Cancer Research and Treatment

Establishment of SNU Cell Lines in Growth Factor and Growth hormone Supplemented Medium: Jae Gahb Park, Nam Sook Kwon, Dong Young Noh, In Gyu Hong, Seung Keun Oh, Kuhn Uk Lee, Yong Hyun Park, Sung Kuk Hong, Kuk Jin Choe, Jin Pok Kim, Soo Tae Kim, Dae Seog Heo, Yung Jue Bang, Seon Yang Pa; J Korean Cancer Assoc. 1990;22(1):1-14.

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Heterogeneity of Lymphokine - Activated Killer Cell Response: Sung Kee Jo, Hae Sun Moon, Weon Seon Hong, Yeon Sook Yun; J Korean Cancer Assoc. 1990;22(1):14-24.

Abstract PDF: This study examined the heterogeneity of lymphokine-activated killer (LAK) cells in terms of phenotype of precursors and effectors, generation pathways, and cellular, lymphokine, phar- macological regulators involved in endogenous and exogenous pathways. The serological phenotype of precursors and effectors of LAK cells against different target cells was not the same: LAK cells against HFL/b(H-2b) could be derived from Thyl, CD4, CD4 CD8, and AsGMl' cells, whereas precursor of LAK cells against P815 cells(H-2d) could be Thyl+, CD4, CD8+, and AsGM1+ cells. Effectors of LAK cells against HFL/b were Thy1+, CD8- cells but LAK cells against P815 were Thy1+, CD8 cells. LAK cells were generated in different pathways: (a) the endogenous pathway in which LAK cells were generated by culturing splenocytes with syngeneic peritoneal macrophages and indomethacin, and (h) the exogenous pathway in which LAK cells were generated by culturing splenocytes with exogenous interleukin-2(IL-2). Depletion of Thy1+, CD4+, AsGM1+ cells from splenocytes suppressed endogenous LAK cell generation, whereas depletion of Thyl+, AsGM1+ cells, not CD4+ cells, suppressed exogenous LAK cell generation against HFL/b. IA+ macrophages and CD4+ T cells were the ancillary cells that were responsible for producing lymphokines in endogenous pathways. Regarding cytokine requirement, interleukin-4 (IL-4) synergized with IL-2 to induce LAK cells both in endogenous and exogenous pathways. Interferon a, B(lIFN a, B) had no effect both in endogenous and exogenous pathways. Interferon r(IFN r) and prostaglandin E2(PGE2) suppressed endogenous LAK cell generation but had no effect in exogenous pathway. Our study demonstrated that LAK cells are heterogeneous both in precursors and effectors, and different cellular, lymphokine, pharmacological regulators might be involved in the generation of efficient LAK cells in endogenous and exogenous pathways.

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신피막하 종양이식 분석법에 의한 부인과악성 종야의 화학감수성 검사에 관한 연구: Soon Beom Kang, Kyeong Hoon Cho, Pil Ryang Lee, Seung Cheol Kim, Young Min Choi, Hyo Pyo Lee, Dong Geun Chung, Noe Kyeong Kim, Jae Gahb Park, Seong Hoe Park; J Korean Cancer Assoc. 1990;22(1):24-32.

Abstract PDF: The chemosensitivity testing is important in the research of cancer biology, development and screening of anticancer drug, and improvement of chemotherapy modalities. Subrenal capsule tumor implant assay (SRCA) is a promising rapid method in the selection of individual chemotherapy for cancer patients clinically. A total of 100 SRCA were performed with several gynecologic malignancies(69 cervical, 10 ovarian, 10 endometrial carcinomas, 6 vulva carcinoma, 4 sarcoma, and 1 choriocarcinoma). 1 mm x 1 mm x 1 mm fragments oi fresh human gynenologic tumors were implanted under the renal capsule of immunocompetent female adult BALB-C mice and tested against several chemotherapeutic agents or their combinations. An average of 75% of tumors showed positive growth. The evaluable assay rate was 91%(91/100). Variable response rate were noted in each gynenologic tumor. An overall predictive accuracy rate of SRCA was 73% in present series. In conclusion, the SRCA is considered as a reliable in vivo clinical chemosensitivity test in the selection of individual cancer chemotherapy.

