The influence of aging on the methylation status of brain-derived neurotrophic factor gene in blood.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of psychiatric disorders in adults and elderly individuals, and as a result, the DNA methylation (DNAm) of the BDNF gene in peripheral tissues including blood has been extensively examined to develop a useful biomarker for psychiatric disorders. However, studies to date have not previously investigated the effect of age on DNAm of the BDNF gene in blood. In this context, we measured DNAm of 39 CpG units in the CpG island at the promoter of exon I of the BDNF gene. METHODS: We analyzed genomic DNA from peripheral blood of 105 health Japanese women 20 to 80 years of age to identify aging-associated change in DNAm of the BDNF gene. In addition, we examined the relationship between total MMSE scores, numbers of stressful life events, and serum BDNF levels on DNAm of the BDNF gene. The DNAm rate at each CpG unit was measured using a MassArray® system (Agena Bioscience), and serum BDNF levels were measured by ELISA. RESULTS: There was a significant correlation between DNAm and age in 13 CpGs. However, there was no significant correlation between DNAm and total MMSE scores, numbers of life events, or serum BDNF levels. CONCLUSION: Despite the small number of subjects and the inclusion of only female subjects, our results suggest that DNAm of 13 CpGs of the BDNF gene may be an appropriate biomarker for aging and useful for predicting increased susceptibility to age-related psychiatric disorders.

Comparison of CVF (Cyclophosphamide+Vinorelbine+5-Fluorouracil) and CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil) Adjuvant Chemotherapy in Early Breast Cancer / 한국유방암학회지

PURPOSE: Our study aimed to evaluate the feasibility of adjuvant cyclophosphamide/vinorelbine/5-fluorourail (CVF) chemotherapy as an alternative to cyclophosphamide/methotrexate/5-fluorouracil (CMF) chemotherapy for treating early breast cancer. METHODS: One hundred and forty-nine patients were randomly assigned to CMF or CVF adjuvant chemotherapy for treating their early stage breast cancer between September 2000 and December 2007. The disease-free survival (DFS), the overall survival (OS), and the toxicity profiles of both groups were compared. RESULTS: Sixty-seven patients underwent CMF chemotherapy whereas 82 patients underwent CVF chemotherapy. The DFS and OS were 88 months (95% confidence interval [CI], 76-101 months) and 94 months (95% CI, 83-104 months), respectively for the CMF group, and 97 months (95% CI, 93-101 months), and 101 months (95% CI, 98-104 months), respectively for the CVF group. However, those survival gains of the CVF group were not statistically significant (p-value=0.069 for the DFS and 0.99 for the OS). The CVF group showed a favorable toxicity profile in terms of the grade 3/4 hematologic toxicities as compared to that of the CMF group. CONCLUSION: Clinical outcome of CVF chemotherapy was comparable to CMF with a favorable toxicity profiles. However, it is difficult to conclude the feasibility of CVF regimen because of small number of studied patients.

Lymphovascular Invasion and HER2/neu Amplification as Predictive Factors for Axillary Lymph Node Metastasis in Early Breast Cancer Patients / 한국유방암학회지

PURPOSE: Axillary lymph node metastasis (ALNM) can occur even in breast cancer smaller than 2 cm in size. This study was performed to investigate the clinicopathologic factors that affect node metastasis in T1 breast cancer. METHODS: We reviewed the medical record of 206 T1 breast cancer patients and we divided them into two groups according to the presence or absence of lymph node metastasis. We analyzed the association between ALNM and various clinicopathological predictive factors such as age, tumor size (T1a, T1b, T1c), multiplicity, the histologic grade, the nuclear grade, the presence of lymphovascular invasion (LVI), the estrogen and progesterone receptor status, an HER2/neu expression, the Ki-67 labeling index and the bcl-2 expression. RESULTS: One hundred and thirty-nine were the node negative group (T1N0) and the remaining 67 cases were allotted to the node positive group (T1N1-3). On the univariate analysis, age (p=0.011), LVI (p<0.001), histologic grade (p=0.019), HER2/neu (p<0.005), Ki-67 (p=0.012) and bcl-2 (p=0.026) were the statistically significant predictive factors related to node metastasis. But on the multivariate analysis, LVI (p<0.001) and HER2/neu (p=0.009) were the statistically significant factors related to node metastasis. CONCLUSION: LVI and HER2/neu overexpression were related to the increased incidence of ALNM in T1 breast cancer patients. LVI was the most predictive factor of ALNM.