Cancer Research and Treatment

Original Articles

An Open-Label, Randomized, Parallel, Phase II Trial to Evaluate the Efficacy and Safety of a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel as First-Line Treatment for Ovarian Cancer: A Korean Gynecologic Oncology Group Study (KGOG-3021): Shin-Wha Lee, Yong-Man Kim, Chi Heum Cho, Young Tae Kim, Seok Mo Kim, Soo Young Hur, Jae-Hoon Kim, Byoung-Gie Kim, Seung-Cheol Kim, Hee-Sug Ryu, Soon Beom Kang; Cancer Res Treat. 2018;50(1):195-203. Published online March 21, 2017; DOI: https://doi.org/10.4143/crt.2016.376

Purpose
Genexol-PM is a biodegradable cremophor EL–free polymeric micelle formulation of paclitaxel. Here,we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment.
Materials and Methods
In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² with 5 area under the curve carboplatin every 3weeks (6 cycles). The primary endpointwas the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR).
Results
Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m² Genexol-PM or 174.24±3.81 mg/m² Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable.
Conclusion
Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.

Citations

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p53 Codon 72 Polymorphism and Cervical Adenocarcinoma Risk in Korean Women: Jeong Hwa Kim, Ju Won Roh, Kyung Sun Kim, Hyeon Jung Jung, Jae Weon Kim, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; Cancer Res Treat. 2001;33(3):243-249. Published online June 30, 2001; DOI: https://doi.org/10.4143/crt.2001.33.3.243

Abstract PDF: PURPOSE
This study was undertaken to analyze whether the p53 codon 72 single nucleotide polymorphism might be correlated with the risk and/or the prognosis of cervical cancer in Korean women.
MATERIALS AND METHODS
Peripheral blood samples derived from patients with cervical squamous cell carcinoma (SCC) (n=68), cervical adenocarcinoma (n=37), cervical intraepithelial neoplasia (CIN) III (n=98) and normal controls (n=98) were examined. Germline genomic DNA was extracted from peripheral blood leukocytes and examined by PCR amplification of the specific alleles assay described by Storey et al.5 Statistical analysis was performed using the Chi-Square test or the Kaplan-Meier survival analysis, logistic regression analysis.
RESULTS
The proportions of individuals who were homozygous for the proline allele, and heterozygous for the two allele, homozygous for arginine allele in each group were 15%, 47%, 38% in the SCC group; 6%, 7%, 24% in the adenocarcinoma group; 7%, 33%, 60% in the CIN III group; and 11%, 38%, 51% in the control group. No significant difference was found between the three groups (p>0.05). However there was a significant difference in the adenocarcinoma group (p<0.05). Arg/Arg homozygote reduced the risk of adenocarcinoma. No significant difference existed in 5-year survival rates in the three groups (p=0.22 in SCC, p=0.91 in adenocarcinoma).
CONCLUSION
These findings suggest that Arg/Arg homozygocity of the p53 codon 72 would be a protective factor against the development of cervical adenocarcinoma.

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p21WAF1/CIP1 Codon 31 Polymorphism in Korean Women: Association with Cervical Cancer Susceptibility and Prognosis: Ju Won Roh, Kyung Sun Kim, Jae Weon Kim, Moon Hong Kim, Hyun Hoon Chung, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 2000;32(6):1050-1058.

Abstract PDF: PURPOSE
The aim of this study was to determine whether certain genotype of p21WAF1/Cip1 might be associated with risk of cervical cancer in Korean women.
MATERIALS AND METHODS
We used the specimens derived from cervical cancer (n=111) composed of two histologic groups; SCCA (n=67) and adenocarcinoma (n=44), CIN III (n=101) and controls (n=98). For the determination of p21WAF1/Cip1 polymorphism, DNA was examined by PCR-RFLP using BsmAI. We compared the distribution of p21WAF1/Cip1 genotype of Korean women with that of other ethnic groups and analyzed the distribution of invasive cancer, CIN III and controls.
RESULTS
The genotype frequency of controls was different from that of Caucasian and Chinese (p<0.001) but similar to that of Japanese (p=0.21). There was no difference in the genotype frequency of p21WAF1/Cip1 among SCCA, CIN III and controls (p>0.05). A significant increase of Ser/Ser genotype was found in adenocarcinoma patients with high-risk HPV compared with the controls (p=0.009). The OR was 3.59, 95% CI=1.55~8.31, when comparing that group with controls. However, we could not find differences of prognosis.
CONCLUSION
We found that codon 31 Ser/Ser homozygote of the p21WAF1/Cip1 would be a risk factor for the adenocarcinoma of cervix associated with high-risk HPV in Korean women.

