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Psycho-oncology Mar 2018Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis, yet many families facing malignant glioma have poor prognostic...
OBJECTIVE
Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis, yet many families facing malignant glioma have poor prognostic awareness (PA), or the awareness of the patient's incurable disease and shortened life expectancy. Accurate PA is associated with favorable medical outcomes at end-of-life for patients and psychosocial outcomes for informal caregivers (ICs) through bereavement. To date, however, no study has specifically examined PA among MG ICs and the information they receive that shapes their awareness.
METHODS
Thirty-two ICs of patients with malignant glioma completed a semi-structured assessment of their awareness of the incurability and life expectancy of their loved one's illness, and to understand their sources of prognostic information and preferences for communication of prognostic information.
RESULTS
Twenty-two (69%) ICs had full PA-awareness of the incurability of malignant glioma and accurate estimates of their loved ones' life expectancy. Twenty-three (72%) felt that prognostic information was extremely or very important to possess, and 16 (50%) desired more prognostic information. The majority of ICs received prognostic information from physicians and the Internet. Qualitative analyses revealed that many ICs had difficulty navigating medical encounters in which they concurrently wanted to elicit prognostic information from physicians and protect patients from such information.
CONCLUSIONS
Accurate and timely PA is necessary for ICs to serve as critical members of health care teams. Interventions are needed to foster ICs' skills in navigating prognostic communication with patients and health care providers and thereby improve their ability to advocate for their loved one's wishes.
Topics: Adult; Aged; Brain Neoplasms; Caregivers; Communication; Family; Female; Glioma; Health Knowledge, Attitudes, Practice; Humans; Male; Middle Aged; Terminal Care; Young Adult
PubMed: 29125714
DOI: 10.1002/pon.4581 -
Advanced Healthcare Materials Dec 2023Resident microglia are key factors in mediating immunity against brain tumors, but the microglia in malignant glioma are functionally impaired. Little immunotherapy is...
Resident microglia are key factors in mediating immunity against brain tumors, but the microglia in malignant glioma are functionally impaired. Little immunotherapy is explored to restore microglial function against glioma. Herein, oleanolic acid (OA) (microglia "restorer") and PPA-1 peptide (immune checkpoint blockade) are integrated on a nano-immuno-synergist ( PAM@OA) to work coordinately. The self-assembled OA core is coated with macrophage membrane for efficient blood-brain barrier penetration and microglia targeting, on which PPA-1 peptide is attached via acid-sensitive bonds for specific release in tumor microenvironment. With the enhanced accumulation of the dual drugs in their respective action sites, PAM@OA effectively promotes the recruitment and activation of effector T cells by inhibiting aberrant activation of Signal transducer and activator of transcription (STAT-3) pathway in microglia, and assists activated effector T cells in killing tumor cells by blocking elevated immune checkpoint proteins in malignant glioma. Eventually, as adjuvant therapy, the rationally designed nano-immuno-synergist hinders malignant glioma progression and recurrence with or without temozolomide. The work demonstrates the feasibility of a nano-formulation for microglia-based immunotherapy, which may provide a new direction for the treatment of brain tumors.
Topics: Humans; Microglia; Glioma; Brain Neoplasms; Macrophages; Peptides; Tumor Microenvironment
PubMed: 37573475
DOI: 10.1002/adhm.202301861 -
Current Neurology and Neuroscience... Jun 2017Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this... (Review)
Review
PURPOSE OF REVIEW
Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses.
RECENT FINDINGS
Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma. Due to their successes in the preclinical arena, many of these therapies have undergone phase I and II clinical testing. These early clinical trials have demonstrated the feasibility, safety, and efficacy of these immunotherapies. Dendritic cell vaccines, adoptive cell transfer, and oncolytic viruses may have a potential role in the treatment of malignant glioma. However, these modalities must be investigated in well-designed phase III trials to prove their efficacy.
Topics: Adoptive Transfer; Brain Neoplasms; Cancer Vaccines; Dendritic Cells; Glioma; Humans; Immunotherapy; Oncolytic Viruses
PubMed: 28488122
DOI: 10.1007/s11910-017-0754-x -
Der Nervenarzt Jun 2015Therapeutic concepts for malignant gliomas increasingly target the genetically non-transformed tumor stroma rather than the tumor cells themselves. There are two... (Review)
Review
Therapeutic concepts for malignant gliomas increasingly target the genetically non-transformed tumor stroma rather than the tumor cells themselves. There are two particular compartments of the tumor stroma which are currently tackled: the vascular compartment by using antiangiogenic treatment with the aim of vascular normalization and the immune compartment with the aim of enhancing or inducing anti-tumor immunity. Although the vascular endothelial growth factor (VEGF) A antibody bevacizumab has not been approved for the treatment of malignant glioma in European countries, there is evidence from smaller trials of biological efficacy particularly in recurrent disease and the results of a large European phase III study testing the clinical efficacy are currently expected. Immunotherapies are on the verge of entering the clinical arena with the first randomized phase III clinical trials having already been completed. In these studies, active vaccination and checkpoint inhibitors which are approved for other tumor entities are being tested. This article provides an overview on the current antiangiogenic and immunological therapies for gliomas, summarizes the results of clinical trials and discusses further developments.
