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  1. AU=Eccles Michael R
  2. AU="Karrison, Theodore"
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  1. Artikel ; Online: Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance.

    Hossain, Sultana Mehbuba / Eccles, Michael R

    International journal of molecular sciences

    2023  Band 24, Heft 2

    Abstract: Melanoma, a highly heterogeneous tumor, is comprised of a functionally diverse spectrum of cell phenotypes and subpopulations, including stromal cells in the tumor microenvironment (TME). Melanoma has been shown to dynamically shift between different ... ...

    Abstract Melanoma, a highly heterogeneous tumor, is comprised of a functionally diverse spectrum of cell phenotypes and subpopulations, including stromal cells in the tumor microenvironment (TME). Melanoma has been shown to dynamically shift between different transcriptional states or phenotypes. This is referred to as phenotype switching in melanoma, and it involves switching between quiescent and proliferative cell cycle states, and dramatic shifts in invasiveness, as well as changes in signaling pathways in the melanoma cells, and immune cell composition in the TME. Melanoma cell plasticity is associated with altered gene expression in immune cells and cancer-associated fibroblasts, as well as changes in extracellular matrix, which drive the metastatic cascade and therapeutic resistance. Therefore, resistance to therapy in melanoma is not only dependent on genetic evolution, but it has also been suggested to be driven by gene expression changes and adaptive phenotypic cell plasticity. This review discusses recent findings in melanoma phenotype switching, immunotherapy resistance, and the balancing of the homeostatic TME between the different melanoma cell subpopulations. We also discuss future perspectives of the biology of neural crest-like state(s) in melanoma.
    Mesh-Begriff(e) Humans ; Melanoma/drug therapy ; Melanoma/genetics ; Tumor Microenvironment/genetics ; Immunotherapy ; Drug Resistance ; Phenotype
    Sprache Englisch
    Erscheinungsdatum 2023-01-13
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24021601
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis.

    Motwani, Jyoti / Eccles, Michael R

    Genes

    2021  Band 12, Heft 10

    Abstract: Melanoma is a serious form of skin cancer that accounts for 80% of skin cancer deaths. Recent studies have suggested that melanoma invasiveness is attributed to phenotype switching, which is a reversible type of cell behaviour with similarities to ... ...

    Abstract Melanoma is a serious form of skin cancer that accounts for 80% of skin cancer deaths. Recent studies have suggested that melanoma invasiveness is attributed to phenotype switching, which is a reversible type of cell behaviour with similarities to epithelial to mesenchymal transition. Phenotype switching in melanoma is reported to be independent of genetic alterations, whereas changes in gene transcription, and epigenetic alterations have been associated with invasiveness in melanoma cell lines. Here, we review mutational, transcriptional, and epigenomic alterations that contribute to tumour heterogeneity in melanoma, and their potential to drive melanoma invasion and metastasis. We also discuss three models that are hypothesized to contribute towards aspects of tumour heterogeneity and tumour progression in melanoma, namely the clonal evolution model, the cancer stem cell model, and the phenotype switching model. We discuss the merits and disadvantages of each model in explaining tumour heterogeneity in melanoma, as a precursor to invasion and metastasis.
    Mesh-Begriff(e) Animals ; Carcinogenesis/genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Genetic Heterogeneity ; Humans ; Melanoma/genetics ; Melanoma/metabolism ; Melanoma/pathology ; Mutation
    Sprache Englisch
    Erscheinungsdatum 2021-09-28
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes12101543
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy.

    Mainini, Francesco / Eccles, Michael R

    Molecules (Basel, Switzerland)

    2020  Band 25, Heft 11

    Abstract: RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve ...

    Abstract RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient's therapeutic response.
    Mesh-Begriff(e) Animals ; Drug Delivery Systems ; Gene Targeting ; Genetic Therapy ; Humans ; Lipids/chemistry ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Neoplasms/genetics ; Neoplasms/therapy ; Polymers/chemistry ; RNA, Small Interfering/administration & dosage ; RNA, Small Interfering/genetics ; Tumor Microenvironment
    Chemische Substanzen Lipids ; Polymers ; RNA, Small Interfering
    Sprache Englisch
    Erscheinungsdatum 2020-06-10
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules25112692
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Co-Expression of Multiple

    Li, Lei / Li, Caiyun G / Almomani, Suzan N / Hossain, Sultana Mehbuba / Eccles, Michael R

    International journal of molecular sciences

    2023  Band 24, Heft 14

    Abstract: Renal cell carcinoma (RCC) is the most common form of kidney cancer, consisting of multiple distinct subtypes. RCC has the highest mortality rate amongst the urogenital cancers, with kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell ... ...

