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Volume 29(1); February 1997
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Original Articles
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Comparison of Efficiency of Infection of Human Cancer Cell Lines Via Retroviral Vector System
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Yeon Soo Kim, Hee Kyung Lim, Joo Hang Kim, Jin Sik Min
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J Korean Cancer Assoc. 1997;29(1):1-10.
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Abstract
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There are several reasons why retroviruses are useful as vectors for gene therapy. However, retroviral vectors also have some limitations. Research in retroviral-mediated gene transfer has struggled with low titer and transduction efficiency on certain human target cells even with the addition of polycations to enhance transduction. Efficient in vivo gene transfer with retroviral vectors will require the availability of large amounts of vector at titers higher than generally possible by most current methods. Therefore, transduction efficiency of various human cell types with retroviral vector system is very important in human gene therapy. In an effort to test the transduction efficiency of a retrovial vector in the human cancer cell lines, a retroviral vector was infected into various human cancer cell lines.
MATERIALS AND METHODS
We generated retrovirus producing cell lines through transfection or infection of amphotropic packaging cell line PA317 with ecotropic retroviruses encoding bacterial lacZ gene. The amphotropic retrovirus vector was used to transduce various human cancer cell lines.
RESULTS
Of eight randomly chosen G418-resistant clones generated by transfection, only two clone produced the vector at up to >10 (6) cfu/ml, while one of five clones generated by infection yielded higher-titer virus in the absence of helper virus, up to 1 X 10 (7) cfu/ml, than the transfected clones. Transduction with supernatant derived from a PA317 producer cell line has resulted in transduction levels from 1% to 15%, 5- to 60-fold lower than those analyzed in NIH3T3 cells.
CONCLUSION
These findings suggest that new improved gene transfer method into human cancer cells using retroviruses is required for efficient in vivo cancer gene therapy.
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Expression and Intracellular Localization of Hepatitis C Viral Core Protein in Human Hepatoma Cell Line Transfected with Viral cDNA
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Dong Wan Kim, Sun Hee Kim
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J Korean Cancer Assoc. 1997;29(1):11-18.
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Abstract
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Establishment of the human liver cell lines which permanently express the HCV proteins is important for the large scale production of viral antigen and analysis of the mechanism of hepatocellular carcinogenesis by HCV. Here, we attempted to establish the human hepatoblastoma cell lines which stably express the HCV core protein and examined the intracellular localization of the core protein.
MATERIALS AND METHODS
The cDNA of HCV core protein and neomycin resistance gene were expressed in HepG2 cells by the SRalpha promoter and human EF-1alpha gene promoter, respectively. The core protein was detected by immunofluorescence assay and western blotting.
RESULTS
We obtained several HepG2 cell clones which express HCV core protein stably. In transient expression assay, the core protein was localized in the cytoplasm in about 90%, and localized in the nucleus in about 10% of the core-expressing HepG2 cells. But, in the stably expressing HepG2 cell clones, the core protein was localized only in the cytoplasm. No HepG2 cell containing core protein in the nucleus was found in all of the cells which stably express the core protein.
CONCLUSION
The EF-1alpha gene promoter is highly efficient in the colony formation by neomycin resistance gene and is very useful for the isolation of human liver cell clones which express foreign genes stably. HCV core protein is localized in both nuclear and cytoplasm of human liver cell in short term but the cells containing the core protein in nucleus seem to disappear in long term culture.
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Antitumor Effect of Methotrexate in SCID Mice with Human Leukemia CCRF-CEM Cell Line
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Yang Kyu Choi, Jae Yoon Choi, Byung Hwa Hyun, Yong Joon Kim, Chul Ho Lee, Won Kee Yoon, Kyu Shik Jeong, Dae Yong Kim
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J Korean Cancer Assoc. 1997;29(1):19-28.
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Abstract
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- No abstract available
Clinical Trial
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Anti-tumor Effect of the Complex of Acriflavine and Guanosine (AG60)
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Eun Kyung Hong, Hwan Mook Kim, Kyung Yung Lee, Young Shin Chung, Bo Im Yoo, Sang Geon Kim, E Tay Ahn, Young Bok Han
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J Korean Cancer Assoc. 1997;29(1):29-37.
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Abstract
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The anti-tumor effect of the complex of acriflavine and guanosine (AG60) was investigated.
MATERIALS AND METHODS
In vitro cytotoxicity of AG60 was measured using SRB assay, and in vivo antitumor activity of AG60 was examined in CDF1 mice intraperitoneally inoculated with the P388 leukemic cells and in ICR mice inguinally implanted with S-180 cells. Tumor size and mean survival time were determined.
