Subcutaneous tumors

Fullerenes should have a photodynamic effect on tumors, if (a) the compound is accumulated in the tumor tissue, (b) a reasonably efficient way to administer the compound to tumor bearing animals is found, and (c) enough excitation light can be delivered to the photosensitized tumors. The first report of fullerenes being used to cany out PDT of actual tumors was by Tabata in 1997 (Tabata et al., 1997). They chemically modified the water-insoluble C60 with polyethylene glycol (PEG), not only to make it soluble in water, but also to enlarge its molecular size. When injected intravenously into mice carrying a subcutaneous tumor on the back, the... 

Cisplatin was first characterized as a radiation sensitizer using hypoxic Bacillus megaterium spores (53). Radiation sensitization by cisplatin was confirmed in vegetative Escherichia coli with a maximum sensitizer enhancement ratio of 1.77 in anoxic bacteria at a cisplatin concentration of 50 uM (54). Zimbrick et al. (55) extended these studies to other platinum complexes. The earliest studies in mammalian cells used hypoxic V-79 Chinese hamster cells and showed a small radiation sensitization with 8 iM of cisplatin (56). Nias and Szumiel (57) first reported that pretreatment of Chinese hamster ovary (CHO) cells with a platinum complex could sensitize well-oxygenated cells to radiation. Wodinsky etal. (58) showed that cisplatin potentiated the effect of whole-body radiation therapy in mice inoculated intraperitoneally with P388 leukemia compared with either modality alone. Therapeutic potentiation was found in MTG-B subcutaneous tumors and intracerebral RBT when the animals were treated with cisplatin and radiation (59). 

In the early 1940s, Leiter et al. (1942) demonstrated that a similar phenomenon occurred with organic extracts of ambient air particles—that is, injection of tars extracted from atmospheric dusts collected at locations throughout New York City produced subcutaneous sarcomas in mice. Shortly thereafter, Leiter and Shear (1943) reported that marginal doses of 3,4-benzpyrene (known today as benzol a jpyrene, BaP, I), the powerful carcinogen earlier isolated from coal tar and synthesized by Cook et al. (1933), also produced subcutaneous tumors in mice. 

Leiter, J., and M. J. Shear, Quantitative Experiments on the Production of Subcutaneous Tumors in Strain A. Mice with Marginal Doses of 3,4-Benzpyrene, J. Natl. Cancer Inst., 3, 455-477 (1943). 

In animals, the first in vivo experiments were performed with bacterial extracts in a guinea pig sarcoma model by Gratia and Linz [88], and with LPS in mouse primary subcutaneous tumors by Shear and Turner [4], The antitumoral effect of LPS on the growth of subcutaneous or intramuscular tumors has been extensively investigated [61,147-153], On ascitic tumors, treatment with LPS was shown to be efficient in some cases [153-155] while failing in others [61,156],... 

Nitrotetrahydro- 1,3-oxazine derivatives show cytotoxic activity in vitro,283,284 and antitumor properties against subcutaneous tumors in mice.84,286 Compound 124 reduced tumors by 70%. The preparation of these compounds is covered by patents.41-46... 

Dillehay, L.E. (1997) Decreasing resistance during fast infusion of a subcutaneous tumor. Anticancer Res., 17, 461 166. 

Pluen, A., Boucher, Y., Ramanujan, S., McKee, T.D., Gohongi, T., di Tomaso, E. et al. (2001) Role of tumor-host interactions in interstitial diffusion of macromolecules Cranial Verses subcutaneous tumors. Proc. Natl. Acad. Sci. USA, 98, 4628 1633. 

Kouri RE, Rude TH, Joglekar R, et al. 1978. 2,3,7,8-Tetrachlorodibenzo-p-dioxin as cocarcinogen causing 3-methylcholanthrene-initiated subcutaneous tumors in mice genetically "nonresponsive" at Ah locus. Cancer Res 38 2777-2783. 

Novak, U. et al., Hyaluronidase-2 overexpression accelerates intracerebral but not subcutaneous tumor formation of murine astrocytoma cells, Cancer Res., 59, 6246, 1999. 

For subcutaneous injections a large skin surface area is available for daily applications. It is recommended to change the site of injections continuously because repeated injection to the same site can cause fibrotic reactions and, in case of treatments for a period of 1 year and longer, induce subcutaneous tumors especially in small rodents. The risk of inducing local skin tumors is high if the pH value of the administration solution is below 5. 

Gupta, B., Levchenko, T. S., Mongayt, D. A., and Torchihn, V. R (2005), Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo, J. Drug Target., 13,337-343. 

Subcutaneous tumors were detected using NIR in a paper by Jarm et al. [160]. Low level electric current used as electrotherapy on solid subcutaneous tumors was followed by NIR analysis of the tumor region. Data showed that oxygenation of the tumors was inhibited after the electrotherapy was applied. 

Strawn LM, Kabbinavar F, Schwartz DP, Mann E, Shawver LK, et al. 2000. Effects of SU101 in combination with cytotoxic agents on the growth of subcutaneous tumor xenografts. Clin. Cancer Res. 6 2931-34... 

Lubet RA. Connelly GM, Nebert DW. et al. 1983a. Dibenz[a,h]anthracene-induced subcutaneous tumors in mice. Strain sensitivity and the role of carcinogen metabolism. Carcinogenesis 4 513- 517. 

Shear MJ, Luter J. 1941. Studies in carcinogenesis XVI. Production of subcutaneous tumors in mice by miscellaneous polycyclic compounds. J Natl Cancer Inst 2 241-258. 

Fukunaga M, Ushigome S, Ishikawa E. Ossifying subcutaneous tumor with myofibroblastic differentiation A variant of ossifying fibromyxoid tumor of soft parts Pathol Int. 1994 44 727-734. 

In in vivo studies with certain of these compounds (experimental subcutaneous tumors in rodents) relatively selective destruction of the tumors compared to overlying skin was found [28], although tumor cell destruction was incomplete. 

Terpenes. Another class of compounds which holds considerable promise as inhibitors of cancer are the terpenes. D-limonene, which is a component of citrus oils, is the terpene which probably has been studied most extensively as an Inhibitor of carcinogenesis. Early studies reported that D-limonene, a mixture of D-limonene with its hydroperoxide, and orange oil were similar in their ability to prevent subcutaneous tumors induced by benzo(rst)pentaphene (DBP) (56) but that spontaneous and DBP-lnduced lung adenomas were reduced in mice fed D-llmonene but not in those fed orange oil or the hydroperoxide of llmonene. 

Subcutaneous tumors that developed after implantation of human mammary carcinoma cells (MX-1) in athymic mice regressed following local injection of hypericin 1 and exposure to visible light [167]. Tissue uptake and distribution of hypericin 1 was measured in rabbits and in nude mice xenografted with P3 human squamous cell carcinoma to assess the value of this naphthodianthrone as in vivo sensitizer for laser photoactivation of solid tumors. Maximum Hypericum levels were seen in... 

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