Cancer Research and Treatment

Annual Report of the Central Cancer Registry in Korea-1998 (Based on Registered Data from 124 Hospitals): Chang In Suh, Kyung Ae Suh, Seong Heum Park, Hee Jin Chang, Jae Wook Ko, Don Hee Ahn; J Korean Cancer Assoc. 2000;32(5):827-834.

Abstract PDF: PURPOSE
Central Cancer Registry Center in Korea conducted a nation-wide hospital-based cancer registry to provide the basic data on cancer statistics.
MATERIALS AND METHODS
In 1998, 124 hospitals participated in the cancer registry program. All cancer registry data, submitted from the participating hospitals by diskettes during the year, were reviewed and sorted out by the committee members who were all board-qualified clinical oncologists and pathologists. To avoid duplication, every resident registration numbers were compared by the computer. Cases diagnosed by histologic examination were preferentially chosen.
RESULTS
Of 89,226 cases registered, 9,163 (10.3%) duplication cases were excluded. Of the remaining 80,063 cases, 3,195 cases (4.0%) of carcinoma in situ (morphology code /2) were excluded. Finally 76,868 cases were analyzed. Of the analyzed cases, 44,037 (57.3%) were male and 32,831 (42.7%) were female. The leading age groups in the order of relative frequency were 60~64 years of age (15.3%), followed by 55~59 (14.4%). The leading primary cancer sites in the order of relative frequency were stomach (20.9%), followed by liver and intrahepatic bile ducts (12.2%), bronchus and lung (11.9%), colorectum (9.6%), breast (6.1%). In male, the leading primary cancer sites were stomach (24.4%), followed by liver and intrahepatic bile ducts (16.4%), bronchus and lung(16.0%), colorectum(9.2%) and urinary bladder (3.5%). In female, stomach (16.3%) was the most common site, followed by breast (14.1%), uterine cervix (13.0%), colorectum (10.1%) and liver and intrahepatic bile ducts (6.5%). Among the 1,190 cases of childhood malignancies, leukemia (33.4%), CNS tumor (15.7%) and sympathetic nervous system tumor (8.4%) were common.
CONCLUSION
We analyzed and reported the registered cancer data from 124 hospitals during 1998.

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p53 Gene Mutation by Direct DNA Sequencing Predicts Poor Survival in Patients with Stomach Cancer: Tae Won Kim, Kyoo Hyung Lee, Je Hwan Lee, Yoon Koo Kang, Jung Shin Lee, Sang Hee Kim, Sang Won Im, Ji Sun Kim, Joon Kim, Woo Kun Kim; J Korean Cancer Assoc. 2000;32(5):835-843.

Abstract PDF: No abstract available.

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Comparison of Clinical Outcome in Para-aortic Lymph Node Dissection (PALD) and D2 for Advanced Gastric Cancer: Chan Dong Kim, Dae Hyun Yang, Ik Haeng Jo, Jin Pok Kim, Won Jin Choi, Il Myung Kim, Jin Youn, Sang Su Park, Byung Ook Yoo, Seung Ik Ahn, Sin Eun Choi; J Korean Cancer Assoc. 2000;32(5):844-851.

Abstract PDF: PURPOSE
We compared the clinical results of paraaortic lymph node dissection (PALD) with those of D2 to evaluate the survival gain and disadvantage of paraaortic lymph node dissection for advanced gastric cancer.
MATERIALS AND METHODS
We analysed the clinical data of 196 patients who underwent curative resection and D2 with or without paraaortic lymph node dissection (PALD or D2) for advanced gastric cancer from May 1990 to June 1999. The operative factors (operative time, the amounts of intraoperative transfusion and hospital stay), operative morbidity and mortality and 5 year survival rates were compared between D2 and PALD groups.
RESULTS
The operative time of subtotal gastrectomy was significantly longer in PALD group than D2 group. The operative morbidity rates were 9.2% in D2 group and 10.3% in PALD group. There were 3 operative mortalities in D2 group and none in PALD group. The 5 year survival rates (5YSR's) of stage IB, II, IIIA, IIIB, IV were 88.9%, 92.3%, 30.2%, 24.2%, 28.9% in D2 group and 93.3%, 75.5%, 61.0%, 0%, 0% in PALD group.
CONCLUSION
The paraaortic lymph node dissection was a rather safe procedure without significant increase of morbidity and mortality. There was no statistically significant difference in survival in any stage of this retrospective study with limited cases and follow-ups.

