• Title/Summary/Keyword: therapeutic agents

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Mutational Analysis of Key EGFR Pathway Genes in Chinese Breast Cancer Patients

  • Tong, Lin;Yang, Xue-Xi;Liu, Min-Feng;Yao, Guang-Yu;Dong, Jian-Yu;Ye, Chang-Sheng;Li, Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5599-5603
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    • 2012
  • Background: The epidermal growth factor receptor (EGFR) is a potential therapeutic target for breast cancer treatment; however, its use does not lead to a marked clinical response. Studies of non-small cell lung cancer and colorectal cancer showed that mutations of genes in the PIK3CA/AKT and RAS/RAF/MEK pathways, two major signalling cascades downstream of EGFR, might predict resistance to EGFR-targeted agents. Therefore, we examined the frequencies of mutations in these key EGFR pathway genes in Chinese breast cancer patients. Methods: We used a high-throughput mass-spectrometric based cancer gene mutation profiling platform to detect 22 mutations of the PIK3CA, AKT1, BRAF, EGFR, HRAS, and KRAS genes in 120 Chinese women with breast cancer. Results: Thirteen mutations were detected in 12 (10%) of the samples, all of which were invasive ductal carcinomas (two stage I, six stage II, three stage III, and one stage IV). These included one mutation (0.83%) in the EGFR gene (rs121913445-rs121913432), three (2.50%) in the KRAS gene (rs121913530, rs112445441), and nine (7.50%) in the PIK3CA gene (rs121913273, rs104886003, and rs121913279). No mutations were found in the AKT1, BRAF, and HRAS genes. Six (27.27%) of the 22 genotyping assays called mutations in at least one sample and three (50%) of the six assays queried were found to be mutated more than once. Conclusions: Mutations in the EGFR pathway occurred in a small fraction of Chinese breast cancers. However, therapeutics targeting these potential predictive markers should be investigated in depth, especially in Oriental populations.

Expression Profile of Genes Modulated by Aloe emodin in Human U87 Glioblastoma Cells

  • Haris, Khalilah;Ismail, Samhani;Idris, Zamzuri;Abdullah, Jafri Malin;Yusoff, Abdul Aziz Mohamed
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4499-4505
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    • 2014
  • Glioblastoma, the most aggressive and malignant form of glioma, appears to be resistant to various chemotherapeutic agents. Hence, approaches have been intensively investigated to targeti specific molecular pathways involved in glioblastoma development and progression. Aloe emodin is believed to modulate the expression of several genes in cancer cells. We aimed to understand the molecular mechanisms underlying the therapeutic effect of Aloe emodin on gene expression profiles in the human U87 glioblastoma cell line utilizing microarray technology. The gene expression analysis revealed that a total of 8,226 gene alterations out of 28,869 genes were detected after treatment with $58.6{\mu}g/ml$ for 24 hours. Out of this total, 34 genes demonstrated statistically significant change (p<0.05) ranging from 1.07 to 1.87 fold. The results revealed that 22 genes were up-regulated and 12 genes were down-regulated in response to Aloe emodin treatment. These genes were then grouped into several clusters based on their biological functions, revealing induction of expression of genes involved in apoptosis (programmed cell death) and tissue remodelling in U87 cells (p<0.01). Several genes with significant changes of the expression level e.g. SHARPIN, BCAP31, FIS1, RAC1 and TGM2 from the apoptotic cluster were confirmed by quantitative real-time PCR (qRT-PCR). These results could serve as guidance for further studies in order to discover molecular targets for the cancer therapy based on Aloe emodin treatment.

Evaluation of Estrogenic Activity of Extract from the Herbal Mixture Cynanchum wilfordii Hemsley, Phlomis umbrosa Turczaninow, and Angelica gigas Nakai

  • Kim, Se Jong;Jin, Sun Woo;Lee, Gi-Ho;Kim, Yong An;Jeong, Hye Gwang
    • Toxicological Research
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    • v.33 no.1
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    • pp.71-77
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    • 2017
  • Hormone replacement therapy (HRT) consists of highly effective prescription medications for treating menopausal symptoms; however, these agents have exhibited side effects including the risk of estrogen-induced carcinogenesis. Therefore, interest in phytotherapy-based materials as a natural source of alternatives to estrogen therapy has increased. However, some of these herbal medicines have been reported to increase the risk of estrogen-induced cancer. Herbal formulations composed of a combination of Cynanchum wilfordii Hemsley (CW), Phlomis umbrosa Turczaninow (PU), and Angelica gigas Nakai (AG) extracts (CPAE) have been used for treating menopausal symptoms. Therefore, in this study, we aimed to examine the safety of CPAE by determining its potential adverse estrogenic activity using the Organization for Economic Cooperation and Development (OECD) test guideline 455 (TG455) in a stably transfected transcriptionally activated human estrogen receptor ${\alpha}$ ($hER{\alpha}$)-HeLa9903 cell model. We found that CPAE did not how any estrogenic activity or stimulate promoters containing estrogen response elements in MCF-7 cells. In addition, CPAE showed no significant selective activity against $hER{\alpha}$ and $hER{\beta}$, non-selective activity against the ER, or effects on ER target gene expression. Furthermore, CPAE did not significantly induce MCF-7 cell proliferation and uterine weight increase in ovariectomized rats. These results demonstrate that CPAE can be used as beneficial herbal drug for prevention and therapeutic intervention of estrogen carcinogenesis in menopausal women.

