Cancer Irradiation

B. J. Stover and H. Eyring, Death from Aging, Cancer, Irradiation and Other Stresses, Abstr. Papers Eighteenth Ann. Meeting Radiation Res. Soc., Dallas, Texas, p. 60, 1970. 

Prevention of disease by modification of risk factors is important in many areas of medicine. For optimal planning and execution of prevention programs it is important to know the dose—response relationship between the risk factor that is modified and the disease that is to be prevented. Such a relationship may take several forms (Rose, 1992 Laurberg et ai, 2001). For example, there seems to be a more or less linear association between irradiation of the thyroid in childhood and later development of thyroid cancer. Irradiation of the thyroid in childhood should be as low as possible. The relationship between iodine intake and the risk of disease is more complicated. Even if the most severe problems are seen when iodine intake is insufficient, a high iodine intake may also lead to disease. The relationship is U-formed (Laurberg et ai, 2001) (Figure 47.1). 

The development of so-called photodynamic therapy uses lasers for treatment of cancer. The patient is injected with a substance called hematoporphyrin derivative [68335-15-9] which is preferentially localized in cancerous tissues. The patient is later irradiated with laser light, often with a dye laser at a wavelength around 630 nm. The light energy catalyticaHy photooxidizes the hematoporphyrin derivative, releasing materials which kill the nearby cancerous tissue. Normal tissue which did not retain the chemical is not harmed. Photodynamic therapy offers promise as a new form of cancer treatment. 

A principal appHcation for photomedicine is the photodynamic treatment of cancer. Photochemical and clinical aspects of this topic have been reviewed (10,11). Direct irradiation of tumors coupled with adininistration of a sensitizer is used to effect necrosis of the malignancy. In this process, an excited state sensitizer interacts with dissolved in vivo to effect conversion of the oxygen from its triplet ground state to an excited singlet state, which is highly cytotoxic. In principle, excited sensitizers in either the singlet or the triplet state can effect this conversion of molecular oxygen (8). In... 

Whereas epidermal growth factor (EGF) enhances the radiosensitivity of human squamous ceU carcinoma cells in vitro (197), addition of EGF to hormone-deprived MCE-7 breast cancer cells prior to irradiation results ia iacreased radioresistance (198). An anti-EGE-receptor monoclonal antibody blocks the abiUty of EGE to enhance growth and radioresistance. Tumor cells, the growth of which is stimulated by EGE, appear to be protected those where growth is iohibited are sensitized (198). 

A clinical trial to evaluate misoprostol as a protector of normal tissue during a course of XRT in cancer patients suggests a reduction in acute normal tissue injury (215). A randomized, prospective, double-blind study indicates that topical misoprostol, administered as an oral rinse 15-20 min before irradiation using conventional 2-Gy (200 rad) fractions, five days a week over 6—7 weeks, significantly protects the oral mucosa from radiomucositis, a frequently observed normal tissue complication during XRT for head and neck cancer (215). 

In the veterinary as in the human patient, neoplasms are often metastatic and widely disseminated throughout the body. Surgery and irradiation are limited in use to weU-defined neoplastic areas and, therefore, chemotherapy is becoming more prevalent in the management of the veterinary cancer victim (see Chemotherapeutics, anticancer). Because of the expense and time involved, such management must be restricted to individual animals for which a favorable risk—benefit evaluation can be made and treatment seems appropriate to the practitioner and the owner. In general, treatment must be viewed not as curative, but as palliative. 

The antineoplastic agent mitindomide (160) in fact represents the well-known product from irradiation of maleimide in benzene [30]. The activity of this old compound was uncovered by one of the large antitumor screens maintained by the National Cancer Institute, The structure is sufficiently complex and the starting materials sufficiently available to lead one to suspect that the product is still produced photochemically. The product can be rationalized by assuming successive 1,4 and 1,2 additions to benzene. Intermediate 159a involves the 1,4 followed by 1,2 addition intermediate 159b presupposes the steps occur in the reverse order. 

The main reason particle accelerators were invented and developed is so that scientists can observe what happens when beams of particles strike ordinary matter. However, particle accelerators are also used in a wide variety of applications, such as irradiating cancers in people. 

Consider an isotope of yttrium, Y-90. This isotope is incorporated into cancer-seeking antibodies so that the cancer can be irradiated by the yttrium and destroyed. How many neutrons are in... 

Male infertility may result from cancer surgery, radiotherapy, hormonal imbalances, or damage of germinal stem cells. Testicular damage from radiotherapy depends on the treatment field, total dose, and fractionation schedule. Depending on the radiation, sperm counts may return to pretreatment levels in 10 to 24 months after therapy or maybe permanent in 80% of men after total-body irradiation for transplant. 

Hormonal therapies that have been studied in the treatment of primary or early breast cancer include antiestrogens, oophorectomy, ovarian irradiation, luteinizing hormone-releasing hormone (LHRH) agonists, and aromatase inhibitors. 

Raabe OG. 1996. Relative biological effectiveness for induction of cancer by protracted alpha versus beta internal irradiation. Health Phys 70(6) S8. 

In a similar way (and as described for the aromatic isocyanides), aliphatic a, 3-un-saturated isocyanides can also be used, leading to similar structures with a cyclo-hexano instead of a benzo moiety [84]. Based on the approach using aromatic isocyanides, a small library of about 20 camptothecin derivatives has been prepared, of which irinotecan and topotecan have entered the clinical treatment of cancer [85]. For the synthesis of the camptothecin derivatives, 3-206 was alkylated with the appropriate propargylic bromides 3-207 to give 3-208, which were irradiated in benzene at 70 °C, together with the respective isocyanide 3-209 and hexamethylditin... 

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