• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.1
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• pp.1-6
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• 2010

Purpose: Chemokines are structurally related, small polypeptide signaling molecules that bind to and activate a family of transmembrane G protein-coupled receptors, the chemokine receptors. Recently, interaction between the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor 1 (SDF-1 or CXCL12), has been found to play an important role in tumorigenicity, proliferation, metastasis and angiogenesis in many cancers such as lung cancer, breast cancer, melanoma, glioblastoma, pancreatic cancer and cholangiocarcinoma. Hence, the goal of this study is to identify the correlation of clinicopathological factors and the up-regulation of SDF-1 expression in oral squamous cell carcinoma. Material and methods: We studied the immunohistochemical staining of SDF-1, quantitative RT-PCR (qRT-PCR) of SDF-1 gene in 20 specimens of 20 patients with oral squamous cell carcinoma. Results: 1. In the immunohistochemical study of poor differentiated and invasive oral squamous cell carcinoma, the high level staining of SDF-1 was observed. And the correlation between immunohistochemical SDF-1 expression and tumor nodes metastases (TNM) classification of specimens was significant.($x^2$ test, P < 0.05) 2. In the SDF-1 gene qRT-PCR analysis, SDF-1 expression was more in tumor tissue than in carcinoma in situ tissue. Paired-samples analysis determined the difference of SDF-1 mRNA expression level between the cancer tissue and the carcinoma in situ tissue.(Student's t-test, P < 0.05) Conclusion: These findings suggest that up-regulation of the SDF-1 may play a role in progression and invasion of oral squamous cell carcinoma.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.2
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• pp.99-107
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• 2020

Objectives: We accessed the various clinico-histopathological factors, and their association with occult metastasis (OM) in oral tongue squamous cell carcinoma (OTSCC). Materials and Methods: One hundred-nine patients with OTSCC were divided into the elective neck dissection (END) group and the watchful waiting (WW) group. Age, sex, T-stage, depth of invasion and differentiation were evaluated to determine the correlation between clinico-histopathological factors and OM. For immunohistochemical analysis, paraffin-embedded blocks of 41 OTSCC specimens were examined with antibodies (VEGF-c, c-Met, and ROR1). Results: The group with tumor thickness of oral tongue cancer ≥3 mm had higher incidence of OM than those with a thickness of <3 mm. The depth of invasion was statistically correlated with OM (P=0.022). Immunohistochemical analysis showed that high expression of VEGF-c (P=0.043), c-Met (P=0.009), and ROR-1 (P=0.003) were statistically correlated with OM. Conclusion: The analysis of these clinico-histopathological and immunohistochemical factors can help to determine neck dissection in clinically negative (cN0) patients.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.5
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• pp.396-402
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• 2011

Introduction: Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids with potent mitogenic activity that stimulates the proliferation of a range of normal and neoplastic cells through an interaction with its specific receptor (epidermal growth factor receptor, EGFR). This interaction plays a key role in tumor progression including the induction of tumor cell proliferation. An increased EGFR copy number have been associated with a favorable response to EGFR tyrosine kinase inhibitors therapy. In contrast, K-ras mutations tend to predict a poor response to such therapy. The aim of this study was to determine the correlation between the clinicopathological factors and the up-regulation of EGFR expression and Kras mutations in oral squamous cell carcinoma. Materials and Methods: This study examined the immunohistochemical staining of EGFR, K-ras mutation detection with peptide nucleic acid (PNA)-based real-time polymerase chain reaction (PCR) clamping in 20 specimens from 20 patients with oral squamous cell carcinoma. Results: 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, a high level of EGFR staining was observed. The correlation between immunohistochemical EGFR expression and histological differentiation, as well as the tumor size of the specimens was significant (Pearson correlation analysis, significance [r] >0.5, P<0.05). 2. In PNA-based real-time PCR clamping analysis, a K-ras mutation was not detected in all specimens. Conclusion: These findings suggest that the up-regulation of the EGFR may play a role in the progression and invasion of oral squamous cell carcinoma that is, independent of a K-ras mutation.

• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.191-198
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• 1998

