Umnqweno wokunqoba umdlavuza uthetha kwiminqweno ebalulekileyo yabantu. Imelela uhlobo lomntu obalaseleyo olufana nokuhamba kwinyanga okanye ukufumana isisombululo sokulamba kwehlabathi.
Ndiqinisekile ukuba abaninzi bethu bacinga ukuba, ukuba abaphandi banakho ukufumana unyango lomhlaza , ukufumanisa oku kuguquka kwehlabathi kuya kuba ngamashumi eminyaka okanye iikholeji kude. Emva koko, umdlavuza unobungozi obunobungozi, obuninzi kwaye obunzima-isifo esiye sinezinto ezininzi zokufunda ngazo.
Nangona kunjalo, abaphandi kwi-Duke University Medical Centre baye bafumanisa into emangalisayo: Kweminye abantu abane-glioblastoma multiforme ephindaphindiweyo, uhlobo lomhlaza womkhuhlane, ukusuleleka kwi-poliovirus ibeka impendulo yomzimba yokubulala umzimba.
Yintoni i-Glioblastoma Multiform?
I-Glioblastoma multiforme (i-GBM) ngumhlaza okhula ngokukhawuleza ovela kwiiseli ze-glial kwingxenye yecerebral yengqondo (iindawo zengingqi kunye neengingqi). Iiseli ze-Glial zihlala zixhasa umsebenzi weeseli zeengqondo eziqhelekileyo, kodwa xa ukukhula kwazo kuhamba nge-haywire, njengokuba kunjalo neBakala IV GBM, umhlaza ushaya abantu abaninzi kwiinyanga ezili-15. Iimvumi ze-GBM zinokuphinda kabini ngobukhulu rhoqo kwiiveki ezimbini.
I-GBM ithinta abantu aba-2 ukuya ku-3 kwi-100,000 kunye neengxelo ezingama-52 ekhulwini zeengxaki zeengqondo eziphambili (i-GBM ayifanekiyo okanye isasazeka). Phakathi ko-2005 no-2009, ubudala bokufa kwesi sifo somhlaza wengqondo sasingu-64.
Ngelishwa, kubantu abane-GBM, impumelelo yeendlela zokhetho zonyango ezibandakanya ukuhlinzwa, i-chemotherapy, kunye ne-radiotherapy zilinganiselwa kwiinyanga nje zokusinda ezongezelelweyo, kwaye ezininzi zezi nyanga ezongezelelweyo ziphucula umgangatho wobomi obuthathaka.
Izibonakaliso ze-GBM zihlobene nokuvuvukala nokuguqulwa kwezakhiwo zeengqondo (umphumo osisiseko) obangelwa yi-tumor kunye ne-edema ehambelana okanye ukuvuvukala. I-tumor, enokubaluleka kwebhola yegolfu, ukushicilela kwezinye izakhiwo zobuchopho obangela ukuba:
- Intloko
- Ukuphelelwa kwesidlo
- Umbono ongezantsi
- Ukuxhamla
- Ukuvutha
- Unzima ngokuthetha
- Inkathazo kunye nokuqonda
Imbali emfutshane ye-Oncolytic Virus
Kungakhathaliseki ukuba kunzima kangakanani, ukusetyenziswa kweentsholongwane ukuphatha abantu abanomdla akuyona into emitsha kwaye kwakuqale kucetyiswa ekuqaleni kwekhulu lama-20. Kule minyaka yokuqala yonyango lomhlaza (indlela phambi kwe-OSHA), sasingenayo indlela efanelekileyo yokunyanga umdlavuza, ngokunjalo oogqirha kunye nomdlavuza wesibeleko bazimisele ukuzama nantoni na kubandakanywa ukuvezwa kwezicubu ezithintekayo okanye izifo zomzimba. Ngokomzekelo, ngo-1949, abantu abanesifo sikaHodgkin, umhlaza we-lymph nodes, basulelekile ngegciwane le-hepatitis.
Njengoko kunokwenzeka ukuba kulindeleke, ukusulela abantu abaneentsholongwane ezingakhethiyo kubangelanga ukuphucula ubomi babantu abanomdlavuza (nangona ngezinye izihlandlo babulala iinxalenye zeentlungu okanye babangela ukuxolelwa kwexesha elifutshane kakhulu).
