scholarly journals A new paradigm for leprosy diagnosis based on host gene expression

2021 ◽  
Author(s):  
Thyago Leal-Calvo ◽  
Charlotte Avanzi ◽  
Mayara A Mendes ◽  
Andrej Benjak ◽  
Philippe Busso ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Transcriptional Profiling ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Therapeutic Interventions ◽  
Diagnostic Tools ◽  
New Paradigm ◽  
Mesenchymal Transition ◽  
Ido1 Expression ◽  
Leprosy Patients

Transcriptional profiling is a powerful tool to investigate and detect human diseases. In this study, we used bulk RNA-sequencing (RNA-Seq) to compare the transcriptomes in skin lesions of leprosy patients or matched controls affected by other dermal conditions such as granuloma annulare, a confounder for paucibacillary leprosy. We identified five genes capable of accurately distinguishing multibacillary and paucibacillary leprosy from other skin conditions. Indoleamine 2,3-dioxygenase 1 ( IDO1 ) expression alone was highly discriminatory, followed by TLR10, BLK, CD38, and SLAMF7, whereas the HS3ST2 and CD40LG mRNA separated multi- and paucibacillary leprosy. Finally, from the main differentially expressed genes (DEG) and enriched pathways, we conclude that paucibacillary disease is characterized by epithelioid transformation and granuloma formation, with an exacerbated cellular immune response, while multibacillary leprosy features epithelial-mesenchymal transition with phagocytic and lipid biogenesis patterns in the skin. These findings will help catalyze the development of better diagnostic tools and potential host-based therapeutic interventions. Finally, our data may help elucidate host-pathogen interplay driving disease clinical manifestations.

scholarly journals Circulating miRNAs Related to Epithelial–Mesenchymal Transitions (EMT) as the New Molecular Markers in Endometriosis

2021 ◽  
Vol 43 (2) ◽  
pp. 900-916
Author(s):  
Anna Zubrzycka ◽  
Monika Migdalska-Sęk ◽  
Sławomir Jędrzejczyk ◽  
Ewa Brzeziańska-Lasota
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Symptoms ◽  
Diagnostic Tools ◽  
Endometrial Stromal Cells ◽  
Disease Etiology ◽  
Diagnostic Biomarkers ◽  
Mesenchymal Transition ◽  
Non Invasive

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial–mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.

scholarly journals Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Xuehua Chen ◽  
Yongquan Huang ◽  
Hui Chen ◽  
Ziman Chen ◽  
Jiaxin Chen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Residual Tumor ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
New Paradigm ◽  
Zeolitic Imidazolate Framework ◽  
Mesenchymal Transition ◽  
Epr Effect

Abstract Background Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. Results Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. Conclusions This work provides a new paradigm for the treatment of residual HCC after IRFA. Graphical Abstract

Analysis of DIP2C as a novel regulator for epithelial-mesenchymal transition of rheumatoid arthritis synovium and a potential therapeutic target

Impact ◽  
2021 ◽  
Vol 2021 (8) ◽  
pp. 28-30
Author(s):  
Masao Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapeutic Target ◽  
Epithelial Mesenchymal Transition ◽  
Poor Response ◽  
Associate Professor ◽  
Therapeutic Interventions ◽  
Response To Treatment ◽  
Potential Therapeutic Target ◽  
Mesenchymal Transition ◽  
Long Time

