• Imaging Science in Dentistry
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• v.31 no.3
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• pp.135-143
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• 2001

Purpose : To evaluate the effect of all-trans-retinoic acid on radiosensitivity and radiation-induced apoptosis in NHOK, HEp-2 and FaDu cell lines. Material and Methods: We measured the changes in survival fraction at 2 Gy (SF2), α and β after treatment of retinoic acid (1μM) prior to irradiation with doses of 2, 4, 6 and 10 Gy and correlated the radiosensitizing effect of retinoic acid with them. Also, apoptosis induction was assayed with the flow cytometry on days 1,2, 3, 4 and 5 after irradiation (2, 10 and 20 Gy) combined with retinoic acid. Results and Conclusion: SF2 values for NHOK, HEp-2 and FaDu cell lines were 0.54, 0.64 and 0.41, respectively and the cell line of FaDu was the most radiosensitive. For cell lines of NHOK and HEp-2, pretreatment of cells with retinoic acid resulted in a significant decrease of the SF2 values. The α/β ratios of x-ray survival curve were 8.714 (NHOK), 4.098 (HEp-2) and 11.79 (FaDu). The α/β ratio for NHOK decreased on pretreatment with retinoic acid, whereas those for HEp-2 and FaDu increased. Radiation induced apoptosis in all cell lines but, retinoic acid did not affect the apoptosis.

• Radiation Oncology Journal
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• v.28 no.1
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• pp.9-15
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• 2010

Purpose: This study was performed to examine the neck failure patterns after a complete response (CR) to definitive radiotherapy for advanced head and neck cancer patients, as well as evaluate the clinical significance of the results of this study. Materials and Methods: Between 1987 and 2008, the clinical data of patients who had been treated with radical radiotherapy for primary squamous cell carcinomas and enlarged cervical lymph nodes was analyzed retrospectively. Ultimately, the cases that showed CR of the cervical lymph node lesions to full-dose radiotherapy were included in this study. The recurrent rate and sites in the cervical lymphatic area were evaluated periodically by radiologic imaging studies, along with some factors which might have affected the rate of recurrence. Results: A total of 73 patients who achieved CR in neck area after radiotherapy were included in this study. The rate of subsequent neck failure among those patients was 19.2%. There was only a 5.5% failure rate in the 55 patients who underwent radiotherapy in their primary site. Eighty percent of the recurrent cases were found within 3 years (median follow-up, 68 months). The majority of neck recurrent cases (47%) were accompanied with the failure of the primary lesions. The initial response of the primary site and the method of radiotherapy simulation were significant prognostic factors associated with the nodal recurrence rate. Conclusion: The recurrence rate of cervical nodes in patients with CR to radiotherapy in the primary site and neck area was about 5%. These patients could be followed up with close observation without a planned neck dissection.

• 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.

• Journal of Life Science
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• v.19 no.6
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• pp.770-780
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• 2009

A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a), was derived from Spirulina platensis. We conducted a series of experiments, in vitro and in vivo, to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-a and 660 nm diode lasers on a squamous carcinoma cell line. We studied the cytotoxic effects of pheophytin-a, 9-HpbD-a, 9-HpbD-a red and 660 nm diode lasers in a human head and neck cancer cell line (SNU-1041). Cell growth inhibition was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of 9-HpbD was higher than those of 9-HpbD-a red or pheophytin-a in PDT. We then tested the cytotoxic effects of 9-hydroxypheophorbide-a (9-HpbD-a) in vitro. The cultured SNU-I041 cells were treated with serial concentrations of 9-HpbD-a followed by various energy doses (0, 0.1, 0.5, 3.2 J/$cm^{2}$) and by various interval times (0, 3, 6, 9, 12 hr) until laser irradiation, then MTT assay was applied to measure the relative inhibitory effects of photodynamic therapy (PDT). Optimal laser irradiation time was 30 minutes and the cytotoxic effects according to incubation time after 9-HpbD-a treatment increased until 6 hours, after which it then showed no increase. To observe the cell death mechanism after PDT, SUN-I041 cells were stained by Hoechst 33342 and propidium iodide after PDT, and observed under transmission electron microscopy (TEM). The principal mechanism of PDT at a low dose of 9-HpbD-a was apoptosis, and at a high dose of 9-HpbD-a it was necrosis. PDT effects were also observed in a xenografted nude mouse model. Group I (no 9-HpbD-a, no laser irradiation) and Group II (9-HpbD-a injection only) showed no response (4/4, 100%), and Group III (laser irradiation only) showed recurrence (1/4,25%) or no response (3/4, 75 %). Group IV (9-HpbD-a + laser irradiation) showed complete response (10/16, 62.5%), recurrence (4/16, 25%) or no response (2/16, 12.5%). Group IV showed a significant remission rate compared to other groups (p<0.05). These results suggest that 9-HpbD-a is a promising photosensitizer for the future and that further studies on biodistribution, toxicity and mechanism of action would be needed to use 9-HpbD-a as a photosensitizer in the clinical setting.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5965-5972
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• 2013

