Ukunyusa ukungazinzi komhlaza kunye neNdebe-A-Ikofu

Iimbalasane

I-Immunotherapy luhlobo lonyango lomhlaza oluvuselela kwaye lusebenzise amajoni omzimba ukulwa nomhlaza. Ikofu, esinye sezona ziselo zidumileyo kwihlabathi liphela, inamandla okuphucula ukugonywa komhlaza kwaye izalisekise iindlela ezahlukeneyo ezisakhulayo ze-pharmacological immunotherapy. Ikofu yongeza ukungakhuseleki komhlaza kwaye izalisekisa i-immunotherapy ngokuphinda isebenze amajoni omzimba kufutshane nethumba elikhulayo, inciphisa ukwakheka komthambo wegazi omtsha kunye nokuthintela ithumba ukuba lingene kwindlela yokulungisa xa lonakele. umhlaza unyango.

Ikofu yenye yezona ziselo zidumileyo eMelika nakwihlabathi liphela. Icandelo eliphambili lekhofi yi-psychostimulant caffeine, ekwayinto ebalulekileyo kwiziselo ezine-caffeine, ii-sodas, amandla okomeleza kunye nezinye iziselo zempilo. Ngaphandle kwekhafeyini, ikofu inezinto ezininzi ezinamachiza e-phytochemical aneepropathi ezichasene nokudumba kunye ne-antioxidant. Kukho izifundo ezingaphezu kwe-15,000 ezivavanye ifuthe lokusela ikofu kwaye ngokubanzi lifumene ukuba lisempilweni kunokuba liyingozi, xa lingasetyenziswanga ngaphezulu.  

Ikofu ibonakalisiwe ukuba inezibonelelo ezininzi zempilo ezinje ngokunciphisa imingxunya, ukonyusa ukusebenza kweembaleki, ukuphucula imood, kunye nokunciphisa iintloko. Iziphumo zekofu zikwabonakalisiwe ukunciphisa umngcipheko wezifo ezingapheliyo kunye nezibi ezinje ngohlobo lweswekile 2, umhlaza wekolon, umhlaza wesibindi, inyongo, isifo sesibindi kunye nesifo sikaParkinson. (Hong okqhubekayo, Izondlo, 2020; Contaldo okqhubekayo, Ukhathalelo lweKlinikhi yokuNyango lweeMetab zeNutrr, 2019; UKolb H okqhubekayo, Izondlo, 2020)

Kule bhlog, siza kuvavanya iindlela ikofu enokuthi iwonyuse ngayo amajoni omzimba okulwa umhlaza kwaye incedise kwiindlela ezahlukeneyo ezikhulayo zeyeza lokuthintela umhlaza. Siza kuchaza ngokufutshane indlela umhlaza awasebenzisana ngayo amajoni omzimba ukulungiselela ukukhula kwawo kunye nokusinda kunye nokubonelela ngesishwankathelo sokuvela kokugxila okutsha ekusebenziseni amajoni ethu omzimba ukujongana nokulawula umhlaza ngokuqhubela phambili kwiindlela ezahlukeneyo ze-immunotherapy, ngenjongo yokuqaqambisa iziphumo ezincumisayo zekofu. 

Umhlaza Immunology 101

Njengoko kusaziwa, umhlaza yimeko ebangelwa kukukhula okungalawulwayo kunye nokusasazeka kweeseli ezithile emzimbeni wethu ezingahambelaniyo kunye ne-haywire. Zininzi izinto ezibangela umhlaza ezahluka ekubeni sesichengeni semfuza kunye nezinto ezinobungozi kusapho, kwindlela yokuphila kunye nezizathu zokusingqongileyo. Ukwaluphala, ukutyeba kakhulu kunye nezinye izinto ezinokubangela ukudumba kunye neemeko zikonyusa umngcipheko womhlaza.

