• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.2
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• pp.137-145
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• 2000

Carcinogenesis is a multi-stage process that generally consists of at least three steps; initiation, promotion, and progression. If one of these carcinogenic steps were suppressed or delayed, the cancer could be prevented. Cancer chemoprevention is defined to be inhibition or reversal of the carcinogenic process by the specific chemical agents and is a novel approach to cancer management alternative to conventional chemotherapy. Chlorophylln(CHL), a water-soluble derivative of chlorophyll, containing sodium and copper, has been known to be strong antimutagen in several test systems, but its mechanism of antimutagenic action is unknown. In the present experiment, the possibility of CHL as chemopreventive drugs on 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch carcinogenesis was investigated by mutagenicity test, carcinogenicity test, and frequency or spectrum of H-ras mutations in the both of DMBA-induced and chlorophylln-pretreated-DMBA induced tumor by polymerase chain reaction and non-isotopic restriction fragment length polymorphism. The treatment of CHL reduced the yields and multiplicity of the 0.5% DMBA-induced tumor, 86% to 62.5% and $3.7{\pm}0.6$ to $1.4{\pm}0.3$, respectively. The occurrence of histidine revertant by $20{\mu}mole$ DMBA was inhibited 25.6 to 81.7% by 1 to $5{\mu}M$ CHL in a dose-dependent manner. The mutation rates of H-ras gene in DMBA-induced and CHL-pretreated-DMBA induced tumor were 96%, 94% of which the most mutations were in codon 12/13. These results suggest that CHL inhibits the carcinogenic action of DMBA by the formation of complex between CHL and DMBA or the inhibition of the activation of DMBA in vivo. But CHL did not affect the mutation rates or its spectrum in already formed tumor.

• Nutritional Sciences
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• v.2 no.2
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• pp.71-75
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• 1999

Epidemiologic studies consistently demonstrate an inverse relationship between risk for colon canter and consumption of fruits and vegetables. Wheat bran, flax and soy contain dietary fiber and phytochemicals, such as lignans and isoflavones, that may inhibit colon carcinogenesis. Orange juice contains hesperidin, a flavanone glucoside that protects against colon carcinogenesis. This study determined if feeding orange juice, wheat bran, soy and flaxseed (combined diet) would inhibit azoxymethane (AOM) induced colon cancer. Cancer was initiated in male Fisher 344 rats by injecting 15 mg AOM/kg of weight at 22 and 29 days of age. One week after the second AOM injection, rats (N = 30) in the combined diet group received dry diet containing wheat bran (4%), soy with ethanol soluble phytochemirals(13%) and flaxseed (8%) and orange juice replaced drinking water. The control group remained on the control diet and received distilled water to drink. The rats were killed 28 weeks later, and colon tissues and tumors were removed for histologic analysis. Feeding the combined diet significantly reduced tumor incidence (p < 0.05), however tumor multiplicity was not changed (p > 0.05, 0.9 tumors/rat fed the combined diet vs 1.2 for controls). Also, tumor burden was only marginally reduced in rats fed the combined diet vs control rats (65 vs 210 mg of tumor/rats, respectively). The reduction in tumor incidence was associated with a decreased labeling index and proliferation zone in normal appearing colon mucosa. Therefore, this study shows that phytochemicals in wheat bran, soy, flax and orange juice reduce colon carcinogenesis, presumably by decreasing cell proliferation and enhancing cell differentiation.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.172-172
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• 2003

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a prototype of many halogenated aromatic hydrocarbons, is a ubiquitous, persistent environmental contaminant and displays high toxicity in animals and has been implicated in human carcinogenesis. Although the mechanism of carcinogenesis by TCDD is unclear, it is considered to be a non-genotoxic and tumor promoter. In this study, we investigated the tumor promotion effect of TCDD on the two-stage skin chemical carcinogenesis using hairless mouse (SKH1). We induced papillomas after treatment with N-methyl -N'-nitro-N-nitorsoguanidine (MNNG) as a initiator and TCDD as a promoter for 30 weeks. We found that the incidence or multiplicity of papillomas and hyperplastic nodules was maximally induced at MNNG-TCDD group compare to control, MNNG, and TCDD alone. These results suggesting that TCDD can acts as a potent promoter in the hairless mouse skin. In addition, we used cDNA microarray to detect the differential gene expression in normal, tumor surrounding, and tumor regions induced in hairless mouse skin by MNNG plus TCDD protocol. We found that 49 and 42 genes out of 5,592 genes associated with protein synthesis, cell organization, lipid transport and oxidative stress in tumor and surrounding regions were up- or down- regulated two fold or more, respectively. We are currently investigating how these genes play a role in TCDD-mediated chemical carcinogenesis.

