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Article ; Online: Advancing translational research for colorectal immuno-oncology.

Thomas, Elaine M / Wright, Josephine A / Blake, Stephen J / Page, Amanda J / Worthley, Daniel L / Woods, Susan L

2023 Volume 129, Issue 9, Page(s) 1442–1450

Abstract: Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely to respond are those with DNA ... ...

Abstract	Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely to respond are those with DNA mismatch repair deficient (dMMR) and microsatellite instability (MSI) disease. However, reliable predictors of ICI response are lacking, even within the dMMR/MSI subtype. This, together with identification of novel mechanisms to increase response rates and prevent resistance, are ongoing and vitally important unmet needs. To address the current challenges with translation of early research findings into effective therapeutic strategies, this review summarises the present state of preclinical testing used to inform the development of immuno-regulatory treatment strategies for CRC. The shortfalls and advantages of commonly utilised mouse models of CRC, including chemically induced, transplant and transgenic approaches are highlighted. Appropriate use of existing models, incorporation of patient-derived data and development of cutting-edge models that recapitulate important features of human disease will be key to accelerating clinically relevant research in this area.
MeSH term(s)	Animals ; Mice ; Humans ; Translational Research, Biomedical ; Medical Oncology ; Brain Neoplasms ; Colorectal Neoplasms ; Microsatellite Instability ; DNA Mismatch Repair
Language	English
Publishing date	2023-08-10
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02392-x
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Article ; Online: Cancer-associated fibroblasts-heroes or villains?

Gieniec, Krystyna A / Butler, Lisa M / Worthley, Daniel L / Woods, Susan L

British journal of cancer

2019 Volume 121, Issue 4, Page(s) 293–302

Abstract: Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in ...

Abstract	Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in vitro and in vivo experiments, pathological association and, more recently, ablation, and it is now widely appreciated that CAFs form a group of highly heterogeneous cells with no single overarching marker. Studies have demonstrated that the CAF population contains different subtypes based on the expression of marker proteins with the capacity to promote or inhibit cancer, with their biological role as accomplices or adversaries dependent on many factors, including the cancer stage. So, while CAFs have been endlessly shown to promote the growth, survival and spread of tumours via improvements in functionality and an altered secretome, they are also capable of retarding tumorigenesis via largely unknown mechanisms. It is important to reconcile these disparate results so that the functions of, or factors produced by, tumour-promoting subtypes can be specifically targeted to improve cancer patient outcomes. This review will dissect out CAF complexity and CAF-directed cancer treatment strategies in order to provide a case for future, rational therapies.
MeSH term(s)	Animals ; Cancer-Associated Fibroblasts/drug effects ; Cancer-Associated Fibroblasts/physiology ; Energy Metabolism ; Extracellular Matrix/physiology ; Humans ; Mice ; Neoplasm Invasiveness ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Phenotype ; Prognosis
Language	English
Publishing date	2019-07-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-019-0509-3
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Article ; Online: The clinical value of "exception item" colonoscopy (MBS item 32228).

Lee See, Michelle / Lee, Antonio / Roberts, Roderick / Friedman, Richard A / Hewett, David G / Worthley, Daniel L

The Medical journal of Australia

2021 Volume 216, Issue 2, Page(s) 94–95

MeSH term(s)	Australia ; Colonic Diseases/diagnosis ; Colonic Polyps/diagnosis ; Colonoscopy/standards ; Colonoscopy/statistics & numerical data ; Colorectal Neoplasms/diagnosis ; Female ; Humans ; Male ; Middle Aged ; Quality Improvement ; Rectal Diseases/diagnosis
Language	English
Publishing date	2021-09-01
Publishing country	Australia
Document type	Evaluation Study ; Letter
ZDB-ID	186082-3
ISSN	1326-5377 ; 0025-729X
ISSN (online)	1326-5377
ISSN	0025-729X
DOI	10.5694/mja2.51241
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Article ; Online: Engineered bacteria detect tumor DNA.

Cooper, Robert M / Wright, Josephine A / Ng, Jia Q / Goyne, Jarrad M / Suzuki, Nobumi / Lee, Young K / Ichinose, Mari / Radford, Georgette / Ryan, Feargal J / Kumar, Shalni / Thomas, Elaine M / Vrbanac, Laura / Knight, Rob / Woods, Susan L / Worthley, Daniel L / Hasty, Jeff

Science (New York, N.Y.)

2023 Volume 381, Issue 6658, Page(s) 682–686

Abstract: Synthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect specific extracellular DNA sequences and mutations. Here, we engineered naturally ... ...

