bims-malgli Biomed News
on Biology of malignant gliomas
Issue of 2021‒10‒31
fourteen papers selected by
Oltea Sampetrean
Keio University
  1. ELTD1 as a multi-focal target for malignant gliomas: preclinical studies.
  2. Radiotherapy is Associated With Global Methylation Alterations in Patient Derived Glioblastoma Cell Lines.
  3. Old Stars and New Players in the Brain Tumor Microenvironment.
  4. Passive targeting of high-grade gliomas via the EPR effect: a closed path for metallic nanoparticles?
  5. Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of imaging in the management of progressive glioblastoma in adults.
  6. Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma.
  7. Identification of De Novo Pyrimidine Synthesis as a Targetable Vulnerability in a Novel IDH1 Mutant Engineered Astrocytoma Model.
  8. Evidence for age-related contributions of DNA damage and epigenetics in brain tumorigenesis.
  9. Inhibition of ERK/MAPK signaling as potential therapy to prevent optic pathway glioma in infants with neurofibromatosis type 1.
  10. Age at diagnosis and sex interact to modify primary malignant glioma incidence and survival.
  11. Role of the Tyrosine Phosphatase SHP-2 in Mediating Adrenomedullin Proangiogenic Activity in Solid Tumors.
  12. A combined treatment regimen of MGMT-modified γδ T cells and temozolomide chemotherapy is effective against primary high grade gliomas.
  13. BOLD Asynchrony: An imaging biomarker of tumor burden in IDH-mutated gliomas.
  14. Seeing more with less: virtual gadolinium-enhanced glioma imaging.
  1. Neurooncol Adv. 2021 Jan-Dec;3(1):3(1): vdab132
    ELTD1 as a multi-focal target for malignant gliomas: preclinical studies.
    Michelle Zalles, Nataliya Smith, Debra Saunders, Mayra Guzman, Megan Lerner, Kar-Ming Fung, Anish Babu, James Battiste, Junho Chung, Kyusang Hwang, Junyeong Jin, Rheal A Towner.
      Background: Glioblastoma (GBM) is the most aggressive malignant primary brain tumor in adults. These high-grade gliomas undergo unregulated vascular angiogenesis, migration and cell proliferation allowing the tumor cells to evade cell-cycle checkpoints and apoptotic pathways. The Epidermal growth factor, latrophilin, and seven transmembrane domain-containing 1 on chromosome 1 (ELTD1) is an angiogenic biomarker that is highly expressed in malignant gliomas. Novel treatments targeting ELTD1 with monovalent monoclonal (mmAb) and single chain variable fragment (scFv) antibodies were effective in increasing animal survival, decreasing tumor volume and normalizing the vasculature. Due to the success of our antibody treatments on angiogenesis, this study sought to determine if our anti-ELTD1 treatments affected other aspects of tumorigenesis (cell proliferation, migration, and apoptosis) in a G55 glioma xenograft preclinical mouse model.Methods: Tumor tissue from untreated, mmAb and scFv anti-ELTD1 treated animals was used to quantify the positivity levels of human mitochondrial antibody, c-MET and Ki-67 for cellular proliferation, migratory markers CD44v6, TRPM8, and BMP2, and cleaved caspase 3 to assess apoptotic activity.
    Results: This approach demonstrated that our anti-ELTD1 treatments directly affected and decreased the human tumor cells within the tumor region. Additionally, there was a significant decrease in both cellular proliferation and migration due to anti-ETLD1 therapy. Lastly, anti-ELTD1 treatments successfully increased apoptotic activity within the tumor region.
    Conclusion: Our data suggest that anti-ELTD1 therapies would be effective against malignant gliomas by having a multi-focal effect and targeting all four aspects of tumorigenesis.
