• 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.

• Radiation Oncology Journal
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• v.10 no.1
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• pp.59-67
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• 1992

From March 1979 through December 1986, 124 patients with early stage carcinoma of the uterine cervix received curative radiation therapy. According to FIGO classification, 35 patients were stage IB and 89 were stge II A. In stage IB, five year locoregional control, five year disease free survival, and five year overall survival was $79.0\%$, $76.4\%$ and $81.8\%$, respectively. In stage II A, five year locoregional control, five year disease free survival, and five year overall survival were $78.0\%$, $66.8\%$, and $72.1\%$, respectively. To identify prognostic factors, pretreatment parameters including age, ECOG performance status, number of pregnancies, history of diabetes mellitus and hypertension, histology, size and shape of primary tumor, CT findings and blood parameters were retrospectively analyzed in terms of locoregional control, disease free survival and overall survival using univariate analysis and multivariate analysis. In univariate analysis, tumor size on physicai examination and rectal invasion on CT significantly affected locoregional control, disease free survival and overall survival. Parametrial involvement on CT was a significant prognostic factor on locoregional control and disease free survival. Hemoglobin level affected disease free survival and overall survival. Histology and age were significant prognostic factors on locoregional control. In multivariate analysis excluding CT finding, tumor size on physical examination was a significant factor in terms of locoregioal control and overall survival. Hemoglobin level was significant in terms of disease free survival. In multivariate analysis including CT, histology was a prognostic factor on locoregional control and disease free survival. Hemoglobin level and rectal invasion on CT were significant factors on locoregional control.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.231-239
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• 1990

From May 1979 through December 1981 a total of 524 patients with carcinoma of the uterine cervix were treated by radiation therapy with curative intent. Among the 524 patients, 350 were treated with a high-dose-rate (HDR), remote-controlled, afterloading intracavitary irradiation (ICR) system using a cobalt source (Ralstron), and 168 patients received a low-dose-rate (LDR) ICR using a radium source. External beam irradiation with a total dose of 40-50 Gy to the whole pelvis followed by intracavitary irradiation with a total dose of 30-39 Gy in 10-13 fractions to point A was the treatment protocol. ICR was given three times a week with a dose of 3 Gy per fraction. Five-year actuarial survival rates in the HDR-ICR group were $77.6{\%}$ in stage IB (N=20), $68.2{\%}$ in stage II (N=182), and $50.9{\%}$ in stage III (N=148). In LDR-ICR group, 5-year survival rates were $87.5{\%}$ in stage IB (N=22), $66.3{\%}$ in stage II (N=91), and $55.4{\%}$ in stage III (N=52). Survival rates showed a statistically significant difference by stage, but there was no significant difference between the two ICR groups. Late bowel complications after radiotherapy were noted in $3.7{\%}$ of the HDR-ICR group and $8.4{\%}$ of the LDR-ICR group. There was no severe complication requiring surgical management. The incidence of bladder complications was $1.4{\%}$ in the HDR-ICR group and $2.4{\%}$ in the LDR-ICR group. The application of HDR-ICR was technically simple and easily performed on an outpatient basis without anesthesia, and the patients tolerated it very well. Radiation exposure to personnel was virtually nil in contrast to that of LDR-ICR. Within a given period of time, more patients can be treated with HDR-ICR because of the short treatment time. Therefore, the HDR-ICR system is highly recommended for a cancer center, particularly one with a large number of patients to be treated. In order to achieve an improved outcome, however, the optimum dose-fractionation schedule of HDR-ICR and optimum combination of intracavitary irradiation with external beam irradiation should be determined through an extensive protocol.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.387-395
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• 1993

To identify pretreatment prognostic factors in carcinoma of the uterine cervix, a retrospective analysis was undertaken of 510 patients treated with curative radiation therapy in Seoul National University Hospital during the 7 year period, from March 1979 through December 1986. According to FIGO classification,35 patients were stage I B,89 were stage IIA, 232 were stage IIB,8 were stage IIIA, 134 were IIIB, and 12 were stage IVA. Five year locoregional control (LRC) rates in stage I B, II A, II B, IIIA, IIIB, and IVA were $79\%,78\%,70\%,58\%,51\%\;and\;27\%,$ respectively. Five year disease free survival (DFS) rates were $76\%,67\%,60\$,57\%,40\%,\;and\;25\%,$ respectively. Overall survival (OS) rates at five years were $82\%,72\%,67\%,67\%,51\%,\;and\;33\%,$ respectively. In univariate analyses, stage, age, initial hemoglobin level, type of histology, tumor size, and several CT findings including pelvic lymph node (LN) status, paraaortic lymph node (PAN) status, extent of parametrial invasion, bladder invasion, and rectal invasion were significant factors in terms of LRC. All these factors and elevation of BUN or creatinine were associated with DFS. In terms of overall survival, stage, initial hemoglobin level, type of histology, tumor size, elevation of BUN or creatinine, and five CT findings associated with LRC were prognostically significant. In multivariate analysis excluding CT findings, stage IV disease, non-squamous histology, and tumor size $\ge$4 cm were associated with poor LRC and DFS. Stage IV disease and tumor size significantly affected OS. in multivariate analysis including CT findings, histology, tumor size, and pelvic LN status on CT were uniformly significant in terms of LRC, DFS, and 05, PAN status on CT affected overall survival only.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.271-276
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• 1991

