Iin Kurnia
Center for Technology of Radiation Safety and Metrology, National Nuclear Energy Agency (BATAN), Indonesia

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KORELASI ANTARA MIB-1, AgNOR DAN APOPTOSIS CASPASE-3 DENGAN RESPONS KEMORADIOTERAPI PADA KANKER SERVIK Kurnia, Iin; Siregar, Budiningsih; Soetopo, Setiawan; Ramli, Irwan; Kurjana, Tjahya; ., Andriono; Tobing, Maringan DL; Suryawathi, Bethy; Tetriana, Devita
Jurnal Sains dan Teknologi Nuklir Indonesia Vol 14, No 1 (2013): Februari 2013
Publisher : BATAN

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Abstract

Salah satu cara pengobatankanker servik adalah dengan kemoradioterapi melalui pemberian radioterapi dan kemoterapisecara bersamaan pada kanker servik stadium lanjut lokal. Respons kemoradioterapidipengaruhi oleh faktor biologis yaitu kinetika sel yang terdiri dari proliferasi dan kematian sel.Pada penelitian ini dipelajari korelasi antara biomarker proliferasi sel kanker, yaitu AgNOR, MIB-1, dan ekspresi apoptosis jalur caspase-3 dengan respons kemoradioterapi pada kanker servik.Dua puluh satu sediaan mikroskopik jaringan kanker servik yang diambil dari biopsi pasiensebelum menerima tindakan kemoradioterapi diberi pewarnaan AgNOR, sedangkan deteksiMIB-1 dan apoptosis caspase-3 dilakukan dengan teknik immunohistokimia. Setelah selesaimenerima kemoradioterapi dilakukan pengamatan respons klinik dengan cara pelvic control.Hasil penelitian menunjukkan bahwa sebelum kemoradioterapi tidak ditemukan korelasi nilaiAgNOR, MIB-1 dengan apoptosis (p>0,05). Proliferasi sel yang diamati dengan AgNOR danMIB-1 sebelum kemoradioterapi tidak menunjukkan adanya korelasi dengan respons jaringankanker setelah kemoradioterapi, namun ekspresi apoptosis menunjukkan korelasi positifdengan respons kemoradioterapi. Indeks apoptosis caspase-3 yang diperoleh dapat dijadikanbahan pertimbangan pada penjadwalan kemoradioterapi kanker servik.
Correlation Between Akt and p53 Protein Expression and Chemoradiotherapy Response in Cervical Cancer Patients KURNIA, IIN; SIREGAR, BUDININGSIH; SOETOPO, SETIAWAN; RAMLI, IRWAN; KURJANA, TJAHYA; ANDRIONO, .; TOBING, MARINGAN DIAPARI LUMBAN; SURYAWATHI, BETHY; KISNANTO, TEJA; TETRIANA, DEVITA
HAYATI Journal of Biosciences Vol 21, No 4 (2014): Desember 2014
Publisher : Bogor Agricultural University, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.4308/hjb.21.4.173-179

Abstract

Akt is a protein that is associated with cell proliferation and is expressed at high levels in cancer cells. Some research indicates it may play a role in increasing the resistance of cancer cells to chemotherapy treatment. P53 is a tumor suppressor protein that influences the cell cycle and apoptosis. The purpose of this study was to examine the relationship between the expression of Akt and p53 in cancerous tissue before chemoradiation treatment, and the clinical response to treatment of cervical cancer patients. Twenty microscopic tissue samples were taken from cervical cancer biopsies obtained from patients before cancer treatment. The tissue samples were stained with p53 and Akt antibodies via immunohistochemistry technique, to measure expression of both proteins. After completion of chemoradiotherapy, patients’ clinical response to treatment was determined using the pelvic control method. Our results revealed no correlation between expression of Akt and p53 index (P = 0.74) as well as between p53 Index and chemoradiotherapy clinical response (P=0.29). There was significant correlation between expression of Akt and cervical cancer chemoradiotherapy response (P = 0.03). There was no correlation found between p53 index and chemoradiotherapy clinical response (P = 0.29). High expression of Akt may related with high cell proliferation and resistance to chemoradiotherapy.
Studi Nilai AgNOR dan MIB-1 pada Kanker Payudara yang Ditangani dengan Operasi Kurnia, Iin; Soetrisno, Esti; Yulian, Erwin D.; Ramli, Irwan; Alatas, Zubaidah
Indonesian Journal of Clinical Pharmacy Vol 1, No 3 (2012)
Publisher : Indonesian Journal of Clinical Pharmacy