    Keywords:  ELTD1; apoptosis | glioblastoma (GBM); migration; proliferation
    DOI:  https://doi.org/10.1093/noajnl/vdab132
  2. Int J Radiat Oncol Biol Phys. 2021 Nov 01. pii: S0360-3016(21)02461-5. [Epub ahead of print]111(3S): e595
    Radiotherapy is Associated With Global Methylation Alterations in Patient Derived Glioblastoma Cell Lines.
    A S Modrek, R Ezhilarasan, M Snuderl, E P Sulman.
      PURPOSE/OBJECTIVE(S): Despite maximal surgical resection, radiotherapy, chemotherapy and re-treatment at re-occurrence, median overall survival time of glioblastoma (WHO grade IV, IDH wild-type) is estimated to be ∼16 months. In glioma, DNA methylation states are the most predictive marker of overall survival and response to therapy. Our understanding of how epigenetic states, such as DNA methylation, are "mis-repaired" after DNA damage repair is scant, hampering our ability to understand how treatment associated DNA methylation alterations may drive tumor resistance and growth.MATERIALS/METHODS: Three different patient derived glioma stem cell (GSC) lines, in duplicates, were treated with 20 Gy in 10 fractions and allowed to recover prior to DNA methylation analysis with 850K methylation arrays. To analyze the methylation array data, we used RnBeads (version 2.4.0) and R (version 3.6.1) packages. We further focused our analysis to various genomic regions, including CpG islands, promoters, gene bodies and CTCF motifs to understand how methylation alterations may differ between these and other genomic contexts.
    RESULTS: We found differential methylation (pre-treatment vs. radiation treatment) changes among the genomic regions examined. Interestingly, we found differential methylation changes at CTCF motifs, which play important DNA-methylation dependent roles in gene expression and chromatin architecture regulation. Hierarchical clustering, PCA and MDS analysis amongst CpG islands, promoters, gene bodies and CTCF domains did not reveal strong inter-sample differences that segregated the samples on the basis of treatment status, suggesting radiation associated methylation alterations are context dependent.
    CONCLUSION: Radiation treatment is associated with wide-spread alterations of DNA methylation states in this patient derived glioblastoma model. Such alterations may drive gene expression changes, or genomic architecture alterations, that lead to treatment resistance in the recurrent setting.
    AUTHOR DISCLOSURE: A.S. Modrek: None. R. Ezhilarasan: None. M. Snuderl: None. E.P. Sulman: None.
    DOI:  https://doi.org/10.1016/j.ijrobp.2021.07.1591
  3. Front Cell Neurosci. 2021 ;15 709917
    Old Stars and New Players in the Brain Tumor Microenvironment.
    Elena Parmigiani, Marta Scalera, Elisabetta Mori, Elena Tantillo, Eleonora Vannini.
      In recent years, the direct interaction between cancer cells and tumor microenvironment (TME) has emerged as a crucial regulator of tumor growth and a promising therapeutic target. The TME, including the surrounding peritumoral regions, is dynamically modified during tumor progression and in response to therapies. However, the mechanisms regulating the crosstalk between malignant and non-malignant cells are still poorly understood, especially in the case of glioma, an aggressive form of brain tumor. The presence of unique brain-resident cell types, namely neurons and glial cells, and an exceptionally immunosuppressive microenvironment pose additional important challenges to the development of effective treatments targeting the TME. In this review, we provide an overview on the direct and indirect interplay between glioma and neuronal and glial cells, introducing new players and mechanisms that still deserve further investigation. We will focus on the effects of neural activity and glial response in controlling glioma cell behavior and discuss the potential of exploiting these cellular interactions to develop new therapeutic approaches with the aim to preserve proper brain functionality.
    Keywords:  OPCs; glial cells; glioblastoma; glioma; neural activity; peritumoral tissue; reactive astrocyte; tumor-associated microglia/macrophages (TAM)
    DOI:  https://doi.org/10.3389/fncel.2021.709917
  4. Biomater Sci. 2021 Oct 28.
    Passive targeting of high-grade gliomas via the EPR effect: a closed path for metallic nanoparticles?
