FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2554398959> ?p ?o ?g. }

• W2554398959 abstract "Abstract Abstract 3437 Poster Board III-325 Previously, we have shown that Allicin, the highly active compound of freshly crushed garlic, produced by the reaction of the enzyme Alliinase with its substrate Alliin, induced the apoptotic killing of B-CLL cells in vitro. In addition, we also reported that generation of Allicin in situ on the surface of B-CLL cells by targeting Alliinase to the cell surface of the CD20+ cells by Rituximab, resulted in the eradication of primary B-CLL in a human-mouse chimeric model, denoting the marked anti-CLL potential of combining these two different molecules, with different mechanism of action, into a single drug entity (Arditti et al., Mol Cancer Ther 2005;4(2)325-331). Indeed, monotherapeutic approaches, even if effective, are usually not sufficient to fully eradicate B-CLL and the most effective therapeutic protocols require the utilization of more than one agent. With this in mind, we took advantage of the high reactivity of Allicin, with SH-containing compounds, and created novel chimeric compounds by the combination of Allicin with 6-Mercapto-Purine (6MP) and 6MP-riboside (6MPR), both SH-containing purine analogs used for decades for the treatment of hematologic malignancies. The resulting novel compounds, S-Allyl-6MP (SA-6MP) and S-Allyl-6MPR (SA-6MPR), were examined against primary B-CLL cells obtained from the peripheral blood of patients at Binnet stage C. In our in vitro assays, Annexin-V staining indicated that SA-6MP acted in a dose dependent manner, inducing the apoptotic death of 37.9% and 95.2% of plated CD19+CD5+ B-CLL cells (10.9% in untreated cells) incubated for 16 h at 37 °C in the presence of 50 uM or 100 uM, respectively. As expected, the original 6MP compound had no impact on the viability of plated B-CLL cells (9.7% and 8.7%) at doses of up to 150 uM. In preliminary in vivo experiments, we compared the anti-BCLL activity of SA-6MP with that of SA-6MPR and the original 6MP compound on primary B-CLL cells from 5 different patients (Binnet stage C) in a human-SCID/Beige mouse model. Following the engraftment of the human B-CLL cells, mice were treated with i.p. injections of 2.5 mg/kg body weight of SA-6MP, SA-6MPR, or 6MP on a daily basis throughout 7 consecutive days, after which, the engraftment of primary B-CLL cells was examined by the recovery of CD45+CD19+CD5+ from injected mice. An additional group of mice injected with vehicle (1% DMSO) was also examined as a control. In close similarity to our in vitro results, engraftment of primary B-CLL cells was considerably reduced following treatment with SA-6MP (>90% reduction), as compared with treatment with the original 6MP drug. In addition, the chimeric riboside 6MP derivative, SA-6MPR, induced a potent anti-BCLL effect comparable to that of SA-6MP. In summary, our results in vitro and in vivo suggests that combining the pro-apoptotic effects of Allicin with the antiproliferative effects of 6MP or 6MPR is superior to the effect of either of the purine analogs alone. This approach may be evaluated at first instance in B-CLL patients with refractory disease. Disclosures No relevant conflicts of interest to declare." @default.
• W2554398959 created "2016-11-30" @default.
• W2554398959 creator A5013424902 @default.
• W2554398959 creator A5029873201 @default.
• W2554398959 creator A5037757199 @default.
• W2554398959 creator A5055705705 @default.
• W2554398959 creator A5056516356 @default.
• W2554398959 creator A5090335644 @default.
• W2554398959 date "2009-11-20" @default.
• W2554398959 modified "2023-10-09" @default.
• W2554398959 title "Evaluation of Novel S-Allyl Derivatives of 6-Mercapto-Purine against B-CLL: Combining the Effects of Different Compounds in A Single Molecule." @default.
• W2554398959 doi "https://doi.org/10.1182/blood.v114.22.3437.3437" @default.
• W2554398959 hasPublicationYear "2009" @default.
• W2554398959 type Work @default.
• W2554398959 sameAs 2554398959 @default.
• W2554398959 citedByCount "0" @default.
• W2554398959 crossrefType "journal-article" @default.
• W2554398959 hasAuthorship W2554398959A5013424902 @default.
• W2554398959 hasAuthorship W2554398959A5029873201 @default.
• W2554398959 hasAuthorship W2554398959A5037757199 @default.
• W2554398959 hasAuthorship W2554398959A5055705705 @default.
• W2554398959 hasAuthorship W2554398959A5056516356 @default.
• W2554398959 hasAuthorship W2554398959A5090335644 @default.
• W2554398959 hasConcept C109246011 @default.
• W2554398959 hasConcept C181199279 @default.
• W2554398959 hasConcept C185592680 @default.
• W2554398959 hasConcept C202751555 @default.
• W2554398959 hasConcept C2776476023 @default.
• W2554398959 hasConcept C2776517821 @default.
• W2554398959 hasConcept C2781005338 @default.
• W2554398959 hasConcept C55493867 @default.
• W2554398959 hasConcept C86803240 @default.
• W2554398959 hasConcept C98274493 @default.
• W2554398959 hasConceptScore W2554398959C109246011 @default.
• W2554398959 hasConceptScore W2554398959C181199279 @default.
• W2554398959 hasConceptScore W2554398959C185592680 @default.
• W2554398959 hasConceptScore W2554398959C202751555 @default.
• W2554398959 hasConceptScore W2554398959C2776476023 @default.
• W2554398959 hasConceptScore W2554398959C2776517821 @default.
• W2554398959 hasConceptScore W2554398959C2781005338 @default.
• W2554398959 hasConceptScore W2554398959C55493867 @default.
• W2554398959 hasConceptScore W2554398959C86803240 @default.
• W2554398959 hasConceptScore W2554398959C98274493 @default.
• W2554398959 hasLocation W25543989591 @default.
• W2554398959 hasOpenAccess W2554398959 @default.
• W2554398959 hasPrimaryLocation W25543989591 @default.
• W2554398959 hasRelatedWork W2259404132 @default.
• W2554398959 hasRelatedWork W2329685879 @default.
• W2554398959 hasRelatedWork W2492343070 @default.
• W2554398959 hasRelatedWork W2528285964 @default.
• W2554398959 hasRelatedWork W2552042013 @default.
• W2554398959 hasRelatedWork W2557688478 @default.
• W2554398959 hasRelatedWork W2557695018 @default.
• W2554398959 hasRelatedWork W2559278294 @default.
• W2554398959 hasRelatedWork W2559468080 @default.
• W2554398959 hasRelatedWork W2559956420 @default.
• W2554398959 hasRelatedWork W2565282098 @default.
• W2554398959 hasRelatedWork W2565291050 @default.
• W2554398959 hasRelatedWork W2566959808 @default.
• W2554398959 hasRelatedWork W2571191919 @default.
• W2554398959 hasRelatedWork W2576882379 @default.
• W2554398959 hasRelatedWork W2592487900 @default.
• W2554398959 hasRelatedWork W2594529713 @default.
• W2554398959 hasRelatedWork W2597991080 @default.
• W2554398959 hasRelatedWork W2979566835 @default.
• W2554398959 hasRelatedWork W2539319907 @default.
• W2554398959 isParatext "false" @default.
• W2554398959 isRetracted "false" @default.
• W2554398959 magId "2554398959" @default.
• W2554398959 workType "article" @default.