Enbart 11-12% diagnostiserade lever efter 5 år. Forskarna har studerat idag godkända terapier/läkemedel till denna cancer och försökt sätta sig in i varför de inte fungerar bättre än för behandling av många andra cancerformer. Resultaten har mynnat ut i ett förslag forskarna tror har avsevärt bättre effekt. För att studera cancercellerna tillsammans med idag godkända läkemedel likväl som studierna med deras förslag där de följt cancerceller med detta har HoloMonitor kommit till flitigt användande. Förslaget de ger är mycket hoppingivande.
Abstract
Pancreatic ductal adenocarcinoma has a high mortality rate, with a 5-year survival rate of ~ 12%. Therefore, developing new targeted therapies is urgently needed. ONC-201, a promising candidate, is currently undergoing clinical trials. The main objective of the present work is to investigate the anti-tumour activity of ONC-201 and its two fluorinated analogues (TBP-134, TBP-135). The viability of two pancreatic adenocarcinoma cell lines (PANC-1, MIA PaCa-2) and three other tumour cell lines (A2058, EBC-1, COLO-205) was assessed after 72-hour treatment with drugs at 0.5, 10, and 25 µM. Significant antiproliferative effects were observed, with 0.5 µM TBP-134 achieving the highest potency, reducing cell viability to approximately 50%. None of the molecules exhibited significant cytotoxicity toward normal human dermal fibroblast cells or cardiomyocytes, indicating a selective anti-tumour profile. The analogues showed more effective results than ONC201 on PANC-1 cells (IC50: 0.35 and 1.8 µM vs. IC50: 6.1 µM, respectively). All analogues induced G2/M phase arrest followed by apoptosis in PANC-1 cells. The site of the fluorination influenced the mechanism of apoptotic action of these compounds. Overall, TBP-134 showed superior efficacy, making it a promising candidate for structural optimization within the imipridone family to develop more effective, selective treatments for pancreatic tumours.
To follow the morphometric changes, a holographic transmission microscope (HoloMonitor M4; Phase Holographic Imaging AB, Lund, Sweden) was used, which uses a laser to produce 3D images of the cells51,52. This in vivo imaging technique allows us to monitor cell morphological changes in real-time. First, the cells were seeded at a concentration of 3.5 × 105 cells/flask/4000 µL cell culture medium. After 24 h of seeding, the cells were treated with the drugs at a concentration of 0.5, 10 and 25 µM, and images were taken at 24, 48 and 72 h after the treatment. At least 5 images were taken from each culture dish, taking care to assess different fields of view. These images were evaluated using the microscope software (Hstudio M4). We assessed the average area and the average optical thickness of the cells.
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The holographic microscopy images of PANC-1 cells after treatment with ONC201, TBP-134, and TBP-135 at 0.5 µM at 72 h. |
99:an gått på semester?
SvaraRaderaNää,men så länge garanterna är kvar i aktien har jag ingen lust att bjussa dem på nåt smaskigt så de kan sälja sina aktier till högre pris än vad som nu gäller. Låt dem kränga sina innehav med största möjliga förlust.
RaderaSen när de är ute ur matchen då jävlarrr :-)
Men ok,en bra studie kan ni få läsa om idag. Kommer strax.
Mvh the99
Tack 99:an :)
SvaraRadera