scholarly journals Histone Modifying Enzymes as Targets for Therapeutic Intervention in Oesophageal Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4084
Author(s):  
Oliver J. Pickering ◽  
Stella P. Breininger ◽  
Timothy J. Underwood ◽  
Zoë S. Walters
Keyword(s):  
Oesophageal Adenocarcinoma ◽  
Cellular Processes ◽  
Incurable Disease ◽  
Cancer Pathogenesis ◽  
Dismal Prognosis ◽  
Histone Modifying Enzymes ◽  
Epigenetic Regulators ◽  
New Treatments ◽  
Potential Use ◽  
Covalent Histone Modifications

Oesophageal adenocarcinoma (OAC) has a dismal prognosis, where curable disease occurs in less than 40% of patients, and many of those with incurable disease survive for less than a year from diagnosis. Despite the widespread use of systematic chemotherapy in OAC treatment, many patients receive no benefit. New treatments are urgently needed for OAC patients. There is an emerging interest in epigenetic regulators in cancer pathogenesis, which are now translating into novel cancer therapeutic strategies. Histone-modifying enzymes (HMEs) are key epigenetic regulators responsible for dynamic covalent histone modifications that play roles in both normal and dysregulated cellular processes including tumorigenesis. Several HME inhibitors are in clinical use for haematological malignancies and sarcomas, with numerous on-going clinical trials for their use in solid tumours. This review discusses the current literature surrounding HMEs in OAC pathogenesis and their potential use in targeted therapies for this disease.

scholarly journals The Roles of Frequently Mutated Genes of Pancreatic Cancer in Regulation of Tumor Microenvironment

2020 ◽  
Vol 19 ◽  
pp. 153303382092096
Author(s):  
Hongzhi Sun ◽  
Bo Zhang ◽  
Haijun Li
Keyword(s):  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Stromal Cells ◽  
Genomic Analysis ◽  
Ductal Adenocarcinoma ◽  
Genetic Mutations ◽  
Cellular Processes ◽  
Dismal Prognosis ◽  
Mutant Genes

Pancreatic ductal adenocarcinoma has extremely high malignancy and patients with pancreatic ductal adenocarcinoma have dismal prognosis. The failure of pancreatic ductal adenocarcinoma treatment is largely due to the tumor microenvironment, which is featured by ample stromal cells and complicated extracellular matrix. Recent genomic analysis revealed that pancreatic ductal adenocarcinoma harbors frequently mutated genes including KRAS, TP53, CDKN2A, and SMAD4, which can widely alter cellular processes and behaviors. As shown by accumulating studies, these mutant genes may also change tumor microenvironment, which in turn affects pancreatic ductal adenocarcinoma progression. In this review, we summarize the role of such genetic mutations in tumor microenvironment regulation and potential mechanisms.

scholarly journals NAD+Metabolism in Aging and Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 105-130 ◽  
Author(s):  
Tyler G. Demarest ◽  
Mansi Babbar ◽  
Mustafa N. Okur ◽  
Xiuli Dan ◽  
Deborah L. Croteau ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Accelerated Aging ◽  
Cancer Therapies ◽  
Nad Metabolism ◽  
Cellular Processes ◽  
Cancer Pathogenesis ◽  
Nicotinamide Mononucleotide ◽  
Age Related

Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.

scholarly journals Making Sense of Current and Emerging Therapies in Pancreatic Cancer: Balancing Benefit and Value

2015 ◽  
pp. e222-e227 ◽  
Author(s):  
Daniel H. Ahn ◽  
Andrew H. Ko ◽  
Neal J. Meropol ◽  
Tanios S. Bekaii-Saab
Keyword(s):  
Pancreatic Cancer ◽  
Standard Of Care ◽  
The United States ◽  
Economic Effects ◽  
Making Sense ◽  
Dismal Prognosis ◽  
Emerging Therapies ◽  
Metastatic Setting ◽  
Localized Disease ◽  
New Treatments

Pancreatic cancer remains the fourth leading cause of cancer deaths in the United States with a dismal prognosis and a 5-year survival of less than 5% across all stages.1In 2014, there were approximately 46,420 new cases of pancreatic cancer with only 9% of patients having localized disease.2Given that the vast majority of patients present with advanced disease, much of the focus for drug development has been in the metastatic setting, which is evident with the advent of two combination chemotherapy regimens for this indication. Although conventional cytotoxic chemotherapy remains the standard of care, an ongoing search for novel therapeutic approaches continues. We will highlight several new approaches here, with a particular emphasis on immunotherapeutic strategies. We will also introduce concepts regarding the potential economic effects associated with the development and implementation of new treatments in pancreatic cancer.

scholarly journals A novel landscape of nuclear human CDK2 substrates revealed by in situ phosphorylation