Objectives: We performed an immunohistochemical study to examine the place of neovascularization in the tumorigenic process of follicular thyroid carcinoma and to determine whether tumor angiogenic activity in follicular carcinoma plays a role in tumor aggression. Materials & Methods: We studied 63 follicular thyroid carcinomas and compared with 22 follicular adenomas. The areas of capsular invasion, vascular invasion and cellular atypism of the tumor were confimed on H & E stains. The paraffin embedded tissues were stained by the use of monoclonal antibodies against Ag CD34. Microvesseles were counted in the area of highest vascular density at 200 times magnification. The microvessel densities(MVD) were analized in relation to histologic type and location of the tumors. Results: There were 59 minimal invasive types and 4 widely invasive types of carcinoma. In the histologic specimens of carcinomas, capsular invasion was identified in all the cases, vascular invasion in 46 and cellular atypism in 24. Mean values of the MVDs of the minimal invasive carcinomas, the widely invasive carcinomas and the adenomas were $263.8{\pm}69.2,\;256.l{\pm}49.3\;and\;241.5{\pm}159.4$, respectively and there was no significant difference between each group. In follicular carcinomas, there was a regional difference of the MVDs. The areas of tumor showing cellular atypism and adjacent to or penetrating the capsule, in which represents the tumorigenic process of carcinoma, had a higher rate of vascularization, than other areas of the tumor(p<0.05). However, these features were not noted in the follicular adenomas. Conclusion: Although there was no significant difference of the MVD between follicular carcinomas and adenomas, there was a regional difference of the MVD within the carcinomas and the values were significantly higher in the more malignant areas, as indicated by cellular atypism and capsular invasion. Therefore, tumor angiogenic activity measured by MVD may play a role in tumor aggression in follicular thyroid carcinoma.

• Korean Journal of Head & Neck Oncology
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• v.15 no.2
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• pp.141-148
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• 1999

Objectives: The development of thyroid tumor has a relationship with carcinogen, oncogene and tumor suppressor gene. With aminotriazole, radioactive iodine and nitrosomethylurea as carcinogens in rat, authors investigate the incidence in type of the thyroid tumors, p21 and p53 protein expression pattern by immunohistochemical stain and the relationship between the tumors and p21-p53 protein expressions. Materials and Methods: 80 experimental animals were divided into four groups; group 1(control, no carcinogen, n=20), group 2(oral administration of aminotriazole for 36 weeks, n=20), group 3(intraperitoneal injection of 131I for one time and oral administration of aminotriazole for 36 weeks, n=20), group 4(oral administration of nitrosomethylurea for 3 days and aminotriazole for 36 weeks, n=20). After 40 weeks they were sacrificed with pathologic examination and we performed immunohistochemical staining with pan-ras monoclonal antibody for p21 protein and CMI polyclonal antibody for p53 protein with paraffin-embedded specimens. Results: 1) No tumors were observed in group I, but 38.3% of nodular goiters, 11.7% of adenomas and 50.0% of carcinomas were observed in carcinogen treated groups(group 2, 3, 4). 2) The incidence of nodular goiter, adenoma and carcinoma were 70%, 20% and 10% in group 2, 40%, 15% and 45% in group 3 and 5%, 0% and 95% in group 4. 3) p21 protein was not expressed in normal thyroid tissues but was expressed in 26.1% of nodular goiters, 42.9% of adenomas and 6.7% of carcinomas. On the other hands, p53 protein was not expressed in normal thyroid tissues, nodular goiters, adenomas and in well differentiated thyroid carcinomas by immunohistochemical stain. Conclusion: The authors suggest that aminotrizole, 131I, nitrosomethylurea can be etiologic agents in the development of thyroid tumor and the p21 protein can be expressed in the early stage and in benign condition of thyroid tumor but p53 protein is not expressed in all conditions of development in rats.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.4
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• pp.106-118
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• 2005

Purpose : Deoyeongjeon(DYJ : 大營煎) is used in female infertility, caused by　ovulation disorder. so this study is to examine what are the effects of the Deoyeongjeon(DYJ) on the vulation and Ovary in Rats Methods : 4weeks Female Sprague-Dawley 12 rats of weighting 160-l80g, were divided into three groups including the DYJ oral administration(4ml/kg) groups(4heads) and DYJ oral administration(8m/lkg) groups(4heads). then we observed changes in the serum concentrations of FSH, LH, and estradiol(E2) and the histological changes of ovary and the immunohistochemical staining for progesterone receptor in ovary of rats. Results : 1. Blood FSH level significantly increased in experimental group as compared with control group. 2. In blood LH level, experimental group showed no efficacy as compared with control group. 3. In blood estradiol(E2) level, experimental group showed no efficacy as compared with control group. 4. In histological observations of ovary, ovulation increased in experimental group as compared with control group, which showed no efficacy. 5. In observations of immunohistochemical staining for progesterone receptor in ovary, immunohistochemical staining score (ISS) of atretic follicles significantly showed a tendency to decrease in experimental group as compared with control group. Conclusion : DYJ influences the pituitary gland and ovary to increase the ovulation of rats.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.3
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• pp.1-16
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• 2005

Purpose : This study is to examine what are the effects of the Guisinhwan(GSH) on the ovulation and ovary in rats. Methods : 4weeks Female Sprague-Dawley 12 rats of weighting 160-l80g, were divided into three groups including the GSH oral administration(4ml/kg) groups(4heads) and GSH oral administration(8ml/kg)　groups(4heads). Then we observed changes in the serum concentrations of FSH, LH, and estradiol($E_2$) and the histological changes of ovary and the immunohistochemical staining for progesterone receptor in ovary of rats. Results : 1. GSH didn't make a difference as compared with control group in serum FSH level. 2. GSH didn't make a difference as compared with control group in serum LH level. 3. GSH significantly increased serum $E_2$ level. 4. GSH significantly increased ovulation in histological observations of ovary. 5. GSH tended to decrease immunohistochemical staining score (ISS) of atretic follicles in immunohistochemical staining for progesterone receptor in ovary. Conclusion : GSH influences ovary to increase the ovulation of rats.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2795-2799
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• 2016

