scholarly journals Angioregulatory microRNAs in Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 71 ◽  
Author(s):  
Mohammad Hasan Soheilifar ◽  
Michael Grusch ◽  
Hoda Keshmiri Neghab ◽  
Razieh Amini ◽  
Hamid Maadi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
The Other ◽  
Angiogenic Response ◽  
Rate Determining Step ◽  
Antiangiogenic Factors ◽  
The One ◽  
Tumor Suppressor Mirnas

Colorectal cancer (CRC) is one of the leading causes of cancer mortality. Angiogenesis is a rate-determining step in CRC development and metastasis. The balance of angiogenic and antiangiogenic factors is crucial in this process. Angiogenesis-related genes can be regulated post-transcriptionally by microRNAs (miRNAs) and some miRNAs have been shown to shuttle between tumor cells and the tumor microenvironment (TME). MiRNAs have context-dependent actions and can promote or suppress angiogenesis dependent on the type of cancer. On the one hand, miRNAs downregulate anti-angiogenic targets and lead to angiogenesis induction. Tumor suppressor miRNAs, on the other hand, enhance anti-angiogenic response by targeting pro-angiogenic factors. Understanding the interaction between these miRNAs and their target mRNAs will help to unravel molecular mechanisms involved in CRC progression. The aim of this article is to review the current literature on angioregulatory miRNAs in CRC.

scholarly journals Assessment of phagocytic activity in live macrophages-tumor cells co-cultures by Confocal and Nomarski Microscopy

2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Dalia Martinez-Marin ◽  
Courtney Jarvis ◽  
Thomas Nelius ◽  
Stéphanie Filleur
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Phagocytic Activity ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Functional Assay ◽  
Loss Of Function ◽  
Multiple Cancer

Abstract Macrophages have been recognized as the main inflammatory component of the tumor microenvironment. Although often considered as beneficial for tumor growth and disease progression, tumor-associated macrophages have also been shown to be detrimental to the tumor depending on the tumor microenvironment. Therefore, understanding the molecular interactions between macrophages and tumor cells in relation to macrophages functional activities such as phagocytosis is critical for a better comprehension of their tumor-modulating action. Still, the characterization of these molecular mechanisms in vivo remains complicated due to the extraordinary complexity of the tumor microenvironment and the broad range of tumor-associated macrophage functions. Thus, there is an increasing demand for in vitro methodologies to study the role of cell–cell interactions in the tumor microenvironment. In the present study, we have developed live co-cultures of macrophages and human prostate tumor cells to assess the phagocytic activity of macrophages using a combination of Confocal and Nomarski Microscopy. Using this model, we have emphasized that this is a sensitive, measurable, and highly reproducible functional assay. We have also highlighted that this assay can be applied to multiple cancer cell types and used as a selection tool for a variety of different types of phagocytosis agonists. Finally, combining with other studies such as gain/loss of function or signaling studies remains possible. A better understanding of the interactions between tumor cells and macrophages may lead to the identification of new therapeutic targets against cancer.

Genetic Engineering of Disease and Pest Resistance in Plants: Present State of the Art

1993 ◽  
Vol 48 (9-10) ◽  
pp. 673-688 ◽  
Author(s):  
Günter Strittmatter ◽  
Dorothee Wegener
Keyword(s):  
Host Plants ◽  
Molecular Mechanisms ◽  
State Of The Art ◽  
Durable Resistance ◽  
The Other ◽  
Rapid Progress ◽  
Pathogenic Viruses ◽  
The One ◽  
Defence Strategies ◽  
Defence Reactions

Abstract Rapid progress in gene technology has allowed, on the one hand, insight to be gained into the complex molecular mechanisms of plant/pathogen recognition and the natural defence strategies of host plants. On the other hand, this technology can also be used for the controlled and efficient generation of genetic variability and for the identification of desirable genotypes, far beyond the possibilities of classical breeding. The first successful attempts have been made to improve resistance against pathogenic viruses, bacteria, fungi and insects by engineering transgenic plants. The majority of these strategies were based on constitutively expressing single proteins that are either toxic to the pathogen/pest, or interfere with its reproductive cycle. More refined strategies, which are at the stage of testing, try to mimic and modify naturally-evolved defence reactions of plants and, thereby, will potentially confer a more durable resistance to a broad range of pathogens