Abstract	Synthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect specific extracellular DNA sequences and mutations. Here, we engineered naturally competent
MeSH term(s)	Animals ; Humans ; Mice ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; DNA, Neoplasm/analysis ; Mutation ; Acinetobacter/genetics ; Cell-Free Nucleic Acids/analysis ; Bioengineering ; Biosensing Techniques
Chemical Substances	DNA, Neoplasm ; Cell-Free Nucleic Acids
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adf3974
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Desmopressin as a Novel Long-Term Treatment in Postural Tachycardia Syndrome Patients with Polyuria.

Seeley, Marie-Claire / Thynne, Tilenka R / Braund, Wilton J / Worthley, Daniel L / Gallagher, Celine / Sanders, Prashanthan / Lau, Dennis H

The American journal of medicine

2021 Volume 134, Issue 9, Page(s) e486–e487

MeSH term(s)	Aldosterone/blood ; Antidiuretic Agents/administration & dosage ; Deamino Arginine Vasopressin/administration & dosage ; Diabetes Insipidus, Neurogenic/blood ; Diabetes Insipidus, Neurogenic/complications ; Diabetes Insipidus, Neurogenic/diagnosis ; Diabetes Insipidus, Neurogenic/drug therapy ; Female ; Glycopeptides/blood ; Humans ; Hypovolemia/etiology ; Hypovolemia/physiopathology ; Middle Aged ; Polyuria/etiology ; Polyuria/physiopathology ; Postural Orthostatic Tachycardia Syndrome/etiology ; Postural Orthostatic Tachycardia Syndrome/physiopathology ; Postural Orthostatic Tachycardia Syndrome/psychology ; Postural Orthostatic Tachycardia Syndrome/therapy ; Quality of Life ; Renin/blood ; Treatment Outcome
Chemical Substances	Antidiuretic Agents ; Glycopeptides ; copeptins ; Aldosterone (4964P6T9RB) ; Renin (EC 3.4.23.15) ; Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2021-04-16
Publishing country	United States
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	80015-6
ISSN	1555-7162 ; 1873-2178 ; 0002-9343 ; 1548-2766
ISSN (online)	1555-7162 ; 1873-2178
ISSN	0002-9343 ; 1548-2766
DOI	10.1016/j.amjmed.2021.03.028
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Article ; Online: Cancer-associated fibroblasts in gastrointestinal cancer.

Kobayashi, Hiroki / Enomoto, Atsushi / Woods, Susan L / Burt, Alastair D / Takahashi, Masahide / Worthley, Daniel L

Nature reviews. Gastroenterology & hepatology

2019 Volume 16, Issue 5, Page(s) 282–295

Abstract: The tumour microenvironment, also termed the tumour stroma or tumour mesenchyme, includes fibroblasts, immune cells, blood vessels and the extracellular matrix and substantially influences the initiation, growth and dissemination of gastrointestinal ... ...

Abstract	The tumour microenvironment, also termed the tumour stroma or tumour mesenchyme, includes fibroblasts, immune cells, blood vessels and the extracellular matrix and substantially influences the initiation, growth and dissemination of gastrointestinal cancer. Cancer-associated fibroblasts (CAFs) are one of the critical components of the tumour mesenchyme and not only provide physical support for epithelial cells but also are key functional regulators in cancer, promoting and retarding tumorigenesis in a context-dependent manner. In this Review, we outline the emerging understanding of gastrointestinal CAFs with a particular emphasis on their origin and heterogeneity, as well as their function in cancer cell proliferation, tumour immunity, angiogenesis, extracellular matrix remodelling and drug resistance. Moreover, we discuss the clinical implications of CAFs as biomarkers and potential targets for prevention and treatment of patients with gastrointestinal cancer.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Cancer-Associated Fibroblasts/physiology ; Gastrointestinal Neoplasms/metabolism ; Gastrointestinal Neoplasms/pathology ; Gastrointestinal Neoplasms/physiopathology ; Gastrointestinal Neoplasms/therapy ; Humans ; Tumor Microenvironment/physiology
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2019-02-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/s41575-019-0115-0
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Zs.A 6020: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The three A's of colonoscopy referral.

