scholarly journals Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 780
Author(s):  
Kishor Pant ◽  
Estanislao Peixoto ◽  
Seth Richard ◽  
Sergio A. Gradilone
Keyword(s):  
Histone Deacetylases ◽  
Potential Role ◽  
Chemotherapy Resistance ◽  
Tumor Development ◽  
Therapeutic Targets ◽  
Cellular Proteins ◽  
Epigenetic Changes ◽  
Post Translational Modifications ◽  
Frequent Relapse

Cholangiocarcinoma (CCA) is a highly invasive and metastatic form of carcinoma with bleak prognosis due to limited therapies, frequent relapse, and chemotherapy resistance. There is an urgent need to identify the molecular regulators of CCA in order to develop novel therapeutics and advance diseases diagnosis. Many cellular proteins including histones may undergo a series of enzyme-mediated post-translational modifications including acetylation, methylation, phosphorylation, sumoylation, and crotonylation. Histone deacetylases (HDACs) play an important role in regulating epigenetic maintenance and modifications of their targets, which in turn exert critical impacts on chromatin structure, gene expression, and stability of proteins. As such, HDACs constitute a group of potential therapeutic targets for CCA. The aim of this review was to summarize the role that HDACs perform in regulating epigenetic changes, tumor development, and their potential as therapeutic targets for CCA.

scholarly journals CXC and CC Chemokines as Angiogenic Modulators in Nonhaematological Tumors

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Matteo Santoni ◽  
Sergio Bracarda ◽  
Massimo Nabissi ◽  
Francesco Massari ◽  
Alessandro Conti ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Current Literature ◽  
Tumor Angiogenesis ◽  
Binding Proteins ◽  
Potential Role ◽  
Tumor Development ◽  
Therapeutic Targets ◽  
Heparin Binding ◽  
Cc Chemokines

Chemokines are a superfamily of structurally homologous heparin-binding proteins that includes potent inducers and inhibitors of angiogenesis. The imbalance between angiogenic and angiostatic chemokine activities can lead to abnormalities, such as chronic inflammation, dysplastic transformation, and even tumor development and spreading. In this review, we summarize the current literature regarding the role of chemokines as modulators of tumor angiogenesis and their potential role as therapeutic targets in patients with nonhaematological tumors.

scholarly journals The potential role of epigenetic modifications in the heritability of multiple sclerosis

2014 ◽  
Vol 20 (2) ◽  
pp. 135-140 ◽  
Author(s):  
Yuan Zhou ◽  
Steve Simpson ◽  
Adele F Holloway ◽  
Jac Charlesworth ◽  
Ingrid van der Mei ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Potential Role ◽  
Transcriptional Gene Silencing ◽  
Epigenetic Changes ◽  
Missing Heritability ◽  
Significant Component ◽  
Post Transcriptional Gene Silencing ◽  
Genetic And Environmental Factors ◽  
Ms Pathogenesis

It is now well established that both genetic and environmental factors contribute to and interact in the development of multiple sclerosis (MS). However, the currently described causal genetic variants do not explain the majority of the heritability of MS, resulting in ‘missing heritability’. Epigenetic mechanisms, which principally include DNA methylation, histone modifications and microRNA-mediated post-transcriptional gene silencing, may contribute a significant component of this missing heritability. As the development of MS is a dynamic process potentially starting with inflammation, then demyelination, remyelination and neurodegeneration, we have reviewed the dynamic epigenetic changes in these aspects of MS pathogenesis and describe how environmental risk factors may interact with epigenetic changes to manifest in disease.

scholarly journals Potential role of p62 in tumor development

Autophagy ◽  
2011 ◽  
Vol 7 (9) ◽  
pp. 1088-1090 ◽  
Author(s):  
Masaaki Komatsu
Keyword(s):  
Potential Role ◽  
Tumor Development

scholarly journals The potential role of miRNAs and exosomes in chemotherapy in ovarian cancer

2018 ◽  
Vol 25 (12) ◽  
pp. R663-R685 ◽  
Author(s):  
Mona Alharbi ◽  
Felipe Zuñiga ◽  
Omar Elfeky ◽  
Dominic Guanzon ◽  
Andrew Lai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Potential Role ◽  
Chemotherapy Resistance ◽  
Predictive Biomarker ◽  
Response To Therapy ◽  
Target Cells ◽  
Repair Mechanisms ◽  
Drug Efflux Pumps

