• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.636-644
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• 1999

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. The mechanisms of TNF cytotoxicity are not clearly understood and some has reported that reactive oxygen species(ROS) might be associated with them, but there is controversy about antioxidant effect on TNF cytotoxicity. This study was designed to compare the TNF cytotoxicity after antioxidant pretreatment with that of control to evaluate the role of ROS in the mechanism of TNF cytotoxicity. Method : We compared the TNF cytotoxicies to WEHI164(murine fibrosarcoma cell line) and ME180(human cervix cancer cell line) after antioxidant pretreatment with those of control by MIT(dimethylthiazolyl-diphenyltetrazolium bromide) assay. Results : In the control group, the TNF cytotoxicities were $92.2{\pm}2.8%$(WEHI164) and $59.9{\pm}7.0%$(MEl80). In the TMTU(tetramethyl thiourea) pretreatment group, those were $91.4{\pm}3.7%$ and $74.6{\pm}7.0%$. In the PMZ(promethazine) pretreatment group, those were $90.2{\pm}2.5%$ and $62.5{\pm}5.7%$. In the BHT(butylated hydroxytoluene) pretreatment group, those were $93.2{\pm}1.3%$ and $66.3{\pm}6.1%$. So there was no reduction in TNF cytotoxicity after antioxidants pretreatment. Conclusion : The ROS may not have major role in the mechanisms of TNF cytotoxicity.

• Progress in Medical Physics
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• v.16 no.1
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• pp.16-23
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• 2005

The objective of this study was to construct multi-element ultrasound applicators for the treatment of gynecologic cancer with high dose rate brachytherapy. For the treatment of uterus, piezo-ceramic crystal transducer (PZT -5A) with outer diameter of 4 mm, wall thickness of 1.3 mm, and length of 24.5 mm was selected. For the treatment of cervix or vagina, it should be possible to insert the applicator into the vagina. Thus, a cylindrical PZT -8 material with outer diameter of 24.5 mm, wall thickness of 1.3 mm, and length of 15.2 mm was selected. The operating frequencies determined by vector impedance measurement were 3.2 MHz for the PZT 5A cylinder (OD=4 mm) and 1.7 MHz for the PZT -8 cylinder (OD: 24.5 mm). The ratios of generated acoustic output power to applied electric power were 33% and 61% for the tandem type crystal and the cylinder type crystal, respectively. The radiated acoustic pressure fields from both transducers were calculated using a Matlab code and measured in water using hydrophone. There was good agreement between measured and calculated acoustic pressure field distribution. For a tandem type transducer, the calculated acoustic pressure field decreased from 0.023 MPa at 10 mm to 0.010 Mpa at 30 mm, the reduction of 57%. For the cylinder type transducer which will be used for the treatment of vagina showed 78% reduction at 15 mm and 66% at 25 mm as compared to values at 5 mm from the surface. Based on the characteristics of the transducers, this study demonstrated the possibility of using the crystals as a heating source. Finally, a 3-element and 4-element prototype applicators were constructed. The 3-element applicator is 75 mm long and 4 mm thick and will be used for the treatment of uterus. The 4-element applicator is 61 mm long and 24.5 mm thick and will be used for the treatment of vagina. Using these applicators, it is possible to generate enough power to increase temperature to therapeutic level.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.143-148
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• 2003

