• Nutritional Sciences
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• 제9권3호
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• pp.212-226
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• 2006

The involvement of arachidonic acid (AA) metabolizing enzyme, lipoxygenase (LOX), in the development of particular tumors in humans has gradually been acknowledged and LOX has emerged as a novel target to prevent or treat human cancers. In the mouse skin carcinogenesis model, which provides an excellent model to study multistage nature of human cancer development, many studies have shown that some of the LOXs are constitutively upregulated in their expression. Moreover, application of LOX inhibitors effectively reduced tumor burdens, which implicates the involvement of LOX in mouse skin tumor development as well. 8S-LOX is a recently cloned LOX, which is specifically expressed in mouse skin after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment but not in normal skin. Unlike other members of the LOX 'family' expressed in mouse skin, this TPA-induced expression of 8S-LOX is prominent only in the skin of the TPA tumor promotion-sensitive strains of mice (SENCAR, CD-1, and NMRI) but not in the promotion-resistant C57BL/6J mice. This is a very unique phenomenon among strains of mice. Constitutive upregulation of 8S-LOX was also found in early stage papillomas and the expression was gradually reduced as the tumors became malignant. Based on these observations, it has been thought that 8S-LOX is involved in TPA-induced tumor promotion as well as in tumor conversion from papillomas to carcinomas. In accordance with this hypothesis, several studies have suggested possible roles of 8S-hydroxyeicosatetraenoic acid (HETE), an AA metabolite of 8S-LOX, in mouse skin tumor development. A clastogenic activity of 8S-HETE was demonstrated in primary keratinocytes and a close correlation between the levels of etheno-DNA adducts and 8S-HETE during skin carcinogenesis was also reported. On the other hand, it has been reported that 8S-LOX protein expression is restricted to a differentiated keratinocyte compartment Moreover, reported findings on the ability of 8S-HETE to cause keratinocyte differentiation appear to be contrary to the procarcinogenic features of the 8S-LOX expression, presenting a question as to the role of 8S-LOX during mouse skin carcinogenesis. In this review, molecular and biological features of 8S-LOX as well as current views on the functional role of 8S-LOX/8S-HETE during mouse skin carcinogenesis are presented.

• Archives of Plastic Surgery
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• 제38권4호
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• pp.339-344
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• 2011

Purpose: The goal of cancer surgery is complete removal of cancer tissue and prevention of recurrence. Surgeons can change the surgical instruments after total resection of the cancer mass. The purpose of this procedure is to prevent dissemination of the cancer cells attached to the surgical instruments. Authors hypothesize the possibility of local recurrence caused by the cancer cells attached to the surgical instruments in the skin cancer cases. Methods: Skin cancers were induced by using DMBA-TPA two-stage carcinogenesis model in 10 of Balb/c mice. In 2-weeks, skin cancer was developed in all 10 mice. cancer cell attached surgical instruments were made by pinching the removed cancer tissue using Adson tissue forcep 10, 20, 30 times each. To count number of cancer cells in each forcep with different number of pinching was done, the forceps were washed in 30 mL of the normal saline and Cytospin preparation was done. To make recurrence models from cancer cell attached surgical instrument, three incisions were made in normal skin of each mouse, and local seeding was done by pinching subcutaneous tissue in 10, 20, 30 times each by using Adson teeth forceps mentioned above as cancer cell attached surgical instrument. Results: All skin cancers were squamous cell carcinoma. Local recurrences were developed in 7 mice (3 in 10 times forceping site, 2 in 20 times forceping and 3 in 30 times forceping). In the cytospin test, the mean number of squamous cells in 100 microscope was 28.6 in 10 times, 47.2 in 20 times, 93.6 in 30 times, respectively. P value was 0.002 in Wilcoxon-Sign test. Conclusion: The number of cell count was significantly increased as number of pinching was increased. And these cells are able to induce local recurrence by local seeding. Considering this result, authors are able to confirm that the minimal handling in cancer surgery is important factor to prevent local recurrence.