RESULTS
AG60 and acriflavine showed strong anti-tumor effect in vitro on lung cancer (A549), renal cancer (UO-31) and colon cancer (COLO205) cells. However, AG60 did not show the cytotoxicity against normal cell line, 3T3. The range of the IC50 of AG60 to the various tumor cell lines was 0.09 microgram/ml through 1.94 microgram/ml. The treatment of ascitic tumor bearing CDF1 mice with AG60 resulted in over 160% increases in the mean survival time. The most effective dose of AG60 was 30 mg/kg body weight in tumor implanted mice. In solid tumor bearing ICR mice tumor growth and progression were suppressed in response to the different doses at 30 days; 69.8% suppression of tumor size in response to acriflavine, 16.0% to guanosine, 87.7% to AG60 and 78.5% to doxorubicin. In addition, 35% increases were observed in the means survival time of AG60 treated group compared with control group.
CONCLUSION
The prominant anti-tumor effects of AG60 shown in this report would represent the possibility of the clinical trials.
Original Articles
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Effect of FCL (5-FU, carboplatin, leucovorin) Chemotherapy in Advanced Head and Neck Cancer
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Samyong Kim, Jee Young Choi, Hyeon Su Kim, Sang Jun Park, Jong Suk Kim, Byung Kook Kim, Deog Yeon Jo
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J Korean Cancer Assoc. 1997;29(1):38-45.
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Abstract
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The purpose of this study was to evaluate the efficacy and the toxicities of recently developed second generation platinum, carboplatin in combination with 5-fluorouracil and leucovorin in head and neck cancer patients.
PATIENTS AND METHODS: Between March 1993 and Apirl 1996, 22 patients with locally advanced/metastatic head and neck cancer were treated with FCL combination chemotherapy. Of these 20 patients were evaluable.
RESULTS
Median age was 58 years. The number of patients with stage III and IV patients was 4 and 18 respectively.
Among the 20 evaluable patients, 1 (7.2%) achieved a complete response and 8 (40%) achieved partial responses.
The median duration of the response was 24 weeks and the median survival duration was 12 months. Out of 77 chemotherapy cycles, 1 patient (1.3%) had anemia of WHO grade 2, 7 patients (9.1%) experienced leukopenia (WHO grade > or =2) and 7 (9.1%) experienced thrombocytopenia (WHO grade > or =2). Non-hematologic toxicities were mild; nausea and voming of WHO grade > or =2 was 12 (15.6%), stomatitis (WHO grade > or =2) was 6 (7.8%).
CONCLUSION
FCL chemotherapy was effective in locally advanced head and neck cancer. Toxocities were minimal compaired to cisplatin based combination chemotherapy.Further studies on increased dose of FCL chemotherapy in head and neck cancer patients is warranted.
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5-Fluorouracil, Leucovorin, Ifosfamide and Cisplatin (FLIP) Combination Chemotherapy for Adevanced Non-Small Cell Lung Cancer
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Hyun Sik Jeong, Keunchil Park, Jung Ae Lee, Young Iee Park, In Sook Woo, Ki Suk Jung, Young Suk Park, Duk Jhe Shun, Won Seog Kim, Jeong A Kim, Sung Soo Yoon, Won Ki Kang, Hong Ghi Lee, Chan Hyung Park
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J Korean Cancer Assoc. 1997;29(1):46-52.
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Abstract
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To evaluate the response rate and toxicity of combination chemotherapy including 5-fluorouracil (F), leucovorin (L), ifosfamide (I) and cisplatin (P) for the previously untreated patients with unresectable stage IIIB or IV non-small cell lung cancer.
MATERIALS AND METHOD
The doses of FLIP were 5-fluorouracil 800 mg/m2 CI days 1-5, leucovorin 20 mg/m2 IV days 1-5, ifosfamide 1000 mg/m2 CI days 1-3, cisplatin 100 mg/m2 IV day 1 respectively. Cycles were repeated every 3 weeks until disease progression. Seventy-three previously untreated patients were enrolled. Age ranged from 30 to 73 (median 56 years); 43 were male, 30 female. Fifty-three patients had performance status (ECOG) 0-1 and 19 performance status 2.
Twenty-two patients had stage IIIB and 51 stage IV.
Follow-up ranged from 7+ to 160weeks (median 57 weeks).
RESULTS
The overall response rate was 46.7% for 62 evaluable patients. (CR 1 patient, PR 28 patients) Median response duration was 24 weeks (range 1+ to 36+ weeks).
Toxicity > Grade II (WHO) included: granulocytopenia 19.8%, anemia 13.5%, nausea and vomiting 31.5% stomatitis 46.5%, neuropathy 24.6%.
