Epigenetic priming in Cancer Epirubicine sol inj. hoton chemotheraphychemototherapy
Chemotherapy (sau da yawa ana takaita sunan zuwa chemo kuma wani lokacin CTX ko CTx ) ya kasance wani nau'in maganin ciwon daji ne wanda ke amfani da magungunan cutar kansa ( magungunan chemotherapeutic ) Sun Kasan ce a matsayin daidaitaccen tsari na chemotherapy. Ana iya kuma ba da ilimin chemotherapy tare da niyyar mai warkarwa (wanda kusan koyaushe ya ƙunshi haɗaɗɗun magunguna), ko yana iya nufin tsawaita rayuwa ko rage alamun bayyanar cututtuka ( palliative chemotherapy). Chemotherapy yana ɗaya daga cikin manyan nau'o'in ilimin likitanci musamman wanda aka keɓe don maganin pharmacotherapy don ciwon daji, wanda ake kira.[1][2]
Kalmar chemotherapy ta zo ne don nuna rashin takamaiman amfani da guba na cikin salula don hana mitosis (rarrabuwar tantanin halitta) ko haifar da lalacewar DNA, wanda shine dalilin da ya sa hana gyaran DNA na iya ƙara ilimin chemotherapy.[3] Ma'anar kalmar chemotherapy ta ƙunshi ƙarin zaɓaɓɓun wakilai waɗanda ke toshe siginar siginar salula ( sigina ). Haɓaka hanyoyin kwantar da hankali tare da takamaiman ƙwayoyin ƙwayoyin cuta ko ƙwayoyin ƙwayoyin cuta, waɗanda ke hana sigina masu haɓaka haɓakawa daga ingantattun ƙwayoyin cuta na endocrin (musamman estrogens don ciwon nono da androgens don kansar prostate) yanzu ana kiran su hanyoyin kwantar da hankali na hormonal. Sabanin haka, sauran hanawa na siginonin girma kamar waɗanda ke da alaƙa da tyrosine kinases mai karɓa ana kiran su azaman maganin da aka yi niyya.
Mahimmanci, yin amfani da kwayoyi (ko chemotherapy, maganin hormonal ko maganin da aka yi niyya) ya ƙunshi tsarin tsarin jiyya don ciwon daji a cikin cewa an shigar da su a cikin jini kuma saboda haka suna iya magance ciwon daji a kowane wuri na jiki a cikin jiki. Ana amfani da tsarin jiyya sau da yawa tare da wasu hanyoyin da suka ƙunshi jiyya na gida (watau jiyya waɗanda ingancinsu ya iyakance ga yankin anatomic inda ake amfani da su) don ciwon daji kamar radiation far, tiyata ko hyperthermia far.
Magungunan chemotherapeutic sun kasan ce kuma sune cytotoxic ta hanyar rarrabawar tantanin halitta (mitosis) amma ƙwayoyin cutar kansa sun bambanta sosai a cikin raunin su ga waɗannan wakilai. Mafi yawa, ana iya tunanin chemotherapy a matsayin hanyar lalacewa ko ƙwayoyin damuwa, wanda zai iya haifar da mutuwar tantanin halitta idan an fara apoptosis.Yawancin sakamako masu illa na ilimin chemotherapy za a iya gano su zuwa lalacewa ga kwayoyin halitta na al'ada waɗanda ke rarraba da sauri kuma suna da hankali ga magungunan anti-mitotic: sel a cikin kasusuwan kasusuwa, tsarin narkewa da gashin gashi. Wannan yana haifar da mafi yawan sakamako masu illa na chemotherapy: myelosuppression (raguwar samar da kwayoyin jini, saboda haka kuma rigakafi ), mucositis (ƙumburi na suturar ƙwayar cuta), da alopecia (rashin gashi). Saboda tasiri akan ƙwayoyin rigakafi (musamman lymphocytes), magungunan chemotherapy sau da yawa suna samun amfani a cikin tarin cututtuka waɗanda ke haifar da cutarwa ga tsarin rigakafi da kai (wanda ake kira autoimmunity ). Wadannan sun hada da rheumatoid amosanin gabbai, tsarin lupus erythematosus, sclerosis mai yawa, vasculitis da sauran su.
Akwai dabaru da yawa a cikin sarrafa magungunan chemotherapeutic da ake amfani da su a yau. Ana iya ba da ilimin chemotherapy tare da manufar warkewa ko kuma yana iya nufin tsawaita rayuwa ko kuma kawar da alamu .
ChemotherapyInduction chemotherapy shine layin farko na maganin kansa tare da maganin chemotherapeutic. Ana amfani da irin wannan nau'in chemotherapy don manufar warkarwa.[1][4]:55–59
Haɗaɗɗen yanayin chemotherapy shine amfani da magunguna tare da wasu magungunan ciwon daji, kamar su tiyata, maganin radiation, ko maganin hyperthermia.
