Marie Ranson

Marie Ranson
University of Wollongong | UOW · School of Biological Sciences

PhD

About

233
Publications
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Publications

Publications (233)
Article
Full-text available
Cutaneous squamous cell carcinoma (cSCC) is a disease with globally rising incidence and poor prognosis for patients with advanced or metastatic disease. Epithelial-mesenchymal transition (EMT) is a driver of metastasis in many carcinomas, and cSCC is no exception. We aimed to provide a systematic overview of the clinical and experimental evidence...
Article
Purpose: The tumour immune microenvironment impacts the biological behaviour of the tumour but its effect on clinical outcomes in head and neck cutaneous squamous cell carcinomas (HNcSCC) is largely unknown. Experimental design: We compared the immune milieu of high-risk HNcSCC that never progressed to metastasis with those that metastasised usi...
Article
Full-text available
Metastatic cutaneous squamous cell carcinoma (CSCC) is a highly morbid disease requiring radical surgery and adjuvant therapy, which is associated with a poor prognosis. Yet, compared to other advanced malignancies, relatively little is known of the genomic landscape of metastatic CSCC. We have previously reported the mutational signatures and muta...
Preprint
Cutaneous squamous cell carcinoma (cSCC) is a disease with globally rising incidence and poor prognosis for patients with advanced or metastatic disease. Epithelial-mesenchymal transition (EMT) is a driver of metastasis in many carcinomas, and cSCC is no exception. We aimed to provide a systematic overview of the clinical and experimental evidence...
Preprint
Purpose The tumour immune microenvironment impacts the biological behaviour of the tumour but its effect on clinical outcomes in head and neck cutaneous squamous cell carcinomas (HNcSCC) is largely unknown. Experimental Design We compared the immune milieu of high-risk HNcSCC that never progressed to metastasis with those that metastasised using m...
Article
Full-text available
Cutaneous squamous cell carcinoma (cSCC) of the head and neck region is the second most prevalent skin cancer, with metastases to regional lymph nodes occurring in 2%–5% of cases. To further our understanding of the molecular events characterizing cSCC invasion and metastasis, we conducted targeted cancer progression gene expression and pathway ana...
Article
Full-text available
Plasminogen activator inhibitor type-2 (PAI-2), a member of the serpin family, is dramatically upregulated during pregnancy and in response to inflammation. Although PAI-2 exists in glycosylated and non-glycosylated forms in vivo, the majority of in vitro studies of PAI-2 have exclusively involved the intracellular non-glycosylated form. This study...
Preprint
Acid-sensing ion channels (ASICs) are transmembrane sensors of extracellular acidosis and potential drug targets in several disease indications, including neuropathic pain and cancer metastasis. The K ⁺ -sparing diuretic amiloride is a moderate non-specific inhibitor of ASICs and has been widely used as a probe for elucidating ASIC function. In thi...
Article
Full-text available
Pancreatic cancer is a highly aggressive malignancy that features high recurrence rates and the poorest prognosis of all solid cancers. The urokinase plasminogen activation system (uPAS) is strongly implicated in the pathophysiology and clinical outcomes of patients with pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of a...
Preprint
Full-text available
Metastatic cutaneous squamous cell carcinoma (cSCC) is associated with a high risk of recurrence and poor prognosis. There is limited published data exploring whole genome sequencing (WGS). The aim of this project was to provide the first comprehensive genomic understanding of the state of metastatic cSCC. In this study, we used WGS on matched tumo...
Article
The urokinase plasminogen activator (uPA) is a widely studied anticancer drug target with multiple classes of inhibitors reported to date. Many of these inhibitors contain amidine or guanidine groups, while others lacking these groups show improved oral bioavailability. Most of the X-ray co-crystal structures of small molecule uPA inhibitors show a...
Article
Neuroserpin is a secreted protease inhibitor known to inhibit amyloid formation by the Alzheimer’s beta peptide (Aβ). To test whether this effect was constrained to Aβ, we used a range of in vitro assays to demonstrate that neuroserpin inhibits amyloid formation by several different proteins and protects against the associated cytotoxicity but, unl...
Article
Full-text available
Prostate cancer is a leading cause of cancer-associated deaths in men over 60 years of age. Most patients are killed by tumor metastasis. Recent evidence has implicated a role of the tumor microenvironment and urokinase plasminogen activator (uPA) in cancer cell migration, invasion, and metastasis. Here, we examine the role of the Na+/H+ exchanger...
