
folate lakshyam

folate target anedi aushadha pampinhee prayojanaala kosam biotechnologylo upayoginche paddhati. eee trojan haars prakriyanu daa. ess. roopondinchaaru. christopher pii. nimmakaya mariyu phillip ess. takkuva, vitamin, folate (folic aamlam) nuu oka anuvu/aushadhaaniki jodinchi "folate conjugate" nuu yerparustundi. folate receptor protein (fr) kuu folate yokka sahaja adhika anubandham aadhaaramgaa, idhi saadhaaranamgaa aneka maanava cancerla uparitalampai vyakteekarinchabadutundi, folate-drugg kanjugetlu kooda fr thoo gattiga bandhistaayi mariyu endocytosis dwara cellular teesukoovadaanni prerepistaayi. chinna radeo diagnostic imaging agentla nundi pedda dna plasmid suutreekaranala varaku vibhinnamaina anuvulu fr-positive kanaalu mariyu kanajaalaala lopala vijayavantamgaa pampinhee cheyabaddaayi.
nepathyam.
folic aamlam (efae, folate ledhaa vitamin bii9), nucleotide biosynthesis kosam mariyu 1-carbon maargaala saraina jeevakriya nirvahana kosam anni jeeva kanaalaku avasaramaina mukhyamaina poeshakam. kanaantara enjaimlaku daani cofactor paathratho paatu, efae folate receptor (fr), glycosylphosphatidinosphatino-linked proteinku adhika anubandhaanni pradarsistundi, idhi extracellular parisaraala nundi daani ligandlanu bandhinchi, vaatini naasanam kaani, recycling endosomal maargam dwara sell lopaliki ravana chestundi. fr anedi gurtimpu pondina kaniti antigen/biomarker kooda. eee kaaranamgaa, cancer kosam fr yokka paniteerunu upayoginchukune roganirdhaarana mariyu chikitsa paddhatulu abhivruddhi cheyabadutunnayi.
cancer mariyu deerghakaalika shotha vyaadhula nirdhaarana mariyu chikitsa kosam fr anedi abhivruddhi chendutunna chikitsa lakshyam. konni praanaantaka kanaalu mariyu sakriyam cheyabadina macrophaselapy fr yokka vyakteekarana empikagaa niyantrinchabadutundi. eee rakamaina kanaalapai fr yokka athi vyakteekarana vaidyaparamgaa mukhyamainadi endukante avi vyaadhi yokka saareeraka lakshanaalu atyanta vistrutamgaa unde praantaalanu suuchistaayi. praanaantaka kanaalu andaasaya, oopiritittulu, rommu, moothrapindaalu, medadu, endometrial mariyu peddapregu cancertho sambandham unna kanitula unikini suuchistaayi. rheumatoid arthuritis, crone 's vyaadhi, vranotpatti peddapregu shotha, psoriasis, atherosclerosis, diabetes mariyu chaalaa itara shotha vyaadhulu vanti deerghakaalika vyaadhulalo macrophaselu sakriyam avtayi.
yaantrika drukpatham nundi, fr anedi bahya ligandlanu kendreekarinchadaaniki panichestundi (udhaa.zii. endocytosis dwara sell cytosolloki foletlu mariyu folate-drugg kanjugetlu). endocytosis anae padam plasma pora atmahuti chesi, chivariki oka pratyaekamaina kanaantara compartmentnu yerparuchukune prakriyanu suuchistumdi. endocytic vesicals (endosomelu) vaegamgaa aamleekarinchabadataayi, tadwara fr daani ligandnu vidudala cheyadaaniki veelu kalpistundi. aaa taruvaata, khaalii fr kana uparitalaaniki tirigi vastundi, akkada adhi ligand-madhyavartitva endocytosis yokka maroka roundloo paalgonavacchu.
mokkalalo vitamin-madhyavartitva aushadham yokka aavishkarana folate-lakshyamgaa unna chikitsalu clinical upayogaaniki sambandhinchinavi kaavacchu anae parikalpanaku daariteesindi. bayotinku samayojaneeyamgaa bandhinchabadina proteins grahaka-madhyavartitva endocytosis dwara mokkala kanaalaloki vijayavantamgaa ravana cheyabadina taruvaata, folate mariyu janthu kanaalatoe idhe vidhamaina saanketikata prayatninchabadindi. lakshita aushadha chikitsa prayojanakaramgaa untundi endukante idhi vyaadhiki chikitsa cheyadamlo atyanta upayogakaramgaa unde nirdishta pradaesamloe aushadhaanni jama chestundi. adevidhamgaa, folate-target imaging therapy adhika sthaayilalo fr vyakteekarinchabadina praantaalanu drushyamaanam cheyadaaniki sahaayapadutundi. bahya agentlu ekkada pampinhee cheyabadutunnayane daanipai ekkuva niyanthranatho, roganirdhaarana mariyu chikitsa chikitsalu marinta prabhaavavantamgaa untaayi mariyu takkuva dushprabhaavaalanu kaligistaayi.
