PNC-27 30mg we yu go yuz

▎ PNC 27 Struktrɔ

▎ PNC 27 Risach

Wetin na di aplikeshɔn dɛn fɔ PNC-27?

1, Tritmɛnt fɔ lukimiya: 

PNC-27 ebul fכ biεn di HDM-2 protin pan di mεmbran fכ di kεnsar sεl dεm εn i de indyuz di fכmeshכn fכ saytכtoksik transmεmbran por dεm. insay wan stכdi pan hכman nכn-stεm sεl akyu mayloid lukimiya sεl layn dεm, dεn fכnshכn se HDM-2 de hεvi εksprεs insay di mεmbran dεm fכ U937 (akyu monosaytik lukimiya), OCI-AML3 (akyu granulomonosaytik lukimiya), εn HL60 (akyu promaylosaytik lukimiya) sεl dεm.PNC-27 de biεn HDM-2 pan mεmbran dεm, εn indyuz nεkroptosis εn LDH (laktat dεhaydrojenεz) de rilis insay 4 awa. (LDH) de rilis insay 4 awa. tכgεt HDM-2 pan di sεl mεmbran kin bi wan pכtεnshal stratεji fכ di tritmεnt fכ lukimiya.PNC-27 sho sכm sכm anti-lukεmik aktiviti in sεvεra lukimiya sεl layn dεm bay we i tכk mεmbran HDM-2 ^[1]..

2. I de mek di tכmכro sεl layz

i de akt lεk intakt pεptida: 

sεvεra stכdi dεn sho se PNC-27 de indyuz tכmכro sεl layz as intakt pεptida pas as fragmεnt. fכ egzampl, insay wan stכdi pan MCF-7 brεst kεnsar sεl dεm εn כntransfכm MCF-10-2A mama εpitεlial sεl dεm, dεn trit sεl dεm wit PNC-27 wit grεn fכrosεnt lεbul amino tεrminכs εn rεd fכrosεnt lεbul kכbכksi tεrminכs. di risalts sho wan difrεnt panktat yכlכ fכrosεns pan di kεnsar sεl mεmbran na 30 min, we sho se di intakt pεptida bin de pan di kεnsar sεl mεmbran εn i inkrεs wit kεnsar sεl laysis. difrεnt frכm dat, di MCF-10-2A sεl dεm we nכ transfכm fכs sho yunifכm yכlכ mεmbran fכrosεns, bכt dεn dכn disappear. Dɛn sɛl dɛn ya we nɔ chenj nɔ bin tan lɛk kansa sɛl dɛn, dɛn bin kɔntinyu fɔ liv. dis sho se PNC-27 de mek di mεmbran klivεj insay kεnsar sεl dεm bay we i de akt lεk wan כl pεptida, pas fכ bi wan fragmεnt ^{[2] .}.

Binding to HDM-2 fכ fכm pore strכkchכ dεm: 

PNC-27 gεt wan HDM-2-binding strכkchכral domεn εn wan sεl-pεnεtratin pεptida (CPP) prεsikεns, we de indyuz di fכmeshכn fכ pore strכkchכ dεm bay we i de biεn to HDM-2 pan di sεl mεmbran, we de lid to tכmכro sεl laysis εn nεkrכsis. kכnfכmeshכnal εnεji kכlkyulshכn sho se PNC-27 de fכm wan kכmpleks wit HDM-2 insay 1: 1 rεshכ, wit di lida sikεns we de pכynt away frכm di kכmpleks. imyunoskan εlektrכn maykroskכpi stכdi dεm sho di prεsεns fכ mכltipכl 6 nm εn 15 nm lεbul gold patikyula dεm pan wan rεshכn we de arawnd 1:1 insay di por dεm na di sεf fכ kεnsar sεl dεm we dεn trit wit PNC-27, we sho se dεn kכmpleks dεm ya imכtant fכ pore strכkchכ. difrεnt frכm dat, nכ pores nכ bin fכm in kכntrכl, כntransfכm fכblas dεm we dεn trit wit PNC-27 ^{[3] .}.

