Fiona Haxho

• BSc, PhD
• Research Associate at Queen's University

Several of the growth factors and their receptor tyrosine kinases (RTK) such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and insulin are promising candidate targets for cancer therapy. Indeed, tyrosine kinase inhibitors...

Poly (lactic-co-glycolic acid) (PLGA) copolymers have been extensively used in cancer research. PLGA can be chemically engineered for conjugation or encapsulation of drugs in a particle formulation. We reported that oseltamivir phosphate (OP) treatment of human pancreatic tumor-bearing mice disrupted the tumor vasculature with daily injections. Her...

Background Triple-negative breast cancers (TNBCs) lack the estrogen, progesterone, and epidermal growth factor (EGF) receptor-2 (HER2/neu) receptors. Patients with TNBC have typical high grading, more frequent relapses, and exhibit poorer outcomes or prognosis compared with the other subtypes of breast cancers. Currently, there are no targeted ther...

Obstructive and nonobstructive forms of hydronephrosis (increased diameter of the renal pelvis and calyces) and hydroureter (dilatation of the ureter) are the most frequently detected antenatal abnormalities, yet the underlying molecular mechanisms are largely undefined. Hedgehog (Hh) proteins control tissue patterning and cell differentiation by p...

G protein-coupled receptors (GPCR) can participate in a number of signaling pathways, and this property led to the concept of biased GPCR agonism. Agonists, antagonists and allosteric modulators can bind to GPCRs in different ways, creating unique conformations that differentially modulate signaling through one or more G proteins. A novel neuromedi...

Today, emerging therapies must effectively shut down multiple enabling characteristics that drive pancreatic cancer invasion and progression. These therapies include the concomitant suppression of growth factor signaling and anti-apoptotic pathways, immune-derived promoters of tumorigenesis, mechanisms of acquired drug resistance, as well as pro-me...

Background Prostaspheres-based three dimensional (3D) culture models have provided insight into prostate cancer (PCa) biology, highlighting the importance of cell–cell interactions and the extracellular matrix (EMC) in the tumor microenvironment. Although these 3D classical spheroid platforms provide a significant advance over 2D models mimicking i...

Gastrointestinal (GI) cancer is an all-encompassing term that refers to the forms of cancers of the digestive system including the esophagus, liver, gallbladder, stomach, small intestine, colon, rectum, anus and pancreas. Of the cancers mentioned, pancreatic ductal adenocarcinoma (PDAC) is the most deadly form of GI cancer owing partially to the la...

One of the primary challenges in developing effective therapies for malignant tumors is the specific targeting of a heterogeneous cancer cell population within the tumor. The cancerous tumor is made up of a variety of distinct cells with specialized receptors and proteins that could potentially be viable targets for drugs. In addition, the diverse...

Multicellular tumor spheroids (MTS) have been at the forefront of cancer research, designed to mimic tumor-like developmental patterns in vitro. Tumor growth in vivo is highly influenced by aberrant cell surface-specific sialoglycan structures on glycoproteins. Aberrant sialoglycan patterns that facilitate MTS formation are not well defined. Matrix...

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Patients with triple-negative breast cancers (TNBCs) lacking the estrogen, progesterone, and epidermal growth factor (EGF) receptor-2 (HER2/neu) receptors have typical high grading, frequent relapses, and exhibit poorer outcomes or prognosis compared with the other su...

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Snail is a transcriptional factor and repressor of E-cadherin. It is well known for its role in cellular invasion, epithelial to mesenchymal transition (EMT), tumor progression and metastases. shRNA lentiviral knockdown (KD) of Snail and its associated member Slug in...

Insulin receptor (IR) signaling plays a key role in the regulation of glucose homeostasis. A dysfunctional and/or unregulated IR activation has been shown to cause a range of clinical manifestations including insulin resistance, type 2 diabetes, obesity, cancer, hypertension, and cardiovascular disorders. The molecular mechanisms mediating IR activ...