Conference Paper
Background and Aim: Interactions between pancreatic cancer (PC) cellsand pancreatic stellate cells (PSCs), which produce PC stroma, promote tu-mor growth and metastasis. One of the pathways that mediate cancer cell–PSC interactions is the urokinase plasminogen activator (uPA) pathway.High serum and tumor uPA levels are associated with poor survival...
Preprint
Full-text available
The urokinase plasminogen activator (uPA) plays a critical role in tumor cell invasion and migration and is a promising anti-metastasis target. 6-Substituted analogs of 5-N,N-(hexamethylene)amiloride (HMA) are potent and selective uPA inhibitors that lack the diuretic and anti-kaliuretic properties of the parent drug amiloride. However, the compoun...
Preprint
The urokinase plasminogen activator (uPA) plays a critical role in tumor cell invasion and migration and is a promising anti-metastasis target. 6-Substituted analogs of 5-N,N-(hexamethylene)amiloride (HMA) are potent and selective uPA inhibitors that lack the diuretic and anti-kaliuretic properties of the parent drug amiloride. However, the compoun...
Preprint
The urokinase plasminogen activator (uPA) is a widely studied anticancer drug target with multiple classes of inhibitors reported to date. Many of these inhibitors contain amidine or guanidine groups, while others lacking these show improved oral bioavailability. Most of the X-ray co-crystal structures of small molecule uPA inhibitors show a key sa...
Article
Full-text available
Gastric and oesophageal cancers (GOCs) are lethal cancers which metastasise early and recur frequently, even after definitive surgery. The urokinase plasminogen activator system (uPAS) is strongly implicated in the invasion and metastasis of many aggressive tumours including GOCs. Urokinase plasminogen activator (uPA) interaction with its receptor,...
Preprint
Full-text available
The urokinase plasminogen activator (uPA) plays a critical role in tumor cell invasion and migration and is a promising anti-metastasis target. 6-Substituted analogs of 5-N,N-(hexamethylene)amiloride (HMA) are potent and selective uPA inhibitors that lack the diuretic and anti-kaliuretic properties of the parent drug amiloride. However, the compoun...
Preprint
The urokinase plasminogen activator (uPA) plays a critical role in tumor cell invasion and migration and is a promising anti-metastasis target. 6-Substituted analogs of 5-N,N-(hexamethylene)amiloride (HMA) are potent and selective uPA inhibitors that lack the diuretic and anti-kaliuretic properties of the parent drug amiloride. However, the compoun...
Article
Full-text available
Significant innovations in next-generation sequencing techniques and bioinformatics tools have impacted our appreciation and understanding of RNA. Practical RNA sequencing (RNA-Seq) applications have evolved in conjunction with sequence technology and bioinformatic tools advances. In most projects, bulk RNA-Seq data is used to measure gene expressi...
Article
Full-text available
Perineural invasion (PNI) is frequently associated with aggressive clinical behaviour in head and neck cutaneous squamous cell carcinoma (HNcSCC) leading to local recurrence and treatment failure. This study evaluates the gene expression profiles of HNcSCC with PNI using a differential expression analysis approach and constructs a tailored gene pan...
Preprint
Full-text available
Urokinase plasminogen activator (uPA) plays a critical role in tumour cell invasion and migration and is a promising anti-metastasis drug target. 6-Substituted analogues of 5-N,N-(hexamethylene)amiloride (HMA) are potent uPA inhibitors while lacking the diuretic and anti-kaliuretic properties of the parent drug amiloride. However, the compounds as...
Preprint
Urokinase plasminogen activator (uPA) plays a critical role in tumour cell invasion and migration and is a promising anti-metastasis drug target. 6-Substituted analogues of 5-N,N-(hexamethylene)amiloride (HMA) are potent uPA inhibitors while lacking the diuretic and anti-kaliuretic properties of the parent drug amiloride. However, the compounds as...
Article
Full-text available
The K+-sparing diuretic amiloride shows off-target anti-cancer effects in multiple rodent models. These effects arise from the inhibition of two distinct cancer targets: the trypsin-like serine protease urokinase-type plasminogen activator (uPA), a cell-surface mediator of matrix degradation and tumor cell invasiveness, and the sodium-hydrogen exch...
Preprint
Full-text available
Perineural invasion (PNI) is frequently associated with aggressive clinical behaviour in head and neck cutaneous squamous cell carcinoma (HNcSCC) leading to local recurrence and treatment failure. This study evaluates the gene expression profiles of HNcSCC with PNI using a differential expression analysis approach and constructs a tailored gene pan...
