Cancer Research and Treatment

A Retrospective Comparison of Infusional 5-Fluorouracil , Doxorubicin , Mitomycin - C ( Modified FAM ) Combination Chemotherapy Versus Palliative Therapy in: Joon Oh Park, Jae Kyung Roh, Hyun Cheol Chung, Hyun Jin Noh, Jae Yong Cho, Sun Young Rha, Chong In Lee, Cheol Woo Kim, Joo Hang Kim, Choong Bai Kim, Sung Hoon Noh, Kyong Sik Lee, Jin Sik Min, Byung S; J Korean Cancer Assoc. 1995;27(2):165-175.

Abstract PDF: In Korea, gastric cancer is the most common cancer and the leading cause of cancer death. About one-third of the patients with gastric cancer is unresectable at the time of diagnosis. Their median survival is less than 6 months with very poor prognosis. Accordingly, various regimens of chemotherapy have been proposed as intensive treatment for unresectable patients. After MacDonald et aL reported 42% response rate and 9 months response duration using combination of 5-Fluorouracil, Doxorubicin and Mitomycin-CFAM), it became the most widely used regimen in the treatment of advanced gastric cancer. However, despite of high initial response rate, there was no survival benefit in randomised comparative trials. To increase the drug effect, we modified the standard FAM regimen by continuously infusing the 5- Fluorouracil instead of bolus injection(modified FAM). We retrospectively reviewed the clinical recoreds of 409 patients with histologically proven advanced gastric cancer in Yonsei University Medical Center and Yonsei Cencer Center between Jan. 1, 1991 and Dec. 31, 1993. The purpose of this study is to assess the efficacy of infusional FAM combination chemotherapy compared with other palliative therapy in advanced gastric cancer. Among 409 patients, 266 were male and 143 were female with a median age of 57-year(range: 15~75). There were 202 patients in mFAM-treated group and 207 patients in control group. In mFAM-treated group, 140 patients had no surgery, 30 patients underwent a palliative bypass and 32 patients underwent a palliative resection. In control group, 151 patients had no surgery, 33 patients underwent a palliative bypass and 23 patients underwent a palliative resection. In preoperative staging, 257 patients had locally advanced disease, 48 had carcinomatosis and 104 had distant metastasis. There was no difference of distribution in age, sex, perfomance status, preoperative stege and treatment modalities between mFAM-treated and control group. 1) Among 154 of evaluable patients, no CRs were observed. PR were seen in 17.5% of patients in mFAM-treated group. The median response duration was 30 weeks and progression free survival was 23 weeks. 2) Higher 1-year survival rate was demonstrated in mFAM-treated group comparing to control group(34.1% vs 22.5)(p=0.0135). 3) Median survival was longer in mFAM-treated group than that of control group(40 week vs 28 week). 4) The toxicities were relatively tolerable and reversible. This results proposed that the infusional FAM combination chemotherapy showed a probalbility of survival pralongation, especially combined with palliative surgery in advanced gastric cancer. Further prospective randomized study will be warranted.

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Detection of Soluble c-erbB-2 Oncoproteins in the Serum of Gastric Cnacer patients as a Tumor Marker: Hyung Cheol Chung, Joong Bae Ahn, Joon Oh Park, Jae Yong Cho, Sun Young Rha, Chong In Lee, Hye Ran Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim, Ho Yeon; J Korean Cancer Assoc. 1995;27(2):175-184.

Abstract PDF: A soluble fragment of the c-erbB-2 oncoprotein become detectable in the serum of the breast cancer petients by enzyme-linked immunosorbent assay(ELISA). To evaluate the clinical sig- nificance of soluble c-erbB-2 in gastric cancer, we measured the serum levels in 45 normal healthy persons and in 86 gastric cancer patients. Fifty-five patients were underwent surgery(47 curative surgery, 8 palliative surgery) and thirty-one patients were inoperable(18 advanced, 8 relapsed, 6 progressed after palliative surgery). The c-erbB-2 serum levels were below 14 U/ml in normal persons. Three of 86(3.5%) sam- ples from gastric cancer patients had elevated serum c-erbB-2 leveL In 55 operated patients, all serum samples were negative for c-erbB-2. Elevated serum levels were predominantly found in patients with initially advanced cancers(3/18: 16.7%). In 22 operated cases, immunohisto- chemical staining showed 36.4% c-erbB-2 positive ratio(8/22) in tissues. Comparing the results from sera and tissues studies, the sensitivity of serum ELISA assay was too low even if the specificity was high. Our data suggest that the soluble c-erbB-2 oncoprotein can be a tumor marker only in advanced stage of gastric cancer. Further studies are warrented to elucidate the discrepancy between the serum and tissue results in oprable early stage gastric cancer.