Ukususela kuma-1950, sazi ezininzi malunga ne-virus; ngoku siwaqonda kakuhle kunokuba nayiphi na into ephilileyo. Siyazi kwakhona indlela yokuvelisa nokuvelisa izifo kwiimpawu zelabhoratri. Ngaloo ndlela, siyakwazi ukwenza iipirisi zibe yi- virtual virus okanye izithinteli zonyango oluye lwasuka kwi-immune system system. Okubaluleke kakhulu, ezi zigulo ezinqabileyo zifuna ukubulala iisilini zeesisu kuphela kwaye azihlaseli izisele zesintu eziqhelekileyo.
Immunotherapy: Xa amaBhunga ethu ebulala ama-Polio-Tumors
Iiseli ezixhamlayo ziyabhubhisa ngenxa yokuba ziphepha umzimba wethu womzimba. I-cancer immunotherapy yintsimi yonyango ehlola indlela yokuxhatshaza umhlaza njengangaphandle, kwaye ngaloo ndlela unamathambo omzimba womzimba wokulwa nomdlavuza. Ukusetyenziswa kwintsholongwane ye-PVS-RIPO ye-oncolytic kubantu abano-GBM imela enye yeyona nto ibaluleke kakhulu kwaye ikhuthaze phambili kuze kube yimini kummandla we-immunotherapy.
Xa intsholongwane ihanjiswa kwi-tumor, kwenzeka umlingo. Ngokomxholo wokuhlaziywa obhaliwe ngabaphandi beDuke kunye nokupapashwa kwiCancer ngoNovemba 2014, le nkqubo iquka:
- I-cytotoxicity ngqo yentsholongwane
- Ukungasebenzi kwe-antitiviral activation
- Ukuvuselela okunyanzelisayo
- Ukuqashwa kwamaphenduleli omzimba omzimba.
Okokuqala, emva kwe-PVS-RIPO (i-pocolytic poliovirus) isasazeka kwi-GBM (ubuchopho), imizimba yethu iyayibona "i-tumor-tumor" njengetyhefu. Olu qwa lasela i-alamu ukuze i-immune system ihambe imfazwe nesifo se-polio. Indawo ephawulekayo kule mpi ukuvuvukala, ukuphendula komzimba wendalo.
Iziphumo ezivela kwi-PVS-RIPO Phase I Trial
KwiDuke kaPreston uRobert Tisch Ubungqingili beBhunga lokuLawula, abaphandi baye bachitha iminyaka yemisebenzi ebhenki ekuphuhliseni nokuvavanya i-PVS-RIPO. Ngokukodwa, aba baphandi baye bathatha ubomi, bagulisa i-poliovirus baza bavala umxhasi we-ribosome obangela ukuba i-polio ibe yinto engenakubungozi ye-rhinovirus ebangela ubanda. Emva koko, kwilingo le-PVS-RIPO yesigaba se-1 esicatshungulwayo, abaphandi baphakamisa (inqubo ebizwa ngokuba yi-intratumoral-enhanced delivery delivery) eyenziwe ngekathetri) le poliovirus ene-pocolytic kwi-tumor tumors of primary adults with GBM.
Iimvumi ezafumana ijoyivirus zaziyi-1 ukuya kwi-5-cm, i-tumm ye-GBM i-tumm tumors ubuncinane i-1 cm ukusuka kwii-ventricle zobuchopho. Ukongezelela ekubeni neengxaki ze-PVS-RIPO I-I-Phase I, abathathi-nxaxheba beklinikhi babenomdla we-GBM obuye wabuyela emva kwonyango lwangaphambili (ukuhlinzwa, i-chemotherapy, kunye ne-radiotherapy), bebengasamkeli unyango olunjalo, kwaye babenomsebenzi omhle kunye nokusebenza kwansuku zonke (i-KPS enkulu ngaphezu okanye lilingana no-70). Ekugqibeleni, abathathi-nxaxheba kufuneka banokugonywa ngeporiyo. Ngesixa-mali, i-virus ye-oncolytic ye-PVS-RIPO okwangoku ivavanywa njengonyango wokugqibela kwindlela yokusebenza kubantu abadala abaneengxaki zeengqondo eziphindaphindiweyo ezingaphelelanga ngobukhulu.