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Abstract

AgNOR dan MIB-1 adalah marker proliferasi sel kanker payudara yang berguna sebagai dasar pemberian radioterapi setelah operasi. Penetapan nilai AgNOR dan indeks MIB-1 dilakukan dengan teknik pewarnaan dan teknik pewarnaan imunohistokimia MIB-1 terhadap 25 sediaan mikroskopik jaringan kanker payudara dari penderita hasil operasi, dan dikelompokkan berdasarkan derajat diferensiasinya menjadi 3 kelompok sediaan berderajat diferensiasi baik (G1), 16 sediaan berderajat diferensiasi menengah (G2), dan 6 sediaan berderajat diferensiasi buruk (antara G2 dan G3). Hasil penelitian menunjukkan nilai AgNOR dan indeks MIB-1 cenderung meningkat seiring dengan meningkatnya derajat diferensiasi. Terdapat pula kecendrungan korelasi positif antara nilai AgNOR dan indeks MIB-1 (r =0,21) pada seluruh derajat diferensiasi, terdapat korelasi negatif antara AgNOR dan MIB-1 pada G1 (r=-0,97), korelasi positif pada G2 (r=0,36) serta korelasi positif antara G2 dan G3 (r=0,33). Korelasi positif antara AgNOR dan MIB-1 terkait dengan peningkatan fase G1, S dan G2 pada sel yang berproliferasi dan peningkatan jumlah sel yang mengalami mitosis. Korelasi negatif disebabkan oleh perbedaan proporsi antara sel yang berada pada fase G1, S dan G2 dengan yang sedang bermitosisKata kunci: Kanker payudara, AgNOR, MIB-1, operasi Study of AgNOR Value and MIB-1 in Breast CancerTreated With Surgery AbstractAgNOR and MIB-1 are marker for breast cancer cell proliferation and can be use as based for radiotherapytreatment after surgery. Value of AgNOR and MIB-1 index were determined using staining and immunohistochemistry staining method respectively from 25 of microscopic slides of breast cancer tissue patients with surgery, and grouped based on degree of differentiation, 3 slides were good degree (G1), 16 slides were medium degree (G2) and 6 slides were poor degree (between G2 and G3). The result shown that the value of AgNOR and MIB-1 index were tended to increase with the increased differentiation degree. There was a positive correlation between the value of AgNOR and index of MIB-1 in all group of differentiation degree (r = 0.21), there is a negative correlation between AgNOR and MIB-1 on G1 (r =-0,97), positive correlation in G2 (r = 0.36) as well as positive correlation between G2 and G3 (r = 0.33). The positive correlation between AgNOR and MIB-1 were associated to the increased of G1, S and G2 phase in the proliferation cell and an increase of cells undergoing mitosis. The negative correlation were caused by the different cell proportion in G1, S and G2 phase, and undergoing mitotis.Key words: Breast cancer, AgNOR, MIB-1, surgery
PENILAIAN EKSPRESI PROTEIN MDM2 DAN P53 SEBAGAI PREDIKTOR RESPON RADIOTERAPI PADA KANKER SERVIKS Rahayu, Kun Mardiwati; Siregar, Budiningsih; Kurnia, Iin
Bioma Vol 12 No 1 (2016): Bioma
Publisher : Biologi UNJ Press