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Effect of Hepatocyte Growth Factor on the Expression of E-cadherin in Gastric Carcinoma Cell Lines: Sang Uk Han, Won Hung Lee, Wook Hwan Kim, Myung Wook Kim, Jae Ho Lee, Sang Yong Song, Kuhn Uk Lee; J Korean Cancer Assoc. 2000;32(5):852-862.

Abstract PDF: PURPOSE
Previously, we reported that the expression of E-cadherin was significantly decreased according to the increase of the level of hepatocyte growth factor (HGF) in gastric cancer tissue. In this work, the effect of HGF on the cell-cell adhesion and intracellular distribution of E-cadherin in the gastric carcinoma cell lines were studied. MATERIALS AND METHODS: Western blot analysis was performed to confirm the presence or abscence of c-Met and E-cadherin in SNU-1, 5, and 16 cells. Tyrosine phosphorylation of c-Met, E-cadherin, alpha-, beta-, gamma-catenins was checked by immunoprecipitation. The morphologic changes induced by HGF were studied with immunocytochemical staining. Functional proportion of E-cadherin was estimated by cell fractionation. The effect of HGF on cell proliferation and invasion was also assessed.
RESULTS
Among SNU-1, 5, and 16 cell lines, only SNU-16 cells expressed both E-cadherin and c-Met. A morphological change from epithelial shape to fibroblastic one was observed in the SNU-16 cells after treatment with HGF. In addition, E-cadherin expression of the SNU-16 cells was shifted from the membrane and to the cytoplasm, and the functional fraction of E-cadherin was decreased in the SNU-16 cells treated with HGF. On the other hand, HGF increased the proliferation and invasion of the SNU-16 cells.
CONCLUSION
These results suggest that HGF may regulate cell adhesion in gastric carcinomas via the cellular redistribution and functional change of E-cadherin.

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Alterations of HLA Class I and II Antigen Expressions in Preinvasive, Invasive and Metastatic Cervical Cancers: Jin Woo Kim; J Korean Cancer Assoc. 2000;32(5):863-874.

Abstract PDF: PURPOSE
The relationship between altered HLA expressions and cervical carcinogenesis is not fully elucidated.
MATERIALS AND METHODS
The histological evaluation comprised of 21 microinvasive squamous cell carcinoma (SCC), 26 invasive SCC, 3 microinvasive adenocarcinoma and 9 invasive adeno carcinoma of cervix. We used monoclonal antibodys (mAbs) to HLA class I beta2-microglobulin (L368), HLA class I B/C heavy chains (HC-10) and HLA class II heavy chain (LG II-612.14).
RESULTS
In tissues from microinvasive SCC, the expressions of B/C heavy chains and class II heavy chain were significantly decreased. The expressions of beta2-microglobulin, B/C chains, and class II heavy chain in SCC were all significantly decreased. Especially, in the metastatic tissue from the same patient, the expressions of beta2-microglobulin and B/C chains showed to be somewhat decreased compared to those in primary tumor tissues, and the expression of class II heavy chain was decreased further than that in primary lesion. In primary invasive adenocarcinoma, the expression of B/C chains was significantly decreased.
CONCLUSION
These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in tumor development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

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Polymorphisms in E6 Gene of Human Papillomavirus Type 16 Found in Cervical Tissues from Korean Women: Jae Weon Kim, Ju Won Roh, Moon Hong Kim, Noh Hyun Park, Yong Sang Song, Soon Beom Kang, Hyo Pyo Lee; J Korean Cancer Assoc. 2000;32(5):875-883.

