• Journal of Microbiology and Biotechnology
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• v.28 no.3
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• pp.375-380
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• 2018

We have previously found that mycelia culture broth of eight kinds of traditional herbal extracts fermented with Phellinus linteus (previously named as 8-HsPLCB) not only inhibited melanin and tyrosinase activity, but also reduced the contents of melanogenesis-related proteins, including tyrosinase and microphthalmia-associated transcription factor, in 3-isobutyl-1-methylxanthine-stimulated B16F0 melanoma cells. For a further study, the effect of 8-HsPLCB against skin pigmentation in brown guinea pigs with ultraviolet B (UVB)-induced hyperpigmentation was investigated. 8-HsPLCB (3%) and arbutin (2%) as positive controls were applied topically twice daily for 4 weeks to the hyperpigmented areas. 8-HsPLCB showed skin-lightening effect as effective as arbutin, one of the most widely used in whitening cosmetics. Melanin index values as the degree of pigmentation showed a significant reduction week by week post 8-HsPLCB treatment and then substantially reduced by 4 weeks. The degree of depigmentation after 4 weeks of topical application with 8-HsPLCB was 32.2% as compared with before treatment (0 week). Moreover, using Fontana-Masson staining and hematoxylin-eosin staining, 8-HsPLCB reduced melanin pigmentation in the basal layer of the epidermis and epidermal thickness changes exposed to the UV-B irradiation as compared with non-treatment and vehicle treatment. The intensity of the skin-lightening effect of 8-HsPLCB was similar to arbutin. These results suggest that the skin-lightening effect of 8-HsPLCB might be resulted from inhibition of melanin synthesis by tyrosinase in melanocytes. To conclude, 8-HsPLCB treatment showed reduction of the melanin pigment and histological changes induced by UV irradiation in brown guinea pigs.

• Korean Journal of Pharmacognosy
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• v.34 no.4 s.135
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• pp.308-313
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• 2003

A bioassay-guided fractionation of the stem bark extract of Eucommia ulmoides Oliver (Eucommiaceae) led to the isolation of three iridoid constituents, genipin (1), geniposide (3), geniposidic acid (4) as well as $({\pm})-guaiacylglycerol$ (2) and fatty acid mixtures as active ingredients of the extract responsible for the antitumoral property. The EtOAc soluble part and BuOH soluble part of the extract demonstrated a potent inhibition on the proliferation of cultured human tumor cells such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCT-15 (colon) in vitro, whereas the remaining water soluble part exhibited a poor inhibition. The intensive investigation of the EtOAc soluble part and BuOH soluble part of the extract yielded genipin, guaiacylglycerol, geniposide, geniposidic acid and large amounts of fatty acid mixtures as active components.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1093-1096
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• 2016

The tumor suppressor p16 is a biomarker for transforming human papilloma virus (HPV) infections that can lead to contradictory results in skin carcinomas. The aim of this study was to evaluate p16 expression and HPV-16 infection in the cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). This case-control study was performed on paraffin blocks of BCCs and SCCs and normal skin (53, 36, and 44 cases, respectively), between 2006 to 2015. Initial sections for groups were stained with hematoxylin and eosin (H & E). Immunohistochemistry was performed for p16 expression and human papilloma virus type 16 (HPV-16) infection. Normal group was skin of mammoplasty specimens and normal skin tissue in the periphery of tumors. The mean age at diagnosis was 42.1, 61.7 and 71.4 years for normal, BCC and SCC groups, respectively. P16 positivity was more in SCC and BCC groups compared to normal group (P<0.05) and HPV was negative in all patients in three groups. Also, the mean age at diagnosis and P16-positivity were higher for the SCC group than the BCC group (P<0.005). In conclusion, in non-melanoma skin cancers (SCC and BCC), p16-positivity can be a prognostic factor but there is no correlation between HPV-16 and p16 in these tumors.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.27 no.1
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• pp.119-131
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• 2001

