Cancer Research and Treatment

Utilization of Alternative Therapies in Cancer Patients: Kun Sei Lee, Hyung Sik Ahn, La Il Hwang, Young Sung Lee, Bum Hwan Koo; J Korean Cancer Assoc. 1998;30(2):203-213.

Abstract PDF: PURPOSE
To determine patient's use of alternative cancer therapies, as well as the characteristics of the patients who used these therapies, descriptive study was conducted at the one college hospital in Seoul.
MATERIALS AND METHODS
Of 950 eligible patients who discharged from October 1, 1996 to Febrary 28, 1997, 283 patients were completed semistructured questionnaire telephone survey finally(response rate is 29.8%).
RESULTS
Alternative therapies were used by 53.0% of patients. The preferred was dietary therapies and oriental(herbs, acupucture) therapies, folk therapies, drug therapies were other popular methods. Any patient characteristics except time prolongation after diagnosis were not associated with use of alternative therapies. The patients were seeking for alternative therapy because they thought conventional medical treatments were not enough to expect to improve their health, The major source of information was relatives and friends, not the mass media. 46.6% of the patients used althenative therapy said that it were not effective but 30.4% of them said it would help to slow the progression of their disease or strengthen their resistance. 45.0% of them were satisfied with it.
CONCLUSION
A significant proportion of cancer patients use one or more forms of alternative therapy. The physicians should recognize and give due consideration to the patients underlying desire for better control of his disease, and should be able to advise his patients on the use of alternative therapy.

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Inquiry about Management of Non-Small Cell Lung Cancer: Jae Young Park, Jung Suk Kim, Sin Kam, Sang Chul Chae, Jun Hee Won, Chang Ho Kim, Jae Chul Kim, Sang Hoon Jun, In Kyu Park, Tae Hoon Jung; J Korean Cancer Assoc. 1998;30(2):214-224.

Abstract PDF: PURPOSE
In recent years there has been a considerable increase in the use of chemotherapy as an adjuvant to surgery, radical radiotherapy and in addition to best supportive care. However, the value of chemotherapy in improving survival is still unclear, despite more than 50 randomised trials addressing this question in the different stages of disease. This study was done to evaluate Korean doctors' personal management preference and their beliefs about prognosis in non-small celllung cancer(NSCLC).
MATERIALS AND METHODS
A mail survey of Korean respirologists, thoracic surgeons, radiation oncologists, and medical oncologists was performed. Four cases of NSCLC were described and respondents were asked to give their treatment recommendations and to estimate the prognosis in each case.
RESULTS
After a complete resection for stage II NSCLC, 27% recommended no adjuvant treatment, 36% recommended radiotherapy, 18% recommended chemotherapy, and 19% recommended both radiotherapy and chemotherapy. After a complete resection for stage IIIA(N2) NSCLC, the vast majority of respondents recommended adjuvant therapy. For an asymptomatic patient with stage IIIB NSCLC, 5% recommended supportive care, 24% recommended radiotherapy, 16% recommended chemotherapy, and 54% recommended chemotherapy combined with radiotherapy. For a patient with stage IV NSCLC, 76% recommended chemotherapy with or without palliative radiotherapy. Doctors' treatment preference was significantly different by their speciliaty in a case with stage II, IIIA(N2), or IV NSCLC. Most respondents believed that chemotherapy would increase survival in NSCLC. Doctors' beliefs about the efficacy of treatment were strongly associated with their treatment recommendations.
CONCLUSION
Korean doctors generally preferred relatively aggressive management although their personal preferences varied widely. Team approach is important in deciding the treatment modality because doctors' treatment preference is different by their speciality.

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Combination Chemotherapy with Cisplatin , Etoposide , and Ifosfamide ( PIE ) in the Advanced Non - Small Cell Lung Cancer: Sang Won Shin, Byung Soo Kim, Jae Jung Shin, Yeul Hong Kim, Kyung Ho Kang, Young Ho Choi, Kwang Tak Kim, Jun Suk Kim; J Korean Cancer Assoc. 1998;30(2):225-230.