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Polymorphisms in E6 Gene of Human Papillomavirus Type 16 Found in Cervical Tissues from Korean Women: Jae Weon Kim, Ju Won Roh, Moon Hong Kim, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 2000;32(5):875-883.

Abstract PDF: PURPOSE
To examine the distribution of HPV 16 E6 polymorphisms and analyse the possible association between the polymorphisms and cervical cancer development in Korean women.
MATERIALS AND METHODS
Fifty-four cases of uterine cervical tissues containing HPV 16 DNA confirmed by polymerase chain reaction (PCR) from Korean women were subjected to investigate the E6 gene mutations. PCR-amplified products were sequenced by the fluorescent dideoxy ter mination method and the results obtained from sequencing were analysed. And newly designed PASA method was tried to develop rapid test for identification of the most commonly detected variation.
RESULTS
Among the 27 cervical cancer cases, only two (7.4%) was found as a prototype. Among 11 kind of variants identified in total, 4 variants (5 nucleotide sites) which were never reported before has been found, registered firstly to GenBank. The most frequently found variation was D25E, absolutely different from the previous reports from the western country. There was no statistically significant trend for the D25E variation to be more frequently detected in cancerous lesions than in noncancerous lesions. All of the DNA sequencing results observed could be confirmed by PASA method.
CONCLUSION
These results suggest that Korean-specific genetic factors might operate during the cervical carcinogenesis.

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The Inefficiency of Routine Performance of a Batch of Tests in the Clinical Staging Work-up of Cervical Carcinoma: Soon Sup Shim, Jae Weon Kim, Yong Beom Kim, Ju Won Rho, Chul Min Lee, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 2000;32(4):705-713.

Abstract PDF: PURPOSE
This study was to evaluate the efficiency of routine performance of a batch of tests in the clinical staging work-up of cervical carcinoma.
MATERIALS AND METHODS
The medical records were reviewed for 1,393 consecutive cervical carcinoma patients who underwent pretreatment staging work-up in Seoul National University Hospital from January 1988 to December 1997. The impression stage -which is designated ten tatively by the findings of pelvic examination and biopsy-, the results of staging work-up, and the finally allotted FIGO clinical stage were reviewed. The annual trend of stage distribution and the positive yields of tests were evaluated.
RESULTS
Annual trend shows that Ia is increasing. The positive yield of chest x-ray was 0.22% (3/1, 379; Ib: 1, IIa: 1, IIb: 1), intravenous pyelography (IVP) 2.50% (31/1, 242; Ib: 2, IIa: 4, IIb: 17, IIIb: 8), cystoscopy 0.55% (6/1, 093; IIb: 4, IIIb: 2), and proctosigmoidoscopy 0.086% (1/1, 157; Ib: 1). After completing the staging work-up, 29 patients (2.08%) were upstaged. The routine performance of IVP in impression stage Ia and cystoscopy in impression stage IIa or less was considered inefficient. The routine performance of proctosigmoidoscopy was considered inefficient because of its very low yield.
CONCLUSION
The selective performance of tests according to the impression stage during staging work-up is recommended to minimize the unnecessary treatment delay, cost, and patients' discomfort.

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p53 and bcl-2 Gene Expression in Gastational Trophoblastic Disease: Noh Hyun Park, Ju Won Roh, Jae Weom Kim, Yong Sang Song, In Ae Park, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1999;31(3):582-589.

Abstract PDF: PURPOSE
p53 and bcl-2 expressions are known as important cell survival factors and their levels of expression are related with patients prognosis in various human malignancies. But there are few data about p53 and bcl-2 expression and their role in the genesis of gestational trophoblastic disease (GTD). The aims of this study are to describe p53 and bcl-2 expression in normal trophoblast and hydatidifonn mole (HM), and to identify the role of p53 and bcl-2 in the genesis of gestational trophoblastic tumor (GlTI from HM.
MATERIALS AND METHODS
Paraffin-embedded tissue sections from 32 cases of HM and 9 cases of normal early pregnancy placentas were obtained. Of 32 HM patients, 15 cases were cured after molar evacuation (group A), and 17 cases progressed to GT1' (group B). p53 and bcl-2 immunohistochemical stainings were done and their reactivity were graded. The positive rates of p53 and bcl-2 overexpression among normal placenta, group A, and group B were compared and analyzed.
RESULTS
p53 mutant gene overexpression was more frequently detected in HM (68%) than in normal placentas (22%)(p<0.05). bcl-2 was overexpressed in 31% of HM and 11% of normal placenta, but the difference was statistically insignificant (P > 0.05). The difference in bcl-2 and p53 expression between group A and group B was not observed (P>0.05). There was no inverse relationship between p53 and bcl-2 expression in group A, and group B (P>0.05).
CONCLUSIONS
p53 gene mutation may play a mle in the process of HM development, but p53 and bcl-2 were not associated with the genesis of GTI' from H-mole. More studies are needed to identify the molecular process in the progression of the GTD.

