• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.2
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• pp.164-173
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• 2000

The p16 protein is a cyclin dependent kinase inhibitor that inhibits cell cycle progression from $G_1$ phase to S phase in cell cycle. Many p16 gene mutations have been noted in many cancer-cell lines and in some primary cancers, and alterations of p16 gene function by DNA methylation have been noticed in various kinds of cancer tissues and cell-lines. There have been a large body of literature has accumulated indicating that abnormal patterns of DNA methylation (both hypomethylation and hypermethylation) occur in a wide variety of human neoplasma and that these aberrations of DNA methylation may play an important epigenetic role in the development and progression of neoplasia. DNA methylation is a part of the inheritable epigenetic system that influences expression or silencing of genes necessary for normal differentiation and proliferation. Gene activity may be silenced by methylation of up steream regulatory regions. Reactivation is associated with demethylation. Although evidence or a high incidence of p16 alterations in a variety of cell lines and primary tumors has been reported, that has been contested by other investigators. The precise mechanisms by which abnormal methylation might contribute to carcinogenesis are still not fully elucidated, but conceivably could involve the modulation of oncogene and other important regulatory gene expression, in addition to creating areas of genetic instability, thus predisposing to mutational events causing neoplasia. There have been many variable results of studies of head and neck squamous cell carcinoma(HNSCC). This investigation was studied on 13 primary HNSCC for p16 gene status by protein expression in immunohistochemistry, and DNA genetic/epigenetic analyzed to determine the incidence, the mechanisms, and the potential biological significance of its Inactivation. As methylation detection method of p16 gene, the methylation specific PCR(MSP) is sensitive and specific for methylation of any block of CpG sites in a CpG islands using bisulfite-modified DNA. The genomic DNA is modified by treatment with sodium bisulfate, which converts all unmethylated cytosines to uracil(thymidine). The primers designed for MSP were chosen for regions containing frequent cytosines (to distinguish unmodified from modified DNA), and CpG pairs near the 5' end of the primers (to provide maximal discrimination in the PCR between methylated and unmethylated DNA). The two strands of DNA are no longer complementary after bisulfite treatment, primers can be designed for either modified strand. In this study, 13 paraffin embedded block tissues were used, so the fragment of DNA to be amplified was intentionally small, to allow the assessment of methylation pattern in a limited region and to facilitate the application of this technique to samlples. In this 13 primary HNSCC tissues, there was no methylation of p16 promoter gene (detected by MSP and automatic sequencing). The p16 protein-specific immunohistochemical staining was performed on 13 paraffin embedded primary HNSCC tissue samples. Twelve cases among the 13 showed altered expression of p16 proteins (negative expression). In this study, The author suggested that low expression of p16 protein may play an important role in human HNSCC, and this study suggested that many kinds of genetic mechanisms including DNA methylation may play the role in carcinogenesis.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.225-231
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• 1997

Purpose : Radiation therapy in combination with surgery has an important role in the therapy of the head and neck cancer We conducted a prospective study for patients with head and neck cancer treated with surgery and radiation to evaluate the effect of therapies on the thyroid gland, and to identify the factors that might influence the development of hypothyroidism. Materials and Methods : From September 1986 through December 1994, 71 patients with head and cancer treated with surgery and radiation were included in this prospective study. Patients' age ranged from 32 to 73 years with a median age of 58 years. There were 12 women and 59 men. The primary tumor sites were larynx in 34 patients, hypopharynx in 13 patients, oral cavity in 12 patients, unknown primary of the neck in 6 patients, salivary gland in 3 patients, maxillary sinus in 2 patients, and oropharynx in 1 patient. Total laryngectomy with neck dissection was carried out in 45 patients and neck dissection alone in 26 patients. All patients were serially monitored for thyroid function (T3, T4, free T4, TSH, antithyroglobulin antibody and antimicrosomal antibody) before and after radiation therapy. Radiation dose to the thyroid gland ranged from 40.6Gy to 60Gy with a median dose of 50Gy The follow-up duration was 3 to 80 months. Results :The overall incidence of hypothyroidism was 56.3\%$);7 out of 71 patients $(9.9\%)$ developed clinical hypothyroidism and 33 patients $(46.4\%)$ developed subclinical hypothyroidism. No thyroid nodules, thyroid cancers, or hyperthyroidism was detected. Hypothyroidism developed earlier in patients who underwent total laryngectomy with neck dissection than in patients with neck dissection alone (P<0.05). The risk factor that significantly influenced the incidence of hypothyroidism was a combination of surgery (total laryngectomy with neck dissection) and radiation therapy (P=0.0000), Four of 26 patients $(15.4\%)$ with neck dissection alone developed hypothyroidism while 36 of 45 patients $(80\%)$ with laryngectomy and neck dissection developed hypothyroidism. Conclusion : The hypothyroidism following surgery and radiation therapy was a relatively common complication. The factor that significantly influenced theincidence of hypothyroidism was combination of surgery and radiation therapy. Evaluation of thyroid function before and after radiation therapy with periodic thyroid function tests is recommended for an early detection of hypothyroidism and thyroid hormone replacement therapy is recommended whenever hypothyroidism develops.