PIN1 is one member of the parvulin PPIase family. By controlling Pro-directed phosphorylation, PIN1 plays an important role in cell transformation and oncogenesis. There are many polymorphisms in the PIN1 gene, including rs2233678 and rs2233679 affecting the PIN1 promoter. Recently, a number of case-control studies were conducted to investigate the association between PIN1 gene rs2233678 and rs2233679 polymorphism and cancer risk. However, published data are still conflicting. In this paper, we summarized data for 5,427 cancer cases and 5,469 controls from 9 studies and attempted to assess the susceptibility of PIN1 gene polymorphism to cancers by a synthetic meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. All analyses were performed using Stata software. Our results suggested that rs2233678 represented a protective factor in overall analysis (CC vs GG: OR= 0.697, 95%CI: 0.498-0.976; CG vs GG: OR=0.701, 95%CI: 0.572-0.858; Dominant model: OR= 0.707, 95%CI: 0.590-0.847; C allele vs G allele: OR=0.734, 95%CI: 0.623-0.867) and especially for squamous cell carcinoma of the head and neck, lung cancer and breast cancer in Asians and Caucasians. The rs2233679 polymorphism was significantly associated with decreased cancer risk in overall analysis (CT vs CC: OR=0.893, 95%CI=0.812-0.981; Dominant model: OR=0.893, 95%CI=0.816-0.976; T allele vs C allele; OR=0.947, 95%CI=0.896-1.000) and especially in Asians. In conclusion, our meta-analysis suggested that -842G>C (rs2233678) and -667C>T (rs2233679) may contribute to genetic susceptibility for cancer risks. Further prospective research with larger numbers of worldwide participants is warranted to draw comprehensive and firm conclusions.

• The Journal of Korean Society for Radiation Therapy
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• v.18 no.1
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• pp.21-28
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• 2006

Purpose: The purpose of this study is to find a optimal beam spoiler condition on the dose distribution near the surface, when treating a squamous cell carcinoma of the head and neck and a lymphatic region with 10 MV photon beam. The use of a optimal spoiler allows elivering high dose to a superficial tumor volume, while maintaining the skin-sparing effect in the area between the surface to the depth of 0.4 cm. Materials and Methods: The lucite beam spoiler, which were a tissue equivalent, were made and placed between the surface and the photon collimators of linear accelerator. The surface-dose, the dose at the depth of 0.4 cm, and the maximum dose at the dmax were measured with a parallel-plate ionization chamber for $5{\times}5cm\;to\;30{\times}30cm^2$ field sizes using lucite spoilers with different thicknesses at varying skin-to-spoiler separation (SSS). In the same condition, the dose was measured with bolus and compared with beam spoiler. Results: The spoiler increased the surface and build-up dose and shifted the depth of maximum dose toward the surface. With a 10 MV x-ray beam and a optimal beam spoiler when treating a patient, a similer build-up dose with a 6 MV photon beam could be achieved, while maintaining a certain amount of skin spring. But it was provided higher surface dose under SSS of less than 5 cm, the spoiler thickness of more than 1.8 cm or more, and larger field size than $20{\times}20cm^2$ provided higher surface dose like bolus and obliterated the spin-sparing effect. the effects of the beam spoiler on beam profile was reduced with increasing depths. Conclusion: The lucite spoiler allowed using of a 10 MV photon beam for the radiation treatment of head and neck caner by yielding secondary scattered electron on the surface. The dose at superficial depth was increased and the depth of maximum dose was moved to near the skin surface. Spoiling the 10 MV x-ray beam resulted in treatment plans that maintained dose homogeneity without the consequence of increased skin reaction or treat volume underdose for regions near the skin surface. In this, the optimal spoiler thickeness of 1.2 cm and 1.8 cm were found at SSS of 7 cm for $10{\times}10cm^2$ field. The surface doses were measured 60% and 64% respectively. In addition, It showed so optimal that 94% and 94% at the depth of 0.4 cm and dmax respectively.

• Korean Journal of Radiology
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• v.22 no.5
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• pp.751-758
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• 2021

Objective: Preoperative differentiation between inverted papilloma (IP) and its malignant transformation to squamous cell carcinoma (IP-SCC) is critical for patient management. We aimed to determine the diagnostic accuracy of conventional imaging features and histogram parameters obtained from whole tumor apparent diffusion coefficient (ADC) values to predict IP-SCC in patients with IP, using decision tree analysis. Materials and Methods: In this retrospective study, we analyzed data generated from the records of 180 consecutive patients with histopathologically diagnosed IP or IP-SCC who underwent head and neck magnetic resonance imaging, including diffusion-weighted imaging and 62 patients were included in the study. To obtain whole tumor ADC values, the region of interest was placed to cover the entire volume of the tumor. Classification and regression tree analyses were performed to determine the most significant predictors of IP-SCC among multiple covariates. The final tree was selected by cross-validation pruning based on minimal error. Results: Of 62 patients with IP, 21 (34%) had IP-SCC. The decision tree analysis revealed that the loss of convoluted cerebriform pattern and the 20th percentile cutoff of ADC were the most significant predictors of IP-SCC. With these decision trees, the sensitivity, specificity, accuracy, and C-statistics were 86% (18 out of 21; 95% confidence interval [CI], 65-95%), 100% (41 out of 41; 95% CI, 91-100%), 95% (59 out of 61; 95% CI, 87-98%), and 0.966 (95% CI, 0.912-1.000), respectively. Conclusion: Decision tree analysis using conventional imaging features and histogram analysis of whole volume ADC could predict IP-SCC in patients with IP with high diagnostic accuracy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2629-2633
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• 2012

