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Neuro-oncology Oct 2017Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and...
BACKGROUND
Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with cancer; however, little is known about PA or prognostic communication in MG. Moreover, research has yet to evaluate the impact of cognitive impairment on PA and preferred forms of communication.
METHODS
Fifty MG patients and 32 paired caregivers were evaluated in this exploratory study with a semi-structured PA assessment aimed to measure their awareness of MG incurability and LE. Full PA was defined as awareness of MG incurability and accurate estimate of LE. The assessment included a survey about preferences for prognostic communication (items from the Prognosis and Treatment Perceptions Questionnaire), neurocognitive assessment (Hopkins Verbal Learning Test-Revised, Trail Making Test Parts A and B, and the Controlled Oral Word Association Test), and measurements of mood (Hospital Anxiety and Depression Scale) and quality of life (Functional Assessment of Cancer Therapy-Brain [FACT-Br]).
RESULTS
Twenty (40%) patients and 22 (69%) caregivers had full PA. Thirty (60%) patients and 23 (72%) caregivers reported that prognostic information was extremely or very important, and 21 (42%) patients and 16 (50%) caregivers desired more prognostic information. Patients with memory impairment more frequently believed that prognostic information was important (P = 0.04, P = 0.03) and desired more information (P = 0.05, P = 0.003) as compared with those without impairment.
CONCLUSIONS
Most MG patients were unaware of their LE. Memory impairment may influence preferences for prognostic information.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Attitude to Health; Caregivers; Cognition; Communication; Female; Follow-Up Studies; Glioma; Health Knowledge, Attitudes, Practice; Humans; Life Expectancy; Male; Middle Aged; Prognosis; Prospective Studies; Quality of Life; Surveys and Questionnaires; Young Adult
PubMed: 28645200
DOI: 10.1093/neuonc/nox117 -
Journal of Cellular and Molecular... Aug 2019Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has... (Review)
Review
Despite aggressive multimodality treatment, the prognosis of glioma, especially malignant glioma, remains very poor. After decades of effort, anti-angiogenic therapy has become an important method of cancer treatment in addition to surgery, radiotherapy and chemotherapy. Although the performance of anti-angiogenic therapy in colorectal cancer is good, its performance in malignant glioma remains unsatisfactory. Several phase III clinical trials showed no overall survival benefits. To solve this problem, the division of patients into groups based on their molecular biomarkers is an important step. This paper provides current insights into anti-angiogenic drugs undergoing clinical trials and discusses the potential of molecular biomarkers to guide glioma diagnosis.
Topics: Angiogenesis Inhibitors; Bevacizumab; Biomarkers, Tumor; Brain Neoplasms; Glioma; Humans; Indoles; Molecular Targeted Therapy; Prognosis; Snake Venoms
PubMed: 31210419
DOI: 10.1111/jcmm.14417 -
International Journal of Molecular... May 2021Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct... (Review)
Review
Malignant glioma represents a fatal disease with a poor prognosis and development of resistance mechanisms against conventional therapeutic approaches. The distinct tumor zones of this heterogeneous neoplasm develop their own microenvironment, in which subpopulations of cancer cells communicate. Adaptation to hypoxia in the center of the expanding tumor mass leads to the glycolytic and angiogenic switch, accompanied by upregulation of different glycolytic enzymes, transporters, and other metabolites. These processes render the tumor microenvironment more acidic, remodel the extracellular matrix, and create energy gradients for the metabolic communication between different cancer cells in distinct tumor zones. Escape mechanisms from hypoxia-induced cell death and energy deprivation are the result. The functional consequences are more aggressive and malignant behavior with enhanced proliferation and survival, migration and invasiveness, and the induction of angiogenesis. In this review, we go from the biochemical principles of aerobic and anaerobic glycolysis over the glycolytic switch, regulated by the key transcription factor hypoxia-inducible factor (HIF)-1α, to other important metabolic players like the monocarboxylate transporters (MCTs)1 and 4. We discuss the metabolic symbiosis model via lactate shuttling in the acidic tumor microenvironment and highlight the functional consequences of the glycolytic switch on glioma malignancy. Furthermore, we illustrate regulation by micro ribonucleic acids (miRNAs) and the connection between mutation status and glycolytic metabolism. Finally, we give an outlook about the diagnostic and therapeutic implications of the glycolytic switch and the relation to tumor immunity in malignant glioma.
