• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.311-314
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• 2007

Paclitaxel (PTX) is an antineoplastic agent approved for the treatment of ovarian and breast carcinomas. However, the use of paclitaxel as an anticancer drug is limited by its extremely poor water solubility (below $0.3\;{\mu}g/mL$). Furthermore, it has very low bioavailability when administered orally because paclitaxel is a substrate of P-glycoprotein (P-gp) efflux pump. In this study, buccal delivery of PTX was investigated as one of the alternatives for PTX delivery. Ethanol and glyceryl monooleate (GMO) were selected as permeation enhancing agents to increase solubility and permeation across buccal mucosa of PTX. At the different concentrations of ethanol solution ($30{\sim}70\;w/w\;%$), PTX permeation was studied, followed effects of GMO in the concentration range of $2.5{\sim}25%$ with ethanol vesicle. The transbuccal ability of PTX was evaluated in vitro using Franz diffusion cells mounted with rabbit buccal mucosa. As a result, incorporation of PTX into ethanol vesicle with GMO significantly enhanced the PTX permeation in rabbit buccal mucosa. Particularly, the mixtures of ethanol:water:GMO at the ratio of 50:47.5:2.5 showed the most excellent enhancing ability. The results showed a promising possibility for buccal delivery of PTX.

• Journal of Pharmaceutical Investigation
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• v.34 no.2
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• pp.125-130
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• 2004

Paclitaxel is an effective antineoplastic drug for various cancers especially ovarian and breast cancer. This study is to find the optimum condition for the preparation of nanoemulsions and to improve the stability and loading amount of paclitaxel in nanoemulsions. Nanoemulsions were prepared by modified spontaneous emulsification solvent diffusion method. It was composed of phosphatidylcholine:cholesterol:1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-[Metoxy (Polyethylene glycol)-2000]:paclitaxel at a weight ratio of 5:3:1:1 and the Tween 80 as a surfactant. The particle size and the shape of nanoemulsions were measured by particle analyzer and SEM, respectively. The loading amount of paclitaxel in nanoemulsion was measured by UV-visible spectroscopy at 227 nm. The particle sizes were $80{\sim}120\;nm$ and the loading efficiency of paclitaxel was $8{\sim}39%$. The optimum conditions for the preparation of nanoemulsions were 8% w/w phospholipid, 16% w/v Tween 80 and 2% w/w paclitaxel, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6513-6519
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• 2015

Background: Recent attention on chemotherapeutic intervention against cancer has been focused on discovering and developing phytochemicals as anticancer agents with improved efficacy, low drug resistance and toxicity, low cost and limited adverse side effects. In this study, we investigated the effects of Curcuma C20-dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical cancer cell lines. Materials and Methods: Antiproliferative, apoptosis induction, and cell cycle arrest activities of Curcuma C20-dialdehyde were determined by WST cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium iodide (PI) staining and PI staining, respectively. Results: Curcuma C20 dialdehyde suppressed the proliferation of HCT116, HT29 and HeLa cells, with IC50 values of $65.4{\pm}1.74{\mu}g/ml$, $58.4{\pm}5.20{\mu}g/ml$ and $72.0{\pm}0.03{\mu}g/ml$, respectively, with 72 h exposure. Flow cytometric analysis revealed that percentages of early apoptotic cells increased in a dose-dependent manner upon exposure to Curcuma C20-dialdehyde. Furthermore, exposure to lower concentrations of this compound significantly induced cell cycle arrest at G1 phase for both HCT116 and HT29 cells, while higher concentrations increased sub-G1 populations. However, the concentrations used in this study could not induce cell cycle arrest but rather induced apoptotic cell death in HeLa cells. Conclusions: Our findings suggest that the phytochemical Curcuma C20-dialdehyde may be a potential antineoplastic agent for colon and cervical cancer chemotherapy and/or chemoprevention. Further studies are needed to characterize the drug target or mode of action of the Curcuma C20-dialdehyde as an anticancer agent.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.225-232
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• 2013

Delayed gastrointestinal (GI) motility is frequent adverse effect associated with chemotherapy, and induced by serotonin releases from enterochromaffin cells. Ijintang-gamibang (IJG) is a digestive polyherbal formula has been traditionally used in Korea and consisted of 8 types of medicinal herbs. This study was conducted to determine whether or not IJG aqueous extracts can prevent delayed GI motility induced by the antineoplastic drug cisplatin chronically administered, once per week for five consecutive weeks (2 mg/kg). 200, 100 and 50 mg/kg of IJG extracts were orally administered, once a day for 14 days from fourth cisplatin treatment, and the changes in body weight gain, fecal parameters, gastrointestinal transit ratio and histopathology were observed. In addition, pylorus gastrin and serotonin contents were also measured with immunohistochemical observations of enterochromaffin cells contains gastrin and serotonin, as compared with ondansetron, a serotonin 5-HT3 receptor antagonist, 1 mg/kg. Cisplatin treatment related body weight decreases, delayed GI motility, decreases of fecal water contents were significantly and dose-dependently inhibited by oral treatment of IJG extracts, and they also inhibited the pylorus gastrin and serotonin changes induced by cisplatin treatment. The overall effects of IJG 100 mg/kg were similar to that of ondansetron 1 mg/kg. The present results supported that IJG aqueous extracts have favorable ameliorating effect on the delayed GI motility induced by chemotheraphy, modulated the GI enterochromaffin cells, serotonin and gastrin-producing cells with antioxidant effects. This effect of IJG may help improve accompanying gastrointestinal symptoms by chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2287-2290
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• 2014

Background: In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro. Materials and Methods: Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTTbased cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel. Results: Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the antineoplastic properties of paclitaxel was apparent under the tested conditions. Conclusions: Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.125-128
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• 2007

