• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4853-4858
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• 2013

Objectives: To investigate whether hypoxia has an effect on regulation of multidrug resistance (MDR) to chemotherapeutic drugs in laryngeal carcinoma cells and explore the role of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$). Methods: Laryngeal cancer cells were cultured under normoxic and hypoxic conditions. The sensitivity of the cells to multiple drugs and levels of apoptosis induced by paclitaxel were determined by MTT assay and annexin-V/propidium iodide staining analysis, respectively. HIF-$1{\alpha}$ expression was blocked by RNA interference. The expression of HIF-$1{\alpha}$ gene was detected by real-time quantitative RT-PCR and Western blotting. The value of fluorescence intensity of intracellular adriamycin accumulation and retention in cells was evaluated by flow cytometry. Results: The sensitivity to multiple chemotherapy agents and induction of apoptosis by paclitaxel could be reduced by hypoxia (P<0.05). A the same time, the adriamycin releasing index of cells was increased (P<0.05). However, resistance acquisition subject to hypoxia in vitro was suppressed by down-regulating HIF-$1{\alpha}$ expression. Conclusion: HIF-$1{\alpha}$ could be considered as a key regulator for mediating hypoxia-induced MDR in laryngeal cancer cells via inhibition of drug-induced apoptosis and decrease in intracellular drug accumulation.

• Clinical and Experimental Pediatrics
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• v.60 no.11
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• pp.365-372
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• 2017

Purpose: The mechanism for the pathogenesis of adriamycin (ADR)-induced cardiomyopathy is not yet known. Different hypotheses include the production of free radicals, an interaction between ADR and nuclear components, and a disruption in cardiac-specific gene expression. Apoptosis has also been proposed as being involved in cardiac dysfunction. The purpose of this study was to determine if apoptosis might play a role in ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were separated into 2 groups: the control group (C group) and the experimental group (ADR 5 mg/wk for 3 weeks through intraperitoneal injections; A group). Echocardiographic images were obtained at week 3. Changes in caspase-3, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, brain natriuretic peptide (BNP), troponin I, collagen 1, and collagen 3 protein expression from the left ventricle tissues of C and A group rats were determined by Western blot. Results: Ascites and heart failure as well as left ventricular hypertrophy were noted in the A group. Ejection fraction and shortening fraction were significantly lower in the A group by echocardiography. The expression of caspase-3, Bax, IL-6, BNP, collagen 1, and collagen 3 were significantly higher in the A group as compared with the C group. Protein expression of Bcl-2 decreased significantly in the A group compared with the C group. Conclusion: ADR induced an upregulation of caspase-3, Bax, IL-6, and collagen, as well as a depression in Bcl-2. Thus, apoptosis and fibrosis may play an important role in ADR-induced cardiomyopathy.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.331-335
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• 1993

From January 1981 to December 1991, forty patients with localized advanced carcinoma of the pancreas were treated at the Department of Therapeutic Radiology, Seoul National University Hospital. The treatment protocol consisted of two split course external radiation therapy with each 2000 cGy over two weeks separated by two week rest period. Intravenous 5-fluorouracil (5-FU) was administered on the first three days of each radiotherapy course. Twenty three of these patients were treated by maintenance 5-FU or FAM (5-FU, adriamycin, mitomycin) chemotherapy. Median survival was 9 months and the 2-year survival rate was $10.0\%.$ Good prognostic indicators were good performance status, palliative bypass surgery and tumor located in the head of pancreas.

• Toxicological Research
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• v.8 no.2
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• pp.171-177
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• 1992

To investigate a short term screening method for carcinogenic quinone compounds, 8-hydroxydeoxyguanosine (8-OHdG), an oxidative DNA damage, was determined in the kidney and liver DNA isolated from Sprague-Dawley rats after i.p.injection of 7 mg/kg adriamycin (AM), 7mg/kg tetrahydropyranyladriamycin (THP), and 10mg/kg daunomycin (DM) by HPLC-electrochemical detector system. 8-OHdG was also determined from rat hepatocvtes and calf thymus DNA exposed to AM, DM and THP. When rats were treated with DM and THP, 8-OHdG was significantly increased in the kidney compared to control group, and remained at high level (7.9~9.0, 8-OHdG/dG${\times}10^4$)at the end of experiments (48hr after treatment). 8-OHdG level in cultured hepatocyte exposed to AM, DM and THP was 1.5~2 fold higher than control at all time points. (1,2,3,4hr after treatment). From calf thymus DNA exposed to AM, DM and THP, 8-OHdG was 2.5 fold higher than of control. These results suggest that quantitation of 8-OHdG may provide a useful marker for identifying target organ in oxidative chemical carcinogenesis and for short term screening of free radical generating carcinogens.

