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International Journal of Nanomedicine 2021Glioma is the most common and malignant primary brain tumour in adults and has a dismal prognosis. Temozolomide (TMZ) is the only clinical first-line chemotherapy drug...
Accurately Controlled Delivery of Temozolomide by Biocompatible UiO-66-NH Through Ultrasound to Enhance the Antitumor Efficacy and Attenuate the Toxicity for Treatment of Malignant Glioma.
BACKGROUND
Glioma is the most common and malignant primary brain tumour in adults and has a dismal prognosis. Temozolomide (TMZ) is the only clinical first-line chemotherapy drug for malignant glioma up to present. Due to poor aqueous solubility and toxic effects, TMZ is still inefficient and limited for clinical glioma treatment.
METHODS
UiO-66-NH nanoparticle is a zirconium-based framework, constructed by Zr and 2-amino-1,4-benzenedicarboxylic acid (BDC-NH) with octahedral microporous structure, which can be decomposed by the body into an ionic form to discharge. We prepared the nanoscale metal-organic framework (MOF) of UiO-66-NH to load TMZ for therapy of malignant glioma, TMZ is released from UiO-66-NH through a porous structure. The ultrasound accelerates its porous percolation and promotes the rapid dissolution of TMZ through low-frequency oscillations and cavitation effect. The biological safety and antitumor efficacy were evaluated both in vitro and in vivo.
RESULTS
The prepared TMZ@MOF exhibited excellent biocompatibility and biosafety due to minimal drug leakage without ultrasound intervention. We further used the flank model of glioblastoma to verify the in vivo therapeutic effect. TMZ@UiO-66-NH nanocomposites could be well delivered to the tumour tissue, which led to local enrichment of the TMZ concentration. Furthermore, TMZ@UiO-66-NH nanocomposites under ultrasound demonstrated much more efficient inhibition for tumor growth than TMZ@UiO-66-NH nanocomposites and TMZ alone. Meanwhile, the bone marrow suppression side effects of TMZ were significantly reduced by TMZ@UiO-66-NH nanocomposites.
CONCLUSION
In this work, TMZ@UiO-66-NH nanocomposites with ultrasound mediation could effectively improve the killing effect of malignant glioma and decrease TMZ-induced toxicity in normal tissues, demonstrating great potential for the delivery of TMZ in the clinical treatment of malignant gliomas.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Cell Line, Tumor; Glioblastoma; Glioma; Humans; Temozolomide; Xenograft Model Antitumor Assays
PubMed: 34675514
DOI: 10.2147/IJN.S330187 -
Acta Radiologica (Stockholm, Sweden :... May 1998To investigate the clinical utility of 3D time-of-flight (TOF) MR angiography (MRA) in the evaluation of pathological vessels in patients with malignant glioma. (Clinical Trial)
Clinical Trial Comparative Study
PURPOSE
To investigate the clinical utility of 3D time-of-flight (TOF) MR angiography (MRA) in the evaluation of pathological vessels in patients with malignant glioma.
MATERIAL AND METHODS
Sixteen patients with malignant glioma (12 with glioblastoma multiforme and 4 with anaplastic astrocytoma) were examined with 3D TOF MRA before and after the injection of gadopentetate dimeglumine. The 3D TOF MRA study was compared with conventional angiography in all patients.
RESULTS
The unenhanced 3D TOF MRAs successfully depicted the feeding arteries in 9 patients but failed to depict small feeding arteries in 2 patients in whom these arteries were shown by conventional angiography. The enhanced MRAs demonstrated draining veins from the lesions in 8 patients but failed to depict a draining vein in 1 patient that was shown by conventional angiography. The stereoscopic view projection effectively depicted displacements of the major cerebral arteries in 14 patients, and deep venous structures in 11 patients which almost accorded with the findings at conventional angiography.
CONCLUSION
Our results indicate that 3D TOF MRA can provide an accurate visualization of pathological vascular structures and thus help establish a diagnosis in patients with malignant glioma.