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Analysis of 38 Cases of Metastatic Cancer of Ovary: Jae Ho Yum, Jae Weon Kim, Yong Beom Kim, Chul Min Lee, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1999;31(3):575-581.

Abstract PDF: PURPOSE
The relative ftequency of ovarian metastases from various organs reported in literature varies with geographic distribution. To our knowledge, there has been no comprehensive report on the subject of metastatic cancer to the ovary in Korea, so we tried to evaluate the clinical characteristics of them.
MATERIALS AND METHODS
We reviewed the files of the Department of Pathology from January 1988 to December 1997 in Seoul National University Hospital and obtained 38 cases diagnosed as metastatic cancer to ovary. We retrospectively reviewed the patients' records and evaluated the clinical characteristics, treatment modalities and clinical outcome.
RESULTS
The mean age of patients was 43.7 years (range: 19-63) and the most common symptom was pelvic pain (21.1%). The origins of primary cancer were as follows in the order of frequency: stomach (65.8%), colon (13.2%), unknown (10.5%), hematologic malignancy (7.9%) and lung (2.6%). The most common pathologic findings were metastatic adenocarcinoma in 34 cases (89.5%), among which 14 cases (36.8%, 14/38) were Krukenberg tumor. The origins of primary cancer were diagnosed preoperatively in only 18 cases (47.4%). Eleven patients (28.9%) received surgery only, while 27 patients (71.1%) received both surgery and adjuvant chemotheiapy. For all patients, the median survival was 17 (range: 11-23) months and the overall 3-year survival rate (3YSR) was 28.6%. There were no significant differences in 3YSR according to primary tumor sites, status of ovarian involvement, pathologic finding, diagnostic time and treatment modalities.
CONCLUSION
Although the overall survival rate and clinical factors which might affect survival were similar to previous reports from Westem countries, the most common origin of primary cancer was different.

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Comparison of HPV 16 Sequence Variations at Upstream Regulatory Region in the Couples of Patients with Cervical Cancer for Determination of HPV Infectivity: Jae Weon Kim, Yong Sang Song, Hye Won Jeon, No Hyun Park, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1999;31(2):403-410.

Abstract PDF: PURPOSE
Although it is now generally accepted that human papillomaviruses (HPVs) are causally related to cervical neoplasia by plentiful epidemioiogic and experimental works, little is known about the direct evidence of sexual transmission of HPV. This study was undertaken to confirm the transmission route and determine the infectivity of HPV by comparison of HPV 16 sequence variations at upstream regulatory region (URR) in the couples of patient with cervical cancer.
MATERIALS AND METHODS
HPV DNAs obtained from genital lesions of forty married couples of patients with cervical cancer were evaluated by polymerase chain reaction (PCR) and PCR-directed sequencing.
RESULTS
HPV 16 was detected in fourteen (63.6%) of twenty-two male consorts whose wives were positive for HPV 16. Of these, six (42.9%) couples demonstrated identical HPV 16 URR variants between patients and male consorts, and eight had mismatching HPV 16 URR sequences. Among six couples showed matching HPV 16 variants, three couples mamed for 10, 19, 25 years respectively carried variant 7728/7779, two couples married for 15 years each carried variant 7728/7762, and one couple married for 18 years carried variant 7728/7797, CONCLUSION: These data suggest that sexual transmission of HPV 16 does occur. A search for more HPV variants in a large cohort is needed to secure high level of precision in molecular epidemiologic study using HPV variant.

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Cytologic Screening History of 249 Patients with Cervical Cancer: Jae Weon Kim, Sok Bom Kang, Dong Ki Seo, Soo Hee Choi, Chul Min Lee, Yong Beom Kim, No Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1998;30(6):1198-1206.

