Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic changes found in human osteogenic sarcoma cells, including loss of the p53 and Rb tumor suppressor elements and overexpression of the cyclin G1 (CYCG1) proto-oncogene, suggest the potential of gene transfer as a treatment for metastatic disease. In this study, we examined the effects of antisense cyclin G1, in comparison with antisense cyclin D1 (CYCD1) and enforced expression of the universal cyclin-dependent kinase inhibitor p21WAF1/CIP1 on the proliferation of human MG-63 osteosarcoma cells. Retroviral vectors bearing antisense CYCG1 as well as antisense CYCD1 and WAF1/CIP1 (in sense orientation) driven by the Moloney murine leukemia virus long terminal repeat promoter inhibited the growth and/or survival of transduced MG-63 cells in 2-7 day cultures. This represents the first demonstration that cyclin G1 is essential for the survival and/or growth of human osteosarcoma cells. Cytostatic and cytopathic effects were accompanied by a significant increase in the incidence of apoptosis, as determined by immunocytochemical analysis of DNA fragmentation. Furthermore, transduction of MG-63 cells with a retroviral vector bearing the suicide gene, herpes simplex thymidine kinase (HStk), induced cell death on treatment with ganciclovir, exhibiting pronounced bystander effects. Taken together, the data affirm the feasibility of modulating inducible cell cycle control enzymes as a potential gene therapy approach in the clinical management of osteogenic sarcoma.
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PMID:Retroviral vector-mediated gene transfer of antisense cyclin G1 (CYCG1) inhibits proliferation of human osteogenic sarcoma cells. 758 20

TREB5 (hXBP-1) protein is a transcription factor that recognizes the CRE-like element in enhancers of human T-cell leukemia virus and MHC class II gene and activates their transcription. TREB5 is a member of the CREB/ATF family, containing a basic amino acid region and leucine zipper structure (b-Zip structure). To characterize the key domain of TREB5 for transcriptional activation, mutational analysis was carried out. The C-terminal region of 148-221 amino acids was identified as an activation domain and was also active when fused to Gal4 DNA binding domain. This domain contains three unique regions rich in glutamic acid, glutamine, or serine/threonine and is active in both osteosarcoma (HOS) and T (Jurkat) cell lines. All of these three regions are essential; however, a part of the serine/threonine region was dispensable in Jurkat, but not in HOS cells. In addition to the activation domain, the N-terminal region showed activity in conjunction with the b-Zip structure, but not with the Gal4 DNA binding domain. Furthermore, this region showed activity in Jurkat cells, but not in HOS cells. These results suggest that TREB5 has two activational functions in transcription and may provide diversity in cell-type-specific transcriptional activation, possibly through dimerization with other b-Zip proteins and phosphorylation.
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PMID:Identification of transcriptional activation domain of TREB5, a CREB/ATF family protein that binds to HTLV-1 enhancer. 760 16

The principles of cancer chemotherapy applied to adult patients today have been substantially derived from experience of cancer in children. Studies of pediatric solid tumors also provided the first evidence that chemotherapy combined with surgery and/or radiotherapy could markedly enhance the curative potential of these local modalities. Conceptual advances in cancer chemotherapy revealed the superiority of intermittent chemotherapy over continuous low-dose therapy with respect to tumor cell kill and the recovery of normal cells. Childrens' Cancer and Leukemia Study Group of Japan applied intensive intermittent chemotherapy for maintenance therapy for leukemia, malignant lymphoma and to adjuvant chemotherapy for solid tumors. Event-free survival rate in treatment of childhood cancer by the Department of Pediatrics, Aichi Medical University, has markedly improved: ALL, 70%; malignant lymphoma, 50%; ANLL, 33%; hepato-blastoma, 100%; osteosarcoma, 65%; neuroblastoma, 54%; and rhabdomyosarcoma, 51%. The 14% rate for brain tumors was the only exception. Current Phase I and II trials based on pharmacokinetics and pharmacodynamics in children were reviewed.
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PMID:[Current status in treatment of childhood cancer]. 766 60

