Kanker ovarium merupakan keganasan ginekologi terbanyak ketiga penyebab kematian perempuan di Indonesia, menempati urutan ke-18 di dunia tahun 2018, histopatologi terbanyak merupakan tipe epitel. ...Tatalaksana pasien kanker ovarium stadium lanjut terdiri dari kombinasi operasi surgical staging atau sitoreduksi dengan kemoterapi. Penelitian ini akan menilai respons pengobatan pasien kanker ovarium tipe epitel yang menjalani kemoterapi kombinasi paklitaksel-karboplatin di RSUP Dr.Mohammad Hoesin Palembang berdasarkan kadar VEGF-A serum. Penelitian ini merupakan uji klinik acak tanpa pembanding. Sampel penelitian adalah semua pasien kanker ovarium tipe epitel di RSUP Dr.Mohammad Hoesin Palembang yang mendapat kemoterapi pada bulan Desember 2018 sampai dengan Mei 2019 sejumlah 30 pasien. Karakteristik umum subyek penelitian ini yaitu usia terbanyak >48 tahun (53,3%), 20 sampel berdomisili di luar kota (66,7%). Pendidikan terbanyak adalah SMA yaitu 14 orang (46,7%). 21 orang (66,7%) merupakan multipara, stadium terbanyak adalah IIIC (56,7%). Didapatkan penurunan bermakna kadar ca125 sebelum dan setelah kemoterapi (p=0.000). Rerata kadar ca125 sebelum dan setelah kemoterapi adalah 840,60 dan 472,02. Rerata kadar VEGF-A serum sebelum kemoterapi adalah 806,03 dan menurun menjadi 703,5 setelah kemoterapi tetapi tidak bermakna secara statistik (p=0,082). 20 pasien (71,43%) dengan respons kemoterapi positif mengalami penurunan kadar VEGF-A namun tidak bermakna secara statistik (p=0,517). Hasil penelitian didapatkan penurunan kadar VEGF-A pada 70% pasien paska kemoterapi paklitakselkarboplatin 3 seri tetapi tidak bermakna secara statistik. Kadar VEGF-A serum belum efektif untuk menilai respon kemoterapi paklitaksel-karboplatin pada pasien kanker ovarium tipe epitel.
Purpose: This study explores the biochemical and functional effects of farnesene, which has potent free radical scavenging and antioxidant properties, on paclitaxel-induced ototoxicity.
Materials and ...Methods: Eighteen male Wistar albino rats were allocated into three groups of six rats at random. No paclitaxel or farnesene was given to the control group throughout the research. Paclitaxel was given four times intraperitoneally at a dose of 5 mg/kg (1st, 7th, 14th & 21st days) in the paclitaxel group. In the Farnesene + Paclitaxel group, 5 mg/kg paclitaxel was given first, followed by 4 times 50 mg/kg farnesene intraperitoneally 30 minutes later (1st, 7th, 14th & 21st days). Otoacoustic emission measurement was taken on days 0 and 21 in all rats. After that, the animals were sacrificed, and their cochleas were extracted for biochemical testing.
Results: Paclitaxel caused oxidative stress in the cochlea, which considerably elevated malondialdehyde levels and lowered glutathione levels in cochlear tissues. Furthermore, the paclitaxel group’s distortion product otoacoustic emission values were significantly lower than the other groups. Improvements in the damage produced by paclitaxel in various biochemical and functional parameters were observed in the Farnesene+Paclitaxel group.
Conclusion: The study findings imply that farnesene, a natural antioxidant, reduced paclitaxel-induced hearing loss in rats, and a combination of farnesene and paclitaxel therapy may have protected from paclitaxel-induced ototoxicity for future clinical use.
Amaç: Bu çalışmanın amacı, güçlü serbest radikal süpürücü ve antioksidan özelliklere sahip farnesenin paklitaksel kaynaklı ototoksisite üzerindeki etkilerini biyokimyasal ve fonksiyonel yönden araştırmaktır.