    Abstract Renal cell carcinoma (RCC) is the most common form of kidney cancer, consisting of multiple distinct subtypes. RCC has the highest mortality rate amongst the urogenital cancers, with kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe carcinoma (KICH) being the most common subtypes. The Paired-box (
    Mesh-Begriff(e) Humans ; Carcinoma, Renal Cell/pathology ; PAX2 Transcription Factor/genetics ; PAX2 Transcription Factor/metabolism ; Kidney Neoplasms/metabolism ; Kidney/metabolism ; Transcription Factors/metabolism
    Chemische Substanzen PAX2 Transcription Factor ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2023-07-14
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241411432
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Protocol for generating high-quality genome-scale DNA methylation sequencing data from human cancer biospecimens.

    Rodger, Euan J / Stockwell, Peter A / Almomani, Suzan / Eccles, Michael R / Chatterjee, Aniruddha

    STAR protocols

    2023  Band 4, Heft 4, Seite(n) 102714

    Abstract: Aberrant DNA methylation is a universal feature of cancer. Here, we present a protocol for generating high-quality genome-scale DNA methylation sequencing data from a variety of human cancer biospecimens including immortalized cell lines, fresh-frozen ... ...

    Abstract Aberrant DNA methylation is a universal feature of cancer. Here, we present a protocol for generating high-quality genome-scale DNA methylation sequencing data from a variety of human cancer biospecimens including immortalized cell lines, fresh-frozen surgical resections, and formalin-fixed paraffin-embedded tissues. We describe steps for DNA extraction considerations, reduced representation bisulfite sequencing, data processing and quality control, and downstream data analysis and integration. This protocol is also applicable for other human diseases and methylome profiling in other organisms. For complete details on the use and execution of this protocol, please refer to Rodger et al. (2023).
    Mesh-Begriff(e) Humans ; DNA Methylation/genetics ; Sequence Analysis, DNA/methods ; Neoplasms/genetics
    Sprache Englisch
    Erscheinungsdatum 2023-11-10
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102714
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Non-coding RNAs as potential biomarkers and therapeutic targets in polycystic kidney disease.

    Zheng, Qi / Reid, Glen / Eccles, Michael R / Stayner, Cherie

    Frontiers in physiology

    2022  Band 13, Seite(n) 1006427

    Abstract: Polycystic kidney disease (PKD) is a significant cause of end-stage kidney failure and there are few effective drugs for treating this inherited condition. Numerous aberrantly expressed non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), may ... ...

    Abstract Polycystic kidney disease (PKD) is a significant cause of end-stage kidney failure and there are few effective drugs for treating this inherited condition. Numerous aberrantly expressed non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), may contribute to PKD pathogenesis by participating in multiple intracellular and intercellular functions through post-transcriptional regulation of protein-encoding genes. Insights into the mechanisms of miRNAs and other ncRNAs in the development of PKD may provide novel therapeutic strategies. In this review, we discuss the current knowledge about the roles of dysregulated miRNAs and other ncRNAs in PKD. These roles involve multiple aspects of cellular function including mitochondrial metabolism, proliferation, cell death, fibrosis and cell-to-cell communication. We also summarize the potential application of miRNAs as biomarkers or therapeutic targets in PKD, and briefly describe strategies to overcome the challenges of delivering RNA to the kidney, providing a better understanding of the fundamental advances in utilizing miRNAs and other non-coding RNAs to treat PKD.
    Sprache Englisch
    Erscheinungsdatum 2022-09-20
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.1006427
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Unveiling the hidden players: The crucial role of transposable elements in the placenta and their potential contribution to pre-eclampsia.

    Keighley, Laura M / Lynch-Sutherland, Chiemi F / Almomani, Suzan N / Eccles, Michael R / Macaulay, Erin C

    Placenta

    2023  Band 141, Seite(n) 57–64

    Abstract: The human placenta is a vital connection between maternal and fetal tissues, allowing for the exchange of molecules and modulation of immune interactions during pregnancy. Interestingly, some of the placenta's unique functions can be attributed to ... ...

