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8 "Adriamycin"
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Original Articles
The Differential Gene Expression Profiles between Sensitive and Resistant Breast Cancer Cells to Adriamycin by cDNA Microarray
Myung-Ju Ahn, Ki-Hwan Lee, Joon-Ik Ahn, Dong-Hyun Yu, Hye-Sook Lee, Jung-Hye Choi, Joung Soon Jang, Jong Min Bae, Yong-Sung Lee
Cancer Res Treat. 2004;36(1):43-49.   Published online February 29, 2004
DOI: https://doi.org/10.4143/crt.2004.36.1.43
AbstractAbstract PDFPubReaderePub
Purpose

Adriamycin® is one of the most commonly used drugs in the treatment of breast cancer. This study was performed to understand the molecular mechanisms of drug resistance in breast cancer cells.

Materials and Methods

We have analyzed the MCF-7 breast cell line and its adriamycin-resistant variants, MCF-7/ADR using human 10 K element cDNA microarrays.

Results

We defined 68 genes that were up-regulated (14 genes) or down-regulated (54 genes) in adriamycin resistant breast cancer cells. Several genes, such as G protein-coupled receptor kinase 5, phospholipase A2, guanylate cyclase 1, vimentin, matrix metalloproteinase 1 are up-regulated in drug resistant cells. Several genes, such as interferon, alpha-inducible protein 27, forkhead box M1, mitogen-activated protein kinase 6, regulator of mitotic spindle assembly 1 and tumor necrosis factor superfamily are down-regulated in adriamycin resistant cells. The altered expression of genes observed in microarray was verified by RT-PCR.

Conclusion

These findings show that cDNA microarray analysis can be used to obtain gene expression profiles reflecting the effect of anticancer drugs on breast cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.

