1kits(10Fiyɛliw) .
| A sɔrɔli: | |
|---|---|
| Hakɛ: | |
▎ PNC 27 Lajɛba
PNC-27 ye p53 donna pepitiri ye min bɛ kɛ ni kimɛriki ye, min bɛ kɛ ni sigicogo yɔrɔ ye (tolen 12-26) p53 farikolojɔlan kɔnɔ min bɛ siri HDM-2 la ani pepitiri doncogo transmembrane. A bɛ transmembrane pore dilan ni a sirilen don HDM-2 proteine la kansɛribanakisɛw ka membranes kɔnɔ, o bɛ na ni membrane lysis ni necrosis ye kansɛribanakisɛw la, ka sɔrɔ a tɛ baga ye cellules normales ma. Nin sugandili fɛɛrɛ in kɛra sababu ye ka kansɛri kɛlɛli baara caman kɛ kansɛribanakisɛ suguya caman na (misali la, sinji kansɛri, kɔnɔbara kansɛri, jolidɛsɛ jugumanba miyɛloyi, a ɲɔgɔnnaw). PNC-27 ɲɔgɔn tɛ yen, bawo a kɛcogo tɛ bɔ p53 baarakɛcogo la, o de b’a to a bɛ se ka nafa sɔrɔ tumuw furakɛli la minnu tɛ se ka furakɛlicogo kɔrɔw kɛ minnu bɛ tali kɛ p53 la. Ka fara o kan, PNC-27 ye jɛɲɔgɔnya nɔ jira ni chimiothérapie furaw ye i n’a fɔ paclitaxel, o ye dɔ fara a furakɛli seko kan.
▎ PNC 27 Jatebɔ
Sɔrɔyɔrɔ: EMBL-EBI |
A kɛcogo: PPLSQETFSDLWKLLKKWKMRRNQFWVKVQRG Formula molekilɛri: C 188H 293N 53O 44S Molecules girinya: 4031,73g/mol CAS nimɔrɔ: 1159861-00-3 |
▎ PNC 27 Sɛgɛsɛgɛli
PNC-27 baarakɛcogo ye mun ye?
1, Jolidɛsɛ furakɛli :
PNC-27 bɛ se ka HDM-2 furakisɛ siri kansɛribanakisɛw ka ɲɛgɛnɛsira la ani ka kɛ sababu ye ka sitotokisi transmembrane pores (banakisɛfagalanw) dilan. Adamadenw ka jolidɛsɛ jugumanba miyɛloyidi selilɛriw ka sɛgɛsɛgɛli dɔ la, a jirala ko HDM-2 bɛ sɔrɔ kosɛbɛ U937 (jolidɛsɛ monositiki jugumanba), OCI-AML3 (jolidɛsɛ granulomonocytique acute), ani HL60 (joubanakisɛ promyelocytique acute) selilɛriw ka membranes kɔnɔ.PNC-27 bɛ siri HDM-2 la membranes kan, ka a bila nekɔrɔptose ni LDH (lactate dehydrogenase) bɔli ye lɛri 4 kɔnɔ. (LDH) bɛ bɔ lɛri 4 kɔnɔ. HDM-2 laɲinini selilɛri kan, o bɛ se ka kɛ fɛɛrɛ ye min bɛ se ka kɛ jolidɛsɛ furakɛli la.PNC-27 ye jolidɛsɛ kɛlɛli baara nafama jira jolidɛsɛbanakisɛ caman na, a kɛtɔ ka Membrane HDM-2 laɲini.