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Effect of Adriamycin in Gastric Chief Cell of Hamster: Byung Chun Kim, Doo Jin Baik, Ho Sam Chung; J Korean Cancer Assoc. 1995;27(2):184-195.

Abstract PDF: Adriamycin, an anthracyclin antibiotics isolated from Streptomes peucetius var caesius, inhibits the synthesis of DNA and reaction of DNA dependent DNA polymerase and it has been widely used as an anticancer drug in the treatment of sarcoma, leukemia and solid tumors. Adriamycin has little specificity to the normal and tumor cells and cytotoxicity of the normal cells happens to the patients as cardiotoxicity and bone marrow depression. The authors have demonstrated the effect of adriamycin on the chief cells of hamster, histologically observing the morphological changes of the cell by the use of light and electron microscope. The animais treated with 50 mg per kg of adriamycin were sacrificed at 24 and 48 hours after the drug administration. The animals of control group were administered only water for injection. All animals were starved for 12 hours before sacrificing them. A part of stomach specimens were fixed 10% neutral formalin and prepared for hematoxylin and eosin stain and the other part of specimens which were prefixed in 2% glutaraldehyde-2.5% paraformaldehyde prepared with phosphate buffer and then post-fixed in the 1% osmic acid, were dehydrated and embedded in the Epon 812. Ultrathin sections, 600-800A thickness, were made and double stained with uranyl acetate and lead citrate. And these preparations were observed with light microscope and JEM 100cx-II electron microscope. The results were as follows; 1) Most of lining cells of gastric glands were atrophied and lumens were dilated. Numbers of chief cells were decreased and indistinct cellular boundary, vacuolar degenertion, pyknosis and karyolysis were observed in the less basophilic chief cells. In the fundus of glands, parietal cells and mucous neck cells were also found. 2) Cisternae of rough endoplasmic reticulum were decreased, and fragmented and membrane bound ribosome were detached. Fusion of irregularly shaped zymogen granules and numerous autophagic vacuoles including whorled membranous bodies were observed#. Irregular shaped mitochondria and atrophied Golgi complex were also found in the chief cells of the gastric mu- cosa of the adriamycin treated rats. 3) Consequently, it is suggested that adriamycin would induce the degenerative changes of the organelles of chief cells in gastric mucosa of hamsters.

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Amplification of the c-erbB-2 Prto - Oncogene in Primary Human Gastric Cancers: Chul Won Choi, Jae Hong Seo, Byung Soo Kim, Sang Won Shin, Jun Suk Kim, Young Jae Mok, Jong Suk Kim, Bum Hwan Koo; J Korean Cancer Assoc. 1995;27(2):195-202.

Abstract PDF: The c-er6B-2 proto-oncogene has been found to be amplified in many human tumors induding breast, stomach, kidney and lung cancers. In order to evaluate the amplification status of c-erbB-2 proto-oncogene in stomach cancer which is the most common cancer in Korea, fortyfive sets of specimens including tumor tissue and normal stomach tissue(5 cm at least away from primary tumor, histologically normal)were measured by Southern hybridization technique. Ten micrograms of EcoRI-digested DNA was electrophoresed in an 0.8% agarose gel and transferred to a nylon memebrane and hybridized with a c-erbB-2 probe, washed under stringent conditions and autoradiographed against Hyperfilm with intenaifying screens at 70`C, for 3 days. In the results. two of the 45 gastric carcinomas(4.4%) were amplified 2-to-4-fold. Thus, the amplified c-erbB-2 gene may have a role in the evolution of gastric carcinoma, as dose in some carcinoma.

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Effect of Radiotherapy in Adenocarcinoma of the Rectum: Eul Sam Chung, Sung Woo Kim, Chul Young Park, Soo Kon Kim; J Korean Cancer Assoc. 1995;27(2):202-209.

