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Biomedical subjects

Woo-Ick Yang

Publications and source records attributed to Woo-Ick Yang.

9 recordsLinked to original sources

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↗

Hypermethylation of death-associated protein (DAP) kinase CpG island is frequent not only in B-cell but also in T- and natural killer (NK)/T-cell malignancies.

Death-associated protein (DAP) kinase is a pro-apoptotic serine/threonine kinase with a death domain, which is involved in apoptosis induced by interferon-gamma, tumor necrosis factor-alpha, and Fas ligand. Down-regulation of DAP kinase gene expression by hypermethylation of its promoter region might result in resistance to apoptotic cell death, and could provide a basis for tumor development. In the present study, we employed methylation-specific polymerase chain reaction to examine the methylation status of CpG islands in the DAP kinase gene in 19 cases of T-cell malignancies (including eight adult T-cell leukemia/lymphoma), 24 of natural killer (NK)/T-cell, and 34 of B-cell. Frequency of methylation was significantly higher in B-cell (27 of 34, 79.4%) than in T-cell malignancies (nine of 19, 47.4%) (P<0.05). Fifteen of 24 (62.5%) NK/T-cell lymphomas showed DNA methylation. One B-cell lymphoma cell line with DNA methylation was resistant to apoptotic stimuli, and treatment of the cells with a demethylating agent restored apoptotic cell death. These findings suggested that suppression of DAP kinase expression by DNA methylation might play a substantial role in the development of not only B-cell, but also T- and NK/T-cell lymphomas.

Antibodies, Monoclonal↗

Primary NK/T cell lymphoma of the testis. A case report and review of the literature.

We report a case of aggressive 'nasal type' natural killer (NK)/T cell lymphoma initially presenting as a testicular tumor in a Korean man, which quickly took a fatal course by widespread dissemination. Histologically, the testicular mass showed a diffuse dense infiltrate of medium-sized and atypical large lymphoid cells with angiocentric and angiodestructive infiltration and areas of coagulative necrosis on hematoxylin-eosin stained sections. Immunophenotyping by immunohistochemistry yielded surface markers consistent with NK/T cell lymphoma. The Epstein-Barr virus genome was detected by in situ hybridization. During involved-field irradiation and chemotherapy following radical orchiectomy, the tumor disseminated shortly to the skin and soft tissue of his anterior chest wall and central nervous system (CNS). Identical lymphoid infiltrates were present in the patient's skin. CNS involvement was interpreted as having a leptomeningeal seeding. To the best of our knowledge, this is the 9th reported case of confirmed NK/T cell lymphoma arising from the testis. Relevant literature is reviewed, and the clinicopathologic features, natural history, and treatment options for primary testicular NK/T cell lymphoma are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Catheter-based adenovirus-mediated local intravascular gene delivery of a soluble TGF-beta type II receptor using an infiltrator in porcine coronary arteries: efficacy and complications.

Enhanced extracellular matrix (ECM) accumulation is an important finding in human restenotic arterial neointima after angioplasty. Transforming growth factor beta1(TGF-beta1) is known to regulate the synthesis and turnover of a variety of ECM components, and may play an important role in restenosis. Recombinant adenoviral vector expressing an ectodomain of the TGF-beta type II receptor fused to the human immunoglobulin Fc portion (AdTbeta-ExR) inhibits the action of TGF-beta probably either by adsorbing TGF-beta or by acting as a dominant negative receptor. We carried out a catheter-based local adenovirus mediated gene delivery using an Infiltrator in porcine coronary arteries to know the pattern of gene expression, efficacy and procedural complications. Twenty four coronary arteries in 13 pigs were used for intravascular gene delivery by intramural injection with either AdTbeta-ExR or adenovirus expressing beta-galactosidase (AdCALacZ). Direct immunofluorescent staining and reverse transcription polymerase chain reaction (RT-PCR) were used for detection of type II TGF-beta receptor and its mRNA respectively. X-Gal histochemistry was performed to identify beta-galactosidase. Both soluble TGF-beta receptor and beta-galactosidase were expressed locally in the media and adventita at injected arterial segments without any significant dissemination to remote area. Intravascular gene transfection performed with various titer of each adenoviral vector showed that AdTbeta-ExR of 5 x 10(8) pfu and AdCALacZ of 2.5 x 10(8) pfu were the minimum titer for the expression of each transgene. Infiltration of CD3 positive T cells was detected by immunohistochemical staining in the area of each transgene expression, and tends to decrease over time after gene delivery. Pathological study of 24 treated arteries showed complications such as disruption of external elastic lamina with hemorrhage (n = 4), minimal disruption of internal elastic lamina and endothelial layer, and medial thickening. In conclusion, catheter-based local intravascular gene delivery of adenoviral vector is feasible and effective in a selected artery, but must be undertaken with caution due to possible lethal complications. Local delivery of soluble TGF-beta type II receptor in this way may provide an effective intravascular gene therapy to inhibit TGF-beta signal pathway without any significant systemic side effect.

