Bayanan cigaban ATO ya kamata ku sani
Arsenic trioxide-wanda aka fi sani da ATO, ko trisenox-wani magani ne na maganin anticancer don ƙaddamar da cutar cutar sankarar myeloid mai zurfi da aka sani da cutar sankarar bargaɗi mai tsanani, ko APL . Wannan cututtukan cutar sankarar bargo ne kuma ana kiranta "M3 subtype" na muraye sankarar myeloid m .
Sakamako ta amfani da ATO a lura da marasa lafiya da aka kamu da marasa lafiya tare da ƙananan halayen APL sun kasance da matukar farin ciki.
Wadannan nasarar sun hada da binciken kimiyya da bincike akan yiwuwar amfani da ATO a cikin magunguna daban daban fiye da APL, ciki har da cutar marasa cutar sankarar jini kamar su ciwon ciwon ciwon daji da ƙwayar kwakwalwa , glioblastoma multiforme.
ATO an haɗa shi tare da dukkanin retinoic acid (ATRA), wani wakili na retinoid da aka yi amfani da shi wajen kula da cutar sankarar barga mai girma. Ma'aikata na Retinoid zasu iya ɗaukar masu karɓa a kan sel don samun ayyuka masu muhimmanci a kan salon hawan salula. Haɗin ATRA tare da ATO an nuna su zama masu fifiko ga ATRA da chemotherapy a maganin marasa lafiya masu dauke da kwayar cutar tare da sabon cutar cutar sankarar bargo (APL).
Ta Yayi Ayyukan ATO?
Hanyoyin aikin ATO basu fahimta ba.
A cikin nazarin gwaje-gwaje na kwayoyin cutar sankarar bargo na mutum, ATO ya haifar da canje-canje a cikin bayyanar kwayoyin kuma ya karya cikin DNA-dukansu biyu na nuna wani tsari da ake kira apoptosis, ko kuma mutuwar kwayar halitta.
ATO kuma yana haddasa lalacewar furotin da wadannan kwayoyin halittar sunyi, wanda ake kira Pro-Myelocytic Leukemia / Retinoic Acid Receptor-alpha (PML / RAR alpha). Furotin sunadarai sunadaran sunadarai ne ta hanyar haɗuwa da kwayoyin halitta biyu ko fiye da aka tsara don sunadaran sunadarai.
ATO ga APL
An amince da ATO don amfani da shi wajen maganin wasu lokuta na cutar cutar sankarar bargo mai lamba , ko APL, kamar haka:
- Sababbin bincikar cutar mai kwakwalwa na APL, inda ake amfani da ATO a hade tare da dukkanin trans-retinoic acid, ko ATRA.
- Rushewar / APL mai banƙyama, a cikin mutanen da suka jiyya a baya da suka hada da retinoid da chemotherapy, a gaban wasu kwayoyin canzawa a cikin kwayoyin cutar kanjamau - t (15; 17) fassarar kuma / ko kasancewar cutar cutar sankarar bargo / retinoic-acid-pro-myelocytic -receptor-alpha (PML / RAR-alpha).
Tsararren jini na jini (WBC) ya ƙidaya a gabatarwa, ko a lokacin da aka fara gwaji da ganewar asali na APL, ana amfani dasu don ƙirƙirar waɗannan rukunin hadarin APL, inda aka yi amfani da waɗannan sassa:
- Low- ko matsakaici-hadarin APL = A farkon WBC ƙidaya ≤10,000 / microL;
- Babban APL mai hadarin gaske = Ƙaddamarwa na WBC> 10,000 / microL.
Tsaro da inganci na ATO a cikin yara da shekarunsu har zuwa shekaru 17 ba a kafa su ba. Babu bayanai da ke samuwa ga yara da ba su da shekaru biyar, kuma bayanai suna iyakance a cikin yara tsofaffi: a cikin wani bincike, an yi maganin marasa lafiya bakwai a ƙarƙashin shekarun 18 zuwa shekaru 5 zuwa 16 tare da ATO a shawarar da ake bukata na 0.15 MG / kg / rana, da kuma marasa lafiya biyar suka sami cikakken amsa.
Sakamakon amsawar sauran magunguna na AML zuwa ATO ba a bincika ba. Nazarin tare da ATO suna gudana, kuma a nan gaba, akwai wasu aikace-aikacen ƙarin ƙarin don wannan wakili a maganin ciwon daji.
ATO + ATRA a matsayin Cutar Gyara
Yin maganin APL ya bambanta da na sauran AML. Mataki na farko na magani, wanda aka sani da ƙaddamarwa, yana nufin kawowa gafara kuma ya haɗa da tilasta kwayoyin halittu na APL, masu promyelocytes, don su girma cikin ƙwayoyin jiki.
