Tumor enhancing properties

To study tumor enhancing properties, various in vitro tests have also been proposed (Yamasaki 1990). They are based on the determination of clinical properties common to a group of promoting agents, such as loss of cell-to-cell communication and outgrowth of partially transformed cells. 

Manganese(II)-A/, A/r -dipyridoxylethylenediamine-A/r, AT-diacetate 5,5 -bis(phosphate) 75 (DPDP) is clinically used for enhancing contrast in the liver (detection of hepatocellular carcinomas) (312). Some dissociation of Mn(II) appears to occur in the liver, and enhancement can also be obtained in functional adrenal tissues (313). Manganese(II)-tetrasulfonated phthalocyanine also shows tumor localization properties and is a more efficient relaxation agent than the analogous Gd(III) complexes (314). 

Eichhorn ME et al (2006) Paclitaxel encapsulated in cationic Hpid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging. Cancer Biol Ther 5 89-96... 

Curnis F, Sacchi A, Borgna L et al. Enhancement of tumor necrosis factor alpha antitumor immunotherapeutic properties by targeted delivery to aminopepti-daseN (CD13). Nature Biotechnol 2000 18 1185-1190. 

Shielded polyplexes with improved blood circulating properties are interesting tools for systemic cancer therapy (see Sect. 4.2). Nanoparticles can take advantage of the enhanced permeability and retention (EPR effect) [89] for passive tumor targeting. The EPR effect is based on the leakiness of tumor vasculature, due to neovascularization in growing tumors, combined with an inadequate lymphatic drainage. Nanoparticles with an elongated plasma circulation time can extravasate and passively accumulate at the tumor site. 

Fenvalerate inhibits intercellular communication between fibroblast cells and enhances the development of hepatocyte foci in rat liver at nonhepatotoxic dose levels. Chemicals that possess these properties are likely to be tumor promoters (Flodstrom et al. 1988). Fenvalerate alone induced no hepatotoxic effects in rat liver, as judged by transaminase activities and histology. However, some rats that were partially hepatectomized and insulted with nitrosodiethylamine — a carcinogen and tumor initiator — had significantly elevated numbers of liver foci after administrations of fenvalerate. This response suggests that fenvalerate is a potential tumor promoter (Flodstrom et al. 1988). 

A few examples to render tetrapyrrolic compounds less phototoxic can be found in the hterature. In one approach, carotenoid structures were employed for the synthesis of some carotenoporphyrin derivatives [92-94]. Figure 8 shows two stuctures by way of example. Due to similar photophysical properties of the two structural components, the excited triplet state of the porphyrin is quenched by the carotenoid moiety, thus inhibiting the formation of singlet oxygen, while its fluorescence capabilities are still preserved. Biodistribution studies revealed enhanced uptake into tumour tissue [39,93,95]. However, microscopy studies have shown that such compounds are associated with connective tissues in the tumors rather than with cancerous cells indicating low specificities for mahgnant transformation [96]. 

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