Tumor potentiators

Xu XC, el-Na ar AK, Lotan R. Differential expression of ga-lectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. Am J Pathol. 1995 147 815-822. 

The ideal cytotoxic dmg is a small molecule that is stiU very potent. A promising class of cytotoxic agents is a group of radiomimetic substances called ene-diyenes these are secondary metaboHtes from Streptomyces that are minor groove DNA-binders and introduce double-strand breaks that may lead to apoptosis [112-114] (Fig. 1.8). Their anti-tumor potential has been investigated in a number of experimental studies [115-117]. 

Unresectable and chemorefractory malignant tumors in the liver are a major cause of death in solid tumors. Potentially curative surgery is uncommon for these patients. A number of liver-directed therapies are now available and are making important contributions to quality of life, prolonged time to liver progression, and overall survival. Limited surgery involving laparoscopy and percutaneous access approaches enables local tumor resection, cryotherapy, laser-induced interstitial thermotherapy, and radiofrequency ablation. 

A recent review of the literature demonstrated a trend toward the use of ethanol for embolization of renal tumors [20]. Ethanol is a nonviscous liquid, and after it is injected into the main renal artery, it diffuses into the distal vascular bed of the tumor, potentially causing tumor necrosis rather than simple occlusion of the embolized artery [21]. Transcatheter administration of ethanol is technically easy, and theoretically, reflux of a small amount of ethanol may not be as toxic as other embolic agents to other organs of the body because alcohol dilutes rapidly in a large volume of blood [22]. In reality. 

Portnow J, Badie B, Chen M, Liu A, Blanchard S, Synold TW. The neuropharmacokinetics of temozolomide in patients with resectable brain tumors potential implications for the current approach to chemoradiation. CUn Cancer Res 2009 15 7092-8. 

The next seven Chapters involve polymers with potential anti-tumor and other medicinal properties. Chapter 11 (Carraher Strothers) deals with the release of methotrexate and/or chloroplatinate while Chapter 12 (Gebelein, et al.) describes the release of 5-fluorouracil from a biodegradable polymer. Chapter 13 (Matsuzaki, et al.) reviews much research on polysaccharides that have anti-tumor properties, and this theme is enhanced in Chapter 14 (Carraher, et al.) which describes tin-modified polysaccharides. The use of nucleic acid analogs in chromatography is the main theme of Chapter 15 (Inaki, et al.), but these same materials also have potential anti-tumor properties. Poly(ICLC), Chapter 16 (Levy Bever) is also a nucleic acid analog with some anti-tumor potential. Finally, Chapter 17 (Trombley, et al.) covers polymers with anti-tumor and other medical properties. 

The experimental systems of special interest which are responsive to this alkaloid are X- 63 plasma cell myeloma, a model system of multiple myeloma in manj Shionogi carcinoma ll5 an androgen-dependent tumor, potentially a model system for prostatic cancer the C-114 98 myelogenous leukemia which is nonresponsive to any of the clinically useful chemotherapeutic agents. 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

The potential for normal brain tissue injury is one of the limiting factors in the use of XRT for brain tumors. Pentobarbital is a cerebral radioprotectant in rodent and primate models after single doses, but is associated with significant risks. Of alternative barbiturates, thiopental given to tats receiving 70-Gy (7000-rad) whole-brain irradiation in a single fraction enhances the 30-day survival similarly to pentobarbital, whereas ethohexital and phenobarbital show no radioprotective activity (250). 

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.). 

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