Kuedza kukunda kenzati kunotaura kune zvido zvevanhu zvakakosha. Iyo inomiririra kadhidi yemunhu yakasiyana-siyana yakadai sokufamba kumwedzi kana kuwana mhinduro yenzara yenyika.
Ndine chokwadi chokuti vazhinji vedu vanofunga kuti, kana vatsvakurudzi vakambogona kuwana mushonga wekenza , kuwanikwa kwenyika ino-kuchange kwave makumi emakore kana mazana emakore kure. Mushure mezvose, kenza chirwere chinotyisa, chakasiyana uye chakaoma-chirwere chatichiri nezvimwe zvakawanda kudzidza nezvazvo.
Zvisinei, vatsvakurudzi veDuke University Medical Centre vakagadzira kushamisika kunoshamisa: Kune vamwe vanhu vane glioblastoma multiform vanogara vachirarama, rudzi rwekenza yeuropi, hutachiona hweporiyovirus hunogadzirisa mhinduro yemusununguko inouraya chiremera.
Chii Chinonzi Glioblastoma Multiform?
Glioblastoma multiforme (GBM) chirwere chinokurumidza kukura chinowanikwa kubva mumasero emagetsi mumucheto wechikamu cheropi (nzvimbo dzepakati uye dzakatangira). Glial cells zvinowanzotsigira basa remasero ehutano, asi apo kukura kwavo kunowedzera haywire, sezvinoitika neBanga IV GBM, kenza inouraya vanhu vazhinji mukati memwedzi inenge gumi nemashanu. Mamiriyo eGMM anogona kudarika muhukuru masvondo maviri.
GBM inokanganisa vanhu 2 kusvika ku3 pa100 000 uye inokwana 52 muzana yemakumbo ekutanga europi (GBM kazhinji haina mashiasi kana kupararira). Pakazosvika 2005 na2009, nguva yepakati yekufa kubva pamukenza uropi iyi yaiva 64.
Zvinosuruvarisa, kune vanhu vane GBM, kubudirira kwemazuva ano maitiro ekurapa kusanganisira kuvhiyiwa, chemotherapy, uye radiotherapy inotarwa mumwedzi mishoma yekuwedzera kuponeswa, uye mazhinji emwedzi iyi yakawedzerwa anorambidza hutsika hwakanaka hwehupenyu.
Zviratidzo zveBGM zvakabatana nekudzima uye kuchinja kwehutano hwehupi (mass effect) inokonzerwa nechirwere uye edema inobatanidza kana kupfugama. Dumbu racho, iro rinogona kuenzana nebhokisi yegorofu, kushandiswa kune zvimwe zvivako zveuropi zvichikonzera:
- Headaches
- Kufirwa kwechido
- Chiratidzo chakasvibiswa
- Kugumburwa
- Kudzora
- Dambudziko nokutaura
- Dambudziko nekugogodza
Nhoroondo Pfupfupi yeOncolytic Virus
Hazvina mhosva kuti ingangodaro yakajeka sei, tsika yekushandisa mavairasi kurapa vanhu vane kenza haina chinhu chitsva uye yakatanga kutaurwa mukutanga kwemazana makumi maviri. Mumakore aya okutanga ekurapa kwekenza (nzira isati yasvika kune OSHA), hatina nzira yakanaka yekurapa kenza, saka vanachiremba uye vanorwara nekenza vakange vachida kuedza chero chinhu chinosanganisira kusvibiswa kune utachiona hunotapukira kana muviri wemvura. Somuenzaniso, muna 1949, vanhu vane chirwere cheHodgkin, kenza yemakirinikodhi, vakatapukirwa ne hepatitis HIV.
Sezvo zvichida zvinogona kutarisirwa, kutapudza vanhu vane mavairasi asingasaruri vakaita zvishomanana kuvandudza hupenyu hweavo vane kenza (kunyange zvazvo pane dzimwe nguva yakauraya zvikamu zvemakumbo kana kukonzera kukanganiswa kwenguva pfupi kwekurapa kwezvirwere).
