Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncolytic virotherapy represents an emerging field with tremendous promise for harnessing the replicative capabilities of viruses against rapidly proliferating cancer cells. Among the different replicating virus technologies being tested, replication-competent retrovirus (RCR) vectors based on murine leukemia virus (MLV) exhibit unique characteristics. MLV exhibits intrinsic tumor selectivity due to its inability to infect quiescent cells, and can achieve highly selective and stable gene transfer throughout entire solid tumors in vivo at efficiencies of up to >99%, even after initial inoculation at MOIs as low as 0.01. RCR vectors with suicide genes mediate synchronized cell killing after prodrug administration, and due to their ability to undergo stable integration, residual cancer cells serve as a reservoir for long-term viral persistence even as they migrate to new sites, enabling multiple cycles of prodrug to achieve prolonged survival benefit. Further testing in various tumor models, new vector targeting and delivery strategies, and development of GMP manufacturing, are being pursued through a multi-national consortium, and preparations are now being undertaken for clinical trials using RCR vectors in glioblastoma.
 ...
PMID:Replication-competent retrovirus vectors for cancer gene therapy. 1798 78

Recent studies suggest that a small subpopulation of malignant cells with stem-like properties is resistant to chemotherapy and may be responsible for the existence of residual cancer after treatment. We have isolated highly tumorigenic cancer cells with 100-fold increase in tumor initiating capacity from the tumor xenografts of human glioblastoma U87 cells in mice. These cells exhibit stem-like properties and show unique energy metabolic characteristics including low mitochondrial respiration, increased glycolysis for ATP generation, and preference for hypoxia to maintain their stemness and tumor forming capacity. Mechanistically, mitochondrial depression in the highly tumorigenic cells occurs mainly at complex II of the electron transport chain with a down-regulation of the succinate dehydrogenase subunit B, leading to deregulation of hypoxia-inducible factors. Under hypoxia, the stem-like cancer cells are resistant to conventional anticancer agents but are sensitive to glycolytic inhibition. Furthermore, combination of glycolytic inhibition with standard therapeutic agents is effective in killing the tumor-initiating cells in vitro and inhibits tumor formation in vivo. Our study suggests that stem-like cancer cells prefer a low oxygen microenvironment and actively utilize the glycolytic pathway for ATP generation. Inhibition of glycolysis may be an effective strategy to eradicate residual cancer stem cells that are otherwise resistant to chemotherapeutic agents in their hypoxic niches.
 ...
PMID:Metabolic alterations in highly tumorigenic glioblastoma cells: preference for hypoxia and high dependency on glycolysis. 2179 17

Glioblastoma is the most common and aggressive adult primary brain cancer. Despite multimodal therapy, it is associated with a survival of less than two years. Greater than 85% of recurrences occur within the original area of surgery and radiotherapy, suggesting a potential for improved local treatments. In addition to cancer cell invasion beyond surgical margins, a plethora of postinjury pro-proliferative stimuli are released from local healing brain, which both protect and nourish remaining cancer cells. This review compiles preclinical and clinical evidence for a dedicated treatment of both residual cancer cells and regional microenvironment using intraoperative radiotherapy (IORT).
...
PMID:Rationale for intraoperative radiotherapy in glioblastoma. 2682 95

The tumorigenic potentials of residual cancer stem-like cells within tumors represent limitations of current cancer therapies. Here, the authors describe the effects of synthesized flexible, ligated, supramolecular self-assembled chair type tetranuclear ruthenium (II) metallacycles (2-5) on glioblastoma and glioma stem like cells. These self-assemblies were observed to be selectively toxic to glioma cells and CD133-positive glioma stem like cells population. Of the self-assembled compounds tested, metallacycle 4 more efficiently induced glioma stem like cells death within a brain cancer cell population and simultaneously inhibited the formation of free-floating gliospheres by reducing the sphere size. Detailed cell death studies revealed that treatment with metallacycle 4 reduced mitochondrial membrane potentials (an indicator of apoptosis) of glioma stem like cells. These results shows the elimination of cancer stem-like cells using an appropriate ligand binding adaptor offers a potential means of developing metal-based compounds for the treatment of chemo-resistant tumors.
 ...
PMID:Flexible ligated ruthenium(II) self-assemblies sensitizes glioma tumor initiating cells in vitro. 2894 63

Glioblastoma (GBM) is the most common primary intracranial neoplasia, and is characterized by its extremely poor prognosis. Despite maximum surgery, chemotherapy, and radiation, the histological heterogeneity of GBM makes total eradication impossible, due to residual cancer cells invading the parenchyma, which is not otherwise seen in radiographic images. Even with gross total resection, the heterogeneity and the dormant nature of brain tumor initiating cells allow for therapeutic evasion, contributing to its recurrence and malignant progression, and severely impacting survival. Visual delimitation of the tumor's margins with common surgical techniques is a challenge faced by many surgeons. In an attempt to achieve optimal safe resection, advances in approaches allowing intraoperative analysis of cancer and non-cancer tissue have been developed and applied in humans resulting in improved outcomes. In addition, functional paradigms based on stimulation techniques to map the brain's electrical activity have optimized glioma resection in eloquent areas such as the Broca's, Wernike's and perirolandic areas. In this review, we will elaborate on the current standard therapy for newly diagnosed and recurrent glioblastoma with a focus on surgical approaches. We will describe current technologies used for glioma resection, such as awake craniotomy, fluorescence guided surgery, laser interstitial thermal therapy and intraoperative mass spectrometry. Additionally, we will describe a newly developed tool that has shown promising results in preclinical experiments for brain cancer: optical coherence tomography.
 ...
PMID:Advances in Brain Tumor Surgery for Glioblastoma in Adults. 2926 Nov 48