• 대한두경부종양학회지
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• 제37권2호
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• pp.33-41
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• 2021

Background/Objectives: Extra-nodal extension (ENE) is one of the strongest prognosticators in oral cancers. Here we tried to evaluate clinicopathological factors associated with the presence of ENE. Materials & Methods: We retrospectively analyzed clinical information of 120 patients who diagnosed with oral cancer and received curative surgery at our hospital from Mar 2012 to Apr 2020. We comparatively analyzed clinicopathological factors associated with the presence of lymph node (LN) metastasis and ENE, respectively. Results: Variable factors of primary tumor characteristics such as lymphovascular invasion, perineural invasion, largest diameter of tumor, depth of invasion and maximum standardized uptake value were significantly associated with the presence of cervical LN metastasis. The largest diameter of tumor was statistically significant also in multivariate analysis for predicting the LN metastasis. Meanwhile, the association between primary tumor characteristics and the presence of ENE were not statistically significant except the primary tumor size. Importantly, factors associated with LN characteristics including the maximum diameter and number of metastatic LNs were significantly associated with ENE. Conclusion: In this study, several factors affecting cervical LN metastasis and ENE in oral cancer patients were identified. The ENE seems to be influenced by the status of the metastatic LNs, such as the number of metastatic LNs, rather than the characteristics of the primary tumor itself.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1675-1679
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• 2014

Objectives: MicroRNAs (miRNAs) are important regulators of many physiological and pathological processes, including tumorigenesis and metastasis. In this study, we sought to determine the underlying molecular mechanisms of metastatic cervical carcinoma by performing miRNA profiling. Methods: Tissue samples were collected from ten cervical squamous cancer patients who underwent hysterectomy and pelvic lymph node (PLN) dissection in our hospital, including four PLN-positive (metastatic) cases and six PLN-negative (non-metastatic) cases. A miRNA microarray platform with 1223 probes was used to determine the miRNA expression profiles of these two tissue types and case groups. MiRNAs having at least 4-fold differential expression between PLN-positive and PLN-negative cervical cancer tissues were bioinformatically analyzed for target gene prediction. MiRNAs with tumor-associated target genes were validated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: Thirty-nine miRNAs were differentially expressed (>4-fold) between the PLN-positive and PLN-negative groups, of which, 22 were up-regulated and 17 were down-regulated. Sixty-nine percent of the miRNAs (27/39) had tumor-associated target genes, and the expression levels of six of those (miR-126, miR-96, miR-144, miR-657, miR-490-5p, and miR-323-3p) were confirmed by quantitative (q)RT-PCR. Conclusions: Six MiRNAs with predicted tumor-associated target genes encoding proteins that are known to be involved in cell adhesion, cytoskeletal remodeling, cell proliferation, cell migration, and apoptosis were identified. These findings suggest that a panel of miRNAs may regulate multiple and various steps of the metastasis cascade by targeting metastasis-associated genes. Since these six miRNAs are predicted to target tumor-associated genes, it is likely that they contribute to the metastatic potential of cervical cancer and may aid in prognosis or molecular therapy.

• 치과방사선
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• 제29권1호
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• pp.149-159
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• 1999

Purpose: The purpose of this study was to evaluate cervical lymph node metastasis of oral squamous cell carcinoma patients by MRI film and neural network system. Materials and Methods: The oral squamous cell carcinoma patients(21 patients. 59 lymph nodes) who have visited SNU hospital and been taken by MRI. were included in this study. Neck dissection operations were done and all of the cervical lymph nodes were confirmed with biopsy. In MR images. each lymph node were evaluated by using 6 MR imaging criteria(size. roundness. heterogeneity. rim enhancement. central necrosis, grouping) respectively. Positive predictive value. negative predictive value. and accuracy of each MR imaging criteria were calculated. At neural network system. the layers of neural network system consisted of 10 input layer units. 10 hidden layer units and 1 output layer unit. 6 MR imaging criteria previously described and 4 MR imaging criteria (site I-node level II and submandibular area. site II-other node level. shape I-oval. shape II-bean) were included for input layer units. The training files were made of 39 lymph nodes(24 metastatic lymph nodes. 10 non-metastatic lymph nodes) and the testing files were made of other 20 lymph nodes(10 metastatic lymph nodes. 10 non-metastatic lymph nodes). The neural network system was trained with training files and the output level (metastatic index) of testing files were acquired. Diagnosis was decided according to 4 different standard metastatic index-68. 78. 88. 98 respectively and positive predictive values. negative predictive values and accuracy of each standard metastatic index were calculated. Results: In the diagnosis of using single MR imaging criteria. the rim enhancement criteria had highest positive predictive value (0.95) and the size criteria had highest negative predictive value (0.77). In the diagnosis of using single MR imaging criteria. the highest accurate criteria was heterogeneity (accuracy: 0.81) and the lowest one was central necrosis (accuracy: 0.59). In the diagnosis of using neural network systems. the highest accurate standard metastatic index was 78. and that time. the accuracy was 0.90. Neural network system was more accurate than any other single MR imaging criteria in evaluating cervical lymph node metastasis. Conclusion: Neural network system has been shown to be more useful than any other single MR imaging criteria. In future. Neural network system will be powerful aiding tool in evaluating cervical node metastasis.