24-Oxa-vitamin D3 (24-oxa-D3) and 24-oxa-1 alpha-hydroxyvitamin D3 were designed as possible inhibitors of the vitamin D metabolic activation pathway. Their affinity for the vitamin D receptor (from pig intestine) and human vitamin binding protein were reduced, and their potency to induce cell differentiation of human leukemia cells (HL 60) or osteosarcoma cells (MG 63) was markedly reduced (19% and 3%, respectively), in comparison with calcitriol. A single or chronic injection of 24-oxa-D3 had no biological activity, whereas chronic administration of 24-oxa-1 alpha-hydroxy-D3 showed weak agonist activity in rachitic chicks. When the 24-oxa-D3 was given prior to a single injection of vitamin D3, lower values of serum calcium (64% of the value obtained in vitamin D-treated animals), osteocalcin (52%), 25-(OH)D3 (45%) and duodenal calbindin-D 28K (9.4%) were found. When given chronically in a 100-fold more excess no clear antagonistic effects were observed. 24-Oxa-D3 is thus a new metabolic weak antagonist of vitamin D3, but adding a hydroxyl group at C-1 creates a weak agonist.
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PMID:Antagonistic activity of 24-oxa-analogs of vitamin D. 767 83

The presence of a high number of activated T cells in the bloodstream and spontaneous proliferation of peripheral blood mononuclear cells in vitro are striking characteristics of human T-cell leukemia virus type I (HTLV-I) infection. The HTLV-I regulatory protein Tax and the envelope protein gp46 have been implicated in mediating the activation process. In this study, HTLV-I-producing cell lines and purified virus from the cell lines were examined for the ability to activate peripheral blood lymphocytes (PBLs) and Jurkat cells. Antisera and monoclonal antibodies against several cellular adhesion proteins involved in T-cell activation and against viral proteins were used to identify which molecules may be participating in the activation process. First, neither virus from a T-cell line, MT2, nor virus produced from the human osteosarcoma cell line HOS/PL was able to induce PBLs to proliferate. In contrast, both fixed and irradiated HTLV-I-producing T-cell lines induced proliferation of PBLs; HOS/PL cells did not activate PBLs. Second, HTLV-I-positive T-cell lines were capable of activating interleukin-2 mRNA expression in Jurkat cells. Induction of interleukin-2 expression was inhibited by anti-CD2 and anti-lymphocyte function-associated antigen 3 (LFA-3) monoclonal antibodies but not anti-human leukocyte antigen-DR, anti-CD4, anti-LFA-1, or anti-intercellular adhesion molecule 1. Similar results were obtained with PBLs as the responder cells. Furthermore, monoclonal antibodies and antisera against various regions of the HTLV-I envelope proteins gp46 and gp21 as well as p40tax did not block activation. These data indicate that HTLV-I viral particles are not intrinsically mitogenic and that infection of target T cells is not necessary for activation. Instead, the mitogenic activity is restricted to virus-producing T cells, requires cell-to-cell contact, and may be mediated through the LFA-3/CD2 activation pathway.
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PMID:The mitogenic activity of human T-cell leukemia virus type I is T-cell associated and requires the CD2/LFA-3 activation pathway. 768 60

The 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolinediones proved to be cytotoxic against the growth of a number of cell lines, including murine and human leukemias. HeLa suspended carcinoma, colon adencarcinoma SW480, KB nasopharynx and glioma tumors. Selected compounds were also active in the human lung bronchogenic MB-9812, and osteosarcoma TE418 screens. These derivatives were active in vivo in the Ehrlich ascites carcinoma screen in CF-1 mice at 8 mg/kg/day I.P. The mode of action in Tmol3 leukemia cells showed that the compounds reduced de novo synthesis of purines and pyrimidines and inhibited dihydrofolate reductase and ribonucleoside reductase activities. The DNA molecule was not a target although limited DNA strand scission may be possible.
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PMID:The cytotoxic activity of 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolidinediones. 773 34

We report here on the construction and use of a novel human immunodeficiency virus (HIV) type 1 reporter vector, HIV-AP, that encodes human placental alkaline phosphatase. Upon staining with chromogenic alkaline phosphatase substrates 24 to 36 h postinfection, cells infected with HIV-AP develop an intense purple color and can then be counted under a dissecting microscope. Alternatively, HIV-AP infectivity can be quantitated and infected cells can be sorted by a fluorescence-activated cell sorter after staining with a fluorescent alkaline phosphatase substrate. The assay is rapid and accurate, has very low background in a variety of cell lines and primary cells, and is not restricted to use in human cells. Infectious HIV-AP can be pseudotyped by various HIV or murine leukemia virus envelope glycoproteins. Using this virus, we have addressed the long-standing question of CD4-independent infection of cells by HIV. Our results confirm the presence on a human osteosarcoma cell line of an alternative receptor for HIV infection that functions with an efficiency approximately 1/20 that of CD4.
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PMID:Use of a novel human immunodeficiency virus type 1 reporter virus expressing human placental alkaline phosphatase to detect an alternative viral receptor. 776 29

