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Ekspresi Hypoxia-Inducible Factor-1α menginduksi Ekspresi Eritropoietin Intraseluler, dan Vascular Endothelial Growth Factor pada Penderita Kanker Payudara dengan Anemia Darwin P, Muhammad; Kalim, Handono; Wahono S, Djoko; W Sudoyo, Aru; Fatchiyah, Fatchiyah
Jurnal Kedokteran Brawijaya Vol 27, No 2 (2012)
Publisher : Fakultas Kedokteran Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (643.499 KB) | DOI: 10.21776/ub.jkb.2012.027.02.5

Abstract

 Anemia merupakan faktor prognostik independen untuk pertahanan hidup pasien kanker. Penurunan kapasitas oksigen pada darah dapat menyebabkan terjadinya kondisi hipoksia pada jaringan kanker . Hipoksia pada jaringan kanker dapat mengaktivasi faktor transkripsi hypoxia-inducible factor-1α (HIF-1α) yang kemudian akan mentranskripsi banyak gen lain yang terlibat dalam invasi sel, angiogenesis, metabolisme anaerobik dan siklus sel, seperti gen eritropoietin (Epo) dan vascular endothelial growth  factor  (VEGF). Penelitian  ini menggunakan sampel berupa 120 slide peraparat  jaringan kanker payudara (60 anemi dan 60 non anemi) dengan melakukan pewarnaan secara  imunofluoresen double staining untuk protein HIF1α dengan VEGF dan Epo dengan EpoR. Sampel dibagi menjadi 2 kelompok, yaitu anemi (Hb 5,5-10,7) dan non anemi (Hb 11-14,9). Hasil imunofluoresen di analisis dengan menggunakan Confocal Laser Scanning Microscope untuk mengetahui ekspresi protein target. Hasil dari penelitian menunjukkan bahwa tidak ada perbedaan yang signifikan pada ekspresi   HIF1α pada jaringan kanker penderita kanker payudara yang   anemi dan   non anemi namun sebaliknya ada perbedaan ekspresi VEGF yang signifikan (p=0,013) antara pasien anemi (754,4±316) dan non anemi (555,1±276,9). Pada kelompok sampel anemi dan non anemi ada hubungan negatif antara Hb dan HIF1α   (p=0,000; r=-0,522) dan hubungan positif  antara HIF1α dengan EPO (p=0,000; r= 0,697), antara HIF1α dengan VEGF (p=0,000; r=0,644), antara Epo dan VEGF (p=0,001; r=0,433). Pada pasien kanker anemi dan non anemi telah terjadi kondisi hipoksia pada lingkungan tumornya sehingga menyebabkan ekspresi HIF1α tidak berbeda signifikan namun hubungan HIF1α dengan EPO dan VEGF sangat kuat.  Kata Kunci: Anemi, epo, HIF1α, hipoksia, VEGF
The Correlation between Serum Concentration of Vitamin D with Vitamin D Receptor Expression and Disease Activity in Indonesian Patients with Systemic Lupus Erythematosus: Preliminary Study Handono, Kusworini; Tanuwijaya, Laksmi Karunia; Fitri, Loeki Enggar; Kalim, Handono
Journal of Tropical Life Science Vol 4, No 2 (2014)
Publisher : Journal of Tropical Life Science