All-trans-retinoic acid, ko ATRA, wani magani ne wanda ba na chemotherapy da ake amfani dashi don shigarwa, saboda yana tilasta masu amfani da magunguna masu girma su yi girma cikin tsaka-tsaki. Gida ne wanda yake da dangantaka da bitamin A. ATRA, kadai, duk da haka, bai zama cikakke ba ne don yin aikin haɓakawa gafara - wato, gyare-gyare tare da ATRA, shi kaɗai, yana da gajeren lokaci, yana da 'yan watanni kawai .
Ta haka ne, ATRA an hade shi da sauran wakilai don yin gafara ga mutane da APL. ATRA haɗuwa tare da maganin rigakafi na anthracycline shine magani na musamman wanda akwai ƙwarewar ɗakunan shan magani da kuma yawancin bayanai.
Akwai wani abu mai ban sha'awa, duk da haka, a cikin amfani da ATO (inda akwai) tare da ATRA, a wurin da ake amfani da chemo na anthracycline. Da farko, ana ganin wannan a matsayin wani zaɓi ga mutanen da basu iya jure wa maganin cutar anthracycline na tushen chemotherapy. Bayanan jarrabawa na baya-bayan nan, duk da haka, sun bayar da shawarar cewa haɗin ATRA + ATO na iya haifar da sakamakon da ke da kyau, idan ba ta da kyau ba, daidaitattun tsarin hada ATRA da chemotherapy-a cikin haƙƙin haƙƙin lafiya.
Yawancin bayanan ATRA + ATO ya fito ne daga nazarin da mutane ke ɗauke da APL mai hadarin gaske da kuma APL matsakaici; akwai žananan bayanai game da yadda ATRA + ATO zai iya kwatanta da ATRA + chemo a cikin marasa lafiya da APL mai tsanani.
Ƙasashe hanyoyin kwantar da hankali
Kamar yadda yake tare da sauran AML, marasa lafiya tare da APL sun ci gaba da karɓar ƙarin magani, da kyau bayan an fara kammala tsarin shigar da su, kuma wannan magani na gaba ne da aka sani da farfadowa.
Ma'anar ƙwayar magungunan ƙwayoyi da ake amfani da su sun dogara ne a kan abin da aka ba da maganin asibiti. Misalan hanyoyin kwantar da hankali sun biyo baya:
- Anthracycline + ATRA ga 'yan hawan keke (daban-daban anthracyclines za'a iya amfani dashi a cikin haɗuwa daban-daban)
- Anthracycline + cytarabine don akalla 2 hawan keke
- ATO na tsawon 2 a kusan kwanaki 75, to, ATRA + anthracycline na tsawon 2
- ATRA da ATO don da yawa hawan keke
Gudanar da Tafiya
Ga wasu marasa lafiya tare da APL, ƙarfafawa tare da ATRA na iya biyowa don akalla shekara guda. Wani lokaci low doses na chemo da kwayoyi 6-mercaptopurine (6-MP) da methotrexate aka ba da.
ATO don Sauran Harkokin Bincike na Raunin Cutar
Nasara tare da ATO a lura da APL sun taimakawa ilimin kimiyya a matsayi mai kyau na ATO a maganin wasu malignancies.
A lokuta da yawa, bincike yana da mahimmanci, wani lokacin iyakance ga "jarrabawar gwaji da nazarin dabba," duk da haka, gaskiyar cewa ana nazarin ATO a irin wadannan shafuka daban-daban da kuma saitunan shine, a kansa, abin mamaki.
Wani samfurin waɗannan sharuɗan bincike yana biyo baya.
Lung Metastases daga Colon Cancer
T-cell farfesa ne magani wanda ake amfani dashi don taimakawa wajen magance ciwon daji da sauran cututtuka. Tarin kwayoyin T an tattara daga masu haƙuri kuma suna girma a cikin dakin gwaje-gwaje don kara yawan ƙananan rashin nasarar tsarin da ba su da lafiya, sa'an nan kuma mayar da su a cikin mai haƙuri don yaki da ciwon daji.
A cikin nazarin dabba da Wang da abokan aiki da aka buga a Oncotarget , ATO da aka hade tare da kwayoyin cytotoxic T sunyi tasirin tasiri da kuma tsawon rayuwar rayuwa a cikin tsarin ƙwayar ƙwayar cuta na ciwon sukari. Wang da masu bincike sun lura cewa an samu nasarar ci gaba tare da tsarin T-cell wanda ke daukar nauyin ƙwayoyin T da kuma cewa ATO na iya samun sakamako mai kyau ta hanyar rage wadannan kwayoyin halitta.
Tashin ƙurar ƙurar ƙura daga Ciwon Cancer
Bisa nasarar nasarar ATO a APL, masu bincike sunyi mamaki ko ATO zai iya samun irin wannan sakamako a cikin cutar ciwon huhu. An nuna alamun na ATO don hana ciwon sukari a cikin ciwon hanta, a cewar rahoton Lu da abokan aiki.