Purpose: To study histomorphological and immunohistochemical patterns of gastro-intestinal stromal tumours (GISTs) in Malaysia. Materials and Methods: A total of 29 GIST cases from Hospital Tuanku Ja'afar, Seremban, were studied retrospectively over a period of 10 years from January 2002 to December 2011. Patient demographic data like age, sex and etnicity were collected. Tumour characteristics like site, maximum dimension and specimen type were analysed. Evaluation was according to established criteria into very low, low, intermediate and high-risk categories. Immunohistochemical characteristics were also analysed. Results: The mean age of patients was 59.7 years. Males (59%) were found to be more commonly affected than females (41%). The Chinese (45%) were commonly affected than Malays (41%), and Indians (10%). The most common symptom was pain in the abdomen (13.8%). More than half of the cases were seen in stomach (53%). The tumour size ranged from 1.5 cm to 17 cm with a mean of 6.94cm. Microscopic findings revealed that the spindle cell type was the most common (76%). It was observed that the majority of the cases (48%) were categorised in the intermediate risk group. Immunohistochemical staining showed positivity for CD117 (78.6%), CD34 (71.4%), vimentin (86.2%), S-100 (27.6%), SMA (35.7%), PKC THETA (46.4%) and PDGRFA (67.9%).

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1149-1155
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• 2016

Background: Examination of sentinel lymph node (SLN) biopsies provides accurate nodal staging for breast cancer and plays a key role in patient management. Procurement of SLNs and the methods used to process specimens are equally important. Increasing the level of detail in histopathological examination of SLNs increases detection of metastatic tumours but will also increase the burden of busy laboratories and thus may not be carried out routinely. Recommendation of a reasonable standard in SLN examination is required to ensure high sensitivity of results while maintaining a manageable practice workload. Materials and Methods: Twenty-four patients with clinically node-negative breast cancer were recruited. Combined radiotracer and blue dye methods were used for identification of SLNs. The nodes were thinly sliced and embedded. Serial sectioning and immunohistochemical (IHC) staining against AE1/AE3 were performed if initial H&E sections of the blocks were negative. Results: SLNs were successfully identified in all patients. Ten cases had nodal metastases with 7 detected in SLNs and 3 detected only in axillary nodes (false negative rate, FNR=30%). Some 5 out of 7 metastatic lesions in the SLNs (71.4%) were detected in initial sections of the thinly sliced tissue. Serial sectioning detected the remaining two cases with either micrometastases or isolated tumour cells (ITC). Conclusions: Thin slicing of tissue to 3-5mm thickness and serial sectioning improved the detection of micro and macro-metastases but the additional burden of serial sectioning gave low yield of micrometastases or ITC and may not be cost effective. IHC validation did not further increase sensitivity of detection. Therefore its use should only be limited to confirmation of suspicious lesions. False negative cases where SLNs were not involved could be due to skipped metastases to non-sentinel nodes or poor technique during procurement, resulting in missed detection of actual SLNs.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.1
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• pp.1-8
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• 2010

Background and Purpose: Vascular endothelial growth factor (VEGF)-C and VEGF receptor (VEGFR)-3 are involved in tumor lymphangiogenesis. Oral mucosal squamous cell carcinoma (OMSCC) preferentially metastasizes to cervical lymph nodes, so we investigated the expression and distribution of VEGFR-3 signaling proteins in OMSCC. Materials and Methods: Tissue samples of 18 OMSCC, 10 oral mucosal leukoplakia, and 3 normal oral mucosa were evaluated for expression of VEGF-C, VEGF-D, and VEGFR-3 by immunohistochemical staining. The presence of lymphatic vessels was determined using D2-40 staining, by which we also measured lymphatic vessel density (LVD). Results: 72% (13/18) and 56% (10/18) of tissue samples showed VEGF-C and VEGF-D immunopositivity in tumor cells and tumor-associated endothelial cells. VEGFR-3 was also expressed in most of OMSCC, which was up-regulated when compared with normal mucosa or with leukoplakia. Furthermore, LVD was higher in OMSCC than in leukoplakia. Conclusion: Taken together, our results suggest that autocrine activation of lymphatic endothelial cell via VEGFR-3 by VEGF-C and/or VEGF-D could be involved in progression of OMSCC. Therefore, VEGF-C/VEGFR-3 signaling pathway can be a molecular target for anti-metastatic therapy in OMSCC.