Mamwe madiki ATO anofambira mberi iwe unofanira kuziva nezvazvo
Arsenic trioxide-inozivikanwawo seAtO, kana trisenox-inorapa mushonga wekodzero yemukati wemuyo myeloid leukemia inonzi acute promyelocytic leukemia, kana APL . Ichi chinonzi leukemia subtype chinonziwo "M3 subtype" yeaicute myeloid leukemia .
Migumisiro inoshandisa ATO mukurapa vatsva vachangobva kuongororwa vane chirwere chepakati-kusvika-chengetedzo APL yakave yakanaka kwazvo.
Aya kubudirira akatsigirawo tsvakurudzo yesayenzi kutsvaga kushandiswa kweAATO mune dzakawanda kanzira kunze kweAppL, kusanganisira kwete-leukemia malignancies yakadai sematenda emugoni wekondon uye chirwere chepfungwa , glioblastoma multiforme.
ATO inowanzobatanidzwa ne-trans-retinoic acid (ATRA) yose, iyo inonzi retinoid inoshandiswa mukurapa acute promyelocytic leukemia. Retinoid makundi anogona kusunga receptors pamasero kuti ave nezviito zvinokosha pamasero ehupenyu hwemagetsi. Kubatanidzwa kweATRA pamwe neAATO kwakaratidzwa kuva yakakwirira kune ATRA pamwe chemotherapy mukurapwa kwevanhu vanowanzoisa pangozi varwere vachangobva kuongororwa acute promyelocytic leukemia (APL).
ATO Inoshanda Sei?
Iyo nzira yekuita kweATO haina kunyatsonzwisiswa.
Muzvikoro zvebhishopi dzemasero evanhu promyelocytic leukemia, ATO yakakonzera kuchinja pakuonekwa kwemasero pamwe nekuputika muDNA-zvose izvo zvinoratidza nzira inonzi apoptosis, kana programmed cell death.
ATO inokonzera kukanganisa puroteni yefusion yakaitwa nemasero aya anonzi promyelocytic, anonzi Pro-Myelocytic Leukemia / Retinoic Acid Receptor-alpha (PML / RAR alpha). Mapuroteni eFusion ndiwo mapuroteni anogadzirwa kuburikidza nekubatanidza kwemaviri kana kupfuura majini ezvinyorwa zvinyorwa zvepuroteni zvakasiyana.
ATO ye APL
ATO inobvumirwa kushandiswa mukurapa mamwe maitiro ehealth promyelocytic leukemia , kana APL, sezvinotevera:
- Ichangobva kuongororwa inosvika kune imwe nzira inowanikwa pangozi APL, iyo iyo ATO inoshandiswa pamwe chete ne-trans-retinoic acid, kana ATRA.
- Kudzorerwa / kukanganisa APL, kune vanhu vane marapirwo akapfuura akabatanidza retinoid uye chemotherapy, mushure mehumwe hutachiona hunochinja mumasero ekenza -t (15; 17) translocation uye / kana kuvapo kwepro-myelocytic leukemia / retinoic-acid -receptor-alpha (PML / RAR-alpha) geni.
Mucherecheche weropa romunhu (WBC) unotarisa pahurukuro, kana panguva yekutanga kuongorora uye kuongororwa kweAAPL, inowanzoshandiswa kugadzira aya mapoka eAAPL, apo izvo zvinotevera zvinoshandiswa:
- Mukana wepasi-kana wepakatikati APL = Pakutanga WBC kuverengwa ≤10,000 / microL;
- High-risk APL = Yokutanga WBC count> 10,000 / microL.
Kuchengetedzwa uye kubudirira kweAATO muvana vane makore kusvika kumakore gumi nemaviri hazvina kusimbiswa. Hapana nhamba inowanika kune vana pasi pemakore mashanu emakore, uye nhamba inongowanikwa muvana vakwegura: mune kumwe kuongororwa, varwere vanomwe vasati vava nemakore gumi nemasere (makore mashanu kusvika kumakore gumi nematanhatu) vakabatwa neAto pamusana wekurudziro we 0.15 mg / kg / zuva, uye varwere vashanu vakawana kupindura kwakakwana.
Mhinduro yekuita kweimwe AML subtypes kune ATO haina kuongororwa. Zvidzidzo neAATO zviri kuenderera mberi, uye mune ramangwana, pangave pane zvimwe zvakasiyana siyana zvekushandiswa kwemugadziri mukurapa kenza.
ATO + ATRA seInduction Therapy
Kurapa kweAAPL kwakasiyana neyeimwe mhando dze AML. Nhanho yekutanga yekurapwa, inozivikanwa sekuderedzwa, inotarisira kuunza kuregererwa uye kunosanganisira kukwikwidza masero asina kukwana eAAPL, the promyelocytes, kukura kuva masero akawanda.
Zvose-kut-retinoic acid, kana ATRA, isiri chemotherapy mishonga iyo inowanzoshandiswa pakugadziriswa, sezvo inokonzera zvinoripira zvinokuvadza kuti zvive muutrophils. Icho chikamu chinowirirana ne vitamini A. ATRA, yega, asi, haisi kukwana kuita basa rekudzikisa kukanganiswa-kureva, kuregererwa neATRA, yoga, kunowanzove kwenguva pfupi, inogara kwemwedzi mishomanana chete .
