• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.327-337
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• 1999

Background: Reactive oxygen species are involved in multi-stage process of carcinogenesis. The moot of cancer cell lines and cancer cells in tumor tissue produce reactive oxygen species and on the other hand, the activities of catalase, Mn- and CuZn-superoxide dismutase in tumor cells are usually low. These persistent oxidative stress in tumor tissue facilitates tumor invasion and metastasis. 12-kDa thioredoxin, which regulates the intracellular redox potential with glutathione and glutaredoxin is involved in cell activation, proliferation, differentiation and redox-mediated apoptosis. It is also purified as 14-kDa and 10-kDa eooinophilic cytotoxic enhancing factor(ECEF) from human histiocytic cell(U937) and 10-kDa ECEF has more than 20 times eosinophilic stimulation activity than 14-kDa ECEF. It has been reported that adult T-cell leukemia, squamous cell carcinoma of uterine cervix, and hepatocellular carcinoma show increased amounts of human thioredoxin and thioredoxin mRNA is increased in lung cancer. In this study, we investigated the expression of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue and the induction of thioredoxin in macrophage cells after treatment of oxidative stress and endotoxin Methods: We measured the amount of conventional antioxidant enzymes such as catalase, CuZn-SOD, and glutathione peroxidase and thioredoxin in lung cancer tissue compared to adjacent normal lung tissue by immunoblot analysis and the induction of thioredoxin in mouse monocyte-macrophage cells(RAW 264.7) by treatment of 5 ${\mu}M$ menadione and 1 ${\mu}g/ml$ endotoxin Results: On immunoblot analysis, the expression of 12-kDa thioredoxin was increased in lung cancer tissue compared to paired normal lung tissue. but the expression of catalase and CuZn-SOD were decreased in lung cancer tissue compared to paired normal tissue and the expression of glutathione peroxidase in lung cancer was variable. The expression of truncated thioredoxin was also increased in lung cancer. When mouse monocyte-macrophage cells were treated with 5 ${\mu}M$ menadione and 1 ${\mu}g/ml$ endotoxin, the expression of thioredoxin was peaked at 12 hrs and sustained to 48 hrs. Conclusion: In contrast with other conventional antioxidants, the expression of 12-kDa and truncated thioredoxin in lung cancer were increased and it is closely associated with persistent oxidative stress in tumor microenvironment. Considering especially the biological functions of truncated thioredoxin, the increased amount of truncated thioredoxin has significant role in tumor growth through cell proliferation.

• Radiation Oncology Journal
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• v.6 no.1
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• pp.63-73
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• 1988

One hundred fifty-four patients with the carcinoma of the uterine cervix were studied retrospectively to assess the result and impact of treatment at Department of Radiation Oncology, Korea University, Hae-Wha Hospital from Feb 1981 through Dec. 1986. Prior to radiotherapy, the patients were evaluated and staged by recommendation of FIGO including physical examination, pelvic examination, cystoscopy, rectosigmoidoscopy, chest X-ray, IVP. Ba enema. Also, an additional pelvic CT scan was obtained for some of the patients. The patients were treated by radiotherapy alone or adjuvant postoperative irradiation; in case of radiation therapy only, whole pelvic irradiation was given with Co-60 teletherapy unit via AP and PA parallel opposing fields or 4-oblique fields, 180 cGy per day, 5 days per week and intracavitary insertion was performed. In satges Ia, Ib, and IIa with small primary lesion, external irradiation was initially given to pelvis up to $2,000\~3,000\;cGy/2frac{1}{2}\;-3frac{1}{2}$ weeks and then intracavitary insertion was performed using Fletcher-Mini-Declos Applicator with cesium-137 cources and followed by external irradiation of $1,000\~2,000\;cGy/1frac{1}{2}\;-2frac{1}{2}$weeks via AP and PA parallel opposing fields with midline shield to spare of bladder and rectum. However, if the primary lesion is large, external irradiation was given without midline shield. More than stages IIb, the patients were treated by external beam irradiation up to 5,400cGy/30f for 6 weeks via 4-oblique portals and at the dose of 5,040cGy/28f the field was cut 5cm from the top margin for spare of small bowel, and followed by intracavitary irradiation, If there was residual tumor an additional dose of $900\~l,200cGy/5\~7f$ was given to parametrium and/or residual tumor area. Total dose of radiation to A and B-point were as follows; A-point; In early stages, Ia, Ib, IIa; $8,000\~9,000$ B-point $5,000\~6,000 cGy$ A-point; In advanced stages IIb, IIIa, IIIb; $9,000\~10,000$ B-point $60,000\~7,000cGy$ The results were obtained and as fellows; 1 The patients distribution according to FIGO staging system were stage Ia 6, Ib 27, IIa 28, IIb 54, IIIa 12, IIIb 18, and stage IVa 9. 2. Value of CT scan were demonstration of cervix tumor mass, parametrial and pelvic side wall tumor spread, pelvic and inguinal lymph nodes metastases, and hydronephrosis. Three dimensional quantitative demonstration of tumor volume is also important in planning radiation therapy. Another advantage of CT scan was detection of recurrent tumor after radiation or surgery. 3. Local control rate of tumor according to the size was $91.3\%$ for less than 5cm in size and $44.6\%$ in tumor over 5cm (p<0.0068). 4. Thirty out of 50 recurrent sites has locoregional failures and 17 cases has distant metastases. And the para-aortic lymph nodes were the most common site for distant metastases. 5. The most common complication was temporal rectal bleeding which was controlled most by conservative management. However, 4 patients required for endoscopic cauterization. 6. The 5-year survival rates showed; stage la and Ib $95\%,\;stage\;IIa\;81\%\;stage\;lIb\;67\%,\;stage\;IIIa\;37.7\%,\;stage\;IIIb\;23\%$ and 3-year survival rate of stage IVa showed $11.6%$, retrospectively.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4197-4201
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• 2014