Imizimba yethu ixhotyiswe ngendlela yethu yokuzikhusela eyinkqubo yomzimba yokuzikhusela. Iqukethe iintlobo ezahlukeneyo zeseli kubandakanya ii-macrophage, iiseli ze-T, iiseli ze-B, iiseli ze-dendritic, iiseli zokubulala zendalo, i-neutrophils kunye nezinye ezijolise ekukhuseleni umzimba ngokuchasene nosuleleko. Amajoni omzimba omntu ophilileyo uneliso elibukhali elichonga nantoni na eyangaphandle, enje ngeentsholongwane ezincinci kunye neentsholongwane, okanye ezonakalisiweyo, ngenxa yokwenzakala okanye ngenxa yeeseli ezithile emzimbeni wethu ezinomhlaza, kwaye uzisule. Sonke sigonyiwe njengabantwana kwizifo ezahlukeneyo ezinjengepoliyo, ingqakaqha, imasisi, uqwilikana nabanye ukunceda amajoni omzimba ukuba azazi ezi ntsholongwane kwaye akulungele ukulwa nazo xa kufuneka njalo.  

Amajoni omzimba alunge kakhulu. Xa ugqithisile, unokuhlasela 'ubuqu' kwaye ubangele ukuphazamiseka komzimba njenge-rheumatoid arthritis, multiple sclerosis kunye nabanye. Xa ukugadwa kwamajoni kuncitshisiwe, kukhokelela kwizifo ezinje ngomhlaza kunye nezinye izifo ezosulelayo. Impilo yamajoni omzimba ichaphazeleka yindlela esiphila ngayo yoxinzelelo oluphezulu, ukutya kwethu okungenampilo, kunye nenkqubo yokuguga yendalo enciphisa amandla okulwa amajoni omzimba.

Yiyo loo nto iiseli zomhlaza zinokukhula kwaye zikhule kakuhle xa zibaleka ukubek 'esweni. Ukongeza, umhlaza udibanisa amajoni omzimba ukuze angasikhuseli nje kuphela, kodwa asebenzise oomatshini bokuzikhusela kwizifo ukuqhubela phambili kwesi sifo ngokukhula kwaso ngamandla nokusasazeka komzimba. Iiseli zomhlaza zikwanakho ukuthomalalisa ukubekwa kweliso lomzimba kwindawo ekufutshane nayo (indawo encinci) kwaye ziyaphumelela kwindawo egonyelwe umzimba.

Isiseko se-Immunotherapy

Ngokusekwe kuphando olunzulu lwenzululwazi kunye nokuqonda indima ebalulekileyo yamajoni omzimba ekuxhaseni umhlaza, kugqityiwe kugxilwe kwiindlela ezahlukeneyo zekhemesti ukukhuthaza kunye nokusebenzisa amajoni omzimba omntu ukulwa nomhlaza. (Waldman AD et al, Nature Reviews Immunology, 2020) Olu hlobo lonyango lomhlaza olusebenzisa amajoni omzimba ukunyanga umhlaza kuthiwa yi-immunotherapy. Kukho iindlela ezahlukeneyo ze-immunotherapy ezijolise ekunciphiseni ukosulelwa komzimba kwi-microenvelo yethumba kunye nokunyusa ukubekwa kweliso lomzimba kunye nokusebenza kweeseli zomzimba. Oku kubandakanya:

• Ukunyanga nge-immune mediators (i-cytokines) ukuze kusebenze iiseli ze-immune ukuze zihlasele umhlaza.
• Ukuthintela imiqondiso yendalo (i-checkpoint inhibitors) ekhoyo ukukhusela iiseli zomzimba ekuzihlaseleni, ezikhethwe ngumhlaza ukunqanda ukwamkelwa njengokungaqhelekanga kwaye kutshatyalaliswe.
• Sebenzisa iiseli zomzimba zokuzikhusela kwizigulana ezikhutshiweyo kwimizimba yazo zaze zalungiswa ngaphandle ukuba ziqonde kwaye zihlasele iiseli zomhlaza kwindlela ebizwa ngokuba lonyango olwamkelayo. I-CAR T (Iiseli ze-antigen receptor T zeseli) ibonakalise impumelelo ekunyangeni isifo seeseli se-B.
• Amayeza okugonya umhlaza yenye indlela ephandwayo.

