Cancer stem cells (CSCs), known also as tumor-initiating cells, are quiescent, pluripotent, self-renewing neoplastic cells that were first identified in hematologic tumors and soon after in solid malignancies. CSCs have attracted remarkable research interest due to their role in tumor resistance to chemotherapy and radiation treatment as well as recurrence. Extensive research has been devoted to the role of CSCs in glioblastoma multiforme (GBM), the most common primary brain tumor in adults, which is characterized by a dismal prognosis because of its aggressive course and poor response to treatment. The aim of the current paper is to provide an overview of current knowledge on the role of cancer stem cells in the pathogenesis and treatment resistance of glioblastoma. The six regulatory mechanisms of glioma stem cells (GSCs)—tumor microenvironment, niche concept, metabolism, immunity, genetics, and epigenetics—are reviewed. The molecular markers used to identify GSCs are described. The role of GSCs in the treatment resistance of glioblastoma is reviewed, along with future treatment options targeting GSCs. Stem cells of glioblastoma thus represent both a driving mechanism of major treatment difficulties and a possible target for more effective future approaches.
In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/ PDGFRA, CD44/PDGFRA, and p21/PDGFRA.
23SUMMARY Introduction. Meningiomas are common primary tumors of brain meninges. These neoplasms develop from arachnoid cap cells and are multiple in 1 -10% cases. Occasionally, significantly higher multiplicity rates have been reported, at least partially due to the increased application of computed tomography and magnetic resonance imaging in the diagnostics of intracranial pathologies. Meningiomas generally express progesterone receptors, but only few studies have focused on sex hormone receptor differences between solitary and multiple meningiomas. Similarly, there is limited information on cell proliferation and adhesion factors in solitary and multiple meningiomas. Aim of the study. Was to evaluate the immunohistochemical differences in sex hormone receptor expression, cell proliferation and adhesion within solitary and multiple meningiomas. Material and methods. In a retrospective study, 11 consecutive multiple meningiomas and 20 grade-matched solitary meningiomas were assessed by immunohistochemistry (IHC) to detect estrogen receptors (ER), progesterone receptors (PR), Ki-67 and neural cell adhesion molecule (NCAM). IHC was followed by quantitative microscopic evaluation. Descriptive and inferential statistics was applied including confidence interval (CI) analysis, Mann-Whitney U test and Spearmen correlation by IBM SPSS Statistics 22.0 software; p values less than 0.05 were regarded as statistically significant. Results. Although PR were found in all samples, the mean expression was significantly lower in multiple meningiomas (p = 0.03): 30.0% (95% CI: 10.4 -49.8) versus 70.6% (95% CI: 56.6 -84.7) in solitary meningiomas. ER were invariably absent in both groups. The proliferation index did not differ in solitary and multiple tumors. There was a trend (p = 0.07) to higher mean expression of NCAM in multiple meningiomas than in control group: 48.3% (95% CI: 25.8 -70.8) versus 24.6% (95% CI: 13.2 -36.0), respectively. The multiple meningiomas showed diverse histological types and immunophenotypes in up to 33.3% patients. Conclusions. Multiple meningiomas are characterized by significant down-regulation of PR and up-regulation of NCAM. The last finding can indicate neural differentiation and/ or peculiarities of cell adhesion and signaling that facilitate multifocal proliferation. Diverse histological types as well as PR and NCAM expression in separate meningiomas within same patient indicate independent multicentric origin.
Gastric cancer induces systemic inflammatory reaction (SIR) manifesting with changes in counts of white blood cell fractions and concentrations of acute phase proteins, clotting factors and albumins. Thus, protein-based scores or blood cell ratios (neutrophil to lymphocyte ratio (NLR); platelet to lymphocyte ratio (PLR)) are used to evaluate SIR. SIR tests are biologically justified by multiple clinically important and fascinating events including bone marrow activation, development of immune-suppressing immature myeloid cells, generation of pre-metastatic niches and neutrophil extracellular trap formation from externalised DNA network in bidirectional association with platelet activation. Despite biological complexity, clinical SIR assessment is widely available, patient-friendly and economically feasible. Here we present concise review on NLR, PLR, Glasgow prognostic score and fibrinogen -parameters that have prognostic role regarding overall, cancer-free and cancer-specific survival in early and advanced cases. Tumour burden can be predicted helping in preoperative detection of serosal or lymph node involvement. Practical consequences abound, including selection of surgical approach in respect to tumour burden, adjustments in treatment intensity by prognosis or evaluation of chemotherapy response. The chapter also scrutinises main controversies including different cut-off levels. Future developments should include elaboration of complex scores as described here. SIR parameters should be wisely incorporated in patients' treatment.
SUMMARYIntroduction. Heterogeneity is a characteristic feature of malignant tumours. It challenges the treatment regimens as well as can impair the diagnostic accuracy. Glioblastoma multiforme (GBM), a high-grade malignant glial tumour, is known for the extreme morphological heterogeneity giving rise also to the term itself. Aim of the study was to evaluate heterogeneity of pathogenetically and diagnostically important cardinal tumour features, namely, cellular proliferation and tumour suppressor protein expression in GBMs. Material and methods. The study group comprised 101 GBMs, retrospectively identified by archive search. The inclusion criteria comprised validated diagnosis (by World Health Organisation criteria) and lack of prior treatment. Recurrent GBMs as well as other glial and non-glial tumours were excluded from the study. Insufficient tissue materials comprising stereotactic biopsies and tissues affected by widespread necrosis (exceeding 90%) were also excluded. Proliferation activity (by Ki-67) and expression of aberrant p53 protein was detected by immunohistochemical investigation (IHC) of formalin-fixed, paraplast-embedded tumour samples. Polymeric visualisation system was used to detect bound primary antibodies. The expression of each antigen was measured by computed morphometry in at least 200 cells of hot and cold spots in each tumour. The data were expressed as the relative value. Heterogeneity was estimated as the mathematical difference between the highest and lowest expression value in each tumour. Descriptive statistics was applied. The 95% confidence intervals (CI) were determined as well. Results. The highest proliferation activity ranged 15 -95%; mean 43.9% ]. The lowest proliferation activity ranged 2 -95%, mean 20. 1% [16.8 -23.4]. The mean proliferation heterogeneity was 23. 8% [21.5 -26.2]; range 0 -67%. The mean heterogeneity of p53 protein expression was 11.7% [8.9 -14.6], ranging 0 -75%. Conclusions. GBM is characterized by marked heterogeneity regarding proliferation rate and expression of p53 protein that may affect diagnostic accuracy and grading of gliomas in small samples of tissue material as well as survival in case of small residual tumour after surgical treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.