Rheumatoid arthritis (RA) is an autoimmune disease that can cause damage to the joints, cartilage and bone. There is no cure but early diagnosis can help mitigate damage. Sometimes RA is particularly difficult to treat, for example when the disease took a long time to be diagnosed. Associate Professor Masao Tanaka, Graduate School of Medicine, Kyoto University, Japan, leads a team of researchers working to improve understanding of the causes of poor response to treatment in RA with a long morbidity. The goal is to restore patients' therapeutic responsiveness, thereby improving outcomes. A previous focus for Tanaka was on a protein called FSTL1. He is now exploring DIP2 as a binding molecule for FSTL1. Other important mechanisms Tanaka is exploring are DNA methylation and the mechanisms of carnitine, which has been found to decrease a variety of activation signalling by inhibiting ceramide production in T cells. He and the team are exploring the involvement of these mechanisms in DIP2. In his most recent investigations, Tanaka is exploring DIP2C as a novel regulator for epithelial-mesenchymal transition of RA synovium and a potential therapeutic target. He is focusing on molecules that are expressed in the cells in joints, making the work directly applicable to RA. The team is carrying out a cohort study called KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) that involves around 2,000 outpatients with RA. Ultimately, Tanaka hopes to identify a reproducible combination of patient conditions and therapeutic interventions that achieve better treatment results for RA patients.

scholarly journals The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3674 ◽  
Author(s):  
Ralf Hass ◽  
Juliane von der Ohe ◽  
Hendrik Ungefroren
Keyword(s):  
Stem Cell ◽  
Phenotypic Plasticity ◽  
Tumor Cell ◽  
Epithelial Mesenchymal Transition ◽  
Resistance Mechanisms ◽  
Current Evidence ◽  
Cell Plasticity ◽  
New Paradigm ◽  
Mesenchymal Transition ◽  
Tumor Cell Plasticity

Intratumoral heterogeneity is considered the major cause of drug unresponsiveness in cancer and accumulating evidence implicates non-mutational resistance mechanisms rather than genetic mutations in its development. These non-mutational processes are largely driven by phenotypic plasticity, which is defined as the ability of a cell to reprogram and change its identity (phenotype switching). Tumor cell plasticity is characterized by the reactivation of developmental programs that are closely correlated with the acquisition of cancer stem cell properties and an enhanced potential for retrodifferentiation or transdifferentiation. A well-studied mechanism of phenotypic plasticity is the epithelial-mesenchymal transition (EMT). Current evidence suggests a complex interplay between EMT, genetic and epigenetic alterations, and clues from the tumor microenvironment in cell reprogramming. A deeper understanding of the connections between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events is crucial to develop novel therapies that mitigate cell plasticity and minimize the evolution of tumor heterogeneity, and hence drug resistance. Alternatively, vulnerabilities exposed by tumor cells when residing in a plastic or stem-like state may be exploited therapeutically, i.e., by converting them into less aggressive or even postmitotic cells. Tumor cell plasticity thus presents a new paradigm for understanding a cancer’s resistance to therapy and deciphering its underlying mechanisms.

scholarly journals EMT-Inducing Molecular Factors in Gynecological Cancers

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Loredana Campo ◽  
Catherine Zhang ◽  
Eun-Kyoung Breuer
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Signs And Symptoms ◽  
Therapeutic Interventions ◽  
Gynecologic Cancers ◽  
Papilloma Virus ◽  
Mesenchymal Transition ◽  
Metastatic Relapse ◽  
Immunodeficiency Virus ◽  
Common Risk Factors ◽  
Molecular Aberrations

Gynecologic cancers are the unregulated growth of neoplastic cells that arise in the cervix, ovaries, fallopian tubes, uterus, vagina, and vulva. Although gynecologic cancers are characterized by different signs and symptoms, studies have shown that they share common risk factors, such as smoking, obesity, age, exposure to certain chemicals, infection with human immunodeficiency virus (HIV), and infection with human papilloma virus (HPV). Despite recent advancements in the preventative, diagnostic, and therapeutic interventions for gynecologic cancers, many patients still die as a result of metastasis and recurrence. Since mounting evidence indicates that the epithelial-mesenchymal transition (EMT) process plays an essential role in metastatic relapse of cancer, understanding the molecular aberrations responsible for the EMT and its underlying signaling should be given high priority in order to reduce cancer morbidity and mortality.

scholarly journals Epithelial–Mesenchymal Transition in Human Prostate Cancer Demonstrates Enhanced Immune Evasion Marked by IDO1 Expression