Background: Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes. Methods: A panel of dinucelotide polymorphic markers were chosen for loss of heterozygosity studies in 93 samples of which 34 were collected from patients with only RBN-chewing habit. Promoter hypermethylation was also investigated. Results: Loss in microsatellite markers D9S1748 and D9S1749, located close to exon $1{\beta}$ of CDKN2A/ARF gene at 9p21, was noted in 40% ESCC samples with the habit of RBN-chewing alone. Involvement of a novel site in the 9p23 region was also observed. Promoter hypermethylation of CDKN2A gene in the samples with the habit of only RBN-chewing alone was significantly higher (p=0.01) than Rb1 gene, also from the samples having the habit of use both RBN and tobacco (p=0.047). Conclusions: The data indicate that the disruption of 9p21 where CDKN2A gene resides, is the most frequent critical genetic event in RBN-associated carcinogenesis. The involvement of 9p23 as well as 13q14.2 could be required in later stages in RBN-mediated carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4335-4338
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• 2015

Background: Oral cancer is the third most common malignancy in Saudi Arabia, the highest incidence of which is reported from Jazan province. The objective of this study was to evaluate the association of various locally used substances, especially shamma, with oral cancer in the Jazan region of Saudi Arabia. Materials and Methods: A hospital-based case-control study was designed and patient records were scanned for histologically confirmed oral cancer cases. Forty eight patients who were recently diagnosed with oral cancer were selected as cases. Two healthy controls were selected for each observed case and they were matched with age (+/- 5 years) gender and location. Use of different forms of tobacco such as cigarettes, pipe-smoking and shamma (smokeless-tobacco) was assessed. Khat, a commonly used chewing substance in the community was also included. Descriptive analysis was first performed followed by multiple logistic regression (with and without interaction) to derive odds ratios (ORs) and 95% confidence interval (CIs). Results: Mean age of the study sample (56% males and 44% females) was 65.3 years. Multinomial regression analysis revealed that shamma use increased the odds of developing oral cancer by 29 times (OR=29.3; 10.3-83.1). Cigarette (OR=6.74; 2.18-20.8) was also seen to have an effect. With the interaction model the odds ratio increased significantly for shamma users (OR=37.2; 12.3-113.2) and cigarette smokers (OR=10.5; 2.88-3.11). Khat was observed to have negative effect on the disease occurrence when used along with shamma (OR=0.01; 0.00 - 0.65). Conclusions: We conclude that shamma, a moist form of smokeless tobacco is a major threat for oral cancer occurrence in the Jazan region of Saudi Arabia. This study gives a direction to conduct further longitudinal studies in the region with increased sample size representing the population in order to provide more substantial evidence.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.9-18
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• 1995

Purpose : A retrospective analysis was performed to investigate the proper management of maxillary sinus carcinoma. Materials and Methods : Authors analysed 33 patients of squamous cell carcinoma of maxillary sinus treated at Chonnam University Hospital from January 1986 to December 1992. There were 24 men and 9 women with median age of 55 years. According to AJCC TNM system of 1988, a patient of T2, 10 patients of T3 and 22 patients of T4 were availalbe, respectively. Cervical lymph node metastases was observed in 5 patients(N 1;4/33, N2b; 1/33). Patients were classified as 3 groups according to management method. The first group, named as 'FAR' (16 patients), was consisted or preoperative intra-arterial chemotherapy with 5-fluorouracil(5-FU;mean of total dosage;3078mg) through the superficial temporal artery with concurrent radiation(mean dose delivered:3433cGy, daily 180-200cGy) and vitamin A(50,000 IU daily), and followed by total maxillectomy and postoperative radiation therapy(mean dose;2351cGy). The second group, named as 'SR'(7 patients), was consisted of total maxillectomy followed by postoperative radiation therapy(mean dose 5920 cGy). The third group, named as 'R'(6 patients), was treated with radiation alone(mean dose;7164cGy). Kaplan-Meier product limit method was used for survival analysis and Mantel-Cox test was performed for significance of survival difference between two groups. Results : Local recurrence free survival rate in the end of 2 year was $100\%$, $50\%$ and $0\%$ in FAR, SR and R group, respectively. Disease free survival rate in 2 years was $88.9\%$, $28.0\%$ and $0\%$ in FAR, SR and R group, respectively. Overall survival rate in 2 years was $88.9\%$, $40\%$ and $50\%$ in FAR, SR and R group, respectively. There were statistically significant difference between FAR and SR or FAR and R group in their local recurrence free, disease free and overall survial rates. But difference of each survival rate between SR and R group was not significant. Conclusion : In this study FAR group revealed better results than SR or R group. In the future prospective randomized study is in need.