2. A bɛ tumokisɛw wulicogo bila mɔgɔ la
A bɛ baara kɛ i n’a fɔ pepitiri min ma tiɲɛ:
Kalan caman y’a jira ko PNC-27 bɛ tumokisɛw bɔli bila mɔgɔ la i n’a fɔ pepitiri min ma tiɲɛ sanni ka kɛ a yɔrɔ dɔ ye. Misali la, MCF-7 sinji kansɛribana banakisɛw ni MCF-10-2A sinji ɲɛgɛnɛsira minnu ma fɛn caman sɛmɛntiya, olu furakɛra ni PNC-27 ye ni amino labanw ye minnu taamasiyɛn ye fluorescent vert ye ani carboxy terminus minnu taamasiyɛn ye fluorescent bilenman ye. Jateminɛw y’a jira ko fluorescence jɛman punctate danfaralen bɛ kansɛri selilɛri kan miniti 30 kɔnɔ, o b’a jira ko pepitiri min ma tiɲɛ, o tun bɛ kansɛri selilɛri membrane kan, wa a bɛ caya ni kansɛri selilɛri sɔgɔli ye. O ni MCF-10-2A selilɛriw ta tɛ kelen ye, a daminɛ na, u ye membrane jaune fluorescence kelen jira, nka o kɔfɛ, u tununna. O farikolokisɛ minnu ma fɛn caman sɛmɛntiya, olu ni kansɛribanakisɛw tɛ kelen ye, u tora ɲɛnamaya la. O b’a jira ko PNC-27 bɛ membrane cleavage bila kansɛribanakisɛw la, a kɛtɔ ka kɛ i n’a fɔ pepitiri kuuru, sanni ka kɛ a yɔrɔ dɔ ye [2] ..
A sirili HDM-2 la walasa ka porozɛw dilan:
PNC-27 kɔnɔ, HDM-2 sirili yɔrɔ dɔ bɛ sɔrɔ a kɔnɔ ani pepitiri min bɛ don selilɛri kɔnɔ (CPP) presequence, o bɛ kɛ sababu ye ka porozɛw jɔ ni a sirili ye HDM-2 la selilɛri kan, o bɛ na ni tumu selilɛriw ka sɔgɔsɔgɔli ni nekɔrɔsi ye. Jateminɛ minnu kɛra fanga cogoya la, olu y’a jira ko PNC-27 bɛ fɛnɲɛnɛma dɔ Kɛ ni HDM-2 ye 1:1 hakɛ la, ni ɲɛmɔgɔya sinsinni bɛ Jigin ka Bɔ fɛnɲɛnɛma in na. Immunoscanning electron microscopy kalanw y’a jira ko sanu fɛnɲɛnamafagalan caman bɛ yen minnu taamasiyɛn ye 6 nm ni 15 nm ye, ni u hakɛ bɛ se 1:1 ma, kansɛribanakisɛw sanfɛla la, minnu furakɛra ni PNC-27 ye, o b’a jira ko nin fɛnɲɛnɛma ninnu nafa ka bon porow jɔli la. O ni fɛnɲɛnamafagalanw ta tɛ kelen ye, ɲɛgɛnɛsira si ma dilan ni PNC-27 ye [3] ..
Pankreyasi kansɛri:
Kansɛri kɛlɛli pepitiri kura PNC-27 bɛ hadamadenw ka pankreyasi MiaPaCa-2 kansɛribanakisɛw fagali bila mɔgɔ la cogo la min bɛ bɔ a tata hakɛ la, nka a tɛ baga ye farikolokisɛw la minnu ka kɛnɛ. Kɔlɔsiliw y’a jira ko PNC-27 ni Gemzar farala ɲɔgɔn kan, o ye chimiothérapie ye min bɛ kɛ ka kɔnɔboli kansɛri furakɛ, o bɛ se ka kɛ sitotokisi ye MiaPaCa-2 selilɛriw la ka tɛmɛ Gemzar walima PNC-27 kelen kan. O bɛ se ka kɛ bawo PNC-27-induite pores bɛ dɔ fara kansɛribanakisɛw ka se ka don Gemzar la, o bɛ a to Gemzar caman bɛ se ka kansɛribanakisɛw laɲini [1] ..
Kansɛri min bɛ sɔrɔ kɔnɔbara la:
Ovari kansɛri selilɛriw la SKOV-3 ani OVCAR-3, HDM-2 farikolojɔli dumuni bɛ jira kosɛbɛ selilɛri la.PNC-27 bɛ sigi ɲɔgɔn fɛ ni HDM-2 ye selilɛri la, o bɛ na ni selilɛriw ka fagali teliya ye. O ni HUVEC ta tɛ kelen ye, Kɔlɔsili selilɛri HUVEC la, PNC-27 ka sigiyɔrɔmali ni a sitotokisisi ma ye ka da HDM-2 jirali dɔgɔyali kan membrane kɔnɔ.
