In thyroid cancer

In thyroid cancer, 131I can be used to eliminate tumor tissue that cannot be removed surgically but still captures iodine in such circumstances, amounts of 100 mCi (4000 MBq) of 131I or more are not unusual ... 

Large amounts of 131I, as used in thyroid cancer therapy, can cause testicular damage as documented from hormonal and sperm analysis (19), but long-term results are nevertheless reassuringly normal (20). 

Petrella, A., Festa, M., Ercolino, S.F., Zerilli, M., Stassi, G., Solito, E., and L. Parente, 2006, Annexin-1 Downregulation in Thyroid Cancer Correlates to the Degree of Tumor Differentiation. Cancer Biol Ther. 5(6) 643-7. 

A sharp increase in thyroid cancer was reported, especially among children living in the affected areas. By the end of 1994, 565 children aged 0-14 years were diagnosed as having thyroid cancer (333 in Belarus, 24 in the Russian Federation, 208 in Ukraine). 

In thyroid cancer, can be used to eliminate tumor Respiratory... 

TSH suppression in thyroid cancer, nodules, euthyroid goiters ... 

Every country in the Northern Hemisphere contains soil that has tested positive for traces of radioactive deposits from the Chernobyl disaster. No one knows the final number of people who will die as a result of this accident. Scientists and doctors in the area have seen a drastic increase in thyroid cancer, mainly in people who were children or teens at the time of the accident. Fortunately, survival rates are high in the case of this type of cancer. Today, work continues to keep the Chernobyl plant from crumbling. Wild horses, boar, wolves, and birds have returned to the area and are thriving. 

A variety of molecular techniques are available to detect point mutations at a specific hot spot (e.g., the KRAS mutation at codons 12 and 13 or the BRAF mutation at codon 600). These methods include realtime PCR amplification and post-PCR melting curve analysis, allele-specific PCR, direct DNA sequencing, pyrosequencing, and PCR-RFLP. o,31-37 q methods demonstrate reliable detection of point mutations, such as the KRAS mutation in colorectal cancer or the BRAF mutation in thyroid cancer. 

Kimura ET, Nikiforova MN, Zhu Z, et al. High prevalence of BRAE mutations in thyroid cancer genetic evidence for constitutive activation of the RET/PTC-RAS-BRAE signaling pathway in papillary thyroid carcinoma. Cancer Res. 2003 63 1454-1457. 

Abu-Amero KK, Alzahrani AS, Zou M, Shi Y. High frequency of somatic mitochondrial DNA mutations in human thyroid carcinomas and complex 1 respiratory defect in thyroid cancer cell lines. Oncogene. 2005 24 1455-1460. 

Levothyroxine is indicated in the treatment of hypothyroidism (0.05 mg initially) of myxedema coma (0.4 mg IV initially) of thyroid-stimulating hormone (TSH) suppression in thyroid cancer of euthyroid and nodules goiter and of thyroid suppression therapy (2.6 mcg/kg/day for 7 to 10 days). Levothyroxine increases the metabolic rate of tissue. It affects protein and carbohydrate metabolism, promotes gluconeogenesis, increases the utilization and mobilization of glycogen stores, stimulates protein synthesis, and regulates cell growth and differentiation. The orally administered... 

Radioactive iodine, a thyroid hormone antagonist, is used in hyperthyroidism and in thyroid cancer (see also Table 20). 

Perhaps the best known use of potassium iodide today is as a treatment for radiation exposure. When a nuclear bomb explodes or a nuclear accident occurs, one of the most dangerous products released to the environment is a radioactive isotope known as iodine-131. Iodine-131 enters the human body and travels to the thyroid, where it attacks cells and tissues, eventually resulting in thyroid cancer. Experts recommend that people exposed to radiation take potassium iodide as a protection against this hazard. The potassium iodide saturates... 

