
elncape

elncap kanaalu anedi oncology rangamlo saadhaaranamgaa upayoginche maanava kanaala kana shreni. elncap kanaalu 1977loe 50 yella caucassian maga nundi edama supracalavicular shosharasa node metastasis nundi udbhavinchina androgen-sensitive human prostate adenocarcinoma kanaalu. avi aggregates mariyu single selsga perige anugunyamaina epithelial kanaalu.
atyanta vaidyaparamgaa sambandhitamaina prostate cancer (pca) parisoedhananu nirvahinchadaaniki oka pradhana addanki maanava vyaadhi purogatini daggaragaa anukarinche kana rekhala lekapovadam. metastatic human prostate cancer yokka rendu mukhya lakshanaalalo androgen-sensitivity nundi androgen insensitive (aii) sthithiki dookudugaa pca maaradam mariyu emukaku metastasize cheyadaaniki pca yokka pravrutti unnaayi. classic" sell linelu du145 mariyu pisi3loe pradarsinchinatlugaa aii sell linela utpatti chaalaa vijayavantamainappatiki, emukaloni eee kanaala pravartana puurtigaa clinical maanava vyaadhini anukarinchadu. rommu cancer vanti itara cancerlalo kanipinche osteolytic gaayaala kante maanava pca emuka metastasis osteoblastic gayalanu yerparustundani baga nirdhaarinchabadindi. adevidhamgaa, pisi-3 mariyu du145 kanaalu osteolytic kanitulanu yerparustaayi. clinical vyaadhini marinta daggaragaa anukarinche aii-pca sell modalnu abhivruddhi cheyadaaniki, ippati varaku atyanta vaidyaparamgaa sambandhita kanajaala samskruti saadhanaalanu andinchadaaniki lncap sublinelu utpatti cheyabaddaayi.
charitra.
maanava prostatic adenocarcinoma yokka metastatic gaayam nundi elncap (prostate yokka shosharasa kanupula cancer) kana rekha sthaapinchabadindi. elncap kanaalu vitrolo (8 x 105 kanaalu/chadarapu sem. mea. varaku; rettimpu samayam, 60 gantalu) sulabhamgaa perugutaayi, clonelanu yerparustaayi mariyu maanava fibroblast interferranku atyanta nirodhakatanu kaligi untaayi. elncap kanaalu 76 nundi 91 varaku modal chromosome sankhyanu kaligi untaayi, idhi aneka marker chromosomelatho kuudina maanava maga kaaryotaipnu suuchistumdi. elncap kanaala praanaantaka lakshanaalu ethemic nagna elukalalo nirvahinchabadataayi, ivi injection sait vadda kanitulanu abhivruddhi chestaayi mariyu "inn vivo" loe idhe vidhamaina rettimpu samayanni chuuputaayi.
cytosol mariyu nuclear bhinnalalo adhika-anubandham gala nirdishta androgen mariyu eastrogen grahakaalu untaayi. lncap line harmon pratispandistundi, idhi kanaala perugudala mariyu assid phosphatase utpatti yokka "inn vitro" 5 alfa-dihydrotestosterone modulation dwara choopabadutundi. elncap kanaalu prostate nirdishta antigen (psa) nuu kooda vyaktam chestaayi. "inn vivo" loe, maga elukalu aadavaalla kante mundugaane mariyu ekkuva frequencytho kanitulanu abhivruddhi chestaayi mariyu harmonela taarumaaru kaniti abhivruddhi yokka frequency seeram androgen sthaayilatho sahasambandham kaligi undani choopistundi. ayithe, kaniti perugudala raetu, atitheyi yokka linga ledhaa harmonela sthithi nundi swatantramgaa untundi.
c4/c5 mariyu c4-2.
vu mariyu itarulu. (1994) ms human emuka fibroblastlatho lncap kanaalanu saha-injection dwara roganirodhaka saktini tagginchina elukalalo maanava-utpanna lncap kanitulanu punarutpatti chesindi. eluka paarsvamloki aneka pradaesaalaloo kanaalanu subcutaneousga inject chesaaru mariyu sumaru 4 vaaraala perugudala taruvaata, kanitulu saareeraka pareeksha dwara sulabhamgaa gurtinchabaddaayi mariyu adhika perugudala retunu kaligi unnaayi (17-33 mm3/roeju).
