Kwayoyin Ciwon Daji

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Kwayoyin Ciwon Daji
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Hoto na 1: Ƙayyadadden ƙwayar cuta

Kwayoyin ciwon daji ( CSCs ), ya kasan ce kuma sune kwayoyin ciwon daji (wanda aka samo a cikin ciwace-ciwacen daji ko ciwon daji ) waɗanda ke da halaye masu alaƙa da kwayoyin halitta na al'ada, musamman ikon haifar da kuma duk nau'in tantanin halitta da kuma aka samu a cikin wani samfurin ciwon daji. Saboda haka CSCs suna da ƙari (tumor-forming), watakila ya bambanta da sauran kwayoyin cutar kansa marasa tumorigenic.[1] CSCs na iya haifar da ciwace-ciwace ta hanyar tsarin ƙwayoyin cuta na sabuntawar kai da bambancewa cikin nau'ikan tantanin halitta da yawa. Irin waɗannan ƙwayoyin ana tsammanin zasu cigaba da kasancewa cikin ciwace-ciwacen ƙwayar cuta a matsayin jama'a daban-daban kuma suna haifar da koma baya da metastasis ta hanyar haifar da sabbin ciwace-ciwace. Sabili da haka, haɓaka takamaiman hanyoyin kwantar da hankali da aka yi niyya a CSCs yana riƙe da bege don inganta rayuwa da ingancin rayuwar marasa lafiyar cutar kansa, musamman ga marasa lafiya da cututtukan metastatic .

Maganin ciwon daji da ake da su galibi an haɓaka su ne bisa nau'ikan dabbobi, inda aka yi la'akarin hanyoyin kwantar da hankali don haɓaka haɓakar ƙwayar cuta. Duk da haka, dabbobi ba su samar da cikakken samfurin cutar ɗan adam ba. Musamman, a cikin berayen, waɗanda kuma tsawon rayuwarsu ba su wuce shekaru biyu ba, sake dawowar ƙari yana da wuyar yin karatu.

Ingancin jiyya na ciwon daji shine, a farkon matakan gwaji, sau da yawa ana auna su ta hanyar raguwar ɓarna na ƙwayar ƙwayar cuta ( kashe kashi ). Kamar yadda CSCs ke samar da ƙaramin rabo na ƙari, wannan ƙila ba lallai ba ne zaɓin magungunan da ke aiki musamman akan sel mai tushe. Ka'idar ta nuna cewa chemotherapies na al'ada suna kashe nau'i daban-daban ko bambance-bambancen sel, waɗanda ke zama mafi yawan ƙwayar ƙwayar cuta amma ba sa haifar da sababbin kwayoyin halitta. Yawan jama'ar CSC, waɗanda kuma suka haifar da ita, na iya zama ba a taɓa su ba kuma suna haifar da koma baya.

John Dick ne ya fara gano ƙwayoyin cutar kansa a cikin m myeloid leukemia a ƙarshen 1990s. Tun daga farkon 2000s sun kasance babban binciken bincike kan kansa. [2] An tsara kalmar da kanta a cikin takarda da aka ambata sosai a cikin 2001 ta masana ilimin halitta Tannishtha Reya, Sean J. Morrison, Michael F. Clarke da Irving Weissman . [3]

Samfurin yaɗuwar ƙwayar cuta[gyara sashe | gyara masomin]

A cikin nau'ikan nau'ikan ƙari daban-daban, sel a cikin yawan ƙwayar ƙari suna nuna nau'ikan aiki iri -iri kuma ana samun ciwace-ciwace daga sel masu iya yaduwa iri-iri da bambanta . [4] Wannan nau'in nau'in nau'in nau'in nau'in ciwon daji ya haifar da ƙirƙirar nau'o'in yaduwa da yawa don yin lissafin nau'i-nau'i da bambance-bambance a cikin iyawar ƙwayar ƙwayar cuta: ƙwayar ciwon daji (CSC) da samfurin stochastic. Duk da haka, wasu ra'ayoyi sun tabbatar da cewa wannan ƙira ta wucin gadi ce, tun da dukkanin hanyoyin biyu suna aiki ne bisa ga madaidaicin halaye dangane da ainihin yawan ƙwayar cuta. Mahimmanci an lura cewa yayin da a cikin lafiyayyan ɗan adam epithelium na esophageal lafiyayyan nauyin yaduwa yana haɗuwa da stochastically rarraba basal epithelium. Bayan sauye-sauyensa zuwa epithelium na Barrett na farko, duk da haka, wani ƙaramin ɗaki mai ɗorewa yana bayyana wanda ke goyan bayan yaɗuwar epithelium yayin da shaidu guda ɗaya na sashin rarraba stochastically wanda ke ba da gudummawa ga kiyaye nama ya ɓace. Don haka, aƙalla don wasu kyallen jikin neoplastic, ɓangarorin ɓangarorin sel da aka keɓe suna kula da haɓaka girman sashin da aka canza [5]

Hoto 2: Matsayin salon salula na yau da kullun wanda ya ƙunshi sel mai tushe a koli, waɗanda ke haifar da gama-gari kuma mafi ƙuntataccen ƙwayoyin sel da kuma a ƙarshe nau'ikan tantanin halitta waɗanda suka ƙunshi nama na musamman.
Hoto na 3 . A cikin tsarin kwayar cutar kansa (CSC), CSCs kawai ke da ikon haifar da ƙari, dangane da abubuwan sabunta kansu da yuwuwar haɓakawa.

Samfurin kwayar cutar kansa[gyara sashe | gyara masomin]

Samfurin kwayar cutar kansa, wanda kuma aka sani da Tsarin Hierarchical Model ya ba da shawarar cewa ciwace-ciwacen ciwace-ciwacen daji suna cikin tsari (CSCs suna kwance a koli [6] (Fig. 3). A cikin yawan ciwon daji na ciwace-ciwacen daji akwai ƙwayoyin cuta masu ciwon daji (CSC) waɗanda ke da ƙwayoyin tumorigenic kuma sun bambanta da ilimin halitta da sauran ƙananan jama'a [7] Suna da siffofi guda biyu: ikon su na dogon lokaci don sabunta kansu da kuma ikon su na bambanta. cikin zuriyar da ba su da ƙari amma har yanzu suna ba da gudummawa ga haɓakar ƙwayar cuta. Wannan samfurin yana ba da shawarar cewa kawai wasu ƙananan ƙwayoyin cuta na ciwon daji suna da ikon haifar da ci gaban ciwon daji, ma'ana cewa akwai takamaiman halaye (na zahiri) waɗanda za a iya gano su sannan kuma a yi niyya don lalata ƙwayar cuta na dogon lokaci ba tare da buƙatar yaƙi da cutar ba. duka ƙari. [8]

Stochastic model[gyara sashe | gyara masomin]

Domin tantanin halitta ya zama mai ciwon daji dole ne ya sami sauye-sauye masu yawa ga jerin DNA. Wannan samfurin tantanin halitta yana nuna waɗannan maye gurbi na iya faruwa ga kowane tantanin halitta a cikin jiki wanda ke haifar da ciwon daji. Ainihin wannan ka'idar tana ba da shawarar cewa duk ƙwayoyin cuta suna da ikon zama ƙari suna yin duk ƙwayoyin ƙari daidai da ikon sabunta kansu ko bambanta, wanda ke haifar da nau'in ƙari yayin da wasu na iya bambanta zuwa waɗanda ba CSCs [9] Ƙarfin tantanin halitta zai iya. Za a rinjayi abubuwan da ba a yi tsammani ba ko abubuwan epigenetic, wanda ke haifar da sel daban-daban a cikin duka ƙwayoyin tumorigenic da waɗanda ba na tumorigenic waɗanda ke haɗa ƙari. Dangane da "samfurin stochastic" (ko "samfurin juyin halitta na clonal") kowane kwayar cutar kansa a cikin ƙari zai iya samun ikon sabunta kansa da bambanta da yawa da nau'ikan zuriyar ƙwayoyin cutar kansa waɗanda ke lalata ƙari [10]

Hoto na 4: A cikin tsarin juyin halitta na clonal, duk ƙwayoyin da ba su da bambanci suna da irin wannan damar don canzawa zuwa kwayar cutar tumorigenic.

Waɗannan maye gurbi na iya ci gaba da tarawa da haɓaka juriya da dacewa da ƙwayoyin sel waɗanda ke ba su damar yin nasara ga sauran ƙwayoyin ƙari, waɗanda aka fi sani da ƙirar juyin halitta na somatic . Samfurin Juyin Halitta na clonal, wanda ke faruwa a cikin nau'in CSC duka da kuma samfurin stochastic, yana ƙaddamar da cewa ƙwayoyin ƙwayar cuta masu rikiɗawa tare da fa'idar girma sun fi sauran. Kwayoyin da ke cikin mafi yawan jama'a suna da irin wannan damar don fara haɓakar ƙari. [11] (Hoto 4).

[12] Waɗannan nau'ikan nau'ikan guda biyu ba su keɓanta juna ba, kamar yadda CSCs da kansu ke fuskantar juyin halitta na clonal. Don haka, na biyu mafi rinjaye na CSC na iya fitowa, idan maye gurbi yana ba da ƙarin kaddarorin mummuna[13] (Fig. 5).

Hoto na 5 : Duk nau'ikan ciwon daji na iya taka rawa wajen kula da ƙwayar cuta. Da farko, an tabbatar da ci gaban ƙari tare da takamaiman CSC (CSC1). Tare da ci gaban ƙari, wani CSC (CSC 2) na iya tasowa saboda zaɓin clonal . Haɓaka sabon ƙarin m CSC na iya haifar da samun ƙarin maye gurbi ko gyare-gyaren epigenetic .

