Khansara yapakhungu ya RDEB (2023)

Ofufuzawo adazindikira mamolekyu omwe maselo a khansa ya RDEB amafunikira kukula. Iwo adatha kuchepetsa kukula kwa maselo a khansa ya RDEB mu labotale pogwiritsa ntchito mankhwala omwe amagulitsidwa omwe amasokoneza mamolekyuwa. Imodzi mwa mankhwalawa ndi yovomerezeka kale kuti ichiritse odwala ambiri a sclerosis ndipo ingagwiritsidwenso ntchito kuthandiza anthu omwe ali ndi khansa ya RDEB. Kuyesera kowonjezereka kumafunika mankhwalawa asanaperekedwe kwa anthu omwe ali ndi khansa ya RDEB mu mayesero a zachipatala, koma amatha kupezeka mofulumira kusiyana ndi chithandizo chatsopano pakakhala umboni wabwino wothandiza.

Ofufuzawa ali ndi maselo ochokera ku khansa khumi ndi imodzi ya RDEB yomwe ikukula mu labotale yawo ndipo ayesa momwe amachitira ndi chithandizo chamankhwala osiyanasiyana. Azindikira majini asanu ndi limodzi omwe amalimbikitsa maselo a khansa ya RDEB kuti achuluke omwe angakhale chandamale chamankhwala.

Ofufuzawa adatulutsa zomwe apeza posachedwa mu 2021.

Wofufuza wamkulu:

Prof Gareth Inman ndi Director of Research Strategy ku The CRUK Beatson Institute for Cancer Research ndi Pulofesa wa Cell Signaling ku Institute of Cancer Sciences, University of Glasgow, Scotland. Zokonda zake zazikulu ndikumvetsetsa gawo lomwe mamembala a banja la transforming growth factor beta (TGFβ) amachita pakukula kwa khansa komanso kukula. Maphunziro ake amayang'ana kwambiri pa squamous cell carcinomas pakhungu, mutu ndi khosi ndi kapamba ndipo tsopano akuphatikizira makhansa awa omwe amabwera mwa odwala omwe amakhala ndi recessive dystrophic epidermolysis bullosa. Pomvetsetsa udindo wa TGFβ monga ochiritsira khansa komanso woletsa khansa Pulofesa Inman akuyembekeza kupanga njira zothandizira mtsogolo za khansa.

Othandiza:

Dr Peter Bailey, Dr Karen Blyth (Glasgow, Scotland, UK) ndi Dr Andrew South (Thomas Jefferson University, Philadelphia, US).

"Odwala a RDEB pamapeto pake adzapindula ndi kafukufukuyu, osati pankhani ya khansa yokha komanso lingalirolo lidziwitse momwe kuwonetsa kwa TGFβ kumathandizira pakuwonongeka kwapang'onopang'ono kwa kapangidwe ka dermal. Machiritso a TGFβ ali m'mayesero azachipatala ndipo lingaliroli liwonetsa nthawi yomwe adzakhale ndi chithandizo chamankhwala kwa odwala a RDEB. SCC yomwe imapezeka mumitundu ina ya EB ingapindulenso ndi maphunzirowa. "

– Prof Gareth Inman

Grant Title: Njira zotsatsira TGF-beta mediated chotupa mu RDEB cSCC.

Recessive Dystrophic epidermolysis bullosa (RDEB) ndi matenda obadwa nawo omwe amayamba chifukwa cha matuza osatha, mabala komanso mabala ochulukirapo akhungu. Odwala ambiri a RDEB amakhala ndi khansa yapakhungu yotchedwa cutaneous squamous cell carcinoma (cSCC), yomwe nthawi zambiri imapha. Maselo mkati mwa thupi amadalira zizindikiro zapadera kuti apulumuke ndi kukula. Mu khansa zizindikiro izi zimatayika kapena zikhoza kukwezedwa kuti zithandize kukula ndi kufalikira kwa chotupa.

Gulu lofufuzira ili ndi ena posachedwapa awonetsa kuti njira yeniyeni yowonetsera, yomwe imaphatikizapo molekyu yotchedwa Transforming Growth Factor- beta (TGF-β), imakwezedwa pakhungu la anthu omwe ali ndi cSCC yokhudzana ndi RDEB. Chofunika kwambiri gulu ili lapeza kuti kutsekereza kuwonetsa kwa TGF-β yogwira kumatha kuletsa (kuyimitsa) kukula kwa khansa mu 50% ya zitsanzo za RDEB zoyesedwa. Chosangalatsa ndichakuti, kutsekereza njira yolumikizira kungathenso kulimbikitsa kukula kwa maselo a khansa mu zitsanzo zosankhidwa za RDEB cSCC.

Zomwe taziwonazi zikuwonetsa kuti ndikofunikira kumvetsetsa nthawi komanso momwe TGF-β imagwirira ntchito kulimbikitsa kapena kupondereza kukula kwa khansa mu RDEB kuti athe kuzindikira odwala omwe angapindule poletsa njira yolumikizira iyi. Mu pulojekitiyi gulu likukonzekera kufufuza momwe TGF-β imalimbikitsira kukula kwa khansa ndipo kuti izi zitheke, gululi likufuna kupanga ma biomarkers a TGFβ signing pogwiritsa ntchito in vitro ndi in vivo state of the art assays biological, (njira zomwe zimagwiritsidwa ntchito pofufuza khalidwe ndi khalidwe ndi khalidwe lachiwerewere). ntchito ya mamolekyu).

Cholinga cha 1. Kuti mumvetse zizindikiro za maselo (biomarkers) momwe TGFβ imachitira mu khansa yapakhungu ya RDEB yomwe idzadziwitse kugwiritsa ntchito mankhwala oletsa anti - TGFβ.

