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"ABSTRAKMenurut Jakarta Cancer Registry tahun 2012, kanker kolorektal merupakan kanker terbanyak kedua pada laki-laki dan terbanyak keempat pada perempuan di Indonesia. Pemeriksaan skrining kanker kolorektal yang saat ini tersedia memiliki berbagai keterbatasan. Matrix metalloproteinase-9 (MMP-9) adalah endopeptidase yang berperan dalam degradasi matriks ekstraseluler, dan disekresi oleh berbagai sel seperti sel tumor, sel radang, dan fibroblas. Penelitian ini bertujuan untuk mengetahui peran diagnostik MMP-9 feses dibandingkan dengan gambaran histopatologi sebagai baku emas. Desain penelitian adalah potong lintang. Penelitian dilakukan terhadap 52 subjek terduga kanker kolorektal yang menjalani kolonoskopi. Kadar MMP-9 feses diperiksa menggunakan kit MMP-9 dari R&D Systems dengan metode ELISA. Akurasi diagnostik kadar MMP-9 feses sebesar 0,855. Titik potong kadar MMP-9 feses didapatkan 1,237 ng/ml dengan sensitivitas 88,9%, spesifisitas 76,7%, nilai prediksi positif 44,4%, dan nilai prediksi negatif 97,1%. Pemeriksaan kadar MMP-9 feses dapat dipertimbangkan dalam skrining kanker kolorektal.

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ABSTRACT

According to Jakarta Cancer Registry 2012, colorectal cancer is the second most common cancer in men and fourth in women in Indonesia. Colorectal cancer screening tests currently available, have various limitations. Matrix metalloproteinase-9 (MMP-9) is endopeptidase which plays a role in the degradation of the extracellular matrix, and is secreted by various cells such as tumor cells, inflammatory cells, and fibroblasts. This is a cross sectional study aims to determine the diagnostic role of faecal MMP-9 compared to histopathological features as gold standard. The study was conducted on 52 subjects with suspected colorectal cancers who underwent colonoscopy. The levels of faecal MMP-9 were examined using MMP-9 kit from R&D Systems using ELISA method. Diagnostic accuracy of faecal MMP-9 levels is 0.855. The cutoff point was 1.237 ng/ml with sensitivity of 88.9%, specificity of 76.7%, positive predictive value of 44.4%, and negative predictive value of 97.1%. Faecal MMP-9 can be considered as a screening test in colorectal cancer."

"Infeksi virus hepatitis B (VHB) merupakan masalah kesehatan global. Terapi yang ada saat ini hanya berdampak minimal terhadap covalently closed circular deoxyribonucleic acid (cccDNA), sehingga eradikasi sulit dicapai. Matriks Metaloproteinase-9 (MMP-9) berperan dalam meningkatkan replikasi VHB, namun belum ada penelitian yang mengevaluasi peran penghambat MMP-9 terhadap replikasi VHB. Kultur primer hepatosit diperoleh dari Tupaia javanica dan diinfeksi dengan VHB manusia, kemudian dibagi menjadi dua kelompok, yaitu kontrol dan intervensi. Kelompok intervensi diberikan penghambat MMP-9 dosis 1 nM, 3 nM, dan 7 nM. Peripheral blood mononuclear cells (PBMC) manusia diperoleh dari pasien hepatitis B kronik, kemudian dibagi menjadi dua kelompok, yaitu kontrol dan intervensi. Kelompok intervensi diberikan penghambat MMP-9 dosis 3 nM. Dilakukan pengukuran HBsAg, DNA VHB, cccDNA, MMP-9, type-1 IFN receptor 1 (IFNAR1), dan interferon-β (IFN-β) sebelum dan 72 jam setelah pemberian intervensi pada kedua kelompok. Pada kultur primer hepatosit T. javanica yang diinfeksi VHB manusia, pemberian penghambat MMP-9 dosis 1 nM, 3 nM, dan 7 nM secara konsisten menurunkan kadar HBsAg, DNA VHB, cccDNA, dan MMP-9. Dosis 3 nM meningkatkan kadar IFNAR1, sedangkan dosis 7 nM meningkatkan kadar IFN-β. Dosis 3 nM menunjukkan efek yang lebih optimal dibandingkan dosis lainnya. Pada PBMC manusia dengan infeksi VHB, pemberian penghambat MMP- 9 dosis 3 nM menurunkan kadar HBsAg, DNA VHB, cccDNA, dan MMP- 9, serta meningkatkan kadar IFN-β, namun menurunkan kadar IFNAR1. Studi ini menunjukkan bahwa pemberian penghambat MMP-9 dapat menurunkan kadar HBsAg, DNA VHB, cccDNA, dan MMP-9, serta meningkatkan kadar IFN-β pada kultur primer hepatosit T. javanica dan PBMC manusia.