Show Abstract | Download Original | Original Source | Check in Google Scholar

Abstract

The vitamin D role on the immune response of systemic lupus erythematosus (SLE) patient is mediated by vitamin D receptor (VDR). Low level of vitamin D correlated with disease activity in SLE patients, and circulating levels of activated vitamin D (1,25(OH)2D) contribute to VDR protein levels and its function. The objective of this study was to determine the correlation between vitamin D status with expression of VDR in peripheral blood mononuclear cell (PBMC) and the disease activity in SLE patients. The Research Subjects were 15 SLE patients (ACR 1997 criteria) from the Rheumato-Immunology Division, dr. Saiful Anwar Hospital, Malang and 5 healthy controls. Serum vitamin D (25(OH)D3) level was assessed using ELISA method. VDR expression in PBMC was assessed using immunocytochemistry technique. The disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. This study showed no difference on VDR expression in PBMC between patient and healthy control group, but patient with vitamin D deficiency had lower VDR expression in PBMC than the other group. No difference on SLEDAI score between the group. Vitamin D status correlated positively with VDR expression in PBMC (p < 0,035, r = 0,473). However vitamin D status did not correlate with disease activity scores (p = 0,686).
Membangun Desa Binaan Tanggap COVID-19, Lupus, Reumatik, dan Alergi: Upaya Menurunkan Angka Kejadian dan Mencegah Kekambuhan di Malang Handono, Kusworini; Wahono, Cesarius Singgih; Barlianto, Wisnu; Dewi, Elvira Sari; Sari, Tita Luthfia; Hasanah, Dian; Rahman, Perdana Aditya; Anshory, Muhammad; Wulandari, Desy; Sari, Dewi Purnama; Endharti, Agustina Tri; Nurdiana, Nurdiana; Kalsum, Umi; Susianti, Hani; Kalim, Handono
International Journal of Community Service Learning Vol 5, No 1 (2021): February 2021
Publisher : Universitas Pendidikan Ganesha

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.23887/ijcsl.v5i1.30161

Abstract

Kurangnya pengetahuan masyarakat tentang COVID-19, lupus, reumatik, dan alergi mempengaruhi keberhasilan terapi, penurunan angka kejadian, dan pencegahan kekambuhan. Tujuan pengabdian masyarakat adalah membangun desa-desa binaan tanggap COVID-19, lupus, reumatik, dan alergi di Malang oleh Tim Kelompok Kajian Lupus, Autoimun, Reumatik, dan Alergi (LAURA) Universitas Brawijaya. Warga desa binaan diberikan penyuluhan berupa seminar awam dan pelatihan tentang pertolongan awal pada penyakit COVID-19, lupus, reumatik, dan alergi, kemudian diminta mengisi kuesioner posttest untuk mengukur pemahaman. Desa-desa binaan diberikan thermo-gun dan wastafel untuk menerapkan protokol kesehatan. Satu bulan kemudian dievaluasi adanya kejadian COVID-19, lupus, reumatik, dan alergi di desa binaan. Hasil evaluasi menunjukkan rata-rata warga desa binaan memahami 78,3% materi yang diberikan dan menerapkan protokol kesehatan sesuai yang diajarkan saat penyuluhan. Dilaporkan tidak ada kejadian COVID-19 serta kekambuhan lupus, reumatik, dan alergi dalam satu bulan terakhir kegiatan. Kesimpulan: pembangunan desa-desa binaan di Malang meningkatkan tanggap warga terhadap COVID-19, lupus, reumatik, dan alergi.
Modulation of Perlecan Protein towards Chondrocyte Secretion Factors at the Articular Cartilage in Hyperglycemic Animal Model Ibrahim Njoto; Fatchiyah Fatchiyah; Kusworini Handono; Abdurrachman Abdurrachman; Djoko W. Soeatmadji; Handono Kalim
The Journal of Pure and Applied Chemistry Research Vol 8, No 1 (2019): Edition January-April 2019
Publisher : Chemistry Department, The University of Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.jpacr.2019.008.01.450

