• BMB Reports
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• 제51권11호
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• pp.584-589
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• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• 대한두경부종양학회지
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• 제19권2호
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• pp.148-157
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• 2003

Background and Objectives: Individual genetic susceptibilities to chemical carcinogens have been recognized as a major important host factors in human cancers. The cytochrome P450 family (CYPs) and glutathione S-transferase(GST) have been reported to be associated with risks to the smoking-related human cancers. Inactivation of tumor suppressor genes like p53 playa key role in tumor progression. The purpose of this study is to demonstrate an association between p53 overexpression and the prevalence of the genetic polymorphisms of CYP1A1 and GSTs in Korean head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The polymorphisms of CYPIA1 and GSTs were analyzed by PCR and PCR-RFLP in 98 Korean head and neck squamous cell carcinoma patients. The expression of p53 was analyzed by immunohistochemistry with anti-p53 Ab (DO7). Results: Overexpression of p53 detected in 45.9% of HNSCC. The odds ratio for p53 overexpression in GSTM1(-), GSTT1(-), GSTP1(val/val) and CYP1A1(val/val) were 1.53, 1.83, 1.17 and 1.47, respectively. Among the combined genotypes, the odds ratio of the CYP1A1 val/val, GSTM1 (-), CYP1A1 val/val, GSTT1(-), and CYP1A1 val/val, GSTT1(-) were 2.0, 2.34 and 4.68, respectively. Conclusion: Based on our results, it might be suggested that p53 overexpression is slightly increased in GSTM1(-), GSTT1(-), GSTP1 val/val, CYP1A1 val/val genotypes. The further study is needed to evaluate the relationship and mechanism between the p53 overexpression and the specific CYP1A1 and GSTs genotypes.

• 대한기관식도과학회지
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• 제8권1호
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• pp.35-41
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• 2002

Background and Objectives : Angiogenesis within malignant tumors has been considered to be essential for the growth and expansion of cancer cells, especially for solid tumors, and has been implicated in the overall growth and metastases of tumors. Such angiogenesis within tumors depends upon the secretion of vascular growth factor to allow the growth of newly formed vessels from peripheral tissue into the malignant tumor. %n, an exploration of the relations between cancer cells and vascular growth factors is absolutely critical to understanding the growth of malignant tumors. According to recent reports, vascular endothelial growth factor(VEGF) has been found to play a role in lymphatic metastases, tumor recurrence and survival in various human tumors. To evaluate the role of VEGF in head and neck squamous cell carcinoma(HNSCC) we performed this study. Materials and Methods : We examined the expression of VEGF and microvessel density in 39 HNSCC by immunohistochemistry and correlated them with various clinical data such as stage, cervical lymphatic metastasis, recurrence, and overall survival. Results : The expression of VEGF was not correlated with overall stage, T stage and N stage. There was no statistical correlation between the expression of VEGF and recurrence in the Primary site, cervical lymph node, and the distant metastases. There was no statistical correlation between the expression of VEGF and microvessel density. Conclusion : Based on these results, it is suggested that the expression of vascular endothelial growth factor is not a major prognostic factor for head and neck squamous cell carcinoma. Further studies are needed to evaluate significance of VEGF expression in head and neck squamous cell carcinoma.

• 대한두경부종양학회지
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• 제31권2호
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• pp.86-90
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• 2015

Cystic lymph node metastasis of head and neck squamous cell carcinoma(HNSCC) which presumed to be mainly originated from oropharynx including Waldeyer's ring may present as a benign cystic mass on lateral neck such as branchial cleft cyst. Branchial cleft cyst is one of the most common lateral neck cystic mass which may result in regional infection or lymph adenopathy. Many of previously reported literatures showed the incidence of cystic lymph node metastasis from oropharynx including Waldeyer's ring. Preoperative imaging studies and fine needle aspiration cytology cannot provide the accurate results until excision of cystic mass for the diagnostic or therapeutic purpose. Recently, we experienced the rare case of cystic lymph node metastasis from ipsilateral tonsil, which mimicked infected 2nd branchial cleft cyst. Thus, we reported our experience with presentation of case and review of literatures.

• 대한후두음성언어의학회지
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• 제29권2호
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• pp.67-69
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• 2018

The development of office-based, unsedated transnasal esophagoscopy (TNE) has proven to be a major technological advance and with time and experience the application of this technology is becoming more widespread. TNE has allowed otolaryngologists to perform a variety of diagnostic and therapeutic procedures in the office setting. Studies consistently demonstrate that the image quality and diagnostic capability of TNE is equivalent to conventional esophagoscopy. The modern TNE endoscopes offer high quality optics, air-insufflation, and irrigation capability through a 2-mm working channel, and the ability to perform biopsies and select procedures. In general, the role of TNE in the head and neck patient is three-fold : to screen for synchronous and metachronous esophageal squamous cell carcinoma (ESCC) ; to differentiate post-treatment changes/symptoms from malignancy ; and to perform certain office-based procedures. TNE offers many specific advantages to the head and neck patient that are not afforded by conventional esophagoscopy. Because of surgical and postirradiation changes, many HNSCC patients have trismus or neck stiffness preventing completion of conventional transoral esophagoscopy. Perhaps most importantly, TNE provides enhanced patient safety, increased tolerability, better practice efficiency, and cost savings. For these reasons, TNE has become a particularly useful tool in the otolaryngologist's armamentarium.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2023년도 임시총회 및 춘계학술대회
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• pp.18-18
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• 2023

