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Article ; Online: Helicobacter pylori and gastric cancer: a lysosomal protease perspective.

Soond, Surinder M / Zamyatnin, Andrey A

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association

2021 Volume 25, Issue 2, Page(s) 306–324

Abstract: The intimate involvement of pathogens with the heightened risk for developing certain cancers is an area of research that has captured a great deal of attention over the last 10 years. One firmly established paradigm that highlights this aspect of ... ...

Abstract	The intimate involvement of pathogens with the heightened risk for developing certain cancers is an area of research that has captured a great deal of attention over the last 10 years. One firmly established paradigm that highlights this aspect of disease progression is in the instance of Helicobacter pylori infection and the contribution it makes in elevating the risk for developing gastric cancer. Whilst the molecular mechanisms that pinpoint the contribution that this microorganism inflicts towards host cells during gastric cancer initiation have come into greater focus, another picture that has also emerged is one that implicates the host's immune system, and the chronic inflammation that can arise therefrom, as being a central contributory factor in disease progression. Consequently, when taken with the underlying role that the extracellular matrix plays in the development of most cancers, and how this dynamic can be modulated by proteases expressed from the tumor or inflammatory cells, a complex and detailed relationship shared between the individual cellular components and their surroundings is coming into focus. In this review article, we draw attention to the emerging role played by the cathepsin proteases in modulating the stage-specific progression of Helicobacter pylori-initiated gastric cancer and the underlying immune response, while highlighting the therapeutic significance of this dynamic and how it may be amenable for novel intervention strategies within a basic research or clinical setting.
MeSH term(s)	Gastric Mucosa/pathology ; Helicobacter Infections/complications ; Helicobacter Infections/pathology ; Helicobacter pylori ; Humans ; Lysosomes/pathology ; Peptide Hydrolases ; Stomach Neoplasms/etiology
Chemical Substances	Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2021-12-16
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	1463526-4
ISSN	1436-3305 ; 1436-3291
ISSN (online)	1436-3305
ISSN	1436-3291
DOI	10.1007/s10120-021-01272-8
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Article ; Online: Beyond basic research: the contribution of cathepsin B to cancer development, diagnosis and therapy.

Zamyatnin, Andrey A / Gregory, Levy C / Townsend, Paul A / Soond, Surinder M

Expert opinion on therapeutic targets

2023 Volume 26, Issue 11, Page(s) 963–977

Abstract: Introduction: In view of other candidate proteins from the cathepsin family of proteases holding great potential in being targeted during cancer therapy, the importance of Cathepsin B (CtsB) stands out as being truly exceptional. Based on its ... ...

Abstract	Introduction: In view of other candidate proteins from the cathepsin family of proteases holding great potential in being targeted during cancer therapy, the importance of Cathepsin B (CtsB) stands out as being truly exceptional. Based on its contribution to oncogenesis, its intimate connection with regulating apoptosis and modulating extracellular and intracellular functions through its secretion or compartmentalized subcellular localization, collectively highlight its complex molecular involvement with a myriad of normal and pathological regulatory processes. Despite its complex functional nature, CtsB is emerging as one of the few cathepsin proteases that has been extensively researched to yield tangible outcomes for cancer therapy. Areas covered: In this article, we review the scientific literature that has justified or shaped the importance of CtsB expression in cancer progression, from the perspective of highlighting a paradigm that is rapidly changing from basic research toward a broader clinical and translational context. Expert opinion: In doing so, we detail its maturation as a diagnostic marker through describing the development of CtsB-specific Activity-Based Probes, the rapid evolution of these toward a new generation of Prodrugs, and the evaluation of these in model systems for their therapeutic potential as anti-cancer agents in the clinic.
MeSH term(s)	Humans ; Cathepsin B/metabolism ; Neoplasms/diagnosis ; Neoplasms/therapy ; Peptide Hydrolases
Chemical Substances	Cathepsin B (EC 3.4.22.1) ; Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2023-01-02
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2022.2161888
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Zs.A 5244: Show issues

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Article ; Online: Targeting G protein-coupled receptors in cancer therapy.

Soond, Surinder M / Zamyatnin, Andrey A

Advances in cancer research

2019 Volume 145, Page(s) 49–97

Abstract: As basic research into GPCR signaling and its association with disease has come into fruition, greater clarity has emerged with regards to how these receptors may be amenable to therapeutic intervention. As a diverse group of receptor proteins, which ... ...