Topics: Angiogenesis Inhibitors; Animals; Brain Neoplasms; Cancer Vaccines; Glioma; Humans; Immunosuppressive Agents; Immunotherapy; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 25962344
DOI: 10.1007/s00115-014-4225-1 -
Neoplasia (New York, N.Y.) Apr 2017Human glioma, in particular, malignant forms such as glioblastoma exhibit dismal survival rates despite advances in treatment strategies. A population of glioma cells... (Review)
Review
Human glioma, in particular, malignant forms such as glioblastoma exhibit dismal survival rates despite advances in treatment strategies. A population of glioma cells with stem-like features, glioma cancer stem-like cells (GCSCs), contribute to renewal and maintenance of the tumor cell population and appear responsible for chemotherapeutic and radiation resistance. Bone morphogenetic protein 4 (BMP4), drives differentiation of GCSCs and thus improves therapeutic efficacy. Based on this observation it is imperative that the clinical merits of BMP4 in treating human gliomas should be addressed. This article reviews BMP4 signaling in central nervous system development and in glioma tumorigenesis, and the potential of this molecule as a treatment target in human gliomas. Further work needs to be done to determine if distinct lineages of GCSCs, associated with different glioma sub-classifications, proneural, neural, classical and mesenchymal, differ in responsiveness to BMP4 treatment. Additionally, interaction among BMP4 and cell matrix, tumor-vascular molecules and microglial immune cells also needs to be investigated, as this will enhance our knowledge about the role of BMP4 in human glioma and lead to the identification and/or development of novel therapeutic approaches that improve treatment outcomes of these devastating tumors.
Topics: Bone Morphogenetic Protein 4; Brain Neoplasms; Carrier Proteins; Cell Transformation, Neoplastic; Central Nervous System; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Glioma; Humans; Phenotype; Protein Binding; Radiation Tolerance; Signal Transduction; Tumor Microenvironment
PubMed: 28278424
DOI: 10.1016/j.neo.2017.01.006 -
Neuro-oncology Jun 2018A rational treatment strategy for glioma, the most common primary central nervous system tumor, should focus on early invasive growth and resistance to current... (Review)
Review
A rational treatment strategy for glioma, the most common primary central nervous system tumor, should focus on early invasive growth and resistance to current therapeutics. Connexin 43 (Cx43), a gap junction protein, plays important roles not only in the development of the central nervous system and but also in the progression of glioma. The different structural domains of Cx43, including extracellular loops, transmembrane domains, and an intracellular carboxyl terminal, have distinct functions in the invasion and proliferation of gliomas. Targeting these domains of Cx43, which is expressed in distinct patterns in the heterogeneous glioma cell population, can inhibit tumor cell invasion and new tumor formation. Thus, this review summarizes the structural characteristics of Cx43, the effects of regulating different Cx43 domains on the biological characteristics of glioma cells, intervention strategies targeting different domains of Cx43, and future research directions.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Connexins; Glioma; Humans; Molecular Targeted Therapy; Prognosis; Protein Domains
PubMed: 29106645
DOI: 10.1093/neuonc/nox207 -
Marine Drugs Sep 2019Malignant glioma (MG) is a poor prognostic brain tumor with inevitable recurrence after multimodality treatment. Searching for more effective treatment is urgently...
Malignant glioma (MG) is a poor prognostic brain tumor with inevitable recurrence after multimodality treatment. Searching for more effective treatment is urgently needed. Differentiation induction via epigenetic modification has been proposed as a potential anticancer strategy. Natural products are known as fruitful sources of epigenetic modifiers with wide safety margins. We thus explored the effects of oligo-fucoidan (OF) from brown seaweed on this notion in MG cells including Grade III U87MG cells and Grade IV glioblastoma multiforme (GBM)8401 cells and compared to the immortalized astrocyte SVGp12 cells. The results showed that OF markedly suppress the proliferation of MG cells and only slightly affected that of SVGp12 cells. OF inhibited the protein expressions of DNA methyltransferases 1, 3A and 3B (DNMT1, 3A and 3B) accompanied with obvious mRNA induction of differentiation markers (, , , , and ) both in U87MG and GBM8401 cells. Accordingly, the methylation of , a DNMT3B target gene, was decreased by OF. In combination with the clinical DNMT inhibitor decitabine, OF could synergize the growth inhibition and induction in U87MG cells. Appropriated clinical trials are warranted to evaluate this potential complementary approach for MG therapy after confirmation of the effects in vivo.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Brain Neoplasms; Cell Differentiation; Cell Line, Tumor; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioma; Humans; Neoplasm Recurrence, Local; Polysaccharides
PubMed: 31500384
DOI: 10.3390/md17090525 -
Cells Dec 2022The fatal clinical course of human glioblastoma (GBM) despite aggressive adjuvant therapies is due to high rates of recurrent tumor growth driven by tumor cells with...