• Journal of Yeungnam Medical Science
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• v.2 no.1
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• pp.259-264
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• 1985

Neuroblastoma is the most common extracranial solid tumor of childhood which presents various clinical symptoms depending on the primary and metastatic sites. However, it has been rarely reported that sudden onset of blindness was the chief complaint of neuroblastoma. A four years old boy was admitted to the Yeungnam University Hospital with the chief complaint of a sudden onset of blindness due to a distant metastasis of abdominal neuroblastoma to the sphenoid sinus. On admission, both side pupils were dilated without light reflex, fundoscopy showed pale optic disk, electroretinogram was subnormal and visual evoked potential showed no response. The liver was palpable in $3{\frac{1}{2}}$ finger breadth from the right costal margin and adult fist sized mass was palpable in the right flank. Skull X-ray showed destructed sphenoid bone and clinoid process and brain CT scan showed tumor mass in the sphenoid sinus and left orbit. Ultrasonogram and CT scan of the abdomen showed large tumor masses around the right kidney and para-aortic and retropancreatic lymph node. IVP showed displaced right calyceal system with preserved contour. Left supraclavicular lymph node which appeared after admission was biopsied and it showed poorly differentiated neuroblasts. He was treated according to the multiagent chemotherapy schedule for stage IV neuroblastoma patient of children's cancer study group. Abdominal tumor masses and sphenoid sinus mass were markedly reduced after 2 courses of the combination chemotherapy of cyclophosphamide, vincristine, DTIC, adriamycin and VM-26. Eventhough the blindness was not improved, the patient has been in good clinical condition.

• Radiation Oncology Journal
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• v.4 no.2
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• pp.141-145
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• 1986

From January,1981 to December,1985,22 patients with locally unresectable carcinoma of the pancreas were treated in the Department of Therapeutic Radiology, Seoul National University Hospital. Radiation was given in two spl it courses; each consisting of 2000 cGy over two weeks sepatated by two-week rest period. 5-FU was administered on the first three days of each radiation therapy course. FAM (5-fluorouracil, adriamycin, mitomycin) was administered for maintenance chemotherapy. For pain control, complete relief was obtained in $22\% (4/18)$ of patients and partial relief in 39% (7/18). Median survival was 31 weeks. Pretreatment performance status was the only statistically significant prognostic factor.

• Journal of Food Hygiene and Safety
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• v.17 no.2
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• pp.106-116
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• 2002

The 70% ethanol extract of Alpinia officinarum and its major flavonoid, galangin showed strong antioxidative effect on the lipid peroxidation of ethyl linolate with Fenton's reagent and free radical scavenging effect to DPPH radical generation. However, they did not reveal any pro-oxidant effect on bleomycin-Fe(III) dependent DNA degradation. They also showed the protective effect against $H_2O$$_2$, KO$_2$ or UV-induced cytotoxicity in mammalian cells. They also showed the suppressive effect of DNA damage induced by $H_2O$$_2$ or KO$_2$ with dose-dependent manner in single cell gel electrophoresis(SCGE) assay. On the other hand, they have an anticlastogenic effect against adriamycin-induced micronucleated reticulocyte in peripheral blood of mice. These results suggest that the mechanism of inhibition by 70% ethanol extract of Alpinia officinarum and galangin against reactive oxygen species (ROS)-induced genotoxicity or cytotoxicity is due, at least partly, to their antioxidative and free radical scavenging properties without pro-oxidant effect. All these results indicate that 70% ethanol extract of Alpinia officinarum and galangin may be useful for protection against ROS-induced cytotoxicity and DNA damage.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.478-487
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• 2000

