Jung-Hyun Yang

Effects of Supervised Exercise Therapy in Patients Receiving Radiotherapy for Breast Cancer

Purpose Postoperative radiotherapy for breast cancer has a number of associated complications. This study examined whether supervised moderate-intensity exercise could mitigate the complications that occur during radiotherapy. Patients and Methods Forty women were randomized before radiotherapy after various operations for breast cancer. Seventeen patients who were assigned to the exercise group performed supervised moderate-intensity exercise therapy for 50 min 3 times per week for 5 weeks. Twenty-three patients in the control group were asked to perform self-shoulder stretching exercise. The World Health Organization Quality of Life-BREF (WHOQOL-BREF), brief fatigue inventory (BFI), range of motion (ROM) of the shoulder, and pain score were assessed before and after radiotherapy. Results There were no significant differences noted at baseline between groups. In the exercise group, there was an increase in the WHOQOL-BREF and shoulder ROM and decrease in BFI and pain score after radiotherapy. On the other hand, patients in the control group showed decrease in the WHOQOL-BREF and shoulder ROM and increase in BFI and pain score after radiotherapy. There were statistically significant differences in the changes in the WHOQOL, BFI, shoulder ROM, and pain score between the groups. Conclusion Patients receiving radiotherapy for breast cancer may benefit in physical and psychological aspects from supervised moderate-intensity exercise therapy.

Accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy in locally advanced breast cancer: Relation to response patterns on MRI

Background. This study evaluated the accuracy of magnetic resonance imaging (MRI) for estimating residual tumor size after neoadjuvant chemotherapy in patients with locally advanced breast cancer and assessed whether the tumor pattern on MRI after chemotherapy influenced the accuracy of the MRI measurement of the residual tumor size. Patients and methods. Fifty patients who received neoadjuvant chemotherapy with doxorubicin and docetaxel for locally advanced breast cancer were evaluated with MRI before and after chemotherapy. We compared the residual tumor size measured by MRI with the pathologically determined size and investigated the influence of the residual tumor pattern on MRI (shrinkage, nest or rim, and mixed) and pathologic characteristics on the accuracy of the MRI measurement. Results. The correlation coefficient between the residual tumor sizes determined by MRI and by pathology was 0.645. The MRI measurement agreed with the pathologically determined size in 36 patients (72%) and disagreed in 14 patients (28%), overestimating the size in 13 (26%) and underestimating the size in one (2%). Disagreement appeared to be more frequent in the cases showing a nest or rim pattern than in those exhibiting a shrinkage pattern, although this was not statistically significant (p=0.119). Conclusions. MRI is an accurate method for predicting the extent of residual tumor after neoadjuvant chemotherapy; however, it may overestimate the residual disease, especially in cases showing a nest or rim tumor pattern and in those having combined lesions with ductal carcinoma in situ or multiple scattered nodules after neoadjuvant chemotherapy.

Characteristics of metastasis in the breast from extramammary malignancies

Breast metastasis from extramammary neoplasm is rare. We present the cases of metastasis to the breast after review of results in one institute and we want to show the difference of previous report.

Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells

Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression are pivotal steps in cancer metastasis. Herein, we investigated the effect of silibinin, a major constituent (flavanolignan) of the fruits of Silybum marianum, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and VEGF expression in MCF-7 human breast cancer cells. The expression of MMP-9 and VEGF in response to TPA was increased, whereas TPA-induced MMP-9 and VEGF expression was decreased by silibinin. To investigate the regulatory mechanism of silibinin on TPA-induced MMP-9 and VEGF expression, we pretreated cells with various inhibitors, such as UO126 (MEK1/2 inhibitor), SP600125 (JNK inhibitor), and SB203580 (p38 inhibitor). Interestingly, TPA-induced MMP-9 expression was significantly inhibited by UO126, but not by SP600125 and SB203580. In addition, we pretreated cells with 100 microM silibinin prior to TPA treatment. TPA-induced MEK and ERK phosphorylation was significantly decreased by silibinin in MCF7 cells. TPA-induced VEGF expression was also suppressed by UO126. On the other hand, we found that adenoviral constitutive active-MEK (Ad-CA-MEK) significantly increased MMP-9 and VEGF expression. Taken together, we suggest that the inhibition of TPA-induced MMP-9 and VEGF expression by silibinin is mediated by the suppression of the Raf/MEK/ERK pathway in MCF-7 breast cancer cells.

Expression of p21Waf1, p27Kip1 and cyclin D1 proteins in breast ductal carcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status

p21Waf1 (p21), p27Kip1 (p27) and cyclin D1 have recently been reported as useful prognostic markers for patients with breast carcinoma. However, studies on these cell cycle regulators in ductal carcinoma in situ (DCIS) have been extremely limited. Therefore, we studied the immunohistochemical expression of p21, p27 and cyclin D1 proteins in 49 DCIS cases and compared the findings with the clinicopathologic parameters (age, tumor size, gross type, histologic type, histologic grade, necrosis and mitotic index), p53 and estrogen receptor (ER) status. A significant correlation was found between positive p21 immunoreactivity (67.3% of the cases) and well‐differentiated histologic grade, non‐comedo type, ER‐positive and p53‐negative (p53–) status. DCIS with p21+/p53– is likely to be the non‐comedo type. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with the ER expression (P = 0.001). The p27 protein expression (46.9% of the cases) correlated with the cyclin D1 immunopositivity (P = 0.0003) and ER expression (P = 0.005). No significant associations were seen in the p27 or cyclin D1 expression and other clinicopathologic parameters. Our results suggest that p21 might be more related to the useful biologic markers in DCIS than p27 or cyclin D1. The significant positive association between p21, p27 or cyclin D1 and ER status, and close association of p27 and cyclin D1 expression might be implicated in the tumor biology of DCIS.