Tumor microenvironment acid-sensitive liposomes enhanced colorectal cancer therapy by acting on both tumor cells and cancer-associated fibroblasts

Nanoscale ◽  
2021 ◽  
Author(s):  
chenglei li ◽  
Zhaohuan Li ◽  
Xue Gong ◽  
Jianhao Liu ◽  
Tingyue Zheng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Crucial Role ◽  
Tumor Invasion ◽  
Cancer Associated Fibroblasts ◽  
Invasion And Metastasis ◽  
Promising Strategy

Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the “soils” in tumor microenvironment (TME). Accordingly, it would be a promising strategy to...

scholarly journals The Drug Developments of Hydrogen Sulfide on Cardiovascular Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-21 ◽  
Author(s):  
Ya-Dan Wen ◽  
Hong Wang ◽  
Yi-Zhun Zhu
Keyword(s):  
Cardiovascular Disease ◽  
Hydrogen Sulfide ◽  
Molecular Mechanisms ◽  
Pathological Process ◽  
The Other ◽  
Acid Oxidase ◽  
Organosulfur Compounds ◽  
Amino Acid Oxidase ◽  
Mercaptopyruvate Sulfurtransferase ◽  
The One

The recognition of hydrogen sulfide (H2S) has been evolved from a toxic gas to a physiological mediator, exhibiting properties similar to NO and CO. On the one hand, H2S is produced from L-cysteine by enzymes of cystathionineγ-lyase (CSE) and cystathionineβ-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST) in combination with aspartate aminotransferase (AAT) (also called as cysteine aminotransferase, CAT); on the other hand, H2S is produced from D-cysteine by enzymes of D-amino acid oxidase (DAO). Besides sulfide salt, several sulfide-releasing compounds have been synthesized, including organosulfur compounds, Lawesson’s reagent and analogs, and plant-derived natural products. Based on garlic extractions, we synthesized S-propargyl-L-cysteine (SPRC) and its analogs to contribute our endeavors on drug development of sulfide-containing compounds. A multitude of evidences has presented H2S is widely involved in the roles of physiological and pathological process, including hypertension, atherosclerosis, angiogenesis, and myocardial infarcts. This review summarizes current sulfide compounds, available H2S measurements, and potential molecular mechanisms involved in cardioprotections to help researchers develop further applications and therapeutically drugs.

scholarly journals Lipid-Induced Mechanisms of Metabolic Syndrome

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Yulia K. Denisenko ◽  
Oxana Yu Kytikova ◽  
Tatyana P. Novgorodtseva ◽  
Marina V. Antonyuk ◽  
Tatyana A. Gvozdenko ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Insulin Response ◽  
The Body ◽  
Diagnostic Methods ◽  
The Other ◽  
Prevention And Treatment ◽  
The One

Metabolic syndrome (MetS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnosis, approaches to the prevention, and treatment of this pathology. Insulin resistance (IR) is the crucial cause of the MetS pathogenesis, which develops against the background of abdominal obesity. In light of recent evidence, it has been shown that lipids, especially fatty acids (FAs), are important signaling molecules that regulate the signaling pathways of insulin and inflammatory mediators. On the one hand, the lack of n-3 polyunsaturated fatty acids (PUFAs) in the body leads to impaired molecular mechanisms of glucose transport, the formation of unresolved inflammation. On the other hand, excessive formation of free fatty acids (FFAs) underlies the development of oxidative stress and mitochondrial dysfunction in MetS. Understanding the molecular mechanisms of the participation of FAs and their metabolites in the pathogenesis of MetS will contribute to the development of new diagnostic methods and targeted therapy for this disease. The purpose of this review is to highlight recent advances in the study of the effect of fatty acids as modulators of insulin response and inflammatory process in the pathogenesis and treatment for MetS.