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21009/Bioma12(1).1

Abstract

Cervical cancer is the second most common malignancy in Indonesia, and most of cases were already in advanced stage where radiotherapy is a tratement to given. Apoptosis is one of the markers for survival assessment of therapeutic response. In animal experiments MDM2 expression in various cell types to act as a survival factor by inhibiting the apoptotic function of p53 that is played by apoptosis can lead to malignant transformation and result in resistance to radiotherapy. Therefore, MDM2 is overexpressed due to alleged damage to p53 can also be used to assess the success of radiotherapy. This study aimed to assess the expression of MDM2 and p53 immunohistochemistry in cervical cancer and its relation to radiotherapy response. This study is a retrospective cross-sectional descriptive. The sample consisted of 23 cases of advanced cervical cancer were biopsied, 17 cases with complete response to radiation and 6 cases of partial radiation response. This study showed complete radiotherapy group MDM2 expression was found in 70.59% (12 cases) and p53 expression was found in 94.11% (16 cases), while the expression of MDM2, a partial response was found in 100% (6 cases), while the expression p53 66.67% (4 cases). MDM2 and p53 expression with SPSS 16 chi square test showed no association with response to radiotherapy in cervical cancer.
TINGKAT KEGANASAN KANKER SERVIKS PASIEN PRA-RADIASI MELALUI PEMERIKSAAN AgNORs, MIB-1 DAN Cas- 3 Kurnia, Iin; Bintari, Siti Harnina; Khaisuntaha, Mafaza
Biosaintifika: Journal of Biology & Biology Education Vol 4, No 2 (2012): September 2012
Publisher : Department of Biology, Faculty of Mathematics and Sciences, Semarang State University . Ro

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15294/biosaintifika.v4i2.2269

Abstract

Kanker serviks sering ditemukan di negara berkembang. Pengobatan kanker melalui radioterapi untuk mengetahui tingkat proliferasi dan mengurangi tingkat keganasan. Biomarker proliferasi dan apoptosis berupa AgNORs, MIB-1, dan Caspase 3. Namun belum dijelaskan mengenai korelasi ketiga biomarker dalam kaitannya dengan proliferasi dan apoptosis pada sel kanker serviks. Tujuan penelitian untuk mengetahui korelasi antara AgNORs, MIB-1, dan apoptosis pada kanker serviks. Penelitian observasional laboratoris menggunakan metode pewarnaan dengan menekankan kontras warna antara sitoplasma dan inti sel. Objek berupa sediaan mikroskopis dari 30 biopsi pasien kanker serviks. Pengambilan data dengan metode crocker dan blind manner. Analisis data menggunakan uji korelasi, dari ju mlah 21 pasien yang diamati menunjukkan. AgNORs dan MIB-1 memiliki angka relatif tinggi. Angka yang diperoleh ini berbanding terbalik dengan apoptosis yang relatif rendah. Korelasi antara AgNORs dengan MIB-1 menunjukkan r= 0,33 dan p= 0,15. AgNORs dengan apoptosis memiliki korelasi negatif yakni, r=-0,08 dan p= 0,73. MIB-1 dengan apoptosis memiliki korelasi negatif pula r= -0,18 dan p= 0,43. Kesimpulannya korelasi AgNORs dengan apoptosis memiliki kecenderungan lebih baik dari pada MIB-1 dengan apoptosis.Cervical cancer is often found in the developing countries. The treatment of cancer through radiotherapy was performed to determine the proliferation level and to reduce the malignancy level of cancer. The proliferation and apoptotic biomarkers were AgNORs, MIB-1, and Cas- 3. However, the correlation between the three biomarkers in relation to the proliferation and apoptosis in cervical cancer cells was not clear. The purpose of the study was to determine the correlation between AgNORs, MIB-1 and apoptosis in cervical cancer. This study was an observational research laboratory using a staining method to emphasize the color contrast between the cytoplasm and the nucleus of the cells. The microscopic preparations of the 30 patients with cervical cancer biopsies had been used as the study objects. Data was collected using the Crocker and Blind method and was then analyzed using correlation test. Data from 21 patients with AgNORs and MIB-1 showed a relatively high value. The figure obtained was inverse proportionally to the relatively low apoptotic value. The correlation between AgNORs and MIB-1 showed r = 0.33 and p = 0.15. There was negative correlation between AgNORs and apoptosis at r = -0.08 and p = 0.73. Meanwhile, between MIB-1 and apoptosis has also a negative correlation at r = -0.18 and p = 0.43. It was concluded that the correlation between AgNORs and apoptosis tended to be better than the MIB-1 and apoptosis.
Preliminary Study on the Single Nucleotide Polymorphism (SNP) of XRCC1 Gene Identificationto Improve the Outcomes of Radiotherapy for Cervical Cancer Tetriana, Devita; Mailana, Wiwin; Kurnia, Iin; Syaifudin, Mukh
Biosaintifika: Journal of Biology & Biology Education Vol 7, No 2 (2015): September 2015
Publisher : Department of Biology, Faculty of Mathematics and Sciences, Semarang State University . Ro

