PURPOSE: Many of the enzymes handling environmental factors are polymorphic and may confer variable susceptibility to renal cell carcinoma (RCC). Among those, the author studied genetic polymorphisms of CYP2D6 (B & T) and CYP1A1 in RCCs and controls in Korean. MATERIALS AND METHODS: Using 132 RCCs and 94 controls, first PCR products were obtained in 104 RCCs and 94 controls with CYP2D6, and 74 RCCs and 56 controls with CYP1A1. Res triction enzyme - BstN I/EcoN I for CYP2D6 (B & T), and NCo I for CYP1A1-digestion was followed to analyze constitutive DNA. RESULTS: In both RCCs and controls, no mutant allele of CYP2D6 (B & T) was detected and the susceptibility for occurrence of RCC was unable to evaluate. With CYP1A1 RFLP, homozy gous wild type (WW) was seen in 68 (52.3%; 37 RCCs, 31 controls), heterozygous mutant type (WM) in 54 (41.5%; 32 RCCs, 22 controls) and homozygous mutant type (MM) in 8 (6.2%; 5 RCCs, 3 controls). The odds ratios (95% CI) of RCC susceptibility for CYP1A1 genotype were 1.15 for WM and 1.36 for MM. Even though not significant statistically, higher tendency in MM presented. CONCLUSION: There is no association between susceptibility for the occurrence of RCC and genetic polymorphism of CYP2D6 (B & T) and CYP1A1.
Alleles ; Carcinoma, Renal Cell* ; Cytochrome P-450 CYP1A1* ; Cytochrome P-450 CYP2D6* ; DNA ; Genotype ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism, Genetic* ; Polymorphism, Restriction Fragment Length

PURPOSE: We conducted a phase II study to determine the antitumor activity of BACOD/EISHAP alternating 9-drug chemotherapy in previously untreated patients with intermediate or high grade non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: Intermediate or high grade non-Hodgkin's lymphoma patients were treated with BACOD/EISHAP (bleomycin, doxorubicin, cyclophosphamide, vincristine, dexame thasone/etoposide, ifosfamide, high dose cytarabine, cisplatin, dexamethasone) alternating com bination chemotherapy. Stage I and IIA lymphoma patients were excluded. BACOD/EISHAP alternating chemotherapy was given to the eligible patients every 3 weeks/4 weeks respectively. RESULTS: Between April, 1995 and December, 1997, among 25 eligible patients, 19 patients were evaluable for response. Six patients could not be evaluated for response because of follow-up loss within 2 cycles of chemotherapy. Complete response (CR) was achieved in 12 patients (63%) after BACOD/EISHAP alternating combination chemotherapy. With a follow-up period of 41 months (25~57 months), the disease free survival did not reach median (4~47 months) and 3-year disease free survival rate was 75%. Major toxicity was marrow suppression and the incidence of severe leukopenia (WBC<2,000/mm3) and thromobocytopenia (<25,000/mm3) were 15%, 5%, respectively. No treatment-related death was observed. For non-hematologic toxicities, nausea and vomiting were observed in 65% of patients, stomatitis in 25%, peripheral neuropathy in 20%. CONCLUSION: BACOD/EISHAP alternating chemotherapy was feasible with acceptable toxicities. The 63% complete response rate was comparable to other regimens but 75% 3year disease-free survival rate was encouraging. Further evaluation of this regimen is warranted.
Bone Marrow ; Cisplatin ; Cyclophosphamide ; Cytarabine ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Drug Therapy, Combination* ; Follow-Up Studies ; Humans ; Ifosfamide ; Incidence ; Leukopenia ; Lymphoma ; Lymphoma, Non-Hodgkin* ; Nausea ; Peripheral Nervous System Diseases ; Stomatitis ; Vincristine ; Vomiting

