Umzamo wokunqoba umdlavuza ukhuluma nezifiso eziyisisekelo zabantu. Imelela uhlobo lomuntu oyimvelo olufana nokuhamba enyangeni noma ukuthola isisombululo sokulamba emhlabeni.
Nginesiqiniseko sokuthi abaningi bethu bacabanga ukuthi, uma abacwaningi beke bakwazi ukuthola ukwelashwa komdlavuza , ukutholakala kokuguqulwa komhlaba kuzoba amashumi eminyaka noma amakhulu eminyaka. Phela, umdlavuza uyisifo esiyingozi, esiyinkimbinkimbi nesinkimbinkimbi-isifo esinezinto eziningi esingayifunda ngazo.
Kodwa-ke, abacwaningi eDuke University Medical Centre baye benza ukutholakala okumangalisayo: Kwezinye abantu abane-glioblastoma multiforme ephindaphindiwe, uhlobo lomdlavuza wengqondo, ukutheleleka nge-poliovirus kusetha impendulo yomzimba yokubulala igciwane.
Yini i-Glioblastoma Multiform?
I-Glioblastoma multiforme (i-GBM) isifo somdlavuza okhula ngokushesha esivela kuma-glial cells engxenyeni ye-cerebral yobuchopho (izifunda zesikhashana nezingaphambili). Ama-glial cell ngokuvamile asekela umsebenzi wezingqamuzana ezivamile zobuchopho, kodwa uma ukukhula kwabo kuhamba nge-haywire, njengoba kunjalo neBanga IV GBM, umdlavuza ubulala abantu abaningi ezinyangeni ezingaba ngu-15. Amathumba e-GBM angaba kabili ngobukhulu njalo emavikini amabili.
I-GBM ithinta abantu abangaba ngu-2 kuya kwezingu-3 ngamaphesenti angu-100 futhi ama-akhawunti angama-52 wamaphesenti ayisisindo oyinhloko (i-GBM ayidluli kalula noma isakazeka). Phakathi kuka-2005 no-2009, iminyaka yobudala bokufa kwalesi sifo somdlavuza ebuchosheni yayingu-64.
Ngeshwa, kubantu abane GBM, ukuphumelela kwezinketho zokwelashwa zamanje ezihlanganisa ukuhlinzwa, i-chemotherapy, ne-radiotherapy kulinganiswa ezinyangeni ezimbalwa zokusinda okungeziwe, futhi eziningi zalezi zinyanga ezengeziwe zenza impilo engafanele.
Izimpawu ze-GBM zihlobene nokuvuvukala nokuguqulwa kwezakhiwo zobuchopho (umphumela omningi) obangelwa isisu kanye ne-edema ehlobene noma ukuvuvukala. I-tumor, engaba ubukhulu bebhola legolfu, imishini yokucindezela kwezinye izakhiwo zobuchopho obangela:
- Izinsizwa
- Ukulahlekelwa kwesifiso
- Umbono ophundlekile
- Ukuzizwa
- Ukuvota
- Kunzima ngenkulumo
- Kunzima ngokuqaphela
Umlando Omfushane we-Virus Oncolytic
Kungakhathaliseki ukuthi kungase kuzwakale kangakanani, umkhuba wokusebenzisa amagciwane ukuphatha abantu abanomdla akuyona into entsha futhi kwaphakanyiswa kuqala ekuqaleni kwekhulu lama-20. Kule minyaka yokuqala yokwelashwa komdlavuza (indlela ngaphambi kwe-OSHA), sasingenayo indlela enhle yokwelapha umdlavuza, ngakho odokotela kanye nabagula umdlavuza bazimisele ukuzama noma yini okubandakanya ukuvezwa kwezicubu ezithathelwanayo noma izifo zomzimba. Ngokwesibonelo, ngo-1949, abantu abane- Hodgkin's disease, umdlavuza we-lymph nodes, babenegciwane lesandulela ngculaza.
Njengoba kungenzeka kulindeleke, ukuthelela abantu abanezinambuzane ezingakhethi kwenza okungenani ukuthuthukisa izimpilo zalabo abanomdlavuza (nakuba ngezikhathi ezithile kwabulala izingxenye zezinambuzane noma kubangele ukukhipha isikhathi esifushane izifo).
