• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.26 no.2
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• pp.133-136
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• 2015

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is an extremely rare type of thyroid tumor, with spares reports on its clinical course. SETTLE is derived from branchial pouch or thymic remnants, and classified as a low grade, malignant neoplasm due to its indolent growth and tendency to develop delayed metastasis. Therefore, stringent initial workups and long-term follow-up are required to prevent misdiagnosis. We present a case of recurrent spindle epithelial tumor with thymus-like differentiation (SETTLE) in the glottis of 57 year-old male patient, who had a history of surgical excision for the SETTLE from the thyroid gland 5 years ago. Transoral CO2 laser surgery was performed to remove the glottic tumor and there was no evidence of local recurrence at 11 months postoperatively.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.28 no.3
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• pp.182-187
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• 2002

Matrix metalloproteinase(MMP) is the proteolytic enzyme of the extracellular matrix. MMPs play a role in the invasion and metastasis of malignant tumor, but it is not known whether the expression of MMPs in squamous cell carcinoma of the tongue is related to the prognostic factors of this tumor. In this study, 32 paraffin-embedded tumor specimens were examined immunohistochemically using monoclonal antibodies of MMP-2, MMP-3, MMP-10 and MMP-13. The possible relationships between the expressions of the MMPs and TNM staging, the differentiation of tumor cells, size of tumor mass and lymph node metastasis were anlaysed statistically. The results were as follows. 1. The expression of MMP-2 increased according to TNM staging (P<0.05) and lymph node metastasis (P<0.05) and the expression of MMP-2 was not affected by the differentiation of tumor cells or tumor size. 2. The expression of MMP-3 increased with increasing tumor size (P<0.05). However it was not related to TNM staging, the differentiation of tumor cells or lymph node metastasis. 3. The expression of MMP-10 was unrelated to TNM staging, differentiation of tumor cells, lymph node metastasis or tumor size. 4. The expression of MMP-13 increased as tumor size increased (P<0.05). However it was not related to TNM staging, the differentiation of tumor cells or lymph node metastasis. We concluded that the expression patterns of MMP-2, MMP-3, and MMP-13 may play a role in the diagnosis, treatment plan and prognostic evaluation of malignant tumors of the tongue.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.91.1-91.12
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• 2018

Objective: To examine the association between tumor grade and survival for women with squamous cervical cancer. Methods: This retrospective observational study utilized the Surveillance, Epidemiology, and End Result program data between 1983 and 2013 to examine women with squamous cervical cancer with known tumor differentiation grade. Multivariable analyses were performed to assess independent associations between tumor differentiation grade and survival. Results: A total of 31,536 women were identified including 15,175 (48.1%) with grade 3 tumors, 14,084 (44.7%) with grade 2 neoplasms and 2,277 (7.2%) with grade 1 tumors. Higher tumor grade was significantly associated with older age, higher stage disease, larger tumor size, and lymph node metastasis (all, p<0.001). In a multivariable analysis, grade 2 tumors (adjusted-hazard ratio [HR]=1.21; p<0.001) and grade 3 tumors (adjusted-HR=1.45; p<0.001) were independently associated with decreased cause-specific survival (CSS) compared to grade 1 tumors. Among the 7,429 women with stage II-III disease who received radiotherapy without surgical treatment, grade 3 tumors were independently associated with decreased CSS compared to grade 2 tumors (adjusted-HR=1.16; p<0.001). Among 4,045 women with node-negative stage I disease and tumor size ${\leq}4cm$ who underwent surgical treatment without radiotherapy, grade 2 tumors (adjusted-HR=2.54; p=0.028) and grade 3 tumors (adjusted-HR=4.48; p<0.001) were independently associated with decreased CSS compared to grade 1 tumors. Conclusion: Our study suggests that tumor differentiation grade may be a prognostic factor in women with squamous cervical cancer, particularly in early-stage disease. Higher tumor grade was associated with poorer survival.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.9-18
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• 2016

Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.

