scholarly journals Lysyl Oxidase Mechanisms to Mediate Gastrointestinal Cancer Progression

2020 ◽  
pp. 1-10
Author(s):  
Ahmadshah Farhat ◽  
Gordon A. Ferns ◽  
Korosh Ashrafi ◽  
Mohammad-Hassan Arjmand
Keyword(s):  
Cancer Progression ◽  
Extracellular Enzymes ◽  
Lysyl Oxidase ◽  
Ecm Remodeling ◽  
Complex Process ◽  
High Prevalence ◽  
Different Types ◽  
Fibrotic Diseases ◽  
Gi Cancers ◽  
Improvement In Survival

<b><i>Background:</i></b> Malignancy is a complex process resulting from different changes such as extracellular matrix (ECM) remodeling and stiffness. One of the important enzymes that contribute to ECM remodeling is lysyl oxidase (Lox) that is overexpressed in different types of human cancers. Because of the high prevalence and poor survival of gastrointestinal (GI) malignancies in this review, we discuss the association between Lox activity and the progression of GI cancers. Lox proteins are a group of extracellular enzymes that catalyzed the cross-linking of collagen and elastin, so they have important roles in the control of structure and homeostasis of ECM. Abnormal activation and expression of the Lox family of proteins lead to changes in the ECM toward increased rigidity and fibrosis. Stiffness of ECM can contribute to the pathogenesis of cancers. <b><i>Summary:</i></b> Dysregulation of Lox expression is a factor in both fibrotic diseases and cancer. ECM stiffness by Lox overactivity creates a physical barrier against intratumoral concentration of chemotherapeutic drugs and facilitates cancer inflammation, angiogenesis, and metastasis. <b><i>Key Message:</i></b> Because of the roles of Lox in GI cancers, development targeting Lox protein isotypes may be an appropriate strategy for treatment of GI cancers and improvement in survival of patients.

scholarly journals Mechanisms of hyperprogressive disease after immune checkpoint inhibitor therapy: what we (don’t) know

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Simone Camelliti ◽  
Valentino Le Noci ◽  
Francesca Bianchi ◽  
Claudia Moscheni ◽  
Francesca Arnaboldi ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Checkpoint ◽  
Detrimental Effect ◽  
Checkpoint Inhibitors ◽  
Clinical Results ◽  
Different Types ◽  
Checkpoint Inhibitor Therapy ◽  
Clinical Phenomenon ◽  
Hyperprogressive Disease ◽  
Improvement In Survival

Abstract Immune checkpoint inhibitors (ICIs) have made a breakthrough in the treatment of different types of tumors, leading to improvement in survival, even in patients with advanced cancers. Despite the good clinical results, a certain percentage of patients do not respond to this kind of immunotherapy. In addition, in a fraction of nonresponder patients, which can vary from 4 to 29% according to different studies, a paradoxical boost in tumor growth after ICI administration was observed: a completely unpredictable novel pattern of cancer progression defined as hyperprogressive disease. Since this clinical phenomenon has only been recently described, a universally accepted clinical definition is lacking, and major efforts have been made to uncover the biological bases underlying hyperprogressive disease. The lines of research pursued so far have focused their attention on the study of the immune tumor microenvironment or on the analysis of intrinsic genomic characteristics of cancer cells producing data that allowed us to formulate several hypotheses to explain this detrimental effect related to ICI therapy. The aim of this review is to summarize the most important works that, to date, provide important insights that are useful in understanding the mechanistic causes of hyperprogressive disease.

scholarly journals Lysyl oxidase G473A (rs1800449) polymorphism influences the risk of cancer progression: a meta-analysis

2020 ◽  
Author(s):  
Rungrawee Mongkolrob ◽  
Phuntila Tharabenjasin ◽  
Aporn Bualuang ◽  
Noel Pabalan
Keyword(s):  
Cancer Progression ◽  
Lysyl Oxidase ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Models ◽  
Primary Data ◽  
Cancer Type ◽  
Case Control Studies ◽  
Gi Cancers ◽  
Risk Of Cancer

