Hyun-Deuk Cho

Detection of BRAF V600E Mutations in Papillary Thyroid Carcinomas by Peptide Nucleic Acid Clamp Real-Time PCR: A Comparison with Direct Sequencing

Background Papillary thyroid carcinoma (PTC) of the thyroid is the most common endocrine malignancy. High prevalence of an activating point mutation of BRAF gene, BRAFV600E, has been reported in PTC. We assessed the efficiency of peptide nucleic acid clamp real-time polymerase chain reaction (PNAcqPCR) for the detection of BRAFV600E mutation in PTC in comparison with direct sequencing (DS). Methods A total of 265 thyroid lesions including 200 PTCs, 5 follicular carcinomas, 60 benign lesions and 10 normal thyroid tissues were tested for BRAFV600E mutation by PNAcqPCR and DS. Results The sensitivity and accuracy of the PNAcqPCR method were both higher than those of DS for the detection of the BRAFV600E mutation. In clinical samples, 89% of PTCs harbored the BRAFV600E mutation, whereas 5 follicular carcinomas, 50 benign lesions and 10 normal thyroid tissues lacked the mutation. The mutation was associated with aggressive clinical behaviors as extrathyroid invasion (p=0.015), lymph node metastasis (p=0.002) and multiple tumor numbers (p=0.016) with statistical significance. Conclusions The PNAcqPCR method is efficiently applicable for the detection of the BRAFV600E mutation in PTCs in a clinical setting.

Foreign Body Granulomas Simulating Recurrent Tumors in Patients Following Colorectal Surgery for Carcinoma: a Report of Two Cases

We report here two cases of foreign body granulomas that arose from the pelvic wall and liver, respectively, and simulated recurrent colorectal carcinomas in patients with a history of surgery. On contrast-enhanced CT and MR images, a pelvic wall mass appeared as a well-enhancing mass that had invaded the distal ureter, resulting in the development of hydronephrosis. In addition, a liver mass had a hypointense rim that corresponded to the fibrous wall on a T2-weighted MR image, and showed persistent peripheral enhancement that corresponded to the granulation tissues and fibrous wall on dynamic MR images. These lesions also displayed very intense homogeneous FDG uptake on PET/CT.

A Rare Case of Primary Tubular Adenocarcinoma of the Thymus, Enteric Immunophenotype: A Case Study and Review of the Literature

Thymic carcinomas are uncommon malignant tumors, and thymic adenocarcinomas are extremely rare. Here, we describe a case of primary thymic adenocarcinoma in a 59-year-old woman. Histological examination of the tumor revealed tubular morphology with expression of cytokeratin 20 and caudal-type homeobox 2 according to immunohistochemistry, suggesting enteric features. Extensive clinical and radiological studies excluded the possibility of an extrathymic primary tumor. A review of the literature revealed only two global cases of primary tubular adenocarcinomas of the thymus with enteric immunophenotype.

Expression of the survivin-2B splice variant related to the progression of colorectal carcinoma

Purpose Recently, two alternatively spliced survivin variants, survivin-ΔEx3 and survivin-2B, were identified in a single copy of the survivin gene. It has been reported that the expressions of survivin splice variants significantly correlates with the clinical results in many types of human carcinoma. We investigated the transcription levels of survivin and its splice variants in human colorectal carcinomas, and analyzed correlations between survivin expression levels and clinicopathologic features. Methods We used Western blot and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) to analyze the protein and mRNA expression levels of survivin variants in 51 colorectal carcinomas. The quantitative RT-PCR was performed using primer pairs specific for survivin and each of its splice variants, then normalized for the gene that encodes glyceraldehydes-3-phosphate dehydrogenase. Results In Western blotting, the protein levels of survivin were higher in the tumor tissue than in normal tissue. The expression of survivin, survivin-2B and survivin-ΔEx3 mRNA was present in 96%, 64.7%, and 82.4% of the samples, respectively. When the pathologic parameters were compared, colorectal cancers of advanced pT stages showed significant decrease in survivin-2B mRNA expression by the quantitative RT-PCR (P < 0.001). Conclusion The decreased expression of survivin-2B might be related to tumor progression in colorectal cancers. This finding indicates that alternatively spliced variants of survivin may be involved in refining the functions of survivin during tumor progression.

Thymoquinone (TQ) inhibits the replication of intracellular Mycobacterium tuberculosis in macrophages and modulates nitric oxide production

BackgroundHuman tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent.MethodsIn this study, the effects of TQ on intracellular mycobacterial replication are examined in macrophages. In addition, its effect on mycobacteria-induced NO production and pro-inflammatory responses were investigated in Mycobacterium tuberculosis (MTB)-infected Type II human alveolar and human myeloid cell lines.ResultsTQ at concentrations ranging from 12.5 to 25xa0μg/mL and 6.25 to 12.5xa0μg/mL reduced intracellular M. tuberculosis H37Rv and extensively drug-resistant tuberculosis (XDR-TB) 72xa0h post-infection in RAW 264.7 cells. TQ treatment also produced a concentration-dependent reduction in nitric oxide production in both H37Rv and XDR-TB infected RAW 264.7 cells. Furthermore, TQ reduced the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory molecules such as tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6) in H37Rv-infected cells and eventually reduced pathogen-derived stress in host cells.ConclusionsTQ inhibits intracellular H37Rv and XDR-TB replication and MTB-induced production of NO and pro-inflammatory molecules. Therefore, along with its anti-inflammatory effects, TQ represents a prospective treatment option to combat Mycobacterium tuberculosis infection.

