6 japanska forskare har studerat en hudcancer orsakad av drabbad människas pigmentering (Xeroderma pigmentosum / XP), vilken är en ärftlig sjukdom som kännetecknas av ljuskänslighet och med stor risk att utveckla hudcancer. Som tur är krävs att bägge föräldrarna bär på anlagen för att den ska blomma ut i nästa generation. Därför är det bara 1 på miljonen som drabbas av denna sjukdom. Den som har oturen att ha XP kan inte vistas i solljus då drabbads hud inte klarar att utsättas för UV-strålning.
Det pga en mutering i kroppens DNA:s reparationssystem som inte återställer solutsatts hudceller till normalläge. Pigmenteringen släpper igenom UV-strålar utan att återskapa nya skyddande celler vilket möjliggör (sol)skadade celler att utveckla tumörer. Den solutsatta och skadade delen kan i första skedet obehandlad fräta bort huden i läpparna,näsan,ögonen,hakan..dvs den del av kroppen som är vanligast utsatt för solen. Nästa förlopp är att tumörer bildas och skapar metastaser vilka går in i kroppen,det med dödlig konsekvens. En ohygglig sjukdom man knappast kan föreställa sig hur eländig den är. Här 2 artiklar om drabbade.
Länk 1 -
Länk 2Wiki berättar mer om
XP. Men till den japanska studien. Hela studien hittas i denna
PDF.
First published: 22 November 2022
Abstract
Xeroderma pigmentosum (XP) is a hereditary disorder
characterized by photosensitivity, predisposition to skin cancers, and
neurological abnormalities including microcephaly and progressive
neurodegeneration. A lack of nucleotide excision repair (NER) in
patients with XP can cause hypersensitivity to the sun, leading to skin
cancer, whereas etiology of the neuronal symptoms of XP remains
ambiguous. There are various neurological disorders that perturb
neuronal migration, causing mislocalization and disorganization of the
cortical lamination. Here, we investigated the role of the XP group-A (Xpa) gene in directed cell migration. First, we adopted an in utero electroporation method to transduce shRNA vectors into the murine embryonic cerebral cortex for the in vivo knockdown of Xpa. Xpa-knockdown
neurons in the embryonic cerebral cortex showed abnormal cell
migration, cell cycle exit, and differentiation. The genotype-phenotype
relationship between the lack of XPA and cell migration abnormalities
was confirmed using both a scratch assay and time-lapse microscopy in
XP-A patient-derived fibroblasts. Unlike healthy cells, these cells
showed impairment in overall mobility and the direction of motility.
Therefore, abnormal cell migration may explain neural tissue
abnormalities in patients with XP-A.
Materials and Methods (urval)
Digital holographic microscopy
Digital holographic microscopy was performed as previously described [16]. The
HoloMonitor® M4 microscope (Phase Holographic Imaging AB, Lund, Sweden) was used
for imaging and tracking healthy control (HC) and XP-A cell movements.
3D holographic
cell images were captured with a 20× magnification objective and a low-power 635 nm diode
laser. Images were converted from wavelength interactions to cellular representations using a
computer algorithm (AppSuite, phase holographic imaging).
HC and XPA fibroblasts were
seeded (1 × 104 cells) in a 6-well plate and allowed to adhere for 24 h. Fibroblasts were
treated with DMEM containing 0.5% FBS and images were captured every 10 min for 72 h.
Live imaging analysis to study the impairment in XPA patient fibroblasts
Next, we compared the motility of fibroblasts derived from a healthy individual with
that of XP101KO cells using a Holo Monitor®. We measured the total distance traveled and
found that the XP101KO cells traveled shorter distances than HC fibroblasts. Moreover, the
average motility of XP101KO cells was lower than that of healthy fibroblasts (Figure 4A).
These results are consistent with those from our scratch assay, confirming that XPA
deficiency impairs motility. To test whether these cells demonstrated additional defects, we
selected several cells and tracked them for 72 h (Figure 4B). Interestingly, while a healthy
person’s fibroblasts moved equivalently in various directions, the XP-A cells moved in only
limited directions (Figure 4B), contrary to the movement exhibited by XP-A cells in the
previous section. This apparent contradiction can be explained by differences in the two
assay systems, with fibroblasts demonstrating a directed mode of migration in the modified
migration assay while migrating randomly in the Holo Monitor®. Nevertheless, we conclude
that the mobility of XP-A patient-derived fibroblasts is clearly lower than that of normal
cells
 |
| Figure 4
The analysis of cell motility and tracking using a HoloMonitor®M4.
(A) The cellular motility distance (upper panel) and the cellular motility speed (lower panel)
are shown. (B) The indicated cells were tracked for 72 h (left panels). Spatial movement
graphs for selected cells (the starting position was the center) are shown in the right panel. |
Forskarnas slutord
Our results in this study indicate a likelihood of the former possibility, at least to some extent,
due to the involvement of cyclopurine [9], though we do not rule out a possible role of
oxidative DNA lesions.
In conclusion, our study sheds some light on the pathomechanisms of neurological symptoms
in XP, and further studies are expected to find treatment strategies for XP in the future.
Min kommentar
En riktigt eländig cancer som påverkar drabbads hela livsöde, från födsel till.....De japanska forskarna gör verkligen en välgärning som tar sig an att studera denna cancer. Genom att observera XP celler,hur de utvecklas och rör sig (via HoloMonitor) har de hittat ny information som förhoppningsvis kan leda till framtida bot för de drabbade.
Mvh the99
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