Topics: Adult; Aged; Angiography; Evaluation Studies as Topic; Female; Gadolinium DTPA; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Angiography; Male; Middle Aged
PubMed: 9571934
DOI: 10.1080/02841859809172185 -
Tumour Biology : the Journal of the... Jan 2016The prognosis of patients with malignant glioma is always quite poor, and this poor prognosis is probably due to our incomplete understanding of the molecular mechanisms...
The prognosis of patients with malignant glioma is always quite poor, and this poor prognosis is probably due to our incomplete understanding of the molecular mechanisms underlying malignant glioma. It is known that myocyte enhancer factor-2D (MEF2D) plays an oncogenic role in hepatocellular carcinoma and promotes the survival of various types of cells. However, little is known about the expression profile and function of MEF2D in malignant glioma. In this study, we investigated the function and expression of MEF2D in malignant glioma. We found that in malignant glioma, there is an aberrantly high expression of MEF2D, which leads to poor prognosis of malignant glioma. The downregulation of MEF2D suppresses the proliferation of malignant glioma cell lines by inducing delay of S and G2/M phases of cell cycle and promoting apoptosis. Furthermore, the overexpression of MEF2D in astrocytes accelerates cell proliferation by regulating cell cycle progression. Furthermore, a mouse malignant glioma model demonstrated that MEF2D deficiency blocks malignant glioma formation in vivo. We conclude that MEF2D may act as a potential oncogene in malignant glioma and thus serve as a candidate target for malignant glioma therapy.
Topics: Animals; Apoptosis; Astrocytes; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Disease Models, Animal; Gene Expression; Gene Expression Regulation, Neoplastic; Glioma; Humans; Immunohistochemistry; MEF2 Transcription Factors; Male; Mice; Neoplasm Grading; Prognosis
PubMed: 26234765
DOI: 10.1007/s13277-015-3791-6 -
The Oncologist Aug 2023In June 2021, the Ministry of Health, Labor and Welfare approved Delytact Injection as a regenerative medical product for oncolytic virus therapy. The active substance...
In June 2021, the Ministry of Health, Labor and Welfare approved Delytact Injection as a regenerative medical product for oncolytic virus therapy. The active substance of Delytact Injection is teserpaturev, a genetically engineered herpes simplex virus type 1 (strain F) in which the α47 gene and both copies of the γ34.5 gene have been deleted and the infected cell protein 6 (ICP6) gene has been inactivated by the insertion of the lacZ gene from Escherichia coli. Delytact Injection, when intratumorally administered to patients with malignant glioma, is expected to exert the following effects: (1) the mutant virus selectively replicates in tumor cells and destroys the infected cells through the replication process, exerting a cytocidal effect, and (2) the administration leads to induction of tumor-responsive T cells, which activates antitumor immunity and thus prolongs the survival of patients with malignant glioma. A Japanese phase II study (Study GD01) was conducted in patients with glioblastoma who had residual or recurrent tumors after radiotherapy with concomitant temozolomide. In Study GD01, however, stable disease continued for an extended period in some patients with glioblastoma. Hence, Delytact Injection is expected to be effective to a certain level. In line with this, Delytact Injection has been approved as an option for the treatment of malignant glioma, with one of the 3 approval conditions including conducting a use-results comparison survey and resubmission of the marketing authorization application within the granted time period of 7 years, under the conditional and time-limited approval scheme described in Article 23-26 of Act on Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices.
Topics: Humans; Oncolytic Virotherapy; Glioblastoma; Neoplasm Recurrence, Local; Glioma; Brain Neoplasms
PubMed: 36917020
DOI: 10.1093/oncolo/oyad041 -
Expert Review of Neurotherapeutics Jul 2005Virtually all malignant gliomas recur. Treatment options at recurrence have relied upon surgical intervention, radiation therapy or cytotoxic chemotherapy.... (Review)
Review
Virtually all malignant gliomas recur. Treatment options at recurrence have relied upon surgical intervention, radiation therapy or cytotoxic chemotherapy. Unfortunately, none are associated with significant improvements in survival. Advances in treatment options at recurrence have been dependent upon the combination of surgical resection, focal radiation and chemotherapy. Despite aggressive interventions, few patients have meaningful improvements. Current research focuses on novel targeted molecular therapy that will hopeful be able to take advantage of advances in our understanding of the biology of glial neoplasms.
