Cancer Research and Treatment

Isolation of Differentially-Displayed cDNAs from a Doxrubicin Resistant Gastric Carcinoma Cell Line: Myung Soo Kang, Jae Ho Lee, Jae Gahb Park; J Korean Cancer Assoc. 1998;30(4):625-631.

Abstract PDF: PURPOSE
This study was aimed to isolate cDNAs putatively associated with doxorubicin resistance or sensitivity in gastric carcinoma cell line.
MATERIALS AND METHODS
A doxorubicin-sensitive parental SNU-16 and doxorubicin resistant SNU-16DOX cell line were used. Differential display-PCR(DD-PCR) was employed to screen for differentially expressed cDNA fragment either in parental or resistant cell line and followed by subtractive hybridization to discriminate true positive from false positive clones. The sequences were determined and compared to the sequence data base registered at the GenBank.
RESULTS
Four clones(16, 19, 21, and 22 clone) were isolated, of which three(16, 19 and 21 clone) was downexpressed, and one(22 clone) was overexpressed in doxorubicin resistant cell line. All four clones were found to be novel sequences. Further analysis for these clones are under characterization.
CONCLUSION
Four partial cDNA clones that are putatively associated with doxorubicin resistance or sensitivity in gastric carcinoma cell line were isolated.

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The Prognostic Significance of Tumor Microvessel Density in Gastric Carcinoma: Jung Kyun Lee, Hyung Bae Moon; J Korean Cancer Assoc. 1998;30(4):632-638.

Abstract PDF: PURPOSE
This study was carried out to evaluate the relationship with other clinicopathologic factors and prognostic significance of tumor microvessel density in gastric carcinoma.
MATERIALS AND METHODS
Eighty three cases of primary gastric carcinoma(stage 1b, II, and III) were analysed retrospectively who underwent curative gastrectomy at Wonkwang university hospital from July, 1987 to June, 1992. Tumor microvessels were stained by immunohistochemical method using anti-CD31 on paraffine embedded tissues, and were counted within 10x objective field(about 0.74 mm2) in the area of the most intense neovascularization.
RESULTS
The overall 5 year survival rate was 57.8%. Depth of invasion, lymph node metastasis, and stage were the prognostic factors(p < 0.05). Mean microvessel count(MVC) was 34.4+/-14.4(range 10~72). MVC was 36.6 in 56 cases of tumor diameter <6cm and 30.0 in 27 cases of diameter > or =6 cm(p=0.049), 33.3 in 45 cases of well differentiated type, 32.9 in 30 cases of poorly differentiated type, and 41.5 in 8 cases of signet ring cell type(p 0.042). But there was no significant difference of MVC between other parameters such as age, sex, tumor location, gross finding, depth of invasion, lymph node metastasis, and stage. The 5 year survival rates of 47 cases of MVC < or = 34 and 36 cases of MVC >34 were 59.6% and 55.6% respectively(p>0.05). There was no significant difference between 5 year survival rates of MVC < or =34 group and >34 group adjusted for other parameters.
CONCLUSION
Tumor microvessl density may related with tumor size and histologic type, and have no significance in 5 year survival rates of gastric carcinoma.

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Results of Hyperthermic Treatment Combiced with Radiotherapy/Chemotherapy in Locally Advanced Inoperable Gastric Cancer: Chang Woo Moon, Ha Yong Yeom, Tae Sik Jung, Young Ho Kim, Ja Young Koo; J Korean Cancer Assoc. 1998;30(4):639-651.

Abstract PDF: PURPOSE
This retrospective study is conducted to evaluate the local response rate, survival rate, median survival times and complication of hyperthermic treatment combined with radiotherapy/chemotherapy in locally advanced inoperable gastric cancer.
MATERIALS AND METHODS
One hundred and twenty-seven patients treated with hyperthermia from April, 1992 to December, 1994 were enrolled. Among 127 patients, 13(10.2%) were treated with thermo-radiotherapy(Group I), 4(3.1%) were treated with thermo-radio-chemotherapy(Group II) and 110(86.6%) were treated with thermo-chemotherapy (Group III). Hyperfractionated radiotherapy(135 cGy/fr., 2 times/day) using 6-MV X-ray Linac was delivered with total doses of 40.5~67.5 Gy(median: 45 Gy). Chemotherapy by FI(5-FU+ Interferon) or EAP(Etoposide+ Adriamycin+ Cisplatin) regimens was administered. Hyperthermia using 8-MHz RF(radiofrequency) capacitive heating eqiupment (CANCERMIA GHT-8) was applied with interval of 2 times/week, 40~60 minutes /session within 10~15 minutes following radiation, and was simultaneously done with chemotherapy. The estimation of local response was used computed tomography and endoscopy, and was divided into complete response(CR), partial response(PR), and no response(NR). The survival rate was calculated by Kaplan-Meier method.
RESULTS
Overall local response rate(CR+ PR) was 68.5% with 6.3% in CR and 62.2% in PR. The local response rates by treatment modality were 92.3% (CR: 15.4%, PR: 76.9%) in Group I, 100%(CR: 75.0%, PR: 25.0%) in Group II and 64.5%(CR: 2.7%, PR: 61.8%) in Group III. There was statistically significant difference(p=0.0001). The overall 1 and 2 years survival rates with median survival time(MST) were 20.5%, 7.1% with 9 months, respectively. The overall 1 and 2 years survival rates(with MST) by treatment modality were 7.7%, 0%(7 months) in Group I, 50.0%, 0%(9 months) in Group II and 20.9%, 8.2%(6 months) in Group III. There was no statistically significant difference. The incidence of side effect by heating was 3.1%(4 patients) and the most serious side effect was subcutaneous fat necrosis in anterior abdominal wall.
CONCLUSION
From this study we concluded that hyperthermic treatment combined with radiotherapy/chemotherapy may increase the local response rate in locally advanced inoperable gastric cancer.