• Microbiology and Biotechnology Letters
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• v.35 no.2
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• pp.158-162
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• 2007

Methicillin-resistant Staphylococcus aureus (MRSA) is one of a major nosocomial pathogen worldwide and the emergence of this strain has become a major clinical problem. This study was performed for 13 hospitals with more than 400 beds in the country by collecting samples including hands and nasal cavities of doctors, nurses, guardians and patients. Also, additional 320 samples of hands and nasal cavities of 160 community resident in different locations and regions were collected. In all of medical environments and community resident, 625 strains of S. aureus were detected. Among 625 strains of S. aureus, 585 strains(93.6%) showed the resistance to at least one kind of antimicrobial and 112 strains (17.9%) showed multi-drug resistance with the resistance to 4 different types of antimicrobial. Total 152 MRSA strains (24.3%) were isolated from medical environment and community resident. In nasal cavity and hand, 49 MRSA (19.4%) and 103 (27.6%) MRSA were isolated, respectively Minimum inhibitory concentration(MIC) test is used to measure for susceptibility of MRSA isolated to oxacillin. At a concentration $16{\mu}g/ml$ of oxacillin, 11 strains were inhibited. 32 strains at $32{\mu}g/ml$, 41 strains at $64{\mu}g/ml$, 3 strains at $128{\mu}g/ml$, 25 stains at $256{\mu}g/ml$ and 40 strains at over $256{\mu}g/ml$ were inhibited. It was considered that medical environment showed higher than livestock and marine environments in MRSA detection rate.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.64-70
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• 2010

Purpose: The aim of the present study was to retrospectively evaluate the incidence of hypothyroidism in locally advanced head and neck cancer patients who received radiotherapy (RT) either with or without neck dissection. Materials and Methods: From January 2000 to December 2005, 115 patients with locally advanced head and neck cancer and who received definitive RT or postoperative RT including standard anterior low-neck field were recruited to be part of this study. Nineteen patients had undergone ipsilateral neck dissection, whereas, 18 patients underwent bilateral neck dissection, and 78 patients were received RT alone. Patients' ages ranged from 28 to 85 years (median, 59 years) and there were a total of 73 male and 42 female patients. The primary tumor sites were the oral cavity, oropharynx, hypopharynx, larynx, and other sites in 18, 40, 28, 22 and 7 patients, respectively. Radiation dose to the thyroid gland ranged from 44 Gy to 66 Gy with a median dose of 50 Gy. Follow-up time ranged from 2 to 91 months, with a median of 29 months. Results: The 1- and 3- year incidence of hypothyroidism was 28.7% (33 patients) and 33.0% (38 patients), respectively. The median time to detection of hypothyroidism was 8.5 months (range, 0 to 36 months). A univariate analysis revealed that neck node dissection was a risk factor for hypothyroidism (p=0.037). However, no factor was statistically significant from the results of a multivariate analysis. Conclusion: Patients treated for advanced head and neck cancer with radiotherapy with or without neck dissection will develop hypothyroidism. It is important to check the thyroid function periodically in these patientsespecially with the risk factor of neck node dissection.