• Korean Journal of Head & Neck Oncology
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• v.17 no.1
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• pp.42-47
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• 2001

Purpose: To evaluate the usefulness of ultrasonogram as a preoperative diagnostic tool in thyroid nodular diseases, this study was carried out. Materials and Methods: From January 1998 to December 1999, 51 patients who underwent thyroidectomy were analyzed retrospectively. We compared the finally histopathological results to ultrasonographical findings such as internal consistency, multiplicity of nodules, nodular ehogenicity, nodular capsule or margin, calcification of nodules. Results: There were 47 females and 4 males with 25 benign tumor, 23 malignant tumor and 3 occult carcinoma in histopathological diagnosis. The solid tumors in ultrasonography carried a probability of malignancy as 66.7%(16/24 cases) whereas cystic or mixed tumors as 16.7%(1/6cases) or 23.8%(5/21cases) (p=0.006). The single nodular diseases carried a high probability of malignancy as 50%(13/26cases) whereas multiple diseases as 28.6%(6/21cases). The hypoechogenicity of thyroid nodular disease showed a probability of malignancy as 60%(9/15cases) whereas mixed-echogenicity as 36.4%(4/11cases). The nodules with poorly-defined margin in ultrasonographic findings showed higher probability of malignancy as 63.6% (7/11cases) than the nodules with well -defined margin as 26.5%(9/34 cases) (p=0.025). The nodules with calcification in ultrasonographic findings were represented to high probability of malignancy as 70.6%(12/17cases) compared to those without calcification as 29.4%(10/34cases) (p=0.005). The differency between ultrasonic and histopathological diagnosis was high in solid nodules(33%), 3-4cm sized nodules (28.6%) and mixed echogenecity(27.3%) whereas low in complex nodules with cystic and solid nature(4.8%), 2-3 cm sized nodules(8.3%) and pooly defined margin(9.1%). The accuracies of sonography in differentiating malignacy from benign thyroid nodules were 7.1% of false positivity, 39.1% of false negativity, 60.9% of sensitivity, 92.9% of specificity and 78.4% of accuracy. Conclusion: Sonographic examination was relatively excellent test as a preoperative diagnostic tool in thyroid nodular diseases when detailed checklists were applied such as internal consistency, multiplicity of nodules, nodular ehogenicity, nodular capsule or margin and calcification of nodules.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10401-10405
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• 2015

Background: Molecular prognostic markers have been under investigation for the last decade and no validated marker to date has been proven to be used in daily clinical practice for urinary bladder cancers. The aim of the present study is to evaluate the significance of HYAL-1 expression in prediction of recurrence and progression in pT1 urothelial carcinomas. Materials and Methods: Eighty-nine urothelial carcinoma cases staged as T1 according to 2004 WHO classification were studied. Representative sections from every case were stained immunohistochemically for HYAL-1 and scored between 0 and +3, according to staining density, and graded as low and high for the scores 0-1 and 2-3, respectively. Results: Of the 89 pT1 bladder cancer patients, HYAL-1 expression was high in 92.1% (82 patients; 72 patients +3 and 10 patients +2) and low in 7.9% (only 7 patients; 6 patients +1 and 1 patient 0) of the cases. Of the 89 patients, 38 (42.7%) had recurrence and 22 (24.7%) showed progression. HYAL-1 staining did not show significant characteristics for tumor grade, accompanying CIS, multiplicity, tumor size, age and sex. HYAL-1 expression did not have any prognostic value in estimating recurrence or progression. Conclusions: HYAL-1 expression was found to be high, but did not have any prognostic importance in T1 bladder urothelial carcinomas.

• Nutrition Research and Practice
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• v.11 no.4
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• pp.281-289
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• 2017

BACKGROUND/OBJECTIVE: The incidence of colorectal cancer (CRC) has been attributed to higher intake of fat and protein. However, reports on the relationship between protein intake and CRC are inconsistent, possibly due to the complexity of diet composition. In this study, we addressed a question whether alteration of protein intake is independently associated with colonic inflammation and colon carcinogenesis. MATERIALS/METHODS: Balb/c mice were randomly divided into 4 experimental groups: 20% protein (control, 20P, 20% casein/kg diet), 10% protein (10P, 10% casein/kg diet), 30% protein (30P, 30% casein/kg diet), and 50% protein (50P, 50% casein/kg diet) diet groups and were subjected to azoxymethane-dextran sodium sulfate induced colon carcinogenesis. RESULTS: As the protein content of the diet increased, clinical signs of colitis including loss of body weight, rectal bleeding, change in stool consistency, and shortening of the colon were worsened. This was associated with a significant decrease in the survival rate of the mice, an increase in proinflammatory protein expression in the colon, and an increase in mucosal cell proliferation. Further, colon tumor multiplicity was dramatically increased in the 30P (318%) and 50P (438%) groups compared with the control (20P) group. CONCLUSIONS: These results suggest that a high protein diet stimulates colon tumor formation by increasing colonic inflammation and proliferation.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.270-280
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• 1998