Topics: Adult; Antineoplastic Agents; Brain Neoplasms; Glioma; Humans; Radiosurgery; Secondary Prevention
PubMed: 16026234
DOI: 10.1586/14737175.5.4.509 -
Oncology (Williston Park, N.Y.) Feb 1998A large number of oncogenes have been identified as aberrant in gliomas, but only the erbB oncogene (gene encoding the epidermal growth factor receptor [EGFR]) is... (Review)
Review
A large number of oncogenes have been identified as aberrant in gliomas, but only the erbB oncogene (gene encoding the epidermal growth factor receptor [EGFR]) is amplified in an appreciable number. The loss or mutation of tumor-suppressor genes located on different autosomes may be associated with progression of malignant gliomas. The p53 tumor-suppressor gene (located on chromosome 17) is frequently associated with the loss of one allele in malignant gliomas, although a large number of malignant gliomas have no p53 mutations. Some of the latter tumors have an amplified murine double minute 2 (MDM2) gene, which suppresses p53 gene activity. Genetic material from chromosome 10 may also be lost, especially in glioblastoma multiforme. In addition to the aberrant expression of EGFR, another growth factor, platelet-derived growth factor, or PDGF (ligand and/or receptors) can be overexpressed, giving cells a selective growth advantage. The blood-brain barrier is substantially altered in malignant gliomas, resulting in cerebral edema. Therapy for malignant gliomas includes surgery, radiation therapy, and chemotherapy. Surgical resection that leaves little residual tumor produces longer survival than less vigorous surgery. Radiation therapy to a dose of at least 60 Gy is required to treat malignant gliomas. Increased survival beyond that produced by standard external radiotherapy requires much larger doses; interstitial radiotherapy permits such dosing. Radiosurgery is being tested. Chemotherapy with nitrosoureas is modestly useful but appears to benefit patients with anaplastic astrocytoma more so than those with glioblastoma.
Topics: Glioma; Humans
PubMed: 9507524
DOI: No ID Found -
Expert Review of Anticancer Therapy May 2020: Recent discoveries in the molecular makeup of gliomas, the relationship of certain molecular drivers, and the patient's response to therapy and overall prognosis have... (Review)
Review
: Recent discoveries in the molecular makeup of gliomas, the relationship of certain molecular drivers, and the patient's response to therapy and overall prognosis have resulted in a paradigm shift and redefined our understanding of glioma and revealed potential vulnerabilities within this recalcitrant and lethal disease.: We summarize the current classification of malignant glioma in the context of the historical background, current data-driven treatment strategies, and recent discoveries of the mechanisms of pathogenesis of this disease which recapitulates the developing brain. We describe the relationship to common genetic alterations found in glioma, and possible avenues to exploit these newly revealed mechanisms.: Improved understanding of the molecular underpinnings of this disease has been directly translated into treatment decisions and an improved ability to counsel patients regarding their prognosis. We are beginning to see the first glimmer of a return on the investment in regard to immunotherapy in malignant glioma, with further anticipated successful exploitations of the unique pathophysiology of glioma.