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Clinicopathologic Features of Multiple Synchronous Gastric Cancer: Jin Bok Kim, Min Kyu Choi, Joo Ho Lee, Seung Ik Ahn, Soo Jin Kim, Hang Jong Yu, Han Kwang Yang; J Korean Cancer Assoc. 1998;30(4):652-659.

Abstract PDF: PURPOSE
With recent advances of diagnostic methods and precise histopathologic examination, the incidence of synchronous multiple gastric cancer has increased. The purpose of this study was to evaluate the clinicopathologic features of patients with synchronous multiple gastric cancer.
MATERIALS AND METHODS
We reviewed the clinicopathologic features of 189 patients with synchronous multiple gastric cancer out of 8,101 patients who underwent gastric resections for gastric cancers during 20 years from January 1977 to December 1996 at the Department of Surgery, Seoul National University Hospital, and compared them with single gastric cancer patients. The clinicopathologic features evaluated were age, sex, diagnostic method and accuracy, location of lesions, tumor size, histologic differentiation, Lauren classification, macroscopic classification, depth of invasion, lymph node metastasis, TNM stage, and type of operation and prognosis.
RESULTS
The overall incidence of multiple synchronous gastric cancer was 2.33%. The mean age was 57.2 years old (27~84) and peak incidence was sixth decade. Male was predominant, that the sex ratio was 3.9: 1. Multiple gastric cancer was more frequent in old age, male and early gastric cancer patients. The number of lesions ranged from 2 to 5. In most cases, the lesions were located in lower two-thirds of the stomach. However, in 13 cases, lesions were located in both upper one-third and lower one-third. Only 33.3% of multiple cancer was diagnosed preoperatively, with the diagnostic accuracy of GFS was 30.0% and that of UGIS 26.1%. The most frequently missed lesions at preoperative examination were located in upper third of stomach, posterior wall of middle third and anterior wall of lower third of stomach. The most common macroscopic type was Borrmann type III (54.5%) in advanced lesions and type IIc (47.0%) in early lesions. Regarding the histologic differentiation, 58.7% of the cases were of the same differentiation and the cases composed of well differentiated adenocarcinomas were most common. According to the Laurens classification, 66.7% of lesions were intestinal type. As to the progression of the lesions, all lesions were early cancers in 75 cases, advanced cancers in 39 cases and advanced cancers were coexist with early cancers in 75 cases. Lymph node metastasis was less frequent than in single gastric cancer. Total gastrectomy was performed more frequently in multiple cancer patients than in single gastric cancer patients. The 5-year survival rate of patients with multiple gastric cancer was 70.2%, which was not significantly different from that of patients with single gastric cancer.
CONCLUSIONS
Surgeons must keep in mind the possibility of multiple gastric lesions. More careful preoperative and intraoperative examination is mandatory to detect the possible accessory lesions, and postoperative periodic follow-up is necessary to detect any missed lesions, especially in the old age, male and early gastric cancer patients.

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Immunohistochemical Study on the Expression of p53 and bcl-2 Protein in Gallbladder Adenocarcinoma: Joon Hyuk Choi, Young Ran Sim, Won Hee Choi; J Korean Cancer Assoc. 1998;30(4):660-667.

Abstract PDF: PURPOSE
This study was carried out to evaluate the expression of p53 and bcl-2 protein in the adenocarcinoma of gallbladder.
MATERIALS AND METHODS
Thirty three cases of adenocarcinoma of gallbladder were immunohistochemically stained for p53 and bcl-2 protein.
RESULTS
p53 protein was expressed in 51.5%(17/33) of adenocarcinoma. p53 protein expression was not significantly correlated with histologic grade of adenocarcinoma, depth of invasion, lymph node metastasis, distant metastasis and TNM stage, respectively(p>0.05). bcl-2 protein was expressed in 12.1%(4/33) of adenocarcinoma. bcl-2 protein expression was not significantly correlated with tumor size, histologic grade, depth of invasion, lymph node metastasis, distant metastasis and TNM stage, respectively(p>0.05). There is no correlation between expression of p53 and bcl-2 in gallbladder adenocarcioma(p > 0.05).
CONCLUSION
This study suggest that p53 gene mutation plays an important role in carcinogenesis of gallbladder adenocarcinoma. The role of bcl-2 protein in gallbladder adenocarcinoma may be not significant.

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Multiple Primary Malignant Neoplasm with Colorectal Cancer: Hee Chul Kim, Chang Nam Kim, Chun Sik Jung, Chang Sik Yu, Jin Cheon Kim; J Korean Cancer Assoc. 1998;30(4):668-674.

Abstract PDF: PURPOSE
The incidence of multiple primary malignant neoplasm has increased in recent decades. The etiologies and epidemiologies of multiple primary malignant neoplasm are still remained to be verified. A group of patients with multiple primary malignant neoplasms accompanied by colorectal cancer was analyzed to determine the relationship between certain cancers and colorectal cancer.
MATERIALS AND METHODS
From Jan. 1989 to Jun 1997, there were 56 patients with colorectal cancers accompanied by cancers of another organs. The retrospective analysis was done on the basis of cancer origin and intervals between the cancers.
RESULTS
The male-to-female ratio was 25 to 31. The characteristics of colorectal cancers in multiple primary malignant neoplasm were similar to the colorectal cancers without other cancers. Among 56 patients, 50 patients had the double primaries and 6 had the triple primaries. In the patients with double primaries, extracolonic cancers were found in the stomach(16), hepatobiliary system(12), urologic system(6), gynecologic organ(6) and others. In the patients with triple primaries, extracolic cancers were found in the stomach(5), uterus(2), lung(2) and others. The patients with family history of malignancy were 10 cases and the rate in the triple primaries seemed to be higher than double primaries.
CONCLUSION
It could be desirable to follow-up and work-up the patients with colorectal cancer keeping in mind that the malignancy in other organs especially stomach might be present.

