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Article ; Online: The role of peroxidasin in solid cancer progression.

Wyllie, Kaitlin / Panagopoulos, Vasilios / Cox, Thomas R

2023 Volume 51, Issue 5, Page(s) 1881–1895

Abstract: Peroxidasin is a heme-containing peroxidase enzyme that plays a vital role in the cross-linking of collagen IV molecules in basement membranes. Collagen IV cross-links are essential for providing structure and mechanical stability throughout tissue ... ...

Abstract	Peroxidasin is a heme-containing peroxidase enzyme that plays a vital role in the cross-linking of collagen IV molecules in basement membranes. Collagen IV cross-links are essential for providing structure and mechanical stability throughout tissue development, homeostasis, and wound healing. During cancer progression, the basement membrane is degraded, and proteins typically found in the basement membrane, including peroxidasin and collagen IV, can be found spread throughout the tumour microenvironment where they interact with cancer cells and alter cell behaviour. Whilst peroxidasin is reported to be up-regulated in a number of different cancers, the role that it plays in disease progression and metastasis has only recently begun to be studied. This review highlights the current literature exploring the known roles of peroxidasin in normal tissues and cancer progression, regulators of peroxidasin expression, and the reported relationships between peroxidasin expression and patient outcome in cancer.
MeSH term(s)	Humans ; Peroxidase/chemistry ; Peroxidase/metabolism ; Extracellular Matrix Proteins/metabolism ; Collagen Type IV/chemistry ; Collagen Type IV/metabolism ; Basement Membrane/metabolism ; Neoplasms/metabolism ; Tumor Microenvironment ; Peroxidasin
Chemical Substances	Peroxidase (EC 1.11.1.7) ; Extracellular Matrix Proteins ; Collagen Type IV
Language	English
Publishing date	2023-10-06
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20230018
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Article: Targeting Lysyl Oxidase Family Meditated Matrix Cross-Linking as an Anti-Stromal Therapy in Solid Tumours.

Setargew, Yordanos F I / Wyllie, Kaitlin / Grant, Rhiannon D / Chitty, Jessica L / Cox, Thomas R

Cancers

2021 Volume 13, Issue 3

Abstract: The lysyl oxidase (LOX) family of enzymes are a major driver in the biogenesis of desmoplastic matrix at the primary tumour and secondary metastatic sites. With the increasing interest in and development of anti-stromal therapies aimed at improving ... ...

Abstract	The lysyl oxidase (LOX) family of enzymes are a major driver in the biogenesis of desmoplastic matrix at the primary tumour and secondary metastatic sites. With the increasing interest in and development of anti-stromal therapies aimed at improving clinical outcomes of cancer patients, the Lox family has emerged as a potentially powerful clinical target. This review examines how lysyl oxidase family dysregulation in solid cancers contributes to disease progression and poor patient outcomes, as well as an evaluation of the preclinical landscape of LOX family targeting therapeutics. We also discuss the suitability of the LOX family as a diagnostic and/or prognostic marker in solid tumours.
Language	English
Publishing date	2021-01-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13030491
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Article: From WWII to Kingston, Ontario: The History of Queen's University School of Medicine, Division of Plastic and Reconstructive Surgery.

Chung, Karen / Wyllie, Kenneth / Davidson, John

Plastic surgery (Oakville, Ont.)

2016 Volume 24, Issue 3, Page(s) 171–172

Abstract: Objective: To describe the origin and development of the Division of Plastic and Reconstructive Surgery at the Queen's University School of Medicine (Kingston, Ontario).: Methods: Resarch ethics board approval and privacy agreements from the Kingston ...

