1 Medi Introd local r differe DDLS expres xenog clinic, of glyc levels (Adria CEBP breaks topois increa 2010 S Clin On Magn R M ical Physics, Mem duction: Well-dif recurrence rate is entiated liposarco which are pote ssed in DDLS. A grafts (3). A non- an early marker colysis has the p in a human DD mycin), an anthr Pα has been show s and cell death omerase II com ased effectivenes Sep 1;70(17):6891- ncol (Meeting Abst Reson Med 2004;5 MRS assessmen Asif Rizwan 1 , Xia orial Sloan-Ketter Stat fferentiated/dedif s high even if ma oma (DDLS) leav ntial therapeutic Administration of -invasive marker r of response/no potential to be a DLS tumor xeno racycline used to wn to induce cel h. Adria is an an mplex. While furth ss compared to a 901. Epub 2010 Au racts) 2010;28(15_ 52(4):902-906. 6. Ti nt of lactate in aohui Ni 1 , Rachael ring Cancer Cente tes, 3 Radiology, M fferentiated lipos argins are negat ves non-surgical targets (1,2). Fo the SN-38 prodr r reflecting the e n-response coul biomarker of pr ograft (DDLS BW o treat sarcomas. ll growth arrest ( ntimitotic and cyt her investigation agents which inte ug 16. 2. Gobble R _suppl):10005. 4. imchenko, NA, Wild n dedifferentia l O'Connor 2 , Samu er, New York, NY, emorial Sloan-Ket sarcomas occur tive and de-differ candidates with or example, CEB rug CPT11 (irino effect of such ag d permit the phy rognosis and trea WH) implanted i h 6 a sacrifi 4583, were o fixed i by he by the volum CPT1 treate vs con had s althou CPT1 showe (PIMO growth vascu week develo Disc acco tum und diffe 6). CPT-11 is als totoxic agent wh n is needed, our erfere with DNA RM, Qin LX, et. al.. He, Q.,Shungu, D. de, M., et. al. Gene ated liposarcom uel Singer 2 , Sean C United States, 2 Sur ttering Cancer Ce mainly in the ab rentiation is pred few options. Re BPα, which is a otecan) caused in ents could be qu ysician to discon atment effect. Th n mice in respo Metho mice a tumor Adria- MRI/M in 7 c were i.p.) w scan. the M home were thickn TE = detect Coher obtain excita Peak lactate Histol ydrochloride (PIM 0 and 40 mg/ dministered via ce (Hoechst 333 Sakura Finetek obtained using a in 4% paraforma matoxylin/eosin e slice volume an me and concentra 1-treated (Fig-1A d group had low ntrol, P = 0.0006 significantly lowe ugh lactate had d 1 vs. control, P < ed regions of red O) in the growing h-halted CPT-11 larized and free in the Adria and opment of necros cussion. As ear ompanied by gro ors. The mecha er investigation erentiation result so known to inhi hich interferes w r data suggest t repair/replication Cancer Res. 2011 C., et. al. J. Magn es Dev. 1996 Apr 1 ma models tre Carlin 3 , Jason Kou rgery, Memorial S enter, New York, N bdomen, and sur dictive of poor ou ecent investigatio transcription fac ncreased CEBPα uite valuable in tinue ineffective he goal of the c onse to CPT-11 ods. Overview: and monitored u r growth delay stu -treated, and 5 MRSI was perfor control, 6 Adria- treated twice pe with the first trea MR Experimen MR experiments built 2-turn sole used. T2-weigh ness = 1 mm, nu 40 ms, matrix= tion was perfo rence (Sel-MQC ned from a 5-mm ations =512, 102 fitting was perf e was performe logy: Selected MO) (hypoxypro /kg, respectively the tail vein at 1 342). Tumors we k), snap-frozen a a cryostat microto aldehyde then bl staining. Data A nd compared to t ation. Results: T A). Adria had litt wer lactate than th 6 for CPT11 vs er lactate conc decreased in the < 0.0001 for CPT duced cell densit g control and Ad 1-treated tumors of hypoxia. The control groups i sis as seen on h rly as 3 days afte owth arrest in C anism by