Two new phenanthrenes, namely, (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene-4(1H)-one (1) and 2,7-dihydroxyphenanthrene-1,4-dione (2), were isolated from the ethyl acetate-soluble fraction of Dendrobii Herba, together with the eleven known compounds, densiflorol B (3), 6,7-dimethoxyphenanthrene2,5-diol (4), dehydroorchinol (5), 1,5,7-trimethoxy-2-phenanthrenol (6), denthyrsinin (7), ephemerantol A (8), lusianthridin (9), moscatilin (10), gigantol (11), 3-[(1E)-2-(3-hydroxyphenyl)ethenyl]-5-methoxyphenol (12) and (-)-syringaresinol (13). Structures of 1 and 2 were elucidated by analyzing 1D and 2D NMR as well as HR-ESI-MS data. The absolute configuration of compound 1 was confirmed by ECD spectroscopic method. In cytotoxicity evaluation using FaDu human hypopharyngeal squamous carcinoma cell line, compounds 3-6, 8, 10 and 12 showed activities, with IC₅₀ values ranging from 2.55 to 17.70 μM. Among them, compound 10 exhibited remarkable cytotoxic activity with IC₅₀ value of 2.55 μM. This is the first report on the anticancer mechanistic study of compound 10 in HNSCC including FaDu cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7603-7609
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• 2014

Glutathione is a thiol compound that plays an important role in the antioxidant defense system of the cell and its deficiency leads to an increased susceptibility to oxidative stress and, thus, progression of many disease states including head and neck cancer. In the present study, alterations of glutathione levels were investigated in study cohort of 500 samples (cohort 1 containing 200 head and neck cancer blood samples along with 200 healthy controls and cohort II with 50 head and neck squamous cell carcinoma tissue samples along with 50 control tissues) by high performance liquid chromatography. The results indicated that mean blood glutathione levels were significantly reduced in head and neck cancer patients (p<0.001) compared to respective controls. In contrast, the levels of glutathione total (p<0.05) and glutathione reduced (p<0.05) were significantly elevated in head and neck squamous cell carcinoma tissues compared to the adjacent cancer-free control tissues. In addition to this, pearson correlation performed to correlate different tissue glutathione levels (GSH) with clinical/pathological parameters demonstrated a significant negative correlation between pT-stage and GSH level ($r=-0.263^{**}$; p<0.01), C-stage and GSH level ($r=-0.335^{**}$; p<0.01), grade and GSH ($r=-0.329^{**}$; p<0.01) and grade versus redox index ($r=-0.213^{**}$; p<0.01) in HNSCC tissues. Our study suggests that dysregulation of glutathione levels in head and neck cancer has the potential to predict metastasis, and may serve as a prognostic marker.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6419-6425
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• 2013

Background: Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. Materials and Methods: Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. Results: Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. Conclusions: Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.

• Molecules and Cells
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• 제38권2호
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• pp.112-121
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• 2015

Ectopic expression of $14-3-3{\zeta}$ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of $14-3-3{\zeta}$ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how $14-3-3{\zeta}$ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that $14-3-3{\zeta}$ is overexpressed. In OSCC cells, $14-3-3{\zeta}$ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, $14-3-3{\zeta}$ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-${\gamma}$ (IFN-${\gamma}$) and lipopolysaccharide (LPS). Furthermore, supernatants from $14-3-3{\zeta}$ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with $14-3-3{\zeta}$ and its disruption relieved the inhibition induced by $14-3-3{\zeta}$ in tumor inflammation. Taken together, our studies provide evidence that $14-3-3{\zeta}$ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.610-620
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• 2021

There has been increasing interest in the head and neck squamous cell carcinoma (HNSCC) that is caused by high-risk human papillomavirus (HR-HPV) and has posed a significant challenge to Otolaryngologists. A rapid, sensitive, and reliable method is required for the detection of HR-HPV in clinical specimens to prevent and treat HPV-induced diseases. In this study, a multiple cross-linking spiral amplification (MCLSA) assay was developed for the visual detection of HPV-16. In the MCLSA assay, samples were incubated under optimized conditions at 62℃ for 45 min, and after mixing with the SYBR Green I (SGI) dye, the positive amplicons showed bright green fluorescence while the negative amplicons exhibited no obvious change. The specificity test revealed that the developed MCLSA technique had high specificity and could effectively distinguish all five HPV-16 strains from other pathogenic microorganisms. In terms of analytical sensitivity, the limit of detection (LoD) of MCLSA assay was approximately 5.4 × 101 copies/tube, which was 10-fold more sensitive than loop-mediated isothermal amplification (LAMP) and RT-PCR. The detection results of laryngeal cancer specimens collected from 46 patients with suspected HPV infection in the Liaoning region demonstrated that the positive detection rates of MCLSA and hybridized capture 2 kit were 32.61% (15/46). The true positive rate of the MCLSA assay was higher than that of RT-PCR (100% vs. 93.33%) and LAMP (100% vs. 86.67%). Therefore, the MCLSA assay developed in the present study could be a potentially useful tool for the point-of-care (PoC) diagnosis of HR-HPV, especially in resource-limited countries.