Haɗa samfuran CSC da stochastic tare[gyara sashe | gyara masomin]

Wani bincike a cikin 2014 yana jayayya da rata tsakanin waɗannan nau'ikan rigima guda biyu za a iya daidaita su ta hanyar samar da wani bayani na daban-daban na ƙari. Suna nuna samfurin da ya haɗa da bangarorin biyu na Stochastic da CSC. Sun bincika filastik mai tushe na kansa wanda a cikinsa ƙwayoyin ƙwayoyin kansa za su iya canzawa tsakanin ƙwayoyin sel marasa ciwon daji (Non-CSC) da CSC ta wurin da ke tallafawa ƙarin ƙirar Stochastic.[14] Amma kasancewar duka nau'ikan halittu daban-daban waɗanda ba CSC ba da CSC suna goyan bayan ƙarin ƙirar CSC, suna ba da shawarar cewa duka samfuran biyu na iya taka muhimmiyar rawa a cikin nau'ikan ƙwayar cuta.

Samfurin rigakafin cutar kansa[gyara sashe | gyara masomin]

Wannan samfurin yana nuna cewa kaddarorin rigakafi na iya zama mahimmanci don fahimtar tumorigenesis da iri-iri. Don haka, CSCs na iya zama da wuya a wasu ciwace-ciwacen daji,[15] amma wasu masu bincike sun gano cewa yawancin ƙwayoyin ƙwayar cuta na iya fara ciwace-ciwace idan an dasa su cikin ɓeraye marasa ƙarfi, [16] don haka suna tambayar dacewar CSCs da ba kasafai ba. Koyaya, duka sel masu tushe [17] da CSCs [18] suna da sifofin rigakafi na musamman waɗanda ke ba su juriya sosai ga rigakafin rigakafi. Don haka, CSCs kawai za su iya haifar da ciwace-ciwacen ƙwayar cuta a cikin marasa lafiya tare da aikin rigakafi na rigakafi, kuma gata na rigakafi na iya zama mahimmin ma'auni don gano CSCs. [19] Bugu da ƙari, samfurin yana nuna cewa CSCs na iya kasancewa da farko sun dogara da ƙananan ƙwayoyin sel, kuma CSCs na iya aiki a can azaman tafki wanda maye gurbi zai iya tara shekaru da yawa ba tare da ƙuntatawa ta tsarin rigakafi ba. Ciwace-ciwacen ciwace-ciwace na iya girma idan: A) CSCs sun rasa dogaro ga abubuwan alkuki (ƙananan ciwace-ciwacen ciwace-ciwacen daji), B) zuriyarsu masu yaɗuwa sosai, duk da haka da farko ƙwayoyin ƙwayar ƙwayar cuta ta al'ada ta haɓaka tana nufin tserewa rigakafi ko C) tsarin rigakafi na iya rasa ta. Ƙarfin ƙwayar cuta, misali saboda tsufa. [20]

Muhawara[gyara sashe | gyara masomin]

Kasancewar CSCs yana ƙarƙashin muhawara, saboda yawancin binciken da aka samu babu sel tare da takamaiman halayen su. [21] Kwayoyin ciwon daji dole ne su kasance masu iya ci gaba da yaduwa da sabuntawar kansu don riƙe da yawancin maye gurbi da ake buƙata don carcinogenesis da kuma ci gaba da ci gaban ƙwayar cuta, tun da sel daban-daban (wanda aka ƙuntata ta Hayflick Limit [22] ) ba zai iya rarraba ba har abada. Don la'akarin warkewa, idan yawancin ƙwayoyin tumor suna da abubuwan da suka dace, niyya girman ƙari kai tsaye dabara ce mai inganci. Idan CSC ƴan tsiraru ne, niyya su na iya zama mafi inganci. Wani muhawara game da asalin CSCs - ko daga dysregulation na kwayoyin halitta na al'ada ko kuma daga ƙwararrun ƙwararrun jama'a waɗanda suka sami ikon sabunta kansu (wanda ke da alaƙa da batun ƙwayar ƙwayar ƙwayar cuta). Rikita wannan muhawara shine gano cewa yawancin ƙwayoyin cutar kansa suna nuna nau'in filastik a ƙarƙashin ƙalubale na warkewa, suna canza rubutun su zuwa yanayi mai kama da kara don guje wa halaka.[ana buƙatar hujja]

Shaida[gyara sashe | gyara masomin]

Tabbatacciyar shaida ta farko don CSCs ta zo a cikin 1997. Bonnet da Dick sun keɓe ƙananan ƙwayoyin cutar sankarar bargo waɗanda suka bayyana alamar CD34, amma ba CD38 ba. [23] Mawallafa sun tabbatar da cewa CD34 + / CD38 - yawan yawan jama'a yana da ikon fara ciwace-ciwace a cikin berayen NOD/ SCID waɗanda suka yi kama da mai bayarwa. Shaida ta farko na ƙaƙƙarfan ƙwayar cutar kansar ƙwayar cuta mai kama da tantanin halitta ta biyo baya a cikin 2002 tare da gano ƙwayar cuta ta clonogenic, tantanin halitta wanda ke ware kuma yana da alaƙa daga gliomas na kwakwalwar ɗan adam balagagge. Ciwon daji na cortical glial na ɗan adam sun ƙunshi sel masu kama da jijiya waɗanda ke bayyana alamun astroglial da alamun neuronal a cikin vitro . [24] Kwayoyin ciwon daji da aka ware daga manyan gliomas na ɗan adam an nuna su haifar da ciwace-ciwacen ciwace-ciwacen daji waɗanda suka yi kama da ƙwayar mahaifa lokacin da aka cusa su cikin ƙirar linzamin kwamfuta tsirara. [25]

A cikin gwaje-gwajen bincike na ciwon daji, wasu lokuta ana allurar ƙwayoyin ƙari a cikin dabbar gwaji don kafa ƙari. Ana ci gaba da ci gaban cuta a cikin lokaci kuma ana iya gwada magungunan novel don ingancin su. Samuwar Tumor yana buƙatar dubunnan ko dubun duban sel don gabatar da su. A al'ada, an bayyana wannan ta hanyar rashin kyaun tsari (watau ƙwayoyin tumor sun rasa ƙarfinsu yayin canja wuri) ko mahimmancin mahimmancin ƙananan ƙwayoyin cuta, musamman mahallin sinadarai na ƙwayoyin allurar. Magoya bayan tsarin CSC suna jayayya cewa kaɗan ne kawai na ƙwayoyin allurar, CSCs, ke da yuwuwar haifar da ƙari. A cikin ɗan adam m myeloid cutar sankarar bargo, mitar wadannan kwayoyin bai wuce 1 cikin 10,000 ba. [26]

Ƙarin shaida ya zo daga histology . Yawancin ciwace-ciwacen ciwace-ciwace iri- iri ne kuma suna ƙunshe da nau'ikan tantanin halitta da yawa waɗanda suka fito daga sashin mai masaukin baki. Ciwon ƙwayar cuta yawanci ana riƙe shi ta hanyar metastases na ƙari. Wannan yana nuna cewa tantanin halitta da ya samar da su yana da ikon samar da nau'ikan tantanin halitta da yawa, alama ce ta al'ada ta kwayoyin halitta . [27]

Kasancewar ƙwayoyin cutar sankarar bargo ya haifar da bincike kan wasu cututtukan daji. Kwanan nan an gano CSCs a cikin ciwace-ciwace da yawa, gami da:

Samfuran injina da na lissafi[gyara sashe | gyara masomin]

Da zarar an yi hasashe hanyoyin zuwa ciwon daji, yana yiwuwa a ƙirƙira ƙirar lissafi na tsinkaya, misali, bisa hanyar sashin sel . Misali, ana iya bayyana ci gaban sel marasa al'ada tare da takamaiman yuwuwar maye gurbi. Irin wannan samfurin ya annabta cewa maimaita cin mutunci ga sel balagagge yana ƙaruwa da samuwar zuriyar da ba ta dace ba da haɗarin ciwon daji. Tasirin asibiti na irin waɗannan samfuran ya kasance mara tushe.

Asalin[gyara sashe | gyara masomin]

Hoto 6: Ƙungiya mai matsayi na ƙari bisa ga tsarin CSC

Asalin CSCs yanki ne mai aiki da bincike. Amsar na iya dogara da nau'in ƙari da nau'in phenotype . Ya zuwa yanzu dai hasashen cewa ciwace-ciwacen ciwace-ciwacen ciwace-ciwacen ciwace-ciwacen ciwace-ciwace sun samo asali ne daga “kwayoyin asali” guda daya ba a nuna su ta amfani da tsarin kwayar cutar kansar ba. Wannan shi ne saboda ƙwayoyin da ke haifar da ciwon daji ba su cikin ciwace-ciwacen mataki na ƙarshe.

Asalin hasashe sun haɗa da maye gurbi a cikin masu tasowa mai tushe ko sel masu tasowa, mutants a cikin sel mai tushe na manya ko manyan ƙwayoyin ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwayoyin cuta waɗanda ke samun sifofi kamar kara. Waɗannan ka'idodin galibi suna mayar da hankali ne kan “kwayoyin asali” ƙari.

