Cancer Research and Treatment

Geographical Variations in the Incidence of Childhood Cancer: Duk Hee Lee, Hai Rim Shin, Kang Weon Park, Yoon Ok Ahn; J Korean Cancer Assoc. 1998;30(3):425-434.

Abstract PDF: PURPOSE
The incidence of childhood cancer in the Korea was studied to compare incidence rates between countries and between different regions in Korea.
MATERIALS AND METHODS
A tatal of 2,891 cases, registered in the Natinal Cancer Registy from 1993 to 1995, were analysied. Death Certificate Only(DCO) cases were not included. DCO % was estimated about 22%. We calculated the incidence rates according to the International Classification of Childhood Cancer. The age-standardized rates by diagnostic group was compared with those of other countries. The total incidence of childhood cancer were compared among 34 cities in Korea with the rates in the rest of the nation.
RESULTS
The crude incidence of all childhood cancer was 94.1 per million. The cumulative incidence to age 15 was 0.137% and the age-standardized rate, calculated using the world standard population, was 96.1 per million. In the incidence rates by diagnostic group, we observed many similarities with other countries in East Asia. The age-standardized rates of E, F and AL cities were significantly higher(p<0.05). In the 0-4 age group, F, AL and BB cities showed higher rates(p<0.05). In 5~9 years and 10~14 years, F city only had higher rates(p<0.05).
CONCLUSION
Further study will be needed in order to investigate possible environmental factors which may account for the regional variations.

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High Risk Group for Female Breast Cancer in Korea: Keun Young Yoo, Sue Kyung Park, Joohun Sung, Daehee Kang, Young Cheol Kim, Han Sung Kang, Jun Suk Suh, Jee Soo Kim, Ik Jin Yun, Sehwan Han, Dong Young Noh, Kyk Jin Choe; J Korean Cancer Assoc. 1998;30(3):435-449.

Abstract PDF: PURPOSE
A hospital-based case-control study was conducted to find out risk factors for developing breast cancer in Korea.
MATERIALS AND METHODS
Histologically confirmed incident cases of breast cancer(n=280) were selected from inpatients at the Department of General Surgery, Seoul National University Hospital during 1994 to 1997. Women with free of self-reporting past history of any malignancies were regarded as controls who were selected from the inpatients at the Department of Obstetrics and Gynecology of the same hospital during 1992 to 1994(n=930). Information on life-styles including reproductive factors were obtained by direct interview using questionnaire. Age- and education-adjusted odds ratio and 95% confidence interval were estimated by unconditional linear logistic regression.
RESULTS
Based on the risk factors identified by both this study and other epidemiologic studies previously performed in Korea, high risk group for female breast cancer in Korea was established as follows. (1) women with age over 50, (2) women who have a family history of breast cancer, (3) women with age at menarche before 14-year old, (4) women with age at menopause after 50-year old, (5) women who were not experienced a full term pregnancy, (5) nulliparous women (6) women with age at her first fullterm pregnancy after 35-year old (7) women who were not experienced breast feeding, (8) women with body mass index more than 25 kg/m2 or with body weight more than 64 kg.
CONCLUSION
Life-time risk of breast cancer, as an indicator of absolute risk, according to the risk factors should be pursued in further prospective studies with community population.

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Overexpression of c-erbB2 and Its Relationship with Chemotherapy in Breast Cancer: Ja Yun Koo, Hy Do Lee, Woo Hee Jung; J Korean Cancer Assoc. 1998;30(3):450-456.

Abstract PDF: PURPOSE
c-erbB2 encodes 185 kDa oncoprotein with tyrosine kinase activity and has homology to the epidermal growth factor receptor. c-erbB2 proto-oncogene is found to be overexpressed in approximately 20 to 30% of primary breast cancer and has been associated with poor prognosis and lower response to conventional chemotherapy.
MATERIALS AND METHODS
We perfonned a study on 40 infiltrating ductal breast cancers treated with primary surgery and adjuvant chemotherapy. We investigated c-erbB2 expression by immunohistochemistry in paraffin-embedded tissue using polyclonal antipeptide antibody(DAKO). We evaluated the relationships between its expression and the results after over 6 cycles of adjuvant chemotherapy including cyclophosphamide, methotrexate and 5-FU.
RESULTS
The median age at diagnosis was 43 years and the median follow-up time was 47.3 months. Thirteen(32.1%) of 40 patients showed the c-erbB2 overexpression in the external domains of protein. There were no correlations among c-erbB2 amplification and other prognostic factors such as hormonal receptors, histologic grade and tumor size. Estrogen receptor and progesterone receptor showed tendency of inverse correlation with c-erbB2 overexpression but it was not statistically significant(p>0.05). c-erbB2 positive patients showed shorter disease free survival compared to c-erbB2 negative patients in univariate analysis(p<0.05)(Kaplan Meire analysis). The patients without c-erbB2 overexpression seemed to survive longer but had no significant survival benefit(p>0.05).
CONCLUSION
These findings suggest that overexpression of c-erbB2 may be a marker of poor response to adjuvant chemotherapy with CMF regimen and may be an indicator of more aggressive therapy.

