tretinoin and Hodgkin-Disease

Topics: Anthraquinones; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Breast Neoplasms; Cisplatin; Dose-Response Relationship, Drug; Female; Genetic Techniques; Hodgkin Disease; Hormones; Humans; Immunotherapy; Interferons; Male; Mechlorethamine; Methotrexate; Mitoxantrone; Neoplasm Metastasis; Neoplasms; Neoplasms, Germ Cell and Embryonal; Nitrosourea Compounds; Osteosarcoma; Prednisone; Procarbazine; Prognosis; Receptors, Cell Surface; Tretinoin; Vincristine

This study aimed to detect the protein expression of HA117 in pediatric solid tumors. Immunohistochemistry was performed to detect the expression of HA117 and P-gp in pediatric solid tumors. In Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), nephroblastoma (WT), and neuroblastoma (NB), the positive expression rate of HA117 was 65.4%, 58.3%, 81.3%, and 74.1%, and that of P-gp was 57.7%, 70.8%, 65.6%, and 66.7%, respectively. HA117 expression was closely related to the clinical stage of HL (P=0.004) and to the International Prognostic Index score, mediastinal lesions, and clinical stages of NHL (P=0.01, 0.03, and 0.01). The expression of HA117 in WT was higher than in adjacent normal tissues, but there was no statistical significance (P=0.21). The positive expression of HA117 in NB was markedly higher than that in normal tissues (P=0.002), which closely associated with histologic type and lymph node metastasis (P=0.03 and 0.001). Spearman correlation analysis revealed that HA117 expression was not correlated with P-gp in these 4 tumors. This suggests that HA117 might be an important resistance gene in pediatric solid tumors. The mechanism underlying the resistance to all-trans retinoic acid conferred by HA117 is different from that of P-gp.

Topics: Adolescent; Antineoplastic Agents; Child; Child, Preschool; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Hodgkin Disease; Humans; Kidney Neoplasms; Lymphoma, Non-Hodgkin; Male; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Nervous System Neoplasms; Neuroblastoma; Tretinoin; Wilms Tumor

The prognosis for patients with Hodgkin lymphoma (HL) has improved in recent decades. On the other hand, not all patients can be cured with the currently established therapy regimes and this therapy is associated with several adverse late effects. Therefore it is necessary to develop new therapy strategies. After treatment of L-540 HL cells with 5'-azacytidine (5AC), we observed increased expression of the preferentially expressed antigen in melanoma (PRAME). In addition, we detected an increased resistance of 5AC-treated cells against cytotoxic drugs. We analyzed the influence of PRAME on cell survival of HL cells by knocking down PRAME in the chemotherapy resistant cell line L-428, a cell line that express PRAME at a high level. After knock-down of PRAME using vector based RNA interference we observed increased sensitivity for cisplatin, etoposide and retinoic acid. DNA microarray analysis of HL cells after PRAME knock-down indicated regulation of several genes including down-regulation of known anti-apoptotic factors. Increased retinoic acid signaling in these cells was revealed by increased expression of the retinoic acid metabolizing cytochrome P450 (CYP26B1), a transcriptional target of retinoic acid signaling. Our data suggest that PRAME inhibits retinoic acid signaling in HL cells and that the knock-down of PRAME might be an interesting option for the development of new therapy strategies for patients with chemo-resistant HL.

Topics: Antigens, Neoplasm; Antineoplastic Agents; Apoptosis; Azacitidine; Cell Line, Tumor; Cytochrome P-450 Enzyme System; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Hodgkin Disease; Humans; Retinoic Acid 4-Hydroxylase; RNA Interference; Signal Transduction; Tretinoin

The authors report a case of therapy-related acute promyelocytic leukemia (t-APL), with typical cytogenetic translocation t(15;17), which appeared following chemotherapy (ABVD), and radiotherapy for Hodgkin's disease (IIB). After treatment with all-trans retinoic acid (Vesanoid(R) 45 mg/m2 daily) complete remission of t-APL was achieved. Then only one course of chemotherapy '3+7' (doxorubicin 45 mg/m2 1-3 d, cytosar 200 mg/m2 1-7d) was applied and the patient interrupted further treatment in July 1994. Four years later she had a normal pregnancy and delivered a healthy female infant in December 1998.