Hasashe[gyara sashe | gyara masomin]

Maye gurbin kwayar halitta[gyara sashe | gyara masomin]

Hasashen "maye gurbi a cikin al'ummomin kwayoyin halitta yayin haɓakawa" hasashe yana iƙirarin cewa waɗannan al'ummomi masu tasowa suna canzawa sannan kuma su haifuwa ta yadda yawancin zuri'a ke raba maye gurbin. Wadannan sel 'ya'ya sun fi kusa da zama ciwace-ciwacen daji kuma adadin su yana kara yiwuwar maye gurbi mai cutar kansa. [44]

Manyan kwayoyin kara[gyara sashe | gyara masomin]

Wata ka’idar tana danganta ƙwan ƙwan ƙwayoyin manya (ASC) tare da samuwar ƙari. Yawancin lokaci ana danganta wannan tare da kyallen takarda tare da yawan juzu'in tantanin halitta (kamar fata ko hanji ). A cikin waɗannan kyallen takarda, ASCs 'yan takara ne saboda yawan rarrabuwar tantanin halitta (idan aka kwatanta da yawancin ASCs) tare da tsawon rayuwar ASCs. Wannan haɗin yana haifar da ingantacciyar yanayin yanayi don maye gurbi don tarawa: tarin maye gurbi shine babban abin da ke haifar da farawar cutar kansa . Shaidu sun nuna cewa ƙungiyar tana wakiltar wani abu na gaske, kodayake an danganta takamaiman cutar kansa da wani takamaiman dalili.

De-banbantawa[gyara sashe | gyara masomin]

Bambance-bambancen sel da aka canza na iya haifar da halaye masu kama da kwayar halitta, suna nuna cewa kowane tantanin halitta zai iya zama kwayar cutar kansa. A wasu kalmomi, cikakkiyar bambance-bambancen tantanin halitta yana fuskantar maye gurbi ko siginar siginar salula waɗanda ke mayar da shi zuwa yanayi mai kama da tushe. An nuna wannan ra'ayi kwanan nan a cikin nau'ikan ciwon daji na prostate, inda sel waɗanda ke fuskantar jiyya na rashin ƙarfi na androgen ke bayyana suna canza rubutun su na ɗan lokaci zuwa na tantanin halitta mai kama da jijiyoyi, tare da ɓarna da kaddarorin masu yawa na wannan nau'in sel masu kama da kara.[ana buƙatar hujja]

Matsayi[gyara sashe | gyara masomin]

Ma'anar matsayi na ƙari yana iƙirarin cewa ƙari shine nau'in nau'in kwayoyin halitta masu kama da juna, dukansu suna raba wasu maye gurbi, amma sun bambanta a takamaiman nau'in phenotype . Ciwon daji yana ɗaukar nau'ikan sel masu tushe da yawa, ɗaya mafi kyau ga takamaiman mahalli da sauran layukan marasa nasara. Waɗannan layukan na biyu na iya zama mafi nasara a wasu wurare, ƙyale ƙwayar ƙwayar cuta ta daidaita, gami da daidaitawa ga saƙon warkewa. Idan daidai ne, wannan ra'ayi yana tasiri akan tsarin tsarin jiyya na musamman na ƙwayoyin cuta. [45] Irin wannan matsayi zai dagula yunƙurin nuna asalin.

Ganewa[gyara sashe | gyara masomin]

CSCs, wanda yanzu aka ruwaito a cikin mafi yawan ciwace-ciwacen mutum, ana gano su da kuma wadatar da su ta amfani da dabarun gano ƙwayoyin sel na yau da kullun waɗanda suke kama da juna a cikin karatu. [46] Waɗannan hanyoyin sun haɗa da rarrabuwar tantanin halitta mai kunna haske (FACS), tare da ƙwayoyin rigakafi da aka ba da umarni a alamomin saman tantanin halitta da hanyoyin aiki gami da ƙididdigar yawan jama'a ko gwajin Aldefluor. [47] Sakamakon wadatar CSC sannan ana shuka shi, a nau'ikan allurai daban-daban, a cikin ɓeraye masu ƙarancin rigakafi don tantance ƙarfin haɓakar ƙwayar cuta. Wannan in vivo assay ana kiransa ƙayyadaddun tantancewar dilution. Rukunin ƙwayar ƙwayar cuta wanda zai iya fara haɓaka ciwace-ciwacen ƙwayar cuta a ƙananan lambobi ana ƙara gwada ƙarfin sabuntawar kai a cikin binciken ƙwayar cuta.[48]

Hakanan za'a iya gano CSCs ta hanyar fitar da riniyoyin Hoechst da aka haɗa ta hanyar juriya da yawa (MDR) da kaset ɗin ATP-binding (ABC) Masu jigilar kaya.

Wata hanya kuma ita ce kima-samfurin kima. Yawancin sel masu tushe na al'ada irin su hematopoietic ko sel mai tushe daga kyallen takarda, a ƙarƙashin yanayin al'ada na musamman, suna samar da nau'i mai nau'i uku waɗanda zasu iya bambanta. Kamar yadda yake da sel mai tushe na al'ada, CSCs da ke ware daga kwakwalwa ko ciwace-ciwacen prostate suma suna da ikon samar da sassa masu zaman kansu. [49]

’Yan shekarun nan an ga bullowar hanyoyin da za a bi don gano kwayar cutar daji a cikin rodents na gwaji. A cikin irin wannan binciken, biyo bayan shigar da ciwon daji (yawanci ta hanyar aikace-aikacen mutagens), ana kunna kaset na kwayoyin halitta wanda ke haifar da bayyanar da alama mai sauƙin ganewa, misali koren furotin (GFP). Wannan ya shawo kan iyakokin hanyoyin al'ada (misali fasahar lakabin Bromodeoxyuridine (BrdU) na gargajiya da aka yi amfani da ita don gano ƙwayoyin jinkirin hawan keke a cikin dabbobi) kamar yadda hanyoyin ƙwayoyin cuta ke zama masu zaman kansu na sake zagayowar tantanin halitta kuma ana iya amfani da su a cikin vivo pulse-chase labeling don gano quiescent. /Slow-cycling Kwayoyin. [50] Wannan dabarar, alal misali, ta kasance kayan aiki don gano abin da ake kira rukunin Lgr5+ azaman sashin kwayar cutar kansa a cikin ciwon hanta da kuma nuna yuwuwar sa a matsayin maƙasudin warkewa. [51]

Bambance-bambance (alamomi)[gyara sashe | gyara masomin]

CSCs heterogeneity wani tafki ne na bambance-bambancen ƙwayoyin ƙari waɗanda ba su da bambanci waɗanda aka cika su ta sel waɗanda ke da duka ƙari da ƙwayar ƙwayar cuta kamar kaddarorin kuma suna da nau'ikan halitta da na rayuwa a cikin ƙwayar ƙwayar cuta guda ɗaya. Akwai ra'ayoyi guda biyu don bayyana yanayin phenotypic da na rayuwa na CSCs; bambancin clonal da ka'idar kwayar cutar kansa. Yayin da tsohuwar ka'idar ta nuna rawar da ke tattare da kwayoyin halitta, epigenetic da micro muhalli inda kwayar cutar ciwon daji ke zaune don samun halayen tumorigenic marasa bambanci. Ka'idar ta ƙarshe ta fi mayar da hankali kan halaye marasa kyau da aka samu ta hanyar sel masu tushe inda waɗannan ƙwayoyin da ba su da bambanci kuma suna da yawa sosai suna sake cika yawan ƙwayar ƙari.[52]

An gano CSCs a cikin nau'ikan ciwace-ciwace iri-iri. Yawanci, ana amfani da alamomi na musamman don sel mai tushe na yau da kullun don ware CSCs daga ciwace-ciwace da ciwace-ciwacen jini. Alamomi mafi akai-akai da ake amfani da su don warewar CSC sun haɗa da: CD133 (wanda kuma aka sani da PROM1 ), CD44, ALDH1A1, CD34, CD24 da EpCAM ( kwayoyin halitta adhesion cell epithelial, wanda kuma aka sani da antigen na musamman na epithelial, ESA ). [53]

CD133 (prominin 1) yanki ne na glycoprotein mai transmembrane guda biyar wanda aka bayyana akan CD34 + kara da sel masu zuwa, a cikin precursors na endothelial da sel kara na tayi . An gano shi ta amfani da epitope na glycosylated wanda aka sani da AC133.

EpCAM (Epithelial cell adhesion molecule, ESA, TROP1) shine hemophilic Ca 2+ - kwayoyin adhesion cell mai zaman kanta wanda aka bayyana akan basolateral surface na yawancin kwayoyin epithelial .

CD90 (THY1) shine glycosylphosylphosphatidylinositol glycoprotein wanda aka kafa a cikin membrane na plasma kuma yana shiga cikin jigilar sigina . Hakanan yana iya daidaita mannewa tsakanin thymocytes da thymic stroma.

CD44 (PGP1) kwayar halitta ce ta mannewa wacce ke da rawar gani a cikin siginar tantanin halitta, ƙaura da homing. Yana da isoforms da yawa, ciki har da CD44H, wanda ke nuna babban kusanci ga hyaluronate da CD44V wanda ke da kaddarorin metastatic.

CD24 (HSA) wani glycosylated glycosylphosphatidylinositol-anchored adhesion molecule, wanda ke da rawar haɗin gwiwa a cikin ƙwayoyin B da T.

CD200 (OX-2) wani nau'i ne na 1 membrane glycoprotein, wanda ke ba da siginar hanawa zuwa ƙwayoyin rigakafi ciki har da ƙwayoyin T, ƙwayoyin kisa na halitta da macrophages .

