Cancer Research and Treatment

Expression of p53 and Tumor Angiogenesis in Gastric Cancer: Sung Chul Lim, Kweong Chun Kim; J Korean Cancer Assoc. 1996;28(1):1-12.

Abstract PDF: p53 is a tumor suppressor gene product identified in a wide variety of tumors. Studies have shown that wild-type p53 has an inhibitory effect on cell proliferation and transformation. Point mutations result in a mutant p53 protein with an altered conformational structure and an increased half life. Mutant p53 protein accumulates within the malignant cells where it is readily detected. Accumulation of mutant p53 protein is believed to be a common feature of malignant disease, and is a new parameter to evaluate the cell biology and prognosis of cancer. Factor VIII-related antigen is one of the three functional components of the antihemophiliac factor. It is synthesized in endothelial cells of blood vessel and is widely used as a nearly specific marker to evaluate the differentiation of endothelial cells. There was a clear distinction between a stage without neovascularization, which correlated with a paucity of metastasis, and a stage in which increasing neovascularization correlated with a rising rate of metastasis. Therefore the authors asked whether the extent of angiogenesis and p53 expression in advanced gastric carcinoma(AGC) and early gastric carcinoma(EGC) of the diffuse type and the intestinal type correlated with nodal status. To investigate whether tumor angiogenesis and p53 expression affect nodal metastasis or not, the authors counted tumor microvessels of 66 patients. (40 cases of AGC- 20 cases of nodal metastasis and 20 cases of no metastasis, 26 cases of EGC- 6 cases of nodal metastasis and 20 cases of no metastasis). Highlighting of the vessels by immunohistochemical staining for factor VIII-related antigen and assessment of p53 expression were done. As a result, of the 28 cases of the diffuse type, only two were positive for p53, but, of the 38 cases of the intestinal type, 20 cases were positive for p53. Nevertheless, no correlation was found between p53 protein accumulation and lymph node metastasis. The degree of tumor angiogenesis in lymph node free group is higher than in lymph node metastasis group. In conclusion, p53 mutations seem to play a role in oncogenesis only in the intestinal type of gastric carcinomas, however, p53 protein accumulation has no prognostic value in gastric carcinoma, but, tumor angiogenesis is a suspected predictor for patient's prognosis.

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Late Jaundice after Curative Resection of Gastric Cancer: Ki Hoon Jung, Eun Sook Lee, Jeoung Won Bae, Cheung Wung Whang; J Korean Cancer Assoc. 1996;28(1):12-19.

Abstract PDF: Surgeons and oncologists consider the development of late jaundice following curative resection in advanced gastric cancer patients to be an untreatable condition of cancer recurrence. Usually they opt for a conservative management approach rather than to attempt aggressive diagnosis and treatment. To evaluate the justify of this approach, authors retrospectively reviewed 629 cases of curative resections for advanced gastric cancer that had been performed at the Korea University Hospital during a six years time period between Jan. 1986 to Jan. 1992. Of the 629 patients, 51 patients had either bilirubin levels greater than 2 mg% or had shown signs of clinical jaundice. The patients were classified in the following method: type 1a: single liver metastasis, 1b; multiple liver metastases, 2; hepatoduodenal ligament LN metastases, 3; GB or CBD stones, 4; chemotherapy toxicity, 5; hepatitis. We observed 3 cases(6%) of type 1a, 10 cases(19%) of type lb, 14 cases(27%) of type 2, 5 cases(10%) of type 1a+2, 7 cases(14 %) of type 1b+2, 6 cases(12%) of type 3, 4 cases(8%) of type 4, 2 cases(4%) of type 5. The onset of jaundice development differed between recurrent and nonrecurrent jaundice. In nonrecurrent cases, the late jaundice developed shortly after the operative procedure, whereas jaundice usually appeared l yerar after the operation in recurrent cases. There was no significant difference in the primary site of advanced gastric cancer between recurrent and nonrecurrent jaundice. Although late jaundice usually developed in patients with TNM stage II and III cancers, there was no significant difference between the recurrent and nonrecurrent cases. Management of late jaundice consisted of aggressive procedures such as choledochotomy, cholecystectomy, PTCD(Percutaneous transhepatic cholangiography with drainage) and conservative approaches for nonrecurrent cases, and hepatectomy, PTCD, RT (Radiotheraphy) and choledochotomy was done in recurrent cases. These procedures resulted in good outcomes with symptomatic improvement and a better quality of life. The duration of survival in patient who received treatment for the jaundice was on average 8 months in the recurrent cases and 33 months in the nonrecurrent cases, whereas a surviva1 of only 2.4 months was observed in patients who received no treatment for the late jaundice. The results of this study strongly suggested that aggressive approaches in the diagnosis and treatment for late jaundice following curative resection of advanced gastric cancer leads to a longer duration of survival and a better quality of life. We concluded that aggressive treatment for patients developing late jaundice should be performed for the better outcome of patients.