Abstract

High carbohydrate influences the cartilage microcellular environment and chondrocytes. Perlecan (HSPG2) conducts an essential role as chondrocytes mechano-transducer and chondrocytes secretion factors. This research aims to fulfill the research gap about hyperglycemia which influences to perlecan of articular cartilage. About twenty male rats were divided into four groups: group I (sugar-treated rats 1.00 mg/kg of BW), group II (sugar-treated rats 1.5 mg/kg of BW), group III (2.00 mg/kg of BW), and control. The Anterior Cruciate Ligament Transection (ACLT) used to generate an unstable joint to be osteoarthritis condition at the right knee. Then, sugar was administrated for two months.  Level expression of the protein was analyzed using Western Blotting. The result showed that perlecan expression was decreased within all sugar-treated rats group as compared to control. The IGF-1 expression was decreased, whereas TGF-β was slightly increased within all treatment groups. Moreover, the expression of FGF-2 was higher in all treatment groups. Of note, IL-1β expression was only elevated in group II and III. The interaction of perlecan to the chondrocyte secretion factors was determined by the cartilage condition within hyperglycemia.
The Effect of Curcumin on Regression of Liver Fibrosis through Decreased Expression of Transforming Growth Factor-β1 (TGF-β1) Supriono Supriono; Asri Nugraheni; Handono Kalim; Mudjiwijono Handaru Eko
The Indonesian Biomedical Journal Vol 11, No 1 (2019)
Publisher : The Prodia Education and Research Institute (PERI)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18585/inabj.v11i1.463

Abstract

BACKGROUND: Transforming growth factor (TGF)-β1 has a pivotal role in liver fibrogenesis. Curcumin effectively prevent the progression of liver fibrosis through inhibition of TGF-β1/Sma and drosophila MAD (Smad) signaling pathway. However, the role of curcumin in the regression of liver fibrosis is still unknown. This study investigated the role of curcumin and TGF-β1 in liver fibrosis regression.METHODS: An experimental Wistar rat model included 6 treatment groups as well as positive and negative control groups. The treatment and positive control groups were injected with carbon tetrachlorid (CCl4) for 9 weeks to induce liver fibrosis. After cessation of injection, 3 of the treatment groups were given curcumin and 3 were given carboxymethylcellulose (CMC) for 2, 5 and 9 weeks, while the positive control was untreated. The negative control was injected with normal saline. TGF-β1 liver tissue levels were analyzed by ELISA, while the TGF-β1 expression in liver cells was analyzed by immunohistochemical assay. The metavir score was used to assess the degree of liver fibrosis. Values of p<0.05 were regarded as statistically significant.RESULTS: Nine weeks of CCl4 injection induced liver fibrosis (metavir F3); and significantly increased TGF-β1 levels and expression in tissues (p=0.00, p=0.021, respectively). Curcumin administration decreased levels and expression of TGF-β1 in the liver and accelerated regression of liver fibrosis. There was a significant correlation between duration of administration of curcumin with an expression of TGF-β1 in the liver tissue (r=0.87; p<0.00).CONCLUSION: Curcumin accelerates regression of liver fibrosis, likely through decreasing of TGF-β1 expression in the liver.KEYWORDS: curcumin, TGF-β1, liver fibrosis regression, CCl4, animal model
Hubungan Kadar Vitamin D Dengan Jumlah Set T Regulator pada Pasien Lupus Eritematosus Sistemik Handono Kalim; Kusworini Handono; Dian Hasanah
Research Journal of Life Science Vol 2, No 1 (2015)
Publisher : Lembaga Penelitian dan Pengabdian kepada Masyarakat, Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (593.976 KB) | DOI: 10.21776/ub.rjls.2015.002.01.5