ALDH wani yanki ne na aldehyde dehydrogenase iyali na enzymes, wanda ke haifar da iskar shaka na aldehydes na aromatic zuwa carboxyl acid . Alal misali, yana da tasiri wajen canza retinol zuwa retinoic acid, wanda yake da mahimmanci don rayuwa.[54][55]

Na farko m malignancy daga wanda CSCs aka ware da kuma gano shi ne nono cancer kuma su ne mafi tsanani nazari. An wadatar da CSCs na nono a cikin CD44 + CD24 -/low, [56] SP [57] da ALDH + .[58][59] CSCs na nono a fili suna da bambanci . Maganar alamar CSC a cikin ƙwayoyin kansar nono a bayyane yake iri-iri ne kuma yawan CSC nono ya bambanta a cikin ciwace-ciwacen daji. [60] Dukansu CD44 + CD24 - da CD44 + CD24 + yawan yawan tantanin halitta sune ƙwayoyin farawar ƙari; duk da haka, CSC sun fi wadatuwa sosai ta amfani da bayanin martaba CD44 + CD49f hi CD133/2 hi .[61]

An ba da rahoton CSCs a yawancin ciwan kwakwalwa. An gano ƙwayoyin cuta ciki har da CD133, [62] SSEA-1 (antigen-takamaiman amfrayo-1), [63] EGFR [64] da CD44.[65] Amfani da CD133 don tantance ƙwayoyin ƙwaƙwalwar ƙwaƙwalwa na iya zama matsala saboda ƙwayoyin cuta na ƙwayar cuta a cikin wasu CD133 + Kwayoyin kwakwalwar CD133 na CD133 na CD13 na CD13 - Kwayoyin kwakwalwa .

An ba da rahoton CSC a cikin ciwon daji na hanji. Don gano su, an yi amfani da alamomin sararin samaniya irin su CD133, CD44 [66] da ABCB5, [67] nazarin aikin ciki har da nazarin clonal [68] da kuma Aldefluor assay. [69] Yin amfani da CD133 azaman tabbataccen alama don CSCs na hanji ya haifar da saɓani. Epitope na AC133, amma ba sunadaran CD133 ba, an bayyana shi musamman a cikin CSCs na hanji kuma an rasa bayanin sa akan bambancewa. [70] Bugu da ƙari, CD44 + ƙwayoyin ciwon daji na hanji da ƙarin ƙananan juzu'i na CD44 + EpCAM + yawan tantanin halitta tare da CD166 suna haɓaka nasarar haɓakar ƙwayar cuta.

An ba da rahoton CSC da yawa a cikin prostate,[71] huhu da sauran gabobin da yawa, gami da hanta, pancreas, koda ko ovary . A cikin ciwon daji na prostate, an gano ƙwayoyin farawar tumor a cikin CD44 +[72] tantanin halitta kamar CD44 + α2β1 +,[73] TRA-1-60 + CD151 + CD166 + [74] ko ALDH + [75] yawan adadin sel. . An ba da rahoton alamomin sakawa na huhu na CSC, ciki har da CD133 +, [76] ALDH +, [77] CD44 + [78] da furotin oncofetal 5T4 + . [79]

Metastasis[gyara sashe | gyara masomin]

Metastasis shine babban dalilin mutuwar ƙari. Duk da haka, ba kowane ƙwayar ƙwayar cuta ba zai iya yin metastasize. [80] Wannan yuwuwar ya dogara da abubuwan da ke ƙayyade girma, angiogenesis, mamayewa da sauran matakai na asali.

Epithelial-mesenchymal canji[gyara sashe | gyara masomin]

A cikin ciwace-ciwacen ciwace-ciwace, ana ɗaukar canjin epithelial-mesenchymal (EMT) a matsayin lamari mai mahimmanci.[81] EMT da jujjuya juyi daga mesenchymal zuwa nau'in nau'in nau'in nau'in nau'in halitta ( MET ) suna shiga cikin haɓakar amfrayo, wanda ya haɗa da rushewar homeostasis na sel na epithelial da kuma samun nau'in yanayin ƙaura na mesenchymal. [82] EMT ya bayyana ana sarrafa shi ta hanyoyin canonical kamar WNT da canza yanayin girma β . [83]

Muhimmin fasalin EMT shine asarar membrane E-cadherin a cikin haɗin gwiwar adherens, inda β-catenin na iya taka muhimmiyar rawa. Canja wurin β-catenin daga haɗin gwiwar adherens zuwa tsakiya na iya haifar da asarar E-cadherin kuma daga baya zuwa EMT. Nuclear β-catenin a fili zai iya kai tsaye, ta hanyar rubutawa ta kunna abubuwan da ke da alaƙa da EMT, irin su E-cadherin gene repressor SLUG (wanda aka fi sani da SNAI2 ). [84] Kayan aikin injiniya na ƙwayar cuta, irin su hypoxia, na iya ba da gudummawa ga rayuwa ta CSC da kuma m metastatic ta hanyar daidaitawa na hypoxia inducible dalilai ta hanyar hulɗa tare da ROS ( jinsunan oxygen mai amsawa ).[85][86]

Kwayoyin Tumor da ke jurewa EMT na iya zama madogara ga ƙwayoyin cutar kansa na metastatic, ko ma CSCs na metastatic. [87] [88] A cikin gefen ɓarna na ciwon daji na pancreatic, an bayyana sassan CD133 + CXCR4 + (mai karɓa don CXCL12 chemokine wanda aka fi sani da SDF1 ligand ). Waɗannan sel sun nuna ƙarfin ƙaura fiye da takwaransu CD133 + CXCR4 - sel, amma duka biyun sun nuna irin ƙarfin haɓakar ƙari.[89] Haka kuma, hana mai karɓar CXCR4 ya rage yuwuwar metastatic ba tare da canza ƙarfin tumorigenic ba.[90]

Tsarin magana mai mataki biyu[gyara sashe | gyara masomin]

Hoto na 7: Ma'anar ƙaura daga ƙwayoyin cutar kansa (MSC). Kwayoyin ciwon daji na tsaye suna kunshe a cikin carcinomas na farko kuma ana iya gano waɗannan sel a cikin bambancin tsakiyar yankin ƙari. Muhimmin mataki zuwa ga malignant shi ne shigar da epithelial mesenchymal miƙa mulki (EMT) a cikin tsaye ciwon daji stem cell (SCS), wanda ya zama mobile ko ƙaura kansa kara Kwayoyin. Kwayoyin karawa suna rarraba asymmetrically. Kwayoyin 'ya'ya daya za su fara yaduwa da bambanta. Ragowar MCS na yin ƙaura daga ɗan gajeren nesa kafin a sami sabon sashin asymmetric, ko kuma ya yadu ta hanyoyin jini ko tasoshin lymphatic kuma yana haifar da metastasis.

A cikin ciwon nono CD44 + CD24 -/ ƙananan sel ana iya gano su a cikin ɓarkewar ƙwayar cuta. [91] Sabanin haka, an gano ƙarin adadin ƙwayoyin CD24 + a cikin metastases mai nisa a cikin masu cutar kansar nono. [92] Yana yiwuwa CD44 + CD24 -/ ƙananan sel da farko su yi metastasize kuma a cikin sabon rukunin yanar gizon suna canza yanayin su kuma suna fuskantar iyakancewa. [93] Hasashen salon magana mai kashi biyu yana ba da shawarar nau'ikan ƙwayoyin cutar kansa guda biyu - tsaye (SCS) da wayar hannu (MCS). An saka SCS a cikin nama kuma suna dagewa a wurare daban-daban a duk tsawon ci gaban ƙari. Ana samun MCS a wurin mahaɗar ƙwayar cuta. Waɗannan sel da alama an samo su daga SCS ta hanyar siyan EMT na wucin gadi (Hoto 7). [94]

Tasiri[gyara sashe | gyara masomin]

CSCs suna da tasiri don maganin ciwon daji, ciki har da don gano cututtuka, zaɓin magungunan ƙwayoyi, rigakafin metastasis da dabarun sa baki.

Magani[gyara sashe | gyara masomin]

CSCs a zahiri sun fi juriya ga magungunan chemotherapeutic . Akwai manyan abubuwa guda 5 da suke haifar da hakan: [95]

1. Abubuwan da suke da shi na kare su daga haɗuwa da babban adadin magungunan cutar kansa.
2. Suna bayyana nau'ikan sunadaran transmembrane, irin su MDR1 da BCRP, waɗanda ke fitar da kwayoyi daga cikin cytoplasm.
3. Suna rarraba sannu a hankali, kamar manyan ƙwayoyin ƙwayoyin cuta suna yin haka, don haka ba a kashe su ta hanyar chemotherapeutic jamiái waɗanda ke yin niyya da sauri kwafi ta hanyar lalata DNA ko hana mitosis.
4. Suna daidaita sunadaran gyaran lalacewar DNA.
5. Ana siffanta su da wuce gona da iri na hanyoyin siginar anti-apoptotic.
Bayan jiyya na chemotherapy, CSCs masu tsira suna iya sake cika ƙwayar cutar da haifar da koma baya. Ƙarin magani da aka yi niyya don cire CSCs ban da ƙwayoyin somatic masu cutar kansa dole ne a yi amfani da su don hana wannan.