Abstract PDF: There have been many reports about radiotherapy(RT) effect(either preoperative or postoperative adjuvant use) in treatment of rectal adenocarcinoma. And recent articles about lowering of locoregiona1 recurrence got attention of colo-rectal surgeon or his(their) coworkers. In a retrospective analysis of 53 cases, from 1984 to l992, we ana1yzed retrospectively locoregional recurrence pattern in patients who received radical curative surgical procedure for rectal cancer plus X-ray irradiation pre-or postoperatively as an adjuvant treatment formulary. 15 patients who were treated with radical curative surgical resection alone by 1 surgeon including Miles op., low anterior resection or anterior resection with the result of 20% locoregional recurrence were a control group in comparison to other grouped people. 20 patients(who received preoperative irradiation followed by curative surgery without intermission) categorized as stage B1,(8 cases), stage B2,(5cases), stage C1,(3 cases), stage C2,(4 cases) but their accumulated 5-year survival rate was 80% in stage B1, 67% in stage B, 60% in stage C,. Only 10% of them received recorded as a tenant of locoregional recurrence. 25 patients who received curative surgery with postoperative irradiation were 6 cases of stage B,iall were disease free more than 5 years), 8 cases of stage B(5 years accumulation survival rate was 80%), 2 cases of stage C1 and 9 cases of stage C;, 44/ of them recorded as locoregional recurrence group. 8 patients received so-called sandwich technique(preoperative irradiation plus surgery and followed Postoperative irradiation) with keeping results of 33% locoregional recurrence pattern. So far, we couldnt pick up significant difference in long-term disease free interval between control group and preoperative irradiation plus radical curative surgery group. But, preoperative radietion therapy casts reducing effect to locoregional recurrence by 10% comparing with control group.

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Metastatic Potential of Human Colon Cancer Cell Lines , LoVo and SW480: Ji Young Sul, In Sang Song, Chin Sun Bae, Eil Sang Chang, Wan Hee Yoon; J Korean Cancer Assoc. 1995;27(2):209-223.

Abstract PDF: Metastatic spread of malignancy is the main cause of the treatment failure and subsequent death in cancer patients. Recent findings indicate that tumors consist of cell populations with various degrees of metastatic potential, and that selective growth of subpopulations with higher metastatic potentials result in metastasis. The purpose of this study was to examine the metastatic potential of human colon cancer cell lines, LoVo and SW480 and to identify some cellular and biochemical determinants of metastasis using various properties which reflect events in metastatic process. The binding activity to ELAM-1, cell-cell aggregation rate, and total MMP activity were significantly higher in LoVo cells relative to SW480 cells. To define the effects of these cellular and biochemical properties on the process of invasion and me- tastasis af colon cancer cells, in vitro invasion and in vivo metastasis assay were performed. LoVo cells had an enhanced ability to penetrate a reconstituted basement membrane to a significantly greater degree than SW480 cells. The capacity to produce tumor nodules in the liver of nude mice subsequent to intrasplenic injection of cells was greater in LoVo cells than in SW480 cells. Also increased nm23-Hl protein expression was observed in SW480 cells in which no gross liver metastases were found. The results of this study suggest that LoVo cells have higher liver metastatic potential than SW480 cells and among various biochemical properties ELAM-1 binding and total MMP activity are significantly implicated in invasion and metastasis of colon cancer cells. And homotypic cell adhesion and downregulated nm23 gene product may be important in the metastatic cascade, but their roles should be further elucidated.

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Assessment of Cell Proliferation in Primary and Recurrent Colorectal Cancers - Expression of Transforming Growth Factor - α and Prolifer: Jin Sil Seong, Sun Hee Sung, Jung Woon Lee, Hyun Soo Shin, Charn Il Park, Oh Hun Kwon; J Korean Cancer Assoc. 1995;27(2):223-230.

