Antiangiogenic therapy with Nintedanib affects hypoxia, angiogenesis and apoptosis in the ventral prostate of TRAMP animals

AbstractThe antiangiogenic therapy for prostate cancer with Nintedanib, a potent inhibitor of important growth factor receptors, has been proven to delay tumor progression and arrest tumor growth; thus, the aim herein is to evaluate Nintedanib effects on tumor cells, besides  angiogenesis and apoptosis processes, metalloproteinases and hypoxia factor in an animal model. Nintedanib promoted growth inhibition and cell death in a dose-dependent manner, showing no tumor selectivity. Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) were treated with Nintedanib (10 m g/kg/day) in different stages of tumor development and the ventral prostate was examined for protein levels by means of immunohistochemistry and Western blotting and apoptosis evaluation. In vitro antiproliferative activity of Nintedanib was also assessed in nine human tumor cell lines. Early Ninted anib treatment has shown decreased levels of FGF-2, VEGFR-1, MMP-9 and HIF-1α and a significantly increased apoptosis of epithelial cells. Furthermore, late Nintedanib treatment decreased FGF-2, VEGFR-1 and FGFR-3 levels. Importantly, even after treatment discontinuation, treated animals displayed a significant decrease in VEGFR-1 as well as MMP-9. Although Nintedanib treatment in late stages of tumor growth has shown some good results, it is noteworthy that the drug presents the best tissue response when administered in the early stages of disease development. Nintedanib treatment has shown to be a p...
Source: Cell and Tissue Research - Category: Cytology Source Type: research

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High bisphenol A concentrations augment the invasiveness of tumor cells through Snail-1/Cx43/ERRγ-dependent epithelial-mesenchymal transition. Toxicol In Vitro. 2019 Oct 17;:104676 Authors: Ryszawy D, Pudełek M, Kochanowski P, Janik-Olchawa N, Bogusz J, Rąpała M, Koczurkiewicz P, Mikołajczyk J, Borek I, Kędracka-Krok S, Karnas E, Zuba-Surma E, Madeja Z, Czyż J Abstract Bisphenol A (BPA) is commonly present in plastics used for food storage and preservation. The release of BPA from these products results in a permanent human exposition to BPA; however, the quality and quantity of BPA advers...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer. Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal cancer, is an uncommon but challenging disease. Its incidence has recently increased highly worldwide (1). The risk factors for GBC include sex, aging, obesity, chronic cholecystitis, and cholelithiasis (2, 3). Because of the lack of an effective early diagnostic method, the disease often is not diagnosed ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions sections. Both authors shared in the final refinement of the manuscript. Funding Salary support for WG by National Science Foundation grant 1624615 is gratefully acknowledged. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Acknowledgments We gratefully acknowledge very useful comments from Peter Klein on an earlier version of this manuscript, and from the reviewers of this paper, whose comments have resulted in improvements. An earlier version of this...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Ginevra Doglioni1,2†, Sweta Parik1,2† and Sarah-Maria Fendt1,2* 1Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium 2Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute, Leuven, Belgium Metastasis formation is the leading cause of death in cancer patients. Thus, understanding and targeting this process is an unmet need. Crucial steps during the establishment of metastases include the (pre)metastatic niche formation. This process relies on the interaction of th...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, we showed hypermethylation of CpGs as a novel mechanism of action for DNMTi agents and identified 638 hypermethylated molecular targets (CpGs) common to decitabine and azacytidine therapy. These novel results suggest that hypermethylation of CpGs should be considered when predicting the DNMTi responses and side effects in cancer patients. Introduction DNA methyltransferase inhibitors (DNMTi) are widely used as chemical tools for hypomethylating the genome, with an aim to understand the role of DNA methylation in multiple processes (e.g., X-chromosome inactivation and DNA imprinting) and as an anti-ca...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin Chunhua Liu1†, Lijing Wang1†, Qingping Jiang2†, Junyi Zhang3†, Litong Zhu1, Li Lin1, Huiping Jiang1, Dan Lin1, Yanyi Xiao1, Weiyi Fang1,3 and Suiqun Guo1* 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China 2Department of Pathology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China 3Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guang...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, we show that αvβ6 expression is required for prostate cancer progression, including castrate-resistant prostate cancer; mechanistically, by promoting activation of JNK1, the αvβ6 integrin causes androgen receptor–increased activity in the absence of androgen and consequent upregulation of survivin. These preclinical results pave the way for further clinical development of αvβ6 antagonists for prostate cancer therapy. Cancer Res; 76(17); 5163–74. ©2016 AACR.
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor and Stem Cell Biology Source Type: research
Conclusions: There is no approved drug that can specifically target AR- independent NEPC tumors. The restricted set of therapeutic options against this subtype of prostate cancer and consequent dismal outcome stem in part from our incomplete understanding of the molecular events underlying its pathogenesis. The discovery that epigenetics can be a key process in distinguishing tumors that are AR-independent and at high risk for NEPC progression represents an important step to highlight the use of epigenetic modifiers as therapeutic agents for this subtype of prostate cancer.Citation Format: Loredana Puca, Dong Gao, Myriam K...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Epigenetic Cancer Therapies Source Type: research
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