Tumor cell killing

The greatest research effort on radiation sensitizers has focused on organic compounds however, platinum complexes conform to the hypotheses for radiation sensitizers since they are electron affinic and react preferentially with the hydrated electron in aqueous solution. Early studies of cisplatin in combination with radiation therapy suggested a synergistic effect in antitumor activity (50,51). Much of the initial data were obtained using cells in tissue culture (52), these data indicated that the potential of cisplatin to inhibit repair of radiation-induced damage to DNA could be an important contributor to the enhanced tumor cell killing seen in vivo by the combination of these two modes of treatment. 

The rationale for concurrent chemoradiation is that the ChT can augment local-regional control by both direct tumor cell killing and radiosensitization at the same time as it addresses systemic micrometastases. Unfortunately, this also has the potential to increase radiation-related mucosal acute toxicity, predominantly esophagitis and pneumonitis. Thus, some of the early trials of concurrent therapy used either attenuated dose ChT or split course RT to ameliorate potential cotoxicity. These trials showed that concurrent therapy is feasible and, as with the sequential approach, improves outcome. 

Lorsbach, R. B., Murphy, W. J., Lowenstein, C. J., Snyder, S. H., and Russell, S. W. (1993). Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide. J. Biol. Chem. 268, 1908-1913. 

In an in vivo study in rats, dietary curcumin with cisplatin modulated tumor marker indices of fibrosarcoma toward normal controls [Navis et al., 1999], Treatment with radiotherapy and curcumin resulted in enhanced tumor cell killing and reduced radioresistance in mice bearing fibrosarcoma, as indicated by the significant inhibition of radiation-induced ERK and NF-kB expression [Kumar Mitra and Krishna, 2004],... 

Number of Treatments Percentage Killed Number of Tumor Cells Killed Each Treatment Number of Surviving Tumor Cells... 

S. Briisselbach, T. Korn, T. Volkel, R. Muller, and R. Kontermann, Enzyme recruitment and tumor cell killing in vitro by a secreted bispecific single-chain diabody, Tumor Targeting 4 115 (1999). 

With the modification of mAbs using a new technology (the Potelligent Technology), binding affinity for Fc receptors was reported to be enhanced and thus ADCC activity increased. As a result, this type of mAb would be expected to achieve a higher tumor cell killing activity than conventional antibodies. 

Matthews, N., Neale, M.L., Jackson, S.K., and Stark, J.M., 1987, Tumor cell killing by tumor necrosis factor inhibition by anearobiotic condition, free-radical scavengers and inhibitors of arachidonate metabolism. Immunology 62 153-155 Miller, M.G., Rodgers, A., and Cohen, G.M., 1986, Mechanisms oftoxicity of naphthoquinones to isolated hepatocytes. Biochem. Pharmacol. 35 1177-1184 Minko, T., Kopeckova, P., and Kopecek, J., 1999, Comparison ofthe anticancer effect of free and HPMA copolymer-bound adriamycin in human ovarian carcinoma cells. Pharmaceut. Res. 16 986-996... 

C-reactive protein Bactericidal activity Tumor cell killing Antigen-specific AFC Proliferation to ConA, PHA... 

Sone S, Matsura S, Ogawara M, et al. Potentiating effect of muramyl dipeptide and its lipophilic analog encapsulated in liposomes on tumor cell killing by human monocytes. J Immunol 1984 132 2105-2110. 

Hematopoietic stem cell transplantation (HSCT) is a process that involves intravenous infusion of hematopoietic stem cells from a donor into a recipient, following the administration of chemotherapy with or without radiation. The rationale is to increase tumor cell kill by increasing the dose of chemotherapy. Immune-mediated effects may also contribute to the tumor cell kill observed after allogeneic HSCT. 

The purpose of the preparative (or conditioning) regimen in traditional myeloablative transplants is two-fold (1) maximal tumor cell kill and (2) immunosuppression of the recipient to reduce the risk of graft rejection (allogeneic HSCT only). 

Kothari V et al (2010) HD AC inhibitor valproic acid enhances tumor cell kill in adenovirus-HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model. Int J Cancer 126 (3) 733-742... 

M., Aebischer, P., Krammer, P.H., Fontana, A., 1995. Local Fas/APO-1 (CD95) ligand-mediated tumor cell killing in vivo. Eur. J. Immunol. 25, 2253-2258. 

Ideally, one would like to measure the mass transfer rates and concentrations in each compartment of a tissue as a function of both time and space and develop precise mathematical models on the basis of these data. Such models could then be used to predict spatial and temporal concentrations of various agents in a variety of normal and neoplastic tissues. Since the selective tumor cell kill depends on the concentration-time history of a drug, such information could be used in developing optimal dose schedule of anticancer agents. However, there are several practical problems in carrying out such detailed measurements directly, and in developing such detailed, dynamic, predictive mathematical models. Nevertheless, it is possible to obtain considerable useful information about mass transfer in tumors, using the experimental and theoretical approaches discussed in the next two sections. 

B.W. Henderson, V.H. Fingar (1989). Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. Photochem. PhotobioL, 49, 299-304. 

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