Radioiodine plays an important role in the diagnosis and treatment of various thyroid disorders. Treatment of thyroid carcinoma and hyperthyroidism with I-pharmaceuticals has been practiced for years, but other isotopes, i.e., I, >231, 1241 and are also produced and used in various medical apphcations. Radioiodine concentrated by the thyroid in large amounts can cause cell death, primarily because of 3ils beta radiation. Large doses of 3il are, therefore, given to treat patients with hyperthyroidism. In contrast, low-dose exposure damage does not kill thyroid cells, but can induce radiation damage and mutations, which can result in thyroid cancer. 

Histone deacetylase inhibitors, depsipeptide (FR901228), trichostatin A (TSA), and valproic acid, increase NIS expression in thyroid cancer cell lines (Kitazono et al., 2001 Kogai et al., 2006). Depsipeptide significantly induces NIS mRNA and iodide uptake in follicular thyroid cancer cell lines (FTC 133 and FTC 236) and two anaplastic cancer cell lines (SW-1736 and KAT-4) at a low concentration (Ing/ml) in vitro (Kitazono et al., 2001). Pharmacokinetics of depsipeptide in patients have indicated that levels of more than 500ng/ml are... 

The goal in thyroid cancer treatment is to optimize iodine uptake. A number of different strategies and agents have been used to stimulate NIS expression and iodine uptake in refractory thyroid cancer, although TSH remains the most potent stimulus. 

It can be seen in Figure 78.6 that the incidence of thyroid cancer (all forms) is at the same level today as in 1971, with about 4.6 (women) and 2.0 (men). The overall thyroid cancer incidence in Sweden is somewhat higher than the incidence reported from the UK (number of cases/100000/year) 1.4 (men) and 3.7 (women), respectively (Office for National Statistics Registrations, UK, 2006) but clearly lower than that reported in the United States 4.3 (men) and 12.5 (women), respectively. In the US, an increase in incidence of about 4.8% was observed from 1992 to 2002 National Cancer Institute. The increase in thyroid cancer incidence has been postulated to be correlated with an increased iodine intake in a population. There is a suggested increase in thyroid cancer of the papillary type about 20 years after the... 

Increased radioactive fallout was first observed by the control system of a nuclear power plant on the east coast of Sweden after the Chernobyl accident. Nonetheless, no increase has later been observed in thyroid cancer incidence among children in that special region, emphasizing the importance of iodine sufficiency. 

It is important to note that iodine deficiency and exposure to nuclides other than may have contributed to the increased risk of thyroid cancer in the young following the Chernobyl reactor explosion (Dolphin, 1968 Boice, 2005, 2006). In comparison, rates of thyroid cancer were not increased in the more than 3000 children exposed to from the Hanford reactor site in an iodine-replete region (Davis et al, 2004). An increase in thyroid cancer has not been observed in about 6000 children who received for diagnostic procedures (Dickman etal, 2003 Boice, 2006). 

The high prevalence of NIS in human breast cancer and the demonstration of functionally active NIS expression in breast cancer tissue in transgenic breast cancer mouse models suggest that endogenous mammary NIS expression may offer the possibifity of NIS-targeted radioiodide imaging and therapy in breast cancer similar to its application in thyroid cancer. 

Using Retinoids to Increase Radioiodine Uptake in Thyroid Cancer Role as Potential Redifferentiation Agents... 

Using Retinoids to increase Radioiodine Uptake in Thyroid Cancer 993... 

NIS expression in thyroid tumors correlates with their ability to concentrate radioiodine. Schmutzler et al. (1997) reported that downregulated expression of the NIS gene resulted in resistance to 1-131 therapy because it reduced iodide uptake in thyroid cancer cells. The regulation of NIS expression in normal and malignant thyroid cells has been extensively investigated, and various agents have been recognized to influence expression. 

On the basis of the apparent redifferentiation in thyroid cancer cell lines by RA, there is significant interest in assessing the efficacy of RA in restoring radioiodine uptake in patients with recurrent or metastatic thyroid cancer. 

In thyroid cancer, their potential to redifferentiate cells and produce increased 1-131 uptake suggests a possible role in the treatment of iodine-resistant disease. 

The exact role of these agents in thyroid cancer and their mechanism of action still needs to be investigated. 

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