Cytotoxic radiation

F. Role in therapy Radioimmunotherapy is a promising new area of cancer treatment that combines the targeting power of monoclonal antibodies with the cell-damaging ability of localized radiation. When infused into a patient, these radiation-carrying antibodies circulate in the body until they locate and bind to the surface of specific cells, and then deliver their cytotoxic radiation directly to malignant cells. Zevalin is the first treatment for cancer that includes a monoclonal antibody that is combined... 

Saran, M., and Bors, W., 1997, Radiation chemistry of physiological saline reinvestigated evidence that chloride-derived intermediates play a key role in cytotoxicity, Radiat. Res. 147 70-77. 

IL-l radiation/cytotoxic injury bacterial infection rodent... 

Nicotinamide potentiates the cytotoxic effects of chemotherapy and radiation treatment against tumor cells. This effect is probably attributable to increased... 

Most recently, a phase-I-study defined a dose of 13-ris-retinoic acid that was tolerable in patients after myeloablative therapy, and a phase-III-trial showed that postconsolidation therapy with 13-cis-retinoic acid improved EFS for patients with high-risk neuroblastoma [7]. Preclinical studies in neuroblastoma indicate that ATRA or 13-cw-RA can antagonize cytotoxic chemotherapy and radiation, such that use of 13-cis-RA in neuroblastoma is limited to maintenance after completion of cytotoxic chemotherapy and radiation. It is likely that recurrent disease seen during or after 13-cis-RA therapy in neuroblastoma is due to tumor cell resistance to retinoid-mediated differentiation induction. Studies in neuroblastoma cell lines resistant to 13-cw-RA and ATRA have shown that they can be sensitive, and in some cases collaterally hypersensitive, to the cytotoxic retinoid fenretinide. Here, fenretinide induces tumor cell cytotoxicity rather than differentiation, acts independently from RA receptors, and in initial phase-I-trials has been well tolerated. Clinical trials of fenretinide, alone and in combination with ceramide modulators, are in development. 

Interestingly, all these monoclonal antibodies have a poor antitumor activity when used as single agents, with overall response rates of about 10%. Thereby, these monoclonal antibodies have all been approved in combination with classical cytotoxic agents or radiation therapy. 

Taya A, Mewhinney JA. 1992. Cytotoxicity, uptake and dissolution of 241Am02 particles in dog alveolar macrophages in vitro. Int J Radiat Biol 62(1) 81-88. 

The surface epithelial cells of the small intestine are renewed rapidly and regularly. It takes about two days for the cells of the duodenum to be renewed completely. As a result of its rapid renewal rate, the intestinal epithelium is susceptible to various factors that may influence proliferation. Exposure of the intestine to ionizing radiation and cytotoxic drugs (such as folic acid antagonists and colchicine) reduces the cell renewal rate. 

The knockout of PARP-1 or PARP-2 significantly reduces the cells ability to repair damaged DNA following their exposure to radiation or cytotoxic insult [6,7]. Poly (ADP-ribose) polymer synthesis consumes substantial amounts of NAD+, and hyperactivation of PARP results in depletion of cellular NAD+ pools and energy stores, leading to cell death by necrosis. 

Bertling, C. J., Lin, F., and Girotti, A. W., 1996, Role of hydrogen peroxide in the cytotoxic effects ofUVA/B radiation on mammalian cells, Photochem. Photobiol. 64 137-142. 

Tang A. Udey MC Doses of ultraviolet radiation that modulate accessory cell activity and ICAM-1 expression are ultimately cytotoxic for murine epidermal Langerhans cells. J Invest Dermatol 1992 99 71S-73S. 

The severe nausea and vomiting induced by cytotoxic drugs and radiation in man can be reduced by metoclopramide given either atone or in combination with other drugs, such as dexamethasone. However, the extrapyramidal side-effects induced by metoclopramide, due to antagonism of dopamine re-... 

Non-surgical methods of cancer treatment, primarily radiation therapy and chemotherapy, rely almost exclusively on procedures that kill cells. The main problem with these treatments is that they do not provide specificity for cancer cells. In the case of radiation therapy, a degree of specificity is achieved by localizing the radiation to the tumour and its immediate surrounding normal tissue. For anti-cancer drugs, it is primarily the rapid proliferation of many of the cancer cells that makes them more sensitive to cell killing than their normal counterparts. However, both modalities are limited by their cytotoxic effects on normal cells. In the case of radiotherapy, normal tissue surrounding the tumour limits the radiation dose, where-... 

Prophylaxis To decrease the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy or radiation therapy. Vaginal candidiasis Vaginal candidiasis (vaginal yeast infections caused by Candida). 

Ohmori T, Arteaga C]L (1998) Protein kinase C epsilon translocation and phosphorylation by cis-diamminedichloroplatinum(II) (CDDP) potential role in CDDP-mediated cytotoxicity. Cell Growth Differ 9 345-353 Ojeda F, Guarda MI, Maldonado C, Folch H, Diehl H (1992) Role of protein kinase-C in thymocyte apoptosis induced by irradiation. Int J Radiat Biol 61 663-667 Oka M, Ogita K, Ando H, Horikawa T, Hayashibe K, Saito N, Kikkawa U, Ichihashi M (1996) Deletion of specific protein tdnase C subspecies in human melanoma cells. J Cell Physiol 167 406-412... 

Significance of Flavonoid Accumulation in Cell Walls Whereas the accumulation of flavonoids in plant cell walls may be difficult to explain, however, it may be considered as a means of eliminating such cytotoxic agents from the cell symplast. Such site for flavonoid accumulation may also be considered as a means of protection against pathogens, predators and ultraviolet radiation (54), especially in the absence of ligni-fied tissues, as in the case of Chrysosplenium. 

Spatial cooperation is a term coined to describe a situation when disease in one particular anatomic site is missed by one modality but is treated adequately by another. The essence of this is that radiation is a local therapy that will not impact on metastatic disease beyond the planned field borders. Systemic cytotoxic chemotherapy is traditionally used to address the potential distant spread of cancer. In the original description of this mechanism there is no assumption of an interaction between the drugs and radiation with the idea being that the best radiation and best chemotherapy be administered independently of toxicities. The classic example used in several textbooks to illustrate this is the treatment of childhood leukemia with systemic chemotherapy, while their central nervous system, a potential sanctuary site where disease is not treated adequately by chemotherapy, is treated by radiation (28). The reality of the interaction between radiation and chemotherapy is that the dose and timing of radiation are adjusted accordingly to minimize their impact on the neural tissues. 

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