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The Expression of Phospholipase C-gamma1 and Its Cellular Characteristics: Dong Young Noh, Han Sung Kang, Young Chul Kim, In Ae Park, Yeo Kyu Yong, Seung Keun Oh, Kuk Jin Choe; J Korean Cancer Assoc. 1998;30(3):457-463.

Abstract PDF: BACKGROUND
The activation of phospholipase C(PLC) is one of the early cellular events in various growth process, including malignant transformation. PLC-gamma1 is activated through direct interaction with growth factor receptor tyrosine kinase. MATERIAL AND METHODS: Using immunoblot assay, we evaluated overexpression of PLC-gamma1 expression in twenty human breast cancer tissues. It was also determined whether there was any connection between other prognostic factors(numbers of metastatic axillary nodes, nuclear and histological grade, c-erbB2, p53 and E-cadherin) and the overexpression of PLC-gamma1 protein.
RESULTS
Seventeen of 20 breast cancer tissues showed overexpression of PLC-gamma1, which was corresponded to that seen on the immunohistochemistry( kappa= 0.8275, p = 0.003). Of 3 tumor markers, immunohistochemically determined, positive expression of E-cadherin only was associated with PLC-gamma1 protein overexpression in a range of statistical significance (p=0.045, kappa=0.607).
CONCLUSION
PLC-gamma1 overexpression might be pathogenic trigger involved in breast cancer and the relationship between expression of E-cadherin and PLC-gamma1 would require further elucidation.

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Brain Metastasis and Leptomeningeal Carcinomatosis in Breast Cancer: Yoon Soo Chang, Jeong Hun Seo, Ruth Lee, Joong Bae Ahn, Kwang Yong Shim, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Chang Ok Suh, Joo Hang Kim, Jae Kyung Rho, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):464-474.

Abstract PDF: PURPOSE
Brain metastasis is estimated to occur in 20 to 40% of cancer patients, and meningeal involvement has been reported in 5% to 8% of cancer patients. Even if the prognosis is grave, standard treatment modality of brain metastasis or leptomeningeal carcinomatosis has not been established. We evaluated the prognosis and the clinical features of the brain and leptomeningeal metastasis of the breast cancer.
MATERIALS AND METHODS
The 43 patients who was diagnosed as brain parenchymal metastasis or leptomeningeal carcinomatosis clinically, radiologically and/or cytologically were included in this study. The median age was 44(range: 27-61) years.
RESULTS
The median duration from brain metastasis to death was 181 days(range: 8~1599), and the median duration from leptomeningeal carcinomatosis to death was 39 days(range: 25~152). Age(p=0.7174) and number of brain metastatic lesion(p=0.4097) did not influence the survival, but the presence of other systemic metastatic lesion affected the survival(p 0.0224). When we compared the survival rates of patients according to treatment modality, the patients with systemic chemotherapy versus patients without systemic chemotherapy showed differences(p= 0.0009). Patients treated with whole brain radiation only versus patients with whole brain radiation and other systemic management also showed different survival rate(p=0.0009). But intrathecal chemotherapy had no effect on survival. Well differentiated, solitary lesions were treated by operation and/or gamma-knife surgery, and their effects were good.
CONCLUSION
Prolongation of survival was suggested with whole brain radiotherapy combined with systemic treatment in brain or leptomeningeal metastasis. Further study is expected to confirm this finding.

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5-Fluorouracil , Cisplatin , and Pirarubicin Combination Chemotherapy for Advanced Gastric Cancer: Jae Hong Seo, In Keun Choi, Suk Jin Kim, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Young Jae Mok, Jong Suk Kim, Jun Suk Kim; J Korean Cancer Assoc. 1998;30(3):475-481.