Ana ba da haɗin gwiwar chemotherapy bayan gafara don tsawaita lokacin gabaɗayan rashin cutar da inganta rayuwa gabaɗaya. Maganin da aka yi amfani da shi daidai yake da maganin da ya sami gafara. [4]:55–59
Intensification chemotherapy yayi kama da ƙarfafa chemotherapy amma ana amfani da wani magani daban da na shigar da chemotherapy. [5]:55–59
Haɗin chemotherapy ya haɗa da jinyar mutum tare da adadin magunguna daban-daban a lokaci guda. Magungunan sun bambanta a tsarinsu da illolinsu. Babban fa'idar ita ce rage yuwuwar haɓaka juriya ga kowane wakili ɗaya. Har ila yau, ana iya amfani da magungunan sau da yawa a ƙananan allurai, rage yawan guba. [4]:55–59[6]:17–18[7]
Neoadjuvant chemotherapy ana ba da shi kafin magani na gida kamar tiyata, kuma an ƙera shi don rage ƙwayar ƙwayar cuta ta farko.[4]:55–59Hakanan ana ba da shi don ciwon daji tare da babban haɗarin cutar micromestatic. [8]:42
Ana ba da chemotherapy adjuvant bayan magani na gida (radiotherapy ko tiyata). Ana iya amfani da shi lokacin da akwai ƙananan shaidar ciwon daji, amma akwai haɗarin sake dawowa.[4]:55–59Hakanan yana da amfani wajen kashe duk wani nau'in ciwon daji da ya yadu zuwa sassan jiki. Wadannan micrometastases za a iya bi da su tare da adjuvant chemotherapy kuma zai iya rage yawan koma bayan da waɗannan sel da aka yaɗa suka haifar. [9]
Kulawa da cutar sankara shine maimaita ƙarancin magani don tsawaita gafara.[4]:55–59
Ana ba da maganin chemotherapy ko maganin kashe kwayoyin cuta ba tare da aniyar warkewa ba, amma kawai don rage nauyin ƙari da ƙara tsawon rai. Ga waɗannan ka'idoji, gabaɗaya, ana sa ran ingantaccen bayanin mai guba.[4]:55–59
Duk tsarin magani na chemotherapy yana buƙatar cewa mai karɓa ya sami damar jurewa magani. Ana amfani da matsayin aiki sau da yawa azaman ma'auni don sanin ko mutum zai iya karɓar chemotherapy, ko ana buƙatar rage kashi. Domin kawai juzu'in sel a cikin ƙwayar cuta suna mutuwa tare da kowane magani ( kashe- kashe ), dole ne a ba da maimaita allurai don ci gaba da rage girman ƙwayar cutar. [10] Tsarin chemotherapy na yanzu yana amfani da maganin ƙwayoyi a cikin hawan keke, tare da mitar da tsawon jiyya ta iyakance ta hanyar guba. [11]
Ingancin ilimin chemotherapy ya dogara da nau'in ciwon daji da mataki. Babban tasiri ya bambanta daga kasancewa mai warkarwa ga wasu cututtuka, irin su wasu cutar sankarar bargo,[12][13] zuwa rashin tasiri, kamar a wasu ciwace-ciwacen kwakwalwa, [14] zuwa rashin buƙata a wasu, kamar yawancin cututtukan fata marasa melanoma.[15]
Alakar amsa kashi na kashe kwayar halitta ta magungunan chemotherapeutic akan al'ada da ƙwayoyin kansa. A babban allurai yawan adadin al'ada da ƙwayoyin kansa da aka kashe suna kama da juna. Saboda wannan dalili, ana zaɓar allurai inda aikin anti-tumour ya wuce mutuwar tantanin halitta ta al'ada.
