Tumor-derived glycoproteins

It was found that the HIV envelope glycoprotein in vitro increases the production of NO by human monocyte-derived macrophages [114]. NO production is increased in patients who have AIDS [115], and the increased concentrations of nitrite in AIDS patients with opportunistic infections is caused by T gondii, Pneumocystis carinii, Mycobacterium tuberculosis, and Mycobacterium avium, whereas nitrite concentrations are normal in symptom-free patients. It was also confirmed that there was increased production of NO in the sera of children with HIV-1 infection, and of circulating cytokines, such as interleukin lp, tumor necrosis factor a, and interferon y. It is postulated that rises in the concentrations of these cytokines may represent a substantial stimulation of NO production [116]. In contrast, it has been shown that there was no altered endogenous nitrate formation in eight patients with AIDS, most of whom had opportunistic infections [117]. It has also been noted that there were high... 

Exatecan is a novel synthetic camptothecin derivative with a unique hexacyclic structure. It does not require metabolic activation, whereas irinotecan does. In vitro experiments in various cell lines have suggested that exatecan may be 6 and 28 times more active than SN-38 (7-ethyl-lO-hydroxycamptothecin, the active metabolite of irinotecan) and topotecan respectively. Furthermore, it has a 2-10 times higher therapeutic index than irinotecan and topotecan. In addition, exatecan may even be active in P-glycoprotein-mediated multidrug-resistant tumor cells. Its dose-limiting adverse effects are neutropenia and liver dysfunction. The recommended dosages of exatecan for phase II trials are 0.5 mg/m /day or 0.3 mg/ m /day as a 30-minute infusion on 5 consecutive days for minimally pretreated and heavily pretreated patients respectively (14,15). 

Etoposide and teniposide are semisynthetic podophyllotoxin derivatives (see Table 124-13). Podophyllin is extracted from the mayapple or mandrake plant. Like the vinca alkaloids, podophyllin itself binds to tubulin and interferes with microtubule formation. Unlike the parent compound, however, etoposide and teniposide damage tumor cells by causing strand breakage through inhibiting topoisomerase Resistance may be caused by differences in topoisomerase II levels, by increased cell ability to repair strand breaks, or by increased levels of P-glycoproteins. Etoposide and teniposide are usually clinically cross-resistant. They are cell-cycle phase-specific and arrest cells in... 

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