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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastoma is the most common and most aggressive primary brain malignancy. The current initial standard of care consists of maximal safe surgical resection followed by radical radiotherapy and adjuvant temozolomide. Despite optimal therapy, median survival is ~15 months from diagnosis in molecularly unselected patients, and <6 months for patients with recurrent disease. Therefore, clinical treatments are currently palliative, not curative. Collectively, current knowledge suggests that the continued tumor growth and recurrence is in part due to the presence of glioma stem-like cells, which display self-renewal and tumorigenic potential. They differ from their more differentiated progeny, as they are more resistant to current treatments. Recurrent disease may be a consequence of the enhancement and/or gain of stem cell-like characteristics during disease progression, together with preferential death of more differentiated tumor cells during treatment, signifying that the cancer stem cell phenotype is a crucial therapeutic target. The limited knowledge of the characteristics of these cells and their response to current clinical treatments warrants intensive investigation with the aim to improve patient survival and/or develop a cure for this disease.
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PMID:Glioblastoma stem-like cells: at the root of tumor recurrence and a therapeutic target. 2550 49

High-grade glioma (HGG) are optimally treated with maximum safe surgery, followed by radiotherapy (RT) and/or systemic chemotherapy (CT). Recently, the treatment of newly diagnosed anaplastic glioma (AG) has changed, particularly in patients with 1p19q codeleted tumors. Results of trials currenlty ongoing are likely to determine the best standard of care for patients with noncodeleted AG tumors. Trials in AG illustrate the importance of molecular characterization, which are germane to both prognosis and treatment. In contrast, efforts to improve the current standard of care of newly diagnosed glioblastoma (GB) with, for example, the addition of bevacizumab (BEV), have been largely disappointing and furthermore molecular characterization has not changed therapy except in elderly patients. Novel approaches, such as vaccine-based immunotherapy, for newly diagnosed GB are currently being pursued in multiple clinical trials. Recurrent disease, an event inevitable in nearly all patients with HGG, continues to be a challenge. Both recurrent GB and AG are managed in similar manner and when feasible re-resection is often suggested notwithstanding limited data to suggest benefit from repeat surgery. Occassional patients may be candidates for re-irradiation but again there is a paucity of data to commend this therapy and only a minority of selected patients are eligible for this approach. Consequently systemic therapy continues to be the most often utilized treatment in recurrent HGG. Choice of therapy, however, varies and revolves around re-challenge with temozolomide (TMZ), use of a nitrosourea (most often lomustine; CCNU) or BEV, the most frequently used angiogenic inhibitor. Nevertheless, no clear standard recommendation regarding the prefered agent or combination of agents is avaliable. Prognosis after progression of a HGG remains poor, with an unmet need to improve therapy.
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PMID:The future of high-grade glioma: Where we are and where are we going. 2578 99

Glioblastoma (GBM) is an aggressive and lethal disease that often results in a poor prognosis. Unlike most solid tumors, GBM is characterized by diffuse infiltrating margins, extensive angiogenesis, hypoxia, necrosis, and clonal heterogeneity. Recurrent disease is an unavoidable consequence for many patients as standard treatment options such as surgery, radiotherapy, and chemotherapy have proven to be insufficient in causing long-term survival benefits. Systemic delivery of promising drugs is hindered due to the blood-brain barrier and non-uniform perfusion within GBM tissue. In recent years, many investigations have highlighted the role of GBM stem cells (GSCs) and their microenvironment in the initiation and maintenance of tumor tissue. Preclinical and early clinical studies to target GSCs and microenvironmental components are currently underway. Of these strategies, immunotherapy using checkpoint inhibitors and redirected cytotoxic T cells have shown promising results in early investigations. But, GBM microenvironment is heterogenous and recent investigations have shown cell populations within this microenvironment to be plastic. These studies underline the importance of identifying the role of and targeting multiple cell populations within the GBM microenvironment which could have a synergistic effect when combined with novel therapies. Pericytes are multipotent perivascular cells that play a vital role within the GBM microenvironment by assisting in tumor initiation, survival, and progression. Due to their role in regulating the blood-brain barrier permeability, promoting angiogenesis, tumor growth, clearing extracellular matrix for infiltrating GBM cells and in helping GBM cells evade immune surveillance, pericytes could be ideal therapeutic targets for stymieing or exploiting their role within the GBM microenvironment. This chapter will introduce hallmarks of GBM and elaborate on the contributions of pericytes to these hallmarks by examining recent findings. In addition, the chapter also highlights the therapeutic value of targeting pericytes, while discussing conventional and novel GBM therapies and obstacles to their efficacy.
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PMID:Pericytes in Glioblastomas: Multifaceted Role Within Tumor Microenvironments and Potential for Therapeutic Interventions. 3114 72