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"Tujuan: Membandingkan kadar vascular endothelial growth factor VEGF dan placental growth factor PlGF plasma dan vitreus pada tikus diabetes dengan kontrol gula darah GD buruk, dengan perbaikan kontrol gula darah, dan tikus nondiabetes, dan melihat pengaruh perbaikan kontrol gula darah terhadap kadar VEGF dan PlGF. Metode: Penelitian ini merupakan uji eksperimental pada hewan coba tikus strain Sprague Dawley. Sebanyak 18 ekor tikus disertakan dalam penelitian dan secara acak dibagi ke dalam kelompok perlakuan n=14 dan kontrol n=4 . Kelompok perlakuan diberikan injeksi Streptozotocin untuk menginduksi diabetes. Tikus dengan kadar GD 72 jam pasca induksi lebih dari 300 mg/dL didiagnosis diabetes. Kadar GD diperiksa secara berkala pada seluruh subyek. Setelah 4 mingu, kelompok perlakuan dibagi ke dalam kelompok I untuk terminasi dan kelompok II untuk perbaikan kontrol GD dengan injeksi insulin selama 4 minggu berikutnya, begitu pula dengan kelompok kontrol. Saat terminasi, sampel plasma darah dan vitreus diambil untuk analisis kadar VEGF dan PlGF melalui pemeriksaan enzyme-linked immunosorbent assay ELISA. Hasil: Sebanyak 17 ekor tikus bertahan hidup hingga akhir penelitian dengan 1 ekor tikus mati dari kelompok perlakuan. Kadar GD kelompok perlakuan II menurun drastis dan mencapai normoglikemia. Pemeriksaan ELISA bulan pertama menunjukkan kadar VEGF vitreus kelompok perlakuan I cenderung lebih tinggi dibandingkan kontrol I, yakni 196,36 65,24 pg/dL dan 123,64 44,99 pg/dL p=0,20 . Pemeriksaan ELISA bulan kedua menunjukkan kadar PlGF vitreus kelompok perlakuan II lebih tinggi dibandingkan kontrol II, yakni 59,04 2,48 dan 51,93 3,15 p=0,01. Kadar VEGF vitreus dan plasma kelompok perlakuan I dan II tidak berbeda bermakna, sedangkan kadar PlGF vitreus dan plasma lebih tinggi pada bulan kedua. Kesimpulan: Kadar VEGF dan PlGF vitreus mengalami peningkatan pada kelompok tikus diabetes dibandingkan nondiabetes, dan perbaikan kontrol gula darah selama 1 bulan belum dapat menurunkan kadar VEGF dan PlGF.

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Aim: To compare plasma and vitreous level of vascular endothelial growth factor VEGF and placental growth factor PlGF in diabetic rats with poor blood glucose BG control, reconstitution of good BG control, and nondiabetic rats, and to investigate the effect of reconstitution of good BG control to VEGF and PlGF plasma and vitreous level.

Methods: This is an experimental study using Sprague Dawley rats. Eighteen rats were divided into intervention group n 14 and control group n 4. Intervention group were given Streptozotocin STZ injection to induce diabetes. Rats with BG level more than 300 mg dL at 72 hours after injection were considered diabetes and successful models. BG levels were monitored periodically in all subjects. After 4 weeks, intervention group was randomly divided into group I for termination and group II for reconstitution of good BG control with insulin for following 4 weeks, and so was the control group. Plasma and vitreous samples were taken. VEGF and PlGF levels were detected with enzyme linked immunosorbent assay ELISA.

Results: Seventeen rats survived and one rat died in intervention group. BG level of intervention group II decreased dramatically to normoglycemia. ELISA at month 1 showed that VEGF vitreous level tend to be higher in intervention group I compared to control I, 196.36 65.24 pg dL and 123.64 44.99, respectively p 0.20. ELISA at month 2 showed that PlGF vitreous level of intervention group I were significantly higher compared to control I, 59.04 2.48 and 51.93 3.15, respectively p 0.01. Vitreous and plasma VEGF of intervention group I and II were not different, while vitreous and plasma PlGF were significantly higher in group II.

Conclusions: Vitreous levels of VEGF and PlGF were increased in diabetic rats compared to nondiabetic, and reconstitution of good BG control for 1 month were unable to reduce VEGF and PlGF levels. "