Cholinga cha 2. Kumvetsetsa momwe kuwonetsera kwa TGFβ kungayambitse kusamuka kwa khansa, kuwukira ndi kukula kwa chotupa ndikuzindikira zolinga zochiritsira (monga puloteni kapena molekyulu yomwe ingasinthidwe pogwiritsa ntchito mankhwala kapena mankhwala kuti agwirizane ndi maselo a khansa).

Kafukufukuyu apereka maziko omvetsetsa bwino za kusaina kwa TGFβ mu RDEB ndipo atha kuzindikira mipherezero yatsopano yamtsogolo yamankhwala ochizira khansa ya squamous. Njira zochiritsirazi zili m'mayesero azachipatala a khansa ina kapena ali m'chitukuko chachipatala kale. Phunziroli lidzadziwitsanso za njira zatsopano zopangira chithandizo chamankhwala.

Kafukufuku wam'mbuyomu wothandizidwa ndi DEBRA mu kusaina kwa TGF-β mu RDEB cSCC ndi Pulofesa Gareth Inman adathandizira pa kafukufuku watsopanoyu.

Transforming growth factor-beta (TGFβ) ndi molekyu yomwe imayendetsa njira yolumikizira yomwe imayang'anira njira zingapo zofunika kuti ma cell agwire bwino ntchito. Kuzindikiritsa kwa TGFβ kumakhudzidwa ndi kuyambitsa khansa, kakulidwe ndi kakulidwe kake koma kumathanso kupondereza kukula ndi kukula kwa chotupa motengera momwe zinthu ziliri. Odwala a RDEB omwe amadwala kwambiri matuza pakhungu amakhala ndi zotupa zapakhungu zomwe zimakula mwachangu ndipo zimakhala zovuta kuchiza zomwe zimapangitsa kuti odwala pafupifupi 90% akafika zaka 55 azimwalira.

Ife ndi ena tapeza kuti odwala khansa ya RDEB awonjezera kuchuluka kwa TGFβ pakhungu ndi zotupa. Sizikudziwika ngati TGFβ ikuchititsa kuti zotupa zikule kapena ayi mu khansa yomwe imapezeka mwa odwala a RDEB.

Pogwiritsa ntchito maselo otengedwa kuchokera kwa odwala khansa ya RDEB, tawonetsa kuti mankhwala omwe amapondereza chizindikiro cha TGFβ akhoza kupindulitsa gulu la odwala khansa yapakhungu ya RDEB kumene TGFβ imayambitsa kukula kwa maselo a chotupa. Ochepa a odwala a RDEB TGFβ amatha kuchitapo kanthu kuti aletse kukula kwa maselo a chotupa, choncho, kugwiritsa ntchito mankhwala osokoneza bongo kuti aletse chizindikiro cha TGFβ mwa odwalawa kungakhale kovulaza.

Tsopano tikufufuza njira zodziwira odwala omwe angapindule ndi mankhwala omwe amayang'ana chizindikiro cha TGFβ ndipo tikufufuza momwe chizindikiro cha TGFβ chimathandizira kukula kwa khansa kuti tithe kuzindikira njira zatsopano zochiritsira. (Kuchokera ku lipoti la 2020).

Recessive Dystrophic epidermolysis bullosa (RDEB) ndi matenda obadwa nawo omwe amabweretsa khungu losalimba lomwe limachita matuza mosavuta, limachira pang'onopang'ono komanso limakonda kukhala ndi zipsera kwambiri. Vuto lina lalikulu ndilakuti anthu ambiri omwe ali ndi RDEB amadwala khansa yapakhungu yotchedwa squamous cell carcinoma (SCC), yomwe nthawi zambiri imapha.

Kugwira ntchito kwa ma cell kumayendetsedwa ndi ma sign omwe amaperekedwa mkati ndi pakati pa ma cell. Gulu lofufuzira ili ndi ena posachedwapa awonetsa kuti ndondomeko yeniyeni yowonetsera, yomwe imaphatikizapo molekyu yotchedwa Transforming Growth Factor- β (TGFβ), imasokonezeka kwambiri pakhungu la anthu omwe ali ndi RDEB. Chofunika kwambiri tapeza kuti TGFβ ikhoza kuchitapo kanthu kuti ilimbikitse kukula kwa maselo a khansa kuposa theka la zitsanzo za RDEB zomwe zaphunziridwa koma zikhoza kulepheretsanso kukula kwa maselo a khansa mwa ena. Izi zikuwonetsa kuti ndikofunikira kwambiri kumvetsetsa nthawi komanso momwe TGFβ imagwirira ntchito polimbikitsa kukula kwa khansa. Tapeza kuti chizindikiro cha TGFβ chimayang'anira bwino njira yowonetsera sphingosine phospholipid komanso kuti maselo a RDEB SCC amafunikira ma enzyme omwe amapanga sphingosine lipid ndi cholandirira chomwe chimawonetsa kuti chikule. Chofunika kwambiri pali mankhwala omwe amagulitsidwa omwe amalepheretsa kinase ndi cholandirira ndipo tidapeza kuti chithandizo ndi mankhwalawa chimalepheretsanso kukula kwa maselo a khansa. Chosangalatsa ndichakuti, mankhwala omwe amayang'ana ku receptor amavomerezedwa kale kuti agwiritsidwe ntchito kwa odwala ambiri a sclerosis omwe akuwonetsa kuthekera kwa kutumizidwa mwachangu kwa odwala a RDEB. Tisanayambe kuyesa mphamvu zake m'mayesero achipatala kwa odwala a RDEB tifunika kuyesa zambiri kuti tilimbikitse nkhani yathu kuti tigwiritse ntchito ndikuzindikira odwala omwe angapindule ndi mankhwalawa. (Kuchokera ku lipoti lomaliza la 2024).