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Biomedical subjects

Byeong-Woo Park

Publications and source records attributed to Byeong-Woo Park.

6 recordsLinked to original sources

The changes of estrogen receptor-beta variants expression in breast carcinogenesis: Decrease of estrogen receptor-beta2 expression is the key event in breast cancer development.

BACKGROUND AND OBJECTIVES: Although more than five variant forms of estrogen receptor-beta (ERbeta) have been identified, their role has not been identified. This study was carried out to investigate the changes of ERbeta variants in breast cancer development. METHODS: Using reverse transcription polymerase chain reaction (RT-PCR) and triple primer PCR (TP-PCR), the expression levels of ERbeta variants mRNA were measured in 66 paired normal and cancer tissues. The relative expression level of ERbeta variants were compared between normal and cancer tissues, and also compared according to various clinicopathological parameters. RESULTS: Among ERbeta variants, ERbeta2 and ERbeta5 consist of the major proportion of ERbeta expression both in normal and cancer tissues. The ERbeta and ERbeta2 expression levels decreased significantly in the cancers compared with corresponding normal tissues, particularly in ERalpha-expressing cancers. However, ERbeta5 expression level increased significantly in the cancers, especially in those of postmenopausal patients. The relative increase of ERbeta5 expression in cancer tissues was associated with favorable differentiation. CONCLUSIONS: Decrease of ERbeta2 is thought to be the key reason for the decrease in ERbeta expression in cancer tissues, and it is particularly associated with the development of ERalpha-expressing breast cancer.

Breast↗

Markedly enhanced cytolysis by E1B-19kD-deleted oncolytic adenovirus in combination with cisplatin.

Oncolytic adenoviruses are currently being developed as novel antitumor therapeutics. To enhance their therapeutic potential, adenoviruses are being administered in combination with standard chemotherapy. Adenoviral vectors used in these clinical trials, however, can be destructive as they encode intact E1B 19-kDa protein, which can block the apoptotic pathway induced by a variety of chemotherapeutic agents. Previously, we have shown that oncolytic adenovirus Ad-DeltaE1B19/55, deleted for sequence encoding E1B 19-kDa and E1B 55-kDa proteins, exhibits marked enhancement in cytolytic and apoptotic activity [Kim, J., Cho, J.Y., Kim, J.H., Jung, K.C., and Yun, C.O. (2002). Cancer Gene Ther. 9, 725-736]. In the current study, we assess the therapeutic value of Ad- DeltaE1B55 and Ad-DeltaE1B19/55 in combination with cisplatin. A marked increase in cytotoxicity was observed for both Ad-DeltaE1B55 and Ad-DeltaE1B19/55 when combined with cisplatin. Relative to each other in all cell lines examined, the combination of the double-deleted adenovirus, Ad-DeltaE1B19/55, plus cisplatin exhibited a greater cell-killing effect than did the single-deleted adenovirus, Ad-DeltaE1B55, plus cisplatin. Propidium iodide staining and TUNEL analysis also revealed that the combination of cisplatin with Ad-DeltaE1B19/55 caused greater induction of apoptosis than that with Ad-DeltaE1B55. Similarly, in vivo, the combination of Ad-DeltaE1B55 or Ad-DeltaE1B19/55 with cisplatin also induced greater antitumor effect in a human cervical xenograft model. TUNEL staining showed that the apoptotic level was significantly higher in tumor tissue treated with Ad-DeltaE1B19/55 plus cisplatin than with any other treatment. In addition, viral presence was confirmed by immunohistological staining, with increased numbers of adenoviral particles detected in wider areas of tumors treated with Ad-DeltaE1B19/55 oncolytic adenovirus plus cisplatin. Taken together, these findings demonstrate that cisplatin in combination with E1B- 19kD-deleted oncolytic adenovirus may enhance therapeutic efficacy (via active induction of apoptosis), eliciting a greater efficacy profile than that with E1B-19kD-expressing oncolytic adenovirus.

Adenoviridae↗

Focal fibrosis of the breast diagnosed by a sonographically guided core biopsy of nonpalpable lesions: imaging findings and clinical relevance.

