Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.
Apoptosis ; Autophagy* ; Caspase 3 ; Chloroquine ; Endothelial Cells* ; Fibroblast Growth Factor 2 ; Helminths ; Intercellular Signaling Peptides and Proteins ; Mebendazole* ; Microtubules ; Phosphorylation ; Phosphotransferases ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A

Plant root hairs are commonly found artifacts in parasitology specimens and may be confused with helminthes by an untrained eye. We report a case of brain tuberculoma where the tissue sample was contaminated with root hair derived from tap water; the presence of this root hair, which mimicked a larva, led to diagnostic confusion. Therefore, tap water should be considered a source of root hair and vegetable matter.
Animals ; Brain Diseases/*diagnosis/pathology ; *Diagnostic Errors ; Helminthiasis/diagnosis ; Helminths/growth & development ; Humans ; Larva/anatomy & histology ; Male ; Middle Aged ; Plant Roots/*anatomy & histology ; Tomography, X-Ray Computed ; Tuberculoma/*diagnosis/pathology ; Water

Hypereosinophilic syndrome (HES) is a heterogeneous disorder characterized by persistent hypereosinophilia with the evidence of organ dysfunction caused by eosinophilic involvement. HES can be induced by various secondary causes, including helminthic infections, adverse drug reactions, and allergic diseases. Primary/clonal bone marrow disease, including genetic mutations in platelet driven growth factor receptor alpha (PDGFRA), platelet driven growth factor receptor beta (PDGFRB), and fibroblast growth factor receptor 1 (FGFR1) could be its causes. Although corticosteroids are the mainstay of therapy in confirmed HES, imatinib is considered a definitive treatment for HES with these mutations. However, there have been few reports about HES with these genetic mutations in Korea. Here, we report a patient who presented with sudden onset of congestive heart failure and hypereosinophilia, proved to have PDGFRB rearrangement, and was controlled successfully with imatinib after left ventricle thrombectomy.
Adrenal Cortex Hormones ; Blood Platelets ; Bone Marrow Diseases ; Drug-Related Side Effects and Adverse Reactions ; Eosinophilia* ; Eosinophils ; Estrogens, Conjugated (USP)* ; Heart Failure* ; Heart Ventricles ; Helminths ; Humans ; Hypereosinophilic Syndrome ; Imatinib Mesylate ; Korea ; Receptor, Fibroblast Growth Factor, Type 1 ; Receptor, Platelet-Derived Growth Factor beta* ; Thrombectomy

There has been a negative association between certain parasite infections at an early age and allergic diseases based on the epidemiological data. Parasitic helminths excrete or secrete products/allergens which develop Th2 responses to increase IgE production and to induce CD4+ T cells. Cytokines such as IL-4, IL-5, IL-9 and IL-13 are produced in parasite infections as similar as in various allergic diseases. The immune responses against helminth infections may cause pathologic effects, and provoke allergic manifestations. However, human hosts use the hypersensitivity response to protect themselves against helminth infection. Meanwhile, the intradermal test would have been used for diagnosis of fluke infections in Korea to take advantage of the hypersensitivity reaction. Chronic infections with parasites in turn induce forms of immune suppression or down regulation. FoxP3+CD4+ Treg cells, alternatively activated macrophages, CD4+ Tr1 secreting IL-10 and TGF-beta, and Th3 cells take part in immunosuppressive regulatory responses. Immunoregulation is likely to play a major part in parasite strategies for survival in a sensitized host. Helminth infections accompanied with immune modulation may protect not only from Th2 inflammation (allergies) but also from Th1 inflammation. CD4+CD25+ FoxP3+ T cells play a major role of modulating experimental allergic asthma upon helminth antigen challenges, which is independent of IL-10. Regulatory B cells also can prevent or reverse allergen-induced airway inflammation via an IL-10 mediated mechanism and Treg cells. More researches are necessary to identify parasite derived molecules for the development of new therapeutics to combat allergies and other diseases caused by inappropriate immune responses.
Asthma ; B-Lymphocytes, Regulatory ; Cytokines ; Down-Regulation ; Helminths ; Humans ; Hypersensitivity ; Imidazoles ; Immunoglobulin E ; Inflammation ; Interleukin-10 ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; Interleukin-9 ; Intradermal Tests ; Korea ; Macrophages ; Nitro Compounds ; Parasites ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Transforming Growth Factor beta ; Trematoda