A series of 510 patients with carcinoma of the uterine cervix given the curative radiation therapy from March 1979 through December 1986 was evaluated to determine the value of intravenous pyelography (IVP), cystoscopy, sigmoidoscopy, and abdomino-pelvic CT as staging work-up prior to treatment. On IVP and cystoscopy, $10.7\%$(49/456) and $5.3\%$(24/452) showed abnormality, respectively, but only $0.7\%$(3/413) did on sigmoidoscopy. As a result of these work-ups prerequisite to FIGO staging, twenty six ($5.1\%$) out of 510 patients were upstaged from the stage determined by the findings of physical examination alone. The proportions of upstaging in each stage were as follows; none in stage IB (35), IIA (89) and IIIA (8), $7.9\%$(20/252) in stage IIB (14 patients to FIGO stage IIIB, 6 patients to FIGO stage IVA), and $4.8\%$(6/126) in stage IIIB (all to FIGO stage IVA). Positive findings of staging work-ups were found only in patients with advanced stages of stage IIB or over determined by physical examination alone but not in those with earlier stages. CT was performed in 337 patients. CT detected pelvic lymph node (LN) enlargement in $25.2\%$ (85/337) and paraaortic LN enlargement in $7.4\%$(25/337). Pelvic LN positivity was well correlated with increasing stage but paraaortic LN positivity was not. In the evaluation of parametrial involvement, CT findings were in accordance with those of physical examination only in $65.6\%$ (442/674). When compared with endoscopic studeies, CT had much lower positive predictive value than negative predicitive value in the evaluation of adjacent organ invasion. The staging work-ups should be individualized by the disease extent of each patient, and then the efficiency of work-uus may be increased without compromising the appropriate FIGO staging and treatment.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.277-284
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• 1991

Survival data, prognostic factors, and patterns of failure were retrospectively analyzed for a total of 76 patients with adenocarcinoma of the uterine cervix treated between January 1981 and December 1987, which represents $4.1\%$ of all primary cervical carcinomas treated, at Department of Radiation Oncology, Yensei Cancer Center, Yonsei University College of Medicine. The mean age of the patients was 49 years (range, $27\~79$ years) and the peak incidence was in the group 50 to 59 years of age. More half of the patients were postmenopausal (46/76= $60.5\%$). Most patients ($76\%$) had abnormal vaginal bleeding either alone or in combination with other symptoms. The proportion of stage IIb was $43.4\%$. There were 4 major histologic subtypes: pure adenocarcinoma (48/76=$63.2\%$), adenosquamous carcinoma (20/76=$26.3\%$), papillary (5/76=$6.6\%$) and clear cell carcinoma (3/76=$3.9\%$). Of the many clinicopathologic variables evaluated for prognosis, the most significant prognostic factors were stage of disease and the size of tumor. The overall 5-year survival rate was $68\%$, and the 5-year survival rates for stage Ib, II and III were $90\%,\;66\%\;and\;54\%$, respectively. Control of pelvic tumors was achieved in $93.8\%,\;90.2\%\;and\;50.0\%$ of cases of stage Ib, II and III disease, respectively. In present study, treatment modalities (radiation therapy alone/combined operative and radiation therapy) did not affect the local control of tumor and the survival.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.143-156
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• 2005

Background: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. Materials and Methods: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of $23.4\~59.4$ Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-IBT) was also peformed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of $14.4\~43.2$ Gy (Median 36.0) of EBRT in 495 patients, while In the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor ($\alpha/\beta$=10) and late-responding tissues ($\alpha/\beta$=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED $Gy_3$ and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED $Gy_3$ and rectal complications and between V-BED $Gy_3$ and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED $Gy_{10}$, and the treatment duration. Results: The overall complication rate for RTOG Grades $1\~4$ toxicities was $33.1\%$. The 5-year actuarial pelvic control rate for ail 743 patients was $83\%$. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 $Gy_{10}$ (median 93.0) for tumors and from 93.6 to 187.3 $Gy_3$ (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED $Gy_3$) and bladder Point BED (V-BED $Gy_3$) were 118.7 $Gy_3$ (range $48.8\~265.2$) and 126.1 $Gy_3$ (range: $54.9\~267.5$), respectively. MD-BED $Gy_3$ showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED $Gy_3$ had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED $Gy_3$. B-BED $Gy_3$ also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. Conclusion: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences In tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very Important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.