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c-myc Oncogens Amplification in Squamous Cell Cancer ( SCC ) of Head and Neck: Han Lim Moon, Chi Wha Han, Hoon Kyo Kim, Choon Choo Kim, Kyung Shik Lee, Dong Jip Kim, Min Sik Kim, Seung Ho Cho, Byung Do Suh; J Korean Cancer Assoc. 1990;22(1):32-37.

Abstract PDF: Proto-oncogenes are highly conservative genes in human cell, which code growth factors, growth factor receptors. enzymes and nuclear protein and are necessary for cell growth and function. Alteration in these genes such as amplification, rearrangement, or mutation appeared to be associated with malignant transfarmation of cells. We examined 14 DNA samples from human squamous cell carcinoma of head and neck with slot blot analysi.. Two out of fourteen samples showed c-myc gene amplification. Nodal involvements (N2a. and N3b) vrere observed in both patients. They were maderately differentiated SCC of larynx. Further studies about c-myc gene rearrangenment and mutaiton should be confirmeg in these samples and examine whether c-myc amplification is correlated with the biologic characteristics of SCC of head and neck.

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Correlation between MDR1 Gene Expression and In Vitro Drug Sensitivity Testing ( DST ) of Human Cancer Cell Lines: Kyung Yung Lee, Jae Gahb Park, Adi F. Gazdar, Lori J. Goldstein, Ee Sook Hwang, Jin Pok Kim; J Korean Cancer Assoc. 1990;22(1):37-48.

Abstract PDF: The MDR1 gene is frequently over-expressed in cell lines selected for multidrug resistance and certain human tumors. We correlated MDR1 gene expression with DST patterns of 6 cancer cell lines from previously untreated patients. MDR1 RNA was measured by a slot blot analysis. The concentrations of 5 drugs (etoposide, colchicine, doxorubicin, vincristine and 5-fluorouracil) that inhibited 50g of cell growth (IC50 values) were determined by the semi-automated MTT assay. Contral cell lines included KB-3-1 (sensitive) and KB-8-5 (resistant). DST indices' were calculated as follows: IC., of test cell/IC,. of KB-3-1. There was no correlation between MDR1 RNA levels and 5-fluorouracil sensitivity. Results of the other drugs (which are substrates for the MDR1 gene product); MDRI RNA DST Index Cell line Type (unit) (median) (range) KB-3-1 Control 1 1 (None) KB-8-5 Control 30 10 (7-209) SNU-1 Gastric Ca ~1 1.3 (1.0-1.4) SNUH-17 Cervix Ca ~1 3.5 (2.2-4.4) SNUH-46 Laryngeal Ca ~1 5.5 (1.8-17) SNU-47 Bone sarcoma ~1 24 (1.7-545) SNU-C4 Colorectal Ca. 30 48 (4.3-150) SNU-61 Colorectal Ca. 10 105 (2.1-440) We conclude: 1) There is no apparent relationship between MDR1 RNA levels and in vitro sensitivity to 5-fluorouracL 2) With 5 carcinoma cell lines (but not with the sarcoma line) there is an apparent relationship between MDR1 RNA levels and in vitro sensitivities to the other 4 drugs tested.

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An Immunohistochemical Study on Differential Diagnosis of Small Round Cell Tumor: Joon Mee Kim, Mi Kyung Shin, Seung Yong Paik, In Sun Kim; J Korean Cancer Assoc. 1990;22(1):48-61.

Abstract PDF: Small round cell tumors in surgical pathology are difficult to be differentiated each other only by routine H & E stain. In this study we applied six antibodies (keratin, vimentin, neuron-specific enolase, S-100 protein, myoglobin and leukocyte common antigen) as a panel marker to 18 cases of primitive neuroectodermal tumor including neuroblastoma, Ewirig's sarcoma, rhabdomyosarcoma, lymphoma, and small cell carcinoma. The results were summerized as follows: I) Primitive neuroectodermal tumor (PNET) and neuroblastoma showed positive reaction for S -100 protein and neuron-specific enolase (NSE). 2) Ewing's sarcomas showed vimentin positivity with occasional positive reaction for NSE and S -100 protein, but it was always negative for myoglobin. 3) Myoglobin was a specific marker for rhabdomyosarcoma, and vimentin might be positive. In myoglobin negative case, immunostaining for desmin was recommended. 4l Leukocyte common antigen positivity always indicated lymphoma. Occasionally vimentin and NSE were positive. 5) In the cases of carcinoma, keratin was positive and occasionally NSE and/or vimentin were positive.