Abstract PDF: Cell proliferation potential has been found to be a significant biological parameter correlated with the clinical outcome. This study was ta investigate the cell proliferation potential in primary and recurrent colorectal tumor tissues. Using paraffin-embedded tissues from the paired primary and recurrent tumors of l0 patients, a simple hematoxylineosin stain was done and immunohistochemical stains for trans- forming growth factor-a(TGF-a) and proliferating cell nuclear antigen(PCNA) were performed through a labeled streptavidine biotin method. DNA contents and S-phase fraction(SPF) of the cells were assessed by flowcytometric DNA analysis. The degree of differentiation was poorer in the recurrent tumors than in primary tumors. In 4 primary tumors with mixed adenocacinoma and mucinous adenocarcinoma, only the mucinous adenocarcinoma companent was shown in the recurrent tumors. There was no difference in TGF-a expression between the primary and the recurrent tumors however, PCNA was overexpressed in the recurrent tumors comparing to the primary tumors. Flow cytometric DNA analysis was successful in 7 paired cases. There was change of the ploidy from the diploidy to the aneuploidy in 4 cases. SPF showed remarkable increase in the recurrent tumors comparing to the primary tumors. These results show high proliferative potential of the recurrent colorectal tumors, which can be measured using PCNA expression and SPF as biomarkers. Based on the results of this study, an effort to establish more refined method to predict recurrence should be pursued.

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A Clinical Analysis of the Small Bowel Tumor: Jun Ho An, Byung Chun Kim, Jae Jung Lee, Joo Seop Kim, Bong Wha Chang; J Korean Cancer Assoc. 1995;27(2):230-238.

Abstract PDF: The small bowel tumor is rare and prognosis is very poor due to nonspecific symptom and delayed diagnosis. The clinical review was made in 17 cases of the small bowel tumor that had been treated from January 1985 to September 1993 at Department of Surgery, College of Medicine, Hallym University. The obtained results are as follows, 1) The most prevalent age group was the 6th decade(47.0%) and the ratio of male to female was 1.42: l. 2) The most common symptom and sign were abdominal pain(52.9%) and abdominal distension(23.5%), respectively. 3) The most frequent site in sma11 bowel was ileum(47.1%), followed by jejunum (35.3%) and duodenum(17.6%). 4) The histopathologic classification was malignancy in 10 cases, benign in 7 cases and the most predominant type was leiomyosarcoma and lipoma, respectively. 5) The most frequent preoperative diagnostic measure was abdominal ultrasonogram(58.8%) and the diagnosis was correct in 9 cases. 6) The most common type of operation technique was segmental resection(64.6%). 7) The postoperative complications deveioped in 4 cases(26.7%). 8) Duration of the median follow up was 10.8 months and 4 cases were impossible to follow up. Among the 5 patients who died, 3 patients were adenocarcinoma and 2 patients were leiomyosarcoma. In conclusion, poor results of small bowel tumors are due to delayed diagnosis. Thus, prompt diagnostic studies should be performed in patient with persietent symptoms and early consideration of exploratory leparotomy may be needed for possibility of malignancy and curative resection.

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Serum Insulin - like Growth Factor Binding Proteins profiles in Hepatocelllular Carcinoma: Dae Yeol Lee, Dae Gon Kim, Jung Soo Kim; J Korean Cancer Assoc. 1995;27(2):238-247.

Abstract PDF: Recent findings have indicated that insulin-like growth factors(IGF-I &-II) and it's binding proteins(IGFBPs) may play a role in neoplasia. Hepatoma is a common malignancy in this country and the liver is probably the source of most circulating IGFs and IGFBP-3. We have studied serum IGFBPs pattern in hepatoma(n=20) and liver cirrhosis(n=10) by using western ligand blot(WLB) and radioimmunoassay(RIA). Serum IGFBP-3 level was signif- icantly decreased in hepatoma and liver cirrhosis. Mean serum IGFBP-31evel was 2443(+- l258) ng/ml in hepatoma, 1308(+-381) ng/ml in liver cirrhosis, and 4706(+-519) ng/ml in healthy subject. There was a discrepancy of IGFBP-3 levels, as determined by RIA and WLB. This discrepancy can be explained by IGFBP-3 protease activity, which was found in serum from some hepatoma but not from liver cirrhosis. We also observed the decreased level of serum IGFBP-2 in both groups. Serum IGFBP-1 and -4 were decreased in only liver cirrhosis. We speculate the alteration of IGFBPs pattern in hepatoma would be due to decreased hepatic synthesis of IGFBPs, especially IGFBP-3 and serum IGFBP-3 protease activity, and the role of serum IGFBPs should be further studied.

