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Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 23, 2019 Category: Cancer & Oncology Source Type: research

Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
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 - April 9, 2019 Category: Allergy & Immunology Source Type: research

Senescence marker protein 30 protects intestinal epithelial cells against inflammation-induced cell death by enhancing Nrf2 activity
Publication date: December 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 12Author(s): Jieun Choo, Gwangbeom Heo, Su Jin Kim, Yunna Lee, Akihito Ishigami, Naoki Maruyama, Hae Young Chung, Eunok ImAbstractSenescence marker protein 30 (SMP30) is a calcium-binding protein whose expression decreases during senescence. SMP30 deficiency increases susceptibility to cytokine-induced apoptosis in the liver and to radiation-induced apoptosis in the small intestine. Furthermore, colonic epithelial cell death is associated with the severity of colitis. Therefore, in the present study, ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - October 5, 2018 Category: Molecular Biology Source Type: research

TNF- α promotes colon cancer cell migration and invasion by upregulating TROP-2.
In conclusion, the present results demonstrated that low concentrations of TNF-α significantly enhanced colon cancer cell migration and invasion by upregulating TROP-2 via the ERK1/2 signaling pathway. PMID: 29467899 [PubMed]
Source: Oncology Letters - February 24, 2018 Category: Cancer & Oncology Tags: Oncol Lett Source Type: research

Cytosolic calcium mediates RIP1/RIP3 complex-dependent necroptosis through JNK activation and mitochondrial ROS production in human colon cancer cells.
In this study, a RIP1/RIP3 complex was formed in 2-methoxy-6-acetyl-7-methyljuglone (MAM)-treated HCT116 and HT29 colon cancer cells. With this formation, mitochondrial reactive oxygen species (ROS) levels increased, mitochondrial depolarization occurred, and ATP concentrations decreased. This process was identified as necroptosis. This finding was confirmed by experiments showing that MAM-induced cell death was attenuated by the pharmacological or genetic blockage of necroptosis signaling, including RIP1 inhibitor necrostatin-1s (Nec-1s) and siRNA-mediated gene silencing of RIP1 and RIP3, but was unaffected by caspase inh...
Source: Free Radical Biology and Medicine - April 14, 2017 Category: Biology Authors: Sun W, Wu X, Gao H, Yu J, Zhao W, Lu JJ, Wang J, Du G, Chen X Tags: Free Radic Biol Med Source Type: research

Increased extracellular pressure stimulates tumor proliferation by a mechanosensitive calcium channel and PKC-β
Large tumors exhibit high interstitial pressure heightened by growth against the constraining stroma. Such pressures could stimulate tumor proliferation via a mechanosensitive ion channel. We studied the effects of 0–80 mmHg increased extracellular pressure for 24 h on proliferation of SW620, Caco-2, and CT-26 colon; MCF-7 breast; and MLL and PC3 prostate cancer cells, and delineated its mechanism in SW620 cells with specific inhibitors and siRNA. Finally, we compared NF-kB, phospho-IkB and cyclin D1 immunoreactivity in the high pressure centers and low pressure peripheries of human tumors.
Source: Molecular Oncology - October 23, 2014 Category: Cancer & Oncology Authors: Marc D. Basson, Bixi Zeng, Christina Downey, Madhu P. Sirivelu, Jetze J. Tepe Source Type: research

Abstract 707: Tumor-targeted delivery of siRNA using stabilized calcium phosphate nanoparticles based on bio-inspired hyaluronic acid conjugate
Conclusion Considering its biocompatibility, transfection efficacy, and tumor targeting capability, this stabilized organic-inorganic hybrid gene delivery platform should be considered a promising candidate carrier for systemic siRNA delivery and targeted cancer therapy. Citation Format: Min Sang Lee, Jung Eun Lee, Eunkyoung Byun, Nak Won Kim, Haeshin Lee, Ji Hoon Jeong. Tumor-targeted delivery of siRNA using stabilized calcium phosphate nanoparticles based on bio-inspired hyaluronic acid conjugate. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Di...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Lee, M. S., Lee, J. E., Byun, E., Kim, N. W., Lee, H., Jeong, J. H. Tags: Experimental and Molecular Therapeutics Source Type: research

TRPM5-mediated calcium uptake regulates mucin secretion from human colon goblet cells
Mucin 5AC (MUC5AC) is secreted by goblet cells of the respiratory tract and, surprisingly, also expressed de novo in mucus secreting cancer lines. siRNA-mediated knockdown of 7343 human gene products in a human colonic cancer goblet cell line (HT29-18N2) revealed new proteins, including a Ca2+-activated channel TRPM5, for MUC5AC secretion. TRPM5 was required for PMA and ATP-induced secretion of MUC5AC from the post-Golgi secretory granules. Stable knockdown of TRPM5 reduced a TRPM5-like current and ATP-mediated Ca2+ signal. ATP-induced MUC5AC secretion depended strongly on Ca2+ influx, which was markedly reduced in TRPM5 k...
Source: eLife - May 28, 2013 Category: Biomedical Science Authors: Mitrovic, S., Nogueira, C., Cantero-Recasens, G., Kiefer, K., Fernandez-Fernandez, J. M., Popoff, J.-F., Casano, L., Bard, F. A., Gomez, R., Valverde, M. A., Malhotra, V. Tags: Cell biology Source Type: research