RDEB ciwon fata (2023)

Masu bincike sun gano kwayoyin da kwayoyin cutar kansa na RDEB ke bukata su girma. Sun yi nasarar rage haɓakar ƙwayoyin cutar kansa na RDEB a cikin dakin gwaje-gwaje ta amfani da magunguna na kasuwanci waɗanda ke tsoma baki tare da waɗannan ƙwayoyin cuta. Ɗaya daga cikin waɗannan magungunan an riga an yarda da asibiti don kula da marasa lafiya na sclerosis da yawa kuma ana iya sake yin amfani da su don taimakawa mutanen da ke fama da ciwon daji na RDEB. Ana buƙatar ƙarin gwaje-gwaje kafin a ba da wannan magani ga mutanen da ke fama da ciwon daji na RDEB a cikin gwaji na asibiti, amma ana iya samar da shi da sauri fiye da sabon magani da zarar an sami kyakkyawar shaida cewa yana taimakawa.

Masu binciken suna da sel daga cututtukan daji na RDEB guda goma sha ɗaya da ke girma a cikin ɗakin binciken su kuma sun gwada yadda suke amsa jiyya daban-daban. Sun gano kwayoyin halitta guda shida waɗanda ke ƙarfafa ƙwayoyin cutar kansa na RDEB don ninka wanda zai iya zama manufa mai kyau don hanyoyin kwantar da hankali.

Masu binciken sun buga sabon binciken su a cikin 2021.

Jagoran bincike:

Farfesa Gareth Inman shi ne Daraktan Dabarun Bincike a Cibiyar Nazarin Ciwon daji ta CRUK Beatson kuma Farfesa na Siginar Halitta a Cibiyar Nazarin Ciwon daji, Jami'ar Glasgow, Scotland. Babban abin da ya fi so shi ne fahimtar rawar da membobin ƙungiyar beta mai canza girma (TGFβ) ke takawa wajen haɓaka cutar kansa da ci gaba. Nazarinsa ya mayar da hankali ne akan ciwon daji na fata, kai da wuyansa da kuma pancreas kuma yanzu ya haɗa da waɗannan ciwon daji da ke tasowa a cikin marasa lafiya da ke zaune tare da dystrophic epidermolysis bullosa. Ta hanyar fahimtar matsayin TGFβ a matsayin duka mai tallata kansa da mai hana kansa Farfesa Inman yana fatan haɓaka dabaru don maganin kansar nan gaba.

Masu haɗin gwiwa:

Dokta Peter Bailey, Dr Karen Blyth (Glasgow, Scotland, UK) da kuma Dr Andrew South (Jami'ar Thomas Jefferson, Philadelphia, Amurka).

"Majinyata na RDEB za su amfana daga wannan bincike a ƙarshe, ba kawai a cikin mahallin ciwon daji ba har ma da shawarar za ta iya ba da labari kan yadda siginar TGFβ ke ba da gudummawa ga tabarbarewar gine-ginen dermal a hankali. Magungunan TGFβ suna cikin gwaji na asibiti kuma wannan shawara za ta ƙayyade lokacin da za su sami amfanin asibiti ga marasa lafiya na RDEB. SCC da ke tasowa a wasu nau'ikan EB na iya amfana daga waɗannan karatun. ”

– Farfesa Gareth Inman

Taken Bada: Hanyoyin haɓakar ƙwayar cuta ta TGF-beta a cikin RDEB cSCC.

Recessive Dystrophic epidermolysis bullosa (RDEB) cuta ce da aka gada wacce ke da alaƙa da ƙumburi na yau da kullun, rauni da wuce gona da iri na fata. Yawancin marasa lafiya na RDEB suna haɓaka ciwon daji na fata da ake kira cutaneous squamous cell carcinoma (cSCC), wanda sau da yawa yakan mutu. Kwayoyin da ke cikin jiki sun dogara da takamaiman sigina don rayuwa da girma. A cikin ciwon daji waɗannan sigina ko dai sun ɓace ko ana iya ɗaukaka su don taimakawa ci gaban ƙari da yaduwa.

Wannan rukunin bincike da wasu sun nuna kwanan nan cewa takamaiman tsarin sigina, wanda ya haɗa da kwayar halitta mai suna Transforming Growth Factor-beta (TGF-β), yana haɓaka a cikin fatar mutanen da ke da alaƙa da RDEB cSCC. Mahimmanci wannan rukunin ya gano cewa toshe siginar TGF-β mai aiki zai iya hana (tsaya) ci gaban kwayar cutar kansa a cikin 50% na samfuran RDEB da aka gwada. Abin sha'awa shine, toshe hanyar siginar kuma na iya haɓaka haɓakar ƙwayoyin cutar kansa a cikin zaɓaɓɓun samfuran RDEB cSCC.

Wadannan abubuwan lura suna nuna cewa yana da mahimmanci don fahimtar lokacin da kuma yadda TGF-β ke aiki don haɓaka ko hana ci gaban ciwon daji a cikin RDEB don ba da damar gano marasa lafiya waɗanda za su amfana daga hana wannan hanyar siginar. A cikin wannan aikin ƙungiyar ta shirya don bincika yadda TGF-β ke haɓaka haɓakar ciwon daji kuma don cimma wannan, ƙungiyar tana da niyyar haɓaka masu siginar biomarkers na siginar TGFβ ta amfani da in vitro da in vivo yanayin ƙirar ilimin halitta, (hanyoyin da aka yi amfani da su don nazarin halin da ake ciki) aiki na kwayoyin).

Manufar 1. Don fahimtar halayen kwayoyin halitta (biomarkers) na yadda TGFβ ke aiki a cikin RDEB ciwon daji na fata wanda zai sanar da amfani da maganin siginar anti-TGFβ.