Bugu da ƙari, ATO an bayar da rahoto zama magani mai mahimmanci wajen magance ƙwayar ƙwayar ƙwayar ƙwayar cuta daga cutar ciwon hanta tare da ciwon ciwon daji. Lu da abokan aiki sun lura cewa nazarin ya nuna cewa ATO na iya hana mamayewa da matakai na ciwon daji na ciwon hanta ta hanyar hana wani kwayar halitta mai suna RhoC kuma RhoC da "'yar uwan", ezrin, na iya shiga cikin aikin anti-tumor na ATO .
Sabili da haka, sun yi nufin nazarin hanyar da aka hana magungunan ciwon ciwon hanta na kwayar cutar ta hanyar ATO. Sun yi amfani da alamomin bayyanar na ezrin kafin da bayan ATO magani a matsayin taga na kallo, kuma sun gano cewa maganin ATO zai iya rage sharuddan bayanin da ake ciki na ezrin a cikin ciwon huhu.
Glioblastoma multiforme
Glioblastoma multiforme, ko GBM, mai cike da sauri ne, mummunan ƙwaƙwalwar kwakwalwa. Wannan shi ne irin ciwon daji wanda ya ɗauki rayuwar Ted Kennedy da wanda aka gano Senator John McCain cikin shekara ta 2017.
An ruwaito Arsenic trioxide don hana shi amma ba ya rage girman ciwon daji na ciki da ya hada da GBM a cikin rashin lafiya na asibiti (1-2 μM). Yoshimura da abokan aiki sun lura cewa ƙaddamarwa mai zurfi (2 μM) na arsenic trioxide zai iya haifar da bambancin jinsunan GBM kuma zai iya inganta tasirin hanyoyin maganin anticancer lokacin amfani da su a haɗuwa a binciken su, kuma shine bege shine wannan zai iya wakiltar sababbin damar don hanyoyin kwastam na gaba na GBM.
Osteosarcoma
Osteosarcoma na da kwayar cutar ciwon daji, kuma maganin magani ba su motsawa a cikin shekaru 25 zuwa 30 ba.
Tsarin da ake kira autophagy yana nufin 'yan kwayoyin ku na' lysosomes da ke lalata da kuma kawar da haɗin gwiwar gina jiki da kuma lalata kwayoyin halitta-da gaske, shan fitar da sharar, don tsaftace tsaftaran gidan salula.
An yi la'akari da yadda ake daukar nauyin haɗin kai a matsayin wata magungunan magani mai mahimmanci don osteosarcoma, kuma binciken da ya gabata ya nuna cewa ATO yana nuna muhimmancin maganin carcinogenic.
Wu da abokan aiki kwanan nan sun nuna cewa ATO ya karu aikin haɗin kai a cikin gwajin kwayoyin osteosarcoma gwaji (layin salula MG-63). Abin sha'awa shine, dagewa na autophagy (amfani da kwayoyi ko aikin injiniya) ya rage yawan mutuwar cell cell ATO, yana nuna cewa ATO yana haifar da mutuwar kwayar halitta a cikin kwayoyin MG-63.
Wu da abokan aiki sun kammala, "A haɗuwa, waɗannan bayanan sun nuna cewa ATO ta haifar da mutuwar kwayar osteosarcoma ta hanyar haifar da matsanancin matsayi na autophagy, wanda aka sanya shi ta hanyar hanyar ROS-TFEB. Binciken na yanzu yana samar da sabon magunguna na ATO a cikin osteosarcoma. "
Kalma Daga
A cikin shekaru talatin da suka gabata, APL ya bar mummunan cututtukan da ya kamu da cutar. Sanya dabarun da ATRA, chemotherapy, kuma, kwanan nan, ATO, ana daukar su a cikin wadannan ci gaba.
Da waɗannan ci gaba, har yanzu akwai wasu "yankunan da ba su da tabbas," duk da haka. Tsawon tsawon lokaci na tsaro da inganci na ATO za a iya dauka a nan, koda yake bayanan lokaci mai tsawo tare da ATO + ATRA ya ruwaito haka har yanzu sun kasance m. Wani yanki wanda ba a san shi ba ne wanda shine mafi mahimmancin maganin magancewa a zamanin ATRA / ATO.
> Sources:
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> Lu W, Yang C. Hanyoyin arsenic trioxide a kan furucin ezrin a cikin carcinoma hepatocellular. Medicine (Baltimore). 2017 Sep; 96 (35): e7602.
> Wang H, Liu Y, Wang X, et al. Cibiyar nazari ta asibitoci da aka ƙaddamar da ilimin likitancin gida da aka hada da arsenic trioxide don maganin hewacellular carcinoma. Ciwon daji . 2015; 121 (17): 2917-25.
> Wang L, Liang W, Peng N, et al. Sakamakon maganin antitumor na arsenic trioxide tare da kwayoyin cytotoxic T a cikin ƙananan ƙwayoyin metastasis. Oncotarget . 2017; 8 (65): 109609-109618.