• Environmental Mutagens and Carcinogens
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• v.19 no.1
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• pp.46-55
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• 1999

To develop a chemopreventive strategy based on the different stages of premalignant lesions, we hypothesized that the inhibitory effect of chemopreventive agents is influenced by different promotion stages during carcinogenesis. DMBA-TPA-induced skin carcinogenesis was used with ICR mice and chlorophyllin (CHL) was applied as a chemopreventive agent. In vitro assay was performed with Salmonella typhi. TA100 to observe any anti-mutagenic activity of CHL against DMBA. Pre-initiation and pre-promotion effects of CHL were observed by CHL treatment before initiation and before promotion. To evaluate the inhibitory effect at different promotion stages, each group was divided into three subgroups after TPA promotion for 6, 18 and 24 weeks, respectively ; the first subgroup was immediately sacrificed after termination of TPA, the second subgroup was treated with CHL, and the third subgroup was sacrificed 8 weeks after termination of TPA without CHL treatment. The degrees of epithelial dysplasia, papilloma formation, and invasive carcinoma were observed histologically, and GST-Pi expression was observed immunohistochemically. ODC mRNA level was analyzed by reverse transcriptase-polymerase chain reaction. Results showed : CHL dose-dependently inhibited the mutation of Salmonella typhi. TA100; the incidence of epithelial dysplasia and papilloma formation was lower in pre-initiation and pre-promotion CHL-treated mice than DMBA-TPA-treated mice; no invasive carcinoma developed in pre-initiation CHL-treated groups, while 67% of DMBA-TPA treated mice had carcinomas; GST-Pi expression decreased when CHL was treated before initiation and before promotion; and when CHL was treated after termination of TPA application at 18 and 24- week-TPA promotion stages, respectively, the incidence of epithelial dysplasia and papilloma was markedly reduced compared to non-treated groups. When comparing the incidence of epithelial dysplasia and papilloma between the immediately-sacrificed subgroup and the non-treated group with a waiting period, we speculated that the 18-week-TPA promotion stage might belong to the promoter-independent progression stage. At the 18-week-TPA promotion stage, the level of ODC mRNA in the CHL-treated group was clearly reduced to the level of normal tissue. Taking these results together, CHL showed both anti-initiation and anti-promotion effects, while the inhibitory effect of CHL was prominent in the 18-week-TPA promotion stage. However, CHL seems to be incapable of completely blocking the progression in the 24-week-TPA promotion stage.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.145-145
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• 2001

Xanthorrhizol is a sesquiterpenoid isolated from Curcuma xanthorrhiza Roxb. (Zingiberaceae) that has been traditionally used in Indonesia for dietary and medicinal purposes. In our studies to evaluate the cancer chemopreventive potential, xanthorrhizol inhibited the mutagenesis induced by reactive oxygen species in Sa;monella typhimurium TA 102 in a dose-related manner and decreased significantly the incidence and the multiplicity of skin tumors initiated by 7, 12-dimethylbenz[$\alpha$]anthracene and promoted by 12-Ο-tetradecanoylphorbol-13-acetate at 19 weeks.(omitted)

• BMB Reports
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• v.40 no.2
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• pp.189-195
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• 2007

Although the incidence and severity of atopic dermatitis (AD) is steadily increasing at an alarming rate, its pathogenic mechanisms remain poorly understood yet. Recently, we found that the expression of Grb7 protein was markedly decreased in AD patients using proteomic analysis. In the present study, human Grb7 gene was fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-Grb7 fusion protein. The expressed and purified PEP-1-Grb7 fusion proteins transduced efficiently into skin cells in a time- and dose-dependent manner when added exogenously in culture media. Once inside the cells, the transduced PEP-1-Grb7 protein was stable for 48 h. In addition, transduced PEP-1-Grb7 fusion protein markedly increased cell viability in macrophage RAW 264.7 cells treated with LPS by inhibition of the COX-2 expression level. These results suggest that the PEP-1-Grb7 fusion protein can be used in protein therapy for inflammatory skin disorders, including AD.