pca kanaala yokka vishishtamaina maarpunu aiki pratibimbimchadaaniki, lncap host elukalanu injection tarvaata sumaru 8 vaaraala samayamlo madhya-crotal kotha dwara castrate chesaaru. castrated hostlalo 4 nundi 5 vaaraala paatu kanitulu nirvahinchabadataayi, aaa samayamlo migilina kanitulu pandinchabadataayi. mottamgaa, castrated atidheyula nundi rendu upa kanaalu sekarinchabaddayih c4 mariyu c5, varusaga 4 mariyu 5 varalalo sekarinchabaddaayi.
aii-pca kanaala kosam marinta empika cheyadaaniki, sii4 subline ms human fibroblastlatho kalisi castrated host loki inject chesaaru. phalitamgaa vachhe kanitulu verucheyabaddaayi mariyu oka adanapu uparekha, c4-2 utpatti cheyabadindi.
caryotype poolikalu suuchistunnaayi
chekkuchedarani atidheyulalo (m subline) perige lncap kanaalu modal chromosome pampinhee sankhya 83, c4 mariyu c5 sublinelu 85, mariyu c4-2 sublinelu 83 kaligi untaayi.
eee kanaalu maanava muulaaniki chendinavani marinta dhruveekarinchadaaniki caryotype vislaeshanha tallidandrula ln cap kanaalaku 7 vibhina marker chromosomelu unnayani, okkokkati rendu kaapeelu unnayani nirdhaarinchindi. m, c4, c5, mariyu c4-2 uparekhalu chaalaa marker chromosomelanu kaligi unnaayi, m uparekha parental lncap kanaalatoe chaalaa pooli untundi. c4, c5 mariyu c4-2 luu elncap mariyu m subline nundi suukshmamgaa bhinnamgaa untaayi, chromosome 6 kii oka vibhaganni jodinchadam valla marker chromosomenu jodinchadam jarugutundi. chaalaa c4, c5 mariyu c4-2 kanaalalo oka y chromosome undadu, idhi pradhana chromosome maarpulanu suuchistumdi.
sii4, sii5, mariyu sii4-2 uparekhalu elncap maadirigaane kanajaala pempakam paristhitulalo samaanamaina vruddhi retlatho baga perugutaayi. parental elncap, emm, sii4, mariyu sii5 sublinelu ornithine decarboxylase (oodeesee) mariyu prostate nirdishta antigen (psa) yokka baseline janyu vyakteekarana sthaayilanu kaligi untaayi, ayithe, emm, sii4, mariyu sii5 sublinelu 5-10 ex marinta psa mrnnu vyaktam chestaayi. m, c4, c5 mariyu c4-2 kooda AI kanaalalo oohinchina vidhamgaa maanava androgen grahaka mrna taggudalanu vyaktam chesaayi.
androgen sunnitatvam
anni sublinelu aarr kosam adhika-anubandha ligand ayina dihydrotestosterone (dehechti) thoo chikitsa cheyabaddaayi. dehechti chikitsa anedi sii4 mariyu sii5 kanaalalo gananeeyamgaa taggina perugudalanu mariyu elncap kanaalalo kanipinche adhika perugudala retutho polchinappudu sii4-2 kanaalalo perugudala ledani, sii4 mariyu sii5loe androgen sunnitatvam taggipoyindani mariyu sii4-2 kanaalalo eaini suuchistumdi. mottam-kana aarr aseh kooda c4-2 (kd = 267 PM) thoo poliste lncap kanaalu ar (kd = 159 PM) yokka chaalaa ekkuva anubandha roopaanni kaligi unnayani suuchimchimdi.
