Tumor therapeutics

Wajant H, Gerspach J, Pfizenmaier K (2005) Tumor therapeutics by design targeting and activation of death receptors. Cytokine Growth Factor Rev 16 55-76... 

The results obtained suggest that such polysaccharide-5FU conjugates can be utilized as tumor therapeutical agents. 

Mechanism of Action A bisphosphonate that inhibits the resorption of mineralized bone and cartilage inhibits increased osteoclastic activity and skeletal calcium release induced by stimulatory factors produced by tumors. Therapeutic Effect Increases urinary calcium and phosphorus excretion decreases serum calcium and phosphorus levels. 

Zhang, R. and Wang, H. (2000a) Antisense oligonucleotides as anti-tumor therapeutics. Recent Res. Dev. Cancer, 2, 61-76. 

Fullerenes and their derivatives are of broad interest in various fields ranging from ferromagnetism [87] over their application as possible HIV inhibitors [88] to tumor-therapeutic active substance in biological systems [89]. Although C6o is insoluble in water, dissolution may be accomplished by using water-soluble polymers [90] or surfactant solutions containing amphiphilic block-copolymers [91], micelles or liposomes [92, 93]. The immobilization of... 

Varfolomeev E, Vucic D (2011) Inhibitor of apoptosis proteins fascinating biology leads to attractive tumor therapeutic targets. Future Oncol 7(5) 633-648... 

Increased FASN expression in tumors is an early, common event (Swinnen et al., 2002 Myers et al., 2001) and its correlation with reduced survival and increased recurrence rationalizes the potential for anti-FASN tumor therapeutics (Kuhajda, 2000, 2006 Kridel et al., 2007). As evidence that lipogen-esis as a whole is important in cancer, many of the enzymes upstream of FASN show altered expression patterns in human tumor cells, as well. For instance, ACL is overexpressed in cancer cells of breast and bladder (Szutowicz et al., 1979 Turyn et al., 2003). ACC is overexpressed in breast and prostate cancer cells (Milgraum et al., 1997 Swinnen et al., 2000b, 2006 Heemers et al.,... 

Woodle MC, Lasic DD, Redemann C (1991) Sterically stabilized liposomes improvements in pharmacokinetics and anti-tumor therapeutic efficacy. Proc Natl Acad Sci USA 88 11460-11464... 

Noncontraceptive Uses of Progestins. Progestins have other therapeutic uses aside from contraception. Hormone-dependent tumors and cysts involving reproductive tissues respond to progestins. Megestrol acetate and MPA are the two most commonly used progestins to treat breast cancer... 

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. 

Not only is TCDO a potent therapeutic agent in acute radiation syndrome, but treatment using TCDO from days 4—11 after TBI increases the survival rate in rats for up to one year, protects against the development of late GI ulcers, and also reduces the development of y-ray-induced leukemias and malignant epitheHal tumors, but not sarcomas (202). The anticarcinogenic effect of TCDO maybe related to the inhibition of PGs, which promote carcinogenesis, or to immunostimulation, which may result in a more effective elimination of malignant cells. 

Uracil is used more effectively, in nucleic acid synthesis within a rat hepatoma than in normal liver. This observation appears to have stimulated the synthesis of 5-fluorouracil (1027) as an antimetabolite mainly because the introduction of a fluorine atom involves a minimal increase in size. In the event, 5-fluorouracil did prove to have antineoplastic activity and it is now a valuable drug for treatment of tumors of the breast, colon or rectum, and to a lesser extent, gastric, hepatic, pancreatic, uterine, ovarian and bladder carcinomas. As with other drugs which interfere with DNA synthesis, the therapeutic index is quite low and great care is required during treatment (69MI21301). 

Poly(malic acid) is of pharmaceutical interest because its chemical derivatives may harbor both tissue-specific homing molecules and therapeutic effectors to be used for tissue (tumor) targeting in chemotherapy [2]. Because of its efficient production by fermentation, its biodegradability and nontoxicity, it is also considered as raw material in the industrial production of detergents, glues, and plastic materials. 

Clinical trials showed therapeutic efficacy in a broad spectrum of tumors these include SCLC, testicular tumors, sarcomas, breast cancer, renal cell cancer, pancreatic tumors and lymphomas. Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. Therefore it is recommended that ifosfamide is coadministered with the thiol compound mesna to avoid hemorrhagic cystitis and to reduce the risk of developing bladder cancer. Other side effects include neurotoxicity and myelosuppression. 

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