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz9899
Author(s):  
Yong Chi ◽  
John H. Carter ◽  
Jherek Swanger ◽  
Alexander V. Mazin ◽  
Robert L. Moritz ◽  
...  
Keyword(s):  
Cell Division ◽  
Protein Complexes ◽  
Nuclear Architecture ◽  
Cyclin Dependent Kinase ◽  
Oncogenic Signaling ◽  
Cellular Processes ◽  
Validation Rate ◽  
Associated Proteins ◽  
Epigenetic Regulators

Cyclin-dependent kinase 2 (CDK2) controls cell division and is central to oncogenic signaling. We used an “in situ” approach to identify CDK2 substrates within nuclei isolated from cells expressing CDK2 engineered to use adenosine 5′-triphosphate analogs. We identified 117 candidate substrates, ~40% of which are known CDK substrates. Previously unknown candidates were validated to be CDK2 substrates, including LSD1, DOT1L, and Rad54. The identification of many chromatin-associated proteins may have been facilitated by labeling conditions that preserved nuclear architecture and physiologic CDK2 regulation by endogenous cyclins. Candidate substrates include proteins that regulate histone modifications, chromatin, transcription, and RNA/DNA metabolism. Many of these proteins also coexist in multi-protein complexes, including epigenetic regulators, that may provide new links between cell division and other cellular processes mediated by CDK2. In situ phosphorylation thus revealed candidate substrates with a high validation rate and should be readily applicable to other nuclear kinases.

scholarly journals MicroRNAs-Based Nano-Strategies as New Therapeutic Approach in Multiple Myeloma to Overcome Disease Progression and Drug Resistance

2020 ◽  
Vol 21 (9) ◽  
pp. 3084 ◽  
Author(s):  
Vanessa Desantis ◽  
Ilaria Saltarella ◽  
Aurelia Lamanuzzi ◽  
Assunta Melaccio ◽  
Antonio Giovanni Solimando ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Tumor Suppressors ◽  
Therapeutic Approach ◽  
Physical Stability ◽  
Cellular Processes ◽  
Non Coding Rnas ◽  
Potential Use ◽  
Nuclease Degradation

MicroRNAs (miRNAs, or miRs) are single-strand short non-coding RNAs with a pivotal role in the regulation of physiological- or disease-associated cellular processes. They bind to target miRs modulating gene expression at post-transcriptional levels. Here, we present an overview of miRs deregulation in the pathogenesis of multiple myeloma (MM), and discuss the potential use of miRs/nanocarriers association in clinic. Since miRs can act as oncogenes or tumor suppressors, strategies based on their inhibition and/or replacement represent the new opportunities in cancer therapy. The miRs delivery systems include liposomes, polymers, and exosomes that increase their physical stability and prevent nuclease degradation. Phase I/II clinical trials support the importance of miRs as an innovative therapeutic approach in nanomedicine to prevent cancer progression and drug resistance. Results in clinical practice are promising.

scholarly journals Noncoding RNAs: Emerging Players in Muscular Dystrophies

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Germana Falcone ◽  
Alessandra Perfetti ◽  
Beatrice Cardinali ◽  
Fabio Martelli
Keyword(s):  
Regulatory Networks ◽  
Noncoding Rnas ◽  
Skeletal Muscle Differentiation ◽  
Physiological Mechanisms ◽  
Rna Molecules ◽  
Disease Biomarkers ◽  
Cellular Processes ◽  
Sequencing Technologies ◽  
Regulatory Functions ◽  
Potential Use

The fascinating world of noncoding RNAs has recently come to light, thanks to the development of powerful sequencing technologies, revealing a variety of RNA molecules playing important regulatory functions in most, if not all, cellular processes. Many noncoding RNAs have been implicated in regulatory networks that are determinant for skeletal muscle differentiation and disease. In this review, we outline the noncoding RNAs involved in physiological mechanisms of myogenesis and those that appear dysregulated in muscle dystrophies, also discussing their potential use as disease biomarkers and therapeutic targets.

The role of Cdx2 in Barrett's metaplasia

2010 ◽  
Vol 38 (2) ◽  
pp. 364-369 ◽  
Author(s):  
Benjamin J. Colleypriest ◽  
J. Mark Farrant ◽  
Jonathan M.W. Slack ◽  
David Tosh
Keyword(s):  
Molecular Mechanisms ◽  
Oesophageal Adenocarcinoma ◽  
Tissue Type ◽  
Conditional Deletion ◽  
Dismal Prognosis ◽  
Barrett's Metaplasia ◽  
Rising Incidence ◽  
Barrett’S Metaplasia ◽  
Small And Large Intestine

Metaplasia (or transdifferentiation) is defined as the transformation of one tissue type to another. Clues to the molecular mechanisms that control the development of metaplasia are implied from knowledge of the transcription factors that specify tissue identity during normal embryonic development. Barrett's metaplasia describes the development of a columnar/intestinal phenotype in the squamous oesophageal epithelium and is the major risk factor for oesophageal adenocarcinoma. This particular type of cancer has a rapidly rising incidence and a dismal prognosis. The homoeotic transcription factor Cdx2 (Caudal-type homeobox 2) has been implicated as a master switch gene for intestine and therefore for Barrett's metaplasia. Normally, Cdx2 expression is restricted to the epithelium of the small and large intestine. Loss of Cdx2 function, or conditional deletion in the intestine, results in replacement of intestinal cells with a stratified squamous phenotype. In addition, Cdx2 is sufficient to provoke intestinal metaplasia in the stomach. In the present paper, we review the evidence for the role of Cdx2 in the development of Barrett's metaplasia.

