Cancer Research and Treatment

Expression of CD44 Standard, Variant 6 and Relationship to the Lymph Node Metastasis in Gastric Adenocarcinoma: Joo Ho Lee, Hang Jong Yu, Byung Jo Suh, Mee Ju, Hae Kyung Lee, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(4):665-673.

Abstract PDF: PURPOSE
The transmembrane glycoprotein CD44 exists in a variety of isoforms generated by alternative splicing of the pre-mRNA. We studied the role of CD44-standard (CD44s) and CD44-variant6 (CD44v6) in gastric adenocarcinoma.
MATERIALS AND METHODS
Immunohistochemical staining was performed in 101 patients with gastric adenocarcinoma who underwent radical gastrectomy at KGCC, Seoul Paik Hospital. The relationship of CD44s, CD44v6 expressions to the clinicopathologic parameters, p53 and Ki-67 were evaluated.
RESULTS
CD44s and CD44-v6 expressions were found in 56.4% and 48.5%, respectively. CD44s expression was significantly correlated with lymph node metastasis, lymphatic invasion, and Borr mann type. CD44v6 expression was significantly correlated with sex, lymph node metastasis, lymphatic invasion, and perineural invasion and had a tendency toward p53 expression. In inte stinal type adenocarcinoma, CD44s expression had correlations with lymph node metastasis and CD44v6 had correlations with lymph node metastasis, lymphatic invasion. However, in diffuse type adenocarcinoma, CD44s and CD44v6 expressions had correlations with only Borrmann type. In multivariate analysis, lymph node metastasis was the most significant risk factor for CD44s and CD44v6 expressions in total cases and intestinal type adenocarcinoma.
CONCLUSION
These data suggest that expression of CD44 v6 may play an important role in the regulation of lymph node metastasis in intestinal type adenocarcinoma of stomach.

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Analysis of Clinicopathological Factors Associated with Lymph Node Metastasis in Early Gastric Cancer Review of 2,137 cases: Chang Shin Kwak, Hyeon Kook Lee, Sam Je Cho, Han Kwang Yang, Kun Uk Lee, Kuk Jin Choe, Jin Pok Kim; J Korean Cancer Assoc. 2000;32(4):674-681.

Abstract PDF: PURPOSE
The majority of patients with early gastric cancer show long-term survival after surgery. So a special attention must be directed to preserving gastric function in these patients. When node-negative early gastric cancer could be diagnosed preoperatively, then minimally invasive surgery can be performed to ensure a postoperative better quality of life.
MATERIALS AND METHODS
The pathological records of 2,137 consecutive patients with early gastric cancer who underwent curative operations from January 1986 to December 1998 at Seoul National University Hospital were reviewed.
RESULTS
Lymph node metastases were observed in 285 patients (13.3%). In mucosal carcinoma, lymph node metastases were observed in 50 of 1,108 cases (4.5%), and in submucosal carcinoma, in 234 of 1,026 cases (22.8%). The tumor size, depth of invasion and gross appearance were associated with lymph node metastasis. In mucosal carcinoma, the size and histologic differ entiation were associated with lymph node metastasis. In submucosal carcinoma, the size and gross appearance were associated with lymph node metastasis.
CONCLUSION
In early gastric cancer, the limited surgery can be applied only to cases satisfying the following criteria; (1) mucosal tumor, (2) size < or =2 cm, (3) elevated type or (4) depressed type which are histologically differentiated and (5) size < or =1 cm among the depressed type his tologically undifferentiated.

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Concurrent Chemoradiation Therapy with Cisplatin and Oral Etoposide for Locally Advanced Non-small Cell Lung Cancer: Chang Won Paek, So Young Yoon, Jae Hong Seo, Chul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jae Jung Shim, Kyung Ho Kang, Jun Suk Kim, Chul Yong Kim, Myung Sun Choi, Young Ho Choi, Kwang Tak Kim; J Korean Cancer Assoc. 2000;32(4):682-689.