Abstract PDF: PURPOSE
Gastric cancer is the most common malignacy in Korea, However, standard systemic combination chemotherapy regimen has not been settled for advanced gastric cancer. 5-FU, Cisplatin, and Pirarubicin combination chemotherpay regimen has been tried to evaluate the response rate and toxicity in advanced gastric cancer patients.
MATERIALS AND METHODS
Elligibility included biopsy proven inoperable or relapsed adenocarcinoma of stomach with adequate bone marrow, hepatic, and renal functon. Thirty seven patients with histologically confinned locally advanced or metastatic gastric cancer were treated with cisplatin 15 mg/m2 IV day 1~5, pirarubicin 60 mg/m2 day 1, 5-fluorouracil 750 mg/m2 day 1~5 as a continuous intravenous infusion.
RESULTS
Twenty nine patients had measurable disease, 5 had received prior chemotherapy. Performance status was 0~1 in 24 and 2 in 13. There was 1 complete response and 13 partial response with an overall response rate of 48.3%(95% confidence interval 29.9~67.1%). The median survival is 7 months(95% confidence interval 5.4~8.6 months) and median response duration is 6 months. 19 patients experienced severe(WHO grade 3~4) leucopenia, 7 was thrombocytopenia, 13 was nausea and vomiting during chemotherapy. 11 patients experienced chemotherapy dose reduction or chemotherapy time delay due to severe hematologic or non-hematologic toxicities. There was no clinically recognizable cardiac toxicities.
CONCLUSION
We experienced 48.3% overall response rate, 7 months median survival, and 51.3% severe hematologic toxicities with 5-fluorouracil, pirarubicin and cisplatin combination chemotherapy regimen in advanced or metastatic gastric cancer patients.

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Postoperative FP ( 5-Fluorouracil , Cisplatin ) Chemotherapy for Patients with High - Risk Gastric Cancer: Kee Hyung Lee, Byeong Seong Ko, Hyung Shik Shin, Seon Mee Park, Sei Jin Youn, Seung Taek Kim; J Korean Cancer Assoc. 1998;30(3):482-487.

Abstract PDF: PURPOSE
Although adjuvant chemotherapy after resection of gastric cancer is a popular practice in Korea, there are still controversies about the effectiveness of the treatment. The fact that the relatively less effective drugs have been used and the rarity of large-scaled controlled studies may be partially responsible for the controversies. FP(5-FU, Cisplatin) combination is one of the most active regimen against advanced gastric cancer, consistently showing a response rate of 50~60%. We tried the FP chemotherapy as an adjuvant treatment for high-risk patients after curative resection of gastric cancer.
MATERIALS AND METHODS
Between February 1992 and June 1996, 35 patients with completely resected high-risk gastric cancer(postoperative stage III or IV except thase with M1) received six courses of FP chemotherapy. Endpoints were toxicities of treatment, relapse free survival, and overall survival.
RESULTS
With a median follow-up time of 17.1 months, Kaplan-Meier estimates of 2-year overall survival was 63.3% and relapse free survival estimates was 49%. There were no differences between stage III and IV patients in terms of overall survival or relapse free survival. Hematologic and non-hematologic toxicities were tolerable for most of the patients.
CONCLUSION
Postoperative FP combination chemotherapy was tolerable for patients with high-risk(stage III and IV) gastric cancer. It is too early to determine the long term survival rates for this patients, but 2-year overall and relapse free survival were comparable to that of historical non-cisplatin containing regimens. Randomized phase III studies are warranted.

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Recurrent Gastric Cancer after Curative Surgery: Cho Hyun Park, Jae Young Byun, Byoung Kee Kim, In Chul Kim; J Korean Cancer Assoc. 1998;30(3):488-496.

Abstract PDF: PURPOSE
Our aim was to determine the patterns of recurrence after curative resection of gastric cancer and to analyze the factors related with recurrence. We hypothesized that aggressive surgical approach including extended lymphadenectomy performed during last several decades may alter the patterns of recurrence.
MATERIALS AND METHODS
A retrospective analysis of 91 patients with recurrent gastric cancer after curative surgery at Department of Surgery, College of Medicine, The Catholic University of Korea, from 1989 to 1992.
RESULTS
Average time to recurrence was 21.8+/-17.9 months and 64 cases(70.3%) were recurred in 24 months after surgery. The most common type of recurrence was peritoneal dissemination(46.2%), followed by distant lymph node metastasis(24.2%), hematogenous metastasis(19.8%), and local recurrence(7.7%). Borrmann type III and IV, serosal invasion, lymph node metastasis, lymphatic and perineural invasion were the factors associated with recurrence. In peritoneal dissemination, serosal invasion and poorly differentiated adenocarcinoma were high risk factors. Mean duration of life after recurrence was 5.4+/-5.2 months. Re-operation was performed in 12 cases(13.2%), and survival was longer in resection cases compared to non-resection cases(10.9 vs 3.8 months)(p=0.034).
CONCLUSION
With the use of aggressive surgical approach, relative incidence of local recurrence has been lowered. On the other hand, peritoneal seeding was the most frequently encountered pattern of recurrence. Serosal invasion, Borrmann type III or IV and poorly differentiated adenocarcinoma were risk factors for peritoneal recurrence. Intensive follow-up examination is strongly suggested during the first 24 months after curative surgery for advanced gastric cancer because of high probability of recurrence in this period. Surgical resection for locally recurrent gastric cancer seems to prolong survival time.