Abstract PDF: PURPOSE
To examine the distribution of HPV 16 E6 polymorphisms and analyse the possible association between the polymorphisms and cervical cancer development in Korean women.
MATERIALS AND METHODS
Fifty-four cases of uterine cervical tissues containing HPV 16 DNA confirmed by polymerase chain reaction (PCR) from Korean women were subjected to investigate the E6 gene mutations. PCR-amplified products were sequenced by the fluorescent dideoxy ter mination method and the results obtained from sequencing were analysed. And newly designed PASA method was tried to develop rapid test for identification of the most commonly detected variation.
RESULTS
Among the 27 cervical cancer cases, only two (7.4%) was found as a prototype. Among 11 kind of variants identified in total, 4 variants (5 nucleotide sites) which were never reported before has been found, registered firstly to GenBank. The most frequently found variation was D25E, absolutely different from the previous reports from the western country. There was no statistically significant trend for the D25E variation to be more frequently detected in cancerous lesions than in noncancerous lesions. All of the DNA sequencing results observed could be confirmed by PASA method.
CONCLUSION
These results suggest that Korean-specific genetic factors might operate during the cervical carcinogenesis.

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The Effects of Interferon/Retinoic Acid on Cervical Cancer Cell Lines According to the Mutational Status of HPV-URR: Tae Yeon Kim, Chan Joo Kim, Eun Joo Kim, Tae Chul Park, Sung Eun Namkoong, Jae Gahb Park, Soo Jong Um, Jong Sup Park; J Korean Cancer Assoc. 2000;32(5):884-894.

Abstract PDF: PURPOSE
We investigated the effects of all-trans-retinoic acid (ATRA) and/or interferon-gamma (IFN-gamma) on the growth of various cervical cancer cell lines and HPV E6/E7 expression. The relationships between the functional activities of HPV-URR and the growth inhibition were identified.
MATERIALS AND METHODS
Four groups of cell lines were included; i) with integrated form of HPV-16 DNA (SNU-17, CaSki), ii) episomal form of HPV-16 (SNU-523), iii) integrated form of HPV-18 (SNU-1160, HeLa) and iv) episomal form of HPV-18 (SNU-1245). The promoter activity of HPV-URR was confirmed by transient transfection assay in C33A using the HPV-18 URR-CAT reporter plasmid.
RESULTS
Selective mutation was detected in TEF-1 (transcriptional enhancer factor) binding site in SNU-17, and the activity of URR in SNU-17 was higher than that of the prototype. The proliferation was more inhibited in SNU-17 by IFN-gamma (10 ng/ml) than in SNU-902, CaSki and HeLa. The increase of the HPV-URR activity might play a role in the inhibition of growth by interferon-g. The expression of HPV-16 E6/E7 were significantly decreased by ATRA or IFN-gamma.
CONCLUSION
Point mutation at TEF-1 binding site of SNU-17 was related with the increased transcriptional activity of URR. Mutation in the HPV-URR and alteration of HPV-URR activity in SNU-17 might be related with significant growth suppression by IFN-gamma.

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Phase I Clinical Trial of Paclitaxel Plus Ifosfamide for the Patients with Refractory Ovarian Cancer: Ho Sawk Saw, Jae Kwan Lee; J Korean Cancer Assoc. 2000;32(5):895-903.

Abstract PDF: PURPOSE
Patients with advanced ovarian carcinoma and refractory to platinum based chemotherapy have a very poor prognosis and effective salvage regimens are needed. This study was conducted in order to determine the maximum tolerated dose (MTD) and dose limiting toxicity of combination with paclitaxel and ifosfamide.
MATERIALS AND METHODS
After premedication, patients received paclitaxel (110~225 mg/m2) as a 24 hour IV infusion on day 1. Ifosfamide (1,000~1,500 mg/m2) was given as a 12 hour IV infusion with standard dose of mesna on day 2~6. All patients received G-CSF (granulocyte colony stimulating factor) on day 6~15.
RESULTS
12 patients with advanced ovarian cancer entered this trial. Toxicity included bone marrow suppression, neuromuscular toxicity, urothelial toxicity, gastrointestinal toxicity, which occurred in 84.6%, 65.3%, 30.7%, 88.4% of cycles.
CONCLUSION
Neuromuscular toxicity was dose limiting toxicity. Maximum tolerated dose in com bination with paclitaxel and ifosfamide was 175 mg/m2 of paclitaxel and 1,500 mg/m2 of ifosfamide.