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Recurrence after Curative Resection for Gastric Cancer: Jin Woo Ryu, Young Jin Kim, Shin Kon Kim; J Korean Cancer Assoc. 1996;28(1):19-27.

Abstract PDF: In an effort to help making plans for follow-up and management in patients after initial operation of gastric cancer, ninty two patients who were found to have recurrence after initial curative resection for gastric cancer at the Department of Surgery, Chonnam University Hospital from January 1985 to December 1994 were studied for the recurrence pattern of gastric cancer. Recurrences were detected based on clinical, radiological, endoscopic findings and by operation, and these results were testified by chi square test. The results were as follows; 1) In 92 patients, total of 108 recurrences were identified. 88.0% of total recurrences were intraabdominal.The most common site of recurrence was peritoneal(38.9%), and next was loco-regional(35.2%), liver(13.9%) and extraperitoneal metastasis(12.0%), in order of frequency. 2) Liver metastasis was more frequent in cancers located in antrum(22.0%, p=0.016l), in well differentiated tumor(38.9%, p=0.0032), in Borrmann type II(50.0%,p=0;0044), and in metastasis to Group 1 regional lymph node(29.0%, p=0.0106). 3) Peritoneal recurrence tended to occur more frequently in poorly differentiated cancers (p = 0.047). 4) Extraperitoneal metastasis was more frequent in stage IIIb(23.0%,p=0.0432). 5) In 92 patients, 13 patients received reoperation(14.1%). Curative reoperation could be carried out in 5 cases(5.4%). One patient had liver metastasis and four patients had locoregional recurrence. 6) There was no differences in patterns of recurrence by DNA ploidy patterns. Recurrence patterns after curative resection of gastric cancer showed different features on celllular differentiation of primary tumor, site of primary tumor, stage, and lymph node metastasis. Therefore, this findings may be helpful in planning for postoperative follow-up and adjuvant therapy, and early detection of radically resectable locoregional recurrences.

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Analysis of High Risk Factors for Lymph Node Metastasis in Early Gastric Cancer: Sung Hoon Noh, Wan Soo Kim, Ki Hyeok Lah, Yong Il Kim, Seung Ho Choi, Coong Bai Kim, Jin Sik Min, Kyung Shik Lee; J Korean Cancer Assoc. 1996;28(1):27-35.

Abstract PDF: The prognosis of early gastric cancer (EGC) is generally excellent, and the proportion of EGC cases to advanced gastric cancer cases is steadily increasing nowadays. The presence or absence of lymph node metastasis in EGC is important prognostic factor, in other words, the survival rate or recurrence rate of node negative EGC is known to be much better than that of node positive ones. Retrospective analysis was performed for 682 EGC cases which underwent more than D2 resection in Yonsei medical center between 1986 Jan. to 1993 Dec, in order to investigate the clinicopathological factors to predict the possibility of lymph node metastasis. In this study, several factors such as age, sex, tumor location, tumor size, multiplicity, depth of invasion, macroscopic and histologic type were evaluated to determine the significance. In the analysis of these eight factors, sex, tumor size, depth of invasion and macroscopic type were statistically correlated with lymph node metastasis. We consider these factors to be possible high risk factors for lymph node metastasis in early gastric cancer.

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Prognosis and Quality of Life of Non - resectable Gastric Cancer: Kang Young Lee, Yong Il Kim, Sung Hoon Noh, Jin Sik Min; J Korean Cancer Assoc. 1996;28(1):35-43.

Abstract PDF: The records of 217 patients with proven non-resectable gastric cancer were studied at Yonsei University Hospital over the 4 years period from January 1990, to December 1993 to clarify Quality of life of gastric cancer patients who could not be resected. The mean survival time of total patients was 10.5 months.(Male: 10.6, Female; 10.4) The survival time was affected by gross type and histologic type. Survivals according to the Borrmann type were as follows; Borrmann type I: 11.5 months, II: 11.3 months, III: 10.2 months, IV; 8.2 months. Survivals according to the histological type were as follows; well differentiated: 20.3 months, moderately differentiated: ll.5 months, poorly differentiated: 9.2 months, signet ring cell carcinoma: 7.9 months. The age, sex and cause of non-resectability did not affect the survival. The mean score of QOL(quality of life) according to Spitzer index was 4.8. The QOL was affected by histological type and type of operation. QOL index scores according to histo logic type were as follows; well differentiated: 6.4, moderately differentiated: 5.5, poorly differentiated: 4.7 and signet ring cell type: 3.5. QOL index scores according to type of operation were as follows; by pass procedure: 5.6, Explo-lapa & closure: 4.0. In conclusion, we could confirm the bad limited survival and quality of life of non-resectable gastric cancer patients. We suggest a new therapeutic approach to improve the survival and QOL of non-resectable gastric cancer patients.