Abstract PDF: PURPOSE
Prognosis of locally advanced inoperable non-small cell lung cancer (NSCLC) treated with radiation therapy alone has been disappointing. In recent years, concurrent chemoradiation therapy has potential of improving both local and metastatic disease-free survival. This phase II study was undertaken to determine the feasibility, toxicity, response rate, local control rate, and survival duration of locally advanced NSCL patients treated with concurrent chemoradiation using cisplatin and oral etoposide. MATERIAL AND METHODS: Forty-seven patients were enrolled and forty-one patients were evaluable. Chemotheray consisted of cisplatin 50 mg/m2/IV on days 1 and 8 and oral etoposide 100 mg/day on days 1 to 5 and 8 to 12 which was repeated, every 4 weeks for two cycles during radiation therapy. Radiation therapy was administered to a total dose of 6300 cGY.
RESULTS
Among 41 evaluable patients, six patients achieved complete response, and twenty had partial response, for an overall response rate of 63.4% (95% confidence interval; 48.4% to 75.4%). Stable disease was reported in 10 patients (24.4%) and another 5 (12.2%) showed disease pro gression. Overall survival rate was 76% at 1 year, 34% at 2 years. Median survival duration was 17 months (range; 3 to 41 ). Eighty-three percents of patients had radiation pneumonitis but only one patients needed medical treatment.
CONCLUSION
Concurrent chemoradiation therapy with cisplatin and oral etoposide at this level is a well tolerated and feasible.

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A Phase II Study with Vinorelbine and Carboplatin in Patients with Advanced Non-small Cell Lung Cancer: Jong Lyul Kim, Bong Seog Kim, Byoung Ju Na, Mi Jin So, Jin Han Lee, Oh Young Chung, Gwi Lae Lee, Yong Ho Roh; J Korean Cancer Assoc. 2000;32(4):690-698.

Abstract PDF: PURPOSE
To evaluate the efficacy and safety of vinorelbine and carboplatin in advanced non- small-cell lung cancer (NSCLC).
MATERIALS AND METHODS
Between August 1998 and July 1999, 25 patients were enrolled. The median age was 68 (range, 46~77) years and male:female ratio was 23:2. Two patients had stage IIIa, 15 had stage IIIb and 8 had stage IV. Sixteen patients had ECOG performance status of 0 or 1 and 9 had 2 or 3. Sixteen patients had squamous cell carcinoma, 8 had adenocarcinoma and 1 had undifferentiated NSCLC. Treatment consists of intravenous carboplatin 400 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8. The treatment was repeated every 28 days.
RESULTS
Twenty-three of 25 patients were evaluable. Partial response were observed in 11 patients. The overall response rate was 48% (95% confidence interval: 27~69%) and the median response duration was 19 (range 7 ~44 ) weeks. The median survival of 25 patients was 52 (range 3~53 ) weeks. Toxicities were evaluated by WHO criteria. During a total of 108 cycles, granulocytopenia worse than WHO grade 3 occurred in 2%, thrombocytopenia in 4% and anemia in 10%, respectively. Treatment-related death occurred in 1 patient due to sepsis during cytopenic period. Non-hematologic toxicity was minor and easily controlled.
CONCLUSION
A combination chemotherapy of intravenous vinorelbine and carboplatin has relatively high activity with acceptable toxicities in patients with advanced NSCLC.

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Venous Irritation Incidence Associated with Vinorelbine Tartrate Injection Time: Kyung Wook Hur, Jin Eui Jung, Jae Hong Seo, Cheul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim; J Korean Cancer Assoc. 2000;32(4):699-704.