CONCLUSION
FLIP chemotherapy was comparable to other combination chemotherapy for advanced non-small cell lung cancer with moderate toxicities.
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Relation Between Hormone Receptor (Enzyme-Immunoassay and Immunohistochemistry), Histologic Grade and Mammographic Findings in Patients with Primary Breast Cancer
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Byung Chul Kang, Ki Keun Oh, Jae Keun Kim, Woo Hee Jung, Hy De Lee, Kyung Soon Song
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J Korean Cancer Assoc. 1997;29(1):53-61.
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Abstract
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To evaluate the relationship between the hormone receptor status, histologic grade and, the film-mammographic findings in primary breast cancer.
MATERIALS AND METHODS
198 breast cancer patients with hormonal receptor assay were included in this study.
Estrogen receptor (ER) and progesterone receptor (PR) were determined by immunohistochemical method and enzyme-immunoassay. And film-mammographic findings were evaluated to disclose the relationship among the three variables (film-mmamographic findings, histologic grade and hormonal receptor status). Film- mammographic findings of the breast cancer are classified as spiculation, increased parenchymal density, calcification and mass.
RESULTS
There is no correlation between estrogen receptor and histologic grade in 154 patients. Some correlation between estrogen receptor by enzyme-immunoassay and by immunohistochemistrical methods with 28 available data were observed (R=0.428). Among high estrogen receptor (ER) patients, there is a high possibility of spiculation or mass in mammography with 79 available data (Modified t-test, P<0.01).
CONCLUSION
Spiculation or/and mass of the mammography can be related to the high possibile factor of the positive estrogen receptor or high level of estrogen receptor in primary breast cancer.
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Quantitative Analysis of Metastatic Lymph Nodes after Curative Surgery in Gastric Cancer
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Wansik Yu, Yeon Sik Ji, Gyu Seok Choi, Ilwoo Whang, In Soo Suh
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J Korean Cancer Assoc. 1997;29(1):62-68.
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Abstract
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A consecutive series of 710 patients who underwent curative gastrectomy for carcinoma was studied with a special reference to the number or frequency of lymph node metastasis and the patient's prognosis.
MATERIAL AND METHODS: Survival rates were calculated by the Kaplan-Meier method, and the difference between each group was evaluated statistically by the log-rank method.
Follow-up was obtained for 709 patients (99.9%).
RESULTS
According to the number of lymph nodal metastases, the five year survival rate for group 1 (1~3 positive nodes) was 50.9%; for group 2 (4~6 positive nodes), 56.7%; and for group 3 (more than 6 positive nodes), 12.0% (p<0.0001).
According to the frequency of lymph node metastases, the five year survival rate for those with up to 25 per cent frequency of metastases was 47.5%; for those with up to 50 per cent frequency of metastases, 15.6%; and for those with greater than 50 per cent metastases, 6.3% (p<0.0001).
According to the frequency of the regional lymph nodes (which include perigastric nodes along the lesser and greater curvatures, nodes located along the left gastric, common hepatic, splenic, and celiac arteries) metastasis, we categorized them as group 0 (N0: no metastasis), 1 (N1: metastasis in up to 25%), and 2 (N2: metastasis in greater than 25%).
CONCLUSION
This subdivision could be successfully applied to the clinical evaluation of gastric carcinoma (five year survival rate for N0, 86.9%; for N1, 49.0%; and for N2, 10.7% (p<0.0001)) without difficulty in dividing certain lymph nodes into the correct location.
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Evaluation of Biologic Phenotype by Midkine Gene Expression in Gastric Cancer as a Target for Biotherapy
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Hyun Cheol Chung, Sun Young Rha, Hei Cheol Chung, Hyun Joo Kwak, Jae Yong Cho, Soo Jung Gong, Sung Hoon Noh, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim
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J Korean Cancer Assoc. 1997;29(1):69-80.
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Abstract
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We studied biological phenotypes of gastric cancer cell lines based on a novel heparin-binding growth/differentiation factor, midkine (MK) expression.
MATERIALS AND METHODS
Nine gastric cancer cell lines and 25 gastric cancer tissues were tested for MK expression by Northern blot analysis. Soft agar assay for in vitro tumorigenesis, cross- feeding assay for paracrine angiogenic activity, ELISA for uPA and PAI-1 measurement were performed.