Sashi na chemotherapy na iya zama da wahala: Idan adadin ya yi ƙasa sosai, zai zama mara amfani a kan ƙwayar cuta, yayin da, a yawan allurai, mai guba ( sakamakon sakamako ) ba zai iya jurewa ga mutumin da ya karɓa ba. [16] Madaidaicin hanyar ƙayyade adadin chemotherapy ya dogara ne akan ƙididdige yankin saman jiki (BSA). Yawanci ana ƙididdige BSA tare da dabarar lissafi ko nomogram, ta yin amfani da nauyin mai karɓa da tsayinsa, maimakon ta hanyar auna yankin jiki kai tsaye. An samo wannan dabarar asali a cikin binciken 1916 kuma an yi ƙoƙarin fassara allurai na magani da aka kafa tare da dabbobin dakin gwaje-gwaje zuwa daidai allurai ga mutane. [17] Binciken ya haɗa da batutuwa tara kawai.[18] Lokacin da aka gabatar da ilimin chemotherapy a cikin 1950s, an karɓi tsarin BSA a matsayin ma'auni na hukuma don maganin chemotherapy don rashin zaɓi mafi kyau.[19][20]
An yi tambaya kan ingancin wannan hanyar wajen ƙididdige allurai na bai ɗaya saboda dabarar tana la'akari da nauyi da tsayin mutum kawai. Shaye-shayen kwayoyi da sharewa suna da tasiri da abubuwa da yawa, ciki har da shekaru, jima'i, metabolism, yanayin cuta, aikin gabobin jiki, hulɗar miyagun ƙwayoyi zuwa magunguna, kwayoyin halitta, da kiba, waɗanda ke da babban tasiri akan ainihin tattara magungunan a cikin jinin mutum.[21][22] A sakamakon haka, akwai babban bambanci a cikin tsarin tsarin maganin chemotherapy a cikin mutanen da BSA ta yi amfani da su, kuma an nuna wannan bambancin ya zama fiye da sau goma ga magunguna da yawa.[23] A wasu kalmomi, idan mutane biyu sun karɓi kashi ɗaya na maganin da aka ba su bisa ga BSA, ƙaddamar da wannan maganin a cikin jinin mutum ɗaya na iya zama sau 10 mafi girma ko ƙasa idan aka kwatanta da na ɗayan. Wannan sauye-sauye yana da kama da yawancin magungunan chemotherapy da BSA ke yi, kuma, kamar yadda aka nuna a kasa, an nuna shi a cikin nazarin magungunan 14 na yau da kullum na chemotherapy.
Gudanar da kashi 5-FU yana haifar da mafi kyawun amsawa da ƙimar rayuwa tare da yin amfani da BSA.[24]
Ya kasan ce a cikin sakamakon wannan canji na pharmacokinetic tsakanin mutane shine cewa mutane da yawa ba sa karɓar daidaitaccen kashi don cimma ingantaccen tasirin jiyya tare da ƙarancin sakamako masu illa. Wasu mutane sun yi yawa yayin da wasu kuma ba su da yawa.[25][26][27][28][29] Misali, a cikin gwaji na asibiti bazuwar, masu binciken sun gano kashi 85% na marasa lafiya da ke fama da cutar kansar metastatic da aka yi musu magani tare da 5-fluorouracil (5-FU) ba su sami mafi kyawun maganin warkewa ba lokacin da aka yi amfani da su ta daidaitattun BSA-68% an yi amfani da su kuma 17% wuce gona da iri.
An kuma sami cece-kuce game da amfani da BSA don ƙididdige allurai na chemotherapy ga mutanen da ke da kiba .[30] Saboda mafi girman BSA, likitoci sukan rage yawan adadin da tsarin BSA ya tsara ba bisa ka'ida ba saboda tsoron wuce gona da iri A yawancin lokuta, wannan na iya haifar da mafi kyawun magani.
Yawancin karatu na asibiti sun nuna cewa lokacin da maganin chemotherapy ya keɓance mutum ɗaya don cimma mafi kyawun bayyanar cututtuka na tsarin, ana inganta sakamakon magani kuma an rage tasirin sakamako mai guba.Ya kasan ce kuma a cikin binciken asibiti na 5-FU da aka ambata a sama, mutanen da aka daidaita kashinsu don cimma burin da aka riga aka ƙaddara sun fahimci haɓakar 84% a cikin ƙimar amsawar jiyya da haɓakar watanni shida a cikin rayuwa gabaɗaya (OS) idan aka kwatanta da waɗanda BSA ta yi.
Gudanar da kashi 5-FU yana guje wa mummunan tasirin sakamako da aka samu tare da maganin BSA [31]
A cikin binciken guda ɗaya, masu binciken sun kwatanta abubuwan da suka faru na gama gari na 5-FU-abokan haɗin gwiwa na 3/4 tsakanin masu daidaita kashi da mutanen da aka ba su ta BSA. Abubuwan da ke haifar da raguwar ma'auni na gudawa an rage su daga 18% a cikin rukunin BSA da aka yi amfani da su zuwa 4% a cikin rukunin da aka daidaita kashi kuma an kawar da mummunan sakamako na hematologic. Saboda rage yawan guba, marasa lafiya da aka daidaita kashi sun sami damar yin magani na tsawon lokaci. An yi wa mutanen da aka yi amfani da BSA magani na tsawon watanni 680 yayin da aka yi wa mutanen da ke cikin rukunin daidaita kashi na jimlar watanni 791. Kammala tsarin jiyya shine muhimmin abu don samun ingantacciyar sakamakon magani.
An samo irin wannan sakamakon a cikin binciken da ya shafi mutanen da ke da ciwon daji na launin fata waɗanda aka yi musu magani tare da sanannen tsarin FOLFOX. [32] An rage yawan kamuwa da zawo mai tsanani daga 12% a cikin rukunin marasa lafiya na BSA zuwa kashi 1.7% a cikin rukunin da aka daidaita kashi, kuma an rage yawan mucositis mai tsanani daga 15% zuwa 0.8%.