Triple-negative, basal-like, and quintuple-negative breast cancers: better prediction model for survival

BackgroundTriple-negative breast cancers (TNBCs) and basal-like breast cancers (BLBCs) are known as poor outcome subtypes with a lack of targeted therapy. Previous studies have shown conflicting results regarding the difference of prognostic significance between TNBCs and BLBCs. In this study, we aimed to characterize the prognostic features of TNBCs, in view of BLBCs and quintuple-negative breast cancers (QNBC/5NPs).MethodsUsing tissue microarray-based immunohistochemical analysis, we categorized 951 primary breast cancers into four or five subtypes according to the expression of ER, PR, HER2, and basal markers (CK5/6, EGFR).ResultsThe results of this study showed that both TNBCs and BLBCs were associated with high histological and/or nuclear grades. When the TNBCs are divided into two subtypes by the presence of basal markers, the clinicopathologic characteristics of TNBCs were mainly maintained in the BLBCs. The 5-subgrouping was the better prediction model for both disease free and overall survival in breast cancers than the 4-subgrouping. After multivariate analysis of TNBCs, the BLBCs did not have a worse prognosis than the QNBC/5NPs. Interestingly, the patients with BLBCs showed significant adjuvant chemotherapy benefit. In addition, QNBC/5NPs comprised about 6~8% of breast cancers in publicly available breast cancer datasetsConclusionThe QNBC/5NP subtype is a worse prognostic subgroup of TNBCs, especially in higher stage and this result may be related to adjuvant chemotherapy benefit of BLBCs, calling for caution in the identification of subgroups of patients for therapeutic classification.

Benign papillary lesions of the breast: sonographic-pathologic correlation.

We reviewed the sonographic findings of 42 benign papillary lesions of the breast and correlated them with pathologic findings. Sonography detected 95% of papillomas (22 intraluminal masses, four extraductal masses, nine purely solid masses, and five mixed type masses). The sonographic margins of the mass were well defined in 20 lesions and poorly defined in 14 lesions. Poorly defined margins on sonography were frequent in papillomas with pathologic pseudoinvasion and in juvenile papillomatosis. Most benign papillary lesions of the breast have the sonographic findings suggestive of intraductal origin. The sonographic findings of papillary lesions correlated well with pathologic findings.

L‐ascorbic acid represses constitutive activation of NF‐κB and COX‐2 expression in human acute myeloid leukemia, HL‐60

There is increasing evidence that l‐ascorbic acid (LAA) is selectively toxic to some types of cancer cells at pharmacological concentrations, functioning as a pro‐oxidant rather than as an anti‐oxidant. However, the molecular mechanisms by which LAA initiates cellular signaling leading to cell death are still unclear. In an effort to gain insight into these mechanisms, the effects of LAA on eukaryotic transcription nuclear factor NF‐κB and cyclooxygenase‐2 (COX‐2) expression were investigated. In the present study, LAA suppressed DNA binding activity of NF‐κB, composed of a p65/p50 heterodimer, through inhibition of degradation of inhibitory κB‐α (IκB‐α) and prevention of nuclear translocation of p65. The inhibitory effect of LAA on NF‐κB activity was dependent upon glutathione levels in HL‐60 cells, as well as generation of H2O2 but not superoxide anion. LAA also downregulated the expression of COX‐2, which has a NF‐κB binding site on its promoter, through repressing NF‐κB DNA binding activity. Moreover, cotreatment of 1 μM arsenic trioxide (As2O3) with various concentrations of LAA enhanced an LAA‐induced repression of NF‐κB activity and COX‐2 expression. In conclusion, our data suggest that LAA exerts its anti‐tumor activity through downregulation of NF‐κB activity and COX‐2 expression, and these inhibitory effects can be enhanced by co‐treatment with As2O3.

Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells

ETHNOPHARMACOLOGICAL RELEVANCE The expression of matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) are pivotal steps in breast cancer pathogenesis. In a previous study, we reported that silibinin suppresses TPA-induced MMP-9 expression through the Raf/MEK/ERK pathway. AIMS OF THE STUDY Herein we determined the co-relationship between MMP-9 and COX-2, as well as the effect of silibinin on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and COX-2 expression in the human breast cancer cells, MCF-7 and MDA-MB231. METHODS The toxicity of silibinin was evaluated by Quick Cell Proliferation Assay Kit II. MMP-9 and COX-2 expression were analyzed by Zymography and Western blotting, respectively. Adenoviral constitutively active (CA)-MEK was used to activate MEK/ERK pathway. RESULTS The expression of MMP-9 and COX-2 in response to TPA was increased, whereas TPA-induced MMP-9 and COX-2 expression was decreased by silibinin. Our results showed that TPA-induced MMP-9 expression was inhibited by celecoxib in a dose-dependent fashion, but not MMP-1-expression. Both MMP-9 and COX-2 expression were significantly increased by CA-MEK overexpression. In contrast, TPA-induced MMP-9 and COX-2 expression was decreased by UO126 (MEK 1/2 inhibitor). CONCLUSION Silibinin down-regulates TPA-induced MMP-9 expression through inhibition of COX-2 expression in breast cancer cells.

The role of PET CT to evaluate the response to neoadjuvant chemotherapy in advanced breast cancer: comparison with ultrasonography and magnetic resonance imaging.

Recently PET is emerged as a method to estimate the response of neoadjuvant chemotherapy (NAC) in advanced breast cancer. This study is aimed to estimate the predictive role of PET CT and other imaging modalities (ultrasound, MRI) through NAC.