RESULTS
MK expression was found in 67% (6/9) of the gastric cancer cell lines, and 56% (14/25) of the primary gastric cancer tissues. Gastric cancer cell lines with MK expression were more tumorigenic in soft agar assay and endothelial cell growth stimulatory in cross-feeding assay than cells which did not express MK. However, urokinase-type plasminogen activator (uPA) expression did not correlate with MK expression. Growth of MK expressing cells was inhibited by a heparin-binding blocking agent, pentosan polysulfate (PPS). In cancer tissues, MK expression correlated with tumor size, suggesting in vivo autocrine and paracrine activity.
CONCLUSION
Gastric cancer cells with increased MK gene expression showed increased tumorigenic and angiogenic activity. Therefore, this proliferation promoting activity of MK can be targeted by an anti-heparin binding agent as a biotherapy model in gastric cancer treatment.
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Synchronous Expression of Circulating Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) During Gastric Cancer Progression
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Hei Cheol Chung, Joon Oh Park, Sun Young Rha, Hyun Cheol Chung, Soo Jung Gong, Choong Bae Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Sung Hoon Noh
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J Korean Cancer Assoc. 1997;29(1):81-92.
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Abstract
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The circulating forms of ICAM-1 (cICAM-1) and VCAM-1 (cVCAM-1) has been reported from supernatant of cytokine activated endothelial cells, cancer cells and from cancer patient serum even though the biological significance of the cCAMs are not fully elucidated.
MATERIALS AND METHODS
To evaluate the correlation of the expression of cICAM-1 and cVCAM-1 and prognosis in gastric cancer, we measured cICAM-1 and cVCAM-1 levels in 20 healthy volunteers and 142 gastric cancer patients' sera by ELISA assay. Also we compared cCAMs levels with vascular endothelial growth factor (sVEGF) and FP. Ninety-five patients were operable and 47 patients were advanced or relapsed state at the time of the study. In 28 operable patients, we simultaneously sampled portal and peripheral vein and measured the cCAMs.
RESULTS
The cCAMs level and positive rate in serum increased with cancer progression from healthy control, operable to advanced or relapsed gastric cancer. In advanced cancer, cICAM-1 level increased with liver metastasis. The cICAM-1 level in portal blood was correlated modestly with that in peripheral blood. And in cVCAM-1 positive subgroup, cCAM-1 level correlated with cVCAM-1 level. The peripheral cICAM-1 level decreased in 6% compared to that of portal cICAM-1 level while peripheral cVCAM-1 level increased in 1% compared to that of portal level. Synchronous expression of both cCAMs was found in 58.3% of the patients with liver metastasis and 22.9% of the patients without liver metastasis (p=0.03). But, there were no correlation between cCAMs and FP expression regardless of liver metastasis. The sVEGF level correlated with neither cICAM-1 nor cVCAM-1 level regardless of liver metastasis. The median disease-free and overall survival of patients with synchronous cICAM-1 and cVCAM-1 expression was 8 months and 9 months, while in patients without co-expression it was more than 24 months and 23 months respectively.
CONCLUSION
We suggest that synchronous cICAM-1 and cVCAM-1 elevation may be a useful monitor of tumor burden and progression in gastric cancer, especially in liver metastasis.
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Immunohistochemical Analysis of the Expression of Cathepsin D in Human Gastric Adenocarninoma
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Sang Uk Han, Hee Jae Joo, Yong Kwan Cho, Kyung Po Lee, Myung Wook Kim
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J Korean Cancer Assoc. 1997;29(1):93-102.
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Abstract
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Cathepsin D is an acidic lysosomal proteinase involved in intracellular protein turnover. Increased levels of this enzyme have been reported to be indicators of aggressive tumor behavior in some human tumors. In gastric cancer, increased expression of cathepsin D has been reported to be an independent prognostic factor.
MATERIALS AND METHODS
We used standard immunohistochemical techniques on formalin- fixed, paraffin-embedded tissues to examine the expression of the cathepsin D in fifty five gastric adenocarcinomas. And we compared these with other indicators of aggressive tumor behavior including stage of disease, tumor size, lymphatic invasion, neural invasion, Lauren classification, disease recurrence and survival.
RESULTS
Positive granular cytoplasmic staining for cathepsin D was detected in 100% of the tumors and strongly positive staining was found in 53%. However, the intensity of the staining varied from cell to cell in the same carcinoma tissue as well as among samples. Positive staining also was seen in normal foveolar epithelial cells, parietal cells, macrophages and ganglion cells. Our results did not show any correlation between the expression of cathepsin D and other indicators of aggressive tumor behavior. But the group having more intensely stained margins showed the tendency to frequent lymphatic invasion.