scholarly journals IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fuqing Hu ◽  
Da Song ◽  
Yumeng Yan ◽  
Changsheng Huang ◽  
Chentao Shen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Complex Formation ◽  
Combination Treatment ◽  
Molecular Mechanisms ◽  
Chemotherapy Resistance ◽  
Predictive Marker ◽  
Pharmacological Agents ◽  
Potential Strategy

AbstractExtracellular cytokines are enriched in the tumor microenvironment and regulate various important properties of cancers, including autophagy. However, the precise molecular mechanisms underlying the link between autophagy and extracellular cytokines remain to be elucidated. In the present study, we demonstrate that IL-6 activates autophagy through the IL-6/JAK2/BECN1 pathway and promotes chemotherapy resistance in colorectal cancer (CRC). Mechanistically, IL-6 triggers the interaction between JAK2 and BECN1, where JAK2 phosphorylates BECN1 at Y333. We demonstrate that BECN1 Y333 phosphorylation is crucial for BECN1 activation and IL-6-induced autophagy by regulating PI3KC3 complex formation. Furthermore, we investigate BECN1 Y333 phosphorylation as a predictive marker for poor CRC prognosis and chemotherapy resistance. Combination treatment with autophagy inhibitors or pharmacological agents targeting the IL-6/JAK2/BECN1 signaling pathway may represent a potential strategy for CRC cancer therapy.

scholarly journals Endothelial to Mesenchymal Transition: An Insight in Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Qingyan Huang ◽  
Yuhong Gan ◽  
Zhikang Yu ◽  
Heming Wu ◽  
Zhixiong Zhong
Keyword(s):  
Molecular Mechanisms ◽  
Plaque Formation ◽  
The Other ◽  
High Morbidity ◽  
Endothelial Cell Dysfunction ◽  
Mesenchymal Transition ◽  
Substantial Body ◽  
Cell Dysfunction ◽  
Endothelial To Mesenchymal Transition ◽  
The One

Atherosclerosis is a fundamental disease of the cardiovascular system that leads to high morbidity and mortality worldwide. The endothelium is the first protective barrier in atherosclerosis. Endothelial cells have the potential to be transformed into mesenchymal cells, in a process termed endothelial to mesenchymal transition (EndMT). On the one hand, EndMT is known to contribute to atherosclerosis by inducing a number of phenotypes ranging from endothelial cell dysfunction to plaque formation. On the other hand, risk factors for atherosclerosis can lead to EndMT. A substantial body of evidence has suggested that EndMT induces the development of atherosclerosis; therefore, a deeper understanding of the molecular mechanisms underlying EndMT in atherosclerosis might provide insights to reverse this condition.

scholarly journals The Interaction Between Long Non-Coding RNAs and Cancer-Associated Fibroblasts in Lung Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Wenqi Ti ◽  
Jianbo Wang ◽  
Yufeng Cheng
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Cancer Associated Fibroblasts ◽  
Protein Coding ◽  
Sequencing Technologies ◽  
Integral Role ◽  
Tumor Growth And Metastasis

Despite great advances in research and treatment, lung cancer is still one of the most leading causes of cancer-related deaths worldwide. Evidence is mounting that dynamic communication network in the tumor microenvironment (TME) play an integral role in tumor initiation and development. Cancer-associated fibroblasts (CAFs), which promote tumor growth and metastasis, are the most important stroma component in the tumor microenvironment. Consequently, in-depth identification of relevant molecular mechanisms and biomarkers related to CAFs will increase understanding of tumor development process, which is of great significance for precise treatment of lung cancer. With the development of sequencing technologies such as microarray and next-generation sequencing, lncRNAs without protein-coding ability have been found to act as communicators between tumor cells and CAFs. LncRNAs participate in the activation of normal fibroblasts (NFs) to CAFs. Moreover, activated CAFs can influence the gene expression and secretion characteristics of cells through lncRNAs, enhancing the malignant biological process in tumor cells. In addition, lncRNA-loaded exosomes are considered to be another important form of crosstalk between tumor cells and CAFs. In this review, we focus on the interaction between tumor cells and CAFs mediated by lncRNAs in the lung cancer microenvironment, and discuss the analysis of biological function and molecular mechanism. Furthermore, it contributes to paving a novel direction for the clinical treatment of lung cancer.