Article
The K⁺-sparing diuretic amiloride elicits anticancer activities in multiple animal models. During our recent medicinal chemistry campaign aiming to identify amiloride analogs with improved properties for potential use in cancer, we discovered novel 6-(hetero)aryl-substituted amiloride and 5-(N,N-hexamethylene)amiloride (HMA) analogs with up to 100-...
Article
Full-text available
Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer. Most patients who develop metastases (2–5%) present with advanced disease that requires a combination of radical surgery and adjuvant radiation therapy. There are few effective therapies for refractory disease. In this study, we describe novel patient-derived cell lines from cSCC met...
Presentation
Full-text available
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and novel therapies are urgently needed. Integrated analyses of accumulated multi-omics data could be useful to investigate potential diagnostic and prognostic biomarkers of PDAC and to explore associated molecular mechanisms which in turn, could lead to the development of novel therap...
Article
Full-text available
Group A Streptococcus (GAS) causes 700 million infections and accounts for half a million deaths per year. Antibiotic treatment failure rates of 20–40% have been observed. The role host cell glycans play in GAS biofilm formation in the context of GAS pharyngitis and subsequent antibiotic treatment failure has not been previously investigated. GAS s...
Article
Full-text available
Among peritumoral cells, cancer-associated fibroblasts (CAFs) are major facilitators of tumor progression. This study describes the effects of two urokinase-derived, novel decapeptides, denoted as Pep 1 and its cyclic derivative Pep 2. In a mouse model of tumor dissemination, using HT1080 fibrosarcoma cells, Pep 2 reduced the number and size of lun...
Article
Full-text available
Purpose Metastases from cutaneous squamous cell carcinoma (cSCC) occur in 2-5% of cases. Surgery is the standard treatment, often combined with adjuvant radiotherapy. Concurrent carboplatin treatment with post-operative radiotherapy may be prescribed, although it has not shown benefit in recent clinical trials in high-risk cSCC patients. The novel...
Article
Sialic acid at the terminus of cell surface glycoconjugates is a critical element in cell–cell recognition, receptor binding and immune responses. Sialyltransferases (ST), the enzymes responsible for the biosynthesis of sialylated glycans are highly upregulated in cancer and the resulting hypersialylation of the tumour cell surface correlates stron...
Article
Full-text available
The urokinase plasminogen activator and its receptor (uPA/uPAR) are biomarkers for metastasis, especially in triple-negative breast cancer. We prepared anti-mitotic N-alkylisatin (N-AI)-loaded liposomes functionalized with the uPA/uPAR targeting ligand, plasminogen activator inhibitor type 2 (PAI-2/SerpinB2), and assessed liposome uptake in vitro a...
Article
Full-text available
The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12‐15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scient...
Article
Full-text available
Circulating tumour cell (CTC) enumeration and profiling has been established as a valuable clinical tool in many solid malignancies. A key challenge in CTC research is the limited number of cells available for study. Ex vivo CTC culture permits expansion of these rare cell populations for detailed characterisation, functional assays including drug...
Article
The oral K+-sparing diuretic amiloride shows anti-cancer side-activities in multiple rodent models. These effects appear to arise, at least in part, through moderate inhibition of the urokinase-type plasminogen activator (uPA, Ki = 2.4 µM), a pro-metastatic trypsin-like serine protease that is upregulated in many aggressive solid malignancies. In a...
Article
Full-text available
Fibroblasts are among the most abundant stromal cells in the tumour microenvironment (TME), progressively differentiating into activated, motile, myofibroblast‐like, pro‐tumorigenic cells referred to as Cancer‐Associated Fibroblasts (CAFs). To investigate the mechanisms by which epithelial cells direct this transition, the early stages of tumorigen...
Article
Objective Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy, most frequently affecting the head and neck. Treatment often requires surgery and can have significant functional morbidity. Research into disease pathogenesis and second line medical management of cSCC is limited. We assess genetic mutations in high-risk, prim...
Article
Cutaneous squamous cell carcinoma from the head and neck typically metastasize to the lymph nodes of the neck and parotid glands. When a primary is not identified, they are difficult to distinguish from metastases of mucosal origin and primary salivary gland squamous cell carcinoma. UV radiation causes a mutation pattern that predominantly features...
Article
Gastroesophageal adenocarcinoma is a common and highly lethal malignancy. Cancer stem cells (CSCs) have a key role in the development and progression of metastatic disease. While expression of CSC markers CD44, CD133 and aldehyde dehydrogenase 1 (ALDH1) in locoregional gastroesophageal cancer is known to be associated with poorer clinical outcomes,...