Abstract PDF: PURPOSE
This study was to determine the incidence and severity of venous irriation in patients receiving vinorelbine tartrate (Navelbine ) in combination chemotherapy. MATERIAL AND METHODS: Twenty four patients histologically confirmed non-small cell lung cancer were enrolled in this study who receiving vinorelbine in combination chemotherapy through a peripheral vein from Oct. 1997 to Mar. 1999 with retrospective study design method. One group was 6~10 minutes infusion rate, the other was 10~20 minutes infusion rate with the same free-flow intravenous infusion.
RESULTS
A total of 126 infusions were observed in this study. Sixty-two infusions were admi nistered at the 6~10 minutes, and 64 infusions were administered at the 10~20 minutes. The incidence of any venous irritation was 3.2% (2/62) in the group that received the infusion in 6~10 minutes and 10.9% (7/64) in 10~20 minutes (p=0.164), so we could not acquire any statistical significance. However the incidence of severe venous irritation (grade 3, 4) was 0% (0/62) in 6~10 minutes infusion group and 9.4% (6/64) in 10~20 minutes infusion group. There was a significant difference between two groups (p=0.028) CONCLUSION: Our results suggest that venous irritation associated with vinorelbine tartrate infusion can be reduced by shorter duration of administration and vinorelbine tartrate might be recom mended to administer at 6~10 minutes infusion in clinical practice.

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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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Results of Radio-thermotherapy in Stage IIIb Uterine Cervical Cancer Local response, survival rate and analysis of prognostic factor: Chang Woo Moon; J Korean Cancer Assoc. 2000;32(4):714-723.

Abstract PDF: PURPOSE
This retrospective study was conducted to obtain local response and survival rates, and to analyze prognostic factors affecting survival of patients treated with radio-thermotherapy for stage IIIb uterine cervical cancer.
MATERIALS AND METHODS
From May 1992 to Dec. 1996, 24 patients treated with radio-thermo therapy for stage IIIb uterine cervical cancer at department of Radiation Oncology in Kosin Medical College, Kosin University were enrolled. Radiotherapy used 6~10 MV linear accelerator was performed in whole pelvis with 4 portals box technique by conventional (180~200 cGy/ fraction, 5 fraction/week) method in 5 patients (20.8%) or hyperfractionated (120~135 cGy/fr., 2 fr./day, 10 fr./wk) in 19 patients (79.2%). Total dose of A-point was 67~112 Gy (median: 77.27 Gy). Hyperthermia used 8 MHz radiofrequency capacitive heating device was applied in pelvic area with 2~3 sessions per wk. Each course started within 15 to 20 minutes after radio therapy and took 40 to 60 minutes. Local progression free (LPFS), disease free (DFS) and overall (OS) rates were calculated in survival analysis. Statistics was calculated by Kaplan-Meier Method in survival and Log-rank test in statistical significance. Multivariate analysis for prognostic factor was applied to Cox Regression model. Follow-up duration was 6~82 months (median: 25 months).
RESULTS
Overall local response rate was 95.8% (45.8% in CR/50.0% in PR). Five year LPFS, DFS, OS were 48.6%, 31.7%, 67.1%, respectively. In univariate analysis, an age was the signi ficant prognostic factor in terms of OS (p=0.03), but was insignificant in LPFS and DFS. In multivariate analysis, none of evaluated factors are important in LPFS, DFS or OS.
CONCLUSION
Radio-thermotherapy for stage IIIb uterine cervical cancer did not increase 5 year LPFS, DFS and OS in spite of higher local response rate. Age was the only significant factor for OS in univariate analysis.

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Changes of Telomerase Activity by Protein Kinase C Modulators in Human Ovarian Cancer Cell Lines: Soo Young Hur, Joon Mo Lee, Sung Eun Namkoong, Jin Woo Kim; J Korean Cancer Assoc. 2000;32(4):724-733.

Abstract PDF: PURPOSE
This study was designed to find out whether protein kinase C (PKC) may affect telomerase activity in human ovarian cancers.
MATERIALS AND METHODS
To determine whether PKC modulators influence PKC activities, NIH: OVCAR-3 and CUMO-2, cells were treated with PKC inhibitors, G 6976 and bisindolyl maleimide I, and PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA). Telomerase acti vity was determined by telomeric repeat amplification protocol (TRAP). Analysis of the expres sion of each telomerase subunits, human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT), was performed by RT-PCR. We also examined the alternative splicing of hTERT.
RESULTS
G 6976 and bisindolylmaleimide I inhibited PKC activity. Telomerase activities appeared to be affected in a time-dependent manner by these two PKC inhibitors. PKC activities were increased in parallel with telomerase activity by TPA at the low dose (10 nM), but their activities were down-regulated at the high dose (1 micrometer). RT-PCR demonstrated the presence of hTR and hTERT mRNA before and after the treatment of PKC modulators, respectively, and showed the presence of one alternatively spliced transcript and full-length hTERT transcripts.
CONCLUSION
These results showed that telomerase activity was affected by PKC and suggested PKC modulation may serve as an useful tool in the regulation of telomerase activity.

