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Recent Developments in the Patho-Physiological Molecular Clocks Lab

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Frequency of the PROMs


In a collaboration led by Pasquale Innominato, we evaluate the impact of different frequencies for the evaluation of patient-reported outcomes (PRO) in cancer. PRO have proven relevant positive clinical impact on patients’ communication with healthcare professionals, decision-making for management, wellbeing and overall survival. However, the optimal frequency of PRO assessment has yet to be defined. Based on the assumption that more frequent sampling would enhance accuracy, we aimed at identifying the optimal sampling frequency that does not miss clinically relevant insight.
Our analysis suggests that in patients receiving chemotherapy for advanced cancer, increasing the density of PRO collection enhances the accuracy of PRO assessment to a clinically meaningful extent. This is valid for both computation of averages symptom burden and for the recognition of episodes of severe symptom intensity.
Thu 06 May 2021, 10:10 | Tags: Publication, 2021

Coffee anyone?


Most organisms with a nervous system have been shown to sleep. Why is not yet clear, but it is clear that the longer an organism stays awake the higher the need for sleep, ie. sleep pressure.

However, the biological clock, also present in virtually all organisms, is modulating sleep need, eg. in people after a night without sleep, sleep pressure is (temporarily) reduced around sunrise courtesy of their circadian drive to become active at that time. Thus, sleep pressure and circadian rhythms influence each other.


Interestingly, caffeine, which is found in coffee and energy drinks promising wings, and one of the world’s most widely consumed psychoactive substances, is reducing sleep pressure by a known mechanism, but also impacting on the circadian clock. So far, the regulatory mechanisms for the interaction are at least partly unclear. 


In this publication, we showed how adenosine A1/A2A receptor antagonists, such as caffeine, shift circadian rhythms and enhance the effects of light on the clock, providing a molecular link between sleep pressure and circadian rhythms. These insights have implications for therapeutic strategies for rhythm disorders. 

Thu 15 Apr 2021, 14:50 | Tags: Publication, 2021

Endocrine Related Cancers review on what stop tumours ticking, how to determine it, and why it might be important

In a great joint effort by ARAP student Ewan Stephenson and MRC DTP student Laura Usselmann with Ewan's Singaporean co-supervisors David Virshup (DUKE-NUS) and Vinay Tergongar (A*STAR), we are providing an in depth look into clocks in tumours.


Mon 01 Mar 2021, 07:00 | Tags: Publication, 2021

Did we wake up in time for better stroke treatment translation?

In a commentary led Warwick colleague Johannes Boltze and Nadine Diwischus and Munich researchers Martha Merrow and Nikolaus Plesnia in the Journal of Cerebral Blood Flow and Metabolism, we argue that recent discoveries on the considerable circadian modulation of treatment in stroke might explain some of translational failures in therapeutic development in this area.

Fri 18 Dec 2020, 14:00 | Tags: Publication, 2020

FY26 a new Osmium complex to treat cancer


Led by Swati Kumar and in collaboration with the Sadler, Perrier and Lévi groups, we investigated the chronotherapy with novel organo-osmium complex [OsII6-p-cym)(PhAzPy-NMe2)I]+ (FY26), and show that FY26 exhibits promising in vitro antitumour activity against mouse hepatocarcinoma Hepa1-6 and other mouse or human cancer cell lines. Here, we drastically enhance water solubility of FY26 through the replacement of the PF6counter-anion with chloride using a novel synthesis method. FY26.PF6 and FY26.Cl displayed similar in vitro cytoxicity in two cancer cell models. We then show the moderate and late anticancer efficacy of FY26.PF6 and FY26.Cl in a subcutaneous murine hepatocarcinoma mouse model. Both efficacy and tolerability varied according to FY26 circadian dosing time in hepatocarcinoma tumour-bearing mice. Tumour and liver uptake of the drug were determined over 48 h following FY26.Cl administration at Zeitgeber 6 (ZT6), when the drug is least toxic (in the middle of the light span when mice are resting). Our studies suggest the need to administer protracted low doses of FY26 at ZT6 in order to optimize its delivery schedule, for example through the use of chrono-releasing nanoparticles.

Fri 11 Dec 2020, 10:00 | Tags: Publication, 2020

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