• 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.23 no.3
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• pp.176-185
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• 2005

Purpose: Film dosimetry as a part of patient specific intensity modulated radiation therapy quality assurance (IMRT QA) was peformed to develop a new optimization method of film isocenter offset and to then suggest new quantitative criteria for film dosimetry. Materials and Methods: Film dosimetry was peformed on 14 IMRT patients with head and neck cancers. An optimization method for obtaining the local minimum was developed to adjust for the error in the film isocenter offset, which is the largest part of the systemic errors. Results: The adjust value of the film isocenter offset under optimization was 1 mm in 12 patients, while only two patients showed 2 mm translation. The means of absolute average dose difference before and after optimization were 2.36 and $1.56\%$, respectively, and the mean ratios over a $5\%$ tolerance were 9.67 and $2.88\%$. After optimization, the differences in the dose decreased dramatically. A low dose range cutoff (L-Cutoff) has been suggested for clinical application. New quantitative criteria of a ratio of over a $5\%$, but less than $10\%$ tolerance, and for an absolute average dose difference less than $3\%$ have been suggested for the verification of film dosimetry. Conclusion: The new optimization method was effective in adjusting for the film dosimetry error, and the newly quantitative criteria suggested in this research are believed to be sufficiently accurate and clinically useful.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.189-193
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• 2009

Purpose: To report on the changes in the patterns of care and survival over time for esthesioneuroblastoma. Materials and Methods: We retrospectively analyzed 42 previously untreated and histologically confirmed esthesioneuroblastoma patients seen between March 1989 and June 2007. According to Kadish's classification, 3 patients (7%) were stage A, 6 (14%) at stage B, and 33 (79%) at stage C. Of the 33 Kadish C patients, 19 and 14 patients were treated from 1989 through 2000 and from 2001 through 2007, respectively. Treatment included surgical resection, radiotherapy, chemotherapy, or a combination of these methods. Chemotherapy was administered to 8 of 19 patients (42%) seen from 1989 through 2000, whereas all of the 14 patients seen from 2001 through 2007 received chemotherapy (p<0.001). No patient was treated by three-dimensional conformal radiotherapy (3D-CRT) from 1989 through 2000, however 8 of 14 patients (67%) seen from 2001 through 2007 underwent 3D-CRT (p<0.001). The median follow-up time for surviving patients was 6.5 years (range, 2.2~15.8 years). Results: The 5-year overall survival (OS) and progression-free survival (PFS) rates for the entire cohort were 53% and 39%, respectively. The 5-year OS was 100% for Kadish stages A or B and 39% for stage C (p=0.007). For patients with stage C disease who were treated from 1989 to 2000 and from 2001 to 2007, the 5-year OS rate was 26% and 59% (p=0.029), respectively and the corresponding 5-year PFS rate was 16% and 46% (p=0.001), respectively. Intraorbital extension and treatment era (1989~2000 vs. 2001~2007) were found as independent factors for OS and PFS in a multivariate analyses. Conclusion: The results of this study suggest that treatment era, which features a distinction in treatment modality and technique with the introduction of 3D-CRT, may be the cause of improved OS and PFS in Kadish stage C patients. To achieve better outcomes for patients with Kadish stage C, combined chemoradiotherapy, especially 3D-CRT, is recommended in addition to surgery.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.526-534
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• 2009

Purpose: We retrospectively investigated the diagnostic performance of $^{18}F$-fluorodeoxyglucose positron emission tomography (PET) and PET/CT for cancer detection in asymptomatic health-check examinees. Materials and Methods: This study consisted of 5091 PET or PET/CT conducted as part of annual health examination at one hospital from March 1998 to February 2008. To find the incidence of cancers, medical records of the subjects were thoroughly reviewed for a follow-up period of one year. The patterns of formal readings of PET and PET/CT were analyzed to assess the sensitivity and specificity for cancer detection. The histopathology and stage of the cancers were evaluated in relation to the results of PET. Results: Eighty-six cancers (1.7%) were diagnosed within one year after PET or PET/CT. When PET and PET/CT results were combined, the sensitivity was 48.8% and specificity was 81.1% for cancer detection. PET only had a sensitivity of 46.2% and a specificity of 81.4%, and PET/CT only had a sensitivity of 75.0% and a specificity of 78.5% respectively. There were no significant differences in cancer site, stage and histopathology between PET positive and PET negative cancers. In 19.3% of formal readings of PET and PET/CT, further evaluation to exclude malignancy or significant disease was recommended. Head and neck area and upper gastrointestinal tract were commonly recommended sites for further evaluation. Conclusions: PET and PET/CT showed moderate performance for detecting cancers in asymptomatic adults in this study. More experience and further investigation are needed to overcome limitations of PET and PET/CT for cancer screening.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.760-765
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• 1998