• The Korean Journal of Cytopathology
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• v.14 no.2
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• pp.71-75
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• 2003

Uterine stromal tumors with features of ovarian sex-cord differentiation are relatively rare. The neoplasms composed of sex cord-like components in more than 50% of the tumor are classified as group II. We report the cytologic findings of a case of uterine tumor resembling ovarian sex-cord tumor. The cervical smears of a 62-year-old woman with submucosal tumor showed loose aggregates of spindle cells as well as glandular or tubular structures of round cells with a distinct ceil membrane and a prominent small nucleolus. Because uterine stromal tumor can have sex cord differentiation, its possibility should be considered in the interpretation of cervical smears.

• Biomedical Science Letters
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• v.13 no.3
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• pp.213-221
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• 2007

This study was designed to investigate the correlation between the expression rate of p53 and p21 proteins, c-erbB-2 oncoprotein and $TGF-{\beta}1$ and tumor prognostic factors in colon cancer including the tumor size, histological differentiation and Dukes' stage. The expression rate of p53 protein was 11.4% (4 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation. In other words, the poorer differentiation, the higher the expression rate of p53 protein (P<0.05). The expression rate of p21 protein was 17.1% (6 cases) at well differentiation, 40.0% (14 cases) at moderately differentiation, and 8.6% (3 cases) at poorly differentiation, indicating that, as the histological malignant degeneration progressed, the expression rate of p21 protein decreased distinctively (P<0.05). However, the correlation of the above mentioned proteins with tumor size and Dukes' stage was not recognized. The expression rate of c-cerbB-2 oncoprotein was 11.4% (4 cases) at well differentiation, 54.3% (19 cases) at moderately differentiation, and 17.1% (6 cases) at poorly differentiation, indicating that the poorer differentiation, the higher expression rate of c-erbB-2 oncoprotein (P<0.05). The expression rate of $TGF-{\beta}1$ was 17.1% (6 cases) at well differentiation, 48.6% (17 cases) at moderately differentiation, and 11.4% (4 cases) at poorly differentiation. As Dukes' stage progressed, the expression rate of $TGF-{\beta}1$ was 8.6% (3 cases) in stage A, 20.0% (7 cases) in stage B, 37.1 % (13 cases) in stage C, and 11.4% (4 cases) in stage D. There was a difference in expression rates between Dukes' stages (P<0.05). In 10 cases, p53 protein was positive while p21 protein was negative, and in 6 cases, p53 protein was negative whereas p21 was positive (P<0.05). Therefore, a statistically significant inverse correlation between the expression rate of p53 protein and that of p21 protein was observed. In conclusion, since there was a signigicant correlation between histological differentiation of colon cancer and the expressions of p53 and p21 proteins and c-erbB-2 oncoprotein, and between Dukes' stage and the expression of $TGF-{\beta}1$, it was conformed that the overexpression of p53 and p21 proteins, c-erbB-2 oncoprotein, and $TGF-{\beta}1$ is closely associated with the occurrence of colon cancer and its progress. Accordingly, this study may be greatly beneficial to the presumption of diagnosis, treatment and prognosis of colon cancer patients.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.532-537
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• 1993

Angiogenesis refers to the formation of new capillary blood vessels, or neovascularization occurring under various physical conditions, such as development of the embryo, formation of corpus luteum, wound healing and pathological conditions including tumor growth and metastases, hemangiomas, diabetic retinopathy, rheumatoid arthritis. There are many evidences that angiogenesis is important for the progressive growth of solid tumors and also permits the shedding of metastatic tumors from the primary site. Thus, treatment of angiogenesis inhibitors might be a novel strategy for tumor growth inhibition. Normal vascular endothelial cells are in a state of differentiation and angiogenic endothelial cells migrate and proliferate, and they subsequently differentiate into vessel-forming quiescent phenotype cells, Therfore, it was speculated that a modifier of cell differentiation could also affect angiogenesis. In order to identify new antiangiogenic factors, the research was conducted to estimate the inhibitory activities of cell differentiation agents by means of chick embryo chorioallantoic membrane(CAM) assay. Hence, we have established the CAM assay for the screening of antiangiogenic agents. Using the CAM assay, we found that ursolic acid, a tumor cell differentiation-inducing agent, showed a markedly inhibitory effect on chick embryonic angiogenesis.