Iindlela apho iiseli zomhlaza zithintela ukuqondwa komzimba

1. Iiseli zomhlaza ezingaqhelekanga zidala imeko-bume engqonge imo yokuzikhusela emzimbeni kwaye inqanda ukusebenza kunye nokusebenza kweeseli zomzimba.
2. Njengoko umhlaza ukhula, iiseli ezingaqhelekanga zifunda ukuphila kwioksijini ephantsi. Le yimeko ebizwa ngokuba yihypoxia. I-Hypoxia kwiiseli zomhlaza ibangela utshintsho olukhulu oluqhubela phambili ukuphucula ukusinda. IHypoxia ibangela imveliso egqithisileyo yabalamli eya kuthi yonyuse ukunikezelwa kwegazi kumhlaza ngaloo ndlela ibonelele ngezinongo, kwaye ivelise nabanye abalamli abanjengoadenosine, enegalelo ekudaleni uxinzelelo lomzimba kwindawo ekufutshane nayo.
3. Iiseli zomhlaza zikwonyusa imveliso yeebhlokhi ngokuthe ngqo kwiimpawu ezisebenzayo kwiiseli zomzimba (iindawo zokujonga ukhuseleko) ezithintela iiseli zomzimba ekutshabalaliseni iiseli zomhlaza ezingaqhelekanga.

Ikhofi ikunceda njani ukukhuthaza ukungazinzi komhlaza?

Zikhankanyiwe apha ngezantsi zezinye zeendlela apho ikofu inokuphucula ukukhuselwa komhlaza.

Ikofu ivuselela amajoni omzimba kufutshane nethumba elikhulayo 

Imeko yehypoxia eyenziwe ngumhlaza ngenxa yokuhluthwa kwemida yeoksijini kwaye ibangela ukuqokelelwa kwamandla aphakathi abizwa ngokuba yi-adenosine ukuba iqokelele ngaphandle kwindawo yomhlaza. I-Adenosine inceda kugqithiso lwamandla eselfowuni ngokwenza imolekyuli yamandla i-ATP. Ikwangumlamli osayinayo kunye nemisebenzi njenge-inhibitory neurotransmitter kwingqondo.

I-Adenosine ibophelela kwii-Adenosine receptors ezineziphumo ezahlukeneyo kwiindidi ezahlukeneyo zeseli. I-Adenosine inqanda ukwenziwa kweeseli ze-T, iiseli ze-B, ii-macrophages kunye neeseli zedendritic kodwa zinokusebenzisa i-subset yolawulo lwee-T-cell, ukudala imeko ye-immunosuppressive ejikeleze ithumba.  

I-caffeine ekhoyo kwikofu nayo ibophelela kwii-receptors ezifanayo ne-adenosine kwaye ikhuphisana nayo, yiyo loo nto ichasa isenzo se-adenosine. Ngale ndlela, icaffeine inokuphazamisana nayo kwaye ithintele i-adenosine ekuthinteleni iiseli zomzimba zokuzikhusela ezifunekayo ukuze ziqonde kwaye zicime iseli yesisu esingaqhelekanga. (UMerighi S okqhubekayo, Mol. Pharmacol, 2007; Tej GNVC okqhubekayo, Int. Immunopharmacol., 2019; Jacobson KA okqhubekayo, Br. J Pharmacol, 2020) 

Ikofu inciphisa ukwenziwa ngokutsha kwemithambo yegazi

I-Adenosine ekhoyo kwi-tumor microenvelo inyusa imveliso yabalamli njenge-interleukin 8 (IL8) kunye ne-vasot endothelial grow factor (VEGF) ekhuthaza ukwenziwa kwemithambo yegazi entsha kwinkqubo ebizwa ngokuba yi-angiogenesis. Oku kuluncedo kwiiseli zomhlaza ukubamba ngakumbi ubonelelo ngezondlo ekukhuleni nasekusindeni kwabo.

Ikofu, ngokungenelela kunye nokuchasa isenzo se-adenosine, inokuthintela eli nyathelo le-angiogenesis yethumba. (UGullanki Naga Venkata Charan Tej , Biomed Pharmacother., 2018)

Ikofu ithintela ithumba ekubeni liye kwimeko yokulungisa xa lonakaliswe ngumhlaza unyango olufana ne-chemotherapy kunye nonyango lwemitha

Unyango lomhlaza njenge-chemotherapy kunye nonyango lwe-radiation luthathe isenzo sabo ngokubangela ukonzakala okugqithisileyo kwe-DNA kwiiseli zomhlaza, ngaloo ndlela kubangele ukuba iiseli zife. Ukufa kweeseli zomhlaza nako kunokwenza ukuba amajoni omzimba afune ukucoca iiseli ezifileyo. Iiseli ezinomhlaza ziphinda ziyenze injineli ngokwazo ukuze zisinde kwaye kwimeko yomonakalo, zilungelelanise oomatshini bokulungisa ngokunyusa imveliso yemfuza yokulungisa efana ne-ATM kunye ne-ATR.   

