Progression of diffuse gliomas - from the first diagnosis to recurrence

Gliomas are the most frequent primary brain tumours. The cardinal features of gliomas are infiltrative growth pattern and progression from low-grade tumours to a more malignant phenotype. These features of gliomas generally prevent their complete surgical excision and cause their inherent tendency to recur after initial treatment and lead to poor long-term prognosis. Increasing knowledge about the molecular biology of gliomas has produced new markers that supplement histopathological diagnostics. Molecular markers are also used to evaluate the prognosis and predict therapeutic response. The purpose of this thesis is to study molecular events involved in the malignant progression of gliomas. Gliomas are highly vascularised tumours. Contrast enhancement in magnetic resonance imaging (MRI) reflects a disrupted blood-brain barrier and is often seen in malignant gliomas. In this thesis, 62 astrocytomas, oligodendrogliomas and oligoastrocytomas were studied by MRI and immunohistochemistry. Contrast enhancement in preoperative MRI was associated with angiogenesis, tumour cell proliferation and histological grade of gliomas. Activation of oncogenes by gene amplification is a common genetic aberration in gliomas. EGFR amplification on chromosome 7p12 occurs in 30-40% of glioblastomas. PDGFRA, KIT and VEGFR2 are receptor tyrosine kinase genes located on chromosome 4q12. Amplification of these genes was studied using in situ hybridisation in the primary and recurrent astrocytomas, oligodendrogliomas and oligoastrocytomas of 87 patients. PDGFRA, KIT or VEGFR2 amplification was found in 22% of primary tumours and 36% of recurrent tumours including low-grade and malignant gliomas. The most frequent aberration was KIT amplification, which occurred in 10% of primary tumours and in 27% of recurrent tumours. The expression of ezrin, cyclooxygenase 2 (COX-2) and HuR was studied immunohistochemically in a series of primary and recurrent gliomas of 113 patients. Ezrin is a cell membrane-cytoskeleton linking-protein involved in the migration of glioma cells. The COX-2 enzyme is implicated in the carcinogenesis of epithelial neoplasms and is overexpressed in gliomas. HuR is an RNA-stabilising protein, which regulates the expression of several proteins including COX-2. Ezrin, COX-2 and HuR were associated with histological grade and the overall survival of glioma patients. However, in multivariate analysis they were not independent prognostic factors. In conclusion, these results suggest that contrast enhancement in MRI can be used as a surrogate marker for the proliferative and angiogenic potential of gliomas. Aberrations of PDGFRA, KIT and VEGFR2 genes, as well as the dysregulated expression of ezrin, COX-2 and HuR proteins, are linked to the progression of gliomas.

Harvesting undelimbed Scots pine (Pinus sylvestris L.) from first thinnings for integrated production of kraft pulp and energy

The present study evaluates the feasibility of undelimbed Scots pine (Pinus sylvestris L.) for integrated production of pulp and energy in a kraft pulp mill from the technical, economic and environmental points of view, focusing on the potential of bundle harvesting. The feasibility of tree sections for pulp production was tested by conducting an industrial wood-handling experiment, laboratory cooking and bleaching trials, using conventional small-diameter Scots pine pulpwood as a reference. These trials showed that undelimbed Scots pine sections can be processed in favourable conditions as a blend with conventional small-diameter pulpwood without reducing the pulp quality. However, fibre losses at various phases of the process may increase when using undelimbed material. In the economic evaluation, both pulp production and wood procurement costs were considered, using the relative wood paying capability of a kraft pulp mill as a determinant. The calculations were made for three Scots pine first-thinning stands with the breast-height diameter of the removal (6 12 cm) as the main distinctive factor. The supply chains included in the comparison were based on cut-to-length harvesting, whole-tree harvesting and bundle harvesting (whole-tree bundling). With the current ratio of pulp and energy prices, the wood paying capability declines with an increase in the proportion of the energy fraction of the raw material. The supply system based on the cut-to-length method was the most efficient option, resulting in the highest residual value at stump in most cases. A decline in the pulp price and an increase in the energy price improved the competitiveness of the whole-tree systems. With short truck transportation distances and low pulp prices, however, the harvesting of loose whole trees can result in higher residual value at stump in small-diameter stands. While savings in transportation costs did not compensate for the high cutting and compaction costs by the second prototype of the bundle harvester, an increase in transportation distances improved its competitiveness. Since harvesting undelimbed assortments increases nutrient export from the site, which can affect soil productivity, the whole-tree alternatives included in the present study cannot be recommended on infertile peatlands and mineral soils. The harvesting of loose whole trees or bundled whole trees implies a reduction in protective logging residues and an increase in site traffic or payloads. These factors increase the risk of soil damage, especially on peat soils with poor bearing capacity. Within the wood procurement parameters which were examined, the CO2 emissions of the supply systems varied from 13 27 kg m3. Compaction of whole trees into bundles reduced emissions from transportation by 30 39%, but these reductions were insufficient to compensate for the increased emissions from cutting and compaction.