Loss of ARID1A Expression in Gastric Cancer: Correlation with Mismatch Repair Deficiency and Clinicopathologic Features

Purpose The AT-rich interactive domain 1A (ARID1A) gene encodes BRG1-associated factor 250a, a component of the SWItch/Sucrose NonFermentable chromatin remodeling complex, which is considered a tumor suppressor in many tumors. We aimed to investigate the prognostic significance of ARID1A expression in gastric cancers and explore its relationship with clinicopathologic parameters such as mismatch repair protein expression. Materials and Methods Four tissue microarrays were constructed from 191 resected specimens obtained at Soonchunhyang University Cheonan Hospital from 2006 to 2008. Nuclear expression of ARID1A was semiquantitatively assessed and binarized into retained and lost expression. Results Loss of ARID1A expression was observed in 62 cases (32.5%). This was associated with more frequent vascular invasion (P=0.019) and location in the upper third of the stomach (P=0.001), and trended toward more poorly differentiated subtypes (P=0.054). ARID1A loss was significantly associated with the mismatch repair-deficient phenotype (P=0.003). ARID1A loss showed a statistically significant correlation with loss of MLH1 (P=0.001) but not MSH2 expression (P=1.000). Kaplan-Meier survival analysis showed no statistically significant difference in overall survival; however, patients with retained ARID1A expression tended to have better overall survival than those with loss of ARID1A expression (P=0.053). In both mismatch repair-deficient and mismatch repair-proficient groups, survival analysis showed no differences related to ARID1A expression status. Conclusions Our results demonstrated that loss of ARID1A expression is closely associated with the mismatch repair-deficient phenotype, especially in sporadic microsatellite instability-high gastric cancers.

Prognostic and Clinicopathological Significance of Transducer-Like Enhancer of Split 1 Expression in Gastric Cancer

Purpose Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. Materials and Methods Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. Results In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. Conclusions We suggested that TLE1 expression is a good prognostic indicator in GCs.

Loss of FAT Atypical Cadherin 4 Expression Is Associated with High Pathologic T Stage in Radically Resected Gastric Cancer.

Purpose Recent studies have revealed recurrent alterations in the cell adhesion gene FAT4, a candidate tumor suppressor gene, in cancer. FAT atypical cadherin 4 (FAT4) is a transmembrane receptor involved in the Hippo signaling pathway, which is involved in the control of organ size. Here, we investigated the loss of FAT4 expression and its association with clinicopathological risk factors in gastric cancer. Materials and Methods We assessed the expression of FAT4 by using immunohistochemistry on three tissue microarrays containing samples from 136 gastric cancer cases, radically resected in the Soonchunhyang University Cheonan Hospital between July 2006 and June 2008. Cytoplasmic immunoexpression of FAT4 was semi-quantitatively scored using the H-score system. An H-score of ≥10 was considered positive for FAT4 expression. Results Variable cytoplasmic expressions of FAT4 were observed in gastric cancers, with 33 cases (24.3%) showing loss of expression (H-score <10). Loss of FAT4 expression was associated with an increased rate of perineural invasion (H-score <10 vs. ≥10, 36.4% vs. 16.5%, P=0.015), high pathologic T stage (P=0.015), high tumor-node-metastasis stage (P=0.017), and reduced disease-free survival time (H-score <10 vs. ≥10, mean survival 62.7±7.3 months vs. 79.1±3.1 months, P=0.025). However, no association was found between the loss of FAT4 expression and tumor size, gross type, histologic subtype, Lauren classification, lymphovascular invasion, or overall survival. Conclusions Loss of FAT4 expression appears to be associated with invasiveness in gastric cancer.

Examination of In vitro and In vivo biocompatibility of alginate-hyaluronic acid microbeads As a promising method in cell delivery for kidney regeneration

In this study, alginate (ALG) and alginate-hyaluronic acid (ALG-HA) injectable microbeads, with the purpose of delivering stem cells for tissue engineering, were prepared by a spraying method into a CaCl2 solution that shows high porosity for the exchange of nutrition and waste. In addition, the size distribution and surface morphology was investigated using optical and scanning electron microscopy, respectively. The chemical structural properties of the ALG-HA microbeads were examined by Fourier transform infrared spectroscopy. The biocompatibility of ALG and ALG-HA microbeads was examined in vitro. Rat bone marrow stem cells were encapsulated in microbeads to investigate cell release, cell viability, proliferation, and secretion of growth factors such as VEGF and PDGF. Growth factors were released for the 21day experimental period. Cells were found to be released from the microbeads after 7days. Furthermore, the in vivo biocompatibility of ALG-HA microbeads was examined using microbeads without cell encapsulation in the kidney capsule, in order to assess the foreign body reaction and inflammatory response, for 14days. The desired in vivo response to ALG-HA microbeads hydrogel makes it an exquisite candidate for subcapsular cell and drug delivery to kidney tissue.

Pleomorphic adenoma of the nasal vestibule

A55-year-old woman presented to our clinic with a sixmonth history of a gradually enlarging mass on the left nasal vestibule. Physical examination revealed a slightly firm, painless mass located on the medial side of the left vestibular skin (Fig 1). It was approximately 1.2 0.9 0.7 cm in size, and the surface was smooth. Small, ectatic blood vessels were noted on the surface of the mass. Under local anesthesia, the mass was removed en bloc along with the vestibular skin, without destroying the underlying structure. Histopathologically, the excised tumor showed irregular epithelial nests dispersed within a loose myxoid stroma. The epithelial areas were mainly formed of ductal type cells. There was no evidence of recurrence at 24 months after the operation.