scholarly journals MOLECULAR MECHANISMS OF FORMATION OF BLOOD EOSINOPHILIA UNDER PULMONARY TUBERCULOSIS

2012 ◽  
Vol 67 (5) ◽  
pp. 58-62 ◽  
Author(s):  
Yu. V. Kolobovnikova ◽  
O. I. Urazova ◽  
V. V. Novitskii ◽  
K. O. Mikheeva ◽  
M. D. Goncharov
Keyword(s):  
Plasma Concentration ◽  
Pulmonary Tuberculosis ◽  
Vascular Endothelium ◽  
Molecular Mechanisms ◽  
Granulomatous Inflammation ◽  
The Other ◽  
Blood Eosinophilia ◽  
Mechanisms Of Formation ◽  
The One

Molecular factors of pathogenesis of the eosinophilic blood reaction under pulmonary tuberculosis are analyzed in the article. It has been established that the key cytokine providing the development of hemic eosinophilia in patients with pulmonary tuberculosis is IL-5. IL-5 plasma concentration turned out to be increased only in patients with eosinophilia. Increase of eotaxin was determined in patients with tuberculosis despite of the presense of eosinophilia. One-directional nature of the defined changes in eotaxin concentration might be explained by dual properties of this chemokine: on the one hand, eotaxin mediates long-term presence of eosinophils in blood; on the other hand, it initiates the process of adhesion of eosinophilic leucocytes to vascular endothelium with their further migration to the focus of granulomatous inflammation. The established increase in number of IL-5R-positive eosinophils presents one more mechanism which explains the basis of long-term presence of eosinophils in peripheral blood in patients with pulmonary tuberculosis. 

scholarly journals Cancer-Associated Fibroblasts Promote the Upregulation of PD-L1 Expression Through Akt Phosphorylation in Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yang Gao ◽  
Zhao Sun ◽  
Junjie Gu ◽  
Zhe Li ◽  
Xiuxiu Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Disease Free Survival ◽  
Epithelial Tissue ◽  
Cancer Associated Fibroblasts ◽  
Tumor Immune Escape ◽  
Akt Phosphorylation

Upregulation of immune checkpoint proteins is one of the main mechanisms for tumor immune escape. The expression of programmed death ligand-1 (PD-L1) in colorectal cancer (CRC) is higher than in normal colorectal epithelial tissue, and patients with higher PD-L1 expression have a poorer prognosis. Additionally, PD-L1 expression in CRC is affected by the tumor microenvironment (TME). As a major component of the TME, cancer-associated fibroblasts (CAFs) can act as immune regulators and generate an immunosuppressive tumor microenvironment. Therefore, we speculated that CAFs may be related to the upregulation of PD-L1 in CRC, which leads to tumor immune escape. We found that CAFs upregulate PD-L1 expression in CRC cells through AKT phosphorylation, thereby reducing the killing of CRC cells by peripheral blood mononuclear cells. The ratio of CAFs to CRC cells was positively correlated with AKT phosphorylation and the expression of PD-L1 in CRC in vitro. Consistent with the in vitro results, high CAF content and high expression of PD-L1 were negatively correlated with disease-free survival (DFS) of CRC patients. These results indicate that the upregulation of PD-L1 expression in CRC by CAFs through the activation of Akt is one of the molecular mechanisms of tumor immune escape. Thus, targeted anti-CAF therapy may help improve the efficacy of immunotherapy.

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