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15294/biosaintifika.v7i2.3949

Abstract

Cervical cancer is the most fatal disease among Indonesian women. In recognition of the substantial variation in the intrinsic response of individuals to radiation, an effort had been done to identify the genetic markers, primarily Single Nucleotide polymorphisms (SNPs), which are associated with responsiveness of cancer cells to radiation therapy. One of these SNPs is X-ray repair cross-complementing protein 1 (XRCC1) that is one of the most important genes in deoxyribonucleic acid (DNA) repair pathways. Meta-analysis in the determination of the association of XRCC1 polymorphisms with cervical cancer revealed the potential role of XRCC1 polymorphisms in predicting cell response to radiotherapy.Our preliminary study with real-time polymerase chain reaction (RT-PCR) showed that radiotherapy affected the XRCC1 gene analyzed in blood of cervical cancer patient. Other published study found three SNPs of XRCC1 (Arg194Trp, Arg280His, and Arg399Gln) that cause amino acid substitutions. Arg194Trp is only SNPs that associated with high risk of cervical cancer but not others. Additionally, structure and function of this protein can be altered by functional SNPs, which may lead to the susceptibility of individuals to cancers. Anotherstudy found G399A polymorphisms. We concluded that SNP of this DNA repair genes have been found to be good predictors of efficacy of radiotherapy.Kanker serviks adalah penyakit yang paling fatal pada perempuan di Indonesia. Untuk memahami variasi substansial respon intrinsik individual terhadap radiasi, suatu usaha telah dilakukan untuk mengidentifikasi petanda genetik, terutama Single Nucleotide polymorphism (SNP), yang berkaitan dengan responsel kanker terhadap terapi radiasi. Satu dari SNP tersebut adalah X-ray repair cross-complementing protein 1 (XRCC1) yang merupakan satu dari gen paling penting dalam lajur perbaikan asam deoksiribonukleat (DNA). Meta-analysis dalam penentuan hubungan polimorfisme XRCC1 dengan kanker serviks menemukan adanya peranan potensial polimorfisme XRCC1 dalam memprediksi respon sel terhadap radioterapi. Studi awal kami menggunakan real-time polymerase chain reaction (RT-PCR) menunjukkan bahwa radioterapi mempengaruhi gen XRCC1yang dianalisis dalam darah pasien kanker serviks. Studi yang telah dipublikasi menemukan tiga SNP dari XRCC1 (Arg194Trp, Arg280His, dan Arg399Gln) yang menyebabkan substitusi asam amino. Arg194Trp merupakan satu-satunya SNP yang berkaitan dengan tingginya risiko kanker serviks, tetapi tidak pada yang lain. Di samping itu, strukturdan fungsi protein ini dapat berubah oleh SNP fungsional, yang mengarah ke kerentanan individu untuk menderita kanker. Studi lain menemukan polimorfisme G399A. Kami menyimpulkan bahwa SNP dari gen perbaikan DNA ini merupakan prediktor yang baik dari keberhasilan radioterapi.
Evaluation of Chromosomal Aberrations and Micronuclei in Medical Workers Chronically Exposed to Low Dose Ionizing Radiation Lusiyanti, Yanti; Kurnia, Iin; Suvifan, Viria Agesti; Sardini, Sardini; Purnami, Sofiati; Rahajeng, Nastiti
Biosaintifika: Journal of Biology & Biology Education Vol 9, No 3 (2017): December 2017
Publisher : Department of Biology, Faculty of Mathematics and Sciences, Semarang State University . Ro