Docetaxel is a taxoid antineoplastic drug, which is widely used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC). Among the adverse dermatological reactions, nail disorders such as bending, onycholysis, hypoor hyperpigmentation are rare. We report a case of a 62-year-old male with advanced NSCLC (cT4N3M1, stage IV), who developed purulent discharge and onycholysis in the nail of all his fingers and the left great toe after five courses of anti-neoplastic chemotherapy, which included docetaxel (cumulative dose: $370mg/m^2$, 590 mg). Seven days after the final session of chemotherapy, the patient had become aware of discoloration and swelling of the nail beds with out pain. Three days later, greenish-yellow purulent discharge oozed out from the involved nails. Microbiologic studies revealed Pseudomonas aeruginosa. Intravenous and topical antibiotics (mupirocin) were applied. After 2 weeks, regrown nails were observed and the onycholysis had improved.

• Applied Microscopy
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• v.28 no.2
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• pp.225-236
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• 1998

Adriamycin is a one of anthracyclin antibiotics isolated from the culture media of Streptomyces peucetius var casius. The formation of reactive oxygen metabolite by redox cycling during the metabolism and the inhibition of DNA synthesis results in antineoplastic effects of adriamycin. The authors have demonstrated the effects of SOD(superoxide dismutase) or DMTU (dimethyl thiourea), which are used as an antioxidant, on the ultrastructural changes of the gastric chief cells after the administration of adriamycin in the rat. Adriamycin (30 mg/kg) was administered intraperitoneally to the Sprague-Dawley rats weighing about 220 gm and SOD (15000 unit/kg) or DMTU (500 mg/kg) were administered intraperitoneally to the rats 30 minutes after the administration of adriamycin. The gastric chief cells 24, 48 and 72 hours after the administration of adriamycin were observed with Hitachi-600 electron microscope. The results were as follows. 1. SOD or DMTU alone did not affect the ultra structures of the gastric chief cells in the rat. 2. Dilation, sacculation and segmentation of the cisternae of rough endoplasmic reticulum, dilation of the saccules of Golgi complex and dilated mitochondria with electron lucent matrix were seen in the adriamycin treated rats. In the course of time, the ultrastructures of the chief cell changed markedly. 72 hours after drug administration, severely dilated cisternae of rough endoplasmic reticulum, with clumping of chromatin around the nuclear envelope and mitochondria with electron lucent matrix and dilated cristae were seen in the chief cell. 3. The treatment of SOD is more effective than DMTU to attenuated the ultrastructural changes of the chief cells in the adriamycin administered rat. Consequently it is suggested that adriamycin would induce the degenerative changes of the organelles of the chief cell. The treatment of SOD is more effective than DMTU to attenuate the adriamycin induced damage.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.47 no.1
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• pp.20-24
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• 2021

Objectives: The aim of this study was to evaluate the profile of patients on antiresorptive therapies for cancer treatment and assess presence of oral lesions, oral hygiene status, and knowledge regarding medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: This was an observational cross-sectional study that evaluated patients treated with antiresorptive medication at a single cancer hospital. Clinical data were collected and oral examination was performed to assess patient oral health. Results: From July 2017 to December 2018, 90 patients were assessed; 64 were female and 26 were male, and the mean age was 61 years. The most common drug was an intravenous bisphosphonate, zoledronic acid. Among the 90 patients, 47 presented with some type of oral disease, isolated or associated. Among these 47 patients, 9 patients (10%) developed osteonecrosis. Oral hygiene was evaluated, and most patients, with or without MRONJ, presented with regular to poor condition. Regarding patient knowledge of the risks of MRONJ and the risks associated with dental surgery, 60% stated that they were not aware of the risks. Conclusion: Identifying the profile of patients and their needs facilitates not only the preventive process, but also the emergence of new therapeutic options. Our study shows that most patients are weakened both by metastatic disease and antineoplastic treatment as well as by issues associated with aging because most were over 60 years of age. Collectively, this information should be considered for management of preventive and therapeutic measures.

• Safety and Health at Work
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• v.14 no.2
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• pp.237-242
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• 2023

Background: This study evaluated occupational exposure levels of doxorubicin in healthcare workers performing rotational intraperitoneal pressurized aerosol chemotherapy (PIPAC) procedures. Methods: All samples were collected during PIPAC procedures applying doxorubicin to an experimental animal model (pigs). All procedures were applied to seven pigs, each for approximately 44 min. Surface samples (n = 51) were obtained from substances contaminating the PIPAC devices, surrounding objects, and protective equipment. Airborne samples were also collected around the operating table (n = 39). All samples were analyzed using ultra-high performance liquid chromatography-mass spectrometry. Results: Among the surface samples, doxorubicin was detected in only five samples (9.8%) that were directly exposed to antineoplastic drug aerosols in the abdominal cavity originating from PIPAC devices. The telescopes showed concentrations of 0.48-5.44 ng/cm² and the trocar showed 0.98 ng/cm² in the region where the spraying nozzles were inserted. The syringe line connector showed a maximum concentration of 181.07 ng/cm², following a leakage. Contamination was not detected on the surgeons' gloves or shoes. Objects surrounding the operating table, including tables, operating lights, entrance doors, and trocar holders, were found to be uncontaminated. All air samples collected at locations where healthcare workers performed procedures were found to be uncontaminated. Conclusions: Most air and surface samples were uncontaminated or showed very low doxorubicin concentrations during PIPAC procedures. However, there remains a potential for leakage, in which case dermal exposure may occur. Safety protocols related to leakage accidents, selection of appropriate protective equipment, and the use of disposable devices are necessary to prevent occupational exposure.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.403-411
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• 2009

Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.