Abstract

Latar Belakang. Lupus Eritematosus Sistemik (LES) merupakan penyakit autoimun yang semakin sering dijumpai dengan angka kematian tinggi. Etiopatogenesis penyakit ini belum begitu jelas, meskipun telah ditunjukkan adanya abnormalitas berbagai sel-sel imun termasuk hiper-reaktivitas sel T, sel B, sel dendrit; dan menurunnya fungsi sel T regulator (Treg). Vitamin D memiliki peran dalam pengaturan sistem imun. Penelitian pada ras Kaukasia menunjukkan bahwa kadar vitamin D yang rendah berkaitan dengan timbulnya penyakit autoimun termasuk LES. Peran vitamin D pada sistem imun pasien LES masih banyak kontroversi. Penelitian ini bertujuan untuk mengetahui hubungan kadar vitamin D dengan jumlah sel Treg.Metoda Penelitian. Penelitian ini adalah penelitian kasus-kontrol yang membandingkan jumlah sel Treg pada pasien LES dan kontrol sehat dengan melihat status vitamin D-nya. Kadar vitamin D pasien LES diukur dengan metoda ELISA, jumlah sel Treg (CD4+,CD25+,FoxP3+) ditentukan dengan metoda flowcytometri.Hasil. Kadar vitamin D pada pasien LES lebih rendah daripada kontrol sehat (p=0,000) dan didapatkan korelasi negatif antara status vitamin D dengan persentase sel Treg (koefisien korelasi -0,358 dan p=0,006). Hal ini mungkin merupakan umpan balik positif untuk menanggulangi hiperreaktifitas dari sel T dan sel B.Kesimpulan. Status vitamin D berkorelasi negatif dengan persentase sel Treg.
INTERLEUKIN-4 DAN INTERFERON GAMMA DI NEFRITIS LUPUS: HUBUNGAN AKTIVITAS PENYAKIT SERTA KEKAMBUHAN Torajasa Achamar; Dany Farida; Hani Susianti; Kusworini Handono; Ati Rastini; R.I R.I; I Putu A.S; Atma Gunawan; Handono Kalim
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY Vol 22, No 2 (2016)
Publisher : Indonesian Association of Clinical Pathologist and Medical laboratory

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24293/ijcpml.v22i2.1117

Abstract

Sampling for urinalysis to see the activity and the degree of recurrence of Lupus Nephritis (LN) is very difficult. New biomarkersthat are more simple, sensitive, specific and non-invasive in assessing the activity of the LN need to be investigated. Interleukin-4 (IL-4)and interferon gamma (IFN-γ) were implicated to LN process. Urine samples from 17 LN patients were taken every month for 6 (six)months to examine the level of uIL-4, uIFN-γ, activity and recurrence of LN. Significant differences were observed in the uIFN-γ levelsbetween the active and inactive LN groups (p=0.012), but not in uIL-4 levels (p=0.187). Correlations between each biomarker andrenal domain score were weak (r=0.201, p=0.042 for uIL-4; r=0.268, p=0.006 for uIFN-γ). Significant differences were also found inthe uIL-4 and uIFN-γ levels against LN recurrence (p=0.033; p=0.017). The best cut off values to assess recurrences and activity of LNwere 8.17 pg/mL for uIL-4 showed a sensitivity of 74%, specificity 71%, NPV 90%, PPV 42% to assess recurrences and to assess activityof LN showed sensitivity 46%, specificity 75%, NPV 48%, PPV 78%. The cut off 18.58 pg/mL for uIFN-γ to predict recurrent and assessthe activity of LN showed sensitivity 68%%, specificity 70%, NPV 88%, PPV 40% to predict the recurrent and to assess the activity of LNshowed sensitivity 57%, specificity 64%, NPV 49%, PPV 73%. Based on the research, uIL-4 and uIFN-γ are not good enough to predictrecurrence and activity of LN
ASOSIASI HLA-DRB1* DAN HLA-DQB1* DENGAN IGM-RF SERUM PADA ARTRITIS REUMATOID Joewono Soeroso; Ferdinandus Maria Judajana; Handono Kalim
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY Vol 18, No 3 (2012)
Publisher : Indonesian Association of Clinical Pathologist and Medical laboratory