Citations

Citations to this article as recorded by  
  • Fabrication of Mn-TPP/RGO Tailored Glassy Carbon Electrode for Doxorubicin Sensing
    Rafia Zafar, Syeda Aqsa Batool Bukhari, Habib Nasir
    ACS Omega.2024; 9(24): 25694.     CrossRef
  • A simple voltammetric method for rapid sensing of daunorubicin in the presence of dacarbazine by graphene oxide/metal–organic framework-235 nanocomposite-modified carbon paste electrode
    Zahra Shamsadin-Azad, Mohammad Ali Taher, Hadi Beitollahi
    Journal of the Iranian Chemical Society.2024; 21(10): 2623.     CrossRef
  • GRK5 Deficiency Causes Mild Cognitive Impairment due to Alzheimer’s Disease
    William Z. Suo, Bruce Citron
    Journal of Alzheimer's Disease.2022; 85(4): 1399.     CrossRef
  • pH-Sensitive chitosan-tripolyphosphate nanoparticles increase doxorubicin-induced growth inhibition of cervical HeLa tumor cells by apoptosis and cell cycle modulation
    Daniele R. Nogueira-Librelotto, Laís E. Scheeren, Letícia B. Macedo, M. Pilar Vinardell, Clarice M.B. Rolim
    Colloids and Surfaces B: Biointerfaces.2020; 190: 110897.     CrossRef
  • Voltammetric detection of anticancer drug Doxorubicin at pencil graphite electrode: A voltammetric study
    S. Deepa, B.E. Kumara Swamy, K. Vasantakumar Pai
    Sensors International.2020; 1: 100033.     CrossRef
  • A surfactant SDS modified carbon paste electrode as an enhanced and effective electrochemical sensor for the determination of doxorubicin and dacarbazine its applications: A voltammetric study
    S. Deepa, B.E. Kumara Swamy, K. Vasantakumar Pai
    Journal of Electroanalytical Chemistry.2020; 879: 114748.     CrossRef
  • Doxorubicin induces an extensive transcriptional and metabolic rewiring in yeast cells
    Hilal Taymaz-Nikerel, Muhammed Erkan Karabekmez, Serpil Eraslan, Betül Kırdar
    Scientific Reports.2018;[Epub]     CrossRef
  • Accelerating Alzheimer’s pathogenesis by GRK5 deficiency via cholinergic dysfunction
    William Z. Suo
    Advances in Alzheimer's Disease.2013; 02(04): 148.     CrossRef
  • Discovery of IL-18 As a Novel Secreted Protein Contributing to Doxorubicin Resistance by Comparative Secretome Analysis of MCF-7 and MCF-7/Dox
    Ling Yao, Yan Zhang, Keying Chen, Xiaofang Hu, Lisa X. Xu, Irina V. Lebedeva
    PLoS ONE.2011; 6(9): e24684.     CrossRef
  • cDNA Microarray Analysis of Differential Gene Expression in Gastric Cancer Cells Sensitive and Resistant to 5-Fluorouracil and Cisplatin
    Myung-Ju Ahn, Young-Do Yoo, Ki-Hwan Lee, Joon-Ik Ahn, Dong-Hyun Yu, Hye-Sook Lee, Ho-Suck Oh, Jung-Hye Choi, Yong-Sung Lee
    Cancer Research and Treatment.2005; 37(1): 54.     CrossRef
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Retinoic Acid Enhances Drug-Induced Cell Death in Anticancer Drug-Resistant Cell Lines
Young Mi Whang, Yeul Hong Kim, Sang Won Shin, Byung Soo Kim, Jun Suk Kim, Young Do Yoo, Sun Hee Park
Cancer Res Treat. 2002;34(3):212-217.   Published online June 30, 2002
DOI: https://doi.org/10.4143/crt.2002.34.3.212
AbstractAbstract PDF
PURPOSE
Retinoids (RA), a group of vitamin A derivatives, is known to be important for regulation of normal cellular growth and differentiation. RA treatment of various cancers resulted in cell growth inhibition and apoptosis. Therefore, the chemotherapeutic and chemopreventative activities of various types of tumor have been examined. Biological actions of RA are mediated through nuclear receptors, including the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In this study, we examined the effect of all-trans-retinoic acid (atRA) as an anticancer drug-sensitiser in cancer cell lines and in its drug- resistant cancer cell lines MATERIALS AND METGODS: Cells were maintained by RPMI 1640 medium containing 10% fetal bovine serum. Cells were treated with 1 micro M atRA for 48 h, then with the desired concentration of anticancer drug for 24 h. Cell viability was measured spectrophotometrically at 540 nm using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Western blot analyses were performed with the desired antibodies.
