Pali ATO pang'ono omwe mukufunika kuti mudziwe
Arsenic trioxide-yemwenso imadziwika kuti ATO, kapena trisenox-ndiyo mankhwala opangira mankhwala okhudza chiwalo choopsa cha myeloid khansa ya m'magazi yotchedwa acute promyelocytic leukemia, kapena APL . Leukemia subtype imatchedwanso "M3 subtype" ya myeloid yodwala khansa ya m'magazi .
Zotsatira zogwiritsira ntchito ATO pochiza odwala atsopano omwe ali ndi chiopsezo chotsika APL akhala okondweretsa kwambiri.
Zopambana izi zathandizanso kafukufuku wa sayansi kufufuza momwe angagwiritsire ntchito ATO m'ma khansa ambiri kupatula APL, kuphatikizapo osagwidwa ndi khansa ya m'magazi monga khansa ya m'matumbo ndi ubongo , glioblastoma multiforme.
ATO nthawi zambiri imakhala pamodzi ndi zonse zowonjezereka zowonjezereka (ATRA), wothandizira odwala retinoid ogwiritsidwa ntchito pochiza acute promyelocytic leukemia. Mapiritsi otha kubwereza akhoza kumanga mapuloteni pa maselo kukhala ndi zofunika pa moyo wa maselo. Kuphatikiza kwa ATRA ndi ATO kwawonetsedwa kuti ndipamwamba kuposa ATRA kuphatikizapo chemotherapy pochiza odwala omwe ali odwala omwe ali ndi kachilombo koyambitsa matenda opatsirana m'magazi (APL).
Kodi ATO Zimagwira Ntchito Bwanji?
Mmene zochita za ATO zimagwirira ntchito sizimveka bwino.
Mu ma laboratories a maselo a human promyelocytic khansa ya m'magazi, ATO inachititsa kusintha maonekedwe a maselo komanso kuswa mu DNA-zonsezi zikusonyeza njira yotchedwa apoptosis, kapena programmed death cell.
ATO imayambitsanso mapuloteni a fusion opangidwa ndi maselo a promyelocytic, otchedwa Pro-Myelocytic Leukemia / Retinoic Acid Receptor-alpha (PML / RAR alpha). Mapuloteni a fusion ndiwo mapuloteni omwe amapangidwa kudzera mu kujowina kwa majini awiri kapena kuposa omwe amayamba kulembedwa kwa mapuloteni osiyana.
ATO ya APL
ATO imavomerezedwa kuti igwiritsidwe ntchito pochiza matenda ena a acute promyelocytic leukemia , kapena APL, motere:
- Matenda atsopano omwe amapezeka kuti ali otsika kwambiri APL, omwe ATO amagwiritsidwa ntchito potsatizana ndi mankhwala onse otchedwa retinoic acid, kapena ATRA.
- Zowonongeka / kukondweretsa APL, mwa anthu omwe kale anali ndi mankhwala ochezera a retinoid ndi chemotherapy, pokhalapo ma genetic kusintha kwa maselo a kansa - kutuluka kwa 15 (17; 17) ndi / kapena kukhalapo kwa pro-myelocytic leukemia / retinoic acid -lolandira-alpha (PML / RAR-alpha) jini.
Selo loyera la magazi (WBC) la munthu likuwerengera, kapena panthawi yoyesa ndikuyang'ana kwa APL, nthawi zambiri amagwiritsidwa ntchito popanga magulu awa a APL omwe amagwiritsidwa ntchito:
- Mavuto apansi kapena apakati APL = Chiwerengero cha WBC choyamba ≤10,000 / microL;
- Mavuto aakulu APL = Yoyamba WBC count> 10,000 / microL.