Snail, a transcriptional factor and repressor of E-cadherin is well known for its role in cellular invasion. It can regulate epithelial to mesenchymal transition (EMT) during embryonic development and in epithelial cells. Snail also mediates tumor progression and metastases. Silencing of Snail and its associate member Slug in human A2780 ovarian ep...

Truncating GLI3 mutations in Pallister-Hall Syndrome with renal malformation suggests a requirement for Hedgehog signaling during renal development. HH-dependent signaling increases levels of GLI transcriptional activators and decreases processing of GLI3 to a shorter transcriptional repressor. Previously, we showed that Shh-deficiency interrupts e...

HH signaling activity in developing murine kidney. Ptc1-lacZ expression and thereby HH signaling activity at E18.5. (A–C) In WT kidneys, Ptc1-lacZ is strongly localized cells surrounding the ureter (not shown) and the medullary stroma (ms). No Ptc1-lacZ activity is observed in the distal collecting ducts (dc) or any structures of the renal cortex....

Ptc1-deficiency does not effect the nephron progenitor population. (A,D) RNA in situ hybridization demonstrates normal expression of Ors1 and Six2 in the mesenchymal precursor population of Ptc1-deficient kidneys. (E,F) Cited-1 immunofluorescence is comparable between WT and Ptc1−/−UB kidneys. (G,H) RNA in situ hybridization demonstrates a reduced...

Ptc1-deficiency does not effect differentiation of the distal epithelium. (A–F) Uroplakin immunofluorescence (red color, arrows) demonstrates normal differentiation of the urothelium in the renal pelvis of Ptc1-deficient kidneys at E18.5. (C,F) Ectopic uroplakin-positive epithelium was not observed in the proximal epithelium. (G–L) Immunofluorescen...

HH signaling is not required in the ureteric cell lineage. (A–H) Immunofluorescence analysis of newborn Smo-deficient kidneys demonstrated no difference in podocyte differentiation (pod) (A,E), normal patterning of the nephrogenic zone (B,F)(green), and comparable densities of proximal tubules (C,G)(green) and collecting ducts (D,H)(red). (I,M) Ure...

Exencephally in Ptc1-deficient mutants. (A–F) Macroscopic analysis of Ptc1-deficient mice at all embryonic time points examined demonstrates severe exencephaly (arrowhead), with 100% penetrance. (G) No difference in body weights was detected between WT and Ptc1−/−UB embryos (WT vs. Ptc1−/−UB: 1.49+0.13 vs. 1.57+0.13, p>0.05). (H) Quantitative real-...

Effect of Gli3 inactivation of metanephric differentiation.(A–L) Immunofluorescence analysis of metanephric differentiation markers. Gli3-deficient kidneys demonstrated no difference in podocyte differentiation (aqua) (A,B), normal patterning of the nephrogenic zone (C,D)(green), comparable densities of proximal tubules (E,F)(green), comparable den...

Early metanephric development in Gli3Delta699/+ mice is normal. RNA in situ hybridization demonstrates normal expression of Ret, Wnt11 and Gdnf in Gli3Delta699/+ kidneys at E13.5. (1.03 MB TIF)

Quantitation of Ptc1-deficient kidneys. (A,B) No histological differences were observed between WT and Ptc1−/−UB kidneys at E13.5. (C,D) NCAM (red) positive nephrogenic structures where similar between WT and Ptc1−/−UB kidneys. (E) Quantitation of nephrogenesis at E13.5 demonstrates no significant difference in the number of NCAM positive nephrogen...

Ptc1-deficiency does not effect metanephric cell survival. (A–D) Analysis of apoptosis in E13.5 kidney tissue using the TUNEL. TUNEL-positive cells (brown color) are rarely detected in the ureteric bud (ub) of WT or Ptc1−/−UB kidneys. There is no observable difference in TUNEL-positive cells in the mesenchyme (mes) between WT and Ptc1-deficient kid...

Mutant Mouse Frequency (0.04 MB DOC)

Mutant Mouse Frequency (0.04 MB DOC)