVIII activity after nonmyeloablative conditioning with busulfan, cyclophosphamide, or fludarabine and immunosuppressive agents CTLA4-Ig + anti-CD40L or anti-(murine)thymocyte serum (ATS).

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Contribution of STAT3 to the activation of survivin by GM-CSF in CD34+ cell lines.

Exp Hematol

June 2007

Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Service, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.

Objective: Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to specifically stimulate proliferation of CD34(+) hematopoietic progenitor cells. Although signal transducers and activators of transcription 3 (STAT3) is believed essential for transduction of GM-CSF-induced cell proliferation, the signaling mediated by STAT3 is not completely understood. Because survivin regulates cell proliferation and survival via its antiapoptotic function, we studied the link between STAT3 signaling and survivin expression in CD34(+) cells.

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Matched sibling donor (MSD) transplant is a life-saving procedure for children with various hematological malignancies and non-malignancies. Traditionally, steady-state bone marrow (S-BM) has been used as the source of stem cells. More recently, peripheral blood stem cell (PBSC) after granulocyte-colony stimulating factor (G-CSF) mobilization has gained popularity.

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The development of inhibitory antibodies directed against factor VIII (fVIII) remains the most significant clinical complication associated with the treatment of hemophilia A. Recently, we demonstrated that transplantation of genetically modified hematopoietic stem cells containing a high-expression porcine fVIII transgene promoted sustained high-level fVIII expression in naïve hemophilia A mice. In the current study, a similar gene transfer strategy was tested in hemophilia A mice harboring clinically significant anti-human factor VIII (anti-hfVIII) inhibitory antibody titers.

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CSK controls retinoic acid receptor (RAR) signaling: a RAR-c-SRC signaling axis is required for neuritogenic differentiation.

Mol Cell Biol

June 2007

Section of Pediatric Hematology/Oncology, Department of Pediatrics, Aflac Cancer Center and Blood Disorders Services, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30022, USA.

Herein, we report the first evidence that c-SRC is required for retinoic acid (RA) receptor (RAR) signaling, an observation that suggests a new paradigm for this family of nuclear hormone receptors. We observed that CSK negatively regulates RAR functions required for neuritogenic differentiation. CSK overexpression inhibited RA-mediated neurite outgrowth, a result which correlated with the inhibition of the SFK c-SRC.

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The humoral response to human factor VIII in hemophilia A mice.

J Thromb Haemost

March 2007

Aflac Cancer Center and Blood Disorders Service, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University, Atlanta, GA 30322, USA.

Background: Inhibitory antibodies (Abs) to factor VIII (FVIII inhibitors) constitute the most significant complication in the management of hemophilia A. The analysis of FVIII inhibitors is confounded by polyclonality and the size of FVIII.

Objectives: The goal of this study was to dissect the polyclonal response to human FVIII in hemophilia A mice undergoing a dosage schedule that mimics human use.

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Recombinant tissue plasminogen activator may reduce frequency of central venous access device infection in hemophilia patients undergoing immune tolerance therapy.

Pediatr Blood Cancer

March 2008

Comprehensive Hemostasis and Thrombosis Program, Aflac Cancer Center and Blood Disorders Service, Emory University, Atlanta, Georgia, USA.

Many patients with hemophilia, particularly those with inhibitory antibodies, utilize central venous access devices (CVADs) to facilitate frequent infusions. Infection of these devices is a common complication of factor replacement therapy. This communication reports our center's experience with CVAD infection in three patients with severe hemophilia A undergoing immune tolerance therapy (ITT) in whom intermittent infusions of recombinant tissue plasminogen activator (rTPA, Cathflo Activase) were utilized.

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Novel therapeutic agents in the management of hemorrhage and thrombosis.

Cardiovasc Hematol Agents Med Chem

October 2006

Aflac Cancer Center and Blood Disorders Service and Winship Cancer Institute, Emory University, Atlanta, GA, USA.

Abnormalities in the hemostatic system can lead to, on one end of the spectrum, hemorrhage, and on the opposite end, thrombosis. Over the past decade, important new agents for the management of hemorrhagic and thrombotic disorders have been developed and more are in development. The care of patients with bleeding disorders has been advanced by the development of techniques to manufacture recombinant factor products with reduced or absent exposure to human or animal proteins, prolonged half-life or with reduced immunogenicity.

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Purpose Of Review: To discuss the advantages and disadvantages of the albumin-free recombinant factor VIII concentrates in the treatment of hemophilia A.

Recent Findings: The third-generation recombinant factor VIII product Advate has been found to be safe and effective in treating bleeding associated with hemophilia A.

Summary: Multiple issues must be considered when selecting a factor VIII concentrate for patients with hemophilia A including efficacy, availability, risk of transmission of infectious agents, risk of inhibitor development and cost.

