9L gliosarcoma

Exposure of 9L gliosarcoma cells to hydrogen peroxide stimulated PPP, which could be attenuated when the neurons were preincubated with the iron chelator desferrioxamine. 

J. R. James, Y. Gao, V. C. Soon, S. M. Topper, A. Babsky and N. Bansal, Controlled radiofrequency hyperthermia using an MR scanner and simultaneous monitoring of temperature and therapy response by H, Na and P magnetic resonance spectroscopy in subcutaneously implanted 9L-gliosarcoma. Int.. Hyperthermia, 2010, 26, 79-90. 

Gadolinium(III) was complexed to the DTPA component of ATN-10 for possible use in neutron capture therapy [113]. An additional benefit of the incorporation of gadolinium(III) into ATN-10 is the increase in the relaxivity of the agent [113]. Injection of Gd-ATN-10 into rats with 9L gliosarcomas demonstrated an increase in the signal intensity of the tumor. The agent potentially has toxicity problems, though, as it was demonstrated that the metal ions may dissociate from the complex. 

Fig. 13.1. This figure demonstrates confinement of the LCM to 9L gliosarcoma tumors in the Fischer rat (top left) and to C6 gliomas in the Sprague-Dawley rat (top right) with Oil Red-O lipid staining. Bottom left panel is the 9L tumor (in Fischer 344 rat) immediately after intravenous injection with diO-labeled LCM. Bottom right panel shows this same tumor. Here nine successive 0.8 pm tomographic sections in the Z axis from the confocal laser microscope illustrates the presence of the intracellular LCM. The scale bar is 10 pm. (Taken from ref. 531.)...

The distribution of LCM in the brain parenchyma was further analyzed using fluorescently labeled LCM and confocal laser scanning microscopy. As in the case of unlabeled LCM, rats bearing 9L gliosarcoma tumors were injected intravenously (i.e., via tail vein) with diO-LCM and sacrificed 2 min later. The brains were processed as described elsewhere (ref. 531). In this case,... 

There is an increased blood flow in brain tumors (ref. 589), and the blood-brain barrier is leaky in and around 9L tumors because the blood vessels associated with these (ref. 568), and other (ref. 565-567), tumors are fenestrated. This well-known leakiness of tumor capillaries, which in the case of brain tumors includes breaches in the blood-brain barrier (ref. 566,568 cf. Section 12.2), would allow extravasation of small particulate matter (cf. ref. 590-594) or LCM. Once in the tumor area, LCM remain there because of an affinity for tumor cell surface components (cf. ref. 531 see also Chapter 14). At least 4 different types of experimental tumors in rats (C6 glioma, 9L gliosarcoma, Novikoff hepatoma, and Walker-256 carcinosarcoma), as well as several spontaneous tumors in dogs (ref. 570), do interact with LCM in a preferential manner (cf. Chapters 12 and 13), suggesting that LCM affinity may be for tumor cells in general (ref. 531). 

Fig. 13.10 This photomicrograph demonstrates the tumor morphology of Fischer 344 rats bearing 9L gliosarcomas treated with cremophor-LCM (A) and paclitaxel-LCM (B,C). Experimental animals received one i.v. injection of 240 pg/kg paclitaxel-LCM each day for 5 consecutive days starting 10 days after the tumor inoculation. Control animals received cremophor-LCM. Tumors from animals treated with paclitaxel-LCM show extensive cell death (B) and hemorrhage (C). (Taken from ref. 532.)...

R.D. Fross, P.C. Wamke and D.R. Groothuis, Blood flow and blood-to-tissue transport in 9L gliosarcomas the role of the brain tumor model in drug delivery research, J. Neuro-Oncol. 11 (1991) 185-197. 

Rat F98 glioma cells were from R. Goodman, Ohio State University (Columbus, OH). The 9L gliosarcoma line was obtained from the Brain Tumor Research Center, University of California, San Francisco. Cells were maintained in 10% fetal calf serum in DMEM supplemented with penicillin/streptomycin and tested by the Gen-Probe Rapid Detection System (Fisher Scientific) to rule out mycoplasma contamination. Cells were harvested with 0.25% trypsin, counted, and resuspended in DMEM solution before intracranial implantation. 

There are experimental data which show a synergistic or a potentiating effect of chemotherapeutic agents on PDT [80]. The combination of ACNU and HPD-mediated PDT results in significantly increased cytotoxicity in the 9L gliosarcoma [81]. This effect could further be increased by adding hyperthermia as a third treatment modality. The RIF-1 tumor proved to be insensitive to PDT and to doxorubicin but sensitive to cisplatin with no increased cytotoxic effect when both modalities were combined. In the EMT-6 tumor model all three modalities showed a mild effect when used independently, doxorubicin enhanced significantly the effect of PDT, whereas cisplatin did not [82]. Mitomycin C potentiates the effect of PDT in adenocarcinoma [83]. There are no reported clinical data on the interaction of PDT and chemotherapy. 

F. Jiang, L. Lilge, B. Logie, Y. Li, M. Chopp (1997). Photodynamic therapy of 9L gliosarcoma with liposome-delivered Photofrin. Photochem. Photobiol., 65(4), 701-706. 