Ukuqinisekiswa, kuthathwa ngaphezu kweminyaka elishumi yophando lwezesayensi lwezonyango (ezenziwe kwiZitya zePetri nakwezilwanyana) kunye nezigidi zeedola kubaphandi ukuba bafumane ukuba iPVS-RIPO ingayiphatha kakuhle i-GBM. Ngokukodwa, i-PVS-RIPO ine-tropism okanye inxanxathela ye-molecule ye-nectin-ne-5 (Necl5), i-molecule-adhesion molecule ichazwe kwii-stm cell stem kwaye zingekho kwiiseli eziqhelekileyo ze-somatic. Ngaphezulu, i-Necl5 iphinda iboniswe kwezinye iimvumi ezifana ne-colorectoma carcinoma, i-lung adenocarcinoma, i-cancer yebele, kunye ne-melanoma, ebonisa ukuba i-PVS-RIPO inokusebenza ngonyango lwezinye i-cancer.
Xa i-poliovirus i-oncolytic ibamba, iimpawu ze-GBM zabathathi-nxaxheba kwisifundo ziyahlolwa ngokusebenzisa i-serial 3-D MRI. Ekuqaleni, imifanekiso ye-MRI ibonisa ukuvuvukala kwe-tumor, uphawu lokuba umzimba womzimba uya kulwa ne-tumor-tumor. Oku kuvutha kunye ne-edema (ukukhukhuma) iimpawu ezinzima ze-GBM njengeengxaki zentetho, ukuqonda kunye neentsilelo zengqondo. Eminye imiphumo emibi yonyango ibandakanya uhudo.
Kwiintlobo ezininzi zezigulane ezisaphila emva kokwelashwa nge-PVS-RIPO, into emangalisayo yenzeke emva kweenyanga ezimbalwa emva kokonyango. Amathumba aqala ukuhla, kwaye kwizigulane zokuqala ezi-2 ziphethwe ngendlela ehamba phambili ngo-2012, izidumbu ziye zaphela!
Nazi ezinye iziphumo ezithile ezivela kwi-PVS-RIPO Isigaba I-esilingo sonyango:
- Kwabantu abangama-22 abaye balawulwa kwi-poliovirus ye-poyviry PVS-RIPO, abayi-11 basaphila.
- Umntu oyedwa wabhalwa ngexesha lokususwa kwecatheter ethwele i-PVS-RIPO.
- Izigulane zokuqala ezi-2 ezilawulwe i-PVS-RIPO ngo-2012 zisaphila! Ngo-2015, umhla wokuqala wokushicilela kweli nqaku, baye baphila iminyaka emithathu baze babale.
- Abaphandi ngoku bakholelwa ukuba umlinganiselo ophakathi we-PVS-RIPO ulungile.
- Abantu abaninzi baye bafa emva kokufumana amanani aphezulu ePVS-RIPO.
- Ukusinda komzimba kwezigulane ezine-GBM ezifumana i-poliovirus kwi-poliovirus ziinyanga ezintandathu. (IMedian isalathisi se-middle point).
Simele sikhumbule ukuba nakweyiphi na esinye isifo, i-50% yezinga lokushona ngokubonakalayo libonakala lingenakwenzeka. Nangona kunjalo, kubantu abane-GBM, enye yezona zihlobo ezinobungozi obukhulu kunoko, ukuba isiqingatha sabantu basaphila emva kokuba unyango lwe-PVS-RIPO luyamangalisa. Kwaye kuqhubekeka iminyaka engama-3 okanye ngaphezulu emva kokunyangwa kwonyango, njengokuba kunjalo nabathathi-nxaxheba aba-2, abayivakalayo.
Nangona iziphumo esizibonayo kwi-Duke clinical trial, ukuba zincinci, zikhuthaze kakhulu, simele sikhumbule ukuba ezi ziphumo zimelela ubungakanani besampula. Sifuna iziphumo eziphakamileyo ezisezantsi ukuze siqinisekise ukuba ezi ziphumo zokuqala azizange zihluthe okanye zimele kuphela isiqendu sabantu ngokubanzi.
Kuyo yonke inyaniso, abaphandi abaDuke bahlala nje ngomlenze wokuqala wohambo lwabo, emva kokuba bazimisele ukufumana i-dose esebenzayo. Unemibuzo ehleliyo yimiba kutheni uphando olongezelelweyo lusebenza kwimisebenzi, kwaye ngokuqinisekileyo ezi zifundo ziza kubonisa ukuba ngubani onokuzuza kwi-PVS-RIPO unyango. Ngokukodwa, siyazi kuphela ukuba i-poliovirus isebenze kubantu abadala abane-GBM, kodwa abantwana banokufumana i-GBM, kwaye banokufumana inzuzo kulolu hlobo. Ngaphezu koko, asiyazi into eyenzekayo xa i-PVS-RIPO kwi-viral virus ilawulwa ngethuba ngexesha lekliniki yomntu ye-GBM.
