Epidemiology of Mucin-Containing Cancers
Mucin-containing cancers are rare types of adenocarcinomas. Mucin is a jelly-like substance. If expressed primarily inside cancer cells they are called signet ring cell cancers, and if outside, mucinous cancer cells. Both subtypes are poorly understood and historically have poor clinical outcomes. A comprehensive epidemiology for both signet ring cell and mucinous adenocarcinomas has been published. These resources can be used by researchers to further their own projects.
Left: Distribution of signet ring cell tumors in SEER (Surveillance, Epidemiology, and End Results Program), 1975-2016, total of 41,847 cases. Right: Distribution of all solid (non blood-borne), non signet ring cell tumor in SEER, 1975-2016, total of 9.56 million cases.
Lysophospholipid signalling and tumor-promoting inflammation
Autotaxin (ATX) is a secreted enzyme that produces a bioactive lipid called lysophosphatidate (LPA) from inactive lysophosphatidylcholine (LPC). Normally in involved in embryonic development and wound healing, ATX/LPA signalling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance. Targeting this signalling axis is a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. The first in-class ATX inhibitor is in late-stage clinical trials for idiopathic pulmonary fibrosis. The advent of ATX inhibitors in clinical practice could herald their applications as adjuvant therapies to improve the therapeutic indexes of existing cancer treatment regimens.
LPA (lysophosphatidate) produced by extracellular ATX (autotaxin) signals through six G-protein coupled receptors (LPARs). This creates a vicious cycle whereby inflammatory cytokine production is upregulated, increasing ATX levels. This induces survival pathways which leads to cancer cell survival against chemotherapies and radiotherapy.
PhD thesis: Autotaxin and Tumor-Promoting Inflammation
Insights into sterol-phospholipid interactions
Cholesterol is one of the most biologically energy expensive molecules, with the last seven steps in the synthetic pathway essentially devoted almost entirely to placing the double bond in between carbons 5 and 6. Through a series of investigations examining the thermodynamics of cholesterol and its precursors with biologically representative phospholipids, we have accurately characterized how cholesterol preferentially orders membrane bilayers to facilitate their biological function. These experimentally-derived parameters can also be used to facilitate rational sterol-drug design.
The top figure in each panel shows views normal to the plane of the sterol ring to highlight differences between the structures of cholesterol (A), 7-dehydrocholesterol (B) and desmosterol (C). The middle row shows 3D views normal to the plane of the ring and the bottom view shows 3D views parallel to the plane of the sterol ring. The functional group at C3 is red and double bonds are yellow.