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A Study of Oncogene Expression in Thyroid Tumor: Moon Oh Bae, Jeong Han Yoon; J Korean Cancer Assoc. 1995;27(2):247-253.

Abstract PDF: Current models for tumorigenesis propose that a series of genetic alterations 'occur during the progression from the normal cell to the malignant phenotype. Expression of three oncogenes(c-myc, c-erb B and c-Ha ras) have been identified in many human neoplasms, in- cluding thyroid nodule. In this study we evaluated expression of oncogenes in benign and malignant thyroid nodules with immunohistochemical staining methods using monoclonal anti- bodies to products of the oncogenes. The rates of expression of c-myc, c-erb B and c-Ha ras oncogenes were 3.6%, 35.7% and 25.0% in benign nodules and 44.4%, 94.4% and 50.0% in carcino- mas. The positive rates of c-myc and c-erb B oncogenes were significantly higher in carcino- mas than in benign nodules. There was positive relationship bwtween the rate of expression of c-myc oncogene and the size of carcinomas. There was no positive relationship bwtween the rates of expression of oncogenes and the status of lymph node metastasis. Results suggest that c-myc anc c-erb B, oncogenes are related to the development and progression of thyroid carci- noma and c-myc oncogene can be used to evaluate prognosis of thyroid cancer patients.

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Prognostic Significance of Tumor Angiogenesis , Metastasis Regulation Gene Protein ( NDP-K / nm23 ) and Histone mRNA Expression in Breast Cancer: Hye Rim Park, Young Sik Kim, In Sun Kim; J Korean Cancer Assoc. 1995;27(2):253-265.

Abstract PDF: Tumor angiogenesis and expression of metastasis regulation gene protein(nm23) and histone mRNA were eveluated in 42 breast cancers to assess their roles in prognosis. Tumor angiogenesis was studied by measuring the FVIIIRA-positive endothelial cells, and nm23 protein expression by immunohistochemical staining. Histone mRNA poisitive cells were examined by non-isotopic in situ hybridization. The results were analyzed according to the patients age, tumor size, presence or absence of lymph node metastais and DNA ploidy. DNA aneuploidy was found in 28 of 38 (74%) and Factor VIIIRA-positive endothelial cells were found within and around the invasive carcinoma and periductal stroma in intraductal carcinoma. Tumor angiogenesis was more active in primary tumors than in metastatic lesions. nm23 protein expresian was strong in normal parenchyme, but it was variable in stainability and extents according to the areas. The intraductal component showed stronger staining than invasive carcinoma in nm23 protein expression. Histone mRNA positive cells were found in both normal and malignant epithelial cells, but more frequent in metastatic lesion than in primary tumor. Tumor angiogenesis and loss of nm23 protein were associated with the presence of metastatic node and large size of primary tumor(23 cm). The expression of histone mRNA was only associated with poor differentiation af tumor, but not with S-phase fraction af cell cycle study. From this study, it is concluded that tumor angiogenesis and expression of nm23 protein could be used as prognostic indicators in breast cancers, but histone mRNA expression had the limited value.

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Prognostic Factors in Node - Negative Breast Cancer: Kyung Hee Lee, Hyun Cheol Chung, Jae Yong Cho, Sun Young Rha, Joong Bae Ahn, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim, Kyung Sik Lee, Kyl Beom Lee, Ho Yeong Lim, Jin Hy; J Korean Cancer Assoc. 1995;27(2):265-275.

