Transformation tumors

If frequency of mutations is equal to x = 10"6 the probability of mutations absence at cells number N = 105 is equal to 0,905, at cells number N = 107 is 0,000045. Due to this reason increase of cell mass by two orders (from 105 up to 107) may transform tumor from curable into incurable. 

Many researchers have shown that tumor growth tends to grow exponentially. Hence, a log-transformation might be useful here. Figure 6.7 presents the mean tumor volume and standard deviation on a log scale. Ln-transformed tumor volume appeared to grow more linearly, although there was some small curvature to the growth curve. More importantly, tumor volume... 

The depsipeptide FK228 (originally called FR901,228) was isolated [28] by Fujisawa Pharmaceuticals from an extract of the bacteria Chromobacterium violaceum No. 968 on the basis of an assay for phenotypic reversal of ras-transformed tumor cells. The compound was shown to be active in a tumor xenograft animal model, and to have effects [29] similar to the known HDAC inhibitors, trichostatin A and trapoxin. Superficially, FK228 (Fig. 12-7) does not... 

Recently, zaragozic acids were shown to inhibit Ras farnesyltransferase, which involves posttranslational famesylation of all Ras proteins. Zaragozic acids blocked Ras processing in Ras transformed tumor cell lines at concentrations as low as 10 nM. Therefore, they potentially have anticancer applications [49]. 

Unlike most of the other FPP competitive inhibitors, manumycin is devoid of negatively charged groups such as carboxylates and phosphates. This structural deficiency, which is a distinct liability in most of the other FPP competitive inhibitors in terms of their cell penetration, actually helps to facilitate the entry of manumycin into cells. Consequently, several reports describing the activity of manumycin A in various ras-transformed cell cultures have appeared [107-109]. More significantly, manumycin A also reduces growth of Ki-ras-transformed tumors in a dose-dependent manner in BALB/c nude mice [110]. 

In vitro, cydopentadienyl metal complexes were able to suppress the proliferation of normal or transformed tumor cells. Best activity was found for vanadocene dichloride in this respect. In vivo, numerous of the cydopentadienyl metal complexes inhibited the development of diverse experimental animal tumors (e.g., Ehrlich asdtes tumor, sarcoma 180, B16 melanoma, colon 38 cardnoma and Lewis lung cardnoma) and the growth of human cardnomas xenografted to nude mice. Espedally certain titanocene and ferricenium compoimds were cytostatically effective against human colorectal cardnomas. Moreover, titanocene complexes were shown to be antiviral agents and potent antiinflammatory compounds comparable to phenylbutazone. 

The possible modes of action of 4HPR have been mostly investigated in already transformed tumor cells. 4HPR suppressed the proliferation of cell lines of different tumor types such as human breast carcinoma [24-27], prostate adenocarcinoma [28, 29], leukemias [30, 31], neuroblastoma [32, 33, 34], ovarian carcinoma [35, 36], cervical carcinoma [37, 38], head and neck squamous cell carcinoma [39], esophageal squamous carcinoma [40] and small-cell lung can-... 

Cumar, F. A., Brady, R. O., Kolodny, E. H., McFarland, V. W., and Mora, P. T., 1970, Enzymatic block in the synthesis of gangliosides in DNA virus-transformed tumor-genic mouse cell lines, Proc. Natl. Acad. Sci. U.S. 67 757. 

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