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Hepatitis B virus (HBV) infection remains a significant global health concern. Current therapies have minimal impact on covalently closed circular deoxyribonucleic acid (cccDNA), making HBV eradication difficult. Matrix Metalloproteinase-9 (MMP-9) enhance HBV replication, but its inhibition has not been studied. Primary hepatocyte cultures were obtained from Tupaia javanica and infected with human HBV, then divided into control and intervention groups. The intervention groups were treated with MMP-9 inhibitors at doses of 1 nM, 3 nM, and 7 nM. Human peripheral blood mononuclear cells (PBMC) were isolated from chronic hepatitis B patients and divided into control and intervention groups. The intervention groups received MMP-9 inhibitors at dose of 3 nM. Measurements of HBsAg, HBV DNA, cccDNA, MMP-9, type-1 IFN receptor 1 (IFNAR1), and interferon-β (IFN-β) were performed before and 72 hours after intervention in both groups. In T. javanica primary hepatocyte culture infected with human HBV, MMP-9 inhibitors at doses of 1 nM, 3 nM, and 7 nM consistently decreased levels of HBsAg, HBV DNA, cccDNA, and MMP-9. The 3 nM dose increased IFNAR1 levels, while the 7 nM dose increased IFN-β levels. The 3 nM dose demonstrated the most optimal effects. In human PBMC with HBV infection, MMP-9 inhibitor at dose of 3 nM decreased levels of HBsAg, HBV DNA, cccDNA, MMP-9, increased IFN-β levels, but reduced IFNAR1 levels. This study shows that administration of MMP-9 inhibitors reduced levels of HBsAg, HBV DNA, cccDNA, and MMP-9, while increased IFN-β levels in T. javanica primary hepatocyte cultures and human PBMC."

"Kanker kolorektal adalah kanker yang terletak pada rektum atau kolon dengan sel-sel yang berkembang dengan tidak terkendali. Obat kanker untuk kanker kolorektal memiliki beberapa kelemahan seperti kurangnya spesifitas dan dapat terjadinya resistensi, sehingga perlu dikembangkan terapi target untuk mengurangi kelemahan tersebut. Berbagai penelitian dilakukan untuk merancang obat yang dapat mentarget protein yang berkaitan dengan perkembangan kanker kolorektal, salah satunya adalah Matrix Metalloproteinase-9. Penghambatan dari protein tersebut memungkinkan untuk menghambat penyebaran kanker, sehingga pencarian senyawa penghambat Matrix Metalloproteinase-9 menarik untuk dilakukan. Penelitian dapat dilakukan dengan memanfaatkan metode penapisan virtual. Tujuan dari penelitian ini adalah mendapatkan 10 senyawa kandidat dengan potensi menjadi inhibitor Matrix Metalloproteinase-9. Penapisan virtual dapat digunakan untuk melakukan pencarian senyawa kandidat inhibitor dari basis data HerbalDB. Berdasarkan hasil penapisan didapatkan 10 peringkat senyawa terbaik berdasarkan energi ikatan bebas dan pose pengikatan yaitu Cassiamin C (-11,1 kkal/mol), Sikloartokarpesin (-10,9 kkal/mol), Prunin 6”-p-kumarat (-10,9 kkal/mol), Isookaninrhamnosida (-10,5 kkal/mol), 5,7,3',4'-tetrahidroksiflavanon 7-alfa-l-arabinofuranosil-(1-6)-glukosida (-10,3 kkal/mol), Kuwanon T (-10,3 kkal/mol), Boesenbergin B (-10,2 kkal/mol), Sianidin 3-arabinosida (-10,2 kkal/mol), Morusin (-10,2 kkal/mol), dan Dehidropipernonalin (-10,1 kkal/mol). Hasil tersebut menunjukkan senyawa memiliki potensi untuk menghambat Matrix Metalloproteinase-9

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Colorectal Cancer is located on the colon or the rectum of the patient with uncontrolled cell growth. Cancer drugs for colorectal cancer have several weaknesses such as lack of specificity, so it is necessary to develop targeted therapies to reduce these weaknesses. Various research were done to design a drug with purpose of targeting the protein in which is related to the growth of colorectal cancer, one of them being Matrix Metalloproteinase-9. Inhibition of Matrix Metalloproteinase-9 possibly inhibits the spread of colorectal cancer, therefore a research to find candidates is appealing. Research can be done by using the virtual screening method. The purpose of this study is to obtain 10 candidate compounds with the potential to inhibit Matrix Metalloproteinase-9. Virtual screening method is used to search for candidate compounds from HerbalDB database. Based on the screening results, the best compound rankings based on the free bond energy and binding pose were obtained, namely Cassiamin C (-11,1 kkal/mol), Cycloartocarpesin (-10,9 kkal/mol), Prunin 6”-p-coumarate (-10,9 kkal/mol), Isookaninrhamnoside (-10,5 kkal/mol), 5,7,3',4'-tetrahydroxyflavanone 7-alpha-l-arabinofuranosyl-(1-6)-glucoside (-10,3 kkal/mol), Kuwanon T (-10,3 kkal/mol), Boesenbergin B (-10,2 kkal/mol), Cyanidin 3-arabinoside (-10,2 kkal/mol), Morusin (-10,2 kkal/mol), dan Dehydropipernonaline (-10,1 kkal/mol). The results indicate potential candidates to inhibit Matrix Metalloproteinase-9."