CONCLUSION
We conclude that the results obtained using polyclonal antibodies to cathepsin D do not support the prognostic usefulness of immunohistochemical analysis of this proteinase in tumor cells in human gastric adenocarcinoma, but this study may offer some useful indicator for further pathophysiological studies on gastric adenocarcinoma.
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A Phase II Study of AP (Doxorubicin, Cisplatin) Chemotherapy in Patients with Advanced Hepatocellular Carcinoma
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Jung Ae Lee, Yoon Koo Kang, Chang Min Kim, Jin Oh Lee, Tae Woong Kang
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J Korean Cancer Assoc. 1997;29(1):103-110.
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Abstract
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Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma and is considered to be a highly malignant tumor with poor prognosis. We evaluated the efficacy and toxicities of AP (doxorubicin, cisplatin) comnination chemotherapy in hepatocellular carcinoma.
MATERIALS AND METHODS
Between October 1989 and February 1991, 21 previously untreated patients with advanced hepatocellular carcinoma were entered and treated with AP combination chemotherapy (adriamycin 60 mg/m2, D1 and cisplatin 60 mg/m2, D1, repeated every 3 weeks).
RESULTS
Among 14 evaluable patients, there was no complete response and 5 patients (36%; 95% C.I=10~62%) achieved partial response. The median survival time of all 21 patients was 17 weeks, and 63 weeks in responders (n=5) and 14 weeks in nonresponders (n=16), and the difference in two groups was statistically significant (p<0.05). The median time to progression of 14 evaluable patients was 13 weeks, and 49 weeks in the responders (n=5) and 6 weeks in the nonresponders (n=9), and the difference in two groups was statistically significant (p<0.05). Myelosuppression was minimal and non-hematologic toxicities were gererally mild and well tolerated.
CONCLUSION
The results suggest that the combination chemotherpy of AP seems to be an effective regimen for hepatocellular carcinoma. Further trials are recommended for its true efficacy.
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The Results of Postoperative Radiation Therapy in the Rectal Cancer
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Mi Ryeong Ryu, Hong Seok Jang, Sei Chul Yoon, Su Mi Chung, Yeon Shil Kim, Se Kyung Kim, In Chul Kim, Kyung Sub Shinn
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J Korean Cancer Assoc. 1997;29(1):111-116.
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Abstract
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This study was designed to evaluate the prognostic factors, survival rate and local recurrence rate of the patients with rectal cancer who received postoperative radiation therapy.
METHODS
& MATERIALS: Seventy patients with rectal cancer received postoperative radiation therapy after curative surgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medial College between May 1984 and April 1993. Of the seventy patients, sixty-four evaluable patients were analysed retrospectively.
There were 34 men and 28 women. Age at diagnosis ranged from 23 to 74 years. The distribution of stage according to the modified Astler-Coller (MAC) system was as follow: 12 in B2+3, 2 in C1, and 50 in C2+3. Postoperative adjuvant therapy included pelvic radiotherapy in all cases and chemotherapy in addition in 55 cases. A total dose of 45 to 60 Gy (median dose: 55.8Gy) was delivered in a period of 5 to 6 weeks and the follow-up period ranged from 26 to 133 months with a median of 55 months.
RESULTS
Overall two-year and five-year actuarial survival rate were 70.3% and 51.4%, 90.9% and 90.9% in stage B2+3, and 68.2% and 53.6% in stage C. Local failure occurred in 13 (20.3%) of the 64 patients and distant failure rate was 18.8% (12/64). Severe late complication was small bowel obstruction in 4 patients and surgery was required in 3 patients (5%). The significant prognostic factors were stage (p=0.0019) and histologic differentiation (p=0.0046).
CONCLUSION
This study suggested a potential adjuvant role for radiation. However, the possible reduction in local failure rates in this study compared with historic control groups must be verified in randomized trial.
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Expression of Gonadotropin-Releasing Hormone Receptor in Human Uterine Endometrial and Ovarian Tissues
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Jin Woo Kim, Sung Eun Namkoong
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J Korean Cancer Assoc. 1997;29(1):117-127.
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Abstract
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Gonadotropin-releasing hormone (Gn-RH) can cause regression of hormonedependent human tumors, including uterine endometrial and ovarian carcinomas. These effects were thought to be mediated through the inhibition of gonadotropic and steroid hormone from the hypothalamus. But, in addition to its classic hypophysiotropic action, Gn-RH might play a role as a modulator of activity in the brain and many peripheral organs. It has been reported that this analog has a direct inhibitory effect on the tumor and that the specific binding sites for Gn-RH were demonstrated in certain tumors responsive to Gn-RH. In support of a possible clinical use of Gn-RH analogs in the treatment of the endometrial and ovarian carcinomas, we tried to find out whether Gn-RH receptors are present on hormone dependent tumors.
