Forms of Non-Apoptotic Cell Death and Their Role in Gliomas-Presentation of the Current State of Knowledge.

In addition to necrosis and apoptosis, the two forms of cell death that have been known for many decades, other non-apoptotic forms of cell death have been discovered, many of which also play a role in tumors. Starting with the description of autophagy more than 60 years ago, newer forms of cell death have become important for the biology of tumors, such as ferroptosis, pyroptosis, necroptosis, and paraptosis. In this review, all non-apoptotic and oncologically relevant forms of programmed cell death are presented, starting with their first descriptions, their molecular characteristics, and their role and their interactions in cell physiology and pathophysiology.

Cellular Components of the Tumor Environment in Gliomas-What Do We Know Today?

A generation ago, the molecular properties of tumor cells were the focus of scientific interest in oncology research. Since then, it has become increasingly apparent that the tumor environment (TEM), whose major components are non-neoplastic cell types, is also of utmost importance for our understanding of tumor growth, maintenance and resistance. In this review, we present the current knowledge concerning all cellular components within the TEM in gliomas, focusing on their molecular properties, expression patterns and influence on the biological behavior of gliomas.

The Spectrum of Molecular Pathways in Gliomas-An Up-to-Date Review.

During the last 20 years, molecular alterations have gained increasing significance in the diagnosis and biological assessment of tumors. Gliomas represent the largest group of tumors of the central nervous system, and the main aim of this review is to present the current knowledge on molecular pathways and their alterations in gliomas. A wide range of new insights has been gained, including evidence for the involvement of the WNT pathway or the hippo pathway in the pathobiology of gliomas, indicating a broad involvement of different pathways formerly not considered to play a central role in gliomas.

Adult-type and Pediatric-type Diffuse Gliomas : What the Neuroradiologist Should Know.

The classification of diffuse gliomas into the adult type and the pediatric type is the new basis for the diagnosis and clinical evaluation. The knowledge for the neuroradiologist should not remain limited to radiological aspects but should be based additionally on the current edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). This classification defines the 11 entities of diffuse gliomas, which are included in the 3 large groups of adult-type diffuse gliomas, pediatric-type diffuse low-grade gliomas, and pediatric-type diffuse high-grade gliomas.

Heterogeneity in malignant gliomas: a magnetic resonance analysis of spatial distribution of metabolite changes and regional blood volume.

First-pass contrast-enhanced dynamic perfusion imaging provides information about the regional cerebral blood volume (rCBV), an increase of which indicates neovascularization. MR spectroscopic imaging informs about metabolite changes in brain tumors, with elevated choline (Cho) values revealing cell proliferation and density, and the glial metabolite creatine (Cr) representing high-energy storage. This study investigates metabolite changes within the tumor voxel of maximal rCBV value (rCBVmax).

Correlation between amplification of the gene for the epidermal growth factor receptor (EGFR), data from preoperative proton-MR-spectroscopy (1HMRS) and histomorphometric data of glioblastomas.

Objective: To investigate a correlation between preoperative data from proton-MR-spectroscopy (1HMRS), genomic alterations (epidermal growth growth factor receptor [EGFR] gene amplification) and histomorphometric data from glioblastomas.

Study Design: In surgical specimens from 18 patients with glioblastomas, the degree of amplification of the gene for EGFR was determined in the region with the largest Ki-67 proliferation index by differential polymerase chain reaction.

Results: Correlation analysis showed significant positive correlation between degree of EGFR gene amplification and choline and total creatine (CHO/TCR) ratio, indicating increased membrane turnover.

The morphology of perinecrotic tumor cell nuclei in glioblastomas shows a significant relationship with survival time.

A deeper knowledge about histopathological criteria with a significant impact on the prognosis of patients with glioblastomas is worthwhile, since these patients may show a considerable difference in the time of survival. Investigation of the morphology of perinecrotic tumor cell nuclei is a promising approach, because the expression of specific molecules in these cells has been associated with a more aggressive behaviour of the tumors. In our series of patients with documented clinical course, 11 patients had a survival of at least 24 months and we compared this group with a group of 10 patients with maximum survival of 12 months.

Application of different methods for nuclear shape analysis with special reference to the differentiation of brain tumors.

Objective: To study the discriminatory power of different methods designed for nuclear shape analysis with reference to the differentiation and grading of brain tumors and the differentiation between proliferating and nonproliferating nuclei.

Study Design: At least 300 tumor cell nuclei per case were measured by means of a digital image analysis system. Fourier amplitudes no.