Purpose: The purpose of this study was to evaluate treatment results in terms of the survival and failure patterns subsequent to radiation therapy in recurrent cervical cancer, fellowing primary surgery. Material and Methods: Between January 1990 and December 1999, 27 patients, with recurrent cervical cancer following primary surgery, were subsequently treated with radiation in the Department of Radiation Oncology, at the Keimyung University Dongsan Medical Center. Their median age was 48, ranging from 31 to 70 years old. With regard to the Initial FIGO stage on presentation, 20 and 7 patients were stages I and II, respectively. Twenty three patients had squamous cell carcinomas and 4 had adenocarcinomas. The time interval from the primary surgery to the recurrence ranged from 2 to 90 months with a median of 29 months. The recurrent sites were the vaginal cuff alone, the pelvic cavity and combined recurrence in 14, 9 and 4 patients, respectively. Radiation was peformed, with external and vaginal intracavitary radiation in 13 patients, external radiation alone in 13 and vaginal intracavitary radiation alone in another one. The median follow-up period was 55 months, ranging from 6 to 128 months. Results: The five year disease free survival (5y DFS) and five year overall survival (5y OS) rates were 68.2 and 71.9$\%$, respectively. There was a marginal statistically significant difference in the 5y DFS in relation to the recurrent site (5y DFS, 85.7$\%$ in vaginal cuff recurrence alone, 53.3$\%$ in pelvic cavity recurrence, p=0.09). There was no difference in the survival according to the time interval between the primary surgery and a recurrence. There was only a 7$\%$ local failure rate in the patients with a vaginal cuff recurrence. The major failure patterns were local failure in the patients with pelvic cavity recurrence, and distant failure in the patients with a combined recurrence. There were no complications above grade 3 after the radiation therapy. Conclusion: Radiation therapy was safe and effective treatment for a recurrent carcinoma of the uterine cervix following primary surgery, especially the external beam radiation and vaginal intracavitary irradiation achieved the best results in the patients with a vaginal cuff recurrence following primary surgery.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.135-142
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• 2003

Purpose: The purpose of this study was to investigate the positional change of the uterus during radiotherapy. Materials and Methods: Between 1997 and 2001, 47 patients received definitive radiotherapy for cervical cancer at the Samsung Medical Center. For each patient, two MRI scans were taken; one before and the other 3$\~$4 weeks after the radiotherapy treatment. In T2 weighted MRI images, the positional change of the uterine was quantified by measuring six quantities; the distance from the cervix os to the isthmus of the uterus (Dcx), the maximum length from the isthmus of the uterus to the uterine fundus (Dco), the maximum vertical distance of the uterine body (Dco-per), the angle between the vertical line and the cervical canal in the sagittal images (Acx), the angle of the uterine corpus from the vertical line in the sagittal plan (Aco-ap), and the relative angle of the uterine corpus from a fixed anatomical landmark in the axial images (Aco-axi). Results: The mean Dcx values, before and during the treatment, were 36.7 and 27.8 mm, respectively. The Dco deviated by more than 10 mm in 14 cases (29.8$\%$). The change in the Acx ranged from 0.1 to 67.8$^{\circ}$ (mean 13.2$^{\circ}$). The Aco-ap changed by a maximum of 84.8$^{\circ}$ (mean 16.9$^{\circ}$). The differences in the Dcx plus the Dco in the smaller (<4 cm) and larger ($geq$4 cm) tumors were 5.3 and 19.4 mm, respectively. With patients less than 60 years old, or with a tumor size larger than 4 cm, the difference in the Acx was statistically significant. Conclusion: The positional changes of the uterus, during radiation treatment, should be considered in the 3DCRT or IMRT treatment planning, particularly in patients under 60 years of age or in those with a tumor size greater than 4 cm in maximum diameter.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1353-1365
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• 1997

Background : Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on its potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majority of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host. In the previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-$\alpha$ cDNA would become highly resistant to TNF, and the probability was shown that the acquired resistance to TNF might be associated with synthesis of some protective protein. Understanding the mechanisms of TNF -resistance in TNF-$\alpha$ cDNA transfected cancer cells would be. an important step for improving the efficacy of cancer gene therapy as well as for better understandings of tumor biology. This study was designed to evaluate the role of MnSOD, an antioxidant enzyme, in the acquired resistance to TNF of TNF-$\alpha$ cDN A transfected cancer cells. Method : We transfected TNF-$\alpha$ c-DNA to WEHI164(murine fibrosarcoma cell line), NCI-H2058(human mesothelioma cell line), A549(human non-small cell lung cancer cell line), ME180(human cervix cancer cell line) cells using retroviral vector(pLT12SN(TNF)) and confirm the expression of TNF with PCR, ELISA, MIT assay. Then we determined the TNF resistance of TNF-$\alpha$ cDNA transfected cells(WEHI164-TNF, NCIH2058-TNF, A549-TNF, ME180-TNF) and the changes of MnSOD mRNA expressions with Northern blot analysis. Results : The MnSOD mRNA expressions of parental cells and genetically modified cells of WEHI164 and ME180 cells(both are naturally TNF sensitive) were not significantly different The MnSOD mRNA expressions of genetically modified cells of NCI-H2058 and A549(both are naturally TNF resistant) were higher than those of the parental cells, while those of parental cells with exogenous TNF were also elevated. Conclusion : The acquired resistance to TNF after TNF-$\alpha$ cDNA transfection may not be associated with the change in the MnSOD expression, but the difference in natural TNF sensitivity of each cell may be associated with the level of the MnSOD expression.