• The Journal of the Korean Society for Microbiology
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• v.21 no.1
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• pp.133-144
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• 1986

This study was undertaken to assess the effect of ginseng administration on T lymphocyte induced local xenogenic graft-versus-host(GVM) reactions which were induced with thymocyte, spleen cell and lymph node cell of ICR mice. Mice received daily 10mg of 70% alcohol ginseng extract oral1y for 100days and control mice remained untreated for the same period of time. The cells from donor mice were injected intradermally into the closely shaven abdominal skin of Sprague-Dawley rats for GVH tests. The thymocyte from control(ginseng-untreated) mice showed a negative local GVH reaction, whereas thymocyte from experimental(ginseng-treated) mice showed a positive reaction with the rate of 17.4%. When spleen cells were injected, the incidence of positive local GVH reaction was 66.7% among ginseng-treated mice, as opposed to incidence of 45.5% of positive local GVH reaction among control mice. The incidence of positive local GVH reaction of the lymph node cells when injected into a recipient was 71.4% among ginseng-treated mice as compared with that of 18.9% among control mice. The relationship between spleen cell inoculum and intensity of the local GVH reaction was assessed in ginseng-untreated mice. The intensity of GVH reaction clearly appears to be dose related. In ginseng-treated mice, a minimum of $1{\times}10^7$ spleen cell was required for production of positive local GVH reaction with almost linear relationship up to an inoculum of $5{\times}10^8$ cells. In control mice, however, a minimum of $1{\times}10^8$ spleen cells was required for positive GVH reaction. These results strongly suggest that the ginseng administration augments significantly the local xenogenic GVH reaction which was used to assess T lymphocyte function and immunocompetence of mice and in addition to this, these results appear to support previous suggestions that the local GVH reaction consitutes a qualitative test of the functional activity of T lymphocytes. These results may be the first to induce local GVH reaction, employing rats as recipient and mice as donor. This study was also desingned to investigate some of the effects of ginseng extract on lymphocyte-macrophage interactions. This was accomplished by in vitro quantification of 1) migratory inhibitory factor(MIF) synthetic capacity of splenic lymphocytes in mice previously primed with ginseng 2) MIF responsiveness of mouse peritoneal macrophages or chicken peripheral leucocytes under the presence of ginseng extract 3) migration ability of chicken peripheral leucocytes by direct stimulation of ginseng extract or ginseng saponin and 4) immunosuppressive effects of immunosuppressants such as cyclophosphamide, cyclosporin A or dexamethasone. Mice divided equally into the ginseng and the saline groups, which received intraperitoneally daily 0.2ml of ginseng absolute alcohol-extract(5mg/ml) and same amount of saline for 15 days, respectively. The cellular immune responsiveness of these mice was assayed 15 days after ginseng pretreatment. Splenic lymphocytes of mice treated with ginseng, when stimulated with sensitized specific-antigen such as sheep red blood cells or toxoplasmin, or with polyclonal activator concanavalin A, produced significantly more MIF than those of control saline group. MIF responsiveness of normal mouse macrophages was significantly augmented when assayed under the presence of ginseng extract (1mg/ml). The migratory ability of normal chicken leucocytes in the absence of MIF was significantly decreased by the stimulation of ginseng extract alone. MIF response was significantly decreased by immunosuppressants and this impaired response was not restored by ginseng pretreatment. This study was additionally performed to evaluate the effect of ginseng on the expulsion of adult Trichinella spiralis in mice. ICR mice were infected experimentally by esophageal incubation of 300 T. spiralis infective muscle larvae prepared by acid-pepsin digestion of infected mice. and received oral administration of 70% alcohol ginseng extract(10mg/mouse/day) for the indicated days plus 4 days before infection. At various times after infection, the number of adult T. spiralis worms in small intestines was determined. Interestingly, ginseng-treatment was accompanied by accelerated expulson of T. spiralis. These results led to the conclusion that Panax ginseng caused some enhancing effect on GVH reaction, macrophage migration inhibition reaction and expulsion of T. spiralis. In addition these results suggested that the mechanisms responsible for this enhancement of ginseng may be chiefly or partially due to nonspecific stimulation of cell-mediated immune response.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4147-4152
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• 2014