Topics: Animals; Brain; Brain Chemistry; Brain Neoplasms; Carbonic Anhydrases; Glioma; Glycolysis; Humans; Hydrogen-Ion Concentration; Lactic Acid; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 34073734
DOI: 10.3390/ijms22115518 -
Diagnostic and Interventional Imaging Oct 2014Detecting a new area of contrast-enhancement at MRI after irradiation of malignant brain tumor arises the problem of differential diagnosis between tumor recurrence and...
Detecting a new area of contrast-enhancement at MRI after irradiation of malignant brain tumor arises the problem of differential diagnosis between tumor recurrence and radiation necrosis induced by the treatment. The challenge for imaging is to distinguish the two diagnoses given: the prognostic and therapeutic issues. Various criteria have been proposed in the literature based on morphological, functional or metabolic MRI. The purpose of this study was to perform an analysis of these tools to identify MRI best criteria to differentiate radiation necrosis lesions from malignant gliomas and brain metastases recurrence. For gliomas, the morphology of the contrast-enhancement cannot guide the diagnosis and the use of perfusion techniques and spectroscopy (multivoxels if possible) are necessary. In the follow-up of metastasis, a transient increase and moderate lesion volume is possible with a good prognosis. Morphological characteristics (volume ratio T2/T1Gd) and perfusion analysis provide valuable tools for approaching the diagnosis of radionecrosis.
Topics: Brain Neoplasms; Glioma; Humans; Magnetic Resonance Imaging
PubMed: 25001364
DOI: 10.1016/j.diii.2014.06.013 -
Cancer Control : Journal of the Moffitt... 2004Despite advances in surgery, radiation therapy, and chemotherapy, only modest improvement has been achieved in the survival of patients with malignant gliomas. (Review)
Review
BACKGROUND
Despite advances in surgery, radiation therapy, and chemotherapy, only modest improvement has been achieved in the survival of patients with malignant gliomas.
METHODS
The authors review the immunologic aspects of gliomas, potential targets for therapy, and issues surrounding current immunotherapeutic strategies directed against malignant gliomas.
RESULTS
The blood-brain barrier and the purported immunological privilege of the brain are not necessarily insurmountable obstacles to effective immunotherapy for brain tumors. Preclinical studies suggest a number of potential therapeutic avenues. Translational studies offer the prospect of providing substantial new information about immunological trafficking in the nervous system and suggesting the most fruitful approaches to immunotherapy for malignant gliomas.
CONCLUSIONS
More effective adjuvant treatments for malignant gliomas are needed. The applicability of immunological approaches in the treatment of these tumors warrants continued study.
Topics: Animals; Antigens, Neoplasm; Blood-Brain Barrier; Brain; Cancer Vaccines; Clinical Trials as Topic; Dendritic Cells; Drug Delivery Systems; Genes, erbB-1; Glioma; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immune Tolerance; Immunotherapy; Interleukin-2; Mutation; Treatment Outcome
PubMed: 15153842
DOI: 10.1177/107327480401100306 -
Ultrasonics Sonochemistry Jul 2017Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include... (Review)
Review
Malignant glioma is one of the most challenging central nervous system diseases to treat, and has high rates of recurrence and mortality. The current therapies include surgery, radiation therapy, and chemotherapy, although these approaches often failed to control tumor progression or improve patient survival. Sonodynamic therapy is a developing cancer treatment that uses ultrasound combined with a sonosensitizer to synergistically kill tumor cells, and has provided impressive results in both in vitro and in vivo studies. The ultrasound waves can penetrate deep tissues and reversibly open the blood-brain barrier to enhance drug delivery to the brain. Thus, sonodynamic therapy has a promising potential in glioma treatment. In this review, we summarize the studies that have confirmed the pre-clinical efficacy of sonodynamic therapy for glioma treatment, and discuss the future directions for this emerging treatment.