"Latar Belakang: Ulkus diabetik merupakan komplikasi diabetes melitus yang menjadi salah satu masalah utama di bidang kesehatan. Di Indonesia, angka mortalitas ulkus diabetik mencapai 17-30%, dengan laju amputasi sekitar 15-30%. Pemberian terapi oksigen hiperbarik (TOHB) dapat meningkatkan oksigenasi endotel dan merangsang produksi vascular endothelial growth factor (VEGF) yang merupakan faktor pertumbuhan paling spesifik dan poten untuk proses angiogenesis sehingga dapat mempercepat proses penyembuhan luka. Tujuan: Penelitian ini bertujuan untuk mengetahui apakah TOHB berpengaruh terhadap peningkatan kadar VEGF pasien ulkus diabetik. Metode: Dilakukan penelitian uji ktinis eksperimental dari bulan Februari 2006 sampai April 2006 terhadap 12 pasien ulkus diabetik yang mendapat TOHB 3 X 30 menit per hari selama 5 hari (kelompok TOHB) dan 10 pasien ulkus diabetik yang tidak mendapat TOHB (kelompok non-TOHB, kelompok kontrol). Kadar VEGF pada kedua kelompok diukur pada hari pertama dan hari kelima. Hasil: Pada kelompok TOHB kadar VEGF hari pertama menunjukkan nilai rerata 1241,325 + 237,6533 pg/ml dan setelah 5 hari nilat rerata menjadi 1244,458 + 264,5641 pg/ml, (p = 0,583). Sedangkan pada kelompok non-TOHB kadar VEGF hari pertama menunjukkan nilai rerata 1262,350 + 227,9603 pg/ml kemudian pada hari ke-5 nilai rerata menjadi 1112,460 + 220,3795 pg/ml, (p = 0,093). Tidak didapatkan perbedaan yang bermakna nilai rerata kadar VEGF antara kelompok TOHB dan kelompok nonTOHB pada hari pertama (p= 1) maupun hari kelima (p = 0,872). Kesimpulan: Terapi oksigen hiperbarik selama 5 hari tidak meningkatkan kadar VEGF pada pasien ulkus diabetik.

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Background: Diabetic ulcer is a complication of diabetes mellitus which one of the main health problem. In Indonesia the mortality rate of diabetic ulcer is about 17-30%, while the amputation rate is about 15-30%. Hyperbaric oxygen therapy (TOHB) increase endothelial oxygenation and stimulates vascular endothelial growth factor (VEGF) as the most specific and potent growth factor for angiogenesis and increases wound heating process.

Aim of the study: The aim of the study is to know if TOHB can increase the level of VEGF in diabetic ulcer patients.

Methods: Clinical experimental study was conducted from February 2006 until April 2006 of 12 diabetic ulcer patients who received TOHB 30 minutes, 3 times a day for 5 days (TOHB group) and 10 diabetic ulcer patients as a control group who did not receive TOHB (non-TOHB group). The VEGF level in both groups was measured on days 1 and 5.

Results: In TOHB group the mean level of VEGF on day 1 was 1241.325 + 237.6533 pg/ml and became 1244.458 + 264.5641 pg/ml (p = 0.583) on day 5, while in non-TOHB group the mean level of VEGF on day | was 1262.350 + 227.9603 pg/ml and became 1112.460 + 220.3795 pg/ml (p = 0.093) on day 5. There were no significant differentiation of VEGF level between TOHB group and non-TOHB, group both on day 1 (p = 1) and day 5 (p = 0.872).

Conclusion: Hyperbaric oxygen therapy for 5 days did not increase the VEGF level of diabetic ulcer patients."

"Latar Belakang: ECP mampu menurunkan frekuensi angina, meningkatkan kualitas hidup, serta memperbaiki exercise–induced ischemia time. Manfaat tersebut dapat bertahan beberapa tahun setelah ECP. Mekanisme manfaat jangka panjang ECP tersebut telah dibuktikan akibat adanya angiogenesis yang diduga diperankan VEGF-A, VEGFR-2, dan miR-92a.Tujuan: Mengetahui efek ECP terhadap VEGF-A dan VEGFR-2, serta hubungannya dengan miR-92a pada pasien angina refrakter.Metode: Studi ini merupakan uji klinis acak tersamar ganda yang melibatkan 50 subjek dengan angina refrakter. Subjek dirandomisasi (1:1) ke dalam kelompok terapi ECP atau sham, yang masing-masing dilakukan selama 1 jam, hingga 35 kali. Kadar VEGF-A, VEGFR-2, dan miR-92a plasma diukur sebelum dan sesudah terapi menggunakan metode enzyme-linked immunosorbent assay (ELISA) untuk VEGF-A dan VEGFR-2, serta quantitative reverse transcription-polymerase chain reaction (qRT-PCR) untuk miR-92a. Keluaran klinis sekunder seperti derajat angina, kualitas hidup, 6-minutes walk test (6MWT), dan ejection fraction (EF) juga dinilai.Hasil: Kadar VEGF-A dan VEGFR-2 dipertahankan pada kelompok ECP, sedangkan kadar VEGF-A dan VEGFR-2 mengalami penurunan yang signifikan pada kelompok sham [ΔVEGF-A ECP vs sham: 1 (-139 to160) vs -136 (-237 to 67) pg/ml, p = 0.026; ΔVEGFR-2 ECP vs sham: -171(-844 to +1166) vs -517(-1549 to +1407) pg/ml, p = 0.021, respectively]. Kadar miR-92a meningkat secara signifikan pada kelompok ECP [5.1 (4.2 – 6.4) to 5.9 (4.8 – 6.4), p<0.001] and sham [5.2 (4.1 – 9.4) to 5.6 (4.8 – 6.3), p=0.008]. Tidak terdapat korelasi antara perubahan kadar VEGF-A, VEGFR-2, dan miR-92a [VEGF-A vs VEGFR-2 (r = 0.243, p = 0.09; uji Spearman), VEGF-A vs miR92-a (r = 0.229, p = 0.11; uji Spearman), dan VEGR-2 vs miR92-a (r = 0.08, p = 0.581; uji Spearman)].Kesimpulan: ECP mampu mempertahankan angiogenesis dengan cara mempertahankan kadar VEGF-A dan VEGFR-2. Pada kondisi iskemia, baik high shear stress (ECP) maupun low shear stress (sham) dapat menginduksi pelepasan miR-92a. ECP mempengaruhi VEGF-A, VEGFR-2, dan miR-92a secara independen.

