▎ PNC 27 Imi
He aha nā noi o PNC-27?
1, Ka mālama ʻana i ka maʻi leukemia:
Hiki i ka PNC-27 ke hoʻopaʻa i ka protein HDM-2 ma ka membrane o nā maʻi kanesa a hoʻoulu i ka hoʻokumu ʻana o nā pores transmembrane cytotoxic. Ma ke aʻo ʻana o ke kanaka non-stem cell acute myeloid leukemia cell lines, HDM-2 i ʻike nui ʻia i nā membrane o U937 (acute monocytic leukemia), OCI-AML3 (acute granulomonocytic leukemia), a me HL60 (acute promyelocytic leukemia). dehydrogenase) hoʻokuʻu i loko o 4 mau hola. (LDH) hoʻokuʻu i loko o 4 hola. ʻO ka hoʻopaʻa ʻana i ka HDM-2 ma ka membrane cell he hoʻolālā kūpono no ka mālama ʻana i ka maʻi maʻi ..
2. Induces tumor cell lysis
Hana ʻia ma ke ʻano he peptide paʻa:
Ua hōʻike ʻia kekahi mau haʻawina e hoʻoulu ʻo PNC-27 i ka lysis cell tumor ma ke ʻano he peptide intact ma mua o kahi ʻāpana. No ka laʻana, ma ke aʻo ʻana i nā pūnaeau maʻi maʻi umauma MCF-7 a me nā pūnana epithelial mammary MCF-10-2A i hoʻololi ʻole ʻia, ua mālama ʻia nā cell me PNC-27 me ka ʻōmaʻomaʻo fluorescently lepili amino terminal a me ka ʻulaʻula fluorescently lepili carboxy terminal. Ua hōʻike ʻia nā hopena i kahi fluorescence melemele punctate ʻokoʻa ma ka membrane cell cancer ma 30 min, e hōʻike ana aia ka peptide intact ma ka membrane cell cancer a hoʻonui ʻia me ka lysis cell cancer. ʻO ka ʻokoʻa, ʻaʻole i hoʻololi ʻia nā pūnaewele MCF-10-2A i hōʻike mua ʻia i ka fluorescence membrane melemele, akā nalo. ʻAʻole like me nā pūnaewele maʻi maʻi, ua mau kēia mau mea i hoʻololi ʻole ʻia. Hōʻike kēia i ka PNC-27 e hoʻoulu i ka wehe ʻana o ka membrane i loko o nā keʻena maʻi maʻi ma o ka hana ʻana ma ke ʻano he peptide holoʻokoʻa, ma mua o kahi ʻāpana [2].
Hoʻopaʻa i ka HDM-2 e hana i nā hale pore:
Aia ka PNC-27 i kahi HDM-2-binding structural domain a me kahi cell-penetrating peptide (CPP) presequence, kahi e hoʻoulu ai i ka hoʻokumu ʻana o nā hale pore ma o ka hoʻopaʻa ʻana iā HDM-2 ma ka membrane cell, e alakaʻi ana i ka lysis cell tumor a me ka necrosis. Ua hōʻike ʻia ka helu ʻana o ka ikehu conformational e hana ʻo PNC-27 i kahi paʻakikī me HDM-2 ma kahi ratio 1:1, me ke kaʻina alakaʻi e kuhikuhi ana mai ka paʻakikī. Ua hōʻike ʻia nā haʻawina ʻo Immunoscanning electron microscopy i ka loaʻa ʻana o nā ʻāpana gula he 6 nm a me 15 nm i hōʻailona ʻia ma kahi ratio o 1: 1 i loko o nā pores ma ka ʻili o nā maʻi maʻi maʻi i mālama ʻia me PNC-27, e hōʻike ana he mea koʻikoʻi kēia mau paʻakikī no ka hoʻolālā pore. I ka hoʻohālikelike ʻana, ʻaʻohe pores i hana ʻia i ka mana, untransformed fibroblasts i mālama ʻia me PNC-27 [3].
ʻO ka maʻi maʻi pancreatic:
ʻO ka moʻolelo anticancer PNC-27 peptide e hoʻoulu i ka necrosis o ke kanaka pancreatic MiaPaCa-2 maʻi maʻi maʻi maʻi ma ke ʻano i hilinaʻi ʻia, akā ʻaʻohe mea ʻawaʻawa i nā cell maʻamau. Ua hōʻike nā haʻawina i ka PNC-27, i ka hui pū ʻana me Gemzar, kahi mea lapaʻau chemotherapeutic i hoʻohana ʻia e mālama i ka maʻi maʻi pancreatic, ʻoi aku ka nui o ka cytotoxic hopena ma nā pūnaewele MiaPaCa-2 ma mua o Gemzar a i ʻole PNC-27 wale nō. ʻO kēia paha ma muli o ka PNC-27-induced pores e hoʻonui i ka permeability o nā maʻi maʻi maʻi iā Gemzar, e ʻae ana i nā Gemzar hou aʻe e kuhikuhi i nā maʻi kanesa [1].