Yin niyya[gyara sashe | gyara masomin]

Zaɓan CSCs mai niyya na iya ba da damar jiyya na ciwace-ciwacen da ba za a iya sake su ba, da kuma hana metastasis da sake dawowa. Hasashen yana nuna cewa akan kawar da CSC, ciwon daji na iya komawa baya saboda bambance-bambance da/ko mutuwar tantanin halitta.[ana buƙatar hujja] Ƙirar ƙwayoyin ƙwayar cuta waɗanda suke CSCs don haka suna buƙatar kawar da su ba a sani ba. [96]

Nazarin ya nemi takamaiman alamomi da kuma sa hannu na ƙwayar cuta da ƙwayoyin cuta waɗanda ke bambanta CSCs daga wasu. [97] A cikin 2009, masana kimiyya sun gano fili salinomycin, wanda zaɓaɓɓen ya rage yawan adadin nono CSCs a cikin mice fiye da 100-ninka dangane da Paclitaxel, wani wakili na chemotherapeutic da aka saba amfani dashi. [98] Wasu nau'ikan kwayoyin cutar kansa na iya tsira da magani tare da salinomycin ta hanyar autophagy, [99] ta yadda sel ke amfani da gabobin kwayoyin acidic kamar lysosomes don lalatawa da sake sarrafa wasu nau'ikan sunadaran. Yin amfani da masu hana autophagy na iya kashe kwayoyin cutar kansa da ke rayuwa ta hanyar autophagy.[100]

The cell surface receptor interleukin-3 receptor-alpha (CD123) an overexpressed a kan CD34+CD38-leukemic stem Kwayoyin (LSCs) a cikin m myelogenous cutar sankarar bargo (AML) amma ba a al'ada CD34 + CD38- kasusuwa marrow Kwayoyin. [101] Yin maganin berayen NOD/SCID da aka sawa AML tare da CD123-takamaiman antibody monoclonal mai lahani LSCs zuwa ga marrow na kasusuwa kuma ya rage yawan jama'ar AML gabaɗaya gami da adadin LSCs a cikin masu karɓar linzamin kwamfuta na biyu.[102]

Nazarin 2015 ya ƙunshi nanoparticles tare da miR-34a da ammonium bicarbonate kuma ya isar da su zuwa CSCs na prostate a cikin ƙirar linzamin kwamfuta. Sannan suka haska wurin da hasken Laser na kusa da infrared . Wannan ya sa nanoparticles su kumbura sau uku ko fiye da girman su suna fashe endosomes kuma suna tarwatsa RNA a cikin tantanin halitta. miR-34a na iya rage matakan CD44. [103][104]

Wani bincike na 2018 ya gano masu hana dangin ALDH1A na enzymes kuma ya nuna cewa za su iya zaɓin rage ƙwayar ƙwayar cutar kansa a cikin layukan ƙwayoyin cutar kansar ovarian da yawa.[105]

Hanyoyi[gyara sashe | gyara masomin]

Ƙirƙirar sababbin magunguna don ƙaddamar da CSCs yana buƙatar fahimtar hanyoyin salula waɗanda ke daidaita yaduwar kwayar halitta. Ci gaba na farko a wannan yanki an yi su ne tare da kwayoyin halitta na hematopoietic (HSCs) da kuma takwarorinsu da suka canza a cikin cutar sankarar bargo, cutar da aka fi fahimtar asalin CSCs. Kwayoyin sassa na gabobin da yawa suna raba hanyoyin salon salula iri ɗaya da cutar sankarar bargo ta HSCs.

Za a iya canza kwayar halitta ta al'ada zuwa CSC ta hanyar dysregulation na yaduwa da hanyoyin bambance-bambancen da ke sarrafa shi ko ta hanyar haifar da ayyukan oncoprotein .

BMI-1[gyara sashe | gyara masomin]

An gano ƙungiyar Polycomb mai jujjuya rubutun Bmi -1 azaman ƙwayar cuta ta gama gari wacce aka kunna a cikin lymphoma [106] kuma daga baya aka nuna don daidaita HSCs. [107] An kwatanta rawar Bmi-1 a cikin ƙwayoyin tushe na jijiyoyi. [108] Hanyar yana bayyana yana aiki a cikin CSCs na ciwan kwakwalwar yara . [109]

Daraja[gyara sashe | gyara masomin]

Hanyar Notch tana taka rawa wajen sarrafa yaduwar kwayar halitta don nau'ikan tantanin halitta da yawa ciki har da hematopoietic, jijiyoyi da mammary [110] SCs. An ba da shawarar sassan wannan hanyar don yin aiki azaman oncogenes a cikin mammary [111] da sauran ciwace-ciwacen daji.

Wani reshe na hanyar siginar Notch wanda ya haɗa da ma'anar rubutun Hes3 yana daidaita yawancin ƙwayoyin al'ada tare da halayen CSC da aka samu daga marasa lafiya na glioblastoma. [112]

Sonic hedgehog da Wnt[gyara sashe | gyara masomin]

Waɗannan hanyoyin haɓakawa sune masu kula da SC.[113][114] Dukansu Sonic hedgehog (SHH) da hanyoyin Wnt galibi ana yin su ne a cikin ciwace-ciwacen daji. Koyaya, abubuwan rubutun Gli waɗanda SHH ke tsara su sun ɗauki sunansu daga gliomas, inda aka bayyana su sosai. Matsayin giciye yana wanzu tsakanin hanyoyin biyu kuma galibi ana kunna su tare. [115] Sabanin haka, a cikin ciwon daji na hanji siginar bushiya yana nuna adawa da Wnt. [116]

Sonic hedgehog blockers suna samuwa, kamar cyclopamine . Cyclopamine mai narkewar ruwa na iya zama mafi tasiri a maganin ciwon daji. DMAPT, wani abu mai narkewa na ruwa na parthenolide, yana haifar da danniya na oxidative kuma ya hana NF-κB siginar [117] don AML (cututtukan sankarar bargo) da yiwuwar myeloma da ciwon daji na prostate. Telomerase batun nazari ne a cikin ilimin halittar jiki na CSC. [118] GRN163L ( Imetelstat ) kwanan nan an fara shi a cikin gwaji don ƙaddamar da ƙwayoyin ƙwayoyin myeloma.

Siginar Wnt na iya zama mai zaman kanta daga abubuwan motsa jiki na yau da kullun, ta hanyar maye gurbi a cikin ƙwayoyin cuta na oncogenes da ƙwayoyin cuta masu hana ƙari waɗanda ke kunna su dindindin duk da cewa mai karɓa na yau da kullun bai sami sigina ba. β-catenin yana ɗaure zuwa abubuwan rubutu kamar furotin TCF4 kuma a hade kwayoyin suna kunna kwayoyin da suka dace. LF3 da ƙarfi yana hana wannan ɗauri a cikin vitro, a cikin layin salula da rage haɓakar ƙari a cikin ƙirar linzamin kwamfuta. Ya hana kwafi kuma ya rage karfin su na yin ƙaura, duk ba tare da cutar da ƙwayoyin lafiya ba. Babu kwayar cutar kansa da ta rage bayan magani. Sakamakon binciken shine samfurin " ƙirar magunguna na hankali", wanda ya haɗa da AlphaScreens da fasahar ELISA . [119]

Ci gaba da karatu[gyara sashe | gyara masomin]

  • Rajasekhar VK, ed. (2014). Cancer Stem Cells. Hoboken, New Jersey: Wiley. ISBN 9781118356166.
  • Milosevic V, et al. (January 2020). "Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5". Int. J. Cancer. 146 (1): 192–207. doi:10.1002/ijc.32419. PMID 31107974. S2CID 160014053.

Manazarta[gyara sashe | gyara masomin]

