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  1. 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

    British journal of cancer

    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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Colorectal carcinogenesis: road maps to cancer.

    Worthley, Daniel-L / Whitehall, Vicki-L / Spring, Kevin-J / Leggett, Barbara-A

    World journal of gastroenterology

    2007  Volume 13, Issue 28, Page(s) 3784–3791

    Abstract: This review explores the chief genetic and epigenetic events that promote pathological progression in colorectal carcinogenesis. This article discusses the molecular and pathological basis for classifying colorectal neoplasia into suppressor, mutator and ...

    Abstract This review explores the chief genetic and epigenetic events that promote pathological progression in colorectal carcinogenesis. This article discusses the molecular and pathological basis for classifying colorectal neoplasia into suppressor, mutator and methylator pathways. These differing mechanisms of genomic instability are associated with specific cancer characteristics, and may provide the opportunity for more effective prevention and surveillance strategies in the future. This is the first review in a series of five topics outlining important and developing aspects of colorectal cancer.
    MeSH term(s) Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/pathology ; DNA Methylation ; Genes, Tumor Suppressor ; Genomic Instability ; Humans
    Language English
    Publishing date 2007-07-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2185929-2
    ISSN 2219-2840 ; 1007-9327
    ISSN (online) 2219-2840
    ISSN 1007-9327
    DOI 10.3748/wjg.v13.i28.3784
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Loss of

    Ng, Jia Q / Jafarov, Toghrul H / Little, Christopher B / Wang, Tongtong / Ali, Abdullah / Ma, Yan / Radford, Georgette A / Vrbanac, Laura / Ichinose, Mari / Whittle, Samuel / Hunter, David / Lannagan, Tamsin Rm / Suzuki, Nobumi / Goyne, Jarrad M / Kobayashi, Hiroki / Wang, Timothy C / Haynes, David / Menicanin, Danijela / Gronthos, Stan /
    Worthley, Daniel L / Woods, Susan L / Mukherjee, Siddhartha

    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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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