FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2301383999> ?p ?o ?g. }

• W2301383999 endingPage "14116" @default.
• W2301383999 startingPage "14116" @default.
• W2301383999 abstract "14116 Background: Nemorubicin hydrochloride (nemorubicin) is a non-conventional anthracycline in Phase II evaluation in hepatocellular carcinoma (HCC). Its mechanism of action is not fully elucidated. Although structurally related to doxorubicin, nemorubicin is a topoisomerase I inhibitor, overcomes anthracyclines resistance, is minimally cardiotoxic and is biotransformed by hepatic CYP3A4 into hundred times more cytotoxic metabolite. Phase I and II trials were conducted in Europe and China to test nemorubicin by hepatic intra-arterial (IHA) infusion in HCC patients (pts). The drug was well tolerated up to 600 mcg/m 2 q4–6w; DLT was transient liver transaminase elevations. Overall, 57 HCC pts were evaluable for efficacy, with 11/57 confirmed liver CR/PRs (RR = 19.3%; 95% ci 10–31.9%) lasting 1–54+ months. Stable disease ≥ 3 months was observed in 17/57 (29.8%) pts, most with AJCC Stage III, IIIA and IVA. These data supported new trials of nemorubicin in HCC. Methods: To further characterize the mechanism of action of the drug, we generated cells (L1210) resistant to nemorubicin. Since resistant cells were more sensitive than the parental ones to UV irradiation, we reasoned that the nucleotide excision repair (NER) system might be involved in mediating the activity of nemorubicin. To test this hypothesis we used isogenic CHO cells proficient or deficient in excision repair cross-complementing (ERCC) genes, namely ERCC1 and ERCC6 genes. Results: In contrast with what is observed for most DNA damaging drugs that show resistance in the presence of high NER activity, nemorubicin is more cytotoxic in NER proficient than in deficient cells. This suggests that NER pathway plays a role in the cytotoxic effect of nemorubicin. Also, cells resistant to nemorubicin are NER-deficient and are highly sensitive to platinum derivatives and alkylating agents and synergism was found combining cisplatin with nemorubicin. Conclusions: Nemorubicin has a peculiar mechanism of action through the NER system providing the rationale for clinical combination studies with platinum derivatives. A Phase I/II trial of nemorubicin with cisplatin in HCC patients started in Italy at the end of 2005. No significant financial relationships to disclose." @default.
• W2301383999 created "2016-06-24" @default.
• W2301383999 creator A5006656859 @default.
• W2301383999 creator A5018214424 @default.
• W2301383999 creator A5040594266 @default.
• W2301383999 creator A5044377393 @default.
• W2301383999 creator A5045422368 @default.
• W2301383999 creator A5075508318 @default.
• W2301383999 creator A5089402672 @default.
• W2301383999 creator A5091714925 @default.
• W2301383999 date "2006-06-20" @default.
• W2301383999 modified "2023-09-26" @default.
• W2301383999 title "Phase I/II trial of nemorubicin hydrochloride in combination with cisplatin is supported by new preclinical evidences of its mechanism of action" @default.
• W2301383999 doi "https://doi.org/10.1200/jco.2006.24.18_suppl.14116" @default.
• W2301383999 hasPublicationYear "2006" @default.
• W2301383999 type Work @default.
• W2301383999 sameAs 2301383999 @default.
• W2301383999 citedByCount "1" @default.
• W2301383999 crossrefType "journal-article" @default.
• W2301383999 hasAuthorship W2301383999A5006656859 @default.
• W2301383999 hasAuthorship W2301383999A5018214424 @default.
• W2301383999 hasAuthorship W2301383999A5040594266 @default.
• W2301383999 hasAuthorship W2301383999A5044377393 @default.
• W2301383999 hasAuthorship W2301383999A5045422368 @default.
• W2301383999 hasAuthorship W2301383999A5075508318 @default.
• W2301383999 hasAuthorship W2301383999A5089402672 @default.
• W2301383999 hasAuthorship W2301383999A5091714925 @default.
• W2301383999 hasConcept C104317684 @default.
• W2301383999 hasConcept C104451858 @default.
• W2301383999 hasConcept C114851261 @default.
• W2301383999 hasConcept C126322002 @default.
• W2301383999 hasConcept C134935766 @default.
• W2301383999 hasConcept C202751555 @default.
• W2301383999 hasConcept C2776120743 @default.
• W2301383999 hasConcept C2776694085 @default.
• W2301383999 hasConcept C2778239845 @default.
• W2301383999 hasConcept C2779309665 @default.
• W2301383999 hasConcept C31760486 @default.
• W2301383999 hasConcept C502942594 @default.
• W2301383999 hasConcept C55493867 @default.
• W2301383999 hasConcept C71924100 @default.
• W2301383999 hasConcept C86803240 @default.
• W2301383999 hasConcept C89423630 @default.
• W2301383999 hasConcept C98274493 @default.
• W2301383999 hasConceptScore W2301383999C104317684 @default.
• W2301383999 hasConceptScore W2301383999C104451858 @default.
• W2301383999 hasConceptScore W2301383999C114851261 @default.
• W2301383999 hasConceptScore W2301383999C126322002 @default.
• W2301383999 hasConceptScore W2301383999C134935766 @default.
• W2301383999 hasConceptScore W2301383999C202751555 @default.
• W2301383999 hasConceptScore W2301383999C2776120743 @default.
• W2301383999 hasConceptScore W2301383999C2776694085 @default.
• W2301383999 hasConceptScore W2301383999C2778239845 @default.
• W2301383999 hasConceptScore W2301383999C2779309665 @default.
• W2301383999 hasConceptScore W2301383999C31760486 @default.
• W2301383999 hasConceptScore W2301383999C502942594 @default.
• W2301383999 hasConceptScore W2301383999C55493867 @default.
• W2301383999 hasConceptScore W2301383999C71924100 @default.
• W2301383999 hasConceptScore W2301383999C86803240 @default.
• W2301383999 hasConceptScore W2301383999C89423630 @default.
• W2301383999 hasConceptScore W2301383999C98274493 @default.
• W2301383999 hasIssue "18_suppl" @default.
• W2301383999 hasLocation W23013839991 @default.
• W2301383999 hasOpenAccess W2301383999 @default.
• W2301383999 hasPrimaryLocation W23013839991 @default.
• W2301383999 hasRelatedWork W1963528972 @default.
• W2301383999 hasRelatedWork W2028622397 @default.
• W2301383999 hasRelatedWork W2099082193 @default.
• W2301383999 hasRelatedWork W2113467423 @default.
• W2301383999 hasRelatedWork W2154925720 @default.
• W2301383999 hasRelatedWork W2155484722 @default.
• W2301383999 hasRelatedWork W3028670831 @default.
• W2301383999 hasRelatedWork W3096286885 @default.
• W2301383999 hasRelatedWork W57764544 @default.
• W2301383999 hasRelatedWork W271058052 @default.
• W2301383999 hasVolume "24" @default.
• W2301383999 isParatext "false" @default.
• W2301383999 isRetracted "false" @default.
• W2301383999 magId "2301383999" @default.
• W2301383999 workType "article" @default.