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In Vitro Chemosencitivity of Doxorubicin on Human Cancer Cell Lines: Chung Gyu Park, Dong Kyun Lim, Yoon Hoh Kook, Chang Yong Cha, Chul Gi Paik; J Korean Cancer Assoc. 1990;22(1):61-66.

Abstract PDF: The anticancer effect of doxorubicin was evaluated on human cancer cell lines (K562, KATOIII, PC-14, HeLa, SNU-C5, NCI-H417 and Nalm-6) after exposure to doxorubicin at 5, 50, 500 ng/ml for 1 hour at 37`C using in vitro agar-methylcellulose clonogenic assay. The drug concentration which produced 50g inhibition of colony formation (ID) of each cell line were as follows: K562, 258.2 (ng/ml); KATO IIL, 473 (ng/ml); PC-14, 268.5 (ng/ml); HeLa, 355.7 (ng/ ml), SNU-C5, 241.5 (ng/ml); NCI-H417, 13 (ng/ml); Nalm-6, 20 (ng/ml). From this assay NCI-H417 and Nalm-6 were considered to be sensitive to doxorubicin on the basis of the fact that the ID,. for these cell lines was within a clinically achievable range.

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In Vitro matrigel Invasion Assay of Cell Lines: Song Kim, Jae Gahb Park, Ee Sook Hwang, Hynda K. Kleinman, Jin Pok Kim; J Korean Cancer Assoc. 1990;22(1):66-86.

Abstract PDF: Considerable progress in tbe study of tumor cell invasion has been made by utilizing in vitro assay systems. Recently, the reconstituted basement membrane systems in blind well chemotaxis chambers have enabled quantitative analyses of the potentiality of the tumor cell invasion. This study was designed to establish the optimal conditions for in vitro invasion assay using matrigel as a basement membrane barrier in blind well chemotaxis chamber and to evaluate the in vitro invasiveness of the established tumor cel1 lines which have been known to be highly invasive in vivo. Two control cell lines(HT-1080, 3T3-Swiss albino) and twenty established cell lines were studied in this investigation. Polyvinylpyrrolidone-free-polycarbonate filters with varying sizes of pores(8pm, 10pm, 12pm) were coated with varying amounts of matrigel(330ug/ml, 500ug/ml, 1,000 ug/ml) and dried under sterile hood for 2 hours. 3T3-Swiss albino-conditioned medium was placed in the lower chamber and each matrigel-coated filter was placed in the blind well chemotaxis chamber. Two hundred thousand cells in the DF-10 media containing 0.1% BSA were added to the upper chamber and assays were carried at 37C in 5% CO,-95g room air for varying durations(2hrs, 4hrs, 6hrs, Shrs). After each incubation period, the number of cells on the lower surface of the matrigel-coated filter were counted as well as the number of cells in the lower chamber. The optimal conditians for in vitro invasion assay were 500 ug/ml of matrigel, 10 pm of filter pore, 4 hrs to 6 hrs of incubation period. No difference was observed in the invasiveness of the cell lines according to the conditioned media of varying cell lines. SUN-Cl and U2OS cell lines had larger number of cells on the matrigel-coated filter and in the lower chamber, but SNV-C4, NCI-H630 cell lines had fewer number af those. Some other cell lines exhibited a few number of matrix barrier- attached cells and larger number of lower chamber invading cells simultaneously or vice versa. This data could provide the possibility of various differences which exists in the tumor cell responsiveness to the conditioned media, the tumor cell attachment to the matrigel-coated filter, and the degree of tumor cell invasiveness. Therefore when comparing the invasiveness of the cell lines using these in vitro matrigel assay systems, it is necessary that the invasiveness to the lower chamber must be cansidered as significant as a matrix barrier-attached invasiveness.

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Phase 1 Trial of Recombinant Interferon Gamma ( LBD - 001 ) in Cancer Patients: Noe Kyeong Kim, Yung Jue Bang, Dae Seog Heo, Heung Tae Kim, Hyo Jin Kim, Keun Chil Park, Keun Chil Park, Dong Bok Shin, Myung Chul Lee, Byoung Kook Kim, Sang Goo Shin, Seong Hoe Park, Han Ik Cho; J Korean Cancer Assoc. 1990;22(1):86-96.