Nokudaro, ATRA inowanzobatanidzwa nevamwe vashandi kuti vape kukuregererwa kune vanhu vane APL. ATRA yakabatanidzwa ne-anthracycline-based chemotherapy ndiyo inoshandiswa yakakwana iyo inonyanya kukoshesa kuchipatara uye yakawanda yemari.
Pano pane zvinyanyofadza, zvisinei, mukushandiswa kweAATO (apo inowanikwa) neATRA, munzvimbo yeanthracycline-based chemo. Pakutanga, izvi zvakaonekwa senzira yevanhu vasingakwanisi kutsungirira anthracycline-based chemotherapy. Recent clinic trial trial, however, inoratidza kuti kusanganiswa kweATRA + ATO kunogona kubudisa migumisiro yakakosha, kana isingaenzani, mitemo yakazara inobatanidza ATRA ne chemotherapy-mune mhando dzevarwere vakarurama.
Nyaya dzakawanda dzeATRA + ATO dhiyabhorosi dzinobva kune zvidzidzo umo vanhu vaiva neAcler-risk risk APL neAIDS-risk risk APL; pane zvishoma zvinyorwa zvinowanikwa pamusoro pekuti ATRA + ATO ingaenzanisa sei naATRA + chemo kune varwere vane ngozi yakawanda APL.
Kubatanidza Matapirwo
Sezvimwe nezvimwe mhando dze AML, varwere vane APL vanoramba vachiwana kurapwa kwakapfurikidza, kana mushure mekunge maitiro avo okutanga ekugadzirwa kwekugadzirisa apera, uye izvi zvinotevera kurapwa kunozivikanwa sekugadzirisa kurapa.
Zvimwe zvinodhaka zvinoshandiswa zvinoshandiswa zvinoshandiswa mune chimwe chikamu pane zvipi zvehutano zvakapiwa se induction therapy. Mienzaniso yekubatanidza kurapa inotevera:
- Anthracycline + ATRA kwezvikamu zvishomanana (anthracycline dzakasiyana dzinogona kushandiswa nenzira dzakasiyana-siyana)
- Anthracycline + cytarabine kweanenge 2 maitiro
- ATO ye 2 maitiro anenge anenge mazuva makumi manomwe, ipapo ATRA + anthracycline kwemamiriyoni maviri
- ATRA plus ATO kwezvikamu zvakasiyana-siyana
Maintenance Therapies
Kune vamwe varwere vane APL, kusunganidzwa kunogona kuteverwa nekugadzirisa chirwere neATRA kwegore rinenge. Dzimwe nguva kuderedza maitiro emishonga chemo 6-mercaptopurine (6-MP) uye methotrexate inopiwawo zvakare.
ATO kune dzimwe nzvimbo dzezvirwere-Preliminary Research
Kubudirira neAtO mukurapa kweAAPL kwakaita kuti svesayenzi inakidzwe mune mabasa anokwanisa kuAtO mukurapa kwezvimwe zvirwere.
Mune zviitiko zvakawanda, kutsvakurudza kunotangira, dzimwe nguva kune "kuongorora mabhesi uye zvidzidzo zvezvipfuwo," asi, chokwadi chokuti ATO iri kuongororwa mune dzakasiyana-siyana dzakasiyana-siyana zvirwere uye zvirongwa, iyo pachayo, inoshamisa.
Muenzaniso wezvirevo zvakasiyana-siyana zvinotsvakurudza zvinotevera.
Lung Metastases kubva kuCaron Cancer
Anobatsira T-cell therapy inorapwa inoshandiswa kubatsira mazvirwere zvekudzivirira zvirwere zvekenza nedzimwe zvirwere. T masero anounganidza kubva kune murwere uye akakura mu laboratori kuti awedzere mikana yekubudirira kwekudzivirira zvirwere zvemuviri, ndokudzorera zvakare murwere kurwisa kenza.
Muchidzidzo chemhuka naWang uye vaaishanda navo vakaparidzirwa muOncotarget , ATO yakabatanidzwa neytotoxic T masero aiva nehutano hwekugadzirisa uye kupona kwenguva yakareba munguva yemapapu emasipasisisi yemuenzaniso wekenza yekoloni. Wang uye vakatsvakurudza vakaona kuti kubudirira nekutora T-cell therapy kunowanzotarisirwa kuderedzwa kwemasero eT t uye kuti ATO inogona kuva nemigumisiro yakanaka kuburikidza nekuderedza aya masero.
Lung Metastases kubva kuLiver Cancer
Zvakapiwa kubudirira kweAto mu APL, vatsvakurudzi vaishamisika kana ATO ingava nemigumisiro yakafanana mukenza yeropa. Kuvhiringidzika kweAATO kwakaratidzwa kuvhara chirwere chichikura mumukenza wechiropa, maererano nemushumo weLu nevamwe vake.
