Cancer biology and molecular genetics of A3 adenosine receptor

AbstractA3 adenosine receptor (A3AR) is a cell membrane protein, which has been found to be overexpressed in a large number of cancer types. This receptor plays an important role in cancer by interacting with adenosine. Specifically, A3AR has a dual nature in different pathophysiological conditions, as it is expressed according to tissue type and stimulated by an adenosine dose-dependent manner. A3AR activation leads to tumor growth, cell proliferation and survival in some cases, while triggering cytostatic and apoptotic pathways in others. This review aims to describe the most relevant aspects of A3AR activation and its ligands whereas it summarizes A3AR activities in cancer. Progress in the field of A3AR modulators, with a potential therapeutic role in cancer treatment are reported, as well.

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MR1-Restricted T Cells in Cancer Immunotherapy

Cancers ◽

10.3390/cancers12082145 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2145

Author(s):

Pedro Flores-Villanueva ◽

Navid Sobhani ◽

Xu Wang ◽

Yong Li

Keyword(s):

T Cells ◽

Cytotoxic T Cells ◽

Acid Synthesis ◽

Cell Receptor ◽

Dependent Manner ◽

Mait Cells ◽

Mucosal Tissues ◽

Wide Range ◽

A Cell ◽

Cell Membrane Protein

Major histocompatibility complex class I-related (MR1) was first identified as a cell membrane protein involved in the development and expansion of a unique set of T cells expressing an invariant T-cell receptor (TCR) α-chain. These cells were initially discovered in mucosal tissues, such as the intestinal mucosa, so they are called mucosal-associated invariant T (MAIT) cells. MR1 senses the presence of intermediate metabolites of riboflavin and folic acid synthesis that have been chemically modified by the side-products of glycolysis, glyoxal or methylglyoxal. These modified metabolites form complexes with MR1 and translocate from the endoplasmic reticulum to the plasma membrane where MAIT cells’ TCRs recognize them. Recent publications report that atypical MR1-restricted cytotoxic T cells, differing from MAIT cells in TCR usage, antigen, and transcription factor profile, recognize an as yet unknown cancer-specific metabolite presented by MR1 in cancer cells. This metabolite may represent another class of neoantigens, beyond the neo-peptides arising from altered tumor proteins. In an MR1-dependent manner, these MR1-restricted T cells, while sparing noncancerous cells, kill many cancer cell lines and attenuate cell-line-derived and patient-derived xenograft tumors. As MR1 is monomorphic and expressed in a wide range of cancer tissues, these findings raise the possibility of universal pan-cancer immunotherapies that are dependent on cancer metabolites.

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Spindle scaling mechanisms

Essays in Biochemistry ◽

10.1042/ebc20190064 ◽

2020 ◽

Vol 64 (2) ◽

pp. 383-396

Author(s):

Lara K. Krüger ◽

Phong T. Tran

Keyword(s):

Cell Size ◽

Spindle Assembly ◽

Dependent Manner ◽

Post Translational Modification ◽

Size Dependent ◽

A Cell ◽

Chromosome Separation ◽

Spindle Elongation ◽

Protein Gradients ◽

Spindle Structure

Abstract The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.

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Natriuretic Peptides Regulate the Expression of Tissue Factor and PAI-1 in Endothelial Cells

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614861 ◽

1999 ◽

Vol 82 (11) ◽

pp. 1497-1503 ◽

Cited By ~ 20

Author(s):

Hajime Tsuji ◽

Hiromi Nishimura ◽

Haruchika Masuda ◽

Yasushi Kunieda ◽

Hidehiko Kawano ◽

...

Keyword(s):

Endothelial Cells ◽

Tissue Factor ◽

Plasminogen Activator ◽

Natriuretic Peptide ◽

Culture Media ◽

Tissue Type ◽

Dependent Manner ◽

Ang Ii ◽

Plasminogen Activator Inhibitor 1 ◽

Pai 1

SummaryIn the present study, we demonstrate that brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) interact with angiotensin II (Ang II) in regulative blood coagulation and fibrinolysis by suppressing the expressions of both tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by Ang II. The expressions of TF and PAI-1 mRNA were analyzed by northern blotting methods, and the activities of TF on the surface of rat aortic endothelial cells (RAECs) and PAI-1 in the culture media were respectively measured by chromogenic assay.Both BNP and CNP suppressed the expressions of TF and PAI-1 mRNA induced by Ang II in a time- and concentration-dependent manner via cGMP cascade, which suppressions were accompanied by respective decrease in activities of TF and PAI-1. However, neither the expression of tissue factor pathway inhibitor (TFPI) nor tissue-type plasminogen activator (TPA) mRNA was affected by the treatment of BNP and CNP.