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24293/ijcpml.v18i3.373

Abstract

Rheumatoid arthritis (RA) is a chronic progressive polygenic autoimmune disease with a high socio-economic burden. Genetic polymorphisms expressed as a shared epitope (SE) at hypervariable regions of HLA-DRB1*01/*04/*10/*14 and linkage disequilibriums of HLA-DRB1*-HLA-DQB1* with some microorganisms, increase the risk of RA. Shared epitopes are also related with the increase of serum IgM-RF as well. A cross-sectional study on 48 RA patients diagnosed by ACR Criteria 1987 from 6 hospitals in Java and Bali was done to determine the associations of HLA-DRB1* and HLA-DQB1* alleles with serum IgM-RF levels. The presence of HLA-DRB1* and HLA-DQB1* alleles were assessed through PCR-SSO. Serum IgM-RF levels (IU/mL) were assessed through ELISA. Man-Whitney U tests were used to measure the associations. Value of p<0.05 is considered to be statistically significant. The results showed that mean ranks IgM-RF levels of subjects who are bearing HLA-DRB1*04 compared to subjects who are not bearing HLA-DRB1*04 were 34.10 IU/ml (n=10) vs 21.97 IU/ml (n=38), p=0.014. While, the mean ranks of IgM-RF levels of subjects who are bearing haplotype combination of HLA-DRB1*04-HLA-DQB1*03 vs subjects who are not bearing haplotype combination of HLA-DRB1*04- HLA-DQB1*03 were 32.89 IU/mL (n=9) vs 22.56 IU/mL (n=39) (p=0.046). It is concluded that there are association of HLA-DRB1*04, and haplotype combination of HLA-DRB1*04-HLA-DQB1*03 with increased levels of IgM-RF among Indonesians with RA.
Validity and reliability fatigue severity scale in patients with Systemic Lupus Erythematosus (SLE) in Indonesia A Rifa’i; Handono Kalim; Kusworini Handono; Cesarius Singgih Wahono
Indonesian Journal of Rheumatology Vol. 8 No. 1 (2016): Indonesian Journal of Rheumatology
Publisher : Indonesian Rheumatology Association

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (206.332 KB) | DOI: 10.37275/ijr.v8i1.5

Abstract

Background: Fatigue is one symptom of Systemic Lupus Erythematosus (SLE), which has an important effect on the quality of life. Fatigue Severity Scale (FSS)is one parameter fatigue symptom in SLE. The purpose of this study was to determine the validity and reliabilitybetween FSS with duration of ilness and disease activity of SLE patients in Indonesia.Methods: FSS performed on 40 patients with SLE. FSS original English version has been converted-translated into Indonesian version by a team of RheumatologyImmunology Medical Faculty of Brawijaya University. Reliability determined by Cronbach’s Alpha values (>0.6). Validity was determined by the value of Corrected Item-Total Correlation which each item was a valid question if below value of Cronbach’s Alpha.Results: The reliability value was determined by Cronbach’s Alpha values (>0.6) in which the SLE patients in this study had a Cronbach’s Alpha value of 0.946. Value of Corrected Item-Total Correlation overall under Cronbach’s Alpha value (range = 0.684-0.859) which indicates that each item was a valid question. There were correlation between the FSS Indonesian version with disease duration (p = 0.000) as well as the value of r = 0.581, with SLEDAI (p = 0.000) with a value of r = 0.833. Conclusion: FSS in Indonesian version has a good reliability and validity and can be used by clinicians andother researchers to assess the condition of fatigue in SLE patients in Indonesia.Keywords: validity, reliability, fatigue, fatigue severity scale, systemic lupus erythematosus
Correlation between anti-cyclic citrullinated peptide antibodies and the severity of clinical manifestation, laboratory manifestation, and radiological joint destruction in rheumatoid arthritis patients Mat Suwito; Kusworini Handono; Bagus Putu Putra Suryana; Handono Kalim; Cesarius Singgih Wahono
Indonesian Journal of Rheumatology Vol. 1 No. 2 (2009): Indonesian Journal of Rheumatology
Publisher : Indonesian Rheumatology Association

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (207.499 KB) | DOI: 10.37275/ijr.v2i1.22