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Salicylate Induced Apoptosis in A549 Cells: Yeon Hee Park, Jae Il Seol, Hyun Il Kim, Mi Ja Kim, Hee Jae Lee, Soon Ae Kim, Chang Ju Kim, Joo Ho Chung; J Korean Cancer Assoc. 2000;32(4):734-741.

Abstract PDF: PURPOSE
Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to exist chemo preventive activity against colon cancers. In this study, we examined whether salicylate affects the survival of A549 cells, and investigated the presence of apoptosis.
MATERIALS AND METHODS
We used A549 human lung cancer cell line. The measurement of cytotoxic concentration of salicylate was performed by MTT assay method. In order to test the involvement of apoptosis, we performed TUNEL assay, DAPI staining, flow cytometric analysis and RT-PCR.
RESULTS
We showed that salicylate can potently induce apoptosis in A549 cells. A549 cells under went apoptosis in treatment with salicylate at pharmacological concentration (5 mM).
CONCLUSION
Herein, our data provide a potential mechanism for chemopreventive activity of salicylate and suggest that salicylate may have therapeutic potential for the treatment of lung cancer.

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Uptake of Ga-67 by Cultured Cells: Transferrin-dependent and Transferrin-independent Mechanisms: Myung Hee Sohn, Seok Tae Lim, Jae Yong Kwak, Chang Yeol Yim; J Korean Cancer Assoc. 2000;32(4):742-749.

Abstract PDF: PURPOSE
We determined whether the uptake of Ga-67 by cultured cells occur by both transferrin (Tf)-dependent and independent mechanisms and the mechanism and magnitude of its uptake may vary as the degree of expression of the transformed phenotype.
MATERIALS AND METHODS
Uptake of Ga-67 between the tansformed and untransformed cells was compared. Cells were incubated with Ga-67 in either the presence or absence of Tf and with complete medium containing Ga-67 after preincubating with anti-Tf receptor antibodies at 37oC in 8% CO2. Monolayers of cells were washed and trypsinized. Radioactivity and protein content of the samples were determined.
RESULTS
Uptake of Ga-67 by cultured cells occurred both in Tf-bound and ionic form and was increased with radioactivity and time. The magnitude for the uptake of Tf-bound form was approximately 3 and 6-fold greater than ionic form. In the presence of Tf, uptake of Ga-67 was 2-fold greater in the transformed cells. Conversely, In the absence of Tf, it was 1.5-fold greater in the untransformed cells. Regardless of blocking the Tf receptor by anti-Tf receptor antibodies, a significant amount of intracellular Ga-67 uptake was found.
CONCLUSION
Dual mechanisms exist for the uptake of Ga-67 by cultured cells. The primary important one was the Tf-dependent system. Tf-dependent and independent mechanisms and the magnitude operated oppositely in the transformed cells when compared to their untransformed counterpart.

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Cell Cylce Regulatory Effects of Cyclic AMP in Cancer Cells Which Lack Wild-type p53: Joung Soon Jang, Joung Hun Kang, Byung Kiu Park, Sang Gu Hwang; J Korean Cancer Assoc. 2000;32(4):750-756.