Anti-Inflammatory Effect of the Root extracts from Hibiscus syriacus in LPS-Stimulated RAW264.7 Cells

  • Kim, Ha Na;Park, Su Bin;Park, Gwang Hun;Eo, Hyun Ji;Song, Jeong Ho;Kwon, Hae Yun;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.31 no.3
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    • pp.211-217
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    • 2018
  • Hibiscus syriacus (H. syriacus) as the national flower of Korea has been used as the herbal medicine in Asia. In this study, we evaluated the anti-inflammatory effect of 70% ethanol extracts from the root of Hibiscus syriacus (RHS-E70) and elucidated the potential signaling pathway in LPS-stimulated RAW264.7 cells. RHS-E70 dose-dependently suppressed NO production by inhibiting iNOS and IL-${\beta}$ expression in LPS-stimulated RAW264.7 cells. RHS-E70 inhibited the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which contributed to the inhibition of p65 nuclear accumulation and NF-${\kappa}B$ activation. Furthermore, RHS-E70 suppressed the phosphorylation of ERK1/2 and p38, which results in the inhibition of ATF2 phosphorylation and subsequent nuclear accumulation. These results indicate that RHS-E70 may exert anti-inflammatory activity by inhibiting NF-${\kappa}B$ and MAPK/ATF2 signaling. From these findings, RHS-E70 has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

Laser therapy in peri-implantitis treatment: literature review (임플란트주위염 처치에서 레이저의 이용: 문헌고찰)

  • Lee, Kyung-Joong;Lee, Jong-Ho;Kum, Kee-Yeon;Lim, Young-Jun
    • Journal of Dental Rehabilitation and Applied Science
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    • v.31 no.4
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    • pp.340-348
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    • 2015
  • Peri-implantitis is the most common reason for a late failure and can occur even after years of successful osseointegration. The role of microbial plaque accumulation in the development of peri-implantitis has been well documented. On the other hand, the ideal method of implant surface decontamination to re-establish the health of peri-implant tissue remains to be determined. Removal of bacterial deposits is essential in the treatment of peri-implant infections, and various therapeutic approaches have been described in the literature, including mechanical debridement, disinfection with chemotherapeutic agents, and laser therapy. Recently, there has been a plenitude of scientific data regarding the use of laser irradiation to achieve titanium surface decontamination. Thus, research is focusing on lasers' potential use in the treatment of peri-implantitis. The aim of this literature review is to analyze and evaluate the efficacy of laser therapy for the treatment of peri-implantitis.

The Effects of Toosendan fructus(TOF) treatment on Hematological and Cyto-pathological Alterations in Non-Bacterial Prostatitis Rat Model (천련자가 만성 비세균성 전립선염 Rat 모델에서 혈액 및 세포조직의 변화에 미치는 영향)

  • Cho, Chung-Sik;Lee, Koo-Hyen;Chang, Sun-Kyu;Choi, Jeong-Sik;Kim, Cheol-Jung
    • The Korea Journal of Herbology
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    • v.22 no.4
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    • pp.145-153
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    • 2007
  • Objective : Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. Toosendan fructus(TOF) has been traditionally used in treatment of abdominal pain and parasite. In this study, we investigated the therapeutic effects and action mechanism of Toosendan fructus (TOF) in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Method : Eight-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histophatological profiles. Toosendan fructus(TOF) and testosterone were administered as an experimental specimen and a positive control, respectively. The prostates were evaluated by histopahological parameters including the epithelial score and epithelio-stromal ratio for glandular damage. Also, the prostates were observed by hematological alterations of WBC, RBC, hemoglobin, hematocrit and platelet. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Toosendan fructus(TOF) showed a diminished range of the tissue damage. Epithelial score was improved in Toosendan fructus(TOF) than that of the control. The epithelio-stromal ratio was lower in Toosendan fructus(TOF) when compared to that of the control. Also, the examination of bloods were not observed hematological change. Conclusions : These findings suggest that Toosendan fructus(TOF) may protect the glandular epithelial cells and may take hematological safety. We concluded that Toosendan fructus(TOF) may could be a useful remedy agents for treating the chronic non-bacterial prostatitis.

