164 research outputs found
Potential of gene therapy in bone marrow transplantation
No full textGene therapy, initiated as a treatment for inherited disorders such as adenosine deaminase deficiency, is now a promising therapeutic strategy for malignancies and other acquired diseases. In particular, in the field of bone marrow transplantation (BMT) for haematological malignancies, the gene transfer of the suicide gene HSV-TK into donor lymphocytes allows control of the severe complication graft-versus-host disease (GVHD). The transfer of the HSV-TK suicide gene confers selective sensitivity to the drug ganciclovir, allowing in vivo elimination of the donor T-cells if severe GVHD occurs. In Italy, the first pilot study on delayed infusion of genetically engineered donor lymphocytes after T-depleted allogeneic BMT documented efficacy of engineered donor lymphocytes in terms of antitumour activity and efficiency of the suicide system. GVHD developed in 3 out of 8 patients and was successfully treated by ganciclovir administration
Suicide gene transduced for the regulation of the graft-versus-leukemia effect
No full textIn allogeneic marrow transplantation (BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia and immune reconstitution. However, their use is limited by the risk of severe graft-vs-host disease (GVHD). Different strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GVHD. In the first pilot study, infusions of donor lymphocytes transduced with the Herpes Simplex virus thymidine kinase (HSV-tk) suicide resulted in anti-tumor activity in 50% of patients. Acute GVHD could be effectively controlled by ganciclovir-induced elimination of the transduced cells. If these results will be confirmed in larger studies, genetic manipulation of donor lymphocytes will increase efficacy and safety of allogeneic marrow transplantation
Perancangan Sistem Informasi Penjualan Berbasis Web di PT. MARKTEL
No full textInformation systems are needed in every company to facilitate fast and accurate data processing. One of them is a sales information system currently used at PT. MARKTEL still has processes that have not been computerized. To meet these information needs, especially to deal with data processing problems, report generation and systems that have not worked as expected, companies need a computer-based information system. The system development method in this study uses the waterfall method which has a systematic and clear flow so that the system development is more detailed. The waterfall method is a structured modeling-based method consisting of Flowmaps, Context Diagrams, Level 0 Data Flow Diagrams (DFD) and Entity Relationship Diagrams (ERD). In designing and implementing the program, the author uses the PHP programming language with MySQL database. The existence of a web-based sales information system at PT.MARKTEL is expected to simplify and speed up data processing and report generation and can minimize errors so that company goals can be achieved optimally
Herpes simplex virus thymidine kinase gene transfer for controlled graft-versus-host disease and graft-versus-leukemia: Clinical follow-up and improved new vectors
No full textWe previously demonstrated that severe graft-versus-host disease (GVHD), associated with the therapeutic infusion of donor lymphocytes after allogeneic marrow transplantation (BMT), can be efficiently controlled by the SFCMM-2-mediated expression of the herpes simplex virus thymidine kinase (HSV-tk) suicide gene into the allogeneic lymphocytes. This was achieved by selective elimination of transduced lymphocytes by ganciclovir (GCV) infusion. Despite the positive results of the pilot clinical trial, two vector-related limitations were observed. The induction of a strong immune response against genetically modified cells was observed in two patients. In addition, the only patient who developed chronic GvHD showed only partial response to ganciclovir treatment. In an attempt to overcome these limitations, we developed a new generation of vectors. The neomycin resistance (neo(R)) gene was removed from the SPCMM-3 and SFCMM-4 retroviral vectors. These vectors are less immunogenic and able to confer higher ganciclovir sensitivity to transduced human lymphocytes. All the vectors carry a modified form of the low-affinity nerve growth factor receptor cDNA, as cell surface selectable marker (Delta LNGFR). The vectors were compared in terms of gene transfer efficiency, and ability to confer high and specific sensitivity to ganciclovir. The SFCMM-3 vector, carrying the entire HSV-tk gene driven by the LTR promoter, allows efficient transduction of human T lymphocytes and confers the highest GCV sensitivity to transduced lymphocytes with a high and a low proliferation index. The expression of the Delta LNGFR marker allows an easier in vitro manipulation and a faster immune selection of transduced cells compared with neo(R) selection. Finally, the elimination of the neo(R) gene removes a potent immunogen from transduced lymphocytes