Abstract PDF: PURPOSE
The activator of protein kinase A, cyclic AMP, has been a recognized growth inhibitor of certain cell types. The present study aimed to investigate the effects of dibutyryl cAMP on the growth of cancer cells which lack wild-type p53 and to determine the mechanism of growth inhibition.
MATERIALS AND METHODS
Prostate and breast cancer cells were treated with dibutyryl cAMP and compared with untreated cells. Growth patterns of cells were assessed by trypan blue-excluding method and western blot was done to determine protein levels of cell cycle regulatory proteins which govern G1 and G1/S phase. Northern blot and immunoprecipitation were done to determine the level of mRNA of p21 and the association between cell cycle regulatory proteins. In vitro immune complex kinase assay was done to assess the activity of cdk2.
RESULTS
cAMP reduced cell growth by 48 h. Cyclin D3 level was downregulated and RB protein level was decreased and mostly unphosphorylated forms remained. The association of RB with E2F1 was increased. While cdk2 levels remained constant throughout cAMP treatment, the activity of cdk2/cyclin E complex, which is responsible for entry into S phase, was downregulated. Cdk inhibitors, p27 and p21 were induced with cAMP treatment.
CONCLUSION
These observation suggest that the growth inhibitory effects of dibutyryl cAMP on prostate and breast cancer cells were mediated by induction of cdk inhibitors such as p21 and p27 and RB activation in accordance with downregulation of cdk2.

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Nausea and Vomiting Induced by Conventional Fractionated Radiotherapy on Abdomen: Won Dong Kim, Woo Yoon Park; J Korean Cancer Assoc. 2000;32(4):757-763.

Abstract PDF: PURPOSE
A retrospective study was intended to assess the incidence, severity, and risk factors of abdominal radiotherapy induced nausea and vomiting and to evaluate the effect of antiemetic drugs like metoclopramide and ondansetron.
MATERIALS AND METHODS
From October 1997 to October 1999, we enrolled 48 patients who received conventional fractionated radiotherapy on abdomen. Patients under 18 years old and who received concomittant chemotherapy were excluded. Evaluation was carried out on the basis of daily check of the intensity of nausea and any episode of vomiting and retching.
RESULTS
Nausea and vomiting occurred in 65% and 25% of patients, respectively. On multivariate analysis, previous experience with chemotherapy was the only significant patients-related risk factor. The irradiated site and field size were also significant in terms of radiotherapy-related risk factors. Nausea and vomiting were markedly diminished in the group given ondansetron.
CONCLUSION
Our study offered useful data on general picture of radiation induced nausea and vomiting in patients given conventional fractionated radiotherapy on abdomen. For the patients with risk factors, prophylactic antiemetic drug prescription may be mandatory to enhance compliance with radiotherapy and ondansetron is more effective than metoclopramide for controlling nausea and vomiting.

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Antiangiogenesis Gene Therapy Using Adenovirus-mediated Antisense-VEGF in Glioblastoma Multiforme: Seock Ah Im, Jeong Soo Kim, Eunmi Nam, Soon Nam Lee; J Korean Cancer Assoc. 2000;32(4):764-774.

Abstract PDF: PURPOSE
Vascular endothelial growth factor (VEGF) is a major positive effector of angiogenesis. We investigated the mechanism of tumor growth inhibition by adenoviral transfer of antisense- VEGF in glioma and the role of VEGF for in vivo growth of human glioma cells according to the stage of the tumor growth.
MATERIALS AND METHODS
Replication-deficient adenoviral vector containing the VEGF cDNA in an antisense orientation (Ad5CMV-alphaVEGF) were constructed to increase the in vivo applicability of antisense sequence. The effect of Ad5CMV-alphaVEGF was studied in vitro and in vivo with human glioma cell line U-87 MG. Immunohistochemical staining of the subcutaneous tumor with anti-VEGF antibody and CD34 antibody were performed to compare VEGF protein expression and the microvessel count respectively.
RESULTS
The growth curve of U-87 MG cells treated with Ad5CMV-alphaVEGF remained as same as that of mock-infected and Ad5(dl312)-infected U-87 MG cells in vitro, suggesting that Ad5CMV-alphaVEGF does not have direct cytotoxic effect. The growth of subcutaneous human glioma xenografts was inhibited by early intratumoral injection of Ad5CMV-alphaVEGF. Immuno histochemical staining of tumors showed that VEGF protein expression and mean microvessel counts were decreased in early Ad5CMV-alphaVEGF treatment group.
CONCLUSION
The efficient down-regulation of VEGF produced by tumor cells using Ad5CMV- alphaVEGF in early stage of glioma growth has an antitumor effect in vivo through antiangiogenic mechanism.