MATERIALS AND METHODS
We have studied endometrial and ovarian tumor specimens and established uterine endometrial and ovarian carcinoma cell lines for the presence of Gn-RH receptor by the detection of its messenger ribonucleic acid (mRNA). We also compared the results obtained from tumor tissue specimens with the results from their corresponding normal tissues. Gn-RH receptor mRNA was determined by reverse transcription-polymerase chain reaction using oligonucleotide primers synthesized according to the published human Gn-RH receptor sequence.
RESULTS
Gn-RH receptor mRNA was detected in all normal endometrium and abnormally proliferative endometrium presenting dysfunctional bleeding, but not all in endometrial carcinomas (83%). Tumor stage and histologic grading had no relationship with receptor positivity. And, Gn-RH receptor mRNA was detected in less than 40% in normal myometrium and myomas. Gn-RH receptor expression was detected in same frequencies (86%) in normal ovarian tissues and ovarian carcinomas. Receptors were detected in a high proportion of the specimens from epithelial carcinomas (92%) and stromal tumors (100%) of the ovary. But, Gn-RH receptor was not detected in germ-cell derived tumors of the ovary.
Established endometrial carcinoma (CUME-1) and epithelial ovarian carcinoma (CUMO-2) cell lines also demonstrated Gn-RH receptor mRNA, respectively.
CONCLUSIONS
The expression of Gn-RH receptor raises the possibility that Gn-RH may play a direct regulatory role in the growth of hormone-dependent normal tissues and their respective tumors, and provides a possible point of attack for therapeutic approaches using Gn-RH analogs in endometrial and ovarian malignancies.
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Chemotherapy of Advanced Soft Tissue Sarcoma with Etoposide, Ifosfamide, and Cisplatin (VIP)
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Won Seog Kim, Kyung Hae Jung, Hyun Ah Kim, Sung Hyun Yang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim
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J Korean Cancer Assoc. 1997;29(1):128-135.
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Abstract
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Soft tissue sarcomas are uncommon primary malignancies. So studies on the effective chemotherapy for soft tissue sarcomas are limited. We started this study to evaluate the effectiveness of VIP (etoposide, ifosfamide, cisplatin) combination chemotherapy for advanced soft tissue sarcomas.
MATERIALS AND METHODS
Thirty patients with recurrent or metastatic soft tissue sarcoma were treated with VIP combination chemotherapy between December 1989 and June 1996. Each patient was given etoposide 75 mg/m2, ifosfamide 1000 mg/m2, cisplatin 20 mg/m2 intravenously for five consecutive days every three weeks. Mesna (sodium-2-mercaptoethansulfonate) was given to avoid the urologic toxicity.
RESULTS
Twenty-eight of 30 patients were evaluable for response, and among the 28 evaluable patients, there were 9 partial response (32%). Duration of response in 9 responders ranged from 4.1 to 16.2 months (median 8.8 months). Overall survival ranged from 1.7 to 41.5 months (median 11 months) and survival was better for patients with partial response (median survival 14.8 months vs. 9.7 months with stable disease vs. 5.1 months with progressive disease p=0.0006).
Nausea and vomiting was noted in more than 90% of cycles, but was markedly severe in only 4%. Leukopenia was noted in 60% of cycles, including 11% of cycles with counts <2,000/mm3. There was no treatment related death, but we had to stop chemotherapy in 2 patients due to leukopenia (1 patient) and neurotoxicity (1 patient).
CONCLUSION
Combination of etoposide, ifosfamide, and cisplatin was fairly active for advanced soft tissue sarcoma, with myelosuppresion and peripheral neuropathy being the most serious toxicities.
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Clinicopathologic Comparison of Intermediate or High Grade Peripheral T-Cell Lymphoma with Diffuse B-Cell Lymphoma
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Kyung Hae Jung, In Sook Woo, Heung Moon Chang, Dae Seog Heo, Yung Jue Bang, Chul Woo Kim, Seonyang Park, Byoung Kook Kim, Noe Kyeong Kim
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J Korean Cancer Assoc. 1997;29(1):136-145.
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Abstract
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Peripheral T-cell lymphoma (PTCL) derived from mature T cells forms morphologically diverse group of non-Hodgkin's lymphomas and the clinicopathologic features remain to be debated. In order to elucidate the specific characteristics of PTCL, comparison with a group of diffuse B-cell lymphomas (DBCL) was done.
MATERIALS AND METHODS
Between Dec. 1989 and Feb. 1993, clinical data of 67 cases of intermediate or high grade NHL identified as T-cell or B-cell origin by immunophenotyping was reviewed.