Abstract	As basic research into GPCR signaling and its association with disease has come into fruition, greater clarity has emerged with regards to how these receptors may be amenable to therapeutic intervention. As a diverse group of receptor proteins, which regulate a variety of intracellular signaling pathways, research in this area has been slow to yield tangible therapeutic agents for the treatment of a number of diseases including cancer. However, recently such research has gained momentum based on a series of studies that have sought to define GPCR proteins dynamics through the elucidation of their crystal structures. In this chapter, we define the approaches that have been adopted in developing better therapeutics directed against the specific parts of the receptor proteins, such as the extracellular and the intracellular domains, including the ligands and auxiliary proteins that bind them. Finally, we also briefly outline how GPCR-derived signaling transduction pathways hold great potential as additional targets.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Humans ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Receptors, G-Protein-Coupled/antagonists & inhibitors ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2019-12-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	127-2
ISSN	2162-5557 ; 0065-230X
ISSN (online)	2162-5557
ISSN	0065-230X
DOI	10.1016/bs.acr.2019.11.002
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Article ; Online: Questionnaire-based survey to determine an at-risk group for coeliac disease among school children in Moscow, Russia.

Antishin, Anton S / Erdes, Svetlana I / Savvateeva, Lyudmila V / Soond, Surinder M / Zamyatnin, Andrey A

Journal of paediatrics and child health

2022 Volume 58, Issue 10, Page(s) 1803–1810

Abstract: Aim: Coeliac disease (CD) is a chronic digestive disorder which presents in diverse ways and is under-diagnosed. The purpose of this study was to provide insights into suspected CD among Russian schoolchildren, through defining the percentage of ... ...

Abstract	Aim: Coeliac disease (CD) is a chronic digestive disorder which presents in diverse ways and is under-diagnosed. The purpose of this study was to provide insights into suspected CD among Russian schoolchildren, through defining the percentage of participants in an 'at-risk' group for CD in a paediatric cohort, by means of a questionnaire as a primary screening tool. Methods: Russian school children of both sexes age 7-18 years were enrolled in a population-based study to identify individuals affected by CD. Each participant was presented with a structured questionnaire based on criteria that can be used to reveal symptomatic signs of CD. Following on, we developed a case-finding strategy for the 'at-risk' group, based on serological and genetic testing and, where possible, endoscopic examination of participants. Results: 10.2% of questionnaire respondents (312/3070) were classified as an at-risk group. Pathobiological CD analysis of this group returned positive test results for 13.5% of participants (42/312), and 0.6% of them (2/312) had CD confirmed by biopsy sample analysis. Conclusions: Our findings suggest that at-risk groups among children with symptomatic or some oligosymptomatic CD presentations can be identified through adopting a questionnaire as part of a population-based screening survey, if generally accepted screening programs are inaccessible.
MeSH term(s)	Adolescent ; Biopsy ; Celiac Disease/diagnosis ; Celiac Disease/epidemiology ; Child ; Female ; Humans ; Male ; Moscow ; Russia ; Surveys and Questionnaires
Language	English
Publishing date	2022-07-08
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1024476-1
ISSN	1440-1754 ; 1034-4810
ISSN (online)	1440-1754
ISSN	1034-4810
DOI	10.1111/jpc.16109
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Article ; Online: 'Patchiness' and basic cancer research: unravelling the proteases.

Soond, Surinder M / Kozhevnikova, Maria V / Zamyatnin, Andrey A

Cell cycle (Georgetown, Tex.)

2019 Volume 18, Issue 15, Page(s) 1687–1701

Abstract: The recent developments in Cathepsin protease research have unveiled a number of key observations which are fundamental to further our understanding of normal cellular homeostasis and disease. By far, the most interesting and promising area of Cathepsin ... ...