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Lymph Node Micrometastases from Dukes'B Colorectal Cacner : Immunohistochemical detection , and prognostic significance: Kwan Sik Lee, Il Woo Whang, Mae Ja Park, Ik Soo Kim, In Soo Suh, Soo Han Jun; J Korean Cancer Assoc. 1996;28(1):43-50.

Abstract PDF: This study was performed to identify micrometastases in lymph nodes from colorectal cancer considered free of disease by the routine hematoxylin-eosin stain, using immunohistochemistry according to ABC method. All 993 lymph nodes from 56 patients with Dukes'B colorectal cancer were stained retrospectively with antibody against cytokeratin(antikeratin AEl/AE3, Boeringer Mannheim). Single tumor cells and small clusters of tumor cells were detected in nodes of 20 patients(35.7%), mainly in the subcapsular sinuses. Twenty nine of the 36 patients with cytokeratin-negative lymph nodes lived after a mean followup of 55 months. But, 8 of the 20 patients with cytokeratin-positive lymph nodes lived over the same time period. Multivariate analyses were performed with several prognostic factors: age, histologic differentiation, vascular and lymphatic invasion, and presence of micrometastases. The most significant factor for both survival and recurrence was the presence of micrometastases(P= 0.0403 and P=0.0364 respectively). The presence of cytokeratin-positive cells within lymph nodes of Dukes'B colorectal cancer correlated with a poor prognosis.

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Expression and Clinical Relevance of c-erbB-3 in Rectal Cancer: Chong In Lee, Sun Young Rha, Jin Oh Park, Hyun Cheol Chung, Jae Yong Cho, Joong Bae Ahn, Nae Choon Yoon, Tae Soo Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sup Choi, Jin Sik Min, Byung Soo Kim, Woo Ick Ja; J Korean Cancer Assoc. 1996;28(1):50-63.

Abstract PDF: Recently, there is an increasing tendency of colorectal cancer in Korea, probably due to changes of diet pattern to western style. In rectal cancer, as the local recurrence is a common and major problem despite of radical resection, it is recommended to use 5-fluorouracil(5-FU)- based chemotherapy in combination with pelvic radiation after radical operation in MAC B,-C, cancers. But until now, there are many controversies about the effective chemotherapeutic agent, radiation dose, route, and chemoradiation schedule. There is increasing evidence that genes involved in normal cell growth and differentiation(oncogenes) or genes that encode for growth factor are important in determining the development and biologic aggressiveness of various cancers. Among many oncogenes thought to be related with cancer, c-erbB-2 is a relatively well known protein to be associated with cancers, especially in breast and colorectal cancers. In addition to c-erbB-2 and Epidermal Growth Factor Receptor(EGFR), c-erbB-3 belongs to Type -I Growth Factor Receptor Family(EGFR-related Family) and is the most recently identified protein in EGFR-related Family. There have been a few reports about the prognostic value of c-erbB-3 in breast and prostate cancers. In this study we performed immunohistochemical staining of 114 surgically resected specimens of rectal cancers to investigate the expression rate and clinical relevance of c-erbB-3 as a prognostic factor and drug selection marker. c-erbB-3 expression rate was 46% in 114 rectal cancers and there were significant differences in recurrence rate and survival rate between c- erbB-3 positive and negative group. Twenty-one cases(40%) recurred in 52 c-erbB-3 positive cases and 10 cases(16%) recurred in 62 c-erbB-3 negative cases(p=0.004). The difference in recurrence rate between c-erbB-3 positive and negative group was significant exclusively in MAC stage C(p=0.0126), but not in MAC stage B(p=0.4357). In c-erbB-3 positive and negative group, 2-year disease free survival rate was 66% and 87%, respectively(p=0.0052), and 2-year overall survival rate was 84% and 95%, respectively(p=0.005). Again, the difference in 2-year disease free survival rate between the two groups was significant only in MAC stage C(p=0. 0137), not in stage B(p=0.4182). There were no significant differences in recurrence rate and 2- year disease free survival rate in chemo-radiation group regardless of c-erbB-3 expression and stage. But in adjuvant radiotherapy alone group, increased recurrence rate and decreased survival rate were found in c-erbB-3 positive group. This finding suggested c-erbB-3 as a possible relative radioresistance marker, in whom a higher radiotherapy dose is needed. In conclusion, c-erbB-3 may be regared as a prognostic marker and as a possible indicator of radioresistance in the treatment of rectal cancer.