• Molecules and Cells
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• 제40권7호
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• pp.476-484
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• 2017

C-X-C chemokine receptor 4 (CXCR4) stimulates cancer metastasis. NF-${\kappa}B$ regulates CXCR4 expression in cancer cells, and O-GlcNAc modification of NF-${\kappa}B$ promotes its transcriptional activity. Here, we determined whether CXCR4 expression is affected by O-GlcNAcylation of NF-${\kappa}B$ in lung metastasis of cervical cancer. We found elevated levels of O-linked-N-actylglucosamine transferase (OGT) and O-GlcNAcylation in cervical cancer cells compared to those in non-malignant epithelial cells and detected increased expression of NF-${\kappa}B$ p65 (p65) and CXCR4 in cervical cancer cells. Knockdown of OGT inhibited the O-GlcNAcylation of p65 and decreased CXCR4 expression levels in HeLa cells. Thiamet G treatment increased O-GlcNAcylated p65, which subsequently enhanced CXCR4 expression levels. Inhibition of O-GlcNAcylation by 6-Diazo-5-oxo-L-norleucine (DON) treatment decreased p65 activation, eventually inhibiting CXCR4 expression in HeLa cells. Lung tissues from mice engrafted with OGT-knockdown HeLa cells (shOGT) exhibited lower expression of Ki-67 and HPV E6 and E7 oncogenes compared to lung tissues from mice engrafted with control HeLa cells (shCTL). In addition, lung tissues from mice engrafted with shOGT cells exhibited lower p65 and CXCR4 immunoreactivity compared to tissues from mice engrafted with shCTL cells. Taken together, our data suggest that p65 O-GlcNAcylation promotes lung metastasis of cervical cancer cells by activating CXCR4 expression.

• Journal of Chest Surgery
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• 제50권5호
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• pp.329-338
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• 2017

Background: The clinical value of 3-field lymph node dissection (3FLND) in esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to identify the patterns and prognostic significance of cervical lymph node metastasis (CLNM) in ESCC. Methods: A retrospective review of 77 patients with E SCC who underwent esophagectomy and 3FLND between 2002 and 2016 was conducted. For each cervical node level, the efficacy index (EI), overall survival, recurrence rate, and complication rate were compared. Results: CLNM was identified in 34 patients (44.2%) who underwent 3FLND. Patients with CLNM had a significantly lower overall survival rate (22.7% vs. 58.2%) and a higher recurrence rate (45.9% vs. 16.3%) than patients without CLNM. CLNM was an independent predictor of recurrence in ESCC patients. Moreover, in patients with pathologic N3 tumors, the odds ratio of CLNM was 10.8 (95% confidence interval, 2.0 to 57.5; p=0.005). Level IV dissection had the highest EI, and level IV metastasis was significantly correlated with overall survival (p=0.012) and recurrence (p=0.001). Conclusion: CLNM was a significant prognostic factor for ESCC patients and was more common among patients with advanced nodal stages. Level IV exhibited the highest risk of metastasis, and dissection at level IV may be crucial when performing 3FLND, especially in advanced nodal stage disease.

