Proton Beam Radiation Therapy in Treating Patients With Low Grade Gliomas - Full Text View - ClinicalTrials.gov
PRIMARY OBJECTIVES:. I. To evaluate the feasibility of proton beam radiation therapy in patients with low grade gliomas. (Phase I). SECONDARY OBJECTIVES:. I. To assess late complications from irradiation using proton beam therapy in place of conventional photon beam therapy for the treatment of low grade gliomas. (Phase II) II. To assess acute side effects from irradiation using proton beam therapy in place of conventional photon beam therapy for the treatment of low grade gliomas. (Phase II) III. To compare the dose distribution to tumor and surrounding normal structures using DVH's (Dose Volume Histograms) generated from the proton plan used to treat the patient and the photon plan generated for comparison purposes. (Phase II) IV. To monitor the rates of local control, overall and disease specific survival using proton radiotherapy. (Phase II) V. To evaluate the time to progression of low grade gliomas treated with protons. (Phase II) VI. ...https://clinicaltrials.gov/ct2/show/NCT01024907
Targeting ER stress for malignant glioma therapy :: University of Southern California Dissertations and Theses
Poor chemosensitivity and the development of chemoresistance remain major obstacles to successful chemotherapy of malignant gliomas. Recently, a new goal has been set: changing malignant glioma from a deadly to a chronic disease. To this end a multidisciplinary approach to malignant glioma treatment has been proposed, in which surgery, radiotherapy and chemotherapy are combined in order to most benefit the patients. We identified endoplasmic reticulum (ER) as a novel target and outlined specific pathways within the ER stress response (ESR) that lead to malignant glioma cell death/apoptosis.; First, we report that ER chaperone GRP78 is significantly elevated in malignant glioma. Knockdown of GRP78 using siRNA in glioblastoma cell lines significantly lowers their resistance to temozolomide (TMZ), the chemotherapeutic agent of choice for treatment of malignant gliomas, as established by colony survival assays.; ...http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/324413/rec/15
Personal History of Diabetes, Genetic Susceptibility to Diabetes, and Risk of Brain Glioma: A Pooled Analysis of Observational...
We observed a 42% reduced risk of glioma for individuals with a history of diabetes versus those without (OR = 0.58; 95% CI, 0.40-0.84). Results were similar by sex, study design (case-control vs. nested case-control), and after restricting the outcome to glioblastoma, the most common histological subtype. The risks for other glioma subtypes were also reduced for those with versus without diabetes, albeit nonsignificantly. Diabetes-associated SNPs identified from GWAS were generally not associated with glioma risk, nor did these SNPs explain the inverse association we observed between glioma risk and diabetes history.. A lower risk of glioma associated with diabetes was first reported in a 1965 study, reporting a lower frequency of intracranial gliomas among diabetics versus nondiabetics but no difference in the frequency of meningiomas and pituitary neoplasms (36). Our finding of an inverse association ...http://cebp.aacrjournals.org/content/23/1/47?rss=1
MicroRNA-375 inhibits glioma cell proliferation and migration by downregulating RWDD3 in vitro
Derived from brain glial cells, gliomas are currently the most common primary tumours in the central nervous system and are characterised by a high recurrence rate and poor prognosis. RWDD3 (RWD domain-containing sumoylation enhancer, also termed RSUME), which can be induced by cellular stress, such as CoCl2, heat shock and hypoxia, may play a crucial role in tumour angiogenesis, growth and metastasis. MicroRNAs (miRNAs) have been demonstrated to act as negative regulators of post-transcriptional gene expression and are involved in tumour growth and metastasis. In the present study, we explored the role of RWDD3 in glioma cell proliferation and invasion by the knockdown of RWDD3 with lentiviral shRNA and demonstrated that miRNA hsa-miR-375, regulates RWDD3 and has an important role in glioma progression. We found that expression of RWDD3 in high-grade gliomas was significantly higher than that noted in normal brain tissues and lower-grade ...https://spandidos-publications.com/10.3892/or.2018.6261
Annexin A2 and Microglia/Macrophages in Glioma Progression