Kutanga muma1950, tinofanira kuziva zvakawanda nezvemavirusi; isu zvino tinovanzwisisa zviri nani kudarika zvimwe zvipenyu zvose. Isuwo tinoziva nzira yekuzvara uye mazita ekugadzirisa mavhairasi muzvirongwa zve laboratori. Nokudaro, tinokwanisa kuita kuti mavairusi ave sevircolytic viruse s kana vatakuri vemishonga inogadzirisa zvirwere zvemuviri. Chinonyanya kukosha, majekiseni aya anokonzera kuuraya masero emuviri chete uye asingasviki masero evanhu.
Immunotherapy: Apo Masimba Edu Anouraya Polio-Mishonga
Tumorome masero anouraya nokuti anodzivirira masimba emuviri wedu. Cancer immunotherapy ndiyo munda wemishonga inotsvaga nzira yekuderedza kenza sevatorwa, uye saka inoshandisa muviri wemuviri wechirwere kuti ukunde kenza. Kushandiswa kwehutachiona hwePVS-RIPO kune vanhu vane GBM inomirira chimwe chezvinhu zvakakosha zvikuru uye zvinokurudzira kusvika panguva ino mumunda wekenza immunotherapy.
Kana kamwe utachiona huchiendeswa kumarara, magetsi anoitika. Maererano nehurukuro yekuongorora yakanyorwa nevanyori veDuke uye yakabudiswa muCancer munaNovember 2014, izvi zvinosanganisira:
- Direct viral cytotoxicity
- Innate antiviral activation
- Stromal proinflammatory stimulation
- Kuchengetwa kwekugadzirisa mafungiro emune effector.
Chaizvoizvo, mushure mokunge PVS-RIPO (oncolytic poliovirus) inopararira mumaronda eBMM (brain), miviri yedu inoziva "tumarara-chironda" sehupfu. Kuzivikanwa uku kunogadzirisa alamu kuitira kuti maitiro ezvirwere zvemajeri ehondo apinde muhondo neyeturi yeporiyo. Chiratidzo chehondo iyi kuputika, maitiro emasikirwo emuviri.
Migumisiro Inobva PVS-RIPO Phase I Ongororo
PaDuke's Preston Robert Tisch Brain Tumor Center, vatsvakurudzi vakapedza makore emabasa ekuchengetedza uye kuedza PVS-RIPO. Kunyanya, avo vanotsvakurudza vakatora mararamiro, vakarwisa poliovirus uye vakashandura tsvina yakaipa ye ribosome inokonzera kuti chirwere cheporiki chisakanganise-chinokonzera rhinovirus. Zvadaro, munguva pfupi yapfuura PVS-RIPO Phase 1 yekuongororwa kwemakiriniki, vatsvakurudzi vakatsvaga (chirongwa chinonzi intratumoral convection-enhanced delivery and done through catheter) ichi chinokanganisa poliovirus mumakumbo ekutanga ehutano hwevanhu vakuru vane GBM.
Mishonga yakagamuchira chirwere chePoliovirus yaiva 1 kusvika ku5-cm, mamasimusi e-supratentorial GBM anenge 1 cm kubva muuropi ventricles. Kuwedzera pakuva nemavhutu akaenzana, PVS-RIPO Phase I yezvechirongwa chekutsvakurudza mutsvaga aive neGGM yakadzokorora mushure mekurapwa kwakapfuura (chirwere, chemotherapy, uye radiotherapy), vakanga vasingachagoni kurapwa kwakadai, uye vakanga vane nhengo yakanaka basa uye zuva nezuva (KPS yakawanda kudarika kana kuenzana nemakumi manomwe). Pakupedzisira, vatori vechikamu vanofanira kunge vakave vachakemerwa chirwere cheporiyo. Muchidimbu, oncolytic virusi PVS-RIPO iri kuongororwa sekupedzisira-mutsara mushonga mukushanda kwevanhu vakuru vane zvipembenene zvepfungwa zvekare zvakakosha muhukuru.