Abstract PDF: PURPOSE
Cervical neoplasias are known to be preventable. But the outcome of our efforts for early detection in Korea is disappointing. This study was undertaken to determine the level of screening participation in Korean women with cervical cancer and how the early detection of cervical cancer might be improved.
MATERIALS AND METHODS
Two hundred and forty-nine women with cervical cancer diag- nosed and treated at Seoul National University Hospital from September 1996 to February 1998 were subjected to this study. Self-reported cervical cancer screening histories, med- ical records obtainable were reviewed and analysed.
RESULTS
One hundred forty-seven women (147/249; 59.0%) hadn't got through the screen- ing at proper intervals. Ninety-nine women (39.9%) had never been screened and remain- ing 48 (19.3%) hadn't had their last Pap test 3 years before their diagnosis of nvasive cancer. Of the 150 women (60.1%) who had ever had a Pap test, only 47 (18.9%) had had annual Pap test during recent 5 years and 55 (22.1%) had had routine Pap test with interval between 1-3 years. Among 102 women who had at least one Pap test during recent 3 year, 73 (71.6%) had had a normal Pap report within three years of diagnosis, including 36 (35.3%) whose last normal Pap report was within a year of diagnosis. This results suggest the possibilities of smear-taking and/or reading errors. Women who had had routine Pap with interval less than 3 years had significantfy less chance of advanced tumor (FIGO stage Ib < ) than unscreened population. There was a statistically significant trend for the more younger and educated groups to be participated at the screening program with more shortened interval. All the other factors had failed to show significant correlation with adequacy or regularity of screening interval.
CONCLUSIONS
Despite widespread chance of opportunistic cervical cancer screening, non-participants form the main reason for the failure of cervical cancer screening in Korea. So, far much efforts should be aimed at participating more women in cervical cytologic screening program, especially in the old-aged and less-educated groups.

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Change of the Antigenecity of Human Papillomavirus Type 16 E7 Oncoprotein according to Phosphorylation: No Hyun Park, Sun Ho Kee, Joo Won Noh, Jae Weon Kim, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1998;30(2):313-320.

Abstract PDF: PURPOSE
It was suggested that immunogenic region of E7 proteins of human papillo- mavirus (HPV) type 16 encompass casein kinase (CK) II phosphorylation site and the resulting negative charge may affect the various biologic function of E7 protein. This study was undertaken to analyze the change of antigenic characteristics of HPV type 16, E7 oncoprotein according to phosphorylation.
MATERIALS AND METHODS
We produced two monoclonal antibodies (VD6 and IB10) which showed different reactivities to E7 proteins expressed from bacteria or extracted from CaSki cell. These reaction were analyzed by Western blotting. Also the antigenic sites estimation of these antibodies using nested deletion sets was done. On the basis of above experiments, we performed in vitro phosphorylation assay using CK II and its specific inhibitor, DRB (5, 6-dichloro-l-beta-D-ribofuranosylbenzimidazole), to analyze the IB10 reactivity to E7 oncoproteins according to phosphorylation.
RESULTS
In Westem blot analysis, VD6 and IB10 antibodies reacted strongly to bacterially expressed E7 protein. But using E7 extracted from CaSki cell, VD6 reacted to 2.0 kDa E7 protein whereas IB10 showed weak reactivity. The antigenic sites estimation of these antibodies showed that antigenic site of VD6 was located in amino terminal region and that of IB10 in the middle portion in the range of approximate amino acid 25-45. The antigenic site of IB10 might contain the possible phosphorylation sites (Ser-31, 32) in E7. Considering this, the different reactivities of IB10 to E7 proteins expressed in bacteria and extracted from CaSki cell might be due to phosphorylation. In in vitro phosphorylation assay using CK II, the phosphorylation of E7 increased according to reaction time. And this phosphorylation reduced the reactivity of IB10 to E7 protein whereas the reactivity of VD6 did not change. Also the reactivity of IB10 to E7 protein increased in a dose dependent manner with CK II specific inhibitor, DRB treated CaSki cell extracts.
CONCLUSION
These result showed the antigenecity is affected by the degree of phosphorylation of E7 protein.