RESULTS
We investigated if pre-treatment with atRA enhanced the drug-sensitivity of various cancer cell lines to either 5-fluorouracil, adriamycin, or cisplatin. 5-FU (SNU638-F2) and CDDP-resistant cell (SNU638-Cis) lines, from a Korean gastric cancer cell line (SNU638) and the ADR-resistant cells (AD600) was established from a colon cancer cell line (SW620). Treatment of each cell line, with 1 micro M atRA, prior to drug exposure resulted in enhanced cell death in these cell lines. Furthermore, the effect of atRA on growth inhibition, in each drug-resistant cell line, was more obvious than in their parent cell lines. Increased activity of Transglutaminase II (TgaseII) and cleavage of Poly (ADP-ribose) polymerase (PARP) were also observed (western blot analysis CONCLUSION: Based on our data, we suggest that atRA enhances anticancer drug-induced cell death and reverses the drug-sensitivity of the drug-resistant cancer cell lines.
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Retrospective Analysis of the Results of Adjuvant Chemotherapy in Breast Cancer Patients with 10 or More Positive Nodes: Nonrandomized Comparison of Adriamycin-Containing Regimens
Jin Hee Ahn, Haeseoung Bahng, Jeong Gyun Kim, Sung Bae Kim, Sei Hyun Ahn, Hyesook Chang, Jung Shin Lee, Sang Hee Kim, Woo Kun Kim
Cancer Res Treat. 2002;34(2):84-90.   Published online April 30, 2002
DOI: https://doi.org/10.4143/crt.2002.34.2.84
AbstractAbstract PDF
PURPOSE
To evaluate the results of adriamycin-based adjuvant chemotherapy with or without high dose chemotherapy (HDC) with stem cell transplantation (SCT) in breast cancer with 10 or more positive axillary nodes.
MATERIALS AND METHODS
Seventy-one breast cancer patients who had undergone surgery and had 10 or more positive axillary nodes were included in this study held between January 1997 and December 1999. The pathologic and clinical records were reviewed retrospectively.
RESULTS
Twenty-nine patients were treated with adriamycin followed by 8 courses of CMF (group I); 22 patients received 4 courses of adriamycin and 7 patients received 3 courses of adriamycin. Twenty-six patients received median 6 courses of CAF (group II) and 16 patients underwent HDC and autologous SCT (group III). With a median follow-up of 27.1 months, relapses were observed in 24 patients (33.8%) and the 3-year disease-free survival (DFS) rate was 57.1%; group I/II 55.4%, and group III 62.7%. The three-year overall survival (OS) rate was 86.1%; group I/II 83.0%, group III 93.8%. There were no difference in the 3-year DFSs or in the OSs of group I and group II. However, patients who received only 3 courses of the sequential adriamycin in group I showed a significantly poorer 3-year OS than those that received 4 courses of adriamycin (42.9% vs. 95.5%).
CONCLUSION
Our study shows that adriamycin-containing combination chemotherapy is as effective as HDC with SCT in patients with 10 or more positive axillary lymph nodes judging by 3-year DFS and OS, and shows that three courses of adriamycin seems to be inadequate.

