• Radiation Oncology Journal
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• v.13 no.3
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• pp.259-266
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• 1995

Purpose : The aim of this study is to analyze the survival rate, treatment failure and complication of radiation therapy alone in stage III uterine cervical cancer. Materials and Methods : From January 1980 through December 1985, 227 patients with stage III uterine cervical cancer treated with radiation therapy at Kosin Medical Center were retrospectively studied. Among 227 patients, 72 patients($317{\%}$) were stage IIIa, and 155 patients($68.3{\%}$) were stage IIIb according to FIGO classification. Age distribution was 32-71 years (median: 62 years). Sixty nine patients($95.8{\%}$) in stage IIIa and 150 patient ($96.8{\%}$) in stage IIIb were squamous cell carcinoma. pelvic lymph node metastasis at initial diagnosis was 8 patients($11.1{\%}$) in stage IIIa and 29 patients($18.7{\%}$) in stage IIIb, Among 72 patients with stage IIIa, 36 patients ($50{\%}$) were treated with external radiation therapy alone by conventional technique (180-200 cGy/fr.) and 36 patients($50{\%}$) were treated with external radiation therapy with intracavitary radiotherapy(ICR) with $Cs^{137}$ sources, and among 155 patients with stage IIIb, 80 patients ($51.6{\%}$) were treated with external radiation therapy alone and 75 patients ($48.4{\%}$) were treated with external radiation therapy with ICR. Total radiation doses of stage IIIa and IIIb were 65-105 Gy(median: 78.5 Gy) and 65-125.5 Gy (median 83.5 Gy). Survival rate was calculated by life-table method. Results : Complete response rates were $58.3{\%}$(42 patients) in stage IIIa and $56.1{\%}$(87 patients) in stage IIIb. Overall 5 year survival rates were $57{\%}$ in stage IIIa and $40{\%}$ in stage IIIb. Five year survival rates by radiation technique in stage IIIa and IIIb were $64{\%},\;40{\%}$ in the group treated in combination of external radiation and ICR, and $50\%,\;40\%$ in the group of external radiation therapy alone(P=NS). Five year survival rates by response of radiation therapy in stage IIIa and IIIb were $90\%,\;66\%$ in responder group and $10\%,\;7\%$ in non-responder group (P<0.001) There were statistically no significant differences of 5 year survival rate by total radiation doses and external radiation doses(40 Gy vs 50 Gy) of whole or true pelvis in stage IIIa and IIIb(P=NS). Treatment failures rates were $40.3\%$(29 patients) in stage IIla and $57.4\%$(89 patients) in stage IIIb. 17 patients ($23.6\%$) in stage IIIa and 46 patients ($29.7\%$) in stage IIIb experienced complications. Total radiation doses more than 85 Gy produced serious complication in both stage IIIa($50\%$) and IIIb($50\%$). Serious complication rates were higher in group received external radiation doses of 50 Gy than 40 Gy to whole or true pelvis in stage IIIa and IIIb. Serious rectal complication developed in rectal doses more than 65 Gy, and serious bladder complication developed in bladder doses more than 75 Gy. Major cause of death was cachexia due to locoregional failure in both stage IIIa($34.7\%$) and IIIb($43.9\%$). Conclusion : From this study, we found that external radiation therapy with ICR was found to have a tendency to be superior to external radiation therapy alone in survival rate, local control rate and complication rate but not different in statistics, and external radiation doses of 50 Gy than 40 Gy to whole or true pelvis produced serious rectal and bladder complications in stage III uterine cervical cancer.

• Radiation Oncology Journal
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• v.7 no.1
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• pp.81-83
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• 1989

This study, involving thirty-two patients with carcinoma of uterine cervix treated by high dose rate intracavitary irradiation using a remotely controlled afterloading system, compares the doss at point A and 8 with the Curie-minutes prescription. A linear least-square regression analysis was used to compare the two sets of date. Correlation coefficients between doses at points A and B and the Ci-min prescription are 0.92 (p<0.001) and 0.90 (p<0.001), respectively, and linear relationship is observed between these two system. The limitation and significance of the comparison of the two approaches to intracavitary dosimetry is discussed.