The fatal clinical course of human glioblastoma (GBM) despite aggressive adjuvant therapies is due to high rates of recurrent tumor growth driven by tumor cells with stem-cell characteristics (glioma stem cells, GSCs). The aldehyde dehydrogenase 1 (ALDH1) family of enzymes has been shown to be a biomarker for GSCs, and ALDH1 seems to be involved in the biological processes causing therapy resistance. Ferroptosis is a recently discovered cell death mechanism, that depends on iron overload and lipid peroxidation, and it could, therefore, be a potential therapeutic target in various cancer types. Since both ALDH1 and ferroptosis interact with lipid peroxidation (LPO), we aimed to investigate a possible connection between ALDH1 and ferroptosis. Here, we show that RSL3-induced LPO and ferroptotic cell death revealed RSL3-sensitive and -resistant malignant glioma cell lines. Most interestingly, RSL3 sensitivity correlates with ALDH1a3 expression; only high ALDH1a3-expressing cells seem to be sensitive to ferroptosis induction. In accordance, inhibition of ALDH1a3 enzymatic activity by chemical inhibition or genetic knockout protects tumor cells from RSL3-induced ferroptotic cell death. Both RSL-3-dependent binding of ALDH1a3 to LC3B and autophagic downregulation of ferritin could be completely blocked by ALDH inhibition. Therefore, ALDH1a3 seems to be involved in ferroptosis through the essential release of iron by ferritinophagy. Our results also indicate that ferroptosis induction might be a particularly interesting clinical approach for targeting the highly aggressive cell population of GSC.
Topics: Humans; Aldehyde Dehydrogenase 1 Family; Autophagy; Ferroptosis; Glioblastoma; Glioma; Neoplasm Recurrence, Local
PubMed: 36552781
DOI: 10.3390/cells11244015 -
Expert Opinion on Investigational Drugs Jul 2020Gliomas are infiltrating brain tumors associated with high morbidity and mortality. Current standard of care includes radiation, chemotherapy, and surgical resection.... (Review)
Review
INTRODUCTION
Gliomas are infiltrating brain tumors associated with high morbidity and mortality. Current standard of care includes radiation, chemotherapy, and surgical resection. Today, survival rates for malignant glioma patients remain dismal and unchanged for decades. The glioma microenvironment is highly immunosuppressive and consequently this has motivated the development of immunotherapies for counteracting this condition, enabling the immune cells within the tumor microenvironment to react against this tumor.
AREAS COVERED
The authors discuss immunotherapeutic strategies for glioma in phase-I/II clinical trials and illuminate their mechanisms of action, limitations, and key challenges. They also examine promising approaches under preclinical development.
EXPERT OPINION
In the last decade there has been an expansion in immune-mediated anti-cancer therapies. In the glioma field, sophisticated strategies have been successfully implemented in preclinical models. Unfortunately, clinical trials have not yet yielded consistent results for glioma patients. This could be attributed to our limited understanding of the complex immune cell infiltration and its interaction with the tumor cells, the selected time for treatment, the combination with other therapies and the route of administration of the agent. Applying these modalities to treat malignant glioma is challenging, but many new alternatives are emerging to by-pass these hurdles.
Topics: Animals; Brain Neoplasms; Glioma; Humans; Immunotherapy; Survival Rate; Tumor Microenvironment
PubMed: 32400216
DOI: 10.1080/13543784.2020.1768528 -
BMC Cancer Feb 2023Gliomas are the most common brain tumours with the high-grade glioblastoma representing the most aggressive and lethal form. Currently, there is a lack of specific...
BACKGROUND
Gliomas are the most common brain tumours with the high-grade glioblastoma representing the most aggressive and lethal form. Currently, there is a lack of specific glioma biomarkers that would aid tumour subtyping and minimally invasive early diagnosis. Aberrant glycosylation is an important post-translational modification in cancer and is implicated in glioma progression. Raman spectroscopy (RS), a vibrational spectroscopic label-free technique, has already shown promise in cancer diagnostics.
METHODS
RS was combined with machine learning to discriminate glioma grades. Raman spectral signatures of glycosylation patterns were used in serum samples and fixed tissue biopsy samples, as well as in single cells and spheroids.
RESULTS
Glioma grades in fixed tissue patient samples and serum were discriminated with high accuracy. Discrimination between higher malignant glioma grades (III and IV) was achieved with high accuracy in tissue, serum, and cellular models using single cells and spheroids. Biomolecular changes were assigned to alterations in glycosylation corroborated by analysing glycan standards and other changes such as carotenoid antioxidant content.
CONCLUSION
RS combined with machine learning could pave the way for more objective and less invasive grading of glioma patients, serving as a useful tool to facilitate glioma diagnosis and delineate biomolecular glioma progression changes.
Topics: Humans; Spectrum Analysis, Raman; Glycosylation; Glioma; Brain Neoplasms; Glioblastoma; Neoplasm Grading
PubMed: 36809974
DOI: 10.1186/s12885-023-10588-w