Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A primate (Macaca speciosa) antiserum prepared against the human chronic myelogenous leukemia cell line K-562 suppressed the growth of the human myelosarcomas in nude mice. The ip administration of 0.5 ml of immune serum plus 0.5 ml of guinea pig complement, starting 7 days after sc tumor transplantation, resulted in a fourfold to fivefold decrease in tumor weight at 15 days when compared to nude mice given pre-immune serum plus complement or complement alone. Whereas the other two groups experienced an exponential increase in tumor volume at 7-9 days after tumor transplantation, the immune serum-treated mice remained in a "lag" phase of tumor growth during which the tumor volume neither increased nor decreased substantially. Histopathologic studies revealed various degrees of tumor alterations ranging form focal hydropic cellular degeneration to massive coagulation necrosis. The incorporation of tritiated thymidine into the tumors was also markedly diminished in the mice given immune serum.
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PMID:Suppression of human myelosarcoma growth in athymic mice by a primate antiserum. 27 18

The present results suggest that some T-cell activities of syngeneic chimeric mice such as T-cells involved in the antibody response to SRBC and MLC reaction are intact. On the other hand, suppressor T-cells involved in the regulation of the immune response to PVP and enhancement of 3LL tumor growth, and cells mediating CML reaction are damaged.
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PMID:Depletion of suppressor T cells in syngeneic chimeric mice. 108 56

Implantation of genetically manipulated fibroblasts is now coming considered to be one of the important methods for gene therapy. Before the clinical application of this method, we still need to resolve several problems encountered. We have recently developed a model system for the fibroblast-mediated cytokine supplementation gene therapy. BMGNeo (bovine papilloma virus-derived plasmid) (gifted from Dr. Karasuyama) was used for expression of hG-CSF cDNA or hIFN-alpha cDNA (gifted from Dr. Nagata). The two plasmid DNAs (BMGNeoG-CSF and BMGNeoIFN) were individually transfected into NIH/3T3 fibroblasts by the calcium phosphate coprecipitation method. Cell clones producing a large amount of G-CSF or IFN-alpha were selected by the enzyme immunoassay methods and were called G-CSF3T3 or IFN3T3 respectively. Nude mice implanted with G-CSF3T3 highly produced G-CSF in vivo. Remarkable increases in both blood neutrophils and spleen hematopoietic stem cells/progenitor cells (CFU-S, BFU-E, CFU-E, CFU-GM and CFU-MK) were observed. To regulate the production of G-CSF by G-CSF3T3 in vivo, we developed a diffusion chamber system as the cells can be treated easily. We could control the peripheral neutrophil count in nude mice. In the same manner, IFN3T3 was implanted in nude mice bearing a CML cell line, KU812. KU812 tumor growth was significantly suppressed by implantation of IFN3T3 into the chamber. The fibroblast-mediated cytokine supplementation gene therapy might be useful for the treatment of patients requiring for continuous dosing of cytokines.
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PMID:[Implantation of genetically manipulated fibroblasts into mice as a model of gene therapy--supplementations of human granulocyte colony-stimulating factor (hG-CSF) and interferon-alpha (IFN-alpha)]. 165 96

Long-term parenteral administration of human alpha-interferon (HuIFN-alpha) is effective in the treatment of several malignancies, including chronic myelocytic leukemia. In the present study, a model for fibroblast-mediated HuIFN-alpha gene therapy for the treatment of chronic myelocytic leukemia is described. Human IFN-alpha 5 complementary DNA was inserted into a bovine papilloma virus plasmid vector (BMGNeo) containing a neomycin resistance gene. The recombinant plasmid (BMGNeo-IFN) was transfected into NIH/3T3 fibroblasts by the calcium phosphate coprecipitation method, and stably transformed cells were isolated by G418 selection. A fibroblast clone secreting a large amount of HuIFN into the culture supernatant was selected by radioimmunoassay using anti-HuIFN-alpha monoclonal antibodies. Southern blot analysis revealed that the transformed cells contained approximately ten copies of the BMGNeo-IFN plasmid per cell, and Northern blot analysis demonstrated high expression of HuIFN-alpha mRNA in the cells. This fibroblast clone strongly suppressed proliferation of a HuIFN-alpha-sensitive chronic myelocytic leukemia cell line (KU812) during cocultivation in vitro. When the HuIFN-alpha-producing fibroblasts were implanted into nude mice bearing KU812 tumors by the subcutaneous diffusion chamber method, tumor growth in vivo was also significantly suppressed. This study suggests the clinical potential of fibroblast-mediated gene therapy in the future.
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PMID:Implantation of genetically manipulated fibroblasts into mice as antitumor alpha-interferon therapy. 216 55