Kolotuguda kansɛri:
PNC-27 bɛ kɔnɔbara kansɛri banakisɛw faga ka kɛɲɛ ni a sugandili ye. Kɔnɔnatumu kansɛri selilɛri wɔɔrɔ kɔnɔ, PNC-27 ni membrane HDM-2 kɛra ɲɔgɔn fɛ ani ka kɛ sababu ye ka selilɛriw faga (tumo cell necrosis, LDH bɔli caman, membrane associated protein V ani cysteine 3 negativity) kansɛribana dɔrɔn de la. In vivo, PNC-27 bɛ kɛ sababu ye ka kurukuruw faga nka a tɛ nɔ bila farikolo yɔrɔw la minnu ka ɲi [1] ..
3. Tumuw kɛlɛli seko ɲɛnabɔli
A sirili Doxil la:
A jirala ko PNC27 pepitiri, n’o ye ligandi laɲini ye, o bɛ se ka Doxil ka tumu kɛlɛli nafa bonya kosɛbɛ kansɛribanakisɛw la minnu bɛ HDM2 sɔrɔ. PNC27 pepitiri hakɛ danfaralenw donna Doxil kɔnɔ, ka flow cytometry ni confocal analysis kɛ C26 kolotuguda kansɛri (HDM2-positif) ani B16F0 melanoma (HDM2-negatif) selilɛriw kan. Jateminɛw y’a jira ko PNC27-Doxil ye selilɛriw tali ni sitotokisi nafama jira C26 selilɛriw la, k’a sɔrɔ o jaabiw ma ye B16F0 selilɛriw la. Misali la, PNC27-Doxil (100 PNC27 peptide) ye dɔ fara kosɛbɛ Doxil furakɛli nafa kan k’a sɔrɔ a ma nɔ bila a ka ɲɛnamaya jɛnsɛnni na C26 kuruw la.
4. Kɔnɔbara kansɛri furakɛli ni pakilitakisili ye ɲɔgɔn fɛ
Paclitaxel bɛ kɛ ka caya muso ka bana jugumanw furakɛli la, nka a bɛ tumokisɛw laɲini minnu bɛ selilɛri M fasa la, ni selilu minnu bɛ fasa wɛrɛw la, olu bɛ balo ani a bɛ se ka kɛ sababu ye ka tumu seginni kɛ.PNC-27 ye pepitiri ye min dilannen don ni asidi aminikiw ye P53-MDM-2 siriyɔrɔ la min bɛ kansɛribanakisɛ suguya caman faga cogo la min bɛ bɔ a tata hakɛ la. Ovari kansɛri ID8 selilɛri minnu kɛra pakilitakɛli la, a jirala ko u bɛ MDM-2 jiracogo caya jira ani ka dɔ fara u ka teli ka PNC-27 sɔrɔ.PNC-27 ka sitotokisi nɔ bɛ bɔ a sirili la MDM-2 la, wa MDM-2 balili bɛ PNC-27 fagali nɔ bali. Fura hakɛ faralenw ja hɛtɛrofuraw tun ye ɲɔgɔndɛmɛ ye, o b’a jira ko jɛɲɔgɔnya bɛ PNC-27 ni paclitaxel cɛ [5] . Kɔnɔnatumu kansɛri (ID8) misali dɔ la, PNC-27 farali pakilitakisi tali kan dɔgɔkun o dɔgɔkun, o ye dɔ bɔ kosɛbɛ kuru bonya la. Nin kunnafoniw b’a jira ko jɛɲɔgɔnya bɛ PNC-27 ni pakilitasɛli cɛ, ni PNC-27 bɛ pakilitakisili laɲini min bɛ balo selilɛriw la ani k’a ka tumu kɛlɛli nɔw ɲɛ.