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Restoration of Wild - type p53 Induces Chemo-sensitization in the Gastric Cancer Cell Line with Mutant p53: Ho Young Maeng, Sun Young Rha, Byung Soh Min, Yong Bae Kim, Hyun Joo Kwak, Tae Soo Kim, Kyu Hyun Park, Nae Choon Yoo, Ho Young Lim, Jin Hyuk Choi, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):497-507.

Abstract PDF: PURPOSE
It has been theorized that p53 may be involved in the sensitivity to chemotherapeutic agents. We evaluated the chemosensitivity of wild p53 after transduction into gastric cancer cell lines with mutant p53.
MATERIALS AND METHODS
YCC-3(parent cell line with mutant p53), YCC-3v(parent cell line transduced with vector alone) and YCC-3C3(clone with wild p53) cell lines were used in this study. p53 protein expression was measured by ELISA assay. Tumorigenicity and drug sensitivity were evaluated by soft agar and proliferation assay, respectively. Cell cycle analysis was performed by flowcytometry. Telomerase activity was measured by TRAP assay and terminal restriction fragment(TRF) length was measured after Southern blot analysis.
RESULTS
Even though p53 production from the YCC-3C3 cell line was three times higher than those of YCC-3 and YCC-3v cell lines, the cell cycle was the same in these three cell lines. In the YCC-3C3 cell line, drug sensitivity to etoposide and cisplatin was increased when we compared it to those of the YCC-3v cell line(etoposide, 50% versus 83%; cisplatin, 67% versus 83%). However, there was no chemo-sensitization effect with vincristine, vinblastine and carboplatin. After exposure to cisplatin, a G0/G1 check-point effect was found in the YCC-3C3 cell line, but not in the YCC-3v cell line. No differences were found in telomerase activity, TRFs length or DNA fragmentation between the YCC-3v and YCC-3C3 cell lines after cisplatin treatment.
CONCLUSION
Wild-type p53 gene transduction in the gastric cancer cell line induced sensitization to the cytotoxicity of etoposide and cisplatin. This suggests the possible application of combined chemo-gene therapy with an EP regimen and wild-type p53 in gastric cancer patients with p53 mutation.

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Effect on Malignant Phenotype of Gastric Cancer Cell Line after p53 Gene Transduction: Sun Young Rha, Tae Soo Kim, Sook Jung Jeong, Joong Bae Ahn, kwang Yong Shim, Soo Jung Kong, Hwa Young Lee, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Joo Young Lim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):508-520.

Abstract PDF: PURPOSE
To evaluate the effect of wild type p53 gene transduction on the malignant phenotypes for metastasis in gastric cancer, we compared the biological phenpotypes of gastric cancer cell lines based on p53 gene status. Then, after retrovirus-mediated wild-type p53 gene transduction, we compared those phenotypes among parent YCC-3 cell line, vector transduced YCC-3v cell line and a clone of YCC-3C3. MATERIAL AND METHODS: Four human gastric cancer celi lines were used; YCC-l(mutant), YCC-2(wild), YCC-3(mutant) and AGS(wild). DNAs of the cell lines were analyzed to evaluate the mobility shift with PCR-SSCP. Tumorigenecity and proliferation were evaluated by soft agar assay and proliferation assay. Migratory capacity was measured by adhesion assay and Boyden chamber assay. p53 protein expression was measured by Western blot analysis and VEGF, WAF-1 were measured by ELISA assay. Angiogenic activity was measured by cross-feeding assay and cell cycle analysis was performed by flowcytometry. In vivo tumorigenicity was measured by xenograft in nude mice.
RESULTS
YCC-3 cell line with mutant p53 gene expressed all the phenotypes for the metastasis such as tumorigenicity, migration and angiogenesis. In a stable clone of YCC-3C3, no differences were found in proliferation, cell cycle and WAP-1 expression when compared to those of the control YCC-3v and parent YCC-3 cell line, even if increased p53 protein production was found by Western blot analysis. However, both in vitro and in vivo tumorigenicity were decreased in a stably transduced YCC-3C3 clone. The adhesive capacity was also decreased in YCC-3C3 clone whereas the endothelial cell growth stimulatory effect and VEGF production showed no difference compared to those of the YCC-3v cell line.
CONCLUSION
Wild-type p53 gene transduction in gastric cancer cell line decreased tumorigenicity which resulted from decreased colony forming activity and adhesive capacity but not formed changes of angiogenic activity. This suggested the possible application of anti- metastasis strategy with p53 gene therapy in gastric cancer.