PURPOSE: Retinonic acid (RA) has been reported to induce differentiation and growth inhibition in various head and neck squamous cancer cell (HNSCC) lines. We hypothesized that this growth inhi bition might be explained by RA-induced apoptosis on cell cycle arrest mechanism. Therefore, we studied the degree of RA-induced apoptosis with variable RA concentration and exposure duration. MATERIAL AND METHODS: The flow cytometric evaluation of apoptosis degree and cell cycles were carried out with 7-amino actinomycin D (7AAD) and propium iodide (PI) respectively, with var ious RA exposure durations (2, 3, 6 day) and concentrations (conrol, 10 6, 10 7, 10 8, 10 9, 10 10 mole). Two different HNSCC lines (1483, SqCC/Y1) were used and the experiment was repeated twice. RESULTS: The maximal fraction of apoptosis in 1483 and SqCC/Y1 cell lines were observed at same concentration and exposure duration (1483: 6th day & 10 6, mole, and SqCC/Y1: 6th day & 10 6 mole). In our experimental model, RA did not induce specific cell cycle arrest in these HNSCC lines. However we observed S phase fraction increase in SqCC/Y1 cell line after RA treatment. CONCLUSION: We suppossed that in HNSCC lines, RA-induced cell growth inhibition could be explained by not only RA-induced apoptosis but also cell cycle arrest. Futher, in vitro study has been carried out to elucidate the RA-iduced cell growth inhibition mechanism in our laboratory.
Apoptosis ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line* ; Dactinomycin ; Head* ; Models, Theoretical ; Neck* ; S Phase ; Tretinoin

PURPOSE: To evaluate treatment results of breast conserving surgery and radiation therapy including survival rates, patterns of failure, and complication and to analyze prognostic factors. MATERIALS AND METHODS: Retrospective analysis was carried out for 111 (112 cases) consecutive patients with breast cancer treated by radiation therapy after breast conserving surgery from October 1994 to April 1997. The median follow up was 45 months (range 10~66). AJCC staging was as follows: 16 cases (14%) for ductal carcinoma in situ, 46 cases (41%) for stage I, 33 cases (30%) for stage IIa, and 17 cases (15%) for stage IIb. Radiation therapy after breast conserving surgery was delivered to whole breast with 50.4 Gy and additional 10 Gy electron beam boost to tumor bed. Adjuvant CMF or CAF chemotherapy was performed in 61 patients. RESULTS: Overall three- and five-year survivals were 99% and 95%, and progression-free survival were 93%, 87%, respectively. Treatment failure occurred in 11 cases (10%); loco-regional recur rence in six; distant metastasis in five. Univariate analysis showed prognostic factor affecting survival was only T-stage. Acute radiation dermatitis were found in five cases (4%), and chronic complications were found in five (4%); one case with amputation of nipple, two cases with lymphedema requiring rehabilitation therapy and two cases with symptomatic radiation pneu monitis requiring steroid therapy. CONCLUSION: Breast conserving therapy of early breast cancer including ductal carcinoma in situ showed high survival rates and low complications, and T stage was prognostic factor for survival. But further follow-up should be needed.
Amputation ; Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Dermatitis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Lymphedema ; Mastectomy, Segmental* ; Neoplasm Metastasis ; Nipples ; Radiotherapy* ; Rehabilitation ; Retrospective Studies ; Survival Rate ; Treatment Failure

PURPOSE: Vascular endothelial growth factor (VEGF) is a major positive effector of angiogenesis. We investigated the mechanism of tumor growth inhibition by adenoviral transfer of antisense- VEGF in glioma and the role of VEGF for in vivo growth of human glioma cells according to the stage of the tumor growth. MATERIALS AND METHODS: Replication-deficient adenoviral vector containing the VEGF cDNA in an antisense orientation (Ad5CMV-alphaVEGF) were constructed to increase the in vivo applicability of antisense sequence. The effect of Ad5CMV-alphaVEGF was studied in vitro and in vivo with human glioma cell line U-87 MG. Immunohistochemical staining of the subcutaneous tumor with anti-VEGF antibody and CD34 antibody were performed to compare VEGF protein expression and the microvessel count respectively. RESULTS: The growth curve of U-87 MG cells treated with Ad5CMV-alphaVEGF remained as same as that of mock-infected and Ad5(dl312)-infected U-87 MG cells in vitro, suggesting that Ad5CMV-alphaVEGF does not have direct cytotoxic effect. The growth of subcutaneous human glioma xenografts was inhibited by early intratumoral injection of Ad5CMV-alphaVEGF. Immuno histochemical staining of tumors showed that VEGF protein expression and mean microvessel counts were decreased in early Ad5CMV-alphaVEGF treatment group. CONCLUSION: The efficient down-regulation of VEGF produced by tumor cells using Ad5CMV- alphaVEGF in early stage of glioma growth has an antitumor effect in vivo through antiangiogenic mechanism.
Adenoviridae ; Cell Line ; DNA, Complementary ; Down-Regulation ; Genetic Therapy* ; Glioblastoma* ; Glioma ; Heterografts ; Humans ; Microvessels ; Vascular Endothelial Growth Factor A