Abstract	The recent developments in Cathepsin protease research have unveiled a number of key observations which are fundamental to further our understanding of normal cellular homeostasis and disease. By far, the most interesting and promising area of Cathepsin biology stems from how these proteins are linked to the fate of living cells through the phenomenon of Lysosomal Leakage and Lysosomal Membrane Permeabilisation. While extracellular Cathepsins are generally believed to be of central importance in tumour progression, through their ability to modulate the architecture of the Extracellular Matrix, intracellular Cathepsins have been established as being of extreme significance in mediating cell death through Apoptosis. With these two juxtaposed key research areas in mind, the focus of this review highlights recent advancements in how this fast-paced area of Cathepsin research has recently evolved in the context of their mechanistic regulation in cancer research.
MeSH term(s)	Animals ; Apoptosis/genetics ; Biomarkers, Tumor ; Cathepsins/chemistry ; Cathepsins/metabolism ; Humans ; Lysosomes/enzymology ; Lysosomes/metabolism ; Neoplasms/enzymology ; Neoplasms/metabolism ; Neoplastic Stem Cells/metabolism ; Peptide Hydrolases/metabolism ; Protein Processing, Post-Translational ; Signal Transduction/genetics
Chemical Substances	Biomarkers, Tumor ; Cathepsins (EC 3.4.-) ; Peptide Hydrolases (EC 3.4.-)
Language	English
Publishing date	2019-06-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2019.1632639
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Zs.A 5881: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article: Integrative p53, micro-RNA and Cathepsin Protease Co-Regulatory Expression Networks in Cancer.

Soond, Surinder M / Kozhevnikova, Maria V / Townsend, Paul A / Zamyatnin, Andrey A

Cancers

2020 Volume 12, Issue 11

Abstract: As the direct regulatory role of p53 and some of its isoform proteins are becoming established in modulating gene expression in cancer research, another aspect of this mode of gene regulation that has captured significant interest over the years is the ... ...

Abstract	As the direct regulatory role of p53 and some of its isoform proteins are becoming established in modulating gene expression in cancer research, another aspect of this mode of gene regulation that has captured significant interest over the years is the mechanistic interplay between p53 and micro-RNA transcriptional regulation. The input of this into modulating gene expression for some of the cathepsin family members has been viewed as carrying noticeable importance based on their biological effects during normal cellular homeostasis and cancer progression. While this area is still in its infancy in relation to general cathepsin gene regulation, we review the current p53-regulated micro-RNAs that are generating significant interest through their regulation of cathepsin proteases, thereby strengthening the link between activated p53 forms and cathepsin gene regulation. Additionally, we extend our understanding of this developing relationship to how such micro-RNAs are being utilized as diagnostic or prognostic tools and highlight their future uses in conjunction with cathepsin gene expression as potential biomarkers within a clinical setting.
Language	English
Publishing date	2020-11-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12113454
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Article ; Online: BH3-mimetics: recent developments in cancer therapy.

Townsend, Paul A / Kozhevnikova, Maria V / Cexus, Olivier N F / Zamyatnin, Andrey A / Soond, Surinder M

Journal of experimental & clinical cancer research : CR

2021 Volume 40, Issue 1, Page(s) 355

Abstract: The hopeful outcomes from 30 years of research in BH3-mimetics have indeed served a number of solid paradigms for targeting intermediates from the apoptosis pathway in a variety of diseased states. Not only have such rational approaches in drug design ... ...

Abstract	The hopeful outcomes from 30 years of research in BH3-mimetics have indeed served a number of solid paradigms for targeting intermediates from the apoptosis pathway in a variety of diseased states. Not only have such rational approaches in drug design yielded several key therapeutics, such outputs have also offered insights into the integrated mechanistic aspects of basic and clinical research at the genetics level for the future. In no other area of medical research have the effects of such work been felt, than in cancer research, through targeting the BAX-Bcl-2 protein-protein interactions. With these promising outputs in mind, several mimetics, and their potential therapeutic applications, have also been developed for several other pathological conditions, such as cardiovascular disease and tissue fibrosis, thus highlighting the universal importance of the intrinsic arm of the apoptosis pathway and its input to general tissue homeostasis. Considering such recent developments, and in a field that has generated so much scientific interest, we take stock of how the broadening area of BH3-mimetics has developed and diversified, with a focus on their uses in single and combined cancer treatment regimens and recently explored therapeutic delivery methods that may aid the development of future therapeutics of this nature.
Language	English
Publishing date	2021-11-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-021-02157-5
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Zs.A 2065: Show issues

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Article ; Online: Intrinsically Connected: Therapeutically Targeting the Cathepsin Proteases and the Bcl-2 Family of Protein Substrates as Co-regulators of Apoptosis.

