Development of drug resistance in tumors during treatment is a major factor limiting the clinical use of anticancer agents. When tumor cells acquire resistance to anticancer drug, they show cross-resistance to other antitumor agents. In the present study, SNU-1 cell was induced adriamycin 10-7 drug resistance, SNU-1/ADR, in vitro culture system. We got the doubling time and number for viability test during 96 hours by MTT assay. To investigate the cross resistance of various anticancer drugs in human stomach cancer cell SNU-1 and SNU-1/ADR, We compared IC50 (drug concentration of 50% reduction) and the relative resistance (RR). SNU-1/ADR was expressed multidrug resistant with vinblastine (RR;>31.62), vincristine (RR;29.50), dactinomycin (RR;21.37), epirubicin (RR;17.78), daunorubicin (RR;14.12), adriamycin (RR;7.76), and etoposide (RR;4.46), and other drugs, 5-fluorouracil, cisplatin, cyclophosphamide, methotrexate, and calarubicin, have not cross resistant with adriamycin. There was double minute chromosome in SNU-1/ADR by karyotyping although this change was not seen in SUN-1.
Antineoplastic Agents ; Cisplatin ; Cyclophosphamide ; Dactinomycin ; Daunorubicin ; Doxorubicin ; Drug Resistance ; Epirubicin ; Etoposide ; Fluorouracil ; Humans ; In Vitro Techniques ; Inhibitory Concentration 50 ; Karyotyping ; Metabolism* ; Methotrexate ; Stomach Neoplasms* ; Stomach* ; Vinblastine ; Vincristine

The development of multidrug-resistant tumor cell population is a major problem in the chemotherapy of human cancer. These cells are often cross resistant to unrelated drugs and the precise mechanisms of multidrug resistant phenotype of tumor cells has not been fully elucidated. Cisplatin resistant tumor cell (SNU-1/Cis₅) was induced from human stomach cancer cell line (SNU-1) in vitro. Growth profiles of survival cells were observed during 5 days by thiazolyl blue (MTT) assay. To investigate the cross resistance of various anticancer drugs in SNU-1 and SNU-1/Cis5, We compared the value of IC₅₀-drug concentration at 50% survival of control and gained relative resistances (RR). The RR for SNC-1/Cis₅ were as follows; vinblastine, > 43.0; epirubicin, 22.9; dactinomycin, 16.0; etoposide, 15.0; vincristine, 9.2; adriamycin, 5.7; aclarubicin, 5.3. But 5-fluorouracil, methotrexate, daunorubicin have not cross resistance with cisplatin. Resistant inhibition values of 10µM verapamil for SNU-1/Cis₅ were as follows; vincristine, 13.1; epirubicin, 10.0; etoposide, 6.3; vinblastine, 4.4; dactinomycin, 3.6; daunorubicin, 2.4. Membrane proteins of 51,400 and 81,300 daltons were identified by radioiodination with SDS-PAGE, which might represented the drug resistance.
Aclarubicin ; Cell Line ; Cisplatin* ; Dactinomycin ; Daunorubicin ; Doxorubicin ; Drug Resistance ; Drug Resistance, Multiple* ; Drug Therapy ; Electrophoresis, Polyacrylamide Gel ; Epirubicin ; Etoposide ; Fluorouracil ; Humans* ; In Vitro Techniques ; Membrane Proteins ; Methotrexate ; P-Glycoprotein ; Phenotype ; Stomach Neoplasms* ; Stomach* ; Verapamil* ; Vinblastine ; Vincristine

OBJECTIVETo evaluate the sensitivity of NT-pro-BNP in daunorubicin (DNR) induced myocardial damage by monitoring the level of NT-pro-BNP and myocardial enzymes (CK, CKMB) before and after DNR treatment in childhood acute leukemia (AL) and performing control study.

METHODSSixty-two cases (total 194 samples) which diagnosed as primary AL were enrolled and had received the conventional chemotherapy. According to the cumulative dose of DNR, they were divided into three groups: cumulative dose ≤ 60 mg/m(2) (group A); cumulative dose 60 - 120 mg/m(2) (group B); cumulative dose > 120 mg/m(2) (group C) and 15 cases with idarubicin (IDA) or mitoxantrone (MXR) as altervative to DNR (group D).