Abstract The genetics of cancer progression is important for the design of optimal therapeutic strategies. Lysyl oxidase (LOX) is a cancer progression gene that has been studied enough to warrant a synthesis of its primary data from association studies. However, reported associations between the LOX G473A (rs1800449) gene polymorphism and cancer have been inconsistent, prompting a meta-analysis so that we could obtain more precise estimates. Database searches of the published literature yielded seven case-control studies. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using four genetic models: homozygous (H), recessive (R), dominant (D) and codominant (C). Subgroup analysis was based on ethnicity and cancer type. Outlier analysis was used to examine sources of heterogeneity. The strength of evidence was based on the magnitude of effects, high associative significance, consistency and homogeneity. H/R outcomes exerted more associative effects than D/C results. Two reasons for this are as follows: (i) H/R analyses precluded outlier treatment; and (ii) the magnitude of H/R (ORs of > 2.0) was twice that of D/C (ORs > 1.0). All else being equal, significant pooled ORs in all genetic models had high significance (Pa < 10-5). Strong evidence for associations was found in the outcomes for Asian and gastrointestinal (GI) cancers. In summary, the LOX rs1800449 polymorphism confers significant overall susceptibility, particularly in GI cancers, and places Asians at risk.

Carbazole Derivatives as Kinase-Targeting Inhibitors for Cancer Treatment

2020 ◽  
Vol 20 (6) ◽  
pp. 444-465 ◽  
Author(s):  
Jessica Ceramella ◽  
Domenico Iacopetta ◽  
Alexia Barbarossa ◽  
Anna Caruso ◽  
Fedora Grande ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Drug Targets ◽  
Mechanisms Of Action ◽  
Biological Pathways ◽  
G Protein Coupled Receptors ◽  
Ability To Act ◽  
Different Types ◽  
Activity Of Enzymes ◽  
Intercalating Agents ◽  
G Protein Coupled

Protein Kinases (PKs) are a heterogeneous family of enzymes that modulate several biological pathways, including cell division, cytoskeletal rearrangement, differentiation and apoptosis. In particular, due to their crucial role during human tumorigenesis and cancer progression, PKs are ideal targets for the design and development of effective and low toxic chemotherapeutics and represent the second group of drug targets after G-protein-coupled receptors. Nowadays, several compounds have been claimed to be PKs inhibitors, and some of them, such as imatinib, erlotinib and gefitinib, have already been approved for clinical use, whereas more than 30 others are in various phases of clinical trials. Among them, some natural or synthetic carbazole-based molecules represent promising PKs inhibitors due to their capability to interfere with PK activity by different mechanisms of action including the ability to act as DNA intercalating agents, interfere with the activity of enzymes involved in DNA duplication, such as topoisomerases and telomerases, and inhibit other proteins such as cyclindependent kinases or antagonize estrogen receptors. Thus, carbazoles can be considered a promising this class of compounds to be adopted in targeted therapy of different types of cancer.

Double, triple or quadruple hits? Exploring the impact of cybercrime on victims in the Netherlands

2021 ◽  
pp. 026975802110106
Author(s):  
Raoul Notté ◽  
E.R. Leukfeldt ◽  
Marijke Malsch
Keyword(s):  
Public Opinion ◽  
Literature Review ◽  
The Netherlands ◽  
Public Discourse ◽  
Moral Judgments ◽  
Victim Blaming ◽  
High Prevalence ◽  
Different Types ◽  
The Impact ◽  
Insight Into

This article explores the impact of online crime victimisation. A literature review and 41 interviews – 19 with victims and 22 with experts – were carried out to gain insight into this. The interviews show that most impacts of online offences correspond to the impacts of traditional offline offences. There are also differences with offline crime victimisation. Several forms of impact seem to be specific to victims of online crime: the substantial scale and visibility of victimhood, victimisation that does not stop in time, the interwovenness of online and offline, and victim blaming. Victims suffer from double, triple or even quadruple hits; it is the accumulation of different types of impact, enforced by the limitlessness in time and space, which makes online crime victimisation so extremely invasive. Furthermore, the characteristics of online crime victimisation greatly complicate the fight against and prevention of online crime. Finally, the high prevalence of cybercrime victimisation combined with the severe impact of these crimes seems contradictory with public opinion – and associated moral judgments – on victims. Further research into the dominant public discourse on victimisation and how this affects the functioning of the police and victim support would be valuable.

