▎ PNC 27 Ubushakashatsi
Ni ubuhe buryo bukoreshwa muri PNC-27?
1, Kuvura leukemia:
PNC-27 ishoboye guhambira poroteyine ya HDM-2 kuri membrane ya selile kanseri kandi bigatuma habaho imyenge ya cytotoxic transembrane. Mu bushakashatsi bwakozwe ku ngirabuzimafatizo z'umuntu utera stem myeloid leukemia, HDM-2 byagaragaye ko igaragara cyane muri membrane ya U937 (acute monocytic leukemia), OCI-AML3 (acute granulomonocytic leukemia), na HL60 (acute promyelocytic leukemia) selile ya PNM-27 dehydrogenase) kurekura mu masaha 4. (LDH) kurekura mu masaha 4. Kwibasira HDM-2 kuri membrane selile bishobora kuba ingamba zishoboka zo kuvura indwara ya leukemia.PNC-27 yerekanye ibikorwa bikomeye byo kurwanya indwara ya leukemic mumirongo myinshi ya selile ya leukemia yibasira Membrane HDM-2 [1].
2. Bitera lysis selile
Ibikorwa nka peptide idahwitse:
Ubushakashatsi bwinshi bwerekanye ko PNC-27 itera lysis selile yibibyimba nka peptide idahwitse aho kuba igice. Kurugero, mubushakashatsi bwakozwe na kanseri yamabere ya MCF-7 hamwe na MCF-10-2A y’inyamabere y’inyamabere idahinduwe, selile zavuwe na PNC-27 hamwe n’icyatsi kibisi cyanditseho amino terminus na fluorescence itukura yanditseho carboxy terminus. Ibisubizo byerekanaga florescence itandukanye yumuhondo kuri kanseri ya kanseri ya min 30, byerekana ko peptide idahwitse yari ihari kuri kanseri ya kanseri kandi ikiyongera hamwe na lysis selile. Ibinyuranye, selile MCF-10-2A idahinduwe yabanje kwerekana florescence yumuhondo umwe, ariko irazimira. Bitandukanye na kanseri, utugingo ngengabuzima tutahinduwe twakomeje kuba ingirakamaro. Ibi byerekana ko PNC-27 itera ururenda rwa kanseri ikora kanseri ikora peptide yose, aho kuba agace [2].
Guhambira kuri HDM-2 gukora imiterere ya pore:
PNC-27 ikubiyemo urwego rwimiterere ya HDM-2 hamwe na peptide yinjira muri selile (CPP), itera kwibumbira mu mwobo uhuza HDM-2 kuri membrane selile, biganisha kuri lysis selile na necrosis. Ibarura ryingufu zerekana ko PNC-27 ikora urwego rufite HDM-2 mukigereranyo cya 1: 1, hamwe nurutonde ruyoboye rwerekana kure yikigo. Ubushakashatsi bwakozwe na immunoscanning electron microscopie bwerekanye ko hariho ibice byinshi bya nm 6 na 15 nm byanditseho uduce twa zahabu ku kigereranyo cya 1: 1 mu byobo biri hejuru y’uturemangingo twa kanseri twavuwe na PNC-27, byerekana ko ibyo bigo ari ingenzi mu miterere y’imyobo. Ibinyuranye na byo, nta byobo byakozwe mu kugenzura, fibroblast idahinduwe ivurwa na PNC-27 [3].
Kanseri y'urwagashya:
Igitabo cyitwa anticancer PNC-27 peptide itera na nérosose ya kanseri yandura ya MiaPaCa-2 ya kanseri muburyo bwa dose, ariko ntabwo ari uburozi kuri selile zisanzwe. Ubushakashatsi bwerekanye ko PNC-27, iyo ihujwe na Gemzar, imiti ya chimiotherapeutique ikoreshwa mu kuvura kanseri yandura, igira ingaruka za cytotoxique kuri selile MiaPaCa-2 kurusha Gemzar cyangwa PNC-27 yonyine. Ibi birashobora kuba biterwa nuko imyenge iterwa na PNC-27 yongerera ubushobozi ingirabuzimafatizo za kanseri kuri Gemzar, bigatuma Gemzar nyinshi yibasira kanseri ya kanseri [1].
