▎ PNC 27 Bincike
Menene aikace-aikacen PNC-27?
1, Maganin cutar sankarar bargo:
PNC-27 yana iya ɗaure furotin HDM-2 akan membrane na ƙwayoyin cutar kansa kuma ya haifar da samuwar pores transmembrane cytotoxic. A cikin nazarin ɗan adam wanda ba shi da ƙwayar cutar sankarar ƙwayar cutar sankarar ƙwayar cuta, an gano HDM-2 da za a bayyana shi sosai a cikin membranes na U937 (m monocytic cutar sankarar bargo), OCI-AML3 (m granulomonocytic cutar sankarar bargo), da kuma HL60 (m promyelocytic cutar sankarar bargo) cell.PNC-27 daura zuwa HDM-27 membranes da nelaccrosis. dehydrogenase) saki a cikin sa'o'i 4. (LDH) saki a cikin sa'o'i 4. Yin niyya HDM-2 akan membrane na tantanin halitta na iya zama dabarun da za a iya magance cutar sankarar bargo.PNC-27 ya nuna babban aikin rigakafin cutar sankarar bargo a cikin layukan cutar sankarar bargo da yawa ta hanyar niyya Membrane HDM-2 [1].
2. Yana haifar da ƙwayar ƙwayar cuta
Yana aiki azaman peptide mara kyau:
Yawancin karatu sun nuna cewa PNC-27 yana haifar da ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar ƙwayar cuta. Misali, a cikin binciken MCF-7 Kwayoyin cutar kansar nono da MCF-10-2A da ba a canza su ba, ƙwayoyin epithelial na mammary, an bi da sel tare da PNC-27 tare da koren kyalli mai alamar amino terminus da ja mai kyalli mai alamar carboxy terminus. Sakamakon ya nuna nau'in haske mai launin rawaya mai ban sha'awa akan membrane cell cell na ciwon daji a cikin minti 30, yana nuna cewa peptide maras kyau ya kasance a kan membrane cell cell kuma ya karu tare da ciwon daji. Sabanin haka, sel MCF-10-2A da ba a canza su ba da farko sun nuna haske mai launin rawaya iri ɗaya, amma sai suka ɓace. Ba kamar ƙwayoyin cutar kansa ba, waɗannan ƙwayoyin da ba a canza su ba sun kasance masu yiwuwa. Wannan yana nuna cewa PNC-27 yana haifar da ɓarkewar membrane a cikin ƙwayoyin kansa ta hanyar aiki azaman peptide gabaɗaya, maimakon guntu [2].
Daure zuwa HDM-2 don samar da sifofin pore:
PNC-27 yana ƙunshe da yanki mai ɗauri na HDM-2 da kuma tsarin peptide mai shiga tantanin halitta (CPP), wanda ke haifar da samuwar sifofin pore ta hanyar ɗaure zuwa HDM-2 akan membrane cell, wanda ke haifar da lysis cell lysis da necrosis. Ƙididdigar makamashi na daidaitawa ya nuna cewa PNC-27 yana samar da hadaddun tare da HDM-2 a cikin rabo na 1: 1, tare da babban jerin abubuwan da ke nunawa daga hadaddun. Immunoscanning electron microscopy binciken ya nuna kasancewar mahara 6 nm da 15 nm labeled gwal barbashi a wani rabo na kusan 1: 1 a cikin pores a saman saman ciwon daji Kwayoyin bi da PNC-27, bayar da shawarar cewa wadannan hadaddun suna da muhimmanci ga pore tsarin. Sabanin haka, ba a samar da pores a cikin sarrafawa ba, fibroblasts marasa canzawa da aka bi da su tare da PNC-27 [3].