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Establishment and Biological Carcterization of Human Colorectal Carcinoma Cell Lines Expressiong Carcinoembryonic Antigen: Jin Cheon Kim, In Chul Lee, Seon Ae Roh, Yoo Kyung Lee, Kyung Sin Kim, Kun Choon Park; J Korean Cancer Assoc. 1996;28(1):63-72.

Abstract PDF: For serum carcinoembryonic antigen (CEA) is not always elevated in recurrence or metastasis of colorectal carcinoma (CRC), activation of colorectal carcinoma cells by CEA may be selective. We have established and characterized two CEA-expressing colorectal carcinoma cell lines which were analysed in relation to the clinical course. Two cell lines originated from rectal carcinoma were cultured in DME enhanced media and subcultured by 40 and 55 times respectively. AMC 4 grew in an anchrage-independent with delayed cell doubling time (93 hrs), while AMC 5 did in an anchorage-dependent with normal doubling time (43 hrs). Tumorigenesis revealed infiltrative moderate-differentiated adenocarcinoma in AMC 4 and expansile well-differentiated adenocarcinoma in AMC 5. Karyotyping by Trypsin-Giemsa banding showed 47, XY, 21(+ ), del (2q, 5q) and 46, XY, 5(+ ), 20(+ ), 12(- ) respectively. Both cell lines were aneuploid. AMC 5 expressed large amount of 55 kD NCA as well as 180 KD CEA, but AMC 4 did traces of them by indirect immunofluorescence and immunoblot. AMC 5 cells bound optimally to solid-phase type IV collegen, laminin, and CEA by 18.7¡¾ 0.4, 21.4 ¡¾ 0.6 and 17.7¡¾0.4, while AMC 4 cells bound less. The patient of AMC 4 showed liver metastasis on 6 months after curative surgery and AMC 5 did no evidence of recurrence. In conclusion, biological characteristics of two CEA-expressing CRC cell lines seemed to be consistent with their clinical course.

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A Clinical Analysis of Primary Small Bowel Cancer: Sang Yong Yun, Ik Jin Yun, Se Hwan Han, Jae Gahb Park, Kuhn Uk Lee, Kuk Jin Choe; J Korean Cancer Assoc. 1996;28(1):72-78.

Abstract PDF: Though small intestine accounts for 75% in the length and 90% in the mucosal surface of the gastrointestinal tract, primary small bowel cancer is relatively rare. So characteristics of smal1 bowel cancer are not known precisely. We analyzed 63 cases of the primary small bowel cancer(except ampulla of Vater cancer) that were operated at the department of surgery, Seoul National University Hospital from 1980 to 1994. The clinical features, diagnostic method, tumor location, histologic findings, preoperative diagnotic accuracy and type of operation were analyzed. The results were as follows; 1) There were 37 men and 26 women, ranging from 24 years to 95 years of age. The most prevalent age group was 6th decade(25 cases, 40%). 2) There were 28 adenocarcinomas, 18 lymphomas, 13 leiomyosarcomas, 3 carcinoid tumors and I liposarcoma, 3) The primary sites were the duodenum in 26, jeiunum in 13, ileum in 25 patients. The adenocarcinoma ocurred most frequently in duodenum(24/28,86%), lymphoma in ileum(17/18, 94%) and leiomyosarcoma in the jejunum(13/19,77%) 4) The most frequent chief complaint was abdominal pain(53%) followed by hemorrhage (21%), abdominal mass, obstructive symptom, jaundice and so on. 5) The average duration of symptoms of adenocarcinoma was 6 months, lymphoma 4 months, leiomyosarcoma 9 months and carcinoid 3 months 6) The correct diagnosis was made preoperatively in 59% of cases. Preoperative diagnosis of duodenal cancer was made by UGI series and/or endoscopy(79%). Jejunal and ileal cancers were diagnosed preoperatively by small bowel series and/or abdominal CT(44%). 7) Curative resection was possible in 54%. Palliative resection, bypass surgery, open biopsy were performed in 46% cases because of the distant metastasis or irresectability. 8) The median duration of recurrence,among the recurrent cases was 15 months. Adenocarcinoma had the poorer prognosis. Median disease free survivals in adenocarcinoma were 12.6 months, lymphoma 16 months and leiomyosarcoma 27 months. Median disease free survivals in curative resection group was 26 manths compared to 10 months in palliation group. We concluded that the most important factor determining the prognosis of small bowel cancer patient may be initial stage of cancer at the time of the first diagnosis.