    Carlos Caro, Ashish Avasthi, Jose M Paez-Muñoz, Manuel Pernia Leal, María L García-Martín.
      Passive tumor targeting via the enhanced permeability and retention (EPR) effect has long been considered the most effective mechanism for the accumulation of nanoparticles inside solid tumors. However, several studies have demonstrated that the EPR effect is largely dependent on the tumor type and location. Particularly complex is the situation in brain tumors, where the presence of the blood-brain tumor barrier (BBTB) adds an extra limiting factor in reaching the tumor interstitium. However, it remains unclear whether these restraints imposed by the BBTB prevent the EPR effect from acting as an efficient tumor targeting mechanism for metallic nanoparticles. In this work, we have studied the EPR effect of metallic magnetic nanoparticles (MMNPs) in a glioblastoma (GBM) model by parametric MRI. Our results showed that only MMNPs ≤50 nm could reach the tumor interstitium, whereas larger MMNPs were unable to cross the BBTB. Furthermore, even for MMNPs around 30-50 nm, the amount of them found within the tumor was scarce and restricted to the vicinity of large tumor vessels, indicating that the BBTB strongly limits the passive accumulation of metallic nanoparticles in brain tumors. Therefore, active targeting becomes the most reasonable strategy to target metallic nanoparticles to GBMs.
    DOI:  https://doi.org/10.1039/d1bm01398j
  5. J Neurooncol. 2021 Oct 25.
    Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of imaging in the management of progressive glioblastoma in adults.
    Derek Richard Johnson, Chad Allan Glenn, Ramin Javan, Jeffrey James Olson.
      TARGET POPULATION: These recommendations apply to adults with glioblastoma who have been previously treated with first-line radiation or chemoradiotherapy and who are suspected of experiencing tumor progression.QUESTION: In patients with previously treated glioblastoma, is standard contrast-enhanced magnetic resonance imaging including diffusion weighted imaging useful for diagnosing tumor progression and differentiating progression from treatment-related changes? Level II: Magnetic resonance imaging with and without gadolinium enhancement including diffusion weighted imaging is recommended as the imaging surveillance method to detect the progression of previously diagnosed glioblastoma.
    QUESTION: In patients with previously treated glioblastoma, does magnetic resonance spectroscopy add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? Level II: Magnetic resonance spectroscopy is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma.
    QUESTION: In patients with previously treated glioblastoma, does magnetic resonance perfusion add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? Level III: Magnetic resonance perfusion is suggested as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma.
    QUESTION: In patients with previously treated glioblastoma, does the addition of single-photon emission computed tomography (SPECT) provide additional useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? Level III: Single-photon emission computed tomography imaging is suggested as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma.
    QUESTION: In patients with previously treated glioblastoma, does 18F-fluorodeoxyglucose positron emission tomography add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? Level III: The routine use of 18F-fluorodeoxyglucose positron emission tomography to identify progression of glioblastoma is not recommended.
    QUESTION: In patients with previously treated glioblastoma, does positron emission tomography with amino acid agents add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? Level III: It is suggested that amino acid positron emission tomography be considered to assist in the differentiation of progressive glioblastoma from treatment related changes.
    Keywords:  Diffusion; Glioblastoma; Imaging; MRI; PET; Perfusion; Spectroscopy
    DOI:  https://doi.org/10.1007/s11060-021-03853-0
  6. J Neurooncol. 2021 Oct 25.
    Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma.
    Evan Winograd, Isabelle Germano, Patrick Wen, Jeffrey J Olson, D Ryan Ormond.
      The following questions and recommendations are pertinent to the following: TARGET POPULATION: These recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation. QUESTION 1: In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RECOMMENDATION: Level III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival. QUESTION 2: In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
    RECOMMENDATION: Level III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity. QUESTION 3: In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
    RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 4: In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
    RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 5: In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
    RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 6: In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
    RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 7: In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
    RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 8: In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
    RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question.
