Youdaoplaceholder0 1.1 Umunyamuryango wihishe mumuryango wisukari ?

Nkibintu byingenzi byingirakamaro byibinyabuzima, sisitemu yo gutondekanya karubone ya hydrata imaze igihe ishimangirwa mubitabo: monosaccharide (nka glucose na fructose), oligosaccharide (nka lactose), na polysaccharide (nka krahisi). Nyamara, umwihariko wa mannose uri muri "indangamuntu ebyiri" - ntabwo igira uruhare mu guhinduranya ingufu gusa ahubwo ni "ijambo ryibanga" ryo gutumanaho. Mannose igaragara cyane muburyo bwubuntu muri pectine yimbuto za citrusi ninkuta za selile ya algae yinyanja. Mu mubiri wumuntu, ihinduka ishingiro ryimikorere yibikorwa byingenzi byumubiri nko kumenyekanisha ubudahangarwa no gufatira ingirabuzimafatizo binyuze muri N-ihuza glycosylation ihindura glycoproteine.

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Youdaoplaceholder0 1.2 Kumenyekanisha Iterambere kuva Mubuzima bwinkari kugeza abapayiniya ba kanseri ?

Nko mu myaka ya za 1980, umuganga w’ubuvuzi yavumbuye ko mannose ishobora gukumira indwara zanduza inkari mu guhagarika amarushanwa ya bagiteri itera indwara. Ubu buryo bwatumye igurishwa rishyushye ryibicuruzwa byubuzima bwa cranberry. Ariko kugeza mu mwaka wa 2018 ni bwo ubushakashatsi bwibanze bwakozwe n’ubushakashatsi bwa Kanseri mu Bwongereza (CRUK) mu kinyamakuru Kamere bwakuyeho umwenda ku mbaraga zabwo zo kurwanya kanseri: Mu buryo bw’imbeba ya kanseri yandura, kongeraho mannose 20% mu mazi yo kunywa byagabanije umuvuduko w’ikibyimba ku kigero cya 40%, kandi iyo uhujwe n’imiti ya chimiotherapie gemcitabine, igihe cyo kubaho cy’imbeba cyongerewe inshuro 2,3. Ubu buvumbuzi bwahinduye imyumvire isanzwe ivuga ko "isukari yose itera kanseri".

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Youdaoplaceholder0 Igice cya 2 Kumenyekanisha uburyo bwo kurwanya kanseri: bitatu "bifunga isukari" Fungura ubuzima bwa Tumor ?

Youdaoplaceholder0 2.1 Gushimuta Metabolic: "Ifarashi ya Trojan" yihinduye nka glucose ?

"Ingaruka ya Warburg" ya selile yibibyimba ituma glucose ifata inshuro icumi z'uturemangingo dusanzwe. Itsinda rya CRUK ryavumbuye binyuze muri tekinoroji ya karubone-13 isotope yerekana ko mannose ishobora kwinjira mu ngirabuzimafatizo za kanseri binyuze mu bwoko bumwe bwo gutwara glucose (GLUT1 / 3) ifite imiterere isa n'iya glucose. Ariko, nyuma yo kwinjira, ihita fosifora na hexokinase kuri mannose-6-fosifate (M6P). Hagati ya metabolike ntishobora kwinjira mu nzira ya glycolitike ahubwo ikusanyiriza mu ngirabuzimafatizo kugira ngo ibe "inzitizi ya metabolike", biganisha ku guhagarika synthesis ya ATP no guturika kw'ubwoko bwa ogisijeni ikora (ROS), amaherezo bigatuma apoptose ya selile ya kanseri (Ishusho 1).

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Youdaoplaceholder0 2.2 Amabwiriza ya Epigenetike: Kwandika "code ya memoire" ya selile kanseri ?

Mu 2023, itsinda ry’ubushakashatsi ryaturutse muri kaminuza ya Fudan muri Cell Metabolism ryongeye kwerekana ko mannose ishobora gukora nk "umwanditsi wa epigenome". Muburyo bwa pancreatic ductal adenocarcinoma (PDAC), kuvura mannose byagabanije cyane urwego rwa acetylation yurubuga rwa histone H3K27, bituma habaho guhagarika ibikorwa byandikirwa kuri oncogène MYC na KRAS. Ndetse igitangaje kurushaho, iyi ngaruka igaragara yo kongera gahunda irakomeza - nubwo ubuyobozi bwibiyobyabwenge bwahagaritswe, selile za kanseri ziracyafite imbaraga nke, zitanga ibitekerezo bishya byo kuvura bikabije.

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Youdaoplaceholder0 2.3 Immune microen ibidukikije ivugurura: Kurandura "kwiyoberanya isukari" ya PD-L1 ?

