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Article ; 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 Volume 24, Issue 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 term(s)	Humans ; Melanoma/drug therapy ; Melanoma/genetics ; Tumor Microenvironment/genetics ; Immunotherapy ; Drug Resistance ; Phenotype
Language	English
Publishing date	2023-01-13
Publishing country	Switzerland
Document type	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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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

Motwani, Jyoti / Eccles, Michael R

Genes

2021 Volume 12, Issue 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 term(s)	Animals ; Carcinogenesis/genetics ; Epigenesis, Genetic ; Gene Expression Regulation, Neoplastic ; Genetic Heterogeneity ; Humans ; Melanoma/genetics ; Melanoma/metabolism ; Melanoma/pathology ; Mutation
Language	English
Publishing date	2021-09-28
Publishing country	Switzerland
Document type	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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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

Mainini, Francesco / Eccles, Michael R

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 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 term(s)	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
Chemical Substances	Lipids ; Polymers ; RNA, Small Interfering
Language	English
Publishing date	2020-06-10
Publishing country	Switzerland
Document type	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
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Article ; 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 Volume 24, Issue 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 term(s)	Humans ; Carcinoma, Renal Cell/pathology ; PAX2 Transcription Factor/genetics ; PAX2 Transcription Factor/metabolism ; Kidney Neoplasms/metabolism ; Kidney/metabolism ; Transcription Factors/metabolism
Chemical Substances	PAX2 Transcription Factor ; Transcription Factors
Language	English
Publishing date	2023-07-14
Publishing country	Switzerland
Document type	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
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Article ; 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 Volume 4, Issue 4, Page(s) 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 term(s)	Humans ; DNA Methylation/genetics ; Sequence Analysis, DNA/methods ; Neoplasms/genetics
Language	English
Publishing date	2023-11-10
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102714
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Article: 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 Volume 13, Page(s) 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.
Language	English
Publishing date	2022-09-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.1006427
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Article ; 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 Volume 141, Page(s) 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 term(s)	Animals ; Female ; Humans ; Pregnancy ; DNA Transposable Elements/genetics ; Placenta ; Pre-Eclampsia/genetics ; Promoter Regions, Genetic ; Mammals
Chemical Substances	DNA Transposable Elements
Language	English
Publishing date	2023-05-27
Publishing country	Netherlands
Document type	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
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Article ; Online: Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

Francesco Mainini / Michael R. Eccles

Molecules, Vol 25, Iss 2692, p

2020 Volume 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 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.
Keywords	nanoparticle ; intracellular delivery ; siRNA ; cancer therapy ; Organic chemistry ; QD241-441
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Melanoma genetics/genomics.

Eccles, Michael R

Frontiers in oncology

2013 Volume 3, Page(s) 309

Language	English
Publishing date	2013-12-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2013.00309
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Article: 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 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.
Keywords	epigenetics ; epigenome ; epithelium ; evolution ; genomics ; melanoma ; metastasis ; models ; neoplasm progression ; phenotype ; skin neoplasms ; stem cells ; transcription (genetics)
Language	English
Dates of publication	2021-0928
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes12101543
Database	NAL-Catalogue (AGRICOLA)

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