• 한국환경보건학회지
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• 제32권5호
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• pp.492-498
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• 2006

Ultraviolet(UV) radiation causes a variety of biological effects on the skin, including inflammation, pigmentation, photoaging and cancer. Free radicals are involved in inflammatory skin reactions induced by UVB radiation. In this study, we investigated the effects of antioxidants(Tea, Korean red ginseng, Ginkgo biloba extract) on UVB-induced skin damage. Tea, KRG and EGb 761 were topically treated to dorsal skin of ICR mouse. The mice were also treated soon after IMED ($1.4KJ/m^{2}$) of UVB irradiation. Skin pigmentation of irradiated mouse was observed by a chromameter after 2 weeks. Topical application of Tea, KRG and EGb 761 for 2 weeks decreased skin pigmentation compared to DVB control group(p<.05). Tea, KRG and EGb 761 also reduced UVB-induced infiltration of inflammatory cells. These results showed that Tea, KRG and EGb 761 as a topical application may have preventive effect against UVB-induced skin damage.

• Nutrition Research and Practice
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• 제7권6호
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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.

• 한국식품영양학회지
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• 제13권5호
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• pp.411-418
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• 2000

결명자차, 녹차 및 밤차가 인체의 생체기능활성화에 미치는 영향을 알아보기 위하여 국소뇌혈류량 및 혈압, in vitro상에서의 면역세포의 활성화, 그리고 암세포가 이식된 동물에서의 면역세포 활성화와 암세포의 증식억제 효과를 관찰한 결과 다음과 같은 결론을 얻었다. 1. 단당류는 현미녹차와 결명자차에는 glucose, ga-lactose등이 들어 있으나 밤차에는 glucose, gal-actose, mannose가 들어 있다. 2. 아미노산은 현미녹차, 밤차, 결명자차 순으로 들어 있다. 3. 카페인은 현미녹차에는 들어 있으나 밤차와 결명자차에는 들어 있지 않았다. 4. 결명자 차는 국소뇌혈류량을 증가시킨 반면 밤차는 감소시켰다. 5. 녹차는 혈압을 증가시켰다. 6. 밤차는 in vitro 상에서 흉선세포와 비장세포의 증식을 유의성있게 증가시켰다. 7. 결명자차와 녹차는 in bitro 상에서 흉선세포의 증식을 감소시켰다. 8. 결명자차와 녹차는 L1210세포가 이식된 동물의 흉선세포 증식을 감소시켰다. 9. 밤차는 L1210세포가 이식된 동물의 비장세포 증식을 촉진시켰다. 10. 밤차와 결명자차는 L1210세포가 이식된 동물의 암세포 증식을 억제하였다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4655-4660
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• 2012

Opuntia humifusa, member of the Cactaceae family, was previously demonstrated to have radical scavenging, anti-inflammatory and anti-proliferative effects in in vitro models. It was suggested that O. humifusa could function in the prevention of carcinogenesis. To investigate the in vivo chemopreventive effect of O. humifusa, mice were fed a diet containing either 1% or 3% following 7, 12-dimethylbenz[a] anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induction of skin carcinogenesis. Significant decrease in the numbers of papilloma and epidermal hyperplasia were observed in mice fed with O. humifusa, compared to the control group. O. humifusa also upregulated high total antioxidant capacity and level of phase II detoxifying enzyme such as superoxide dismutase and glutathione S-transferase activity in the skin. Lipid peroxidation activity level was measured in skin cytosol and significantly inhibited in 3% OH fed group compared to the control group. These results suggest that O. humifusa exerts chemopreventive effects on chemical carcinogenesis in mouse skin and that prevention effects are associated with reduction of oxidative stress via the modulation of cutaneous lipid peroxidation, enhancing of total antioxidant capacity especially in phase II detoxifying enzyme system and partial apoptotic influence.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.115-115
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• 1997

A new capsaicin analog modified with 4-hydroxyl and alkyl chain of capsaicin was a very potent antiinflammatory analgesic drug and may be clinically useful for those who have rheumatoid arthritis, diabetic neuropathy and cancer. The purpose of this study was to investigate histopathology after short and long term application of poloxamer-based gels, and percutaneous absorption of various topical formulations. Poloxamer-based gel was prepared by cold method using poloxamer 407. The poloxamer gels was applied to dorsal sites of hairless mouse skin during one week or one month for the evaluation of skin irritation. The applied site was then sectioned for histopathologic examination. The topical formulations were also prepared using CMC, HPMC, MC, carbopol and glycerylmono stearate. Skin variation of poloxamer gels was studied using excised hairless mouse, rat, hamster and human penis skin. Franz-type diffusion cells were used far skin penetration of drug against receptor phase filled with about 10$m\ell$ of 0.9% saline solution kept at 32$^{\circ}C$. The concentration of drug was determined by the reverse phased C18, Symmetry HPLC with fluorometeric detector. No skin erythema was observed after dorsal application of poloxamer-based gels for one week or one month. No histopathologic changes was also examined, suggesting no skin toxicity of poloxamer-based gels. The order of flux rate was HPMC > MC ( CMC > poloxamer >> glycerylmono stearate ( carbopol. There was a skin variation of poloxamer gels. The flux rate of poloxamer gels was highest in case of hairless mouse followed by rat, human and hamster skin. The Partial support-Ministry of Science and Engineering (HAN project).