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Expression of p53, bcl-2 Protein in Small Cell Lung Cancer (SCLC) Cell Lines in Relation to Sensitivity to Chemotherapy: In Sook Woo, Myung Jae Park, Young Seok Park, Sung Won Jung, Mi Ae Yeo, Soo Hyun Park, Si Young Kim, Hwi Joong Yoon, Kyung Sam Cho, Jae Kyung Park, Young Il Kim; J Korean Cancer Assoc. 2000;32(5):904-910.

Abstract PDF: PURPOSE
Sensitivity of tumor cells to chemotherapeutic regimen may be accentuated by their abnormal expression of oncogene. p53 is required for the efficient activation of apoptosis following irradiation or treatment with chemotherapeutic agents. The aim of this study was to evaluate the relationship between chemosensitivity and apoptosis related proteins such as p53, bcl-2 in small cell lung cancer cell lines. MATERIAL AND METHODS: Six human small cell lung cancer cell lines, NCI-H69, NCI-H128, NCI-H1436, NCI-H1092, derived from untreated and treated patients were tested for chemo sensitivity and the expression of the p53, bcl-2 genes were examined in each cell lines with western blot analysis. We used 4 drugs including adriamycin, cisplatin, vincristine and VP-16.
RESULTS
NCI-H128 was the most sensitive cell line to four drugs. NCI-H82 and NCI-H1092 were highly resistant to VP-16, adriamycin and vincristine and determination of an IC50 was not possible. In western blot analysis, NCI-H128 alone was strong positive to p53 monoclonal antibody and the rest of cell lines were negative. All but NCI-H128 were positive to bcl-2 monoclonal antibody. NCI-H128 which was strong positive to p53 and negative to bcl-2. NCI-H1092 was strong positive to bcl-2 and negative to p53 monoclonal antibody.
CONCLUSION
We were not able to explain the expression of p53 in small cell lung cancer cell lines in relation to senitivity to anti-cancer chemotherapeutic agents. But the expression of bcl-2 in small cell lung cancer cell lines was correlated with the chemosensitivity well.

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Combination Chemotherapy with Cisplatin and Vinorelbine in Patients with Non-Small-Cell Lung Cancer: Kee Won Kim, Suk Young Park, Ji Won Suhr, Seung Joon Kim, Dong Hoen Yang, Eun Hee Lee, Kyung Shick Lee; J Korean Cancer Assoc. 2000;32(5):911-917.

Abstract PDF: PURPOSE
To determine the therapeutic effect and toxicities of cisplatin and vinorelbine combination chemotherapy in patients with inoperable non-small-cell lung cancer.
MATERIALS AND METHODS
Between Jan 1998 and Dec 1999, 28 patients with inoperable non- small-cell lung cancer were treated with cisplatin and vinorelbine combination chemotherapy as induction treatment. A combination of vinorelbine 25 mg/m2 day 1,8 and cisplatin 60 mg/m2 day 1 were given and repeated every 3 weeks. Then we assessed response and toxicity according to WHO grades.
RESULTS
According to response criteria, there were 1 complete response, 12 partial response (42.9%), 12 stable disease (42.9%), and 3 progression (10.7%). The median survival was 12 months. According to toxicity grades, 24 grade 3 myelosuppression (24.7%), 12 grade 4 myelo suppression (10.7%), 6 grade 3 and 4 constipation (6.1%), and mild 7 (7.2%) thrombophlebitis were experienced in evaluable 97 cycles. There was no other clinically severe toxicity.
CONCLUSION
These results suggest that combination chemotherapy with cisplatin and vinorelbine in patients with inoperable non-small-cell lung cancer was effective and safe.