  1. Sreepadmanabh M, Toley BJ (2018). "Investigations into the cancer stem cell niche using in-vitro 3-D tumor models and microfluidics". Biotechnology Advances. 36 (4): 1094–1110. doi:10.1016/j.biotechadv.2018.03.009. PMID 29559382.
  2. Mukherjee, Siddhartha (2010-10-29). "The Cancer Sleeper Cell". New York Times. Retrieved 15 July 2014.
  3. Reya T, Morrison SJ, Clarke MF, Weissman IL (November 2001). "Stem cells, cancer, and cancer stem cells". Nature. 414 (6859): 105–11. Bibcode:2001Natur.414..105R. doi:10.1038/35102167. hdl:2027.42/62862. PMID 11689955. S2CID 4343326.
  4. Heppner GH, Miller BE (1983). "Tumor heterogeneity: biological implications and therapeutic consequences". Cancer and Metastasis Reviews. 2 (1): 5–23. doi:10.1007/BF00046903. PMID 6616442. S2CID 2769686.
  5. Pan Q, Nicholson AM, arr H, Harrison LA, Wilson GD, Burkert J, Jeffery R, Alison MR, Looijenga L, Lin WR, McDonald SA, Wright NA, Harrison R, Peppelenbosch MP, Jankowski JA (April 2013). "Identification of lineage-uncommitted, long-lived, label-retaining cells in healthy human esophagus and stomach, and in metaplastic esophagus" (PDF). Gastroenterology. 144 (4): 761–70. doi:10.1053/j.gastro.2012.12.022. PMID 23266557.
  6. Bonnet D, Dick JE (July 1997). "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell". Nature Medicine. 3 (7): 730–7. doi:10.1038/nm0797-730. PMID 9212098. S2CID 205381050.
  7. Beck B, Blanpain C (2013), "Unravelling cancer stem cell potential", Nat Rev Cancer, 13 (10): 727–38, doi:10.1038/nrc3597, PMID 24060864, S2CID 11882727
  8. Heppner GH, Miller BE (1983). "Tumor heterogeneity: biological implications and therapeutic consequences". Cancer and Metastasis Reviews. 2 (1): 5–23. doi:10.1007/BF00046903. PMID 6616442. S2CID 2769686.
  9. Wang W, Quan Y, Fu Q, Liu Y, Liang Y, Wu J, Yang G, Luo C, Ouyang Q, Wang Y (2014), "Dynamics between cancer cell subpopulations reveals a model coordinating with both hierarchical and stochastic concepts", PLOS ONE, 9 (1): e84654, Bibcode:2014PLoSO...984654W, doi:10.1371/journal.pone.0084654, PMC 3886990, PMID 24416258
  10. Kreso A, Dick JE (2014), "Evolution of the cancer stem cell model", Cell Stem Cell, 14 (3): 275–91, doi:10.1016/j.stem.2014.02.006, PMID 24607403
  11. Barabé F, Kennedy JA, Hope KJ, Dick JE (April 2007). "Modeling the initiation and progression of human acute leukemia in mice". Science. 316 (5824): 600–4. Bibcode:2007Sci...316..600B. doi:10.1126/science.1139851. PMID 17463288. S2CID 34417642.
  12. Nowell PC (October 1976). "The clonal evolution of tumor cell populations". Science. 194 (4260): 23–8. Bibcode:1976Sci...194...23N. doi:10.1126/science.959840. PMID 959840.
  13. Clark EA, Golub TR, Lander ES, Hynes RO (August 2000). "Genomic analysis of metastasis reveals an essential role for RhoC". Nature. 406 (6795): 532–5. Bibcode:2000Natur.406..532C. doi:10.1038/35020106. PMID 10952316. S2CID 4301092.
  14. Cabrera MC, Hollingsworth RE, Hurt EM (2015), "Cancer stem cell plasticity and tumor hierarchy", World J Stem Cells, 7 (1): 27–36, doi:10.4252/wjsc.v7.i1.27, PMC 4300934, PMID 25621103
  15. Gupta PB, Chaffer CL, Weinberg RA (September 2009). "Cancer stem cells: mirage or reality?". Nature Medicine. 15 (9): 1010–2. doi:10.1038/nm0909-1010. PMID 19734877. S2CID 14167044. [permanent dead link]>
  16. Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ (December 2008). "Efficient tumour formation by single human melanoma cells". Nature. 456 (7222): 593–8. Bibcode:2008Natur.456..593Q. doi:10.1038/nature07567. PMC 2597380. PMID 19052619.
  17. Ichiryu N, Fairchild PJ (2013). "Immune Privilege of Stem Cells". In Zavazava N (ed.). Embryonic Stem Cell Immunobiology. Methods in Molecular Biology. 1029. pp. 1–16. doi:10.1007/978-1-62703-478-4_1. ISBN 978-1-62703-477-7. PMID 23756938.
  18. Maccalli C, Volontè A, Cimminiello C, Parmiani G (February 2014). "Immunology of cancer stem cells in solid tumours. A review". European Journal of Cancer. 50 (3): 649–55. doi:10.1016/j.ejca.2013.11.014. PMID 24333096.
  19. Bruttel VS, Wischhusen J (2014). "Cancer stem cell immunology: key to understanding tumorigenesis and tumor immune escape?". Frontiers in Immunology. 5: 360. doi:10.3389/fimmu.2014.00360. PMC 4114188. PMID 25120546.
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  22. Empty citation (help)
  23. Bonnet D, Dick JE (July 1997). "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell". Nature Medicine. 3 (7): 730–7. doi:10.1038/nm0797-730. PMID 9212098. S2CID 205381050.
  24. Ignatova TN, Kukekov VG, Laywell ED, Suslov ON, Vrionis FD, Steindler DA (September 2002). "Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro". Glia. 39 (3): 193–206. doi:10.1002/glia.10094. PMID 12203386. S2CID 37236481.
  25. Sundar SJ, Hsieh JK, Manjila S, Lathia JD, Sloan A (December 2014). "The role of cancer stem cells in glioblastoma". Neurosurgical Focus. 37 (6): E6. doi:10.3171/2014.9.FOCUS14494. PMID 25434391.
  26. Empty citation (help)
  27. Empty citation (help)
  28. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (September 2003). "Identification of a cancer stem cell in human brain tumors". Cancer Research. 63 (18): 5821–8. PMID 14522905.
  29. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (April 2003). "Prospective identification of tumorigenic breast cancer cells". Proceedings of the National Academy of Sciences of the United States of America. 100 (7): 3983–8. Bibcode:2003PNAS..100.3983A. doi:10.1073/pnas.0530291100. PMC 153034. PMID 12629218.
  30. O'Brien CA, Pollett A, Gallinger S, Dick JE (January 2007). "A human colon cancer cell capable of initiating tumour growth in immunodeficient mice". Nature. 445 (7123): 106–10. Bibcode:2007Natur.445..106O. doi:10.1038/nature05372. PMID 17122772. S2CID 4419499.
  31. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (June 2008). "Identification and characterization of ovarian cancer-initiating cells from primary human tumors". Cancer Research. 68 (11): 4311–20. doi:10.1158/0008-5472.CAN-08-0364. PMC 2553722. PMID 18519691.
  32. Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, Silasi DA, Steffensen KD, Waldstrom M, Visintin I, Mor G (January 2009). "Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance". Cell Cycle. 8 (1): 158–66. doi:10.4161/cc.8.1.7533. PMC 3041590. PMID 19158483.
  33. Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF, Simeone DM (February 2007). "Identification of pancreatic cancer stem cells". Cancer Research. 67 (3): 1030–7. doi:10.1158/0008-5472.CAN-06-2030. PMID 17283135.
  34. Maitland NJ, Collins AT (June 2008). "Prostate cancer stem cells: a new target for therapy". Journal of Clinical Oncology. 26 (17): 2862–70. doi:10.1200/JCO.2007.15.1472. PMID 18539965.
  35. Lang SH, Frame FM, Collins AT (January 2009). "Prostate cancer stem cells". The Journal of Pathology. 217 (2): 299–306. doi:10.1002/path.2478. PMC 2673349. PMID 19040209.
  36. Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga-Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH (January 2008). "Identification of cells initiating human melanomas". Nature. 451 (7176): 345–9. Bibcode:2008Natur.451..345S. doi:10.1038/nature06489. PMC 3660705. PMID 18202660.
  37. Boiko AD, Razorenova OV, van de Rijn M, Swetter SM, Johnson DL, Ly DP, Butler PD, Yang GP, Joshua B, Kaplan MJ, Longaker MT, Weissman IL (July 2010). "Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271". Nature. 466 (7302): 133–7. Bibcode:2010Natur.466..133B. doi:10.1038/nature09161. PMC 2898751. PMID 20596026.
  38. Schmidt P, Kopecky C, Hombach A, Zigrino P, Mauch C, Abken H (February 2011). "Eradication of melanomas by targeted elimination of a minor subset of tumor cells". Proceedings of the National Academy of Sciences of the United States of America. 108 (6): 2474–9. Bibcode:2011PNAS..108.2474S. doi:10.1073/pnas.1009069108. PMC 3038763. PMID 21282657.
  39. Civenni G, Walter A, Kobert N, Mihic-Probst D, Zipser M, Belloni B, Seifert B, Moch H, Dummer R, van den Broek M, Sommer L (April 2011). "Human CD271-positive melanoma stem cells associated with metastasis establish tumor heterogeneity and long-term growth". Cancer Research. 71 (8): 3098–109. doi:10.1158/0008-5472.CAN-10-3997. PMID 21393506.
  40. Matsui W, Huff CA, Wang Q, Malehorn MT, Barber J, Tanhehco Y, Smith BD, Civin CI, Jones RJ (March 2004). "Characterization of clonogenic multiple myeloma cells". Blood. 103 (6): 2332–6. doi:10.1182/blood-2003-09-3064. PMC 3311914. PMID 14630803.
  41. Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, McNiece I, Lin L, Ambinder RF, Peacock C, Watkins DN, Huff CA, Jones RJ (January 2008). "Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance". Cancer Research. 68 (1): 190–7. doi:10.1158/0008-5472.CAN-07-3096. PMC 2603142. PMID 18172311.
  42. Colmont CS, Benketah A, Reed SH, Hawk NV, Telford WG, Ohyama M, Udey MC, Yee CL, Vogel JC, Patel GK (January 2013). "CD200-expressing human basal cell carcinoma cells initiate tumor growth". Proceedings of the National Academy of Sciences of the United States of America. 110 (4): 1434–9. Bibcode:2013PNAS..110.1434C. doi:10.1073/pnas.1211655110. PMC 3557049. PMID 23292936.