• BMB Reports
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• v.55 no.2
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• pp.81-86
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• 2022

Macrophages are a major cellular component of innate immunity and are mainly known to have phagocytic activity. In the tumor microenvironment (TME), they can be differentiated into tumor-associated macrophages (TAMs). As the most abundant immune cells in the TME, TAMs promote tumor progression by enhancing angiogenesis, suppressing T cells and increasing immunosuppressive cytokine production. N-myc downstream-regulated gene 2 (NDRG2) is a tumor suppressor gene, whose expression is down-regulated in various cancers. However, the effect of NDRG2 on the differentiation of macrophages into TAMs in breast cancer remains elusive. In this study, we investigated the effect of NDRG2 expression in breast cancer cells on the differentiation of macrophages into TAMs. Compared to tumor cell-conditioned medium (TCCM) from 4T1-mock cells, TCCM from NDRG2-over-expressing 4T1 mouse breast cancer cells did not significantly change the morphology of RAW 264.7 cells. However, TCCM from 4T1-NDRG2 cells reduced the mRNA levels of TAM-related genes, including MR1, IL-10, ARG1 and iNOS, in RAW 264.7 cells. In addition, TCCM from 4T1-NDRG2 cells reduced the expression of TAM-related surface markers, such as CD206, in peritoneal macrophages (PEM). The mRNA expression of TAM-related genes, including IL-10, YM1, FIZZ1, MR1, ARG1 and iNOS, was also downregulated by TCCM from 4T1-NDRG2 cells. Remarkably, TCCM from 4T1-NDRG2 cells reduced the expression of PD-L1 and Fra-1 as well as the production of GM-CSF, IL-10 and ROS, leading to the attenuation of T cell-inhibitory activity of PEM. These data showed that compared with TCCM from 4T1-mock cells, TCCM from 4T1-NDRG2 cells suppressed the TAM differentiation and activation. Collectively, these results suggest that NDRG2 expression in breast cancer may reduce the differentiation of macrophages into TAMs in the TME.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.35.1-35.16
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• 2023

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8⁺ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8⁺ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8⁺ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8⁺ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8⁺ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8⁺ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.2
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• pp.128-135
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• 2007

This study was designed to investigate the correlation between the expression rate of p53 and p21 proteins by immunohistochemical staining and tumor prognostic factors including the tumor size, histological differentiation and Dukes' stage of tumor prognostic factors in colon cancer, and to acquire necessary data for the presumption of diagnosis, treatment and prognosis of colon cancer patients. From January 2000 to January 2003 at Hanyang University Guri Hospital, the paraffin blocks of 35 patients diagnosed with colon cancer whose pathologic reports were possible to review were selected. Harris hematoxylin & eosin (H&E) staining and immunohistochemical staining by ABC (Avidin Biotin Conjugate) method were performed. The histological differentiation grade and stage were classified according to the classification of the World Health Organization (WHO) and modified Dukes's stage from H&E staining. The expression rate of p53 and p21 proteins were analyzed by immunohistochemical staining. The results was analyzed statistically by SPSS (Windows version 8.0). As a result, the expression rate of p53 protein was 11.4% (4 cases) in clear differentiation, 48.6% (17 cases) in moderate differentiation, and 17.1% (6 cases) in poor differentiation. In other words, the poorer the differentiation, the higher the expression rate of p53 protein (p<0.05). The expression rate of p21 was 17.1% (6 cases) in clear differentiation, 40.0%(14 cases) in moderate differentiation, and 8.6% (3 cases) in poor differentiation, According to the progression of histological malignant degeneration, the expression rate of p21 protein decreased distinctively (p<0.05). However, the correlation between the two above mentioned proteins and the tumor-size and Dukes' stage was not of statistical significance. In the comparison of the expression rate of p53 protein with that of p21 protein, in 10 cases, p53 protein expression was positive while p21 protein expression was negative, and in 6 cases, p53 protein expression was negative whereas p21 protein expression was positive. Consequently a statistically significant inverse correlation between the expression rate of p53 protein and that of p21 protein was observed (p<0.05). In conclusion, we found a significant correlation between histological differentiation and the expression rate of p53 and p21 proteins (p<0.05), and a significant inverse correlation between the expression rate of p53 protein and that of p21 protein (p<0.05). Also, it could be confirmed that the over expression of p53 and p21 proteins is closely associated with the occurrence of colon cancer and its progress. Therefore, it is thought that this study may be greatly beneficial to the presumption of diagnosis, treatment and prognosis of colon cancer patients.