RESULTSThere was a significant difference (P = 0.000) in the level of NT-pro-BNP before and after DNR therapy, but did not in the myocardial enzymes activities (CK, P = 0.085 and CKMB, P = 0.076). The level of NT-pro-BNP appeared obviously elevated (P = 0.001) when DNR cumulative dose > 60 mg/m(2). While the level of CKMB did (P = 0.022) until DNR cumulative dose > 120 mg/m(2). In the 15 cases used IDA or MXR as alternative to DNR, the level of NT-pro-BNP fall from (239.9 ± 230.0) ng/L to (137.0 ± 131.9) ng/L (P = 0.024).

CONCLUSION(1) Compared with myocardial enzymes detection, NT-pro-BNP level can predict earlier DNR-induced cardiotoxicity. (2) Selection of the second or third generation anthracycline to treat AL can significantly reduce the cardiotoxicity in children.

Anthracyclines ; Cardiotoxicity ; Daunorubicin ; administration & dosage ; Humans ; Idarubicin ; administration & dosage ; Leukemia ; drug therapy

OBJECTIVETo compare the complete remission rate (CRR) and adverse reaction of the 3 different chemotherapy regimens (daunorubicin, idarubicin, imported idarubicin combined with cytarabine) for the treatment of adult patients with newly diagnosed non-M3 acute myeloid leukemia (AML).

METHODSSeventy-one adult patients with newly diagnosed non-M3 AML were divided into 3 groups: 17 cases treated with daunorubicin plus cytarabine as group A, 24 cases treated with idarubicin plus cytarabine as group B, 30 cases treated with the imported idarubicin plus cytarabine as group C. The curative effects and adverse reactions were compared among the 3 groups after treatment.

RESULTSCCR in group C (86.67%) was significantly higher than that in group A (52.94%) and group B (70.83%), and the CRR in group B was significantly higher than that in group A (P<0.05). The incidence of adverse reaction such as nausea, vomiting, myelosuppression and infection among 3 groups were not statistically significantant (P>0.05).

CONCLUSIONThe curative effect of idarubicin for the treatment of non-M3 AML patients is better than that of daunorubicin, especially the curative efficiency of imported darubicin is much higher; the adverse reaction after treatment by daunorubicin and idarubicin can be controllable, so daunorubicin and idarubicin can be used as first-line drug for the patients with AML, and patients can choose more appropriate drug according to their own economic ability.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Daunorubicin ; Humans ; Idarubicin ; Leukemia, Myeloid, Acute ; Remission Induction

BACKGROUND: Anthracycline is the most important chemotherapy drug of acute myelocytic leukemia (AML). It has been reported that idarubicin could have better complete remission (CR) rate than daunorubicin. However, it is not completely established concerning the effectiveness of idarubicin. There are many prognostic indicators of AML, however, many discrepancies still exist in prognostic indicators among each centers. METHODS: We analyzed initial CR rate of 39 AML patients treated with combination of cytarabine plus idarubicin or daunorubicin at Samsung Medical Center from April, 1995 to December, 1997. We subgrouped the patients according to age, sex, initial WBC count, status of initial CR, CD34, and chromosome. We analyzed the initial CR rate and long term survival of each subgroups. RESULTS: Initial CR rates of idarubicin and daunorubicin were 76.5% and 72.7%, respectively. The median survival days of 39 patients was 727+/-308.8 days. 1-year survival rate and 1-year event free survival rate were 64.2% and 59.6%, respectively. Patients who had failure of initial CR, old age (>60 years), and initial high WBC counts (>100,000/L) showed a statistically significant shorter survival in univariate analysis. However, we could not find the significant difference in the positivity of CD34 and chromosomal abnormalities. CONCLUSION: The effectiveness of idarubicin may be equivalent to that of daunorubicin. Failure of initial CR, old age, and high WBC counts were regarded as a prognostic risk factors of AML. However, a more definitive characterization of prognostic factors is warranted in further prospective study.
Chromosome Aberrations ; Cytarabine ; Daunorubicin* ; Disease-Free Survival ; Drug Therapy ; Humans ; Idarubicin* ; Leukemia, Myeloid, Acute* ; Risk Factors ; Survival Rate