Exposure of the human skin to UV-light can cause sun-tanning, photoaging and even photo-carcinogenesis. Melanin is important in protecting the skin against UV damage, but excessive or uneven melanin production can lead to the formation of freckles and aged spot. Control of hyperpigmentation is becoming even more important as aged population continues to grow. These needs led us to develop effective and safe depigmenting-agent, kojyl 3-aminopropyl phosphate (kojyl-APPA), called Whitegen. The development of whitegen was based on the fact that phosphate group of 3-aminopropyl phosphate can make kojic acid more compatible to the skin membrane and more stable. Instability of kojic acid has been a problem in cosmetic use. The insertion of phosphoester group has been recognized as a powerful tool to improve such physical properties as solubility and stability, because the phosphodiester residue is well characterized as a non-toxic moiety, having a high affinity for cell membranes. Kojyl-APPA showed no tyrosinase inhibition effect compared to kojic acid in vitro, but showed tyrosinase inhibition effect in situ. It means that kojyl-APPA is converted to kojic acid enzymatically in cells. Kojyl-APPA showed the inhibitory activity on melanin synthesis in mouse melanoma and normal humal melnaocytes and also showed long-lasting stability in comparison with its original form (kojic acid). Kojyl-APPA showed depigmenting effects when applied to UVB-induced hyperpigmentated region of guinea pig skin. Based on these results, kojyl 3-aminopropyl phosphate can be used as a safe and effective ingredient for the brightness and cleanness of skin.

• Journal of Ginseng Research
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• v.33 no.3
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• pp.177-182
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• 2009

Macrophages play an important role in the first line of immunologic effects against tumor cells. The effects of nonsaponin red ginseng (NSRG) components on macrophage functions like tumoricidal activity, phagocytic activity, and NO production in young (8-weeks-old) and aged (82-weeks-old) male C57BL/6 mice were assessed in vitro, respectively. The treatment of tumor cells (melanoma B16 cells) with the supernatants of NSRG-treated macrophages resulted in an increase of cytotoxicity at 300 $\mu$g/ml in the aged mice, whereas the supernatants did not have a cytotoxic effect in the young mice. It was observed that the supernatants induced the increase of tumor cell proliferation at 150 $\mu$g/ml in the young mice, suggesting that the supernatants contain growth factors rather than cytotoxic molecules. In addition, NSRG alone had a direct cytotoxic effect on the B16 tumor cells. NSRG had no effect on the NO production by the macrophages in the young mice, while it significantly increased the level of NO release in the aged mice. There was no difference in the phagocytic activities of the macrophages by NSRG in both groups of mice. These results suggest that NSRG has differential effects on the macrophage functions in young and aged mice.

• Archives of Plastic Surgery
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• v.40 no.6
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• pp.748-753
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• 2013

Background Nasal reconstruction is one of the most difficult challenges for the head and neck surgeon, especially in the case of complex full thickness defects following malignant skin tumor resection. Full-thickness defects require demanding multi-step reconstruction. Methods Seven patients underwent surgical reconstruction of full-thickness nasal defects with a bi-pedicled forehead flap shaped appropriately to the defect. Patients were aged between 58 and 86 years, with a mean age of 63.4 years. All of the tumors were excised using traditional surgery, and in 4 of the patients, reconstruction was performed simultaneously following negativity of fresh frozen sections of the margins under general anesthesia. Results Nasal reconstruction was well accepted by all of the patients suffering non-melanoma skin tumors with acceptable cosmetic outcomes. The heart-shaped forehead flap was harvested in cases of subtotal involvement of the nasal pyramid, while smaller defects were reconstructed with a wing-shaped flap. No cartilaginous or osseous support was necessary. Conclusions This bi-pedicled forehead flap was a valid, versatile, and easy-to-implement alternative to microsurgery or multi-step reconstruction. The flap is the best indication for full-thickness nasal defects but can also be indicated for other complex facial defects in the orbital (exenteratio orbitae), zygomatic, and cheek area, for which the availability of a flap equipped with two thick and hairless lobes can be a valuable resource.