PURPOSE: A retrospective study was intended to assess the incidence, severity, and risk factors of abdominal radiotherapy induced nausea and vomiting and to evaluate the effect of antiemetic drugs like metoclopramide and ondansetron. MATERIALS AND METHODS: From October 1997 to October 1999, we enrolled 48 patients who received conventional fractionated radiotherapy on abdomen. Patients under 18 years old and who received concomittant chemotherapy were excluded. Evaluation was carried out on the basis of daily check of the intensity of nausea and any episode of vomiting and retching. RESULTS: Nausea and vomiting occurred in 65% and 25% of patients, respectively. On multivariate analysis, previous experience with chemotherapy was the only significant patients-related risk factor. The irradiated site and field size were also significant in terms of radiotherapy-related risk factors. Nausea and vomiting were markedly diminished in the group given ondansetron. CONCLUSION: Our study offered useful data on general picture of radiation induced nausea and vomiting in patients given conventional fractionated radiotherapy on abdomen. For the patients with risk factors, prophylactic antiemetic drug prescription may be mandatory to enhance compliance with radiotherapy and ondansetron is more effective than metoclopramide for controlling nausea and vomiting.
Abdomen* ; Adolescent ; Antiemetics ; Compliance ; Drug Prescriptions ; Drug Therapy ; Humans ; Incidence ; Metoclopramide ; Multivariate Analysis ; Nausea* ; Ondansetron ; Radiotherapy* ; Retrospective Studies ; Risk Factors ; Vomiting*

PURPOSE: The activator of protein kinase A, cyclic AMP, has been a recognized growth inhibitor of certain cell types. The present study aimed to investigate the effects of dibutyryl cAMP on the growth of cancer cells which lack wild-type p53 and to determine the mechanism of growth inhibition. MATERIALS AND METHODS: Prostate and breast cancer cells were treated with dibutyryl cAMP and compared with untreated cells. Growth patterns of cells were assessed by trypan blue-excluding method and western blot was done to determine protein levels of cell cycle regulatory proteins which govern G1 and G1/S phase. Northern blot and immunoprecipitation were done to determine the level of mRNA of p21 and the association between cell cycle regulatory proteins. In vitro immune complex kinase assay was done to assess the activity of cdk2. RESULTS: cAMP reduced cell growth by 48 h. Cyclin D3 level was downregulated and RB protein level was decreased and mostly unphosphorylated forms remained. The association of RB with E2F1 was increased. While cdk2 levels remained constant throughout cAMP treatment, the activity of cdk2/cyclin E complex, which is responsible for entry into S phase, was downregulated. Cdk inhibitors, p27 and p21 were induced with cAMP treatment. CONCLUSION: These observation suggest that the growth inhibitory effects of dibutyryl cAMP on prostate and breast cancer cells were mediated by induction of cdk inhibitors such as p21 and p27 and RB activation in accordance with downregulation of cdk2.
Antigen-Antibody Complex ; Blotting, Northern ; Blotting, Western ; Breast Neoplasms ; Cell Cycle Proteins ; Cyclic AMP* ; Cyclic AMP-Dependent Protein Kinases ; Cyclin D3 ; Down-Regulation ; Immunoprecipitation ; Phosphotransferases ; Prostate ; Retinoblastoma Protein ; RNA, Messenger ; S Phase

