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Biomedical subjects

Ju-Han Lee

Publications and source records attributed to Ju-Han Lee.

10 recordsLinked to original sources

Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase.

Recently, pegylated arginine deiminase (ADI; EC 3.5.3.6) has been used to treat the patients with hepatocellular carcinoma or melanoma, in which the level of argininosuccinate synthetase (ASS) activity is low or undetectable. The efficacy of its antitumor activity largely depends on the level of intracellular ASS, which enables tumor cells to recycle citrulline to arginine. Thus, we examined the expression levels of ASS in various cancer cells and found that it is low in renal cell carcinoma (RCC) cells, rendering the cells highly sensitive to arginine deprivation by ADI treatment. Immunohistochemical analysis revealed that in biopsy specimens from RCC patients (n = 98), the expression of ASS is highly demonstrated in the epithelium of normal proximal tubule but not seen in tumor cells. Furthermore, RCC cells treated with ADI showed remarkable growth retardation in a dose dependent manner. ADI also exerted in vivo antiproliferative effect on the allografted renal cell carcinoma (RENCA) tumor cells and prolonged the survival of tumor-bearing mice. Histological examination of the tumors revealed that tumor angiogenesis and vascular endothelial growth factor (VEGF) expression were significantly diminished by ADI administration. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of RCC in ways of inhibitions of arginine availability and neovascularization.

Adult↗

Expression of liver-intestine cadherin and its correlation with lymph node metastasis in gastric cancer: can it predict N stage preoperatively?

BACKGROUND: Reliable method to predict lymph node metastasis is not yet available. In the present study, therefore, we examined LI-cadherin expression in human gastric cancer and attempted to find its relationship with clinicopathologic data, especially with lymph node metastasis. We also analyzed the expression in preoperative biopsy specimen to uncover its possibility of prognostication for lymph node metastasis. METHODS: The paired preoperative endoscopic biopsy and postoperative resected specimens from 208 patients who had surgically been treated for gastric cancer were retrospectively analyzed immunohistochemically for expression of LI-cadherin. RESULTS: There were 47 (22.6%) and 161 (77.4%) tumors which had positive and negative LI-cadherin expression, respectively. LI-cadherin expression was significantly correlated with tumor histology and lymph node metastasis: Furthermore, reduced expression of LI-cadherin was closely associated with tumor progression and lymph node metastasis in human gastric carcinoma. LI-cadherin expressions in both resected tumor and preoperative endoscopic tissues were found to be independent factors associated with lymph node metastasis. CONCLUSIONS: There is a close association between reduced expression of LI-cadherin and lymph node metastasis in human gastric cancer. Immunohistochemical study of LI-cadherin is relatively simple compared to sentinel node navigation surgery, and it could be a practical prediction method for lymph node metastasis in patients with this malignancy.

Biomarkers, Tumor↗

Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma.

The tissue inhibitor of metalloproteinase-1 (TIMP-1) is a stromal factor that promotes plasmablastic differentiation, and the survival of germinal center B-cells. The expression of TIMP-1 is known to be correlated with a subset of non-Hodgkin lymphoma at the mRNA level, and Epstein-Barr virus infection in vitro. To characterize TIMP-1(+) diffuse large B-cell lymphoma, TIMP-1 expression was investigated in tissue microarrays from 182 cases of de novo diffuse large B-cell lymphoma and compared with prognostic factors, immunophenotypes, and Epstein-Barr virus infection status. TIMP-1 was expressed not only in tumor cells themselves, in 14 of 182 cases (8%), designated as TIMP-1(+) diffuse large B-cell lymphoma, but also in stromal cells like fibroblasts and endothelial cells. In univariate analysis and hierarchical clustering, our findings suggest that TIMP-1 expression may represent a distinct subgroup. In multivariate analysis, TIMP-1(+) diffuse large B-cell lymphoma (n=14) was associated with unfavorable outcomes compared to TIMP-1(-) diffuse large B-cell lymphoma (n=168) (odds ratio=2.5, P=0.049). Together with TIMP-1 expression, age (greater than 60 years), the presence of B-symptoms, abnormal lactate dehydrogenase level, or more advanced stage (III/IV) was correlated with a poor overall survival. However, TIMP-1 expression in diffuse large B-cell lymphoma was not correlated with other prognostic factors including: clinical stage, international prognostic index score, and nongerminal center B-cell phenotype, as well as Epstein-Barr virus infection. Our results suggest that TIMP-1 expression may be an independent negative prognostic factor in patients with diffuse large B-cell lymphoma.

Adolescent↗

Acute arthritis of carpal bones secondary to metastatic gastric cancer.

A 39-year-old woman presented with acute onset of arthralgia in both wrists. Although her primary gastric cancer was in remission after previous treatment, carcinomatous arthritis was suggested by the osteolytic radiographic findings and refractoriness to nonsteroidal anti-inflammatory drugs, which was then confirmed by synovial fluid cytopathology. In view of the high incidence of gastric cancer in Korea, gastric cancer involving the carpal bones should be considered when we encounter a patient presenting with inflammatory peripheral joint arthritis, which might be the first sign of recurrence.