• Korean Journal of Clinical Pharmacy
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• v.28 no.1
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• pp.65-75
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• 2018

Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3817-3823
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• 2014

Background: The MDM2 oncogene, a negative regulator of p53, has a functional polymorphism in the promoter region (SNP309) that is associated with multiple kinds of cancers including non-melanoma skin cancer. SNP309 has been shown to associate with accelerated tumor formation by increasing the affinity of the transcriptional activator Sp1. It remains unknown whether there are other factors involved in the regulation of MDM2 transcription through a trans-regulatory mechanism. Methods: In this study, SNP309 was verified to be associated with overexpression of MDM2 in tumor cells. Bioinformatics predicts that the T to G substitution at SNP309 generates a stronger E2F1 binding site, which was confirmed by ChIP and luciferase assays. Results: E2F1 knockdown downregulates the expression of MDM2, which confirms that E2F1 is a functional upstream regulator. Furthermore, tumor cells with the GG genotype exhibited a higher proliferation rate than TT, correlating with cyclin D1 expression. E2F1 depletion significantly inhibits the proliferation capacity and downregulates cyclin D1 expression, especially in GG genotype skin fibroblasts. Notably, E2F1 siRNA effects could be rescued by cyclin D1 overexpression. Conclusion: Taken together, a novel modulator E2F1 was identified as regulating MDM2 expression dependent on SNP309 and further mediates cyclin D1 expression and tumor cell proliferation. E2F1 might act as an important factor for SNP309 serving as a rate-limiting event in carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.269-273
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• 2016

Presently, the world population of the elderly is growing. By improving health hygiene and welfare indicators, mortality and birth rates decrease and life expectancy increases, making the present century the century of elderly. Aging is one of the main risk factors for development of cancer, which itself is the second cause of death in old people. This study was conducted to assess the prevalence of cancer in the elderly covered by the Islamic Republic of Iran Broadcasting (IRIB) insurance program and to obtain suitable programs for cancer screening and early detection, increase patient survival, improve elderly care and to reclaim the cost of treatment in comparison to the national and international statistics. This is a cross-sectional study conducted on all elderly patients diagnosed with malignancy based on their pathology reports. In this study, of the total 75,500 patients covered by IRIB insurance, 17.2% belonged to the elderly group, males accounting for 53.3%. The most common cancers in old men were prostatic cancer (61.3%), colon cancer (10.3%) cancer of the hematologic system, bladder cancer (9.6%), lung cancer (9.1%), thyroid cancer (3.9%) and brain tumors (1.3%). In the elderly women, the most common cancers were breast cancer (80.1%), colon cancer (5.1%), thyroid cancers (4.4%), bladder and hematologic system malignancies (3.6), lung cancer (2.9%) and brain tumors (0.7%). In addition, the prevalence of cancer was almost the same as national and international statistics. With the exception of non-melanoma skin cancer no difference was shown in prevalence of cancer between IRIB elderly patients and the other groups of cancer patients in Iran.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5189-5193
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• 2012

Kemerovo is an industrial region of the Russian Federation characterized by highly developed mining, chemical, metallurgical and power industries. Many of the factories were closed down due to the socioeconomical crisis in the early 90's, and economic potential of the survivors has also decreased significantly. Paradoxically, this has led to the improvement of the ecological situation in the region and elimination of exposure to many chemical carcinogens. This factor, in combination with the improvement of oncological care, might be expected to have lead to a decline of cancer incidence and mortality in the region. To assess trends of cancer incidence and mortality in Kemerovo Region, we therefore carried out an analysis of relevant epidemiological data during 1991-2010. In fact, a significant increase of cancer incidence overall was revealed during 2001-2010. Male cancer incidence was significantly higher than female cancer incidence. Regarding gastric cancer incidence, statistically significant differences during 2001-2010 were found only for men, and male incidence exceeded female incidence. Concerning colorectal cancer incidence, it was lower during 2001-2005 and 2006-2010 as compared to the period of 1991-1996. Lung cancer incidence was significantly higher during 1991-2000 compared to 2001-2010. Among urban populations, cancer incidence was higher in comparison with rural population, but a gradual steady convergence of trends of cancer incidence among urban and rural populations was noted. Lung cancer, breast cancer, colorectal cancer, non-melanoma skin cancer, and gastric cancer are the most prevalent cancer forms in Kemerovo Region. There were no differences in cancer mortality between 2001-2005 and 2006-2010; however, male cancer mortality exceeded female cancer mortality. A similar situation was observed for gastric cancer, colorectal cancer, and lung cancer. Cancer mortality among urban populations exceeded mortality among rural population, for both genders. We suggest that these data can be used for development of modern programs of cancer prevention and early diagnostics in industrial regions of Siberia.