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Background: Development of an inhibitory antibody to factor VIII is currently the most serious complication of hemophilia A treatment. The rate of inhibitor development in those that have been previously treated with factor concentrates is poorly defined. Understanding the baseline rate of inhibitor development in the population of previously treated patients (PTPs) is important when evaluating the effect of exposure to new factor replacement products on inhibitor formation.

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Recipient inflammation affects the frequency and magnitude of immunization to transfused red blood cells.

Transfusion

September 2006

Department of Pediatric Hematology/Oncology, Emory University School of Medicine, Children's Healthcare of Atlanta, AFLAC Cancer Center and Blood Disorders Service, Atlanta, Georgia 30322, USA.

Background: Most alloantigens on transfused red blood cells (RBCs) are weakly immunogenic, with only a 2 to 6 percent overall immunization rate even in patients receiving multiple transfusions. Although recipient genetics may contribute to responder and/or nonresponder status, in most cases HLA type does not predict humoral response to RBC antigens. In contrast, rates of alloimmunization do correspond to the underlying disease status of transfusion recipients, suggesting that acquired host factors may play an important role.

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Complete regression of large solid tumors using engineered drug-resistant hematopoietic cells and anti-CD137 immunotherapy.

Hum Gene Ther

August 2006

Division of Hematology/Oncology and Blood and Marrow Transplantation, Department of Pediatrics, Emory University School of Medicine, AFLAC Cancer Center and Blood Disorders Services, Atlanta, GA 30322, USA.

Combining chemotherapy and immunotherapy is problematic because chemotherapy can ablate the immune responses initiated by modulators of the immune system. We hypothesized that protection of immunocompetent cells from the toxic effects of chemotherapy, using drug resistance gene therapy strategies, would allow the combined use of chemotherapy and immunotherapy. In wild-type mice, the antitumor effectiveness of an immunotherapy regimen employing an agonistic anti-CD137 antibody is diminished with escalating doses of the antifolate trimetrexate (TMTX).

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Background: Inhibitory antibodies to factor (F) VIII (FVIII inhibitors) present a major clinical challenge as a complication of hemophilia A and as acquired autoantibodies in non-hemophiliacs. Porcine FVIII is a potentially useful therapeutic agent because of its low crossreactivity with many inhibitors. Recombinant porcine FVIII (rpFVIII) is undergoing clinical trials in inhibitor patients.

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Prophylaxis and von Willebrand's disease (vWD).

Thromb Res

August 2006

Aflac Cancer Center and Blood Disorders Service, Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.

Von Willebrand disease (vWD) is an inherited bleeding disorder with a prevalence of approximately 1% in the general population. The bleeding occurs in this disorder primarily because of abnormalities in platelet adhesion, due to a primary deficiency or defect in the von Willebrand factor (vWF) often with a concomitant decrease in factor VIII (FVIII) levels. The mainstay of treatment for the majority of patients with vWD is desmopressin, which releases vWF from endothelial cells.

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Current issues in prophylactic therapy for persons with hemophilia.

Acta Haematol

April 2006

AFLAC Cancer Center and Blood Disorders Service, Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.

Factor VIII or IX replacement in a prophylactic manner is utilized for many patients with moderate to severe hemophilia A or B. Studies have shown it to be effective in reducing or preventing degenerative joint disease in many but not all patients. However, many unanswered questions still exist and optimization of this expensive treatment regimen is needed.

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Factor VIII (fVIII) is the plasma protein that is missing or deficient in hemophilia A. In contrast, elevated levels of fVIII are associated with an increased risk of arterial and venous thrombosis. fVIII is activated by thrombin to form a non-covalently linked A1/A2/A3-C1-C2 heterotrimer.

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The MYCN enigma: significance of MYCN expression in neuroblastoma.

Cancer Res

March 2006

AFLAC Cancer Center, Department of Pediatrics and Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.

MYCN amplification strongly predicts adverse outcome of neuroblastoma. However, the significance of MYCN expression in the clinical and biological behavior of neuroblastoma has been unclear. To address this question, we first examined the expression of MYCN in combination with TrkA (a favorable prognostic indicator of neuroblastoma) in 91 primary neuroblastoma by quantitative reverse transcription-PCR and investigated the relationship among patient survival, MYCN, and TrkA expressions.

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Childhood and adolescent acute myeloid leukemia (AML) is traditionally one of the hardest childhood cancers to successfully treat and had an overall survival well under 10% in the 1960s. Initial progress was made by three major events: (1) active chemotherapeutic agents were identified which led to remissions for the first time in this disease; (2) cooperative groups were instituted leading to important clinical trials; and (3) several single institutions began experimenting with the role of allogeneic matched sibling donor (MSD) BMT as effective intensification. Over the last 25 years, the cure rate has improved from <20% to 50% or higher.

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