Kwiyeza, igama elithi "unyango" lilayishwa ngegama. Nangona kunjalo, kwizigulane ezi-2 ezifumana i-poliovirus ye-poliovirus ngo-2012 kwaye ngoku ayinayo imbonakalo ebonakalayo yomhlaza wengqondo (inokukhululwa okuqhubekayo), ngokuqinisekileyo kubonakala ngathi i-PVS-RIPO yonyango. Nangona kunommangaliso kunokonyanga komhlaza wengqondo obulalayo, nangona kunjalo, ithemba lokuba iPVS-RIPO ingasetyenziselwa ukunyanga (unyango) nezinye iintlobo zomhlaza ezifana ne colorectoma, i-lung adenocarcinoma, i-cancer yebele kunye ne-melanoma.
Kuphela ixesha kunye nabasindileyo be-GBM baya kubaxelela ukuba i-PVS-RIPO ingayiphilisa ngokwenene iGMM. Kukulindeleke ukuba i-PVS-RIPO njengonyango lwe-GBM izakufumana ngokukhawuleza ukunyulwa kwe-ADA yokunika unyango oluza kunika ufikeleleko olubanzi loluntu kulolu hlobo lwonyango lwe-poliovirus. Abantu abaninzi befumana unyango kwaye bahlale bexolelwa, unyango luya kuba yinkcazelo efanelekileyo yezenzo ze-PVS-RIPO.
Inqaku kumfundi: Injongo yam epheleleyo yokudliwano-ndlebe nabaphandi bomdlavuza kwiYunivesithi yaseDuke eqhuba isilingo se-PVS-RIPO Isigaba I. Ndivuma ngokuqinisekileyo ukuba eli nqaku lisekelwe kuphela kwisicatshulwa sam sophando olunqongophele kunye nokupapashwa kwesi sihloko. Ukuze kulungiselelwe abafundi ukuba bahlolisise, bahlalutye kwaye bachaneke ukuvavanya kwefuthe le-PVS-RIPO kwi-GBM, ndifuna uncedo lwengcali. Ngelishwa, ekuhambeni kwayo yonke ingqwalaselo yeendaba ezisezantsi ukuya kuma-60 imizuzu yokunika ingxelo kwiingcaphephe zabaphengululi be-Duke, ndakwazi ukufumana udliwano-ndlebe phambi kokushicilelwa ngokukhawuleza kwesi siqwenga. Ngenxa yoko, ndaqokelela yonke ingcaciso kwaye ndenza ukuhlola kwam kwesihloko. Ngaba ndimele ndinikwe udliwano-ndlebe nommeli weqela lophando lomdlavuza weDuke, ndiceba ukushicilela i-addendum kweli nqaku elineenkcukacha zam ziphumo.
Imithombo ekhethiweyo:
Inqaku elihlaziyiweyo elibizwa ngokuthi "i-Pocolytic Virotherapy yeCarcer" yi-MC Brown kunye nababhali be- Cancer ngo-2014.
I-Abstract enegama elibizwa ngokuthi "I-ONCOLYTIC POLIO / RHINOVIRUS RECOMBINANT (PVSRIPO) KWI-GLIOBLASTOMA (GBM) EQHUBEKILEYO: ISIGABA SOKUQALA ISIQOQO SOKUKHALWA KWESIKHONI
ULAWULO "ngu-A. Desjardins kunye nababhali be-co-oshicilelwe kwi- Neuro-Oncology ngo-2014.
I-Article ethi "Ukulungiselela i-pocolytic recombinant oncolytic recombinant application for clinic against glioblastoma multiforme" ngo-C Goetz kunye no-M Gromeier epapashwe kwi- Cytokine kunye ne-Growth Factor Reviews ngo-2010.
I-Article ethi "Imbali ye-Virtual Oncolytic: iGenesis ukuya kwi-Genetic Engineering" ngu-E Kelly no-SUS Russell ukusuka kwi- Molecular Treatment epapashwe ngo-2007.
Imizuzu engama-60 ekhethekileyo yokubulala i-Cancer yokubulala ingqungquthela eyenziwe ngoMatshi 29, 2015. UScott Pelley (umthunywa), uMichael Radutzky (umlimi) kunye noDenise Schrier Cetta (umvelisi)