ABSTRACT
The PRAME gene encodes an antigen recognized by autologous T lymphocytes and is expressed in trophoblasts, testis and frequently in human solid cancers and acute leukemias, making it a candidate for immunotherapy and for detecting MRD. We demonstrate expression of PRAME by RT-PCR in the peripheral blood or bone marrow of 26% of 58 patients with CLD (38 cases of CLL, 4 cases of PLL and 16 cases of NHL). Seven out 16 cases of MCL, 2 out 4 of PLL and 6 cases of CLL demonstrated some degree of gene expression. Thus, CLD are among the hematopoietic malignancies for which PRAME may be the target of immunological therapy or used to evaluate MRD. The stronger and more frequent expression of PRAME in MCL is apparently an additional distinguishing feature on this group of lymphoproliferative disorders.
Subject(s)
Antigens, Neoplasm/biosynthesis , Lymphoproliferative Disorders/metabolism , Antigens, Neoplasm/genetics , Chronic Disease , Gene Expression Regulation , Humans , Immunophenotyping , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Leukemia, Prolymphocytic/genetics , Leukemia, Prolymphocytic/metabolism , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/metabolism , Lymphoproliferative Disorders/genetics , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Treatment with interferon-alpha is effective for chronic myelogenous leukemia in the chronic phase (CML-CP), but the immunological mechanisms of the antileukemic effect of this substance are still unclear. The objective of this study was to investigate the immunological effects of interferon-alpha in CML patients. Markers of cellular activation and apoptosis, natural killer (NK) cell cytotoxicity and production of intracellular cytokines (IFN-gamma, IL-2 and IL-4) were determined by flow cytometry in the peripheral blood mononuclear cells (PBMC) of 26 CML-CP patients before and 3, 6 and 9 months after IFN-alpha treatment. The results were correlated with the hematological response. In the whole group of patients, INF-alpha use was followed by a significant increase of lymphocytes producing IL-2 and IFN-gamma, an increase in NK activity and a decrease in the number of CD34+ cells. Out of 26 CML patients, 15 achieved hematological remission and 7 achieved partial cytogenetic remission after 9 months of IFN-alpha treatment. There was an increase in the percentage of CD8/FasL+, DR/CD3+, DQ/CD3+, CD34/Fas+, DR/CD56+, CD56/FasL+ cells and of IFN-gamma- and IL-2-producing lymphocytes and an increase in NK cytotoxicity only in the group of patients who achieved complete hematological remission. Our results indicate that IFN-alpha use in CML-CP reduces the number of CD34+ cells, activates T cells, enhances stem cell apoptotic markers and increases the production of intracellular IFN-gamma and IL-2 by lymphocytes. Taken together, these results indicate that the therapeutic effect of IFN-alpha in CML-CP is mediated at least in part by immunological mechanisms.
Subject(s)
Interferon-alpha/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Adult , Antigens, CD34/biosynthesis , Apoptosis , Cytokines/biosynthesis , Cytokines/metabolism , Female , Flow Cytometry , Humans , Immunophenotyping , Interferon-gamma/blood , Interleukin-2/blood , Interleukin-4/blood , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , Remission Induction , Reverse Transcriptase Polymerase Chain Reaction , Stem Cells/immunology , Time FactorsABSTRACT
Procurou-se neste trabalho comparar o efeito da administraçäo de GnRH utilizando-se a via endovenosa (E.V.) e subcutânea (S.C.) em 2 pacientes com amenorréia por deficiência de GnRH. Os resultados mostram que ocorreu a ovulaçäo nas duas pacientes quando se utilizou a via E.V. e nenhuma das duas vezes quando se utilizou a via S.C.. Os resultados sugerem que doses maiores seräo necessárias quando se usa a via S.C., aumentando o custo e duraçäo do tratamento, embora esta via de administraçäo seja mais cômoda e fácil de ser usada
Subject(s)
Adult , Humans , Female , Amenorrhea/drug therapy , Gonadotropin-Releasing Hormone/administration & dosage , Ovulation Induction , Follicle Stimulating Hormone/blood , Injections, Intravenous , Injections, Subcutaneous , Luteinizing Hormone/bloodABSTRACT
Os autores descrevem o uso de uma bomba pulsátil de infusäo para injeçäo de LHRH como um método de induçäo da anovulaçäo especialmente indicado para pacientes portadoras de anovulaçäo crônica hipotalâmica