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  • 1
    ISSN: 1573-7373
    Keywords: high grade astrocytoma ; dibromodulcitol ; BCNU ; radiation therapy ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We performed a randomized trial to comparesurvival distributions and toxicity of radiation therapy (RT)and DBD with RT and BCNU in patientswith high-grade astrocytoma. Methods: A total of 238patients with supratentorial grade 3 and grade 4astrocytoma were studied. Patients were stratified by age,extent of surgery, tumor grade, and performance scoreand randomly assigned to receive RT 55-60 Gyand either DBD, 200 mg/m2 orally on Days1–10 every five weeks or BCNU, 200 mg/m2intravenously every seven weeks. Median age was 60years; 62% were 55 years or older. Eighty-threepercent had subtotal resection, 58% had grade 4tumors, and 83% had performance scores of 0–2.Results: Survival distributions for all patients in thetwo arms were similar, with median survival of41 weeks in each arm. Time to progressiondistributions were virtually identical, with medians of 22weeks. BCNU produced significantly greater hematologic toxicity; medianleukocyte and platelet nadirs on the first cyclewere 3.6 vs. 4.7 (P=0.0001) and117 vs. 162 (P 〈 0.0001), and overallplatelet nadirs were 80.5 vs. 114 (P =0.0019). Non-hematologic toxicities were also significantly greater withBCNU, including nausea (57% vs. 31%; P 〈0.0001) and vomiting (45% vs. 17%; P 〈0.0001). Conclusion: This trial found no evidence ofdifferences in treatment efficacy when either DBD orBCNU is combined with radiation therapy for patientswith high-grade astrocytoma.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7403
    Keywords: pituitary ; HP75 cells ; STATs and SOCS-3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leptin is an adipocyte-derived cytokine with many functions including signaling the status of body energy stores through activation of the leptin receptor (OB-R). Activation of the long form of OB-R (OB-Rb) results in JAK2 phosphorylation, activation of STATs, and subsequent gene expression. Activated STAT3 induces SOCS-3 expression in some cell types, which in turn down-regulates the JAK/STAT pathway. Although both leptin and OB-R are expressed in pituitary cells, the mechanism of signal transduction and its regulation in this organ has not been studied extensively. In these experiments we show that leptin reduces proliferation in a human pituitary cell line (HP75) and also increased apoptosis in these cells. Leptin also increased SOCS-3 mRNA and protein expression and tyrosine-phosphorylation in the HP75 human pituitary cell line. These findings suggest that SOCS-3 plays an important role in the inhibition of proximal leptin signal transduction in the anterior pituitary.
    Type of Medium: Electronic Resource
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