    Keywords:  Guidelines update; Immunotherapy; Progressive glioblastoma; Targeted therapy
    DOI:  https://doi.org/10.1007/s11060-021-03876-7
  7. Int J Radiat Oncol Biol Phys. 2021 Nov 01. pii: S0360-3016(21)01075-0. [Epub ahead of print]111(3S): S86
    Identification of De Novo Pyrimidine Synthesis as a Targetable Vulnerability in a Novel IDH1 Mutant Engineered Astrocytoma Model.
    D D Shi, A C Wang, W Gao, J Khanal, M M Levitt, R B Jennings, S Signoretti, Q D Nguyen, J E Endress, M Xu, S Gradl, A Sutter, M Jeffers, A Janzer, D P Cahill, K G Abdullah, K L Ligon, I S Harris, W G Kaelin, S K McBrayer.
      PURPOSE/OBJECTIVE(S): Despite high prevalence of IDH1-R132H mutations in grade II-III gliomas, effective therapies remain limited. We sought to identify tumor-specific vulnerabilities induced by the IDH1-R132H oncogene and test the translational relevance of targeting them using a new genetically engineered mouse model (GEMM) of IDH1 mutant anaplastic astrocytoma.MATERIALS/METHODS: We conducted a synthetic lethality screen using isogenic IDH1 mutant and IDH1 wild-type (WT) glioma cells and a novel drug screening platform developed by our group, called MAPS. To create a GEMM of anaplastic astrocytoma, we developed a strategy to engineer Tp53, Atrx, Pik3ca, and Idh1 mutations in the brains of adult mice. We intracranially injected adeno-associated virus (AAV) expressing Cre recombinase and CRISPR sgRNAs targeting murine Atrx and Tp53 genes into 4 mouse strains: 1) LSL-Cas9; 2) LSL-Cas9; LSL-Pik3caH1047R, 3) LSL-Cas9; LSL-Idh1R132H, and 4) LSL-Cas9; LSL-Idh1R132H; LSL-Pik3caH1047R.
    RESULTS: Our screen revealed that IDH1 mutant cells are hypersensitive to drugs targeting enzymes in the de novo pyrimidine nucleotide synthesis pathway, including dihydroorotate dehydrogenase (DHODH). We demonstrated that these cytotoxic effects are on-target and are associated with increased DNA damage in IDH1 mutant cells. Next, we showed that IDH1 mutant patient-derived glioma stem-like cell lines (GSCs) are also hyperdependent on de novo pyrimidine synthesis compared to IDH1 WT lines. In addition, we found that the novel brain penetrant DHODH inhibitor, BAY2402234 (currently undergoing testing in leukemia patients), decreased tumor growth in an orthotopic xenograft model of IDH1 mutant, but not IDH1 WT, glioblastoma. We then sought to create and use a GEMM of IDH1 mutant anaplastic astrocytoma to test whether dependence on de novo pyrimidine synthesis manifests across tumor grade. Following intracranial AAV injection (see methods), astrocytomas preferentially formed after 9-14 months in mice carrying both Idh1 and Pik3ca conditional alleles. These tumors histologically resembled grade III astrocytomas, expressed astrocytoma lineage markers, and displayed elevated (R)-2-hydroxyglutarate. To create an additional model with shorter tumor latency, we performed secondary transplants of GSCs derived from our GEMM into recipient mice. We found that BAY2402234 blocked tumor growth in these orthotopic astrocytoma allografts.
    CONCLUSION: Our findings establish IDH1 mutations as predictive biomarkers of DHODH inhibitor efficacy in gliomas across tumor grade, highlight BAY2402234 as a candidate glioma therapeutic, and unveil new genetically faithful mouse models of IDH1 mutant glioma. In addition, we show that BAY2402234 induces preferential DNA damage in IDH1 mutant cells, thereby supporting evaluation of BAY2402234 as a potential tumor-selective radiosensitizer.