Kutetezeka ndi kuthandizira kwa ATO kwa ana a zaka zoposa 17 sikunayambe. Palibe deta yomwe ilipo kwa ana osakwanitsa zaka zisanu, ndipo deta ndi yochepa mwa ana okalamba. Pakufufuza koyamba, odwala asanu ndi awiri osachepera zaka 18 (zaka zisanu ndi zisanu ndi zisanu ndi zisanu ndi zitatu) anachitidwa ndi ATO pa mlingo woyenera wa 0.15 mg / kg / tsiku, ndi odwala asanu adalandira yankho lathunthu.
Zotsatira za ma AML subtypes kwa ATO sizinayesedwe. Zofufuza ndi ATO zikupitirira, ndipo m'tsogolomu, pakhoza kukhala zoonjezerapo zoonjezera zosiyanasiyana za wothandizilayu pakuchiza khansara.
ATO + ATRA monga Thandizo la Kuchiza
Chithandizo cha APL chimasiyana ndi cha mtundu wina wa AML. Gawo loyamba la chithandizo, lodziwika ngati kulowetsa, likufuna kubweretsa kukhululukidwa ndipo kumaphatikizapo kukakamiza maselo osadziwika a APL, promyelocytes, kuti akule kukhala maselo ambiri.
Matenda onse otchedwa retinoic acid, kapena ATRA, ndi mankhwala osagwiritsa ntchito mankhwala omwe amagwiritsidwa ntchito popanga mavitamini, chifukwa amachititsa kuti mankhwalawa asapitirire kukhala a neutrophils. Ndilo mankhwala omwe ali okhudzana ndi vitamini A. ATRA, komabe, sikokwanira kuchita ntchito yochepetsera-kutanthauza kuti, kuchotsedwa ndi ATRA, kokha, kumakhala kanthawi kochepa, kumakhala miyezi ingapo .
Motero, ATRA nthawi zambiri imakhala pamodzi ndi othandizira ena kuti apange chikhululukiro mwa anthu omwe ali ndi APL. ATRA kuphatikizapo anthracycline-based chemotherapy ndi chithandizo choyenera chomwe chiri ndi zambiri zomwe zimachitikira kuchipatala komanso kuchuluka kwa deta.
Pali zowonjezereka, komabe, pogwiritsa ntchito ATO (komwe kulipo) ndi ATRA, m'malo mwa chemo ya anthracycline. Poyamba, izi zimawoneka ngati mwayi kwa anthu omwe sangathe kulekerera mankhwala a anthracycline-based chemotherapy. Deta yam'mbuyo yam'mbuyo yamakono, komabe, ikusonyeza kuti kuphatikiza kwa ATRA + ATO kungabweretse zotsatira zomwe ziri zabwino, ngati zosapambana, zida zogwirizana ndi ATRA ndi chemotherapy-mu mitundu yoyenera ya odwala.
Deta zambiri za ATRA + ATO zimachokera ku maphunziro omwe anthu anali ndi chiopsezo chachikulu cha APL ndi APL yoopsa; pali zambiri zochepa zokhudzana ndi mmene ATRA + ATO ingafanane ndi ATRA + chemo kwa odwala omwe ali ndi chiopsezo chachikulu cha APL.
Kugwirizanitsa Mankhwala
Mofanana ndi mitundu ina ya AML, odwala omwe ali ndi APL amapitiliza kulandila chithandizo chamankhwala, pokhapokha atatha kukonzanso mankhwalawa, ndipo mankhwalawa amadziwika kuti mankhwala othandizira.
Mankhwala ogwiritsira ntchito omwe amagwiritsidwa ntchito amadalira mbali zina zomwe chithandizo chinaperekedwa ngati mankhwala odulidwa. Zitsanzo za mankhwala othandizira amatsatira:
- Anthracycline + ATRA kwa maselo angapo (anthracyclines osiyana angagwiritsidwe ntchito mosiyana)
- Anthracycline + cytarabine kwa maola awiri
- ATO kwa masekondi awiri pa masiku pafupifupi 75, ndiye ATRA + anthracycline kwa masekondi awiri
- ATRA plus ATO kwa maulendo angapo
Zochiritsira Zokonza
Kwa odwala ena omwe ali ndi APL, kuphatikiza kungathandizidwe ndi chithandizo chokonzekera ndi ATRA kwa chaka chimodzi. Nthawi zina kuchepa kwa mankhwala a chemo 6-mercaptopurine (6-MP) ndi methotrexate amaperekanso.