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.105.1-105.1
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• 2003

The purpose of this study is to investigate the biological effects in black mouse by neutron irradiation at HANARO reactor in KAERI. Neutrons readily penetrate the charged field of an atomic nucleus because they are electrically neural. And so it can fight cancer with the radiation released when an atom of the element boron absorbs a neutron. The main patient in BNCT facility is brain cancer and sometimes skin cancer in foreign countries until now. Therefore, mice were laid flat and so irradiated at the direction of the front. (omitted)

• 한국식품영양과학회지
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• 제41권4호
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• pp.462-470
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• 2012

본 연구의 결과, TPA 종양촉진 시작과 함께 실험식이를 급여하였을 때, 장뇌삼은 대조군과 인삼군보다 낮은 피부종양발생수를 나타내었으며 종양발생률에서도 대조군과 인삼군에 비해 장뇌삼군에서 종양의 발생이 지연되는 것으로 나타났다. 반면, DMBA 종양개시 한 달 전부터 실험 종료 시까지 실험식이를 급여하였을 때는 대조군과 장뇌삼군에 비해 인삼군의 종양발생수가 감소된 것으로 나타나 인삼은 암 예방효능이 장뇌삼보다 더 높은 것으로 나타났다. 장뇌삼과 인삼은 마우스 피부암이 아닌 다른 상피세포성 암에 대해서도 각각 이러한 효능을 보일 것인지에 대해서 후속연구가 요구되며 또한 앞으로 인삼과 장뇌삼의 유효성분을 발굴하고 이를 더욱 효과적으로 섭취할 수 있는 방법이 개발되어야 할 것으로 생각된다. 아울러 질적으로 우수한 우리나라 장뇌삼과 인삼이 건강기능식품으로서 뿐만 아니라 암 예방과 암치료에 사용될 수 있는 대체의약품으로 개발되기 위해서는 실질적인 임상치료 연구와 더불어 보다 구체적인 과학적 기능 규명연구가 필요하다고 생각된다.

• Preventive Nutrition and Food Science
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• 제16권4호
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• pp.283-290
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• 2011

The recent increase of colon, breast, and prostate cancer incidence in Korea has been attributed to a diet pattern change to a more Western style, in which the foods eaten are higher in protein and fat. Whether high protein intake itself stimulates tumor cell growth and exacerbates disease status has been investigated, however, many epidemiological studies have inconsistent results between meat intake and the risk of certain cancers. These inconsistent results are partly because of the difficulty of studying the effects of just the meat intake. Other factors, such as overall meal context, could not be completely excluded in the study. To address the question of whether high protein itself is independently associated with carcinogenesis, we initiated ICR mice with 200 nmol ($50{\mu}g$) 7,12-dimethylbenz[a]anthracene (DMBA) and fed animals either a normal diet (ND, 14% casein) or a high protein diet (HPD, 50% casein) for 15 weeks with 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in two-stage skin carcinogenesis protocol. There was no significant difference between ND and HPD group in food intake and body weight throughout the experiment. However, tumor multiplicity of the HPD group was decreased by 75.5% compared to that of the ND group. In addition, HPD inhibited skin hyperplasia and epidermal cell proliferation. Western analyses with whole skin lysates showed that HPD inhibited TPA-induced Akt (S473), S6K (T389), 4E-BP1 (Thr 37/46) and Erk1/2 (Thr202/Tyr204) phosphorylation as well as COX-2 expression. Taken together, these data suggest that a high protein diet has an anticarcinogenic effect by inhibiting the TPA-induced Akt signaling pathway.