Pankrias Kansa: 

di nכvel antikansa PNC-27 pεptida de indyuz nεkrכsis fכ hכman pankrεas MiaPaCa-2 kεnsar sεl dεm insay wan dכz-dipεndεnt we, bכt i nכ tכxik to nכmal sεl dεm. stכdi dεn sho se PNC-27, we dεn kכmbayn wit Gemzar, we na kεmothεrapi ejen we dεn kin yus fכ trit pankrεas kεnsar, i gεt bכku saytכtoksik ifekt pan MiaPaCa-2 sεl dεm pas Gemzar כ PNC-27 nכmכ. dis kin bi biכs di pכr dεm we PNC-27 indyuz de inkrεs di pεrmiabiliti fכ di kεnsar sεl dεm to Gemzar, we de alaw mכr Gemzar fכ tכk bכt di kεnsar sεl dεm ^{[1] .}.

Kansa na di ovarian: 

insay ovarian kεnsar sεl layn dεm SKOV-3 εn OVCAR-3, di HDM-2 protin de hεvi εksprεs na di sεl mεmbran.PNC-27 de kכ-lכkal wit HDM-2 na di sεl mεmbran, we de mek di sεl nεkrכsis kwik kwik wan. difrεnt frכm dat, in di nכn-transfכm kכntrכl sεl layn HUVEC, kכ-lokalεyshכn εn saytכtoksisiti fכ PNC-27 nכ bin obsεv biכs fכ minimכl mεmbran HDM-2 εksprεshכn ^[1]..

Kɔlɔn Kansa: . 

PNC-27 selektivli kil di kכlon kεnsar stεm sεl dεm. insay siks kכlon kεnsar sεl layn dεm, PNC-27 kכ-lכkal wit mεmbran HDM-2 εn i mek sεl dεd (tכmכr sεl nεkrכsis, hεy LDH rilis, mεmbran asosiet protin V εn sistayn 3 nεgεtiviti) nכmכ insay kεnsar sεl dεm. in vivo, PNC-27 de mek nεkrכsis fכ di tכmכro nכdul dεm bכt i nכ de afekt nכmal tisu ^[1]..

3. Impruv anti-tumor efficacy

Binding to Dɔksil: 

i fכnshכn se PNC27 pεptida, as tכgεt ligεnd, kin sכmtεm εnhans di anti-tכmכr efikכs fכ Doxil in HDM2-positiv kεnsar sεl dεm. difrεnt amoun dεm fכ PNC27 pεptida bin insay Doxil, εn fכ fכlכ saytכmetri εn kכnfכkal analisis bin de pan C26 kכlon kεnsar (HDM2-positiv) εn B16F0 melanoma (HDM2-nεgεtiv) sεl dεm. di risalts sho se PNC27-Doxil sho signifyant sεlyul כptek εn saytotoksisiti in C26 sεl dεm, we dεn risכlt ya nכ bin obsεv in B16F0 sεl dεm. fכ egzampl, PNC27-Doxil (100 PNC27 pεptida) sכmtεm inkrεs di tεrapi efikכs fכ Doxil we nכ afekt in bayodistribushכn insay C26 tכmכro dεm ^[4]..

4. Sinajistik tritmεnt fכ ovarian kεnsar wit paklitaksεl

paklitaksεl dεn de yuz am bכku bכku wan fכ trit gaynεkכlכjik malignεns dεm, bכt i de tכk tכmכro sεl dεm na di M fεz na di sεl saykl, wit sεl dεm we de insay כda fεz dεm we de liv εn i kin mek tכmכro kam bak.PNC-27 na pεptida we dεn sεntez frכm amino asid dεm insay di P53-MDM-2 binding domεn we de kil difrεn kεnsar sεl layn dεm insay wan we we dipεnd pan di dכz. ovarian kεnsar ID8 sεl dεm we dεn εkspכz to paklitaxel dεn fכnshכn fכ sho inkrεs εksprεshכn fכ MDM-2 εn inkrεs sεnsitiviti to PNC-27.Di saytכtoksik ifekt fכ PNC-27 de dipεnd pan in binding to MDM-2, εn blכk MDM-2 de inhεbit di kil ifekt fכ PNC-27. di hεterodrug imej dεm fכ di dכz kכmbaynshכn dεm bin sinagεstik, we sכgεst wan sinagεstik ifekt bitwin PNC-27 εn paklitaksεl ^[5] . insay wan intrapεritoneal mכdel fכ ovarian kεnsar (ID8), di adishכn fכ PNC-27 to wik paclitaxel administreshכn sכmtεm rεdכks tכmכro growth. dis data dεm de sho wan sinagεstik ifekt bitwin PNC-27 εn paklitaksεl, wit PNC-27 we de tכk bכt sεl-sכvayv paklitaksεl εn impruv in antitכmכr ifekt dεm.