OBJECTIVE: The purpose of this study was to evaluate the frequency of focal fibrosis of the breast diagnosed by a sonographically guided core biopsy of nonpalpable lesions, to characterize imaging features, and to evaluate their clinical relevance. METHODS: In a retrospective review of 724 lesions that underwent sonographically guided core biopsy of nonpalpable breast lesions, 62 cases had a diagnosis of focal fibrosis. Two radiologists analyzed the sonographic and mammographic findings according to the Breast Imaging Reporting and Data System. The results were compared with histologic findings at surgery or imaging findings during surveillance. RESULTS: The incidence of focal fibrosis was 8.6% (62/724). Sonographic films were available in 56 cases, so 56 cases were reviewed for their sonographic findings. Among the mammograms reviewed, 64.7% (33/51) had negative findings. Among the sonograms reviewed, the most common features were oval shape (32/56, 57.1%), parallel orientation (36/56, 64.3%), microlobulated margin (24/56, 42.9%), abrupt interface (50/56, 89.3%), isoechoic pattern (42/56, 75.0%), and a lack of posterior acoustic features (45/56, 80.4%). The Breast Imaging Reporting and Data System final assessment was category 3 in 27 (48.2%) and category 4 in 29 (51.8%). Most of the category 4 lesions were category 4A (26/29, 89.7%). Surgical excision (n = 7) and follow-up for at least 1 year (n = 49) showed no malignancy. CONCLUSIONS: Focal fibrosis was found in 8.6% by a sonographically guided core biopsy of nonpalpable breast lesions. Most of the lesions were categorized as probably benign (category 3) or having a low suggestion of malignancy (category 4A). Focal fibrosis diagnosed at core biopsy can be managed with a 6-month follow-up protocol.

Adult↗

Expression of estrogen receptor-beta in normal mammary and tumor tissues: is it protective in breast carcinogenesis?

Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor-beta (ERbeta) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ERbeta in BC development and progression. ERbeta expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ERbeta mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ERbeta mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ERbeta expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ERbeta expression. Collectively, ERbeta mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.

Biomarkers, Tumor↗

Impact of patient age on the outcome of primary breast carcinoma.

BACKGROUND AND OBJECTIVES: The poorer outcome amongst younger breast cancer patients continues to be an issue of debate. In order to clarify the prognostic value of patient age, we retrospectively analyzed the data of 1098 breast cancer patients. METHODS: Patients were divided into two groups based on the age 35 (Group I, women aged 35 or younger, and Group II, women aged over 35). Clinico-pathological parameters, 10-year loco-regional recurrence-free (10LRRFS), distant relapse-free (10DRFS), and overall (10OS) survival estimates were determined. RESULTS: Among the 1098 patients, approximately 16.7% (183) were allocated to Group I and the other 83.3% (915) to Group II. There were no significant differences between the two groups in terms of histopathologic features or mean follow-up. Group I had a poorer 10LRRFS of 86.8% (P = 0.036), 10DRFS of 57.7% (P < 0.0001), and 10OS of 68.3% (P = 0.0001), compared with 93.9, 76.2, and 81.4% for Group II, respectively. Group I also showed a poorer 10DRFS when matched for stage and lymph node status as well. With lymph node status and tumor size, a patient age of younger than 35 was determined to be an independent prognostic factor by multivariate analysis. CONCLUSIONS: These results indicate that patient age (younger than 35) shows an independent prognostic value and that survival differences by age may reflect differences in the tumor biology.

Adult↗

The role of sonography in patients with breast cancer presenting as an axillary mass.

OBJECTIVE: To compare sonography and mammography in terms of their diagnostic value in breast cancer cases which initially presented as an axillary mass without a palpable mass or other clinical symptoms. MATERIALS AND METHODS: Seven patients with enlarged axillary lymph nodes who first presented with no evidence of palpable breast lesions and who underwent both mammography and sonography were enrolled in this study. In six of the seven, the presence of metastatic adenocarcinoma was confirmed preoperatively by axillary needle aspiration biopsy; in four, subsequent sonographically-guided breast core biopsy performed after careful examination of the primary site indicated that primary breast cancer was present. In each case, the radiologic findings were evaluated by both breast sonography and mammography. RESULTS: Breast lesions were detected mammographically in four of seven cases (57%); in three of the four, the lesion presented as a mass, and in one as microcalcification. In three of these four detected cases, fatty or scattered fibroglandular breast parenchyma was present; in one, the parenchyma was dense. In the three cases in which lesions were not detected, mammography revealed the presence of heterogeneously dense parenchyma. Breast sonography showed that lesions were present in six of seven cases (86%); in the remaining patient, malignant microcalcification was detected at mammography. Final pathologic examination indicated that all breast lesions except one, which was a ductal carcinoma in situ, with microinvasion, were infiltrating ductal carcinomas whose size ranged from microscopic to greater than 3 cm. At the time of this study, all seven patients were alive and well, having been disease free for up to 61 months after surgery. CONCLUSION: In women with a palpable axillary mass confirmed as metastatic adenocarcinoma, breast sonography may be a valuable adjunct to mammography.

Adenocarcinoma↗