Primitive, high-proliferative potential hemopoietic progenitors can be routinely maintained for many weeks in long-term marrow cultures (LTC) in the absence of added hemopoietic growth factors. Nevertheless, these progenitors are clearly responsive to both positive and negative regulatory control mechanisms that operate within the adherent layer as evidenced by cyclic changes in their proliferative activity each time the medium is replaced. The key event appears to be the addition of a constituent of fresh horse serum that is not found in fetal calf serum. Analogous primitive neoplastic progenitor cell types from CML or PV patients are insensitive to the negative arm of this proliferation control mechanism both in vitro and in vivo. A model to explain the progenitor cell cycle changes normally observed in the LTC system is proposed. This model suggests that perturbations of nonhemopoietic mesenchymal cells determine the net positive or negative influence that these regulatory cells exert on adjacent primitive hemopoietic cells, possibly by a mechanism involving direct cell contact. Recently, we have identified a number of cytokines that can simulate the transient positive effect of fresh horse serum, as well as another cytokine, that is, tumor growth factor-beta (TGF-beta), that can mimic the negative but reversible effect exerted by mesenchymal cells. These studies demonstrating the effects of positive and negative regulatory cytokines on the control of hemopoiesis in the adherent layer of LTC suggest new approaches for analyzing the basis of both normal and abnormal stem cell regulation by marrow stromal elements.
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PMID:Maintenance and proliferation control of primitive hemopoietic progenitors in long-term cultures of human marrow cells. 322 86

Observations of cancer risk in irradiated human populations over time after exposure suggest that there are at least two, and perhaps more, very different patterns of temporal distribution of risk for radiation-induced cancer. The first, exemplified by bone sarcoma following therapeutic injection of 224Ra and chronic granulocytic leukemia in Japanese A-bomb survivors, is an early, wave-like pulse consisting of an increase in risk followed by a gradual decline back to baseline levels. The second, exemplified by breast cancer following a brief exposure to external gamma ray or X ray, and by lung cancer and stomach cancer in A-bomb survivors, is an increase in relative risk over about 10 years to a value which appears to remain constant over time thereafter. The first pattern suggests that tumor growth kinetics may play a central role in the temporal distribution of risk following exposure, while the second seems more consistent with multi-event models for carcinogenesis, in which radiation or some other cause of early events must be followed by one or more later events whose frequencies depend mainly on attained age. There are, however, other data that appear to conform to neither of the two models just mentioned. Influences of other cancer causes, like tobacco smoking, are potentially serious confounding factors in studies of induction period.
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PMID:Temporal distributions of risk for radiation-induced cancers. 331 74

In order to test the possibility that tumor-enhancing T lymphocytes can suppress other lymphoid cells, such as those with anti-tumor activity, their effect was tested in an allogeneic response of cell-mediated lysis. Normal thymocytes and spleen cells from mice with advanced tumors, two populations which enhance the growth of solid tumors, both suppressed the generation of CML. Since these results suggest that the mechanism of enhancement by T cells may resemble suppression in other immune responses, we looked for Fc receptors on the sensitized cells involved in tumor enhancement. Cells expressing Fc receptors appeared to be necessary for enhancement of tumor growth to occur.
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PMID:Tumor enhancing T lymphocytes in mice: further studies on characteristics and mechanism of activity. 697 22