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.15294/biosaintifika.v9i3.12382

Abstract

Medical workers representing the group is the most consistently are exposed to low doses of ionizing radiation, prolonged low-level ionizing radiation can induce chromosomal aberrations (CAs). This study would evaluate the cytogenetic effect using the CAs based on dicentric, and cytokinesis-blocked micronucleus (CBMN) assay on hospital workers. The exposed group dividedto Interventional and Diagnostic groups then compared to non exposed group. The accumulated absorbed doses calculated for the radiation workers were below 5mSv. Blood samples were obtained from 29 samples of medical workers , and 15 samples of control. The Study showed that the frequency of dicentric chromosomes both in exposed and control were not found. In case of micronuclei, the mean frequencies were observed in exposed group that was (19 6.22) and (16.25 6.04) respectively and the control group was (10.47.79). Frequency MN/1000 cell in the lymphocytes both in the two exposed group was relatively higher compared to control group. However the MN frequencies in all sample group was still in normal range . In this study chronic low radiation dose exposure in the hospital had no significant effect on chromosome aberration nor micronuclei. The benefit of the study is to enrich the potential usefulness of cytogenetic assay providing safety index in medical surveillance programs. The results suggest that education and retraining of staff concerning radiation safety guidelines need to be done to maintain the safety aspects of radiation.
Expression of γ-H2AX Using Immunofluorescence Assay as an Adaptive Response of PBMC in Radiation Workers at Dharmais Cancer Hospital Musthafa, Arifin; Djuita, Fielda; Kurnia, Iin
Indonesian Journal of Cancer Vol 12, No 2 (2018): April-June
Publisher : National Cancer Center - Dharmais Cancer Hospital

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.33371/ijoc.v12i2.576

Abstract

Background: Exposure ionizing of radiation in radiation workers has the potential to cause DNA damage in the form of double strand break as the beginning of genomic instability. DNA damage can be observed with γ-H2AX as the biomarker of DNA double strand breaks (DSBs). The formation of γ-H2AX in the nucleus can occur after radiation exposure of 1 mGy. This study aims to determine the radiation effects in radiation work environments as a study of adaptive responses of peripheral blood mononuclear cell (PBMCs) after radiation by observing γ-H2AX foci expression..  Methods: Blood samples from nine radiation workers and nine non-radiation workers were irradiated with doses 0 Gy, 1 Gy, 1.5 Gy, and 2 Gy. Detection of γ-H2AX foci was done by immunofluorescence assay. The mean of γ-H2AX foci was counted in 50 PBMCs per sample. The comparison mean of γ-H2AX foci was analyzed using tindependent test.  Result: Based on the result study, there were no significant differences in the number of γ-H2AX foci without treatment (p = 0.807). The results of study showed that the formation of 2-3 foci per cell after exposure of 2 Gy increases along with the increasing irradiation doses.  Conclusion: The mean of index of γ-H2AX foci in PBMCs within normal limits between non-radiation workers and radiation workers and level of risk DSBs damage is relatively similar after exposure at doses 1 Gy, 1.5 Gy, and 2 Gy.  
Correlation Between Akt and p53 Protein Expression and Chemoradiotherapy Response in Cervical Cancer Patients KURNIA, IIN; SIREGAR, BUDININGSIH; SOETOPO, SETIAWAN; RAMLI, IRWAN; KURJANA, TJAHYA; ANDRIONO, .; TOBING, MARINGAN DIAPARI LUMBAN; SURYAWATHI, BETHY; KISNANTO, TEJA; TETRIANA, DEVITA
HAYATI Journal of Biosciences Vol 21, No 4 (2014): December 2014
Publisher : Bogor Agricultural University, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.4308/hjb.21.4.173

