• Archives of Pharmacal Research
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• v.17 no.1
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• pp.11-16
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• 1994

Cis-dichlorodiammineplatinum(II)(cisplatin) is one of the most effective antitumor agents currently available for cancer therapy. However, its clinical use has been limited by its severe side effects, especially nephrotoxicity. To evaluate the effect or radical scavengers on cisplatin nephrotoxicity in rats, cisplatin and Vitamin C were given intraperitoneally. Remarkable protective effects of Vitamin C against nephrotoxicity of cisplatin were observed when Vitamin C was administered to rats 1hr before cisplatin injection. hepatotoxicity induced by combination treament of cisplatin and Vitamin C was evaluated by measuring serum glutamic pyruvate transmainase(sGPT) and serum glutamic oxalate transminase(sGOT). Combination treatment did not affect the levels of sGPT and sGOT, and any combination treatment did not induce metallothionein biosynthesis in kidny, Vitamin C which has radical scavenging effect induce metallothionein biosynthesis in kidney. Vitamin C which has radical scavenging effect directly reduced nephrotoxicity of cisplatin in vivo. Thus, it seems that free radical is the cause of cisplatin nepthrotoxicity. Also, combination treatment did not reduce anticancer activity of cisplatin. The present results indicate that Vitamin C, when it is given with cisplatin, may provide protection against cisplatin nephrotoxicity without reducing anticancer activity.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.103-107
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• 1994

Cisplatin is one of the most effective antitumor agents currently available for cancer therapy. However, its clinical use has been limited by its severe side effects, especially nephrotoxicity. Therefore, brazilin, which has a radical scavenging effect, was given intraperitoneally to evaluate the effect on cisplatin nephrotoxicity in rats. Remarkable protective effects against nephrotoxicity of cisplatin were observed when brazilin was administered to rats simultaneously with cisplatin. Hepatotoxicity induced by combination treatment of cisplatin and brazilin was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase. Combination treatment did not affect the levels of sGPT and SGOT, and any combination treatment did not induce metallothionein in kidney. Brazilin which has radical scavenging effect directly reduced nephrotoxicity of wisplatin in vivo. Thus, it seems that nephrotoxicity of cisplatin was caused by free radicals. The present results Indicate that brazilin, when it is given with cisplatin, may provide protection against cisplatin nephrotoxicity in rats.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3023-3028
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• 2013

Objective: Photodynamic therapy (PDT ) is a promising modality for the treatment of various tumors. In order to assist in optimizing treatment, we applied 5-ALA/PDT in combination with low-dose cisplatin to evaluate cytotoxicity in Hela cells. Methods: Antiproliferative effects of 5-ALA/PDT and cisplatin, alone and in combination, were assessed using MTT assay. To examine levels of apoptosis, Hela cells treated with 5-ALA/PDT, and combination treatment were assessed with Annexin-V/PI by flow cytometry. To investigate the molecular mechanisms underlying alterations in cell proliferation and apoptosis, Western blot analysis was conducted to determine the expression of p53, p21, Bax and Bcl-2 proteins. Results: MTT assays indicated that combination treatment obviously decreased the viability of Hela cells compared to individual drug treatment. In addition, it was confirmed that exposure of Hela cells to 5-ALA/PDT in combination with low-dose cisplatin resulted in more apoptosis in vitro. Synergistic anticancer activity was related to upregulation p53 expression and alteration in expression of p21, Bcl-2 and Bax. Conclusion: Our findings suggest that administration of 5-ALA/PDT in combination with the low-dose cisplatin may be an effective and feasible therapy for cervical cancer.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.525-533
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• 1997