N-Substituted indan-1.3-diones have proven to be potent cytotoxic agents effective against the growth of single cell leukemia tumors and cell lines derived from solid tumors. A number of the derivatives were active against growth of solid tumors e.g. colon, lung bronchogenic and osteosarcoma for which few effective agents are available to inhibit their growth. These agents inhibited DNA and RNA synthesis of L1210 cells. The de novo purine synthetic pathway was inhibited at PRPP amido transferase and IMP dehydrogenase. The pyrimidine synthetic pathway was inhibited at aspartate transcarbamylase. Other sites which demonstrate minor inhibition were DNA polymerase alpha, r- and t-RNA polymerase, ribonucleoside reductase, dihydrofolate reductase, nucleoside kinases and thymidylate synthetase. In addition d(NTP) pool levels were reduced by the drugs. L1210 DNA strand scission was evident after exposure to drugs for 24 hr. at 100 microM.
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PMID:Cytotoxicity and mode of action of substituted indan-1, 3-diones in murine and human tissue cultured cells. 784 49

Adjuvant chemotherapy is currently employed in the treatment of patients with osteosarcoma, but the drug regimens, although effective in improving disease-free survival, are unsuccessful in 20-40% of patients and very toxic. It would be useful to know whether tumor cells are sensitive to a given drug prior to its use. To this end, we developed a method of assessing Adriamycin (doxorubicin) binding to tumor nuclei as a possible means of detecting sensitivity to the drug. Adriamycin-sensitive murine osteosarcoma cells were used to develop the assay. The in vitro conditions (drug concentration, duration of incubation, and temperature) were optimized with use of the murine osteosarcoma cells in culture. After the cells had been incubated with Adriamycin, cell viability was determined and Adriamycin fluorescence intensity was measured with a cytofluorometer. The optimal parameters for Adriamycin binding were found to be a 30-minute incubation in a 10 micrograms/ml concentration of Adriamycin at 37 degrees C; the frequency of cells that emitted Adriamycin fluorescence from the nucleus compared with the total number of living cells reached 100% under these conditions. In a murine leukemia cell line with known sensitivity to Adriamycin, the cells emitted red fluorescence from the nucleus and cytoplasm, whereas in a resistant line the cells emitted Adriamycin fluorescence from only the cytoplasm. We demonstrated that it is possible to differentiate nuclear from cytoplasmic concentration of Adriamycin in a tumor cell with use of a fluorescent microscope and that resistant cell lines can be distinguished from sensitive cell lines by this method.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An assay to measure adriamycin binding in osteosarcoma cells. 793 78

The surveillance, epidemiology, and end-results (SEER) data on 5-year relative survival rates (1973-1987) for the most common pediatric tumors (ages 0-14) were analyzed. The SEER data are population based, so the observed progress in survival from childhood cancer represents the real impact that development in cancer treatment had on the population followed by the registry. The greatest increase in survival rate from 1973 until 1987 has been achieved in hematopoietic tumors such as acute lymphocytic leukemia (ALL), in which survival increased from 47.6% (1973-1977) to 60.8% (1983-1987), and Burkitt's lymphoma in which survival increased from 27.6% (1973-1977) to 68.7% (1983-1987). Solid tumors showed a less steep, but steady increase in survival rates. Flattening in the survival rates since 1978-1982 has been observed for acute leukemia, astrocytoma, medulloblastoma, and osteosarcoma. Females have better survival rates for most pediatric tumors, except Hodgkin's disease. Analysis of race of childhood leukemia confirmed that black children have worse survival than white. When solid tumors were analyzed by stage at presentation, there was no indication that diagnosis in earlier stages of disease accounted for the improved survival. Observed flattening in the survival rates since 1978-1982 of leukemia and some solid tumors warrants further follow-up.
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PMID:U.S. childhood cancer survival, 1973-1987. 793 74


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