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Barthel Barlogie

Publications and source records attributed to Barthel Barlogie.

3 recordsLinked to original sources

Gene expression profiling and multiple myeloma.

Gene expression profiling is a powerful tool through which the biology of multiple myeloma can be dissected. We will describe in this chapter how early studies using this technology have provided meaningful insights into myeloma biology, have led to the identification of new therapeutic targets, and have identified powerful prognostic and pharmacogenomic markers. Specifically, we will demonstrate that gene expression profiling can be used to segregate myeloma patients into prognostic categories within which known IgH translocation signatures can be readily defined. We also show that expression signatures can identify patients with chromosome 13 deletion. Finally, we demonstrate that global gene expression signatures can be distilled to short lists of three genes or more which together impart clinical outcome information, which is significantly more powerful than any previously defined prognostic tool. Expression profiling has also led to the identification of a number of new therapeutic targets not only in myeloma cell survival but also in the pathogenesis of the osteolysis which is a hallmark of this disease.

Bone Diseases↗

Testing recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen, multiple myeloma HM1.24.

Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generates significant and rapid (one stimulation per week) cytotoxic T-lymphocyte (CTL) responses in vitro against viral antigens. As a more extensive analysis of the rAAV system, we have used a self-antigen, HM1.24, expressed in multiple myeloma (MM). Again, with one stimulation, significant major histocompatibility complex (MHC) class 1-restricted, anti-HM1.24-specific CTL killing was demonstrated against MM cells. Furthermore, higher expression of interferon-gamma (IFN-gamma) in T cells and higher expression levels of, in order of significance, CD80 (2.6- to 3.8-fold increase), CD86, and CD40 on DCs were also observed. The use of synthetic HM1.24-positive target cells further demonstrated the antigen specificity of these CTLs. There was also no evidence of natural killer cell involvement. These data extend our earlier studies and suggest that the rAAV-loading of DCs may be a particularly good protocol for generating CTLs against self-antigens, which may not otherwise be considered good targets because of their low immunogenicity. We also show that HM1.24 may be an effective antigen for targeting MM.

Antigens, Neoplasm↗

Outcome from mechanical ventilation after autologous peripheral blood stem cell transplantation.

STUDY OBJECTIVE: To report the outcome of patients with autologous peripheral blood stem cell transplantation (PBSCT) receiving mechanical ventilation. DESIGN: Retrospective observational study. SETTING: Active hematopoietic stem cell transplantation center and a university hospital medical ICU. PATIENTS: Patients with autologous PBSCT receiving mechanical ventilation. METHOD: A review of the medical records of patients with autologous PBSCT receiving mechanical ventilation. Data collection was restricted to the first episode of mechanical ventilation. RESULTS: A total of 78 autologous PBSCT patients received mechanical ventilation for > 24 h. Twenty patients (26%) were extubated and discharged alive from the hospital. Thirteen hospital survivors (60%) were alive at 6 months. Lung injury (LI), vasopressor use, and hepatic and renal failure (HRF) were used to predict survival after mechanical ventilation. Sixty patients (76%) had no organ failure, or had isolated LI or only required treatment with vasopressors. Their hospital survival and 6-month survival were 32% and 20%, respectively. Hospital and 6-month survival for the patients with HRF or LI and vasopressor use was 6% and 0%, respectively. CONCLUSIONS: Prolonged mechanical ventilation and aggressive ICU support is justified for autologous PBSCT patients receiving mechanical ventilation with no organ failure, or who have only isolated LI, or who only require treatment with vasopressors.

Adult↗