scholarly journals Epigenetic Regulation of Angiogenesis in Development and Tumors Progression: Potential Implications for Cancer Treatment

2021 ◽  
Vol 9 ◽  
Author(s):  
Veronica Mãdãlina Aspriţoiu ◽  
Ileana Stoica ◽  
Coralia Bleotu ◽  
Carmen Cristina Diaconu
Keyword(s):  
Cancer Cells ◽  
Current Knowledge ◽  
Early Stage ◽  
Tumor Development ◽  
Adult Life ◽  
Genetic Alterations ◽  
Control Mechanisms ◽  
Placental Development ◽  
Cardiac Damage ◽  
Epigenetic Markers

Angiogenesis is a multi-stage process of new blood vessel development from pre-existing vessels toward an angiogenic stimulus. The process is essential for tissue maintenance and homeostasis during embryonic development and adult life as well as tumor growth. Under normal conditions, angiogenesis is involved in physiological processes, such as wound healing, cyclic regeneration of the endometrium, placental development and repairing certain cardiac damage, in pathological conditions, it is frequently associated with cancer development and metastasis. The control mechanisms of angiogenesis in carcinogenesis are tightly regulated at the genetic and epigenetic level. While genetic alterations are the critical part of gene silencing in cancer cells, epigenetic dysregulation can lead to repression of tumor suppressor genes or oncogene activation, becoming an important event in early development and the late stages of tumor development, as well. The global alteration of the epigenetic spectrum, which includes DNA methylation, histone modification, chromatin remodeling, microRNAs, and other chromatin components, is considered one of the hallmarks of cancer, and the efforts are concentrated on the discovery of molecular epigenetic markers that identify cancerous precursor lesions or early stage cancer. This review aims to highlight recent findings on the genetic and epigenetic changes that can occur in physiological and pathological angiogenesis and analyze current knowledge on how deregulation of epigenetic modifiers contributes to tumorigenesis and tumor maintenance. Also, we will evaluate the clinical relevance of epigenetic markers of angiogenesis and the potential use of “epi-drugs” in modulating the responsiveness of cancer cells to anticancer therapy through chemotherapy, radiotherapy, immunotherapy and hormone therapy as anti-angiogenic strategies in cancer.

scholarly journals Cancer Genetics and Epigenetics in Cancer Risk Assesment

2021 ◽  
Vol 5 (2) ◽  
pp. 41
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Cancer Cells ◽  
Cancer Genetics ◽  
Point Mutations ◽  
Genetic Alterations ◽  
Genetic Mutations ◽  
Control Mechanisms ◽  
Normal Tissues ◽  
Knowing That ◽  
Whole Exome ◽  
Methylation Patterns

Compared to the normal tissues, cancer cells tend to have higher proliferation rate and often lost their ability to undergo apoptosis. In addition, cancer cells can separate themselves from their original tissue thus causing metastasis in other part of body. While undergoing program cell death, disordered cellular programming can happen. The main causes of this cellular programming anomaly are epigenetic and genetic alterations, which have been known as two separate mechanisms in carcinogenetic. A recent outcome of whole exome sequencing of thousands of human cancers has been the unexpected discovery of many inactivating mutations in genes that control the epigenome. These mutations have the potential to disturb the DNA methylation patterns, histone modifications, and nucleosome positioning, hence, the causing gene expression alternation. Genetic alteration of the epigenome therefore contributes to cancer just as epigenetic process can cause point mutations and disable DNA repair functions. Epigenetic mechanisms changes could cause genetic mutations, and genetic mutations in epigenetic regulators could cause epigenome changes. Knowing that epigenome play a major role in the hierarchy of gene control mechanisms suggests that mutations might have impact on multiple pathways related to cancer phenotype. This pinpoint the fact that recently, the way the genes are organized and controlled are suggested to be a relevant factor for human carcinogenesis.Keywords: cancer genetic, cancer epigenetic, oncogens, tumor suppressor genes, driver mutation, passenger mutation

scholarly journals Regulation of antitumor immunity by inflammation-induced epigenetic alterations

2021 ◽  
Author(s):  
Michael Karin ◽  
Shabnam Shalapour
Keyword(s):  
Cancer Cells ◽  
Chronic Inflammation ◽  
Antitumor Immunity ◽  
Immune Escape ◽  
Tumor Development ◽  
Treatment Resistance ◽  
Genetic Alterations ◽  
Cancer Development ◽  
Epigenetic Alterations ◽  
Regulatory Processes