RESULTS
There were 30 cases of PTCL and 37 cases of DBCL.
PTCL had more advanced stage and B symptoms at diagnosis.
Frequent sites of extranodal involvement were bone marrow, nasal cavity/paranasal sinus, and skin in PTCL and gastrointestinal tract in DBCL. Based on NCI Working Formulation, 40% of PTCL and 14% of DBCL were high grade.
Patients with DBCL had a better 3-year overall survival rate (67% vs 47%), however, there was no difference in complete remission rate and disease-free survival rate between two groups with intensive treatment. A subgroup of PTCL patients who had died earlier was found to have more advanced stage and poor performance status.
CONCLUSION
Although patients with PTCL had worse survival in advanced stage, the outcome of patients with PTCL who received intensive treatment was comparable to that of DBCL.
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VACOP-B (Etoposide/Doxorubicin/Cyclophosphamide/Vincristine/Prednisolone/Bleomycin) Combination Chemotherapy for the Treatment of Intermediate and High Grade Non-Hodgkin's Lymphoma
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Young Im Kwak, Young Kug Cheon, Young Hyuck Im, Yoon Koo Kang, Soon Nam Lee, Jhin Oh Lee, Tae Woong Kang
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J Korean Cancer Assoc. 1997;29(1):146-159.
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Abstract
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To determine the antitumor activity of VACOP-B regimen for advanced non- Hodgkin's lymphoma (NHL) in terms of complete response rate, disease free survival, and overall survival, to assess the toxicities of this regimen, and to analyze the prognostic factors influencing the treatment results.Patients and methods: Between Apr. 1991 and Aug. 1993, thirty-six previously untreated patients with the intermediate or high grade NHL were treated with VACOP-B (etoposide/doxorubicin/cyclophosphamide/vincristine/prednisolone/bleomycin) combination chemotherapy. In case of initial bulky disease or residual disease after chemotherapy, radiation therapy of involved field was added.
RESULTS
Complete response (CR) was achieved in 69% (25/36) of the eligible patients after VACOP-B chemotherapy, and 5 of 11 patients who remained in partial response (PR) after chemotherapy achieved CR after additional radiation therapy of involved field, resulting in 83% (30/36) of CR rate. With a median follow-up of 47.2 months, the disease free survival was 1~42.1+ months, and its median was 24 months. The range of survival time was 7~49.1+ months, and the median survival time was not reached at this time. The projected 3-year survival rate was 70%. Leukopenia was observed in 43% of chemotherapy cycles and thrombocytopenia in 2.3%. However, no treatment-related death was observed. For non-hematologic toxicities, nausea and vomiting were observed in 58% of patients, stomatitis in 58%, peripheral neuropathy in 58%, pulmonary toxicity in 3% and congestive heart failure in 3%.
These toxicities were tolerable and all reversible. The prognostic factors influencing the complete response rate were performance status of patient (p=0.026) and relative dose intensity of cyclophosphamide (p=0.013).
CONCLUSION
VACOP-B regimen is an effective and tolerable regimen for the intermediate and high grade NHL. And long term follow-up and phase III study will be needed for evaluation of these results compared to previous other treatment modality.
Clinical Trial
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Effect of Cytosine Arabinoside and Daunorubicin (AD) Combination Chemotherapy in Acute Myelogenous Leukemia
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Yeoung Sook Kang, Hyun Sik Jeong, Tae Seok Kim, Hyun Seon Yun, Deuk Jo Kim, Jeong Ho Yun, Seong Goyng Lee, Hyeon Gyoo Ji, Gui Hyun Ham, Jae Hoon Lee, Dong Bok Shin
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J Korean Cancer Assoc. 1997;29(1):160-170.
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Abstract
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Important advances in the treatment of acute myelogenous leukemia have been made with the introduction of cytosine arabinoside (ara-C) and anthracyclines (daunorubicin) over the past 20 years. Currently, 60 to 80% of patients with acute myelogenous leukemia achieve complete remission with induction chemotherapy consisting of ara-C and daunorubicin (adriamycin) AD ("7+3"). The one-fourth of complete responders will have extended long-term survival and may be cured. Therefore wetreated patients with acute myelogenous leukemia admitted to our hospital with AD ("7+3") regimen.
METHODS
Induction therapy; Thirty four patients with previously untreated acute myelogenous leukemia received AD ("7+3") regimen (ara-C, 200 mg/m2/d by continuous infusion for seven days, and daunorubicin, 45 mg/m2/d for 3 days).