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Germline Mutation of BRCA2 Gene in Korean Breast / Ovarian Cancer Families: Yong Jin Won, Jae Hwan Oh, Ji Hyun Kim, Dong Young Noh, Kuk Jin Choe, Soon Beom Kang, Lee Su Kim, Man Su Ro, Nam Sun Paik, Dae Hyun Yang, Se Min Oh, Soon Nam Lee, Kyung Kook Kim, Jae Gahb Park; J Korean Cancer Assoc. 1998;30(2):242-252.

Abstract PDF: PURPOSE
Recent discovery of BRCA1 and BRCA2 genes has made it possible to perform presymptomatic diagnosis in hereditary breast/ovarian cancer families. We have previously reported germline mutations of the BRCA1 gene in Korean hereditary breast/ovarian cancer families. In that study two out of 13 families were found to have germline mutations in BRCA1 gene. One was a nonsense mutation in codon 1815, and the other was a frameshift mutation due to 2 base-pair deletion in codon 1701 of BRCA1 gene. This study was intended to identify germline mutations of the BRCA2 gene in Korean breast/ovarian cancer families.
MATERIALS AND METHODS
Peripheral blood DNA was obtained from 10 breast cancer patients registered at the Korean Hereditary Tumor Registry with positive family history of breast and/or ovarian cancer. Exons 11 and 27 of the BRCA2 gene(together accounting for 50% of the coding region of the BRCA2 gene) were amplified by polymerase chain reaction(PCR) and screened for mutations by in vitro transcription/translation method. For confirmation of the mutations, automatic sequencing of the PCR products displaying abnormal truncated protein bands was perfomed.
RESULT
We identified an abnormal truncated protein in the exon 11 of the BRCA2 gene from a member of hereditary breast cancer family, SNU-B4. Sequencing analysis revealed a 4 bp deletion in codons 1248-49 of the exon 11, resulting in frameshift that led to premature stop codon and truncation of the protein product.
CONCLUSION
We have identified a germline mutation from a Korean hereditary breast cancer family. So far only one case of the same mutation has been registered in Database of BRCA2 mutation (BIC) by a commercial genetic diagnosis company, Myriad Genetics, Inc. Identification of the germline mutation in BRCA2 gene should aid in the accurate presymptomatic diagnosis of the at-risk members in this family.

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Germline Mutations of BRCA1 Gene in Korean Breast and/or Ovarian Cancer Families: Yong Jin Won, Jae Hwan Oh, Xiao Hong Huang, Dong Young Noh, Kuk Jin Choe, Soon Beom Kang, Lee Su Kim, Man Su Noh, Nam Sun Paik, Dae Hyun Yang, Se Min Oh, Soon Nam Lee, Jae Gahb Park; J Korean Cancer Assoc. 1997;29(5):713-723.

Abstract PDF: PURPOSE
To understand the involvement of BRCA1 gene in Korean breast and/or ovarian cancer families.
MATERIALS AND METHODS
Germline mutations of BRCA1 gene were analyzed in 13 families which included 3 hereditary site-specific breast cancer families, 6 suspected breast cancer families, and 3 suspected breast-ovarian cancer family, and one Li-Fraumeni family by screening BRCA1 gene using single strand conformation polymorphism (SSCP) analysis on polymerase chain reaction (PCR) amplified genomic DNA and confirmed the results by sequencing.
RESULTS
Including one family with previously reported nonsense mutation of BRCA1 gene, we detected two mutations in unrelated families. One newly identified mutation was frame shift mutation resulting from TG deletion in codon 1701, which results in a truncated BRCA1 protein, at codon 1714.
CONCLUSION
The proportion of families who inherit the mutated BRCA1 gene seems to be small among Korean breast and/or ovarian cancer families.

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Clinical and pathologic characteristics of uterine sarcoma: Soon Beom Kang, Jong Hyeok Kim, Sung Gi Son, Joong Shin Park, Hyo Pyo Lee; J Korean Cancer Assoc. 1991;23(4):769-776.

Abstract PDF: No abstract available.

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Value of PAPAN score as parameter of subrenal capsule tumor implant assay in gynecological malignant tumors: Soon Beom Kang, Jong Hyeok Kim, Dong Geun Chung, Kyoung Hoon Cho, Seung Chul Kim, Hyo Pyo Lee; J Korean Cancer Assoc. 1991;23(4):728-739.

Abstract PDF: No abstract available.