Citations

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  • Alternative Therapy and Abnormal Liver Function During Adjuvant Chemotherapy in Breast Cancer Patients
    Jin-Hee Ahn, Sung-Bae Kim, Mi Ra Yun, Jung-Shin Lee, Yoon-Koo Kang, Woo Kun Kim
    Journal of Korean Medical Science.2004; 19(3): 397.     CrossRef
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Transarterial Chemoembolization ( TACE ) for Hepatocellular carcinoma: Comparison of Adriamycin alone vs . Cisplatin alone vs . Adriamycin + Cisplatin
Jung Ae Lee, Keun Chil Park, Bong Seog Kim, Young Soo Do, Duk Lim, Tae Sung Park, Chang Min Kim, Jhin Oh Lee, Taik Koo Yun
J Korean Cancer Assoc. 1998;30(6):1156-1167.
AbstractAbstract PDF
PURPOSE
Although transarterial chemoembolization (TACE) has been widely used for the treatment of unresectable hepatocellular carcinoma, it has not been determined yet which chemotherapeutic agents were best for TACE. To determine the best chemotherapeutic regimen for TACE, we performed a prospective randomized study comparing 3 chemo- therapeutic regimen (adriamycin alone vs. cisplatin alone vs. adriamycin + cisplatin).
MATERIALS AND METHODS
The patients with unresectable hepatocellular carcinoma were eligible for this study and were randomly assigned to three treatment groups (A: adriamycin 30 mg/m(2), B: cisplatin 60 mg/m(2), C: adriamycin 30 mg/m(2) + cisplatin 60 mg/m(2)). The TACE were performed by administering the mixture of lipiodol and the assigned chemotherapeutic drugs through the hepatic artery, followed by embolization with gelfoam powder. The treatment was planned to be repeated every 4 weeks.
RESULTS
After 40 patients (14 in group A, 16 in group B, 10 in group C) entered, the study was stopped prematurely because of serious treatment-related complications including 15% of local complications, 18% of hepatic encephalopathy, and 8% of deaths. Because TACE could result in necrosis without reduction of mass size, the response could not be evaluated by the change of mass size, but by the change of serum alpha-fetoprotein level. Of 25 patients who had elevated serum alpha-fetoprotein and were assessable for response, there were one complete response (CR) and 5 partial responses (PR) out of 10 in group A, 5 PRs out of 10 in group B, and 2 PRs out of 5 in group C. There was no difference in response rates among the 3 treatment groups (p > 0.05). The response rate in patients treated with gelform embolization was higher than patients without embolization (63% (12/19) vs 19% (1/6): p<0.05). The median survival (OS) was 23 weeks for all 40 patients, 15 weeks for group A, 42 weeks for group B and 24 weeks for group C. The difference of OS between group A and B was statistically significant (p=0.02). However, the OS was not associated with any prognostic factors including treatment group in multivariate analysis.
CONCLUSION
Although cisplatin seemed to be more effective in TACE than adriamycin, no firm conclusion could be drawn from this prematurely ended study. However, we could conclude that the TACE with gelform powder is so toxic that it could not be given safely to the patients with unresectable hepatocellular carcinoma
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Results of CHOP-Bleo / CMED Alternating Chemotherapy for Aggressive Non - Hodgkin's Lymphoma
Suk Jin Kim, In Keun Choi, Sang Chul Oh, Jae Hong Seo, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim
J Korean Cancer Assoc. 1998;30(2):350-356.
AbstractAbstract PDF
PURPOSE
To assess the efficacy and toxicity of a new protocol that consists of CHOP- Bleo alternated with a new regimen of Cyclophosphamide, methotrexate, etoposide, and dexamethasone(CMED) for aggressive Non-Hodgkin's Lymphoma(NHL). PATIENTS AND METHODS: Between January 1991 and December 1996, forty-six patients with Ann Arbor stages II-IV aggressive NHL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. All eligible patients were evaluated for response, disease-free survival, and overall survival.
RESULTS
Twenty-two patients(47.8%) achieved a complete response and overall response rate was 83.9%. The range of survival duration was 1-68+months and the median survival time was 42 months. Overall 3-year survival rate was 54%. The range of disease-free survival time was 6-63+months and 3-year disease-free survival rate was 61%. The most common hematologic toxicity was leukopenia and the incidence of severe leukopenia(<1,000/mm3) was 11%. And alopecia(84.8%) was the most common non-hematologic toxicity.
CONCLUSION
The results of CHOP-Bleo/CMED alternating chemotherapy for patients with aggressive Non-Hodgkin's Lymphoma is not superior to other results of previous studies. Therefore further study will be warranted to determine clinical effectiveness of alternating chemotherapy.
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A Phase II Study of AP (Doxorubicin, Cisplatin) Chemotherapy in Patients with Advanced Hepatocellular Carcinoma
Jung Ae Lee, Yoon Koo Kang, Chang Min Kim, Jin Oh Lee, Tae Woong Kang
J Korean Cancer Assoc. 1997;29(1):103-110.
AbstractAbstract PDF
PURPOSE
Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma and is considered to be a highly malignant tumor with poor prognosis. We evaluated the efficacy and toxicities of AP (doxorubicin, cisplatin) comnination chemotherapy in hepatocellular carcinoma.
MATERIALS AND METHODS
Between October 1989 and February 1991, 21 previously untreated patients with advanced hepatocellular carcinoma were entered and treated with AP combination chemotherapy (adriamycin 60 mg/m2, D1 and cisplatin 60 mg/m2, D1, repeated every 3 weeks).
