Thank you, UEF staff!

A funny thing happened last Friday. Earlier this summer, around June the management of the UEF offered a gift as a compensation for the hard work during the COVID-19 spring period and there were few places listed for which you could request a gift-card (same sum for each), including a restaurant, cafeteria, bookstore, and health club. I'm not going to talk about if everyone deserved this, most of the people probably worked fewer hours than normal according to my experience, but then there were also a lot of people who over-exceeded their normal working time by many times. I would say, that I tried to keep it as similar as possible, but I must admit that the course of the days was different and I was actually able to do a lot of writing (manuscripts, grant application), more than I could imagine, since there was less interruption in my days, of course. But on the other side, I worried all the time that I wasn't present to my group members as much as I would have liked to be... And in the beginning, in March, most of the people were just learning how to use e-communication software, so there was a lot of fewer meeting in the beginning, but unfortunately, the amount of them gradually increased as the summer was approaching... Luckily then came the summer break! :)

Anyway, about the gift-card, I selected something that would benefit not only me, but my dearest ones, so it chose the gift-card to a restaurant called Morton. And last Friday, as it was such a sunny day and I've got the feeling that summer was slowly ending and the autumn with new COVID-19 wave is coming, that it's better to use the gift-card before this restaurant closes its doors, forever. Morton is a street-food burger restaurant with a small sea container kitchen and outside tables, so many times there is a queue, for us, it was about 30-40 min waiting. And just when we sat down to wait for our burgers, a band started to play around the corner in front of the Sisko-tyttö statue. And guess who was singing in the street-band... our rector! So as a thanks-giving from the UEF, I didn't only receive a free dinner with my family, but also a free dinner accompanied by UEF rector's songs. :)

Read more about Morton from their webpages (this link).

Another paper accepted!

I also forgot to tell you that during the summer we got another paper accepted and published. The link for the paper is below:

L-type amino acid transporter 1 (LAT1)-utilizing efflux transporter inhibitors can improve the brain uptake and apoptosis-inducing effects of vinblastine in cancer cells

The study describes how chemotherapeutics can be delivered more effectively across the blood-brain barrier and into the cancer cells by co-treating them with a targeted efflux inhibitor that we have developed. The function of efflux pumps is one of the main mechanisms for chemoresistance and also the prevention of drugs accumulating into the brain. Efflux pump inhibitors have been developed for decades to improve anti-cancer therapy, but unfortunately, with lack of success, since efflux pumps have also a crucial role in healthy cells. Therefore, in our attempt, we created a prodrug of an efflux pump inhibitor that was able to utilize a familiar transporter, LAT1 (L-type amino acid transporter 1), which is over-expressed in many different types of cancer. Thus, in our study, the LAT1-utilizing derivative of probenecid was able to increase the brain uptake of another anti-cancer drug, vinblastine, and consequently its accumulation into the cancer cells, which in turn improved the apoptosis-inducing effects of vinblastine. Moreover, the LAT1-utilizing derivative of the efflux pump inhibitor was found to be hemocompatible, meaning that it is safe in the systemic circulation. This study was a continuation of our previous study:

Targeted efflux transporter inhibitors - A solution to improve poor cellular accumulation of anti-cancer agents 

and the present study was carried out in a collaboration with Dr. Magdalena Markowicz-Piasecka from the Medical Univerisity of Lodz. So thanks for all who contributed to this study and the one preceding it!

Back to School

The summer holidays are mainly over in Finland and the school, as well as the semester at the Universities, have already started. I had a relaxing summer break, however, the scientists never have a real break, which is sometimes difficult fo non-scientists (like my husband) to understand. But this summer was not that bad, only a few manuscript readings, galley proof checkings and "some emails and phone calls" :). 

We luckily get one of the very challenging and long-lasting projects published in Molecular Neurobiology. The studied under the title

"Targeting of Perforin Inhibitor into the Brain Parenchyma Via a Prodrug Approach Can Decrease Oxidative Stress and Neuroinflammation and Improve Cell Survival" (link to the publication)

describes how a prodrug that utilizes LAT1 transporter and is delivered more effectively into the brain (across the blood-brain barrier) and into the brain parenchymal cells (e.g., neurons, microglia, and astrocytes) can improve its pharmacological effects. The parent drug of this prodrug is a perforin inhibitor (molecules that I worked with at the Auckland Cancer Society Research Centre in New Zealand 2009-2011) and it is supposed to inhibit endogenous perforin protein that is released e.g., in neurodegenerative diseases and which aids in destroying brain cells. Moreover, with LAT1-utilizing prodrug we were able to affect several different factors related to inflammation and oxidative stress in the brain (which is also associated with several neurodegenerative diseases) and to our surprise, the compound also inhibited an enzyme function, very special hallmark to Alzheimer's disease (BACE1; β-site amyloid precursor protein (APP) cleaving enzyme 1) and thus, our prodrug was functioning as a multitargeted drug within the brain. Most importantly, this publication is one of the first ones to show that rationally developed LAT1-utilizing prodrugs of a selected parent drug can really result in improved brain drug delivery and subsequently improved pharmacological effects! 

Thanks for the team for the great effort! :)