Quality of Life in Pulmonary Arterial Hypertension: Qualitative Insights From Patients and Caregivers

2012 ◽  
Vol 10 (4) ◽  
pp. 222-226 ◽  
Author(s):  
Sean M. Studer ◽  
Christina Migliore
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Functional Limitations ◽  
Lifestyle Changes ◽  
Exertional Dyspnea ◽  
Incurable Disease ◽  
Functional Exercise ◽  
Functional Exercise Capacity ◽  
Pulmonary Arterial ◽  
New Treatments

Pulmonary arterial hypertension (PAH) is a progressive and presently incurable disease resulting in distressing and debilitating symptoms for patients, including exertional dyspnea, fatigue, chest pain/discomfort, and feeling dizzy or lightheaded.12 These symptoms cause profound functional limitations that often require patients to make significant lifestyle changes and cope with formidable psychological challenges as they face this progressive disease. While the introduction of new treatments over the past decade has expanded options for improving functional exercise capacity,3 we still have limited insight into the nature of the psychological challenges facing patients and the secondary impact on their caregivers.

Regulation of MicroRNAs by Phytochemicals: A Promising Strategy for Cancer Chemoprevention

2018 ◽  
Vol 18 (7) ◽  
pp. 640-651 ◽  
Author(s):  
Sadegh Babashah ◽  
Babak Bakhshinejad ◽  
Maryam Tahmasebi Birgani ◽  
Katayoon Pakravan ◽  
William C. Cho
Keyword(s):  
Target Genes ◽  
Cell Cycle Control ◽  
Cancer Chemoprevention ◽  
Mirna Regulation ◽  
Cellular Processes ◽  
Natural Agents ◽  
Promising Strategy ◽  
Cancer Types ◽  
Bioactive Phytochemicals ◽  
Potential Use

A growing body of evidence suggests that phytochemicals are potentially able to affect a variety of cellular processes, including proliferation, apoptosis, cell-cycle control, angiogenesis, inflammation, and DNA repair. Phytochemicals may typically play pleiotropic regulatory roles in cancer cells. Chemoprevention, which can be achieved by using these natural agents, has emerged as a helpful strategy to manage a variety of malignancies. With regard to cancer-associated chemopreventive mechanisms, phytochemicals can act by modulating microRNAs (miRNAs) and their target genes. This review aims to present an overview of recent findings on the effects of some wellcharacterized bioactive phytochemicals on miRNA regulation in different cancer types. The potential use of these phytochemicals for the chemoprevention and treatment of cancer is also discussed.

scholarly journals miRNAs as Potential Biomarkers for Viral Hepatitis B and C

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1440
Author(s):  
Dimitri Loureiro ◽  
Issam Tout ◽  
Stéphanie Narguet ◽  
Sabrina Menasria Benazzouz ◽  
Abdellah Mansouri ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Chronic Infection ◽  
Current Knowledge ◽  
Early Stage ◽  
Cellular Processes ◽  
Non Invasive ◽  
Fibrosis Progression ◽  
B Virus ◽  
Non Coding Rnas ◽  
Potential Use

Around 257 million people are living with hepatitis B virus (HBV) chronic infection and 71 million with hepatitis C virus (HCV) chronic infection. Both HBV and HCV infections can lead to liver complications such as cirrhosis and hepatocellular carcinoma (HCC). To take care of these chronically infected patients, one strategy is to diagnose the early stage of fibrosis in order to treat them as soon as possible to decrease the risk of HCC development. microRNAs (or miRNAs) are small non-coding RNAs which regulate many cellular processes in metazoans. Their expressions were frequently modulated by up- or down-regulation during fibrosis progression. In the serum of patients with HBV chronic infection (CHB), miR-122 and miR-185 expressions are increased, while miR-29, -143, -21 and miR-223 expressions are decreased during fibrosis progression. In the serum of patients with HCV chronic infection (CHC), miR-143 and miR-223 expressions are increased, while miR-122 expression is decreased during fibrosis progression. This review aims to summarize current knowledge of principal miRNAs modulation involved in fibrosis progression during chronic hepatitis B/C infections. Furthermore, we also discuss the potential use of miRNAs as non-invasive biomarkers to diagnose fibrosis with the intention of prioritizing patients with advanced fibrosis for treatment and surveillance.

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