onsdag 13 december 2023

Doktorsavhandling om barncancer

Den spanska cancerforskaren Candela Cives-Losada från Universidad de Salamanca

har doktorerat på en jobbig cancer som enbart drabbar barn,ofta yngre än 3 år. 
Hepatoblastom heter eländet och uppstår oftast i buken,magen eller levern hos dessa olycksdrabbade barn.
En svensk undersökning av 181 barn som diagnostiserats med denna cancer berättar hur svårt det varit att ställa rätt diagnos tidigt i förloppet.

Alice fick sin diagnos tidigt,vid 2 års ålder,men drabbades ändå av elaka tumörer och har vid 7 års ålder genomgått mer än vad många cancerdrabbade vuxna har behövt göra. Läs hennes historia här.

Men till Candelas doktorsavhandling. 

Hepatoblastoma (HB) is the most frequent pediatric liver cancer. Despite its incidence is low (2 children per million per year) this has increased over the last few years. Surgical resection, liver transplantation and chemotherapy based mainly on cisplatin and doxorubicin are the current options for treating these patients. Unfortunately, 20% of patients still have very poor prognosis mainly due to the lack of response to treatment. Moreover, 12% of patients in complete remission are likely to relapse. This refractoriness may be due to the presence of a multidrug resistance (MDR) phenotype in cancer cells, conferred by complex and powerful mechanisms of chemoresistance (MOCs). These may be intrinsically present in tumor cells or may be acquired during treatment. Our research group has classified MOCs into seven groups. In this thesis, we have focused on studying in depth one of them, MOC-1, which refers to the reduction of the amount of intracellular drug due to decreased expression and/or function of plasma membrane solute carriers (SLCs) involved in drug uptake (MOC-1a) or increased expression and/or function of transporters of the ATP-binding cassette (ABC) superfamily of proteins involved in drug export (MOC-1b). The identification of plasma membrane transporters responsible for anticancer drug refractoriness in HB could be extremely useful as diagnostic and prognostic biomarkers or as targets for designing chemosensitization strategies. Given this background, the overall aim of this PhD thesis was to characterize the role of the transportome in the lack of response of HB to chemotherapy and subsequently design pharmacological strategies to overcome HB chemoresistance.

Materials and Methods (urval)
The HoloMonitor® M4 live cell imaging system (Phase Holographic Imaging PHI, Sweden) was used to adquire cell migration and proliferation data in real time by phase holographic imaging, with the App Suite software for analysis.

Cell proliferation assays 
Cells were seeded in 24-well plates coated with ibiTreat® polymer (Ibidi, Inycom, Zaragoza) at different cell densities (10000 to 50000 cells/cm2 ) to follow the proliferation rate of each cell line. After 24 h, cells were imaged using a Holomonitor M4 Live Cell Imaging System placed in an incubator at 37 °C and 5% CO2. Images of 4-5 regions per well were captured every 60 min for 72 h. Time-lapse image analysis was performed with App Suite software. Time-course of cell number and culture confluency compared to the initial time was determined for each region. 

Cell migration assays 
The wound healing assay was used to study cell migration. Cells were seeded in 24-well plates at the appropriate cell density for each cell line. In the case of the HepG2-derived cell lines, cells were seeded on collagen-coated supports to facilitate their adhesion to the surface and the formation of a monolayer. 24 h after seeding the cells, when they were attached to the plate and have reached the adequate confluence, a wound was made on the cell monolayer with a sterile pipette tip. The plate was placed in the Holomonitor M4 within an incubator at 37 °C and 5% CO2. At least 5 regions from each wound per well were followed and analyzed for 72 h. Timelapse image analysis was performed with App Suite software.

Slutsatser och resultat av forskningen står dessvärre på spanska så ni får översätta det själva.
Candela har bedrivit forskning i 8 år och ser ut att ha specialiserat sig på cancerforskning de senaste 5 åren. Hennes bidrag återfinns på Researchgate och hittas här.

Min kommentar
Ni vet vad jag tycker om barn och cancer så det ska jag inte gå in på (alldeles för många svordomar).
Istället vill jag ösa beröm över Candelas doktorsavhandling som förhoppningsvis räddar livet på fler barn än vad som sker idag. Hon kan nu titulera sig Doctor och med det åtnjuter hon tillträde till den sofistikerade skaran av forskare som tar sig an den mer avancerade cancerforskningen. Bloggen vill gratulera Candela till välförtjänt doktorstitel och hoppas få se mer av hennes forskning.
Naturligtvis kan bloggen inte undgå att lyfta fram HoloMonitor i sammanhanget. Cancerforskning behöver HoloMonitor. Basta.
Universidad de Salamanca finns inte upptaget på PHI,s Userlista så det bör vara en ny kund.

Ps. Bloggens rapportering om de koreanska forskarnas studier om svamp kontra bröstcancer har nu amerikanska National Library of Medicine uppmärksammat och lagt in på sin sida. Länk

                                                Mvh the99


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