Abstract PDF: A phase I study of recombinant gamma-interferon (LBD-001) was conducted in 23 patients with advanced malignancy. The schedule was the intramuscular administration of recombinant interferon-gamma 6 consecutive days a week for 2 weeks followed by 2 weeks of rest and was repeated every 28 days. Patients were assigned to six dose levels. The maximum tolerated dose was 10.0x10(6) units/m/day and the major toxicities were flulike symptoms. After intramuscular injection, the pharmacological data fit the single compartmental modeL More than 2/3 of the dose administered was absorbed. The absorbance T 1/2 was longer with values of 247.6 minutes but interferon-gamma was cleared with a short half life of 49.9 minutes from the circulation. Antitumor effects occurred in patients with chronic myelogenous leukemia and malignant melanoma.

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Clinical Trial of Human Recombinant Interleukin-2 ( IL-2: Joung Soon Jang, Jae Bum Jun, Joon Soo Hahm, Min Ho Lee, Il Young Choi, Te June Chung; J Korean Cancer Assoc. 1990;22(1):96-106.

Abstract PDF: The effects of immunotherapy with IL-2 were evaluated in 10 patients with advanced cancers for whom standard anticancer chemotherapy had been ineffective from Apr. 1988 to Mar. 1989. Of total 10 patients, five were treated witn 24 hr continuous IV infusion of IL-2 with the dosage of 1 x 10(4) u/kg/day or 1 x 10(5) u/kg/day respectively for 5 days and another five with intraperitoneal bolus infusion of IL-2 with the dosage of 1 x10(4) u/kg/day or 1 x 10(5) u/kg/day after removal of ascites by paracenthesis for 5 days. Of the 10 evaluable patients, 9 (90%) patients had no response and only 1 (10%) had minimal response. One patient who had minmal response had squamous cell ca of esophagus and has received IL-2 intravenously. Most common side effects were fever and chills and they could be prevented or alleviated by use of NSAIDs or IV infusion of Meperidine in severe cases. Serious side effects were capillay leak syndrome and its complication which show hypotension, generalized edema, weight gaine and azotemia. GI symptom, rigor and skin lesion were also obseved. But pulmonary edema was not observed. All of the above side effects were well overcome by conservative management. In the intraperitoneal infusion group the side effects occurred less frequently than IV infusion group. Anemia, neutropenia, eosinophilia, azotemia and abnormal liver function test were observed, but they have returned to normal range after discontinuation of IL-2 infusion. The absolute lymphocyte counts decreased I day after IV infusion of IL-2 and came back to show revound lymphocytosis from the next day after discontinuation of IL-2 infusion. They returned to pretreatment level from the 4th day of discontinuation of IL-2 infusion. In the intraperitoneal infusion group total WBC counts in ascites began to increase from 24 hrs after IL-2 infusion and reached peak at the end day of infusion. They began to decreased with discontinuation of infusion. Compared with WBC counts in ascites, those in peripheral blood showed delayed increase. In conclusion, 1 x 10' and 1 x 10 u/kg/day infusion of IL-2 were enough to increase the lymphocyte pool in vivo respectively, although no effective clinical response was obtained. There was no difference in the clinical and side effects between 1 x 10(4) and 1 x 10(5) u/kg/day infusion groups. This study warrants for further investigation into the determination of effeective therapeutic concentration of IL-2 and its route of adminstration.

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Clinical Result of Combined Radiotherapy and Hypertermia Indured by 915 MHz Microwave and Ultrasound in Locally Advanced Malignant Tumors: Kyoung Hwan Koh, Kyoung Hwan Koh, Chul Koo Cho, Seong Yul Yoo; J Korean Cancer Assoc. 1990;22(1):106-112.

Abstract PDF: Sixty six lesions of 66 patients with locally advanced malignant tumors were received thermoradiotherapy with ultrasound and/or 915 MHz microwave. Most of all patients were failed with previous conventional therapeutic trial. Hyperthermia had been done immediately after radiotherapy, twice a week, 43'C for one hour and radiotherapy had been done 5 fractions per week with a fraction size of 2 Gy up to total 30 to 60 Gy. Conclusions are as follows. 1) Total response rate (CR+ PR) to thermoradiotherapy with microwave and ultrasound was 85 %. 2) Tumor depth, minimum temperature of tumor center, number of heat fraction and irradiation dose were statistically significant factors affecting response. 3) Hyperthermia with microwave and ultrasound can be used efficiently to control locally advanced malignant tumars whether previously received near tolerance dose of radiotherapy or not.