• Radiation Oncology Journal
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• v.13 no.4
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• pp.349-357
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• 1995

Purpose : To analyze survival rate and late rectal and bladder complication for patients with stage I and II carcinoma of uterine cervix treated by radiation alone or combined with chemotherapy Materials and Methods : Between November 1984 and December 1993, 127 patients with stage I and II carcinoma of uterine cervix treated by radiation alone or combined therapy of radiation and chemotherapy. Retrospective analysis for survival rate was carried out on eligible 107 patients and review for complication was possible in 91 patients. The median follow-up was 47 months (range 3-118) and the median age of patiens was 56 years (range 31-76). 26 patients were stage IB by FIGO classification, 40 were stage IIA and 41 were stage IIB. 86 cases were treated by radiation alone and 21 were treated by radiation and chemotherapy. 101 patients were treated with intracavitary radiation therapy (ICRT), of these, 80 were received low dose rate (LDR) ICRT and 21 were received high dose rate (HDR) ICRT. Of the patients who received LDR ICRT, 63 were treated by 1 intracavitary insertion and 17 were underwent 2 insertions And we evaluated the external radiation dose and midline shield. Results : Actuarial survival rate at 5 years was $92{\%}$ for stage IB, $75{\%}$ for stage IIA, $53{\%}$ for stage IIB and $69{\%}$ in all patients Grade 1 rectal complications were developed in 20 cases ($22{\%}$), grade 2 were in 22 cases ($24{\%}$). 22 cases ($24{\%}$) of grade 1 urinary complications and 17 cases ($19{\%}$) of grade 2 urinary complications were observed But no patient had severe complications that needed surgical management or admission care. Maximum bladder dose for the group of patients with urinary complications was higher than that for the patients without urinary complications (7608 cGy v 6960cGy. p<0.01) Maximum rectal dose for the group of patients with rectal complications was higher than that for the patients without rectal complications (7041cGy v 6269cGy, p<0.01). While there was no significant difference for survival rate or bladder complication incidence as a function of dose to whole pelvis, Grade 2 rectal complication incidence was significantly lower for the patients receiving less than 4500cGy ($6.3{\%}$ v $25.5{\%}$, p<0.05). There was no significant differance between HDR ICRT group and LDR ICRT group for survival rate according to stage, on the other hand complication incidence was higher in the HDR group than LDR group, This was maybe due to different prescription doses between HDR group and LDR group. Midline shield neither improved survival rate nor decreased complication rate. The number of insertion in LDR ICRT group did not affect on survival and compication rate. Conclusion : In stage I and II carcinoma of uterine cervix there was no significant differance for 5 year survival rate by radiation therapy technique. Rectal complication incidence was as a function of dose to whole pelvis and there were positive correlations of maximum dose of rectum and bladder and each complication incidence. So we recommand whole pelvis dose less than 4500cGy and maximum dose of rectum and bladder as low as possible.

• Korean Journal of Medicinal Crop Science
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• v.20 no.3
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• pp.153-158
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• 2012

In order to develop as a natural source of anticancer materials of Cudrania tricuspidata, the cytotoxicity of methanol extracts by harvesting parts and times against 8 cell lines including 293 (normal kidney cells) and A-431 (epidermoid carcinoma cells) were investigated using MTT assay. All harvesting parts had hardly cytotoxicity against 293. And methanol extracts of stem bark and root bark showed very high cytotoxicities against 7 cancer cell lines. The cytotoxicity was the highest against HeLa (cervix adenocarcinoma cells) and followed by MCF-7 (breast adenocarcinoma cells), AGS (stomach adenocarcinoma cells), HT-29 (colon adenocarcinoma cells), HepG2 (hepatoblastoma cells), A549 (lung carcinoma cells) and A-431. By the way, leaf extract had a cytotoxicity against only AGS and ripe fruit extract had no cytotoxicity. Among harvesting times, the cytotoxicity of root bark were high from April to September but that of stem bark showed a little difference. These results showed that anticancer activities of Cudrania tricuspidata extracts were eventful changes by harvesting parts and times.

• Journal of Digital Convergence
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• v.16 no.3
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• pp.311-319
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• 2018

This research attempted to identify the factors associated with the intention of human papilloma virus vaccination among mothers of elementary school daughters. The subject of study is 132 mothers of elementary school students. Data collection was conducted from July 1 to August 30 in 2017, and analyzed using SPSS 23.0 Program. Results showed that 94.7% children of the participants had not been vaccinated, whose reasons were the low knowledge about HPV vaccination, concerns about its side effects, burden for cost. The attitude toward HPV vaccination appeared to be the most important predictor of vaccination, which was followed by perceived behavior control and subjective norm as meaningful predictors, as well. Based on these results, further researches should be conducted to develop educational programs, which are able to offer exact information about the effect and side effect of HPV vaccination, and verify the effectiveness.