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Background: ECP is able to reduce angina frequency, improve quality of life, and improve exercise time-induced ischemia time. These benefits can last several years after the ECP. The mechanism for the long-term benefit of ECP has been proven by the presence of angiogenesis, which is thought to be mediated by VEGF-A, VEGFR-2, and miR-92a.

Objective: To determine the effect of ECP on VEGF-A and VEGFR-2, and its relationship with miR-92a in patients with refractory angina.

Methods: This study was a double-blind randomized clinical trial involving 50 subjects with refractory angina. Subjects were randomized (1:1) into either ECP or sham therapy groups, each administered for 1 hour, up to 35 times. Plasma VEGF-A, VEGFR-2, and miR-92a levels were measured before and after therapy using the enzyme-linked immunosorbent assay (ELISA) method for VEGF-A and VEGFR-2, as well as quantitative reverse transcription-polymerase chain reaction (qRT-PCR). ) for miR-92a. Secondary clinical outcomes such as degree of angina, quality of life, 6-minute walk test (6MWT), and ejection fraction (EF) were also assessed.

Results: VEGF-A and VEGFR-2 levels are maintained in the ECP group, while VEGF-A and VEGFR-2 levels decrease in the sham group [ΔVEGF-A ECP vs sham: 1 (-139 to160) vs -136 (-237 to 67) pg/ml, p = 0.026; VEGFR-2 ECP vs sham: -171(-844 to +1166) vs -517(-1549 to +1407) pg/ml, p = 0.021, respectively]. MiR-92a levels increase significantly in the ECP group [5.1 (4.2 – 6.4) to 5.9 (4.8 – 6.4), p<0.001] and sham [5.2 (4.1 – 9.4) to 5.6 (4.8 – 6.3), p=0.008]. There is no correlation between changes in VEGF-A, VEGFR-2, and miR-92a levels [VEGF-A vs VEGFR-2 (r = 0.243, p = 0.09; Spearman's test), VEGF-A vs miR92-a (r = 0.229 , p = 0.11; Spearman's test), and VEGR-2 vs. miR92-a (r = 0.08, p = 0.581; Spearman's test)].

Conclusion: ECP therapy is able to maintain angiogenesis by maintaining VEGF-A and VEGFR-2 levels. In ischemic conditions, both high shear stress (ECP) and low shear stress (sham) can induce the release of miR-92a. ECP affects VEGF-A, VEGFR-2, and miR-92a independently."

"Latar belakang: Kanker serviks merupakan salah satu kanker yang paling banyak ditemui dengan angka kematian yang tinggi di seluruh dunia. Vascular Endothelial Growth Factor (VEGF) merupakan salah satu biomarker yang berfungsi sebagai faktor prognosis pada kanker serviks. Data ekspresinya terkait berbagai karakteristik kanker serviks yang ditemui pada hasil pemeriksaan Ultrasonografi (USG) dan Magnetic Resonance Imaging (MRI) pada pasien kanker serviks di Indonesia masih terbatas.Tujuan: Untuk mengetahui hubungan antara tingkat ekspresi VEGF, pemeriksaan USG, dan pemeriksaan MRI pada pasien kanker serviks.Metode: Studi diagnostik dengan metode cross-sectional dilakukan pada pasien kanker serviks yang datang ke RSUPN Cipto Mangunkusumo pada bulan September 2021 hingga Agustus 2022. Pasien yang didiagnosis kanker serviks yang belum mendapatkan terapi apapun dilakukan biopsi serviks dan pemeriksaan USG dan MRI. Pasien yang tidak dilakukan pemeriksaan USG dan MRI serta biopsi dikeluarkan dari penelitian. Pemeriksaan VEGF dilakukan pada jaringan serviks dan diinterpretasikan menggunakan H-score. Sensitivitas dan spesifisitas pemeriksaan VEGF dan USG dibandingkan dengan hasil MRI.Hasil: Terdapat 65 subjek yang diikutsertakan dalam penelitian (10 subjek stadium awal dan 55 subjek stadium lanjut). Tidak ada perbedaan ekspresi VEGF di antara pasien kanker serviks dihubungkan dengan stadium, tipe histologi, atau ukuran tumor yang berbeda. Ada interreliabilitas minimum antara pemeriksaan VEGF dan MRI. Ada interreliabilitas yang baik antara pemeriksaan USG dan MRI untuk menentukan stadium kanker, invasi parametrium, invasi kelenjar getah bening dan invasi mukosa vesika urinaria dan rektumKesimpulan: Tidak terdapat perbedaan ekspresi VEGF pada pasien kanker serviks dengan karakteristik yang berbeda. Hasil pemeriksaan USG dan MRI sebanding dalam menentukan stadium klinis pada pasien kanker serviks.

