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Total 17 results found since Jan 2013.
DDR1 and MT1-MMP Expression Levels Are Determinant for Triggering BIK-Mediated Apoptosis by 3D Type I Collagen Matrix in Invasive Basal-Like Breast Carcinoma Cells
In conclusion, and in agreement with the other studies (Ford et al., 2007; Koh et al., 2015; Toy et al., 2015; Takai et al., 2018), our data suggest that during the acquisition of mesenchymal features, the level of full-length DDR1 expression should be considered, in addition to the other markers, as an important biomarker in the prognosis of aggressive breast carcinomas. As summarized in Figure 9, the regulation of cell proliferation and apoptosis by the collagen/DDR1 axis involves a differential activation of DDR1 signaling pathway and thus BIK expression. In the case of the basal-like bre...
Source: Frontiers in Pharmacology - May 2, 2019 Category: Drugs & Pharmacology Source Type: research
The JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Conclusion and Perspectives
The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer.
This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research
Ability to Suppress TGF- β-Activated Myofibroblast Differentiation Distinguishes the Anti-pulmonary Fibrosis Efficacy of Two Danshen-Containing Chinese Herbal Medicine Prescriptions
Conclusion: This study suggests that a clinically efficacious cardiovascular Chinese herbal medicine (DLP) can be successfully repurposed to treat a lung disease in pulmonary fibrosis guided by TCM theory. Our comparative study between DLP and DHP demonstrated a critical requirement of suppressing both pro-inflammatory and pro-fibrotic pathways for the treatment of pulmonary fibrosis, supporting that a multi-component prescription capable of “removing both phlegm and blood stasis” will better achieve co-protection of heart and lung in PHD.
Introduction
Idiopathic pulmonary fibrosis (IPF) is a chronic ...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research
Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion
In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy.
Ethics Statement
All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007).
Author Contributions
H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research
Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals.
Author Contributions
LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research
Systems Biology Approaches and Precision Oral Health: A Circadian Clock Perspective
Conclusion
Most head and neck pathologies show a broad cellular heterogeneity making it difficult to achieve an accurate diagnosis and efficient treatment (Graf and Zavodszky, 2017; Lo Nigro et al., 2017). Single cell analysis of circadian omics (Lande-Diner et al., 2015; Abraham et al., 2018), may be a crucial tool needed in the future to fully understand the circadian control of head and neck diseases. It becomes more obvious that there is only a small genetic component but a largely unknown epigenetics and/or environmental component for most of the head and neck pathologies (Moosavi and Motevalizadeh Ardekani, 2016; He...
Source: Frontiers in Physiology - April 15, 2019 Category: Physiology Source Type: research
Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion
The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research
High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer
In this study, the immunohistochemistry results demonstrated that DEPDC1 was high-expressed in breast cancer tissues compared with the paired adjacent normal breast tissues, and its tendency at protein level was consistent with mRNA level from TCGA data. Moreover, DEPDC1 mRNA level revealed the strongest association with poor prognosis and development in breast cancer. In vitro assays showed that DEPDC1 overexpression resulted in significant promotion of proliferation by regulating cell cycle in MCF-7 cells, whilst an opposite effect was found in the MDA-MB-231 cells with DEPDC1 deletion. Notably, further investigation ind...
Source: Frontiers in Oncology - April 11, 2019 Category: Cancer & Oncology Source Type: research
SOCS and Herpesviruses, With Emphasis on Cytomegalovirus Retinitis
Christine I. Alston1,2 and Richard D. Dix1,2*
1Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA, United States
2Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States
Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomega...
