Cytostatic effect

Cytostatic drugs for which inhibitors are primarily needed are often not only substrates of P-gp but also inducers of P-gp overexpression with one or even several type II units. An important point to clarify would be whether or not type II units are required to achieve a cytostatic effect. If they were not required, it might be possible to eliminate the P-gp-inducing effect that causes multidrug resistance by eliminating type II units. So far, the only other possibility of overcoming multidrug resistance is to inhibit the transporters involved. Inhibition can be achieved essentially by two different concepts ... 

TNF fails to induce death of all tumour cell types. Although many transformed cells are TNF sensitive, the cytokine exerts, at best, a cytostatic effect on others and has no effect on yet others. The cytotoxic activity is invariably enhanced by the presence of IFN-y. The concurrent presence of this interferon increases the range of transformed cell types sensitive to TNF-a, and can upgrade its cytostatic effects to cytotoxic effects. It can also render many untransformed cells, in particular epithelial and endothelial cells, susceptible to the cytotoxic effects of TNF-a. 

For labelled S-phase fraction, both compounds and all treatments of cell number was reduced, comparing to control, as expected to Topi mechanism of action. Cytostatic effects were found for unlabeled cells as show in normalized curves (Figure 8) with a progressive cytotoxicity at a longer time (48-72h) starting to 100 nM for edotecarin and 300 nM for SN-38. Cytotoxic effects... 

In contrast, LysoPC could not reverse the cytostatic effect of ET-18-OCH3 (Boggs etal, 1998). Likewise overexpression ofCT could prevent the apoptosis induced by ET-I8-OCH3, but could not restore proliferation of the HeLa cells in the presence of this ether lipid (Baburina and Jackowski, 1998). 

Apicomplexan parasites cause life threatening diseases like malaria, cryptosporid-iosis, toxoplasmosis, coccidiosis. Suberic acid bisdimethylamide which also inhibits HDA selechvely arrests tumor cells as opposed to normal mammalian cells, has an in vivo cytostatic effect against the acute murine malaria Plasmodium berghei (Andrews et al, 2000). 

As individual G actin molecules are always oriented in the same direction relative to one another, F actin consequently has polarity, it has two different ends, at which polymerization takes place at different rates, if the ends are not stabilized by special proteins (as in muscle cells), then at a critical concentration of G actin the (+) end of F actin will constantly grow, while the (-) end simultaneously decays. These partial processes can be blocked by fungal toxins experimentally. Phalloidin, a toxin contained in the Amanita phalloides mushroom, inhibits decay by binding to the (-) end. By contrast, cytochalasins, mold toxins with cytostatic effects, block polymerization by binding to the (+) end. 

Experiments performed in vitro revealed that in contrast to DFO, which has a major cytotoxic effect only on trophozoites and early schizonts of P. falciparum, reversed siderophores have a cytotoxic effect on ring-stage and cytostatic effects on trophozoites and schizonts . These observations provided the basis for studying combinations of iron chelators for antimalarial therapy. When DFO is added to malaria parasites cultured in erythrocytes in combination with the more lipophilic and more permeate reversed siderophore 66, a strong synergistic inhibitory effect on parasite growth is observed. This effect may result from the different speeds of permeation of the two chelators... 

Uterine atonia, postpartum bleeding, migraine, orthostatic circulatory disturbances, senile cerebral insufficiency, hypertension, hyperprolactinemia, acromegaly, and Parkinsonism [36]. New therapeutic uses have recently emerged, such as, e.g., against schizophrenia, applications based on its newly discovered antibacterial and cytostatic effects, and immunomodulatory and hypolipemic activity [37-39]. 

Mechanism of Action Selectively inhibits inosine monophosphate dehydrogenase in the de novo pathway of purine synthesis, producing potent cytostatic effects on T and B lymphocytes... 

A variety of biological activities have been associated with labdane diterpenes including antibacterial, antifungal, antiprotozoal, enzyme induction, anti-inflammatory modulation of immune cell functions, as well as cytotoxic and cytostatic effects against human leukemic cell lines. 

G. Lemaire, F.-J. Alvarez-Pachon, C. Beuneu, M. Lepoivre and J.-F. Petit, Differential cytostatic effects of NO donors and NO producing cells, Free Radic. Biol. Med., 26 (1999) 1274-1283. 

Alakhov, V., et al. 1990. Increasing cytostatic effects of ricin A chain and Staphylococcus aureus enterotoxin A through in vitro hydrophobization with fatty acid residues. Biotechnol Appl Biochem 12 94. 

A known strain of S. antibioticus was found to produce a compound designated simocyclinon D8 (44) [31]. The compound exhibits antibiotic activity against Gram-positive bacteria and cytostatic effects against various cancer cells. Its structure and biosynthesis were clarified on the basis of physical-chemical methods, mainly by ID and 2D NMR and ESI-MS. It was found that during its biosynthesis the incorporation of 180 into the aminocoumarine residue is probably catalyzed by a monooxygenase. 

For nickel (II) at concentrations lower than 10 mmole/1 toxic action was not found at the level of method sensitivity (cytoneutrality), in concentrations diapason 0,1-1,0 mmole/1 poison revealed cytostatic effect. At concentrations higher than 2 mmole/1 ions of nickel (II) rendered cytocide action on yeast. 

Greater celandine was traditionally used to improve eyesight and in modem times has been used as a mild sedative, and antispasmodic in the treatment of bronchitis, whooping cough, asthma, jaundice, gallstones, and gallbladder pain. The latex is used topically to treat warts, ringworm, and corns. A semisynthetic thiophosphate derivative of alkaloids from C. majus, called Ukrain, has cytotoxic and cytostatic effects on tumor cells (1). 

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