5. Tritmεnt fכ praymari εpitεlial ovarian kεnsar

wan stכdi dεn establish praymar kכltכr dεm fכ fכs isolεt εpitεlial ovarian kεnsar sεl dεm frכm pasεnshכn dεm we dεn nyu we dεn dכn no ovarian cystadenocarcinoma. Wan pan dɛn na frɔm mucinous cystadenocarcinoma ɛn di ɔda wan na frɔm ay-grɛd papillary plasmacytoid carcinoma. Di terapi efficacy of PNC-27 bin kwantiti asɛs bay kwalitatif layt maykroskɔpik ɔbshɔbishɔn ɛn MTT sɛl proliferashɔn assay ɛn bak mɛzhɔmɛnt fɔ laktat dihaydrojɛnɛz (LDH). di risalts sho se PNC-27 inhεbit di growth fכ hכman praymar kεnsar sεl dεm we dεn fכs ayzכlεt frכm tu ovarian εpitεlial kכrεs in wan dכz-dipεndεnt we εn i bin saytכtoksik to dεm. di kontrכl pεptida PNC-29 nכ bin gεt nכ ifekt pan praymar kεnsar sεl dεm. apat frכm dat, PNC-27 na saytכtoksik bak to di hכman ovarian kεnsar sεl layn dεm we dεn bin de εstablish fכ lכng tεm εn we de rεsistεnt kεmothεrapi ^{[6] .}.

fכ sכmari, PNC-27, as nכvel antikansa pεptida, sho sכm sכm pכtεnshal fכ aplikεshכn insay difrεn kεnsar tεrapi dεm. insay di fild fכ lukimiya, PNC-27 sho selektiv kil ifekt pan akyu mayloid lukimiya (εgz., U937, OCI-AML3, εn HL60 sel layn dεm) εn p53-dεficient K562 sεl dεm, εn i achyv hεli efyushכn antitכmכr ifekt bay we i indyuz sεl nεkrכsis εn laktat dεhaydrojenεz rilis. insay di tritmεnt fכ ovarian kεnsar, di kכmbaynshכn fכ PNC-27 εn paclitaxel sho wan sinagεstik ifekt, we kin sכmtεm inhεbit tכmכro growth εn stil gεt kil aktiviti εgεst kεmothεrapi-rεsistant sεl dεm. apat frכm dat, di kכmbaynshכn fכ PNC-27 wit liposomal dכg dεm (εgz. Doxil) as tכgεt ligεnd kin εnhans di spεsifi k dεlivεri εn anti-tכmכr efikכs fכ di dכg to HDM2-positiv tכmכro sεl dεm. in inhibitory ifekt pan praymari εpitεlial ovarian kεnsar projenitor sεl dεm de validet di klinik transleshכnal valyu fכs. Naw, PNC-27 dɔn go insay di faz I klinik trayal, ɛn dɛn nid fɔ du mɔ klinik stɔdi fɔ validet in sef ɛn lɔng tɛm ɛfifikɛshɔn, so dat dɛn go protɛkt am as nyu sɔlvishɔn fɔ kansa tritmɛnt.

Bɔt di pɔsin we rayt di buk

Di tin dɛn we wi dɔn tɔk bɔt ɔp, na ɔl di tin dɛn we Cocer Peptides dɔn du risach, ɛdit ɛn kɔmpilayt.