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MACOP - B Chemthrapy for the Treatment of Malignant Lymphoma: Kyung Shik Lee, Hoon Kyo Kim, Young Seon Hong, Han Lim Moon, Je Ho Han, Chi Hong Kim; J Korean Cancer Assoc. 1990;22(1):112-116.

Abstract PDF: Between September 1987 and April 198S, 18 patients with advanced aggressive non-Hodgkin's lymphoma completed treatment with MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Among them, 14 patients were evaluable for the response and toxicity. Twelve patients (86%) achieved a complete response and 2 patients (14%,) had a partial response. The most frequent toxicity was leukopenia. Thus, MACOP-B is an effective and safe treatment for advanced aggressive lymphoma.

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Role of Chemofherapy in Unresectable Stage Biliary Tract Cancer: Hyun Cheol Chung, Eun Hee Koh, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(1):116-125.

Abstract PDF: Twenty evaluable patients with disseminated unresectable biliary tract cancer received chemotherapy after biliary tract drainage procedures. Two cambination chemotherapy protocols were applied; FAM (5-fluorouracil 1000 mg/m 24-hour infusion, day 1-3, adriamycin 40 mg/m i.v. day 1, mitomycin 10 mg/m i.v. day 1) in 13 patients, and MDF (5-fluorouracil 1000 mg/m' 24-hour infusion day 1-3, mitomycin 10 mg/m(2) i.v, day 1, cisplatin 80 mg/m i.v. day 4) in 7 patients. Course were repeated every three weeks. Seven patients(35%) achieved partial response. The median survival was 13.5 months in responders and 8.0 months in non-responders. No difference of drug response rate was observed between two chemotherapy protocols. Comparing the survival of biliary drainage plus chemotherapy group with that of billary drainage alone group, there was a trend of survival benefit in chemotherapy group with a median follow-up duration of 10 months. Gallbladder cancer and distal bile duct cancer showed favorable response rate and median survivals with chemotherapy and bile drainage than bile drainage alone. Most serious drug toxicities were myelosuppression and infection. But no chemotherapy related death was observed. Further randomized controlled trials to evaluate the effect of chemotherapy in advanced biliary tract cancer would be warrented.

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Combination Chemotherapy with 5-fluorouacil , ACNU and Mitomycin-C ( FUM ) for Carcinoma of the Pancreas and Gallbladder: Joong Jik Cha, Seok Kyun Kim, In Young Hyun, Weon Seon Hong, Jhin Oh Lee; J Korean Cancer Assoc. 1990;22(1):125-131.

Abstract PDF: Ten patients with pancreatic cancer and four with gailbladder cancer were treated with FUM: 5-fluorouracil (5-FU), ACNU and mitomycin-C (MMC): 5-FV 1,000 mg/m' i.v. on day 1 5, ACNU 60 mg/m(2) i.v. on day 1 and MMC 10 mg/m i.v. on day 5, everv four weeks. All patients had previously untreated and unresectable cancer due to direct invasion and/or distant metastasis. No complete response was observed. Three of 14 patients (21.4%) obtained partial response. Four patients (28.6%) showed no change and seven (50.0%) evidenced progressive disease. The median survival was 7.1 months for all patients, i.5 months for patients without metastasis and 3.8 months for patients with metastasis. Nine vf 14 patients (64.3%) have survived more than six months and four (28.6%) are still alive. Response rate were analyzed with regard to the age, sex, distant metastasis, serum carcinoem- bryonic antigen (CEA) level and jaundice. Patients with more than 50 years old, no metastasis, high CEA (>10 ng/ml) and low bilirubin (<2.0 mg/ml) showed higher response rate compared with those with less than 50 years old, metastasis, low CEA (<10 ng/ml) and high bilirubin (>=2.0 mg/ml), however, there was no statistical significance between these factors and response rate. The toxicity was mild to moderate. Patients were generally well tolerated, although all patients experienced nausea, vomiting and alopecia. Three patients had moderate degree of stomatitis and four showed severe myelosuppression for more than four weeks, however, myelosuppression was recovered by five or six weeks after treatment in all casea We think that these results provide a rationale for the conduction of the initiation of a large prospective randomized controlled trials with FVM therapy for the carcinorna of pancreas and gallbladder.