scholarly journals Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3466
Author(s):  
Ismahane Belhabib ◽  
Sonia Zaghdoudi ◽  
Claire Lac ◽  
Corinne Bousquet ◽  
Christine Jean
Keyword(s):  
Cancer Progression ◽  
Cancer Diagnosis ◽  
Neoplastic Cell ◽  
Multiple Roles ◽  
Solid Cancer ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Niche ◽  
Ecm Remodeling ◽  
Patient Prognosis ◽  
Cancer Diagnosis And Therapy

Solid cancer progression is dictated by neoplastic cell features and pro-tumoral crosstalks with their microenvironment. Stroma modifications, such as fibroblast activation into cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) remodeling, are now recognized as critical events for cancer progression and as potential therapeutic or diagnostic targets. The recent appreciation of the key, complex and multiple roles of the ECM in cancer and of the CAF diversity, has revolutionized the field and raised innovative but challenging questions. Here, we rapidly present CAF heterogeneity in link with their specific ECM remodeling features observed in cancer, before developing each of the impacts of such ECM modifications on tumor progression (survival, angiogenesis, pre-metastatic niche, chemoresistance, etc.), and on patient prognosis. Finally, based on preclinical studies and recent results obtained from clinical trials, we highlight key mechanisms or proteins that are, or may be, used as potential therapeutic or diagnostic targets, and we report and discuss benefits, disappointments, or even failures, of recently reported stroma-targeting strategies.

scholarly journals LOXL2 Inhibitors and Breast Cancer Progression

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 312
Author(s):  
Sandra Ferreira ◽  
Nuno Saraiva ◽  
Patrícia Rijo ◽  
Ana S. Fernandes
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
Lysyl Oxidase ◽  
Breast Cancer Progression ◽  
Special Focus ◽  
Amine Oxidases ◽  
Cross Link ◽  
Promising Strategy

LOX (lysyl oxidase) and lysyl oxidase like-1–4 (LOXL 1–4) are amine oxidases, which catalyze cross-linking reactions of elastin and collagen in the connective tissue. These amine oxidases also allow the cross-link of collagen and elastin in the extracellular matrix of tumors, facilitating the process of cell migration and the formation of metastases. LOXL2 is of particular interest in cancer biology as it is highly expressed in some tumors. This protein also promotes oncogenic transformation and affects the proliferation of breast cancer cells. LOX and LOXL2 inhibition have thus been suggested as a promising strategy to prevent metastasis and invasion of breast cancer. BAPN (β-aminopropionitrile) was the first compound described as a LOX inhibitor and was obtained from a natural source. However, novel synthetic compounds that act as LOX/LOXL2 selective inhibitors or as dual LOX/LOX-L inhibitors have been recently developed. In this review, we describe LOX enzymes and their role in promoting cancer development and metastases, with a special focus on LOXL2 and breast cancer progression. Moreover, the recent advances in the development of LOXL2 inhibitors are also addressed. Overall, this work contextualizes and explores the importance of LOXL2 inhibition as a promising novel complementary and effective therapeutic approach for breast cancer treatment.

scholarly journals The Interactome of Cancer-Related Lysyl Oxidase and Lysyl Oxidase-Like Proteins

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 71
Author(s):  
Sylvain D. Vallet ◽  
Coline Berthollier ◽  
Romain Salza ◽  
Laurent Muller ◽  
Sylvie Ricard-Blum
Keyword(s):  
Protein Folding ◽  
Cancer Progression ◽  
Cellular Response ◽  
Lysyl Oxidase ◽  
Chaperone Activity ◽  
Cross Linking ◽  
Binding Assays ◽  
Vessel Development ◽  
New Interactions