aushadha pampinhee paddhatulu.
fr kosam folate samyogaala yokka vishishtata uchita foletto pootii pareekshala dwara choopabadindi. efrnu bandhinche eee ligand, folate conjugate kante ekkuvagaa jodinchabadinappudu, idhi kanjugetnu adhigamistundi, idhi folate conjugate pratyaekamgaa efrnu bandhistundani, itara grahakalanu kaadu, grahaka-madhyavartitva endocytosis prakriyaloo suuchistumdi. sell membrane nundi folate receptornu vidipinche enjaimnu jodinchadam mariyu efrku pratiroedhakaalanu jodinchadam kooda folate kanjugetla antargatakarananu tippikodataayi, folate kanjugetlu efrnu nirdishtatatoe bandhistaayanedaaniki marinta aadhaaraalanu andistaayi.
konni mandulu mariyu radeo imaging agentlu folate-tuu-vann-conjugate nishpattilo folate kanjugetluga kanaalaku pampinhee cheyabadataayi, folate-lakshyamgaa unna liposomelu pedda mottamlo chemotherapetic agentla pampinheeki anumatistaayi. eee saanketikatalo, aushadha kanaalu plasma pora-kattubadi unna vesikallo kappabadi untaayi. pora phospholipids yokka fasfate talalaku kattubadi unna polyethylene glycoltho folate jatacheyabadutundi, tadwara liposomlanu kaniti kanaala frs kuu nirdesistundi, tadwara avi munigipotayi.
fr-positive cancer.
mukhyamgaa dookudugaa perugutunna cancerlatho sambandham unnappudu, aneka maanava praanaantakaalaloo fr yokka adhika vyakteekarana sambhavistundi. iteevala, eee sambandhaanni bahusha rooga niruupana prayojanaala kosam upayoginchavacchani pratipaadinchabadindi. shleshmam kaani andaasaya cancer (andaasaya cancerlalo ekkuva bhaagam) anedi fr "ovar-expression" thoo sambandham unna modati kaniti rakam, mariyu eee antigen kebi kaniti kanaalapai mariyu plaasental kanajaalamlo kanipinche daanitoe samanamga undani taruvaata choopabadindi. andaasaya kanitula yokka ~80-90% anedi fr nii atigaa vyaktam chestundani aneka adhyayanalu dhruvikarinchayi. itara stree jananendri cancerlu kooda graahakamtho paatu pediatric ependimal medadu kanitulu, mesothelioma mariyu rommu, peddapregu, moothrapinda mariyu oopiritittula kanitulanu atigaa vyaktam chestaayi. mukhyamgaa myeloid leukemia mariyu bahusha thala mariyu meda cancerlaku sambandhinchinappudu, fr cancertho sambandham kaligi unnatlu kooda kanugonavacchu. mottamgaa choosthe, efrni vyakteekarinchae kanitula mottam sankhya chaalaa peddadi; anduvalla, fr-positive vyaadhitho badhapaduthunna rogulaku cancer chikitsapai fr-lakshyamgaa unna vyuuhaalu gananeeyamaina prabhavanni chuuputaayi.
roganirdhaarana.
fr aneka rakaala praanaantaka kanajaalaalapai mariyu pedda parimaanamlo vyakteekarinchabadutundi. conny, oka nirdishta suuchanalooni anni maanava cancerlu efrni vyaktam cheyavu. kotta fr-lakshyamgaa unna chikitsalu ippudu vaidyaparamgaa pareekshinchabadutunnaayi kabatti, fr-positive vyaadhi kosam rogulanu pareekshinchagala saamarthyam kaligi undatam khachitamgaa eee kotta agentla clinical parisoedhanala saamarthyaanni penchutundi mariyu taggistundi.
prastutam, roogi yokka "fr sthithi" nii anchanaa vaeyadaaniki rendu pradhana paddhatulu upayoginchabadutunnaayi. veetilo invasive tissue-aadhaarita immunohystochemical aseh mariyu naan-invasive radeo diagnostic vidhanam unnaayi. taruvaati paddhatini ippudu 99emtisi-isi20 upayoginchi vaidyaparamgaa pareekshistunnaaru.
