Tse ling tsa ATO tse tsoelang pele u lokela ho li tseba
Arsenic trioxide-eo hape e tsejoang e le ATO, kapa trisenox-ke phekolo ea likokoana-hloko bakeng sa karoloana ea lefu lena la myeloid leukemia le tsejoang e le acute promyelocytic leukemia, kapa APL . Lefu lena la leukemia le boetse le bitsoa "M3 subtype" ea lefu le kotsi la myeloid leukemia .
Liphello tse sebelisang ATO ha ho phekoloa bakuli ba sa tsoa fumanoa ba nang le kotsi e tlaase ho ea boemong bo botle ba APL e bile e ntle haholo.
Liphello tsena li boetse li khothalletsa lipatlisiso tsa saense hore li hlahlobe tšebeliso e ka sebelisoang ke ATO liphatseng tsa kankere tse ngata ntle le APL, ho kenyelletsa le likokoana-hloko tse sa tšoaneng le kankere ea methapo le kankere ea boko , glioblastoma multiforme.
ATO hangata e kopantsoe le 'mele o mong oa transtinoic acid (ATRA), moemeli oa retinoid o sebelisetsoang ho phekola lefu le kotsi la leukemia. Lik'hemik'hale tsa retinoid li ka tlama li-receptors lisele hore li be le liketso tsa bohlokoa mecheng ea bophelo ba cellular. Ho kopantsoe ha ATRA hammoho le ATO ho bontšitsoe hore e phahametse ATRA hammoho le chemotherapy ha ho phekoloa bakuli ba kotsing ba tloaelehileng ba nang le tšoaetso e matla ea lefu la lethalemia (APL).
ATO e Sebetsa Joang?
Mechine ea khato ea ATO ha e utloisisoe ka ho feletseng.
Liphuputsong tsa laboratori tsa lisele tsa human promyelocytic leukemia, ATO e entse liphetoho ponahalong ea lisele hammoho le ho qhoma ho DNA-tseo ka bobeli li bontšang mokhoa o tsejoang e le apoptosis, kapa cellmed lefu la lefu.
ATO e boetse e baka tšenyo ea protheine ea fusion e entsoeng ke lisele tsena tsa promyelocytic, tse bitsoang Pro-Myelocytic Leukemia / Retinoic Acid Receptor-alpha (PML / RAR alpha). Liprotheine tsa fusion ke liprotheine tse entsoeng ka ho kopanya liphatsa tsa lefutso tse peli kapa tse ling tse qalileng ho ngolisoa bakeng sa liprotheine tse fapaneng.
ATO bakeng sa APL
ATO e lumelloa ho sebelisoa ha ho phekoloa linyeoe tse ling tsa acute promyelocytic leukemia , kapa APL, ka tsela e latelang:
- Tšoaetso e sa tsoa fumanoa e le tlase ho ea boemong bo botle ba APL, moo ATO e sebelisetsoang ho kopantsoe le li-trans-retinoic acid, kapa ATRA.
- Ho tsosolosoa / ho hanyetsa APL, ho batho bao mekhoa ea bona ea phekolo e kileng ea e-ba le retinoid le chemotherapy, ha ho na le liphetoho tse itseng tsa liphatsa tsa lefutso meleng ea kankere - translocation ea t (15; 17) le / kapa ho ba teng ha pro-myelocytic leukemia / retinoic acid -eceptor-alpha (PML / RAR-alpha) liphatsa tsa lefutso.
Lisele tsa mali tse tšoeu tsa motho (WBC) li bala ka nako ea tlhahiso, kapa nakong ea tlhahlobo ea pele le ho hlahlojoa ha APL, hangata li sebelisoa ho bopa lihlopha tsena tsa kotsi tsa APL, moo lihlopha tse latelang li sebelisoang:
- Kotsi e tlase kapa e bohareng ea APL = Palo ea pele ea WBC ≤ 10,000 / microL;
- E kotsing e kholo APL = Palo ea pele ea WBC> 10,000 / microL.