Minor trauma to the uterine cervix is supposed to induce local immunity to prevent cervical lesions caused by human papillomavirus (HPV) infection. This study aimed to investigate the local cervical immunity in women with low grade squamous intraepithelial lesion (LSIL) and effects of abrasion after cryosurgery or Pap smear. One hundred women with LSIL and known results of HPV detection were recruited. HPV positive women were randomly divided according to abrasion into cryotherapy and Pap smear observation groups. Cervical tissues and cervico-vaginal lavage (CVL) were collected at 6 and 12 months after allocation. The levels of cytokines at first recruitment were compared with cytokine levels at 6 months after abrasions. The mRNA of IFN-${\gamma}$, TNF-${\alpha}$ and IL-10 in cervical tissues and these cytokines secreted in CVL were determined using real time PCR and ELISA, respectively. Anti-HPV16 IgG and IgA antibodies in CVL were assessed by western blotting. At first recruitment of women with LSIL (100 cases), IL-10 mRNA and cytokine in HPV positive group (60 cases) was significantly higher than negative group (40 cases). IFN-${\gamma}$ and TNF-${\alpha}$ mRNA level in both groups were comparable but their secretions in CVL were significantly increased in HPV negative group. After abrasion for 6 months in HPV-positive women, all mRNA and secreted cytokines were changed, but no significant difference was observed between cryotherapy and observation groups. When individuals were compared between first recruitment and after abrasion for 6 months, IFN-${\gamma}$ mRNA and anti-HPV16 L1 IgA antibodies were significantly increased in the cryotherapy group. The results suggest that modulation of local cervical immunities by abrasion might promote different effects in clearance of HPV-related cytological abnormalities.

• The Journal of Korean Society for Radiation Therapy
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• v.17 no.1
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• pp.1-8
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• 2005