Adenoviridae↗

Frequent mutations of Fas gene in nasal NK/T cell lymphoma.

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling through binding of Fas ligand. Mutation of Fas gene in lymphoid cells results in accumulation of these cells, which might thus contribute to lymphomagenesis. We examined the open reading frame of Fas cDNA in 14 cases of nasal NK/T-cell lymphoma. Mutations of Fas gene were detected in seven (50%) of 14 cases which comprised four frameshift, two missense, and one silent mutations. Frameshift mutations were caused by insertion of 1 bp (A) at nucleotide 1095 in two cases and by deletion of 1 bp at nucleotide 597 and at 704, respectively, in one each. Mouse T-cell lymphoma cells transfected with two missense mutated genes and frameshift mutations caused by insertion of 1 bp (A) at nucleotide 1095 were resistant to apoptosis induced by the anti-Fas antibody. These findings suggested that accumulation of lymphoid cells with Fas mutations provides a basis for the development of nasal NK/T-cell lymphoma.

Apoptosis↗

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↗

Decrease in apoptosis and increase in polyploidization of megakaryocytes by stem cell factor during ex vivo expansion of human cord blood CD34+ cells using thrombopoietin.

Thrombopoietin (TPO) is widely used for ex vivo expansion of hematopoietic stem cells. Previously, we have reported that TPO induces a characteristic pattern of apoptosis, and the TPO-induced apoptosis is closely associated with megakaryocyte (MK) differentiation. In the present study, several cytokines, flt3-ligand, stem cell factor (SCF), interleukin-3 (IL-3), IL-6, IL-11, leukemia inhibitory factor, G-CSF, and erythropoietin, which are known to affect megakaryocytopoiesis, have been evaluated to elucidate their effects on the TPO-induced apoptosis. Measurement of apoptosis by flow cytometry revealed that only SCF absolutely reduced the TPO-induced apoptosis in MK fractions, particularly in the late phase of ex vivo expansion. Platelet production was demonstrated by electron microscopy in a later phase when SCF was added. Simultaneous measurement of DNA contents with immunophenotyping demonstrated a significant increase in polyploidization in the CD41+ cell fraction when cultured with SCF. These results suggested that SCF not only inhibited premature senescence but also enhanced maturation of the differentiating cells of MK lineage during ex vivo expansion using TPO.

Antigens, CD34↗

Measles-related appendicitis.

Owing to the characteristic Warthin-Finkeldey giant cells found in hyperplastic mucosa-associated lymphoid tissue, it has been emphasized that pathologists can make a diagnosis of measles from appendectomy specimens even in the prodromal stage before diagnostic rashes develop. However, to date, those reported cases of measles-related appendicitis have dealt with the histologic features of the prodromal stage and we found no reports in the English literature describing the histopathologic findings of appendicitis during the full-blown stage of measles. Here, we describe 2 cases of measles-related appendicitis that show contrasting histologic features according to stage, one discovered during the prodromal stage and the other occurring during the full-blown stage. This report describes heretofore unreported histopathologic findings of measles-related appendicitis observed during the full-blown stage of the infection and highlights histopathologic changes caused by replication of the virus in different compartments of the same organ during the course of infection.

Appendicitis↗