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Dose-Response Relationship of Radiotherapy for Locally Advanced Hepatocellular Carcinoma: Dae Yong Kim, Joon Hyoek Lee, Kwang Cheol Koh, Seung Woon Paik, Yong Chan Ahn, Seung Jae Huh, Inhwan J Yeo, Suk Won Park, Seung Hee Chang; J Korean Cancer Assoc. 2000;32(5):918-924.

Abstract PDF: PURPOSE
Recently radiotherapy is applied alone or in conjunction with transcatheter arterial chemoembolizaion (TACE) or percutaneous ethanol injection therapy (PEIT) for locally advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate dose-response relationship of radiotherapy for local control and toxicity in inoperable HCC.
MATERIALS AND METHODS
Twenty-eight patients who were not eligible for TACE and PEIT or had showed no response to these treatment were treated with a total dose of 40 Gy with 2 Gy per fraction or 30 Gy with 3 Gy per fraction (low dose group, 18 patients) or 45 Gy with 3 Gy per fraction (high dose group, 10 patients).
RESULTS
The median survival duration was 8 months and 1-year survival rate was 37%. The treatment results were as follows; partial response in 11% and 70% (p=0.001), stable disease in 56% and 30%, and progressive disease in 33% and 0% in low dose group and high dose group, respectively. The incidence of gastrointestinal (G-I) toxicity by the criteria of Southwest Oncology Group was as follows; grade 1 in 22% and 40%, grade 2 in 17% and 10%, respectively (p=0.56). There was no patient with severe G-I toxicity above grade 3. The incidence of G-I toxicity by site was as follows; grade 1 in 24% and 29%, and grade 2 in 0% and 57% in patients with right lobe and left lobe lesion, respectively (p=0.001).
CONCLUSION
This study indicates that there is clear dose-response relationship in local control. The G-I toxicity does not increase significantly with increment of radiation dose within the dose range tested in this study. And careful attention should be paid for G-I toxicity when the tumor is located in left lobe.

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The Effect of Sucralfate on the Reduction of Radiation Esophagitis: Clinical and Laboratory Data: Seunghee Kang, Mison Chun, Ki Baik Hahm, Young Taek Oh, Jin Hong Kim, Jae Hoo Park; J Korean Cancer Assoc. 2000;32(5):925-932.

Abstract PDF: No abstract available.

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The Treatment Results of Preoperative Concurrent Chemoradiation in Locally Advanced Rectal Cancer: Jun Sang Kim, Jae Sung Kim, Ji Young Jang, Wan Hee Yoon, Kyu Sang Song, Hae Kyeung In, Moon June Cho; J Korean Cancer Assoc. 2000;32(5):933-942.

Abstract PDF: PURPOSE
To assess the tumor response, sphincter preservation, acute toxicity and survival with preoperative concurrent chemoradiation in locally advanced rectal cancer.
MATERIALS AND METHODS
Fifty-four patients were treated with preoperative chemoradiaton for tumor downstaging and sphincter preservation. Radiation was delivered to whole pelvis to 45 Gy followed by a boost 5.4 Gy to primary tumor site. Chemotherapy consists of concurrent 2 cycles of 5-fluorouracil (500 mg/m2/day) and leucovorin (20 mg/m2/day). Surgery was performed approximately 6 weeks after treatment.
RESULTS
Median follow-up period and rate were 48 months and 98%, respectively. The downstaging including primary tumor and lymph node occurred in 64%. Three of 53 patients (6%) had pathologic complete response. The resectability of tumor was 98%. A sphincter preservation was possible in 61%. Three patients developed grade 4 hematologic toxicity. Grade 3 skin erythema and diarrhea were 24% and 18%, respectively. The 5-year survival and local disease-free survival were 62% and 89%, respectively. Local failure and distant metastasis rate were 9% and 35%, respectively.
CONCLUSION
Preoperative chemoradiation affords considerable downstaging with acceptable acute toxicity and postoperative morbidity. Also sphincter preservation is feasible by improved downstaging of tumor. This treatment could be improved local control of tumor, and may have a potential for long-term survival.