BACKGROUND: The combination of cytarabine plus anthracycline has been considered standard chemotherapy for acute myelogenous leukemia (AML). We retrospectively analyzed the treatment results of the patients with de novo AML who received cytarabine plus daunorubicin or idarubicin as induction chemotherapy. METHODS: From 1989 to 1998, 149 patients with AML were included. For induction chemotherapy, the patients received cytarabine 100~ 200 mg/m2/day given by continuous 7-day in fusion plus either daunorubicin 40~45 mg/m2/ day (A+D) or idarubicin 12 mg/m2/day (A+I) administered for the first 3 days of treatment. We reviewed clinical records of the patients and analyzed the treatment results such as complete remission (CR) rate, disease free survival (DFS), and overall survival (OS). RESULTS: The CR rates were 67.1% (100 of 149); 69.3% (70 of 101) in A+D group and 62.5 % (30 of 48) in A+I group (P=0.409). The frequent reason of induction failure was resistant disease in A+D group (54.8%) and early death in A+I group (66.7%). The median DFS was 344 days; 344 days in A+D group and 314 days in A+I group. The median OS was 379 days; 389 days in A+D group and 379 days in A+I group. Age < or =60 years and allogeneic BMT as postremission therapy were independent favorable factors both for DFS and OS. AML M3 was favorable factor only for DFS. CONCLUSION: The combination of cytarabine plus daunorubicin or idarubicin was effective for the treatment of AML. We can not find significant difference in CR rate, disease free survival and overall survival between A+D and A+I group.
Cytarabine* ; Daunorubicin* ; Disease-Free Survival ; Drug Therapy ; Humans ; Idarubicin* ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute* ; Leukemia, Promyelocytic, Acute ; Retrospective Studies

BACKGROUND: About 60~80% of previously untreated patients with acute myelogenous leukemia (AML) achieve complete remission (CR) when treated with cytarabine and anthracycline. Anthracycline is one of the most important chemotherapeutic agents in AML. It has been claimed that idarubicin showed superior complete remission rate than daunorubicin, which is not completely established. We evaluated idarubicin in combination with cytarabine (AI) as an induction chemotherapy in patient with AML. METHODS: Thirty one patients with newly diagnosed acute myelogenous leukemia were enrolled. Remission induction emotherapy was consisted of cytarabine (100mg/m2 IV over 24 hours on day 1~7) and idarubicin (12mg/m2 IV over 30 minutes on day 1~3). After achievement of CR, patients underwent consolidation therapy with high- dose cytarabine and/or bone marrow transplantation. RESULTS: Median age of the patients was 43 years (range; 17~62) and M2 was the most common subtype. The CR rate was 71% (22/ 31). The median overall and disease-free survival were 67 weeks (95% confidence interval, CI; 43~91) and 65 weeks (95% CI; 26~104), respectively with a median follow-up of 48 weeks. Major toxicities were fever and infection during the neutropenic period. There were three treatment-related mortalities. Causes of death were refractory AML in 1 patient and infection in 2 patients. CONCLUSION: AI induction chemotherapy seems to be effective and safe regimen as an induction chemotherapy in AML.
Bone Marrow Transplantation ; Cause of Death ; Cytarabine* ; Daunorubicin ; Disease-Free Survival ; Fever ; Follow-Up Studies ; Humans ; Idarubicin* ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute* ; Mortality ; Remission Induction

OBJECTIVETo investigate the effects of arsenic trioxide (As(2)O(3)) on the apoptosis and P-glyco-protein (P-gp) expression of multidrug-resistant human leukemia K562/ADM cells, and the combined effects of As(2)O(3) with conventional chemotherapeutic agents.

METHODSMultidrug-resistant human leukemia cell line K562/ADM that overexpresses mdr-1 gene was used as the target cells. The cell proliferating activity was assessed with a MTT assay. Cell morphology was examined by light microscopy, confocal microscopy and electron-microscopy. P-gp expression, cell-cycle status were determined by flow cytometry.

RESULTSK562/ADM cells were highly resistant to adriamycin, and cross-resistant to daunorubicin and etoposide. As(2)O(3) at concentrations of 0.5 to 20 micromol/L inhibited the proliferation of K562/ADM cells, and K562/ADM cells were more sensitive to As(2)O(3) than their parent K562 cells did. As(2)O(3) induced marked apoptosis of K562/ADM cells showed by typical apoptotic morphological changes and the appearance of high sub-G(1) cell population. As(2)O(3) significantly inhibited the P-gp expression in K562/ADM cells, and exerted a synergistic effect on the enhancement of the cell sensitivity to adriamycin, daunorubicin and etoposide.