Abstract

Akt is a protein that is associated with cell proliferation and is expressed at high levels in cancer cells. Some research indicates it may play a role in increasing the resistance of cancer cells to chemotherapy treatment. P53 is a tumor suppressor protein that influences the cell cycle and apoptosis. The purpose of this study was to examine the relationship between the expression of Akt and p53 in cancerous tissue before chemoradiation treatment, and the clinical response to treatment of cervical cancer patients. Twenty microscopic tissue samples were taken from cervical cancer biopsies obtained from patients before cancer treatment. The tissue samples were stained with p53 and Akt antibodies via immunohistochemistry technique, to measure expression of both proteins. After completion of chemoradiotherapy, patients? clinical response to treatment was determined using the pelvic control method. Our results revealed no correlation between expression of Akt and p53 index (P = 0.74) as well as between p53 Index and chemoradiotherapy clinical response (P=0.29). There was significant correlation between expression of Akt and cervical cancer chemoradiotherapy response (P = 0.03). There was no correlation found between p53 index and chemoradiotherapy clinical response (P = 0.29). High expression of Akt may related with high cell proliferation and resistance to chemoradiotherapy.
Studi Nilai AgNOR dan MIB-1 pada Kanker Payudara yang Ditangani dengan Operasi Kurnia, Iin; Soetrisno, Esti; Yulian, Erwin D.; Ramli, Irwan; Alatas, Zubaidah
Indonesian Journal of Clinical Pharmacy Vol 1, No 3 (2012)
Publisher : Universitas Padjadjaran

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Abstract

AgNOR dan MIB-1 adalah marker proliferasi sel kanker payudara yang berguna sebagai dasar pemberian radioterapi setelah operasi. Penetapan nilai AgNOR dan indeks MIB-1 dilakukan dengan teknik pewarnaan dan teknik pewarnaan imunohistokimia MIB-1 terhadap 25 sediaan mikroskopik jaringan kanker payudara dari penderita hasil operasi, dan dikelompokkan berdasarkan derajat diferensiasinya menjadi 3 kelompok sediaan berderajat diferensiasi baik (G1), 16 sediaan berderajat diferensiasi menengah (G2), dan 6 sediaan berderajat diferensiasi buruk (antara G2 dan G3). Hasil penelitian menunjukkan nilai AgNOR dan indeks MIB-1 cenderung meningkat seiring dengan meningkatnya derajat diferensiasi. Terdapat pula kecendrungan korelasi positif antara nilai AgNOR dan indeks MIB-1 (r =0,21) pada seluruh derajat diferensiasi, terdapat korelasi negatif antara AgNOR dan MIB-1 pada G1 (r=-0,97), korelasi positif pada G2 (r=0,36) serta korelasi positif antara G2 dan G3 (r=0,33). Korelasi positif antara AgNOR dan MIB-1 terkait dengan peningkatan fase G1, S dan G2 pada sel yang berproliferasi dan peningkatan jumlah sel yang mengalami mitosis. Korelasi negatif disebabkan oleh perbedaan proporsi antara sel yang berada pada fase G1, S dan G2 dengan yang sedang bermitosisKata kunci: Kanker payudara, AgNOR, MIB-1, operasi Study of AgNOR Value and MIB-1 in Breast CancerTreated With Surgery AbstractAgNOR and MIB-1 are marker for breast cancer cell proliferation and can be use as based for radiotherapytreatment after surgery. Value of AgNOR and MIB-1 index were determined using staining and immunohistochemistry staining method respectively from 25 of microscopic slides of breast cancer tissue patients with surgery, and grouped based on degree of differentiation, 3 slides were good degree (G1), 16 slides were medium degree (G2) and 6 slides were poor degree (between G2 and G3). The result shown that the value of AgNOR and MIB-1 index were tended to increase with the increased differentiation degree. There was a positive correlation between the value of AgNOR and index of MIB-1 in all group of differentiation degree (r = 0.21), there is a negative correlation between AgNOR and MIB-1 on G1 (r =-0,97), positive correlation in G2 (r = 0.36) as well as positive correlation between G2 and G3 (r = 0.33). The positive correlation between AgNOR and MIB-1 were associated to the increased of G1, S and G2 phase in the proliferation cell and an increase of cells undergoing mitosis. The negative correlation were caused by the different cell proportion in G1, S and G2 phase, and undergoing mitotis.Key words: Breast cancer, AgNOR, MIB-1, surgery