Sayɛns Jɔnal Author

Sarafraz-Yazdi E na wan risachman we gɛt fɔ du wit sɔm ɔganayzeshɔn dɛn, lɛk NomoCan, Nyu Yɔk Blɔd Sɛnta, SUNY Downstate Health Sciences University, ɛn New York Harbor VA Med Ctr. Dɛn afilieshɔn ya de sho aw i de involv pan difrɛn risach ɛn mɛdikal ɛnvayrɔmɛnt dɛn.

In risach intɛres span akɔdin to difrɛn sɔbjɛkt kategori dɛm lɛk Ɔnkɔlɔji, Mɛdikal Labɔrɔtɔri Tɛknɔlɔji, Famakɔlɔji & Famasi, Bayokɛmistri & Mɔlikul Bayoloji, ɛn Risach & Ɛkspirimɛnt Mɛdisin. Di wok we i de du pan dɛn tin ya de sho se i sabi bɔku tin ɛn i de wok tranga wan fɔ mek pipul dɛn no mɔ bɔt dɛn impɔtant tin dɛn ya we gɛt fɔ du wit mɛdikal sayɛns ɛn risach. na di list na di rεfrεns fכ saytεshכn [3].

▎ Saytayshɔn dɛn we gɛt fɔ du wit dis

[1] Thadi A, Gleeson E. M., Khalili M, ɛn ɔda pipul dɛn. Anti-Kansa Tכmכr Sεl Nεkrכsis fכ di Epithelial Ovarian Kεnsar Sεl Layn dεm de dipεnd pan di hכy εksprεshכn fכ HDM-2 protεin insay dεn mεmbran dεm[J]. Annals of Klinik ɛn Labɔrɔtɔri Sayns, 2020,50(5):611-624. https://pubmed.ncbi.nlm.nih.gov/33067207/ Di wan dɛn we de stɔdi bɔt di Baybul.

[2] Sookraj K. A., Bowne W. B., Adler V., ɛn ɔda pipul dɛn. di anti-kansa pεptida, PNC-27, de indyuz tכmכro sεl layz as di intakt pεptida[J]. Kansa Kimotɛrapi ɛn Famakɔlɔji, 2010,66(2):325-331.DOI:10.1007/s00280-009-1166-7.

[3] Sarafraz-Yazdi E, Mumin S, Cheung D, ɛn ɔda pipul dɛn. PNC-27, wan Chimeric p53-Penetratin Pεptid de Bind to HDM-2 in wan p53 Pεptid-layk Struktכr, I de Indyuz Sεlektiv Mεmbran-Pכr Fכmeshכn εn Lid to Kεnsar Sεl Lysis[J]. Bayomedisin, 2022,10(5).DOI:10.3390/bayomedisin10050945.

[4] Darban SA, Badiee A, Jaafari M R. PNC27 antikansa pεptida as tכgεt ligεnd sכmtεm improv antitכmכr efikכs fכ Doxil in HDM2-εksprεs sεl dεm[J]. Nanomedisin, 2017, 12 (12): 1475-1490.DOI: 10.2217/nnm-2017-0069.

[5] Alagkiozidis I, Gɔrɛlik C, Shah T, ɛn ɔda pipul dɛn. Sεnaji bitwin Paclitaxel εn Anti-Kεnsar Pεptid PNC-27 in di Tritmεnt כf Ovarian Kεnsar (Rεtrakshכn כf Vol 47, Pg 271, 2017)[J]. Annals of Klinik ɛn Labɔrɔtɔri Sayns, 2017,47(4). https://pubmed.ncbi.nlm.nih.gov/28667027/ Di wan dɛn we de stɔdi bɔt di Baybul.

[6] Sarafraz-Yazdi E, Gorelick C, Wagreich A. R., ɛn ɔda pipul dɛn. Ex vivo Efikεsi כf Anti-Kεnsar Drug PNC-27 in di Tritmεnt כf Patiεnt-Dεrivεd εpitεlial Ovarian Kεnsar[J]. Annals of Klinik ɛn Labɔrɔtɔri Sayns, 2015,45(6):650-658. https://pubmed.ncbi.nlm.nih.gov/26663795/ Di wan dɛn we de stɔdi bɔt di Baybul.

ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.  

Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.