Purpose : An effect of a packing to uterine treatment of a cervical cancer using a dose-volume histogram for a point dose and a volume dose of the bladder and the rectum was analyzed by establishing a three-dimensional treatment plan using a CT image. Materials and methods : Reference points of the bladder and the rectum were marked, respectively at a treatment plan device (plato brachytherapy V14.2.4) by photographing CT(marconi, USA) when the packing was used and removed under the same condition and a treatment plan was performed to Apoint depending on ICRU38. However, in case of the rectum, a maximum point was looked up and compared with the above point because the point presented from the ICRU is not proper as a representative value of a rectum point dose. Further, the volume dose depending on volume of $50\%,\;80\%,\;and\;100\%$ point doses of the rectum and the bladder was measured. The measured values were used to analyze the effect of the packing through a Wilcoxon Signed Rank Test (a SAS statistical analysis process program). Result : The reference points at the bladder and rectum doses when the packing was removed were $116.94\;35.42\%$ and $117.59\;21.08\%$, respectively. The points when the packing was used were $107.08\;38.12\%$ and $95.19\;21.32\%$, respectively. After the packing was used, the reference points at the bladder and the rectum were decreased by $9.86\%$ and $22.4\%$, respectively. When the packing was removed, the maximum points at the bladder and the rectum were $164.51\;50.89\%,\;128.81\;33.05\%$, respectively. When the packing was used, the maximum points at the bladder and the rectum were $142.31\;44.79,\;110.08\;37.03\%$, respectively. After the packing was used, the maximum points at the bladder and the rectum were decreased by $22.2\%$ and $18.73\%$, respectively. When the packing was removed, the bladder volume at $50\%,\;80\%,\;and\;100\%$ point doses of the rectum and the bladder were $48.62{\pm}18.09\%,\;16.12{\pm}11.15\%,\;and\;7.51{\pm}6.63\%$, respectively and its rectum volume were $23.41{\pm}14.44\%,\;6.27{\pm}4.28\%,\;2.79{\pm}2.27\%$, respectively. When the packing was used, the bladder volume at $50\%,\;80\%,\;and\;100\%$ point doses of the rectum and the bladder were $40.33{\pm}16.72,\;11.63{\pm}8.72,\;and\;4.87{\pm}4.75\%$, respectively and its rectum volume were $18.96{\pm}8.37\%,\;4.75{\pm}2.58\%,\;and\;1.58{\pm}1.06\%$, respectively. After the packing was used, the bladder volume at $50\%,\;80\%,\;and\;100\%$ point doses of the rectum and the bladder were decreased by $8.29\%,\;4.49\%,\;and\;2.64\%$, respectively and its bladder volume were decreased by $4.45\%,\;1.52\%,\;and\;1.21\%$, respectively. Conclusion : Values at Reference point doses of the bladder and the rectum recommended from the ICRU 38 were 0.0781 and 0.0781, respectively and values of their maximum point doses were 0.0156 and 0.0156, respectively, as a result of which an effect of the packing using at the uterine intracavitary treatment of an uterine cervical cancer through the three-dimensional treatment plan used CT were measured. That is, the values at reference point doses and the values at maximum point doses show similar difference. However, P value was 0.15 at over $50\%,\;80\%,\;and\;100\%$ volume doses and the value shows no similar difference. In other words, the effect of the packing looks like having a difference at the point dose, but actually shows no difference at the volume dose. The reason is that the volume of the bladder and the rectum are wide but the volume of the packing is only a portion. Therefore, the effect of decreasing the point dose was not great. Further, the farer the distance is, the more weak the intensity of radiation is because the intensity of radiation is proportional to inverse square of a distance. Therefore, the effort to minimize an obstacle of the bladder and the rectum by using the packing should be made.

• 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.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.335-344
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• 2001

Purpose : The aim of this study was to clarify the role of VEGF expression as an independent prognostic factor and to identify the patients at high risk for poor prognosis in stage IB cervical cancer. Materials and methods : A total of 118 patients with stage IB cervical cancer who had radical hysterectomy and pelvic lymph node dissection were included in the study. All known high risk factors of the patients were pathologically confirmed from the surgical specimen. Of the 118 patients, n patients were treated with postoperative radiotherapy and/or chemotherapy. VEGF expression was examined using immunohistochemistry in formalin-fixed, paraffin-embedded specimens of post-hysterectomy surgical materials. A semiquantitative analysis was made using a scoring system of 0, +, ++, and +++ for increasing intensity of stain. We classified the patients with scores from 0 to ++ as low VEGF expression and the patients with a score of +++ as high VEGF expression. Results : Of the 118 patients, 35 patients $(29.7\%)$ showed high VEGF expression. Strong correlations were found between the high VEGF expression and both deep stromal invasion (p=0.01) and the positive pelvic node (p=0.03). The 5-year overall and disease-free survival rates for all 118 patients were $95.5\%\;and\;93.8\%$. The 5-year overall (p=0.03) and disease-free survival (p<0.001) rates were $98.5\%\;and\;100%$ for low VEGF expression (0, +, and ++) and $85.5\%\;and\;79.7\%$ for high VEGF expression, respectively. Pelvic and distant failures for low versus high VEGF expression were $1.2\%$ versus $17.1\%$, (p=0.001) and $0\%$ versus $14.3\%$ (p<0.001), respectively. In a Cox multivariate analysis of survival, the high VEGF expression (p=0.02) and the bulky mass (p=0.02) were significant prognostic factors for overall survival. The high VEGF expression (p=0.002), and bulky mass (p=0.01) demonstrated as significant prognostic indicators for disease free survival. Conclusion : These results showed that VEGF expression was a highly significant predictor for pelvic and distant failure and the most significant prognostic factor of overall and disease free survival for the patients with stage IB cervix cancer treated with radical surgery. We strongly suggest that the immune-histochemistry for VEGF expression be performed in a routine clinical setting in order to identify the patients at high risk for poor prognosis in early stage cervical cancer. Furthermore, postoperative and/or chemotherapy did not reduce the pelvic failure and distant metastasis. To improve the cure rate for the patients with high VEGF expression in stage IB cervical cancer, antiangiogenic therapy including anti-VEGF Ab may be new treatment option.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.129-135
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• 1999