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A Clinical Study on Patients with Thyrid Cancer: Chin Sun Bae, Seok Whan Hong, Wan Hee Yoon, Eil Sang Chang, Kwang Sun Suh; J Korean Cancer Assoc. 1996;28(1):78-88.

Abstract PDF: One hundred and seven patients with thyroid cancer who were undertaken operation at the Department of Surgery, Chungnam National University Hospital during 5 years from January 1990 until December 1994 were clinically analysed and the results were as follows. 1) Female was predominated over male by the ratio of 5.3: l. 2) The most prevalent age was 4th decade, followed by 5th, 6th, and 7th decade in order of frequency. 3) The most common clinical manifestation was mass in anterior neck(86.0%), followed by fatigue (19.0%), palpitation(15.9%), and lateral neck mass(14.0%). 4) Thyroid function test was in normal range in 92.5% of patients, and cold nodules were revealed in 86.0% of patients on thyroid scintigraphy. 5) As to the duration of disease, 33.6% of patients were within 3 months, 55.1% of cases within 1 year; and in 7 patients, it was over 10 years. 6) 45.8% of cases were located in the right lobe, 38.3% in the left lobe, 14.0% in both lobes, and 1.9% in the isthmus. 7) As to the operative procedures, lobectomy was undertaken in 45 cases, total thyroidectomy in 20 cases, lobectomy with isthmectomy in 12 cases, lobectomy with node dissection in 11 cases, total thyroidectomy with node dissection in 8 cases, and subtotal thyroidectomy in 7 cases. 8) As to the pathologic classification, papillary carcinoma was revealed in 83 cases (77.6 %), follicular carcinoma in 18 cases(16.8%), medullary carcinoma in 4 cases(3.9%), and anaplastic carcinoma in 1 case(0.9%). 9) Regional node metastasis was seen in 34 cases(31.8%), and distant metastasis was seen in 14 cases (13.0%). 10) The most common post-operative complication was transient hypocalcemia in 28 cases(26.2%), followed by permanent hypocalcemia in 8 cases(7.5%), and transient recurrent nerve paralysis in 2 cases(1.9%)

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Local Complications after Surgical Treatment for Thyroid carcinoma: Suk Hyung Kang, Ki Hoon Jung, Jeoung Won Bae; J Korean Cancer Assoc. 1996;28(1):88-94.

Abstract PDF: There is considerable controversy concerning the most appropriate surgica1 treatment of patients with differentiated thyroid cancer. This study was conducted to determine the op timal surgical operation by analysis of morbidity and mortality according to the operative method adopted. The clinical records were reviewed from 128 cases with thyroid cancer treated at the department of Surgery, Korea University Hospital. between January 1985 and December 1992. Local complications were defined as those occurring in the operative areas or as local results after the surgery during the hospitalization. Forty-five patients (35%) underwent total thyroidectomy, 30(23%) total thyroidectomy with radical lymph node dissection, 20(16%) subtotal thyroidectomy, and 33(26%) thyroid lobectomy. Nineteen patients(14.8%) experienced temporary local complications. Out of 19(14.8%) transient hypocalcemia, 1 case occurred after subtotal thyroidectomy and 18 cases after total thyroidectomy. Four cases(3%) of bleeding occured after various types of thyroidectomy(l case after lobectomy, 1 case after subtotal thyroidectomy, 2 cases after total thyroidectomy). One case of wound infection after lobectomy and one case of recurrent laryngeal nerve in jury after total thyroidectomy were also identified. There were no postoperative deaths. The most frequent morbidity was transient hypocalcemia following the total thyroidectomy. Although total thyroidectomy relatively induced more postoperative complications than other procedure, the temporary postoperative complications were less important. Our data suggest that total thyroidectomy could be considered as an operative treatment of the thyroid cancer.

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Combination Chemotherapy with 5-Fluorouracil and Carboplatin for Advanced Head and Neck Cancer: Eun Kyung Cho, Won Sup Lee, Chul Won Jung, Keun Seok Lee, Won Seog Kim, Ki Hyeong Lee, Dae Seog Heo, Yung Jue Bang, Kwang Hyun Kim, Charn II Park, Noe Kyeong Kim; J Korean Cancer Assoc. 1996;28(1):94-104.