Abstract PDF: Breast cancer is the third most common malignant neoplasm in Korean women. The effect of postoperative adjuvant systemic therapy in the treatment of primary breast cancer with pathologic involvement of the axillary lymph nodes has been well established. But, 20 30% of node-negative breast cancer patients will develop recurrent disease and risk death within 10 years after initial local therapy without adjuvant treatment. Therfore, it is reasonable to identify those node-negative breast cancer patients at significant risk for recurrence and who could be treated with adjuvant therapies. A clinical study was perofrmed in 184 cases of primary node-negative breast cancers from January 198l to December 1991 to study the natural course of the diaease and to find-out the prognostic factors. The following results were obtained; l) During 73 monthe(9-143) of follow-up duration, 5-year and 10-year relapse free survival rates were 88%, 77% respectively, and overall survival rates were 89%, 88%, respectively. 10 year recurrence rate was 19%. 2) Median disease-free and survival durations were 80 month, 17 months, respectively, in tumor size<2 cm group and 68.5 months, 62 months respectively in tumor size 2-5 cm group. 3) Median disease-free and overall survival durations were 73 months, 61 months, respectively, in premenopause patients and 74 months, 73 months in postmenopause patients. 4) No differences were found in disease-free and survival duration based on types of operation. 5) With adjuvant treatment, there was a decreasing tendency of systemic relapse. In conclusion, continuous relapse was found in node-negative breast cancer even after 5 years of operation. Even if decreasing tendency of systemic relapse was induced with adjuvant treatment, no clinically useful prognostic factors were found from surgical and pathologic factors until now. Further study of biological factors in node-negative breast cancer is warrented.

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A Clinical Analysis fo Breast Carcinoma in Women 35 Years of Age or Younger: Yoon Seok Chae, Hee Cheol Chang, Sung Soo Oh, Yoon Kyu Park, Eul Sam Chung; J Korean Cancer Assoc. 1995;27(2):275-284.

Abstract PDF: There is one perception that the prognosis of breast carcinoma in young women, especially those less than 35 years of age is unfavorable. However the relationship of the age and progno- sis in breast carcinoma remains still controversiaL The authors have studied 56 patients treated for breast carcinoma who were 35 years of age or younger at the time of diagnosis in the Department of Surgery at Presbyterian Medical Center, Chonju Korea, from January l980 to December 1993. The following results were obtained; 1) Median age of 56 patients was 31 years and the peak incidence was 30-35 years, comprising of 75%(42 patients). 2) The major symptoms were painless mass(70%), nipple discharge(11%), local redness (5.8%) in order of frequency. 3) Considering the relationship between age and metastatic axillary lymph nodes, there was no significant differences between them. 4) The most common histopathologic type was invasive ductal carcinoma, comprising of 73.2 % in 56 patients and followed by intraductal carcinoma 12.5%(7 patients), colloid carcinoma 3.57 %(2 patients) in order of frequency. 5) The most common site of 56 breast carcinomas was right upper outer quadrant and there was no difference in the incidence between right and left. 6) The survival rate according to treatment modality in the same stage show that for stage I (Scases), the 5-year suvival rate was 90% in 5 cases receiving opereation and chcmotherapy, 100 % in 1 case receiving operation only and 100% in 1 case receiving operation, chemotherapy and radiotherapy. For stage II(30cases), the 5-year survival rate was 78% in 18 cases receiving operation, chemotherapy and radiotherapy, and 100% in 2 cases receiving operation and radiotherapy. For stage III (13 cases), the 5-year survival rate was 38% in 8 cases receiving operation and radiotherapy and 40% in 5 cases recceiving operation and chemotherapy. For stage IV (4 cases), all received operation, chemotherapy and radiotherapy and 5-year survival rate was 25%. 7) The 5-year determinate survivel rate according to the number of axillary node metastasis revealed that the lesser numbers of metastatic nades, the better survival rate(in case of no metastatic node, 88.8% vs. more than 4 metastatic nodes, 29.4%).

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5-Fluorouracil , Ifosfamide and Cisplatin ( FIP ) Combination Chemotherapy for Advanced Non - Small Cell Lung Cancer: Young II Seo, Yougn Suk Park, Jae Myung Lee, Jo Young Choi, Hyun Soo Kim, Byung Dong Cho, Yu Mi Seo, Yun Chang Han, Ho joong Kim, In Gyu Hyun, Ki Suk Shun, Keun Chil Park, Duk Jhe Shun; J Korean Cancer Assoc. 1995;27(2):284-292.