Topics: Animals; Brain Neoplasms; Glioma; Humans; Immunotherapy; Prognosis
PubMed: 32301635
DOI: 10.1080/14737140.2020.1757440 -
Seminars in Oncology Dec 2003Despite many technologic advances in neuroimaging, neurosurgery, and radiation therapy, there has been little improvement in survival for patients with malignant glioma.... (Review)
Review
Despite many technologic advances in neuroimaging, neurosurgery, and radiation therapy, there has been little improvement in survival for patients with malignant glioma. Given the failure of traditional treatment approaches to significantly improve survival in patients with malignant gliomas, research in this field has focused on gaining a better understanding of the molecular pathogenesis of gliomas with the goal of identifying novel drug targets and therapeutic strategies. The influence of molecular genetics on response and survival has been best shown in oligodendrogliomas. The hallmarks of low-grade and anaplastic oligodendrogliomas are their exquisite sensitivity to chemotherapy and favorable prognosis, which are correlated with loss of heterozygosity of chromosomes 1p and 19q. Together, loss of heterozygosity of 1p and 19q appears to confer responsiveness to chemotherapy and to correlate with improved survival. In contrast, deletion of the CDKN2A gene is correlated with poor response to chemotherapy and poor survival, and loss of heterozygosity of chromosome 10q is associated with shorter progression-free and overall survival compared with intact 10q. A variety of other molecular genetic abnormalities have been recognized in gliomas, and these genetic changes are not only important prognostic factors, but also offer new therapeutic targets. With the increased use of improved surgical and radiotherapy techniques and targeted biologic therapy over the next 20 years, many patients with malignant gliomas may be cured or their disease may be controlled for the long term. Molecular profiling of patients using gene chip technology will likely become commonplace, and many patients will receive a tailored treatment regimen based on the unique genetic profile of their tumor.
Topics: Antineoplastic Agents; Biological Therapy; Biomarkers, Tumor; Brain Neoplasms; Disease-Free Survival; Glioma; Humans; Patient Selection; Survival Rate
PubMed: 14765391
DOI: 10.1053/j.seminoncol.2003.11.036 -
No To Shinkei = Brain and Nerve Sep 2003Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Among the new treatments... (Review)
Review
Despite advances in radiation and chemotherapy along with surgical resectioning, the prognosis of patients with malignant glioma is poor. Among the new treatments currently being investigated for malignant glioma, immunotherapy is theoretically very attractive, since it offers the potential for high tumor-specific cytotoxicity. There are increasing reports demonstrating that systemic immunotherapy using dendritic cells is capable of inducing an antiglioma response. Therefore, dendritic cell-based immunotherapy could be a new treatment modality for patients with glioma. Dendritic cell-based immunotherapy strategies appear promising as an approach to successfully induce an antitumor immune response and increase survival in patients with glioma. The development of methods for manipulating dendritic cells for the purpose of vaccination will enhance the clinical usefulness of these cells for biotherapy for malignant glioma.
Topics: Animals; Brain Neoplasms; Dendritic Cells; Glioma; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunotherapy, Adoptive; Interleukin-4; Tumor Necrosis Factor-alpha
PubMed: 14571839
DOI: No ID Found -
Scientific Reports Sep 2017Malignant glioma is the most common brain cancer with dismal outcomes. Individual variation of the patients' survival times is remarkable. Here, we investigated the...
Malignant glioma is the most common brain cancer with dismal outcomes. Individual variation of the patients' survival times is remarkable. Here, we investigated the transcriptome and promoter methylation differences between patients of malignant glioma with short (less than one year) and the patients with long (more than three years) survival in CGGA (Chinese Glioma Genome Atlas), and validated the differences in TCGA (The Cancer Genome Atlas) to identify the genes whose expression levels showed high concordance with prognosis of glioma patients, as well as played an important role in malignant progression. The gene coding a key enzyme in genetic material synthesis, dCMP deaminase (DCTD), was found to be significantly correlated with overall survival and high level of DCTD mRNA indicated shorter survival of the patients with malignant glioma in different databases. Our finding revealed DCTD as an efficient prognostic factor for malignant glioma. As DCTD inhibitor gemcitabine has been proposed as an adjuvant therapy for malignant glioma, our finding also suggests a therapeutic value of gemcitabine for the patients with high expression level of DCTD.
Topics: Adolescent; Adult; Aged; Computational Biology; DCMP Deaminase; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Genomics; Glioma; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Neoplasm Grading; Prognosis; RNA, Messenger; Transcriptome; Young Adult
PubMed: 28912488
DOI: 10.1038/s41598-017-11962-y