• Biomedical Science Letters
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• v.21 no.2
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• pp.69-76
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• 2015

Cervical cancer is the third most common cancer in women worldwide and there is a significant association between human papillomavirus (HPV) infection and cervical cancer. Certain HPV groups, labeled high-risk (HR) HPV groups, are strongly associated with malignancies of the human cervix. HPV prevalence and genotype distribution were analyzed using the REBA $HPV-ID^{(R)}$ (YD Diagnostics, Yongin, Korea) assay based on the reverse blot hybridization assay (REBA) with a total of 324 liquid-based cytology samples from women in Western Shandong Province, East China and results were compared with cytological diagnosis. Most of the HPV genotypes that were detected in high-grade cervical lesions were HR-HPV genotypes such as HPV 16, 18, 33, 53, and 58. The prevalence of these HR-HPV genotypes increased in high-grade cervical lesions. However, from low- to high-grade cervical lesions, the ability to detect LR-HPV genotypes decreased. Additionally, in general, the single HPV genotype infection rate increases in proportion to the severity of the lesion. The study findings suggest that a currently available preventive vaccine against HPV 16 and 18 may have limited effectiveness for prevention of all HPV infection in this province. Finally, based on these findings, these data could guide national or regional vaccination programs in the Western Shandong Province of East China to substantially reduce the burden of cervical lesions.

• Radiation Oncology Journal
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• v.29 no.3
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• pp.191-198
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• 2011

Purpose: Although the role of squamous cell carcinoma antigen (SCC-Ag) as a predictive and prognostic factor for uterine cervical cancer has been identified in previous studies, 1) the effective patient group of screening for recurrence with SCC-Ag, 2) the relationship between SCC-Ag and recurrence site, and 3) the relationship between the change of SCC-Ag and treatment outcome or recurrence have not been described. Materials and Methods: The study included 506 patients with histologically proven uterine cervical cancer between January 1994 and December 2010. We determining the serum SCC-Ag level before treatment and after treatment, and conducted a retrospective review of the patients' records. We evaluated the sensitivity and specificity of SCC-Ag for the detection of tumor recurrence by comparing biochemical recurrence with clinical recurrence. Results: The pretreatment SCC-Ag level and the proportion of patients over 1.5 ng/mL were higher in poor prognostic patient group. In the univariate and multivariate analysis, pretreatment SCC-Ag showed a statistically significant correlation with tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology. In patients with biochemical recurrence vs. those without, 5-year DFS and OS were 27.6 vs. 92.7% (p ${\leq}$ 0.001) and 53.7 vs. 92.5% (p ${\leq}$ 0.001), respectively. Conclusion: Our study reconfirmed the known function of pretreatment SCC-Ag, but could not confirm the function of biochemical response as a predictive factor for treatment and as a prognostic factor. There was no statistically significant relationship between SCC-Ag level and recurrence site. We confirmed the role of SCC-Ag as a follow-up tool for recurrence of disease and which patient groups SCC-Ag was more useful for.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6935-6940
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• 2013

