PURPOSE: The cytotoxicity by 5-fluorouracil (5-FU) is mediated by inhibition of thymi- dylate synthase (TS), which is a rate-limiting enzyme for DNA synthesis. To test whether the resistance to 5-FU would be associated with cellular TS activity, we analyzed TS gene expression from human gastrointestinal cancer cell lines. MATERIALS AND METHODS: We established the experimental conditions for quantitating TS mRNA expression by competitive RT-PCR using mimic DNA. Based on this method, we compared TS mRNA expression between 5-FU resistant cell line and parent cell line and investigated the expression of TS mRNA following 5-FU administration in 6 human gas- trointestinal cancer cell lines. RESULTS: Competitive RT-PCR using mimic DNA seemed to be more effective than Northern blot analysis for quantitation of TS gene expression. The quantity of TS mRNA and IC50 value of 5-FU in 5-FU resistant H630 was found to be 2.5 and 10 times higher than in parent cell line, respectively. And also, we observed linear relationship between TS mRNA level and IC50 value of 5-FU (r 0.76) in 6 gastrointestinal cancer cell lines. CONCLUSION: These results suggest that overexpression of TS mRNA may play a role in the development of 5-FU resistance in human gastrointestinal malignancies
Blotting, Northern ; Cell Line ; DNA ; Drug Resistance* ; Fluorouracil* ; Gastrointestinal Neoplasms ; Gene Expression ; Humans* ; Inhibitory Concentration 50 ; Parents ; RNA, Messenger* ; Thymidylate Synthase*

No abstract available.
Colorectal Neoplasms* ; Fluorouracil* ; Leucovorin*

BACKGROUND: About 20% of small cell lung cancer (SCLC) patients have bone marrow (BM) metastasis at the time of diagnosis and the remaining patients are also considered with micrometastasis. In an att empt to detect BM micrometastasis, we used cytokeratin (CK)-20 as a molecular marker, which is specific for epithelial cells. METHOD: A sensitive RT-PCR assay was used to compare CK-20 expression both in SCLC cell line H209 and normal leukocyte and to evaluate BM aspirates of 28 SCLC patients. RESULT: H209 cell line showed CK-20 expression but normal leukocyte did not, suggesting CK-20 expression is lung tissue-specific. Of 28 patients (11 limited disease, 17 extensive disease), only 2 (1/11, 1/17) samples tested revealed positive signal for CK-20. Two patients with CK-20 expression had BM metastasis or multiple bone involvement during follow-up. CONCLUSION: Although circulating tumor cells were detected in BM of small portion of patients with bone metastasis, CK-20 doesn't seem to be a reliable marker for the detection of micrometastasis in SCLC. This study emphasizes that identification of more specific marker for micromatastsis is mandatory prior to clinical application.
Bone Marrow* ; Cell Line ; Diagnosis ; Epithelial Cells ; Follow-Up Studies ; Humans ; Keratins ; Leukocytes ; Lung ; Neoplasm Metastasis ; Neoplasm Micrometastasis* ; Neoplastic Cells, Circulating ; Small Cell Lung Carcinoma*

No abstract available.
Antiemetics* ; Drug Therapy, Combination* ; Humans ; Ondansetron*

PURPOSE: A combination of paclitaxel and cisplatin is an effective and safe regimen for advanced non-small cell lung cancer (NSCLC). We conducted a multi-center, phase II trial to evaluate the efficacy and safety of Genexol(R) (paclitaxel) and cisplatin in patients with NSCLC. MATERIALS AND METHODS: Chemotherapy-na ve patients having histologically confirmed NSCLC were enrolled. Genexol(R) was administered at 175 mg/m2 as a 3-hour intravenous infusion and cisplatin at 75 mg/m2 as an intravenous infusion on day 1 every 3 weeks. RESULTS: Twenty-five of 27 patients that were entered from 5 hospitals between Jan 2001 and Aug 2001 received chemotherapy. On an intent-to-treat basis, 9 patients (36%) achieved a partial response, 7 patients (28%) a stable disease, and 5 patients (20%) The overall response rate was 36% (95% CI, 17 to 55%). progressed. The median duration of the response was 7.8 months (95% CI, 6.6 to 9.0 months). The median time to progression was 7.4 months (95% CI, 5.3 to 9.5 months), and median overall survival was 13.3 months (95% CI, 10.8 to 15.9 months) for the intent-to-treat population. The major oxicity was hematological, with grade 3 and 4 neutropenia in 10% (10/106) of the total cycles. The non-hematologic oxicity was mild, and grade 3 emesis was observed in 2 patients (8%). One patient experienced a moderate degree hypersensitivity reaction. CONCLUSION: The results suggest that a combination of Genexol(R) and cisplatin is an effective and well-tolerated regimen for patients with NSCLC.
Carcinoma, Non-Small-Cell Lung* ; Cisplatin* ; Drug Therapy ; Humans ; Hypersensitivity ; Infusions, Intravenous ; Neutropenia ; Paclitaxel ; Vomiting

