Adenomatous Polyposis Coli and Ras Association Domain Family 1A Gene Methylation in Breast Cancer Patients / 한국유방암학회지

PURPOSE: Of the many carcinogenic mechanisms, DNA methylation is a strong factor in various cancers, including cancer of the breast. The genes related to breast cancer include 14.3.3 sigma, Cyclin D2, RARbeta, Twist, Ras association domain family 1A gene (BASSF1A), HIN-1, p16, and Adenomatous polyposis coli (APC). Of these, hypermethylation of the APC and RASSF1A genes is, found in breast cancer patients, and especially in those with a poor prognosis. This study investigated whether hypermethylation of the APC and RASSF1A genes is related with breast cancer metastasis. METHODS: Of the 110 patients who received surgical operation at our hospital's department of surgery from January 2001 to December 2003, 16 patients with metastatic lesion found during the follow-up period were selected. Seventeen patients without metastasis selected as the tissue group after considering their age, cancer stage, and physical state. Forty seven patients were selected as the serum group, including 6 patients with metastasis, and they were evaluated for metastasis and methylation. Serum and tissue were collected and after being processed by the methylation specific PCR (MSP), and the methylation of the APC and RASSF1A genes was observed. RESULTS: In the tissue study group, the APC gene methylation ratio of the patients whose stages are between the stage 2 and 3 was 50:94%, and that of RASSF1A gene methylation was 68.7:65% respectively. Methylation rates of both genes was found in 42.9% of the stage 2 recurrent patients (non-recurrent patients: 22%) and in 77.8% (non-recurrent patients: 50%) in stage 3 recurrent patients. In the serum study group, a statistical correlation was shown (p=0.013) between methylation of RASSF1A and recurrence, where 5 of the 16 patients with methylation showed recurrences and only 1 patient of the 31 nonmethylated patients showed recurrence. CONCLUSION: We determined the correlation between APC and RASSF1A methylation and recurrence of breast cancer. Further studies with large sample populations and more advanced method are needed to confirm our findings.

The Effects of Genistein to Expression of Fatty Acid Synthase in Breast Cancer Cells / 한국유방암학회지

PURPOSE: The relatively low incidence of breast cancer in Asian countries with cultures which traditionally eat a large amount of soy is worth noticing in research fields. Genistein is a isoflavone phytoestrogen found in soy and its consumption may have a role in cancer etiology. We have established a hypothesis that a diet high in soy consumption is related to a low incidence of breast cancer. Fatty acid synthase (FAS) is a multi-protein enzyme responsible for de novo biosynthesis of fatty acids. Recent studies have demonstrated that high levels of FAS occurs in a subset of human cancers, such as breast cancer, ovarian cancer, and prostate cancer. High level of FAS are associated with a poor prognosis. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate genes involved in lipid metabolism, including FAS. Recent studies show that expression of SREBP1c is correlates with FAS expression. The aim of this study is to investigate the effect of genistein on the expression of FAS in breast cancer cells. METHODS: We performed immunofluorescent staining to examine the expression of FAS under different concentration of genistein. RT-PCR was also performed to investigate the mRNA expression of FAS and SREBP1c in different conditioned breast cancer cells treated with different concentration of FAS inhibitor and genistein. RESULTS: By immunofluorescent staining, the FAS expression after treatment with the FAS inhibitor, C75, decreased at a micron10 M concentration. However the expression of FAS decreased at all concentrations of genistein (0.5, 1, 5, 10 micronM). The mRNA levels of FAS and SREBP1c after treatment with C75 decreased constantly according to time and concentration. However the effect was noted only after 12 hr. The mRNA level of FAS and SREBP1c following treatment with genistein decreased at only a 10 micronM concentration (p<0.005). CONCLUSION: Genistein may down regulate FAS expression in breast cancer cells through modulation of SREBP-1c. This finding may account for the relatively low incidence of breast cancer in Asians who consume a large amount of soy in their diet.

Introduction of Electrochemical Therapy (EChT) and Application of EChT to The Breast Tumor / 한국유방암학회지

PURPOSE: To introduce the history and principle mechanism of electrochemical treatment (EChT) with animal study and report two cases successfully treated breast cancer and hemangioma by EChT. METHODS: In animal study, the breast cancer tumor in nude mouse treated with EChT (100 Coulomb/cm3) were reviewed for histologic changes. In the case studies, we reported method of EChT and clinical results after EChT. Case 1: 74 yr old female with locally advanced breast cancer received 3 times EChT with 1,000 Coulomb/time, 8 Volt. Case 2: 51 yr old female with breast hemagioma received one time EChT with 80 Coulomb, 8 Volt. RESULTS: In animal study, There were destructive change including vaculated cell fragment and extensive coagulative necrosis. Case 1 showed no local recurrence during 18 monthes after EChT. Case 2 also showed no evidence of recurrence of hemangioma. CONCLUSION: The EChT is easy to use. It is effective, safe, less traumatic and makes patients recover quickly. This is a new and effective method to treat patients with tumours that are inoperable and can not receive chemotherapy or radiotherapy.