Topics: Animals; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Glioma; Humans; Ultrasonic Waves
PubMed: 28427672
DOI: 10.1016/j.ultsonch.2017.02.020 -
Cell Research Jun 2021Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis....
Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.
Topics: Carcinogenesis; Glioblastoma; Glioma; Humans; Neoplastic Stem Cells; Neural Stem Cells
PubMed: 33390587
DOI: 10.1038/s41422-020-00451-z -
Journal of Neuro-oncology Jun 2017Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided... (Review)
Review
Malignant gliomas (MG), tumors of glial origin, are the most commonly diagnosed primary intracranial malignancies in adults. Currently available treatments have provided only modest improvements in overall survival and remain limited by inevitable local recurrence, necessitating exploration of novel therapies. Among approaches being investigated, one of the leading contenders is immunotherapy, which aims to modulate immune pathways to stimulate the selective destruction of malignant cells. Dendritic cells (DCs) are potent initiators of adaptive immune responses and therefore crucial players in the development and success of immunotherapy. Clinical trials of various DC-based vaccinations have demonstrated the induction of anti-tumor immune responses and prolonged survival in the setting of many cancers. In this review, we summarize current literature regarding DCs and their role in the tumor microenvironment, their application and current clinical use in immunotherapy, current challenges limiting their efficacy in anti-cancer therapy, and future avenues for developing successful anti-tumor DC-based vaccines.
Topics: Animals; Brain Neoplasms; Cancer Vaccines; Dendritic Cells; Glioma; Humans
PubMed: 28434112
DOI: 10.1007/s11060-017-2446-4 -
Neuroscience Bulletin Feb 2008The immunotherapy for malignant glioma faces unique difficult, due to some anatomical and immunological characteristics including the existence of blood brain barrier,... (Review)
Review
The immunotherapy for malignant glioma faces unique difficult, due to some anatomical and immunological characteristics including the existence of blood brain barrier, the absence of lymphatic tissues and dendritic cells (DCs) in the central nervous system (CNS) parenchyma, and the presence of an immunosuppressive microenvironment. Therefore, immunotherapeutic approaches will not be beneficial unless the compromised immune status in malignant glioma patients is overcome. DC-based immunotherapy, vaccinating cancer patients with DCs pulsed with various tumor antigens, is one of the most promising immunotherapeutic approaches for treatment of malignant glioma because it seems able to overcome, at least partially, the immunosuppressive state associated with primary malignancies. The preparation of DCs, choice of antigen, and route and schedule of administration are improving and optimizing with rapid development of molecular biology and gene engineering technology. DC vaccination in humans, after a number of pre-clinical models and clinical trials, would increase the clinical benefits for malignant glioma immunotherapy.
Topics: Dendritic Cells; Glioma; Humans; Immunotherapy
PubMed: 18273075
DOI: 10.1007/s12264-008-1107-1 -
BMC Cancer Apr 2024Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia....
BACKGROUND
Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients.
METHODS
The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too.
RESULTS
Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers.
CONCLUSIONS
Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.
Topics: STAT3 Transcription Factor; Humans; Animals; Mice; Glioma; Male; Female; Brain Neoplasms; Cell Line, Tumor; Middle Aged; Biomarkers, Tumor; Aged; Adult; Glioblastoma; Gene Expression Regulation, Neoplastic; Hypoxia
PubMed: 38654280
DOI: 10.1186/s12885-024-12221-w