A pilot 'window of opportunity' neoadjuvant study of metformin in localised prostate cancer.

BACKGROUND: Metformin is an inhibitor of complex 1 in the respiratory chain, and is widely used to reduce insulin resistance. It has also been described to have pleotropic effects including via AMPK on inhibiting the mTOR kinase. Pre-clinical and epidemiological studies suggest an ability to modulate disease evolution in prostate cancer. In this study, we aimed to (i) demonstrate safety and tolerability of neoadjuvant metformin administration and (ii) document changes in proliferative (Ki67) and AMPK-related signalling indices between matching biopsies and prostatectomies METHODS: Men were treated in a single-arm 'window of opportunity' study between their decision to undergo radical prostatectomy and the operation itself. Forty patients were planned but only 24 patients were enrolled owing to slow accrual. Twenty-one patients were evaluable for pathological outcomes and 22 for serum metabolic indices. Metformin was given at doses to 500 mg t.i.d. Ki67 index was calculated using the Aperio-positive pixel count algorithm, whereas immunohistochemical measurements were by consensus H-Score. Comparative statistics were analysed by students t-tests and/or Wilcoxon matched pairs signed rank test. RESULTS: Baseline characteristics included median PSA 6 ng ml(-1) (3.22-36.11 ng ml(-1)). Median duration of drug treatment was 41 days (18-81). Treatment was well tolerated with only three patients developing G3/4 toxicities. In a per patient and per tumour analyses, metformin reduced the Ki67 index by relative amounts of 29.5 and 28.6 % (P=0.0064 and P=0.0042) respectively. There was also a significant decrease in P-4EBP1 staining (P<0.001) but no change in P-AMPK or P-ACC. There were no correlations between any metabolic, morphometric or cancer-related serum indices. There was a trend towards PSA reduction (P=0.08). The study is limited by small patient numbers and tumour heterogeneity. CONCLUSIONS: Neoadjuvant metformin is well tolerated prior to radical prostatectomy. Data to date indicate promising effects on metabolic and tissue proliferation and signalling parameters.

Femtosecond microscopy of radial energy transport in a micrometer-scale aluminum plasma excited at relativistic intensity.

Using femtosecond microscopy, we observe subpicosecond transport of thermal energy radially outward from a micrometer-sized spot of an aluminum target following P-polarized excitation at >10(18) W/cm2 with a 24 fs pulse. The rapid expansion coincides with the onset of nonlocal energy transport dominated by radiation and hot electrons.

Conservation of the British National Begonia Collection by micropropagation.

Regeneration was investigated in non-sterile leaf explants taken from 87 Begonia lines after culturing for up to 10 weeks in vitro on Knop's mineral salts agar medium with no exogenous growth substances present. For many lines, only very limited supplies of leaf samples were available; nevertheless, in 66 lines de novo regeneration of roots and buds occurred and potted plants were recovered from 49 lines. Additionally in 13 Begonia lines, buds were excised from stock plants and cultured under non-sterile conditions on Knap's agar. In seven of these the buds rooted and gave rise to potted plants. In six lines organogenic cultures (derived from sterile leaf explants) have been established in long-term culture on Murashige & Skoog medium supplemented with growth substances and potted plants have been recovered. Sterile explants from a further 12 lines showed regeneration and have been sub-cultured. The establishment of such sterile cultures, with continued regenerative capacity, is a significant step in the development of a programme for the conservation of rare and endangered begonias.

The occurrence of shoot teratomata in tissue cultures of Taraxacum officinale.

Tissue cultures of Taraxacum officinale have been isolated showing either normal organogenesis, callus growth only, or teratological shoots. The latter are apparently stable and the teratomata range from tumerous outgrowths, to flattened thalloid forms and short shoots with strap shaped leaves. The proximal regions of such shoots are tumerous and no distinction between apex, leaf and bud primordia is possible.