Gereç ve Yöntem: On sekiz erkek Wistar albino sıçan, altı sıçandan oluşan üç gruba rastgele ayrıldı. Araştırma boyunca kontrol grubuna paklitaksel veya farnesen verilmedi. Paklitaksel grubuna, 5mg/kg paklitaksel intraperitoneal olarak dört kez (1., 7., 14. ve 21. günlerde) verildi. Farnesen + paklitaksel grubuna, önce 5 mg/kg paklitaksel, 30 dakika sonra 50 mg/kg farnesen intraperitoneal olarak 4 kez (1., 7., 14. ve 21. günlerde) verildi. 0. ve 21. günlerde tüm sıçanların otoakustik emisyon ölçümü yapıldı. Daha sonra hayvanlar sakrifiye edildi ve biyokimyasal testler için kokleaları çıkarıldı.
Bulgular: Paklitaksel, önemli ölçüde malondialdehit seviyelerini yükselterek ve glutatyon seviyelerini düşürerek kokleada oksidatif strese neden oldu. Ayrıca paklitaksel grubunun distorsiyon ürünü otoakustik emisyon değerleri diğer gruplara göre anlamlı derecede düşüktü. Farnesen+paklitaksel grubunda ise paklitakselin çeşitli biyokimyasal ve fonksiyonel parametrelerde oluşturduğu hasarda iyileşmeler gözlendi.
Sonuç: Çalışma sonuçları doğal bir antioksidan olan farnesen’in sıçanlarda paklitaksel kaynaklı işitme kaybını azalttığını, farnesen ve paklitaksel kombinasyonunun gelecekte klinik kullanım için paklitaksel kaynaklı ototoksisiteden koruyabileceğini göstermektedir.
Purpose: Paclitaxel, is one of the most commonly used chemotherapeutic, causes neuron damage with some serious side effects such as neutropenia and peripheral neuropathy. In current study, we used ...phloretin and phloridzin to investigate their neuroprotective effects on paclitaxel-induced neuronal damage.
Materials and Methods: The neuroprotective effects of phloretin and phloridzin has been analyzed on cell culture of primary neuron cells and evaluated by testing cell viability, total oxidant and total antioxidant capacities and expression of caspase-3, caspase-9 and TNF-α. Paclitaxel administration caused cell death and significant increase of total oxidant levels and activation of apoptotic genes such as caspase-3, caspase-9 and TNF-α.
Results: Phloretin and phloridzin treatments at micromolar concentrations reduced paclitaxel-induced cell death by increasing total antioxidant levels. Also these two flavonoids protect neuron cells from apoptosis by decreasing caspase-3, caspase-9 and TNF-α gene expression. For this reason, these molecules may recover the oxidative damage, and restore normal cellular conditions.
Conclusion: This study shows the promising neuroprotective ability of the phloretin and phloridzin able to protect neuron cells from injury induced by paclitaxel, actively increasing antioxidant capacity, normalizing oxidant levels and consequently avoiding cell death.
Amaç: Kemoterapide sıklıkla kullanılan paklitaksel, nötropeni ve periferik nöropati gibi bazı ciddi yan etkilerle nöron hasarına neden olur. Biz bu çalışmada, floretin ve floridzin’ in paklitaksel kaynaklı nöronal hasar üzerindeki nöroprotektif etkilerini araştırdık.
Gereç ve Yöntem: Floretin ve floridzin’ in nöroprotektif etkileri primer nöron hücreleri üzerindeki etkileri, hücre canlılığı, total oksidan ve antioksidan kapasiteleri ve kaspaz-3, kaspaz-9 ve TNF-α ekspresyonu test edilerek değerlendirilmiştir.
Bulgular: Paklitaksel uygulaması hücre ölümüne, toplam oksidan seviyelerinin önemli ölçüde artmasına ve kaspaz-3, kaspaz-9 ve TNF-α gibi apoptotik genlerin aktivasyonuna neden oldu. Mikromolar konsantrasyonlardaki floretin ve floridzin tedavileri, toplam antioksidan seviyelerini artırarak paklitaksel kaynaklı hücre ölümünü azalttı. Ayrıca bu iki flavonoid, kaspaz-3, kaspaz-9 ve TNF-α gen ekspresyonlarını azaltarak nöron hücrelerini apoptozdan korudu. Bu nedenle, bu moleküller oksidatif hasardan geri kazanımı indükleyebilir ve normal hücresel koşulları düzenleyebilir.
Sonuç: Bu çalışma, floretin ve floridzin’ in nöron hücrelerini paklitaksel kaynaklı hücre hasarından koruyabilen, antioksidan kapasitesini aktif olarak arttıran, oksidan seviyelerini normalleştiren ve sonuç olarak hücre ölümünü önlemede umut verici nöroprotektif potansiyelini göstermektedir.
Sıçanlarda paklitaksel (PTX) kaynaklı akciğer hasarına karşı misoprostol’ün (MP) koruyucu etkilerinin incelendiği bu çalışmada, yirmi bir adet dişi Sprague-Dawley cinsi sıçan kullanıldı. Bu ...hayvanlardan rastgele bir seçimle Kontrol, PTX ve PTX + MP olmak üzere 3 grup (n=7) oluşturuldu. Kontrol grubuna 1 mL %0,9 NaCl intraperitoneal (i.p.) ve 1 mL %0,9 NaCl oral yolla 6 gün boyunca verildi. PTX ve PTX + MP gruplarına çalışmanın 0., 2., 4. ve 6. günlerinde her sıçana 2 mg/kg PTX i.p. olarak verildi. PTX + MP grubuna ayrıca 6 gün süreyle 0,2 mg/kg/gün MP oral olarak verildi. Doku numuneleri sıçanlardan anestezi altında alındıktan sonra bu numunelerde biyokimyasal ve histopatolojik analizler yapıldı. Yapılan analizlerde PTX grubu sıçanlarda akciğer dokusundaki süperoksit dismutaz (SOD) ve katalaz (CAT) aktiviteleri ile glutatyon (GSH) düzeyinin azaldığı, malondialdehit (MDA) düzeyinin ise yükseldiği belirlendi. Yapılan histopatolojik incelemelerde ise, PTX grubu sıçanlarda alveol yapısında düzensizlik ve kalınlaşma, perivasküler ödem ve perivasküler alanda inflamatuar hücre infiltrasyonu gibi histopatolojik değişikliklerin şekillendiği tespit edildi. PTX + MP grubunda ise, PTX grubunda tespit edilen patolojik değişikliklerin büyük oranda önlendiği görüldü. Elde edilen bu sonuçlar; PTX’in neden olduğu akciğer hasarının önlenmesinde MP’nin etkili olduğunu göstermekte olup, kanser tedavisinde bu iki ilacın birlikte kullanılmasının faydalı olacağını düşündürmektedir.
The effects of drugs used in cancer treatment are not only specific to cancer cells but also negatively affect healthy cells. This study, it was aimed to investigate the protective effects of ...silymarin (SLY), which stands out with its antioxidant effects, against the possible harmful effects of paclitaxel (PAX), an anticancer drug, on kidney tissue. A total of 28 Sprague-Dawley female rats were randomly selected into four groups (n=7): Control, PAX, SLY, and PAX + SLY. PAX was administered 2 mg/kg to the PAX group by intraperitoneally (i.p.); SLY was administered 100 mg/kg to the SLY group by oral gavage. Also, The PAX + SLY group was administered the same dose and route of PAX and SLY as the previous groups. In the biochemical analyzes performed in blood and kidney tissues taken from animals at the end of the experimental procedures, it was determined that PAX increased oxidative stress in kidney tissue and creatinine (Cr) and blood urea nitrogen (BUN) levels in serum. In the histopathological examinations of the kidney tissue, it was observed that PAX caused pathological changes such as renal corpuscle atrophy, damage to the brush border, vacuolar degeneration, and desquamation. The administration of SLY, a pharmacological agent with anti-inflammatory, anti-apoptotic, and antioxidant effects, largely prevented these pathological changes that occurred as a result of PAX use. The results obtained in the current study showed that SLY can be used as a protective agent against harmful effects on kidney tissue in treatments with PAX.
Bovine serum albumin (BSA) nanoparticles loaded with paclitaxel (PTX) were prepared using a desolvation technique. A 32 full factorial design (FFD) was employed to formulate nanoparticles. ...Nanoparticles were characterized for particle size by photon correlation spectroscopy and surface morphology by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Encapsulation efficiency, zeta potential and particle yield were also determined. Response surface linear modelling (RSLM) was used to predict the optimal formulation. Various models were applied to determine the release mechanism from PTX nanoparticles. The effect of drug-polymer ratio on the release profile of formulations was observed and was applied to determine the suitability of the predicted optimal formulation. A preliminary study to determine the feasibility of targeting the prepared nanoparticles to brain was also carried out using mice as in vivo models.
Opisana je priprava albuminskih nanočestica s paklitakselom (PTX) metodom desolvatacije. Za pripravu je korišten goveđi serumski albumin (BSA) i 32 potpuni faktorijalni dizajn (FFD). Pomoću fotonske korelacijske spektroskopije određena je veličina čestica, dok je površina čestica proučavana pretražnom elektronskom mikroskopijom (SEM) i transmisijskom elektronskom mikroskopijom (TEM). Nadalje, određena je učinkovitost kapsuliranja, zeta potencijal i iskorištenje. Linearno modeliranje odzivnih površina (RSLM) upotrebljeno je za predviđanje optimalne formulacije. Različiti modeli primijenjeni su za određivanje mehanizma oslobađanja iz PTX nanočestica. Proučavan je utjecaj omjera lijeka i polimera na profil oslobađanja i njegova upotrebljivost za predviđanje optimalne formulacije. Mogućnost ciljane isporuke u mozak preliminarno je ispitana in vivo na miševima.
İnfiltratif duktal karsinomu tanısı olan 46 yaşındaki bir kadın hastanın paklitaksel ile tedavisinin on ikinci haftasında tırnak toksisitesi gelişti. Paklitaksel taksan ailesinden bir kemoterapötik ...ajandır. Taksan grubu kemoterapötik ajanların tırnak değişiklikleri de dahil olmak üzere çeşitli kutanöz yan etkileri bildirilmiştir. Subungual kanamalar da paklitaksel kullanımı sonrasında gelişebilir
A 46-year-old woman with infiltrating ductal carcinoma of the breast cancer developed nail toxicity while she was being treated with paclitaxel for twelve weeks. Paclitaxel is a chemotherapeutic agent of the taxane family. Various cutaneous side effects, including nail changes, have been associated with taxane chemotherapeutic agents. The subungual haemorrhages could be developed following to paclitaxel usage
U zdravstvenih radnika koji pripremaju ili primjenjuju citotoksične lijekove zdravstveni rizici zbog izloženosti su realni, čak i pri dozama nižima od onih koje se primjenjuju u bolesnika jer, ...načelno, nijedna doza nije neškodljiva za zdravlje. Najčešći i najproblematičniji put izlaganja jest koža, napose zato što radne površine gdjekad ostanu kontaminirane i nakon njihova čišćenja. Cilj ovoga preliminarnog istraživanja bio je pokazati koliko je važno osmisliti djelotvoran protokol za dekontaminaciju na temelju pokazatelja kontaminacije radnih površina jedinice za pripremu lijekova, jedinice za njihovu primjenu te bolesničkoga zahoda onkološke ambulante trima najčešćim citotoksičnim onkološkim lijekovima: ciklofosfamidom, 5-fluoroacilom i paklitakselom. Uzorke smo prikupljali prije rada s lijekovima te tri sata od početka rada s njima te ih analizirali tekućinskom kromatografijom s detektorom s nizom dioda (engl. high performance liquid chromatography with diode array detection, krat. HPLC-DAD). Od 29 uzoraka prikupljenih prije rada s lijekovima, 23 su bila kontaminirana, od kojih pet s više lijekova. Od 30 uzoraka prikupljenih tri sata nakon početka rada s lijekovima, njih 25 bilo je kontaminirano, od kojih osam s više lijekova. Kontaminacija površina prije i nakon početka rada s lijekovima nije bila značajno različita, što upozorava na raširenu kontaminaciju i nedjelotvorno čišćenje. Stoga bi trebalo revidirati postojeći protokol čišćenja i rukovanja lijekovima te svesti kontaminaciju na najmanju moguću mjeru.
Provider: - Institution: - Data provided by Europeana Collections- Multi-drug resistance (MDR) is a major obstacle to successful cancer treatment. The efficacy of paclitaxel (PTX) is often limited by ...appearance of drug resistance. The aim of this study was to explore molecular and phenotypic alterations during development of MDR induced by PTX in human colon carcinoma (DLD1) and glioblastoma (U87) cell lines. We also tested the usefulness of developed MDR models in the evaluation of four anti-cancer agents. Continuous treatment with PTX led to the development of MDR in both tested cancer cell lines that became resistant to structurally and functionally unrelated chemotherapeutics. After confirmation of the cross-resistance in newly established DLD1-TxR and U87-TxR, we analyzed the mRNA expression of membrane transporters involved in MDR. The cells had increased levels of mdr1 gene expression, while mrp1 was decreased. Over-expression of P-glycoprotein (P-gp), coded by mdr1, was observed in both MDR cancer cell lines. Flow cytometry analyzes showed that the accumulation of P-gp substrates (rhodamine 123 and doxorubicin) in DLD1-TxR and U87-TxR was significantly lower compared to DLD1 and U87, respectively. The significant depletion of gst-π gene expression and glutathione (GSH) concentration was observed in U87-TxR. Vascular Endothelial Growth Factor (VEGF) secretion was inhibited by single PTX treatment of colon cancer and in continuous treatment of glioblastoma cell lines. The analysis of cell cycle kinetics revealed extensive cell death in colon cancer cells that were accumulated in subG0 phase after PTX treatment, while glioblastoma cells died through interphase (G1, S or G2). The MDR cancer cell lines acquired novel structural or numerical chromosomal aberrations. Polyploidy reduction was observed after development of MDR in U87-TxR. Losses of 6q in both resistant cancer cell lines and inactivation of p53 in U87-TxR and PTEN in DLD1-TxR were also revealed. We evaluated the anti-cancer activities and MDR reversal potential of the Akt inhibitor (GSK690693), the Ras inhibitor (Tipifarnib) and two P-gp inhibitors (jatrophane diterpenoids Euphodendrophane H-Euph H and Euphodendrophane S -Euph S). Their effects vary due to the cell-type differences, existence of MDR phenotype or tumor suppressors’ alterations. Tipifarnib, Euph H and S, significantly sensitized MDR cancer cells to PTX. In conclusion, continuous PTX treatment caused the over-expression of P-gp and acquisition of MDR in colon cancer and glioblastoma cell lines. MDR cancer cells obtained new molecular and cytogenetic characteristics, while some mechanisms of MDR and tumor progression such as GSH detoxification system and VEGF secretion were suppressed. The results implicate the PTX treatment as an important clinical tool for colon carcinoma and glioblastoma treatment even in the presence of MDR. Despite limitations discussed in literature due to the usefulness of MDR in vitro models, further examinations of changes provoked by artificially developed MDR are still emerging. Therefore, our MDR cancer cell lines present valuable tool for pre-clinical evaluation of new anti-cancer agents.- Glavni uzrok neuspeha hemioterapije u lečenju kancera je pojava višestruke (engl. „multi-drug“) rezistencije (MDR). Efikasnost paklitaksela (PTX) je često ograničena pojavom rezistencije. Cilj ove doktorske disertacije je bio ispitivanje molekularnih i fenotipskih promena u toku razvoja MDR-a indukovanih PTX-om kod ćelijskih linija humanog karcinoma debelog creva (DLD1) i glioblastoma (U87). Takođe je testirana upotrebljivost dobijenih MDR modela u evaluaciji četiri anti-kancer agensa. Kontinuirani tretman PTX-om doveo je do razvoja MDR-a kod obe ispitivane ćelijske linije koje su postale rezistentne na strukturno i funkcionalno različite hemioterapeutike. Nakon potvrde prisustva ukrštene rezistencije kod novouspostavljenih ćelijskih linija DLD1-TxR i U87-TxR, analizirana je ekspresija membranskih trasportera uključenih u razvoj MDR-a na nivou iRNK. Ćelije su imale povišen nivo ekspresije mdr1 gena i smanjen nivo ekspresije mrp1 gena. Prekomerna ekspresija P-glikoproteina (P-gp), koji kodira mdr1 gen, je uočena kod obe MDR ćelijske linije. Analiza na protočnom citofluorimetru je pokazala da je akumulacija Pgp supstrata (rodamina 123 i doksorubicina) kod DLD1-TxR i U87-TxR ćelija značajno manja u poređenju sa odgovarajućim parentalnim ćelijama, DLD1 i U87. Značajno smanjenje ekspresije gst-π gena i koncentracije glutationa (GSH) je uočeno kod U87- TxR ćelija. Sekrecija vaskularnog endotelijalnog faktora rasta (VEGF) je inhibirana u jednokratnom tretmanu kod ćelijskih linija karcinoma debelog creva i u kontinuiranom tretmanu kod ćelijske linije glioblastoma. Analiza ćelijskog ciklusa je pokazala da je jednokratni tretman PTX-om kod ćelijskih linija humanog karcinoma debelog creva praćen porastom subG0 faze, odnosno povećanjem procenta mrtvih ćelija, dok je kod ćelija glioblastoma došlo do umiranja tokom interfaze (G1, S ili G2). MDR tumorske ćelijske linije su stekle nove strukturne i numerićke hromozomske aberacije. Sticanje MDR fenotipa kod U87-TxR ćelija je praćeno smanjenem jednog nivoa ploidije. Takođe je uočen gubitak hromozomskog regiona 6q kod obe rezistentne ćelijske linije, kao i inaktivacija p53 tumor spresor gena kod U87-TxR ćelija i PTEN tumor supresor gena kod DLD1-TxR ćelija. Dalje je analizirana anti-kancer aktivnost i potencijal za reverziju MDR-a Akt inhibitora (GSK690693), Ras inhibitora (Tipifarnib) i dva inhibitora P-gp-a (jatrofanski diterpenoidi Eufodendrofana H-Euph H i Eufodendrofane S -Euph S). Njihova efikasnost varira u zavisnosti od razlika u tipu ćelija, postojanja MDR fenotipa ili promena u tumor supresorima. Tipifarnib, Euph H i S su značajno povećali senzitivnost MDR ćelijskih linija na PTX. Kontinuirani tretman PTX-om dovodi do prekomerne ekspresije P-gp-a i sticanja MDR fenotoipa kod ćelijskih linija humanog karcinoma debelog creva i glioblastoma. MDR ćelije su stekle nove molekularne i citogenetske karakteristike, dok su suprimirani neki mehanizmi MDR-a i progresije tumora kao što su GSH detoksifikacioni sistem i sekrecija VEGF-a. Ovi rezultati ukazuju da tretman PTX-om može imati veliki značaj u terapiji karcinoma debelog creva i glioblastoma, čak i u prisustvu MDR-a. Uprkos ograničenjima o kojima se govori u literaturi u vezi upotrebljivosti MDR in vitro modela, ispitivanja promena izazvanih veštačkim razvojem MDR-a su i dalje neophodna i aktuelana. Zbog toga, ove MDR tumorske ćelijske linije predstavljaju značajan eksperimentalni model za testiranje novih antikancer agenasa.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana
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