Ciwon daji na Pancreatic:
Sabon maganin ciwon daji na PNC-27 peptide yana haifar da necrosis na ƙwayoyin ciwon daji na MiaPaCa-2 na pancreatic na ɗan adam ta hanyar dogaro da kashi, amma ba mai guba bane ga sel na al'ada. Nazarin ya nuna cewa PNC-27, lokacin da aka haɗa shi tare da Gemzar, wani maganin chemotherapeutic da ake amfani da shi don magance ciwon daji na pancreatic, yana da tasirin cytotoxic a kan kwayoyin MiaPaCa-2 fiye da Gemzar ko PNC-27 kadai. Wannan na iya zama saboda PNC-27-induced pores ƙara permeability na ciwon daji Kwayoyin zuwa Gemzar, ƙyale mafi Gemzar zuwa hari kansa Kwayoyin [1].
Ciwon daji na Ovarian:
A cikin layin kwayar cutar daji na ovarian SKOV-3 da OVCAR-3, ana nuna furotin HDM-2 sosai a cikin kwayar halitta. Sabanin haka, a cikin layin salula na HUVEC wanda ba a canza shi ba, ba a lura da haɗin kai da cytotoxicity na PNC-27 ba saboda ƙarancin membrane HDM-2 [1].
Ciwon daji:
PNC-27 yana kashe kwayoyin cutar kansar hanji. A cikin layin kwayar cutar ciwon hanji guda shida, PNC-27 tare da membrane HDM-2 kuma ya haifar da mutuwar kwayar halitta (necrosis cell necrosis, babban sakin LDH, furotin da ke hade da membrane V da cysteine 3 negativity) kawai a cikin kwayoyin cutar kansa. A cikin vivo, PNC-27 yana haifar da necrosis na nodules na ƙari amma baya shafar nama na al'ada [1].
3. Inganta ingancin maganin ciwon daji
Daure zuwa Doxil:
An gano cewa PNC27 peptide, a matsayin ligand mai niyya, na iya haɓaka tasirin antitumor na Doxil a cikin ƙwayoyin cutar kansa na HDM2. An saka adadi daban-daban na peptide PNC27 a cikin Doxil, kuma an gudanar da cytometry mai gudana da kuma nazarin confocal akan C26 ciwon ciwon hanji (HDM2-positive) da B16F0 melanoma (HDM2-korau). Sakamakon ya nuna cewa PNC27-Doxil ya nuna mahimmancin ɗaukar salula da cytotoxicity a cikin ƙwayoyin C26, yayin da ba a lura da waɗannan sakamakon a cikin ƙwayoyin B16F0 ba. Misali, PNC27-Doxil (100 PNC27 peptide) yana haɓaka tasirin warkewa na Doxil ba tare da tasirin tasirinsa a cikin ciwan C26 ba [4].
4. Synergistic maganin ciwon daji na ovarian tare da paclitaxel
Ana amfani da Paclitaxel sosai a cikin maganin cututtuka na gynecological, amma yana kaiwa ga kwayoyin tumor a cikin M lokaci na sake zagayowar tantanin halitta, tare da sel a cikin wasu nau'o'in rayuwa da kuma yiwuwar haifar da sake dawowa da ƙari. Kwayoyin ciwon daji na Ovarian ID8 da aka fallasa su zuwa paclitaxel an samo su don nuna ƙarar magana na MDM-2 da kuma ƙara yawan hankali ga PNC-27. Sakamakon cytotoxic na PNC-27 ya dogara ne akan ɗaurinta ga MDM-2, da kuma toshe MDM-2 yana hana sakamakon kisa na PNC-27. Hotunan heterodrug na haɗuwa da kashi sun kasance masu haɗin gwiwa, suna nuna tasirin haɗin gwiwa tsakanin PNC-27 da paclitaxel [5] . A cikin samfurin intraperitoneal na ciwon daji na ovarian (ID8), ƙari na PNC-27 zuwa gudanarwar paclitaxel na mako-mako yana rage girman girma. Waɗannan bayanan suna nuna tasirin haɗin gwiwa tsakanin PNC-27 da paclitaxel, tare da PNC-27 da ke niyya paclitaxel mai tsira tantanin halitta da haɓaka tasirin antitumor.