Kanseri y'intanga ngore:
Mu murongo wa kanseri yintanga ngore SKOV-3 na OVCAR-3, poroteyine ya HDM-2 igaragara cyane kuri membrane selile.PNC-27 ifatanya na HDM-2 kuri selile, biganisha kuri nérosose yihuta. Ibinyuranye na byo, mu murongo utagenzuwe wo kugenzura umurongo HUVEC, gufatanya hamwe na cytotoxicity ya PNC-27 ntibyagaragaye kubera imvugo ntoya ya HDM-2 [1].
Kanseri y'amara:
PNC-27 itoranya yica kanseri y'urura runini. Mu mirongo itandatu ya kanseri y'inkondo y'umura, PNC-27 yafatanije na membrane HDM-2 kandi itera urupfu rw'uturemangingo (selile selile necrosis, kurekura LDH, membrane ifitanye isano na poroteyine V na sisitemu 3 negativite) gusa muri selile. Muri vivo, PNC-27 itera necrosis ya nodules yibibyimba ariko ntigire ingaruka kumubiri usanzwe [1].
3. Kunoza imikorere yo kurwanya ibibyimba
Guhambira Doxil:
Byagaragaye ko peptide ya PNC27, nka ligand yibasiwe, ishobora kongera cyane imbaraga zo kurwanya ibibyimba bya Doxil muri selile ya kanseri nziza ya HDM2. Umubare utandukanye wa peptide ya PNC27 winjijwe muri Doxil, hanyuma cytometrie itemba hamwe nisesengura rya conocal byakorewe kanseri ya C26 (HDM2-positif) na B16F0 melanoma (HDM2-mbi). Ibisubizo byerekanye ko PNC27-Doxil yerekanye uburyo bukomeye bwo gufata selile na cytotoxicity muri selile C26, mugihe ibisubizo bitagaragaye muri selile B16F0. Kurugero, PNC27-Doxil (peptide 100 PNC27) yongereye cyane uburyo bwo kuvura Doxil itagize ingaruka ku ikwirakwizwa ry’ibinyabuzima mu bibyimba bya C26 [4].
4. Kuvura kanseri yintanga hamwe na paclitaxel
Paclitaxel ikoreshwa cyane mu kuvura indwara mbi z’abagore, ariko yibasira uturemangingo tw’ibibyimba mu cyiciro cya M cy’ingirabuzimafatizo, hamwe na selile zo mu bindi byiciro bikomeza kubaho kandi bikaba byanashoboka ko ibibyimba byongera kubaho. Indwara ya kanseri ya Ovarian ID8 ingirabuzimafatizo za paclitaxel zagaragaye ko zigaragaza imvugo ya MDM-2 ndetse no kongera ubukangurambaga kuri PNC-27.Ingaruka za cytotoxic ya PNC-27 ziterwa no guhuza MDM-2, kandi guhagarika MDM-2 bibuza ingaruka zica PNC-27. Amashusho ya heterodrug yerekana ibipimo byahujwe, byerekana ingaruka zifatika hagati ya PNC-27 na paclitaxel [5] . Muburyo budasanzwe bwa kanseri yintanga (ID8), kongeramo PNC-27 mubuyobozi bwa paclitaxel buri cyumweru byagabanije cyane gukura kwikibyimba. Aya makuru yerekana ingaruka zifatika hagati ya PNC-27 na paclitaxel, hamwe na PNC-27 yibasira paclitaxel ikomeza kubaho no kunoza ingaruka zayo.
