Tumor mechanisms

Tabata S, et al. Anti-tumor mechanisms of 3 -ethynyluridine and 3 -eth5mylcytidine as RNA synthesis inhibitors development and characterization of 3 -etyh5niyluri-dine-resistant cells. Cancer Lett 1997 116 225. 

The complete in vivo anti-tumor mechanism of action of ellipticine and its derivatives is still not well understood. However, a tremendous amount of work has... 

Brain tumor Mechanical obstruction Usually clear 0-80 lymphocytes 15-200 (usually normal)... 

Cooper C, Liu G-Y, Niu Y-L, Santos S, Murphy LC, Watson PH (2004) Intermittent hypoxia induces proteasome-de-pendent down-regulation of estrogen receptor a in human breast carcinoma. Clin Cancer Res 10 8720 8727 Dachs GU, Tozer GM (2000) Hypoxia modulated gene expression Angiogenesis, metastasis and therapeutic exploitation. Eur J Cancer 36 1649 1660 Di Paolo A, Bocci G (2007) Drug cUstribution in tumors mechanisms, role in drug resistance, and methods for modification. Curr Oncol Rep 9 109 114 Douple EB, Richmond RC (1978) Platinum complexes as radiosensitizers of hypoxic mammalian cells. Br J Cancer Suppl 3 98-102... 

Enediynes hold substantial promise as anti cancer drugs because of their potency and selectivity Not only do they inhibit cell growth they have a greater tendency to kill cancer cells than they do normal cells The mechanism by which enediynes act involves novel chemistry unique to the C C—C=C—C C unit which leads to a species that cleaves DNA and halts tumor growth... 

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. 

Calcitonin is secreted when abnormally high calcium levels occur in plasma. Although plasma concentrations are normally minute (<100 pg/mL), they increase two- to threefold after calcium infusion. Calcitonin has a short plasma half-life (ca 10 min). Certain thyroid tumors are the result of CT concentrations 50—500 times normal. The mechanism of action is a direct inhibition of bone resorption. Calcitonin is used clinically in various diseases in which hypercalcemia is present, eg, Paget s disease (46). 

The novel agent sulofenur (69) has entered clinical trials based on its broad spectmm antitumor activity in tumor models, its unusual mechanism of action, and its lack of cross-resistance to other agents (33). In Phase I clinical trials, the dmg was well tolerated and some clinical responses were noted. 

Research and clinical experience on dmg resistance suggests that tumor cells are particularly adept at genetic selections leading to alterations in the stmcture, function, or synthesis of proteins involved in the antitumor dmg action and detoxification. Multiple mechanisms of resistance have been shown to account for the resistance seen in the clinic (46). 

In summary, structural studies of Ras and Gq with GTP-yS and a transition state analog have illuminated the catalytic mechanism of their GTPase activity, as well as the mechanism by which GTP hydrolysis is stimulated by GAP and RGS. In addition, these structural studies have shown how tumor-causing mutations affect the function of Ras and Gq. 

Pelin, K. (1994). Asbestos-related malignant mesothelioma Tumor cel characteristics and mechanisms m fibre carcinogenesis. Academic diss.. University of Helsinki. 

Interference with specific cell-cell and cell-matrix adhesion mechanisms is another rapidly advancing approach to therapeutically interfere with angiogenesis. Antagonistic antibodies (Vitaxin) to the integrin heterodimer av 33 have been shown to act on the blood vessels of tumors but not on the resting organ vasculature. Vitaxin demonstrated some promise in Phase II clinical trials. 

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