Bampton, Peter / Sammour, Tarik / Brown, Gregor Je / Hewett, David G / Worthley, Daniel L

The Medical journal of Australia

2018 Volume 209, Issue 10, Page(s) 461–462

MeSH term(s)	Australia ; Colonoscopy/economics ; Colorectal Neoplasms/diagnosis ; Hospitals, Private/economics ; Hospitals, Public/economics ; Humans ; Referral and Consultation ; Time Factors
Language	English
Publishing date	2018-11-14
Publishing country	Australia
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	186082-3
ISSN	1326-5377 ; 0025-729X
ISSN (online)	1326-5377
ISSN	0025-729X
DOI	10.5694/mja18.00851
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Article: Loss of

bioRxiv : the preprint server for biology

2023

Abstract: Osteoarthritis (OA), which carries an enormous disease burden across the world, is characterised by irreversible degeneration of articular cartilage (AC), and subsequently bone. The cellular cause of OA is unknown. Here, using lineage tracing in mice, we ...

Abstract	Osteoarthritis (OA), which carries an enormous disease burden across the world, is characterised by irreversible degeneration of articular cartilage (AC), and subsequently bone. The cellular cause of OA is unknown. Here, using lineage tracing in mice, we show that the BMP-antagonist
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.29.534651
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Article ; Online: Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia.

Gurbatri, Candice R / Radford, Georgette A / Vrbanac, Laura / Im, Jongwon / Thomas, Elaine M / Coker, Courtney / Taylor, Samuel R / Jang, YoungUk / Sivan, Ayelet / Rhee, Kyu / Saleh, Anas A / Chien, Tiffany / Zandkarimi, Fereshteh / Lia, Ioana / Lannagan, Tamsin R M / Wang, Tongtong / Wright, Josephine A / Kobayashi, Hiroki / Ng, Jia Q /

Lawrence, Matt / Sammour, Tarik / Thomas, Michelle / Lewis, Mark / Papanicolas, Lito / Perry, Joanne / Fitzsimmons, Tracy / Kaazan, Patricia / Lim, Amanda / Stavropoulos, Alexandra M / Gouskos, Dion A / Marker, Julie / Ostroff, Cheri / Rogers, Geraint / Arpaia, Nicholas / Worthley, Daniel L / Woods, Susan L / Danino, Tal

Nature communications

2024 Volume 15, Issue 1, Page(s) 646

Abstract: Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) ...

Abstract	Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.
MeSH term(s)	Animals ; Humans ; Mice ; Adenoma/diagnosis ; Adenoma/therapy ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/therapy ; Escherichia coli/genetics ; Prospective Studies ; Salicylates ; Double-Blind Method
Chemical Substances	Salicylates
Language	English
Publishing date	2024-01-20
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Multicenter Study
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-44776-4
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Article ; Online: Stem cell-directed therapies for osteoarthritis: The promise and the practice.

Ng, Jia / Little, Christopher B / Woods, Susan / Whittle, Samuel / Lee, Francis Y / Gronthos, Stan / Mukherjee, Siddhartha / Hunter, David J / Worthley, Daniel L

Stem cells (Dayton, Ohio)

2020 Volume 38, Issue 4, Page(s) 477–486

Abstract: Osteoarthritis (OA) is a disease of an entire synovial joint characterized by clinical symptoms and distortion of joint tissues, including cartilage, muscles, ligaments, and bone. Although OA is a disease of all joint tissues, it is a defined accessible ... ...

Abstract	Osteoarthritis (OA) is a disease of an entire synovial joint characterized by clinical symptoms and distortion of joint tissues, including cartilage, muscles, ligaments, and bone. Although OA is a disease of all joint tissues, it is a defined accessible compartment and is thus amenable to topical surgical and regenerative therapies, including stem cells. All tissues arise from stem progenitor cells, and the relative capacity of different cellular compartments, and different individuals, to renew tissues into adulthood may be important in the onset of many different degenerative diseases. OA is driven by both mechanical and inflammatory factors, but how these factors affect the proliferation and differentiation of cells into cartilage in vivo is largely unknown. Indeed, our very basic understanding of the physiological cellular kinetics and biology of the stem-progenitor cell unit of the articular cartilage, and how this is influenced by mechano-inflammatory injury, is largely unknown. OA seems, rather deceptively, to be the low-hanging fruit for stem cell therapy. Without the basic understanding of the stem cell and progenitor unit that generate and maintain articular cartilage in vivo, we will continue to waste opportunities to both prevent and manage this disease. In this review, we discuss the biology of chondrogenesis, the stem cell populations that support articular cartilage in health and disease, and future opportunities afforded through the translation of basic articular chondrocyte stem cell biology into new clinical therapies.
MeSH term(s)	Humans ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/metabolism ; Osteoarthritis/therapy ; Regenerative Medicine/methods
Language	English
Publishing date	2020-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1002/stem.3139
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