Avicins are proapoptotic and anti-inflammatory triterpene electrophiles isolated from an Australian desert tree, Acacia victoriae. The presence of two α,β unsaturated carbonyl groups (Michael reaction sites) in the side chain of the avicin molecule prompted us to study its effects on NF-E2–related factor 2 (Nrf2), a redox-regulated transcription factor that controls the expression of a battery of detoxification and antioxidant proteins via its binding to antioxidant response element (ARE). Avicin D–treated Hep G2 cells showed translocation of Nrf2 into the nucleus and a time-dependent increase in ARE activity. These properties were sensitive to DTT, suggesting that avicins affect one or more critical cysteine residues, probably on the Keap1 molecule. Downstream of ARE, an activation of a battery of stress-induced proteins occurred. The implications of these findings were evaluated in vivo in mouse skin exposed to an ancient stressor, UV light. Avicins inhibited epidermal hyperplasia, reduced p53 mutation, enhanced apoptosis, decreased generation of 8-hydroxy-2′-deoxyguanosine, and enhanced expression of NADPH:quinone oxidoreductase 1 and heme oxygenase-1. These data, combined with our earlier published work, demonstrate that avicins represent a new class of plant stress metabolites capable of activating stress adaptation and suppressing proinflammatory components of the innate immune system in human cells by redox regulation. The relevance for treatment of clinical diseases in which stress responses are dysfunctional or deficient is discussed

Objective: We assessed the prognostic factors related to 10-year overall survival and disease-free survival in cervical cancer patients that underwent primary surgical protocols in 1 institution. Materials and Methods: A total of 102 patients with uterine cervical cancer at FIGO stages IA2-IIB that underwent a Piver type III radical hysterectomy and pelvic lymphadenectomy between 1998 and 2001 were included. Univariate and multivariate analyses of 10-year overall survival and 10-year disease-free survival were performed. Results: Univariate analysis revealed that only lymphovascular space invasion significantly affected 10-year overall survival (p = 0.04), but it had no effect on the 10-year disease-free survival rate. Multivariate analysis demonstrated that survival rates were significantly affected by FIGO stage (p = 0.02, 95% CI: 1.18-5.55, for 10-year overall survival; p = 0.03, 95% CI: 1.07-6.12, for 10-year disease-free survival) and metastases to the pelvic lymph nodes (p = 0.0005, 95% CI: 1.81-8.53, for 10-year overall survival; p = 0.01, 95% CI: 1.26-7.24, for 10-year disease-free survival). Conclusions: The only independent prognostic factors for 10-year survival rates in patients with cervical cancer at FIGO stages IA2-IIB were clinical stage and presence of metastases to the pelvic lymph nodes. The presence of lymphovascular space invasion adversely affected 10-year overall survival.

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Carcinogen-mediated labilization of lysosomal enzymes such as β-glucuronidase (βG) is often associated with the general process of inflammation. Therefore, the primary goal of this study was to demonstrate that exposing the skin of SENCAR mice to the natural βG inhibitor D-glucaro-1,4-lactone (1,4-GL) and its precursor D-glucuronic acid-γ-lactone (GUL), prior to and during 7,12-dimethylbenz[α]anthracene (DMBA) treatment inhibits not only epidermal hyperplasia but also inflammation in the mouse skin complete carcinogenesis model, i.e., the 4-week inflammatory-hyperplasia assay. Topical administration of 1,4-GL or GUL prior to repetitive, high-dose DMBA treatment markedly and in a dose-related manner inhibited DMBA-induced epidermal hyperplasia (i.e., up to 57%). DMBA-mediated Ha-ras mutations in codon 61 were reduced by up to 78% by 1,4-GL. DMBA-induced inflammation, as measured by dermal leukocyte counts and immunologically, was inhibited by up to 37% by topical 1,4-GL but not by GUL. The inhibition of cellular proliferation and inflammation coincided with the inhibition of βG expression. Thus, the present study suggests that in the DMBA-induced complete skin carcinogenesis model, 1,4-GL when applied topically had both anti-proliferative properties as well as anti-inflammatory properties, whereas GUL had only anti-proliferative when applied topically. However, the number of inflammatory cells in the dermal portion of the skin of mice was significantly reduced by dietary treatment of GUL, whereas both topical and dietary treatments with 1,4-GL were very effective.

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