Abstract PDF: Twenty-nine patients with previously untreated, locally advanced head and neck cancer were treated with two or three cycles of combination chemotherapy consisting of 5- fluorouracil infusion and carboplatin, followed by surgery and/or curative radiotherapy. Nine patients with recurrent head and neck cancer were treated with the same combination chemotherapy. The results were as follows; 1) Among 28 evaluable patients, response rate was 71.4%(partial response) after neoadjuvant chemotherapy. Following local modality(surgery and/or radiotherapy), response rate was 79%(complete response 51.4%, and partial response 25%). 2) One year survival rate in neoadjuvant group was 83% and one year progression-free survival rate, 68.8%. The progression-free survival of responders was significantly prolonged in comparison with that of non-responders(p<0.05). 3) In palliative treatment group, one partial response(11%) was observed among nine patients. Median time to progression was 6.8 weeks and median survival was 17.7 weeks; there was no significant difference between responders and non-responders. 4) Nausea and vomiting were frequently observed but easily controlled. Hematologic toxicities-leukopenia and thrombocytopenia were observed but were reversible. In conclusion, combination chemotherapy with carboplatin and 5-FU was effective for locally advanced head and neck cancer in neoadjuvant setting, but it had limited benefits for recurrent diseases. Toxicities were tolerable and neurotoxicity, ototoxicity, and nephrotoxicity were not observed.

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Alternating Combination Chemotherapy of CAV with EP in Small Cell Lung Gancer and Effect of Concurrent Thoracic Radiotherapy in Limited Stage: Kyung Hee Lee, Jin Jong Jeon, Byung Hoon Kim, Eun Jeong Lee, Jun Young Do, Jin Hong Chung, Kwan Ho Lee, Myung Soo Hyun, Bong Sub Shim, Hyun Woo Lee, Hyun Cheol chung; J Korean Cancer Assoc. 1996;28(1):104-113.

Abstract PDF: In order to assess the efficacy of alternating schedule chemotherapy on the outcome of patients with small cell lung cancer and effect of concurrent thoracic radiotherapy in limited disease, fifty five eligible patients with SCLC were treated with chemotherapy consisting of cyclophosphamide, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(EP). Thoracic radiotherapy was administered to the patients with limited stage disease Overall response rate was 64% with 20% of complete response. The response rate was 78%(CR 39%,PR 39%)in the patients with limited stage disease, and 53%(CR 6%, PR 47%)in those with extensive stage disease. With median follow-up period of 14 months (341+), the median survivals in patients of limited stage and extended disease were 15 months and 10 month, respectively (p<0.02) and median survivals in patients with CR, PR, and SD+PD were 20, 11.3, 8.5months, respectively(p<0.01) In patients with limited stage patients with or without concurrent use of thoracic radiotherapy, the response rates were 82%(CR 42%, PR 41%) and 67%(CR 33%, PR 34%) and median survivals were 15.8 months and 11.8 months, respectively.There were no life threatening side effects. This results suggest that alternating chemotherapy with CAV and EP may be useful as a treatement strategy in small cell lung cancer and concurrent use of thoracic radiotherapy in limited stage patients improve survival, but it was not significant statistically.

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Expression of p53 Protein in Human Gliomas: Yoo Jin Kim, Geong Sin Lee, Hae Jin Jeong, Man Ha Huh; J Korean Cancer Assoc. 1996;28(1):113-122.

Abstract PDF: In an attempt to evaluate expression of p53 and to characterize the role af p53 alterations in pathogenesis and progression of gliomas, 49 tumors were immunostained with monoclonal antibodies against p53, TGF-a, PCNA on archival formalin-fixed, paraffin-embedded materials. The tumors were divided into low-grade(19 cases) and high-grade(30 cases) gliomas. We evaluated whether expression of these proteins are associated with differentiation of the tumor, and analyzed correlations among these proteins. The results are summarized as follows. The overall incidence of p53 expression in 49 gliomas was 49%(24/49). The extent of p53 immunolabelling of tumor ce11s increased from low-grade to high-grade tumors(p=0.002, Chi-Square Score): Low-grade tumors revealed 21 %(4/19) immunoreactivity, whereas, 67%(20/30) reactivity was seen in high-grade ones. A significant correlation between p53 and TGF-a expression was demonstrated(p=0.024). A correlation between expression of p53 and PCNA revealed borderline significance(p=0.064). The results suggest that p53 could be a useful independent prognostic indicator in human gliomas, possibly in combination with TGF-a and PCNA. And also, the results support the hypothesis that p53 mutations play a role in the progression from low-grade to high-grade gliomas.