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Background: Cervical cancer is one of the most common cancers with a high mortality rate worldwide. Vascular Endothelial Growth Factor (VEGF) is a biomarker that functions as a prognostic factor in cervical cancer. Expression data related to various characteristics of cervical cancer found on the results of Ultrasonography (US) and Magnetic Resonance Imaging (MRI) examinations in cervical cancer patients in Indonesia are still limited.

Purpose: To determine the relationship between VEGF expression levels, ultrasound examination and MRI examination in cervical cancer patients.

Methods: A diagnostic study using the cross-sectional method was conducted on cervical cancer patients who came to Cipto Mangunkusumo General Hospital from September 2021 to August 2022. Patients diagnosed with cervical cancer who had not received any therapy had cervical biopsies and ultrasound and MRI examinations. Patients who did not undergo ultrasound and MRI examinations and biopsies were excluded from the study. VEGF examination was performed on cervical tissue and interpreted using the H-score. The sensitivity and specificity of VEGF and ultrasound examinations were compared with MRI results.

Results: There were 65 subjects enrolled in the study (10 early-stage subjects and 55 advanced-stage subjects). There were no differences in VEGF expression among cervical cancer patients associated with different stages, histological types, or tumor sizes. There is minimal interreliability between VEGF and MRI examinations. There is good interreliability between ultrasound and MRI examinations for determining the stage of cancer, parametrial invasion, lymph node invasion and mucosal invasion of the bladder and rectum.

Conclusions: There are no differences in VEGF expression in cervical cancer patients with different characteristics. The results of ultrasound and MRI examinations are comparable in determining clinical staging in cervical cancer patients."

"Tujuan : Penelitian ini bertujuan membandingkan kadar serum petanda biologik: Interleukin-6, Tumor Necrosis Factor-alpha, Matrix-Metalloproteinase-2 Dan Vascular Endothelial Growth Factor pada endometriosis stadium I-II dan stadium III-IV.Metode : Empat puluh pasien endometriosis yang terdiagnosis berdasarkan laparoskopi diambil sampel serum sebelum operasi untuk pemeriksaan petanda biologik. Pemeriksaan petanda biologik dilakukan di akhir penelitian dengan cara ELISA. Rerata dari kadar serum dilakukan uji T tidak berpasangan. Variabel yang terdapat perbedaan bermakna dilakukan pemeriksaan ROC dan ditentukan titik potong optimal.Hasil : Rerata kadar serum petanda biologik: IL-6, TNF-a, MMP-2 dan VEGF pada subjek dengan stadium endometriosis I-II dan III-IV adalah [1,39 vs 1,33] pg/ml (p>0,05); [1,5 ±0,47 vs 1,49±0,29] pg/ml (p>0,05); [152,04 ± 27,32 vs 140,98 ± 28,08] ng/ml (p>0,05) dan [238,78 vs 426,57] pg/ml (p<0,05). Perbedaan rerata VEGF memiliki nilai AUC 74,5%. Titik potong optimal VEGF ≥ 323,95 pg/ml dengan sensitivitas 71,4% dan spesifisitas 69,2%.Kesimpulan : Kadar serum IL-6, TNF-a dan MMP-2 tidak berbeda bermakna pada perempuan endometriosis stadium I-II dan stadium III-IV. Hanya kadar VEGF yang memiliki perbedaan rerata yang bermakna.

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Purpose : The focus of this study is to compare serum biomarkers of : interleukin-6, tumor necrosis factor-alpha, matrix-metalloproteinase-2 and vascular endothelial growth factor in endometriosis stage I-II and stage III-IV.

Method : Forty endometriosis patient was diagnosed by laparoscopy. Serum sample was taken before the surgery. The serum biomarkers were analyzed with ELISA method at the end of research. Mean of serum biomarkers were tested with unpaired T test. Variable that had significant mean different was thorough ROC measurement and determined the optimal cut of point.

Result : Mean serum biomarkers level of IL-6, TNF-a, MMP-2 and VEGF of endometriosis stage I-II and stage III-IV were [1,39 vs 1,33] pg/ml (p>0,05); [1,5 ±0,47 vs 1,49±0,29] pg/ml (p>0,05); [152,04 ± 27,32 vs 140,98 ± 28,08] ng/ml (p>0,05) and [238,78 vs 426,57] pg/ml (p<0,05). Mean different of VEGF have AUC 74,5%. Optimal cut of point for VEGF ≥ 323,95 pg/ml with sensitivity 71,4% and spesificity 69,2%.

Conclusion : Mean serum level of IL-6, TNF-a and MMP-2 are not different between endometriosis stage I-II and stage III-IV. Only VEGF has significant mean different."