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Primary Signet Ring Cell Carcinoma of the Colon and Rectum: Hee Chul Kim, Chang Nam Kim, Choon Sik Jeong, Chang Sik Yu, Byung Sik Kim, Hun Kyung Lee, Jin Cheon Kim; J Korean Cancer Assoc. 1998;30(3):521-526.

Abstract PDF: PURPOSE
Signet ring cell carcinoma is a rare type of adenocarcinoma in the colon and rectum. We evaluated the differences of clinical features between colorectal signet ring cell carcinoma and ordinary adenocarcinoma.
MATERIALS AND METHODS
The clincopathologic data of 13 cases with primary colorectal signet ring cell carcinoma were reviewed. The primary colorectal signet ring cell carcinoma was diagnosed when following criteria were met: 1) the tumor was primary; 2) histologic material was adequate; 3) signet ring cells represented more than 50% of the cancer.
RESULTS
Patients ranged in age from 20 to 68 (median, 45) years; 7 were male, and 6 were female. Three tumors were located in the proximal colon, 3 in the distal colon, and 7 in the rectum. There was no case that had family history. Most cases (77%) were stage III, one was stage II, and two were stage IV with peritoneal seeding. There were 9 cases that showed local recurrence or distant metastases during follow-up periods 6 cases with peritoneal seeding, 3 with bone metastases, 2 with brain metastases and 1 with pelvic recurrence (two cases had either bone and brain metastasis, and one case had bone and peritoneal seeding). Prognosis was extremely poor, and overall two years survival rate was 25%. CONCLUSION: Early onset, mode of metastasis and poor prognosis may imply the different biologic behavior of signet ring cell carcinoma, compared with ordinary adenocarcinoma. To improve outcome, early diagnosis and radical operation should be stressed.

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The p16INK4A Expression in Stomach Cancer , Colon Cancer and Hepatoma Cell Lines: Sun Ju Choi, Soo Kie Kim, Se Jong Kim, Choon Myung Koh, Yoon Sun Park; J Korean Cancer Assoc. 1998;30(3):527-535.

Abstract PDF: PURPOSE
The p16(INK4A) gene encodes a specific inhibitor of cell cycle progression. In recent years, genetic deletion and altered expression of p16(INK4A) gene were frequently showed in many human cancers. So, the p16(INK4A) gene is considered as tumor suppressor gene. However, there has been a few data for the p16(INK4A) in gastric cancer, colon cancer, and hepatoma.So.we investigated the genetic deldtion and altered expression of p16(INK4A) in gastric cancer, colon cancer and hepatoma cell lines.
MATERIALS AND METHODS
The homozygous deletion of p16(INK4A) was examined by using PCR and the protein expression of p16(INK4A) by using Western blotting in cancer cell lines established from Korean patients: stomach cancer, colon cancer and hepatoma cell lines.
RESULTS
Homozygous deletion of p16(INK4A) was detected only 1 stomach cancer cell line out of 13 cell lines examined. The p16(INK4A) was detected in 3 of 13 cancer cell line. These results showed the low frequency of p16(INK4A) homozygous deletion and high frequency of p16(INK4A) expression alteration in stomach cancer, colon cancer and hepatoma cell lines.
CONCLUSION
In this study, it may be suggested that the altered pl6(INK4A) expression as well as p16(INK4A) gene deletion play important role in oncogenesis. Further studies to determine the mechanism of p16(INK4A) gene inactivation are expected.

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Simultaneous Elevation of Epidermal Growth Factor Receptor and Transforming Growth Factor - alpha in the Serum of Colorectal Cancer Patients: Kang Sup Shim, Kwang Ho Kim, Ju Young Seoh, Eung Bum Park; J Korean Cancer Assoc. 1998;30(3):536-543.

Abstract PDF: No abstract available.

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Microsatellite Instability in Korean Hepatocellular Carcinoma using Fluorescent - PCR: Young Suk Park, Hee Jung Wnag, Moon Ju Oh, Eun Ha Kim, Kyung Ok Lee, Myung Wook Kim, Young Gyu Chai; J Korean Cancer Assoc. 1998;30(3):544-552.