• Biomedical Science Letters
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• v.2 no.2
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• pp.153-158
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• 1996

Verapamil, a potent calcium channel blocker, has been proved to be one of the modulators to overcome drug resistance in cancer chemotherapy. In the present experiment, the possibility of verapamil as a MDR modulator was investigated by using MTT assay. Sole treatment of verapamil on the HeLa and Caski cervical cancer cell line revealed dose dependent cytotoxicity within a range of tested dose. Combined treatment of verapamil with 5-FU, DDP on two human cervical cancer cell line led to a significant synergistic cytotoxicity. Therefore , these studies showed that verapamil had a possibility to be applicable to cancer chemotherapy in gynecological oncology.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.4
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• pp.47-60
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• 2006

Purpose : This study was conducted to investigate the inhibitory effects of Scutellaria barbata D. D on on the cell proliferation of HeLa Cells. Methods : Human uterine cervical carcinoma HeLa cells were cultured in the 1%, 5% and 10% concentration of Scutellaria barbata D. D on solution for 24, 48 and 72 hours for the direct inhibitory effects of Scutellaria barbata D. D on. Then we examined the effect of Scutellaria barbata D. D on solution on the cell proliferation inhibition by XTT assay. DNA fragmentation, MAP kinase activity and caspase activity by FACS analysis in HeLa cells. Results : We found that the proliferation of HeLa cells was significantly decreased in Scutellaria barbata D. D on solution containing groups comparing with a control group in a concentration-dependant manner. When HeLa cells were cultivated for 24 hours with 5% Scutellaria barbata D. D on solution containing group, the percentage of HeLa cells with activated caspase was the highest. Scutellaria barbata D. D on solution reduced the MAP kinase activity of HeLa cells comparing with the control group. By the XTT assay, the cell's activity was decreased in 5% and 10% Scutellaria barbata D. D on solution containing groups in 24 and 72 hours cultivation and 10% group in 48 hours. DNA fragmentation and caspase-3 activity of HeLa cells, however, were changed insignificantly. Conclusion : From this study we could suggest that Scutellaria barbata D. D on is available to the inhibition and apoptosis of human cervical carcinoma cell line, HeLa cells in vitro.

• The Journal of Korean Medicine
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• v.27 no.1 s.65
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• pp.23-35
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• 2006

Objectives : This study was conducted to investigate the inhibitory effects of Gaejibokryunghwan on cell proliferation in HeLa cells. Methods : Human uterine cervical carcinoma HeLa cells were cultured in the 1%, 5% and 10% concentration of Gaejibokryunghwan extract solution. All three were cultured for 24 hours, 48 hours and 72 hours each, to examine the inhibitory effects of Gaejibokryunghwan. Afterwards, we drew out the effect of Gaejibokryunghwan extract solution by making 5 analysis. First analysis was to measure the proliferation rate of cells. Second was FACS analysis. Third was to estimate the activity or caspase-3. Fourth, we used XTT assay to analyze the activation or cells. Ana lastly, a molecular biological method was used to determine activation of MAP kinase in the HeLa cells. Results : After 24, 48 and 72 hours cultivation, the proliferation of HeLa cells showed the dose-dependent decrease in all Gaejibokryunghwan extract solution groups compared to the control group. In the FACS analysis, Gaejibokryunghwan extract solution groups showed increased caspase expression compared to the control group, except for the group for 48 and 72 hours in 1 % concentrate. Caspase-3 activities were increased in all, except tile group cultured for 24 hours in 5% concentrate and the groups cultured for 48 hours in 1% and 5% concentrate. In the XTT study, 1% Gaejibokryunghwan extract solution groups showed increase compared to the control group, but other Gaejibokryunghwan extract solution containing groups showed significant decrease compared to the control after 24, 48 and 72 hours of cultivation. The expressions of MAP kinase were decreased in all Gaejibokryunghwan extract solution containing groups compared to the control group after 24, 48 and 72 hours of cultivation. Conclusions : From this study, we could suggest that Gaejibokryunghwan be available to the inhibition of proliferation of human cervical carcinoma cell line, HeLa cells in vitro.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.2
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• pp.34-48
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• 2006

Purpose : This study was conducted to investigate the inhibitory effects of Dangguijakyaksan on cell proliferation in HeLa cells. Methods : Human uterine cervical carcinoma HeLa cells were cultured in the 1%, 5% and 10% concentration of Dangguijakyaksan extract solution for 24 hours, 48 hours and 72 hours for the direct inhibitory effects of Dangguijakyaksan. Afterwards, we executed the analysis of the effect of Dangguijakyaksan extract solution on cell proliferation inhibition using XTT assay, molecular biological method through MAP kinase activity and FACS analysis of caspase activity in the HeLa cells. Results : After 24, 48 and 72 hours cultivation, Dangguijakyaksan extract solution group showed significant decrease of HeLa cells except 1% solution after 24 hours compared with the control group. In the FACS analysis, Dangguijakyaksan extract solution groups showed increase of caspase activity except 1% solution after 48 hours compared with the control group. In the XTT assay, the caspase-3 activities were increased in Dangguijakyaksan extract solution groups except 1% solution after 24 hours in a dose-dependent manner. In the XTT study, cell activities were significantly decreased in 10% Dangguijakyaksan extract solution groups after 48 and 72 hours cultivation compared with the control group. In all Dangguijakyaksan extract solution groups, The activities of MAP kinase were decreased after 24, 48 and 72 hours cultivation compared with the control group. Conclusion : It could be concluded that Dangguijakyaksan is available to the inhibition of proliferation of human cervical carcinoma cell line in vitro.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.396-404
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• 2002

