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)

Difluoromethylornithine (DFMO), a specific, irreversible, enzyme-activated inhibitor of ornithine decarboxylase activity, the first and rate-limiting step in polyamine biosynthesis, has been shown to inhibit neoplastic cell proliferation in culture. In most cases, such inhibition is not accompanied by cell loss, with the exception of multiple cell lines of human small cell lung carcinoma (SCC), a human leukemia cell line (HL-60), and possibly the B16 melanoma cell line. The first two cell types grow as anchorage-independent suspension cultures, the HL-60 as single cells and the SCC as multicellular spheroid aggregates. Moreover, in the spectrum of human lung carcinoma cells in culture, the SCC cells respond in a cytotoxic manner to DFMO, whereas the non-small cell lung carcinoma (non-SCC) cells, which are anchorage dependent, show only growth inhibition, without actual cell loss. In the present study, we have investigated relationships between anchorage-dependent and -independent growth patterns of cells in culture and their response to DFMO treatment. Two non-SCC lung cancer cell lines, which normally grow as anchorage-dependent monolayers, show growth inhibition but no cell loss with the addition of DFMO. When these anchorage-dependent cells were forced to grow as multicellular aggregates, by coating the culture flask with Teflon, the cells developed an increased sensitivity to DFMO. They showed not only inhibition of cell proliferation but also cell death. Two SCC cell lines, which normally grow as anchorage-independent spheroids, developed adherence to the culture dishes coated with fibronectin. These cells, which show a cytotoxic response to DFMO during normal anchorage-independent growth, developed a decreased sensitivity to DFMO, showing only cell growth inhibition, but no cell death when treated during anchorage-dependent growth. Our data thus suggest that the state of anchorage dependence of lung cancer cells in culture is a critical factor in determining their response to polyamine depletion during treatment with DFMO.
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PMID:Anchorage dependency effects on difluoromethylornithine cytotoxicity in human lung carcinoma cells. 300 7

We have immortalized rat central nervous system (CNS) cells of primary cultures of rat optic nerve with murine leukemia virus psi-2,SV-40-6, which is defective in assembly and contains the SV-40 large T antigen and neomycin resistance genes, to produce a cell line that we named A7. After drug selection, greater than 90% of the growing cells expressed nuclear SV-40 large T cells and a fraction of these contained the astrocyte-specific marker, glial fibrillary acidic protein. The majority of these cells also expressed surface marker A4 (specific for neural tube derivatives), Ran 2, p185 (the 185-kD phosphoprotein product of the neu oncogene), and fibronectin, but did not express the astrocyte enzymes glutamine synthetase and monoamine oxidase B. Surface markers characteristic of glial progenitors (A2B5) and oligodendrocytes (galactocerebroside) were not detected. After two rounds of cell cloning, subclone A7.6-3 expressed Ran 2, fibronectin, and the neural cell adhesion molecule (N-CAM) but not glial fibrillary acidic protein and A4. The A7 cell line and subclones also displayed certain functions of type 1 astrocytes: the conditioned medium of these cells had a potent mitogenic activity for glial progenitor cells which could be neutralized by anti-platelet-derived growth factor antibodies and monolayers of these cells supported the growth of embryonic hypothalamic neurons. We conclude that a retrovirus containing SV-40 large T antigen can immortalize rat CNS cells and that such immortalized glial cells retain at least two important functions of type 1 astrocytes: the ability to secrete platelet-derived growth factor and to support the growth of embryonic CNS neurons. Moreover, such stable immortalized clonal cell lines can be used to study gene regulation in glial cells.
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PMID:Antigenic and functional characterization of a rat central nervous system-derived cell line immortalized by a retroviral vector. 305 37

The specificity and sensitivity of malignancy marker determinations in cerebrospinal fluid (CSF) are often insufficient. Even at the subclinical stage of the disease the marker should be present. The effect of therapy should be monitored and relapses noted. Thus high standards of methodology are required. There are many substances that may indicate a malignant process in the central nervous system. However, there are many pitfalls in their determination. Malignant cells may occur in CSF via processes involving leptomeningeal structures such as metastases and leukaemia, but primary brain tumours seldom show cells in CSF. Human chorionic gonadotrophin and alpha-fetoprotein determinations assist in the early detection of cerebral germ cell tumours and of relapses, even in the subclinical stage. Desmosterol may aid in the diagnosis of medulloblastomas and malignant gliomas and in monitoring therapy. Putrescine levels are elevated in CSF of patients with medulloblastoma and correlate with the clinical state, and serial analyses may reveal relapses. Fibronectin, when determined in CSF at the time of diagnosis, appears to be of great significance for the prognosis of acute lymphoblastic leukaemia. Ferritin and beta-2-microglobulin may help in some well-defined conditions. Brain-specific proteins and antibodies to them are non-specific markers whereas tumour-specific antigens and growth factors may be more significant.
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PMID:Malignancy markers in the cerebrospinal fluid. 305 81