Abstract PDF: PURPOSE
Hepatocellular carcinoma (HCC) is one of the most common cancers in many parts of the world, however the molecular mechanisms underlying liver cell transformation remain obscure. The instability of microsatellite sequences dispersed in the genome has been linked to a deficiency in cellular mismatch repair. This phenotype has been frequently observed in various human neoplasms and is regarded as a major factor in tumorigenesis. To investigate cumulative genetic changes related with apoptosis during development and progression of HCC, we examined DNAs isolated from 12 Korean HCCs and their adjacent non-tumorous parts to look for evidence of microsatellite instability (MSI).
MATERIALS AND METHODS
Twelve microsatellite loci (D6S271, D6S426, D13S153, D13S263, D17S849, D17S938, D17S945, D18S474, D18S64, D19S420, D.19S418 and D19S210) were amplified by PCR from 12 Korean HCCs, and analyzed using an automated DNA analyzer.
RESULTS
The high percentages of the MSI were found for the loci of D6S426 (33.3%) and D17S945 (25.0%). The related genes with high frequency of MSI were noted in the wafl (41.7%) and p53 (25.0%). From this study, fifty eight percent of HCCs (7/12) showed MSI with at least one marker.
CONCLUSION
This results suggest that the analysis of MSI in HCC might be useful for identifying genes whose loss of function contributes to the development of liver cancer. Furthennore, this method may give a more rapid and accurate sizing of the PCR products of microsatellite; making the routine assessment of MSI possible in many clinical fields.

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Comparison of Two Different Hepatoma cell Lines Expressing Herpes Simplex Virus Thymidine Kinase ( HSVtk ) on Their Semsotovotu and Bystander Effect of Ganciclovir (GCV ): Eun Jung Suh, Tae Wan Chung, Seon Hee Kim, Teoan Kim, Jae Bok Park, Yong Wun Ryu, Chong Won Lee; J Korean Cancer Assoc. 1998;30(3):553-560.

Abstract PDF: No abstract available.

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Urinary Gonadotropin Fragment ( UGF ) Measurements , Its Efficacy in Patients with Gynecologic and Various Malignancies: Joo Hyun Nam, Jong Hyeok Kim, Sang Yoong Park, Roger Walker, Laurence A Cole; J Korean Cancer Assoc. 1998;30(3):561-572.

Abstract PDF: No abstract available.

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Effects of IFN - gamma on Spheroid and Raft Culture of Squamous Cell Carcinoma of the Head and Neck: Seung Ju Lee, Chun Dong Kim, Tae Young Koh, Keun Ho Chang, Chae Seo Rhee, Seong Jun Yoon, Sagn Goo Lee, Hyun Ju Lee, Kwang Hyun Kim; J Korean Cancer Assoc. 1998;30(3):573-582.

Abstract PDF: PURPOSE
To establish new in vitro model systems that better reflect in vivo condition, multicellular tumor spheroids(MTS) and raft culture were developed using cell lines of squamous cell carcinoma(SCCHN) of the head and neck. In these 3-dimensional systems, the expression of cell surface molecules which are important for modulation of physiology of tumor cells were studied with or without the treatment of interferon(IFN)-gamma.
MATERIALS AND METHODS
Four SCCHN cell lines were used for MTS and raft culture. The effects of interferon-gamma on SCCHN cells were examined by immunohistochemistry.
RESULTS
All cell lines formed MTS, but only Tu-138 showed a good stratification at the air-liquid interface in the raft culture system. Immunohistochemical studies of MTS using monoclonal antibodies revealed a strong staining for MHC class I, no staining for MHC-DR, a weak patch expression of ICAM-1 and a central strong staining for integrin a 6. Staining patterns were similar for the raft cultures except integrin a 6(intense full-thickness positivity). In both systems, IFN-gamma enhanced the expression of MHC-DR and ICAM-1. No significant change was found in the expression of MHC class I and integrin a 6.
CONCLUSIONS
MTS and raft culture system were established successfully from the SCCHN cell lines. IFN-gamma can modulate the surface molecules of tumor cells in the 3-dimensional culture systems.

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Fractionated Stereotactic Radiation Therapy for Intracranial Malignant Tumor: Preliminary Results of Clinical Application: Dae Young Kim, Yong Chan Ahn, Seung Jae Huh, Dong Rak Choi, Jung Il Lee, Jong Hyun Kim, Hyung Jin Shin, Do Hoon Lim, Hong Gyun Wu; J Korean Cancer Assoc. 1998;30(3):583-590.