Using rat flank and intracranial 9L gliosarcoma models, Tamargo et al. (70) initially compared the efficacy of polymer and systemically based BCNU. EVAc polymer delivery in the flank model produced significant tumor growth delay relative to systemic administration (15.3 vs. 11.2 days, p < 0.05). In the intracranial model, a 10 mg polymer with 20% (w/w) BCNU polymers dramatically improved survival in animals with established 9L gliosarcoma. EVAc and pCPP SA polymers conferred respective survival advantages of 7.3-fold and 5.4-fold over controls. Systemic BCNU, in contrast, increased survival only 2.4-fold compared to controls. 

A second study in the same established rat intracranial 9L gliosarcoma model evaluated the efficacy of 20% (w/w) BCNU-loaded pCPPrSA polymers vs. direct stereotactic injec-... 

In vitro kinetics studies with 20-40% (w/w) paclitaxel-loaded pCPPrSA (20 80) pol3maers demonstrated sustained drug release approaching 1000 h. Biodistribution studies concordantly revealed tiunorcidal pachtaxel concentrations in the rat brain for > 30 days post-implantation. Median survival in the established rat 9L gliosarcoma model improved from 19.5 days in rats treated with blank polymers to 61.5 days with 20% paclitaxel-loaded pol3rmers (p < 0.001) (105). 

A final study of local paracrine dehvery identified IL-12, a c3rtokine with antiangiogenesis properties in addition to its immimoregulatory effects, as a potential substrate candidate (114). Using the estabhshed rat intracranial 9L gliosarcoma model, the study examined intracranial implantation of IL-12 transduced tumor cells. Reverse transcriptase-poly... 

Efficacy studies in the rat intracranial 9L gliosarcoma model compared systemic and EVAc polymer dexamethasone administration (28). Water weight percentage served as the edema endpoint both intracranial dexamethasone-loaded polymers (79.15% p<0.05) and intraperitoneal dexamethasone injections (79.16% p0.05) were superior to controls (79.45%) and intraperitoneal pol3nner implantation (79.39%). Thus, intracranial pol3nner implantation achieved equivalent edema reduction without the theoretical potential for systemic toxicity. 

Figure 7 (Facing page) (A) Kaplan-Meier survival curve for animals treated with intracranial 10 mg 3.8% (w/w) BCNU pCPP SA (20 80) polymers placed on day 5 after 9L gliosarcoma implantation with or without daily oral quinacrine gavages (20mg/kg) starting day 5 and lasting 14 days. (B) Kaplan-Meier survival curve for animals treated with intracranial BCNU polymers placed on day 5 after 9L ghosarcoma implantation with or without intracranial 10 mg 15% (w/w) quinacrine pCPPrSA (20 80) polymers placed on day 3 after tumor implantation. (C) Kaplan-Meier survival curve for animals treated with intracranial BCNU polymers placed on day 5 after 9L gliosarcoma implantation with or without intracranial 10 mg 15% (w/w) quinacrine pCPP SA (20 80) polymers concurrently on day 3 after tumor implantation.

Tamargo RJ, Myseros JS, Epstein JI, Yang MB, Chasin M, Brem H. Interstitial chemotherapy of the 9L gliosarcoma controlled release polymers for drug delivery in the brain. Cancer Res 1993 53 329-333. 

Storm PB, Moriarity JL, Tyler B, Burger PC, Brem H, Weingart J. Polymer delivery of camptothecin against 9L gliosarcoma Release, distribution, and efficacy. Journal of Neuro-Oncology 2002 56 209—217. 

DiMeco F, Rhines LD, Hanes J, Tyler BM, Brat D, Torchiana E, Guarnieri M, Colombo MP, PardoU DM, Pinocchiaro G, Brem H, Olivi A. Paracrine delivery of IL-12 against intracranial 9L gliosarcoma in rats. J Neurosurg 2000 92 419—427. 

Schiltz PM, Gomez GG, Read SB, Kulprathipanja NV, Kruse CA. Effects of IFN-gamma and interleukin-1 beta on major histocompatibihty complex antigen and intercellular adhesion molecule-1 expression by 9L gliosarcoma relevance to its cyto-lysis by alloreactive cytotoxic T lymphocytes. J Interferon Cytokine Res 2002 22 1209-1216. 

For example. Fig. 1.1 shows elemental images of brain sections from a rat bearing an intracranial 9L gliosarcoma tumor after treatment with/(-boronophenylalanine (BPA) (7). Boron neutron... 

Fig. 1.1. SIMS imaging. Interface between the MTM and the normal brain of a male Fischer 334 rat bearing a 9L gliosarcoma. (a) FI E-stained adjacent 4-ixm thick ayosec-tion used for optical imaging. White arrows indicate the interface between the MTM (main tumor mass) and CNT (continuous normal tissue). The corresponding SIMS images for (b) 10B, (c) 24 Mg, (d) 39 K, (e) 23Na, and (f) 40Ca are presented from the same tissue region of analysis. Dotted lines indicate the interface between the MTM and CNT portions. (Reprinted with pemiission from ref. (7).)...

---