Ho sireletseha le katleho ea ATO ho bana ba lilemo li ka holimo ho 17 ha e e-s'o thehoe. Ha ho na lintlha tse fumanehang ho bana ba ka tlase ho lilemo tse hlano, 'me boitsebiso bo lekanyelitsoe ho bana ba baholo: tlhahlobo e le' ngoe, bakuli ba supileng ba ka tlaase ho lilemo tse 18 (lilemo tse 5 ho isa ho tse 16) ba ile ba tšoaroa le ATO ka tekanyo e khothalletsoang ea 0.15 mg / kg / letsatsi, le bakuli ba bahlano ba fihletsoe karabo e feletseng.
Lipalo tsa likarabo tsa tse ling tsa AML subtypes ho ATO ha lia hlahlojoa. Liphuputso le ATO li ntse li tsoela pele, 'me nakong e tlang, ho ka' na ha e-ba le mekhoa e fapaneng ea lisebelisoa tsa moemeli ena ea ho phekola kankere.
ATO + ATRA e le phekolo ea ho khahla
Phekolo ea APL e fapane le ea mefuta e meng ea AML. Mohato oa pele oa phekolo, o tsejoang e le ho kenya lihlahisoa, o ikemiselitse ho tlisa phetoho 'me e akarelletsa ho qobella lisele tse sa tloaelehang tsa APL, li-promyelocytes, ho hōla ho lisele tse tloaelehileng.
Ntho e 'ngoe le e' ngoe ea trans-retinoic acid, kapa ATRA, ke moriana o sa sebeliseng chemotherapy o atisang ho sebelisoa bakeng sa ho kenngoa, kaha o susumetsa li-promyelocyte tse kotsi ho hōla li-neutrophils. Ke motsoako o amanang le vithamine A. ATRA, leha ho le joalo, ka kakaretso, ha e lekane ho etsa mosebetsi oa ho fokotsa ho fokolloa-ke hore, ho fokotsoa ke ATRA, ka boeona, e atisa ho phela nako e khutšoanyane, e tšoarellang likhoeli tse seng kae feela .
Kahoo, ATRA e atisa ho kopantsoe le mahlahana a mang ho etsa hore batho ba nang le APL ba tšoareloe. ATRA e kopantsoe le chemotherapy e thehiloeng ho anthracycline ke phekolo e tloaelehileng eo ho nang le phihlelo e kholo ka ho fetisisa ea bongaka le boitsebiso bo boholo ka ho fetisisa.
Ho na le thahasello e kholo, leha ho le joalo, tšebelisong ea ATO (moo e leng teng) le ATRA, sebakeng sa chemo e tloaelehileng ea anthracycline. Qalong, sena se ne se nkoa e le khetho bakeng sa batho ba neng ba sitoa ho mamella chemotherapy e thehiloeng ho anthracycline. Ditaba tsa morao tjena tsa liteko tsa kliniki, li fana ka tlhahiso ea hore motsoako oa ATRA + ATO o ka hlahisa liphello tse ntle, haeba li sa phahametse, mefuta e tloaelehileng e kopantseng ATRA le chemotherapy-mefuteng e nepahetseng ea mokuli.
Boholo ba data ea ATRA + ATO bo tsoa liphuputsong tseo batho ba neng ba e-na le kotsing e tlaase ea APL le APL ea kotsi ea bobeli; ho na le tlhahisoleseding e fokolang e teng mabapi le hore na ATRA + ATO e ka bapisoa le chemo ea ATRA + joang ho bakuli ba nang le kotsing e kholo ea APL.
Meriana ea ho kopanya
Joaloka mefuta e meng ea AML, bakuli ba nang le APL ba tsoela pele ho fumana phekolo e eketsehileng, hantle ka mor'a hore puso ea bona ea pele ea ho kenya lihlahisoa e phethoe, 'me kalafo ena ea morao-rao e tsejoa e le phekolo ea ho kopanya.