Gliomas are highly invasive brain tumors with the occurrence of numerous microglia/macrophages (MG/MP) in and around the tumor. Annexin A2 is overexpressed in many cancers and correlates with increased plasmin activity on the tumor cell surface. Plasmin mediates degradation of extracellular matrix and angiogenesis to facilitate tumor growth. In this study, we used a mouse glioma cell line, GL261-EGFP, and stable clones transfected with an annexin A2 knockdown (annA2KD) construct, GL261-EGFP-annA2KD. We found that the annA2KD decreased glioma cell migration in vitro and decreased membrane-bound plasmin activity. In vivo we injected GL261-EGFP cells into the mouse brain and the glioma progression was followed. Knockdown of annexin A2 in glioma cells decreased tumor size and slowed down tumor progression, characterized by decreased invasion, angiogenesis and proliferation, as well as increased apoptosis in tumor tissue of the ...https://dspace.sunyconnect.suny.edu/handle/1951/55694
AZD7451 for Recurrent Gliomas - Full Text View - ClinicalTrials.gov
BACKGROUND:. Recurrent glioma patients have very limited treatment options. A major cause of gliomarelated morbidity and mortality is the extensive infiltrative and invasive nature of glioma cells. Thus, inhibition of glioma invasion is a potentially promising strategy.. Work in the Neuro-Oncology Branch laboratory of Dr. Howard Fine has identified TrkA as an important signaling receptor for mediating glioma cell invasion. Both genetic and pharmacological inhibition of Trk potently inhibits glioma invasion and tumor progression in vitro and in vivo. AZD7451 is a first in-class inhibitor of Trk.. OBJECTIVES:. To establish the maximally tolerated dose (MTD) of continuous twice a day AZD7451 dosing in patients with recurrent glioblastoma not on enzyme-inducing anti-epileptic drugs (EIAED).. To generate pharmacokinetic data on continuous twice a day AZD7451 dosing.. ELIGIBILITY:. Patients with histologically ...https://clinicaltrials.gov/ct2/show/NCT01468324
Study of Gamma-Knife Radiosurgery Using Magnetic Resonance Imaging (MRI) Spectroscopy for Recurrent Glioma - Full Text View -...
Study Design: A single-center, single-arm, one-stage phase II clinical trial for patients with recurrent grade IV glioma (glioblastoma), with two additional exploratory arms for patients with recurrent grade II and grade III gliomas.. Patient Numbers: A total of 40 patients with recurrent glioblastoma will be enrolled. In addition, a minimum of 10 patients with recurrent grade III (anaplastic) glioma and a minimum of 10 patients with recurrent grade II (low-grade) glioma will be enrolled independently into separate exploratory arms.. Summary of Patient Eligibility Criteria Histological confirmation of glioma, grades II - IV; prior first-line treatment with surgery, radiotherapy and chemotherapy for malignant (grades III and IV) gliomas; age , 18 years; life expectancy ,8 weeks; Karnofsky Performance Status ≥ 60; adequate organ function; signed patient informed consent; willingness to forego additional ...https://clinicaltrials.gov/ct2/show/NCT01011231
Signs of Glioma Susceptibility 5 - RightDiagnosis.com
Signs of Glioma Susceptibility 5 including medical signs and symptoms of Glioma Susceptibility 5, symptoms, misdiagnosis, tests, common medical issues, duration, and the correct diagnosis for Glioma Susceptibility 5 signs or Glioma Susceptibility 5 symptoms.http://www.rightdiagnosis.com/g/glioma_susceptibility_5/signs.htm
Cancers | Free Full-Text | Extra-Neural Metastases of Malignant Gliomas: Myth or Reality?
Malignant gliomas account for approximately 60% of all primary brain tumors in adults. Prognosis for these patients has not significantly changed in recent years-despite debulking surgery, radiotherapy and cytotoxic chemotherapy-with a median survival of 9-12 months. Virtually no patients are cured of their illness. Malignant gliomas are usually locally invasive tumors, though extra-neural metastases can sometimes occur late in the course of the disease (median of two years). They generally appear after craniotomy although spontaneous metastases have also been reported. The incidence of these metastases from primary intra-cranial malignant gliomas is low; it is estimated at less than 2% of all cases. Extra-neural metastases from gliomas frequently occur late in the course of the disease (median of two years), and generally appear after craniotomy, but spontaneous metastases have also been reported. Malignant glioma ...http://www.mdpi.com/2072-6694/3/1/461
Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer
Background: Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods: Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer. The genomic areas covering TP53, ...http://www.diva-portal.org/smash/record.jsf?pid=diva2:765420
Hypofractionated Stereotactic Radiotherapy With Bevacizumab in the Treatment of Recurrent Malignant Glioma - Full Text View -...