Abstract	Objective: To describe the origin and development of the Division of Plastic and Reconstructive Surgery at the Queen's University School of Medicine (Kingston, Ontario). Methods: Resarch ethics board approval and privacy agreements from the Kingston General Hospital (KGH, Kingston, Ontario) medical archives were obtained. Primary and secondary data sources were identified. A systematic examination of newspaper archives, research literature, KGH medical advisory committee meeting minutes, and testimonies from Dr Kenneth Wyllie and Dr John Davidson were obtained. Results: In 1949, Dr Albert Ross Tilley arrived at Queen's University in Kingston, Ontario. There, Tilley initiated the Burn Unit at the KGH and began monthly teaching during the academic semester. Ken Wyllie (Meds '55), Lloyd Carlson (Meds '57) and John Emery (Meds '57) were the notable progeny of his early initiatives. In 1963, Kenneth Wyllie founded the Division of Plastic and Reconstructive Surgery in Kingston, Ontario, having completed plastic surgery training in Toronto and Edinburgh with experiences in Stockholm (Sweden), Paris (France) and Baltimore (Maryland, USA). He was shortly joined by Pat Shoemaker (Meds '66). John Davidson (Meds '82) arrived in 1989, bringing an interest in microsurgery and critical inquiry to the division. Five notable surgeons, Cartotto (Meds '88), Watkins, Watters, Meathrel (Meds '03) and McKay, further enhanced the Division's clinical and academic mission. Conclusions: The collective activity of the Division of Plastic and Reconstructive Surgery at Queen's School of Medicine in its 66-year history has encouraged more than 40 others to pursue distinguished careers in the specialty throughout North America, including three past presidents of the Canadian Society of Plastic Surgeons.
Language	English
Publishing date	2016-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2869727-3
ISSN	2292-5511 ; 2292-5503
ISSN (online)	2292-5511
ISSN	2292-5503
DOI	10.4172/plastic-surgery.1000970
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Article: A review of ultraviolet treatment for psoriasis at Waikato Hospital.

Oakley, A M / Wyllie, K

The Australasian journal of dermatology

1996 Volume 37, Issue 3, Page(s) 132–136

Abstract: Details of 79 courses of UVB and 40 courses of PUVA for patients with chronic plaque psoriasis at Waikato Hospital were prospectively collected when a new Phototherapy Unit opened. Efficacy was assessed by clearance rates (73% for UVB, 87.5% for PUVA). ... ...

Abstract	Details of 79 courses of UVB and 40 courses of PUVA for patients with chronic plaque psoriasis at Waikato Hospital were prospectively collected when a new Phototherapy Unit opened. Efficacy was assessed by clearance rates (73% for UVB, 87.5% for PUVA). There was significant improvement in Psoriasis Disability Index, which was derived from a questionnaire assessing functional disability and completed by the patients before and after treatment. It took a median number of 24 treatments for psoriasis in the patients receiving UVB to clear, and for the PUVA patients the median was 19 treatments. The efficacy could not be correlated with skin type. Fifty per cent of UVB patients and 25% of PUVA patients received symptomatic burns, all localized and minor in nature. LIfetime PUVA dose was calculated, 90% of patients having received less than 400 J/cm2.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Attitude to Health ; Burns/etiology ; Child ; Chronic Disease ; Dermatitis, Phototoxic/etiology ; Female ; Humans ; Male ; Middle Aged ; New Zealand ; PUVA Therapy/adverse effects ; Prospective Studies ; Psoriasis/drug therapy ; Psoriasis/psychology ; Psoriasis/radiotherapy ; Radiotherapy Dosage ; Remission Induction ; Time Factors ; Ultraviolet Therapy/adverse effects ; Ultraviolet Therapy/classification
Language	English
Publishing date	1996-08
Publishing country	Australia
Document type	Journal Article
ZDB-ID	138052-7
ISSN	1440-0960 ; 0004-8380
ISSN (online)	1440-0960
ISSN	0004-8380
DOI	10.1111/j.1440-0960.1996.tb01030.x
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Zs.A 236: Show issues

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Article ; Online: Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.

Filipe, Elysse C / Velayuthar, Sipiththa / Philp, Ashleigh / Nobis, Max / Latham, Sharissa L / Parker, Amelia L / Murphy, Kendelle J / Wyllie, Kaitlin / Major, Gretel S / Contreras, Osvaldo / Mok, Ellie T Y / Enriquez, Ronaldo F / McGowan, Suzanne / Feher, Kristen / Quek, Lake-Ee / Hancock, Sarah E / Yam, Michelle / Tran, Emmi / Setargew, Yordanos F I /

Skhinas, Joanna N / Chitty, Jessica L / Phimmachanh, Monica / Han, Jeremy Z R / Cadell, Antonia L / Papanicolaou, Michael / Mahmodi, Hadi / Kiedik, Beata / Junankar, Simon / Ross, Samuel E / Lam, Natasha / Coulson, Rhiannon / Yang, Jessica / Zaratzian, Anaiis / Da Silva, Andrew M / Tayao, Michael / Chin, Ian L / Cazet, Aurélie / Kansara, Maya / Segara, Davendra / Parker, Andrew / Hoy, Andrew J / Harvey, Richard P / Bogdanovic, Ozren / Timpson, Paul / Croucher, David R / Lim, Elgene / Swarbrick, Alexander / Holst, Jeff / Turner, Nigel / Choi, Yu Suk / Kabakova, Irina V / Philp, Andrew / Cox, Thomas R

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2024 , Page(s) e2307963

Abstract: In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding ... ...