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Preliminary Results of Postoperative Radiotherapy after Breast Conserving Surgery in Early Breast Cancer: Seung Hee Chang, Seung Jae Huh, Jung Hyun Yang, Do Hoon Lim, Seok Jin Nam, Sung Soo Yoon, Yong Chan Ahn, Dae Yong Kim, Suk Won Park, Moon Kyung Kim; J Korean Cancer Assoc. 2000;32(4):775-782.

Abstract PDF: PURPOSE
To evaluate treatment results of breast conserving surgery and radiation therapy including survival rates, patterns of failure, and complication and to analyze prognostic factors.
MATERIALS AND METHODS
Retrospective analysis was carried out for 111 (112 cases) consecutive patients with breast cancer treated by radiation therapy after breast conserving surgery from October 1994 to April 1997. The median follow up was 45 months (range 10~66). AJCC staging was as follows: 16 cases (14%) for ductal carcinoma in situ, 46 cases (41%) for stage I, 33 cases (30%) for stage IIa, and 17 cases (15%) for stage IIb. Radiation therapy after breast conserving surgery was delivered to whole breast with 50.4 Gy and additional 10 Gy electron beam boost to tumor bed. Adjuvant CMF or CAF chemotherapy was performed in 61 patients.
RESULTS
Overall three- and five-year survivals were 99% and 95%, and progression-free survival were 93%, 87%, respectively. Treatment failure occurred in 11 cases (10%); loco-regional recur rence in six; distant metastasis in five. Univariate analysis showed prognostic factor affecting survival was only T-stage. Acute radiation dermatitis were found in five cases (4%), and chronic complications were found in five (4%); one case with amputation of nipple, two cases with lymphedema requiring rehabilitation therapy and two cases with symptomatic radiation pneu monitis requiring steroid therapy.
CONCLUSION
Breast conserving therapy of early breast cancer including ductal carcinoma in situ showed high survival rates and low complications, and T stage was prognostic factor for survival. But further follow-up should be needed.

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The Mechanism of Retinoic Acid-induced Growth Suppression in Head and Neck Squamous Cancer Cell Lines: Seok Jin Kim, Chang Won Paek, Jae Hong Seo, Chul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Aree Kim, Kap No Lee, Sun Han Kim, Geon Choi, Young A Yoo; J Korean Cancer Assoc. 2000;32(4):783-792.

Abstract PDF: PURPOSE
Retinonic acid (RA) has been reported to induce differentiation and growth inhibition in various head and neck squamous cancer cell (HNSCC) lines. We hypothesized that this growth inhi bition might be explained by RA-induced apoptosis on cell cycle arrest mechanism. Therefore, we studied the degree of RA-induced apoptosis with variable RA concentration and exposure duration. MATERIAL AND METHODS: The flow cytometric evaluation of apoptosis degree and cell cycles were carried out with 7-amino actinomycin D (7AAD) and propium iodide (PI) respectively, with var ious RA exposure durations (2, 3, 6 day) and concentrations (conrol, 10 6, 10 7, 10 8, 10 9, 10 10 mole). Two different HNSCC lines (1483, SqCC/Y1) were used and the experiment was repeated twice.
RESULTS
The maximal fraction of apoptosis in 1483 and SqCC/Y1 cell lines were observed at same concentration and exposure duration (1483: 6th day & 10 6, mole, and SqCC/Y1: 6th day & 10 6 mole). In our experimental model, RA did not induce specific cell cycle arrest in these HNSCC lines. However we observed S phase fraction increase in SqCC/Y1 cell line after RA treatment.
CONCLUSION
We suppossed that in HNSCC lines, RA-induced cell growth inhibition could be explained by not only RA-induced apoptosis but also cell cycle arrest. Futher, in vitro study has been carried out to elucidate the RA-iduced cell growth inhibition mechanism in our laboratory.

