Morphology of Tumor Cell Nuclei Is Significantly Related with Survival Time of Patients with Glioblastomas

Nafe, Reinhold; Franz, Kea; Schlote, W.; Schneider, Berthold

doi:10.1158/1078-0432.ccr-04-1198

Cited by 27 publications

(21 citation statements)

References 19 publications

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“…Clinical studies have linked properties of tumor cell mass and patient survival to variations in individual cells8 and nuclear morphology9. In particular, breast cancer cell line morphologies have been correlated to invasiveness and gene expression profile10.…”

Section: Resultsmentioning

confidence: 99%

A physical sciences network characterization of non-tumorigenic and metastatic cells

Agus¹,

Alexander²,

Arap³

et al. 2013

Sci Rep

150

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To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.

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Section: Resultsmentioning

confidence: 99%

A physical sciences network characterization of non-tumorigenic and metastatic cells

Agus¹,

Alexander²,

Arap³

et al. 2013

Sci Rep

150

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“…For the analysis of the nuclear shape in the control and drug-treated cells, the roundness factor was used [22, 23] with value 1 for a circle and smaller values for increasing irregularities of nuclear shape. For visualisation of the nucleus, the cells were stained with Hoechst 33342 at a final concentration of 80 μg/ml for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Apoptosis induction in human glioblastoma multiforme T98G cells upon temozolomide and quercetin treatment

et al. 2013

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Glioblastoma multiforme is the most aggressive primary brain tumour. At the cellular and molecular levels, several mechanisms responsible for apoptosis or autophagy induction are blocked. Identification of molecular targets stimulating cells to initiate programmed cell death should be performed for therapeutic purposes. A promising solution is the combination of temozolomide and quercetin. The aim of our study was to evaluate the effect of both drugs, applied alone and in combinations, on apoptosis and autophagy induction in human glioblastoma multiforme T98G cells. Our results clearly indicate that quercetin and temozolomide induce apoptosis very significantly, having no effect on autophagy induction. At the molecular level, it was correlated with caspase 3 and 9 activation, cytochrome c release from the mitochondrium and a decrease in the mitochondrial membrane potential. Both drugs are also potent Hsp27 and Hsp72 inhibitors. This suggests that the apoptotic signal goes through an internal pathway. Increased expression of caspase 12 and the presence of several granules in the cytoplasm after temozolomide treatment with or without quercetin preceding appearance of apoptosis may suggest that apoptosis is initiated by ER stress. Additionally, it was accompanied by changes in the nuclear morphology from circular to ‘croissant like’.

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“…It is of interest to note, that KI-67 labeling index in controls corresponds to values found in highly aggressive patient GBMs. 27,28 Vascular density was also measured in these samples. As anticipated from biomicroscopy, there was a significant reduction of blood vessels in both single knockdowns compared to control tumors (Fig.…”

Section: Effect Of Il6 Knockdown In Vitromentioning

confidence: 99%

Combined targeting of interleukin‐6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness

Saidi

Hagedorn

Allain

et al. 2009

Intl Journal of Cancer

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Interleukin‐6 (IL6) and vascular endothelial growth factor (VEGFA) are abundantly produced by glioma cells and contribute to malignancy by promoting angiogenesis, cell proliferation and resistance to apoptosis. We compared the effect of inhibiting IL6 and VEGF on U87‐derived experimental glioma grown on the chick chorio‐allantoic membrane (CAM) or in the brain of xenografted mice. Tumor growth was monitored by biomicroscopy and immunohistology. In vitro, IL6 knockdown had no effect on proliferation but substantially enhanced invasion. In the CAM experimental glioma, IL6 or VEGF knockdown reduced growth and vascularization of the tumors with a comparable efficiency, but increased invasion of residual tumor cells. In contrast, combined IL6/VEGF knockdown not only showed enhanced reduction of tumor growth and angiogenesis but also significantly prevented invasion of residual tumor cells. In mice, combining IL6 knockdown and Avastin™ treatment completely abrogated tumor development and infiltration. Molecular response of tumor cells to single or combined treatment was studied by transcriptomic profiling. Many cell cycle promoting genes and chromatin components were silenced in the double knockdown. In addition, specific migratory signatures detected in tumors under single IL6 or VEGF knockdown were partially erased in combined IL6/VEGF knockdown tumors. Our results show that treatment with a combination of IL6 and VEGF inhibitors brings synergistic antitumoral benefit and reduces global activity of major pathways of cell survival, proliferation and invasiveness in remaining tumor cells that may be induced by using VEGF or IL6 inhibitors alone. © 2009 UICC

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Morphology of Tumor Cell Nuclei Is Significantly Related with Survival Time of Patients with Glioblastomas

Cited by 27 publications

References 19 publications

A physical sciences network characterization of non-tumorigenic and metastatic cells

A physical sciences network characterization of non-tumorigenic and metastatic cells

Apoptosis induction in human glioblastoma multiforme T98G cells upon temozolomide and quercetin treatment

Combined targeting of interleukin‐6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness

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