Maƙasudi 2. Fahimtar tsarin yadda siginar TGFB zai iya haifar da ƙaura na ciwon daji, mamayewa da haɓakar ƙari da gano maƙasudin magungunan warkewa (misali furotin ko kwayoyin da za'a iya canzawa ta amfani da magani ko magani don ƙaddamar da ƙwayoyin cutar kansa).

Wannan binciken zai ba da tushe don ƙarin fahimtar siginar TGFβ a cikin RDEB kuma zai iya gano sababbin maƙasudi don ci gaban ƙwayoyi na gaba don magance ciwon daji na squamous. Wadannan hanyoyin kwantar da hankali suna cikin gwaje-gwaje na asibiti a cikin wasu cututtuka ko kuma suna cikin ci gaban farko na asibiti. Har ila yau, binciken zai ba da bayani kan hanyoyin ci gaba na novel therapeutics.

Binciken da aka ba da kuɗin DEBRA na baya a cikin siginar TGF-β a cikin RDEB cSCC ta Farfesa Gareth Inman ya ba da gudummawa ga wannan sabon bincike.

Canza yanayin girma-beta (TGFβ) kwayoyin halitta ne da ke tafiyar da tsarin sigina wanda ke sarrafa kewayon matakai masu mahimmanci don aiki na yau da kullun na sel. Siginar TGFβ tana da hannu a cikin farawar kansa, haɓakawa da ci gaba amma kuma yana iya hana haɓakar ƙari da haɓaka ta hanyar dogaro da mahallin. Marasa lafiya na RDEB da ke fama da matsananciyar kumburin fata suna haifar da ciwace-ciwacen fata da ke ci gaba da sauri kuma suna da wahalar magani wanda ke haifar da mutuwar kusan kashi 90% na marasa lafiya da shekaru 55.

Mu da wasu mun gano cewa masu fama da ciwon daji na RDEB sun kara yawan matakan TGFβ a cikin fata da ciwace-ciwacen daji. Ba a bayyana ba idan TGFβ yana haifar da ciwace-ciwacen ciwace-ciwacen daji ko a'a a cikin cututtukan daji da ke tasowa a cikin marasa lafiya na RDEB.

Yin amfani da sel da aka samo daga masu ciwon daji na RDEB, mun nuna cewa magungunan da ke hana siginar TGFβ zasu iya amfana da wani yanki na RDEB masu ciwon daji na fata inda TGFβ ke haifar da ci gaban ƙwayar ƙwayar cuta. A cikin ƙaramin adadin marasa lafiya na RDEB TGFβ na iya yin aiki don dakatar da haɓakar ƙwayar ƙwayar cuta, sabili da haka, yin amfani da kwayoyi don toshe siginar TGFβ a cikin waɗannan marasa lafiya na iya zama da lahani.

Yanzu muna bincika hanyoyin da za a gano waɗanne marasa lafiya za su amfana daga hanyoyin kwantar da hankali waɗanda ke da alaƙa da siginar TGFβ kuma suna binciken yadda siginar TGFβ ke haɓaka haɓakar ciwon daji don ba mu damar gano sabbin dabarun warkewa. (Daga rahoton ci gaba na 2020).

Recessive Dystrophic epidermolysis bullosa (RDEB) cuta ce da aka gada wacce ke haifar da raƙuman fata da ke fitowa cikin sauƙi, tana warkarwa a hankali kuma tana saurin kamuwa da tabo mai yawa. Wani mawuyacin hali shine yawancin mutanen da ke da RDEB zasu haifar da ciwon daji na fata da ake kira squamous cell carcinoma (SCC), wanda sau da yawa yakan mutu.

Ana sarrafa duk aikin tantanin halitta ta sigina da ake wucewa ciki da tsakanin sel. Wannan rukunin bincike da wasu sun nuna kwanan nan cewa takamaiman tsarin sigina, wanda ya haɗa da kwayar halitta mai suna Transforming Growth Factor- β (TGFβ), yana da matukar rauni a cikin fata na mutanen da ke da RDEB. Mahimmanci mun gano cewa TGFβ na iya yin aiki don inganta haɓakar ƙwayar cutar kansa a cikin fiye da rabin samfuran RDEB da aka yi nazari amma kuma yana iya hana ci gaban ƙwayar cutar kansa a wasu daga cikin sauran. Waɗannan abubuwan lura suna nuna cewa yana da matuƙar mahimmanci don fahimtar lokacin da kuma yadda TGFβ ke aiki don haɓaka haɓakar ciwon daji. Mun gano cewa siginar TGFβ yana daidaita tsarin siginar sphingosine phospholipid kuma cewa RDEB SCC Kwayoyin suna buƙatar duka enzyme wanda ke haifar da lipid sphingosine da mai karɓar siginar ta hanyar girma. Mahimmanci akwai magunguna na kasuwanci waɗanda ke hana kinase da mai karɓa kuma mun gano cewa jiyya tare da waɗannan magungunan kuma yana toshe haɓakar ƙwayar cutar kansa. Abin sha'awa, an riga an yarda da maganin da aka yi niyya ga mai karɓa don amfani da shi a cikin marasa lafiya na sclerosis da yawa wanda ke nuna yiwuwar saurin turawa a cikin marasa lafiya na RDEB. Kafin gwada tasirin sa a cikin gwaje-gwaje na asibiti a cikin marasa lafiya na RDEB muna buƙatar yin ƙarin gwaje-gwaje don ƙarfafa shari'ar mu don amfani da shi da kuma gano waɗanne marasa lafiya za su amfana daga wannan magani. (Daga rahoton karshe na 2024).