Kusukela kuma-1950, sazi okuningi mayelana nama-virus; manje siwaqonda kangcono kunanoma iyiphi enye imvelo ephilayo. Siphinde sazi ukuthi singakhiqiza kanjani futhi sizenze kanjani izakhi amagciwane kuma-laboratory izilungiselelo. Ngakho-ke, singenza amandla amagciwane ukuba abe yi- virus s syndrome noma abathwali bokunakekelwa okwenqabela isimiso somzimba samasosha omzimba. Okubaluleke kakhulu, lezi amagciwane ezingenalutho kudingeka zibulale amaseli we-tumor kuphela futhi zingahlaseli amangqamuzana avamile angabantu.
Immunotherapy: Uma Amalungu Athu Ebulala Amapulazi-Amathumba
Amangqamuzana omzimba abulalayo ngoba avikela isimiso sethu somzimba omzimba. I-cancer immunotherapy yinkambu yezokwelapha ehlola indlela yokukhipha umdlavuza njengangaphandle, futhi ngaleyo ndlela ihlanganisa umzimba wesiguli somzimba ukuze unqobe umdlavuza. Ukusetshenziswa kwegciwane le-PVS-RIPO ye-oncolytic kubantu abano-GBM kubonisa ukuthuthuka okuphawulekayo nokukhuthazayo kuze kube manje emkhakheni we-cancer immunotherapy.
Uma igciwane linikezwa esihlakalweni, imilingo yenzeka. Ngokwe-athikili yokubuyekeza eyabhalwa abacwaningi bamaDuke futhi yanyatheliswa eCancer ngoNovemba 2014, le nqubo ihilela:
- I-cytotoxicity ngqo yegciwane
- Ukuqalisa ukusebenza kwe-antiviral
- Ukugqugquzela okuphazamisayo okuphazamisayo
- Ukuqashwa kwezimpendulo zomthelela we-immune effect.
Ngokuyinhloko, ngemva kwe-PVS-RIPO (i-poliovirus e -colytic) ehlakaza isisu se-GBM (ubuchopho), imizimba yethu iyaqaphela "i-tumor-tumor" njengobuthi onobuthi. Lokhu kuqashelwa kubeka i-alamu ukuze amasosha omzimba ahambe empini ngesifo se-polio. Okuphawulekayo kule mpi ukuvuvukala, impendulo yemvelo yomzimba.
Imiphumela Kusukela ku-PVS-RIPO Isigaba I-Trial I
Ku-Duke's Preston uRobert Tisch Brain Tumor Centre, abacwaningi basebenze iminyaka yokusebenza kwamabhentshi athuthukisa nokuhlola i-PVS-RIPO. Ngokucacile, laba baphandi bathathe impilo, baphazamisa i-poliovirus futhi banqamula i-ribosome eguquguqukayo edala i-ribosome edala i-rhinovirus ebangela ukungabi nengozi. Khona-ke, kulesi sivivinyo somtholampilo se-PVS-RIPO Phase 1, laba cwaningi bafaka ngokuphazamisa (inqubo ebizwa ngokuthi i-intratumoral-enhanced delivery delivery) eyenziwe nge-catheter) le poliovirus engakhohlisi emathunjini okuqala e-brain.
Izidumbu ezithola umjovo we-poliovirus zaziyi-1 kuya ku-5 cm, izikhumba ze-GBM ezizimele zingaphansi kwamamitha angu-1 ukusuka ku-ventricles yobuchopho. Ngaphandle kokuba nezicubu ezilinganiselwe, ama-PVS-RIPO Phase I abacwaningi bezokwelapha babe ne-GBM ephindaphindiwe ngemuva kokwelashwa kwangaphambilini (ukuhlinzwa, chemotherapy, kanye ne-radiotherapy), bebengasatholi ukwelashwa okunjalo, futhi bebenomzimba omuhle nokusebenza kwansuku zonke (i-KPS enkulu ngaphezu noma elingana no-70). Okokugcina, abahlanganyeli kumele baphinde bagonywe ngezokwelapha. Ngokwengqikithi, i-oncolytic virus PVS-RIPO okwamanje ihlolwe njengokwelashwa kokugcina emidlalweni yabantu abadala abasebenzisa izicubu ezibucayi ezivamile.
