Cancer Research and Treatment

Analysis of 103 Patients with Unknown Primary Carcinoma: Retrospective Study: Jae Jin Lee, Si Young Kim, Kyung Sam Cho, Juhie Lee, Hwi Joong Yoon; J Korean Cancer Assoc. 2001;33(1):1-8.

Abstract PDF: PURPOSE
Unknown primary carcinoma takes up approximately 0.5-10% of the oncology patients evaluated, and the patients have poor survival of between 3 to 11 months. Despite the short survival, certain clinically defined subsets of patients were reported to have a better prognosis. Thus, the objective of this study was to identify prognostic factors.
MATERIALS AND METHODS
The present study was con ducted with 103 patients who were referred from January 1988 to July 1999. The primary end point was survival. The survival curves were estimated using the Kaplan-Meier method and compared using the Log-rank test and Cox's proportional hazards regression analysis.
RESULTS
Most patients had histologic evidence of ade nocarcinoma or squamous cell carcinoma. Univariate and multivariate analyses identified good prognostic factors including performance status (grade 0-2), female and adenocarcinoma with more than moderate level of differentiation. The responders of chemotherapy in squamous cell carcinoma and lung, breast, ovary -estimated- cancer showed good survival rates.
CONCLUSION
Unknown primary carcinoma tended to show a poor prognosis. However, when treatment modality of unknown primary carcinoma is to be determined through the prognostic factors, the patients quality of life can be improved through reducing the treatment side effects and economic burden on the patients.

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Apoptosis in Renal Cell Carcinoma: Correlation to Apoptosis Related Genes and Cell Proliferation, and Its Prognostic Significance: Ji Shin Lee, Jong Jae Jung, Sung Taek Lee, Chang Soo Park; J Korean Cancer Assoc. 2001;33(1):9-15.

Abstract PDF: PURPOSE
To investigate the prognostic role of apoptosis and to evaluate the relationship between apoptosis and apoptosis-related genes, as well as cell proliferation in renal cell carcinoma (RCC).
MATERIALS AND METHODS
Apoptosis was detected by using the terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) technique in 67 formalin-fixed and paraffin-embedded RCC specimens. Immunohistochemical stainings for p53 and retinoblastoma (Rb) proteins and proliferating cell nuclear antigen (PCNA) were also conducted simultaneously.
RESULTS
The apoptotic index (AI) varied from 0.2% to 25.5%. The PCNA index (PI) ranged from 2.1% to 70.3%. The expression of p53 protein was found in 31 of 67 (46.3%) cases. Abnormal expression of Rb was seen in 23 of 67 (34.3%) cases. There was a statistically significant positive correlation between AI and increasingnuclear grade (p<0.001). A significant correlation was found between AI and PI (r=0.329, p<0.01). When comparing the AI with the expression of p53 and Rb proteins, there was no significant difference. In univariate survival analysis, nuclear grade, TNM stage, PI, expression of Rb and AI were significantly associated with shortened survival. However, TNM stage was the only independent prognostic factors by multivariate analysis.
CONCLUSION
The present findings indicate that apoptosis in RCC is closely associated with cell proliferation, but not with the expression of p53 and Rb proteins. In multivariate analysis, the AI does not carry an independent prognostic significance.

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The Change of Tumor Interstitial Fluid Pressure Affected by Radiation Therapy in Patients with Uterine Cervix Cancer: Ji Young Jang, Moon June Cho, Jae Sung Kim, Intae Lee, Jun Sang Kim, Ki Hwan Kim; J Korean Cancer Assoc. 2001;33(1):16-20.

Abstract PDF: No abstract available.

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Results of Definitive Radiation Therapy in Adenosquamous Cell Carcinoma of the Uterine Cervix: Sang Wook Lee, Chang Ok Suh, Eun Ji Chung, Gwi Eon Kim, Kyung Ran Park, Kang Kyoo Lee, Ik Jae Lee, Tchan Kyu Park, Jaewook Kim, Jong Taek Park, Jae Uk Shim, Joon Oh Park; J Korean Cancer Assoc. 2001;33(1):21-26.