The second course of therapy was AD ("5+2"), if the patients failed to enter remission. Consolidation therapy; three cycles of consolidation chemotherapy were administered with at least 4 week interval following remission. Course 1; ara-C at 100 mg/m2 by subcutaneous injection every 12 hour for seven days, 6-thioguanine at every 12 hour 100 mg/m2 orally every 12 hour for 7 days). Course 2; ara-C (same as course 1) at 100 mg/m2 by subcutaneous injection every 12 hour for seven days, vincristine at 1.5 mg/m2 (maximum 2 mg) by bolus injection for 1 day, prednisolone at 40 mg/m2 (maximum 60 mg) orally for 7 days. Course 3; ara-C (same as course 1) daunorubicin at 45 mg/m2 by 1 hour infusion for 3 dyas.
RESULTS
Sixty-eight percent of the 34 patients entered complete remission. The remission duration for all patients in complete remission ranged from 4 weeks to 3122+ weeks, with the median of 50 weeks. The median duration of survival in complete responder group was 62 weeks. Twenty-Six percent of patients with complete remission are alive at 5 years.
Case
s with extramedullary leukemic involvement were found in four patients; M2 with orbital mass, M3 and M4 with CNS leukemia, M5a with subcutaneous nodules. Among the potential prognostic variables including age, initial WBC count, percent of blast in peripheral blood,none was statistically related to prognosis.
CONCLUSION
Combination chemotherapy with cytosine arabinoside and daunorubicin is a effective regimen for acute myelogenous leukemia as much as other regimen. Futher clinical trials for effective treatment regimen and method are necessary to raise the complete remission rate.
Original Articles
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A Case of Head and Neck Cancer Diagnosed In a Systemic Lupus Erythematosus Patient
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Sang Cheul Oh, Suk Jin Kim, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Gwan Gyu Song, Jun Suk Kim
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J Korean Cancer Assoc. 1997;29(1):171-175.
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Abstract
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- Systemic lupus erythematosus (SLE) is one of the connective diseases characterized by altered immunity and has a high incidence of cancers, such as malignant lymphoma, leukemia, breast cancer and cervical cancer. Lymphadenopathy is one of the clinical findings of SLE. But it is also seen in cancer metastasis. Therefore, if the SLE patient has lymphadenopathies from cancer metastasis it is very difficult to make a differential diagnosis between the manifestation of SLE and that of cancer metastasis. In Korea, there is no report on SLE associated with lymphadenopathies from cancer metastasis. This is the first report of a case of SLE with a cervical lympadenopathy that comes from the metastasis of head and neck squamous cell carcinoma.
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A Case of Cervical Adenocarcinoma with Pulmonary Metastasis Resembling Miliary Tuberculosis
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So Hee Sohn, Nah Hae Meung, Heung Tae Kim
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J Korean Cancer Assoc. 1997;29(1):176-181.
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Abstract
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- Cervical cancer is the most common gynecologic cancer, accounting for 22.2% of all cancers in Korean women and is almost of squamous cell type. The reported incidence of adenocarcinoma of the uterine cervix varies from 4 to 20% of all cervical malignancies, and have shown an increase in the percentage of adenocarcinoma. Adenocarcinoma may have a slightly poorer prognosis than squamous cell carcinoma for each stage of disease. Pulmonary metastases are observed in 2~9% of patients and correlates with stage of disease. We report a case of cervical adenocarcinoma with pulmonary metastases simulating miliary tuberculosis. These metastases was confirmed by open lung biopsy.
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A Case of Solitary Bone Plasmacytoma of the Middle Cranial Fossa
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Soo Mee Bang, Won Sup Lee, In Ho Kim, Dae Seog Heo, Yung Jue Bang, Dae Hee Han, Noe Kyeong Kim
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J Korean Cancer Assoc. 1997;29(1):182-182.
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Abstract
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- Solitary plasmacytoma consists of solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma. Its frequency is about 7% among the total plasma cell neoplasm. Solitary bone plasmacytoma of the cranial cavity occurs in 0~18% of patients with SBP. We experienced a case of SBP originated from the middle cranial fossa in a 68-year-old man. After surgical removal of the mass, biopsy specimen revealed plasmacytoma, kappa type. There was no evidence of systemic involvement. Additional radiotherapy was performed.
Twenty-one months after the diagnosis of SBP, pathologic fracture of the left humerus happened. Biopsy specimen of the operation revealed same diagnosis. At that time, Bence Jones proteinuria was detected in immuno-electrophoresis of urine and simple bone X-rays showed multiple osteolytic lesions.A case of SBP of the orbit and middle cranial fossa in a 68-year-old man is presented and the literature is reviewed.
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