ATO kwa Malo Ena Odwala-Kafukufuku Woyamba
Zopambana ndi ATO pochiza APL zathandiza chidwi cha sayansi pa maudindo omwe angakhale nawo pa ATO pochiza machitidwe ena oipa.
Kawirikawiri, kafukufukuyo ndiwotheka, nthawi zina amangofuna "kuyesa ma tubes ndi maphunziro a zinyama," komabe, kuti ATO ikufufuzidwa m'madera osiyanasiyana osiyanasiyana a matenda ndi zozizwitsa.
Chitsanzo cha njira zotsatirazi zofukufuku zimatsatira.
Lung Metastases kuchokera ku khansa ya Colon
Kuthandizana ndi T-cell therapy ndi mankhwala ogwiritsidwa ntchito kuthandizira chitetezo cha mthupi kumenyana ndi khansa ndi matenda ena. Matenda a T amasonkhanitsidwa kuchokera kwa wodwalayo ndi wamkulu mu labotale kuti awonetsetse kuti chitetezo cha chitetezo cha mthupi chitetezeka, ndikubwezeranso wodwalayo kuti amenyane ndi khansa.
Phunziro la nyama la Wang ndi anzake omwe adasindikizidwa ku Oncotarget , ATO pamodzi ndi maselo a cytotoxic T anali ndi mphamvu zolimbitsa thupi komanso nthawi yaitali yopulumuka ku khansa ya m'matumbo ya khansa ya colon. Wang ndi ochita kafukufuku adanena kuti kupambana ndi T-cell mankhwala othandiza kumachitika chifukwa chochepetsedwa ndi maselo olamulira a T komanso kuti ATO ikhoza kukhala ndi zotsatira zabwino mwa kuwononga maselowa.
Lung Metastases kuchokera ku khansa ya chiwindi
Chifukwa cha ATO mu APL, ochita kafukufuku anadabwa ngati ATO ingakhale ndi zotsatira zofanana ndi khansa ya chiwindi. Zizindikiro za ATO zakhala zikusonyezedwa kuti ziletsa chiphuphu kukula mu khansa ya chiwindi, malinga ndi lipoti la Lu ndi anzake.
Kuonjezerapo, ATO imati ndi mankhwala othandiza pochizira matenda a mapapo ku khansa ya chiwindi ndi ululu wokhudzana ndi khansa. Lu ndi anzake apeza kuti kafukufuku wasonyeza kuti ATO ikhoza kulepheretsa kuwonongeka kwa maselo a khansa ya chiwindi ndi kuteteza puloteni yotchedwa RhoC ndi RhoC ndi "cousin-molecule," ezrin, zomwe zingagwire ntchito yoteteza thupi la ATO .
Choncho, iwo ankafuna kuphunzira njira yothetsera maselo a khansa ya chiwindi ndi ATO. Iwo amagwiritsa ntchito mafotokozedwe a ezrin asanayambe ndi pambuyo pa mankhwala a ATO monga mawonekedwe awo, ndipo adapeza kuti ATO mankhwala akhoza kuchepetsa kwambiri mawu a ezrin mu khansa ya chiwindi.
Glioblastoma multiforme
Glioblastoma multiforme, kapena GBM, ndi kukula mofulumira, kosautsa kwa ubongo. Ichi ndi mtundu wa khansa yomwe inatenga moyo wa Ted Kennedy ndi yomwe Senator John McCain anapezeka m'chaka cha 2017.