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Establishment of SNUH Cell Lines in Serum - free Defined Medium and SNU Cell Lines in Serum Supplemented Medium: Jae Gahb Park, Nam Sook Kwon, Jin Pok Kim, Seung Keun Oh, Kuhn Uk Lee, Kuk Jin Choe, Soo Tae Kim, Yung Jue Bang, Noe Kyeong Kim, Soon Beom Kang, Myon Woo Shin, Sang Hoon Lee, Joo Hyun Kim, Chong Wook; J Korean Cancer Assoc. 1988;20(2):105-117.

Abstract PDF: Serum-free, defined medium ACL-4 has proven to be useful for the establishment and maintenance of human colorectal carcinoma and lung adenocarcinoma cell lines. To determine the general usefulness of ACL-4 as a medium for establishing cell lines, we compared the growth of cells from many different tumor specimens in R10, ACL-4 and AR5 (ACL-4 plus 5% FBS). From June 1987 to July 1988, 69 specimens from a wide variety of human tumors were cultured in R10 and ACL-4 or AR5. Eleven cancer cell lines were established ...... seven cell lines (4 stomach carcinoma, 1 rectal carcinoma, 1 ovarian carcinoma, 1 osteosarcoma) in R10; two cell lines (1 uterine cervical cancer, 1 laryngeal carcinoma) in ACL-4; and two cell lines in AR5 (1 colon carcinoma, 1 rectal carcinoma) (Table I & 2). Of interest, two B lymphoblastoid (non-neoplastic) cell iines were established from a stomach cancer and an acute myeloblastic leukemia specimen grown in ACL-4. We have found that sodium pyruvate, transferrin, and insulin were very important for the growth of uterine cervical cancer cells. Early in this study, we also found that fibroblast growth was effectively suppressed by culturing tumor cells in the serum free medium ACL-4. Therefore, in later attempts, when possible loss of cultures by fibroblast overgrowth was observed, serum containing media were replaced by ACL-4 to suppress and eventually eliniinate the fibroblast contamination. Although we were able tu establish only 11 new cancer cell lines from 69 specimens, our study has extended the use of ACL-4 medium with or without serum for the growth of uterine cervical and laryngeal cancer cells.

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Clinico - pathological Study of Endometrial Cancer in Seoul National University Hospital: Soon Beom Kang, Dong Geun Chung, Seung Cheol Kim, Hyo Pyo Lee, Myon Woo Shin; J Korean Cancer Assoc. 1988;20(2):160-172.

Abstract PDF: Clinical and pathological studies were performed on 56 patients with endometrial cancer who were diagnosed and treated in the Department of OB/GY of Seoul National University Hospital from Jan. 1975 ta Dec. 1986. The results were as follows; 1) Of 56 cases, 17 (30.4%) were in stage la, 22 (39.3%) in stage Ib, 5 (8.9%) in stage II, 10 (17.9%) in stage III, and 2 (3.6%) in stage IV according to FIGO classification. 2) The average age was 54.2 and the range 28 to 73. 3) Forty two (75.0%) patients were postmenopausal and the average menopausal age was 49.8 years. 4) All cases except two were symptomatic and in 51 (91.9%) cases, abnormal vaginal bleeding was noted as a chief complaint. 5) The major complications were obesity (37.5%), hypertension (48.2%), diabetes mellitus (16.1%), and irifertility (23.2%). In 5 cases (8.9%), obesity, hypertension, and diabetes mellitus were complicated at the same time. 6) When the depth of the invasion was classified into 3 grades, less than 1/3 of the muscular layer, between 1/3 and 2/3, and over 2/3 in 52 cases examined, they were observed in 15 (2S.8%), 9 (17.3%), 14 cases (26.9%) respectively. And in 14 cases (26.9%), there was no myometrial invasion and the cancer was limited within the endometrium. 7) There were 2 cases (11.1%) with lymph node involvement in 18 cases examined. In one case, the depth of myometrial invasion was less than I/3, and in another case, the depth of invasion was over 2/3. And the histological grade of these cases was G2 in both. 8) The three year survival rate was 69.7% (23/33) for all cases. The clinical stage and age of the patients may be correlated with t.he prognosis of the endometrial cancer (p<0.05). 9) The three year survival rate for the group treated by surgical treatment with pelvic lymph node dissection was 100% (9/9) which was significantly higher than the 68.2% (15/22) of the group treated by simple hysterectomy (p<0.05). We can think that the effort to diagnose the endometrial cancers in the earlier clinical stages and the surgical treatment with pelvic lymph node dissection may improve the prognosis of the endometrial cancer.

