Tumor growth inhibition

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

To evaluate PARP inhibition in a realistic setting, olaparib (7) was tested in a BrcflI / p53 / mouse breast cancer model. Treatment with olaparib caused tumor growth inhibition without generating signs of toxicity [14]. Interestingly, upon cessation of treatment and tumor... 

Bartlett DW, Davis ME (2008) Impact of tumor-specific targeting and dosing schedule on tumor growth inhibition after intravenous administration of siRNA-containing nanoparticles. Biotechnol Bioeng 99 975-985... 

In other study,79 Samuelsson and coworkers (Sweden) investigated the efficacy of either ECT or radiotherapy or a combination of the two in destroying experimental colon carcinoma tumor in rats. The combined treatment resulted in tumor growth inhibition, and, total regression was obtained in 75% of the cases with radiotherapy alone, 75% of the tumors remained. As mentioned above78 with ECT alone, the regression rate was 50%, the same as surgery alone. 

Tumor Growth Inhibition Study with DQAsomal Encapsulated Paclitaxel (43)... 

Figure 9 Tumor growth inhibition study in nude mice implanted with human colon cancer cells. The mean tumor volume from each group was blotted against the number of days. Each group involved eight animals. For clarity, error bars were omitted. Note that after 1.5 weeks the dose, normalized for paclitaxel, was tripled in all treatment groups. Source. From Ref. 43...

Dose in mg/kg x 8-10 days (i.p.). Key to activity -, 0-25% tumor growth inhibition +, 26-50% tumor growth inhibition + +, 51-75% tumor growth inhibition + + +, 76-100%, tumor growth inhibition T, toxic in 50% of treated animals. 

HKI-272 has shown activity in animal models daily doses of 40 mg/kg result in greater than 75% tumor growth inhibition in xenograft models of both BT-474 breast carcinoma and A431 epidermal carcinoma [93]. Reports of the phase I evaluation of HKI-272 are not yet available. 

Model pERKl/2 response in excised tumors (EC50 [ xg/ml]) Tumor growth inhibition (EC50 [ixg/ml])... 

EGFR activation, correlates with tumor growth inhibition. ProcAm Assoc Cancer Res 2000 41 2552 (abstr). 

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