Nazarin FOLFOX kuma ya nuna ci gaba a cikin sakamakon jiyya. Amsa mai kyau ya karu daga 46% a cikin rukunin da aka yi amfani da BSA zuwa 70% a cikin rukunin da aka daidaita kashi. Matsakaicin ci gaba na rayuwa kyauta (PFS) da rayuwa gabaɗaya (OS) duka sun inganta da watanni shida a cikin rukunin da aka daidaita kashi. [33]
Hanya ɗaya da za ta iya taimaka wa likitocin su keɓance maganin chemotherapy shine don auna matakan miyagun ƙwayoyi a cikin jini na jini a kan lokaci da daidaita kashi bisa ga tsari ko algorithm don cimma mafi kyawun bayyanar. Tare da kafaffen bayyanar da manufa don ingantaccen ingancin jiyya tare da ƙarancin guba, ana iya keɓance allurai don cimma buƙatuwar manufa da sakamako mafi kyau ga kowane mutum. Anyi amfani da irin wannan algorithm a cikin gwaje-gwajen asibiti da aka ambata a sama kuma ya haifar da ingantaccen sakamako mai mahimmanci.[ana buƙatar hujja]
Likitocin Oncologists sun riga sun keɓance adadin wasu magungunan cutar kansa dangane da fallasa. Carboplatin :4da busulfan allurai sun dogara da sakamakon gwajin jini don ƙididdige mafi kyawun kashi ga kowane mutum. Hakanan ana samun gwajin jini mai sauƙi don haɓaka kashi na methotrexate, 5-FU, paclitaxel, da docetaxel.
Matsakaicin matakin albumin nan da nan kafin gudanar da aikin chemotherapy shine mai hasashen mai zaman kansa na rayuwa a cikin nau'ikan ciwon daji daban-daban.
Tushen DNA guda biyu waɗanda ke haɗe da mustard nitrogen. Matsalolin nitrogen daban-daban za su sami ƙungiyoyin sinadarai daban-daban (R). Nitrogen mustards yawanci alkylate N7 nitrogen na guanine (kamar yadda aka nuna a nan) amma sauran atoms na iya zama alkylated. [34]
Ma'aikatan Alkylating sune mafi tsufa rukuni na chemotherapeutics da ake amfani da su a yau. Asalin da aka samu daga iskar mustard da aka yi amfani da shi a yakin duniya na daya, yanzu ana amfani da nau'ikan abubuwan alkylating iri-iri. Suna haka ne saboda iyawarsu na alkylate da yawa kwayoyin halitta, gami da sunadaran, RNA da DNA . Wannan ikon ɗaure covally ga DNA ta hanyar rukunin alkyl shine babban dalilin maganin cutar kansa. DNA an yi shi ne da igiyoyi biyu kuma ƙwayoyin na iya ɗaure sau biyu zuwa madaidaicin DNA guda ɗaya (intrastrand crosslink) ko kuma suna iya ɗaure sau ɗaya zuwa duka igiyoyin biyu (interstrand crosslink). Idan tantanin halitta yayi ƙoƙarin yin kwafin DNA mai haɗe-haɗe yayin rarraba tantanin halitta, ko yayi ƙoƙarin gyara shi, igiyoyin DNA na iya karye. Wannan yana haifar da wani nau'i na tsarin mutuwar kwayar halitta wanda ake kira apoptosis . Alkylating jamiái za su yi aiki a kowane lokaci a cikin tantanin halitta sake zagayowar kuma don haka aka sani da cell sake zagayowar-m kwayoyi masu zaman kansu. Saboda wannan dalili, tasirin akan tantanin halitta ya dogara da kashi; juzu'in sel da suka mutu yana daidai da adadin ƙwayoyi.
Deoxycytidine (hagu) da magungunan anti-metabolite guda biyu (tsakiya da dama); Gemcitabine da decitabine . Magungunan sunyi kama da juna amma suna da bambance-bambance a cikin tsarin sinadarai .Chemotherapy
Anti-metabolites rukuni ne na kwayoyin da ke hana DNA da kira na RNA. Yawancinsu suna da tsari iri ɗaya ga tubalan ginin DNA da RNA. Tubalan ginin sune nucleotides ; kwayoyin halitta wanda ya ƙunshi nucleobase, sukari da ƙungiyar phosphate. An raba nucleobases zuwa purines ( guaninedan adenine ) da pyrimidine ( cytosine, timindan uracil ). Anti-metabolites suna kama da ko dai nucleobases ko nucleosides (wani nucleotide ba tare da rukunin phosphate ba), amma sun canza ƙungiyoyin sinadarai. [36] Waɗannan magungunan suna yin tasirin su ta hanyar toshe enzymes ɗin da ake buƙata don haɗin DNA ko zama cikin DNA ko RNA. Ta hanyar hana enzymes da ke cikin haɗin DNA, suna hana mitosis saboda DNA ba zai iya kwafin kanta ba. Har ila yau, bayan ƙaddamar da kwayoyin halitta a cikin DNA, lalacewar DNA na iya faruwa kuma an haifar da mutuwar kwayar halitta ( apoptosis ) . Ba kamar magungunan alkylating ba, anti-metabolites sun dogara da sake zagayowar tantanin halitta. Wannan yana nufin cewa suna aiki ne kawai a lokacin takamaiman yanki na sake zagayowar tantanin halitta, a cikin wannan yanayin S-phase (lokacin haɗin DNA). Saboda wannan dalili, a wani ƙayyadadden sashi, tasirin plateaus kuma daidai gwargwado babu sauran mutuwar tantanin halitta tare da ƙarin allurai. Subtypes na anti-metabolites sune anti-folates, fluoropyrimidines, deoxynucleoside analogues da thiopurines.