Morphology of tumor cell nuclei is significantly related with survival time of patients with glioblastomas.

Purpose: To investigate whether histomorphology of tumor cell nuclei has a significant and independent relation to survival time of patients with glioblastomas.

Experimental Design: Seventy-two tumors from 72 patients were investigated by means of digital image analysis. Proliferating and nonproliferating nuclei were separately measured and parameters of nuclear size, shape, texture, and spatial relationships (topometric parameters) were detected.

Fourier analysis of intracranial aneurysms: towards an objective and quantitative evaluation of the shape of aneurysms.

Shape irregularities of intracranial aneurysms may indicate an increased risk of rupture. To quantify morphological differences, Fourier analysis of the shape of intracranial aneurysms was introduced. We compared the morphology of 45 unruptured (UIA) and 46 ruptured intracranial aneurysms (RIA) in 70 consecutive patients on the basis of 3D-rotational angiography.

Morphology of proliferating and non-proliferating tumor cell nuclei in glioblastomas correlates with preoperative data from proton-MR-spectroscopy.

In contrast to the growing interest in proton-MR-spectroscopy (1HMRS) for preoperative examination of patients with brain tumors, there is nearly no knowledge about a correlation between data from 1HMRS and histomorphology as confirmed by quantitative morphological methods. Whether a correlation can be confirmed between data from 1HMRS and quantitative histomorphology of glioblastomas representing the most frequent type of brain tumors was investigated in the present study. Furthermore, it was of interest, whether correlations between spectroscopic data and histomorphology can be confirmed for proliferating and non-proliferating tumor cell nuclei independently.

Regional heterogeneity of EGFR gene amplification and nuclear morphology in glioblastomas. An investigation using laser microdissection and pressure catapulting.

Objective: To study the regional heterogeneity of epidermal growth factor receptor (EGFR) gene amplification (EGFR-GA) in glioblastomas, considering the relationship between this mutation and morphology of tumor cell nuclei.

Study Design: Tissue samples gained by laser microdissection and pressure catapulting were used for the performance of differential polymerase chain reaction in 32 morphologically different regions from 7 glioblastomas. Semiquantitative determination of EGFR expression and image analysis of tumor cell nuclei were performed in the same regions.

Laser microdissection and pressure catapulting (LMPC) in paraffin sections mounted on glass slides. A methodological report.

The technique of laser microdissection together with laser pressure catapulting (LMPC) is demonstrated in paraffin sections obtained from surgical specimens of brain tumors mounted on glass slides. A sufficient and precise application of microdissection techniques in tissue on glass slides is worthwhile, since it offers the possibility of a retrospective analysis of archived paraffin sections in histopathology. We could demonstrate a precise dissection of areas in tissues of different thicknesses (4 microm and 20 microm).

Preoperative proton-MR spectroscopy of gliomas--correlation with quantitative nuclear morphology in surgical specimen.

A comparison between data from proton-MR spectroscopy (1HMRS) and quantitative histomorphology of tumor cell nuclei in gliomas has not been reported up to now. Therefore, the question must be answered, if there are any significant correlations between histomorphology of gliomas and quantitative data from 1HMRS concerning tissue metabolites. Surgical glioma specimen (glioblastomas, astrocytomas, oligodendrogliomas) from 46 patients with tumor grades II-IV according to WHO have been evaluated by means of a digital image analysis system using Ki-67-immunostained paraffin sections.

Correlation between preoperative magnetic resonance spectroscopic data on high grade gliomas and morphology of Ki-67-positive tumor cell nuclei.

Objective: To investigate possible statistical correlations between metabolic data from preoperative proton magnetic resonance spectroscopy (1HMRS) and morphology of proliferating tumor cell nuclei in anaplastic gliomas and glioblastomas.

Study Design: Ki-67-positive tumor cell nuclei in paraffin sections of surgical specimens from 36 patients (7 anaplastic gliomas, World Health Organization grade 3; 29 glioblastomas, World Health Organization grade 4) were investigated by means of a digital image analysis system. Stringent inclusion criteria were formulated for all cases with respect to histologic quality and spectroscopic examination.

Topometric analysis of diffuse astrocytomas.

Objective: To investigate differences between astrocytomas of WHO grade 2 and anaplastic astrocytomas of WHO grade 3 in terms of topometric variables characterizing individual tumor cell nuclei.

Study Design: Paraffin sections from surgical specimens from 25 astrocytomas (grade 2, n = 11; grade 3, n = 14) were analyzed by means of an image analysis system. At least 300 tumor cell nuclei were measured in the region with the highest Ki-67 proliferation index.