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Potentials of Fractionated Infusions of Low-dose Peripheral Blood Stem Cells (PBSCs) to Overcome the Hematologic Toxocities after Combination Chemotherapy: Seok Goo Cho, Jun Mo Lee, Jin No Park, Hoon Kyo Kim, Sung Eun Namkoong, Kyung Shick Lee, Chun Choo Kim; J Korean Cancer Assoc. 2000;32(5):943-953.

Abstract PDF: PURPOSE
We tried to evaluate the clinical usefullness of fractionated low-dose infusions of peripheral blood stem cells (PBSCs) as a supportive care.
MATERIALS AND METHODS
Four patients were entered onto this study who were diagnosed to have gastric lymphoma (n=1) and advanced ovarian carcinomas (n=3). To overcome the hematologic toxicities, G-CSF-mobilized PBSCs were collected early in disease course. Harvested products were cryopreserved in aliquotes and then infused after each cycle. Planned therapeutic schedules should be performed without changes of dose and interval regardless of hematologic toxicities.
RESULTS
20 cycles of chemotherapies were performed and data of infused cell doses were as follows: median number of PBSCs infusions, 4.5 (3~5); median MNCs, CFU-GM colony counts per infusion of low-dose PBSCs, 1.7 108/kg (1.0~2.4), 3.2 104/kg (2.1~11.8). Among 20 cycles, delayed recovery of thrombocytopenia was shown on 10 cycles. Leukopenia (III/IV) and thrombocytopenia (III/IV) were shown on 8/6 cycles and 8/2 cycles. In spite of myelosuppression, they were successfully treated with planned dose-intensity. Especially incomplete platelet recovery was successfully rescuced by using fractionated infusions of low-dose PBSCs.
CONCLUSION
These data warrant further clinical trials to evaluate the potentials of fractionated low-dose infusions of PBSCs collected early in disease course for overcoming accumulated hematologic toxicities, especially thrombocytopenia complicated by repeated chemotherapies.

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Prognostic Implications of Cytarabine Dose in Consolidation Chemotherapy for the Patients with Acute Myelogenous Leukemia: Jung Hee Lee, Je Hwan Lee, Kyoo Hyung Lee, Hyeseung Bahng, Jin Hee Ahn, Jung Shin Lee, Sang Hee Kim, Woo Kun Kim; J Korean Cancer Assoc. 2000;32(5):954-961.

Abstract PDF: PURPOSE
Increasing the dose of cytarabine in consolidation chemotherapy has been suggested to improve treatment outcome of the patients with acute myelogenous leukemia (AML) in complete remission (CR). We studied an effect of cytarabine dose in consolidation chemotherapy on the survival times.
MATERIALS AND METHODS
From 1989 to 1998, AML patients in CR who received two or more courses of consolidation chemotherapy were included. At the first course of consolidation chemo therapy, all patients received standard dose of cytarabine (100 or 200 mg/m2/day by a continuous infusion for 5 days) plus anthracyclines. At the second or third course, one of three dose levels of cytarabine was given with anthracyclines. Three dose levels of cytarabine were standard dose (SD), intermediate dose (ID, 1 or 2 g/m2/day by a 3-hour infusion for 5 days), and high dose (HD, 3 g/m2 in a 3-hour infusion every 12 hours for total six doses). We retrospectively reviewed clinical records of study patients.
RESULTS
64 patients were included. The median follow-up duration of alive patients was 1,143 days. Estimated 3-year overall survival times were 24% in SD group, 41% in ID group and 56% in HD group (P=0.737). Estimated 3-year disease free survival times were 18%, 16% and 44% in each group (P=0.592). There was no significant difference in toxicity of consolidation chemotherapy between three groups.
CONCLUSION
Although the survival times showed a trend to be longer in the patients who received higher dose of cytarabine as consolidation chemotherapy, there were no statistically significant differences.

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Obesity Related to Breast Cancer Risk by Hormonal Receptor Status: Keun Young Yoo, Sue Kyung Park, Daehee Kang; J Korean Cancer Assoc. 2000;32(5):962-971.