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Genomic Identification of N-Trminal Domail Exons of Carcinoembryonic Antigen in Human Colon Carcinoma: Jin Cheon Kim, Sun Ae Noh, Kun Choon Park, In Kwon Jung; J Korean Cancer Assoc. 1998;30(4):675-682.

Abstract PDF: No abstract available.

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GEnetic Change in Transforming Growth Factor-B (TGF-B) Receptor Type I and Type II Genes with Resistance to TGF-B of Human Breast Cancer Cells: Hwa Young Lee, Sung Sil Jeon, Hyun Ja Kwon, Soo Jung Kong, Seon Young Rah, Joong Bae Ahn, Kwang Yong Sim, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Kyung Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Chul Chung; J Korean Cancer Assoc. 1998;30(4):683-691.

Abstract PDF: PURPOSE
Transforming growth factor-Bs (TGF-Bs) are prototypic multifunctional negative growth factors that inhibit the growth of many cell types. TGF-B type I and II receptors(RI, RII) are transmembrane receptors containing cytoplasmic serine/ threonine kinase domain and have been implicated in mediating TGF-B activity. Because a heteromeric complex of RI and RII is required for TGF-B signal transduction, cancer cells may reduce the expression of either RI or RII to escape from growth inhibition of TGF-B. We examined the correlation between the growth inhibitory activity of TGF-B1 and the genetic expression of RI &RII genes in human breast cancer cell lines.
MATERIALS AND METHODS
We examined the growth inhibitory activity of TGF-B1 in 5 breast cancer cell lines by incorporation of [3H] thymidine. To investigate the correlation between TGF-B1 insensitivity and genetic change of TGF-B receptor genes (RI, RII), Southem blot analysis, Northern blot analysis, and Western blot analysis were performed. We also examined whether microsatellite instability(RER) was associated with RII mutation.
RESULTS
We found that 3 breast cancer cell lines (MCF-7, YCC-B101, YCC-B151) were resistant to growth inhibitory effect of TGF-B1. MCF-7 cell line expressed no detectable RII mRNA and RII protein, but showed normal structure of RII gene and normal expression of RI gene. And we did not find any abnormal expression of mRNA, protein, and genetic structure of RI &RII in YCC-B101 and YCC-B151.
CONCLUSION
Our results suggest that aquired resistance to the growth inhibitory effect of TGF-B1> could be transcription regulation system of RII in MCF-7 cell line, and could be postreceptor signal transduction pathway in YCC-B101 and YCC-B151 cell lines.

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Telomerase Activity in Invasive Breast Cancer: Deok Hwan Kim, Dae Sik Kim, Myung Soon Kim, Jung Ho Han, Yeon Rim Seo, Young Hye Ko, Chul Keun Park, Jung Hyun Yang, Hoe Jung Lee, Jong Sang Choi; J Korean Cancer Assoc. 1998;30(4):692-700.

Abstract PDF: No abstract available.

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Flow Cytometric Analysis of BRCA1 Protein in Sporadic Breast Cancer: Seung Moo Lee, Kyung Soon Sons, Hee Dae Lee; J Korean Cancer Assoc. 1998;30(4):701-710.

Abstract PDF: PURPOSE
To study the subcellular localization with flow-cytometry and to evaluate their prognostic values.
MATERIALS AND METHODS
The breast tissues were obtained from 28 patients with breast cancer and 6 patients with benign mass. The expression of BRCA1 protein was analyzed with the flow cytometry(Coulter Epics-XL, Coulter Corps, FL, USA) using the monoclonal antibody(BRCA1(Ab-1), Calbiochem, MA, USA) before and after nuclear and cytoplasmic permeabilization in association with DNA ploidy analysis. Several BRCA1 protein indices were derived including 95 percentile channel fluorescence(95% CF) and mean channel fluorescence(MCF) and percentage of BRCA 1 positive cell population arbitarily defined as those above 0.12 channel fluorescence.
RESULTS
Cytoplasmic 95% CF were higher in breast cancer(n=28, 0.65+/-0.26) than in benign mass(n=6, 0.40+/-0.13, p=0.0211). Cytoplasmic BRCAl positive cell percentages were significantly higher in malignant tissues(24.0+/-10.3) than in benign mass(43.4+/-15.2, p=0.0059). Cytoplasmic BRCA1 positive cell percentages were significantly different according to the stages(stage I vs II, 32.6+/-9.8 vs 48.3+/-18.8, p=0.048, stage I vs stage III, 32.6+/-9.8 vs 47.0+/-10.9, p=0.010). The BRCA1 protein indices were not significantly correlated with histologic grades and DNA indices(aneuploidy, S phase and proliferation fractions).
CONCLUSIONS
Flowcytometric assay offers an alternative approach to evaluating BRCA1 protein status of breast cancer tissue and detection of cytoplasmic BRCA1 protein by this method may help to understand the role of BRCA1 in breast cancer cell biology. The further study on cytoplasmic or nuclear BRCA1 protein in association with clinical therapeutic response or prognosis seems to be warranted.