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

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

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The Results of Radiation Therapy for Metastatic Spinal Cord Compression: Ji Youn Han, Jae You Kim, Hong Suk Chang, Byung Ok Choi, Byung Gil Choi, Hanlim Moon, Young Sun Hong, Sei Chul Yoon, Hoon Kyo Kim, Kyung Shick Lee, Dong Jip Kim; J Korean Cancer Assoc. 1996;28(1):138-145.

Abstract PDF: Spinal cord compression is a common neurologic complication of advanced cancer, and it is a medical emergency because delay in treatment often results in irreversible paralysis. The treatment-goal of metastatic spinal cord compression is the preservation or restoration of neurologic function. We retrospectively analyzed the results of radiation therapy for metastatic spinal cord compression from January 1987 to May 1992 to assess the neuro1ogic recovery rate of metastatic spinal cord compression by radiation therapy. The results were as follows: ¨cThe most common cause of metastatic spinal cord compression was lung cancer (24%), followed by hepatoma (18%), gastric cancer (8%). ¨e Eighty seven percent of patients presented with localized back pain which preceded diagnosis of spinal cord compression by several weeks. ¨e At diaanosis, 71 % of patients were presented in paralytic status. 27 % of the patients who were ambulatory and 15 % of the paralytic patients before treatment were remained ambulatory or became ambulatory after radiation therapy. ¨eThe duration of survival of all patients were 6 to 159 days (median 55 days). It seemed that the poor outcome of radiation therapy was related to the aggressive biologic features and radioresistance of the primary tumors rather than the neurologic status before the treatment. The prospective study with other treatment modalities such as anterior resection with or without radiation therapy is necessary for improving the neurologic recovery rate.

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The Cytotoxic Activity of Sterol Derivatives from Pulsatilla Chinensis Regal: Jin Won Hyun, Yong Man Yang, Min Sook Sung, Ha Sook Chang, Woo Hun Paik, Sam Sik Kang, Jae Gahb Park; J Korean Cancer Assoc. 1996;28(1):145-151.

Abstract PDF: In order to search for antineoplastic components from plants, cytotoxic activity against human carcinoma cell lines was measured in 266 extracts from 236 plants using the MTT (3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method. As a result, the root of Pulsatilla chinensis (Ranunculaceae), which has been used as an insecticide in oriental medicine, showed a cytotoxic effect. Its structure was determined to be a mixture of ￥a-sitosterol-3-O-glucoside and stigmasterol-3-O-glucoside (3:1). Its IC value was 26￥ig/ml against SNU-I stomach cancer cell line.

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Cloning and Expression of Stromelysin-3 gene in Escherichia Coli: Mi Ae Lyu, Bum Joon Kim, Il Kyoo Park, Yong Joo Goh, Yoon Hoh Kook, Chang Yong Cha; J Korean Cancer Assoc. 1996;28(1):151-159.

Abstract PDF: It has long been proposed that secreted proteinases, including the matrix metalloproteinases, play an important role in tumor progression. Recently, human stromelysin-3, a new member of the matrix metalloproteinase family, was known to be expressed specifically in stromal cells surrounding invasive breast carcinomas and in tissues undergoing the active remodeling associated with embryonic development, wound healing and tumor invasion. But its physicochemical and biological characteristics are still not clearly known. We tried to make probes that may be useful for the study of stromelysin-3 experiments. The stromelysin-3 cDNA(108bp) was produced by reverse transcription-polymerase chain reaction from a fetal lung fibroblast treated with 12-O-tetradecanoylphorbol-13-acetate. And another stromelysin-3 DNA fragment(108bp) was produced by polymerase chain reaction using genomic DNA from human peripheral blood cells and fetal lung fibroblasts. These stromelysin-3 DNA products were cloned into pIH821 at the StuI site resulting in an in-frame fusion between maltose binding protein and stromelysin-3 and sequenced. The 45 kDa fusion protein was expressed in Escherichia coli XL1-Blue and detected by Western blot using anti-maltose bindging protein antibody.

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Localization of Urokinase Type Plaminogen Activator Receptor on Tumor Cells by Tmmunohistochemistry: Hye Won Park, Yoon Hoh Kook, Sung Bae Choi, ng Yong Cha; J Korean Cancer Assoc. 1996;28(1):159-168.