    DOI:  https://doi.org/10.1016/j.ijrobp.2021.07.205
  8. Int J Exp Pathol. 2021 Oct 30.
    Evidence for age-related contributions of DNA damage and epigenetics in brain tumorigenesis.
    Adrian Tira, Lela Buckingham.
      Glioblastoma (GBM) is a highly malignant primary brain tumour displaying rapid cell proliferation and infiltration. GBM primarily occurs at older age; however, younger populations have also been affected. In GBM and other cancers, genetic and epigenetic alterations promote tumorigenesis causing increased cell proliferation and invasiveness. This investigation explored epigenetic events as contributing factors, especially in gliomas that arise in patients aged 40-60 years. Furthermore, DNA damage in tumours with respect to age was assessed. Archival fixed tissues from 88 cases of glioblastoma and adjacent non-malignant tissues were tested. Global methylation and DNA damage were measured using ELISA detection of 5-methyl cytosine and 8-hydroxy guanine, respectively. IDH mutations and CDKN2 promoter hypermethylation were analysed by pyrosequencing. Tumour tissue was hypomethylated compared with non-malignant tissue (P = .001), and there was a trend towards increased methylation with increasing age. There was a significant increase in DNA damage in patients older than forty years compared with those aged forty years or younger (P = .035). CDKN2 promoter methylation levels followed the age trends of global methylation in this patient group. Patients younger than 60 had more frequently mutated IDH (P = .004). Conclusions: The data support the potential of epigenetic factors in promoting tumorigenesis in younger patients, while increased DNA damage contributes to tumorigenesis in the older patients.
    Keywords:  Brain cancer; DNA injury; epigenetics; methylation
    DOI:  https://doi.org/10.1111/iep.12402
  9. Dev Cell. 2021 Oct 25. pii: S1534-5807(21)00771-1. [Epub ahead of print]56(20): 2785-2786
    Inhibition of ERK/MAPK signaling as potential therapy to prevent optic pathway glioma in infants with neurofibromatosis type 1.
    Fulvio D'Angelo, Anna Lasorella.
      Pediatric low-grade gliomas (pLGGs) arise primarily at early stages of development. The molecular mechanisms of pLGG gliomagenesis are unclear, as is the progenitor cell of origin. In this issue of Developmental Cell, Jecrois et al. show that NF1-associated optic pathway gliomas originate from migrating glial progenitors that have distinct MEK/ERK dependency.
    DOI:  https://doi.org/10.1016/j.devcel.2021.10.001
  10. Neuro Oncol. 2021 Oct 25. pii: noab250. [Epub ahead of print]
    Age at diagnosis and sex interact to modify primary malignant glioma incidence and survival.
    Judith Schwartzbaum, Randall Harris.
      
    DOI:  https://doi.org/10.1093/neuonc/noab250
  11. Front Oncol. 2021 ;11 753244
    Role of the Tyrosine Phosphatase SHP-2 in Mediating Adrenomedullin Proangiogenic Activity in Solid Tumors.
    Romain Sigaud, Nadège Dussault, Caroline Berenguer-Daizé, Christine Vellutini, Zohra Benyahia, Mylène Cayol, Fabrice Parat, Kamel Mabrouk, Ramiro Vázquez, Maria E Riveiro, Philippe Metellus, L'Houcine Ouafik.