Abstract PDF: PURPOSE
Combination chemotherapy with cisplatin and etoposide have been considered as one of the chemotherpy regimen for non small cell lung cacer(NSCLC) with the response rate of 20~40%. Ifosfamide is one of the most active agent against NSCLC. And so, we initiated a phase II trial for advanced NSCLC to determine the effect of PIE(cisplatin, ifosfamide, etoposide) regimen.
MATERIALS AND METHODS
36 patients with inoperable non-small cell lung cancer who had no prior systemic chemotherapy were treated with combined ifosfamide (1,800 mg/m2 plus mesna 1,100 mg/m2 by intravenous continuous infusion daily for 3 days) with cisplatin (20 mg/m2 intravenous for 3 days) and etoposide (80 mg/m2 intravenous for 3 days). We evaluated the response rate, survival and toxicities of these patients.
RESULTS
The objective response rate was 28%(CR; 2/36, 6%, PR; 8/36, 22%). Among 10 responders, 7 patients were in good ECOG performance status(0~1). The mean survival of all these patients were 43 weeks(8~141 weeks); the responding patients survived longer than the non-responders(median survival; 59 weeks vs 28 weeks, p<0.05). The toxicities of this regimen were acceptable without treatment related toxic death.
CONCLUSION
We concluded that PIE regimen is effective in the treatment of advanced non-small cell lung cancer with acceptable toxicities and long-term follow up is warranted.

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Semi - quantitative Comparison of Terminal Restriction Fragment Length and Telomerase in Breast Cancer for Biotherapy: Sun Young Rha, Kyu Hyun Park, Tae Soo Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(2):231-241.

Abstract PDF: PURPOSE
We determined the clinical significance of telomerase activity and telomere length in breast cancer patients and also developed the measuring system of telomerase activity change with RNAse A pre-treatment.
MATERIALS AND METHODS
We measured the telomerase activity in 71 breast cancer tissues and paired normal tissues with TRAP (Telomeric Repeat Amplification Protocol) assay. Telomerase activity was calculated by computer-assisted densitometry compared to telomerase activity of the 293 control cell line. To develop the measuring system of telomerase activity modulation, we measured the telomerase activity after the treatment with RNAse A, 150microgram/ml, which inhibited 70% of telomerase activity compared to control in the 293 control cell line. In 59 paired tissues with telomerase activity, terminal restriction fragment (TRFs) length were measured using Southern blotting.
RESULTS
Sixty-three out of 71 cancer tissues showed telomerase activity (88.7%), while no telomerase activity was detected in their paired normal tissues. Telomerase activity was correlated to the node metastasis (p=0.02) and stage (p=0.005), but not to the tumor size or the hormonal receptor status. TRFs were neither specific to tumor tissues nor related to any of the clinical parameters. However, changes of TRFs of the tumor tissues from their paired normal tissues were correlated to the telomerase activities. Also the patients with different TRFs between cancer and normal tissues were in more advanced stage. After pre-treatment with the 150microgram/ml of RNAse A, telomerase activity in the tumor tissues showed variable inhibition. Relative inhibition, the ratio of inhibited telomerase activity in each tumor tissue compared to the inhibition of 293 control cell line, was proportional to the telomerase activity.
CONCLUSION
In breast cancer, telomerase activity was specific to the tumor tissues and correlated to tumor progression. A combination of telomerase activity and TRFs changes can be used as a guidline in detecting a better candidate for telomerase inhibition. Semi-quantitative assay with RI system can be used in evaluating the changes of telomerase activity after treatment with a new telomerase inhibitor with TRAP assay.

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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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Parasternal Recurrence after Curative Resection of Breast Cancer: Eun Ji Chung, Chang Ok Suh, Won Park, Hy Do Lee, Kyung Shik Lee, Gwi Eon Kim; J Korean Cancer Assoc. 1998;30(2):253-261.

Abstract PDF: PURPOSE
We tried to find the patients characteristics of parasternal recunence, to classify the parasternal recunence according to the radiological and clinical features, and to evaluate the efficacy of local radiotherapy.
MATERIALS AND METHODS
Between August 1987 and April 1997, twenty one patients with parastemal recurrence of breast cancer after surgery with or without adjuvant chemotherapy were treated with radiotherapy. Age distribution at initial operation was ranged from 31 to 79 years(median 48 years). Sixteen(76.2%) cancers were in the right breast and five(23.8%) were in the left. The pathologic types were infiltrative ductal carcinoma in 18 patients and medullary carcinoma in 3 patients. Eight patients had stage I, three had stage IIa, six had stage IIb, one had stage IIIa diseases and we had no information about the initial stage of the other 3 patients. Parasternal recurrence were diagnosed by biopsy in 7 patients, and the other 14 recurrences were diagnosed by clinical and radiologic findings such as chest CT, whole body bone scan. All the patients were treated with radiation for the parasternal recurrent tumors. In addition, five patients also received chemotherapy(FAC or Taxol based protocol) and one patient also received partial resection before radiotherapy. Radiotherapy was delivered with Co-60 gamma-ray or 4~6 MV X-ray or electron beam to both supraclavicular lymph nodes and parasternal areas with total doses of 3000~6480 cGy(median 6100 cGy).
RESULTS
The range of interval between curative resection and parasternal recurrence were 4~110 months(median 34 months). The main symptoms of the parasternal recurrence were a painless mass(n=10). The duration of symptom before diagnosis ranged from one to 36 months(median 7 months). Among 21, five patients(23.8%) presented distant metastses at the diagnosis of parasternal recurrences. The parasternal recurrences were classified into three groups according to radiologic and clinical findings; the recurrent tumors originated from sternum and invaded into adjacent tissues(Group 1, n=5), tumors originated from intemal mammary lymph nodes and invaded into sternum or parasternal tissues(Group 2, n=6), tumors originated from medial chest wall and invaded into sternum or parasternal tissues(Group 3, n=10). In nineteen patients(19/21; 90.5%) there was complete response of parasternal recurrence following radiotherapy. Although the follow up period was relatively short(3~78 montbs, median 14 months), there were no local recurrence in radiation field in 19 patients with complete response. Among the 16 patients without distant metastases at diagnosis of parasternal recurrence, nine patients were alive without any evidence of disease.
CONCLUSION
Chest CT scan is necessary and effective in patients with parastemal discomfort, pain, swelling or palpable mass after mastectomy. And we found that radiotherapy was very effective for the local treatment of parasternal recunence in terms of symptom palliation and local control of tumor. Although we classified the parasternal recurrence into three groups, we could not reach any conclusive results because of short follow up duration and insufficient patients number.

