Glioblastoma multiforme (GBM) is the most common malignant glioma, which has high proliferative rate and an extremely invasive phenotype. Major limitations in the effective treatment of malignant gliomas are the proliferation and infiltration into the surrounding brain tissue. Although studies have shown that various stimuli promote glioma cell proliferation and invasion, the underlying mechanisms remain largely unknown. Glioma cells secrete significant amount of glutamate into surrounding tissue and intracellular signaling is thought to be initiated upon glutamate-induced modulation of the ion channels in GBM cells. The objective of the study was to investigate the effect of activation of NMDA (N-methyl-D-aspartate) receptors of glutamate on gelatinase subfamily MMPs and on proliferation of glioma cells. U251MG and U87MG cell lines were maintained in Dulbecco's Modified Eagle's Medium. Proliferation assay was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole (MTT) assay. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was investigated by gelatin zymography assay. We demonstrate that activated NMDA receptors (NMDAR) increased the activity of MMP-2 only in U251MG glioma cells at concentrations of 100 and 200 μM and increased the proliferation of both U87MG and U251MG glioma cells at concentrations of 50, 100, 150 and 200 μM. Inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly inhibited the effect of activation of NMDAR on MMP-2 activity and on proliferation. We conclude that NMDA receptor activation has role in activity of MMP-2 and proliferation of glioma cells.
311tributed to an increased frequency of severe fungal infections in patients with neoplastic diseases. Incidence due to filamentous fungi becomes life-threatening and their diagnosis and treatment can be challenging, especially in species with intrinsic resistance. Diagnosis of filamentous fungi in both the clinic and the laboratory remains difficult, leading to unsatisfactory treatment and high mortality rates.Methods & Materials: A total of 40 clinical specimens including surgical tissues, biopsies and wound swabs were collected from Cancer patients and cultured on fungal isolation medium. The presence of fungal elements on tissue specimens were demonstrated using PAS stain by histopathological analysis. The positive fungal isolates were presumptively identified based on macroscopic and microscopic features and species were further confirmed by PCR amplification of ITS followed by sequencing the amplicons. The Antifungal susceptibility profiles of fungal isolates to Amphotericin B and Itraconazole was determined by microbroth dilution assay as per CLSI guidelines.Results: Out of 40 specimens collected, 16 were positive for filamentous fungi. Based on phenotypic identification and ITS sequencing 9 were found to be rare isolates and were identified as Geotrichum candidum (03), Curvularia verruculosa (01), Alternaria alternata (01), Fusarium incarnatum (01), Syncephalastrum racemosum (01), Penicillium oxalicum (01) and Onychocola canadensis (01).The MIC values of Amphotericin B and Itraconazole ranged from 0.0625 to > 16 g/ml. All the isolates were found to be susceptible to Amphotericin B and Itraconazole, while G. candidum showed resistance to Itraconazole and single isolate of O. canadensis showed resistance to both the antifungals.Conclusion: The results obtained in the study showed the occurence of rare fungal isolates such as G. candidum, C. verruculosa, A. alternata, F. incarnatum, S. racemosum, P. oxalicum and O. canadensis in cancer patients. The Amphotericin B and Itraconazole were found to be more effective antifungals against all the species tested except few rare isolates with intrinsic resistance. However, therapeutic success in cases of fungal infections primarily depends on early diagnosis of the fungal infection, correct identification of the etiologic agent, and timely antifungal treatment.http://dx. Background:Cryptococcal meningitis remains one of the leading causes of morbidity and mortality among immunosuppressed individuals, particularly those with HIV infection. Globally, approximately one million cases occur each year resulting in more than six lakh deaths.
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