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The Prognostic Value of Epidermal Growth Factor Receptor in Primary Breast Cancer: Bong Geun Park, Sung Jae Cha, Sung Joon Park; J Korean Cancer Assoc. 1998;30(4):711-718.

Abstract PDF: PURPOSE
The objective of this study was to ascertain the relationship between epidermal growth factor receptor(EGFR) status and estrogen receptor(ER) and other prognostic factors in primary human breast cancer patients. We tried to evaluate the value of EGFR as a prognostic factor.
MATERIALS AND METHODS
EGFR and ER were measured by immunohistochemical staining. It was performed on section from paraffin blocks of 60 primary breast cancer patients who underwent mastectomy at Chung-Ang University Hospital. And we evaluate the relationship between EGFR and ER and other prognostic factors.
RESULTS
In 20 of 60 patients(33.3%), the staining was positive for the expression of EGFR. Of the 60 patients, 6 were both positive for EGFR and ER, 25 were both negative, 14 were EGFR positive and ER negative, 15 were EGFR negative and ER positive. Between EGFR and estrogen receptor(ER) status, previously known clear inverse relationship was not observed in our study. The EGFR status was not correlated with axillary lymph node involvement, histologic type, and histologic grading. But it was correlated with tumor size(p=0.049), and there was a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors(p=0.078).
CONCLUSION
EGFR status may be valuable as a prognostic factor in determining the prognosis of breast cancer. However, the study of more cases will be needed for the significance of the information about the EGFR as an independent prognostic factor.

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Involvement of Polyamine in the Proliferation of Estrogen-Responsive Human Breast Cancer Cells: Jung Hoon Joo, Byung Ki Kim; J Korean Cancer Assoc. 1998;30(4):719-727.

Abstract PDF: No abstract available.

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Phase II Study of Ifosfamide, Epirubicin and Cisplatin(IEP) in Patients with Small Cell Lung Cancer: Hwi Joong Yoon, Hyun Joo Park, Si Young Kim, Kyung Sam Cho, Jung Hee Kim, Sung Eon Hong; J Korean Cancer Assoc. 1998;30(4):728-736.

Abstract PDF: PURPOSE
Although it is well recognized that SCLC is a chemo and radiosensitive tumor, only fraction of treated patients have a complete remission, fewer still have durable remissions. This study was performed to evaluate the clinical effects of IEP chemotherapy in patients with SCLC.
MATERIALS AND METHODS
Patients with histologically proven SCLC who has measurable disease and previously untreated, were eligible. Treatment consisted of ifosfamide 1000 mg/m2 iv infusion for 1 hour on days 1~5 with mesna uroprotection; epirubicin 60 mg/m2 iv on day 1; and cisplatin 20 mg/m2 iv infusion on days 1~5 with hydration; repeated treatment every 4 weeks RESULTS: Twenty four patients(20 males, 4 females) were eligible for response to IEP chemotherapy. The two patients were excluded because one died before evaluating response to chemotherapy and the other had brain metastasis. The median age was 61(range 34-74). Fifteen patients had a limited disease(LD), nine patients had a extensive disease(ED). The overall response rate was 86.4%(CR 36.4%, PR 50%). In LD, response rate was 86.7%(CR 46.7%) and in ED, response rate was 85.7%(CR 14.3%). The median overall survival time was 43.5 weeks. The median survival time of LD and ED was 46.5 weeks and 43.5 weeks respectively. The median time to progression was 20 weeks in responders. The toxicity was moderate. One toxic death was observed. Grade 1 or 2 non-hematologic toxicities consisted of alopecia, nausea and vomiting in all cases, peripheral neuropathy in 3, hematuria in 2, mucositis in 11, and fever/infection in 6. Hematologic toxic effects included leukopenia(> or =grade.3, 16.5%), anemia(> or =grade 3, 1%), and thrombocytopenia(> or =grade 3, 6.8%).
CONCLUSIONS
These results suggest that IEP chemotherapy may be useful as a treatment strategy in small cell lung cancer, but its efficacy is equivalent. The phase III study should be needed.

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A Case of Paraneoplastic Membranous Nephropathy Associated with Adenocarcinoma of the Lung: Ji Hyun Kim, Hyung Won Yang, Sung Hee Kwon, In Sook Woo, Young Iee Park, Myung Jae Park, No Won Jun, Jung Woo Noh, Jung Won Sim, Hye Kyung Ahn, Hyun Soon Lee; J Korean Cancer Assoc. 1998;30(4):737-742.

Abstract PDF: The paraneoplastic nephrotic syndrome can be diagnosed by clinical and immunologic features. We have had a case of paraneoplastic nephrotic syndrome in the patients with aadeno-carcinoma of the lung, whose diagnosis was made by excluding other causes of nephrotic syndrome. The type of renal lesion was membranous glomerulopathy which commonly occurs in carcinoma. The quantity of proteinuria in this patient had decreased according to the improvement of lung cancer with combination chemotherapy. After fourth chemotherapy he was refractory to treatment, and unfortunately he had passed away with cardiac tamponade.

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Thymic Carcinoma: Report of Eight Cases: Young Don Joo, Joon Hee Kim, Chang Hak Son, Ye Hoe Kim, Chan Hwan Kim, Hyun Sook Seo; J Korean Cancer Assoc. 1998;30(4):743-751.