• International journal of thyroidology
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• 제11권2호
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• pp.117-122
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• 2018

Metastases to regional cervical lymph nodes occur frequently in patients with thyroid cancer. The appropriate management of regional lymph node is important to achieve good disease control and to classify risk stratification for adjuvant radioactive iodine. However, there are some occasions that neck dissection is difficult and embarrassing in thyroid cancer. Especially, extensive or unusual nodal metastases bring challenges and makes neck dissection more difficult. Carotid artery management is one of the most difficult procedure in neck dissection. The management of patients who have persistent or recurrent cervical metastasis involving the carotid artery has been controversial and treatment dilemma to the surgeon. Metastasis of well differentiated thyroid cancer to the retropharyngeal lymph nodes is rare but occasionally encountered. The complete surgical excision is usually recommended for retropharyngeal lymph node metastasis of well differentiated thyroid cancer. An extensive mediastinal dissection in advanced differentiated thyroid carcinoma is occasionally required. This paper will review recent reports of management of advanced nodal metastasis of thyroid cancer and share the author's personal experience.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3891-3895
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• 2013

The purpose of this study was to evaluate the association of expression of ${\alpha}5{\beta}1$-integrin with clinicopathologic features and prognosis in cervical cancer. Levels of ${\alpha}5{\beta}1$-integrin in normal cervical mucosa and cervical cancer tissue were detected with immunohistochemistry. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. ${\alpha}5{\beta}1$-integrin expression was detected in 84.6% (143/169) cervical cancer samples, significantly different from that in normal cervical mucosa (P < 0.05). Positive expression rates of ${\alpha}5{\beta}1$-integrin in patients with poor histologic differentiation, lymph node metastasis, and recurrence were elevated. Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expression of ${\alpha}5{\beta}1$-integrin revealed a highly significant difference in human cervical cancer cases (P < 0.05), suggesting that overexpression of ${\alpha}5{\beta}1$-integrin is associated with a worse prognosis.The ${\alpha}5{\beta}1$-integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of cervical cancer. The current study indicated that ${\alpha}5{\beta}1$-integrin may be an independent prognostic factor for cervical cancer patients.

• Journal of the Optical Society of Korea
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• 제15권2호
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• pp.155-160
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• 2011

Lymph node metastasis is an important prognostic factor in cervical cancer patients. We report THz imaging for detecting micro-metastatic foci in the lymph nodes of early-stage uterine cervical cancer patients. Five paraffin-embedded metastatic lymph nodes from two cervical cancer patients were imaged using a THz time-domain spectroscopy system in the reflection mode. The size and shape of the tumor regions were compared with those from histopathologic examinations. The metastatic portions of lymph nodes as small as 3 mm were well delineated by THz imaging. The reflected peak amplitudes were lower in metastatic portions than in the normal portions of lymph nodes, and the difference in their peak-to-peak amplitudes was ~5%.

• 대한기관식도과학회지
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• 제6권2호
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• pp.147-151
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• 2000

Background and Objectives： Metastasis to the submental and submandibular lymph nodes rarely occurs in squamous cell carcinoma of the larynx and hypopharynx. The aim of this study is to evaluate the effectiveness of level I neck dissection in squamous cell carcinoma of larynx and hypopharynx. Materials and Methods : Forty-three patients with pathologically positive cervical nodal involvement in squamous cell carcinoma of larynx and hypopharynx treated between 1989 to 1998 were reviewed. Fifteen patients were treated with neck dissection including level 1,28 patients were treated with neck dissection excluding the level 1. Results : The regional recurrence at the level I in patients treated with neck dissection excluding the level I, was shown in only one case (recurrence rate 3.6%), but this patient was efficiently managed with salvage operation and adjuvant radiotherapy. No recurrence was shown in patients treated with neck dissection including the level I. So, total recurrence rate at the level I was 2.3%. Conclusion : This study suggests that dissection of the level I is not justified in squamous cell carcinoma of larynx and hypopharynx even if metastasis to cervical lymph node was confirmed preoperatively (cN+).

• BMB Reports
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• 제48권6호
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• pp.330-335
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• 2015

Apoptosis inhibitor 5 (API5) has recently been identified as a tumor metastasis-regulating gene in cervical cancer cells.However, the precise mechanism of action for API5 is poorly understood. Here, we show that API5 increases the metastatic capacity of cervical cancer cells in vitro and in vivo via up-regulation of MMP-9. Interestingly, API5-mediated metastasis was strongly dependent on the Erk signaling pathway. Conversely, knock-down of API5 via siRNA technology decreased the level of phospho-Erk, the activity of the MMPs, in vitro invasion, and in vivo pulmonary metastasis. Moreover, the Erk-mediated metastatic action was abolished by the mutation of leucine into arginine within the heptad leucine repeat region, which affects protein-protein interactions. Thus, API5 increases the metastatic capacity of tumor cells by up-regulating MMP levels via activation of the Erk signaling pathway. [BMB Reports 2015; 48(6): 330-335]