    Abstract The human placenta is a vital connection between maternal and fetal tissues, allowing for the exchange of molecules and modulation of immune interactions during pregnancy. Interestingly, some of the placenta's unique functions can be attributed to transposable elements (TEs), which are DNA sequences that have mobilised into the genome. Co-option throughout mammalian evolution has led to the generation of TE-derived regulators and TE-derived genes, some of which are expressed in the placenta but silenced in somatic tissues. TE genes encompass both TE-derived genes with a repeat element in the coding region and TE-derived regulatory regions such as alternative promoters and enhancers. Placental-specific TE genes are known to contribute to the placenta's unique functions, and interestingly, they are also expressed in some cancers and share similar functions. There is evidence to support that aberrant activity of TE genes may contribute to placental pathologies, cancer and autoimmunity. In this review, we highlight the crucial roles of TE genes in placental function, and how their dysregulation may lead to pre-eclampsia, a common and dangerous placental condition. We provide a summary of the functional TE genes in the placenta to offer insight into their significance in normal and abnormal human development. Ultimately, this review highlights an opportunity for future research to investigate the potential dysregulation of TE genes in the development of placental pathologies such as pre-eclampsia. Further understanding of TE genes and their role in the placenta could lead to significant improvements in maternal and fetal health.
    Mesh-Begriff(e) Animals ; Female ; Humans ; Pregnancy ; DNA Transposable Elements/genetics ; Placenta ; Pre-Eclampsia/genetics ; Promoter Regions, Genetic ; Mammals
    Chemische Substanzen DNA Transposable Elements
    Sprache Englisch
    Erscheinungsdatum 2023-05-27
    Erscheinungsland Netherlands
    Dokumenttyp Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603951-0
    ISSN 1532-3102 ; 0143-4004
    ISSN (online) 1532-3102
    ISSN 0143-4004
    DOI 10.1016/j.placenta.2023.05.017
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

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    Zs.A 1578: Hefte anzeigen Standort:
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  8. Artikel ; Online: Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

    Francesco Mainini / Michael R. Eccles

    Molecules, Vol 25, Iss 2692, p

    2020  Band 2692

    Abstract: RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve ...

    Abstract RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response.
    Schlagwörter nanoparticle ; intracellular delivery ; siRNA ; cancer therapy ; Organic chemistry ; QD241-441
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2020-06-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel: Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis

    Motwani, Jyoti / Eccles, Michael R.

    Genes. 2021 Sept. 28, v. 12, no. 10

    2021  

    Abstract: Melanoma is a serious form of skin cancer that accounts for 80% of skin cancer deaths. Recent studies have suggested that melanoma invasiveness is attributed to phenotype switching, which is a reversible type of cell behaviour with similarities to ... ...

    Abstract Melanoma is a serious form of skin cancer that accounts for 80% of skin cancer deaths. Recent studies have suggested that melanoma invasiveness is attributed to phenotype switching, which is a reversible type of cell behaviour with similarities to epithelial to mesenchymal transition. Phenotype switching in melanoma is reported to be independent of genetic alterations, whereas changes in gene transcription, and epigenetic alterations have been associated with invasiveness in melanoma cell lines. Here, we review mutational, transcriptional, and epigenomic alterations that contribute to tumour heterogeneity in melanoma, and their potential to drive melanoma invasion and metastasis. We also discuss three models that are hypothesized to contribute towards aspects of tumour heterogeneity and tumour progression in melanoma, namely the clonal evolution model, the cancer stem cell model, and the phenotype switching model. We discuss the merits and disadvantages of each model in explaining tumour heterogeneity in melanoma, as a precursor to invasion and metastasis.
    Schlagwörter epigenetics ; epigenome ; epithelium ; evolution ; genomics ; melanoma ; metastasis ; models ; neoplasm progression ; phenotype ; skin neoplasms ; stem cells ; transcription (genetics)
    Sprache Englisch
    Erscheinungsverlauf 2021-0928
    Erscheinungsort Multidisciplinary Digital Publishing Institute
    Dokumenttyp Artikel
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes12101543
    Datenquelle NAL Katalog (AGRICOLA)

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  10. Artikel: Melanoma genetics/genomics.

    Eccles, Michael R

    Frontiers in oncology

    2013  Band 3, Seite(n) 309

    Sprache Englisch
    Erscheinungsdatum 2013-12-17
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2013.00309
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