folate-lakshyamgaa chemotherapy.
eee roeju varaku, naalugu vibhina efae-drugg kanjugetlu cancer chikitsa kosam clinical trialsloki pravesinchaayih
"vintafolide (ii. sii. 145)" anedi saktivantamaina suukshma naalikala asthirapariche agent, desasetylvinblastine monohydrazide (dowl; sahaja utpatti, winblastin yokka utpannam) yokka neetilo karige kotta phaa samyogaanni suuchistumdi. baga thattukogala niyamaalanu upayoginchi baga sthirapadina, subcatanius fr-positive tumour genographtlaku vyatiraekamgaa gurtinchadagina anty-tumour prabhavanni utpatti cheyagaladani isi145 kanugonabadindi. clinical trialslo moolyaankanam cheyabadina modati efae-drugg kanjugetnu kooda isi145 suuchistumdi, mariyu idhi prastutam (2009) pegilated liposomal doxorubicin (doxil) thoo kalipi bahula-jaateeya yaadruchchika dasha 2bii triallo pareekshinchabadutondi.
"ec0225" "anedi nivedinchavalasina" "fust inn class" "bahula-aushadha, efae-target agentnu suuchistumdi". idhi oke phaa bhaagamtho nirminchina anuvu mariyu hydrophilic peptide aadhaarita spacer dwara vistarinchabadindi, idhi 2 vibhina disulfide-kaligina linkerla dwara "vinka" alcoloid mariyu mitomycin unitlatho anusandhaaninchabadi untundi. baga sthirapadina maanava kaniti genographtlanu kaligi unna jantuvulu isi 145kii avasaramaina daanikante sumaru 3 retlu takkuva teevrata kaligina motaadu niyamaalato isi 0225 chikitsaku puurtigaa spandistaayani kanugonabadindi. isi 0225 kosam dasha 1 trial purogatilo undhi.
"bms-753493" anedi endocyte ink vadda saastravettala madhya sahakaram nundi janminchina anuvu. mariyu bristol myers squib (bms). idhi epothylone eah yokka pakshika-synthetic analog thoo nirminchina phaa kanjugetnu suuchistumdi. bms-753493 prastutam bms spaansar chesina 2va dasha clinical trialslo bhadrata mariyu samarthatha kosam anchanaa veyabadutondi.
"ii. sii. 0489" anedi endocyte spaansar chesina clinical trialsloki pravesinchadaaniki taja folate-lakshyamgaa unna chemotherapetic. eee anuvu vaastavaaniki kaaleyam dwara parimitamaina nirdishtamaina clearance lakshanaalanu kaligi undela roopondinchabadina isi145 (paina chudandi) yokka utpannam. hepatic clearancenu tagginchadam dwara, takkuva aushadham pitta visarjana maargam dwara ravana avutundi; paryavasanamga, takkuva lakshya vishapuurita lakshanaalu (preclinical pareekshala nundi anchanaa veyabadinavi) anchanaa vaeyabadataayi.
sakriyam cheyabadina macrophage lakshyam.
macrophaselu anevi maanava sareeram yokka modati rakshana maargam, ivi rogakaarakaalu daadi cheyakunda nirodhistaayi. saadhaaranamgaa, avi nidraanamaina sthithilo raktapravaahamlo prasaristaayi, conny gaayam ledhaa swayam pratirakshaka vyaadhi kaaranamgaa vaapu unna pradaesamloe, avi sakriyam avtayi, aakaraanni maarustaayi mariyu vividha kana uparitala gurtulanu vyaktam chestaayi. fr yokka kramabaddheekarinchina vyakteekarana sakriyam cheyabadina macrophaselanu folate-lakshyamgaa unna chikitsalo upayogakaramaina saadhanamgaa chestundi. sakriyam cheyabadina, tnf-alfa utpatti chese macrophaselu fr yokka beata isopharmnu vyaktam chestaayi, mariyu avi "inn vivo" loe folate kanjugetlatho lakshyamgaa untaayi. udaaharanaku, 99emtisi-isi20 folate-aadhaarita yantraangam dwara sahayaka-prerita arthoritic elukala kaaleyaalu, spleens mariyu arthoritic antya bhagalalo kendrikrutamai unnatlu nivedinchabadindi. vaapu chikitsa kosam folate-drugg conjugates abhivruddhi jarugutondi. kriyaaseela macrophaselanu (arthuritis, psoriasis mariyu inflammatory pregu vyaadhi vantivi) kaligi unna vyaadhulu edho oka roeju folate-lakshyamgaa unna mandulatho chikitsa cheyagalavani bhaavistunnaaru.