Chemoresistance is one of the major obstacles in the treatment of cancer patients. It poses a fundamental challenge to the effectiveness of chemotherapy and is often linked to relapse in patients. Chemoresistant cells can be identified in different types of cancers; however, ovarian cancer has one of the highest rates of chemoresistance-related relapse (50% of patients within 5 years). Resistance in cells can either develop through prolonged cycles of treatment or through intrinsic pathways. Mechanistically, the problem of drug resistance is complex mainly because numerous factors are involved, such as overexpression of drug efflux pumps, drug inactivation, DNA repair mechanisms and alterations to and/or mutations in the drug target. Additionally, there is strong evidence that circulating miRNAs participate in the development of chemoresistance. Recently, miRNAs have been identified in exosomes, where they are encapsulated and hence protected from degradation. These miRNAs within exosomes (exo-miRNAs) can regulate the gene expression of target cells both locally and systemically. Exo-miRNAs play an important role in disease progression and can potentially facilitate chemoresistance in cancer cells. In addition, and from a diagnostic perspective, exo-miRNAs profiles may contribute to the development of predictive models to identify responder and non-responder chemotherapy. Such model may also be used for monitoring treatment response and disease progression. Exo-miRNAs may ultimately serve as both a predictive biomarker for cancer response to therapy and as a prognostic marker for the development of chemotherapy resistance. Therefore, this review examines the potential role of exo-miRNAs in chemotherapy in ovarian cancer.

Chemotherapy resistance in pancreatic cancer – potential role of cancer stem cells

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
A Renner ◽  
Y Zhao ◽  
I Ischenko ◽  
P Camaj ◽  
JW Ellwart ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Potential Role ◽  
Chemotherapy Resistance

scholarly journals Sphingolipid-Transporting Proteins as Cancer Therapeutic Targets

2019 ◽  
Vol 20 (14) ◽  
pp. 3554 ◽  
Author(s):  
Doaa Samaha ◽  
Housam H. Hamdo ◽  
Max Wilde ◽  
Kevin Prause ◽  
Christoph Arenz
Keyword(s):  
Potential Role ◽  
Therapeutic Targets ◽  
Transport Proteins ◽  
Biochemical Data ◽  
Sphingolipid Metabolism ◽  
Potential Target ◽  
The Past ◽  
Essential Components ◽  
Rate Limiting

The understanding of the role of sphingolipid metabolism in cancer has tremendously increased in the past ten years. Many tumors are characterized by imbalances in sphingolipid metabolism. In many cases, disorders of sphingolipid metabolism are also likely to cause or at least promote cancer. In this review, sphingolipid transport proteins and the processes catalyzed by them are regarded as essential components of sphingolipid metabolism. There is much to suggest that these processes are often rate-limiting steps for metabolism of individual sphingolipid species and thus represent potential target structures for pharmaceutical anticancer research. Here, we summarize empirical and biochemical data on different proteins with key roles in sphingolipid transport and their potential role in cancer.

scholarly journals Potential role of cancer stem cells as biomarkers and therapeutic targets in cervical cancer

2018 ◽  
Vol 2 (2) ◽  
pp. e1144
Author(s):  
Niyati Sudhalkar ◽  
Nidul P. Rathod ◽  
Ashwathi Mathews ◽  
Supriya Chopra ◽  
Harshini Sriram ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Potential Role ◽  
Therapeutic Targets

The potential role of homocysteine mediated DNA methylation and associated epigenetic changes in abdominal aortic aneurysm formation

2013 ◽  
Vol 228 (2) ◽  
pp. 295-305 ◽  
Author(s):  
Smriti Murali Krishna ◽  
Anthony Dear ◽  
Jeffrey M. Craig ◽  
Paul E. Norman ◽  
Jonathan Golledge
Keyword(s):  
Dna Methylation ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Potential Role ◽  
Epigenetic Changes ◽  
Aneurysm Formation ◽  
Abdominal Aortic

scholarly journals Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease

2020 ◽  
Vol 21 (11) ◽  
pp. 4113
Author(s):  
Julio M. Martinez-Moreno ◽  
Miguel Fontecha-Barriuso ◽  
Diego Martin-Sanchez ◽  
Juan Guerrero-Mauvecin ◽  
Elena Goma-Garces ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Epigenetic Regulation ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Sglt2 Inhibitors ◽  
Post Translational Modifications ◽  
Diabetic Kidney ◽  
Bet Inhibitor

Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications—histone methylation, acetylation and crotonylation—in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of β-hydroxybutyrate, a molecule that generates a specific histone modification, β-hydroxybutyrylation, which has been associated with the beneficial health effects of fasting. To what extent this impact on epigenetic regulation may underlie or contribute to the so-far unclear molecular mechanisms of cardio- and nephroprotection offered by SGLT2 inhibitors merits further in-depth studies.

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