Ngokuqinisekile, kuthathwa okungaphezu kweyishumi ucwaningo lwesayensi lwezokwelapha oluyisisekelo (olwenzelwe izitsha zikaPetri nasezilwaneni) kanye nezigidi zamaRandi ukuze abacwaningi bakwazi ukubona ukuthi i-PVS-RIPO ingaphatha nge-GBM ngokuphumelelayo. Ngokucacile, i-PVS-RIPO ine-tropism noma i-intimate for molecule ye-nectin-5 (Necl5), i-molecule yokunamathela kweseli evezwe ngama-GBM stem cells hhayi emaseli ajwayelekile we-somatic. Ngaphezu kwalokho, i-Necl5 ibuye iboniswe kwezinye izicubu ezihlukahlukene njenge-colorectal carrectoma, i-lung adenocarcinoma, i-cancer yamabele, ne-melanoma, ekhomba ukuthi i-PVS-RIPO ingase isebenze ekwelapheni kwamanye amagciwane.
Uma isifo se-poliovirus esingazimele sithatha, izicubu ze-GBM zabahlanganyeli ocwaningweni zihlolwa ngokusebenzisa i-serial 3-D MRI. Ekuqaleni, imifanekiso ye-MRI ibonisa ukuvuvukala kwesisu, isibonakaliso sokuthi isimiso somzimba samasosha omzimba sizolwa nesifo se-polio. Lokhu ukuvuvukala nokuhlelwa kwe-edema (ukuvuvukala) kwandisa izimpawu ze-GBM njengezinkinga ngenkulumo, ukuqonda kanye nokulahlekelwa kwezinzwa. Eminye imiphumela emibi yokwelashwa ihlanganisa isifo sohudo.
Eziningi zeziguli ezisaphila ngemuva kokwelashwa nge-PVS-RIPO, into emangalisayo yenzeke ezinyangeni ezimbalwa ngemuva kokwelashwa. Izidumbu ziqala ukuwohloka, futhi ezigulini zokuqala ezimbili ziphethwe emuva ngo-2012, izicubu zinyamalale!
Nazi ezinye izinto ezitholakalayo ezivela ku-PVS-RIPO Isigaba se-Phase I sokuhlola:
- Kulaba bantu abangu-22 abahlinzekwe nge-poliovirus ye-poliovirus PVS-RIPO, abangu-11 basaphila.
- Umuntu oyedwa waqeda ngesikhathi sokususwa kwe-catheter ethwele i-PVS-RIPO.
- Iziguli ezimbili zokuqala ezihlinzekwa i-PVS-RIPO ngo-2012 zisaphila! Ngonyaka ka-2015, usuku lokuqala lokushicilelwa kwalesi sihloko, bebephila iminyaka emithathu futhi bebala.
- Abacwaningi manje bakholelwa ukuthi umthamo ophakathi we-PVS-RIPO uhamba phambili.
- Kushone abantu abaningi ngemuva kokuthola isilinganiso esiphezulu se-PVS-RIPO.
- Ukusinda okuphakathi kweziguli ezine-GBM ezithola i-poliovirus engavamile kuyinyanga ezingu-6. (I-Median iyinkhomba yephakathi nendawo.)
Kumele sikhumbule ukuthi kunoma yisiphi esinye isifo, izinga lokushona kwamaphesenti angu-50 cishe libonakala lingasebenzi. Kodwa-ke, kubantu abane GBM, enye yezinto ezimbi kunazo zonke zomdlavuza ngaphandle, iqiniso lokuthi isigamu sabantu basaphila ngemuva kokwelashwa nge-PVS-RIPO imangalisa kakhulu. Futhi ukusinda kweminyaka engu-3 noma ngaphezulu ngemuva kokwelashwa kokuhlola, njengoba kunjalo nabathintekayo abacwaningi ababili, akuzwakala.
Nakuba imiphumela esiyibonayo ekuvivinyweni koMtholampilo weDuke, ukusho okungenani, ekhuthaza kakhulu, kumelwe sikhumbule ukuthi le miphumela ibonisa usayizi wesampula omncane ngempela. Sidinga imiphumela enikwe amandla aphezulu ukuze siqiniseke ukuthi lezi ziqalo zokuqala azizange zishintshe noma zifaneke kuphela isiqephu sabantu ngokubanzi.
Kulo lonke iqiniso, abacwaningi bakaDuke basengumlenze wokuqala wokuhamba kwabo, njengoba nje bazimisele ukuthola umthamo osebenzayo. Kukhona imibuzo eningi ekhona ukuthi kungani izifundo ezengeziwe zikhona emisebenzini, futhi ngokuqinisekile lezi zifundo zizocacisa ukuthi ubani ongazuza ku-PVS-RIPO ukwelashwa. Ngokucacile, siyazi ukuthi leyo poliovirus isebenze kubantu abadala abane-GBM, kepha abantwana bathola i-GBM futhi futhi bangazuza kulolu hlobo lwezokwelapha. Ngaphezu kwalokho, asazi ukuthi kwenzekani uma i-PVS-RIPO igciwane lesandulela ngculaza linikezwa ekuqaleni ngesikhathi somtholampilo womuntu we-GBM.