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신피막하 종양이식 분석법에 의한 부인과악성 종야의 화학감수성 검사에 관한 연구: Soon Beom Kang, Kyeong Hoon Cho, Pil Ryang Lee, Seung Cheol Kim, Young Min Choi, Hyo Pyo Lee, Dong Geun Chung, Noe Kyeong Kim, Jae Gahb Park, Seong Hoe Park; J Korean Cancer Assoc. 1990;22(1):24-32.

Abstract PDF: The chemosensitivity testing is important in the research of cancer biology, development and screening of anticancer drug, and improvement of chemotherapy modalities. Subrenal capsule tumor implant assay (SRCA) is a promising rapid method in the selection of individual chemotherapy for cancer patients clinically. A total of 100 SRCA were performed with several gynecologic malignancies(69 cervical, 10 ovarian, 10 endometrial carcinomas, 6 vulva carcinoma, 4 sarcoma, and 1 choriocarcinoma). 1 mm x 1 mm x 1 mm fragments oi fresh human gynenologic tumors were implanted under the renal capsule of immunocompetent female adult BALB-C mice and tested against several chemotherapeutic agents or their combinations. An average of 75% of tumors showed positive growth. The evaluable assay rate was 91%(91/100). Variable response rate were noted in each gynenologic tumor. An overall predictive accuracy rate of SRCA was 73% in present series. In conclusion, the SRCA is considered as a reliable in vivo clinical chemosensitivity test in the selection of individual cancer chemotherapy.

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Krukenberg Tumors of the Ovary : A Clinical Analysis of 16 Cases: Soon Beom Kang, No Hyun Park, Young Min Choi, Hyo Pyo Lee; J Korean Cancer Assoc. 1990;22(1):194-202.

Abstract PDF: The records of ovarian tumor registry in the SNUH were reviewed from 1983 to 1987. The charts of the patients diagnosed as Krukenberg tumors were screened as to clinical history, physical and operative finding, postoperative chemotherapy and so forth. The survival data was analyzed by Kaplan-Meier method. The results were as follows. 1l The incidence of Krukenberg tumors in all neoplastic ovarian tumors and all malignant ovarian tumors was 3.78% (16/421) and 10.96% (16/146) respectiveIy. 2) The average age was 41.4+8.4 years with range from 28 to 61. 3) The most common presenting symptoms, abdominal pain, gastrointestinal symptoms, abdominal distension, postmenopausal bleeding in order. 4) Except one of unknown origin, primary tumor was all found in the stomach. 5) The largest tumor f ound was 1,080 g and measured 17 x 13 x 8 cm, and the sma 1 lest was 8 g and measu red 3 x 1.5 x 1 cm. 6) Among the cases that could be evaluated for bilaterality, both ovaries were involved in 92.9(13/14). 7) Among the cases that stomach cancer occured prior to Krukenberg tumor (7 cases), the average interval from the diagnosis of stomach cancer to the diagnosis of Krukenberg tumor was 24 4+15. 7 months (range from 10 to 60 months) B) Chemotherapy was performed in ll cases and the regimens are FAM (5 FU, Adriamycin, Mitomycin), FP (5--FU, Cisplatinum), VPB (Vincristin, Cisplatinum, Bleomycin).and FM (5 FU, Mitomycin). 9) The 6 manth, 9-month, 15 month survival rate by Kaplan-Meier method was 66%, 44% 29% respectively Until now there is little hope to cure this disease. But it is possible to improve survival rate by early diagnosis, operation and combination chemotherpy.

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Cislatin , Vincristine , Bleomycin and Methotrexate ( PVBM ) Combination Chemotherapy for Advanced Uterine Cervix Cancer: Young Hyuk Im, Kee Hyung Lee, Young Suk Park, Chang In Suh, Won Ki Kang, Hyo Jin Kim, Heung Tae Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim, Soon Beom Kang, Hyo Pyo Lee, Jin Yong Lee, Seung Wook; J Korean Cancer Assoc. 1990;22(3):505-518.