Abstract PDF: Thymic carcinoma is a rare malignant neoplasm of the thymic epithelium, distinguished from benign or invasive thymoma by the presence of malignant cytology and a greater incidence of local invasion and embolic metastases. The true incidence of this neoplasm is unknown. Nearly three fourth of their patients had symptoms of an anterior mediastinal mass, including cough, chest pain, and superior vena cava syndrome. These patients rarely have myasthenia gravis or other thymoma-associated paraneoplastic syndromes. The treatment of thymic carcinoma remains a controversial matter. We report eight cases of thymic carcinoma treated in our institution from 1990 to 1997.

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Everamplification of GER-2/neu Oncogene Detected by Differential PCR and its Prognostic Significance in Advanced Epithelial Ovarian Cancer: Sang Soo Lee, Jong Hyok Kim, Chang Won Ko, Joon Hee Na, Yong Man Kim, Young Tak Kim, Joo Hyun Nam, Jung Eun Mok; J Korean Cancer Assoc. 1998;30(4):752-761.

Abstract PDF: PURPOSE
S: The objectives of this study were to investigate the prevalence of HER-2/neu oncogene amplification by differential polymerase chain reaction and to examine whether HER-2/neu oncogene overamplification has any prognostic significance in advanced epithelial ovarial cancer patients.
MATERIALS AND METHODS
The study population comprised thirty patients with stage III or IV epithelial ovarian cancer who were managed at Asan Medical Center between January 1994 and December 1996. Fresh frozen tumor samples of primary lesion were analysed by differential polymerase chain reaction to assess amplification of HER-2/neu oncogene. The correlation between HER-2/neu oncogene overamplification and histologic subtype or tumor grade or serum CA 125 level after second chemotherapy were evaluated using chi-square test, and for survival analysis, Kaplan-Meier curves were plotted and the differences between the curves were tested for significance using Log-rank test.
RESULTS
HER-2/neu oncogene was amplified in all of the cases (100% 30/30), but significant overamplification [gene copy number > or =1.5 a.u.(arbitrary unit)] was observed in 46.7% (14/30). There was no significant correlation between HER-2/neu oncogene overamplification and histologic subtype or tumor grade or serum CA 125 level after second chemotherapy and there was no correlation between HER-2/neu oncogene overamplification and overall survival.
CONCLUSION
The prevalence of HER-2/neu oncogene overamplification is 46.7%, but it may not be a significant prognostic factor in advanced epithelial ovarian cancers.

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The Effects of the Induction Chemotherapy on the Radical Radiotherapy in the Locally Advanced Cervical Cancer: Ki Mun Kang, Sei Chul Yoon, Hong Seok Jang, Mi Ryeong Ryu, Yeon Shil Kim, Sung Eun Namkoong, Seung Jo Kim; J Korean Cancer Assoc. 1998;30(4):762-771.

Abstract PDF: PURPOSE
We evaluated the prognostic factors, survivals and patterns of failure of the patients with locally advanced cervical cancer who received radical radiotherapy alone and induction chemotherapy followed by radiotherapy respectively.
MATERIALS AND METHODS
Between May 1985 to December 1992, one hundred and sixty three patients with locally advaneed cervical cancer received curative radiotherapy. Patients were divided into two groups: control group included 69 patients who received curative radiotherapy and combined group included 94 patients who received induction chemotherapy followed by curative radiotherapy. The curative radiotherapy consisted of external pelvic radiotherapy and intracavitary brachytherapy. Induction chemotherapy was delivered in VBP (vincristine, bleomycin, cisplatin) and FP (5-FU, cisplatin). Follow up period ranged from 2 months to 99 months with median of 50 months.
RESULTS
The overall response rate was 94.2% in the control group and 89.4% in the combined group. The response rate by control group was 66.7% for CR (complete response), 27.5% for PR (partial response), 5.8% for NR (no response). The response rate by combined group of CR, PR, NR were 64.9%, 24.5%, 10.6%, respectively. There was no difference in response for control group and combined group (p> 0.05). The 5-year overall survival had no significant difference in between control group and combined group (54.6% vs. 57.3%). The 5-year disease free survival also had no significant difference (52.9% vs. 55.0%). In the control group, 23 patients (33.3%) had treatment failure: twelve (17.4%) at a local recurrence, 9 (13.0%) as distant metastasis, and 2 (2.9%) with both local recurrence and distant metastasis. In the combined group, Thirty patients (31.9%) failed therapy, with local recurrence in 21 patients (22.3%), distant metastasis in 7 patients (7.5%), and both in 2 patients (2.1%). The difference between the two groups was not significant in view of patterns of failure. The major toxicities were nausea/ vomiting, leukopenia, anemia, and diarrhea. The prognostic factors affecting were hemoglobin level, KPS (karnofsky performance status), and treatment response in both group by multivariate analysis.
CONCLUSION
This study did not prove the efficacy of induction chemotherapy followed by radiotherapy in locally advanced cervical cancer.

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Effects of REtinoic Acid and Radiation on the Growth of Cell Lines of Human Head and Neck Squamous Cell Carcinoma: Jae Hong Seo, Young Ah Yoo, In Keun Choi, Seok Jin Kim, Chul Won Choi, Byung Soo Kim, Chul Yong Kim, Sang Won Shin, Yeol Hong Kim, Myung Sun Choi, Joon Seok Kim; J Korean Cancer Assoc. 1998;30(4):772-780.