Plasma fibronectin concentration was determined by electroimmunodiffusion and laser nephelometry in 40 healthy persons and 321 patients with myelo- and lymphoproliferative diseases and other malignancies. Decreased fibronectin concentrations were found in patients with leukemia, Hodgkin's and non-Hodgkin's lymphomas, myelofibrosis, polycythaemia rubra vera and angioimmunoblastic lymphadenopathy. Elevated fibronectin level was detected in patients with multiple myeloma. In patients with cancer of the lung, stomach and colon, fibronectin level was found in the normal range. Decreased fibronectin concentration was observed in patients with cancer of the breast and prostate. Lower plasma fibronectin concentrations were detected in all groups of patients with infectious septical complications as compared to the patients without infections.
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PMID:[Determination of plasma fibronectin in myeloproliferative and lymphoproliferative diseases and other malignancies]. 308 43

The plasma levels of the opsonic glycoprotein fibronectin are decreased in patients with fulminant hepatic failure, which may be an important factor in their impaired host-defense. Twenty-nine patients in fulminant hepatic failure were studied on admission, and the mean fibronectin level in Grade 0-2 encephalopathy was 82 micrograms per ml (range = 0 to 150) and in Grade 3-4 encephalopathy 61 micrograms per ml (range = 5 to 158) as compared to normal controls (268 micrograms per ml, range = 178 to 380, n = 62). No fibronectin degradation products could be detected in fulminant hepatic failure plasma by sodium dodecyl sulfate-gel electrophoresis on a polyacrylamide gradient (5 to 15%) followed by immunoblotting onto nitrocellulose with detection using a rabbit antihuman fibronectin antiserum visualized with a peroxidase conjugate. The plasma levels of the marker proteolytic enzyme cathepsin D were significantly elevated in fulminant hepatic failure (120 +/- 31 mU per ml per hr) as compared to the normal controls (18 +/- 2.1 mU per ml per hr, n = 10, p less than 0.01). Cross-immunoelectrophoresis of fulminant hepatic failure plasma for fibronectin on agarose plates gave an additional slower migrating peak in 15 of the 29 patients, as well as that of fibronectin, which corresponded to the fibronectin complex reported by other workers in leukemia. An intermediate gel containing antihuman fibrinogen demonstrated fibrinogen to be one component of this complex. Binding of other substances to fibronectin will reduce its apparent biological activity and may be the result of their lack of clearance by the damaged liver.
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PMID:Characterization of the molecular forms of fibronectin in fulminant hepatic failure. 309 66

Plasma fibronectin and phagocytic activity play important roles in combating infections. The question is discussed, whether both defense systems are also of importance in immunosuppressed patients. Further, the behaviour of plasma fibronectin determined by laser nephelometry, and phagocytic activity determined by chemiluminescence is demonstrated in patients with leukaemia under the conditions of selective decontamination of the intestinal tract. The following results are shown: Plasma fibronectin concentration decreases 10 to 14 days before onset of the first clinical signs of an infection. Plasma fibronectin level changes appear earlier than that of C-reactive protein (Crp). Therefore, it is suitable as a parameter for assessment of the course of an infection. Decreased plasma fibronectin levels occurring over longer periods have to be regarded as unfavourable prognostic criterion. The phagocytic activity of immunosuppressed patients selectively decontaminated is significantly below that of healthy adults. A clear assignment of phagocytic activity to the clinical picture, the number of granulocytes and plasma fibronectin level is not possible at present. Additional studies are necessary. Both plasma fibronectin level and phagocytic activity do not appear to be influenced by selective decontamination of the intestinal tract.
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PMID:Changes of plasma fibronectin concentration and phagocytic activity in immunosuppressed patients during selective decontamination. 313 55