Abstract PDF: PURPOSE
To define the clinical features and pattern of failure and to evaluate the results of radiation treatment in of adenosquamous cell carcinoma of the uterine cervix.
MATERIALS AND METHODS
From Jun. 1981 to Dec. 1997, 43 patients with adenosquamous cell carcinoma of the uterine cervix were retrospectively analyzed external radiation treatment and HDR-ICR from Yonsei cancer center and Wonju cristian hospital. The median age was 51. Stage distribution according to FIGO were stage 1b in 10, 2a in 5, 2b in 18, 3b in 9, 4a in 1. Median follow-up period was 41 months.
RESULTS
Overall survival rate and disease free survival rate were 57.2% and 60.2%. Complete response rate was 86.0%. Locoregional failure was observed in seven patients.
CONCLUSION
Major pattern of failure was locoregional failure. Adenosquamous cell carcinoma was not more aggressive than other pathologic types.

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Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy for Intracranial Schwannoma: Dae Yong Kim, Yong Chan Ahn, Jung Il Lee, Do Hyun Nam, Jeong Eun Lee, Do Hoon Lim, Inhwan J Yeo, Seung Jae Huh, Young Joo Noh, Hyung Jin Shin, Kwan Park, Jong Hyun Kim; J Korean Cancer Assoc. 2001;33(1):27-33.

Abstract PDF: PURPOSE
To assess the radiologic response and cranial nerve morbidity in intracranial schwannoma patients treated with stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT).
MATERIALS AND METHODS
Twenty-six patients with intracranial schwannoma were treated with linear accelerator- based SRS or FSRT between February 1995 and October 1999. The origin of schwannoma was acoustic nerve in twenty-one patients, facial nerve in two, trigeminal nerve in two, and glossopharyngeal nerve in one. SRS were performed with the median peripheral dose of 14 Gy (range 12-16), and FSRT were done with the median peripheral dose of 25 2 Gy (range 50-60).
RESULTS
With a median follow-up period of 33 months (range 12-67), the local control rate was 100%. Tumorregression was noted in eleven patients, and tumor stabilization was found in the remaining fifteen. Useful hearing preservation was achieved in two of three patients. Facial nerve neuropathy was shown in two patients and one patients developed trigeminal nerve neuropathy.
CONCLUSION
Stereotactic radiotherapy including SRS and FSRT provided excellent local control in intracranial schwannoma. It shows the possibility of a high rate of hearing preservation and an acceptable neurotoxicity, although the number of patients are small and follow-up is relatively short.

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Leptomeningeal Carcinomatosis in Solid Tumors; Clinical Manifestation and Treatment: Joon Oh Park, Hyun Joon Shin, Hyung Jong Kim, Sang Wook Lee, Hei Cheul Jeung, Seung Min Kim, Nae Choon Yoo, Hyun Cheol Chung, Joo Hang Kim, Byung Soo Kim, Jin Sik Min, Jae Kyung Roh; J Korean Cancer Assoc. 2001;33(1):34-40.

Abstract PDF: PURPOSE
Leptomeningeal carcinomatosis occurs in about 5% of patients with solid tumor and is being diagnosed with increasing frequency as patients live longer and as neuro-imaging studies improve. In general, the most commom cancers that involved the leptomeninges are breast cancer, lung cancer, and malignant melanoma.
MATERIALS AND METHODS
We investigated 25 patients presented with multiple neurologic symptoms and signs who were diagnosed with leptomeningeal carcinomatosis at the Yonsei Cancer Center from January 1990 to December 1999.
RESULTS
The primary disease of leptomeningeal carcinomatosis were stomach cancer (10 cases), breast cancer (7 cases), lung cancer (5 cases), unknown primary cancer (2 cases) and common bile duct cancer (1 case). All patients were presented with multiple neurologic symptoms and signs involving the central nervous system (CNS), cranial nerve or spinal nerves. Twenty-one of twenty- five patients were treated with intrathecal chemotherapy, radiotherapy, or combination therapy. Fourteen of them (66.7%) experienced improvement or stabilization of neurologic symptom and sign. The median survival was 122 days (10-2190).
CONCLUSION
In conclusion, although early diagnosis and active treatment of leptomeningeal carcinomatosis may improve the quality of life in selected patients, the median survival was relatively short. Therefore, new diagnostic and therapeutic strategy for leptomeningeal carcinomatosis were needed.

