[EXPRESSION OF PFKFB, HK2, NAMPT, TSPAN13 AND HSPB8 GENES IN PEDIATRIC GLIOMA].

We studied the peculiarity of the expression of several key genes related to dysregulation of cell proliferation and surviving processes in pediatric glioma (glioblastoma multiforme) tissue from five children with age from 5 to 8 years as well a sin corresponding nonmalignant tissue counterparts as control from the same patients. RNA was isolated from glioma tissue and corresponding non-malignant tissue counterparts and PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8 gene expressions were studied by quantitative polymerase chain reaction. It was shown that the expression level of genes PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8 is increased in pediatric gliomas as compared to corresponding non-malignant tissue counterparts, but in different grade. More significant changes were demonstrated for PFKFB3, PFKFB4 HK2, NAMPT, TSPAN13, and HSPB8 genes. Thus, the changes in pediatric glioma tissues of the expression of PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8 genes, which control cell proliferation and apoptosis, possibly contribute to enhance the tumor growth, because these genes control cell proliferation and surviving.

20th-century advances in drug therapy in oncology--Part. II.

Ongoing research in cancer therapy has led to the development of antineoplastic agents which target specific components of the cell cycle. In Part II of this series, we discuss agents which target the mitotic mechanism by inhibiting microtubules. Although many of these agents are being shown to have multiple effects, the Vinca alkaloids and the taxanes are known as antimitotic drugs. They are among the most important anticancer agents currently available, and because of their unique mechanisms, can be combined with a wide variety of other antineoplastic agents in a spectrum of diseases. In addition, in part II, we are discussing agents that target DNA and prevent replication and thus cell growth by inhibiting the enzymes which protect DNA during replication, the topoisomerases. These drugs, too, have unique mechanisms of action and have become major components of combination regimens. The topoisomerase I inhibitors are new drugs derived from an older parent drug, and their full possibilities are still being explored.

Therapeutic efficacy of theophylline in chronic lymphocytic leukemia.

Theophylline, a methylxanthine commonly used as a treatment for asthma, has been shown to induce apoptosis in chronic lymphocytic leukemia (CLL) cells both in vitro and in vivo. We have treated three advanced CLL patients with theophylline, and seen responses in two. The clinical courses of the responders are presented, and the literature concerning theophylline as therapy for CLL is reviewed.

Phase II protocol for the evaluation of new treatments in patients with advanced gastric carcinoma: results of ECOG 5282.

The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma. Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium. The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m2 were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer.

Familial erythroleukemia: a distinct clinical and genetic type of familial leukemias.

A family with erythroleukemia is presented, in which father and son were diagnosed at the same age, but 20 years apart, with almost identical clinical and morphological features of the disease. No environmental factors were identified. The karyotypic abnormalities of the bone marrow blasts in the son demonstrated 2 major clones, involving chromosomes 5 and 7, as well as 8, 13, 16 and 21. Both patients demonstrated a poor response to chemotherapy. Previously described families with erythroleukemia are reviewed with available specific karyotypic aberrations.

Therapeutic effect of cyclosporine A in thrombocytopenia after myeloablative chemotherapy in acute myeloid leukaemia.

Four patients with acute myelogenous leukaemia (AML), who developed isolated thrombocytopenia after anti-leukaemic chemotherapy, were treated with cyclosporine A and showed significantly enhanced platelet recovery. All four patients demonstrated decreased bone marrow megakaryocytes without dysplastic features, absence of identifiable peripheral autoimmune platelet destruction or cytogenetic evidence of secondary myelodysplasia. The duration of response to cyclosporine A ranged from 6 days to 40 months. The mechanism of cyclosporine A-induced platelet recovery may include inhibition of negative modulators and induction of thrombopoietic cytokines mediated by bone marrow regulatory cells.