Mutational activation of the ras proto-oncogenes is frequently found in skin cancers. However, the nature of downstream signaling pathways from Ras involved in skin carcinogenesis remains poorly understood. Recently, we and others identified phospholipase C (PLC) ⑀ as an effector of Ras. Here we have examined the role of PLC⑀ in de novo skin chemical carcinogenesis by using mice whose PLC⑀ is genetically inactivated. PLC⑀ ؊/؊ mice exhibit delayed onset and markedly reduced incidence of skin squamous tumors induced by initiation with 7,12-dimethylbenz(a)anthracene followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the papillomas formed in PLC⑀ ؊/؊ mice fail to undergo malignant progression into carcinomas, in contrast to a malignant conversion rate of approximately 20% observed with papillomas in PLC⑀ ؉/؉ mice. In all of the tumors analyzed, the Ha-ras gene is mutationally activated irrespective of the PLC⑀ background. The skin of PLC⑀ ؊/؊ mice fails to exhibit basal layer cell proliferation and epidermal hyperplasia in response to TPA treatment. These results indicate a crucial role of PLC⑀ in ras oncogene-induced de novo carcinogenesis and downstream signaling from TPA, introducing PLC⑀ as a candidate molecular target for the development of anticancer drugs.

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Objective This study was to evaluate the fermentation dynamics, structural and nonstructural carbohydrate composition and in vitro gas production of rice straw ensiled with lactic acid bacteria and molasses. Methods Fresh rice straw was ensiled in 1-L laboratory silos with no additive control (C), Lactobacillus plantarum (L), molasses (M) and molasses+ Lactobacillus plantarum (ML) for 6, 15, 30, and 60 days. After storage, the silages were subjected to microbial and chemical analyses as well as the further in vitro fermentation trial. Results All additives increased lactic acid concentration, and reduced pH, dry matter (DM) loss and structural carbohydrate content relative to the control (p<0.05). The highest organic acid and residual sugar contents and lignocellulose reduction were observed in ML silage. L silage had the highest V-score with 88.10 followed by ML silage. L and ML silage improved in vitro DM digestibility as compared with other treatments, while in vitro neutral detergent fibre degradability (IVNDFD) was increased in M and ML silage (p<0.05). M silage significantly (p<0.05) increased propionic acid (PA) content and decreased butyric acid content and acetic acid/PA as well as 72-h cumulative gas production. Conclusion The application of ML was effective for improving both the fermentation quality and in vitro digestibility of rice straw silage. Inclusion with molasses to rice straw could reduce in vitro ruminal gas production.

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The results of this study suggested that strain GG13 is a good LAB inoculant for producing well-fermented silages during the high temperatures of summer times. © 2016 Society of Chemical Industry.