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The Treatment Results of Combination of Radiotherapy and chemotherapy in Limited Stage Small Cell Lyug Cancer: Chang Ok Suh, Jun Kyu Loh, Kyung Ran Park, Chang Ok Suh, Gwi Eon Kim, Jae Kyung Roh, Seong Kyu Kim, Byung Soo Kim; J Korean Cancer Assoc. 1990;22(1):131-144.

Abstract PDF: A total of 72 patients with limited stage small cell lung cancer treated with combination of chemotherapy and radiotherapy at Department of Radiation Oncology, Yonsei University College of Meidcine between Jan. 1975 and Dec. 1986 were retrospectively analysed. 1) Age distribution of patients was between forty and seventy-one with median age fifty-five and male to female ratio was 5:l. 2) Complete response rate by treatment modality was as follows; CV+RT was 33.3%; CAV+RT, 43.59o, MOCA+RT. 28.6% and CAV+VP+RT was 62.5%. CAV+VP+RT group showed best result and this was statistically significant to MOCA+RT group (p=0.02) but insignificant to CV+ RT or CAV+RT grouP (P>0.1). 3) Median survival and 5 year actuarial survival rate by treatment modality were as follows; CVt RT was 15 3 months and 16.2%. CAV+RT, 14months and 16.396; MOCA+RT, 7month and 09; and CAV+ VP+ RT was 24 month and 30.7% respectively. CAV+VP+ RT groulp shawed the best results and these were statistically significant to MOCA+RT group(p<0.05) but insignificant to CV+RT or CAV+RT group (p>0,05). 4l Patterns of failure in complete response group were as follows; local failure was 24%, distant failure, 52% and local and distant failure was 24%. 5) Local control rate by radiation dosage in complete response group was as follows; when total dose of 4500-4900 cGv was given, local control rate was 50%; 5000 cGy, 43% however when total dose was given between 5100-7000 cGy, local control rate was significantly improved to 100%. 6) The incidences of brain metastsis in PCI (prophylactic cranial irradiation) group and control group were 20% and 32% respectively, although this was statistically insignificant (p=0.32). 7) Statistically significant factors affecting prognosis were performance status, TNM stage, initial status of presentation of superior vena cava syndrome and pleural effusion, location of tumor, response status to treatment and whether or not maintenance chemotherapy is added.

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Treatment of Advance Inoperable Stomach Cancer with Cisplatin Adriamycin and 5-FU ( FAC: Duck Kyung Gong, Sang Wook Lee, Byung Hoon Han, Seung Yeon Suh, Man Ha Huh, Byung Chae Park; J Korean Cancer Assoc. 1990;22(1):144-151.

Abstract PDF: Twenty-four evaluable patients with advanced inoperable stomach cancer were treated with a combination of cisplatin (40 mg/m, IV, day 1), Adriamycin (30 mg/m, IV, day 2) and 5-FU (500 mg/ m, IV, day 3-5) every three weeks. The tumor responses and survival of the treated patients were compared to the untreated control patients (15 cases) who had similar tumor burden and performance status. There were four objective partial resPonses, giving a response rate of 16.7%. Eleven patients (45.8%) achieved disease stabilization and 9 cases (37.596) had tumor progression. No complete response was observed. FAC produced signficantly (P<0.0i) superior overall survival comPared to cvntrol. One-year survival rate for FAC regirnen was 53% compared to 15% for the control and median survival times ware 12.5 months versus 6 months, respectively. Toxicity was moderated and consisted of nausea, vomiting and hair loss. In conclusion, FAC regimen appears to have not so satisfactory effect in tumor responses in patients with advanced stomach cancer, but it is helpful for prolongation of survival times as compared to the untreated control patients.

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COPBLAM Combination Chemotherapy in Advanced , Intermediate and High - grade Non - Hodgkin's Lymphomas: Byung Hyun Yoon, Ki Young Kwon, Hong Suck Song; J Korean Cancer Assoc. 1990;22(1):151-162.

Abstract PDF: Between June 1985 and November 1988, 30 patients with advanced stage, intermediate and high- grade non-Hodgkin's lymphoma were treated with a COPBLAM regimen including cyclophos- phamide, oncovin, prednisolone, bleomycin, adriamycin, procarbazine. Median age was 50.1 years and 10 patients were 60 years or old. 15 patients (50%) achieved a complete response (CR) and 10 patients (30%) had a partial response. Of the 15 CRs, 6 patients (40%) suffered a relapse. 3-year survival was 48.2% and disease-free survival for CRs was 54.5% with a median follow-up of 16.5 months. Constitutional symptoms were negatively associated with response rate and survival but not in disease free survival. Prognostic significance of age, histologic type, stage, and serum LDH were not demonstrated. Overall toxicity was acceptible without any treatment-related deaths. The incidenca of nonfatal infection was 16.7.