Background: Glucose uptake has been found to be increased in cancer cells, and FDG-PET imaging is used for diagnosis of cancer using this phenomenon. However, the exact mechanism of increased glucose uptake in cancer cells has not been clarified. Recent studies demonstrated the presence of glucose transporter(GLUT) mRNA expression in gastrointestinal cancer and head and neck cancer, and suggested that GLUT may be associated with glucose uptake in cancer cells. In lung cancer cells, glucose metabolism is also known to be increased. We evaluated GLUT mRNA expression in human lung cancer cell lines in order to find out the mechanism of increased glucose uptake in lung cancer. Method: Total RNA was isolated from 15 human lung cancer cell lines and immortalized bronchial epithelial cell line(BEAS-2B). After electrophoresis of $20{\mu}g$ total RNA, Northern blot analysis was done using GLUT1 cDNA and GLUT3 cDNA as probes. Results: Thirteen of 14 human lung cancer cell lines expressed GLUT1 mRNA and 10 of 14 human lung cancer cell lines expressed GLUT3 mRNA. Eight human lung cancer cell lines expressed both GLUT mRNAs. BEAS-2B expressed GLUT1 mRNA and did not express detectable GLUT3 mRNA. Conclusion: The increase of glucose metabolism in lung cancer may be associated with GLUT1 and GLUT3 expression.

• Journal of Life Science
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• v.21 no.3
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• pp.412-416
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• 2011

Taste sensation plays a crucial role in selecting and ingesting foods with different qualities which convey information about their nutrient content and/or safety. Sweetness is one of the five modalities in humans and serves as an energy resource for metabolism. There are reports on allelic polymorphisms which influence perception of sweetness in mice and humans. Since the influence of genetic factors on taste disorder has not been studied, we investigated the association of genetic polymorphisms in TAS1R3 and guanine nucleotide binding protein, alpha transducing 3 (GNAT3) genes and taste disorder. A total of 150 individuals composed of 50 patients with taste disorder and 100 healthy controls were recruited for the study and PCR-mediated directing sequencing method was used to genotype for two different single nucleotide polymorphisms (SNPs) - rs307355 (T>C) and rs35744813 (T>C) in the TAS1R3 gene, and rs7792845 (T>C) and rs1524600 (C>T) in the the GNAT3 gene. The allele and genotype frequencies of rs307355 and rs35744813 in the TAS1R3 gene showed a significant association between patients with taste disorder (p=0.022 and p=0.013 in both of SNPs, respectively). In addition, the frequency of T-T haplotype in the TAS1R3 gene was higher in taste disorder cases than in the controls (OR, 1.93: 95%. CI, 1.09-3.39, p=0.022). In the GNAT3, the genotype frequency of rs7792845 in the patients was also different from the controls (p=0.048), but allele frequency was not significantly associated in either group. Our result provides the frequencies of SNPs and haplotypes of the TAS1R3 and GNAT3 genes for the fundamental information of nutrigenetics in perception of the taste of sweetness in the Korean population. Also, the study suggests that the allelic polymorphisms of TAS1R3 and GNAT3 genes may be useful as a molecular marker for evaluating patients with taste disorder. Further studies with large samples are required to clarify our observation.

• The Journal of Korean Society for Radiation Therapy
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• v.30 no.1_2
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• pp.117-128
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• 2018

Purpose : To evaluate the usability of plan transfer between TOMO HD and Radixact, we compared the differences of dose in transferred plans by evaluating the dose of normal organ and target. TOMO HDA and Radixact. The completed plans were transferred each other and we compared the differences of dose by evaluating the DVH of each plans. Materials and Methods : We planned 4 different plans assuming the treatment of 2 cases in Head and Neck Cancer and 2 cases Prostate cancer. Each plan was designed so that 95 % of the prescription dose was irradiated over 99 % of the target volume, and the normal organ constraints dose was based on the SMC tolerance dose protocol. Each plan was transferred to each equipment and DVH(dose volume histogram) analysis of the transferred plans was compared and evaluated. Results : The Mean dose of CTV and GTV was increased and decreased in the transferred plans, but there was no significant differences. The target coverage of CTV and GTV was decreased in all cases of transferred plans from TOMO HAD to Radixact, and the change of CI and HI in CTV was within 0.1. Normal organ dose was increased in most cases when transferring from HAD to Radixact in both treatment plans. Conclusion : According to the results of this experiment, the target coverage was above the standard and the normal organ dose was almost same or decreased when transferring the plans from Radixact to HDA equipment. However the target coverage was reduced when transferring the plans from HDA to Radixact and there was an increase in dose in normal organs that could cause sever side effects such as Optic Chiasm ($D_{max}$1.38 Gy), Bladder ($D_{max}$3.07 Gy), Penile Bulb ($D_{max}$1.14 Gy). Therefore, it is necessary to pay attention to the dose change when transferring the plan and one-time transfer due to equipment inspection will be useful for efficient radiation therapy, but if the transferred treatment plans continue for several consecutive days, the treatment plan should be resumed.