Histologically confirmed low grade (WHO grade II) gliomas (such as low grade astrocytoma, low grade oligodendroglioma, low grade oligo-astrocytoma (mixed gliomas), or low grade glioma NOS) IF there is radiographic evidence by MRI of malignant transformation but histologic confirmation of high grade (malignant) transformation would not be otherwise undertaken for routine clinical care. Inclusion of patients in this group will allow increased accrual rapidity by enrolling patients who are otherwise ineligible for almost all malignant glioma trials yet whom are treated presumptively for malignant glioma. The primary aim of the phase I study is not determination of efficacy. Therefore, inclusion of such patients will not affect efficacy analyses ...https://clinicaltrials.gov/ct2/show/NCT01392209?cond=%22Anaplastic+oligoastrocytoma%22&rank=1
Inhibition of Rat C6 Glioma Cell Proliferation by Endogenous and Synthetic Cannabinoids. Relative Involvement of Cannabinoid...
In the present study, the effects of endogenous and synthetic cannibinoids upon the proliferation of C6 glioma cells were investigated to resolve some of the conflicting data in the literature concerning the receptor systems involved in the effects of these compounds. The choice of a glioma cell line was prompted by the finding that cannabinoids reduce their cell proliferation in vivo (Galve-Roperh et al., 2000). Indeed, the recent finding by this group of a high frequency of CB2 receptor expression in human astrocytomas, and that the expression correlated with tumor malignancy (Sánchez et al., 2001), raises the possibility that modulation of cannabinoid receptors in vivo may provide a possible avenue for treatment of patients with glioma and motivate per se further experimentation in glioma cells. We have previously shown that the effects of Δ9-THC upon C6 glioma cell viability are highly dependent upon the assay serum ...http://jpet.aspetjournals.org/content/299/3/951?ijkey=896a5b59f8752b2f1d0eb02ccf8953260ccd92b6&keytype2=tf_ipsecsha
Erlotinib Hydrochloride and Isotretinoin in Treating Patients With Recurrent Malignant Glioma - Full Text View - ClinicalTrials...
Inclusion Criteria:. Histologically proven malignant glioma (glioblastoma multiforme, anaplastic astrocytoma, anaplastic oligodendroglioma, or anaplastic mixed oligoastrocytoma) which is progressive or recurrent after radiation therapy +/- chemotherapy; patients with previous low grade glioma who progressed after radiotherapy +/- chemotherapy and are biopsied and found to have a high grade glioma are eligible Karnofsky performance status of ,= 60% Patients - both males and females - with reproductive potential (i.e., premenopausal or menopausal for less than 1 year and not surgically sterilized) must practice at least 2 contraceptive measures throughout the study Patients must be registered and meet all the requirements of iPLEDGE in order to receive 13-cis-Retinoic Acid (CRA) Patients must provide verbal and written informed consent to participate in the study Patients must have a Mini Mental Status Exam score ,= 15 Patients must have a ...https://clinicaltrials.gov/ct2/show/NCT01103375?cond=%22Anaplastic+oligodendroglioma%22&rank=11
The chemokine GRO-α (CXCL1) confers increased tumorigenicity to glioma cells : Carcinogenesis - oi
The chemokine GRO-α (CXCL1) has been found to mediate the proliferation of glia progenitor cells during neural development. As malignant gliomas are thought to arise from glia progenitors or their differentiated counterparts, astrocytes or oligodendrocytes, we have investigated whether GRO-α regulates the tumor characteristics of glioma cells. We found first that resected glioma specimens were strongly immunoreactive for GRO-α expression in cells with the morphology of tumor cells. In culture, the U251 glioma line transfected to overexpress GRO-α had elevated levels of motility and invasiveness. GRO-α transfectants increased their expression of several proteins associated with migratory behavior, including matrix metalloproteinase-2, β1-integrin and SPARC. The implantation of GRO-α glioma clones into the brain of nude mice caused the early demise of mice and this was associated with the formation of larger intracerebral ...http://oxfordindex.oup.com/view/10.1093/carcin/bgi182
Semaphorin 5A and plexin-B3 inhibit human glioma cell motility through RhoGDIα-mediated inactivation of Rac1 GTPase |...