Ka ma'i 'ovarian:
Ma ovarian cancer cell laina SKOV-3 a me OVCAR-3, HDM-2 protein i hōʻike nui ʻia ma ka membrane cell.PNC-27 co-localizes me HDM-2 ma ka membrane cell, e alakaʻi ana i ka necrosis cell wikiwiki. I ka hoʻohālikelike ʻana, ʻaʻole i ʻike ʻia ka hoʻololi ʻole ʻana i ka laina cell control HUVEC, co-localization a me cytotoxicity o PNC-27 ma muli o ka liʻiliʻi o ka membrane HDM-2 expression [1].
Ka maʻi maʻi ʻaʻai:
ʻO ka PNC-27 e hoʻopau i nā pūnaewele maʻi maʻi ʻaʻai. I loko o ʻeono mau lālani maʻi maʻi maʻi ʻaʻai, PNC-27 i hui pū ʻia me ka membrane HDM-2 a ua make ke kelepona (necrosis cell tumor, hoʻokuʻu LDH kiʻekiʻe, pili i ka protein V a me ka cysteine 3 negativity) wale nō i loko o nā pūnana maʻi. I loko o vivo, PNC-27 ke kumu o ka necrosis o nā nodules tumor akā ʻaʻole pili i ke kino maʻamau [1].
3. Hoʻomaikaʻi i ka maikaʻi anti-tumor
Hoʻopaʻa iā Doxil:
Ua ʻike ʻia ʻo PNC27 peptide, ma ke ʻano he ligand targeting, hiki ke hoʻomaikaʻi nui i ka pono anti-tumor o Doxil i loko o HDM2-positive cancer cells. Ua hoʻokomo ʻia nā ʻano like ʻole o ka peptide PNC27 i loko o Doxil, a ua hana ʻia ka cytometry kahe a me ka nānā ʻana i ka confocal ma ka C26 colon cancer (HDM2-positive) a me ka B16F0 melanoma (HDM2-negative) pūnaewele. Ua hōʻike nā hopena i ka PNC27-Doxil i hōʻike i ka nui o ka cellular uptake a me ka cytotoxicity i nā cell C26, akā ʻaʻole i ʻike ʻia kēia mau hopena i nā cell B16F0. No ka laʻana, PNC27-Doxil (100 PNC27 peptide) i hoʻonui nui i ka therapeutic efficacy o Doxil me ka ʻole o ka hoʻopili ʻana i kāna biodistribution i nā ʻōpū C26 [4].
4. ʻO ka mālama ʻana i ka maʻi maʻi ovarian me ka paclitaxel
Hoʻohana nui ʻia ʻo Paclitaxel i ka mālama ʻana i nā maʻi maʻi gynecological, akā hoʻopaʻa ʻo ia i nā cell tumor i ka M phase o ke kaʻina cell cell, me nā cell i nā ʻāpana ʻē aʻe e ola ana a hiki ke alakaʻi i ka hoʻi hou ʻana o ka maʻi maʻi. Uaʻikeʻia nā pūnaewele ID8 o ka maʻi maʻi ovarian i hōʻikeʻia e hōʻike i ka hoʻonuiʻana o ka MDM-2 a me ka hoʻonuiʻana i ka naʻau i ka PNC-27. ʻO ka hopena cytotoxic o PNC-27 e pili ana i kona paʻaʻana i MDM-2, aʻo ka paleʻana i ka MDM-2 ke kāohi i ka hopena pepehi o PNC-27. He synergistic nā kiʻi heterodrug o ka hui pū ʻana, e hōʻike ana i kahi hopena synergistic ma waena o PNC-27 a me paclitaxel [5] . Ma kahi ʻano hoʻohālike intraperitoneal o ka maʻi maʻi ovarian (ID8), ʻo ka hoʻohui ʻana o PNC-27 i ka hoʻokele paclitaxel pule i hoʻemi nui i ka ulu ʻana o ka maʻi. Hōʻike kēia mau ʻikepili i kahi hopena synergistic ma waena o PNC-27 a me paclitaxel, me ka PNC-27 e kuhikuhi ana i ka cell-surviving paclitaxel a hoʻomaikaʻi i kāna mau hopena antitumor.
