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  • 1
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Tumour `budding' as an index to estimate the potential of aggressiveness in rectal cancer Aims: Although the characteristic of invasive pattern which contributes to Jass's classification is a sensitive prognostic marker in rectal cancer, reproducibility of its assessment has been shown to be problematic. As another histological parameter of invasive margin, we examined the prognostic significance of tumour ‘budding’ and attempted to establish its appropriate criteria. Methods and results: A total of 638 rectal cancer specimens was examined. We defined tumour `budding' as an isolated single cancer cell or a cluster composed of fewer than five cancer cells. We divided these into two groups by their intensity, i.e. the number of `budding' foci within a microscopic field of × 250. Rectal cancer with high-grade `budding' (≥ 10 foci in a field) was observed in 30.1% of patients, and was associated with lower 5-year survival rates (40.7%) than patients with low-grade `budding' (84.0%) (P 〈 0.0001). Based on multivariate analysis, tumour `budding' was selected as the significant independent variable, together with the number of nodes involved, extramural spread, lymphocytic infiltration, apical nodal involvement and tumour differentiation. Kappa coefficient of two-graded tumour `budding' in the intraobserver study was 0.84. Conclusions: Because of its value as a prognostic indicator and its reproducibility, tumour `budding' would be a good index to estimate the aggressiveness of rectal cancer.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: To investigate the effects of nerve growth factor (NGF)and cyclic AMP (cAMP) on the level of the nicotinic acetylcholine receptorsubunit α3 mRNA, we used PC12h cells, PC12 cells expressingdominant-negative Ras protein, and the parental PC12 cells. PC12h cells haveNGF-responsive tyrosine hydroxylase activity. Expression of dominant-negativeRas protein prevents the signaling through the Ras-mitogen-activated proteinkinase cascade. The morphological changes of the parental PC12 cells inresponse to NGF and 8-(4-chlorophenylthio)adenosine 3′,5′-cyclicmonophosphate (CPTcAMP), a cell-penetrating cAMP analogue, were similar tothose of PC12h cells. NGF up-regulated the α3 mRNA level in PC12h cellsand down-regulated the α3 mRNA level in the parental PC12 cells.Expression of dominant-negative Ras protein and an inhibitor ofmitogen-activated protein kinase kinase inhibited the effects of NGF onα3 mRNA level. CPTcAMP down-regulated the α3 mRNA level in allthree PC12 cell lines. An inhibitor of protein kinase A inhibited theCPTcAMP-induced down-regulation of α3 mRNA. The α3 mRNAdown-regulation required prolonged treatment with CPTcAMP even after cAMPresponse element binding protein phosphorylation was decreased. Membranedepolarization with high K+ had no effect on the α3 mRNA level in PC12h cells. Based on these results, we propose that at least two unknown effectors regulate α3 mRNA levels in PC12 cells.
    Type of Medium: Electronic Resource
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