tumerigenesity
tallidandrula lncap kanaala maadirigaa kakunda, chekkuchedarakunda unna maga elukalalo inject chesinappudu sii4 mariyu sii5 sublinelu baga perigina tumerigenesityni pradarsistaayi. ms human fibroblastlatho saha-inject chesinappudu castrated elukalalo sii4 mariyu sii5 kooda adhika vascularised carcinomelanu yerparuchukunnayi. sii4 mariyu sii5 sublinela kante sii4-2 subline chekkuchedarani atidheyalalo kanitulanu marinta sulabhamgaa yerparustundi mariyu ms maanava emuka fibroblastla saha-injection lekunda castrated atidheyalalo kanitulanu yerparuchukune ekaika kanaalu avi. adhe sii4-2 kanitulu psa kosam marakalu veyabadi, adhika sthaayi psnu vruddhi maadhyamamloki sravistaayi.
c4-2b.
emuka metastatic subline utpatti cheyadaaniki, c4-2 kanaalu keellanoppito kuudina maga elukalalo keellanoppito inject cheyabaddaayi. eee kanaalu prostate, shosharasa kanupulu, alaage ossius kanitula yokka pedda praadhamika kanitulanu yerparustaayi. eee ossius kanitulanu verucheyadam valla sii4-2బii subline erpadindi.
sii4-2బii kanaalu psa mariyu cytocheratin 8kii sanukoolamgaa unnaayi, ivi vaati prostatic muulaanni nirdharinchaayi. murry mukhyamgaa, sii4-2బii kanitula yokka immunohystochemical steining osteoblast kaaryakalaapaalaku sanukoolamgaa undhi, idhi maanava pca purogatini pratibimbimchae osteoblastic kaniti erpadataanni suuchistumdi.
ascorbic aamlam (osteoblastlalo asthipanjaram lanty ecm nirmaanaanni prothsahinchadaaniki prasiddhi chendinadi) mariyu fasfate yokka muulaanni (hydroxypatite erpadataaniki) kaligi unna "pramukha madhyamam" loe samskarinchinappudu, sii4-2బii kanaalu parental elncap kanaala kante sumaru 8 retlu ekkuva khanija calciumnu utpatti chesi, nilupukuntaayi. sii4-2బii kanaalu bolu emukala protein (opg), alkaleen phosphatase, emuka sialoprotein (bsp), osteocalacin (ocn), rankle mariyu osteonectin (osn) mrna adhika sthaayilanu kooda vyaktam chestaayi, ivanni osteoblastla dwara ekkuvagaa vyakteekarinchabadataayi.
cbfa1 transcription phyaaktar expression dwara suuchimchinatlugaa, lncap thoo poliste c4-2b kanaalalo osteoblast promoter activity kooda ekkuvagaa untundi. adhe samayamlo, cbfa1 yokka telisina prerakamaina bMP7 kooda c4-2b kanaalalo marinta ekkuvagaa vyakteekarinchabadutundi, idhi aneka osteoblast lanty lakshanaalanu suuchistumdi.
androgen swatantra rakalu.
ln95 kanaalu rpmi-1640 (final erupu lekunda) loe 10 saatam boggu tolaginchina pindam bovin seeram thoo culture cheyabadina ln cap nundi udbhavinchaayi. ln95 kanaalu parental elncap kanaala nundi padanirmaanaparamgaa, dendritic podigimpulatoe, mariyu paramaanugaa, aarr-vii7 hye vacp kanaala maadirigaane androgen grahaka roopaantara vyakteekaranhatho bhinnamgaa untaayi. mukhyamgaa, ln95 kanaalu vaati tallidandrula sahacharula "vivo" kante gananeeyamgaa ekkuva kanitini praarambhistaayi.
elncap-ii (ledhaa elncap-ii) kanaalu boggu tolaginchina seeramlo elncap parental kanaala 6 nelala culture nundi udbhavinchaayi. elncap-ii puurtigaa androgen swatantramgaa unnappatikee, avi androgen grahakam yokka adhika vyakteekarananu, aarr-vii7 yokka takkuva vyakteekarananu kaligi untaayi mariyu androgen pratispandinchevigaa untaayi. elncap-aii kanaala yokka atyanta vistarinche samalakshanam yokka yantraangam kana chakra niyantrana vyakteekarana (pii21, pii16) kolpovadam mariyu anty-apoptotic bii. sii. ell2 vyakteekarana peragadam.