Abstract PDF: PURPOSE
Fractionated stereotactic radiation therapy(FSRT) is a new modality that combines the accurate focal dose delivery of stereotactic radiosurgery with the biological advantages of conventional radiotherapy. We report our early experience using FSRT for intracranial malignant tumor.
MATERIALS AND METHODS
Between October 1995 and December 1996, 16 patients(9 males and 7 females aged between 10~64 years) with central nerve system malignancy were treated using FSRT. Sixteen patients had the following diagnosis: 6 high-grade gliomas, 1 pineoblastoma, 4 germinomas, 2 medulloblastomas, and 3 solitary brain metastases. Using the Gill-Thomas-Cosman relocatable head frame and multiple non-coplanar therapy, the daily dose of 2 Gy(3 Gy in metastasis) was irradiated at 85~100% isodose surface.
RESULTS
Although the follow-up period is relatively short(range; 2~18 months), post- treatment clinical courses in 16 patients have been consistent with changes similar to those found after conventional radiation therapy. No significant adverse effects were observed in our neurological and radiological studies. Four out of 5 patients with high grade glioma died from progressive disease, surviving from 7 to 17 months(median 14 months), but patients with pineoblastoma, germinoma and medulloblastoma showed no evidence of recurrence. All patients with metastasis obtained a neurologic response, but two among them died with extracranial progression and one die from multiple intracranial metastasis.In overall patient setup with scalp measurements, reproducibility was found to have mean of 1.1+/-0.6 mm from the baseline reading.
CONCLUSION
FSRT and relocatable stereotactic head frames were well tolerated with minimal transient acute side effects. Subacute or late complications were not observed, because the follow-up period was short. We expect that FSRT might be a good indication for; recurrent disease with previous radiation therapy history, tumors of relatively large volume, lesions adjacent to radiosensitive organs, and as a boost, following conventional radiation therapy.

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The Survival Rate of Stage IIB Ostosarcoma after Neoadjuvant Chemotherapy ( Modified T10 Protocol ): Jae Do Kim, Jeong Soo Bae, Myung Rae Cho; J Korean Cancer Assoc. 1998;30(3):591-598.

Abstract PDF: PURPOSE
The survival rate according to the methods of treatment was significantly higher in the osteosarcoma patients in which limb salvage operation with neoadjuvant chemotheraphy. The purpose of this study is to analyze the results of treatment in the Stage IIB osteosarcoma patients who treated with modified T10 protocol.
MATERIALS AND METHODS
From Jun. 1990 to Oct. 1997, thirty eight cases of Enneking's stage IIB osteosarcoma in extremities, were treated with neoadjuvant chemotherapy by modified T10 protocol of Rosen. Their mean age was 22 years old (8 months to 55 years). And average duration of follow up is 29 months(10 manths to 88 months). The preoperative chemotherapy consisted of high dose methotrexate(HDMTX)(above 12 years old: 8 g/m2, below 12 years old: 12 g/m2), adriamycin(ADR)(30 mg/m2/day x 2), intraarterial cisplatin(CDDP)(100 mg/m2) or ifosfamide (IFO)(1.8 g/m2/day x5). The preoperative tailoring was performed according to the radiologic response after chemotherapy. If the patient revealed good response, we continued the chemotherapy next one more cycle and if not, stoped the chemotherapy or changed the cisplatin to ifosfamide. The postoperative chemotherapy consisted of HDMTX, adriamycin, ifosfamide or cisplatin with 4 cycles. According to the pathologic response to the pre-operative chemotherapy, we use HDMTX, ADR, CDDP in good response group and HDMTX, ADR, IFO in poor response group respectively.
RESULTS
On the latest follow up, 27 patients were continuous disease free(CDF 27/38), 4 patients were alive with disease(AWD) and 6 patients were died of disease(DOD) and I case was died of bone marrow and hepatic failure due to complication of chemotherapy. According to Kaplan-Meier's plot, the overall 5 years survival rate was 73.6%, and continuous disease free 5 years survival rate being 64%. The comparison of continuous disease free survival rates between good radiologic response group and poor response group showed 73% and 55%. The continuous disease free survival rates according to the pathologic response in good response group and poor were 90 % and 55%. During the chemotherapy, the most serious complications were leukocytopenia and bone marrow failure. These were controled by granulocyte colony stimulating factor(G-CSF) and leukotrophic agent. Other minor complications were nausea, vomiting, headache and extrapyramidal symptom, which were easily managed by simple conservative measure.
CONCLUSION
It was obtained that the overall 5 years survival rate was 73.6%, and continuous disease free 5years survival rate being 64% with modified T10 protocol.

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Limb - Conserving Surgery and Interstitial Brachytherapy Plus External Radiation Therapy in Extremity Soft Tissue Sarcoma: Yong Chan Ahn, Do Hoon Lim, Jai Gon Seo, Moon Kyung Kim, Hong Gyun Wu, Dae Young Kim, Seung Jae Huh; J Korean Cancer Assoc. 1998;30(3):599-607.