Uyezve, ATO inonzi inove mushonga unoshanda mukurapwa kwemapapasi emapapu kubva mukenza yeropa uye ane chirwere chinokonzera chirwere. Lu nevakashanda navo vakaona kuti zvidzidzo zvakaratidza kuti ATO inogona kudzivisa kupindira uye metastasis yekenza yesero chechiropa nekudzivisa puroteni inonzi RhoC uye kuti RhoC ne "cousin-molecule," ezrin, inogona kuve yakabatanidzwa mukurwisa-tumarara basa re ATO .
Nokudaro, vaine chinangwa chekudzidza nzira yekudzivirira kwemasero emukenza weAIDS. Vakashandisa maitiro emiti ezrin kare uye shure kweAATO kurapwa sewindo ravo rekucherechedza, uye vakaona kuti ATO kurapa kunogona kuderedza kushandiswa kwekutaura kwe ezrin mukenza yeropa.
Glioblastoma multiforme
Glioblastoma multiforme, kana GBM, inokurumidza kukura, hutsinye hunokanganisa ubongo. Uyu ndiwo mhando yemukenza yakatora hupenyu hwaTed Kennedy uye iyo Seneti John McCain akaongororwa muna 2017.
Arsenic trioxide yakataurwa kuti inhibit asi isingadzokeri kukura kwezvipembenene zvakasiyana-siyana zvechiremera kusanganisira GBM pane chirwere chakachengetedzeka mumakirini (1-2 μM). Yoshimura nevamwe vaaishanda vakacherechedza kuti mafungiro akaderera (2 μM) emu arsenic trioxide anogona kukonzera kusiyana kweGMM masero uye anogonawo kuwedzera humwe humwe hutano hwekare hunoshandiswa mukubatanidzwa mukudzidza kwavo, uye tariro ndeyokuti izvi zvinogona kureva mikana mitsva nezvemamiriyoni ekurapa kweBMM.
Osteosarcoma
Osteosarcoma inowanzova nekenza yemapfupa, uye mushonga wehutachiwana hauna kutora zvakawanda mumakore 25 kusvika ku30 akapfuura.
Imwe nzira inonzi autophagy inoreva kuti lysosomes yako masero inoshatisa uye inopedza mapuroteni aggregates uye nhengo dzezvinhu zvinokuvadza-kunyanya, kubvisa tsvina, kuchengetedza kero yelasitiki yakachena.
Autophagy modulation yave ichinzi ingangodaro nzira yekurapa yehutachiona, uye chiitiko chekare chakaratidza kuti ATO inoratidzira basa rinorwisana necarcinogenic.
Wu nevanoshanda navo munguva pfupi yapfuura vakaratidza kuti ATO yakawedzera basa rekuzvipira mumasero evanhu vanoongorora masero osteosarcoma (cell line MG-63). Zvinofadza kuti kuvhara kwekutsvaga (kushandisa madhiragi kana kuti genetic engineering) kwakaderedza ATO-induced cell cell, zvichireva kuti ATO inokonzera kushandiswa kwechiremera kufa muMG-63 masero.
Wu nevamwe vaaishanda navo vakapedzisa, "Kutorwa pamwe, idzi idzi dzinoratidza kuti ATO inokonzera masero eropaosarcoma kufa kuburikidza nekuderedza kuwedzerwa kwemoto, iyo inopindirana nemugwagwa weROS-TFEB. Chidzidzo chezvino chinopa hutsva hunopesana nemararamiro eATO kurapa mu osteosarcoma. "
Shoko Rinobva
Pamakore makumi matatu ekupedzisira, APL yakabva kune chirwere chinouraya kusvika kune chinoporesa zvikuru. Maitiro ekurapwa neATRA, chemotherapy, uye, munguva pfupi yapfuura, ATO, inofungidzirwa kuti inobatsira mune izvi kufambira mberi.
Nekufambira mberi uku, pane imwe nzvimbo "nzvimbo isina kugadzikana," zvakadaro. Nguva refu yakachengeteka nekushanda kweAATO inogona kuonekwa pano, kunyange zvazvo nguva yakareba data neAtO + ATRA yakashuma iye zvino yakave yakanaka. Imwe nzvimbo isina kuvhiringidzika inogona kuva iyo ndiyo inofanirwa kugadziriswa mishonga munguva yeATRA / ATO.
> Sources:
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> Lu W, Yang C. Migumisiro yeArsenic trioxide pamusoro pemashoko ezrin mu hepatocellular carcinoma. Medicine (Baltimore). 2017 Sep; 96 (35): e7602.
> Wang H, Liu Y, Wang X, et al. Randomized kliniki yekudzidzira kuongororwa kwenhararegional therapy pamwe ne arsenic trioxide yekurapa hepatocellular carcinoma. Cancer . 2015; 121 (17): 2917-25.
> Wang L, Liang W, Peng N, et al. Iyo synergistic antitumor inokonzerwa neArsenic trioxide yakabatana ne cytotoxic T masero mumapirmita masastasis muenzaniso wekenza yekoloni. Oncotarget . 2017; 8 (65): 109609-109618.