"Latar Belakang: Karsinoma sel skuamosa laring (KSSL) dengan metastasis ke kelenjar getah bening (KGB) leher memiliki angka kelangsungan hidup 5 tahun kurang dari 50%. Banyak penelitian menunjukkan bahwa MMP-9 dan CCR7 berhubungan dengan metastasis ke KGB leher. Overekspresi MMP-9 dan CCR7 berhubungan dengan sifat sel tumor yang lebih agresif dan prognosis yang lebih buruk dikarenakan cenderung bermetastasis ke KGB leher. Tujuan: Penelitian ini bertujuan untuk mengetahui perbedaan ekspresi MMP-9 dan CCR7 pada KSSL yang bermetastasis dan tidak metastasis ke KGB leher. Metode: Penelitian analitik observasional dengan desain potong lintang pada sediaan operasi laringektomi parsial maupun total dengan diseksi leher di RSCM periode Desember 2017 sampai Desember 2019. Sampel penelitian dibagi menjadi 2 kelompok, yaitu KSSL dengan metastasis KGB leher dan tanpa metastasis. Pengambilan sampel penelitian dilakukan secara konsekutif dari kasus yang memenuhi kriteria inklusi dan eksklusi sesuai perhitungan besar sampel untuk masing-masing kelompok. Pemeriksaan imunohistokimia menggunakan antibodi primer MMP-9 dan CCR7. Data imunoekspresi dianalisis untuk mengetahui hubungannya dengan terjadinya metastasis ke KGB leher. Hasil: Kejadian metastasis KSSL ke KGB leher berhubungan dengan ekspresi MMP-9 (P<0,05). Ditemukan ekspresi MMP-9 yang tinggi pada KSSL-M sebesar 41,7% sedangkan KSSL-NM 8,3%. Ekspresi CCR7 juga berkorelasi dengan metastasis KSSL ke KGB leher (P<0,05), ekspresi CCR7 yang tinggi pada KSSL-M sebanyak 48,3% sedangkan KSSL-NM hanya 10%. Ditemukan pula hubungan antara ekspresi MMP-9 dan CCR7 dengan terjadinya metastasis KSSL ke KGB (p=0,001). Kesimpulan: Metastasis KSSL ke KGB berhubungan dengan ekspresi MMP-9 dan CCR7. Terdapat adanya hubungan antara ekspresi MMP-9 dan CCR7 pada kejadian metastasis KSSL ke KGB leher.

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Background: Laryngeal squamous cell carcinoma (LSCC) with metastasis to the lymph nodes of the neck has a 5-year survival rate of less than 50%. Many studies have shown that MMP-9 and CCR7 are associated with metastasis to cervical lymph nodes. Overexpression of MMP-9 and CCR7 are associated with a more aggressive cell tumour and poor prognosis because they are more likely to metastasis to cervical lymph nodes.

Purpose: This study aims to determine the expression of MMP-9 and CCR7 in metastasis and non-metastatis KSSL to cervical lymph nodes.

Methodology: An observational analytic study with a cross-sectional design on partial and total laryngectomy surgery preparations with neck dissection at RSCM for the period December 2017 to December 2019. The study sample was divided into 2 groups, namely KSSL with cervical lymph nodes metastasis and without metastasis. The research sample was taken by consecutive sampling from cases that met the inclusion and exclusion criteria according to the calculation of the sample for each group. Immunohistochemical examination using primary antibodies MMP-9 and CCR7. Immunoexpression data were analyzed to determine their relationship with metastasis to cervical lymph nodes.

Results: The incidence of SCC metastases to cervical lymph nodes was associated with MMP-9 expression (P<0.05). High MMP-9 expression was found in KSSL-M by 41.7% while in KSSL-NM 8.3%. CCR7 expression also correlated with KSSL metastases to cervical lymph nodes (P<0.05), high CCR7 expression in KSSL-M was 48.3% while KSSL-NM was only 10%. It was also found that there was a relationship between the expression of MMP-9 and CCR7 with the occurrence of SLCC to lymph node metastasis (p=0.001).

Conclusion: Metastasis SLCC to lymph node was associated with MMP-9 and CCR7 expression. There is a relationship between the expression of MMP-9 and CCR7 in the incidence of SCC metastases to cervical lymph nodes."