Abstract	In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues. It is shown that heightened cell survival is driven by enhanced metabolism of fatty acids within TNBC cells exposed to softer microenvironments. It is demonstrated that uncoupling cellular mechanosensing through integrin β1 blocking antibody effectively causes stiff primed TNBC cells to behave like their soft counterparts, both in vitro and in vivo. This work is the first to show that softer tumor microenvironments may be contributing to changes in disease outcome by imprinting on TNBC cells a greater metabolic flexibility and conferring discrete cell survival advantages.
Language	English
Publishing date	2024-04-11
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2808093-2
ISSN	2198-3844 ; 2198-3844
ISSN (online)	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202307963
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Article ; Online: Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis.

Papanicolaou, Michael / Parker, Amelia L / Yam, Michelle / Filipe, Elysse C / Wu, Sunny Z / Chitty, Jessica L / Wyllie, Kaitlin / Tran, Emmi / Mok, Ellie / Nadalini, Audrey / Skhinas, Joanna N / Lucas, Morghan C / Herrmann, David / Nobis, Max / Pereira, Brooke A / Law, Andrew M K / Castillo, Lesley / Murphy, Kendelle J / Zaratzian, Anaiis /

Hastings, Jordan F / Croucher, David R / Lim, Elgene / Oliver, Brian G / Mora, Fatima Valdes / Parker, Benjamin L / Gallego-Ortega, David / Swarbrick, Alexander / O'Toole, Sandra / Timpson, Paul / Cox, Thomas R

Nature communications

2022 Volume 13, Issue 1, Page(s) 4587

Abstract: The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays a crucial role in shaping their progression. Many desmoplastic tumours including breast cancer involve the significant accumulation of ... ...

Abstract	The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays a crucial role in shaping their progression. Many desmoplastic tumours including breast cancer involve the significant accumulation of type I collagen. However, recently it has become clear that the precise distribution and organisation of matrix molecules such as collagen I is equally as important in the tumour as their abundance. Cancer-associated fibroblasts (CAFs) coexist within breast cancer tissues and play both pro- and anti-tumourigenic roles through remodelling the ECM. Here, using temporal proteomic profiling of decellularized tumours, we interrogate the evolving matrisome during breast cancer progression. We identify 4 key matrisomal clusters, and pinpoint collagen type XII as a critical component that regulates collagen type I organisation. Through combining our proteomics with single-cell transcriptomics, and genetic manipulation models, we show how CAF-secreted collagen XII alters collagen I organisation to create a pro-invasive microenvironment supporting metastatic dissemination. Finally, we show in patient cohorts that collagen XII may represent an indicator of breast cancer patients at high risk of metastatic relapse.
MeSH term(s)	Breast Neoplasms/pathology ; Collagen ; Collagen Type I ; Collagen Type XII/metabolism ; Extracellular Matrix/pathology ; Female ; Humans ; Neoplasm Metastasis/pathology ; Neoplasm Recurrence, Local/pathology ; Proteomics ; Tumor Microenvironment
Chemical Substances	COL12A1 protein, human ; Collagen Type I ; Collagen Type XII ; Collagen (9007-34-5)
Language	English
Publishing date	2022-08-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-32255-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Primary school children's perceptions of the effects of sun on skin.

Rademaker, M / Wyllie, K / Collins, M / Wetton, N

The Australasian journal of dermatology

1996 Volume 37, Issue 1, Page(s) 30–36

Abstract: To assess whether young children understand the dangers and results of sun exposure, a novel Draw and Write technique was used to survey a group of 5-8 year old primary school children. One hundred and ninety-four children were invited to draw and write ... ...