Kutaura chokwadi, zvakatorwa kudarika makore gumi ekutsvakurudza kwesayenzi yezvokurapa (yakaitwa paPetri ndiro uye mumhuka) pamwe nemamiriyoni emadhora kuti vatsvakurudzi vaone kuti PVS-RIPO inogona kubata zvakasimba GBM. Kunyanya, PVS-RIPO ine inotyisa kana kuti yakabatana nectin-semamolekari 5 (Necl5), se-cell-adhesion molecule inotsanangurwa muGGM stem masero uye kwete mumasero evanhu vanoita seastic. Uyezve, Necl5 inoratidzwawo mune dzimwe mishonga dzakasiyana-siyana sedororectal carcinoma, mapapu adenocarcinoma, makondombera emvere, uye melanoma, iyo inoratidza kuti PVS-RIPO inogona kushanda mukurapwa kweimwe kenza, zvakare.
Kana imwechete yepolystytic poliovirus inotora, matumire e GBM evatori vechikamu muchidzidzo anoongororwa achishandisa serial 3-D MRI. Pakutanga, MRI zviratidzo zvinoratidza kuvhiringidzika kwechirwere, chiratidzo chokuti muviri wechirwere chemuviri ucharwisana nechirwere cheporiyo. Izvi zvinopesana uye kuenderana edema (kukuputira) kunowedzera zviratidzo zveGGM sezvinetso nekutaura, cognition uye kukanganisa kwenzwi. Mimwe migumisiro yakaipa yekurapa inosanganisira marara.
Muzhinji vevarwere avo vachiri vapenyu mushure mekurapwa nePVS-RIPO, chimwe chinhu chinoshamisa chinoitika mwedzi mishomanana mushure mekurapa. Maviri acho anotanga kuderera, uye mune vekutanga 2 varwere vanobatwa nenzira zvakare muna 2012, matumara apera!
Heano zvimwe zviwanikwa zvakabva kuPVS-RIPO Phase I kuongororwa kwechipatara:
- Pakati pevanhu makumi maviri nevatatu vakashandiswa pacolytic poliovirus PVS-RIPO, 11 vachiri vapenyu.
- Mumwe munhu akaparara panguva yekubvisa katheter inotakura PVS-RIPO.
- Vokutanga 2 varwere vanopiwa PVS-RIPO muna 2012 vachiri vapenyu! Pakazosvika gore ra2015, chinyorwa chekutanga chakanyorwa chinyorwa ichi, vakagara makore matatu uye vachiverenga.
- Vanotsvakurudza iye zvino vanofunga kuti chiyero chepakati chePVS-RIPO chakanakisisa.
- Vanhu vanoverengeka vakafa mushure mekunge vawedzerwa kuwedzera kwePVS-RIPO.
- Kupona kwemajeri kwevarwere vane GBM vanowana pacolytic poliovirus mwedzi mitanhatu. (Midhiyamu inoratidza chiratidzo chekatikati.)
Tinofanira kuyeuka kuti kune chero humwe hutano, 50 muzana yehutano hwehuwandu inogona kunge inoratidzika isisina kunaka. Zvisinei, kune vanhu vane GBM, imwe yemhando dzakaipa dzekenza kunze uko, nokuti hafu yevanhu vachiri vapenyu mushure mekurapwa nePVS-RIPO inoshamisa chaizvo. Uye kupona kwemakore matatu kana kupfuura mushure mekurapa kwekuedza, sezvakaitika kune 2 vatsvakurudzi vekutsvaga, hakunzwisisiki.
Kunyange zvazvo mhinduro yatinoona kubva kuDucko muedzo wechipatara ndeyekuti, kutaura zvishomanana, kukurudzira zvikuru, tinofanira kuyeuka kuti izvi zvinogumira zvinomiririra soro duku duku. Tinoda zvikwereti zvakapiwa simba kuti tive nechokwadi chekuti izvi zvitsva zvitsva zvakanga zvisingacharegi kana kuti zvinomiririra chidimbu chevanhu vakawanda.
Muzvokwadi yose, vaDuke vatsvakurudzi vachiri mugove wokutanga wekufamba kwavo, vachangotora mukana unoshanda. Pane mibvunzo yakawanda inosara iyo ndechikonzero nei zvidzidzo zvinowedzera zviri mumabasa, uye zvidzidzo izvi pasina mubvunzo zvicharatidza kuti ndiani angabatsirwa nePVS-RIPO therapy. Kunyanya, tinoziva chete kuti poliovirus yakashanda kune vakwegura vane GBM, asi vana vanowana GBM, zvakare, uye vanogona kubatsirwa nechirwere chakadaro. Uyezve, hatizivi zvinoitika apo PVS-RIPO incolytic virusi inotarisirwa mberi panguva yekliniki yemunhu ye GBM.