Topics: Adolescent; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Leukemia, Promyelocytic, Acute; Neoplasms, Second Primary; Pregnancy; Pregnancy Outcome; Treatment Outcome; Tretinoin; Vinblastine

The neoplastic Hodgkin's Reed-Sternberg (H-RS) cells in Hodgkin's disease are surrounded in vivo by abundant reactive cells, the function of which may be attributed in part to their elaboration of various cytokines. Thus, a study of the interaction of H-RS cells with exogenous cytokines may provide information as to the mechanism of the clinical and histopathologic changes observed in Hodgkin's disease. This study examined the effect of various cytokines, and of phorbol ester (TPA) and retinoic acid, on the differentiation and proliferation of cultured H-RS cells (cell lines HDLM-1 and KM-H2). In addition, it was determined whether these cells were able to secrete cytokines after being treated with exogenous cytokines. The cytokines used included various types of interleukins (1, 2, and 3), colony-stimulating factors (GM, G, and M), interferons (alpha, beta, and gamma), and tumor necrosis factor (alpha). It was found that these cytokines, used alone or in combination, were not effective in modulating the proliferation and differentiation of cells, or the production of cytokines, in cultured H-RS cells. In contrast, this study revealed that retinoic acid can potentiate TPA-induced growth inhibition in cultured H-RS cells. Retinoic acid, when used alone, exhibited a minimal effect on cell differentiation. No synergistic effects of cytokines and retinoic acid on H-RS cells were observed. The failure of cultured H-RS cells to respond to exogenous cytokines suggests that, during the course of neoplastic transformation, of progression of disease, or of establishment of the cells in culture, H-RS cells lose their dependence on cytokines, although they retain the capacity to produce various cytokines.

Topics: Aged; Biological Factors; Cell Line; Cell Transformation, Neoplastic; Colony-Stimulating Factors; Cytokines; Hodgkin Disease; Humans; Interferons; Interleukins; Lymphoma; Male; Phorbol Esters; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Necrosis Factor-alpha

Two Hodgkin's Reed-Sternberg cell (H-RS) lines, HDLM-1 and KM-H2, have phenotypes and functional properties very similar to those of H-RS cells in tissues. These two types of cells were induced to differentiate with a combination of phorbol ester, retinoic acid, and extracellular matrix. The induced cells displayed the morphology of histiocytes or histiocytelike cells, with a small, round or oval, eccentric nucleus and abundant cytoplasm. In ultrastructural studies, many cytoplasmic projections and rugae were observed. These induced cells exhibited abundant cytoplasmic lysosomal enzymes, such as esterase, acid phosphatase, alpha 1-antitrypsin, or lysozyme. The histiocytic nature of these induced cells was further confirmed by the increased expression of many monocyte/histiocyte markers, including CD11b, CD11c, CD13, CD14, CD15, CD33, CD68, Mac387, and 1E9. In functional tests, the induced cells were shown to produce interleukin-1, tumor necrosis factor, macrophage colony-stimulating factor, and/or prostaglandin E2. Phagocytosis was detected in less than 5% to 10% of the cells when Candida albicans was added to cultures. The results strongly suggest that H-RS cells are related to cells of histiocyte lineage.

Topics: Adult; Antigens, Differentiation; Antigens, Neoplasm; Arachidonic Acids; Biological Factors; Cell Transformation, Neoplastic; Cytokines; Extracellular Matrix; Gene Rearrangement; Histiocytes; Hodgkin Disease; Humans; Ki-1 Antigen; Lymphocytes; Male; Phagocytosis; Phenotype; Tetradecanoylphorbol Acetate; Tretinoin; Tumor Cells, Cultured

Topics: Hodgkin Disease; Humans; Leukemia, Promyelocytic, Acute; Tretinoin