• Phonetics and Speech Sciences
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• v.11 no.3
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• pp.69-76
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• 2019

This study aimed to investigate the effects of vocal aerobic treatment (VAT) on the improvement of voice in patients with voice disorders. Twenty patients (13 males, 7 females) were diagnosed with voice disorders on the basis of videostroboscopy and voice evaluations. Acoustic evaluation was performed with the Multidimensional voice program (MDVP) and Voice Range Profile (VRP) of Computerized Speech Lab (CSL), and aerodynamic evaluation with PAS (Phonatory Aerodynamic System). The changes in F0, Jitter, Shimmer, and NHR before and after treatment were measured by MDVP. F0 range and Energy range were measured with VRP before and after treatment, and the changes in Expiratory Volume (FVC), Phonation Time (PHOT), Mean Expiratory Airflow (MEAF), Mean Peak Air Pressure (MPAP), and Aerodynamic Efficiency (AEFF) with PAS. Videostroboscopy was performed to evaluate the regularity, symmetry, mucosal wave, and amplitude changes of both vocal cords before and after treatment. Voice therapy was performed once a week for each patient using the VAT program in a holistic voice therapy approach. The average number of treatments per patient was 6.5. In the MDVP, Jitter, Shimmer, and NHR showed statistically significant decreases (p < .001, p < .01, p < .05). VRP results showed that Hz and semitones in the frequency range improved significantly after treatment (p < .01, p < .05), as did PAS, FVC, and PHOT (p < .01, p < .001). The results for videostroboscopy, functional voice disorder, laryngopharyngeal reflux, and benign vocal fold lesions were normal. Thus, the VAT program was found to be effective in improving the acoustic and aerodynamic aspects of the voice of patients with voice disorders. In future studies, the effect of VAT on the same group of voice disorders should be studied. It is also necessary to investigate subjective voice improvement and objective voice improvement. Furthermore, it is necessary to examine the effects of VAT in professional voice users.

• Korean Journal of Optics and Photonics
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• v.31 no.1
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• pp.1-6
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• 2020

The chest wall, an organ directly affected by environmental particles through respiration, consists of ribs, a pleural layer and intercostal muscles. To diagnose early and treat disease in this body part, it is important to visualize the details of the chest wall, but the structure of the pleural layer cannot be seen by chest computed tomography or ultrasound. On the other hand, optical coherence tomography (OCT), with a high spatial resolution, is suited to observe pleural-layer response to talc, one of the fine materials. However, intensity-based OCT is weak in providing information to distinguish the detailed structure of the chest wall, and cannot distinguish the reaction of the pleural layer from the change in the muscle by the talc. Polarization-sensitive OCT (PS-OCT) takes advantage of the fact that specific tissues like muscle, which have optical birefringence, change the backscattered light's polarization state. Moreover, the birefringence of muscle associated with the arrangement of myofilaments indicates the muscle's condition, by measuring retardation change. The PS-OCT image is interpreted from three major perspectives for talc-exposure chest-wall imaging: a thickened pleural layer, a separation between pleural layer and muscle, and a phase-retardation measurement around lesions. In this paper, a rabbit chest wall after talc pleurodesis is investigated by PS-OCT. The PS-OCT images visualize the pleural layer and muscle, respectively, and this system shows different birefringence of normal and damaged lesions. Also, an analyisis based on phase-retardation slope supports results from the PS-OCT image and histology.

• The Journal of Korean Society for Radiation Therapy
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• v.34
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• pp.7-12
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• 2022

Purpose: When it is difficult to secure the skin dose when treating Irregularly Shaped Skin Surface such as the nose where it is difficult to apply a bolus, increase the skin dose with a treatment plan that combines the IMRT (Intensity Modulated Radiation Therapy) delivery technique and FFF (Flattening Filter Free), It was tried to find out whether or not through the phantom experiment. Materials & Methods: Based on the 6MV-FF (Flattening Filter) and VMAT (Volumetric-Modulated Arc Therapy) treatment plans, which are the most commonly used treatment plans for head and neck cancer, A comparison group was created by combining VMAT and IMRT, FF and FFF, and the presence or absence of 5 mm bolus application. A virtual target was created on the Rando Phantom's nose, and a virtual bolus of 5 mm was applied assuming full contact on the Rando Phantom's nose. Five measurement points were determined based on the phantom's nose, and the absorbed dose was measured by irradiating each treatment plan 3 times per treatment plan according to the treatment technique and whether or not the bolus was applied. Result: The difference in skin dose in FF vs FFF increased in the case of FFF in VMAT bolus off, and there was no difference in case of IMRT bolus off. In VMAT bolus 5 mm and IMRT bolus 5 mm, it was confirmed that the skin dose was rather decreased in FFF. The difference in skin dose between VMAT and IMRT increased only in the case of FFF bolus off, and there was no statistical difference in the rest. For the difference in skin dose between bolus off vs bolus 5 mm, it was confirmed that the skin dose increased at bolus 5 mm, except for the case of using IMRT FFF. The treatment plan combining IMRT and FFF did not find any statistically significant difference as a result of analyzing the measured values of the treatment plan skin dose applied with a 5 mm bolus using the commonly used VMAT and FF. Therefore, it is thought that by using IMRT_FFF, it is possible to deliver a skin dose similar to that of applying a 5 mm bolus to VMAT_FF, which can be useful for patients who need a high skin dose but have difficulty applying a bolus. Conclusion: For patients who find it difficult to apply bolus, an increase in skin dose can be expected with a treatment plan that properly combines IMRT and FFF compared to VMAT and FF.