When diagnostics meets translational research : detection of hemoglobin fractions in cellular lysates from in vitro erythroid cultures by Capillarys 2 Flex Piercing analyzer (Sebia)
No full textDetection of hemoglobin (Hb) variants represents an important issue for diagnosis and adequate treatment of hemoglobinopathies. The Capillarys 2 Flex Piercing analyzer (Capillarys) by Sebia is routinely used in our clinical laboratories to detect Hb variants in peripheral blood (PB). This automated method separates Hb fractions by capillary electrophoresis, giving a spectrophotometric measure of their relative proportion. The scientific research in the field of hemoglobinopathies needs robust procedures to evaluate the efficacy of experimental therapies, as gene therapy. We investigated for the first time the feasibility to use Capillarys on cellular lysates from in vitro erythroid cultures. Because total Hb concentration in erythroid lysates is up to 20-fold lower than in hemolysates from PB, we analyzed diluted blood samples, thanks to the manual mode included in the Capillarys setting. We compared analytical precision, accuracy, sensitivity, and specificity of this procedure to the automatic method, routinely used in diagnostics. For instance, adult Hb intra- and interassay precision were estimated as coefficient of variation 0.2% and 0.3%, respectively. The manual mode is less robust for detection of fractions <3% and the lower level of sensitivity is 2 g/L of total Hb. Specificity of manual and automatic settings was equivalent. We confirmed the performance of the method by analyzing erythroid lysates from thalassemic patients' cultures. Our study demonstrated that the Capillarys 2 Flex Piercing manual method is comparable to the automatic one. The analysis is very robust at low Hb concentrations, as in erythroid cultures from patients affected by hemoglobinopathies, representing a useful tool also in translational research
Hematopoietic stem cell gene therapy for adenosine deaminase deficient-SCID
No full textGene therapy is a highly attractive strategy for many types of inherited disorders of the immune system. Adenosine deaminase (ADA) deficient-severe combined immunodeficiency (SCID) has been the target of several clinical trials based on the use of hematopoietic stem/progenitor cells engineered with retroviral vectors. The introduction of a low intensity conditioning regimen has been a crucial factor in achieving stable engrafment of hematopoietic stem cells and therapeutic levels of ADA-expressing cells. Recent studies have demonstrated that gene therapy for ADA-SCID has favorable safety profile and is effective in restoring normal purine metabolism and immune functions. Stem cell gene therapy combined with appropriate conditioning regimens might be extended to other genetic disorders of the hematopoietic system
Locoregional intrasplenic chemotherapy for hypersplenism in myelofibrosis
No full textA 79-year-old patient with post-polycythaemic myelofibrosis presented with severe hypersplenism. After splenic artery catheterization, cytosine arabinoside was given intrasplenically from November 1999 to March 2000 for 5 d/month at 10 mg/m2 and increased each month by 10 mg/m2. It was then administered by continuous infusion until June 2000, starting at 20 mg/m2/d and tapering by 5 mg/m2 every 2 weeks to a final daily dose of 5 mg/m2/d. The drug was then stopped. The spleen had decreased to one third of the initial volume. Clinical conditions and haematological indices improved substantially. Intrasplenic therapy could be a new therapeutic tool for hypersplenism in chronic idiopathic and post-myeloproliferative myelofibrosis
Locoregional intrasplenic chemotherapy for hypersplenism in myelofibrosis
No full textA 79-year-old patient with post-polycythaemic myelofibrosis presented with severe hypersplenism. After splenic artery catheterization, cytosine arabinoside was given intrasplenically from November 1999 to March 2000 for 5 d/month at 10 mg/m(2) and increased each month by 10 mg/m(2). It was then administered by continuous infusion until June 2000, starting at 20 mg/m(2)/d and tapering by 5 mg/m(2) every 2 weeks to a final daily dose of 5 mg/m(2)/d. The drug was then stopped. The spleen had decreased to one third of the initial volume. Clinical conditions and haematological indices improved substantially. Intrasplenic therapy could be a new therapeutic tool for hypersplenism in chronic idiopathic and post-myeloproliferative myelofibrosis
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