Initiators, cancer

Oncogenesis is the process of cancer initiation the term is essentially synonymous with carcinogenesis. 

It has been suggested that tamoxifen, one of the most effective therapeutic and chemopreventive agent for breast cancer, modulates protein kinase C through oxidative stress in breast cancer cells [194], Unfortunately, most breast cancers initially responsive to tamoxifen treatment later become resistant. Schiff et al. [195] suggested that the conversion of breast tumors to a tamoxifen-resistant phenotype is associated with oxidative stress and depends on significantly enhanced SOD activity in tumors. 

The hypothesis that stress can modulate MMP expression is also supported by studies in mice. Using social isolation as a stressor, the mRNA levels of MMP-2, MMP-9, matrix-type matrix metalloproteinase-1 (MT1-MMP), and urokinase-type plasminogen activator were higher in the tumor and liver tissues of the isolated mice than in control mice.91 Furthermore, a recent study has shown that restraint stress causes an increase in expression of the plasminogen activator inhibitor-1, another key player in the plas-minogen/plasmin enzyme system in mice.92 As these enzymes have been described to have functions besides their role in ECM remodeling,93 studies on stress-related effects on MMP/TIMP balance have implications in the relationship between stress and cancer initiation and progression.. 

Gelderblom, W.C. et al.. Cancer promoting potential of different strains of Fusarium moniliforme in a short-term cancer initiation/promotion assay. Carcinogenesis, 9, 1405, 1988. 

The specific type of harm we call cancer is left to later chapters, because it is so important and because there are so many aspects of cancer initiation and development that are unique. It would be a mistake... 

Ricci-Vitiani L, Lombardi DG, Pilozzi E et al (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445 111-115... 

Coy P, Hodson BM, Payne D, et al. The effect of dose of thoracic irradiation on recurrence in patients with limited stage small-cell lung cancer. Initial results of a Canadian multicenter randomized trial. Int J Radiat Oncol Biol Phys 1987 14 219-226. 

Martenson J, WillettC, SargentC, etal. Aphase III study of adjuvant radiation therapy (RT), 5-fluorouracil (5-FU), and levamisole (LEV) vs 5-FU and LEV in selected patients with resected, high risk colon cancer initial results of INT 0130 [abstract]. Proc Am Soc Clin Oncol 1999 235a. 

Tepper JE, O Connell MJ, Petroni GR, et al. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer initial results of Intergroup 0114. J Clin Oncol 1997 15(5) 2030-2039. 

M. Tornqvist, J. Mowrer, S. Jensen and L. Ehren-berg, Monitoring of environmental cancer initiators through hemoglobin adducts by a modified Edman degradation method, Anal. Biochem., 154, 255-266 (1996). 

Nevertheless, at this time there is no persuasive evidence from epidemiological studies that any individual fatty acid is associated with the risk of breast cancer (Willett, 1997). A pooled analysis of nine prospective studies showed no association between the intake of various dairy products and the risk of breast cancer (Missmer et al., 2002). However, in epidemiological studies there is often a high degree of correlation between individual fatty acids in the diet. This reduces the ability to detect an independent association between a single acid and cancer risk. Furthermore, dietary assessment during an epidemiological study may not reflect an individual s diet at the time of cancer initiation, which in the case of breast cancer may be in early life. 

Gelderblom WC, Semple AE, Marasas WFO, Farber E The cancer-initiating potential of the fumonisin B mycotoxins. Carcinogenesis 1992 13 433-437. 

Gelderblom WCA, Cawood ME, Snyman SD, Marasas WFO Fumonisin Bj dosimetry in relation to cancer initiation in rat liver. Carcinogenesis 1994 15 209-214. 

Other studies in animal models show that a choline-deficient diet promotes liver carcinogenesis (256-261). In fact, choline is the only known nutrient for which deficiency is directly linked to liver cancer in the absence of any known carcinogen (262, 263). Choline deficiency is therefore considered to have both cancer initiating and cancer promoting activities. 

Chronic dermal applications of kerosene caused skin carcinoma in mice. Kerosene has been reported to have weak cancer-promoting activity but no cancer-initiating activity. Repeated applications of kerosene to the skin of laboratory animals caused moderate to severe skin irritation with an increase in skin tumors after long latency periods. The increase in skin tumors was considered to be the result of the severe skin damage. This explanation is consistent with the general lack of activity of kerosene in genotoxicity assays. 

Butadiene is converted to butadiene monoepoxide, which is believed to be responsible for carcinogenesis in rodents but not in humans. In humans, butadiene monoepoxide is further converted to butenediol and conjugation with glutathione results in no toxicity. In rodents, however, there is direct conjugation of butadiene monoepoxide with glutathione, which presumably is not adequate, and thus cancer initiation occurs. In this example, it can be seen that rodent data are a poor indicator for prediction of risk in humans because the detoxification pathways differ. 

Medical Research Council Prostate Cancer Working Party Investigators Group. Immediate versus deferred treatment for advanced prostate cancer Initial results of the Medical Research Council Trial. Br J Urol... 

Reisco-Eizaguirre, G., and Santisteban, R (2007). Molecular biology of thyroid cancer initiation. Clin Transl Oncol, 9(11), 686-693. 

Melendez-Colon, V. J., Luch, A., Seidel, A., and Baird, W. M. (1999a). Cancer initiation by polycyclic aromatic hydrocarbons results from formation of stable DNA adducts rather than apurinic sites. 

---