Biomedical subjects

Jacqueline M Kraveka

Publications and source records attributed to Jacqueline M Kraveka.

4 recordsLinked to original sources

PubMed2005

Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial.

PURPOSE: The Pediatric Oncology Group adopted a histology-based approach to non-Hodgkin's lymphoma and treated patients with advanced large-cell lymphoma on a separate protocol (doxorubicin, vincristine, prednisone, 6-mercaptopurin, and methotrexate; APO regimen). In this study, we assessed the effects of an intense antimetabolite therapy alternating with APO on overall survival (OS) and event-free survival (EFS) and looked into biologic correlates. PATIENTS AND METHODS: From December 1994 to April 2000, we enrolled 180 eligible pediatric patients with stage III/IV large-cell lymphoma (LCL); 90 patients were randomly assigned to the intermediate-dose methotrexate (IDM) and high-dose cytarabine (HiDAC) arm, 85 patients to the APO arm, and five patients directly to the APO arm by study design due to CNS involvement. Planned therapy duration was 12 months. RESULTS: The 4-year EFS for all patients was 67.4% (SE, 4.2%), and OS was 80.1% (SE, 3.6%) without any significant difference between the two arms. The 4-year EFS and OS were 71.8% (SE, 6.1%) and 88.1% (SE, 4.4%), respectively, for patients with anaplastic large-cell lymphoma, and 63.8% (SE, 10.3%) and 70.3% (SE, 9.0%), respectively, for patients with diffuse large B-cell lymphoma. Only 11 patients required radiation (due to unresponsive bulky disease or CNS involvement). The IDM/HiDAC arm was associated with more toxicity. CONCLUSION: The efficacy of incorporating IDM/HiDAC in the treatment plan of pediatric and adolescent patients with advanced-stage LCL was inconclusive as to its effect on EFS, regardless of the lymphoma phenotype. It cannot be excluded that with a higher number of patients, one treatment could prove superior and future studies will build on these data.

Adolescent↗

PubMed2004

CD19 negative precursor B acute lymphoblastic leukemia presenting with hypercalcemia.

A 9-month-old infant presented with hypercalcemia and lytic bone lesions. Suspicion for malignancy led to a bone marrow examination, which showed replacement of the marrow by a small round blue cell infiltrate. Flow cytometric analysis of these cells showed an unusual immunophenotype in that these cells were dim CD45, HLA-DR, and CD10 positive, but CD19, CD20, CD79a, and CD34 negative. Southern blotting showed clonal rearrangement of immunoglobulin heavy chain (IgH) which confirmed a diagnosis of precursor B acute lymphoblastic leukemia (ALL). He received supportive treatment with hydration and pamidronate, but had recurrent episodes of hypercalcemia. Once the correct diagnosis of ALL was established, the patient was treated with an infantile ALL chemotherapeutic regimen and the hypercalcemia resolved. This case highlights the usefulness of immunoglobulin gene rearrangement studies in atypical cases of ALL.

Gene Rearrangement, B-Lymphocyte, Heavy Chain↗

PubMed2003

Involvement of endogenous ceramide in the inhibition of telomerase activity and induction of morphologic differentiation in response to all-trans-retinoic acid in human neuroblastoma cells.

In this study, we examined the role of endogenous ceramide in the inhibition of telomerase and induction of morphologic differentiation in response to all-trans-retinoic acid (ATRA) in the SK-N-SH and SK-N-AS human neuroblastoma cell lines. The results showed that ATRA inhibited the activity of telomerase significantly in a time- and dose-dependent manner, as determined by telomere repeat amplification protocol (TRAP). The inhibition of telomerase by ATRA was maximum (about 50-80% of untreated controls) at 5-10 microM for 4-8 days. Treatment of cells with ATRA (5 microM) also resulted in the inhibition of growth by about 30-70% after 4 and 8 days of treatment, respectively, which was measured by trypan blue exclusion method. Measurement of accumulation of endogenous ceramide by high pressure liquid chromatography coupled with mass spectroscopy (LC/MS) showed that treatment of cells with ATRA resulted in increased levels of mainly C24:0 and C24:1 ceramides at days 2, 4, and 8, respectively. Also, treatment of cells with ATRA in the presence of myriocin blocked the accumulation of ceramide significantly, and more importantly, presence of myriocin partially prevented the inhibition of telomerase. Mechanistically, inhibition of telomerase by endogenous ceramide in response to ATRA treatment involves, at least in part, down-regulation of the expression of telomerase reverse transcriptase (hTERT) mRNA, as determined by semi-quantitative RT-PCR, in these cells. In addition, the modulation of telomerase activity by ATRA correlated with the induction of morphologic differentiation, which was also blocked by myriocin, as determined by extension of neurites using phase-contrast microscopy. These results, therefore, reveal an important effect of ATRA on telomerase inhibition and induction of morphologic differentiation in human neuroblastoma cells. These data also demonstrate that endogenous ceramide is one of the upstream regulators of telomerase activity in human neuroblastoma cells in response to ATRA.

Cell Differentiation↗

PubMed2002

Ceramide regulation of apoptosis versus differentiation: a walk on a fine line. Lessons from neurobiology.

One of the characteristics of ceramide-mediated biology is the variety of biological outcomes observed in response to its intracellular accumulation. The molecular mechanisms that govern the cell "decision-making" in response to ceramide remain largely unclear. In this perspective, the study of neural models has begun to provide important insight into the understanding of these mechanisms that regulate differentiation and cell death. Indeed, differentiation and cell death are among the most common effects elicited by ceramide in most cell types and in neural cells, too. Therefore, the lessons we may learn from the study of ceramide regulation of neurobiology would also shed light on the regulation of ceramide-mediated biology in other cellular models. Since increasing evidence links aberrant metabolism of ceramide to different pathologies, the understanding of the mechanisms underlying these events may represent the key to the design of novel therapeutic approaches.

Animals↗