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Abstract:Fermented broth has a long history of applications in the food, pharmaceutical and cosmetic industries. Recently, the use of fermented broth in skin care products is in ascendance. This review investigates the efficacy of fermented broth in inhibiting tyrosinase and melanogenesis. Possible active ingredients and hypopigmentation mechanisms of fermented broth are discussed, and potential applications of fermented broth in the cosmetic industry are also addressed.

In addition to genetic changes, epigenetic aberrations also play important roles in radiation- and chemical-induced disorders and carcinogenesis. The present study investigated whether epigenetic therapy with a histone deacetylase (HDAC) inhibitor has dual benefits for radiation-induced oral mucositis and chemical-induced oral carcinogenesis, which should be treated at the same time. The HDAC inhibitor phenylbutyrate was first tested to determine if it influences DNA damage repair and survival in irradiated normal cells in vitro by investigating the patterns and dynamics of phospho-gammaH2AX foci, Rad51 foci and phospho-gammaH2AX/Rad51 colocalization and using the comet and clonogenic assays. Oral mucositis or carcinogenesis was induced in hamsters using radiation or 7,12-dimethylbenz[a]anthracene (DMBA) irritation to the cheek pouch. The ability of phenylbutyrate formed in proper carriers to prevent radiation-induced oral mucositis and inhibit chemical-induced oral carcinogenesis was assessed. The treated or untreated irradiated or DMBA-irritated oral tissues or mucosal epithelia were subjected to the studies of histology, immunohistochemistry, gene expression, comet assay, HDAC activity or oxidative stress. We found that phenylbutyrate promoted DNA repair and survival in normal cells after radiation. Compared with blank or vehicle-treated hamsters, the irradiated mucosa treated with phenylbutyrate had significantly lower oxidative stress and tumor necrosis factor-alpha expression and less severe oral mucositis of a shorter duration. A reduction of the oral tumor incidence, burden and progression by phenylbutyrate correlated with the suppression of oncomiRs and Rad51 overexpression, the upregulation of differentiation markers and the decrease of intracellular HDAC activity and oxidative stress during DMBA-induced oral carcinogenesis. Thus, epigenetic therapy using the HDAC inhibitor as an adjuvant to radiotherapy for chemical-induced oral cancer may provide a promising strategy combining the prevention of radiation-induced oral mucositis and the inhibition of oral carcinogenesis.

The expression of Rab proteins has been associated with cancer. However, few data are available on Rab5A expression in human breast cancer or its impact on disease progression. First, we examined the functional role of Rab5A in breast cancer cells. The expression of Rab5A in MDA-MB-231 cells can be stimulated by epidermal growth factor in a dose-dependent manner. The epidermal growth factor-induced increase of Rab5A expression correlated well with enhanced migration in wound healing migration assays in these cells. Furthermore, we evaluated the expression of Rab5A in breast cancer specimens using immunohistochemical staining, then analyzed the relationship between the expression of Rab5A and clinicopathological parameters. The increased expression of Rab5A protein in 123 breast cancer samples was associated with higher histological grade (P = 0.004), more lymphovascular invasion (P = 0.027), more axillary lymph node (LN) metastasis (P = 0.008), and a higher number of axillary LN metastases (P = 0.043). Among 218 axillary LNs of more than 10 breast cancer patients with node metastases, 167 metastatic LNs were found to have increased Rab5A expression. Rab5A is associated with axillary LN metastasis in breast cancer patients. (Cancer Sci 2011; 102: 2172-2178 T he majority of deaths from breast cancer are attributed to metastasis. Axillary LNs are often the first sites of metastasis in breast cancer patients.(1) The presence of axillary LN metastasis is a major criterion in the prognosis and in the decision-making for additional chemotherapy after primary tumor surgeries.(2) Only 20% of systemic metastases derived from tumor cells bypass the lymphatic route.(3) Therefore, axillary LN metastasis is one of the most important issues in breast cancer.Rab GTPases, which are members of the Ras superfamily of small GTPases, are key regulators of membrane trafficking in both exocytic and endocytic pathways as well as receptor localization in eukaryotic cells. (4,5) Many studies have revealed the association between Rab GTPase dysfunction and human diseases, including cancer.(6) Rab5 is one of the most extensively studied members of Rab GTPases.(7) It plays important roles in a variety of cellular trafficking and signaling events, including receptor internalization, targeting and fusion of endocytic vesicles with early endosomes, fusion between early endosomes, actin remodeling, and signaling to the nucleus.(8) Recent studies have revealed that the overexpression of Rab5A is associated with the metastatic potential of lung and gastric cancer, (9,10) is involved in the migration of hepatocellular carcinomas, (11) and promotes ovary cancer cell proliferation.(12) Rab5A mediates the formation of EGFR-containing endosomes. (13,14) The EGFR signaling cascades can promote cell proliferation, angiogenesis, and invasion, and inhibit apoptosis, resulting in tumor growth and progression.(15) Poor prognosis was confirmed in patients of locally advanced breast cancer with overexpression of EGFR. (16) Whether Rab5A played any role in th...

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