Clinical effects of dupilumab: A novel treatment for Kimura disease.

BACKGROUND: Kimura disease (KD) is a rare chronic inflammatory disorder involving the Th2 pathway. Although medical treatment with steroids or other immunosuppressants is available, they may cause developmental issues in the pediatric population. Surgical intervention has also been suggested; however, it is associated with high recurrence rates. CASE PRESENTATION: A 14-year-old boy presented with left retroauricular lymph node enlargement at the age of 5 years. At the age of 7 years, he was diagnosed with nephrotic syndrome which subsided after steroid treatment for approximately 6 years. The retroauricular lymph node was surgically excised, and KD was confirmed. However, recurrent enlargement of the left retroauricular and neck lymph nodes occurred after 2 years. Persistently high IgE levels and fluctuating eosinophil counts were observed following steroid treatment. Dupilumab was prescribed because of the difficulty in tapering the steroid dosage. A loading dose of 600 mg was administered, followed by a maintenance dose of 300 mg every 2 weeks. The IgE level decreased after 3 months, and a low eosinophil count was maintained after steroid discontinuation. Follow-up computed tomography revealed a decrease in the size of the lymph nodes with no side effects such as conjunctivitis. CONCLUSION: Traditional treatments have raised developmental concerns in the pediatric population and are associated with high recurrence rates. Dupilumab targets the Th2 pathway and provides effective results, with few adverse effects. Dupilumab may be a therapeutic option for KD and other diseases involving the Th2 pathway.

CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells.

Osteosarcoma is the most frequent bone tumor, characterized by a high metastatic potential. However, the crosstalk between chemokine (C-C motif) ligand 3 (CCL3), which facilitates tumor progression and metastasis. Vascular endothelial growth factor-A (VEGF-A), an angiogenesis inducer and a highly specific mitogen for endothelial cells, has not been well explored in human osteosarcoma. Here we demonstrate the correlation of CCL3 and VEGF-A expressions, quantified by immunohistochemistry, with the tumor stage of human osteosarcoma tissues. Furthermore, CCL3 promotes VEGF-A expression in human osteosarcoma cells that subsequently induces human endothelial progenitor cell (EPC) migration and tube formation. Phosphorylation of JNK, ERK, and p38 was found after CCL3 stimulation. In addition, JNK, ERK, and p38 inhibitors also abolished CCL3-induced VEGF-A expression and angiogenesis. We noted that CCL3 reduces the expression of miR-374b and miR-374b mimic by reversing CCL3-promoted VEGF-A expression and angiogenesis in vitro and in vivo. This study shows that CCL3 promotes VEGF-A expression and angiogenesis in human osteosarcoma cells by down-regulating miR-374b expression via JNK, ERK, and p38 signaling pathways. Thus, CCL3 may be a new molecular therapeutic target in osteosarcoma angiogenesis and metastasis.

IL-6 promotes ICAM-1 expression and cell motility in human osteosarcoma.

Osteosarcoma is characterized by a high malignant and metastatic potential. Interleukin-6 (IL-6) is a multifunctional cytokine that is associated with the disease status and outcomes of cancers. However, the effect of IL-6 on migration activity in human osteosarcoma cells is mostly unknown. Here we found that IL-6 increased the migration and expression of intercellular adhesion molecule-1 (ICAM-1) in human osteosarcoma cells. Transfection of cells with ICAM-1 siRNA reduced IL-6-mediated cell migration. We also found that expression of IL-6 was significantly greater in human osteosarcoma tissues than in normal bone. The integrin-linked kinase (ILK)/Akt/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced expression of ICAM-1 and migration activity was inhibited by the specific inhibitor and siRNA of ILK, Akt, and AP-1 cascades. In addition, over-expression of IL-6 shRNA inhibited the migratory ability and ICAM-1 expression in osteosarcoma cells. Taken together, these results indicate that IL-6 and IL-6 receptor interaction occurs through ILK and Akt, which in turn activates AP-1, resulting in the activations of ICAM-1 and contributing the migration of human osteosarcoma cells.

The CCL2/CCR2 axis enhances vascular cell adhesion molecule-1 expression in human synovial fibroblasts.

BACKGROUND: Chemokine ligand 2 (CCL2), also known as monocyte chemoattractant protein-1 (MCP-1), belongs to the CC chemokine family that is associated with the disease status and outcomes of osteoarthritis (OA). Here, we investigated the intracellular signaling pathways involved in CCL2-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human OA synovial fibroblasts (OASFs). METHODOLOGY/PRINCIPAL FINDINGS: Stimulation of OASFs with CCL2 induced VCAM-1 expression. CCL2-mediated VCAM-1 expression was attenuated by CCR2 inhibitor (RS102895), PKCδ inhibitor (rottlerin), p38MAPK inhibitor (SB203580), and AP-1 inhibitors (curcumin and tanshinone IIA). Stimulation of cells with CCL2 increased PKCδ and p38MAPK activation. Treatment of OASFs with CCL2 also increased the c-Jun phosphorylation and c-Jun binding to the AP-1 element on the VCAM-1 promoter. Moreover, CCL2-mediated CCR2, PKCδ, p38MAPK, and AP-1 pathway promoted the adhesion of monocytes to the OASFs monolayer. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CCL2 increases VCAM-1 expression in human OASFs via the CCR2, PKCδ, p38MAPK, c-Jun, and AP-1 signaling pathway. The CCL2-induced VCAM-1 expression promoted monocytes adhesion to human OASFs.

Antenatal detection of a congenital pancreatic cyst.

Congenital pancreatic cyst is very rare. Antenatal detection can potentially decrease the neonatal morbidity because the appropriate preparation can be made in advance of delivery. We report a case of congenital pancreatic cyst detected prenatally by routine obstetric sonography in a fetus at 33 weeks' gestation. The cyst, located at the pancreatic tail, was excised at the age of 10 days. Pathology results confirmed a pancreatic cyst. Differential diagnosis of cystic abdominal lesions occurring in utero should include congenital pancreatic cyst.