Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma.

Identifying therapeutic targets for cancer treatment relies on consistent changes within particular types or sub-types of malignancy. The ability to define either consistent changes or sub-types of malignancy is often masked by tumor heterogeneity. To elucidate therapeutic targets in cutaneous squamous cell carcinoma (cSCC), the most frequent skin neoplasm with malignant potential, we have developed an integrated approach to gene expression profiling beginning with primary keratinocytes in culture. Candidate drivers of cSCC development were derived by first defining a set of in vitro cancer genes and then comparing their expression in a range of clinical data sets containing normal skin, cSCC and the benign hyper-proliferative condition psoriasis. A small interfering RNA (siRNA) screen of the resulting 21 upregulated genes has yielded targets capable of reducing xenograft tumor volume in vivo. Small-molecule inhibitors for one target, Polo-like kinase-1 (PLK1), are already in clinical trials for other malignancies, and our data show efficacy in cSCC. Another target, C20orf20, is identified as being overexpressed in cSCC, and siRNA-mediated knockdown induces apoptosis in vitro and reduces tumor growth in vivo. Thus, our approach has shown established and uncharacterized drivers of tumorigenesis with potent efficacy as therapeutic targets for the treatment of cSCC.

Investigation of the reliability of 24 h urine excretion as a biomarker of isoflavone exposure over time and over a wide range of isoflavone intakes.

OBJECTIVE: To study the variation in genistein + daidzein intake over a 6-month period and test the reliability of 24 h urinary isoflavones as a biomarker of exposure over time. DESIGN: Dietary genistein + daidzein intake was assessed at various time points throughout six months in 15 healthy subjects. Group 1 (n=8) followed nonsupplemented diets and Group 2 (n=7) took a 35 mg/d isoflavone supplement for 3 months and each subject provided a 24 h urine collection, validated with para-aminobenzoic acid, during weeks 7, 15 and 19. Urine was analysed for genistein and daidzein using LC-MS. RESULTS: Isoflavone intake in Groups 1 and 2 ranged from 0.00 to 1.1 mg/d and 0.1 to 53.1 mg/d, respectively. Urine excretion for both groups ranged from 0.20 to 9.56 mg/d. The relationship between 24 h excretion and isoflavone intake is y=0.44 x +/- 0.03(standard deviation) + 1.57; r=0.89, P<0.001. CONCLUSION: The 24 h urinary isoflavones can be used as biomarkers of isoflavone exposure over time.

Evaluation of intraruminal devices for combined facial eczema control and trace element supplementation in sheep.

Intraruminal devices containing zinc oxide are very effective in preventing facial eczema in sheep. In the present study such devices augmented with various amounts of selenium and cobalt have been evaluated for their ability to improve the Se and CO status of pregnant ewes, as reflected by changes in blood Se and serum Vitamin B12 concentrations. Devices containing 16.4 mg of Se (as sodium selenate) and 20.4 mg of Co (as cobalt sulphate) were effective in increasing and maintaining elevated blood Se concentrations for at least 84 days and serum Vitamin B12 for 42 days. Such devices will therefore prevent trace element deficiencies in sheep as well as providing protection against facial eczema.

Wound compression pads are of no value after local anaesthetic breast biopsy.

In a randomised study of 120 patients undergoing breast biopsy, wound compression pads did not reduce the frequency of postoperative bruising or haematoma formation, and 12% of the 62 patients having pads had complaints regarding their use. Wound compression pads are of no value after local anaesthetic breast biopsy.