Kahkashan Perveen

Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment

Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumors. Despite advances in treatment modalities it remains largely incurable. The objective of our review is to provide a holistic picture of GBM epidemiology, etiology, pathogenesis, clinical findings and treatment. A literature search was conducted for GBM at PubMed and Google Scholar, with relevant key words like glioblastoma multiforme, pathogenesis, signs and symptoms, treatment etc., and papers published until 2015 were reviewed. It was found that radiation and certain genetic syndromes are the only risk factors identified to date for GBM. Depending on the tumor site patients may present to the clinic with varying symptoms. To confirm the presence and the extent of tumor, various invasive and non-invasive imaging techniques require employment. The literature survey revealed the pathogenesis to involve aberrations of multiple signaling pathways through multiple genetic mutations and altered gene expression. Although several treatment options are available, including surgery, along with adjuvant chemo- and radio-therapy, the disease has a poor prognosis and patients generally succumb within 14 months of diagnosis.

Protective Efficacy of N-(2-Hydroxyphenyl) Acetamide against Adjuvant-Induced Arthritis in Rats

Rheumatoid arthritis is a chronic inflammatory joint disease characterized by synovial proliferation and tissue destruction. Proinflammatory cytokines like interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) play a key role in the disease process and elevate energy expenditure, which further increases the joint pain and stiffness. To explore the effects of N-(2-hydroxyphenyl) acetamide (NA-2) on the development of arthritis, clinical signs, histopathology of knee joints, nociception analysis, and the serum levels of IL-1β and TNF-α were monitored. Arthritis was induced by intradermal administration of heat-killed adjuvant Mycobacterium tuberculosis H37Ra in rats. NA-2 and indomethacin treatments were started in their respective group on the same day when adjuvant was administered. Experiments were terminated when arthritic score of 4 was observed in arthritic control group. NA-2 (5 mg/kg) treatment significantly ameliorated the disease severity. Reduction in body weight and increase in paw oedema were significantly reversed in arthritic animal receiving NA-2. The nociceptive sensation was also inhibited in the NA-2 treated arthritic rats. Remission was associated with improved histology and significant decreased expression of serum proinflammatory cytokines (P < 0.05 for IL-1β and TNF-α). Based on our observations, it can be suggested that NA-2 possesses promising anti-arthritic property, and it can be used as a therapeutic agent for arthritis.

Verapamil potentiates anti-glioblastoma efficacy of temozolomide by modulating apoptotic signaling

Glioblastoma Multiforme (GBM) is the most malignant and invasive tumor of the CNS. Although temozolomide (TMZ) has improved the survival, long-lasting responses have not been reported. Therefore, there is a need to develop improved treatments, one of which might be newly identified drugs which can be used in combination therapy with low doses of standard drugs. Verapamil (VP) a known antihypertensive drug has been shown to enhance the activity of bis-chloroethylnitrosourea (BCNU), a drug used to treat GBM. Since, TMZ has replaced BCNU as the standard GBM chemotherapy; therefore, we aimed to study in vitro interaction of VP and TMZ against GBM. Anti-proliferative and apoptotic activities were studied using MTT, TUNEL assay and DAPI staining. Synergy was assessed using combination index method. Apoptotic markers were evaluated by RT-PCR, and immunocytochemistry. Both VP and TMZ significantly inhibited the growth of U87 cells in dose dependent manner. The combine effect of TMZ with VP was synergistic with a CDI value of <1. Combination of TMZ and VP increased the ratio of Bax to Bcl-2 expression and thus shifted the equilibrium of cells towards apoptosis. Our findings suggest that the synergistic growth inhibition that was observed in combination treatment group may in part relate to increase in apoptosis. The combine administration of VP and TMZ may be therapeutically exploited for the management of GBM.