amakuru

Cachexia ni indwara itunganijwe irangwa no kugabanya ibiro, imitsi na adipose tissue atrophy, hamwe no gutwika sisitemu. Cachexia nimwe mubibazo nyamukuru bitera impfu kubarwayi ba kanseri. Usibye kanseri, cachexia irashobora guterwa n'indwara zitandukanye zidakira, zitari mbi, zirimo kunanirwa k'umutima, kunanirwa kw'impyiko, indwara zidakira zifata ibihaha, indwara zifata ubwonko, sida, na rubagimpande ya rubagimpande. Bigereranijwe ko indwara ya cachexia ku barwayi ba kanseri ishobora kugera kuri 25% kugeza kuri 70%, ibyo bikaba bigira ingaruka zikomeye ku mibereho y’abarwayi (QOL) kandi bikongera uburozi bujyanye no kuvura.

Gutabara neza kwa cachexia bifite akamaro kanini mukuzamura imibereho no kumenyekanisha abarwayi ba kanseri. Nubwo, nubwo hari intambwe imaze guterwa mu kwiga uburyo bwa pathophysiologique ya cachexia, imiti myinshi yakozwe ishingiye ku buryo bushoboka irakora neza cyangwa ntigire icyo ikora. Kugeza ubu nta muti ufatika wemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA).

Hariho impamvu nyinshi zo kunanirwa kwipimisha kwa clinique kuri cachexia, kandi impamvu yibanze irashobora guterwa no kudasobanukirwa neza imikorere ninzira karemano ya cachexia. Vuba aha, Porofeseri Xiao Ruiping n’umushakashatsi Hu Xinli bo mu Ishuri Rikuru ry’ikoranabuhanga rya kaminuza ya Peking bafatanije gusohora inyandiko muri Nature Metabolism, bagaragaza uruhare rukomeye rw’inzira ya lactique-GPR81 mu gihe cya kanseri ya kanseri, itanga igitekerezo gishya cyo kuvura cachexia. Turabivuze muri make muguhuza impapuro zo muri Nat Metab, Ubumenyi, Nat Rev Clin Oncol nibindi binyamakuru.

Kugabanuka k'ibiro mubisanzwe biterwa no kugabanya ibiryo no / cyangwa kongera ingufu zikoreshwa. Ubushakashatsi bwibanze bwerekanye ko izo mpinduka zifatika ziterwa na cachexia zifata ibibyimba ziterwa na cytokine zimwe na zimwe zasohowe na microen ibidukikije. Kurugero, ibintu nkibintu bitandukanya imikurire 15 (GDF15), lipocalin-2 na protein 3 (INSL3) nka insuline bisa na insuline (INSL3) birashobora kubuza gufata ibiryo uhuza imbuga zigenga ibyokurya muri sisitemu yo hagati yuburwayi, bigatera anorexia kubarwayi. IL-6, PTHrP, activin A nibindi bintu bitera kugabanya ibiro hamwe na tissue atrophy mugukoresha inzira ya catabolika no kongera ingufu zikoreshwa. Kugeza ubu, ubushakashatsi ku mikorere ya cachexia bwibanze cyane kuri izo poroteyine zasohotse, kandi ubushakashatsi buke bwagize uruhare mu isano riri hagati y’ibibyimba metabolite na cachexia. Porofeseri Xiao Ruiping n'umushakashatsi Hu Xinli bafashe uburyo bushya bwo kwerekana uburyo bw'ingenzi bwa cachexia ifitanye isano n'ibibyimba bivuye kuri metabolite y'ibibyimba

Ubwa mbere, itsinda rya Porofeseri Xiao Ruiping ryasuzumye metabolite ibihumbi n’ibihumbi mu maraso yo kugenzura neza n’imbeba zerekana kanseri y'ibihaha cachexia, basanga aside ya lactique ari yo yazamuye cyane metabolite mu mbeba hamwe na cachexia. Urwego rwa acide lactique rwiyongereye hamwe no gukura kwikibyimba, kandi rwerekanye isano ikomeye nihinduka ryibiro byimbeba zifite ibibyimba. Ingero za serumu zegeranijwe ku barwayi ba kanseri y'ibihaha zemeza ko aside ya lactique nayo igira uruhare runini mu iterambere rya cachexia ya kanseri y'abantu.

Kugira ngo hamenyekane niba aside irike nyinshi itera cachexia, itsinda ry’ubushakashatsi ryagejeje aside ya lactique mu maraso y’imbeba zifite ubuzima bwiza binyuze muri pompe osmotic yatewe munsi y’uruhu, ikazamura ibihimbano bya aside ya lactique ya acide kugeza ku mbeba hamwe na cachexia. Nyuma yibyumweru 2, imbeba zagize fenotipike isanzwe ya cachexia, nko kugabanya ibiro, ibinure hamwe nimitsi ya atrophy. Ibisubizo byerekana ko kuvugurura ibinure biterwa na lactate bisa nibiterwa na selile kanseri. Lactate ntabwo ari metabolite iranga kanseri ya cachexia gusa, ahubwo ni umuhuza wingenzi wa kanseri iterwa na hypercatabolic phenotype.

Ibikurikira, basanze gusiba reseptor ya lactate GPR81 byagize akamaro mukugabanya ibibyimba hamwe na serumu lactate-iterwa na cachexia itabangamiye urwego rwa lakate. Kuberako GPR81 igaragarira cyane mubice bya adipose no guhinduka mubice bya adipose hakiri kare kuruta imitsi ya skeletale mugihe cyo gukura kwa cachexia, ingaruka yihariye ya knockout ya GPR81 mumyanya ya adipose yimbeba isa niyakomanze kuri sisitemu, kunoza ibiro biterwa nibibyimba hamwe no kurya imitsi ya skelete. Ibi byerekana ko GPR81 muri tipusi ya adipose isabwa kugirango habeho kanseri ya cachexia iterwa na aside ya lactique.

Ubundi bushakashatsi bwemeje ko nyuma yo guhuza GPR81, molekile ya acide lactique itwara ibinure bya Browning, lipolysis ndetse no kongera ubushyuhe bwa sisitemu binyuze muri Gβγ-RhoA / ROCK1-p38 yerekana inzira, aho kuba inzira ya PKA ya kera.

Nubwo hari ibisubizo bitanga umusaruro mu gutera indwara ya cachexia ifitanye isano na kanseri, ubu bushakashatsi ntabwo bwigeze buhindurwa mu buryo bunoze bwo kuvura, ku buryo kugeza ubu nta mahame ngenderwaho yo kuvura aba barwayi bafite, ariko imiryango imwe n'imwe, nka ESMO n'Umuryango w’ibihugu by’i Burayi byita ku mirire ya Clinical na Metabolism, yashyizeho umurongo ngenderwaho w’amavuriro. Kugeza ubu, umurongo ngenderwaho mpuzamahanga urasaba cyane guteza imbere metabolisme no kugabanya catabolisme binyuze mu mirire, imyitozo ngororamubiri n'imiti