The Tumour Cell and Vascular Bed Size Relationship in Experimental Metastases

Review for "CD5 blockade enhances ex vivo CD8 + T cell activation and tumour cell cytotoxicity"

10.1002/eji.201948309/v2/review1 ◽

2019 ◽

Keyword(s):

T Cell ◽

T Cell Activation ◽

Tumour Cell ◽

Cell Activation ◽

Ex Vivo ◽

Cell Cytotoxicity

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Screening of Venezuelan medicinal plant extracts for cytostatic and cytotoxic activity against tumour cell lines

Planta Medica ◽

10.1055/s-0032-1320482 ◽

2012 ◽

Vol 78 (11) ◽

Author(s):

P Taylor ◽

M Arsenak ◽

MJ Abad ◽

Á Fernández ◽

R Gonto ◽

...

Keyword(s):

Medicinal Plant ◽

Cytotoxic Activity ◽

Cell Lines ◽

Plant Extracts ◽

Tumour Cell ◽

Medicinal Plant Extracts ◽

Tumour Cell Lines

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Cytotoxic activity against tumour cell lines and anti-inflammatory effects of compounds isolated from Xylopia aromatica

Planta Medica ◽

10.1055/s-0033-1352067 ◽

2013 ◽

Vol 79 (13) ◽

Author(s):

O Estrada ◽

L González ◽

M Mijares ◽

Á Fernández ◽

M Ruiz ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Tumour Cell ◽

Tumour Cell Lines ◽

Anti Inflammatory

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Epigenetic modifiers reduce proliferation of human neuroendocrine tumour cell lines

Endocrine Abstracts ◽

10.1530/endoabs.31.p149 ◽

2013 ◽

pp. 1-1

Author(s):

E Kate Lines ◽

U Katherine Gaynor ◽

Mark Stevenson ◽

J Paul Newey ◽

E Sian Piret ◽

...

Keyword(s):

Cell Lines ◽

Tumour Cell ◽

Neuroendocrine Tumour ◽

Epigenetic Modifiers ◽

Tumour Cell Lines

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The warburg effect and tumour cell survival in human GBMs

Clinical & Investigative Medicine ◽

10.25011/cim.v30i4.2878 ◽

2007 ◽

Vol 30 (4) ◽

pp. 97 ◽

Cited By ~ 1

Author(s):

A Wolf ◽

J Mukherjee ◽

A Guha

Keyword(s):

Cytochrome C ◽

Cell Survival ◽

Expression Profile ◽

Tumour Cell ◽

Warburg Effect ◽

Glycolytic Enzymes ◽

Cytochrome C Release ◽

Apoptotic Pathway ◽

The Warburg Effect

Introduction: GBMs are resistant to apoptosis induced by the hypoxic microenvironment and standard therapies including radiation and chemotherapy. We postulate that the Warburg effect, a preferential glycolytic phenotype of tumor cells even under aerobic conditions, plays a role in these aberrant pro-survival signals. In this study we quantitatively examined the expression profile of hypoxia-related glycolytic genes within pathologically- and MRI-defined “centre” and “periphery” of GBMs. We hypothesize that expression of hypoxia-induced glycolytic genes, particularly hexokinase 2 (HK2), favours cell survival and modulates resistance to tumour cell apoptosis by inhibiting the intrinsic mitochondrial apoptotic pathway. Methods: GBM patients underwent conventional T1-weighted contrast-enhanced MRI and MR spectroscopy studies on a 3.0T GE scanner, prior to stereotactic sampling (formalin and frozen) from regions which were T1-Gad enhancing (“centre”) and T2-positive, T1-Gad negative (“periphery”). Real-time qRT-PCR was performed to quantify regional gene expression of glycolytic genes including HK2. In vitro functional studies were performed in U87 and U373 GBM cell lines grown in normoxic (21% pO2) and hypoxic (< 1%pO2) conditions, transfected with HK2 siRNA followed by measurement of cell proliferation (BrdU), apoptosis (activated caspase 3/7, TUNEL, cytochrome c release) and viability (MTS assay). Results: There exists a differential expression profile of glycolytic enzymes between the hypoxic center and relatively normoxic periphery of GBMs. Under hypoxic conditions, there is increased expression of HK2 at the mitochondrial membrane in GBM cells. In vitro HK2 knockdown led to decreased cell survival and increased apoptosis via the intrinsic mitochondrial pathway, as seen by increased mitochondrial release of cytochrome-C. Conclusions: Increased expression of HK2 in the centre of GBMs promotes cell survival and confers resistance to apoptosis, as confirmed by in vitro studies. In vivo intracranial xenograft studies with injection of HK2-shRNA are currently being performed. HK2 and possibly other glycolytic enzymes may provide a target for enhanced therapeutic responsiveness thereby improving prognosis of patients with GBMs.

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