RESULTS
Among 14 evaluable patients, there was no complete response and 5 patients (36%; 95% C.I=10~62%) achieved partial response. The median survival time of all 21 patients was 17 weeks, and 63 weeks in responders (n=5) and 14 weeks in nonresponders (n=16), and the difference in two groups was statistically significant (p<0.05). The median time to progression of 14 evaluable patients was 13 weeks, and 49 weeks in the responders (n=5) and 6 weeks in the nonresponders (n=9), and the difference in two groups was statistically significant (p<0.05). Myelosuppression was minimal and non-hematologic toxicities were gererally mild and well tolerated.
CONCLUSION
The results suggest that the combination chemotherpy of AP seems to be an effective regimen for hepatocellular carcinoma. Further trials are recommended for its true efficacy.
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Effect of Adriamycin in Gastric Chief Cell of Hamster
Byung Chun Kim, Doo Jin Baik, Ho Sam Chung
J Korean Cancer Assoc. 1995;27(2):184-195.
AbstractAbstract PDF
Adriamycin, an anthracyclin antibiotics isolated from Streptomes peucetius var caesius, inhibits the synthesis of DNA and reaction of DNA dependent DNA polymerase and it has been widely used as an anticancer drug in the treatment of sarcoma, leukemia and solid tumors. Adriamycin has little specificity to the normal and tumor cells and cytotoxicity of the normal cells happens to the patients as cardiotoxicity and bone marrow depression. The authors have demonstrated the effect of adriamycin on the chief cells of hamster, histologically observing the morphological changes of the cell by the use of light and electron microscope. The animais treated with 50 mg per kg of adriamycin were sacrificed at 24 and 48 hours after the drug administration. The animals of control group were administered only water for injection. All animals were starved for 12 hours before sacrificing them. A part of stomach specimens were fixed 10% neutral formalin and prepared for hematoxylin and eosin stain and the other part of specimens which were prefixed in 2% glutaraldehyde-2.5% paraformaldehyde prepared with phosphate buffer and then post-fixed in the 1% osmic acid, were dehydrated and embedded in the Epon 812. Ultrathin sections, 600-800A thickness, were made and double stained with uranyl acetate and lead citrate. And these preparations were observed with light microscope and JEM 100cx-II electron microscope. The results were as follows; 1) Most of lining cells of gastric glands were atrophied and lumens were dilated. Numbers of chief cells were decreased and indistinct cellular boundary, vacuolar degenertion, pyknosis and karyolysis were observed in the less basophilic chief cells. In the fundus of glands, parietal cells and mucous neck cells were also found. 2) Cisternae of rough endoplasmic reticulum were decreased, and fragmented and membrane bound ribosome were detached. Fusion of irregularly shaped zymogen granules and numerous autophagic vacuoles including whorled membranous bodies were observed#. Irregular shaped mitochondria and atrophied Golgi complex were also found in the chief cells of the gastric mu- cosa of the adriamycin treated rats. 3) Consequently, it is suggested that adriamycin would induce the degenerative changes of the organelles of chief cells in gastric mucosa of hamsters.
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Studies on the pathological Changes of Human Hepatocellular Carcinomase and Their Cell Lines Induced by Adriamycin
Sang Yong Song, Chul Woo Kim, Woo Ho Kim, Chong Jai Kim, Gyeong Hoon Kang, Yong Il Kim
J Korean Cancer Assoc. 1996;28(4):611-622.
AbstractAbstract PDF
Through our study on morphologic changes occurring in hepatocellular carcinomas (HCCs) treated with trans-arterial chemo-embolization(TAE), we noticed that significant differences of morphologic features and proliferative activity existed between HCCs before and after TAE. In order to investigate whether such changes could be explained by adriamycin, we performed in vitro administration of adriamycin to HCC cell lines. Using three HCC cell lines(SNU-354, SNU-398, SNU-449) established in our hospital, we added 20 ¥ig of adriamycin to the culture dishes at the beginning and doubled the dose every three days. Three cell lines showed different drug susceptibility and SNU-398 was the most sensitive one. Initial morphologic changes were cellular edema and clearing. Damaged cells showed decrease of the size of cytoplasm and the cell processes became thinner and longer. Ultrastructurally, treated cells had small cytoplasm and scanty organelles. Some of the cells contained many lipid vacuoles. Nuclear chromatins demonstrated clumping tendency in the treated cell lines. Adriamycin caused shortening of doubling time in SNU-449, which was statistically not significant. No difference of ploidy was seen between untreated and treated cell lines. In summary, the morphological changes of hepatocellular carcinoma cell line induced by adriamycin in vitro is not exactly the same pattern as that of in vivo chemo-embolization procedure. The above findings suggested that the morphological changes of hepatocellular carcinoma induced by adriamycin chemo-embolization was induced not only by chemotherapeutic drug but also by accompanying environmental factors such as hypoxic insult.
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