Abstract PDF: PURPOSE
Mammalian tumor cells differ in their response to ionizing radiation to a degree that some patients are readily curable with conventional doses of radiation, while others are rarely controlled. In experimental systems, it is possible to demonstrate differences between cell lines both in intrinsic radiosensitivity and in the apparent capacity to repair damage. Retinoic acid is a substance that has previously been reported to increase radiosensitivity, but at concentrations likely to have cytostatic effects or induce cellular differentiation. We chose several head and neck cancer cell lines to investigate radiation sensitivity and synergism in combination with retinoic acid. Material and Methods: Seventeen head and neck cancer cell lines (MDA886, P1, P13, A-431, PCI-50, UMSCC-10A, UMSCC-10B, UMSCC-11A, UMSCC-11B, UMSCC-17A, UMSCC-17B, UMSCC-19, UMSCC-22B, UMSCC-30, UMSCC-38, 1YA, 1YB) are irradiated with variable dose of radiation (1 Gy, 5 Gy, 9 Gy) for determination of radiosensitivity of each cell lines. The less radiosensitive cell lines are treated with retinoic acid for evaluation of the effects of retinoic acid on cellular X-ray sensitivity and recovery from X ray-induced potentially lethal damage.
RESULTS
Lowest growth inhibition rates are seen UMSCC-11A and 1YA cell lines in 1 Gy, so that we treated with retinoic acid such cell lines. We obtained the following RESULTS: 1) two cell lines appear not inhibitory effect on recovery from X-ray induced potentially lethal damage but growth inhibition synergism when irradiated with retinoic acid in 1 Gy of radiation dose. 2) two cell lines were little effect on radiosensitivity and inhibitory effect on recovery from X-ray damage in 0.5 Gy radiation dose.
CONCLUSION
We found that direct radiosensitizing effects of retinoic acid on 1 Gy of radiation dose may act synergistically for cell growth inhibition in vitro study(three cell lines: UMSCC-11A, 1YA, UMSCC-11B). Further in vitro and in vivo experiments are now necessary to evaluate retinoic acid as radiosensitizer for head and neck cancer radiation therapy.

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Effect of Oral Nutritional Support During Radiation Therapy in Patients with Thoracic and Gead/Neck Cancer: Mi Sun Chun, Seung Hee Kang, Hye Kyung Kwon, Young Taek Oh, Joo Ri Kim, Hyun Joo Lee, Soon Young Lee, Sun Jeong Choi; J Korean Cancer Assoc. 1998;30(4):781-789.

Abstract PDF: PURPOSE
This study was designed to evaluate the role of oral nutritional support and nutritional counseling by dietician during radiation therapy.
MATERIALS AND METHODS
This study included total 58 patients with head/neck, lung, or esophageal cancers who received radiation therapy with radical purpose between February and December, 1996. They were randomized either into nutrient supplement group (Group I) or control group (Group II). In Group I, the dietician advised patients to take high density nutrient supplement (NuCare, 250 kcal/can, Miwon co., LTD) based on dieticians initial evaluation for oral intake from initiation to completion of radiation therapy. In Group II, patients received nutritional support other than high density nutrient supplement only when patients lose weight more than 2 Kg during radiation treatment. All patients were evaluated for nutritional status and diet pattern and received nutritional counseling before radiation therapy and then weekly during treatment.
RESULTS
Total 45 patients (22 patients in group I, 23 patients in group II) were available. In group I, all patients received average 3 cans (2~4 cans) a day. The calory from nutrient supplement was 43.9% of their daily energy intake (25.9~68.7%). About 72.7% of patients in Group I could keep up with their oral intake over 80% of daily requirement energy comparing to only 12.3% for patients in Group II(p<0.05). The patients in Group I started to lose weight 2 weeks later and lost weight more than 3 Kg less often than patients in Group II (5/22 vs 8/23, p>0.05).
CONCLUSION
There was less significant weight loss in patients who started oral nutritional supplement based on the daily requirement energy early in radiation therapy. We think it is better to recommend nutritional supplement before weight loss started because radiation induced side effects such as esophagitis and oral mucositis prohibited patients to continue to take nutrient supplement.

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Germline Mutations of the NF2 Gene in Korean Neurofibromatosis 2 Patient: Hee Jin Yang, Yong Jin Won, Kyu Joo Park, Hee Won Jung, Kil Soo Choi, Jae Gahb Park; J Korean Cancer Assoc. 1998;30(4):790-799.

Abstract PDF: PURPOSE
Neurofibromatosis 2(NF2) is an autosomal dominant disease characterized by development of bilateral acoustic neuroma and various central nervous system tumors such as meningiomas, ependymomas, and schwannomas. Recent cloning of the gene responsible for NF2, the NF2 gene, permits the presymptomatic genetic diagnosis of affected individuals by direct analysis of the gene. This paper was intended to identify germline mutations in Korean NF2 patients.
MATERIALS AND METHODS
We collected blood samples from 15 clinically diagnosed NF2 patients treated at the Department of Neurosurgery, Seoul National University Hospital. Purified genomic DNA samples were analyzed for mutations of the NF2 gene by using polymerase chain reaction(PCR)-single strand conformation polymorphism(SSCP) method followed by direct DNA sequencing.
RESULTS
We were able to identify germline mutation of the NF2 gene in one patient. The mutation identified was 1 base pair deletion(A) at codon 318, resulting in premature stop codon due to frameshift.
CONCLUSION
Identification of the germline mutation in NF2 gene should enable us to test all individual family members at risk to determine whether or not they carry the mutant NF2 gene.

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Genistein Induced Inginition of Cell Proliferation and Programmed Cell Death in the Human Cancer Cell Lines: Young Hyun Choi, Soo Jae Lee, Min Kim, Lijuan Zhang, Won Ho Lee, Kun Young Park; J Korean Cancer Assoc. 1998;30(4):800-808.