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Interaction between Genetic Polymorphisms of CYP2E1 & NAT1 and Smoking in Lung Cancer Development (Preliminary report): Kyoung Mu Lee, Seung Joon Lee, Sue Kyung Park, Sang Yun Lee, Hyung June Im, Ki Jung Yoon, In Mi Choi, Young Ju Lee, Soo Ung Kim, Hwang Choi, Seung Ho Choi, Young Whan Kim, Soo Han Cho, Daehee Kang; J Korean Cancer Assoc. 2001;33(1):41-48.

Abstract PDF: PURPOSE
The interactive effects of genetic polymorphisms of cytochrome P4502E1 (CYP2E1) & N-acetyltransferase 1 (NAT1) and smoking on lung cancer development were evaluated in hospital based case-control study.
MATERIALS AND METHODS
Male lung cancer patients (N= 157) and the male patients with no present or previous history of systemic illnesses who visited the urology department (N=138) were recruited (1998-1999). CYP2E1 & NAT1 genotypes were determined by PCR-RFLP method using RsaI and MboII digestion, respectively.
RESULTS
CYP2E1 c2 or NAT1 *10 allele did not increased the risk of lung cancer. Heavy smokers (35CONCLUSION
These results suggest the gene-environment interaction between genetic polymorphisms of CYP2E1 & NAT1 and smoking in lung cancer development.

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Membrane-type Matrix Metalloproteinase-1 Induced Invasive and Angiogenic Activities in Chick Chorioallantoic Membrane (CAM) Model: Joo Won Jeong, Tae Kwon Sohn, Dae Yeul Yu, Kyu Won Kim; J Korean Cancer Assoc. 2001;33(1):49-55.

Abstract PDF: PURPOSE
Matrix metalloproteinases (MMPs) have been reported to play critical roles in the endothelial cell migration and matrix remodeling during angiogenic process. To investigate the roles of the membrane type MMP (MT1-MMP) by the matrix remodeling of endothelial cells, MT1-MMP expression vector was transfected into bovine aortic endothelial cells (BAECs). Increased ex+pression of MT1-MMP in BAECs enhanced the activation of MMP-2, invasion and migration of BAECs. Moreover, the capacity of tube formation was increased by MT1-MMP transfectants. These observations indicate that MT1-MMP is involved in the angiogenic process of endothelial cells in vitro. In this study, we attempted these effects were confirmed in vivo system.
MATERIALS AND METHODS
In this study, we used MT1- MMP or Antisense MT1-MMP stable transfectants in HT1080 human fibrosarcoma cells. Chorioallantoic membrane (CAM) assay was used for the detection of angiogenesis in vivo and modified CAM assay for quantification of invasion of MT1-MMP transfected cells.
RESULTS
In CAM assay, the formation of microvessels was stimulated by MT1-MMP transfectants. Invasive capacity of HT1080 cells was also increased in a novel in vivo metastasis model, PCR based CAM assay.
CONCLUSION
These results identify the function of MT1- MMP during the neovascularization process.

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Accelerated Induction of Dysplastic Lesion by TPA in HPV18 URR E6/E7 Gene Expressing Transgenic Mice: Yongil Kwon, Taechul Park, Jongsup Park, Soojong Um, Jauheung Yu, Junmo Lee, Seungeun Namkoong; J Korean Cancer Assoc. 2001;33(1):56-63.