PURPOSE: We determined whether the uptake of Ga-67 by cultured cells occur by both transferrin (Tf)-dependent and independent mechanisms and the mechanism and magnitude of its uptake may vary as the degree of expression of the transformed phenotype. MATERIALS AND METHODS: Uptake of Ga-67 between the tansformed and untransformed cells was compared. Cells were incubated with Ga-67 in either the presence or absence of Tf and with complete medium containing Ga-67 after preincubating with anti-Tf receptor antibodies at 37oC in 8% CO2. Monolayers of cells were washed and trypsinized. Radioactivity and protein content of the samples were determined. RESULTS: Uptake of Ga-67 by cultured cells occurred both in Tf-bound and ionic form and was increased with radioactivity and time. The magnitude for the uptake of Tf-bound form was approximately 3 and 6-fold greater than ionic form. In the presence of Tf, uptake of Ga-67 was 2-fold greater in the transformed cells. Conversely, In the absence of Tf, it was 1.5-fold greater in the untransformed cells. Regardless of blocking the Tf receptor by anti-Tf receptor antibodies, a significant amount of intracellular Ga-67 uptake was found. CONCLUSION: Dual mechanisms exist for the uptake of Ga-67 by cultured cells. The primary important one was the Tf-dependent system. Tf-dependent and independent mechanisms and the magnitude operated oppositely in the transformed cells when compared to their untransformed counterpart.
Antibodies ; Cells, Cultured* ; Phenotype ; Radioactivity ; Transferrin ; Trypsin

PURPOSE: Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to exist chemo preventive activity against colon cancers. In this study, we examined whether salicylate affects the survival of A549 cells, and investigated the presence of apoptosis. MATERIALS AND METHODS: We used A549 human lung cancer cell line. The measurement of cytotoxic concentration of salicylate was performed by MTT assay method. In order to test the involvement of apoptosis, we performed TUNEL assay, DAPI staining, flow cytometric analysis and RT-PCR. RESULTS: We showed that salicylate can potently induce apoptosis in A549 cells. A549 cells under went apoptosis in treatment with salicylate at pharmacological concentration (5 mM). CONCLUSION: Herein, our data provide a potential mechanism for chemopreventive activity of salicylate and suggest that salicylate may have therapeutic potential for the treatment of lung cancer.
Apoptosis* ; Cell Line ; Colonic Neoplasms ; Humans ; In Situ Nick-End Labeling ; Lung Neoplasms

PURPOSE: This study was designed to find out whether protein kinase C (PKC) may affect telomerase activity in human ovarian cancers. MATERIALS AND METHODS: To determine whether PKC modulators influence PKC activities, NIH: OVCAR-3 and CUMO-2, cells were treated with PKC inhibitors, G 6976 and bisindolyl maleimide I, and PKC activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA). Telomerase acti vity was determined by telomeric repeat amplification protocol (TRAP). Analysis of the expres sion of each telomerase subunits, human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT), was performed by RT-PCR. We also examined the alternative splicing of hTERT. RESULTS: G 6976 and bisindolylmaleimide I inhibited PKC activity. Telomerase activities appeared to be affected in a time-dependent manner by these two PKC inhibitors. PKC activities were increased in parallel with telomerase activity by TPA at the low dose (10 nM), but their activities were down-regulated at the high dose (1 micrometer). RT-PCR demonstrated the presence of hTR and hTERT mRNA before and after the treatment of PKC modulators, respectively, and showed the presence of one alternatively spliced transcript and full-length hTERT transcripts. CONCLUSION: These results showed that telomerase activity was affected by PKC and suggested PKC modulation may serve as an useful tool in the regulation of telomerase activity.
Alternative Splicing ; Cell Line* ; Humans* ; Ovarian Neoplasms* ; Protein Kinase C* ; Protein Kinases* ; RNA ; RNA, Messenger ; Telomerase* ; Tetradecanoylphorbol Acetate