Abstract PDF: Urokinase type plasminogen activator(uPA) plays important role in invasion and metastasis of cancer. Its actions are activated and amplified by a specific cell-surface receptor (urokinase type plasminogen activator receptor: uPAR). The present study was undertaken to determine the importance of the uPAR for migration and invasion of cancer cells through immunohistochemical localization of uPAR. HEp3 cells were cultured in monolayer and suspended, then they were stained by immunofluorescence, APAAP(alkaline phosphatase anti-alkaline phosphatase) and immunoperoxidase method. The receptor(uPAR) was found to be located at cellular contact sites. In suspension uPAR staining of HEp3 cells showed focal distribution. In vivo model of invasion, the uPAR was localized on leading edge of tumor of cholioallatoic membrane(CAM) inoculated with HEp3 cells. This suggests that uPAR might play crucial role in migration and invasion of cancer cells through mediating proteolysis at cellular contact sites especially in leading edge of the tumor.

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Carcinosarcoma of the Esophagus: Seock Ah Im, Ki Youl Seo, Hye Young Son, Mi Sung Shin, Doe Young Kim, Soon Nam Lee, Soo Seung Choi, Mi Jung Kim, Sung Sook Kim, Young Guk Lim; J Korean Cancer Assoc. 1996;28(1):168-175.

Abstract PDF: Carcinosarcoma of the esophagus is a rare neoplasm composed of both carcinomatous and sarcomatous area. Usually the carcinomatous component is a squamous cell carcinoma. The histogenesis of the sarcomatous component is still unknown but consider as transformation from carcinomatous portion. We report a case of carcinosarcoma of esophagus in a 65 year-old male patient who was taken radical esophagectomy with lymph node dissection, Microscopically it was composed of squamous cell carcinoma intermingled with sarcomatous component in polypoid portion.

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Aggressive Hepatic Resection of Hepatocellular Carcinoma with Tumor Emboli of Main Portal Vein: Hong Jin Kim, Chang Sig Kim, Min Chul Chim, Koing Bo Kwun; J Korean Cancer Assoc. 1996;28(1):175-182.

Abstract PDF: Degree of portal vein involvement is fairly reliable in predicting longterm survival. And tumor thrombus in the trunk of protal vein has been considered contraindication for liver resection and transcater arterial chemoembolization(TAE). At recent as development of operative technique of liver, cumulative experience of operation and development of ability to pre- and post-operative management of metabolism of liver, aggressive surgical resection has been applied to these patient group that has tumor thrombi in main protal vein by some surgeon. Tumor thrombus in the trunk of the portal vein has been considered dotraindication for liver resection. However, the negative results of conservative therapy have encouraged us to remove the tumor. We performed right lobectomy successfully for the hapatocellular carcinoma(HCC) with tumor thrombus in the first order branch of portal vein and the patient is alive for 37 months without recurrence. In conclusion the aggressive surgical approach for the HCC presenting with tumor throumbus in right first order branch of portal vein should be considered for long term survival.

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A Case of Acute Lymphocytic Leukemia in Adolescent Down Syndrome: Se Jin Oh, Kwang Ho Kim, Hun Sik Jeong, Dong Gu Choi, Dong Bok Shin, Wan Kim; J Korean Cancer Assoc. 1996;28(1):182-190.

Abstract PDF: Adolescent Down syndrome with leukemia is very rare and distinctive disease. The association of Down syndrome and leukemia has been documented for over 50 years. The age of onset for leukemia in this disease is bimadal, peaking first in the newborn period and again at 36 years. The association risk of these two conditions-Down syndrome and leukemia - is about 10- to 20-fold higher than in the general population. This increased risk extends into adulthood. Down syndrome associated with acute leukemia has usually poor prognosis, but some cases went to spontaneous remission in previously published papers. The proportion of acute leukemia type of these patients shows no difference compared to non-Down syndrome leukemia. A 20 year old male patient was admitted to our hospital due to frequent common cold history and recently developed periumbilical pain and poor oral intake. He was born second of 5 siblings from normal parents by normal spontaneous vaginal delivery. Conaenital appearance was mongoloid face and simian crease in both hands. The facial appearance was hyperteloric eyes and opened mouth and small face, flat nose at a glance. His CBC showed severe anemia and abnormal leukocyte counts with differential counts. So he was admitted to Hemato-Oncology department of internal medicine and then we carefully did physical examination and laboratory tests. His clinical features, peripheral blood smear and bone marrow aspiration-cytology and biposy revealed acute lymphocytic leukemia (ALL) Ll subtype. The chromosome study revealed 47, XY, +21 in karyotype. Thus, he was diagnosed as ALL with Down syndrome. Treatment was not given to this patient due to incorporation of patient because of retarded mentality. The patient was expired about 4 month's later. Thus, we report the first case of acquired ALL in adolescent Down syndrome in Korea,

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