Ezokwelapha, igama elithi "ukwelashwa" lilayishwa nge-connotation. Kodwa-ke, ezigulini ezingu-2 ezitholwe nge-poliovirus ezingekho emthethweni ngonyaka ka-2012 futhi manje azikho umkhondo obonakalayo womdlavuza womqondo (zisekuseni okuqhubekayo), ngokuqinisekile kubonakala sengathi i-PVS-RIPO iyindlela yokwelapha. Okumangalisa nakakhulu kunokwelashwa komdlavuza obulalayo wengqondo, noma kunjalo, i-PVS-RIPO ingasetshenziswa ukuphatha (ukwelapha) ezinye izinhlobo zomdlavuza njenge-colorectal carcinoma, i-lung adenocarcinoma, i-cancer, ne-melanoma.
Isikhathi kanye nabasindile be-GBM abengeziwe kuphela bazokwazisa ukuthi i-PVS-RIPO ingayiphilisa ngempela i-GBM. Kulindeleke ukuthi i-PVS-RIPO njengokwelashwa kwe-GBM ingashesha ukuthola ukwamukelwa kwe-FDA yokuphefumula okuzokwenza kube nokufinyelela okubanzi komphakathi kulolu hlobo lwezokwelapha ze-poliovirus. Abantu abengeziwe bathola ukwelashwa futhi bahlale ekulalelweni, ukwelashwa kuyoba incazelo ecacile yezenzo ze-PVS-RIPO.
Inothi kumfundi: Kwakuwumgomo wami ogcwele ukuxoxa nabacwaningi bomdlavuza eDuke University eqhuba uhlolo lwezokwelapha lwe-PVS-RIPO Phase I. Ngiyavuma ngokugcwele ukuthi lesi sihloko sisekelwe kuphela ekuchazeni kwami ukucwaninga okulinganiselwe kanye nokwaziswa kwalesi sihloko. Ukuze unikeze abafundi ukuhlolwa okunamandla, okuhambisanayo kanye okunembile komphumela we-PVS-RIPO ku-GBM, ngidinga ukufakwa kochwepheshe. Ngeshwa, ngemuva kokunakekelwa kwezindaba zonke kumaminithi angama-60 okubika ekutholeni abacwaningi bomdlavuza weDuke, angikwazi ukugcina ingxoxo ngaphambi kokushicilela okwesikhashana kwalesi siqephu. Ngenxa yalokho, ngaqoqa lonke ulwazi futhi ngenza ukuhlola kwami kwesihloko. Ngabe kufanele ngike nginikezwe ingxoxo nommeleli weqembu likaDuke lomcwaningomdlavuza, ngihlela ukushicilela isithasiselo kulesi sihloko okuchaza imininingwane yami.
Imithombo ekhethiwe:
Isihloko sokubuyekeza esibizwa ngokuthi "Virotherapy ye-Polio Veterinary of Cancer" yi-MC Brown nababhali be- Cancer ngo-2014.
I-Abstract ebizwa ngokuthi "I-ONCOLYTIC POLIO / RHINOVIRUS RECOMBINANT (PVSRIPO) NGOKWENZA I-GLIOBLASTOMA (GBM): ISIKHATHI SOKUQALA I-CLINICAL TRIAL EVALUATING INTRATUMORAL
UKUPHATHISWA "ngu-A. Desjardins nabambhali abambisene nabo abashicilelwe ku- Neuro-Oncology ngo-2014.
Isihloko esibizwa ngokuthi "Ukulungiselela i-poliovirus engavumelani ne-poliovirus yesicelo somtholampilo ngokumelene ne-glioblastoma multiforme" yi-C Goetz no-M Gromeier eshicilelwe ekubuyekezweni kwe- Cytokine ne-Growth Factor ngo-2010.
Isihloko esithi "Umlando Wezakhi Zama-Oncolytic: Genesise kuya ku-Genetic Engineering" ngu-E Kelly no-S Russell kusukela ku- Methrapie Therapy eyanyatheliswa ngo-2007.
Imaminithi engama-60 ekhethekile yokwelapha umdlavuza owabulala ngoMashi 29, 2015. UScott Pelley (umlobi), uMichael Radutzky (umkhiqizi) noDenise Schrier Cetta (umkhiqizi)