Abstract PDF: Twenty-nine patient with advanced cervix cancer were treated with a combination chemotherapy of cisplatin, vincristine, bleomycin, and methotrexate between January, 1987 and December, 1988. 1) Among 19 evaluable patients, 4 patients (20.1%) achieved complete response and 6 patients (31. 6%) achieved partial response, giving an overall response rate of 51.7%. The median duration of remission was 23 weeks in the responders. 2) The median survival of overall patients was 50 7 weeks. The median survival of the responders did not reach the median value during the follow-up period of 15-81 weeks. In contrast, the median survival of the non-responders was 30.7 weeks, which was significantly shorter than that of the responders (p<0.05). 3) The only factor influencing remission rate was the pattem of failure, and the patients with distant metastasis showed higher remission rates (p<0.01). There were no prognostic factors influencing the remission duration. The factors improving survival rates were the early stage at diagnosis (p< 0. 005), the previous history of curative operation (p<0.005), and the presence of distant metastasis (p<0.01). 4) Considerable number of patients experienced toxicities. Among these, leukopenia (50%) and thrombocytopenia (4.7%) were the main hematologic toxicities. Most patients experienced nausea, vomiting, diarrhea (89.49o), stomatitis (26 3%), and alopecia (73.7%). Neurotoxicity due to vincristine or cispatin was found in 36.896 of patients, and 2 patients showed pulmonary fibrosis due to bleomycin toxicity. In conclusion, this regimen (PVBM) seems to be effective in terms of remission rates, but did not show any additional benifits in terms of remission duration or overall survival. In addition, the large number of patients experienced considerable side effects. Based on these findings, further studies are needed to find out the new regimen which is more effective and less toxic for the patients with advanced uterine cervix cancer.

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Germline Mutation of BRCA1 Gene in Korean Breast and Overian Cancer Patients: Jae Hwan Oh, Dong Young Noh, Kuk Jin Choe, Soon Beom Kang, Lee Su Kim, Man Su Ro, Nam Sun Paik, Dae Hyun Yang, Se Min Oh, Soon Nam Lee, Jae Gahb Park; J Korean Cancer Assoc. 1995;27(6):1061-1070.

Abstract PDF: We analyzed germline mutations of the BRCAl gene in 29 Korean breast cancer patients, which included ¨c 10 breast cancer patients with family history of breast or ovarian cancer, ¨e 7 early onset breast cancer patients without family history of breast or ovarian cancer(1ess than 40 years old at diagnosis) and ¨e 12 breast cancer patients without family history of breast or ovarian cancer(more than 40 years old at diagnosis), and 1 hereditary ovarian cancer patient. One nonsense mutation at codon 1815 encoding a truncated protein was detected in a breast cancer patient with family history of ovarian cancer. One missense mutation at codon 1630 was detected in a group of breast cancer patients without family history(more than 40 years old at diagnosis), but still not determined whether it was polymorphism or not. Three polymorphisms were detected, which included 2 cases of silent mutation and a case of missense mutation. In early onset breast cancer group and a familial ovarian cancer patient, there was no detected mutation. We confirmed a germline BRCAl gene mutation in one Korean patient of hereditary breast-ovarian cancer family.

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The Association of p53 Mutation with Human Papillomavirus Type 16 , 18 Infection and its Clinical Significance: Chang Soo Park, Yong Sang Song, Chang Won Koh, Hye Won Jeon, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 1996;28(1):122-138.

Abstract PDF: Recent several studies have suggested that inactivation of p53 gene could occur by two theoretical mechanisms in cervical cancer. The E6 transforming protein of oncogenic human papillomavirus(HPV) binds to and promotes the degradation of p53 protein, or the mutation of the p53 gene could result in its inactivation without HPV infection. The purpose of this study were to investigate HPV infection and p53 mutation according to the status of lymph node metastasis and to analyse the relationship and role of HPV infection and p53 alteration in the advance and metastasis of cervical cancer. Paraffin embedded tissue sections were obtained from 30 patients with cervical cancer, each l5 patients with or without lymph node metastasis. The PCR and Southern blotting were used for the detection of HPV l6/18 DNA. Alteration of p53 activity was evaluated by immunohistochemistry using MAb DO7 and polymerase chain reaction with single stranded conformation polymorphism(PCR-SSCP). There was no significant difference in HPV infection between two groups, 73.3%(l l/15) in negative lymph node group and 80.0%(l2/15) in positive lymph node group. Although by immunohistochemistry p53 alterations were found more frequently in positive lymph node group(46.7%) than in negative lymph node group(20.0%), there was no significant difference between two groups. HPV negative cervical cancers had more p53 alterations(57.l%) than HPV positive cervical cancers(26.1%). However, there was no significant inverse relationship between HPV infection and p53 alteration. In conclusion, these data suggest that HPV infection and p53 alteration may play an important role independantly in the development of cervical cancer and p53 alteration may be associated with the advance and metastasis in some cases.

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