Background: This study aimed to develop a prognostic model in patients with early-stage cervical squamous cell carcinoma based on clinicopathological features, including invasive margin characteristics. Materials and Methods: Clinicopathological features and outcomes of 190 patients with FIGO stage IB-IIA cervical squamous cell carcinoma treated by surgery were collected and analyzed for factors associated with tumor recurrence. In addition to well-recognized pathological risk factors, the pathological characteristics of invasive margin (type of invasive pattern and degree of stromal desmoplasia and peritumoral inflammatory reaction) were also included in the analysis. Multiple scoring models were made by matching different clinicopathological variables and/or different weighting of the score for each variable. The model with the best performance in the prediction of recurrence and decreased survival was selected. Results: The model with the best performance was composed of a combined score of invasive pattern, lymphovascular space invasion (LVSI), and degree of inflammatory reaction and stromal desmoplasia (total score =10). Compared to those with score ${\leq}8$, the patients with score 9-10 had a significantly higher recurrence rate in the overall group (p<0.001) and the subgroup without adjuvant therapy (p<0.001), while the significance was marginal in the subgroup with adjuvant therapy (p=0.069). In addition, the patients with score 9-10 had a higher rate of tumor recurrence at distant sites (p=0.007). The disease-free survival was significantly lower in the patients with score 9-10 than those with score ${\leq}8$ among the overall patients (p<0.001), in the subgroup without adjuvant therapy (p<0.001), and the subgroup with adjuvant therapy (p=0.047). Conclusions: In this study, a prognostic model based on a combination of pathological characteristics of invasive margin and LVSI proved to be predictive of tumor recurrence and decreased disease-free survival in patients with early-stage cervical squamous cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7633-7640
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• 2015

Background: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of cervical uterine cancer. Although HPV infections of the cervix do not always progress to cancer, 90% of cervical cancer cases have been found to be associated with high risk HPV (HR-HPV) infection. HPV DNA testing is widely used, along with Papanicolaou (Pap) testing, to screen for cervical abnormalities. However, there are no data on the prevalence of genotype-specific HPV infections assessed by measuring HPV E6/E7 mRNA in women representative of the Chinese population across a broad age range. Materials and Methods: In the present study, we compared the results with the CervicGen HPV RT-qDx assay, which detects 16 HR-HPV genotypes (Alpha-9: HPV 16, 31, 33, 35, 52, and 58; Alpha-7: HPV 18, 39, 45, 51, 59, and 68; and Alpha-5, 6: HPV 53, 56, 66, and 69), and the REBA HPV-ID assay, which detects 32 HPV genotypes based on the reverse blot hybridization assay (REBA) for the detection of oncogenic HPV infection according to cytological diagnosis. We also investigated the prevalence and genotype distribution of HPV infection with a total of 324 liquid-based cytology samples collected in western Shandong province, East China. Results: The overall HPV prevalences determined by HPV DNA and HPV E6/E7 mRNA assays in this study were 79.9% (259/324) and 55.6% (180/324), respectively. Although the positivity of HPV E6/E7 mRNA expression was significantly lower than HPV DNA positivity, the HPV E6/E7 mRNA assay showed greater specificity than the HPV DNA assay (88.6% vs. 48.1%) in normal cytology samples. The prevalence of Alpha-9 (HPV 16, 31, 33, 35, 52, and 58) HPV infection among these women accounted for up to 80.3% and 76.1% of the high-grade lesions detected in the HPV mRNA and DNA tests, respectively. The HR-HPV genotype distribution, based on HPV DNA and E6/E7 mRNA expression by age group in patients with cytologically confirmed lesions, was highest in women aged 40 to 49 years (35.9% for cytologically confirmed cases, Pearson correlation r value=0.993, p<0.001) for high-grade lesions. Among the oncogenic HR-HPV genotypes for all age groups, there was little difference in the distribution of HPV genotypes between the HPV DNA (HPV -16, 53, 18, 58, and 33) and HPV E6/E7 mRNA (HPV -16, 53, 33, 58, and 18) assays. HPV 16 was the most common HPV genotype among women with high-grade lesions. Conclusions: Our results suggest that the HPV E6/E7 mRNA assay can be a sensitive and specific tool for the screening and investigation of cervical cancer. Furthermore, it may provide useful information regarding the necessity for early cervical cancer screenings and the development of additional effective HPV vaccines, such as one for HPV 53 and 58. Additionally, gaining knowledge of HPV distribution may also inform us about ecological changes in HPV after the vaccination.

• Journal of Life Science
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• v.32 no.4
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• pp.271-278
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• 2022

The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.