PURPOSE: IMVP-16 (Ifosfamide/Methotrexate/VP-16) regimen consists of drugs that are not commonly used as the first-line therapy of non-Hodgkin's lymphoma. This study was performed to determine the efficacy of this relatively non-cross resistant regimen, with the addition of prednisone, in patients with primary refractory or relapsed non-Hodgkin's lymphoma. MATERIALS AND METHODS: Patients with primary refractory or relpased intermediate to high grade non-Hodgkin's lymphoma were treated with ifosfamide (1000 mg/m2 iv, D1-5 with mesna), methotrexate (30 mg/m2 iv, D 3 & 10), VP-16 (100 mg/m2 iv, D 1-3), and prednisone (120 mg devided by 3 doses, D1-5). The treatment was repeated every 3 weeks. RESULTS: Between Jan. 1988 and Aug. 1993, thirty eight patients were included. In 33 evaluable patients (4 loss-to follow up and 1 ineligibility) the median age was 49 years. The common histologic types were diffuse large cell type (52%) and immunoblastic type (18%). The proportion of patients with relapsed and refractory NHL was 39% and 61%, respectively. The rate of complete remission was 21% (7/33) and overall response rate was 48% (16/33). The median-response duration was 8 months (1.5~45+). Hematologic toxicities were tolerable. Non-hematologic side effects were also tolerable including stomatitis, peripheral neuropathy, and toxic hepatitis. Three treatment-related deaths were associated with sepsis, ARDS (adult respiratory distress syndrome) and acute gastrointestinal bleeding. CONCLUSION: Based on these results, IMVP-16/Pd combination chemotherapy seems to have a moderate efficacy for the relapsed or refractory non-Hodgkin's lymphoma with tolerable toxicities.
Drug Therapy, Combination* ; Drug-Induced Liver Injury ; Etoposide ; Follow-Up Studies ; Hemorrhage ; Humans ; Ifosfamide ; Lymphoma, Non-Hodgkin* ; Methotrexate ; Peripheral Nervous System Diseases ; Prednisone ; Sepsis ; Stomatitis

PURPOSE: Non-Hodgkins lymphoma (NHL) is recognized as not a single disease but a group of diseases heterogeneous in biology and clinical characteristics. Recently, a new pathologic classification system, the REAL classification, has been introduced into the clinic. Although REAL classification has tried to define the subtypes biologically more correctly, its clinical usefulness has not been established yet. A retrospective study was performed to define the clinical characteristics of Korean NHLs according to the REAL classification and to determine its clinical usefulness. MATERIALS AND METHODS: Pathologies of NHLs managed at 3 major hospitals in Korea between 1989 and 1995 were reviewed with immunophenotyping to determine the pathologic subtypes according to REAL classification. Clinical characteristics at the presentation and treatment outcomes of the eligible patients were analyzed. To determine the differences from the NHLs in the western countries, data of Non-Hodgkins Lymphoma Classification Project (NHLCP) were also compared. RESULTS: Total 802 cases were eligible for this study. Although it was similar to NHLCP study that B-cell subtypes were the majority and diffuse large B-cell lymphoma was the most common subtype, the proportion of T-cell subtypes were much higher in our patient population than in the western population. It was because peripheral T-cell lymphomas, angiocentric lymphoma in particular, were more common and follicular lymphomas were less common in our patients. Eleven common pathologic subtypes could be classified into 3 prognostic groups. Marginal zone B-cell lymphoma and lymphoplasmacytoid lymphoma of which 5-year overall survival rate (5-yOSR) were > 80% were classified in the good prognostic group. Precursor T-lymphoblastic lymphoma was classified in the poor prognostic group because its 5-yOSR was less than 30%. The other 9 subtypes were classified in the intermediate prognostic group with S-yOSR of 30-79%. CONCLUSION: The clinical. character' tics and prognoses of Korean NHLs could be defined according to REAL classification. These information would be helpful for the clinicians in formulating treatment strategies of Korean NHLs according to REAL classification.
B-Lymphocytes ; Biology ; Classification* ; Hodgkin Disease* ; Humans ; Immunophenotyping ; Korea ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, B-Cell, Marginal Zone ; Lymphoma, Follicular ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell, Peripheral ; Pathology ; Prognosis ; Retrospective Studies ; Survival Rate ; T-Lymphocytes ; Tics ; Waldenstrom Macroglobulinemia

PURPOSE: The purpose of this study was to evaluate the outcome of adjuvant chemoradiotherapy (CRT) after distal pancreatectomy (DP) in patients with pancreatic adenocarcinoma, and to identify the prognostic factors for these patients. MATERIALS AND METHODS: We performed a retrospective review of 62 consecutive patients who underwent curative DP followed by adjuvant CRT between 2000 and 2011. There were 31 men and 31 women, and the median age was 64 years (range, 38 to 80 years). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes with a median dose of 50.4 Gy (range, 40 to 55.8 Gy). All patients received concomitant chemotherapy, and 53 patients (85.5%) also received maintenance chemotherapy. The median follow-up period was 24 months. RESULTS: Forty patients (64.5%) experienced relapse. Isolated locoregional recurrence developed in 5 patients (8.1%) and distant metastasis in 35 patients (56.5%), of whom 13 had both locoregional recurrence and distant metastasis. The median overall survival (OS) and disease-free survival (DFS) were 37.5 months and 15.4 months, respectively. On multivariate analysis, splenic artery (SA) invasion (p=0.0186) and resection margin (RM) involvement (p=0.0004) were identified as significant adverse prognosticators for DFS. Also, male gender (p=0.0325) and RM involvement (p=0.0007) were associated with a significantly poor OS. Grade 3 or higher hematologic and gastrointestinal toxicities occurred in 22.6% and 4.8% of patients, respectively. CONCLUSION: Adjuvant CRT may improve survival after DP for pancreatic body or tail adenocarcinoma. Our results indicated that SA invasion was a significant factor predicting inferior DFS, as was RM involvement. When SA invasion is identified preoperatively, neoadjuvant treatment may be considered.
Adenocarcinoma* ; Chemoradiotherapy, Adjuvant* ; Disease-Free Survival ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Maintenance Chemotherapy ; Male ; Multivariate Analysis ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Pancreatectomy* ; Pancreatic Neoplasms ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Splenic Artery*