5. Kansɛri fɔlɔ min bɛ sɔrɔ kɔnɔbara la, o furakɛli
Kalan dɔ ye kɔnɔbara basigilen kansɛribana banakisɛ minnu bɔra kɛnɛ kan kokura, olu ka sɛnɛ fɔlɔw sigi senkan ka bɔ banabagatɔw la minnu ka kɔnɔbara basigilen kansɛri sɔrɔla kura ye. U dɔ bɔra mucinous cystadenocarcinoma la ani tɔ kelen tun bɔra papillaire plasmacytoïde carcinome haute la. PNC-27 furakɛli nafa jateminɛna hakɛ la ni yeelen mikoroskɔpi kɔlɔsili ye min bɛ kɛ ni MTT selilɛri caya sɛgɛsɛgɛli ye ka fara laktati dehidrojɛnazi (LDH) sumani kan. Jateminɛw y’a jira ko PNC-27 ye hadamadenw ka kansɛri fɔlɔ banakisɛw falenni bali minnu bɔra kɔnɔbara basigilen kansɛri fila la kura ye cogo la min bɛ bɔ a tata hakɛ la, wa a tun ye sitotokisi ye u bolo. Kɔlɔsili pepitiri PNC-29 ma nɔ foyi bila kansɛri banakisɛ fɔlɔw la. Ka fara o kan, PNC-27 fana ye sitotokisi ye hadamadenw ka kɔnɔbara kansɛri selilɛriw la minnu sigira sen kan kabini tuma jan ani minnu tɛ se ka furakɛli kɛ [6] ..
Kuma surun na, PNC-27, i n’a fɔ kansɛri kɛlɛli pepitiri kura, o bɛ se ka kɛ kansɛri furakɛli suguya caman na. Jolidɛsɛ siratigɛ la, PNC-27 ye fagali nɔ sugandilenw jira jolidɛsɛ jugumanba miyɛloyi (misali la, U937, OCI-AML3, ani HL60 selilɛriw) ani K562 selilɛriw la minnu tɛ p53 sɔrɔ, wa a ye tumu kɛlɛli nɔ ɲumanw sɔrɔ kosɛbɛ, a kɛtɔ ka selilɛriw ka sɔgɔsɔgɔninjɛ ni laktati dehidrojɛnazi bɔli bila mɔgɔ la. O kɔnɔbara kansɛri furakɛli la, PNC-27 ni paclitaxel faralen ɲɔgɔn kan, o ye ɲɔgɔndɛmɛ nɔ jira, o bɛ se ka tumuw falenni bali kosɛbɛ, wa hali bi, mɔgɔfaga baara bɛ kɛ farikolokisɛw la minnu bɛ se ka chimiothérapie kɛlɛ. Ka fara o kan, PNC-27 ni lipozomi furaw (misali la Doxil) faralen ɲɔgɔn kan i n’a fɔ laɲini ligandi, o bɛ se ka fura in dili kɛrɛnkɛrɛnnen ni a ka tumu kɛlɛli nafa bonya HDM2-positif tumuw la. A ka balili nɔ min bɛ sɔrɔ kɔnɔbara basigilen kansɛri fɔlɔw la, o bɛ kɛnɛyako bamanankan nafa sinsin ka taa a fɛ. Sisan, PNC-27 donna furakɛli sɛgɛsɛgɛliw dakun fɔlɔ la, wa kɛnɛyako sɛgɛsɛgɛli caman ka kan ka kɛ walasa k’a lakanani n’a nafa kuntaalajan sinsin, walasa k’a yiriwa i n’a fɔ fura kura kansɛri furakɛli la.
A sɛbɛnbaga ko la
Fɛn minnu kofɔlen dòn san fɛ, olu bɛɛ ɲinini Kɛra, k’u Labɛn ani k’u Lajɛ Cocer Peptides fɛ.
Dɔnniya gafe sɛbɛnbaga
Sarafraz-Yazdi E ye ɲininikɛla ye min ni jɛkulu caman bɛ ɲɔgɔn fɛ, i n’a fɔ NomoCan, New York Blood Center, SUNY Downstate Health Sciences University, ani New York Harbor VA Med Ctr. O jɛkuluw b’a ka sendon ɲinini ni furakɛli sigida suguya caman na.
A ka ɲininiw ɲɛsinnen bɛ kalansen suguya caman ma i n’a fɔ Kansɛri, Dɔgɔtɔrɔso laboratuwari Teknoloji, Furakɛcogo & Furakɛcogo, Biyokimisi & Molecules Biologi, ani ɲinini & Kɔrɔbɔli furakɛli. A ka baara minnu kɛra o ko ninnu na, olu b’a ka dɔnniyaba n’a ka cɛsiri jira walasa ka dɔnniya yiriwa furakɛli dɔnniya ni ɲinini yɔrɔ nafama ninnu na. bɛ sɛbɛn citation (citation) ɲɛfɔli sɛbɛn kɔnɔ [3].