Abstract PDF: PURPOSE
In order to avoid functional disability that may be caused by radical excision or amputation in extremity soft tissue sarcomas, authors employed limb-conserving surgery together with extemal radiation therapy plus interstitial brachytherapy.
MATERIALS AND METHODS
From June 1995 to Febrary 1997, 10 extremity soft tissue sarcoma patients were treated with limb-conserving surgery and external radiation therapy plus interstitial brachytherapy. In six patients, whose histologic diagnoses were made at the time of surgery, wide or marginal excision and interstitial brachytherapy was done 4 weeks before postoperative external radiation therapy. In four patients whose histologic confinnations were done before definitive treatment, preoperative external radiation therapy was given 4 weeks before surgery and interstitial brachytherapy. The types of surgery were wide excision in five patients, and marginal excision in five patients. Gross or microscopic residual was left at the surgical resection margins in four patients. The brachytherapy dose ranged from 17.5 Gy to 24 Gy and external beam radiation did from 40 Gy to 45 Gy.
RESULTS
With the median follow-up duration of 21.5 months(range: 13 to 29 months); one local recurrence, and three new distant metastases were observed. There were three patients with wound complications attributable to the current treatment regimen.
CONCLUSION
Satisfactory local tumor control may be achievable with limb-conserving surgery and external radiation therapy plus brachytherapy in patients with extremity soft tissue sarcomas, while more caution should be used to avoid wound problems.

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A Case of Placental Metastasis from Advanced Gastric Carcinoma: Mi Sook Lee, Sang Hee Kim, Je Hwan Lee, Sung Bae Kim, Cheol Won Suh, Kyoo Hyung Lee, Jung Shin Lee, Woo Kun Kim, Sang We Kim; J Korean Cancer Assoc. 1998;30(3):608-612.

Abstract PDF: Placental and fetal involvement by matenal malignancy is rare. We report a case of placental metastasis from advanced gastric carcinoma in a 27 year-old woman. The patient also had disseminated bone metastasis, bone marrow involvement, malignant ascites, multiple lymphadenopathy, and disseminated intravascular coagulopathy. Cut surface of the placental body showed many, variable-sized, grayish white nodules and plaques. Light microscopic finding showed sheets of poorly differentiated adenocarcinoma in intervillous spaces. Villi were not invaded. Despite palliative chemotherapy the patient died of massive gastric cancer bleeding. But the patients child is alive and doing well with age of 11 months. We suggest that the presence of malignancy in pregnancy demands complete evaluation of the placenta and adequate follow-up of the infant for the sign of involvement.

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A Case of Adenocarcinoma of the Lung In Patient with Chronic Lymphpcoytic Leukemia: Sun Ae Lee, Young Jin Kim, Kyu Chul Lim, Chong Il Jung, Sang Yong Jung, Mi Kyung Shin, Young Joo Park, Tae Eui Song; J Korean Cancer Assoc. 1998;30(3):613-619.

Abstract PDF: In Korea chronic lymphocytic leukemia(CLL) is a rare diesase with evidence immunologic incompetence. The immunodeficiency of patients with CLL could place them at increased risk of new cancers. The incidence of secondary malignancy, including lung cancer has increased in patients with CLL and this should be also considered in the differential diagnosis of a new pulmonary infiltrate appearing in patients with known CLL. A-73-year old male patient with CLL was admitted to our hospital because of dyspnea. Chest X-ray showed multiple scattered small nodules in both lung fields and alveolar consolidation mass at right lower lung. Histopathological examination of the bronchoscopic biopsy specimen demonstrated that he had a moderatly differentiated adenacarcinoma of lung. Since we experienced a case of metachronous adenocarcinoma of lung in patient with known CLL, we report this with a review of literatures.

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A Case of Adrenal Carcinosarcoma: Joong Wha Chung, Ki Ju Lee, Ji Hyun Lee, Hyun Lee Kim, Gyoo Moon, Bong Kyu Lee, Dong Min Kim, Hak Yeon Bae, Sung Chul Lim; J Korean Cancer Assoc. 1998;30(3):620-624.

Abstract PDF: An adrenal carcinosarcoma is extremely rare with reported three cases. This neoplasm is extremely aggressive with distant metastasis arising from the sarcomatous component. A 48-year-old female was present with abdominal distention for 1 month. All laboratory studies were within normal reference range including urinary and serum corticosteroids. The tumor consist typical areas of adrenal carcinoma and sarcoma. Sarcomatous elements were identified and confirmed both immunohistochemically and ultrastructurally. After radical resection, the patient developed rapid local and distant metastatic recurrence and died three months after surgery. This is the first reported case of adrenal carcinosarcoma in korea.

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