Abstract PDF: PURPOSE
The research of HPV has been severely hampered by the inability to propagate HPVs in culture, particularly those of the mucosotrophic types which produce few virions in vivo. In order to study the regulation of HPV-18 expression in vivo, we constructed transgenic mice and caused cervical neoplasia.
MATERIALS AND METHODS
We investigated whether tetradecanoyl phorbol acetate (TPA) increase the transcriptional activity of the URR in the C33A cervical carcinoma cells or not. And we asked whether chronic exposure of female HPV-18 URR E6/E7 transgenic mice to TPA could render the reproductive tract squamous epithelium permissive for HPV neoplasia.
RESULTS
It was confirmed by RT-PCR that transgene was specifically expressed in epithelial tissues. TPAupregulated the transcriptional activity of the URR in the C33A cervical carcinoma cells. There were diffuse changes on the squamous epithelium in the cervix of the transgenic mice at fifth month following TPA treatment.
CONCLUSION
We established the transgenic mice model which have the ability to reproduce the development of cervical dysplasias. Moreover this animal model will allow preclinical testing of compounds designed to interfere with the actions of the HPV oncogenes or other critical aspects of the cancer phenotype.

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Effect of Chitosan Oligosaccharide on Enzymes for Cancer Chemoprevention: To Hun Kim, Young Jung Jo, Young Min Ha, Yun Hee Shon, Byung Jo Bae, Kyung Soo Nam; J Korean Cancer Assoc. 2001;33(1):64-70.

Abstract PDF: PURPOSE
Two types of chitosan oligosaccharides (COSs), COS I and COS II, were investigated for the effects on ascitic tumor and enzymes for cancer chemoprevention.
MATERIALS AND METHODS
Chitosan oligosaccharides were administered once daily for 10 days after the tumor implantation. The change of body weight was observed for 20 days, and the survival rate of mice was determined after 21 days. Chitosan oligosaccharides were administered once daily for 10 days before the tumor implantation (1 106 cells). The number of ascitic tumor cells were measured at 6 days after tumor implantation. Chemopreventive potential of chitosan oligosaccharides was examined by the induction of quinone reductase and inhibition of cytochrome P450 1A1.
RESULTS
Chitosan oligosaccharides exerted antitumor activity by inhibiting the growth of Ehrlich ascites tumor cells in vivo. Mice given Ehrlich cells and 10 or 100 mg/kg body weight of chitosan oligosaccharides had 33% survival after 21 days. Quinone reductase activity was increased with chitosan oligosaccharides. There were 26% and 33% inhibition in the activity of cytochrome P450 1A1 enzyme with the treatment of COS I and COS II, respectively.
CONCLUSION
These results suggest that chitosan oligosaccharides has antitumor activity and cancer chemo preventive potential by inducing QR activity and inhibiting cytochrome P450 1A1.

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Induction of Apoptosis and Inhibition of Cellular Proliferation in Aspirin-treated SNU-668 Human Gastric Adenocarcinoma Cell Lines: Joon Hee Kim, Re Hwe Kim, Kwon Yoo; J Korean Cancer Assoc. 2001;33(1):71-76.

Abstract PDF: PURPOSE
The aims of this study was to examine the anti-proliferative effect and apoptosis induction by aspirin using SNU-668 human gastric adenocarcinoma cell lines.
MATERIALS AND METHODS
After treating SNU-668 cell lines with various concentrations of aspirin, cell growth was quantified by MTT assay. Apoptosis was determined by comparing aspirin treated cell lines by immunofluores cence with control cells after Hoechst 33258 staining. Cell lines were further examined using ELISA. Cell cycle was evaluated by FACS.
RESULTS
Inhibition of cellular proliferation occurred when cells were treated with aspirin at concetrations of 1 mM or more. Aspirin also induced apoptosis =in these cell lines. Percentages of induction were 3.0+/- 0.6% , 4.8, +/- 0.6%, 17.5+/-0.8%, and 19.2+/-0.7% at 0, 0.5, 1 and 2 mM concentration of aspirin, respectively. ELISA confirmed apoptosis in these cells. However, cell cycle was not affected.
CONCLUSION
These results indicate that induction of apoptotic cell death contribute to the anti-proliferative effect of aspirin on SNU-668 human gastric adenocarcinoma cell lines without affecting cell cycle. These findings suggest aspirin may play an important role in cancer prevention and tumor regression in humans.