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Breast Cancer of 35 Years Old or Less: Han Sung Kang, Han Kwang Yang, Dong Young Noh, Yeo Kyu Yong, Sang Joon Kim, Seung Keun Oh, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 1998;30(2):262-271.

Abstract PDF: PURPOSE
The age of onset of Korean breast carcinoma is younger than that in western countries by some 10 years, thus the criteria of young age in manuscript from western countries cannot reflect the characteristics of young breast cancer properly in Korea.
MATERIALS AND METHODS
We studied 290 breast cancer patients, 35 years old or younger retrospectively, from Jan. 1980 to Dec. 1995 in the Department of Surgery, Seoul National University Hospital. The age criteria of 30 and 35 years was utilized to define two groups.
RESULTS
The group(age< or =35) had larger primary tumors, more metastatic lymph nodes, and worse stages than older counterpart(p=0.015, 0.0066, 0.0329 respectively). They had worse disease-free survival but not overall survival(p=0.0312, 0.2427 respectively). The other group(age < or =30) showed significantly worse outcome in overall as well as disease free survival(p=0.0056, 0.0013) compared to the group(age>30). When we compared the group of age< or =30 to that of 31< or = age < or =35, there was statistically significant difference in primary tumor size, axillary nodal status and pathological stage(p=0.023, 0.019, 0.022 respectively).
CONCLUSION
The age of 30 might be better criteria to define young age as prognostic factor rather than age of 35 in Korea.

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FPL ( 5-Fluorouracil / Cisplatin / Levamisole ) Combination Chemotherapy for Metastatic or Recurrent Gastric Carcinoma: Byeong Seong Ko, Kee Hyung Lee, Kang Hyeon Choe, Seon Mee Park, Sei Jin Youn, Seung Taek Kim; J Korean Cancer Assoc. 1998;30(2):272-277.

Abstract PDF: PURPOSE
FP(5-FU, Cisplatin) combination is one of the most active regimen for the advanced gastric cancer with a response rate of 50~60%. In spite of this high response rate, there is little evidence that FP regimen results in survival benefit for patients with advanced gastric cancer. This study was performed to evaluate the efficacy and toxicity of this regimen with the addition of levamisole, an immunomodulatory agent, known as enhancing the antitumor effects of 5-FU in other cancer.
MATERIALS AND METHODS
Previously untreated patients with metastatic or recurrent gastric cancer were treated with 5-FU(1000 mg/M2 civ, D1~5), cisplatin(60 mg/M2 iv, Dl) every 3 weeks, and levamisole(150 mg/day, Dl~3) every 2 weeks. The major endpoints were response rate, response duration, and toxicities.
RESULTS
Between June 1992 and Aug. 1996, thirty three patients were included in this study. Patients received 2~18 cycles of chemotherapy(median 5). Among the evaluable 31 patients, 18 patients(58%, 95% C.I. 40.4~75.7) showed objective responses including one(3.2%) clinical complete response. The median response duration was 7.7 months(95% C.I. 3.6~11.8). During total of 189 cycles of chemotherapy, 79 episodes(41.7%) of leucopenia were observed. There was no death from concurrent infection.
CONCLUSION
FPL combination therapy is at least as effective as conventional FP chemotherapy, but resulted in somewhat more myelosuppression.