Purpose : This study evaluated early bowel complications in cervix cancer patients, following external radiotherapy (ERT and high dose rate intracavitary radiation (HDR ICR). Factors affecting the risk of developing early bowel complications and its incidence are analyzed and discussed Materials and Methods : The study is the retrospective review of 66 patients who received radiotherapy at Chungbuk National University Hospital from April 1994 to December 1998. The patients underwent 41.4 or 50.4 Gy ERT according to FIGO stage and tumor size, then A point dose was boosted to 71.4 or 74.4 Gy using a remotely controlled afterloading Buchler HDR ICR. The EORTC/RTOG morbidity criteria were used to grade early bowel complications, which are valid from day 1, the commencement of therapy, through day 90. The actuarial incidence, severity of complications were investigated and clinical pretreatment factors relevant to complications were found through univariate (Wilcoxon) and multivariate (Cox proportional hazard model) analysis. Results : Of the 66 patients, 30 patients (46$\%$) developed early bowel complications; 25 patients (38$\%$) with grade 1 or 2, 4 patients (0$\%$) with grade 3 and 1 patient (2$\%$) with grade 4. The complications usually began to occur 3 weeks after the commencement of radiotherapy. The actuarial incidence of early bowel complications was 41$\%$ at 10 weeks. The early bowel complications were associated significantly with an old age and a history of previous abdomino-pelvic surgery. All three patients who had a protracted overall treatment time (about 2 weeks) due to severe bowel complication, suffered from pelvic recurrences. Conclusion : Forty six percent of patients experienced early bowel complications, most of which were grade 1 or 2 and relieved spontaneously or by medication. The patients with an old age or a previous surgery have a high probability of early complications and they may be less compliant with planned radiotherapy. So more careful precaution is necessary for these patients.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.37-43
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• 2006

Purpose: We wanted to determine the clinical characteristics and prognosis according to the VEGF expression in stage II cervical carcinoma patients treated with definitive radiotherapy. Materials and Methods: We enrolled 31 patients who were diagnosed with cervical cancer from 1995 to 2003 at Samsung Medical Center and their paraffin block tissue samples were available for study. The median age of the patients was 65 years. The mean tumor size was 4.1 cm $(range:\;1.2{\sim}8.2cm)$. Seven patients (22.6%) were suspected of having pelvic lymph node metastasis. An external beam irradiation dose of 45-56.4 Gy was administered to the whole pelvis with a 15 MV linear accelerator, and an additional 24 Gy was given to point A by HDR intracavitary brachytherapy. VEGF staining was defined as positive when more than 10% of the tumor cells were stained. The median follow-up duration was 58 months. Results: A positive VEGF expression was observed in 21 patients (67.7%), There was no significant correlation between the VEGF expression and pelvic lymph node metastasis, tumor size and the response of radiotherapy. During follow-up, 7 patients had recurrence. The complete response rate was not significant between the VEGF(-) and VEGF(+) tumors. However, the VEGF(+) tumors showed a significantly higher recurrence rate in comparison with the VEGF(-) tumors (p=0.040), The three year disease-free survival rates were 100% and 66.7%, respectively, for patients with VEGF(-) or VEGF(+) tumor (p=0.047), Conclusion: The VEGF expression was a significant factor for recurrence and disease-free survival. However, the significance of the VEGF expression is still controversial because of the various definitions of VEGF expression and the mismatches of the clinical data in the previous studies.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.200-207
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• 2004

Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.210-216
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• 2007

There is increasing evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. The aim of our study is to analyze the relation between the increase in mast cell number and the expression CD34 and alpha-smooth muscle actin (${\alpha}$-SMA) in the stroma of cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). We investigated a total of 29 CIN (1,2,3) and 21 SCC (microinvasive and invasive) specimens and compared the distribution of $CD34^+$ stromal cells, ${\alpha}-SMA^+$ cells, transforming growth factor-${\beta}1$ $(TGF-{\beta}1)^+$ cells, and the density of mast cells using immunohistochemistry with antibodies against CD34, ${\alpha}$-SMA, TGF-${\beta}1$, and c-Kit (CD117) respectively. Computerized image analysis was to evaluate the positive area (%) and density of the respective immunoreactive cells. In CIN $CD34^+$ cells were abundant in the stroma but no ${\alpha}-SMA^+$ cells were identified except the wall of blood vessels. $CD34^+$ cells were progressively decreased along the continuum from CIN 2 to microinvasive SCC and not observed in the stroma of invasive SCC. Whereas ${\alpha}-SMA^+$ cells were only observed in the stroma of microinvasive and invasive SCC. We found more intense TGF-${\beta}1$ expression in the increased mast cells in the stroma of invasive SCCs than that in the stroma of CIN. These results indicate that disappearance of $CD34^+$ stromal cells and appearance of ${\alpha}-SMA^+$ cells are associated with the stromal change of CIN to SCC and the transformation of $CD34^+$ stromal cells into ${\alpha}-SMA^+$ cells is mediated by TGF-${\beta}1$ secretions in the stromal mast cell of SCC.