The members of the lysyl oxidase (LOX) family are amine oxidases, which initiate the covalent cross-linking of the extracellular matrix (ECM), regulate ECM stiffness, and contribute to cancer progression. The aim of this study was to build the first draft of the interactome of the five members of the LOX family in order to determine its molecular functions, the biological and signaling pathways mediating these functions, the biological processes it is involved in, and if and how it is rewired in cancer. In vitro binding assays, based on surface plasmon resonance and bio-layer interferometry, combined with queries of interaction databases and interaction datasets, were used to retrieve interaction data. The interactome was then analyzed using computational tools. We identified 31 new interactions and 14 new partners of LOXL2, including the α5β1 integrin, and built an interactome comprising 320 proteins, 5 glycosaminoglycans, and 399 interactions. This network participates in ECM organization, degradation and cross-linking, cell-ECM interactions mediated by non-integrin and integrin receptors, protein folding and chaperone activity, organ and blood vessel development, cellular response to stress, and signal transduction. We showed that this network is rewired in colorectal carcinoma, leading to a switch from ECM organization to protein folding and chaperone activity.

scholarly journals The role of m6A modification in the biological functions and diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiulin Jiang ◽  
Baiyang Liu ◽  
Zhi Nie ◽  
Lincan Duan ◽  
Qiuxia Xiong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Rna Modification ◽  
Biological Functions ◽  
Rna Methylation ◽  
Downstream Target ◽  
Different Types ◽  
M6a Rna Methylation

AbstractN6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.

scholarly journals The genetics of amelogenesis imperfecta: a review of the literature

2005 ◽  
Vol 13 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Maria Cristina Leme Godoy dos Santos ◽  
Sergio Roberto Peres Line
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Dental Enamel ◽  
Matrix Proteins ◽  
Specific Gene ◽  
Enamel Formation ◽  
Complex Process ◽  
Different Types ◽  
Kallikrein 4

A melogenesis imperfecta (AI) is a group of inherited defects of dental enamel formation that show both clinical and genetic heterogeneity. Enamel findings in AI are highly variable, ranging from deficient enamel formation to defects in the mineral and protein content. Enamel formation requires the expression of multiple genes that transcribes matrix proteins and proteinases needed to control the complex process of crystal growth and mineralization. The AI phenotypes depend on the specific gene involved, the location and type of mutation, and the corresponding putative change at the protein level. Different inheritance patterns such as X-linked, autosomal dominant and autosomal recessive types have been reported. Mutations in the amelogenin, enamelin, and kallikrein-4 genes have been demonstrated to result in different types of AI and a number of other genes critical to enamel formation have been identified and proposed as candidates for AI. The aim of this article was to present an evaluation of the literature regarding role of proteins and proteinases important to enamel formation and mutation associated with AI.

scholarly journals Enhancement and assessment of students’ systems thinking skills by application of systemic synthesis questions in the organic chemistry course

2016 ◽  
Vol 81 (12) ◽  
pp. 1455-1471 ◽  
Author(s):  
Tamara Hrin ◽  
Dusica Milenkovic ◽  
Mirjana Segedinac ◽  
Sasa Horvat
Keyword(s):  
Organic Chemistry ◽  
Systems Thinking ◽  
Higher Order Thinking ◽  
Thinking Skills ◽  
Assessment Tools ◽  
School Students ◽  
Complex Dimension ◽  
Complex Process ◽  
Different Types ◽  
Teaching Learning

Many studies in the field of science education have emphasized the fact that systems thinking is a very important higher-order thinking skill which should be fostered during classes. However, more attention has been dedicated to the different ways of systems thinking skills assessment, and less to their enhancement. Taking this into consideration, the goal of our study was not only to validate secondary school students? systems thinking skills, but also to help students in the complex process of their development. With this goal, new instructional and assessment tools - systemic synthesis questions [SSynQs], were constructed, and an experiment with one experimental (E) and one control (C) group was conducted during organic chemistry classes. Namely, the instructional teaching/learning method for both E and C groups was the same in processing the new contents, but different on classes for the revision of the selected organic chemistry contents. The results showed that students exposed to the new instructional method (E group) achieved higher performance scores on three different types of systems thinking than students from the C group, who were taught by the traditional method. The greatest difference between the groups was found in the most complex dimension of systems thinking construct - in the II level of procedural systems thinking. Along with this dimension, structural systems thinking and I level of procedural systems thinking were also observed.

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