Abstract PDF: We conducted a phase II trial of combining 5-fluorouracil(5-FU), ifosfamide(IFM), and cisplating(DDP) in previously untreated patients with advanced, unresectable, non-small cell lung cancer(NSCLC). Each cycle consisted of 5-FU 100 mg/m i. v. days 1-5, IFM 1000 mg/m i. v. days 1-3 with mesna, and DDP 100 mg/m i. v. day 1. Cycles were repeated at 3 week intervals. Twenty eight patients were enralled. Age ranged from 36 to 73(median 57 yearsk 24 were male, 4 female. Eleven patients had stage IIIb disease and 17 stage IV. Two patients were not evaluable because of lost to follow up. None had a complete response, 13 patients(50%) had par- tial responses, 8(31%) had stable diseases, and 5(19%) had progressive disesses. The median response duration was 11.2 weeks; the median time to progression was l2 weeks. The overall median survival was 19 weeks(27.5 weeks for responders, 12.8 weeks for non-responders). Majar side effects were alopecia, nausea/vomiting and stomatitis, all of which were we11 tolerated and reversible. By univariate analysis, stage and performance status correlated with time to progression and overall survival time. In conclusion, FIP combination chemotherapy for patients with advanced, unresectable non- small cell lung cancer seems to be an effective and well-tolerated regimen.

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Expression of c-myc , c-Ha-ras , c-rafl and c-mos Oncogenes During HL-60 Cell Differentiation: Seong Il Suh, Jong Wook Kim, Won Ki Baek, Jong Wook Park, Byung Kil Choe, Min Ho Suh; J Korean Cancer Assoc. 1995;27(2):292-303.

Abstract PDF: The acute myelogeous leukemia cell line, HL-60 is capable of differentiating to granulocytes or monocytes, it provides a good model to understand gene expressions that are associated with cell differentiation. The present study has been investigated the effects of dimethyl sulfoxide(DMSO) and phorbol 12-myristate 13-acetate(TPA) on HL-60 cell differentiation and expressions of protooncogenes(c-myc. c-Ha-ras, c-rafl, and c-mos). DMSO(1.25%) and TPA (32 nM) induced HL-60 cells to more differentiated phenotypes as determined by various analytic methods. These inductions of differentiation were associated with a loss of proliferative capacity and decreases in clonogenic survivaL To determine if modulations of these oncogenes were important in the differentiation of HL-60 cells to either granulocytes or monacytes, levels of mRNAs of these oncogenes were determined by Northen blot analysis at various times following treatment with DMSO and TPA. DMSO induced granulocytic differentiation of HL-60 cells and resluted in a down-regulation of c-myc expression and a transient up-regulation of c- Ha-ras expression. TPA induced monocytic differentiation of HL-60 cells and resulted in also a rapid decline of c-myc expression, while no detactable change in the level of c-Ha-ras mRNA was found. But there were not found detectable mRNA levels of c-rafl and c-mos in control group and DMSO- and TPA-treated group. These results suggest that changes in c-myc expression can be associated with the monocytic and gralulocytic differentiation of Hl-60 cells and the transient elevation of c-Ha-ras mRNA in HL-60 cells may correlated temporally with differentiation to granulocyte-lineage cells. These results also suggest that expression of c-rafl and c-mos may not be play a role in differentiation of HL-60 cells but further evaluations will be needed.

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Effects of cancer nervous System Irradiation on Neuropsychologic Functioning in Long - term Survivors of Childhood Acute Lymphoblastic Leukemia: Ji Eun Choi, Hee Young Shin, In One Kim, Kyung Mo Yeon, In Young Chae, Soo Churl Cho, Yong Seung Hwang, Hyo Seop Ahn; J Korean Cancer Assoc. 1995;27(2):303-316.

Abstract PDF: Long-term adverse neuropsychologic sequelae are frequently observed in pediatric patients treated for acute lymphoblastic leukemia(ALL). In this study, 10 children in continuous com- plete remission from ALL were given tests of IQ, neuropsychologic assessment, waking EEG, brain MRI to assess neuropsychologic functioning minimum 2 years after CNS prophylaxis. All children were free of CNS disease at diagnosis and had received CNS prophylactic treatment with 1,800 cGy cranial irradiation plus intrathecal methotrexate. Male patients had a significant decline in coding compared with female patients(P<0.01) and those evaluated beyond age of 10-year-old had a greater decline in performance IQ compared with those evaluated under age of 10-year-old(P<0.01). One of the 10 children(10%) showed white matter changes on MRI attributable to therapy. All children had no significant lower mean IQ, but lower achievement with regard to arithmetic skills, picture arrangement than other tests. We conclude that prophylactic CNS therapy may cause cognitive dysfunctions and the white matter changes but its value and significance during follow-up should be assessed in well designed longitudinal research studies.

