Publications

First passage time analysis of spatial mutation patterns reveals sub-clonal evolutionary dynamics in colorectal cancer

The signature of early cancer dynamics on the spatial arrangement of tumour cells is poorly understood, and yet could encode information about how sub-clones grew within the expanding tumour. Novel methods of quantifying spatial tumour data at the cellular scale are required to link evolutionary dynamics to the resulting spatial architecture of the tumour. Here, we propose a framework using first passage times of random walks to quantify the complex spatial patterns of tumour cell population mixing.

Porphyromonas gingivalis promotes malignancy and chemo-resistance via GSK3β-mediated mitochondrial oxidative phosphorylation in human esophageal squamous cell carcinoma

Our prior studies have confirmed that long-term colonization of Porphyromonas gingivalis (Pg) and overexpression of the inflammatory factor glycogen synthase kinase 3β (GSK3β) promote the malignant evolution of esophageal squamous cell carcinoma (ESCC). We aimed to investigate the functional mechanism by which Pg could promote ESCC malignancy and chemo-resistance through GSK3β-mediated mitochondrial oxidative phosphorylation (mtOXPHOS), and the clinical implications.

Roles of PI3Kγ and PI3Kδ in mantle cell lymphoma proliferation and migration contributing to efficacy of the PI3Kγ/δ inhibitor duvelisib

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma that is incurable with existing therapies, and therefore presents a significant unmet clinical need. The ability of this disease to overcome therapy, including those that target the B cell receptor pathway which has a pathogenic role in MCL, highlights the need to develop new treatment strategies.

Lrig1-expressing epidermal progenitors require SCD1 to maintain the dermal papilla niche

Niche cells are widely known to regulate stem/progenitor cells in many mammalian tissues. In the hair, dermal papilla niche cells are well accepted to regulate hair stem/progenitor cells. However, how niche cells themselves are maintained is largely unknown. We present evidence implicating hair matrix progenitors and the lipid modifying enzyme, Stearoyl CoA Desaturase 1, in the regulation of the dermal papilla niche during the anagen-catagen transition of the mouse hair cycle. Our data suggest that this takes place via autocrine Wnt signalling and paracrine Hedgehog signalling.

Characterization of serum and tissue oxytocinase and tissue oxytocin in the pregnant and non-pregnant mare

Oxytocin is a hormone with functions in: reproduction, maternal bonding, milk ejection, and feeding/social behavior, and is reported to be present in a variety of tissues. Our goal is to characterize oxytocin and leucyl and cystinyl aminopeptidase (LNPEP/oxytocinase), a key regulator of oxytocin in mares. We measured serum and tissue LNPEP by ELISA from ovulation (D0) until D21-22 in non-pregnant (n = 5) and pregnant mares (n = 6); and in periparturient and postpartum mares (n = 18).

Repertoire of P-glycoprotein drug transporters in the zoonotic nematode Toxocara canis

Toxocara canis has a complex lifecycle including larval stages in the somatic tissue of dogs that tolerate macrocyclic lactones. In this study, we investigated T. canis permeability glycoproteins (P-gps, ABCB1) with a putative role in drug tolerance. Motility experiments demonstrated that while ivermectin failed to abrogate larval movement, the combination of ivermectin and the P-gp inhibitor verapamil induced larval paralysis. Whole organism assays revealed functional P-gp activity in larvae which were capable of effluxing the P-gp substrate Hoechst 33342 (H33342).

The mast cell exosome-fibroblast connection: A novel pro-fibrotic pathway

In addition to the traditional activation of resident receptors by release of local mediators, new evidence favors the existence of exosomes in cell-to-cell communication that mediates delivery of specific cargo to modulate recipient cell function.

Mfge8 is expressed by pericytes in human gastric antrum submucosa from obese patients

The main function of the stomach is to digest ingested food. Gastric antrum muscular contractions mix ingested food with digestive enzymes and stomach acid and propel the chyme through the pyloric sphincter at a rate in which the small intestine can process the chyme for optimal nutrient absorption. Mfge8 binding to α8β1 integrins helps regulate gastric emptying by reducing the force of antral smooth muscle contractions. The source of Mfge8 within gastric muscles is unclear.

DKK1 is a predictive biomarker for response to DKN-01: Results of a phase 2 basket study in women with recurrent endometrial carcinoma

Dickkopf-1 (DKK1) is a Wnt signaling modulator promoting tumor growth, metastasis, angiogenesis, and immunosuppression by regulating innate immunity. DKK1 is over-expressed in gynecologic cancers and is associated with shortened survival.

MYB RNA detection by in situ hybridisation has high sensitivity and specificity for the diagnosis of adenoid cystic carcinoma

Adenoid cystic carcinoma (ACC) is one of the most common primary salivary gland cancers. ACC has several benign and malignant mimics amongst salivary gland neoplasms. An accurate diagnosis of ACC is essential for optimal management of the patients and their follow-up. Upregulation of MYB has been described in 85-90% of ACC, but not in other salivary gland neoplasms. In ACC, MYB upregulation can occur as a result of a genetic rearrangement t(6;9)(q22-23;p23-24), MYB copy number variation (CNV), or enhancer hijacking of MYB.

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