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- W2784043644 abstract "PM00104 is a new synthetic alkaloid related to Jorumycin and the Renieramycins with in vitro growth-inhibitory properties in the low nanomolar range as well as anti-tumor activity in vivo against several adult and pediatric tumors. PM00104 affects cell cycle, displays DNA binding properties and transcriptional inhibition. Currently PM00104 is under late Phase I development in solid tumors.The in vivo antitumor activity of PM00104 administered as a single agent or in combination (with Sorafenib) has been investigated in two xenografted hepatocellular carcinoma (HCC) models, namely HepG2 and PLC/PRF/5. Briefly, athymic nude female mice were subcutaneously implanted with matrigel-cell suspensions (HepG2 or PLC/PRF/5). When tumors reached ca. 150 ± 100 mg, mice were randomly allocated into treatment and control groups (n=10-15 animals/group); an experiment involving larger tumors (ca. 300 mg) was also performed (HepG2). Treatments were initiated (Day 0) and administered on an individual body weight basis. Tumor dimensions and body weights were recorded twice weekly starting with the first day of treatment. Treatments producing >20% lethality and/or 20% net body weight loss were considered as toxic. Mean, standard deviation and standard error of the mean were determined for tumor volume for all dose groups at all assessments. PM00104 was intravenously dosed at 0.9, 0.6 or 0.45 mg/kg/day on a weekly schedule for 3 consecutive weeks (q7dx3). In the combination studies, PM00104 was dosed as previously described and Sorafenib was orally administered at 60 or 30 mg/kg/day for 21 consecutive days (qd21). Both compounds were co-administered at the same time, with no attempt to explore whether the sequence may affect the final result. Results demonstrated that Zalypsis (q7dx3 at 0.9, 0.6 or 0.45 mg/kg/day) produced statistically significant antitumor activity (P Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2018." @default.
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- W2784043644 date "2009-05-01" @default.
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- W2784043644 title "Abstract #2018: Antitumor activity of PM00104 in hepatocellular carcinoma (HCC) experimental models" @default.
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