Tumor promotion

Integrin otvfi3 Antagonists Promote Tumor Regression by Inducing Apoptosis of Angiogenic Blood Vessels... 

Intriguingly, besides providing the essential function of increased tumor perfusion, new vessel growth may also promote tumor growth through a separate mechanism. Neural stem cells and likely brain tumor stem cells reside in a perivascular niche, or specialized miaoenvironment, that both supports the cells and controls proliferation and fate determination (Calabrese et al. 2007). New vessel growth may therefore, also support brain tumor stem cells by providing new niche sites. 

Catectin promotes tumor cytotoxicity activates macrophages and neutrophils enhances IL-2 receptor expression on T cells inhibits antibody secretion... 

A second study examined the effects of DMBA initiated mi rex-promoted tumors in female mice on ovarian hormones. This study found that the loss of ovary (OVX) protected the female mice (40%) from mirex tumor promotion. Tumor promotion was unaffected in DMBA-initiated OVX mice promoted with TPA. Based on the data, the authors also concluded that there is a structural specificity in the tumor-promoting ability of mirex in mouse skin and that mirex is a much more effective skin tumor promoter in female CD-1 mice than in male CD-1 mice or OVX mice (Meyer et al. 1994). 

In animal studies, mirex (a nonmutagenic hepatocarcinogen) promoted mouse skin squamous carcinomas and papillomas after initiation with 7,12-dimethyl-benz[a]anthracene (DMBA) for 1 week. Mirex, also, potentiated the promotional potency of the phorbol ester tumor promoter, 12-0 -tetradecanoylphorbol-13-acetate (TPA). There was a 90% incidence (activation) of the c-Ha-ras tumor gene in these co-promoted tumors. When both mirex and TPA gave a similar tumor yield, only the TPA response was associated with biochemical markers of enhanced cell proliferation, induction of epidermal ornithine decarboxylase activity and increased DNA synthesis, and hyperplasia. Thus, there is evidence for a dual effect of mirex during co-promotion first, as an independent tumor promoter with a mechanism different than that of phorbol esters and second, as a compound that also potentiates skin tumor promotion by TPA (Meyer et al. 1993, 1994 Moser et al. 1992, 1993). 

Tumor-educated macrophages. (From Pollard, J.W., Tumor-educated macrophages promote tumor progression and metastasis, Nat. Rev. Cancer, 4, 71-74, 2004. Copyright year 2004, Macmillan Magazines Ltd and the author. Reproduced with permission from Macmillan.)... 

A mutation of one copy of the gene in a cell is sufficient to promote tumor growth Mutations of both copies (two hits) of the gene are typicaUy necessary to promote tumor growth... 

The in vitro invasive assay consisted of grafting rat tracheas by implanting into severe combined immxmodeficiency disease (SCID) mice. The tracheas were first injected with the adenocarcinoma cells to promote tumor growth. Invasiveness was determined by histochemical staining of the iso-... 

Orally active agents used in the treatment of ED are more affected by aging and disease processes than are those injected intracavernosally. In addition, alterations in hepatic metabolism and/or renal clearance in the elderly man (see Chapter 6) influence the frequency of appearance of adverse reactions between several coadministered drugs in the treatment of ED. For example, the concomitant use of sildenafil and nitroglycerin is contraindicated by cardiovascular complications. Also, the use of testosterone in the presence of androgen-dependent tumors may promote tumor growth. 

Mutations that trigger and promote tumor formation may be caused by a number of processes. Briefly summarized, the following factors are involved ... 

The activity of Ser/Thr-specific protein kinases is often controlled by autoinhibitory sequences (see 7.1.5). Loss or lack of function of autoregulatory sequences due to an oncogenic mutation can remove Ser/Hir kinase activity bound into mitogenic signaling pathways from normal control and thereby promote tumors. An example is the Raf kinase (see 9.6). Viral v-Raf oncoproteins are characterized by a deletion of the NH2-terminal regulatory sequences. 

Tumor suppressor genes are genes that, by their inactivation due to mutations or deletion, promote tumor formation. The proteins for which they code are known as tumor suppressor proteins. Many of the known tumor suppressor proteins have a suppressing and negatively regulating effect on processes that are either directly associated with regulation of cell division or influence this in an indirect way. Other, equally important functions of tumor suppressor proteins are in the areas of DNA repair and cell adhesion. Inactivation of tumor suppressor genes can have various consequences ... 

Toxicities are numerous and include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered mental status, seizures, and hirsutism. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) have been observed in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because the drug induces TGF-B, which promotes tumor invasion and metastasis. 

Short-term dermal studies with 2,3,7,8-TCDD had controversial results. Some studies reported its inhibitory effects on the development of skin tumors in mice otherwise initiated by 13-dimethylbenz-(o)anthracene (Berry et al. 1978, 1979). Others cited its ability to promote tumors initiated by N-methyl-N-nitro-N-nitrosoguanidine (Hebert et al. 1990 Poland et al. 1982). Further, intraperitoneal injection of... 

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