Abstract	To assess whether young children understand the dangers and results of sun exposure, a novel Draw and Write technique was used to survey a group of 5-8 year old primary school children. One hundred and ninety-four children were invited to draw and write comments to six scenarios involving sun exposure. Of the children surveyed, 84% gave a negative sentiment to sunburn, with only 6% displaying positive sentiments towards sunbathing. Sixty-five per cent of children suggested the use of sun blocks, 69% the use of protective clothing, 45% the wearing of hats and 43% the use of shade as a mechanism for protecting the skin from sun damage. Only 2% of children made any reference to skin cancer. The primary school children surveyed had a good level of awareness of the dangers of sunburn and the need to take appropriate actions to avoid sun damage.
MeSH term(s)	Attitude to Health ; Child ; Child, Preschool ; Data Collection ; Female ; Humans ; Male ; New Zealand ; Skin Neoplasms/prevention & control ; Sunlight/adverse effects ; Sunscreening Agents/administration & dosage
Chemical Substances	Sunscreening Agents
Language	English
Publishing date	1996-02
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	138052-7
ISSN	1440-0960 ; 0004-8380
ISSN (online)	1440-0960
ISSN	0004-8380
DOI	10.1111/j.1440-0960.1996.tb00991.x
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Article ; Online: A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer.

Chitty, Jessica L / Yam, Michelle / Perryman, Lara / Parker, Amelia L / Skhinas, Joanna N / Setargew, Yordanos F I / Mok, Ellie T Y / Tran, Emmi / Grant, Rhiannon D / Latham, Sharissa L / Pereira, Brooke A / Ritchie, Shona C / Murphy, Kendelle J / Trpceski, Michael / Findlay, Alison D / Melenec, Pauline / Filipe, Elysse C / Nadalini, Audrey / Velayuthar, Sipiththa /

Major, Gretel / Wyllie, Kaitlin / Papanicolaou, Michael / Ratnaseelan, Shivanjali / Phillips, Phoebe A / Sharbeen, George / Youkhana, Janet / Russo, Alice / Blackwell, Antonia / Hastings, Jordan F / Lucas, Morghan C / Chambers, Cecilia R / Reed, Daniel A / Stoehr, Janett / Vennin, Claire / Pidsley, Ruth / Zaratzian, Anaiis / Da Silva, Andrew M / Tayao, Michael / Charlton, Brett / Herrmann, David / Nobis, Max / Clark, Susan J / Biankin, Andrew V / Johns, Amber L / Croucher, David R / Nagrial, Adnan / Gill, Anthony J / Grimmond, Sean M / Pajic, Marina / Timpson, Paul / Jarolimek, Wolfgang / Cox, Thomas R

Nature cancer

2023 Volume 4, Issue 9, Page(s) 1326–1344

Abstract: The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. Using small-molecule drug-design ...

Abstract	The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. Using small-molecule drug-design approaches, we generated and validated PXS-5505, a first-in-class highly selective and potent pan-lysyl oxidase inhibitor. We demonstrate in vitro and in vivo that pan-lysyl oxidase inhibition decreases chemotherapy-induced pancreatic tumor desmoplasia and stiffness, reduces cancer cell invasion and metastasis, improves tumor perfusion and enhances the efficacy of chemotherapy in the autochthonous genetically engineered KPC model, while also demonstrating antifibrotic effects in human patient-derived xenograft models of pancreatic cancer. PXS-5505 is orally bioavailable, safe and effective at inhibiting lysyl oxidase activity in tissues. Our findings present the rationale for progression of a pan-lysyl oxidase inhibitor aimed at eliciting a reduction in stromal matrix to potentiate chemotherapy in pancreatic ductal adenocarcinoma.
MeSH term(s)	Humans ; Gemcitabine ; Protein-Lysine 6-Oxidase ; Pancreatic Neoplasms/drug therapy ; Pancreatic Diseases
Chemical Substances	Gemcitabine ; Protein-Lysine 6-Oxidase (EC 1.4.3.13)
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-023-00614-y
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Article: Relative effectiveness of three repair strategies on the visual-identification of misperceived words.

Gagné, J P / Wyllie, K A

Ear and hearing

1989 Volume 10, Issue 6, Page(s) 368–374

Abstract: Experimental videotapes were used to assess the effectiveness of three repair strategies: (1) repetitions, (2) synonyms, and (3) paraphrases. Three groups of normal-hearing adults viewed one of three videotapes. The same 50 test-words were used on each ... ...