Abstract PDF: PURPOSE
A hospital-based case-control study was designed to assess whether obesity may differ in breast cancer risk according to the estrogen receptor (ER) or progesterone receptor (PR) status.
MATERIALS AND METHODS
Information on life-styles was obtained in a hospital-based cancer registry at the Aichi Cancer Center Hospital, Japan, 1988~1992. Newly diagnosed cases with breast cancer (n=1,154) and controls with no history of cancer (n=21,714) were selected. Body mass index with known and suspected risk factors for breast cancer was included simultaneously in the logistic regression model. Hypothesis tests for differences in odds ratios were done by Wald test based on the polytomous logistic regression models.
RESULTS
Both current weight and body mass index were significantly related to the risk of breast cancer; OR for body weight per 5 kg=1.11 (1.05~1.73), OR for body mass index per 10 kg/m2=1.54 (1.25~1.90). The risks of both body weight and body mass index, however, was not modified by ER, nor by PR.
CONCLUSION
This study strongly suggests that obesity may be associated with breast cancer risk. The possibility that obesity differs according to hormonal receptor status should be pursued in further studies.

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Study of Ex Vivo Growth Characteristics of N-Nitrosomorpholine Treated Rat Hepatocytes: Sung Sik Kang, Min Chan Kim, Jin Sook Jeong, Yong Chun Choi, Sang Soon Kim; J Korean Cancer Assoc. 2000;32(5):972-980.

Abstract PDF: PURPOSE
The early carcinogenic effect of N-nitrosomorpholine (NNM) on acquisition of increased survival and growth was investigated using ex vivo culture of 5th to 10th week rat liver hepatocytes after NNM treatment.
MATERIALS AND METHODS
Rats were fed with NNM (200 mg/l). Hepatocytes were isolated by two step perfusion techniques and grown on tissue culture. These ex vivo hepatocytes were then subjected to analysis of growth related signal molecules resided in nucleoli.
RESULTS
One of the most characteristic differences of the NNM-treated liver from normal liver was genesis of megahepatocytes. These megahepatocytes survived approximately 2~3 times as long as normal hepatocytes in ex vivo conditions. There was also a significant increase in various nucleolar proteins, including Erk1/2, p38, hsp72 and nucleophosmin (B23).
CONCLUSION
At promotion stage of tumorigenesis induced by NNM, it was possible to isolate and characterize abnormal hepatocytes. These abnormal hepatocytes showed increased survival in in vitro (ex vivo) than normal hepatocytes, although they were not immortal.

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K-ras Mutation in Ampulla of Vater Cancer: Sang Jae Park, Sun Whe Kim, Woo Ho Kim, Jin Young Jang, Yong Hyun Park; J Korean Cancer Assoc. 2000;32(5):981-988.

Abstract PDF: PURPOSE
The aims of this study was to elucidate the role of the K-ras mutation (codon 12) in the carcinogenesis of ampulla of Vater cancer.
MATERIALS AND METHODS
31 cases of radically resected ampullary cancer cases were enrolled. 18 cases harbored the adenomatous portions adjacent to carcinomatous portions. Utilizing a two-step nested PCR with RFLP method, we examined the K-ras mutation in a total of 90 samples (normal mucosas (N=31), carcinomatous portions (N=31), adenomatous portions (N=18), and metastatic lymph nodes (N=10)).
RESULTS
In the carcinomatous portion, K-ras mutations in codon 12 were detected in 48.4%. In the adenomatous portions, 10 cases (55.6%) out of 18 displayed the K-ras mutation. In the metastatic lymph nodes, K-ras mutation was found in 4 cases out of 10. After sequencing, 4 mutant types (GTT, GAT, GCT and TGT) of codon 12 (normally GGT) in the ampulla of Vater cancer were detected and the mutated types in the adenomatous portions, carcinomatous portions and metastatic lymph nodes in the same cases were identical. CONCLUSION: The presence of concomitant K-ras mutation in both the adenomatous and carcinomatous portions in some cases may suggest the role of K-ras mutation in the early carcinogenesis of ampulla of Vater cancer.

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