Abstract PDF: PURPOSE
Genistein, a natural isoflavonoid phyto-oestrogen present in plant foods including citrus fruits and soybean, is a specific inhibitor of tyrosine kinase and topoisomerase II. In this paper we examined the effect of genistein on cell cycle progression and programmed cell death in the human prostate carcinoma PC-3 and Ewing's sarcoma CHP-100 cells. MATERIAL AND METHODS: Effect of genistein on cell cycle was measured by DNA flow cytometric analysis. In order to understand anticancer effect of genistein on cell cycle, Western blot analysis, immune complex kinase assay, DAPI staining and DNA fragmentation analysis were conducted.
RESULTS
DNA flow cytometric analysis indicated that genistein induced cell cycle arrest at the G2/M transition phase. Western blot analyses showed that genistein selectively reduced expression of cyclin B1 and cdk2-dependent kinase activity in both cell lines. Genistein also induced apoptosis that was demonstrated by direct visualization of morphological nuclear changes and confirmed by the production of characteristic ladder patterns of genomic DNA fragmentation.
CONCLUSION
The chemopreventive activity of genistein is proven to be related with the induction of cell cycle arrest at the G2/M transition phase by reducing the expression of cyclin B1 and cdk2-dependent kinase activity, and also with the induction of apoptosis in the tested cancer cells.

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Primary CHOP Chemotherapy Followed by Involved Field Radiation Therapy in Clinical Stage I or II Aggressive Non-Hodgkin's Lymphomas: Chang Hee Lee, Young Hyuck Im, Baek Yeol Ryoo, Seung Mo Nam, Mi Sook Kim, Yong Sik Lee, Kyung Kyun Oh, Yoon Sang Shim, Seong Yul Yoo, Jhin Oh Lee, Tae Woong Kang, Yoon Koo Kang; J Korean Cancer Assoc. 1998;30(4):809-817.

Abstract PDF: PURPOSE
Although radiation therapy had been the treatment of choice for localized non-Hodgkin's lymphoma(NHL), recent studies have revealed that treatment result after radiation therapy alone is not successful for localized aggressive NHL, if it is not pathologically but clinically staged. A prospective phase II trial was conducted to evaluate the therapeutic results of 4 cycles of CHOP chemotherapy followed by involved field radiation therapy in clinically staged localized aggressive NHL.
MATERIALS AND METHODS
Patients with a diagnosis of aggressive NHL(all intermediate grade and immunoblastic histology in NCI working formulation), Ann Arbor stage I or II without poor prognostic factors(presence of B symptoms, bulky diseases, or 2 or more extranodal involvement) were treated with 4 cycles of CHOP(cyclophosphamide, doxorubicin, vincristine, prednisolone) followed by involved field radiation therapy of 3,000~6,000(median: 4,500) cGy.
RESULTS
Between April 1990 and March 1995, 62 consecutive patients entered this trial. Forty six patients with measurable diseases were evaluable for response. Complete response was achieved in 41(89.1%) patients after CHOP chemotherapy and 4 more patients after subsequent radiation therapy, making total CR rate of 98%. Progression free survival(PFS) of all 62 patients were 2.2+~73+ months and 5 year PFS rate was 64.6%. Overall survival(OS) were 2.4+~75+ months and 5 year OS rate was 75.2%. Old age (> 60) was the only significant prognostic factor, which-affected overall survival negatively. Treatment was relatively well tolerated, but 3 patients died associated with treatment.
CONCLUSIONS
Four cycles of CHOP chemotherapy followed by involved field radiation therapy is highly curative and safe treatment for clinically staged, localized aggressive NHLs.

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COPP/ABV Hybrid Chemotherapy in Pateints with Hodgkin's Disease: Jin Seok Ahn, Keun Seok Lee, Jong Tae Lee, Seok Ah Lim, Dae Seok Heo, Young Joo Bang, Sun Yang Park, Byung Kook Kim, No Kyung Kim; J Korean Cancer Assoc. 1998;30(4):818-826.

Abstract PDF: PURPOSE
MOPP/ABV hybrid regimen incorporates MOPP and ABVD into a single regimen on the tenets of the Goldie-Coldman hypothesis. This study was performed to determine the efficacy of COPP/ABV hybrid regimen, in which cyclophosphamide was substituted for mechlorethamine, in patients with advanced Hodgkin's disease.
MATERIALS AND METHODS
Patients with advanced Hodgkin's disease were treated with cyclophosphamide(600 mg/m2 iv, Dl), vincristine(1.4 mg/m2 iv, D1), procarbazine(100 mg/m2/d po, D1-7), prednisolone(40 mg/m2/d po D1-14), doxorubicin(35 mg/m2 iv, D8), bleomycin(10 mg/m2 iv, D8) and vinblastine(6 mg/m2 iv, D8). The treatment was repeated every 4 weeks.
RESULTS
Between Aug. 1989 and Aug. 1996, 28 patients were enrolled. The median age was 33 years. Twenty one(75%) were previously untreated, newly diagnosed patients and 7(25%) were those who had relapsed after previous radiotherapy(RT). The common histologic types were nodular sclerosis(46%) and mixed cellularity(36%). Twenty three (82%) patients achieved complete remission(CR), three(11%) with the assistance of involved-field RT. Only one patient was primary treatment failure. The median follow-up duration was 56 months. Of the 23 patients achieving CR, three(13%) relapsed. Five-year relapse-free survival was 84.4%. Eight patients died. Five-year overall survival rate was 66.6% and 5-year failure-free survival rate was 66.3%. The survival rate of those who had relapsed after previous RT was significantly lower than that of newly diagnosed patients(P=0.03). The hematologic toxicities were common, but nonhernatologic toxicities were uncommon. Five patients died of treatment-related pneumonia or sepsis. Among them, four were those who had relapsed after previous RT.
CONCLUSION
COPP/ABV hybrid regimen could cure significant proportion of patients with advanced Hodgkin's disease but the treatment-related mortality was high, especially in those who had relapsed after previous RT. Another regimen should be considered for those who received previous RT.

