Normal tissue

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. 

Phosphorothioates generally protect normal tissues more than tumors. Tumor protection reported in some animal studies can pardy be explained by physiological effects of the particular dmgs, which are specific to rodents (4). WR-2721 does not appear to protect human and most animal tumors, apparentiy because of the low availabiUty of the dmg to tumor cells (4). Many tumors appear to have a reduced capillary density (44), which may mean that these tumors have altered levels of alkaline phosphatase, the enzyme that converts WR-2721 to WR-1065. A reduced abiUty of thiols to protect the hypoxic cells characteristic of many tumors may also contribute to their selectivity for normal tissues. The observation that WR-1065 protects cultured normal human fibroblasts, but not fibrosarcoma tumor cells, suggests that additional factors may contribute to the selectivity of radioprotection by WR-2721 m vivo (18). 

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). 

Tb allium, which does not occur naturaHy in normal tissue, is not essential to mammals but does accumulate in the human body. Levels as low as 0.5 mg/100 g of tissue suggest thallium intoxication. Based on industrial experience, 0.10 mg /m of thallium in air is considered safe for a 40-h work week (37). The lethal dose for humans is not definitely known, but 1 g of absorbed thallium is considered sufficient to kHl an adult and 10 mg/kg body weight has been fatal to children. In severe cases of poisoning, death does not occur earlier than 8—10 d but most frequently in 10—12 d. Tb allium excretion is slow and prolonged. For example, tb allium is present in the feces 35 d after exposure and persists in the urine for up to three months. 

Sensitizer A sensitizer is defined by OSHA as "a chemical that causes a substantial proportion of exposed people or animals to develop an allergic reaction in normal tissue after repeated exposure to the chemical." The condition of being sensitized to a chemical is also called chemical hypersensitivity. Certain chemicals have no immediate health effect. But if you are exposed to them several times, they can make you allergic or sensitive to other chemicals. A classic example is formaldehyde (HCHO). Typical reactions to sensitizers can include skin disorders such as eczema. When working with sensitizers, always use proper protective equipment such as gloves, respirators, etc. Once you are sensitized to a particular chemical, even minute amounts will cause symptoms. Sensitization is usually a lifelong effect. 

The mitomycins do not react directly with DNA, but require prior activation by reduction of the quinone. This property of bioreductive activation has inspired the design and development of synthetic anticancer drugs that are also activated by reduction, as this is expected to confer a degree of tumor selectivity [45, 46]. Many solid tumors are short of oxygen relative to normal tissue, so reductive activation of the mitomycins and other bioreductive drugs can proceed in tumors, while it is inhibited by the oxidizing environments in normal tissues. 

German investigators (Brock et al) worked on the creation of alkylating pro-drugs that have cytostatic activity after specific biotransformation in the tumor tissue. Cyclophosphamide (CTX) has well pronounced antitumor activity with the broadest spectrum. It is metabolized to the cytotoxic phosphoamide mustard. In normal tissues with high enzyme level cyclophosphamide is converted to its inactive metabolites (Fig. 2). These differences in biotransformation can explain the relative selectivity of cyclophosphamide towards... 

Cancers are tumors that have acquired the ability to invade and disrupt surrounding normal tissues. Such lesions can arise in any tissue of the human body, and so cancers represent a heterogeneous group of diseases that have certain biological features in common. 

Though DNA damage-based therapies havebeen in use for many years, it has remained unclear why such treatment often causes the selective death of tumor cells while sparing adjacent normal tissue. The genetic alterations that occur in cancers that alter the DNA damage reponse may explain why such therapy can be efficacious. 

Limitations are obvious if the diseased tissue does not differ from normal tissue or successfully treated tissue in respect of the above-mentioned criteria. Under these conditions, even a contrast agent with high absorption of X-rays is of no help. Another drawback is the short-lasting contrast which requires repeated injections if the diagnosis is missed during the first scan or if persistent visualization of a lesion is required during an interventional procedure. 

In cancer treatment, passive targeting of macromolecular carriers to tumors is a commonly used approach. This passive targeting is based on the enhanced permeability and retention (EPR) effect, which leads to an accumulation of the high molecular weight carrier in the tumor tissue. The EPR effect arises from the different physiology of tumor vasculature, where the vessel walls are highly porous and lack the tight junctions that are present in healthy tissue. As a result, macromolecular carriers extravasate and accumulate preferentially in tumor tissue relative to normal tissues [63, 64]. 

Of the thousands of different enzymes present in the human body, those that fulfill functions indispensable to cell vitality are present throughout the body tissues. Other enzymes or isozymes are expressed only in specific cell types, during certain periods of development, or in response to specific physiologic or pathophysiologic changes. Analysis of the presence and distribution of enzymes and isozymes— whose expression is normally tissue-, time-, or circumstance-specific—often aids diagnosis. 

An interesting application of the photodynamic properties of porphyrins is their possible use in the treatment of certain types of cancer, a procedure called cancer phototherapy. Tumors often take up more porphyrins than do normal tissues. Thus, hematopor-phyrin or other related compounds are administered to a patient with an appropriate mmor. The mmor is then exposed to an argon laser, which excites the porphyrins, producing cytotoxic effects. 

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