Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model

The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be “clathrin-mediated” endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC

Utility of anti-immunoglobulin IgA, IgG, IgM, Kappa, Lambda - FITC (conjugate) cocktail in routine renal pathology practice

Abstract Background Immunofluorescence studies on frozen sections are an essential component in the evaluation of renal biopsies. The basic panel in most centres constitutes IgG, IgA, IgM, C3c, C1q, Kappa and Lambda light chain antibody testing. The purpose of this panel is to detect immunoglobulin or complement deposits and further subclassify the disease based on the location, intensity and pattern of immunoglobulin and complement staining. However, there are a substantial proportion of nephropathies that do not show any obvious immune-deposits on immunofluorescence. We currently, do not have any evidence-based alternative immunofluorescence panel to rule out these conditions. This study aims to evaluate the utility of anti-immunoglobulin IgA, IgG, IgM, Kappa, Lambda - FITC cocktail immunofluorescence on renal biopsy frozen sections with emphasis on its role as a primary screening panel in conjunction with C3c and C1q. Methods Anti-immunoglobulin IgA, IgG, IgM, Kappa, Lambda light chain - FITC cocktail immunofluorescence was performed on 593 consecutive native renal biopsies along with the routine panel comprising of the individual FITC labelled IgG, IgA, IgM, C3c, C1q, Kappa and Lambda light chain immunofluorescence stains. Results In 235 (39.6%) cases immune deposits (immune-complex mediated and monoclonal gammopathy-related) were present and the rest 354 (59.7%) cases were negative for immunoglobulin or complement deposits. Overall, the sensitivity, specificity, positive predictive value and negative predictive values of anti-immunoglobulin IgA, IgG, IgM, Kappa and Lambda - FITC cocktail in distinguishing immune-complex/immunoglobulin-mediated glomerulopathies from non-immune complex/immunoglobulin-mediated glomerulopathies were 100% each. Conclusion Anti-immunoglobulin IgA, IgG, IgM, Kappa and Lambda - FITC cocktail when used in conjunction with C3c and C1q, can be an effective first line investigation in all native renal biopsies. Further, testing with the individual FITC labelled IgG, IgA, IgM, Kappa and Lambda light chain immunofluorescence can be performed, depending on the initial screening as described above. Overall, this algorithmic approach can save valuable resources

A rare case of eyelid sarcoidosis presenting as an orbital mass

Intraorbital sarcoidosis presenting externally as a solitary eyelid mass has been described in the literature as isolated case reports. We describe a rare case of asymptomatic sarcoidosis with orbital mass as the presenting feature in a young woman. The lesion was excised with the clinical possibility of a thrombosed varix. On histology, the lesion was characterized by numerous nonnecrotizing epithelioid cell granulomas with several multinucleated giant cells containing abundant asteroid bodies and oxalate crystals. No tubercular bacilli were detected. A diagnosis of sarcoidosis was rendered and on further clinical work-up, she was detected to have hilar lymphadenopathy. Sarcoidosis should be considered in the differential diagnosis of orbital mass as it could be the initial manifestation of the disease process

A Novel Homozygous Nonsense HYDIN Gene Mutation p.(Arg951*) in Primary Ciliary Dyskinesia

International audienceNo abstract availabl