2018 ◽  
Vol 78 (16) ◽  
pp. 4671-4679 ◽  
Author(s):  
Kimberley Kolijn ◽  
Esther I. Verhoef ◽  
Marcel Smid ◽  
René Böttcher ◽  
Guido W. Jenster ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Evasion ◽  
Epithelial Mesenchymal Transition ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Mesenchymal Transition ◽  
Ido1 Expression

scholarly journals Potential clinical use of miRNA molecules in the diagnosis of prostate cancer

2021 ◽  
Vol 75 ◽  
pp. 491-501
Author(s):  
Paweł Porzycki
Keyword(s):  
Prostate Cancer ◽  
Gene Expression Regulation ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Process ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Diagnostic Tools ◽  
Transcriptional Level ◽  
Mesenchymal Transition

Prostate cancer (PCa) is the most common type of cancer among men in Europe and this applies to almost the whole world. Current recommendations for screening and diagnosis are based on prostate specific antigen (PSA) measurements and the digital rectal examination (DRE). Both of them trigger the prostate biopsy. Limited specificity of the PSA test brings, however, a need to develop new and better diagnostic tools. In the last few years, new approaches for providing significantly better biomarkers, an alternative to PSA, have been introduced. Modern biomarkers show improvement not only as a diagnostic procedure, but also for staging, evaluating aggressiveness and managing the therapeutic process. The most promising group are molecular markers; among them microRNAs (miRNAs, miRs) are most frequent. miRNAs represent a class of about 22 nucleotides long, small non-coding RNAs, which are involved in gene expression regulation at the post-transcriptional level. This article reports a revision about the role of miRNAs in PCa including data of Adreno Receptor (AR) signaling, cell cycle, epithelial mesenchymal transition (EMT) process, cancer stem cells (CSCs) regulation and even the role of miRNAs as PCa therapeutic tool. Finding better PCa biomarkers, replacing the current PSA measurement, is firmly needed in modern oncology practice.

scholarly journals Hypoxia-induced TGF-β–RBFOX2–ESRP1 axis regulates human MENA alternative splicing and promotes EMT in breast cancer

NAR Cancer ◽  
2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Neha Ahuja ◽  
Cheemala Ashok ◽  
Subhashis Natua ◽  
Deepak Pant ◽  
Anna Cherian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Alternative Splicing ◽  
Transcriptional Repression ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Global Changes ◽  
Invasion And Metastasis ◽  
New Paradigm ◽  
Mesenchymal Transition ◽  
Splicing Regulator

Abstract Hypoxic microenvironment heralds epithelial–mesenchymal transition (EMT), invasion and metastasis in solid tumors. Deregulation of alternative splicing (AS) of several cancer-associated genes has been instrumental in hypoxia-induced EMT. Our study in breast cancer unveils a previously unreported mechanism underlying hypoxia-mediated AS of hMENA, a crucial cytoskeleton remodeler during EMT. We report that the hypoxia-driven depletion of splicing regulator ESRP1 leads to skipping of hMENA exon 11a producing a pro-metastatic isoform, hMENAΔ11a. The transcriptional repression of ESRP1 is mediated by SLUG, which gets stimulated via hypoxia-driven TGF-β signaling. Interestingly, RBFOX2, an otherwise RNA-binding protein, is also found to transcriptionally repress ESRP1 while interacting with SLUG. Similar to SLUG, RBFOX2 gets upregulated under hypoxia via TGF-β signaling. Notably, we found that the exosomal delivery of TGF-β contributes to the elevation of TGF-β signaling under hypoxia. Moreover, our results show that in addition to hMENA, hypoxia-induced TGF-β signaling contributes to global changes in AS of genes associated with EMT. Overall, our findings reveal a new paradigm of hypoxia-driven AS regulation of hMENA and insinuate important implications in therapeutics targeting EMT.

Sign in / Sign up

Export Citation Format

Share Document