Anti-folates sun haɗa da methotrexate da pemetrexed . Methotrexate yana hana dihydrofolate reductase (DHFR), wani enzyme wanda ke sake farfado da tetrahydrofolate daga dihydrofolate. Lokacin da methotrexate ya hana enzyme, matakan salula na folate coenzymes suna raguwa. Ana buƙatar waɗannan don samar da thymidylate da purine, waɗanda suke da mahimmanci ga haɗin DNA da rarrabawar tantanin halitta. :55–59[37]:11Pemetrexed wani anti-metabolite ne wanda ke shafar samar da purine da pyrimidine, sabili da haka kuma yana hana DNA kira. Da farko yana hana enzyme thymidylate synthase, amma kuma yana da tasiri akan DHFR, aminoimidazole carboxamide ribonucleotide formyltransferase da glycinamide ribonucleotide formyltransferase. Magungunan fluoropyrimidine sun hada da fluorouracil da capecitabine. Fluorouracil shine analog na nucleobase wanda ke narkewa a cikin sel don samar da aƙalla samfuran aiki guda biyu; 5-fluourouridine monophosphate (FUMP) da 5-fluoro-2'-deoxyuridine 5'-phosphate (fdUMP). FUMP ya zama cikin RNA kuma fdUMP yana hana enzyme thymidylate synthase; duka biyun suna haifar da mutuwar tantanin halitta. :11Capecitabine shine prodrug na 5-fluorouracil wanda aka rushe a cikin sel don samar da magani mai aiki. Analogues na deoxynucleoside sun hada da cytarabine, gemcitabine, decitabine, azacitidine, fludarabine, nelarabine, cladribine, clofarabine, da pentostatin. thiopurines sun hada da thioguanine da mercaptopurine.
Vinca alkaloids sun hana haɗuwa da microtubules, yayin da haraji ke hana rarraba su. Duk hanyoyin biyu suna haifar da mitosis mara kyau.
Magungunan anti-microtubule sune sinadarai da aka samo daga tsire-tsire waɗanda ke toshe rarraba tantanin halitta ta hanyar hana aikin microtubule. Microtubules wani muhimmin tsarin salula ne wanda ya ƙunshi sunadarai guda biyu, α-tubulin da β-tubulin . Suna da sarari, sifofi masu siffar sanda waɗanda ake buƙata don rarraba tantanin halitta, a tsakanin sauran ayyukan salula. Microtubules sune tsarukan tsauri, wanda ke nufin cewa sun kasance na dindindin a cikin yanayin taro da rarrabawa. Vinca alkaloids da taxes sune manyan ƙungiyoyi biyu na magungunan ƙwayoyin cuta, kuma ko da yake waɗannan rukunin magungunan biyu suna haifar da tabarbarewar microtubule, tsarin aikin su gaba ɗaya ya sabawa: Vinca alkaloids suna hana haɗuwar microtubules, yayin da haraji ke hana rushewar su. Ta yin haka, suna hana ƙwayoyin cutar kansa kammala mitosis. Bayan wannan, kamawar kwayar halitta yana faruwa, wanda ke haifar da mutuwar kwayar halitta ( apoptosis ). Hakanan waɗannan kwayoyi na iya shafar haɓakar jini, wani muhimmin tsari wanda ciwace-ciwacen daji ke amfani da su don girma da metastasis.
Vinca alkaloids an samo su ne daga Madagascar periwinkle, Catharanthus roseus, wanda aka fi sani da Vinca rosea. Suna ɗaure ga takamaiman shafuka akan tubulin, suna hana haɗuwar tubulin cikin microtubules. Asalin alkaloids na vincasamfuran halitta ne waɗanda suka haɗa da vincristine da vinblastine. Bayan nasarar wadannan kwayoyi, an samar da alkaloids na semi-synthetic vinca alkaloids: vinorelbine (wanda aka yi amfani da shi wajen maganin ciwon huhu mara ƙananan ƙwayoyin cuta[38][39][40] ), vindesine, da vinflunine. Waɗannan magungunan suna da ƙayyadaddun tantanin halitta . Suna ɗaure ga ƙwayoyin tubulin a cikin S-phase kuma suna hana ingantaccen tsarin microtubule da ake buƙata don M-phase.