Mefuta e tobileng ea lithethefatsi e sebelisitsoeng e itšetlehile ka karolo e 'ngoe holim'a lits'ebeletso tsa phekolo tse fanoang e le phekolo ea induction. Mehlala ea phekolo ea ts'ebetso e latela:
- Anthracycline + ATRA bakeng sa li-cycle tse 'maloa (li-anthracycline tse sa tšoaneng li ka sebelisoa ka mekhahlelo e fapaneng)
- Anthracycline + cytarabine bakeng sa bonyane likoloi tse 2
- ATO ka likoloto tse 2 ka matsatsi a ka bang 75, joale ATRA + anthracycline bakeng sa mekoloko e 2
- ATRA hammoho le ATO bakeng sa mekoloko e 'maloa
Therapies ea Maintenance
Bakeng sa bakuli ba nang le APL, ho kopantsoe ho ka lateloa ke phekolo ea tlhokomelo le ATRA bakeng sa bonyane selemo. Ka nako e 'ngoe ho fanoa ka tekanyo e fokolang ea lithethefatsi tsa chemo 6-mercaptopurine (6-MP) le methotrexate.
ATO bakeng sa Libaka tse ling tsa Maloetse-Patlisiso ea Pele
Katleho le ATO ha ho phekoloa APL li khothalelitse thahasello ea saense mesebetsing e ka etsoang bakeng sa ATO ha ho phekoloa mekhoa e meng ea malimabe.
Maemong a mangata, lipatlisiso ke tsa pele, ka linako tse ling li lekanyelitsoe "ho hlahloba li-tubes le lithuto tsa liphoofolo," leha ho le joalo, taba ea hore ATO e ntse e hlahlojoa libakeng tse fapa-fapaneng tsa maloetse le mekhoa e fapaneng, ke eona e ikhethang.
Mohlala oa litsela tsena tse fapaneng tsa lipatlisiso li latela.
Lung Metastases ho tloha Kankere ea Colone
T-cell therapy e amohelehang ke phekolo e sebelisetsoang ho thusa 'mele oa' mele ho loantša kankere le maloetse a mang. Lisele tsa T li bokelloa ho tloha mokuli 'me li hōlileng ka laboratoring ho eketsa menyetla ea katleho ea' mele ea ho itšireletsa mafung, 'me e khutlisetsa mokuli ho loantša kankere.
Phuputsong ea liphoofolo ea Wang le basebetsi-'moho le eena ba hatisitsoeng ho Oncotarget , ATO e kopantsoe le lisele tsa cytotoxic T li ne li e-na le tšusumetso e matla le ho phela nako e telele mokhoeng oa metastasis oa kankere ea colone. Wang le bafuputsi ba ile ba hlokomela hore katleho e nang le phekolo ea T-cell e amohelang hangata e bakoa ke ho fokotseha ha lisele tsa T le hore ATO e ka ba le liphello tse ntle ka ho senya lisele tsena.
Lung Metastase ho tswa ho Kankere ea Kankere
Ka lebaka la katleho ea ATO ho APL, bafuputsi ba ile ba ipotsa hore na ebe ATO e ka ba le phello e tšoanang le kankere ea sebete. Tlaleho ea Lu le basebetsi-'moho le eena e bontšitse hore ho na le tšoaetso ea mafu a li-ATO a thibelang hlahala ea kankere ea sebete.
Ho phaella moo, ATO e tlalehoa e le meriana e atlehang ha ho phekoloa metastases ea matšoafo ho tloha kankere ea sebete ka bohloko bo bakoang ke kankere. Lu le basebetsi-'moho le eena ba hlokometse hore liphuputso li bontšitse hore ATO e ka thibela tlhaselo le metastasis ea lisele tsa kankere ea sebete ka ho thibela protheine e bitsoang RhoC le hore RhoC le "motsoala-molek'hule", erin, ba ka kenella mosebetsing o thibelang tumor ea ATO .
Ka hona, ba ne ba ikemiselitse ho ithuta mekhoa ea ho thibela li-cancer tsa sebete sa sebete ka ATO. Ba ne ba sebelisa lipatlisiso tsa ezrin pele le ka morao kalafo ea ATO e le fensetere ea bona, 'me ba fumana hore phekolo ea ATO e ka fokotsa haholo polelo ea ezrin ka kankere ea sebete.
Glioblastoma multiforme
Glioblastoma multiforme, kapa GBM, ke lefu le ntseng le hōla ka potlako le le mabifi la boko. Ena ke mofuta oa kankere e ileng ea nka bophelo ba Ted Kennedy le eo Sénator John McCain a neng a fumanoa ka eona ka 2017.