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A3 Adenosine Receptor Antagonists

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557510101040417 ◽

2001 ◽

Vol 1 (4) ◽

pp. 417-427 ◽

Cited By ~ 12

Author(s):

C. Muller

Keyword(s):

Adenosine Receptor ◽

Receptor Antagonists ◽

A3 Adenosine Receptor

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Recent Advances on QSAR-Based Profiling of Agonist and Antagonist A3 Adenosine Receptor Ligands

Current Topics in Medicinal Chemistry ◽

10.2174/1568026611313090007 ◽

2013 ◽

Vol 13 (9) ◽

pp. 1048-1068 ◽

Cited By ~ 4

Author(s):

Changliang Deng ◽

Feng Luan ◽

Maykel Cruz- Monteagudo ◽

Fernanda Borges ◽

M. Natalia D. S. Cordeiro

Keyword(s):

Adenosine Receptor ◽

Receptor Ligands ◽

Recent Advances ◽

A3 Adenosine Receptor ◽

Agonist And Antagonist ◽

Adenosine Receptor Ligands

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PapRIV, a BV-2 microglial cell activating quorum sensing peptide

Scientific Reports ◽

10.1038/s41598-021-90030-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yorick Janssens ◽

Nathan Debunne ◽

Anton De Spiegeleer ◽

Evelien Wynendaele ◽

Marta Planas ◽

...

Keyword(s):

Quorum Sensing ◽

Cell Model ◽

Dependent Manner ◽

Communication Signals ◽

Gram Positive Bacteria ◽

A Cell ◽

Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

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A Truncated Form of Herpes Simplex Virus Type 1 Immediate-Early Protein Vmw110 Is Expressed in a Cell Type Dependent Manner

Virology ◽

10.1006/viro.1993.1651 ◽

1993 ◽

Vol 197 (2) ◽

pp. 751-756 ◽

Cited By ~ 69

Author(s):

Roger D. Everett ◽

Anne Cross ◽

Anne Orr

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

Herpes Simplex Virus Type ◽

Dependent Manner ◽

Cell Type ◽

Truncated Form ◽

Early Protein ◽

A Cell ◽

Simplex Virus

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Enterotoxigenicity of Mature 45-Kilodalton and Processed 35-Kilodalton Forms of Hemagglutinin Protease Purified from a Cholera Toxin Gene-Negative Vibrio cholerae Non-O1, Non-O139 Strain

Infection and Immunity ◽

10.1128/iai.74.5.2937-2946.2006 ◽

2006 ◽

Vol 74 (5) ◽

pp. 2937-2946 ◽

Cited By ~ 27

Author(s):

A. Ghosh ◽

D. R. Saha ◽

K. M. Hoque ◽

M. Asakuna ◽

S. Yamasaki ◽

...

Keyword(s):

Cholera Toxin ◽

Vibrio Cholerae ◽

Hela Cells ◽

Histopathological Examination ◽

Short Circuit ◽

Ussing Chamber ◽

Short Circuit Current ◽

Toxin Gene ◽

Dependent Manner ◽

A Cell

ABSTRACT Cholera toxin gene-negative Vibrio cholerae non-O1, non-O139 strain PL-21 is the etiologic agent of cholera-like syndrome. Hemagglutinin protease (HAP) is one of the major secretory proteins of PL-21. The mature 45-kDa and processed 35-kDa forms of HAP were purified in the presence and absence of EDTA from culture supernatants of PL-21. Enterotoxigenicities of both forms of HAP were tested in rabbit ileal loop (RIL), Ussing chamber, and tissue culture assays. The 35-kDa HAP showed hemorrhagic fluid response in a dose-dependent manner in the RIL assay. Histopathological examination of 20 μg of purified protease-treated rabbit ileum showed the presence of erythrocytes and neutrophils in the upper part of the villous lamina propria. Treatment with 40 μg of protease resulted in gross damage of the villous epithelium with inflammation, hemorrhage, and necrosis. The 35-kDa form of HAP, when added to the lumenal surface of rat ileum loaded in an Ussing chamber, showed a decrease in the intestinal short-circuit current and a cell rounding effect on HeLa cells. The mature 45-kDa form of HAP showed an increase in intestinal short-circuit current in an Ussing chamber and a cell distending effect on HeLa cells. These results show that HAP may play a role in the pathogenesis of PL-21.

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