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Expression of Cell Cycle Regulatory and Apoptosis-related Proteins in Etoposide-treated Human Skin Fibroblast: Jae We Cho, Min Ho Suh; J Korean Cancer Assoc. 2001;33(1):77-83.

Abstract PDF: PURPOSE
This study was designed to investigate effect of the etoposide on expression of cell cycle regulatory proteins and apoptosis-related proteins in human skin fibroblast (HSF).
MATERIALS AND METHODS
HSF cells were treated with etoposide. After treatment, expression patterns of cell cycle regulatory proteins and apoptosis-related proteins were analyzed by using Immunoprecipitation-Western blot method and RT-PCR.
RESULTS
Immediately after etoposide treatment, E2F-1 was up- regulated following MDM2 down-regulation. After E2F-1 up-regulation, p53 and p21WAF1 level was markedly increased without or with mRNA up-regulation, respectively. Consistent with these results, cell cycles arrested in mainly G1 phase 24 hr after etoposide treatment. However, HSF cells progressed into apoptosis 72 hr after etoposide treatment. In this process, caspase-3 activation and Bax up-regulation were observed.
CONCLUSION
In early response of etoposide treatment, E2F-1 plays an important role in p53 accumulation through MDM2 down- regulation. The increased p53 induce an increase of p21WAF1 level through p21WAF1 mRNA up-regulation. However, after long term treatment of etoposide, HSF cells resulted in apoptotic cell death through caspase-3 activation and Bax up-regulation.

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Clinical Significance of p53, c-erbB-2, Chromogranin A and PCNA in the Ampullary Carcinoma: Ki Hwan Kim, Sun Whe Kim, Woo Ho Kim, Yong Hyun Park; J Korean Cancer Assoc. 2001;33(1):84-91.

Abstract PDF: PURPOSE
To determine the clinical significance of p53, c-erbB-2, chromogranin A (CgA), proliferating cell nuclear antigen (PCNA) expression in ampullary carcinoma, a retrospective study was performed.
MATERIALS AND METHODS
The cases of 96 patients who underwent curative resection for ampullary carcinoma during the ten-year period (1986-95) were reviewed. And, using paraffin-embedded tumor tissues, immunohistochemical (IHC) staining for p53, c-erbB-2, CgA, and PCNA was performed.
RESULTS
The overall five-year survival rate (5-YSR) for these 96 patients was 58%. With regard to TNM stage, the 5-YSR was 71% for stage I (n=36), 62% for stage II (n=29), and 39% for stage III (n=31), respectively. IHC expression rate was 17.6% for c-erbB-2, 19.2% for CgA, and 42.9% for p53. The relative proportion of labelling index of PCNA (<25%, 25-50%, >50%) was 30.8%, 25.3%, and 44.0%, respectively. The PCNA labelling index showedsignificant correlation with tumor size (p=0.032). The PCNA labelling index, c-erbB-2, CgA and p53 were not correlated to extent of invasion, lymph node metastasis, stage, or histologic type. CgA and c-erbB-2 expression and the PCNA labelling index thus had no prognostic value. With regard to p53, the 5-YSR of p53 negative cases was 68.6%; that of p53 positive cases was 47%, with significant difference (p=0.038).
CONCLUSION
This result suggests that p53 expression is related to poor prognosis of ampullary carcinoma, and that c-erbB-2 and CgA expression, and the PCNA labelling index, are not significant prognostic factors.

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