Tumor therapy

Heterocycles, calcium channels blockers, as auxiliary agents in resistant tumor therapy 97YZ455. 

The reduced symmetry of the chromophore, which still contains 187t-electrons and is therefore an aromatic system, influences the electronic spectrum which shows a bathochromic shift and a higher molar extinction coefficient of the long-wavelength absorption bands compared to the porphyrin, so that the photophysical properties of the chlorins resulting from this structural alteration render them naturally suitable as pigments for photosynthesis and also make them of interest in medical applications, e.g. photodynamic tumor therapy (PDT).2... 

The photophysical properties of porphycenes make these structures potential sensitizers for an application in Photodynamic Tumor Therapy (PDT). To improve the photophysical properties and to modify possible biological activity it is necessary to have porphycenes with an extended chromophore and/or with additional functional groups for further modifications. The Diels-Alder reaction of a vinyl porphycene allows for the preparation of benzoporphycenes with an extended chromophore9 and additional functional groups (cf. Section 1.1.2.4.). 

Keywords Bioorganic chemistry, Cellular signal transduction, Enzyme-Inhibition, Ras-farne-syltransferase, Tumor-therapy... 

Novel nitroxide malonate methanofullerenes (Fig. 1.3), thanks to the presence of nitroxide radicals and fullerene moiety, are able to protect cells from toxic side effects of cyclophosphamide (Gubskaya et al., 2007). Experiments were carried out on mice, in which leukemia P-388 was transplanted. Cyclophosphamide or fullerene individually injected did not increase the average life span of the animals, while the combination of the anticancer drug and nitroxide fullerene derivative resulted in the survival of 70% animals, classifying these compounds as promising modifiers of biological reaction for tumor therapy. 

In order to prove the efficiency of the liposomal system in tumor therapy (administration of the liposomes after tumor induction), seven animals were treated with 2 x 10 B16 tumor cells (injection of a suspension in 200 pL HBSS into tail vein). After four and seven days the formulation [AVE 3 TRP-2 (10 pg TRP-2) and AVE 3 1826 CpG (1.3 pg CpG)] was given into the foot pad of the hind legs of the mice intradermally. Twenty-one days after the injection of the tumor cells, the animals were sacrificed and the metastases in the prepared lungs were counted. A second group of seven animals received the tumor cells, but no liposomal treatment was applied. Table 2 indicates the high antitumor potency of the formulation. 

Although tumors begin as clones of single cells, subsequent mutations generally result in tumors that are genetically heterogeneous, one of the problems for tumor therapy. 

Kleinberg, L, Grossman, S.A., Carson, K., Lesser, G., O Neill, A., Pearlman, J., Phillips, P., Herman, T., and Gerber, M. Survival of patients with newly diagnosed glioblastoma multiforme treated with RSR13 and radiotherapy results of a phase 11 new approaches to brain tumor therapy CNS consortium safety and efficacy study. J. Clin. Oncol. 2002, 20, 3149-3155. 

Wang CY, Cusack JCJr, Liu R, Baldwin ASJr (1999b) Control of inducible chemore-sistance enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med 5 412-417... 

Friedrich J, Ebner R, Kunz-Schughart LA (2007) Experimental anti-tumor therapy in 3-D spheroids—old hat or new challenge Int JRadiatBiol 83 849-871... 

Schlaeppi JM, Wood JM. Targeting vascular endothelial growth factor (VEGF) for anti-tumor therapy, by anti-VEGF neutralizing monoclonal antibodies or by VEGF receptor tyrosine kinase inhibitors. Cancer Metastasis Rev 1999 18 4734-81. 

Vaupel P, Kelleher DK, Hockel M. Oxygen status of malignant tumors pathogenesis of hypoxia and significance for tumor therapy. Semin Oncol 2001 28(2 Suppl 8) 29-35. 

Boron seems to have an affinity for cancerous tumors, and this property has been exploited in radiation therapy (Hamada et al. 1983 Hatanaka 1986). Boron-10 has been used in neutron capture therapy to cure malignant sarcomas implanted in the hind legs of mice, as well as spontaneous malignant melanomas in pigs (Slatkin etal. 1986). The sulfhydral borane monomer (Bi2HnSH) is used as a B-10 carrier in neutron therapy of malignant human brain tumors and seems to be most effective at 30 pg B-lO/kg tissue (Hatanaka 1986). Polyhedral boranes attached to monoclonal antibodies that are tumor specific may become useful in tumor therapy by neutron irradiation (Parry... 

A link between bacteria and tumor therapy was found early, at the beginning of the XVIII century [10]. By the end of the XIX century, Coley [11] developed a treatment for cancer with a mixture of bacterial toxins. In 1943 Shear and Turner [4] found that the antitumor effect of Coley s toxin was due to endotoxins, and after several decades it was shown that the biological activity of LPS was due to the lipid A [5]. We investigated the structures of lipids A with regard to their antitumor activities [12], finding that the optimum in vivo activity is obtained with diglucosamines acylated by 3 long chain fatty acids. 

Hirsch LR, Sershen SR, Halas NJ, Stafford RJ, Hazle J, West JL. Nanoshell mediated near infrared photothermal tumor therapy. 2003 Summer Bioengineering Conference, June 25-29, Key Biscayne, FL. 

Singlet oxygen was discovered originally by Raab who first reported the photodynamic effect of dyestuffs, light, and oxygen [311]. The biomedical implications of this discovery have only recently been made clear, particularly by Dougherty and his co-workers, who have demonstrated the implications of the photodynamic effect in tumor therapy [312]. 

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