  43. Patel GK, Yee CL, Terunuma A, Telford WG, Voong N, Yuspa SH, Vogel JC (February 2012). "Identification and characterization of tumor-initiating cells in human primary cutaneous squamous cell carcinoma". The Journal of Investigative Dermatology. 132 (2): 401–9. doi:10.1038/jid.2011.317. PMC 3258300. PMID 22011906.
  44. Wang Y, Yang J, Zheng H, Tomasek GJ, Zhang P, McKeever PE, Lee EY, Zhu Y (June 2009). "Expression of mutant p53 proteins implicates a lineage relationship between neural stem cells and malignant astrocytic glioma in a murine model". Cancer Cell. 15 (6): 514–26. doi:10.1016/j.ccr.2009.04.001. PMC 2721466. PMID 19477430.
  45. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM (October 2006). "Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells". Cancer Research. 66 (19): 9339–44. doi:10.1158/0008-5472.CAN-06-3126. PMID 16990346.
  46. Golebiewska A, Brons NH, Bjerkvig R, Niclou SP (February 2011). "Critical appraisal of the side population assay in stem cell and cancer stem cell research". Cell Stem Cell. 8 (2): 136–47. doi:10.1016/j.stem.2011.01.007. PMID 21295271.
  47. Scharenberg CW, Harkey MA, Torok-Storb B (January 2002). "The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors". Blood. 99 (2): 507–12. doi:10.1182/blood.V99.2.507. PMID 11781231.
  48. Pastrana E, Silva-Vargas V, Doetsch F (May 2011). "Eyes wide open: a critical review of sphere-formation as an assay for stem cells". Cell Stem Cell. 8 (5): 486–98. doi:10.1016/j.stem.2011.04.007. PMC 3633588. PMID 21549325.
  49. Nicolis SK (February 2007). "Cancer stem cells and "stemness" genes in neuro-oncology". Neurobiology of Disease. 25 (2): 217–29. doi:10.1016/j.nbd.2006.08.022. PMID 17141509. S2CID 25401054.
  50. Cao W, Chen K, Bolkestein M, Yin Y, Verstegen MM, Bijvelds MJ, Wang W, Tuysuz N, Ten Berge D, Sprengers D, Metselaar HJ, van der Laan LJ, Kwekkeboom J, Smits R, Peppelenbosch MP, Pan Q (October 2017). "Dynamics of Proliferative and Quiescent Stem Cells in Liver Homeostasis and Injury". Gastroenterology. 153 (4): 1133–47. doi:10.1053/j.gastro.2017.07.006. PMID 28716722.
  51. Cao W, Li M, Liu J, Zhang S, Noordam L, Verstegen MM, Wang L, Ma B, Li S, Wang W, Bolkestein M, Doukas M, Chen K, Ma Z, Bruno M, Sprengers D, Kwekkeboom J, van der Laan LJ, Smits R, Peppelenbosch MP, Pan Q (April 2020). "LGR5 marks targetable tumor-initiating cells in mouse liver cancer". Nature Communications. 11 (1): 1961. Bibcode:2020NatCo..11.1961C. doi:10.1038/s41467-020-15846-0. PMC 7181628. PMID 32327656.
  52. Yadav UP, Singh T, Kumar P, Sharma P, Kaur H, Sharma S, Singh S, Kumar S, and Mehta K (2020). "Metabolic Adaptations in Cancer Stem Cells". Frontiers in Oncology. 10 (Metabolic Plasticity of Cancer): 1010. doi:10.3389/fonc.2020.01010. PMC 7330710. PMID 32670883.
  53. Empty citation (help)
  54. Meng E, Mitra A, Tripathi K, Finan MA, Scalici J, McClellan S, Madeira da Silva L, Reed E, Shevde LA, Palle K, Rocconi RP (September 12, 2014). "ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling". PLOS ONE. 9 (9): e107142. Bibcode:2014PLoSO...9j7142M. doi:10.1371/journal.pone.0107142. PMC 4162571. PMID 25216266.
  55. Visvader JE, Lindeman GJ (October 2008). "Cancer stem cells in solid tumours: accumulating evidence and unresolved questions". Nature Reviews. Cancer. 8 (10): 755–68. doi:10.1038/nrc2499. PMID 18784658. S2CID 40382183.
  56. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (April 2003). "Prospective identification of tumorigenic breast cancer cells". Proceedings of the National Academy of Sciences of the United States of America. 100 (7): 3983–8. Bibcode:2003PNAS..100.3983A. doi:10.1073/pnas.0530291100. PMC 153034. PMID 12629218.
  57. Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel U, Goodell MA, Brenner MK (September 2004). "A distinct "side population" of cells with high drug efflux capacity in human tumor cells". Proceedings of the National Academy of Sciences of the United States of America. 101 (39): 14228–33. Bibcode:2004PNAS..10114228H. doi:10.1073/pnas.0400067101. PMC 521140. PMID 15381773.
  58. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (November 2007). "ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome". Cell Stem Cell. 1 (5): 555–67. doi:10.1016/j.stem.2007.08.014. PMC 2423808. PMID 18371393.
  59. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP (January 2010). "Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content". Cell. 140 (1): 62–73. doi:10.1016/j.cell.2009.12.007. PMID 20074520. S2CID 5547104.
  60. Deng S, Yang X, Lassus H, Liang S, Kaur S, Ye Q, Li C, Wang LP, Roby KF, Orsulic S, Connolly DC, Zhang Y, Montone K, Bützow R, Coukos G, Zhang L (April 2010). Cao Y (ed.). "Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers". PLOS ONE. 5 (4): e10277. Bibcode:2010PLoSO...510277D. doi:10.1371/journal.pone.0010277. PMC 2858084. PMID 20422001.
  61. Meyer MJ, Fleming JM, Lin AF, Hussnain SA, Ginsburg E, Vonderhaar BK (June 2010). "CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer". Cancer Research. 70 (11): 4624–33. doi:10.1158/0008-5472.CAN-09-3619. PMC 4129519. PMID 20484027.
  62. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (November 2004). "Identification of human brain tumour initiating cells". Nature. 432 (7015): 396–401. Bibcode:2004Natur.432..396S. doi:10.1038/nature03128. PMID 15549107. S2CID 4430962.
  63. Son MJ, Woolard K, Nam DH, Lee J, Fine HA (May 2009). "SSEA-1 is an enrichment marker for tumor-initiating cells in human glioblastoma". Cell Stem Cell. 4 (5): 440–52. doi:10.1016/j.stem.2009.03.003. PMC 7227614. PMID 19427293.
  64. Mazzoleni S, Politi LS, Pala M, Cominelli M, Franzin A, Sergi Sergi L, Falini A, De Palma M, Bulfone A, Poliani PL, Galli R (October 2010). "Epidermal growth factor receptor expression identifies functionally and molecularly distinct tumor-initiating cells in human glioblastoma multiforme and is required for gliomagenesis". Cancer Research. 70 (19): 7500–13. doi:10.1158/0008-5472.CAN-10-2353. PMID 20858720.
  65. Anido J, Sáez-Borderías A, Gonzàlez-Juncà A, Rodón L, Folch G, Carmona MA, Prieto-Sánchez RM, Barba I, Martínez-Sáez E, Prudkin L, Cuartas I, Raventós C, Martínez-Ricarte F, Poca MA, García-Dorado D, Lahn MM, Yingling JM, Rodón J, Sahuquillo J, Baselga J, Seoane J (December 2010). "TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human Glioblastoma". Cancer Cell. 18 (6): 655–68. doi:10.1016/j.ccr.2010.10.023. PMID 21156287.
  66. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (June 2007). "Phenotypic characterization of human colorectal cancer stem cells". Proceedings of the National Academy of Sciences of the United States of America. 104 (24): 10158–63. Bibcode:2007PNAS..10410158D. doi:10.1073/pnas.0703478104. PMC 1891215. PMID 17548814.
  67. Wilson BJ, Schatton T, Zhan Q, Gasser M, Ma J, Saab KR, Schanche R, Waaga-Gasser AM, Gold JS, Huang Q, Murphy GF, Frank MH, Frank NY (August 2011). "ABCB5 identifies a therapy-refractory tumor cell population in colorectal cancer patients". Cancer Research. 71 (15): 5307–16. doi:10.1158/0008-5472.CAN-11-0221. PMC 3395026. PMID 21652540.
  68. Odoux C, Fohrer H, Hoppo T, Guzik L, Stolz DB, Lewis DW, Gollin SM, Gamblin TC, Geller DA, Lagasse E (September 2008). "A stochastic model for cancer stem cell origin in metastatic colon cancer". Cancer Research. 68 (17): 6932–41. doi:10.1158/0008-5472.CAN-07-5779. PMC 2562348. PMID 18757407.
  69. Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM (April 2009). "Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis". Cancer Research. 69 (8): 3382–9. doi:10.1158/0008-5472.CAN-08-4418. PMC 2789401. PMID 19336570.
  70. Kemper K, Sprick MR, de Bree M, Scopelliti A, Vermeulen L, Hoek M, Zeilstra J, Pals ST, Mehmet H, Stassi G, Medema JP (January 2010). "The AC133 epitope, but not the CD133 protein, is lost upon cancer stem cell differentiation". Cancer Research. 70 (2): 719–29. doi:10.1158/0008-5472.CAN-09-1820. PMID 20068153.
  71. Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG (February 2011). "The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44". Nature Medicine. 17 (2): 211–5. doi:10.1038/nm.2284. PMC 3076220. PMID 21240262.
  72. Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG (March 2006). "Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells". Oncogene. 25 (12): 1696–708. doi:10.1038/sj.onc.1209327. PMID 16449977. S2CID 28427525.
  73. Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, García-Echeverría C, Schultz PG, Reddy VA (January 2009). "The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations". Proceedings of the National Academy of Sciences of the United States of America. 106 (1): 268–73. Bibcode:2009PNAS..106..268D. doi:10.1073/pnas.0810956106. PMC 2629188. PMID 19116269.
  74. Rajasekhar VK, Studer L, Gerald W, Socci ND, Scher HI (January 2011). "Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signalling". Nature Communications. 2 (1): 162. Bibcode:2011NatCo...2..162R. doi:10.1038/ncomms1159. PMC 3105310. PMID 21245843.
  75. Empty citation (help)
  76. Eramo A, Lotti F, Sette G, Pilozzi E, Biffoni M, Di Virgilio A, Conticello C, Ruco L, Peschle C, De Maria R (March 2008). "Identification and expansion of the tumorigenic lung cancer stem cell population". Cell Death and Differentiation. 15 (3): 504–14. doi:10.1038/sj.cdd.4402283. PMID 18049477. S2CID 2484961.