"Latar Belakang: Derajat keparahan karsinoma hepatoselular (KHS) yang dinilai dengan klasifikasi Barcelona Clinic Liver Cancer (BCLC) merupakan faktor prognostik utama KHS. Penilaian kadar serum Vascular Endothelial Growth Factor (VEGF) dianggap dapat mencerminkan tingkat keparahan KHS. Namun, belum ada kesepakatan mengenai hubungan tingkat keparahan KHS dengan kadar serum VEGF. Tujuan : Mengetahui hubungan kadar serum VEGF dengan tingkat keparahan KHS dengan menilai perbedaan rerata kadar serum VEGF pada berbagai tingkat keparahan KHS. Metode : Penelitian ini adalah studi potong lintang untuk menentukan hubungan antara kadar serum VEGF dengan tingkat keparahan KHS berdasarkan klasifikasi BCLC. Penelitian ini dilakukan di Rumah Sakit Cipto Mangunkusumo antara bulan Januari 2015 dan Mei 2015. Uji statistik yang digunakan untuk menilai hubungan kadar serum VEGF dengan klasifikasi BCLC ialah analisis one way ANOVA, dan dilanjutkan dengan analisis post hoc Tukey Schaffe. Hasil : Sebanyak 61 subyek KHS diikutkan dalam penelitian ini. Pada penelitian ini tidak ditemukan subyek dengan BCLC stage 0. Rerata kadar serum VEGF BCLC stage A adalah 288,26±156,6 pg/ml; BCLC stage B: 434±164,8 pg/ml; BCLC stage C: 785,57±194,25 pg/ml; BCLC stage D: 1537,97±660,62 pg/ml. Analisis one way ANOVA menunjukkan perbedaan bermakna (P<0,001) antara kadar serum VEGF dengan tingkat keparahan KHS berdasarkan klasifikasi BCLC. Analisis post hoc dengan Tukey Schaffe menunjukkan adanya perbedaan bermakna antara BCLC stage A dan C (p<0,05) serta BCLC stage A dan D (p< 0.001), BCLC stage B dan D (p<0.001), dan BCLC stage C dan D (p<0.001). Tidak ditemukan perbedaan bermakna antara subyek dengan BCLC stage A dan B, dan antara BCLC stage B dan C. Kesimpulan : Didapatkan kadar serum VEGF yang meningkat sesuai dengan tingkat keparahan KHS berdasarkan klasifikasi BCLC terutama untuk BCLC stage B ke atas.

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Background : The severity of Hepatocellular Carcinoma (HCC) stratified by Barcelona Clinic Liver Cancer (BCLC) staging classification has been one of the main prognostic factors of patients with HCC. Serum vascular endothelial growth factor (VEGF) examination can be reflect to predict the severity of HCC. Although, there is no consensus among experts about the severity of HCC staging and serum VEGF levels.

Aim : To determine the association between serum VEGF levels and severity of HCC.

Methods : A cross-sectional study to determine the association between serum VEGF levels and the severity of HCC stratified by BCLC staging classification. The study was conducted at Cipto Mangunkusumo Hospital between January 2015 and May 2015. One way ANOVA analysis was used to assess the association between serum VEGF levels and BCLC classification staging. Post hoc analysis will be done using Tukey Schaffe test.

Results: There were 61 HCC subjects included to this study. There were no subjects with BCLC stage 0. The mean VEGF serum level in patients with BCLC stage A was 288.26 ± 156.6 pg / ml; BCLC stage B: 434 ± 164.8 pg / ml; BCLC stage C: 785.57 ± 194.25 pg/ml; and BCLC stage D: 1537.97 ± 660.62 pg/ml. One way ANOVA showed significant statistical difference (P <0.001) between mean serum VEGF levels and the severity in all BCLC stages. Post hoc analysis using Tukey Schaffe test showed significant stastical difference between BCLC stage A and C (p<0.05), BCLC stage A and D (p<0.001), BCLC stage B and D (p<0.001), and BCLC stage C and D (p<0.001). There were no significant statistical differences between patients with BCLC stage A and B, and between BCLC stage B and C.

Conclusion: We found that increased levels of serum VEGF were associated with the severity of HCC based on BCLC staging classification, especially in patients with BCLC stage B and upwards."