Abstract

Background. The second generation anti-cyclic citrullinated peptide test (CCP2) displays sensitivity comparable to that of rheumatoid factor (RF) (approximately 80%) but with superior specificity (98%) . Several observations have indicated that early rheumatoid arthritis (RA) patients with positive anti-CCP may develop a more erosive disease than those without anti-CCP.Objective. The purpose of this cross-sectional study was to investigate the correlation between anti-CCP antibodies and clinical and laboratory parameters and radiological joint destruction in RA patients.Methods. We studied 31 patients with RA fulfilling the 1987 revised criteria of American College of Rheumatology in Rheumatology Clinic of Saiful Anwar General Hospital, Malang, Indonesia. Clinical parameters were collected such as age, sex, visual analog scale,disease duration and diseases activity score (DAS28-3(CRP)). Laboratory parameters were WBC, hemoglobin, platelet count, erythrocyte sedimentation rate, and Creactive protein. Analyzed autoantibody profiles were RF and anti-CCP (ELISA methode). Radiological jointdestruction was evaluated from bilateral postero-anterior manus x ray (Sharp score).Results. Anti-CCP antibodies were detected in 48.4% of RA patients with mean antibody concentration was 291.24±143.67 (range 16-523.8) units. Anti CCP level was significantly correlated with duration of RA (month) (p=0.04, r=0.371), RF level (p=0.002, r=0.542) andSharp score (p=0.048, r=0.358), but was not significantly correlated with other clinical and laboratory parameters.Conclusion. Anti-CCP level was correlated with duration of disease, RF, and Sharp score.
Co-Authors A Rifa’i Abd. Rasyid Syamsuri Abdurrachman Abdurrachman Achmad Rifa’i, Achmad Achmad Rifa’i Achmad Rudijanto Agustina T Endharti, Agustina T Agustina Tri Endharti Aru W Sudoyo Asri Nugraheni Ati Rastini Atma Gunawan Atma Gunawan Bambang Setyohadi Benny A Pradana, Benny A BP Putra Suryana Dany Farida Deddy Nur Wachid Achadiono Desfryda, Elynca Putri desy wulandari Dewi Purnama Sari Dian Hasanah Djoko W. Soeatmadji Djoko Wahono S Dona Marisa, Dona Dwinadella, Sephia Eko, Mudjiwijono Handaru Elvira Sari Dewi Engli, Katherina Erawati, Dini Rachma fatchiyah . Fatchiyah Fatchiyah Ferdinandus Maria Judajana Fikriah, Ika Firdaningrum, Nimas Eka Hani Susanti, Hani Hani Susianti Hanik Ruliani Harry Isbagio Harun Al Rasyid Harun Al Rasyid I Putu A.S Ibrahim Njoto Ivan A Hartono, Ivan A Joewono Soeroso Joewono Soeroso Kusworini Handono Kusworini Handono Kusworini Handono Kusworini Handono Kusworini Kusworini Laksmi Karunia Tanuwijaya Laksmi Karunia Tanuwijaya Loeki Enggar Fitri M Aris Widodo Mat Suwito Moch Sasmito Djati Mudjiwijono Handaru Eko Muhammad Anshory Muhammad Anshory, Muhammad Muhammad Darwin P Nurdiana Nurdiana Perdana Aditya Rahman Pratama, Mirza Zaka Putri, Choirinnisa Meilia Ayu R.I R.I Rachmat Gunadi Wachjudi Radhitio A Nugroho, Radhitio A Respati Suryanto Dradjat Ria Famuji, Siti Roziah Rifa’i, A Rizky Fachry, Ade Wlidan Rooije R.H. Rumende Sari, Tita Luthfia Solly Aryza Sumarta, Norma Hanifah Supriono Supriono Suryana, Bagus Putu Putra Suwito, Mat Tamaulina Br Sembiring Torajasa Achamar Wahono, Caesarius Singgih Wahono, Cesarius Singgih Wisnu Barlianto Yona One Sidarta, Yona One Zaenal Kusuma