Standard therapy for advanced head and neck cancer consists of a combination of surgery and radiation. However, survival of this patient population has not improved during the past 20 years. Many different multimodality treatment schedules have been proposed, and chemotherapy is often used with the intent of organ preservation. The present study was intended to establish the efficacy of concomitant chemoradiation with a single agent carboplatin in advanced head and neck cancers.The objectives were to investigate the feasibility of concomitant administration of carboplatin, monitor acute toxicity during radiotherapy, and determine subacute side effects, such as wound healing following surgery after chemoradiotherapy. A prospective study was conducted wherein a total of 40 patients with stage III and IV squamous cell carcinomas of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were treated with external beam radiotherapy and weekly carboplatin area under curve (AUC of 5). Radiotherapy was given in single daily fractions of 1.8-2 grays (Gy) to a total dose of 66-72 Gy. Salvage surgery was performed for any residual or recurrent locoregional disease. Neck dissection was recommended for all patients with neck disease showing less than a complete response after chemoradiation. A total of 40 patients were enrolled of whom 32 were males and 8 were females. Highest incidence of cancer was seen in the 5th-6th decades of life with a median age of 47.7 years. Oropharyngeal tumours constituted a maximum of 21 patients followed by hypopharynx in 10, larynx in 7 and oral cavity in 2. 80% of the patients had a neck node on presentation of which 40% had N2-N3 nodal status. TNM staging revealed that 58% of patients were in stage III and 43% in stage IV. Evaluation of acute toxicity revealed that 50% had grade II mucositis, 25% grade III mucositis, 2.5% grade IV mucositis. 50% of patients had grade I skin reactions, 65% of patients had grade I thrombocytopenia, and 24% of patients had grade I anaemia. After completion of treatment 65% of patients had complete response at the primary and regional sites, and 35% of patients had a partial response of whom 23% underwent neck dissection and 5% of them underwent salvage surgery at the primary site. At the end of one year there were six deaths and four recurrences and 70% were free of disease. Concurrent chemoradiation with carboplatin provided good locoregional control for locally advanced head and neck cancers. This regimen, although toxic, is tolerable with appropriate supportive intervention. Primary site conservation is possible in many patients. Chemoradiotherapy appears to have an emerging role in the primary management of head and neck cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10445-10449
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• 2015

Objective: To observe treatment effects and safety of fluvoxamine combined with oxycodone prolonged-release tablets in treating patients with moderate to severe cancer pain. Methods: Patients confirmed pathologically with cancer and complicated with moderate to severe pain, were divided into control and experimental groups. Oxycodone prolonged-release tablets, with or without fluvoxamine, were administrated to all study patients until pain relief. Degree of pain relief, dose of oxycodone prolonged-release tablets, side effects and quality of life were compared before and after treatment. Results: In total, 120 patients were recruited. No statistically significant difference was detected regarding age, gender, types of cancer, KPS between two groups of patients (P>0.05). Baseline pain score of patients with moderate pain in treatment and control group was $4.9{\pm}0.8$ and $5.1{\pm}0.8$, respectively; and decreased to $1.8{\pm}1.1$ and $1.2{\pm}1.1$ after treatment, respectively. Pain intensity was significantly reduced in the treatment group (P=0.028). Average daily consumption of oxycodone prolonged-release tablets was ($54.0{\pm}19.6$) mg and ($44.7{\pm}18.7$) mg respectively, which is lower in treatment grpup than in control group, but the difference was not statistically significant (P=0.065). Baseline pain score of patients with severe pain in treatment and control groups were $8.3{\pm}1.1$ and $8.3{\pm}1.1$, respectively; and pain intensity after treatment decreased to $2.9{\pm}1.0$ and $2.3{\pm}1.0$. Pain intensity was significantly reduced in the treatment group, with statistical significance (P=0.026). Average daily consumption of oxycodone prolonged-release tablets was ($132.0{\pm}42.2$) mg and ($110.7{\pm}33.9$) mg, respectively, which is lower in treatment group than in control group, and the difference was statistically significant (P=0.035). In terms of quality of life, patients in treatment group had better performance status, daily activity, mood, and sleep than that in control group (P < 0.05). Patients in two groups had similar side effects, eg., constipation, nausea/vomiting, lethargy, dizziness, itchy skin, dysuria, and ataxia. Lower incidence of nausea/vomiting, lethargy, was obtained from patients in treatment than in control group, while significant low constipation was observed in treatment than in control group (35.0% vs 49.2%, P=0.026). Conclusion: Fluvoxamine combined with oxycodone prolonged-release tablets could be more effective in treating patients with cancer pain, and could reduce the dosage of oxycodone prolonged-release tablets and thus be associated with lower side effects, and improved quality of life.