5. Magani na farko epithelial ovarian cancer
Wani bincike ya kafa al'adu na farko na sabbin keɓaɓɓen ƙwayoyin ciwon daji na ovary daga majiyyata tare da sabon cystadenocarcinoma na ovarian. Ɗaya daga cikinsu ya fito ne daga cystadenocarcinoma na mucinous kuma ɗayan ya kasance daga ƙwayar papillary plasmacytoid carcinoma mai girma. An kimanta tasirin maganin warkewa na PNC-27 da ƙididdigewa ta hanyar hangen nesa na haske mai ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙwayoyin cuta da ƙididdigar haɓakar ƙwayoyin MTT da ma'aunin lactate dehydrogenase (LDH). Sakamakon ya nuna cewa PNC-27 ya hana haɓakar ƙwayoyin cutar kansa na farko na ɗan adam wanda ya keɓanta daga carcinomas epithelial na ovarian guda biyu ta hanyar dogaro da kashi kuma ya kasance cytotoxic a gare su. Mai sarrafa peptide PNC-29 ba shi da wani tasiri akan ƙwayoyin cutar kansa na farko. Bugu da kari, PNC-27 kuma cytotoxic ne ga dogon kafa da chemotherapy-resistant ɗan adam ciwon daji cell Lines [6].
A taƙaice, PNC-27, a matsayin novel anticancer peptide, yana nuna gagarumin yuwuwar aikace-aikace a cikin nau'ikan hanyoyin maganin kansar. A fagen cutar sankarar bargo, PNC-27 ya baje kolin tasirin kisa akan cutar sankarar myeloid mai tsanani (misali, U937, OCI-AML3, da layin salula na HL60) da kuma sel K562 masu ƙarancin p53, kuma sun sami ingantaccen tasirin antitumor ta hanyar haifar da necrosis cell da sakin lactate dehydrogenase. A cikin maganin ciwon daji na ovarian, haɗuwa da PNC-27 da paclitaxel sun nuna sakamako mai tasiri, wanda zai iya hana ci gaban ƙwayar cuta kuma har yanzu yana da kashe ayyukan da ke da kwayoyin cutar chemotherapy. Bugu da ƙari, haɗin PNC-27 tare da magungunan liposomal (misali Doxil) a matsayin ligand mai niyya na iya haɓaka ƙayyadaddun isarwa da ingantaccen tasirin maganin ƙwayar cuta zuwa ƙwayoyin tumor HDM2. Tasirinsa na hanawa akan ƙwararrun ƙwararrun ciwon daji na ovary na farko yana ƙara tabbatar da ƙimar fassarar asibiti. A halin yanzu, PNC-27 ya shiga cikin gwaji na asibiti na lokaci na I, kuma ana buƙatar ƙarin nazarin asibiti don tabbatar da amincin sa da ingancinsa na dogon lokaci, don haɓaka shi azaman ingantaccen maganin cutar kansa.
Game da Marubuci
Abubuwan da aka ambata a sama duk bincike ne, gyara su kuma Cocer Peptides ne suka haɗa su.
Mawallafin Jaridar Kimiyya
Sarafraz-Yazdi E mai bincike ne mai alaƙa da ƙungiyoyi da yawa, gami da NomoCan, Cibiyar Jini ta New York, Jami'ar Kimiyyar Kiwon Lafiya ta SUNY Downstate, da New York Harbor VA Med Ctr. Waɗannan alaƙa suna nuna sa hannu a cikin bincike daban-daban da wuraren kiwon lafiya.
Bukatun bincikensa sun mamaye nau'ikan batutuwa daban-daban kamar Oncology, Fasahar Laboratory Medical, Pharmacology & Pharmacy, Biochemistry & Molecular Biology, da Bincike & Magungunan Gwaji. Ayyukansa a waɗannan fagagen suna nuna fa'idar ƙwarewarsa da sadaukarwa don haɓaka ilimi a waɗannan mahimman fannoni na kimiyyar likitanci da bincike. An jera a cikin ambaton ambaton [3].