which n. One could ts in a convers bit the activity of with DNA repair b that the CPT-11 n. References ( Apr 1;71(7):2697- n. Reson B. 106(3) ;10(7):804-15 eated with che utcher 1 , and Kristen Sloan-Kettering Ca NY, United States rgery is the mai utcome. The lack ons have reveale ctor involved in a α expression and pre-clinical drug treatment witho urrent study was . A second coh 35 BWH tumors until the volume udies, tumor volu CPT-11-treated rmed serially at d -treated, and 5 er week (Adria 0 atment given imm ts: Mice were an on a Bruker 4.7 enoid coils with hted sagittal MR umber of slices= 512 X 256, num ormed using th C) editing seque m thick center s 24 data points, formed in Matla ed using the p d animals wer be-1, HPI) and H y. These agent hour before sac ere excised, em and stored at −8 ome (Microm Int ocked in Superb Analysis: The la the lactate conte The non-treated t tle effect on tum he control and A Adria). At day 6 centrations than ese groups com T11 vs Adria). Hi ty, reduced vasc dria-treated tumo s, the tissue app e trend toward re is probably due t istology. er treatment, a r CPT-11-treated B lactate concen speculate that sion to a less g f topoisomerase by complexing w ’s induction of C (1). 1. Brill E, Gob -705. Epub 2011 F ) pp. 203-11. 5. Mu emotherapy n L. Zakian 1 ancer Center, New nstay of treatme k of effective che ed genes abnorm adipocyte differe d growth delay in g evaluations. Fu ut delay. Lactate s to assess the ort was treated were grown in th was approximate ume was monito d mice (V= (π/6 day 1 (baseline), CPT-11 treated 0.9 mg/kg i.p., C mediately after th nesthetized with 7-T Biospec Spe diameters of 10 R images were 10, FOV =24 mm mber of acquisitio he Selective M ence (4,5). Lacta slice with TR = 2 and spectral w ab (Natick, MA) phantom substit re injected wit Hoechst 33342 ( ts were dissolv crifice (PIMO) an mbedded in cuttin 80°C. 10μm thic ternational GmbH block-PBS (Pierc actate peak area ent of a phantom umors grew mor mor growth. On d Adria groups (P = 6, the CPT-11 tre the control an pared to baselin istologic and IHC ularization (Hoec ors at 1 week. I peared fairly ho educed lactate c to reduced cell d reduction in lacta BWH dedifferenti tration is reduce t CEBPα’s rol glycolytic phenot I, resulting in do with DNA and in CEBPα express bble R, Angeles C, eb 18 3. Angeles C uruganandham M, w York, NY, United ent. However, th emotherapy of de mally expressed i entiation, is unde n DDLS cells an urthermore, in th e, an end-produc change in lactat with doxorubici he flanks of SCID ely 100 mm 3 . Fo red in 7 control, 6)* L * W * D , day 3 and day mice. The mic CPT11 100mg/k he baseline MRS Isoflurane durin ectrometer. Tw mm and 14 mm e collected (slic m, TR = 3000ms ons = 4). Lactat Multiple Quantum ate spectra wer 2 sec, number o idth of 2510 Hz ). Quantitation o tution technique th Pimonidazol Sigma-Aldrich) a ved in PBS an nd 5 minutes pre ng medium (OCT k frozen section H). Sections wer ce, USA) followe a was normalize section of know re rapidly than th day 3, the CPT1 = 0.001 for CPT1 eated tumors sti nd Adria groups ne ( P<0.0001 fo C analysis (Fig. 2 chst) and hypoxi n contrast, in th mogeneous, we concentration at density and/or th ate was observe ated liposarcom ed by CPT-11 i le in promotin type. In addition ouble-strand DNA terfering with th ion may result i , et. al. Cancer Res CV, Laxa B, et. al. Koutcher JA, et. a d e e- n er d e ct e n D or 5 ). 6 e g S g o m e s, e m e of z. of e. e at d e- T s e d d n e 1 1 ill s, or 2) a e ell 1 e d a s g n, A e n s. J al. 3059 Proc. Intl. Soc. Mag. Reson. Med. 20 (2012)