Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice with severe combined immunodeficiency (SCID) were injected with 1 x 10(7) MOLT-3 human T-lineage acute lymphoblastic leukemia cells to provide a model for the evaluation of anti-CD7-pokeweed antiviral protein (PAP) immunotoxin directed against the human CD7 antigen. Of control SCID mice (treated with phosphate-buffered saline, PBS) challenged intravenously with 1 x 10(7) MOLT-3 cells, 5/5 died at 29 to 35 days after inoculation, with a median event-free survival of 33 days. Similarly, 6/6 anti-CD19-PAP treated control SCID mice died of MOLT-3 leukemia at a median of 36 days. In contrast, treatment with anti-CD7-PAP (15 micrograms total dose in 5 micrograms intraperitoneal injections on days 1-3) significantly improved event-free survival of SCID mice challenged with 1 x 10(7) MOLT-3 cells. Of nine SCID mice treated with anti-CD7-PAP, four died at 54-149 days and five remained alive for > 172 days without clinical evidence of leukemia (median event-free survival > 172 days). When long-term survivors among the anti-CD7-PAP treated SCID mice were electively killed at 173 days to assess their leukemia burden, histopathologic examination and polymerase chain reaction provided evidence of disseminated leukemia in some of these mice. Intriguingly, marked differences in morphology, tissue distribution, and histologic pattern of organ invasion existed between leukemic blasts killing 100% of PBS-treated control mice at a median of 33 days and 'therapy-refractory' leukemic blasts detected in anti-CD7-PAP-treated long-term survivors. This novel SCID mouse model of disseminated human T-lineage ALL provides a unique in vivo system to investigate the therapeutic potential of new treatment strategies and to study possible mechanisms of in vivo immunotoxin resistance.
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PMID:In vivo anti-leukemic efficacy of anti-CD7-pokeweed antiviral protein immunotoxin against human T-lineage acute lymphoblastic leukemia/lymphoma in mice with severe combined immunodeficiency. 767 82

A procedure for separation of leukemic T-cells from normal lymphocytes, using lectin-affinity column chromatography, is described. CNBr-activated Sepharose 6MB was used as a non-mobile phase. The gel was covalently coupled with soybean agglutinin (SBA), then served as an affinity probe for fractionation of mixture of normal lymphocytes and leukemic cells. Leukemic cell lines, derived from acute lymphoblastic leukemia (Jurkat, MOLT-4, RPMI-8402), were tested. The elution of normal lymphocytes was carried out by PBS(-). The leukemic T-cells, interacting with SBA, were removed by N-acetyl-D-galactosamine or low-concentration acetic acid. The type and viability of the separated cell fractions were analyzed by flow cytometry and fluorescent microscopy, using adequate fluorescent antibodies. The interaction of leukemic T-cells with free SBA, as well as with SBA-conjugated Sepharose beads, was examined fluorimetrically and visualized by fluorescent microscopy, using FITC-SBA as a marker. The rate of cell elution on SBA-affinity column decreased in order: normal > leukemic T-cells. Both normal lymphocytes and leukemic T-cells were removed in a mixture from SBA-free Sepharose 6MB by PBS(-) and were not fractionated discretely. The leukemic T-cells specifically interacted with SBA as well as with SBA-affinity adsorbent. In contrast, the normal lymphocytes did not interact with free SBA as well as with SBA-conjugated Sepharose beads in the concentrations applied. The method potentially combines a discrete cell fractionation with manifestation of a specific target cytotoxicity of SBA against leukemic T-cells, without any influence on normal lymphocytes.
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PMID:Interaction of soybean agglutinin with leukemic T-cells and its use for their in vitro separation from normal lymphocytes by lectin-affinity chromatography. 1283 89

We attempted to screen for telomerase inhibitingactivity in vitro from a total of 304 marine algae samples which were collected from various Japancoasts by nonradioisotope telomeric repeatamplification protocol (Non-RI TRAP) assay using humanleukemia MOLT-4 cells. Ten of the MeOH extracts andtwo of the PBS extracts from those algal samplesshowed telomerase inhibiting activity. In particular,the MeOH extract from a green alga, Caulerpasertularioides strongly inhibited telomerase activitywhen added to MOLT-4 cell culture at a level of 1.25%(v/v), suggesting that it may be possible to developa novel anti-cancer agent in view of its specificanti-telomeric property.
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PMID:Telomerase inhibiting activity in vitro from natural resources, marine algae extracts. 1900 29

L-asparaginase (ASNase) from Escherichia coli is currently used in some countries in its PEGylated form (ONCASPAR, pegaspargase) to treat acute lymphoblastic leukemia (ALL). PEGylation refers to the covalent attachment of poly(ethylene) glycol to the protein drug and it not only reduces the immune system activation but also decreases degradation by plasmatic proteases. However, pegaspargase is randomly PEGylated and, consequently, with a high degree of polydispersity in its final formulation. In this work we developed a site-specific N-terminus PEGylation protocol for ASNase. The monoPEG-ASNase was purified by anionic followed by size exclusion chromatography to a final purity of 99%. The highest yield of monoPEG-ASNase of 42% was obtained by the protein reaction with methoxy polyethylene glycol-carboxymethyl N-hydroxysuccinimidyl ester (10kDa) in 100 mM PBS at pH 7.5 and PEG:ASNase ratio of 25:1. The monoPEG-ASNase was found to maintain enzymatic stability for more days than ASNase, also was resistant to the plasma proteases like asparaginyl endopeptidase and cathepsin B. Additionally, monoPEG-ASNase was found to be potent against leukemic cell lines (MOLT-4 and REH) in vitro like polyPEG-ASNase. monoPEG-ASNase demonstrates its potential as a novel option for ALL treatment, being an inventive novelty that maintains the benefits of the current enzyme and solves challenges.
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PMID:Novel site-specific PEGylated L-asparaginase. 3164 62