The four kinds of plant polysaccharides, i.e., pachyman polysaccharides (PPS), Acanthopanax senticosus polysaccharides (ASPS), polysaccharides of tremella fuciformis (TF) and lentinan, have obviously inhibitory action against the animal tumor growth and have been applied to the treatment of cancer. The mechanism was that they could enhance the body immune function, but whether the tumor cells were killed is not clear. In this paper, the effects of the four plant polysaccharides on cell proliferation in mice sarcoma (ascitic type) S180 and human chronic myelogenous leukemia K562 cells were studied with MTT chromometry. Tt was found That TF and lentinan had no effect on both cell line, but PPS and ASPS could obviously inhibit the proliferation of them, the IC50 of PPS was 1.5mg/ml in both cell line, that of ASPS was 0.38 mg/ml (S180 cells) and 0.28mg/ml (K562 cells) respectively. This result indicated that the PPS and ASPS were able to kill the tumor cell directly. To investigate the mechanism of antitumor action of PPS and ASPS, the sialic acid (SA), phospholipid (PI) and cholesterol (Ch) contents of S180 cell membrane were examined after the PPS or ASPS application for 24 hours. No significant changes were observed for the Ch and Ch/Pl ratio, the amount of SA increased and that of PI lowered respectively (P < 0.05). The results suggested that the antitumor action of PPS and ASPS not only related to the action of enhancing the body immune function but also related to the changes of cell membrane.
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PMID:[Effects of plant polysaccharides on cell proliferation and cell membrane contents of sialic acid, phospholipid and cholesterol in S 180 and K 562 cells]. 784 57

The (3;21)(q26;q22) translocation associated with treatment-related myelodysplastic syndrome, treatment-related acute myeloid leukemia, and blast crisis of chronic myeloid leukemia results in the expression of the chimeric genes AML1/EAP, AML1/MDS1, and AML1/EVI1. AML1 (CBFA2), which codes for the alpha subunit of the heterodimeric transcription factor CBF, is also involved in the t(8;21), and the gene coding for the beta subunit (CBFB) is involved in the inv(16). These are two of the most common recurring chromosomal rearrangements in acute myeloid leukemia. CBF corresponds to the murine Pebp2 factor, and CBF binding sites are found in a number of eukaryotic and viral enhancers and promoters. We studied the effects of AML1/EAP and AML1/MDS1 at the AML1 binding site of the CSF1R (macrophage-colony-stimulating factor receptor gene) promoter by using reporter gene assays, and we analyzed the consequences of the expression of both chimeric proteins in an embryonic rat fibroblast cell line (Rat1A) in culture and after injection into athymic nude mice. Unlike AML1, which is an activator of the CSF1R promoter, the chimeric proteins did not transactivate the CSF1R promoter site but acted as inhibitors of AML1 (CBFA2). AML1/EAP and AML1/MDS1 expressed in adherent Rat1A cells decreased contact inhibition of growth, and expression of AML1/MDS1 was associated with acquisition of the ability to grow in suspension culture. Expression of AML1/MDS1 increased the tumorigenicity of Rat1A cells injected into athymic nude mice, whereas AML1/EAP expression prevented tumor growth. These results suggest that expression of AML1/EAP and AML1/MDS1 can interfere with normal AML1 function, and that AML1/MDS1 has tumor-promoting properties in an embryonic rat fibroblast cell line.
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PMID:The chimeric genes AML1/MDS1 and AML1/EAP inhibit AML1B activation at the CSF1R promoter, but only AML1/MDS1 has tumor-promoter properties. 857 11

This review considers the relationship between differentiation mechanisms and the genesis and maintenance of tumor phenotype. To a certain extent, carcinomas preserve differentiation markers of normal tissue, and hemoblastoses precisely reflect the direction and differentiation level of their precursor cells. Both tumor types retain the ability to differentiate. Mechanisms of T and B cell differentiation are reviewed considering the activation of protooncogenes by translocation to the region of tissue-specific genes including the immunoglobulin (Ig) and T cell receptor (TCR) genes. Apart from the classical oncogenes (MYC, PRAD, BCL-2), heterologous differentiation of trans-factors can be activated in a similar manner. Their activation at inappropriate time and place induces oncogenic transformation in a number of hemoblastoses. Chimeric genes and fused proteins are analyzed, including their genesis by specific translocation resulting in transformation and their role in differentiation and maintenance of the tumor phenotype. Induction of terminal differentiation in leukemia can have significant therapeutic effect. These hemoblastoses include hairy cell leukemia, promyelocytic leukemia, and in part chronic myeloid leukemia. Specific attention is given to the role of intercellular interactions in the control of tumor growth and maintenance of a differentiated state of the cells. It is suggested that alterations in these interactions during tumor progression simultaneously stimulate malignant growth and decrease differentiation level, thus inducing re-expression of embryonic antigens in the tumors.
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PMID:Differentiation mechanisms and malignancy. 1070 45


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