• BMB Reports
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• v.38 no.5
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• pp.619-623
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• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• BMB Reports
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• v.50 no.8
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• pp.417-422
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• 2017

Cisplatin is the most effective and widely used chemotherapeutic agent for many types of cancer. Unfortunately, its clinical use is limited by its adverse effects, notably bone marrow suppression leading to abnormal hematopoiesis. We previously revealed that neuropeptide Y (NPY) is responsible for the maintenance of hematopoietic stem cell (HSC) function by protecting the sympathetic nervous system (SNS) fibers survival from chemotherapy-induced bone marrow impairment. Here, we show the NPY-mediated protective effect against bone marrow dysfunction due to cisplatin in an ovarian cancer mouse model. During chemotherapy, NPY mitigates reduction in HSC abundance and destruction of SNS fibers in the bone marrow without blocking the anticancer efficacy of cisplatin, and it results in the restoration of blood cells and amelioration of sensory neuropathy. Therefore, these results suggest that NPY can be used as a potentially effective agent to improve bone marrow dysfunction during cisplatin-based cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10045-10051
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• 2015

Chemotherapy is a major therapeutic approach for malignant neoplasms; however, due to the most common adverse events of nausea and vomiting, scheduled chemotherapeutic programs may be impeded or even interrupted, which severely impairs the efficacy. Aprepitants, 5-HT3 antagonists and dexamethasone are primary drugs used to prevent chemotherapy-induced nausea and vomiting (CINV). These drugs have excellent efficacy for control of acute vomiting but are relatively ineffective for delayed vomiting. Aprepitant may remedy this deficiency. Substance P was discovered in the 1930s and its association with vomiting was confirmed in the 1950s. This was followed by a period of non-peptide neurokinin-1 (NK-1) receptor antagonist synthesis and investigation in preclinical studies and clinical trials (phases I, II and III). The FDA granted permission for the clinical chemotherapeutic use of aprepitant in 2003. At present, the combined use of aprepitant, 5-HT3 antagonists and dexamethasone satisfactorily controls vomiting but not nausea. Therefore, new therapeutic approaches and drugs are still needed.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3057-3062
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• 2013

Background: Selecting chemotherapy regimens guided by chemosensitivity tests can provide individualized therapies for cancer patients. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, inner salt (MTS) assay is one in vitro assay which has become widely used to evaluate the sensitivity to anticancer agents. The aim of this study was to evaluate the clinical applicability and accuracy of MTS assay for predicting chemotherapeutic response in unresectable NSCLC patients. Methods: Cancer cells were isolated from malignant pleural effusions of patients by density gradient centrifugation, and their sensitivity to eight chemotherapeutic agents was examined by MTS assay and compared with clinical response. Results: A total of 37 patients participated in this study, and MTS assay produced results successfully in 34 patients (91.9%). The sensitivity rates ranged from 8.8% to 88.2%. Twenty-four of 34 patients who received chemotherapy were evaluated for in vitro-in vivo response analysis. The correlation between in vitro chemosensitivity result and in vivo response was highly significant (P=0.003), and the total predictive accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for MTS assay were 87.5%, 94.1%, 71.4%, 88.9%, and 83.3%, respectively. The in vitro sensitivity for CDDP also showed a significant correlation with in vivo response (P=0.018, r=0.522). Conclusion: MTS assay is a preferable in vitro chemosensitivity assay that could be use to predict the response to chemotherapy and select the appropriate chemotherapy regimens for unresectable NSCLC patients, which could greatly improve therapeutic efficacy and reduce unnecessary adverse effects.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5191-5197
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• 2015

A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

• Parasites, Hosts and Diseases
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• v.25 no.2
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• pp.199-208
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• 1987