Adult↗

Calretinin, CD34, and alpha-smooth muscle actin in the identification of peritoneal invasive implants of serous borderline tumors of the ovary.

The correct identification of invasive implants in the peritoneum in serous borderline tumors (SBTs) of the ovary is an important determinant of diagnosis, treatment, and prognosis. Although the histologic criteria to distinguish noninvasive from invasive implants have been defined, the distinction can still be difficult. We examined the presence and distribution of mesothelial cells, stromal fibrocytes, and myofibroblasts in invasive and noninvasive peritoneal implants in 100 noninvasive, 100 invasive, and 100 metastatic nests/foci from 20 cases of SBTs with peritoneal implants, 10 serous carcinomas with peritoneal metastasis, and 10 cases of endosalpingiosis by immunostaining for calretinin, CD34, and alpha-SMA. All 100 invasive nests from seven SBTs and all 100 metastatic nests from the cases of serous carcinoma showed loss of calretinin+ mesothelial cells and stromal CD34+ fibrocytes around the nests. In contrast, 72/100 noninvasive nests displayed the presence of mesothelial cells around the nests and 68 displayed preservation of surrounding stromal fibrocytes. Alpha-smooth muscle actin positive myofibroblasts were present as a stromal response in 100/100 metastatic nests, 100/100 invasive nests and 54/100 noninvasive nests. The loss of mesothelial cells and stromal fibrocytes surrounding invasive nests together with a proliferation of myofibroblasts as demonstrated by immunostaining proved to be a sensitive and specific tool to separate invasive from noninvasive implants and represents an important adjunct to morphologic diagnosis. Combined sensitivity and specificity of the three antibodies was 100 and 81%, respectively. These methods, however, may not be helpful for small biopsies of noninvasive desmoplastic implants. The distribution of these cells provides some insights into the histogenesis of invasive and noninvasive implants in SBTs.

Actins↗

BRAF mutation and AKAP9 expression in sporadic papillary thyroid carcinomas.

AIM: We aimed to determine the BRAF mutation and AKAP9 expression in papillary thyroid carcinomas (PTCs). METHODS AND RESULTS: In this study, we analysed 100 sporadic PTC specimens and we detected mutation in 62.2% of the conventional type PTCs (51/82), in 50% of the follicular variant type PTCs (3/6), in 50% of the diffuse sclerosing variant type PTCs (1/2), and in 30% of the microcarcinomas (3/10). All mutations involved a T-->A transversion at the nucleotide 1796. The cases with BRAF mutation were significantly associated with extrathyroidal extension. We also evaluated the expression of AKAP9 protein by immunohistochemistry. The AKAP9 protein was seen as a single perinuclear dot in all the PTCs. Therefore, 58% of the specimens harboured the BRAF mutation and no case had AKAP9-BRAF fusion in the sporadic PTCs. CONCLUSION: Our results suggest that the BRAF mutation can be a useful diagnostic and prognostic marker and a target for exploring novel cancer therapies to treat PTCs. AKAP9-BRAF fusion may be a very rare event in sporadic PTCs.

A Kinase Anchor Proteins↗

nm23-H1 protein expression and gene mutation in 150 patients with non-Hodgkin's lymphomas.

The metastasis-suppressing role of the nm23 gene in the metastatic spread of malignant tumor is still debated. We examined the nm23-H1 protein expression and gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic parameters. The expression of nm23-H1 protein was immunohistochemically examined in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DL-BCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25 peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1 protein was associated with the high IPI score (p=0.019) and the low survival rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in 10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon 1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the mutational change of gene may operate in the lymphomagenesis.

Base Sequence↗

Follicular dendritic cell sarcoma arising in the dura mater of the spine.

There have been some individual case reports and a few large series of reports describing the clinicopathologic features of follicular dendritic cell sarcoma. This tumor originates from the dendritic cells of lymphoid follicles and is extremely rare in the extranodal location. We report the case of a 68-year-old man who presented with low back pain. A mass was found in the lumbar dura mater and extended to the right epidural space. The tumor was composed of nodules, sheets, and interlacing fascicles of oval-to-spindle cells intermingled with the dense infiltrates of small lymphocytes. Immunohistochemical staining revealed that the tumor cells were positive for CD21, CD23, CD35, and clusterin, and focally positive for CD68, CD20, and CD79a. To our knowledge, this is the first case of follicular dendritic cell sarcoma occurring in the dura mater of the spine.

Aged↗

Mesenteric Castleman's disease.

We report here a rare case of mesenteric Castleman's disease presenting as a mesenteric mass. A 13-year-old female child was admitted to our hospital complaining of intermittent vague abdominal pain. She had hypochromic anemia, thrombocytosis and an elevated erythrocyte sedimentation rate (ESR). Ultrasonography and computed tomography indicated an intra- abdominal mass might represent a lymphoma or gastrointestinal stromal tumor or leiomyoma, but the definitive preoperative diagnosis couldn't be confirmed. The surgical resection of the mass revealed the mesenteric hyaline vascular-type Castleman's disease.

Adolescent↗