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1.
Clin Immunol ; 252: 109646, 2023 07.
Article in English | MEDLINE | ID: mdl-37209807

ABSTRACT

BACKGROUND: Kikuchi-Fujimoto disease (KFD) is a self-limited inflammatory disease of unknown pathogenesis. Familial cases have been described and defects in classical complement components C1q and C4 have been identified in some patients. MATERIAL AND METHODS: We describe genetic and immune investigations of a 16 years old Omani male, a product of consanguineous marriage, who presented with typical clinical and histological features of KFD. RESULTS: We identified a novel homozygous single base deletion in C1S (c.330del; p. Phe110LeufsTer23) resulting in a defect in the classical complement pathway. The patient was negative for all serological markers of SLE. In contrast, two female siblings (also homozygous for the C1S mutation), one has autoimmune thyroid disease (Hashimoto thyroiditis) and a positive ANA and the other sibling has serology consistent with SLE. CONCLUSION: We report the first association between C1s deficiency and KFD.


Subject(s)
Histiocytic Necrotizing Lymphadenitis , Adolescent , Humans , Male , Complement C1s/genetics , Histiocytic Necrotizing Lymphadenitis/genetics , Histiocytic Necrotizing Lymphadenitis/complications , Histiocytic Necrotizing Lymphadenitis/pathology , Loss of Function Mutation
2.
Molecules ; 26(12)2021 Jun 13.
Article in English | MEDLINE | ID: mdl-34199287

ABSTRACT

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cisplatin/pharmacology , Ovarian Neoplasms/drug therapy , Peptides, Cyclic/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Cisplatin/administration & dosage , Drug Resistance, Neoplasm , Drug Synergism , Female , Humans , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Peptides, Cyclic/administration & dosage
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