      VE-cadherin is an essential adhesion molecule in endothelial adherens junctions, and the integrity of these complexes is thought to be regulated by VE-cadherin tyrosine phosphorylation. We have previously shown that adrenomedullin (AM) blockade correlates with elevated levels of phosphorylated VE-cadherin (pVE-cadherinY731) in endothelial cells, associated with impaired barrier function and a persistent increase in vascular endothelial cell permeability. However, the mechanism underlying this effect is unknown. In this article, we demonstrate that the AM-mediated dephosphorylation of pVE-cadherinY731 takes place through activation of the tyrosine phosphatase SHP-2, as judged by the rise of its active fraction phosphorylated at tyrosine 542 (pSHP-2Y542) in HUVECs and glioblastoma-derived-endothelial cells. Both pre-incubation of HUVECs with SHP-2 inhibitors NSC-87877 and SHP099 and SHP-2 silencing hindered AM-induced dephosphorylation of pVE-cadherinY731 in a dose dependent-manner, showing the role of SHP-2 in the regulation of endothelial cell contacts. Furthermore, SHP-2 inhibition impaired AM-induced HUVECs differentiation into cord-like structures in vitro and impeded AM-induced neovascularization in in vivo Matrigel plugs bioassays. Subcutaneously transplanted U87-glioma tumor xenograft mice treated with AM-receptors-blocking antibodies showed a decrease in pSHP-2Y542 associated with VE-cadherin in nascent tumor vasculature when compared to control IgG-treated xenografts. Our findings show that AM acts on VE-cadherin dynamics through pSHP-2Y542 to finally modulate cell-cell junctions in the angiogenesis process, thereby promoting a stable and functional tumor vasculature.
    Keywords:  SHP-2; adrenomedullin; angiogenesis; cell-cell adhesions; endothelial cell; glioblastoma-associated endothelial cells
    DOI:  https://doi.org/10.3389/fonc.2021.753244
  12. Sci Rep. 2021 Oct 26. 11(1): 21133
    A combined treatment regimen of MGMT-modified γδ T cells and temozolomide chemotherapy is effective against primary high grade gliomas.
    Lawrence S Lamb, Larisa Pereboeva, Samantha Youngblood, G Yancey Gillespie, L Burton Nabors, James M Markert, Anindya Dasgupta, Catherine Langford, H Trent Spencer.
      Chemotherapeutic drugs such as the alkylating agent Temozolomide (TMZ), in addition to reducing tumor mass, can also sensitize tumors to immune recognition by transient upregulation of multiple stress induced NKG2D ligands (NKG2DL). However, the potential for an effective response by innate lymphocyte effectors such as NK and γδ T cells that recognize NKG2DL is limited by the drug's concomitant lymphodepleting effects. We have previously shown that modification of γδ T cells with a methylguanine DNA methyltransferase (MGMT) transgene confers TMZ resistance via production of O6-alkylguanine DNA alkyltransferase (AGT) thereby enabling γδ T cell function in therapeutic concentrations of TMZ. In this study, we tested this strategy which we have termed Drug Resistant Immunotherapy (DRI) to examine whether combination therapy of TMZ and MGMT-modified γδ T cells could improve survival outcomes in four human/mouse xenograft models of primary and refractory GBM. Our results confirm that DRI leverages the innate response of γδ T cells to chemotherapy-induced stress associated antigen expression and achieves synergies that are significantly greater than either individual approach.
    DOI:  https://doi.org/10.1038/s41598-021-00536-8
  13. Neuro Oncol. 2021 Oct 25. pii: noab248. [Epub ahead of print]
    BOLD Asynchrony: An imaging biomarker of tumor burden in IDH-mutated gliomas.
    Behroze Adi Vachha, Raymond Y Huang.
      
    Keywords:  BOLD; FLAIR; IDH; asynchrony; stereotactic
    DOI:  https://doi.org/10.1093/neuonc/noab248
  14. Lancet Digit Health. 2021 Oct 20. pii: S2589-7500(21)00219-3. [Epub ahead of print]
    Seeing more with less: virtual gadolinium-enhanced glioma imaging.
    Alexandros Ferles, Frederik Barkhof.
      
    DOI:  https://doi.org/10.1016/S2589-7500(21)00219-3
This page is being maintained by Thomas Krichel. It was last updated on 2021‒10‒31 at 00:35:45.