Background : No ideal combination chemotherapy for lung cancer has been established even though lots of combination anticancer chemotherapies have been tried. For the combination of anticancer drugs, the interaction of anticancer drugs is very important but unpredictable factor. In this experiment, we designed and tested new experiment to measure the interaction of two anticancer drugs using MIT assay in an attempt to predict clinical response of the combination regimen. Methods : With human lung adenocarcinoma cell line (PC-14), the cytotoxic effect of cisplatin, adriamycin, mitomycin C and etoposide were measured by in vitro chemosensitivity test (MIT assay). The combined cytotoxic effects of combination of two drugs were also measured in every combination of the drug concentrations and analyzed the interaction by Anava analysis of two way factorial design. Results : Four individual drugs showed cytotoxic effects on PC-14 by dose dependent fashion. Comparison of two drug combinations revealed that mitomycin C + cisplatin and adriamycin + cisplatin combinations showed stronger synergistic cytotoxic effects. Conclusion : From this experiment, we suggest two combinations of mitomycin C + cisplatin and adriamycin + cisplatin as chemotherapeutic regimens for unresectable non-small cell lung cancer. Furthermore, this experimental design could be applied to other types of cancer requiring combination anticancer chemotherapy.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.44-49
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• 1993

cis-Dichlorodiammineplatinum(cisplatin) is one of the most effective antitumor agents currently available for cancer therapy. However, its clinical use has been limited by its severe side effects, especially nephrotoxicity. So, to evaluate the effects of 2(3)-tert-butyl-4-hydroxyanisole(BHA) on cisplatin nephrotoxicity in rats, both compounds were given intraperitoneally. Remarkable protective effects of BHA against nephrotoxicity of cisplatin were observed when BHA was administered to rats 1hr after cisplatin injection. On the other hand pretreatment with BHA 1hr prior to cisplatin did not reduce weight loss, blood urea nitrogen and creatinine levels. Hepatotoxicity induced by combination treatment of cisplatin and BHA was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase. Combination treatment did not affect the levels of SGPT and sGOT except 1hr pretreatment. The present results indicate that BHA may provide protection against cisplatin nephrotoxicity, when it is given 1hr after cisplatin.

• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.125-131
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• 1998

Cisplatin is one of the most effective antitumor agents currently available for cancer chemotherapy. However its clinical use has been limited by its severe side effects, especially nephrotoxicity. To evaluate the effect of schizandrin, one of radical scavengers and constituents of Schizandra chimensis, cisplatin and schizandrin were given intraperitoneally. Protective effect of schizandrin against nephrotoxicity of cisplatin was observed when schizandrin was administerd to rats 1,24 hr after cisplatin injection. Hepatotoxicity induced by combination treatment of cisplatin and schizandrin was evaluated by measuring sGPT and sGOT. Combination treatment did not affect the levels of sGPT and sGOT. The present result indicate that schizandrin when it is given after cisplatin, may provide protection against cisplatin nephrotoxicity without hepatotoxicity.

• The Journal of the Korea Contents Association
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• v.20 no.6
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• pp.124-130
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• 2020

The present study investigated the anti-proliferate and anti-invasive of Phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase (MMP-2) and MMP-9 activities of combined treatment with cisplatin and ethyl acetate fractions of Paeonia japonica. Cell Proliferation was detected by the MTS assay and the activity and mRNA expression of MMP-2/-9 were examined by zymography and RT-PCR. As results, cisplatin or p. japonica treatment of YD-10B cells resulted in a dose-dependent inhibition of cell growth. Also, the viability of YD-10B cells treated with combination of 200 μM cisplatin and 50 ㎍/ml p. japonica was inhibited to 50% in compared with the cisplatin alone. In PMA-treated YD-10B cells, co-treatment of 200 μM cisplatin with 50 ㎍/ml p. japonica significantly inhibited mRNA expression and protein activation of MMP-2/-9. Therefore, This study suggest that the combination treatment of cisplatin and p. japonica potentiates a promising anti-invasive agent and has more potential anti-cancer drug for oral cancer therapy than cisplatin alone.

• Radiation Oncology Journal
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• v.24 no.4
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• pp.272-279
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• 2006