Ho tlalehoa hore Arsenic trioxide e thibela ho hōla ha mafu a mangata a mangata ho kopanyelletsa le GBM setsing se sireletsehileng sa tikoloho (1-2 μM). Yoshimura le basebetsi-'moho le eena ba ile ba bolela hore metsoako e tlase ea metsing (2 μM) ea arsenic trioxide e ka etsa hore ho be le likarolo tse fapaneng tsa li-GBM lisele le tse ka ntlafatsang phello ea mekhoa e meng ea phekolo ea likokoana-hloko ha e sebelisoa ka ho kopanya lithutong tsa tsona tsa mouse, 'me tšepo ke hore sena se ka emela menyetla e mecha bakeng sa phekolo ea GBM e tlang.
Osteosarcoma
Osteosarcoma ke kankere e tloaelehileng ea masapo, 'me litefello tsa phekolo ha li e-s'o tsamaee lilemong tse 25 ho isa ho tse 30 tse fetileng.
Tshebetso e bitsoang autophagy e bolela lysosomes ea lisele tsa hao e nyenyefatsa le ho felisa liprotheine tse nang le li-protein tse senyang-haholo-holo, ho ntša lithōle, ho boloka lisele tsa sele li hloekile.
Ho feto-fetoha ha motsoako oa Autophagy ho 'nile ha nkoa e le mokhoa oa ho phekola osteosarcoma,' me phuputso e fetileng e bontšitse hore ATO e bontša mosebetsi o moholo oa ho thibela lefu la kankere.
Wu le basebetsi-'moho le bona ba sa tsoa bontša hore ATO e eketsehile mosebetsi oa ho iketsetsa metsi ho lisele tsa batho tsa osteosarcoma (cell line MG-63). Ho thahasellisang ke hore ho thibela ho iketsetsa likokoana-hloko (ho sebelisa lithethefatsi kapa mochine oa liphatsa tsa lefutso) ho fokotsehile lefu la seleng le bakoang ke ATO, e leng se bontšang hore ATO e etsa hore sele e bolaeang lisele tsa MG-63.
Wu le basebetsi-'moho le eena ba ile ba phetha ka ho re, "Ho bokellana, litlaleho tsena li bontša hore ATO e etsa hore lefu la sele ea osteosarcoma le bebofatsoe ka tsela e feteletseng ea motlakase oa li-autophagia, e leng moeeng oa ROS-TFEB. Thuto ea hona joale e fana ka mekhoa e mecha ea ho loantša tumor ea phekolo ea ATO ho osteosarcoma. "
Lentsoe le Tsoang ho
Lilemong tse mashome a mararo tse fetileng, APL e tlohile lefu le bolaeang haholo ho ea phekolehang haholo. Mekhoa ea phekolo e nang le ATRA, chemotherapy, 'me, morao tjena, ATO, e nkoa e le thuso ho tsoelo-pele ena.
Ka tsoelo-pele ena, ho na le "sebaka se sa tsitsang," leha ho le joalo. Ho sireletseha ha nako e telele le katleho ea ATO ho ka nkoa e le mona, le hoja litlaleho tsa nako e telele le ATO + ATRA e tlalehiloeng ho fihlela joale li bile tse ntle. Sebaka se seng se sa tsitsang se ka 'na sa e-ba tse ling tsa phekolo ea tlhokomelo e khethiloeng nakong ea ATRA / ATO.
> Mehloli:
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> Lu W, Yang C. Litholoana tsa arsenic trioxide ka polelo ea ezrin ka hepatocellular carcinoma. Medicine (Baltimore). 2017 Sep; 96 (35): e7602.
> Wang H, Liu Y, Wang X, le al. Tlhokomelo ea tlhokomelo ea meriana e sebelisoang ka nako e telele ho hlahloba phekolo ea sebaka seo ho kopantsoeng le arsenic trioxide bakeng sa phekolo ea hepatocellular carcinoma. Kankere . 2015; 121 (17): 2917-25.
> Wang L, Liang W, Peng N, et al. The antitumor synergistic ka lebaka la arsenic trioxide e kopantsoe le lisele tsa cytotoxic T ka mokhoa oa metastasis oa pulmonary ea kankere ea colon. Oncotarget . 2017; 8 (65): 109609-109618.