Taxanes ne na halitta da Semi-Synthetic kwayoyi. Magungunan farko na ajin su, paclitaxel, an samo asali ne daga Taxus brevifolia, Pacific yew. Yanzu wannan magani da kuma wani a cikin wannan ajin, docetaxel, ana samar da su ta hanyar sinadarai na wucin gadi daga wani sinadari da aka samu a cikin bawon wata bishiyar yew, Taxus baccata .[ana buƙatar hujja]
Podophyllotoxin shine lignan antineoplastic wanda aka samo asali daga mayapple na Amurka ( Podophyllum peltatum ) da Himalayan mayapple ( Sinopodophyllum hexandrum ). Yana da aikin anti-microtubule, kuma tsarinsa yana kama da na vinca alkaloids a cikin abin da suke ɗaure da tubulin, yana hana ƙwayar microtubule. Ana amfani da Podophyllotoxin don samar da wasu magunguna guda biyu tare da hanyoyin aiki daban-daban: etoposide da teniposide .
Masu hana Topoisomerase kwayoyi ne da ke shafar ayyukan enzymes guda biyu: topoisomerase I da topoisomerase II . Lokacin da helix ɗin DNA mai igiya biyu ba a yi rauni ba, yayin yin DNA ko rubutawa, alal misali, iskar DNA ɗin da ba a buɗe ba tana da ƙarfi (supercoils), kamar buɗe tsakiyar igiya murɗaɗi. Damuwar da ke haifar da wannan tasirin yana cikin wani ɓangare na taimakon enzymes topoisomerase. Suna haifar da ɓarna guda ɗaya ko biyu cikin DNA, suna rage tashin hankali a cikin madaidaicin DNA. Wannan yana ba da damar kwancen DNA na yau da kullun ya faru yayin kwafi ko kwafi. Hana topoisomerase I ko II yana tsoma baki tare da waɗannan hanyoyin guda biyu.
Biyu na topoisomerase I inhibitors, irinotecan da topotecan, an samo asali ne daga camptothecin, wanda aka samo daga itacen ado na kasar Sin Camptotheca acuminata . Ana iya raba magungunan da ke kaiwa topoisomerase II zuwa rukuni biyu. Topoisomerase II guba yana haifar da ƙara yawan matakan enzymes da ke ɗaure zuwa DNA. Wannan yana hana kwafin DNA da kwafi, yana haifar da karyewar layin DNA, kuma yana haifar da mutuwar kwayar halitta ( apoptosis ). Wadannan sun hada da etoposide, doxorubicin, mitoxantrone da teniposide. Ƙungiya ta biyu, masu hana catalytic, kwayoyi ne waɗanda ke toshe ayyukan topoisomerase II, don haka suna hana haɗin DNA da fassarar saboda DNA ba zai iya jurewa da kyau ba. Wannan rukunin ya haɗa da novobiocin, merbarone, da aclarubicin, waɗanda kuma suna da wasu mahimman hanyoyin aiwatarwa.
Magungunan rigakafi na cytotoxic rukuni ne daban-daban na magunguna waɗanda ke da hanyoyin aiki daban-daban. Jigon gama gari da suke rabawa a cikin nunin chemotherapy shine suna katse rarrabawar tantanin halitta. Mafi mahimmancin rukuni shine anthracyclines da bleomycins ; wasu fitattun misalan sun haɗa da mitomycin C da actinomycin.
'Yan mata biyu masu fama da cutar sankarar bargo ta lymphoblastic suna karɓar chemotherapy. Yarinyar da ke hagu an saka mata catheter na tsakiya a wuyanta. Yarinyar da ke hannun dama tana da catheter na gefe . Allomar hannu tana daidaita hannu yayin saka allura. Anti-cancer IV drip ana gani a saman dama.
Yawancin chemotherapy ana isar da su ta cikin jini, kodayake ana iya gudanar da adadin wakilai ta baki (misali, melphalan, busulfan, capecitabine ). Bisa ga sake dubawa na kwanan nan (2016) na yau da kullum, hanyoyin kwantar da hankali na baka suna ba da ƙarin ƙalubale ga marasa lafiya da ƙungiyoyin kulawa don kiyayewa da tallafawa bin tsarin kulawa.