"Luka diabetes merupakan komplikasi mikrovaskular yang sering dikeluhkan oleh pasien diabetes melitus (DM) tipe 2. Vaskularisasi berperan penting dalam penyembuhan luka, yang aktivitasnya diperantarai aktivitas hypoxia-inducible factor 1-alpha (HIF-1α) dan vascular endothelial growth factor (VEGF). Belum ada studi klinis yang mengevaluasi aktivitas HIF-1α dan VEGF pada manusia, khususnya pasien DM tipe 2 yang mengalami luka kaki diabetes. Tujuan penelitian adalah untuk mengevaluasi vaskularisasi jaringan, HIF-1α, dan VEGF pada luka kaki diabetes yang menjalani amputasi dan non-amputasi.Studi potong lintang dilakukan di Rumah Sakit Umum Pusat Nasional dr. Cipto Mangunkusumo (RSCM) pada tahun 2020–2021. Subjek penelitian adalah pasien luka kaki diabetik yang dilakukan debridemen/amputasi. Kemudian diambil jaringan viabel tepi luka untuk diperiksa vaskularisasi jaringan (densitas mikrovaskular), ekspresi VEGF, serta area granulasi, di Departemen Patologi Anatomi FKUI-RSCM. Konsentrasi HIF-1α jaringan dikuantifikasi di Departemen Biokimia dan Biologi Molekuler FKUI-RSCM. Data numerik yang diperoleh diuji normalitasnya dengan uji Saphiro-Wilk. Data distribusi normal dianalisis dengan uji t tidak berpasangan. Dilakukan uji regresi logistik bila terdapat > 2 variabel independen dengan nilai p < 0,25.Dari 67 subjek terdapat 30 pasien amputasi dan 34 pasien debridemen yang dianalisis. Proporsi subjek laki-laki pada kelompok amputasi lebih tinggi dibandingkan kelompok debridemen (p = 0,041). Tidak terdapat perbedaan bermakna pada status gizi, usia, kejadian hipertensi, gagal ginjal, dan status merokok antar kedua kelompok. Profil glikemik, hematologi rutin, penanda inflamasi, kadar elektrolit, penanda fungsi hati, fungsi ginjal tidak berhubungan dengan tindakan pasien, kecuali kadar albumin. Pada analisis bivariat, kadar albumin lebih tinggi pada kelompok debridemen 2,53/0,49 dibandingkan amputasi 2,94/0,51, p = 0,002. Kelompok amputasi memiliki nilai median HIF-1α 5,77 (0,55–53,47) pg/mg protein yang jauh lebih rendah dibandingkan kelompok debridemen 26,56 (2,23–211,12) pg/mg protein (p = 0,001). Hal serupa juga ditemukan pada nilai VEGF (p < 0,001). Pasien dengan HIF-1α < 8,8065 pg/mg protein, MVD < 68,7%, VEGF < 30,443%, dan area granulasi < 33,2802% memiliki aOR 11,116 (IK 95% 1,441–85,752), 10,934 (IK 95% 1,604–74,55), 7,973 (IK 95% 1,301–48,86), 15,589 (IK 95% 1,39–174,867) untuk mengalami amputasi. Kepadatan mikrovaskular, konsentrasi HIF-1α, ekspresi VEGF, dan area jaringan granulasi lebih banyak pada pasien non-amputasi. Pasien dengan penurunan jumlah parameter tersebut memiliki risiko lebih tinggi untuk mendapat tindakan amputasi.

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Diabetic wounds are microvascular complications often complained by people with type 2 diabetes mellitus (DM). Tissue vascularization plays an essential role in wound healing, whose activity is mediated by the activity of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). However, no clinical studies evaluate its activity in humans, especially in type 2 diabetes mellitus patients who have diabetic foot ulcers. This study attempts to evaluate whether there are differences in tissue vascularization, HIF-1 α, and VEGF in diabetic foot wounds that received amputation and non-amputation procedures.

A cross-sectional study was conducted at the Cipto Mangunkusumo National Central General Hospital (RSCM) in 2020–2021. Diabetic foot wound patients who received debridement/amputation were included in this study. Viable tissue at the wound edges was taken. The expression of VEGF, microvascular density, and area of granulated tissue were evaluated in the Department of Pathology and Anatomy, FKUI-RSCM. HIF-1 levels in tissue were quantified at the Department of Biochemistry and Molecular Biology FKUI-RSCM. All numerical data were tested for normality by the Shapiro-Wilk test. Variables with normally distributed data were analyzed by unpaired t-test. A logistic regression test was performed if there were more than two independent variables with a p-value < 0.25.

This study included 67 patients. There were 30 amputees, and 34 debridement patients included in the data analysis. The proportion of male patients in the amputation group was found to be higher than the debridement group (p = 0.041). There were no differences in nutritional status, age, the incidence of hypertension, kidney failure, and smoking status between the two groups. The glycemic profile, routine haematological findings, markers of inflammation, electrolyte levels, markers of liver function, and markers of kidney function were not found to be related to the patient's condition, except for albumin levels. In bivariate analysis, albumin levels were found to be higher in the debridement group [2.53 (0.49)] than in the amputee [2.94 (0.51)], p = 0.002. The amputee group had a median HIF-1α value of 5,77 (0,55–53,47) pg/mg protein, which was much lower than the debridement group of 26,56 (2,23–211,12) pg/mg protein (p = 0.001). Similar condition was also found in the VEGF value (p < 0.001). Patients with HIF-1α < 8.8065 pg/mg protein, MVD < 68.7%, VEGF < 30.443%, and granulation area < 33.2802% had risk odds of 11.116 (95% CI 1.441–85.752), 10.934 (95% CI 1.604–74.55), 7,973 (95% CI 1.301–48.86), 15.589 (95% CI 1.39–174.867) for amputation. Microvascular density, HIF-1α levels, VEGF expression, and granulation tissue area were higher in non-amputated patients. Patients with a decrease in these parameters have a higher risk of amputation."