  77. Sullivan JP, Spinola M, Dodge M, Raso MG, Behrens C, Gao B, Schuster K, Shao C, Larsen JE, Sullivan LA, Honorio S, Xie Y, Scaglioni PP, DiMaio JM, Gazdar AF, Shay JW, Wistuba II, Minna JD (December 2010). "Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling". Cancer Research. 70 (23): 9937–48. doi:10.1158/0008-5472.CAN-10-0881. PMC 3058307. PMID 21118965.
  78. Leung EL, Fiscus RR, Tung JW, Tin VP, Cheng LC, Sihoe AD, Fink LM, Ma Y, Wong MP (November 2010). Jin DY (ed.). "Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties". PLOS ONE. 5 (11): e14062. Bibcode:2010PLoSO...514062L. doi:10.1371/journal.pone.0014062. PMC 2988826. PMID 21124918.
  79. Damelin M, Geles KG, Follettie MT, Yuan P, Baxter M, Golas J, DiJoseph JF, Karnoub M, Huang S, Diesl V, Behrens C, Choe SE, Rios C, Gruzas J, Sridharan L, Dougher M, Kunz A, Hamann PR, Evans D, Armellino D, Khandke K, Marquette K, Tchistiakova L, Boghaert ER, Abraham RT, Wistuba II, Zhou BB (June 2011). "Delineation of a cellular hierarchy in lung cancer reveals an oncofetal antigen expressed on tumor-initiating cells". Cancer Research. 71 (12): 4236–46. doi:10.1158/0008-5472.CAN-10-3919. PMID 21540235.
  80. Gonzalez-Villarreal CA, Quiroz-Reyes AG, Islas JF, Garza-Treviño EN (2020-08-20). "Colorectal Cancer Stem Cells in the Progression to Liver Metastasis". Frontiers in Oncology. 10: 1511. doi:10.3389/fonc.2020.01511. PMC 7468493. PMID 32974184.
  81. Thiery JP (June 2002). "Epithelial-mesenchymal transitions in tumour progression". Nature Reviews. Cancer. 2 (6): 442–54. doi:10.1038/nrc822. PMID 12189386. S2CID 5236443.
  82. Angerer LM, Angerer RC (June 1999). "Regulative development of the sea urchin embryo: signalling cascades and morphogen gradients". Seminars in Cell & Developmental Biology. 10 (3): 327–34. doi:10.1006/scdb.1999.0292. PMID 10441547.
  83. Mani SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA (June 2007). "Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers". Proceedings of the National Academy of Sciences of the United States of America. 104 (24): 10069–74. Bibcode:2007PNAS..10410069M. doi:10.1073/pnas.0703900104. PMC 1891217. PMID 17537911.
  84. Conacci-Sorrell M, Simcha I, Ben-Yedidia T, Blechman J, Savagner P, Ben-Ze'ev A (November 2003). "Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK". The Journal of Cell Biology. 163 (4): 847–57. doi:10.1083/jcb.200308162. PMC 2173691. PMID 14623871.
  85. Comito G, Calvani M, Giannoni E, Bianchini F, Calorini L, Torre E, Migliore C, Giordano S, Chiarugi P (August 2011). "HIF-1α stabilization by mitochondrial ROS promotes Met-dependent invasive growth and vasculogenic mimicry in melanoma cells". Free Radical Biology & Medicine. 51 (4): 893–904. doi:10.1016/j.freeradbiomed.2011.05.042. hdl:2158/496457. PMID 21703345.
  86. Spill F, Reynolds DS, Kamm RD, Zaman MH (August 2016). "Impact of the physical microenvironment on tumor progression and metastasis". Current Opinion in Biotechnology. 40: 41–48. doi:10.1016/j.copbio.2016.02.007. PMC 4975620. PMID 26938687.
  87. Empty citation (help)
  88. Empty citation (help)
  89. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, et al. (September 2007). "Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer". Cell Stem Cell. 1 (3): 313–23. doi:10.1016/j.stem.2007.06.002. PMID 18371365.
  90. Yang ZF, Ho DW, Ng MN, Lau CK, Yu WC, Ngai P, et al. (February 2008). "Significance of CD90+ cancer stem cells in human liver cancer". Cancer Cell. 13 (2): 153–66. doi:10.1016/j.ccr.2008.01.013. PMID 18242515.
  91. Empty citation (help)
  92. Empty citation (help)
  93. Empty citation (help)
  94. Empty citation (help)
  95. Zhao J (2016). "Cancer stem cells and chemoresistance: The smartest survives the raid". Pharmacol Ther. 160: 145–58. doi:10.1016/j.pharmthera.2016.02.008. PMC 4808328. PMID 26899500.
  96. Dirks P (July 2010). "Cancer stem cells: Invitation to a second round". Nature. 466 (7302): 40–1. Bibcode:2010Natur.466...40D. doi:10.1038/466040a. PMID 20596007. S2CID 205056717.
  97. Haskins WE, Eedala S, Jadhav YL, Labhan MS, Pericherla VC, Perlman EJ (May 2012). "Insights on neoplastic stem cells from gel-based proteomics of childhood germ cell tumors". Pediatric Blood & Cancer. 58 (5): 722–8. doi:10.1002/pbc.23282. PMC 3204330. PMID 21793190.
  98. Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES (August 2009). "Identification of selective inhibitors of cancer stem cells by high-throughput screening". Cell. 138 (4): 645–659. doi:10.1016/j.cell.2009.06.034. PMC 4892125. PMID 19682730.
  99. Jangamreddy JR, Ghavami S, Grabarek J, Kratz G, Wiechec E, Fredriksson BA, Rao Pariti RK, Cieślar-Pobuda A, Panigrahi S, Łos MJ (September 2013). "Salinomycin induces activation of autophagy, mitophagy and affects mitochondrial polarity: differences between primary and cancer cells". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1833 (9): 2057–69. doi:10.1016/j.bbamcr.2013.04.011. PMID 23639289.
  100. Vlahopoulos S, Critselis E, Voutsas IF, Perez SA, Moschovi M, Baxevanis CN, Chrousos GP (2014). "New use for old drugs? Prospective targets of chloroquines in cancer therapy". Current Drug Targets. 15 (9): 843–51. doi:10.2174/1389450115666140714121514. PMID 25023646.
  101. Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL, Meyerrose T, Rossi R, Grimes B, Rizzieri DA, Luger SM, Phillips GL (October 2000). "The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells". Leukemia. 14 (10): 1777–84. doi:10.1038/sj.leu.2401903. PMID 11021753. S2CID 9467715.
  102. Jin L, Lee EM, Ramshaw HS, Busfield SJ, Peoppl AG, Wilkinson L, Guthridge MA, Thomas D, Barry EF, Boyd A, Gearing DP, Vairo G, Lopez AF, Dick JE, Lock RB (July 2009). "Monoclonal antibody-mediated targeting of CD123, IL-3 receptor alpha chain, eliminates human acute myeloid leukemic stem cells". Cell Stem Cell. 5 (1): 31–42. doi:10.1016/j.stem.2009.04.018. PMID 19570512.
  103. "'Nanobombs' that blow up cancer cells | KurzweilAI". www.kurzweilai.net. 2015-12-07. Retrieved 2016-02-20.
  104. Wang H, Agarwal P, Zhao S, Yu J, Lu X, He X (January 2016). "A Near-Infrared Laser-Activated "Nanobomb" for Breaking the Barriers to MicroRNA Delivery". Advanced Materials. 28 (2): 347–55. doi:10.1002/adma.201504263. PMID 26567892.
  105. Huddle BC, Grimley E, Buchman CD, Chtcherbinine M, Debnath B, Mehta P, Yang K, Morgan CA, Li S, Felton JA, Sun D, Metha G, Neamati N, Buckanovich RJ, Hurley TD, Larsen SD (2018). "Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy". J Med Chem. 61 (19): 8754–8773. doi:10.1021/acs.jmedchem.8b00930. PMC 6477540. PMID 30221940.
  106. Haupt Y, Bath ML, Harris AW, Adams JM (November 1993). "bmi-1 transgene induces lymphomas and collaborates with myc in tumorigenesis". Oncogene. 8 (11): 3161–4. PMID 8414519.
  107. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF (May 2003). "Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells" (PDF). Nature. 423 (6937): 302–5. Bibcode:2003Natur.423..302P. doi:10.1038/nature01587. hdl:2027.42/62508. PMID 12714971. S2CID 4403711.
  108. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ (October 2003). "Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation". Nature. 425 (6961): 962–7. Bibcode:2003Natur.425..962M. doi:10.1038/nature02060. PMC 2614897. PMID 14574365.
  109. Hemmati HD, Nakano I, Lazareff JA, Masterman-Smith M, Geschwind DH, Bronner-Fraser M, Kornblum HI (December 2003). "Cancerous stem cells can arise from pediatric brain tumors". Proceedings of the National Academy of Sciences of the United States of America. 100 (25): 15178–83. Bibcode:2003PNAS..10015178H. doi:10.1073/pnas.2036535100. PMC 299944. PMID 14645703.
  110. Empty citation (help)
  111. Empty citation (help)
  112. Empty citation (help)
  113. Milosevic, V. et al. Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistancein mesothelioma initiating cells by inducing ABCB5.Int. J. Cancer, https://doi.org/10.1002/ijc.32419
  114. Beachy PA, Karhadkar SS, Berman DM (November 2004). "Tissue repair and stem cell renewal in carcinogenesis". Nature. 432 (7015): 324–31. Bibcode:2004Natur.432..324B. doi:10.1038/nature03100. PMID 15549094. S2CID 4428056.
  115. Zhou BP, Hung MC (June 2005). "Wnt, hedgehog and snail: sister pathways that control by GSK-3beta and beta-Trcp in the regulation of metastasis". Cell Cycle. 4 (6): 772–6. doi:10.4161/cc.4.6.1744. PMID 15917668. S2CID 31467958.
  116. Akiyoshi T, Nakamura M, Koga K, Nakashima H, Yao T, Tsuneyoshi M, Tanaka M, Katano M (July 2006). "Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation". Gut. 55 (7): 991–9. doi:10.1136/gut.2005.080333. PMC 1856354. PMID 16299030.
  117. She M, Chen X (January 2009). "Targeting Signal Pathways active in Cancer Stem Cells to Overcome Drug Resistance". Zhongguo Fei AI Za Zhi = Chinese Journal of Lung Cancer. 12 (1): 3–7. doi:10.3779/j.issn.1009-3419.2009.01.001. PMID 20712949.
  118. Bollmann FM (August 2008). "The many faces of telomerase: emerging extratelomeric effects". BioEssays. 30 (8): 728–32. doi:10.1002/bies.20793. PMID 18623070. S2CID 205478338.
  119. Hodge R (2016-01-25). "Hacking the programs of cancer stem cells". medicalxpress.com. Medical Express. Retrieved 2016-02-12.