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Study on Growth Suppression Effect of Vetamin D3 Mediated by Transfrorming Growth Factor-B1(TGF-B1) in Acute Myelogenous Leukemic Cell: Chul Won Jung, Sang Jae Lee, Myung Joo Ahn, Tae Joon Jung, In Soon Kim, Il Young Choi, Jae Koo Seol, Eun Sil Kim, Byung Kook Kim, Young Yeol Lee; J Korean Cancer Assoc. 1998;30(4):827-841.

Abstract PDF: PURPOSE
Vitamin D3 was shown to arrest the growth of acute myelogenous leukemic cells and transforming growth factor- B1 (TGF- B1) was reported to be involved in the mechanism of vitamin D3. We studied the growth inhibitory effect of 1,25(OH)2-vitamin D3(C) and its analogue (EB1089) in leukemic cell lines and the changes in the secretion or the activation of TGF-B1 in the supernatant and the status of TGF-B1 type II receptor.
MATERIALS AND METHODS
Growth inhibition by vitamin D3 and TGF-B1 in 5 leukemic cell lines (HEL, HL-60, U937, KG-1, K562) were assessed with clonogenic and [3H]thymidine assay respectively. TGF-B type II receptor status was examined by Southern and Northern blotting. The concentrations of TGF- B1 in the supernatant were quantitated by enzyme immunoassay.
RESULTS
The growth of HEL, HL-60, U937 were inhibited in a dose-dependent fashion by both C and EB1089, more markedly by the latter. Anti-TGF-B neutralizing antibody partially reversed the growth inhibition. TGF-B1 markedly inhibited the growth of HEL, U937, KG-1, SNU-16 dose dependently while HL-60 and K562 showed no growth inhibition. HEL secreted latent TGF- 1 and HL-60 activated latent TGF- B1 or secreted active TGF-B1 irrespective of the treatment with vitamin D3. In U937, vitamin D3 increased the concentration of both active and latent TGF-B1. Deletion or abnormal expression of TGF- B type II receptor gene was not found in the 5 cell lines examined.
CONCLUSION
Vitamin D3 has various pattern of growth inhibition in acute myelogenous leukemia and inhibits the growth of some cell lines by secretion or activation of TGF-B1. Abnormality of TGF-B type II receptor DNA or mRNA seems to be rare.

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The Effect of Cytosine Arabinoside and Daunorubicin(AD) Combination Chemotherapy in Acute Myelogeous Leukemia: Chang Hoon Moon, Sung Hyun Kim, Hyung Ryoul Park, Jung Hwan Cho, Hyok Chan Kwon, Jae Seok Kim, Hyo Jin Kim; J Korean Cancer Assoc. 1998;30(4):842-852.

Abstract PDF: PURPOSE
Important advances in the treatment of acute myelogenous leukemia have been made with the introduction of cytosine arabinoside(ara-C) and anthracycline(daunorubicin) over the past 20 years. Currently, 50 to 85% of patients with acute myelogenous leukemia achieve complete remission with induction chemotherapy consisting of ara-C and daunorubicin. About 25% of complete responders will have extended long-term survival and may be cured. Therefore we treated patients having acute myelogenous leukemia with AD(7+3) regimen and analyzed factors complete remission rate, remission duration, and survival duration.
MATERIALS AND METHODS
Induction therapy; Thirty seven patients with previously untreated acute myelogenous leukemia treated with AD(7+ 3) regimen(ara-C, 200 mg/m2/d by continuous infusion for seven days, and daunorubicin, 45 mg/m2/d for 3 days). The second course of therapy was AD(5+2), if the patients failed to enter remission. Consolidation therapy; three cycles of consolidation chemotherapy were administrated with at least 4 week interval following remission. Course 1; ara-C at 100 mg/m2 by continuous infusion every 12 hour for five days, 6-thioguanine at 100 mg/m2/day orally for 5 days. Course 2; ara-C is same as course 1, vincristine at 1.2 mg/m2(maximum 2 mg) by bolus injection for 1 day, prednisolone at 40 mg/m'(maximum 60 mg) orally for 5 days. Course 3; ara-C is same as course 1, daunorubicin at 45 mg/m2 by 1 hour infusion for 2 days.
RESULT
62.2 percent of the 37 patients entered complete remission. The remission duration for all patients in complete remission ranged from 2 months to 63+ months, with the median of 15.1 months. The median duration of survival in complete responder group was 23.3 months. Among various prognostic factors, females and groups with normal chromosome and t(8;21) or t(15;17) had significantly higher complete remission rate than males and groups with other chromosomal abnormalities, respectively. Factors influencing on survival duration were female, normal chromosome, t(8;21) or t(15;17), Auer rod-positive, and peripheral blast % less than 50% at diagonosis. Groups with Auer rod-positive, normal chromosome, and t(8;21) or t(15;17) also had significantly longer remission duration.
CONCLUSION
Combination chemotherapy with cytosine arabinoside and daunorubicin is a effective regimen for acute myelogenous leukemia as much as other regimen for acute myelogenous leukemia. Further clinical trials for effective treatment regimen are necessary to increase the complete remissioin rate.

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