"Pendahuluan: Sekretom sel punca mesenkimal dipercaya mengandung faktor pertumbuhan yang bekerja melalui mekanisme parakrin di situs cedera. Di antara banyaknya faktor-faktor pertumbuhan, beberapa disinyalir memiliki efek osteogenik antara lain bone morphogenetic protein-2 (BMP-2), epidermal growth factor (EGF), dan vascular endothelial growth factor (VEGF).Tujuan: Tujuan penelitian ini adalah untuk mengidentifikasi kuantitas BMP-2, EGF dan VEGF pada sekretom sel punca mesenkimal jaringan adiposa dan tali pusat.Metode: Sampel sekretom dari sel punca mesenkimal jaringan adiposa dan tali pusat dibedakan berdasarkan perlakuan pemberian serum atau non serum dan waktu pengambilan saat penggantian medium terakhir atau saat panen, dan dianalisa dengan metode ELISA sandwich assay menggunakan Human BMP-2, VEGF, and EGF ELISA Kits.Hasil: Sebaran nilai BMP-2 tersentrasi pada nilai 0 pada sekretom jaringan adiposa maupun tali pusat. Kadar EGF dan VEGF memiliki perbedaan bermakna pada sampel jaringan adiposa yang berbeda (p<0,009 dan p<0,005). Kadar EGF dan VEGF pada jaringan adiposa adalah 2,67 (0-22,53) dan 1473,5 (136,1-5335) sedangkan pada jaringan tali pusat adalah 2,67 (0-13,29) dan 0 (0-1675).Kesimpulan: Sekretom jaringan adiposa dan tali pusat kemungkinan hanya mengandung BMP-2 dalam nilai yang sangat rendah. Baik jaringan adiposa maupun jaringan tali pusat mengandung EGF dalam jumlah yang moderat. Kadar VEGF pada jaringan adiposa secara signifikan lebih tinggi.

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Background: The secretome derived from mesenchymal stem cells has been suggested contain growth factors that works via a paracrine mechanism in the injured area. Of these factors, some are thought to have an osteogenic effect, including bone morphogenetic protein-2 (BMP-2), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF).

Objective: The aim of this study is to identify the quantity of BMP-2, EGF, VEGF in secretome from adipose tissue (AT-MSC) and umbilical cord-derived mesenchymal stem cells (UC-MSC).

Methods: Secretome samples from AT-MSC and UC-MSC were grouped based on serum administration and harvesting time, and were analyzed with an ELISA sandwich assay method using Human BMP-2, VEGF, and EGF ELISA Kits. This study aims to identify whether BMP-2 is contained in the secretome of AT-MSC and UC-MSC, which has never been reported before, and to measure the level of EGF and VEGF within the secretome.

Results: The distribution of value for BMP-2 was nearly zero in the secretome of AT-MSC and UC-MSC. The level of EGF and VEGF were significantly different between different donor samples of AT-MSC (p<0,009 and p<0,005). The level of EGF and VEGF of AT-MSC are 2,67 (0-22,53) and 1473,5 (136,1-5335) compare to 2,67 (0-13,29) and 0 (0-1675) of UC-MSC.

Conclusion: The secretome of AT-MSC and UC-MSC may contain BMP-2 in a very low level. Both AT-MSC and UC-MSC contain EGF in moderate amount. VEGF is significantly higher in of AT-MSC."

"ABSTRAKLatar Belakang. Tindakan pembedahan radikal pada pasien dengan kanker seringkali menyebabkan komplikasi limfedema. Limfedema dapat diatasi dengan operasi transfer jaringan atau rekonstruksi limfatik. Penelitian ini bertujuan untuk membuktikan adanya pembentukan pembuluh limfe baru dengan penambahan flap jaringan pasca diseksi kelenjar limfe, dilihat dari peningkatan ekspresi VEGF-C, infiltrasi makrofag, dan pembentukan fibrosis.Metode. Penelitian ini merupakan penelitian eksperimental pada 20 ekor tikus Sprague Clawley jantan berumur 8-12 minggu, yang dibagi rata kedalam tiap kelompok perlakuan, di Animal House Skill Lab Fakultas Kedokteran Universitas Indonesia pada Januari-Maret 2018. Tiap tikus akan menjalani diseksi, kemudian diacak untuk menerima flap jaringan maupun hanya diseksi inguinal, dan dievaluasi setelah 2 bulan. Pemeriksaan histopatologi dilakukan pada akhir penelitian untuk menilai pembentukan fibrosis dan dilanjutkan pemeriksaan immunohistokimia. Analisis data dilakukan dengan program SPSS 20.0.Hasil. Sebanyak 8 tikus 88.9 yang menerima flap jaringan menunjukkan hasil positif pada tes methylene blue dibandingkan 2 tikus 22.2 pada kelompok kontrol p < 0.05 . Pada 18 tikus tersebut, pewarnaan HE juga menunjukkan adanya pembentukan jaringan ikat pembuluh yang lebih lebar pada tikus yang diberi perlakuan, meski tidak signifikan secara statistik. Pemeriksaan immunohistokimia juga menunjukkan ekspresi VEGF-C yang lebih jelas dengan dominasi warna coklat pada tikus perlakuan p < 0.05 . Ekspresi protein CD68 juga lebih jelas pada tikus perlakuan meski perbedaannya tidak signifikan.Kesimpulan. Penambahan flap jaringan dapat membantu memperbaiki aliran limfa yang dibuktikan dengan peningkatan aliran limfe dan ekspresi VEGF-C.