$\underline{Purpose}$: This study investigated the influence of irradiation and cisplatin on PrxI & PrxII expression and on their survival rates (SR) in SK-N-BE2C and Rat2 cell lines. $\underline{Materials\;and\;Methods}$: The amount of PrxI & PrxII production with or without N-acetyl-L-cysteine (NAC) pretreatment was studied using a western blot after 20 Gy irradiation to determine the degree of inhibition of ROS accumulation. In addition, the amount of PrxI & PrxII production after cisplatin and after combination with cisplatin and 20 Gy irradiation was studied. The SRs of the cell lines in SK-N-BE2C and Rat 2 cells, applied with 20 Gy irradiation only, with various concentrations of cisplatin and with the combination of both, were studied. The 20 Gy irradiation-only group and the combination group were each subdivided according to NAC pretreatment, and corresponding SRs were observed at 2, 6, 12 and 48 hours after treatment. $\underline{Results}$: Compared with the control group, the amount of PrxI in SK-N-BE2C increased up to 60 minutes after irradiation and slightly increased after irradiation with NAC pretreatment 60 minutes. It did not increase in Rat2 after irradiation regardless of NAC pretreatment. PrxII in SK-N-BE2C and Rat2 was not increased after irradiation regardless of NAC pretreatment. The amounts of PrxI and PrxII in SK-N-BE2C and Rat2 were not increased either with the cisplatin-only treatment or the combination treatment with cisplatin and irradiation. SRs of irradiation group with or without NAC pretreatment and the combination group with or without NAC pretreatment were compared with each other in SK-N-BE2C and Rat2. SR was significantly high for the group with increased amount of PrxI, NAC pretreatment and lower the cisplatin concentration. SR of the group in SK-N-BE2C which had irradiation with NAC pretreatment tended to be slightly higher than the group who had irradiation without NAC pretreatment. SR of the group in Rat2 which had irradiation with NAC pretreatment was significantly higher than that the group which had irradiation without NAC pretreatment. Compared to the combination group, the irradiation-only group revealed statistically significant SR decrease with the maximal difference at 12 hours. However, at 48 hours the SR of the combination group was significantly lower than the irradiation-only group. $\underline{Conclusion}$: PrxI is suggested to be an antioxidant enzyme because the amount of PrxI was increased by irradiation but decreased pretreatment NAC, a known antioxidants. Furthermore, cisplatin may inhibit PrxI production which may lead to increase cytotoxicity of irradiation. The expression of PrxI may play an important role in cytotoxicity mechanism caused by irradiation and cisplatin.

• Korean Journal of Clinical Pharmacy
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• v.12 no.1
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• pp.1-6
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• 2002

Central Cancer Registry of Korean National Cancer Center in 1999 reported that mortality from lung cancer is higher than mortality from stomach cancer or hepatocellular carcinoma in Korean male. Lung cancer is classified into small cell cancer and non-small cell lung cancer (NSCLC), and NSCLC patients account for $70\%$ of the whole lung cancer patients. The purpose of this study was to evaluate the efficacy and toxicity of docetaxel and cisplatin combination in Korean patients with NSCLC. All patients who had received the combination therapy of docetaxel and cisplatin for histologically confirmed NSCLC in Ajou University Hospital between 2000. $2\~2001$. 4 were retrospectively evaluated for the responses and toxicities of that combination therapy. Nineteen patients were treated with docetaxel 75 $mg/m^2$ on Day 1 and cisplatin 25 $mg/m^2$ on Day 1-3 every 4 weeks. The response for combination regimen was evaluated by CT scans after 2 or 3 cycles of treatments. Seventeen patients were evaluated for the responses and the 19 patients far the toxicities. Among the 19 patients (14 men and 5 women), there were one patient $(5.3\%)$ with stage I disease, 4 patients $(21.1\%)$ with stage III disease, and 14 patients $(73.1\%)$ with stage IV disease. Of the 17 patients who were evaluable for response, complete response (CR) was not observed in any patient while partial response (PR) was observed in 5 patients $(29.4\%)$. The overall response rate (CR+PR) was $29.4\%$. Stable disease (SD) was observed in 11 patients $(64.7\%)$ and progressive disease (PD) in 1 patient $(5.9\%)$. The toxicities were graded by NCI (National Cancer Institute) Common Toxicity Criteria for the evaluable 70 cycles. Grade 3 or 4 neutropenia occurred in 53 cycles $(76\%)$. Four patients were hospitalized due to febrile neutropenia. The combination chemotherapy of docetaxel and cisplatin was effective as NSCLC treatments, however, the regimen must be administered carefully due to its hematological side effects.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.237-242
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• 2013

Cervical cancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic and apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We demonstrate here, that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines. Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects. The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptotic Bax proteins, as well as down-regulation of the anti-apoptotic Bcl-2, Bcl-$X_L$ proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines.