Hasil Pencarian  ::  Simpan CSV :: Kembali

Abstrak :
Doksorubisin adalah kemoterapi yang efektif namun dapat menyebabkan toksisitas jantung, salah satunya dengan menginduksi disfungsi mitokondria. Penemuan atau pengembangan agen kardioproteksi dari bahan alam merupakan salah satu peluang potensial. Penelitian ini dilakukan untuk mengetahui efek kardioproteksi ekstrak air daun Moringa oleifera (MO) dalam mengurangi toksisitas doksorubisin dan mekanismenya melalui regulasi biogenesis mitokondria. Sebanyak 22 ekor tikus Sprague-Dawley jantan dirandomisasi ke dalam 4 kelompok. Kelompok pertama adalah kontrol normal yang diinjeksi NaCl. Ketiga kelompok lainnya diberikan injeksi doksorubisin 4 mg/kg BB/minggu (Dox) atau doksorubisin 4 mg/kg BB/minggu dan MO-200 mg/kg BB/hari (Dox+MO-200) atau doksorubisin 4 mg/kg BB/minggu dan MO-400 mg/kg BB/hari (Dox+MO-400), selama 4 minggu. Pada akhir minggu keempat, tikus didekapitasi, lalu darah dan jantung diambil untuk dianalisis. Kelompok Dox menunjukkan kerusakan histopatologi jantung sedang, peningkatan aktivitas LDH, CK-MB, kadar 8-OH-dG dan ekspresi mRNA caspase-3. Selain itu, diamati perubahan regulasi biogenesis mitokondria yang ditandai oleh penurunan ekspresi mRNA PGC-1α, TFAM, SOD2, dan copy number mtDNA pada kelompok Dox. Pemberian MO memperbaiki berbagai efek akibat doksorubisin tersebut, kecuali kadar 8-OH-dG. Ekstrak Moringa oleifera dosis 200 mg/kg BB dan 400 mg/kg BB menunjukkan tendensi dalam mengurangi toksisitas doksorubisin pada tikus melalui regulasi biogenesis mitokondria. ......Doxorubicin is an effective chemotherapeutic agent but can cause cardiac toxicity, one of which is by inducing mitochondrial dysfunction. Developing cardioprotective agents from natural resources is a potential opportunity. This study was conducted to determine the cardioprotective effect of Moringa oleifera (MO) leaves aqueous extract against doxorubicin-induced toxicity and its possible mechanism by regulating mitochondrial biogenesis. Twenty-two male Sprague-Dawley rats were randomized into 4 groups. The first group was a normal control, received NaCl injections. The other three groups were given injections of doxorubicin 4 mg/kgBW/week (Dox) or doxorubicin 4 mg/kg BW/week and MO-200 mg/kg BW/day (Dox+MO-200) or doxorubicin 4 mg/kg BW/week and MO-400 mg/kg BW/day (Dox+MO-400), for 4 weeks. After four weeks, rats were decapitated, then blood and heart were analyzed. Dox group showed moderate cardiac histopathological alterations, increased LDH, CK-MB activity, 8-OH-dG levels, and caspase-3 mRNA expression. In addition, changes in mitochondrial biogenesis regulation were observed, which were decreased mRNA expressions of PGC-1α, TFAM, SOD2, and mtDNA copy number in the Dox group. Administration of MO ameliorated these effects, except for 8-OH-dG levels. Moringa oleifera extract doses of 200 mg/kg BW and 400 mg/kg BW showed a tendency to reduce doxorubicin toxicity in rats by regulating mitochondrial biogenesis.

Abstrak :
Doksorubisin (DOX) merupakan agen kemoterapi antrasiklin yang bekerja dengan memperlambat atau menghentikan pertumbuhan sel kanker. Namun, penggunaan DOX memiliki efek toksik pada sel normal serta efek samping kardiotoksisitas. Penelitian ini bertujuan membuat sistem penghantaran DOX dengan SPION-PAMAM-HA, mengkarakterisasi, dan mengevaluasi konjugat superparamagnetic iron oxyde nanoparticle-poliamidoamin G4-asam hialuronat-doksorubisin (SPION-PAMAM-HA-DOX). Hasil karakterisasi SPION-TC menunjukkan kristal magnetit dengan ukuran 2,79 nm. Konjugat SPION-PAMAM-HA-DOX menunjukkan diameter rata-rata 292,57 ± 4,86 nm, indeks polidispersitas 0,216 ± 0,002 nm, dan nilai zeta potensial -53,37 ± 3,68 mV. Studi pelepasan pada 10 jam dapat terlihat bahwa sebanyak 99% doksorubisin dilepaskan di lingkungan pH 5, sementara kurang dari 10% doksorubisin dilepaskan di lingkungan pH 7,4. Uji sitoksisitas menunjukkan konjugat SPION-PAMAM-HA-DOX memiliki efek toksik pada sel HeLa dan sel Vero dengan IC50 2,54 ± 0,27 µM pada sel HeLa dan CC50 2,18 ± 0,019 µM pada sel Vero serta memiliki nilai SI SPION-PAMAM-HA-DOX lebih besar dibandingkan SI DOX yang menandakan bahwa konjugat SPION-PAMAM-HA-DOX masih aman digunakan dan masih memiliki efek anti kanker. ......Doxorubicin (DOX) is an anthracycline chemotherapy agent that works by slowing or stopping the growth of cancer cells. However, DOX has a toxic effect on normal cells as well as a side effect of cardiotoxicity. This study aims to develop a DOX delivery system with SPION-PAMAM-HA, characterize, and evaluate of superparamagnetic iron oxide nanoparticle-polyamidoamine G4-hyaluronic aciddoxorubicin (SPION-PAMAM-HA-DOX). Superparamagnetic iron oxide nanoparticle (SPION) could be used as diagnostic agent, polyamidoamine G4 (PAMAM) was used as carrier and hyaluronic acid (HA) was used as active targeting moiety. SPION were prepared by co-precipitation method, then SPION-PAMAM-HA-DOX were produced by conjugation of SPION with PAMAM-HA and DOX. SPION-PAMAM-HA-DOX were characterized by particle size analyzer (PSA), UV-Vis spectrophotometry, fourier transform infrared spectroscopy (FTIR), fluorescence spectrophotometry, and transmission electron microscopy (TEM). The release study was conducted by using pH 5 and pH 7.4. Cytotoxicity study was conducted on HeLa cells and Vero cells by using MTT [3-(4,5-Dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] assay. The characterization results of SPION-TC showed magnetite crystals with a size of 2.79 nm. The mean particle size, polydispersity index, and zeta potential of SPION-PAMAM-HADOX were 57 ± 4.86 nm, 0.216 ± 0.002 nm, and -53.37 ± 3.68 mV. The release study at 10 hours showed that 99% of DOX was released in pH 5, while less than 10% DOX was released in pH 7.4. The cytotoxicity study showed that SPION-PAMAM-HA-DOX has toxicity effect on HeLa cells and Vero cells with IC50 2,54 ± 0,27 µM on HeLa cells, CC50 2,18 ± 0,019 µM on Vero cells sel Vero, and SI value of SPION-PAMAM-HA-DOX greater than SI DOX which indicates that SPION-PAMAM-HA-DOX conjugate is still safe to use and has anti-cancer effects

Abstrak :
[ABSTRAK
Latar belakang. Doksorubisin (DOK), suatu antibiotika antrasiklin, digunakan secara luas untuk terapi antikanker, namun penggunaan DOK dapat menimbulkan efek samping, salah satunya gangguan kognitif. Penggunaan kemoterapi berbasis DOK menunjukkan hingga 76% pasien mengalami penurunan kognitif. Kerusakan otak akibat penggunaan DOK disebabkan oleh peningkatan TNF-α di otak melalui uptake reseptor di sawar darah otak dan peningkatan produksi melalui aktivasi NF-κB. Peningkatan TNF-α lebih lanjut dapat menyebabkan inflamasi kronis yang dapat menimbulkan kematian sel saraf atau penyakit degenerasi saraf. Mangiferin (MAG) merupakan salah satu senyawa neuroprotektif, akan tetapi efek terhadap kerusakan otak akibat pemberian DOK belum diketahui. Penelitian ini bertujuan untuk mengetahui efek MAG terhadap kerusakan otak yang ditimbulkan oleh pemberian DOK. Metode. Penelitian dilakukan terhadap tikus Sprague-Dawley yang diinduksi menggunakan DOK dengan dosis total 15 mg/kgBB secara i.p mulai minggu kedua. Pemberian MAG dilakukan secara p.o dengan dosis 30 dan 60 mg/kgBB selama 7 minggu. Parameter yang diamati adalah fungsi kognitif, inflamasi (TNF- α, NF-κB dan iNOS), stres oksidatif (SOD dan MDA) dan histopatologi dengan pewarnaan HE. Hasil. Pemberian DOK menyebabkan gangguan kognitif yang ditandai dengan penurunan penggiliran labirin Y dan penurunan indeks diskriminasi pada pengenalan obyek baru, disertai peningkatan parameter inflamasi yaitu ekspresi TNF-α, NF-κB dan iNOS. Pemberian MAG bersama DOK menyebabkan peningkatan fungsi kognitif, penurunan inflamasi dan penurunan stres oksidatif serta histopatologi dewan pewarna HE. Kesimpulan. Berdasarkan hasil pemeriksaan parameter pada penelitian mengindikasikan bahwa mangiferin memiliki efek neuroproteksi terhadap pemberian DOK.

---

ABSTRACT
Introduction. Doxorubicin (DOK), an anthracycline antibiotic, is widely used for anticancer therapy, but the use of DOK causing side effects, one of them is cognitive impairment. Up to 76% of patients experienced cognitive decline caused by DOK-based chemotherapy. Brain damage due to the use of DOK lead by an increase in TNF-α in the brain through the receptors uptake in the blood brain barrier and increasing production through activation of NF-κB. Increased TNF-α can further lead to chronic inflammation which can lead nerve cells death or nerve degeneration diseases. Mangiferin (MAG) is one of the neuroprotective compound, but the effect on brain damage induced by DOK is still unknown. This study aims to determine the effect of MAG on brain damage induced by DOK. Methods. Research carried out on Sprague-Dawley rats induced by DOK i.p with total dose 15 mg/kg that divided into 6 dose and given within 2 weeks, started from 2nd week. The rats was administrated by MAG p.o with dose 30 and 60 mg/kg daily for 7 weeks. Parameters measured were cognitive function, inflammatory parameters (TNF-α, NF-κB and iNOS), oxidative stress parameters (SOD and MDA) and histopatology using HE staining. Results. DOK cause cognitive disorders that characterized by decreased Y maze alteration and discrimination index in new object recognition, and accompanied by increasing inflammatory parameters that showed in increasing TNF-α, NF-κB and iNOS expressions. Coadministration MAG with DOK led an increasing on cognitive function, reducing the inflammation and oxidative stress. Conclusion. Based on the results of the study, MAG indicated has a neuroprotective effect on brain damage induced by DOK;Introduction. Doxorubicin (DOK), an anthracycline antibiotic, is widely used for anticancer therapy, but the use of DOK causing side effects, one of them is cognitive impairment. Up to 76% of patients experienced cognitive decline caused by DOK-based chemotherapy. Brain damage due to the use of DOK lead by an increase in TNF-α in the brain through the receptors uptake in the blood brain barrier and increasing production through activation of NF-κB. Increased TNF-α can further lead to chronic inflammation which can lead nerve cells death or nerve degeneration diseases. Mangiferin (MAG) is one of the neuroprotective compound, but the effect on brain damage induced by DOK is still unknown. This study aims to determine the effect of MAG on brain damage induced by DOK. Methods. Research carried out on Sprague-Dawley rats induced by DOK i.p with total dose 15 mg/kg that divided into 6 dose and given within 2 weeks, started from 2nd week. The rats was administrated by MAG p.o with dose 30 and 60 mg/kg daily for 7 weeks. Parameters measured were cognitive function, inflammatory parameters (TNF-α, NF-κB and iNOS), oxidative stress parameters (SOD and MDA) and histopatology using HE staining. Results. DOK cause cognitive disorders that characterized by decreased Y maze alteration and discrimination index in new object recognition, and accompanied by increasing inflammatory parameters that showed in increasing TNF-α, NF-κB and iNOS expressions. Coadministration MAG with DOK led an increasing on cognitive function, reducing the inflammation and oxidative stress. Conclusion. Based on the results of the study, MAG indicated has a neuroprotective effect on brain damage induced by DOK, Introduction. Doxorubicin (DOK), an anthracycline antibiotic, is widely used for anticancer therapy, but the use of DOK causing side effects, one of them is cognitive impairment. Up to 76% of patients experienced cognitive decline caused by DOK-based chemotherapy. Brain damage due to the use of DOK lead by an increase in TNF-α in the brain through the receptors uptake in the blood brain barrier and increasing production through activation of NF-κB. Increased TNF-α can further lead to chronic inflammation which can lead nerve cells death or nerve degeneration diseases. Mangiferin (MAG) is one of the neuroprotective compound, but the effect on brain damage induced by DOK is still unknown. This study aims to determine the effect of MAG on brain damage induced by DOK. Methods. Research carried out on Sprague-Dawley rats induced by DOK i.p with total dose 15 mg/kg that divided into 6 dose and given within 2 weeks, started from 2nd week. The rats was administrated by MAG p.o with dose 30 and 60 mg/kg daily for 7 weeks. Parameters measured were cognitive function, inflammatory parameters (TNF-α, NF-κB and iNOS), oxidative stress parameters (SOD and MDA) and histopatology using HE staining. Results. DOK cause cognitive disorders that characterized by decreased Y maze alteration and discrimination index in new object recognition, and accompanied by increasing inflammatory parameters that showed in increasing TNF-α, NF-κB and iNOS expressions. Coadministration MAG with DOK led an increasing on cognitive function, reducing the inflammation and oxidative stress. Conclusion. Based on the results of the study, MAG indicated has a neuroprotective effect on brain damage induced by DOK]

Abstrak :
Latar belakang: Terapi farmakologi kanker payudara triple negative (KPTN) terbatas pada obat sitostatika seperti doksorubisin. Namun, resistensi doksorubisin sulit dihindari. Salah satu jalur pensinyalan yang penting pada resistensi KPTN terhadap doksorubisn adalah TGF-β. TMEPAI (transmembran prostat androgen-induced protein), regulator negatif sekaligus gen target pada jalur TGF- β diduga merupakan salah satu kunci dalam resistensi KPTN terhadap doksorubisin. Metode: Teknik CRISPR-Cas9 digunakan untuk menghilangkan TMEPAI pada galur sel KPTN, BT549. Sel diberi perlakuan TGF-β 2 ng / mL dan doksorubisin selama 24 jam. Pengukuran konsentrasi sitotoksik doksorubisin pada 50% populasi sel (CC50) dilakukan terhadap sel KPTN wildtype (WT) dan knock out (KO). Setelah itu, sel dipanen dan dihitung. Rantai Polimerase Waktu Nyata Reaction (RT-PCR) dan western blot (WB) digunakan untuk mengukur tingkat ekspresi penande proliferasi, apoptosis, EMT, dan transporter. Selain itu, SMAD yang terfosforilasi dan aktivitas PI3K / Akt juga belajar. Hasil: Galur sel yang tidak memiliki TMEPAI (KO) berhasil diperoleh dari sel KPTN, BT549. Sel WT terbukti lebih resistan terhadap doksorubisin dibandingkan sel KO yang ditunjukkan dengan peningkatan CC50 dan Ki-67. TMEPAI menurunkan efek apoptosis doksorubisin dengan memodulasi ekspresi bcl-2 dan kaspase-3, namun tidak kaspase-9 dan bax. Efek TMEPAI mengurangi doksorubisin dengan menekan fosforilasi SMAD. Namun TMEPAI meningkatkan penghambatan PI3K / Akt oleh doksorubisin. TMEPAI juga meningkatkan EMT dan transporter efluks yang diinduksi oleh doksorubisin. Kesimpulan: TMEPAI terhadap pertarungan dalam resistensi sel KPTN doksorubisin melalui aktivasi jalur sinyal TGF-β non-canonical beserta protein dan gen targetnya. Background: Triple negative breast cancer (KPTN) pharmacological therapy limited to cytostatic drugs such as doxorubicin. However, doxorubicin resistance hard to avoid. One of the important signaling pathways of resistance KPTN against doxorubisn is TGF-β. TMEPAI (transmembrane prostate androgen-induced protein), a negative regulator as well as a target gene in the TGF- β is thought to be one of the keys in the resistance of KPTN to doxorubicin. Method: The CRISPR-Cas9 technique was used to remove TMEPAI on KPTN cell lines, BT549. Cells were treated with TGF-β 2 ng / mL and doxorubicin for 24 hours. Measurement of the cytotoxic concentration of doxorubicin at 50% cell population (CC50) was carried out against wildtype KPTN (WT) cells and knockout (KO). After that, cells are harvested and counted. Real Time Polymerase Chain Reaction (RT-PCR) and western blot (WB) were used to measure levels expression markers of proliferation, apoptosis, EMT, and transporters. Apart from that, SMAD the phosphorylated and PI3K / Akt activities also learn. Results: Cell lines that did not have TMEPAI (KO) were obtained from the cells KPTN, BT549. WT cells have been shown to be more resistant to doxorubicin compared to cell knockout shown with increased CC50 and Ki-67. TMEPAI decreases the apoptotic effect of doxorubicin by modulating expression bcl-2 and caspase-3, but not caspase-9 and bax. TMEPAI reducing effects doxorubicin by suppressing SMAD phosphorylation. However TMEPAI is improving PI3K / Akt inhibition by doxorubicin. TMEPAI also increases EMT and doxorubicin-induced efflux transporters. Conclusion: TMEPAI against the fight against KPTN cell resistance doxorubicin via activation of the non-canonical TGF-β signaling pathway along with proteins and its target genes.

Abstrak :
Kanker serviks merupakan salah satu jenis kanker dengan prevalensi dan penyebab kematian tertinggi di dunia. Salah satu metode pengobatan kanker serviks adalah kemoterapi dengan menggunakan doxorubicin. Doxorubicin merupakan salah satu senyawa obat kelas antrasiklin yang dapat menghambat kerja enzim Topoisomerase II. Topoisomerase II diketahui memiliki peranan dalam mempertahankan struktur kromosom. Namun, hingga saat ini pengaruh doxorubicin terhadap kromosom sel kanker belum diketahui. Perubahan struktur kromosom yang terdeteksi lebih cepat dapat menjadi pertimbangan dalam optimasi dosis doxorubicin pada kemoterapi kanker serviks. Penelitian ini bertujuan untuk mengetahui pengaruh pemberian doxorubicin terhadap jumlah, panjang, dan luas area kromosom sel HeLa menggunakan mikroskop cahaya. Kultur sel HeLa ditumbuhkan dan dipanen kromosomnya di atas coverslip. Kultur sel HeLa kemudian diberi perlakuan doxorubicin dengan konsentrasi 4 μg/mL selama 24 jam. Kromosom metafase sel HeLa kontrol dan perlakuan kemudian dipanen dan diwarnai dengan pewarna Giemsa untuk pengamatan dengan mikroskop cahaya. Hasil pengamatan kromosom sel HeLa kontrol menunjukkan jumlah kromosom 41—75 kromosom per sel, panjang kromosom sebesar 2—5 μm, dan luas area sebesar 4—15 μm2 per kromosom. Kromosom metafase tidak diperoleh dari sel yang diberi perlakuan doxorubicin. Hal tersebut kemungkinan disebabkan oleh pengaruh inhibisi doxorubicin terhadap aktivitas enzim Topoisomerase II sehingga terjadi kerusakan DNA yang memicu apoptosis sel. ......Cervical cancer is one of the cancers with the highest prevalence in the world. One of the treatments commonly used for cervical cancer is chemotherapy using doxorubicin. Doxorubicin is one of the compounds belong to the antracycline class which responsible for inhibiting the Topoisomerase II enzyme. Topoisomerase II has also been reported to be correlated with the maintenance of chromosome structure. Nevertheless, to date, the information about the effects of doxorubicin on chromosome structure has yet to be revealed. Alterations in chromosome structure which are detected more quickly can be a consideration in optimizing the dose of doxorubicin in cervical cancer chemotherapy. This study aimed to evaluate the effects of doxorubicin on the HeLa chromosome number, length, and area using a light microscope. HeLa cell was cultured and treated with 4 μg/mL doxorubicin for 24 hours. The cells were then harvested on the coverslips. Metaphase chromosomes of HeLa cells treated with doxorubicin and the control were stained with Giemsa and finally observed by using a light microscope. The results obtained from this study showed that the number, length, and area of the control chromosomes were 41—75 chromosomes per cell, 2—5 μm, and 4—15 μm2, respectively. Furthermore, the metaphase chromosome from the cells treated with doxorubicin could not be obtained. This result indicated that the doxorubicin treatment might inhibits the activity of the Topoisomerase II enzyme, causing DNA damage that triggers cell apoptosis.

Abstrak :
Demam neutropenia merupakan efek samping yang sering terjadi setelah kemoterapi. Demam neutropenia dapat menyebabkan penundaan dosis kemoterapi sehingga dapat mengurangi efektivitas terapi. Kejadian demam neutropenia paskakemoterapi dapat dicegah dengan pemberian Granulocyte-colony Stimulating Factor (G-CSF). Regimen kemoterapi yang digunakan dapat memengaruhi kejadian demam neutropenia. Selain itu, usia, stadium kanker, riwayat kemoterapi dan kadar hemoglobin sebelum kemoterapi merupakan faktor risiko demam neutropenia paskakemoterapi. Penelitian ini bertujuan untuk mengetahui perbandingan kejadian demam neutropenia regimen TAC (dosetaksel, doksorubisin, siklofosfamid) dengan profilaksis primer G-CSF dan regimen FAC (fluorourasil, doksorubisin, siklofosfamid) pada pasien kanker payudara di RSUP Dr. Hasan Sadikin Bandung periode Januari 2017-Juni 2019. Desain penelitian adalah cross sectional uji dua populasi. Jumlah sampel sebanyak 61 regimen TAC dan 102 regimen FAC. Kejadian demam neutropenia dianalisis menggunakan chi-square. Hasil penelitian menunjukkan kejadian demam neutropenia paskakemoterapi lebih banyak terjadi pada regimen TAC dengan profilaksis primer G-CSF dibandingkan dengan regimen FAC. Kejadian demam neutropenia 12 kali lebih banyak terjadi pada regimen TAC dengan GCSF dibanding regimen FAC. Usia, stadium kemoterapi, riwayat kemoterapi dan kadar hemoglobin sebelum kemoterapi secara statistik tidak signifikan memengaruhi kejadian demam neutropenia paskakemoterapi.

---

Febrile Neutropenia is a common side effect of chemotherapy. Febrile neutropenia can cause delayed chemo doses that can reduce the effectiveness of therapy. The incidence of febrile neutropenia can be prevented by administering Granulocyte-colony Stimulating Factor (G-CSF). The chemotherapy regimen can affect the incidence of febrile neutropenia. In addition, age, stage of cancer, history of chemotherapy and prechemotherapy hemoglobin level are risk factors for febrile neutropenia. This study aimed to compare the incidence of febrile neutropenia between TAC (docetaxel, doxorubicin, cyclophosphamide) regimen with G-CSF primary prophylaxis and FAC regimen (fluorouracil, doxorubicin, cyclophosphamide) in breast cancer patients at RSUP Dr. Hasan Sadikin Bandung period January 2017 - June 2019. The study design was cross sectional test of two populations. The sample consisted of 61 TAC regimen and 102 FAC regimen. The incidence of febrile neutropenia were analyzed using chi-square. The results showed that the incidence of post-chemotherapy febrile neutropenia is more common in TAC regimen with G-CSF primary prophylaxis than FAC regimen. The incidence of neutropenia is 12 times more common in TAC regimens with G-CSF than FAC regimen. Age, stage of chemotherapy, history of chemotherapy and pre-chemotherapy hemoglobin levels did not statistically significantly influence the incidence of febrile neutropenia.