Figure 4 STS (steroid sulfatase) and SULT1E1 (estrogen sulfotransferase 1E1) in high-grade serous ovarian carcinoma. Immunoreactivity of STS and SULT1E1 is demonstrated in paraffin-embedded tissue sections from ovarian carcinoma. Sections were probed with an antibody … Further studies in estrogen receptor alpha-expressing OVCAR-3 cells showed that STS is inhibited by the STS inhibitor STX64. As STS expression is highly variable and found at high levels in tumors of nearly all patients, blocking

the sulfatase pathway may be of values for these DNA-PK inhibitor clinical trial patients [75]. Also the aromatase pathway to convert the androgens to estrogen is active in ovarian cancer cells and will lead via the Inhibitors,research,lifescience,medical conversion of dehydroepiandrostenedione to androstenedione Inhibitors,research,lifescience,medical to the production of E2. Therefore, a combined inhibitor for both, STS and aromatase, might be suitable for these patients [76]. 4.4. Colorectal Cancer Estimated new cases and deaths from colon and rectal cancer in the USA, in 2012, were 103.170 new cases of colon cancer and 40.290 cases of rectal cancer. 51.690 deaths were from colorectal cancer [30]. These cancers accounts for approx. 10% of new cancer diagnoses among women worldwide with an incidence of 571.204 cases and a

mortality of 288.654 worldwide [31]. Colorectal cancer is the third leading cause of cancer for women after lung and breast cancer. Screening Inhibitors,research,lifescience,medical programmes for colorectal cancer in man and woman over the age of 50, now widely applied in many industrialized countries, are leading to a reduction in the incidence and mortality of colorectal cancer (similar to data shown for the USA) [77]. Estrogens were found to play a role in the pathogenesis of colorectal Inhibitors,research,lifescience,medical carcinomas and may have a protective role [78]. Many epidemiological studies have found a reduction in the risk of colon cancer associated with use of estrogen/progesterone-based regimens of HRT. Inhibitors,research,lifescience,medical Although overall diagnoses were decreased, a larger proportion of poor prognosis tumors was detected among these patients [79]. In the estrogen-alone group, there was no reduction in the risk of colorectal cancer. Therefore, a recent evaluation

of the outcome of various studies on HRT led to the conclusion that application of Carnitine palmitoyltransferase II any HRT regimen to prevent colorectal cancer is not recommended [80]. In many colon carcinoma specimens and colon cancer cell lines, ERbeta [81], aromatase, STS, SULT1E1 [82], and 17βHSDs [83] are expressed. It was also demonstrated that concentrations of estrogens in the cancer tissue were twice of those in normal colonic mucosa [82]. Moreover, higher intratumoral concentrations of total estrogens were significantly associated with poorer survival. Thereby, the ratio between STS and SULT1E1 will determine the intratumoral concentration of total estrogens and determine the clinical outcome of the patients. However, these findings are not fully supported by epidemiological data on the application of estrogens to prevent colon cancer (see above).