We have employed ethanol-fixed wax embedded sections of human breast tumours and smears of rat leukaemia cells to provide test systems with recognisable tumour cells amongst normal cells. We have used 9-aminoacridine to locate cells possesing guanidinobenzoatase, an enzyme which degrades fibronectin and which binds 9-aminoacridine to its active centre. The binding of 9-aminoacridine to tumour cells allows these cells to be located by fluorescent microscopy. Pre-treatment of these sections with BZAR, a known inhibitor of guanidinobenzoatase inhibited the binding of 9-aminoacridine to the tumour cells. These techniques defined the tumour cells in the sections; we then demonstrated by fluorescent microscopy that both Texas red-agmatine and BZAR also bound to the guanidinobenzoatase of these tumour cells. These fluorescent probes have been used as model compounds to illustrate the ability of both N-substituted agmatines and N-substituted arginines to deliver desired molecules to an enzyme on the surface of tumour cells. Replacement of these fluorescent moieties by cytotoxic moieties attached to the same ligands could lead to selective drug delivery to tumour cells.
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PMID:A fluorescent study of ligands for guanidinobenzoatase, a protease associated with tumour cells. 321 54

Guanidinobenzoatase is a proteolytic enzyme capable of degrading fibronectin and is a tumour associated enzyme. Guanidinobenzoatase has been shown to be an arginine selective protease and is distinct from trypsin, plasminogen activator, plasmin, thrombin and a newly described tumour associated enzyme specific for guanidino phenylalanine residues. These conclusions have been derived from inhibition studies employing 4-methyl-p-guanidinobenzoate as substrate. Three active site titrants for trypsin have been shown to be good substrates for guanidinobenzoatase. A new active site titrant for trypsin, rhodamine bisguanidinobenzoate, can also be used to assay guanidinobenzoatase in a stoichiometric manner. This active site titrant can be employed to label guanidinobenzoate on the surface of leukaemia cells.
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PMID:Further inhibition studies on guanidinobenzoatase, a trypsin-like enzyme associated with tumour cells. 333 44

Plasma fibronectin concentrations were measured in 49 patients with chronic myeloproliferative disorders and compared to sex- and age-matched controls. A significantly lower plasma fibronectin concentration was observed in patients with idiopathic myelofibrosis as compared with the control group (p less than 0.01). In addition, plasma fibronectin concentrations in myelofibrosis patients differed significantly, when compared with patients with polycythaemia vera (p less than 0.01), whereas no significant difference was found between myelofibrosis patients and those with a transitional myeloproliferative disorder or chronic myelogenous leukaemia (p greater than 0.05). An inverse relationship was demonstrated between plasma fibronectin and spleen size, the lowest plasma fibronectin levels being found in patients with large spleens. It is supposed that low plasma fibronectin concentrations in splenomegalic patients may be due to enhanced consumption of the opsonin in the expanded splenic mononuclear-macrophage system.
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PMID:Plasma fibronectin in idiopathic myelofibrosis and related chronic myeloproliferative disorders. 347 50

The platelet membrane glycoproteins IIb (GpIIb) and GpIIIa form calcium-dependent heterodimers containing binding sites for fibrinogen, von Willebrand factor, and fibronectin. Although GpIIb and GpIIIa are distinct proteins, both GpIIb and GpIIIa are deficient in platelets from individuals with the recessive disorder Glanzmann's thrombasthenia. To gain a better understanding of the genetic basis for GpIIb and GpIIIa synthesis, we studied their synthesis by two human leukemia cell lines, HEL and K562. HEL cells contained complexes of GpIIb and GpIIIa, and K562 cells expressed GpIIIa, but not GpIIb, when stimulated with phorbol-12-myristate-13-acetate (PMA). RNA from HEL cells directed the in vitro synthesis of a 110,000-Mr precursor for GpIIb and a 92,000-Mr precursor for GpIIIa, which indicates that the synthesis of GpIIb and GpIIIa by HEL cells is directed by separate mRNAs. In contrast, RNA from PMA-stimulated K562 cells only directed the synthesis of a 92,000-Mr precursor for GpIIIa. The dissociation of GpIIb and GpIIIa synthesis in K562 cells suggests that GpIIb and GpIIIa may be the products of separate genes.
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PMID:The in vitro synthesis of polypeptides for the platelet membrane glycoproteins IIb and IIIa. 354 42


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