Andhika Rachman

Antibodies against dengue virus nonstructural protein-1 induce heme oxygenase-1 via a redox-dependent pathway in human endothelial cells

Heme oxygenase (HO)-1, the inducible isoform of the first and rate-limiting enzyme of heme degradation, affords anti-inflammatory protection via its cell-type-specific effects in endothelial cells (ECs). In dengue hemorrhagic fever (DHF), which is the life-threatening form of dengue virus (DV) infection, endothelial interactions of cross-reactive antibodies against the DV nonstructural glycoprotein-1 (NS1) are associated with endothelial dysfunction. In this study, we investigated whether anti-NS1 antibodies might regulate HO-1 gene expression in human ECs. Serum from DHF patients with high anti-NS1 titers and a monoclonal anti-NS1 antibody upregulated HO-1 gene expression in human umbilical vein ECs, which was blocked by purified NS1 antigen. Immunoprecipitation studies showed that anti-NS1 antibodies specifically bound to the oxidoreductase protein disulfide isomerase (PDI) on ECs. Moreover, anti-NS1-mediated HO-1 induction was reduced by inhibition of PDI enzyme activity. Reactive oxygen species, which were generated by NADPH oxidase and in turn activated the phosphatidylinositol 3-kinase (PI3K)/Akt cascade, were involved in this upregulation of HO-1 gene expression. Finally, apoptosis of ECs caused by anti-NS1 antibodies was increased by pharmacological inhibition of HO-1 enzyme activity. In conclusion, HO-1 gene expression is upregulated by anti-NS1 antibodies via activation of a redox-dependent PDI/PI3K/Akt-mediated pathway in human ECs.

Nimotuzumab combined with radiotherapy reduces primary tumor and nodal volume in advanced undifferentiated nasopharyngeal carcinoma

Aim:  A high expression of epidermal growth factor receptor (EGFR) is found in most human epithelial tumors, including nasopharyngeal carcinomas (NPC). The overexpression of EGFR has been shown to play an influential role in tumorigenesis and the progression of malignant tumors. Therefore, blocking EGFR might be a potential targeted treatment for NPC. Nimotuzumab is an anti‐EGFR monoclonal antibody that exhibits remarkable anti‐proliferative, anti‐angiogenic, and pro‐apoptotic effects.

Association of Peripheral Monocyte Count with Soluble P-Selectin and Advanced Stages in Nasopharyngeal Carcinoma

Introduction Inflammation is widely recognized to play an important role in cancer progression and is related to thrombosis. Soluble P-selectin (sP-selectin) is one of several biomarkers that may be predictive of thrombosis in cancer. This study aimed to investigate the correlation between monocyte count and sP-selectin in various stages of nasopharyngeal carcinoma. Methods Fifty-five patients with nasopharyngeal carcinoma were divided into three groups according to nodal and distant metastasis (group of stages I-IVA, IVB, and IVC). Monocyte count was calculated from routine peripheral blood examination, while sP-selectin level was measured using commercial ELISA kit. Results The monocyte count of subjects in groups IVB and IVC was significantly higher compared to group I-IVA (707/μL versus 528/μL, p = 0.022; 841/μL versus 528/μL, p = 0.005). Plasma levels of sP-selectin in group IVC were higher than group I-IVA (59.5 ng/mL versus 41.97 ng/mL, p = 0.001) and group IVB (59.5 ng/mL versus 45.53 ng/mL, p = 0.007). In subjects with high monocyte count (>665/μL), there was moderate correlation between monocyte count and sP-selectin (r = 0.436, p = 0.022). Conclusion Advanced stages of nasopharyngeal carcinoma had higher levels of monocyte count and sP-selectin compared to earlier stages. Monocyte count was correlated with sP-selectin especially in high monocyte count subgroup.

Perbandingan Kadar Soluble Platelet-Selectin pada Berbagai Stadium Karsinoma Nasofaring Dan Korelasinya Dengan Hitung Trombosit

Pendahuluan . Karsinoma nasofaring (KNF) merupakan jenis keganasan yang unik dengan distribusi geografis dan etnis tertentu. Daerah Cina Selatan dan Asia Tenggara memiliki insidens kejadian yang tinggi. Indonesia memiliki insidens 5,66 kasus per 100.000 penduduk per tahun. Salah satu penyebab kematian pada pasien dengan keganasan adalah trombosis. Kadar soluble Platelet-selectin ( sP-selectin ) yang tinggi dalam plasma, hasil dari aktivasi sel-sel endotel dan trombosit, adalah salah satu prediktor kejadian trombosis. Penelitian ini bertujuan untuk mengetahui kadar sP-selectin pada berbagai stadium karsinoma nasofaring dan korelasinya dengan hitung trombosit. Metode . Dilakukan studi potong lintang pada 60 kasus karsinoma nasofaring yang baru terdiagnosis di Rumah Sakit Cipto Mangunkusumo pada periode Maret hingga November 2012. Kadar sP-selectin pada berbagai stadium yang diukur dengan teknik Enzyme Linked Immunosorbent Assay akan dibandingkan dan dikorelasikan dengan hitung trombosit. Hasil . Dari 60 pasien KNF didapatkan rerata usia 43,9 tahun. Rasio laki-laki dengan perempuan 3:1 dan jenis patologi terbanyak adalah karsinoma tidak berdiferensiasi (83,3%). Sepuluh persen pasien mengalami trombositosis. Median kadar sP-selectin adalah 45,73 ng/mL dengan rentang interkuartil: 42,02-57,66 ng/mL. Secara statistik terdapat perbedaan kadar sP-selectin diantara stadium IVC dengan stadium lainnya (stadium IVB, p = 0,001 dan kelompok stadium I-IVA, p < 0,001). Hitung trombosit tidak berkorelasi dengan sP-selectin (r: 0,185; p = 0,158) pada karsinoma nasofaring. Simpulan . Terdapat perbedaan kadar sP-selectin pada berbagai stadium karsinoma nasofaring. Hitung trombosit tidak berkorelasi dengan kadar sP-selectin .