▎ Sɛbɛn minnu bɛ tali kɛ o la
[1] Thadi A, Gleeson E. M., Khalili M., ani mɔgɔ wɛrɛw. Kansɛri kɛlɛli tumu selilɛriw ka nekɔrɔsi epiteliyali kansɛri selilɛriw la, o bɛ bɔ HDM-2 poroteyini jirali caya la u ka ɲɛgɛnw kɔnɔ[J]. Annals de science clinique et laboratoire, 2020,50(5):611-624. https://pubmed.ncbi.nlm.nih.gov/33067207/ Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.
[2] Sookraj K. A., Bowne W. B., Adler V., ani mɔgɔ wɛrɛw. Kansɛri kɛlɛli pepitiri, PNC-27, bɛ tumokisɛw bɔli bila mɔgɔ la i n’a fɔ pepitiri min ma tiɲɛ[J]. Kansɛri furakɛli ni furakɛli, 2010,66(2):325-331.DOI:10.1007/s00280-009-1166-7.
[3] Sarafraz-Yazdi E, Mumin S, Cheung D, ani a ɲɔgɔnnaw. PNC-27, o ye Chimeric p53-Penetratin Peptide ye min bɛ siri HDM-2 la p53 Peptide-like Structure kɔnɔ, a bɛ Selective Membrane-Pore Formation bila mɔgɔ la ani ka na ni Cancer Cell Lysis ye[J]. Biomedicines, 2022,10(5).DOI:10.3390/biyofurakɛli10050945.
[4] Darban SA, Badiee A, Jaafari M R. PNC27 kansɛribana pepitiri min bɛ ligandi laɲini, o ye Doxil ka tumu kɛlɛli nafa ɲɛ kosɛbɛ HDM2 jirali seliluw la[J]. Nanofurakɛli, 2017,12(12):1475-1490.DOI:10.2217/nnm-2017-0069.
[5] Alagkiozidis I, Gorelick C, Shah T, ani a ɲɔgɔnnaw. Paclitaxel ni kansɛri kɛlɛli péptide PNC-27 ka jɛɲɔgɔnya bɛ kɔnɔbara kansɛri furakɛli la (Retraction of Vol 47, Pg 271, 2017)[J]. Annals de science clinique et laboratoire, 2017,47(4) Bamako, Mali. https://pubmed.ncbi.nlm.nih.gov/28667027/ Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.
[6] Sarafraz-Yazdi E, Gorelick C, Wagreich A. R., ani mɔgɔ wɛrɛw. Kansɛri kɛlɛli fura PNC-27 nafa ex vivo banabagatɔ ka kansɛri furakɛli la min bɛ sɔrɔ ɲɛgɛnɛsira la[J]. Annals of Clinical and Laboratory Science, 2015,45(6):650-658. https://pubmed.ncbi.nlm.nih.gov/26663795/ Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.
BƐƐRƐ KUNNAFONIW NI FƐRƐW KUNNAFONIW BƐƐ MIN BƐ NI WEBSITE KAN NA, U BƐ KUNNAFONIW FƆLƆ DƆRƆN NI KALANSENW YE.
Fɛn minnu bɛ di nin siti in kan, olu dabɔra ɲininiw dɔrɔn kama in vitro. Sɛgɛsɛgɛli in vitro (latinkan na: *glasi kɔnɔ*, o kɔrɔ ye gilasi kɔnɔ) bɛ kɛ hadamaden farikolo kɔkan. Nin fura ninnu tɛ furaw ye, Ameriki ka dumuniko ni furako ɲɛmɔgɔso (FDA) ma sɔn u ma, wa u man kan ka kɛ ka furakɛli bana, bana walima bana si bali, k’a furakɛ, walima k’a furakɛ. A dagalen don kosɛbɛ sariya fɛ ka nin fɛn ninnu don hadamaden walima bagan farikolo la cogo o cogo.