Mukurapa, izwi rokuti "kurapa" rinotakurwa nezwi. Zvisinei, kune vatachiri 2 vakagamuchira pacolytic poliovirus muna 2012 uye iye zvino havana ruzivo rwakaratidzwa rwekenza yeuropi (iri mukuregererwa kwakasimba), iyo chokwadi inoratidzika sePVS-RIPO inoporesa. Kunyangwe zvinoshamisa kudarika mushonga wekenza yehupombwe inouraya, zvakadaro, ndiyo tariro iyo PVS-RIPO inogona kushandiswa kurapa (kurapa) mamwe maitiro ekenza sa colorectal carcinoma, lung adenocarcinoma, kenza yemazamu, uye melanoma.
Nenguva chete uye vazhinji vanopona neGMM vacharatidza kana PVS-RIPO inogona kuporesa zvechokwadi GBM. Zvinotarisirwa kuti PVS-RIPO sekusarudzwa kweGGM ingakurumidza kugamuchira chirongwa cheDAA chinoparadzanisa chirongwa chinozopa vanhu vakawanda ruzivo rwechirwere chechirwere cheporiyovirus. Kamwezve vanhu vanogamuchira kurapwa uye vanoramba vari mukuregererwa, chirwere chichave tsanangudzo yakajeka yezviito zvePVS-RIPO.
Nherechedzi kune muverengi: Yaiva chinangwa changu chakakwana chekubvunzurudza vatsvakurudzi vekenza kuDuke University vachiita chirongwa chePVS-RIPO Phase I kuchipatara. Ndinonyatsobvuma kuti nyaya ino inongobva pane zvangu zvangu zvitsanangudzo zvishoma nezvekutsvakurudza uye kugoverwa kwechinyorwa ichi. Mukupa kupa vaverengi kuongororwa kwakasimba, kwakanyatsorongeka uye kwakarurama kwePVS-RIPO kushanda kweGGM, ndinoda nyanzvi yekuita. Zvinosuruvarisa, pamusana pezvinhu zvose zvemashoko ekucherechedza kusvika kumaminitsi makumi matanhatu ezitaurire pamusoro pevatsvakurudzi vekenza yeDuke, ndakanga ndisingakwanisi kuwana dhaurirano mushure mekubudiswa kwakakodzera kwenguva ino. Nemhaka yei, ndakaunganidza zvose zvese uye ndakazviita ini pachedu. Ndinofanira here kubvunzurudzwa nemumiririri weboka rekutsvakurudza kenza reDuke, ndinoronga kuparidzira chinyorwa ichi chinyorwa chinotsanangura zvandinowana.
Zvisarudzo Zvitsva:
Nyaya yekuongorora inonzi "Oncolytic Polio Virotherapy yeCanscer" naCro Brown uye vanyori vanyori kubva kuCancer muna 2014.
Abstract yakanzi "ONCOLYTIC POLIO / RHINOVIRUS RECOMBINANT (PVSRIPO) MUNA RECURRENT GLIOBLASTOMA (GBM): FIRST PHASE I CLINICAL TRIAL KUZIVA NECHINHU
KUPARIDZA "naA Desjardins uye vanyori vanyori vakabudiswa muNeuro-Oncology muna 2014.
Chinyorwa chakanzi "Kugadzirira pecolytic poliovirus recombinant kune kliniki yekushandura glioblastoma multiforme" naC Goetz naM M Gromeier yakabudiswa muCytokine uye Growth Factor kuongorora muna 2010.
Chinyorwa chakanzi "History of Oncolytic Viruses: Genesisi kusvika kuGenetic Engineering" naE Kelly naS Russell kubva kuMuchipatara Kuchengetedzwa muna 2007.
Maminitsi makumi matanhatu kuurayiwa kenza inofanirwa musi waMarch 29, 2015. Scott Pelley (munyori), Michael Radutzky (mugadziri) uye Denise Schrier Cetta (mugadziri)