This study was carried out to find new anti-tumor agent producing microbe and to characterize the anti-tumor agent produced from the microbe. Purified compound that has a high cytotoxicity against tumor cell-lines could be obtained from the broth culture filtrates of Streptomyces sp.409 strain isolated from soil in Korea. The in vitro cytotoxicity the in vivo evaluation of acute toxicity the safety assessment of the anti-tumor compounds and the taxonomic characteristics of the anti-tumor agent were measured. The antitumor compound 1 and 2 were obtained from the broth culture filtrates of Streptomyces sp.409 strain. The cytotoxicity of the compound 1 against tumor cell-line P388D$_1$ showed almost 4.5 times higher than that of adriamycin. However in the cytotoxicity against normal cell line Vero E6, adriamycin showed adversely 4 times higher than the compound 1 ($IC_{50}$/ value: 228.7 $\mu\textrm{g}$/$m\ell$). In comparison study with compound 1 and compound 2 in the in vitro cytotoxin productivity against tumor cell lines, $IC_{50}$/ value of the compound 1 was 0.25 $\mu\textrm{g}$/$m\ell$ in tumor cell line P388D$_1$and 0.53 $\mu\textrm{g}$/$m\ell$ in tumor cell-line L1210, and that of the compound 2 was 7.18 $\mu\textrm{g}$/$m\ell$ and 35.71 $\mu\textrm{g}$/$m\ell$, respectively; LD$_{50}$ value of the compound 1 in the in vivo acute toxicity in mice was 22.62 $\mu\textrm{g}$/kg body weight. These results suggest that compound 1 purified from Streptomyces sp. 409 has anti-tumor activity and will be developed as an anti-tumor drug.g.

• Journal of Chest Surgery
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• v.56 no.5
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• pp.295-303
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• 2023

Background: The use of Adriamycin (ADR), also known as doxorubicin, as a chemotherapy agent is limited by its detrimental adverse effects, especially cardiotoxicity. Recent studies have emphasized the crucial role of angiotensin II (Ang-II) in the development of ADR-induced cardiomyopathy. This study aimed to explore the potential cardioprotective effects of losartan in a rat model of ADR-induced cardiomyopathy. Methods: Male Sprague-Dawley rats were randomly divided into 3 groups: a control group (group C), an ADR-treated group (ADR 5 mg/kg/wk for 3 weeks via intraperitoneal injections; group A), and co-treatment of ADR with losartan group (same dose of ADR and losartan; 10 mg/kg/day per oral for 3 weeks; group L). Western blot analysis was conducted to demonstrate changes in brain natriuretic peptide, collagen 1, tumor necrosis factor (TNF)-α, interleukin-6, matrix metalloproteinase (MMP)-2, B-cell leukemia/lymphoma (Bcl)-2, Bcl-2-associated X (Bax), and caspase-3 protein expression levels in left ventricular (LV) tissues from each group. Results: Losartan administration reduced LV hypertrophy, collagen content, and the expression of pro-inflammatory factors TNF-α and MMP-2 in LV tissue. In addition, losartan led to a decrease in the expression of the pro-apoptotic proteins Bax and caspase-3 and an increase in the expression of the anti-apoptotic protein Bcl-2. Moreover, losartan treatment induced a reduction in the apoptotic area compared to group A. Conclusion: In an ADR-induced cardiomyopathy rat model, co-administration of ADR with losartan presented cardioprotective effects by attenuating LV hypertrophy, pro-inflammatory factors, and apoptosis in LV tissue.

• Journal of Nutrition and Health
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• v.24 no.3
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• pp.166-178
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• 1991

This present study was designed to evaluate whether supplementaion of dietary coenzyme $Q_{10}$ protects the lipid peroxidation damage in adriamycin (ADR)-treated rats. Two experiments were conducted in this study. Experiment I was undertaken under the condition of simultaneous administration of ADR and coenzyme $Q_{10}$ for 4 weeks. Experiment 2 was undertaken under the same condition as experiment I after feeding the experimetal diets alone without administration of ADR for 4 weeks. Results obtained from the present study were as follows. Lipid peroxide value of plasma and heart mitochondria was elevated by ADR treatment. but decreased according to dietary coenzyme $Q_{10}$ supplementation. Pretreatment with dietary coenzyme $Q_{10}$ was more efficient in reducing ADR-induced lipid peroxide value. The simultaneous use of ADR and coenzyme $Q_{10}$ enhanced the heart glutathione peroxidase (GSH-Px) activity. particularly at higher level of coenzyme $Q_{10.}$ The change of superoxide dismutase(SOD) activity was similar to that of GSH-Px activity. In case of pretreatment with coenzyme $Q_{10, }$ these enzyme activities were more enhanced by dietary coenzyme $Q_{10.}$ However, there was little difference in catalase activity.