Soond, Surinder M / Kozhevnikova, Maria V / Savvateeva, Lyudmila V / Townsend, Paul A / Zamyatnin, Andrey A

International journal of molecular sciences

2021 Volume 22, Issue 9

Abstract: Taken with the growing importance of cathepsin-mediated substrate proteolysis in tumor biology and progression, the focus and emphasis placed on therapeutic design and development is coming into fruition. Underpinning this approach is the invariable ... ...

Abstract	Taken with the growing importance of cathepsin-mediated substrate proteolysis in tumor biology and progression, the focus and emphasis placed on therapeutic design and development is coming into fruition. Underpinning this approach is the invariable progression from the direction of fully characterizing cathepsin protease members and their substrate targets, towards targeting such an interaction with tangible therapeutics. The two groups of such substrates that have gained much attention over the years are the pro- and anti- apoptotic protein intermediates from the extrinsic and intrinsic signaling arms of the apoptosis pathway. As proteins that are central to determining cellular fate, some of them present themselves as very favorable candidates for therapeutic targeting. However, considering that both anti- and pro- apoptotic signaling intermediates have been reported to be downstream substrates for certain activated cathepsin proteases, therapeutic targeting approaches based on greater selectivity do need to be given greater consideration. Herein, we review the relationships shared by the cathepsin proteases and the Bcl-2 homology domain proteins, in the context of how the topical approach of adopting 'BH3-mimetics' can be explored further in modulating the relationship between the anti- and pro- apoptotic signaling intermediates from the intrinsic apoptosis pathway and their upstream cathepsin protease regulators. Based on this, we highlight important future considerations for improved therapeutic design.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis/physiology ; Apoptosis Regulatory Proteins/metabolism ; Biomimetic Materials/pharmacology ; Cathepsins/metabolism ; Humans ; Mitochondria/metabolism ; Molecular Targeted Therapy ; Peptide Fragments/metabolism ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Signal Transduction ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-2-Associated X Protein/metabolism ; bcl-X Protein/metabolism
Chemical Substances	Apoptosis Regulatory Proteins ; Bax protein (53-86) ; Peptide Fragments ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-2 ; bcl-2 Homologous Antagonist-Killer Protein ; bcl-2-Associated X Protein ; bcl-X Protein ; Cathepsins (EC 3.4.-)
Language	English
Publishing date	2021-04-28
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/ijms22094669
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Article: Cysteine Cathepsin Protease Inhibition: An update on its Diagnostic, Prognostic and Therapeutic Potential in Cancer.

Soond, Surinder M / Kozhevnikova, Maria V / Townsend, Paul A / Zamyatnin, Andrey A

Pharmaceuticals (Basel, Switzerland)

2019 Volume 12, Issue 2

Abstract: In keeping with recent developments in basic research; the importance of the Cathepsins as targets in cancer therapy have taken on increasing importance and given rise to a number of key areas of interest in the clinical setting. In keeping with driving ... ...

Abstract	In keeping with recent developments in basic research; the importance of the Cathepsins as targets in cancer therapy have taken on increasing importance and given rise to a number of key areas of interest in the clinical setting. In keeping with driving basic research in this area in a translational direction; recent findings have given rise to a number of exciting developments in the areas of cancer diagnosis; prognosis and therapeutic development. As a fast-moving area of research; the focus of this review brings together the latest findings and highlights the translational significance of these developments.
Language	English
Publishing date	2019-06-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph12020087
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Article: Harnessing the Potential of Killers and Altruists within the Microbial Community: A Possible Alternative to Antibiotic Therapy?

Ikryannikova, Larisa N / Kurbatov, Leonid K / Soond, Surinder M / Zamyatnin, Andrey A

Antibiotics (Basel, Switzerland)

2019 Volume 8, Issue 4

Abstract: In the context of a post-antibiotic era, the phenomenon of microbial allolysis, which is defined as the partial killing of bacterial population induced by other cells of the same species, may take on greater significance. This phenomenon was revealed in ... ...

Abstract	In the context of a post-antibiotic era, the phenomenon of microbial allolysis, which is defined as the partial killing of bacterial population induced by other cells of the same species, may take on greater significance. This phenomenon was revealed in some bacterial species such as
Language	English
Publishing date	2019-11-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics8040230
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