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Treatment results of Definitive Radiation Therapy in Esophagaeal Cancer: Kyung Ran Park, Jun Kyu Loh, Chung Sik Rhee; J Korean Cancer Assoc. 1990;22(1):162-171.

Abstract PDF: A total of 88 patients with epidermoid carcinoma of esophagus treated with definitive radiotherapy at Department of Radiation Oncology. Yonsei University College of Medicine between Jan. 1971 and Dec. 1986 were retrospectivelv analysed. 1) Age distribution of patients was between thirty two and eighty with median age of sixty four and male to female ratio was 12:l. 2) Distributions of esophageal carcinoma were 8% at cervical esophagus, 68. 2% at thoracic upper two third. 22.7% Bt thoracic lower one third and 1.1% at multiple site. 3) Response rates were complete response 26.5%, partial response 67.6% and no response 5.9% 4) Median survival was 12 months, Two year and 5 year actuarial survival rate were 23% and 7% respec ti vely. 5) Median survival and 4 year actuarial survival rate by treatment modality were as follows; radiation therapy alc!ne was 12 months and 12.6% and combined chemo-radiotherapy was 11 months and 7.8%. There was no difference in survival rate between two groups. 6) Patterns of treatment failure were locoregional failure 43.2%, distant failure 21.6% and both locoregional and distant failure 35.2%. 7) Statistically significant prognastic factors were tumar response to radiotherapy (P=0.000) and tumor location (P=0.043), while all others such as age, sex, tumor size, chernotherapy and radiation dose were not important.

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Effects of α-difluormethylornithine ( DFMO ) on Growth Inhibition of Human Gastric and Colorectal Carcinoma Cell Lines: Ho Kyung Chun, Jae Gahb Park, Ee Sook Hwang, Sung Kuk Hong; J Korean Cancer Assoc. 1990;22(1):171-183.

Abstract PDF: DFMO, an irreversible inhibitor of ornithine decarboxylase, blocks polyamine biosynthesis, is reported to have antitumor effects in vitro at the peak achievable plasma concentration (about 0.5 mM). We determined the effects of DFMO on the growth of gastric and colorectal carcinoma cell lines using the semiautomated tetrazollum MTT assay. At a concentration of 0.5 mM and a 4 day incubation periad, DFMO inhibited the growth of 4 gastric cell lines by a median value of 5% and the growth of 7 colorectal cell lines by a median value of 22%. These effects were reversible by the addition of 0.1 mM of putrescine. Conciusians: 1) at the peak achievable plasma concentration, DFMO has very modest inhibitory effects on the growth of gastrointestinal carcinoma cell lines: and 2) DFMO may have a greater growth inhibitory effect on colorectal than on gastric carcinoma cell lines.

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Microangiopathic Hemolytic Anemia ( MAHA ) Associated with Cancer: Keun Chil Park, Dong Bok Shin, Keun Chil Park, Jae Hoon Lee, Yung Jue Bang, Seon Yang Park, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1990;22(1):183-194.

Abstract PDF: MAHA has been recognized as an uncommon, but fatal complication of cancer or its chemotherapy. From May, 1982 to Sep., 1988, we have experienced 29 cases of MAHA in cancer patients, of which 23 were thought to be cancer-associated and 6 to be chemotherapy-related. The clinical characteristica of MAHA in these patients are presented. Adenocarcinoma of the stomach was the most common primary cancer in cancer-associated MAHA. Mitomycin-C(MMC) was thought to be an offending agent of chemotherapy-related MAHA, and cumulative dose of MMC was 32-190 mg(mean 117 mg). Most patients presented abruptly with anemia or bleeding tendency. In some patients with chemotherapy-related MAklA, pulmonary edema or seizure was also observed. The most consistent laboratory findings were hemolytic anemia with characteristic schistocytes in the peripheral blood smear and thrombocytopenia. The most characteristic finding in cancer-associated MAHA was leukoerythroblastosis which was present in 74% of the patients, and that in chemotherapy-related MAHA was azotemia with microscopic hematuria or proteinuria which characterized the chemotherapy-related MAHA as chemotherapy-related hemolytic uremic syndrome (HUS). While MAHA was rapidly fatal in most patients managed with supportive treatment only, improve- ment of MAHA with partial response of cancer was achieved in 4 among 9 patients treated with FP (5-fluorouracil+cisplatin) chemotherapy. In case of chemotherapy-related MAHA, we treated 3 patients with plasmapheresis and MAHA was improved but azotemia was not. In conclusion, MAHA in cancer could be classified into cancer-associated MAHA and chemotherapy-related HUS. An early differential diagnosis and aggressive treatment could improve the prognosis of these previousiy fatal syndromes.

