Knockdown of NF-κB p65 subunit expression suppresses growth of nude mouse lung tumour cell xenografts by inhibition of Bcl-2 apoptotic pathway

2015 ◽  
Vol 33 (5) ◽  
pp. 320-325 ◽  
Author(s):  
Yun Qu ◽  
Bo Qu ◽  
Xiaofang Wang ◽  
Rong Wu ◽  
Xiaoye Zhang
Keyword(s):  
Nude Mouse ◽  
Tumour Cell ◽  
Mouse Lung ◽  
Lung Tumour ◽  
Apoptotic Pathway ◽  
Subunit Expression

The warburg effect and tumour cell survival in human GBMs

2007 ◽  
Vol 30 (4) ◽  
pp. 97 ◽  
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.

Monitoring of lung tumour cell growth in artificial membranes

2004 ◽  
Vol 20 (3) ◽  
pp. 442-447 ◽  
Author(s):  
Ying Yang ◽  
Josep Sulé-Suso ◽  
Alicia J El Haj ◽  
Paul R Hoban ◽  
RuiKang Wang
Keyword(s):  
Cell Growth ◽  
Tumour Cell ◽  
Lung Tumour ◽  
Artificial Membranes ◽  
Tumour Cell Growth

scholarly journals Bromodeoxyuridine induces keratin protein synthesis at a posttranscriptional level in human lung tumour cell lines

1999 ◽  
Vol 64 (3) ◽  
pp. 185-193 ◽  
Author(s):  
Shirley McBride ◽  
Derek Walsh ◽  
Paula Meleady ◽  
Noel Daly ◽  
Martin Clynes
Keyword(s):  
Protein Synthesis ◽  
Cell Lines ◽  
Tumour Cell ◽  
Human Lung ◽  
Lung Tumour ◽  
Tumour Cell Lines ◽  
Posttranscriptional Level

scholarly journals USP12 downregulation orchestrates a protumourigenic microenvironment and enhances lung tumour resistance to PD-1 blockade

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhaojuan Yang ◽  
Guiqin Xu ◽  
Boshi Wang ◽  
Yun Liu ◽  
Li Zhang ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Immune Cell ◽  
Tumour Response ◽  
Immune Checkpoint Blockade ◽  
Tumour Cells ◽  
Mouse Lung ◽  
Lung Tumour ◽  
Immunosuppressive Microenvironment ◽  
Mtor Signalling

AbstractOncogenic activation of KRAS and its surrogates is essential for tumour cell proliferation and survival, as well as for the development of protumourigenic microenvironments. Here, we show that the deubiquitinase USP12 is commonly downregulated in the KrasG12D-driven mouse lung tumour and human non-small cell lung cancer owing to the activation of AKT-mTOR signalling. Downregulation of USP12 promotes lung tumour growth and fosters an immunosuppressive microenvironment with increased macrophage recruitment, hypervascularization, and reduced T cell activation. Mechanistically, USP12 downregulation creates a tumour-promoting secretome resulting from insufficient PPM1B deubiquitination that causes NF-κB hyperactivation in tumour cells. Furthermore, USP12 inhibition desensitizes mouse lung tumour cells to anti-PD-1 immunotherapy. Thus, our findings propose a critical component downstream of the oncogenic signalling pathways in the modulation of tumour-immune cell interactions and tumour response to immune checkpoint blockade therapy.

Monoclonal-antibody-defined human lung tumour cell-surface antigens

1985 ◽  
Vol 35 (6) ◽  
pp. 769-775 ◽  
Author(s):  
Julie G. Reeve ◽  
Denis A. Wulfrank ◽  
Jonathan Stewart ◽  
Peter R. Twentyman ◽  
Hugo Baillie-Johnson ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cell Surface ◽  
Tumour Cell ◽  
Human Lung ◽  
Surface Antigens ◽  
Lung Tumour ◽  
Cell Surface Antigens

scholarly journals Tumour‐derived exosomal miR‐3473b promotes lung tumour cell intrapulmonary colonization by activating the nuclear factor‐κB of local fibroblasts

2020 ◽  
Vol 24 (14) ◽  
pp. 7802-7813 ◽  
Author(s):  
Cancan Du ◽  
Xixi Duan ◽  
Xiaohan Yao ◽  
Jiajia Wan ◽  
Yanru Cheng ◽  
...  
Keyword(s):  
Tumour Cell ◽  
Nuclear Factor Κb ◽  
Lung Tumour ◽  
Nuclear Factor
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