Ginseng is one of the most widely used medicinal plants, particularly in East Asian countries. Certain fractions or purified ingredients of ginseng have been shown to exert inhibitory effects on growth of cancer cells in culture or on tumorigenesis in experimental animals. Moreover, a recent epidemiologic study reveals that ginseng intake is associated with a reduced risk for environmentally related cancers such as esophageal, gastric, colorectal, and pulmonary tumors. Heat treatment of Panax ginseng C. A. Meyer at the temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed ginseng (designated as'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in f Xl 74 supercoiled DNA Induced by UV photolysis of H2O2 and was also capable of scavenging superoxide generated in vitro by xanthine/xanthine oxidate or in differentiated human promyelocytic leukemia (HL-60) cells by the tumor promoter,12-0-tetvade- canoylphorbol-13-acetate (TPA). Since tumor promotion is closely linked to oxidative stress, we have determined possible anti-tumor promotional effects of NGMe on two-stage mouse skin tumorigenesis. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA significantly ameliorated skin papillomagenesi s initiated by 7,12-dimethylbenz (a) anthracene (DMBA).'Likewise, TPA-induced epidermal ornithine decarboxylase activity and elevation of tumor necrosis factor-a were suppressed signifies%fly by NGMe pretreatment. NGMe topically applied onto surface of hamster buccal pouch 10 min before each topical application of DMBA inhibited oral carcinogenesis by 76olo in terms of multiplicity. Taken together, these results suggest that processed Panax ginseng C. A. Meyer has potential cancer chemopreventive activities.

• Journal of Radiation Industry
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• v.5 no.3
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• pp.203-210
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• 2011

To evaluate the ability of Bamboo (Phyllostachys nigra var. henenis Strapf) leaf extract (BL) to protect the skin from photodamage, the gross and microscopic changes in the skin of hairless mice and BL-treated mice exposed chronically to ultraviolet (UV) were examined. The skin of the UV-irradiated mice showed characteristic signs of photoaging, such as deep wrinkles across the back, increased epidermal thickeness, numerous cell infiltration, and many enlarged keratinizing cysts. BL-treated mice showed a significantly decreased wrinkling score and lack of proliferation of cysts. By the 22nd week, 88.9% (i.p. with saline) or 60.0% (topical administration with cream base) of the UV-irradiated mice developed at least one tumor. BL delayed tumor onset significantly. BL (i.p.) was also effective in reducing the occurrence of UV radiation-induced skin tumors and reduced the number of tumors per mouse. After 22 weeks of treatment, 37.5% (i.p.) of the mice treated with BL were tumor-free. Tumor multiplicity was reduced by 81.2% (i.p.) in the BL treated groups. It is noted that skin that is chronically exposed to UV is subject to photoaging and photocarcinogenesis and regular use of BL would prevent these photodamaging effects of UV.

• Nutrition Research and Practice
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• v.7 no.6
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• pp.439-445
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• 2013

It has been shown that dysregulation of IGF-1 signaling is associated with tumor incidence and progression, whereas blockade of the signaling can effectively inhibit carcinogenesis. Although several mechanisms of anticancer activity of quercetin were proposed, molecular targets of quercetin have not been identified yet. Hence, we assessed the effect of quercetin on IGF-1 signaling inhibition in BK5.IGF-1 transgenic (Tg) mice, which over-expresses IGF-1 in the skin epidermis. A quercetin diet (0.02% wt/wt) for 20 weeks remarkably delayed the incidence of skin tumor by 2 weeks and reduced tumor multiplicity by 35% in a 7,12-dimethylbenz(a)anthracene (DMBA)-tetradecanoyl phorbol-13-acetate (TPA) two stage mouse skin carcinogenesis protocol. Moreover, skin hyperplasia in Tg mice was significantly inhibited by a quercetin supplementation. Further analysis of the MT1/2 skin papilloma cell line showed that a quercetin treatment dose dependently suppressed IGF-1 induced phosphorylation of the IGF-1 receptor (IGF-1R), insulin receptor substrate (IRS)-1, Akt and S6K; however, had no effect on the phosphorylation of PTEN. Additionally, the quercetin treatment inhibited IGF-1 stimulated cell proliferation in a dose dependent manner. Taken together, these data suggest that quercetin has a potent anticancer activity through the inhibition of IGF-1 signaling.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.230-237
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• 2015

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.