Article
Full-text available
Plasmin(ogen)acquisition is critical for invasive disease initiation by Streptococcus pyogenes (GAS). Host urokinase plasminogen activator (uPA)plays a role in mediating plasminogen activation for GAS dissemination, however the contribution of tissue-type plasminogen activator (tPA)to GAS virulence is unknown. Using novel tPA-deficient ALBPLG1 mice...
Article
Full-text available
Protein misfolding underlies the pathology of a large number of human disorders, many of which are age-related. An exception to this is preeclampsia, a leading cause of pregnancy-associated morbidity and mortality in which misfolded proteins accumulate in body fluids and the placenta. We demonstrate that pregnancy zone protein (PZP), which is drama...
Article
Full-text available
Background 5‐Fluorouracil (5‐FU) is administered with leucovorin (LV) to enhance clinical activity. However, simultaneous administration is not feasible due to their chemical incompatibility, so conditions for the maximum possible beneficial interaction cannot be met. To overcome this, we developed a novel all‐in‐one, pH neutral stable solution of...
Article
Full-text available
Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disease characterized in its early stages by synovial hyperplasia and inflammatory cell infiltration and later by irreversible joint tissue destruction. The plasminogen activation system (PAS) is associated with a wide range of physiological and pathophysiological states involving...
Article
Full-text available
Metastasis is the cause of death in the majority (~90%) of malignant cancers. The oral potassium-sparing diuretic amiloride and its 5-substituted derivative 5-N,N-(hexamethylene)amiloride (HMA) reportedly show robust anti-tumor/metastasis effects in multiple in vitro and animal models. These effects are likely due, at least in part, to inhibition o...
Conference Paper
Full-text available
Introduction Circulating Tumour Cells (CTCs) are important biomarkers in many solid tumours including gastroesophageal cancer. Cultures derived from CTCs provide many potential benefits, including an in vitro model to assist selection of systemic treatment for personalised treatments. This study aimed to determine the sensitivity of a CTC derived p...
Article
Background: Colon cancer is common in the elderly, but owing to under representation in clinical trials, the benefit of standard therapies is uncertain in this age group. We aimed to clarify the efficacy and complications of adjuvant oxaliplatin and fluoropyrimidine chemotherapy for patients 70 years and older with stage III colon cancer. Patient...
Article
The development of therapeutic resistance to targeted anticancer therapies remains a significant clinical problem, with intratumoral heterogeneity playing a key role. In this context, improving the therapeutic outcome through simultaneous targeting of multiple tumor cell subtypes within a heterogeneous tumor is a promising approach. Liposomes have...
Article
Despite the longstanding existence of liposome technology in drug delivery applications, there have been no ligand-directed liposome formulations approved for clinical use to date. This lack of translation is due to several factors, one of which is the absence of molecular tools available for the robust quantification of ligand density on the surfa...
Article
Full-text available
AIM To demonstrate the feasibility of cryopreservation of peripheral blood mononuclear cells (PBMCs) for prognostic circulating tumor cell (CTC) detection in gastroesophageal cancer. METHODS Using 7.5 mL blood samples collected in EDTA tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by epithelial cell adhesion molecule...
Article
Cutaneous squamous cell carcinoma is the second most prevalent malignancy, most frequently occurring in the head and neck (head and neck cutaneous squamous cell carcinoma). Treatment of locally advanced or metastatic disease is associated with functional morbidity and disfigurement. Underlying genetic mechanisms are poorly understood. Targeted sequ...
Article
Full-text available
The misfolding of proteins and their accumulation in extracellular tissue compartments as insoluble amyloid or amorphous protein aggregates is a hallmark feature of many debilitating protein deposition diseases such as Alzheimers disease, prion diseases and type II diabetes. The plasminogen activation system (PAS) is best known as an extracellular...
Article
Head and neck cutaneous squamous cell carcinoma (HNcSCC) can present with cervical metastases without an obvious primary. Immunohistochemistry for p16 is established as a surrogate marker of human papillomavirus (HPV) in oropharyngeal cancer. p16 expression in HNcSCC needs to be elucidated to determine its utility in predicting the primary site. Th...
Article
Programmed cell death (PD-1) and its ligand (PD-L1) inhibitors have shown clinical response in many tumours. PD-L1 data are limited in head and neck cutaneous squamous cell carcinoma (HNcSCC) and no clinical trials of PD-1/PD-L1 inhibitors are published. We performed PD-L1 immunohistochemistry on 74 cases of high risk HNcSCC with 38 matched metasta...