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ABSTRACT

Background. Radical surgeries for patients with cancer often cause lymphedema complications. Lymphedema may be solved with tissue transfer or lymphatic reconstruction surgery. This research aims to prove new formations of lymphatic vessels by the addition of tissue flap post dissection of lymphatic vessels, marked by increased expression of VEGF-C, macrophage infiltration, and fibrosis formation.Methods. This is an experimental study on 20 male Sprague Clawley mice aged 8-12 weeks, divided evenly for each experiment group, at Animal House Skill Lab Faculty of Medicine Universitas Indonesia from January-March 2018. Each mouse underwent dissection, randomized for flap addition or only inguinal dissection, and evaluated after 2 months. Histopathologic assessment was conducted at the end of study period to evaluate fibrosis formation and followed by immunohistochemistry analysis. Data analysis was conducted with statistical program SPSS 20.0Results. 8 mice 88.9 , which received tissue flap showed positive results on methylene blue test compared to 2 mice 22.2 from control group p < 0.05 . From the 18 mice, HE staining also showed wider formation of lymphatic connective tissue on flap-receiver mice, although it was not statistically significant. Immunohistochemistry analysis also showed clearer VEGF-C formation showed by brown coloration in flap-receiver mice p < 0.05 . Expression of CD68 protein was also clearer in flap-receiver mice although the difference was not significant.Conclusion. Addition of tissue flap may help improve lymphatic circulation proven by increased lymphatic circulation and VEGF-C expression."

"Kanker kolorektal merupakan kanker penyebab kematian kedua tertinggi di dunia. Pengobatan kanker kolorektal memiliki kelemahan dari segi biaya, toksisitas, dan efektivitas. Lunasin mampu menghambat kanker secara in vitro sehingga lunasin dapat menjadi solusi terapi yang efektif biaya untuk kanker kolorektal. Penelitian ini menyelidiki pengaruh ekstrak kedelai kaya lunasin (EKKL) pada ekspresi vascular endothelial growth factor (VEGF) yang berperan dalam proses angiogenesis pada kanker kolorektal. Tiga puluh mencit Swiss Webster dibagi menjadi enam kelompok. Semua kelompok kecuali kelompok normal diinduksi dengan azoxymethane (AOM) dan dextran sodium sulfate (DSS). Kelompok kontrol negatif diberikan larutan garam fisiologis, sedangkan kelompok kontrol positif diberi aspirin. EKKL diberikan kepada ketiga kelompok percobaan dengan dosis yang berbeda (250 mg/KgBB, 300 mg/KgBB, dan 350 mg/KgBB). Pada minggu kelima, setelah mencit diterminasi, jaringan kolon distal mencit diambil dan diwarnai imunohistokimia, kemudian diamati di bawah mikroskop dan dianalisis menggunakan IHC profiler pada ImageJ. Indeks yang diperoleh dari IHC profiler dihitung untuk mendapatkan indeks H-score. Ekspresi VEGF menurun secara signifikan pada kelompok EKKL dosis 300 mg/KgBB (p=0,031) dengan penurunan rata-rata skor 33,202% dan 350 mg/KgBB (p=0,003) dengan penurunan rata-rata skor 43,334%. Namun, tidak ditemukan adanya perbedaan yang signifikan secara statistik antara kedua kelompok tersebut.

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Colorectal cancer is the world’s second highest cause of cancer death. Current treatments for colorectal cancer lack in cost, toxicity, and effectivity. Lunasin has the effect of inhibiting cancer in vitro, hence lunasin might offer the solution of cost-effective therapy for colorectal cancer. We investigate the effect of lunasin-rich soybean extract (LSRE) on vascular endothelial growth factor (VEGF) expression which is responsible for angiogenesis in colorectal cancer. Thirty Swiss Webster mice were divided into six groups. All groups except the normal group were induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). Negative control group received normal saline solution, whereas positive control group were treated with aspirin. LSRE were given to three experimental groups, each with different dosing (250 mg/KgBW, 300 mg/KgBW, and 350 mg/KgBW). On the fifth week, after the mice were terminated, the distal colon tissues were obtained and received immunohistochemistry staining, then observed under a microscope and analyzed using IHC profiler in ImageJ. Index acquired from IHC profiler were calculated to achieve H-score. VEGF expression was significantly decreased in 300 mg/KgBW (p=0.031) and 350 mg/KgBW (p=0.003) of EKKL by an average reduction of 33.202% and 43.334% respectively. However, there was no statistically significant difference between both groups."