Source: Frontiers in Immunology - April 10, 2019 Category: Allergy & Immunology 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
Abstract 767: Oncogenic mutant KRAS modulates EZH2 expression through MEK-ERK and PI3K/AKT signaling in NSCLC: differential effects of different KRAS mutations and increased efficacy of inhibition combined with EZH2 targeted therapy
Conclusions. Our findings suggest that: 1. oncogenic KRAS G12C and G12D mutations differentially modulate EZH2 expression through MEK-ERK and PI3K/AKT signaling respectively - indicating the need for specific KRAS mutation guided therapy; 2. Inhibition of MEK-ERK and PI3K/AKT in combination with an EZH2 inhibitor should result in a significant increased sensitivity to MEK-ERK and PI3K/AKT targeted therapy in KRAS mutant lung cancers. (Grant support: 5 R01 CA155196 and P50CA70907)Citation Format: Erick M. Riquelme, Li Shen, Jing Wang, Carmen Behrens, George Simon, Vassiliki Papadimitrakopoulou, John D. Minna, Ignacio I. Wis...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Riquelme, E. M., Shen, L., Wang, J., Behrens, C., Simon, G., Papadimitrakopoulou, V., Minna, J. D., Wistuba, I. I. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4372: Phosphodiesterase 10A inhibition suppresses lung tumor cell growth by activating PKG to inhibit ras and Wnt signaling
We recently reported that phosphodiesterase 10A (PDE10) is overexpressed in colon tumors and essential for colon tumor cell growth (Li et al., Oncogene 2014), but a role in lung cancer has not been well studied. Human non-small cell lung cancer (NSCLC) cell lines were found to express appreciably higher PDE10 levels compared with normal airway epithelial cells, while silencing of PDE10 expression with siRNA or inhibition of PDE10 activity with small molecule inhibitors selectively inhibits NSCLC cell growth. Here we study the mechanism by which PDE10 inhibitors suppress NSCLC cell growth. At concentrations effective for in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Zhu, B., Lee, K., Canzoneri, J., Ramirez-Alcantara, V., Sigler, S., Gary, B., Butler, E., Keeton, A., Chen, X., Boyd, M., Piazza, G. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4405: Tumor-targeted nanotherapeutics
Directing anticancer agents specifically to tumors and/or cancer cells by targeting specific extracellular receptors fulfills the following three most important tasks: (1) preventing or at least substantially limiting adverse side effects on healthy tissues, (2) enhancing drug internalization by cancer cells, and (3) overcoming (at least in part) resistance mechanisms that are based on the active efflux of exogenous drugs from cancer cells.We developed several tumor-targeted nanoscale-based formulations: various nanocarriers (liposomes, lipid nanoparticles, dendrimers, polymers, quantum dots, mesoporous silica and supermag...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Garbuzenko, O. B., Kuzmov, A., Sapiezynski, J. E., Taratula, O., Shah, V., Zhang, M., Savla, R., John, S., Rodriguez-Rodriguez, L., Minko, T. Tags: Experimental and Molecular Therapeutics Source Type: research
Abstract 4751: 25-hydroxyvitamin D3 induces vitamin D signaling independent of CYP27B1 in non-small cell lung cancer cells
Conclusions NSCLC cells expressing high levels of VDR display increased responsiveness to vitamin D metabolites. Although NSCLC cells express CYP27B1, our results demonstrate that the enzyme may not be required to achieve vitamin D signaling. Rather, 25(OH)D3 may act via the VDR to elicit an anti-tumor responses. The implication of these findings is that dietary supplementation to increase circulating 25(OH)D3 may be beneficial in a subset of NSCLC patients.
Funding provided by NIH RO1 CA132844, training grant 5T32CA009072-37 and P30CA47904
Citation Format: Alissa R. Verone, Suzanne Shoemaker, Robert Parise, Jan H. Beumer,...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Verone, A. R., Shoemaker, S., Parise, R., Beumer, J. H., Hershberger, P. A. Tags: Endocrinology Source Type: research
Abstract 2332: Oncogenic mutant KRAS modulates EZH2 expression through MEK-ERK signaling by remodeling gene expression in NSCLC
In this study, we investigated whether pharmacological disruption of signaling MEK-ERK pathway would affect EZH2 expression in a panel of NSCLC cell lines with and without KRAS mutation. Moreover, we analyzed the transcriptome expression following knockdown of EZH2 expression in NSCLC cell lines with different types of KRAS mutations.
Methods. NSCLC cell lines were treated with different doses of MEK inhibitor AZD6244 (0, 0.5 and 1μM) and the expressions of EZH2, MEK and MAPK were determined by Western-blots. Cell lines were transfected with gene-specific EZH2 siRNA and control siRNA. Gene expression profiling was perform...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Riquelme, E. M., Shen, L., Wang, J., Behrens, C., Minna, J. D., Wistuba, I. I. Tags: Molecular and Cellular Biology Source Type: research