AbstractChronic inflammation promotes tumor development, progression, and metastatic dissemination and causes treatment resistance. The accumulation of genetic alterations and loss of normal cellular regulatory processes are not only associated with cancer growth and progression but also result in the expression of tumor-specific and tumor-associated antigens that may activate antitumor immunity. This antagonism between inflammation and immunity and the ability of cancer cells to avoid immune detection affect the course of cancer development and treatment outcomes. While inflammation, particularly acute inflammation, supports T-cell priming, activation, and infiltration into infected tissues, chronic inflammation is mostly immunosuppressive. However, the main mechanisms that dictate the outcome of the inflammation-immunity interplay are not well understood. Recent data suggest that inflammation triggers epigenetic alterations in cancer cells and components of the tumor microenvironment. These alterations can affect and modulate numerous aspects of cancer development, including tumor growth, the metabolic state, metastatic spread, immune escape, and immunosuppressive or immunosupportive leukocyte generation. In this review, we discuss the role of inflammation in initiating epigenetic alterations in immune cells, cancer-associated fibroblasts, and cancer cells and suggest how and when epigenetic interventions can be combined with immunotherapies to improve therapeutic outcomes.

Clinical, Cellular, and Molecular Aspects of Cancer Invasion

2003 ◽  
Vol 83 (2) ◽  
pp. 337-376 ◽  
Author(s):  
Marc Mareel ◽  
Ancy Leroy
Keyword(s):  
Cancer Cells ◽  
Cross Talk ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Platelet Activating Factor ◽  
Tumor Development ◽  
Genetic Alterations ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Host Cells

Invasion causes cancer malignancy. We review recent data about cellular and molecular mechanisms of invasion, focusing on cross-talk between the invaders and the host. Cancer disturbs these cellular activities that maintain multicellular organisms, namely, growth, differentiation, apoptosis, and tissue integrity. Multiple alterations in the genome of cancer cells underlie tumor development. These genetic alterations occur in varying orders; many of them concomitantly influence invasion as well as the other cancer-related cellular activities. Examples discussed are genes encoding elements of the cadherin/catenin complex, the nonreceptor tyrosine kinase Src, the receptor tyrosine kinases c-Met and FGFR, the small GTPase Ras, and the dual phosphatase PTEN. In microorganisms, invasion genes belong to the class of virulence genes. There are numerous clinical and experimental observations showing that invasion results from the cross-talk between cancer cells and host cells, comprising myofibroblasts, endothelial cells, and leukocytes, all of which are themselves invasive. In bone metastases, host osteoclasts serve as targets for therapy. The molecular analysis of invasion-associated cellular activities, namely, homotypic and heterotypic cell-cell adhesion, cell-matrix interactions and ectopic survival, migration, and proteolysis, reveal branching signal transduction pathways with extensive networks between individual pathways. Cellular responses to invasion-stimulatory molecules such as scatter factor, chemokines, leptin, trefoil factors, and bile acids or inhibitory factors such as platelet activating factor and thrombin depend on activation of trimeric G proteins, phosphoinositide 3-kinase, and the Rac and Rho family of small GTPases. The role of proteolysis in invasion is not limited to breakdown of extracellular matrix but also causes cleavage of proinvasive fragments from cell surface glycoproteins.

scholarly journals Galectins in Early Pregnancy and Pregnancy-Associated Pathologies

2021 ◽  
Vol 23 (1) ◽  
pp. 69
Author(s):  
Milica Jovanović Krivokuća ◽  
Aleksandra Vilotić ◽  
Mirjana Nacka-Aleksić ◽  
Andrea Pirković ◽  
Danica Ćujić ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Early Pregnancy ◽  
Cell Function ◽  
Current Knowledge ◽  
Early Stage ◽  
Trophoblast Cell ◽  
Placental Development ◽  
The Past ◽  
Lines Of Evidence ◽  
In Pregnancy

Galectins are a family of conserved soluble proteins defined by an affinity for β-galactoside structures present on various glycoconjugates. Over the past few decades, galectins have been recognized as important factors for successful implantation and maintenance of pregnancy. An increasing number of studies have demonstrated their involvement in trophoblast cell function and placental development. In addition, several lines of evidence suggest their important roles in feto-maternal immune tolerance regulation and angiogenesis. Changed or dysregulated galectin expression is also described in pregnancy-related disorders. Although the data regarding galectins’ clinical relevance are still at an early stage, evidence suggests that some galectin family members are promising candidates for better understanding pregnancy-related pathologies, as well as predicting biomarkers. In this review, we aim to summarize current knowledge of galectins in early pregnancy as well as in pregnancy-related pathologies.