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cDNA Sequencing of the Sh Region of Phospholipase C-γ1 from Human Cervix Carcinomas Using RT-PCR: Yee Sook Cho, Yong Ki Baek, Young Min Song, Byung Chan Oh, Uh Hyun Kim; J Korean Cancer Assoc. 1995;27(2):316-322.

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Effect of rhGM-CSF on the Chemotherapy - induced Neutropenia of Children with Solid Tumors: Jong Jin Seo, Sang Won Cha, Sang Mee Lee, Kyu Don Kim; J Korean Cancer Assoc. 1995;27(2):322-331.

Abstract PDF: To investigate the clinical effectiveness of recombinant human GM-CSF(rhGM-CSF; Leucogen) on the chemotherapy-induced neutropenia, twelve children with malignant solid tumor who had neutropenia after chemotherapy received 250 pg/M(2)/day of rhGM-CSF subcutaneouly for 10 consecutive days from the fifth day of next chemotherapy were schedule using the same rekimen. rhGM-CSF significantly increased leukocyte, neutrophil and eosinophil counts on the tenth day of GM-CSF course compared to the control course(P<0.05), but there was no significant difference in the counts of monocyte, lymphocyte, platelet or hemoglobin(p>0.1). The nadir of leukocyte and neutrophil were significantly higher in GM-CSF course than those of control course (P<0.05), but there was no significant difference in that of monocyte, lymphocyte, eo- sinophil, platelet or hemoglobin(P: 0.1). The duration of chemotherapy-induced leukopenia and neutropenia were decreased significantly in GM-CSF course than those of control course(P< 0.05). The duration of antibiotics administration and febrile period during chemotherapy were shorter in GM-CSF course without statistical significance. No significant side effect was observed during rhGM-CSF course. These results indicate that rhGM-CSF(Leucogen') is effective in alleviating the chemotherapy-induced neutropenia of children with malignant solid tumors.

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A Study of the Runctional and Biochemical Charcteristics and Antigenic Expression of Hematopoietic Cells Using Monoclonal Antibodies to a Thymocyte Surface Antigen: Cheung Seog Park, Seong Hoe Park, Myung Hwan Cho; J Korean Cancer Assoc. 1995;27(2):331-340.

Abstract PDF: In order to investigate functional variation of antigenic epitopes and expression patterns of hematopoietic cells and biachemical characteristics, we produced murine monoclonal antibodies, anti-YG 14 and anti-YG 15, against human thymocytes. We found that these monoclonal antibodies recognized same surface molecule which has been confirmed by immuno-precipitation analysis. This antigen was expressed in peripheral monocytes, subset of T cells, platelets, and epidermis of skin, but not expressed in granulocytes and peripheral B cells. It was approximately 24KDa protein in malecular weight and expressed as monomer. Its expression patterns and biochemical characteristics were similar to those of leukocyte differntiation antigen, CDB. With blocking test, we found out that YG14, YG15 monoclonal antibodies recognized different epitopes of same molecule, using flow cytometry. With the results of colony forming assay, it is very intriguing to see that YG15 monoclonal antibody showed increased colony forming activity but the YG14 monoclonal antibody did not. These results strongly suggest that engagement of different epitopes of same molecule can show different functional activity.

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A Case of Synchronous Multiple Primary Cancers in Stomach and Esophagus , Which Were Resected Curatively: Seung Jae Chung, Young Don Min, Chan Guk Park; J Korean Cancer Assoc. 1995;27(2):340-347.

Abstract PDF: A case of synchronous multiple primary tumors in a 63-year-old man is described. The tumors included a squamous cell carcinoma of the esophagus and a mucinous adenacarcinoma of the stomach. As we could perform the curative resection of the tumors successfully, we report this case with review of literatures about the criteria, incidence, organ relationship and tumorogenesis of the multiple primary tumors.

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Bone Metastasis as the Initial Symptom of Gastric Cancer: Laercio Gomes Lourenco, Rodrigo Gorayeb, Jesus Garcia Filho, Jose Roberto Ferraro, Ramiro Colleroni, Jose Carlos Del Grande, Chibly Michael Haddad; J Korean Cancer Assoc. 1995;27(2):347-352.

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