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   Table of Contents - Current issue
September-October 2018
Volume 4 | Issue 5
Page Nos. 117-142

Online since Tuesday, October 30, 2018

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Enhanced anticancer effect by combination of proteoglucan and Vitamin K3 on bladder cancer cells p. 117
Michael Zhang, Kelvin Zheng, Muhammad Choudhury, John Phillips, Sensuke Konno
Aim: Mushroom extract, PDF, is a bioactive proteoglucan with anticancer/antitumor activity, and Vitamin K3 (VK3) is a synthetic VK derivative with antitumor activity as well. An unconventional approach using these two agents was tested to see their anticancer effects on bladder cancer cells in vitro. Methods: Human bladder cancer T24 cells were treated with PDF, VK3, or their combination, and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. To explore the anticancer mechanism, cell cycle and epigenetic alterations were specifically studied. Results: PDF ≥ 500 μg/mL led to a ~ 35% reduction in cell viability while VK3 had little effects. However, when PDF (300 μg/mL) was combined with VK3 (5 μM), a ~ 75% cell viability reduction was attained. This specific combination induced a G1 cell cycle arrest with the downregulation of G1-specific regulators. In addition, histone deacetylase was inactivated while histones 3 and 4 were highly acetylated. Two apoptotic regulators were significantly activated with PDF/VK3 combination as well. Conclusion: The specific combination of PDF and VK3 appears to potentiate anticancer effect on T24 cells. This is primarily attributed to a G1 cell cycle arrest with chromatin modifications, ultimately leading to apoptosis. Thus, the PDF/VK3 combination may offer a potential therapeutic option for bladder cancer.
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Molecular insights turning game for management of ependymoma: A review of literature p. 123
Ajay Sasidharan, Rahul Krishnatry
Molecular biology of ependymoma is being extensively studied in recent years, providing insights into newer therapeutic strategies. The different anatomic subgroups of ependymoma, namely supratentorial, posterior fossa (PF), and spinal, pose entirely different clinical behavior and prognosis. Recently, nine molecular subgroups of ependymoma have been identified, one of which has been incorporated into the WHO classification. Further understanding of the molecular biology of ependymoma is vital to expand its clinical utility. Here, we performed a review of the literature on the molecular biology of ependymoma. Therapeutic avenues include: (1) targeted agents against – (a) chromothripsis-induced nuclear factor-kappa beta signaling, (b) gene silencing by DNA methylation, (c) increased telomerase activity, and (d) microRNA and (2) de-escalating treatment in good prognostic subgroup such as PFB. The prognostic value of different chromosomal gain or loss is being better understood and may serve as prognostic signatures in future. Faster adoption of molecular classification into clinical practice requires simpler identification techniques using immunohistochemical surrogates for molecular subgroups, for example, cell adhesion molecule L1 for v-rel reticuloendotheliosis viral oncogene homolog A (RELA) fusion, laminin subunit alpha 2, tenascin-C, and neural epidermal growth factor-like 2 for PFA and PFB. Identification of poor prognostic markers such as RELA fusion and PFA has necessitated future research impetus to be directed to find more efficacious treatment approach in these groups.
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IDH gene mutation in glioma p. 129
Leping Liu, Xuejun Li
Glioma is one of the most common intracranial malignant tumors. Its development is associated with mutations in the isocitrate dehydrogenase (IDH) gene. IDH plays an important role in the tricarboxylic acid cycle, and when mutated, it can downregulate the expression of α-ketoglutarate and convert it to 2-hydroxypentaric acid (2-HG), activating the HIF-1 pathway to promote the development of glioma. This article briefly describes the role of IDH mutations in glioma development and progression and its relationship with other gene mutations. This information may provide a new perspective toward the treatment, molecular pathological grading, and prognosis of glioma.
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Challenges and advances in the management of pediatric intracranial germ cell tumors: A case report and literature review p. 134
Gerard Cathal Millen, Karen A Manias, Andrew C Peet, Jenny K Adamski
Intracranial germ cell tumors are a heterogeneous group of tumors, broadly classified into germinomatous, nongerminomatous, or teratoma subtypes. Treatment has evolved over recent decades to include multimodal therapy combining surgery, radiotherapy, and chemotherapy. Although the majority of intracranial germs cell tumors are treated successfully, management can be fraught with complexities and present significant clinical challenges. Bifocal disease is well described, but rare, and therefore its behavior is not well characterized, particularly in nongerminomatous disease. This case report presents an interesting case, with both rare and common complications, in particular, to emphasize the challenges of germ cell tumor management. With a focus on bifocal disease, we review the published cases and highlight how advanced imaging and magnetic resonance spectroscopy can be used in management. Advances in biology, targeted agents, and novel diagnostic tools are also discussed.
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