Akuti arsenic trioxide imaletsa koma siigwirizanitsa kukula kwa ziwalo zolimba zambiri kuphatikizapo GBM pa mlingo wathanzi (1-2 μM). Yoshimura ndi anzake amagwira ntchito kuti msampha wotsika (2 μM) wa arsenic trioxide ukhoza kuyambitsa kusiyana kwa GBM maselo ndipo ingathandizenso zotsatira za mankhwala ena amtundu wa antiticancer pamene agwiritsidwa ntchito palimodzi pakuphunzira kwawo, ndipo chiyembekezo ndi chakuti izi zikhoza kuimira mwayi watsopano za mankhwala amtsogolo a GBM.
Osteosarcoma
Osteosarcoma ndi khansa yambiri ya mafupa, ndipo mankhwala ochiritsidwa sakhala akuyenda zaka 25 mpaka 30 zapitazo.
Njira yomwe imatchedwa autophagy imatanthawuza kuti maselo a maselo anu amachititsa kuti thupi lanu likhale loyera komanso kuthetseratu mapuloteni omwe amawonongeka.
Kugwiritsa ntchito mawu ovomerezeka kwa autophagy kunayesedwa kuti ndi njira yothetsera matenda a osteosarcoma, ndipo phunziro lapitalo linasonyeza kuti ATO imasonyeza ntchito yaikulu yotsutsa khansa.
Wu ndi anzake akugwira ntchito posachedwapa anasonyeza kuti ATO inayamba kugwira ntchito yodzipangira autophagy m'maselo a anthu osteosarcoma (selo line MG-63). Chochititsa chidwi, kutseka kwa autophagy (kugwiritsira ntchito mankhwala osokoneza bongo) kunachepetsanso maselo a ATO-omwe amachititsa kuti maselo azifa, zomwe zikusonyeza kuti ATO imachititsa kuti maselo azifa m'maselo a MG-63.
Wu ndi anzake adagwirizana kuti, "Zonsezi zikuwonetseratu kuti ATO imapangitsa kuti maselo a osteosarcoma aphedwe kudzera mwa kuyendetsa magalimoto ochuluka, omwe amathera pakati pa msewu wa ROS-TFEB. Kafukufuku wamakono akupereka mankhwala atsopano a anti-tumor a ATO mu osteosarcoma. "
Mawu Ochokera
Pazaka makumi atatu zapitazi, APL yatha kudwala matenda oopsa kwambiri mpaka kuchiritsidwa kwambiri. Njira zothandizira ndi ATRA, chemotherapy, ndipo, posachedwapa, ATO, amawoneka kuti ndi othandiza pazitukukozi.
Ndi chitukuko ichi, palinso "gawo losalephereka," komabe. Kutetezeka kwa nthawi yaitali kwa ATO kungathenso kulingalira pano, ngakhale kuti deta ya nthawi yaitali ndi ATO + ATRA yakhala ikuthandizira. Malo ena osokonezeka angakhale omwe ali ochiritsira ochiritsira operekera mu nthawi ya ATRA / ATO.
> Zotsatira:
> Abaza Y, Kantarjian H, Garcia-Manero G, et al. Zotsatira zam'tsogolo za acute promyelocytic khansa ya m'magazi imagwiritsidwa ntchito ndi trans-retinoic acid, arsenic trioxide, ndi gemtuzumab. Magazi . 2017; 129 (10): 1275-1283.
> Lu W, Yang C. Zotsatira za arsenic trioxide ponena za ezrin mu hepatocellular carcinoma. Medicine (Baltimore). 2017 Sep; 96 (35): e7602.
> Wang H, Liu Y, Wang X, ndi al. Kugwiritsa ntchito njira zothandizira anthu kuti azitha kulandira mankhwalawa ndi arsenic trioxide pochiza matenda a hepatocellular carcinoma. Khansa . 2015; 121 (17): 2917-25.
> Wang L, Liang W, Peng N, ndi al. Mankhwalawa amachititsa kuti arsenic trioxide ikhale ndi maselo a cytotoxic T m'matumbo a metastasis. Oncotarget . 2017; 8 (65): 109609-109618.