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BACOD/EISHAP Alternating Combination Chemotherapy for Intermediate and High Grade Non-Hodgkin's Lymphoma: Jung Hun Kang, Young Ho Park, Soo Jin Kim, Ji Chul Yun, Gyeong Won Lee, Hun Gu Kim, In Gyu Hwang, Won Sup Lee, Joung Soon Jang, Jong Seok Lee; J Korean Cancer Assoc. 2000;32(4):793-800.

Abstract PDF: PURPOSE
We conducted a phase II study to determine the antitumor activity of BACOD/EISHAP alternating 9-drug chemotherapy in previously untreated patients with intermediate or high grade non-Hodgkin's lymphoma (NHL).
MATERIALS AND METHODS
Intermediate or high grade non-Hodgkin's lymphoma patients were treated with BACOD/EISHAP (bleomycin, doxorubicin, cyclophosphamide, vincristine, dexame thasone/etoposide, ifosfamide, high dose cytarabine, cisplatin, dexamethasone) alternating com bination chemotherapy. Stage I and IIA lymphoma patients were excluded. BACOD/EISHAP alternating chemotherapy was given to the eligible patients every 3 weeks/4 weeks respectively.
RESULTS
Between April, 1995 and December, 1997, among 25 eligible patients, 19 patients were evaluable for response. Six patients could not be evaluated for response because of follow-up loss within 2 cycles of chemotherapy. Complete response (CR) was achieved in 12 patients (63%) after BACOD/EISHAP alternating combination chemotherapy. With a follow-up period of 41 months (25~57 months), the disease free survival did not reach median (4~47 months) and 3-year disease free survival rate was 75%. Major toxicity was marrow suppression and the incidence of severe leukopenia (WBC<2,000/mm3) and thromobocytopenia (<25,000/mm3) were 15%, 5%, respectively. No treatment-related death was observed. For non-hematologic toxicities, nausea and vomiting were observed in 65% of patients, stomatitis in 25%, peripheral neuropathy in 20%.
CONCLUSION
BACOD/EISHAP alternating chemotherapy was feasible with acceptable toxicities. The 63% complete response rate was comparable to other regimens but 75% 3year disease-free survival rate was encouraging. Further evaluation of this regimen is warranted.

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Correlation between Genetic Polymorphism of CYP2D6 and CYP1A1 and Susceptibility of Renal Cell Carcinoma in Korean: Kyu Wook Park, Se Il Jung, Gyung Woo Jung, Heon Young Kwon, Jin Sook Jeong, Jin Ho Chun, Jin Han Yoon; J Korean Cancer Assoc. 2000;32(4):801-809.

Abstract PDF: PURPOSE
Many of the enzymes handling environmental factors are polymorphic and may confer variable susceptibility to renal cell carcinoma (RCC). Among those, the author studied genetic polymorphisms of CYP2D6 (B & T) and CYP1A1 in RCCs and controls in Korean.
MATERIALS AND METHODS
Using 132 RCCs and 94 controls, first PCR products were obtained in 104 RCCs and 94 controls with CYP2D6, and 74 RCCs and 56 controls with CYP1A1. Res triction enzyme - BstN I/EcoN I for CYP2D6 (B & T), and NCo I for CYP1A1-digestion was followed to analyze constitutive DNA.
RESULTS
In both RCCs and controls, no mutant allele of CYP2D6 (B & T) was detected and the susceptibility for occurrence of RCC was unable to evaluate. With CYP1A1 RFLP, homozy gous wild type (WW) was seen in 68 (52.3%; 37 RCCs, 31 controls), heterozygous mutant type (WM) in 54 (41.5%; 32 RCCs, 22 controls) and homozygous mutant type (MM) in 8 (6.2%; 5 RCCs, 3 controls). The odds ratios (95% CI) of RCC susceptibility for CYP1A1 genotype were 1.15 for WM and 1.36 for MM. Even though not significant statistically, higher tendency in MM presented.
CONCLUSION
There is no association between susceptibility for the occurrence of RCC and genetic polymorphism of CYP2D6 (B & T) and CYP1A1.

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Immunohistochemical Expression of p53 and Cathepsin D in Prostatic Carcinoma: Dae Joong Kim, Eui Han Kim, Seung Ha Yang, Chang Jin Kim; J Korean Cancer Assoc. 2000;32(4):810-816.