Akwai hanyoyi da yawa na isar da magunguna ta cikin jijiya, waɗanda aka sani da na'urorin samun damar jijiya. Waɗannan sun haɗa da na'urar jiko mai fuka -fuki, catheter na gefe, catheter na tsakiya, catheter na tsakiya (PICC), catheter na tsakiya da tashar tashar da za a iya shukawa . Na'urorin suna da aikace-aikace daban-daban dangane da tsawon lokacin jiyya na chemotherapy, hanyar bayarwa da nau'ikan wakili na chemotherapeutic. :94–95
Dangane da mutum, ciwon daji, matakin ciwon daji, nau'in chemotherapy, da sashi, ana iya ba da chemotherapy ta cikin jijiya akan ko dai a asibiti ko na waje. Don ci gaba da gudanar da aikin chemotherapy na jijiya akai-akai ko kuma na tsawon lokaci, ana iya shigar da tsarin daban-daban ta hanyar tiyata a cikin vasculature don kiyaye shiga. :113–118Tsarukan da aka fi amfani da su sune layin Hickman, da Port-a-Cath, da kuma layin PICC. Waɗannan suna da ƙananan haɗarin kamuwa da cuta, suna da ƙarancin kamuwa da phlebitis ko ƙari, kuma suna kawar da buƙatar maimaita shigar da cannulae na gefe.[ana buƙatar hujja]
Keɓewar gaɓoɓin gaɓoɓi (sau da yawa ana amfani da shi a cikin melanoma ), ko keɓaɓɓen jiko na chemotherapy a cikin hanta ko huhu an yi amfani da su don magance wasu ciwace-ciwace. Babban manufar waɗannan hanyoyin shine a sadar da babban adadin chemotherapy zuwa wuraren ciwon daji ba tare da haifar da lahani mai yawa na tsarin ba. Wadannan hanyoyin za su iya taimakawa wajen sarrafa keɓaɓɓen ko ƙayyadaddun metastases, amma ta hanyar ma'anar ba tsari ba ne, kuma, sabili da haka, kada ku bi da rarraba metastases ko micrometastases .[ana buƙatar hujja]
Dabarun ilimin chemotherapeutic suna da kewayon illolin da suka dogara da nau'in magungunan da ake amfani da su. Magungunan da aka fi sani suna shafar ƙwayoyin sel masu saurin rarrabuwa na jiki, kamar ƙwayoyin jini da ƙwayoyin da ke rufe baki, ciki, da hanji. Abubuwan da ke da alaƙa da ilimin chemotherapy na iya faruwa sosai bayan gudanarwa, cikin sa'o'i ko kwanaki, ko na yau da kullun, daga makonni zuwa shekaru. [42]:265
A lokuta da yawa, karuwa a cikin haƙuri / raguwa a cikin sakamako masu illa da kuma inganta ingantaccen maganin warkewa ta hanyar azumi na gajeren lokaci a cikin kwanakin jiyya an lura da su a cikin mutum da kuma gwaje-gwajen dabba.[43][44][45][46]
A cikin mummunan myelosuppression, wanda ke faruwa a cikin wasu tsarin, kusan dukkanin kwayoyin halitta na kasusuwa (kwayoyin da ke samar da farin jini da jajayen jini ) an lalata su, ma'ana allogenic ko autologouskasusuwan kasusuwan kasusuwa ya zama dole. (A cikin BMTs na autologous, ana cire sel daga mutum kafin magani, ninka sannan a sake yin allura daga baya; a cikin BMTs na allogenic, tushen mai bayarwa ne. ) Duk da haka, wasu mutane har yanzu suna fama da cututtuka saboda wannan tsangwama tare da kasusuwa.[ana buƙatar hujja]
Ko da yake ana shawartar mutanen da ke karbar maganin chemotherapy da su wanke hannayensu, su guje wa marasa lafiya, da kuma daukar wasu matakai na rage kamuwa da cuta, kusan kashi 85% na cututtuka na faruwa ne sakamakon wasu kwayoyin cuta da ke faruwa a jikin jikin mutum (ciki har da cavity na baki ) da kuma fata. [47]:130Wannan na iya bayyana a matsayin cututtuka na tsarin, irin su sepsis, ko a matsayin annoba ta gida, irin su Herpes simplex, shingles, ko wasu mambobi na Herpesviridea. [48] Ana iya rage haɗarin rashin lafiya da mutuwa ta hanyar shan maganin rigakafi na yau da kullun kamar quinolones ko trimethoprim/sulfamethoxazole kafin wani zazzabi ko alamar kamuwa da cuta ya bayyana. [49] Quinolones yana nuna ingantaccen rigakafi musamman tare da ciwon daji na hematological. [49] Duk da haka, a gaba ɗaya, ga kowane mutum biyar da aka hana rigakafi bayan maganin chemotherapy da suka sha maganin rigakafi, za a iya hana zazzabi daya; ga kowane mutum 34 da ya sha maganin rigakafi, ana iya hana mutuwa daya. [49] Wani lokaci, ana jinkirta jiyya na chemotherapy saboda an danne tsarin garkuwar jiki zuwa ƙananan matakin.