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The Prognostic Significance of the p53 Overexpession on Complete Response and Survival in Preoperative Chemoradiotherapy Treated Squamous Cell Esophageal Carcinoma: Sung Bae Kim, Sang Hee Kim, Hwoon Yong Jung, Hun Kyung Lee, Gyeong Hoon Kang, Jong Hoon Kim, Ho Young Song, Seung Il Park, Dong Kwan Kim, Hae Ryun Kim, Won Sun Hong, Je Hwan Lee, Sang We Kim, Cheol Won Sun, Kyoo Hyung Lee, Jung Shin Lee, Woo Kun Kim, Young Il Min; J Korean Cancer Assoc. 1998;30(2):278-287.

Abstract PDF: PURPOSE
To determine the frequency of p53 overexpression and to analyse the relationship between p53 overexpression and complete response rate, survival in locoregionl squamous cell esophageal cancers treated with preoperative chemoradiation multimodality approaches.
MATERIALS AND METHODS
Using a microwave oven heating method, we have detected p53 overexpression by immunohistochemically with a monoclonal antibody(DO-7) in formalin- fixed paraffin-embedded samples of 42 patients with locoregional squamous cell esophageal cancer, who treated with concurrent chemotherapy and radiatian followed by surgery.
RESULTS
In 27 of 42 tumors(64.2%), nuclear immunoreactivity for the p53 protein was detected. Complete response rate, evaluated in surgical specimen 3-4 weeks after chemoradiation seemed to be high in p53 positive group compared to p53 negative group, however, there was no statistically significant difference in acquiring better complete response rate, overall survival and progression free survival between p53 positive and p53 negative group(p=0.0546, p=0.0599, p= 0.6832). Complete response group(n=17) survived longer than non-complete response group(n=25)(p=0.0010).
CONCLUSION
The results indicate that p53 is not a statistically significant prognostic factor in obtaining better complete response rate, overall survival and progression free survival of the patients with esophageal carcinoma treated with preoperative chemoradiotherapy. Additional studies are warranted for further evaluation.

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Studies on Relationship between Expression of ras , p53 , c-erbB2 and p53 and Phenotypic Expression Using Mucin Histochemistry in Human Gastric Carcinomas: Kyung Kook Kim, Se Woong Kim, Young Bae Ko, Jun Hee Lee, Won Gon Kim, Soon Gu Cho, Joon Mee Kim, Young Chae Joo, Tae Sook Hwang, Han Kwang Yang, Jin Pok Kim; J Korean Cancer Assoc. 1998;30(2):288-299.

Abstract PDF: PURPOSE
Recent studies have shown that the expression of mucin is organ- and cell-type specific and it is increasingly possible that its change could result from oncogene activation.To evaluate histogenesis and prognostic factors for gastric carcinoma, we studied the oncoprotein expression in gastric cancer cells classified by mucin phenotye.
MATERIALS AND METHODS
Mucin histochemistry and immunohistochemistry for ras, c-erbB2, and p53 oncoprotein expression were performed in 101 surgically resected gastric carcinoma specimens. PAS-Con A, GOS, and HID-AB staining techniques were employed in identifying mucosubstances, RESULTS: Of the 101 specimens studied, 73(72.3%) revealed as having mixture of various mucin-secreting cancer cells. Overall, ras immunoreactivity was observed in 72(71.3%), c-erbB2 in 7(6.9%), and p53 in 47(46.5%). Of the 73 mucus-secreting carcinomas, the surface mucous cell type were shown in 65 (89.0%), the pyloric gland cell type in 48(65,8%), the sialomucin type in 47(64.4%), and the sulfomucin type in 54(74.0%). There was significant association between mucin secretion and ras expression, but not c-erbB2 and p53 expression. There was no significant association between mucin secreting cell types and Lauren classification. Ras expression was correlated with serosal invasion, lymph node metastasis and poor prognosis.
CONCLUSION
The phenotypic expression by mucin histochemistry may be not more important for studying of histogenesis in gastric carcinoma than Lauren classification. Ras expression is a poor prognostic indicator and may be correlated with phenotypic expression of surface mucous cell and intestinal cell type in gastric carcinoma.

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Combined Chemoradiation of Advanced Pancreatic Cancer: Jee Young Jang, Ki Mun Kang, In Ah Kim, Ihi Bong Choi, Jai Hak Lee, Eung Kook Kim, Seung Nam Kim, Hee Sik Sun, Kyu Won Chung, Meung Kyu Choi, Joon Yeol Han, Han Lim Mun; J Korean Cancer Assoc. 1998;30(2):300-305.