Purpose : Many papers support a correlation between rectal complications and rectal doses in uterine cervical cancer patients treated with radical radiotherapy. In vivo dosimetry in the rectum following the ICRU report 38 contributes to the quality assurance in HDR brachytherapy, especially in minimizing side effects. This study compares the rectal doses calculated in the radiation treatment planning system to that measured with a silicon diode the in vivo dosimetry system. Methods : Nine patients, with a uterine cervical carcinoma, treated with Iridium-192 high dose rate brachytherapy between June 2001 and Feb. 2002, were retrospectively analysed. Six to eight-fractions of high dose rate (HDR)-intracavitary radiotherapy (ICR) were delivered two times per week, with a total dose of $28\~32\;Gy$ to point A. In 44 applications, to the 9 patients, the measured rectal doses were analyzed and compared with the calculated rectal doses using the radiation treatment planning system. Using graphic approximation methods, in conjunction with localization radiographs, the expected dose values at the detector points of an intrarectal semiconductor dosimeter, were calculated. Results : There were significant differences between the calculated rectal doses, based on the simulation radiographs, and the calculated rectal doses, based on the radiographs in each fraction of the HDR ICR. Also, there were significant differences between the calculated and measured rectal doses based on the in-vivo diode dosimetry system. The rectal reference point on the anteroposterior line drawn through the lower end of the uterine sources, according to ICRU 38 report, received the maximum rectal doses in only 2 out of the nine patients $(22.2\%)$. Conclusion : In HDR ICR planning for conical cancer, optimization of the dose to the rectum by the computer-assisted planning system, using radiographs in simulation, is improper. This study showed that in vivo rectal dosimetry, using a diode detector during the HDR ICR, could have a useful role in quality control for HDR brachytherapy in cervical carcinomas. The importance of individual dosimeters for each HDR ICR is clear. In some departments that do not have the in vivo dosimetry system, the radiation oncologist has to find, from lateral fluoroscopic findings, the location of the rectal marker before each fractionated HDR brachytherapy, which is a necessary and important step of HDR brachytherapy for cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3281-3285
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• 2012

Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffin-embedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load ${\leq}5.00$ copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5165-5169
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• 2013

Background: To evaluate the pathological characteristics of invasive margins in early-stage cervical squamous cell carcinomas and their association with other clinicopathological features including clinical outcomes. Materials and Methods: Patients with FIGO stage IB-IIA cervical squamous cell carcinomas who received surgical treatment and had available follow-up information were identified. Their histological slides were reviewed for prognostic variables including tumor size, grade, extent of invasion, lymphovascular invasion, involvement of vaginal margin or parametrium, and lymph node metastasis. The characteristics of invasive margins including invasive pattern (closed, finger-like, or spray-like type), degree of stromal desmoplasia, and degree of peritumoral inflammatory reaction were evaluated along the entire invasive fronts of tumours. Associations between the characteristics of invasive margins and other clinicopathological variables and disease-free survival were assessed. Results: A total of 190 patients were included in the study with a median follow-up duration of 73 months. Tumour recurrence was observed in 18 patients (9%). Spray-like invasive pattern was significantly more associated as compared with closed or finger-like invasive pattern (p=0.005), whereas the degree of stromal desmoplasia or peritumoral inflammatory reaction was not. Low degree of peritumoral inflammatory reaction appeared linked with lymph node metastasis (p=0.021). In multivariate analysis, a spray-like invasive pattern was independently associated with marked stromal desmoplasia (p=0.013), whilst marked desmoplasia was also independently associated with low inflammatory reactions (p=0.009). Furthermore, low inflammatory reactions were independently associated with positive margins (p=0.022) and lymphovascular invasion (p=0.034). The patients with spray-like invasive pattern had a significantly lower disease-free survival compared with those with closed or finger-like pattern (p=0.004). Conclusions: There is a complex interaction between cancer tissue at the invasive margin and changes in surrounding stroma. A spray-like invasive pattern has a prognostic value in patients with early-stage cervical squamous cell carcinoma.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.