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Plaque Removing Efficacy and Effect on Gingival Inflammation of Newly Developed Tooth Cleansing Instrument (새롭게 개발된 치아청결기의 치태제거 및 치은염증에 대한 효과)

  • Han, Dong-Kwan;Pang, Eun-Kyung;Kim, Chan-Sung;Choi, Seong-Ho;Cho, Kyoo-Sung;Chai, Jung-Kiu;Kim, Chong-Kwan
    • Journal of Periodontal and Implant Science
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    • v.33 no.3
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    • pp.475-484
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    • 2003
  • Many tooth cleansing instruments and agents have been developed for removal of plaque, inhibition of plaque formation and reduction of gingival inflammation. The aim of this study was to evaluate the plaque control effect and the therapeutic effect of newly developed tooth cleansing instrument(Belloblanco(R)). 40 healthy subjects with gingivitis or early periodontitis were divided into two groups. Subjects in control group only used manual tooth brushing and in experimental group used manual tooth brush and additive tooth cleansing instrument(Belloblanco(R)). Additive tooth cleansing instrument was used once a week. At baseline scaling and tooth brushing instruction was performed. Probing depth, bleeding on probing, plaque index, gingival index were scored at baseline, 2weeks, 4weeks. Probing depth of control and experimental group were significantly reduced at 2 weeks, 4weeks, hut there were no differences between two groups(P<(0.05). Bleeding on probing, plaque index and gingival index of control and experimental group were significantly reduced at 2weeks and 4weeks and there was significantly more reduction in the experimental group than the experimental group than the control group(p<(0.05). From these finding. it can be conclude that newly developed tooth cleansing instrument(Belloblanco(R)) are effective on the removal of plaque and the reduction of gingival inflammation

Differential Expression of Metabolism-related Genes in Liver of Diabetic Obese Rats

  • Seo, Eun-Hui;Park, Eun-Jin;Park, Mi-Kyoung;Kim, Duk-Kyu;Lee, Hye-Jeong;Hong, Sook-Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.2
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    • pp.99-103
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    • 2010
  • The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.

Apoptotic Effect of Co-treatment with Curcumin and Cisplatin on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line

  • Sohn, Hyeon-Jin;Kim, In-Ryoung;Kim, Yong-Ho;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.39 no.3
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    • pp.159-167
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    • 2014
  • Curcumin is a widely used flavoring agent in food, and it has been reported to inhibit cell growth, to induce apoptosis, and to have antitumor activity in many cancers. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatment with curcumin and cisplatin on human tongue SCC25 cells. To investigate whether the co-treatment efficiently reduced the viability of the SCC25 cells compared with the two treatments separately, an MTT assay was conducted. The induction and the augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining, and an analysis of DNA hypoploidy. Western blot, MMP and immunofluorescence tests were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following the co-treatment. In this study, following the co-treatment with curcumin and cisplatin, the SCC25 cells showed several forms of apoptotic manifestation, such as nuclear condensation, DNA fragmentation, reduction of MMP, increased levels of Bax, decreased levels of Bcl-2, and decreased DNA content. In addition, they showed a release of cytochrome c into the cytosol, translocation of AIF and DFF40 (CAD) to the nuclei, and activation of caspase-7, caspase-3, PARP, and DFF45 (ICAD). In contrast, separate treatments of $5{\mu}M$ of curcumin or $4{\mu}g/ml$ of cisplatin, for 24 hours, did not induce apoptosis. Therefore, our data suggest that combination therapy with curcumin and cisplatin could be considered as a novel therapeutic strategy for human oral squamous cell carcinoma.

THE EFFECTS OF ALOE VERA ON WOUND HEALING OF $CO_2$ LASER-GINGIVECTOMY SITES IN WHITE RATS. (백서에서 $CO_2$ 레이저를 이용한 치은절제술후 Aloe vera가 치유과정에 미치는 영향)

  • Song, Won-Seok;Chai, Jung-Kiu;Cho, Kyoo-Sung;Kim, Chong-Kwan
    • Journal of Periodontal and Implant Science
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    • v.24 no.2
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    • pp.283-302
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    • 1994
  • Gingivectomy has been utilized as a therapeutic method to remove diseased periodontal pocket wall in order to aid in root planing. Although chemical agents and electrosurgery has been used in addition to the conventional method of using surgical blades, difficulties in controling the depth of chemical penetration and effectively regenerating the gingival tissue as well as the slow wound healing has been pointed out as shortcomings of these methods. This study was designed to assess the effect of Aloe vera on wound healing of gingivectomy sites created by $CO_2$ laser on palatal gingiva of maxillary molar region of white rats. Those sites treated by surgical blades were designated as control, by $CO_2$ laser as Experimental group I, by surgical blades in addition to topical application of Aloe vera as Experimental group II, and by $CO_2$ laser and Aloe vera application as Experimental group III. Animals were sacrificed at 2 days, 3 days, 1 week, 2 weeks and 3 weeks postoperatively, and the specimens were histologically analyzed. The results were as follows : 1. Resorption of blood clots were observed in the control at 3rd day, followed by the rest of the experimental groups at 1 week postoperatively. 2. Persistent inflammation was observed up to 1 week in the control and Experimental group II and III, and until the 2nd week in Experimental group I. 3. Granulation tissue was observed up to 1 week in the control, and 2 weeks in the rest of the groups. 4. Epithelization started on the 2nd day. The control showed the most rapid epithelization, and the process was completed by the 2nd week in all groups. 5. Experimental group II and III, which were treated with Aloe vera, showed similar healing patterns to the control and Experimental group I.

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