Itsinda rimwe ryasanze mubushakashatsi bwakurikiyeho ko mannose ishobora gukuraho uburyo bwo kwirinda indwara yibibyimba bivanga na glycosylation ihindura gahunda yurupfu rwa ligand 1 (PD-L1). Isesengura rusange ryakozwe ryerekanye ko mannose yabujije N-glycosylation ya asparagine ku mwanya wa 192 wa poroteyine ya PD-L1, bigatuma idashobora kuzunguruka neza hamwe na ankeri kuri selile. PD-L1, itakaza uburinzi bwa "isukari y'isukari", yanditseho E3 ubiquitin ligase FBXW41 kandi itesha agaciro proteasome. Imbeba za melanoma, guhuza antibodiyite za mannose na anti-PD-1 byongereye igipimo cyuzuye cyo gusubira inyuma kuva 28% kugera kuri 79% (Ishusho 2).

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Youdaoplaceholder0 Igice cya 3 Kuva kucyitegererezo cyinyamanswa kugeza kubigereranyo byubuvuzi bwa muntu: Umuhanda wamahwa wubuvuzi bwubuhinduzi ?

Youdaoplaceholder0 3.1 Iterambere nimbibi zubushakashatsi bwibanze ?

Muri kanseri ya pancreatic kanseri ya CRUK, nubwo monotherapy hamwe na mannose yatinze gutera ibibyimba, ntibyashoboye kugera kuburwayi bwuzuye. Ariko, iyo uhujwe na gahunda ya chimiotherapie ya FOLFIRINOX, igihe cyo kubaho hagati yimbeba cyongerewe kuva muminsi 42 kugeza ku minsi 98, kandi nta kwiyongera k'uburozi. Iki gisubizo cyagarutsweho mu buryo butatu-bubi bwa kanseri y'ibere mu kigo cya kanseri ya MD Anderson: Mannose yongereye igipimo cyo guhagarika ikibyimba cya paclitaxel kiva kuri 45% kigera kuri 72%. Abashakashatsi basanze kandi hafi 15% by'ibibyimba bititabira mannose. Isesengura ryakozwe ryagaragaje ko utugingo ngengabuzima turwanya ibiyobyabwenge twagaragaje cyane mannose-fosifate isomerase (PMI), ishobora guhindura M6P muri fructose-6-fosifate hanyuma igahurira mu nzira ya glycolitike.

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Youdaoplaceholder0 3.2 Umuseke witonze wibigeragezo byabantu ?

Igeragezwa rya mbere ry’amavuriro ya mannose ryatangiye mu 2022 (NCT05220739) ryarimo abarwayi 32 bafite ibibyimba bikomeye. Mu itsinda rya dose yubuyobozi bwa buri munsi bwa 5g mannose, ikibyimba kizenguruka ADN (ctDNA) cy’abarwayi 8 cyagabanutseho hejuru ya 50%, muri byo ingano ya metastase y’umwijima ku murwayi umwe wa kanseri yandura yagabanutseho 31%. Ariko, mugihe ikinini cyazamutse kigera kuri 10g, impiswi yo mucyiciro cya III yagaragaye ku barwayi 3, byerekana ko ingamba z'ubuyobozi zigomba kunozwa. Kugeza ubu, imyiteguro ya mannose yimitsi ikoresheje tekinoroji ya nano-liposome ikora. Preclinical data yerekana ko uburyo bwabo bwo kubyara bwibibyimba bugera kuri 78%, kandi uburozi bwabo bwaragabanutse cyane.

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Youdaoplaceholder0 Igice cya 4 Guhindura inganda no gutongana: Inzitizi nyazo za Revolution nziza ?

Youdaoplaceholder0 4.1 Ibinyabuzima byubukorikori bikemura umusaruro mwinshi Puzzle ?

Ubusanzwe mannose yakuweho irazimvye (hafi kilo)

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Biragoye kuzuza ibisabwa byo kurwanya kanseri (burimunsi)

Inzira ni ukongera umusaruro kuri

Igiciro cyaragabanutse kugera kuri 1200), bikaba bigoye kuzuza ibisabwa byo kurwanya kanseri (10-20g kumunsi). Igihangange cyibinyabuzima cyitwa GinkgoBioworks cyongereye umusaruro kugera kuri 30g / L kandi kigabanya igiciro kugera kuri 50 / kg muguhindura mannose-1 - guanosine fosifate yohereza (MPG) inzira ya Escherichia coli. Tekinoroji yateye imbere nka CRISPR-Cas9 yatunganijwe na Saccharomyces cerevisiae yakozwe na bagiteri yashoboye gukora neza mannose yera cyane mugihe cya fermentation ikomeza.