Abstract PDF: PURPOSE
This study was designed to evaluate the survival rate and prognostic factor of patients with advanced pancreatic cancer who received chemoirradiation. MATERIAL AND METHODS: From March 1993 to November 1995, twenty patients with unresectable pancreatic cancer were treated at the Department of Therapeutic Radiology, St Mary's Hospital, Catholic University Medical College. There were 11 men and 9 women. Age at diagnosis ranged from 34 to 75 years. All patient were treated according to a protocol consisting of 40 Gy external radiation by split course concomitant with intravenous 5-fluorouracil (5-FU) 500 mg/m2 given in a bolus injection 4 hours before radiatian on each of the first 3 days of each treatment course. Among them, 5 patients received incomplete radiotherapy. The follow-up period ranged from 1.3 to 29 months.
RESULTS
In all the patients, median survival is 5.0 months and one and two-year overall survival rate was 34.3% and 25.8%, respectively. Median survival was 9.0 months and one-year survival rate was 33.3% in 15 patients with complete radiotherapy. The significant prognostic factors were stage, tumor location, and completion of chemoradio- therapy(p < 0.05).
CONCLUSION
A combination of radiotherapy and chemotherapy resulted in improved median survival. However, the significant prognostic factars affecting survival rate in this analysis need to be verified further through randomized trial.

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The Comparative Study between Peripharal Venous Blood and Draining Venous Blood CEA Levels in Colorectal Cancer: Kyung Bum Lee, Eun Sook Lee, Young Chul Kim; J Korean Cancer Assoc. 1998;30(2):306-312.

Abstract PDF: PURPOSE
In colon cancer, CEA(carcinoembryonic antigen) has become one of the useful tools for the management of patients because the antigen has been found to be useful as a monitor for detection, staging, recurrence, determining the response to therapy, and estimating the prognosis or survival. Many investigators have been analyzing the peripheral CEA levels for these purpose. Correlation between CEA levels of peripheral and portal blood, and histopathologic variables, was examined in 92 patients. This study evaluates importance of draining vein CEA levels in sensitivity and specificity of the prognosis.
MATERIALS AND METHODS
In 92 patients, comparison between peripheral and draining venous blood CEA levels was performed in order to get better sensitivity and specificity and precise prognosis of CEA in colorectal cancer. Stage, tumor site, tumor emboli, lymph nodes, ascitic fluid cytology and differentiations were considered.
RESULTS
There was no significant difference in peripheral and draining venous blood CEA levels in these variables. CEA positive rate of peripheral and draining vein were 57% and 60%. It has statistically no significance. More elevated CEA levels of draining vein than peripheral levels was detected in Duke C comparison (p=0.013). And more elevated CEA levels was observed in more advanced stages(33%, 59%, 63%, 83%) in draining vein(p < or = 0.01).
CONCLUSION
The prognosis of elevated CEA level in draining venous blood CEA levels in advanced stage is significant in prediction of patients prognosis and degree of advanced cancers.

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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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Irradiation alone in Stage IB , IIA and IIB Cervix Cancer: 2 Correlation between Treatment Factors and Pelvic Tumor Control: Sung Ja Ahn, Woong Ki Chung, Byung Sik Nah, Taek Keun Nam, Ho Sun Choi, Ji Soo Byun; J Korean Cancer Assoc. 1998;30(2):321-328.

Abstract PDF: No abstract available.

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Peripheral T - cell Lymphomas Presenting as Fever of Unknown Origin: Dae Seog Heo, Keun Seok Lee, Joor Yung Huh, Yung Jue Bang, Seon Yang Park, Chul Woo Kim, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1998;30(2):329-337.

Abstract PDF: PURPOSE
Peripheral T-cell lymphomas(PTCL) show diverse clinical and histological characteristics and should be understood as mixtures of heterogeneous entities. Although many clinical and biological parameters have been proposed for classifying PTCL into different prognostic groups, few parameters have turned out to be appropriate for classification. To investigate the clinical significance of FUO presentation in PTCL, comparisons of clinical parameters were performed using non-FUO presentation as a control.
MATERIALS AND METHODS
66 cases of Korean PTCL were divided into FUO group and non-FUO group according to the presentation and compared with each other.
RESULTS
Among 66 patients of PTCL, 19 patients presented with FUO. Compared with non-FUO group, FUO group showed no significant age and sex ratio differences. FUO group showed more advanced stage, worse performance status than non-FUO group. Predominant sites of definite diagnosis were skin, gastrointestinal tract and liver in FUO group and nasal cavity and paranasal sinus in non-FUO group. There were no significant differences between histologic classifications of both groups. Survival analysis revealed significant differences between both groups. FUO group showed significantly shorter survival. Prognostic factor analysis(multivariate) was done with stage, LDH level, performance status, and FUO status. FUO status, stage and performance status were significant determinants of survival, but LDH level proved to have no prognostic implication.
CONCLUSION
PTCL with FUO presentation showed such distinct characteristics that the authors propose fever of unknown origin(FUO) as a clinical parameter for classifying PTCL. Further studies are needed to identify biological parameters which characterize PTCL with FUO presentation.

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Subtypes of Epstein - Barr Virus in Malignant Lymphoma in Korea: Kyung Eun Choi, Eun Yoon Cho, Chan Kum Park, Won Keun Lee, Young Hyeh Ko; J Korean Cancer Assoc. 1998;30(2):338-349.

Abstract PDF: PURPOSE
Epstein-Barr virus(EBV) exists in the human population in two genetic forms, usually referred to as type 1 and type 2 which have been defined on the basis of sequence divergence in the EBNA-2 and EBNA-3 family genes. In this study, we were intended to investigate whether the subtypes of EBV in malignant lymphoma in Korea were associated with specific disease entities and geographical distribution.
MATERIALS AND METHODS
Biopsy samples obtained from 18 Korean patients with malignant lymphoma including Hodgkin's disease(3 cases), B cell lymphoma(1 case), and NK/T cell lymphoma(14 cases) were analyzed to determine the subtype of EBV infected therein. DNA was extracted from formalin-fixed, paraffin-embeded tissues by ordinary method and specific viral sequences were sought using the polymerase chain reaction(PCR) and Southern blot hybridization assay. Oligonucleotide primers used for examination of EBV strain type were derived from the EBNA-3B and EBNA-3C coding regions. As a control, four cases of reactive hyperplasia were analyzed.
RESULTS
The two of four reactive hyperplasia cases were associated with type 1 and the rest of two cases with both types. Among the 18 cases with malignant lymphoma, thirteen cases(72%) had type 1, one(6%) had type 2, and four(22%) had dual infections with both types. In case of NK/T cell lymphoma(14 cases) occupying 78% of 18 biopsy samples, 86%(12 cases) were associated with type 1, 7%(1 case) with type 2, and 7%(1 case) with both types. In case of Hodgkin's disease, all of three cases had both types. B cell lymphoma taking only one case of twenty two cases was determined as type 1.
CONCLUSION
These observations indicated that type 1 EBV was predominant in Korean patients with malignant lymphoma, especially NK/T cell lymphoma and showed high frequency of dual viral infections(22%) in Hodgkin's disease as well as in reactive hyperplasia.

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Results of CHOP-Bleo / CMED Alternating Chemotherapy for Aggressive Non - Hodgkin's Lymphoma: Suk Jin Kim, In Keun Choi, Sang Chul Oh, Jae Hong Seo, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim; J Korean Cancer Assoc. 1998;30(2):350-356.

Abstract PDF: PURPOSE
To assess the efficacy and toxicity of a new protocol that consists of CHOP- Bleo alternated with a new regimen of Cyclophosphamide, methotrexate, etoposide, and dexamethasone(CMED) for aggressive Non-Hodgkin's Lymphoma(NHL). PATIENTS AND METHODS: Between January 1991 and December 1996, forty-six patients with Ann Arbor stages II-IV aggressive NHL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. All eligible patients were evaluated for response, disease-free survival, and overall survival.
RESULTS
Twenty-two patients(47.8%) achieved a complete response and overall response rate was 83.9%. The range of survival duration was 1-68+months and the median survival time was 42 months. Overall 3-year survival rate was 54%. The range of disease-free survival time was 6-63+months and 3-year disease-free survival rate was 61%. The most common hematologic toxicity was leukopenia and the incidence of severe leukopenia(<1,000/mm3) was 11%. And alopecia(84.8%) was the most common non-hematologic toxicity.
CONCLUSION
The results of CHOP-Bleo/CMED alternating chemotherapy for patients with aggressive Non-Hodgkin's Lymphoma is not superior to other results of previous studies. Therefore further study will be warranted to determine clinical effectiveness of alternating chemotherapy.

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Chemopotentiation of Fresh Acute Myelogenous Leukemic Cells by Recombinant Human Granulocyte - Macrophage Colony - Stimulating Factor ( GM-CSF ) and Methotrexate: Heung Tae Kim, Jin Seok Ahn, Eun Shil Kim, Yung Jue Bang, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1998;30(2):357-369.

Abstract PDF: No abstract available.

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Retroperitoneal Sarcoma: Ji Soo Kim, Won Shik Han, Dong Young Noh, Yeo Kyu Yong, Seung Keun Oh, Kuk Jin Choe; J Korean Cancer Assoc. 1998;30(2):370-377.

Abstract PDF: PURPOSE
To determine the clinical feature, surgical management of primary and recurrent disease, predictive factors for outcome, and impact of multimodality therapy in retroperitoneal sarcoma.
MATERIALS AND METHODS
60 patients were confirmed pathologically as soft-tissue sarcoma of the retroperitoneum by operation or needle biopsy in Seoul National University Hospital from 1983 to 1995. A retrospective analysis was performed.
RESULTS
The abdominal mass was common presenting symptom. Histologically liposarcomas(25%) and leiomyosarcomas(23.3%) were most common, and MFHs(11.7%) and malignant schwannomas(11.7%) followed. The overall 5 year survival rate was 54.6%. Complete resection was possible in 51.7% of patients and strongly predicts outcome (<0.0001). These patients had a median survival of 130 months compared to 20 months for those undergoing partial resection and 9 months for those with unresectable tumors. 11(35%) of completely resected patients have had local recurrence. These patients underwent reoperation when feasible. Complete resection of recurrent disease was performed in 10 patients(90%), with a 42 months median survival time after reoperation. Resection of adjacent organ was performed in 19 patients. 14 of these were completely resected, and showed 100% of 5 year survival rate. Tumor grade was not a significant predictor of outcome. Gender, histologic type, encapsulation, stage, resectability, combined resection were significant prognostic factors by univariate analysis. But resectability was only independent prognostic factor on mutivariate analysis. Radiation therapy and chemotherapy could not be shown to have significant impact on survival.
CONCLUSION
Complete resection is the most important prognostic factor of retroperitoneal sarcoma. Extensive and aggressive surgery must be considered including resection of adjacent organs. Multiple resection seems to improve survival in recunent cases.

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Urinary Nuclear Matrix Protein ( NMP 22 ) in the Detection of Transitional Cell Carcinoma of the Bladder: Soo Bang Ryu, Bong Ryoul Oh, Soon Pal Suh, Dong Deuk Kwon, Je Woong Ryu, Yang Il Park; J Korean Cancer Assoc. 1998;30(2):378-383.

Abstract PDF: PURPOSE
The detection of bladder cancers by noninvasive techniques remains an unsolved problem. We evaluate the availability of an immunoassay for urinary nuclear matrix protein, NMP 22, as an indicator for transitional cell carcinoma of the bladder.
MATERIALS AND METHODS
Three groups of subjects participated in this trial of NMP 22: 22 patients with transitional cell carcinoma (group 1), 12 patients with urinary tract infection (group 2) and 31 healthy volunteers (group 3). NMP 22 was determined by ELISA using a commercial test kit (NMP 22 Test Kit, Matritech Inc., USA), We compared urinary NMP 22 levels to the grade, stage, cytology and DNA flowcytometry of transitional cell carcinoma of bladder.
RESULTS
NMP 22 values in these 3 groups were significantly different (group 1, median 24.81 U/mL; group 2, median 8.41 U/mL; and group 3, median 5.12 U/mL; Mann-Whitney U test for differences between 3 medians, p < 0.05). The patients with transitional cell carcinoma had significantly greater urinary NMP 22 levels than those with no evidence of tumor (Mann-Whitney U test for differences between 2 medians, p<0.01). There was no zelationship between the urinary NMP 22 levels and tumor grade, stage, cytology or DNA flowcytometry.
CONCLUSIONS
It is possible that urinary NMP 22 could improve the detection of bladder transitional cell carcinoma.

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Restrospective Cohort Study of Survival and Prognostie Factors in Patients with Terminal Cancer: Young Ho Yun, Dae Seog Heo, Jong Myon Bae, Seock Ah Im, Tai Woo Yoo, Bong Yul Huh, Noe Kyeong Kim; J Korean Cancer Assoc. 1998;30(2):384-393.

Abstract PDF: PURPOSE
Cancer has become the major cause of deaths in Korea. Planning care for patients with terminal cancer is difticult. The prediction of length and prognostic factors of survival in the terminal cancer can facilitate the planning of a supportive care program aimed at patients need. The aim of this study was to identify length and those related factor of survival in the patients with terminal cancer.
MATERIALS AND METHODS
This retrospective study was performed on 271 patients, who were diagnosed as terminal cancer in Seoul National University Hospital from March 1991 to February 1996. For getting the further informations about the patient, we interviewed with surviving relatives by telephone, and we requested administrative helps in order to take the informations about date of death. We examined the relations of 10 factors with survival in patients with terminal cancer.
RESULTS
We could confirm 229 patients' death(84.5%) in 271 subjects. The median length of survival in patients with terminal cancer was 11 weeks(95%CI 10.0~14.0). By univariate analysis, history of surgery(p<0.01), performance(p<0.05), severity of pain(p <0.001), and dyspnea(p<0.05) were clinical factors in predicting survival. According to Cox's proportional hazard model including sex, age, history of surgery, performance, severity of pain, and dyspnea as variables, absence of surgery history(RR 1.398, 95%CI 1.038~1.882) and severity of pain(RR 1.398, 95%CI 1.044 ~1.872) showed independent prognostic value.
CONCLUSION
The median survival was 11 weeks, and absence of surgery history and severity of pain were the independent prognostic factors for patients with terminal cancer.

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Molecular Screening and Analysis of Ligand Proteins Association with Unique - SH3 Domain of c - Yes: Sahng June Kwak, Yeon Sun Seong; J Korean Cancer Assoc. 1998;30(2):394-401.

Abstract PDF: No abstract available.

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Application of Mitochondrial Morphology for Diagnosis of Steroidogenous Cell Origin Tumor: on the basis of the primary and the metastatic ovarian tumors: Sung Chul Lim, Jae Hong Seo; J Korean Cancer Assoc. 1998;30(2):402-413.

Abstract PDF: PURPOSE
The purpose of this study is to evaluate the diagnostic availability of the morphology of mitochondria to identify the nature or the origin of neoplasms. MATRIALS AND METHODS: We analysed two cases of ovarian malignancy- a case of malignant steroid cell tumor, unclassified and a case of metastatic carcinosarcoma from the adrenal cortex- which were difficult to identify the origin and the nature of the tumor for special staining, immunohistochemical and ultrastructural methods.
RESULTS
To evaluate the nature or the origin of neoplasms, we performed immuno histochemistry for various antigens and special stains, however the specific diagnostic clues were not provided by these modalities. The ultrastructural characteristics of mitochondria of neoplastic cells showing tubular or tubulo-vesicular inner mitochondrial membranes provided diagnostic clues as a marker for steroidogenic potential. The morphology of mitochondria is related to the enzyme activity and steroid-biosynthetic capacity of cells. Especially, the inner mitochondrial membrane structure is believed to be related to the steroid biosynthetic activity. In hypofunctional state of corticosteroid productian, a reduced number of inner mitochondrial membranes showing tubular patterns is noted. In cantrast, the stimulation of steroidogenesis result in a progressive increase of mitochondrial membrane showing densely packed rounded vesicular patterns via tubulo-vesicular patterns according to the activity of steroidogenesis.
CONCLUSION
The tubular, the vesicular and the tubulo-vesicular mitochondria will be valuable to identify the uncertainty of nature and origin of tumor as a stemidogenic.

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A Case of Early Gastric Cancer Associated with Small Cell Lung Cancer: Mi Kyeong Park, Tae Hun Kwon, Jin Hong Park, Seol Young Yun, Seong Ho Choi, Seong Pyo Son; J Korean Cancer Assoc. 1998;30(2):414-420.

Abstract PDF: The incidence of multiple primary cancers is low than that of single primary cancer. In gastric cancer, incidence of occurrence of multiple primary cancer is 3 to 11.3%. Because stomach and lung are unrelated organs, the combination of gastric cancer and lung cancer is rare. Its estimated incidence is about 10% of all multiple primary cancers. The histologic types of secondary lung cancer in one series, squamous cell carcinomas were 49%; adenocarcinomas were 28%; large cell carcinomas were 14%; small cell carcinomas were 9%; others were 6%. This patient had been diagnosed as early gastric cancer 3 years ago, but he refused operation for cancer and wasnt followed up. After 3 years, he revisited us for dry coughing and diagnosed as small cell lung cancer. At this time, previous gastric cancer was remained as well differentiated, early gastric adenocarcinoma. For its rarity, we report this case with review of literatures.

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Primary Leiomyosarcoma of the Breast: Jeong Hyun Yang, Hae Kyung Lee, Seok Jin Nam, Gyu Rae Kim; J Korean Cancer Assoc. 1998;30(2):421-424.

Abstract PDF: We describe a 42-year-old woman with a primary leiomyosarcoma of the breast. It is an extremely rare tumor, with only about 16 cases reported. Usually it is presented with palpable mass of benign characters. The origin of the tumor is controversal and the differential diagnosis includes other sarcomas and metastatic ones. The uncertain behavior of it makes the management difficult but conservative surgery is available in the case of anatomically suitable. Axillary lymphatic dissection is not needed and the roles of the chemotherapy and radiotherapy are not clear. Some studies revealed a local invasion and degree of cellular atypia as some prognostic predictive value.

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