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Krukenberg Tumors of the Ovary : A Clinical Analysis of 16 Cases: Soon Beom Kang, No Hyun Park, Young Min Choi, Hyo Pyo Lee; J Korean Cancer Assoc. 1990;22(1):194-202.

Abstract PDF: The records of ovarian tumor registry in the SNUH were reviewed from 1983 to 1987. The charts of the patients diagnosed as Krukenberg tumors were screened as to clinical history, physical and operative finding, postoperative chemotherapy and so forth. The survival data was analyzed by Kaplan-Meier method. The results were as follows. 1l The incidence of Krukenberg tumors in all neoplastic ovarian tumors and all malignant ovarian tumors was 3.78% (16/421) and 10.96% (16/146) respectiveIy. 2) The average age was 41.4+8.4 years with range from 28 to 61. 3) The most common presenting symptoms, abdominal pain, gastrointestinal symptoms, abdominal distension, postmenopausal bleeding in order. 4) Except one of unknown origin, primary tumor was all found in the stomach. 5) The largest tumor f ound was 1,080 g and measured 17 x 13 x 8 cm, and the sma 1 lest was 8 g and measu red 3 x 1.5 x 1 cm. 6) Among the cases that could be evaluated for bilaterality, both ovaries were involved in 92.9(13/14). 7) Among the cases that stomach cancer occured prior to Krukenberg tumor (7 cases), the average interval from the diagnosis of stomach cancer to the diagnosis of Krukenberg tumor was 24 4+15. 7 months (range from 10 to 60 months) B) Chemotherapy was performed in ll cases and the regimens are FAM (5 FU, Adriamycin, Mitomycin), FP (5--FU, Cisplatinum), VPB (Vincristin, Cisplatinum, Bleomycin).and FM (5 FU, Mitomycin). 9) The 6 manth, 9-month, 15 month survival rate by Kaplan-Meier method was 66%, 44% 29% respectively Until now there is little hope to cure this disease. But it is possible to improve survival rate by early diagnosis, operation and combination chemotherpy.

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Stomach Carcinoma in the Young Adults - Analysis of 111 Cases , and Review from Literatures -: Dong Soo Suk; J Korean Cancer Assoc. 1990;22(1):202-208.

Abstract PDF: There are lll cases under 40 years old out of 584 stomach carcinoma from Seoul and Pusan Paik hospitals, Korea. It is 19. 0% of the total stomach carcinoma, and male-female ratio is 1 2: l. Under 35 years, it is 10.0%(62 cases), and male-female ratio is 0.9: l. Undifferentiated carcinoma is the predominant type, 76.7%, and differentiated type 23.3%. Proximal parts of stomach (body, fundus, cardia) are affected more, 46.8%, and antrum 38.5%, and body with antrum 14.7%. The present data (10.6%) of the incidence under 35 years old is notably higher than that of Japan (1.7-2.8%) and America (0.49~2.2%). These data of the incidence appear proportionally high with the degree of risk factors of these three countries. There are more undifferentiated or diffusely infiltrating type in the young adults, and the incidence of this type is stable without affected much by the environmental factor. Only differentiated or intestinal type of stomach cancer is variable with the enviromentai risk factor. These facts suggest that enviromental factor is mostly responsible for the development of intestinal type, and hereditary factor for the diffuse type. Based upon these presumptions, it is easily understandable ta find an each different male-female ratio in older and younger age groups (2: 1, 1: 1, respectively). These principal findings can be expected to exist in other human cancers which are developed by known or suspected carcinogenic agents. Leukemia and nasopharyngeal carcinoma are good examples. For, it is speculated that in young age group, hereditary factor is the cause, and in older age group, environmental factor is the cause in the above cancers.

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