I-Caffeine inokuthintela i-ATM kunye neeprotein ze-ATR kunye nokuthintela ukulungiswa komonakalo womhlaza we-DNA, yiyo loo nto isenza ukuba iseli yomhlaza isesichengeni sokubulawa lolunye unyango lomhlaza. (U-Li N et al., IBiomed Res Int., 2018Ngokuthintela oomatshini bokulungisa iiseli kwiiseli ezinomhlaza, icaffeine iyanceda ekuncediseni iziphumo zekhemotherapy kunye nonyango lwemitha nayo, kunye nezenzo zayo ekunciphiseni uxinzelelo lomzimba kwi-tumor microenvelo.

isishwankathelo

Iziphumo ezininzi eziluncedo zekofu ziye zagxininiswa ngokusekelwe kuphando lwezenzululwazi. Kukho ukuvela kokugxila kwiindlela ezahlukeneyo ze-pharmacological immunotherapy, zisebenzisa ukhuselo lwethu lomzimba ukulwa umhlaza, kunye nokuqonda ukuba kutheni amajoni omzimba ecinezelwe kwaye akakwazi ukubona iiseli zomhlaza ezingaqhelekanga emzimbeni. Oku kuqhubele phambili kukhangelo lwendalo kunye nezincedisi ezikhuselekileyo ezinokunciphisa ukuxhathisa amajoni omzimba kunye nokwandisa uphononongo lwamajoni omzimba. Imiphumo yokulawula i-immune yekofu, ngokuchasa i-adenosine kwi-tumor microenvironment kwaye ngaloo ndlela inciphisa ukunyanzeliswa kwe-immune, inokuzuza kwaye incedise i-immunotherapy yokulawula umhlaza. Nangona kunjalo, ngaphandle kweenzuzo ezinokubakho zekofu ekwandiseni ukugonywa komhlaza kunye nokuxhasa i-immunotherapy, idosi egqithisileyo yecaffeine inokubulala. Ikofu iyinto evuselela ingqondo kwaye kufuneka ithathwe ngokwemilinganiselo elawulwayo kunye nephakathi ukuze isebenzise iziphumo zayo eziluncedo.

Kukuphi ukutya okutyayo kwaye okuncedisayo kukuthatha sisigqibo osithathayo. Isigqibo sakho kufuneka sibandakanye ukuthathelwa ingqalelo kotshintsho lomhlaza kuhlobo lomhlaza, unyango oluqhubekayo kunye nezongezelelo, nakuphi na ukwaliwa, ulwazi ngobomi bakho, ubunzima, ukuphakama kunye nemikhwa.

Isicwangciso sesondlo somhlaza esivela kwi-addon asisekelwanga kukhangelo lwe-Intanethi. Isebenza ngokuzenzekelayo ukwenza izigqibo zakho kusekwe kwisayensi yemolekyuli ephunyezwe ngoososayensi kunye neenjineli zesoftware. Nokuba ukhathalele na ukuqonda iindlela ezisisiseko seemolekyuli okanye hayi - zokucwangciswa kwesondlo somhlaza ukuqonda kuyafuneka.

Qalisa NGOKU ngokucwangciswa kwesondlo ngokuphendula imibuzo ngegama lomhlaza, uguquko kwimfuza, unyango oluqhubekayo kunye nezincedisi, nakuphi na ukwaliwa, imikhwa, indlela yokuphila, iqela lobudala kunye nesini.

Izigulana ezinomhlaza zihlala zisebenza ngeendlela ezahlukeneyo iziphumo ebezingalindelekanga ezichaphazela umgangatho wobomi babo kwaye bajonge ezinye iindlela zonyango lomhlaza. Ukuthatha isondlo esifanelekileyo kunye nezongezelelo ezisekwe kuqwalaselo lwenzululwazi (ukunqanda ukuqikelela kunye nokukhetha okungahleliwe) sesona sixhobo sendalo somhlaza kunye neziphumo ebezingalindelekanga zonyango.

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