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Youdaoplaceholder0 4.2 Umukino uri hagati yubucuruzi Ubwoko nubwitonzi bwa siyansi ?

Hamwe n’igitekerezo cya "isukari yo kurwanya kanseri" kimaze kumenyekana, amagana y’ibicuruzwa by’ubuzima bwa mannose avuga ko ari "imiti ifasha ibibyimba" byagaragaye ku rubuga rwa Amazone, hamwe n’ibiciro byikubye inshuro icumi. Mu 2023, FDA yo muri Amerika yahaye amabaruwa yo kuburira ibigo 23, ishimangira ko "inyongeramusaruro zitagomba kuvuga ko zifite ingaruka zo kuvura indwara." Abahanga bahangayikishijwe nuko gufata buhumyi urugero rwinshi rwa mannose bishobora guhungabanya amara yo mu mara - ubushakashatsi bw’inyamaswa bwerekanye ko gufata igihe kirekire bituma kugabanuka kwa 80% ubwinshi bwa Faecalibacterium prausnitzii no kwiyongera kwa gatanu kwa nucleusum ya Fusobacterium. Iyanyuma ifitanye isano rya hafi niterambere rya kanseri yibara.

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Youdaoplaceholder0 Igice cya gatanu Icyerekezo kizaza: Inyanja nini y’ibiyobyabwenge bishingiye kuri Glyco ?

Youdaoplaceholder0 5.1 Impinduramatwara ya Glycolike mubuvuzi bwuzuye ?

Ingamba zo kuvura umuntu ku giti cye zishingiye ku kibyimba cya metabolike itandukanye. Icyitegererezo cya "Mannose Sensitivity Score" (MSS) cyakozwe n'Ikigo Cyagutse cyo muri Amerika gishobora guhanura ko abarwayi bashobora kwitabira mannose mu kumenya urwego rwa GLUT1, ibikorwa bya hexokinase ndetse na PMI ihinduka mu ngingo z’ibibyimba. Mu gishushanyo mbonera cy’ibizamini byo mu cyiciro cya II, abarwayi ba kanseri yandura bafite kanseri ya MSS amanota ≥ 75% bazahabwa umwanya wa mbere kugira ngo hongerwe ibisubizo by’ubuvuzi.

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Youdaoplaceholder0 5.2 Kwambuka imipaka ihuza isukari Imiti yubuhanga ?

Ubushakashatsi bwimbibi ntibwongeye kunyurwa no gukoresha mannose karemano. Itsinda rya MIT ryateguye conjugate "mannose-paclitaxel", ikoresha uburyo bwinshi bwo gufata mannose na selile yibibyimba kugirango igere ku muti wa chimiotherapie. Mu ngero za kanseri y'ibere, ingaruka zica ibibyimba ziyi conjugate yikubye inshuro eshatu iy'umuco gakondo wa paclitaxel, kandi umutima wacyo wagabanutseho 60%. Iyindi ntambwe yaturutse muri kaminuza ya Shanghai Jiao Tong: muguhuza mannose na fotosensitizer Ce6, "ubuvuzi bushingiye ku isukari bushingiye ku isukari" bushobora gukoreshwa n’umucyo uri hafi ya infragre, bwerekanye ubushobozi bwo gukuraho ibibyimba byimbitse.

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Youdaoplaceholder0 Umwanzuro: "molekile nziza" yandika amategeko arwanya kanseri ?

Urugendo rwo kurwanya kanseri ya mannose ni ikibatsi cyiza cyatewe no kugongana kwa siyansi yibanze hamwe nubuvuzi bukenewe. Kuva kwivanga kwa metabolike kugeza kugenzura ubudahangarwa, kuva monotherapie kugeza kuri gahunda yo guhuza, iyi molekile yisukari isenya umurongo wo kwirinda ibibyimba hamwe nuburyo bwinshi bwo gutera. Nubwo inzira yo gucuruza ikomeje guhura n’ibibazo nko gukoresha urugero rwiza, uburyo bwo kurwanya ibiyobyabwenge, ndetse n’amahame ngengamikorere, umuryango w’ubumenyi urabyizeye cyane - nk'uko uwahawe igihembo cyitiriwe Nobel, James Watson yabivuze, "Intandaro ya kanseri ni indwara ya genomique, kandi mannoglucose itwigisha ko kwivanga kwa metabolike bishobora kugarura gahunda." Iyobowe ninziga ebyiri zubuvuzi bwuzuye na biologiya yubukorikori, iyi "revolution nziza" irashobora gutangiza ibihe bishya byo kuvura kanseri.