Abstract	Experimental videotapes were used to assess the effectiveness of three repair strategies: (1) repetitions, (2) synonyms, and (3) paraphrases. Three groups of normal-hearing adults viewed one of three videotapes. The same 50 test-words were used on each videotape. Each test-item consisted of three stimuli: a test-word, a stimulus that incorporated the repair strategy under investigation, and a repetition of the initial test-word. Each videotape displayed one of the three repair strategies under investigation. The subjects were required to identify test-words presented in a visual-only mode. The results indicated that the performance of the subjects who were provided with synonyms or paraphrases was significantly better than the performance of the subjects who were shown repetitions. Also, subjects who were shown paraphrases performed significantly better than those who were shown synonyms. These findings indicate that repair strategies that incorporate the use of substitute stimuli such as synonyms and paraphrases may be more effective than the simple repetition of the misperceived stimulus.
MeSH term(s)	Adult ; Communication ; Communication Barriers ; Evaluation Studies as Topic ; Hearing Loss/rehabilitation ; Hearing Loss, Functional/rehabilitation ; Humans ; Photic Stimulation ; Pilot Projects ; Random Allocation ; Videotape Recording ; Vocabulary
Language	English
Publishing date	1989-12
Publishing country	United States
Document type	Clinical Trial ; Controlled Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603093-2
ISSN	1538-4667 ; 0196-0202
ISSN (online)	1538-4667
ISSN	0196-0202
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Zs.A 1548: Show issues

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Article: The HEV Ventilator

Buytaert, J. / Abud, A. Abed / Allport, P. / 'Alvarez, A. Pazos / Akiba, K. / Francisco, O. Augusto de Aguiar / Bay, A. / Bernard, F. / Baron, S. / Bertella, C. / Brunner, J. / Bowcock, T. / Jode, M. Buytaert-De / Byczynski, W. / Carvalho, R. De / Coco, V. / Collins, P. / Collins, R. / Dikic, N. /

Dousse, N. / Dowd, B. / Dumps, R. / Durante, P. / Fadel, W. / Farry, S. / Prieto, A. Fern'andez / Flynn, G. / Lima, V. Franco / Frei, R. / Torreira, A. Gallas / Guida, R. / Hennessy, K. / Henriques, A. / Hutchcroft, D. / Ilic, S. / Jevtic, A. / Joram, C. / Kapusniak, K. / Cid, E. Lemos / Lindner, J. / Lindner, R. / Milovanovic, M. / Mico, S. / Morant, J. / Morel, M. / Manne, G. / Murray, D. / Nasteva, I. / Neufeld, N. / Neuhold, I. / L'opez, F. Pardo-Sobrino / Trigo, E. P'erez / Jallas, G. Pichel / Pilorz, E. / Piquilloud, L. / Pons, X. / Reiner, D. / Roosens, C. / Rostalski, P. / Schmidt, B. / Saucet, E. / Sanders, F. / Sigaud, C. / Schoettker, P. / Schwemmer, R. / Schindler, H. / Sharma, A. / Svihra, P. / Leemput, J. van / Vignaux, L. / Vasey, F. / Woonton, H. / Wyllie, K.

Abstract: HEV is a low-cost, versatile, high-quality ventilator, which has been designed in response to the COVID-19 pandemic. The ventilator is intended to be used both in and out of hospital intensive care units, and for both invasive and non-invasive ... ...

Abstract	HEV is a low-cost, versatile, high-quality ventilator, which has been designed in response to the COVID-19 pandemic. The ventilator is intended to be used both in and out of hospital intensive care units, and for both invasive and non-invasive ventilation. The hardware can be complemented with an external turbine for use in regions where compressed air supplies are not reliably available. The standard modes provided include PC-A/C(Pressure Assist Control),PC-A/C-PRVC(Pressure Regulated Volume Control), PC-PSV (Pressure Support Ventilation) and CPAP (Continuous Positive airway pressure). HEV is designed to support remote training and post market surveillance via a web interface and data logging to complement the standard touch screen operation, making it suitable for a wide range of geographical deployment. The HEV design places emphasis on the quality of the pressure curves and the reactivity of the trigger, delivering a global performance which will be applicable to ventilator needs beyond theCOVID-19 pandemic. This article describes the conceptual design and presents the prototype units together with their performance evaluation.
Keywords	covid19
Publisher	ArXiv
Document type	Article
Database	COVID19

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