Journal ArticleDOI
HIF-1alpha attenuates tumor growth in spite of augmented vascularization in an A549 adenocarcinoma mouse model.
Rajkumar Savai,Ralph T. Schermuly,Robert Voswinckel,Aparna Renigunta,Bernd Reichmann,B. Eul,Friedrich Grimminger,Werner Seeger,Frank Rose,Jörg Hänze +9 more
TLDR
It is concluded that in lung A549 cells, overexpression of HIF-1alpha negatively affects tumor growth due to decreased proliferation and increased apoptosis, despite augmented angiogenesis.Abstract:
The hypoxia-inducible transcription factor, HIF-1, adapts cells to low oxygen tension. In addition to the activation of angiogenesis by induction of VEGF, HIF-1 may trigger hypoxia-induced growth arrest and apoptosis. The aim of this study was to analyze the overall effect of HIF-1 on tumor growth in a mouse model, employing human lung adenocarcinoma A549 cells. The A549 cells were transfected to overexpress HIF-1alpha. These cells displayed decreased proliferation, cell-cycle entry, colony formation in soft agar and elevated levels of apoptosis, when compared to control cells transfected with empty vector. The cells were employed in a tumor model by subcutaneous injection into CD-1 nude mice. Persistent overexpression of HIF1alpha and VEGF was demonstrated in these tumors. The HIF-1alpha-overexpressing tumors displayed less tumor growth when compared to tumors formed by control cells. Tumors derived from HIF-1alpha-overexpressing cells revealed an increase in apoptosis when compared to control tumors, in spite of a marked increase in vascular density. We conclude that in lung A549 cells, overexpression of HIF-1alpha negatively affects tumor growth due to decreased proliferation and increased apoptosis, despite augmented angiogenesis.read more
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Review: Implications of In Vitro Research on the Effect of Radiotherapy and Chemotherapy Under Hypoxic Conditions
TL;DR: An overview of preclinical and clinical research on radiotherapy, chemotherapy, and chemoradiation under hypoxic conditions and the effects of hypoxia per se on some critical biological pathways is focused on.
Journal ArticleDOI
Phosphodiesterase-4 promotes proliferation and angiogenesis of lung cancer by crosstalk with HIF.
Soni Savai Pullamsetti,Gamal-Andre Banat,Anja Schmall,Marten Szibor,Dawid Pomagruk,Jörg Hänze,Ewa Kolosionek,Jochen Wilhelm,Thomas Braun,F. Grimminger,Werner Seeger,Werner Seeger,Ralph T. Schermuly,Ralph T. Schermuly,Rajkumar Savai +14 more
TL;DR: The findings suggest that PDE4 is expressed in lung cancer, crosstalks with HIF signaling and promotes lung cancer progression and may represent a therapeutic target for lung cancer therapy.
Journal ArticleDOI
HIF-1α in epidermis: oxygen sensing, cutaneous angiogenesis, cancer, and non-cancer disorders
Hamid Reza Rezvani,Hamid Reza Rezvani,Nsrein Ali,Nsrein Ali,Lars J Nissen,Lars J Nissen,Ghida Harfouche,Ghida Harfouche,Hubert de Verneuil,Hubert de Verneuil,Alain Taieb,Alain Taieb,Frédéric Mazurier,Frédéric Mazurier +13 more
TL;DR: The role of HIF-1α in cutaneous angiogenesis, skin tumorigenesis, and several skin disorders is reviewed and its high expression level in the epidermis is reviewed.
Journal ArticleDOI
Role of Src Tyrosine Kinases in Experimental Pulmonary Hypertension
Soni Savai Pullamsetti,Eva Berghausen,Swati Dabral,Aleksandra Tretyn,Elsa Butrous,Rajkumar Savai,Ghazwan Butrous,Bhola K. Dahal,Ralf P. Brandes,Hossein Ardeschir Ghofrani,Norbert Weissmann,Friedrich Grimminger,Werner Seeger,Stephan Rosenkranz,Ralph T. Schermuly +14 more
TL;DR: It is suggested thatDual inhibition of PDGF receptor and Src kinases potently inhibits mitogenic and motogenic responses to growth factors in PASMCs and pulmonary vascular remodeling in vivo so that dual inhibition may represent an alternative therapeutic approach for pulmonary arterial hypertension.
Journal ArticleDOI
Expression and activity of phosphodiesterase isoforms during epithelial mesenchymal transition: the role of phosphodiesterase 4.
Ewa Kolosionek,Rajkumar Savai,Hossein Ardeschir Ghofrani,Norbert Weissmann,Andreas Guenther,Friedrich Grimminger,Werner Seeger,Werner Seeger,Gamal Andre Banat,Ralph T. Schermuly,Ralph T. Schermuly,Soni Savai Pullamsetti,Soni Savai Pullamsetti +12 more
TL;DR: It is suggested that TGF-beta1 mediated up-regulation of PDE4 promotes EMT in alveolar epithelial cells and targeting PDE 4 isoforms may be a novel approach to attenuate EMT-associated lung diseases such as pulmonary fibrosis and lung cancer.