5. Kuvura kanseri yibanze ya epiteliyale
Ubushakashatsi bwerekanye imico yibanze ya kanseri ya epiteliyale ya kanseri ya kanseri ivuye ku barwayi barwaye indwara ya ovarian cystadenocarcinoma. Umwe muribo yavaga muri mucinous cystadenocarcinoma undi akomoka muri kanseri yo mu rwego rwo hejuru papillary plasmacytoid kanseri. Ubuvuzi bwa PNC-27 bwasuzumwe ku buryo bugaragara hifashishijwe uburyo bwiza bwo kureba microscopique y’umucyo hamwe no gukwirakwiza selile ya MTT kimwe no gupima dehydrogenase (LDH). Ibisubizo byerekanye ko PNC-27 yabujije imikurire ya selile yibanze ya kanseri yumuntu itandukanijwe na kanseri yintanga ebyiri epithelial kanseri muburyo buterwa na dose kandi yari cytotoxic kuri bo. Kugenzura peptide PNC-29 ntacyo byagize ku ngirabuzimafatizo za kanseri y'ibanze. Byongeye kandi, PNC-27 nayo ni cytotoxic kumurongo wa kanseri yintanga ya kanseri imaze igihe kirekire kandi irwanya chimiotherapie ..
Muri make, PNC-27, nka peptide ya anticancer peptide, yerekana imbaraga zikomeye zo gukoreshwa muburyo butandukanye bwo kuvura kanseri. Mu rwego rwa leukemia, PNC-27 yerekanye ingaruka zica zitoranijwe ziterwa na leukemia ikaze (urugero, U937, OCI-AML3, na HL60 selile) hamwe na selile K562 idafite p53, kandi igera ku ngaruka nziza za antitumor itera necrosis selile na lactate dehydrogenase. Mu kuvura kanseri yintanga, guhuza PNC-27 na paclitaxel byagaragaje ingaruka zifatika, zishobora kubuza cyane ikibyimba kandi kikaba kigifite ibikorwa byica selile zirwanya chimiotherapie. Byongeye kandi, guhuza PNC-27 hamwe nibiyobyabwenge bya liposomal (urugero Doxil) nka ligand yibasiwe birashobora kongera uburyo bwihariye bwo gutanga no kurwanya ibibyimba byibiyobyabwenge kuri selile yibibyimba ya HDM2. Ingaruka zayo zo kubuza epiteliyale ovarian kanseri kanseri progenitor irusheho kwemeza agaciro k'ubuvuzi. Kugeza ubu, PNC-27 yinjiye mu cyiciro cya mbere cy’amavuriro, kandi hakenewe ubundi bushakashatsi bw’amavuriro kugira ngo hemezwe umutekano wabwo n’igihe kirekire, kugira ngo butere imbere nk'igisubizo gishya cyo kuvura kanseri.
Ibyerekeye Umwanditsi
Ibikoresho byavuzwe haruguru byose byakorewe ubushakashatsi, byahinduwe kandi byakozwe na Cocer Peptides.
Umwanditsi w'ikinyamakuru
Sarafraz-Yazdi E ni umushakashatsi ufatanije n’imiryango myinshi, nka NomoCan, Ikigo cy’amaraso cya New York, kaminuza y’ubumenyi bw’ubuzima bwa SUNY Downstate, na New York Harbour VA Med Ctr. Ihuriro ryerekana uruhare rwe mubushakashatsi butandukanye ndetse nubuvuzi butandukanye.
Ibyifuzo bye mubushakashatsi mubyiciro bitandukanye nka Oncology, Medical Laboratory Technology, Pharmacology & Pharmacy, Biochemistry & Molecular Biology, and Research & Experimental Medicine. Ibikorwa bye muriki gice byerekana ubuhanga bwe nubwitange mugutezimbere ubumenyi muribi bice byingenzi byubumenyi bwubuvuzi nubushakashatsi. ni urutonde rwerekanwe [3].