CONCLUSIONAs(2)O(3) induces growth-inhibition and apoptosis of multidrug-resistant K562/ADM cells, and augments synergistically the sensitivity of the cells to conventional chemotherapeutic agents via down-regulation of P-gp expression.

ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; drug effects ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Daunorubicin ; pharmacology ; Doxorubicin ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Drug Synergism ; Etoposide ; pharmacology ; Humans ; K562 Cells ; Oxides ; pharmacology

BACKGROUND: A number of anticancer agents are known to induce many adverse reactions in the skin. Related cutaneous adverse drug reactions influence the morbidity, mortality, and anti-cancer regimen of the patients. A multidisciplinary approach to cancer management has been emphasized. OBJECTIVE: To identify the causative anticancer agents and frequency of adverse reactions in the skin. METHODS: We retrospectively reviewed the medical records of patients who consulted at the Dermatology Department of Busan Paik Hospital and Haeundae Paik Hospital from January 2013 to February 2015. RESULTS: A total of 140 patients were enrolled. Among the 45 patients treated with antimetabolite analogs (30 cytarabine, 7 gemcitabine, 3 methotrexate, 2 fludarabine, 2 doxifluridine, and 1 decitabine), exanthematous drug eruption (49.1%) was the most common reaction, followed by hand-foot syndrome (28.3%). Among the 35 patients treated with fluorouracil (22 5-fluorouracil and 13 capecitabine), hand-foot syndrome (47.2%) was the most common, followed by acneiform eruption (25.0%). Among the 24 patients treated with epidermal grow factor receptor inhibitors (10 erlotinib, 10 cetuximab, and 4 gefitinib), acneiform eruption (54.8%) was the most common, followed by xerosis (19.4%). Among the 11 patients treated with anthracyclines (9 doxorubicin, 1 daunorubicin, and 1 idarubicin), acneiform eruption (45.5%) was the most common, followed by hand-foot syndrome (36.4%). Among the 7 patients treated with taxanes (4 docetaxel and 3 paclitaxel), hand-foot syndrome (42.8%) was the most common. Among the 6 patients treated with angiogenesis-inducing inhibitors (3 sorafenib, 2 pazopanib, and 1 sunitinib), hand-foot skin reaction (66.7%) was the most common. Only 2 patients (1.4%) changed treatments due to intolerable skin reactions. CONCLUSION: Clinicians should be aware of the various skin reactions of anticancer agents and predict their clinical course effectively.
Acneiform Eruptions ; Anthracyclines ; Antineoplastic Agents ; Busan ; Cetuximab ; Cytarabine ; Daunorubicin ; Dermatology ; Doxorubicin ; Drug Eruptions ; Drug-Related Side Effects and Adverse Reactions ; Erlotinib Hydrochloride ; Fluorouracil ; Hand-Foot Syndrome ; Humans ; Medical Records ; Methotrexate ; Mortality ; Retrospective Studies* ; Skin ; Taxoids

OBJECTIVESTo investigate the reversal effect of gene MDR1 and MRP with combinational antisense phosphorothioate oligonucleotide on Drug-resistant human hepatocellular carcinoma cells SMMC-7721/ADM.

METHODSSMMC-7721/ADM was transfected with synthetic antisense phosphorothioate oligonucleotides complementary to gene MDR1 and MRP mediated by Lipofectamine. Drug sensitivity was measured by MTT assay, Fluorescence intensity of cells was determined by flow cytometric analysis, RH123 and DNR retention was assayed by confocal scanning laser microscopy.

RESULTSASODN of MDR1+MRP increased the sensitivity of SMMC-7721/ADM to chemotherapeutic drug more significantly than that any of MDR1 and MRP did separately. But they did not enhance the inhibition expression of protein of p190 or p170.

CONCLUSIONDrug-resistance could be reversed significantly when antisense phosphorothioate oligonucleotide of MDR1+MRP were transfected into drug-resistant human hepatocellular carcinoma cells SMMC-7721/ADM together.

Carcinoma, Hepatocellular ; drug therapy ; genetics ; Cell Line, Tumor ; Daunorubicin ; metabolism ; pharmacology ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Genes, MDR ; Humans ; Liver Neoplasms ; drug therapy ; genetics ; Multidrug Resistance-Associated Proteins ; genetics ; Oligonucleotides, Antisense ; pharmacology ; Rhodamine 123 ; metabolism