5. Hoʻomaʻamaʻa ʻana i ka maʻi maʻi ovarian epithelial mua
Ua hoʻokumu ʻia kahi haʻawina i nā moʻomeheu mua o nā pūnana maʻi maʻi ovarian epithelial hou mai nā maʻi me ka cystadenocarcinoma ovarian hou. ʻO kekahi o lākou mai ka mucinous cystadenocarcinoma a ʻo kekahi mai ka kiʻekiʻe papillary plasmacytoid carcinoma. Ua helu ʻia ka maikaʻi o ka PNC-27 e ka qualitative light microscopic observation a me MTT cell proliferation assay a me ke ana ʻana o ka lactate dehydrogenase (LDH). Ua hōʻike ʻia nā hopena ua pale ka PNC-27 i ka ulu ʻana o nā keʻena maʻi maʻi mua o ke kanaka i hoʻokaʻawale hou ʻia mai ʻelua ovarian epithelial carcinomas ma ke ʻano i hilinaʻi ʻia a he cytotoxic iā lākou. ʻAʻohe hopena o ka mana peptide PNC-29 i nā maʻi maʻi maʻi mua. Eia kekahi, he cytotoxic nō hoʻi ka PNC-27 i nā laina maʻi maʻi maʻi ovarian kanaka lōʻihi a me ka chemotherapy ..
I ka hōʻuluʻulu ʻana, ʻo PNC-27, ma ke ʻano he peptide anticancer novel, e hōʻike ana i ka mana koʻikoʻi no ka noi ʻana i nā ʻano lapaʻau maʻi kanesa. Ma ke kahua o ka ma'i leukemia, ua hō'ike 'o PNC-27 i nā hopena pepehi kanaka ma luna o ka ma'i leukemia myeloid acute (eg, U937, OCI-AML3, a me HL60 cell lines) a me ka p53-deficient K562 pūnaewele, a loa'a i nā hopena antitumor maika'i loa ma o ka ho'oulu'ana i ka necrosis cell a me ka ho'oku'u lactate dehydrogenase. I ka mālama ʻana i ka maʻi maʻi ovarian, ʻo ka hui pū ʻana o PNC-27 a me paclitaxel i hōʻike i kahi hopena synergistic, hiki ke kāohi nui i ka ulu ʻana o ka maʻi ʻaʻai a loaʻa mau ka hana pepehi kanaka e kūʻē i nā pūnaeho kūʻē i ka chemotherapy. Eia kekahi, ʻo ka hui pū ʻana o PNC-27 me nā lāʻau liposomal (eg Doxil) ma ke ʻano he ligand e hoʻopaʻa ʻia e hiki ke hoʻonui i ka hāʻawi kikoʻī a me ka pono anti-tumor o ka lāʻau lapaʻau i HDM2-positive tumor cells. ʻO kona hopena paʻa i ka epithelial ovarian cancer progenitor cell e hōʻoia hou i ka waiwai unuhi. I kēia manawa, ua komo ʻo PNC-27 i nā hoʻokolohua lapaʻau ma ka pae I, a ʻoi aku ka nui o nā noiʻi lāʻau lapaʻau e pono ai e hōʻoia i kona palekana a me ka maikaʻi lōʻihi, i mea e hoʻolaha ai iā ia ma ke ʻano he hopena hou no ka mālama ʻana i ka maʻi kanesa.
No ka mea kakau
ʻO nā mea i ʻōlelo ʻia ma luna nei ua noiʻi ʻia, hoʻoponopono ʻia a hōʻuluʻulu ʻia e Cocer Peptides.
Mea kākau moʻolelo ʻepekema
He kanaka noiʻi ʻo Sarafraz-Yazdi E me kekahi mau hui, me NomoCan, New York Blood Center, SUNY Downstate Health Sciences University, a me New York Harbor VA Med Ctr. Hōʻike kēia mau pili i kona komo ʻana i nā ʻano noiʻi like ʻole a me nā wahi olakino.
Loaʻa kāna mau noiʻi noiʻi ma nā ʻano kumuhana like ʻole e like me Oncology, Medical Laboratory Technology, Pharmacology & Pharmacy, Biochemistry & Molecular Biology, a me Research & Experimental Medicine. Hōʻike kāna hana ma kēia mau kahua i kona ʻike ākea a me kona kūpaʻa i ka holomua ʻana i ka ʻike ma kēia mau wahi koʻikoʻi o ka ʻepekema lapaʻau a me ka noiʻi. ua helu ʻia ma ka ʻōlelo kuhikuhi [3].