The chemotherapeutic efficacy of trimethoprim-sulfamethoxazole ($Bactrim^{\circledR}$) in mice experimentally infected with Toxoplasma gcndii was evaluated. The average survival days and survival rate of mice infected intraperitoneally with $1{\times}10^5$ trophozoites and treated with $Bactrim^{\circledR}$ were compared with those of untreated group. The hematologic findings of blood samples of experimental mice were observed for comparison of side elects between $Bactrim^{\circledR}$ and pyrimethamine ($Daraprim^{\circledR}$), the latter of which has been one of the favorable drugs for the treatment of toxoplasmosis. The results are summarized as follows: 1. $Bactrim^{\circledR}$ showed a strong evidence of potent anti-Toxoplasma activity. The survival rate of mice administered with 24 mg of $Bactrim^{\circledR}$ per mouse per day for 7 days, was 83.3%, and the rate was increased to 100% in mice administered with two-fold concentrated dose of the drug. 2. The average numbers of white blood cells (W.B.C.) in the mouse groups treated with $Bactrim^{\circledR}$ or $Daraprim^{\circledR}$ were more increased than those only infected with T. gondii. The mice treated with $Daraprim^{\circledR}$ however, showed remarkably decreased numbers of W.B.C. as compared with those treated with $Bactrim^{\circledR}$ . 3. The average numbers of red blood cells (R.B.C.) and platelets both in the drug-treated and untreated T. gondii-infected mice were decreased as compared with normal mice. The numbers of R. B. C. in $Daraprim^{\circledR}-treated$ mice, however, were more decreased than in $Bactrim^{\circledR}-treated$ mice. 4. The average levels of hemoglobin both in the drug.treated and untreated T. gondii-infected mice were decreased, compared with normal mice. But there was no difference in the levels of hemoglobin between $Bactrim^{\circledR}$ and $Daraprim^{\circledR}-treated$ groups. In conclusion, trimethoprim.sulfamethoxasole ($Bactrim^{\circledR}$) was proven to be effective and safe for the treatment of murine toxoplasmosis. The efficacy was comparable with pyrimethamine ($Daraprim^{\circledR}$), but bone marrow depression was less severe with $Bactrim^{\circledR}$ treatment.

• Korean Journal of Pharmacognosy
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• v.35 no.2 s.137
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• pp.122-127
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• 2004

This study was conducted to investigate the safety and efficacy of an oriental herbal composition, Kamihonghwatang(KH-19), for the reduction of the side effects of chemotherapeutic drug. KH-19 prevented the reduction of white blood cells including lymphocytes, monocytes and eosinophiles in C57BL/6 mice injected with fluorouracil, a commonly used anticancer drug. KH-19 also prevented the reduction of cell densities in bone marrow and spleen of fluorouracil-injected mice. To evaluate the safety of KH-19, single-dose toxicity test was conducted using SD rats. No dead animal was found and the minimum lethal dose of KH-19 was more than 5000 mg/kg.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.59-65
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• 2011

Nanotechnology for cancer therapy is playing a pivotal role in dramatically improving current approaches to cancer detection, diagnosis, and therapy while reducing toxic side effects associated with previous cancer therapy. A widespread understanding of these new technologies will lead to develop the more refined design of optimized nanoparticles with improved selectivity, efficacy and safety in the clinical practice of oncology. This review provides an integrated overview of applications and advances of nanotechnology in cancer therapy, based on molecular diagnostics, treatment, monitoring, target drug delivery, approved nanoparticle-based chemotherapeutic agents, and current clinical trials in the development of nanomedicine and ultimately personalized medicine.

• Toxicological Research
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• v.33 no.1
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• pp.1-5
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• 2017

Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, controls the expression of genes encoding cytoprotective proteins, including antioxidant enzymes that combat oxidative and electrophilic stress to maintain redox homeostasis. However, recent studies demonstrated that, in cancer, aberrant activation of Nrf2 by epigenetic alterations promotes high expression of cytoprotective proteins, which can decrease the efficacy of anticancer drugs used for chemotherapy. In this review, we summarize recent findings regarding the relationship between oxidative stress, Nrf2, epigenetic modification, and anticancer drug resistance, which should aid in development of new strategies to improve chemotherapeutic efficacy.

• Korean Journal of Veterinary Research
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• v.54 no.2
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• pp.117-120
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• 2014

Chemotherapeutic treatment is still the foundation of tick control programs. This study investigated the acaricidal efficacy of cypermethrin alone and in combination with chlorpyrifos against Haemaphysalis (H.) longicornis. Unfed larval ticks were exposed to 0.1, 1.0, and 10 mg/mL cypermethrin for 60 min, after which the acaricidal efficacy was examined based on tick mortality. All compounds showed similar suppression curves, with the best control being achieved by cypermethrin and chlorpyrifos (1 : 1 ratio) at 10 mg/mL. Effective cypermethrin concentrations for tick control were two to seven times higher than the recommended doses, indicating resistance by H. longicornis.