Abstract PDF: PURPOSE
To evaluate the prognostic significances of p53 and cathepsin D in the prostatic carcinoma, we compared them to other prognostic factors, such as nuclear grade and clinical stage.
MATERIALS AND METHODS
The material consisted of 40 paraffin-embedded, primary prostate carcinomas. We examined the expression of p53 and cathepsin D using immunohistochemical staining and compared their expression with the grade and stage.
RESULTS
The expressions of p53 were noted in the nucleus of tumor cells and cathepsin D were noted in the cytoplasm of tumor cells. Thirteen of 40 tumors were positive for p53. There were more expressing p53 in samples (40%) from prostatic cancer with a high Gleason score group than in samples (28%) from prostatic cancer with low Gleason score group. The expression of p53 was 22% in clinical stage B and C groups and 35% in clinical stage D group. These results showed that p53 expression was not statistically correlated with Gleason score and clinical stage, but there were trends to increased p53 expression with high Gleason score and progressed clinical stage (p>0.05). Progressed clinical stage group showed higher expression of cathepsin D than early clinical stage group. However, there were no statistical correlations between expression of cathepsin D and Gleason score, and clinical stage (p>0.05).
CONCLUSION
These results suggest that the overexpression of p53 and cathepsin D may be associated with tumor differentiation and clinical stage, but have limited prognostic value in prostatic carcinoma.

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A Case of Triple-Alkylating Regimen and Peripheral Blood Stem Cell Transplantation for a Patient with Relapsed Ovarian Carcinoma: Jun Mo Lee, Seok Goo Cho, Jin No Park, Young Sun Hong, Hoon Kyo Kim, Sung Eun Namkoong, Kyung Shick Lee, Chun Choo Kim; J Korean Cancer Assoc. 2000;32(4):817-821.

Abstract PDF: Despite an aggressive surgical debulking followed by front-line chemotherapy, most patients with advanced ovarian carcinoma die of drug-resistant disease. Drug resistance can be overcome in a subset of patients with hematologic malignancies and lymphoma with high-dose therapy (HDT) and hematopoietic stem cell transplantation, suggesting that this therapy may also be value in ovarian carcinoma. We report the successful outcome of HDT and peripheral blood stem cell transplantation (PBSCT) in a 41-year-old nulliparous woman who initially was diagnosed with advanced ovarian carcicnoma with FIGO stage IIIc. Her disease relapsed after 19 months from initial therapy of definitive surgery and intra- and post-operative chemotherapy. Subsequently, she received optimal debulking surgery and salvage chemotherapy followed by HDT with triple- alkylating regimen, composed of cyclophosphamide (100 mg/kg), thiotepa (500 mg/m2), and melphalan (100 mg/m2). Her pretranplant characteristics were platinum-sensitive and complete response state. She showed rapid hematologic recovery and mild regimen-related toxicity (Bear man's toxicity criteria), stomatitis (grade I), cardiac toxicitiy (grade II). She has been followed up for 36 months after the inital therapy and is doing well without relapse.

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Secretory Carcinoma of the Breast in Three Year-old Girl: A Case report: Woo Chul Noh, Nam Sun Paik, Kyung Ja Cho, Jin Haeng Chung, Seung Kon Nam, Doo Hwan Choe, Nan Mo Moon; J Korean Cancer Assoc. 2000;32(4):822-826.

Abstract PDF: Secretory carcinoma is one of the least common forms of breast cancer and demonstrates distinctive clinical and pathological characteristics. We herein report a case of secretory carcinoma of the breast in 3 year and 1 month-old girl. At presentation, the patient had a 2.5cm sized mass on her left breast which was firmly attached to the overlying nipple. The aspiration cytologic findings of the tumor were consistent with a secretory carcinoma. After confirming malignancy by frozen section diagnosis, a modified radical mastectomy was performed and secretory carcinoma was finally diagnosed. To our knowledge, secretory breast carcinoma in children has not been reported previously in Korea and this seems to be the youngest case of secretory carcinoma of the breast which had been reported in English literature.

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