Inhibition of Tissue Factor (TF) Pathway Blunts Hepatic Tumor Development in a Rat Colorectal Cancer Model.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 920-920
Author(s):  
Philippe Zerbib ◽  
Alexandre Grimonprez ◽  
Delphine Corseaux ◽  
Lars Petersen ◽  
Brigitte Jude
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Tissue Factor ◽  
Early Stage ◽  
Tumor Development ◽  
Coagulation Factor ◽  
Tumor Cell Line ◽  
Hepatic Tumor ◽  
Control Group ◽  
Hepatic Tumors

Abstract Occurrence of hepatic metastasis (HM) is the leading cause of death in colorectal cancer, making their prevention a major challenge. Tissue factor (TF), the principal initiator of coagulation after binding to its ligand, coagulation factor FVIIa, is expressed by most colorectal cancer cells, and has been demonstrated to be associated to tumor invasion and metastasis. The aim of this study was to analyze the effects of inhibition of the TF pathway in a rat model of HM of colorectal cancer. Methods DHDK12 Pro B cells (20.106 cells), a tumor cell line established from chemically induced colon carcinoma in BDIX rats, were injected in the portal vein of syngenic rats. Inhibition of TF was achieved in 19 rats (treat ment group) through intraperitoneal injection of active site-inactivated factor VIIa (FFR-FVIIa, Novo Nordisk, Denmark) (10μg/g, once a day from day 3 to day 8 after HM induction). Additionally, 18 rats underwent cancer cell infusion according to the same procedure, without FFR-FVIIa treatment (control group). Rats were sacrificed at day 14. Results In the control group, infusion of cancer cells resulted in the development of macroscopical hepatic tumors in 17 out of 18 rats. In rats treated by FFR-FVIIa, no macroscopical or histological hepatic tumors were visible on the liver surface in 16 out of 19 rats (p=0.002, versus control group). Conclusion These results suggest that blockage of TF with proteolytically inactive FFR-VIIa inhibits hepatic tumor development at an early stage of tumoral development and TF is a target for adjuvant therapy in the prevention of HM.

scholarly journals Distinct mutational backgrounds and clonal architectures implicated prognostic discrepancies in small-cell carcinomas of the esophagus and lung

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Zhengbo Song ◽  
Yueping Liu ◽  
Guoping Cheng ◽  
Lianpeng Chang ◽  
Zicheng Yu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Early Stage ◽  
Tumor Development ◽  
Genetic Alterations ◽  
Small Cell ◽  
Driver Mutations ◽  
Carcinoma Of The Esophagus ◽  
Genomic Changes ◽  
Therapeutic Outcomes ◽  
Organ Specific

AbstractSmall-cell carcinoma of the esophagus (SCCE) is a rare and aggressive cancer. Although several consistent genomic changes were observed previously between SCCE and small-cell lung cancer (SCLC), detailed mutational landscapes revealing discrepancies in genetic underpinnings of tumorigenesis between these two cancers are scarce, and little attention has been paid to answer whether these genetic alterations were related to the prognosis. Herein by performing whole-exome sequencing of 48 SCCE and 64 SCLC tumor samples, respectively we have shown that the number of driver mutations in SCCE was significantly lower than in SCLC (p = 0.0042). In SCCE, 46% of recurrent driver mutations were clonal, which occurred at an early stage during tumorigenesis, while 16 driver mutations were found clonal in SCLC. NOTCH1/3, PIK3CA, and ATM were specifically clonal in SCCE, while TP53 was clonal in SCLC. The total number of clonal mutations differed between two cancers and presented lower in SCCE compared to SCLC (p = 0.0036). Moreover, overall survival (OS) was shorter in patients with higher numbers of clonal mutations for both cancers. In summary, SCCE showed distinct mutational background and clonal architecture compared with SCLC. Organ-specific clonal events revealed different molecular mechanisms underlying tumorigenesis, tumor development, patients’ prognosis, and possible variations in therapeutic outcomes to candidate treatments.

scholarly journals An Overview of the Role of Long Non-Coding RNAs in Human Choriocarcinoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6506
Author(s):  
Riccardo Di Fiore ◽  
Sherif Suleiman ◽  
Ana Felix ◽  
Sharon A. O’Toole ◽  
John J. O’Leary ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Early Stage ◽  
Female Genital Tract ◽  
Tumor Development ◽  
Good Prognosis ◽  
Poorly Differentiated ◽  
Novel Method ◽  
Diverse Biological Activity ◽  
Female Genital

Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

scholarly journals Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1155
Author(s):  
Meihui Tian ◽  
Zhipeng Cao ◽  
Hao Pang
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Early Stage ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Cardiac Damage ◽  
Postmortem Diagnosis ◽  
Specific Expression ◽  
Forensic Practice ◽  
Artery Disease

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.

scholarly journals Colorectal Cancer Apoptosis Induced by Dietary δ-Valerobetaine Involves PINK1/Parkin Dependent-Mitophagy and SIRT3

2021 ◽  
Vol 22 (15) ◽  
pp. 8117
Author(s):  
Nunzia D’Onofrio ◽  
Elisa Martino ◽  
Luigi Mele ◽  
Antonino Colloca ◽  
Martina Maione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Dependent Manner ◽  
Colon Cancer Cells ◽  
Protein Levels

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.

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