Trilaciclib shine mai hana cyclin-dogara kinase 4/6 wanda aka amince da shi don rigakafin myelosuppression wanda chemotherapy ya haifar. Ana ba da miyagun ƙwayoyi kafin chemotherapy don kare aikin ƙwayar kasusuwa. [51]
Typhlitis na gaggawa ne na likita. Yana da mummunan tsinkaya kuma sau da yawa yana da mutuwa sai dai idan an gane shi da sauri kuma an yi masa mugun nufi. [53] Nasarar jiyya ya dogara ne akan ganewar asali da wuri da aka bayar ta babban ginshiƙi na zato da kuma yin amfani da sikanin CT, magani mara aiki don lokuta marasa rikitarwa, da kuma wani lokacin zaɓin hemicolectomy na dama don hana sake dawowa. [53]
Tashin zuciya, amai, anorexia, gudawa, ciwon ciki, da maƙarƙashiya ne na gama gari-sakamakon magungunan chemotherapeutic wanda ke kashe sel masu rarraba cikin sauri. [54]Rashin abinci mai gina jiki da rashin ruwa na iya haifarwa lokacin da mai karɓa bai ci ko sha ba, ko kuma lokacin da mutum ya yi amai akai-akai, saboda lahani na ciki. Wannan na iya haifar da saurin raguwar kiba, ko kuma a samu kiba lokaci-lokaci, idan mutum ya ci abinci da yawa a kokarinsa na kawar da tashin zuciya ko ƙwannafi. Hakanan ana iya haifar da karuwar nauyi ta wasu magungunan steroid. Ana iya rage waɗannan lahani akai-akai ko kuma a kawar da su tare da magungunan hana kumburi. Shaida maras tabbas ta kuma nuna cewa probiotics na iya samun rigakafin rigakafi da tasirin maganin gudawa dangane da chemotherapy kadai kuma tare da aikin rediyo. [55] Duk da haka, babban ƙididdiga na zato ya dace, tun da zawo da kumburi suma alamun alamun cutar typhlitis ne, gaggawar gaggawa mai tsanani da kuma yiwuwar rayuwa wanda ke buƙatar magani na gaggawa .[ana buƙatar hujja]
↑Wood M, Brighton D (2005). The Royal Marsden Hospital handbook of cancer chemotherapy: a guide for the multidisciplinary team. St. Louis, Mo: Elsevier Churchill Livingstone. ISBN978-0-443-07101-0.
↑Du Bois D, Du Bois EF (1989). "A formula to estimate the approximate surface area if height and weight be known. 1916". Nutrition. 5 (5): 303–11, discussion 312–3. PMID2520314.
↑Felici A, Verweij J, Sparreboom A (September 2002). "Dosing strategies for anticancer drugs: the good, the bad and body-surface area". European Journal of Cancer. 38 (13): 1677–84. doi:10.1016/s0959-8049(02)00151-x. PMID12175683.
↑Pinkel D (August 1958). "The use of body surface area as a criterion of drug dosage in cancer chemotherapy". Cancer Research. 18 (7): 853–6. PMID13573353.
↑Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M (May 2008). "Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer". Journal of Clinical Oncology. 26 (13): 2099–105. doi:10.1200/jco.2007.13.3934. PMID18445839. S2CID9557055.
↑Beumer JH, Chu E, Salamone SJ (November 2012). "Body-surface area-based chemotherapy dosing: appropriate in the 21st century?". Journal of Clinical Oncology. 30 (31): 3896–7. doi:10.1200/JCO.2012.44.2863. PMID22965963.
↑Gamelin E, Delva R, Jacob J, Merrouche Y, Raoul JL, Pezet D, Dorval E, Piot G, Morel A, Boisdron-Celle M (May 2008). "Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: results of a multicenter randomized trial of patients with metastatic colorectal cancer". Journal of Clinical Oncology. 26 (13): 2099–105. doi:10.1200/jco.2007.13.3934. PMID18445839. S2CID9557055.
↑Saam J, Critchfield GC, Hamilton SA, Roa BB, Wenstrup RJ, Kaldate RR (September 2011). "Body surface area-based dosing of 5-fluoruracil results in extensive interindividual variability in 5-fluorouracil exposure in colorectal cancer patients on FOLFOX regimens". Clinical Colorectal Cancer. 10 (3): 203–6. doi:10.1016/j.clcc.2011.03.015. PMID21855044.
↑Capitain O, Asevoaia A, Boisdron-Celle M, Poirier AL, Morel A, Gamelin E (December 2012). "Individual fluorouracil dose adjustment in FOLFOX based on pharmacokinetic follow-up compared with conventional body-area-surface dosing: a phase II, proof-of-concept study". Clinical Colorectal Cancer. 11 (4): 263–7. doi:10.1016/j.clcc.2012.05.004. PMID22683364.
↑Hunter RJ, Navo MA, Thaker PH, Bodurka DC, Wolf JK, Smith JA (February 2009). "Dosing chemotherapy in obese patients: actual versus assigned body surface area (BSA)". Cancer Treatment Reviews. 35 (1): 69–78. doi:10.1016/j.ctrv.2008.07.005. PMID18922643.
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