Semaphorins and plexins are implicated in the progression of various types of cancer, although the molecular basis has not been fully elucidated. Here, we report the expression of plexin-B3 in glioma cells, which upon stimulation by its ligand Sema5A results in significant inhibition of cell migration and invasion. A search for the underlying mechanism revealed direct interaction of plexin-B3 with RhoGDP dissociation inhibitor α (RhoGDIα), a negative regulator of RhoGTPases that blocks guanine nucleotide exchange and sequesters them away from the plasma membrane. Glioma cells challenged with Sema5A indeed showed a marked reduction in Rac1-GTP levels by 60%, with a concomitant disruption of lamellipodia. The inactivation of Rac1 was corroborated to contribute to the impediment of glioma cell invasion by Sema5A, as supported by the abolishment of effect upon forced expression of a constitutively active Rac1 mutant. Furthermore, silencing the endogenous ...http://scholarbank.nus.edu.sg/handle/10635/127127
Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas - Full Text View - ClinicalTrials.gov
Malignant gliomas (MG), including anaplastic gliomas (AG) and glioblastoma (GBM), are the most common primary brain tumor. Standard of care (surgery, radiotherapy, and temozolomide at initial diagnosis) results in a median survival of only 14 months. For patients with recurrent disease, conventional chemotherapy is generally ineffective with response rates ,20%. Clearly there is need for improved treatments. Recent genome-wide studies have confirmed that GBM is a heterogeneous group of diseases that can be subclassified by shared genetic aberrations. The implication is that, in part, the underlying genetics may determine responsiveness to treatments and thus allow us to personalize therapy.. This is an, open-label, non-randomized, phase II study with oral nilotinib in adult patients with biomarker-enriched, recurrent malignant gliomas who have developed tumor progression after standard therapy. Patients will be treated with oral nilotinib (starting with the ...https://clinicaltrials.gov/ct2/show/NCT01140568
5766 Propylthiouracil [PTU] induced decline in blood free thyroxine[fT4] correlates with survival in recurrent high grade glioma. Aim :- to prolong survival in recurrent glioma patients by PTU induced thyroid hormone depletion Rationale :- Recurrent glioma patients are generally unresponsive to conventional chemotherapy and have very short survival .The thyroid hormones free thyroxine[fT4] and tri-iodothyronine[T3] physiologically modulate metabolism but also are mitogenic in glioma and other neoplastic cell lines via interaction with cell membrane α1Vβ3 integrin, and upregulation of EGFR, IGF-1,II, Cyclins D, E and cdk2. Hormone depletion results in cell cycle arrest and decreased proliferation. We attempted to improve survival in recurrent high grade glioma patients by inducing thyroid suppression with PTU in patients who also received high dose tamoxifen for its reported cytostatic effect in glioma. . ...http://cancerres.aacrjournals.org/content/65/9_Supplement/1355.3
6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients - Full Text View - ClinicalTrials.gov
The goal of this clinical research study is to learn if the combination of 6-Thioguanine, Xeloda (capecitabine), and Celebrex (celecoxib) with Temodar (temozolomide) or Lomustine (CCNU) is effective in the treatment of recurrent or progressive anaplastic glioma or glioblastoma multiforme in patients who have failed previous treatments. The safety of these combination treatment will also be studied.. Objectives:. 1.1 To determine the efficacy, as measured by 12 month progression-free survival, of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in the treatment of patients with recurrent and/or progressive anaplastic gliomas or glioblastoma multiforme.. 1.2 To determine the long-term toxicity of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in recurrent anaplastic glioma or glioblastoma multiforme patients treated in this manner.. 1.3 To determine the clinical relevance of genetic subtyping tumors ...https://clinicaltrials.gov/ct2/show/NCT00504660
6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients - Full Text View - ClinicalTrials.gov
The goal of this clinical research study is to learn if the combination of 6-Thioguanine, Xeloda (capecitabine), and Celebrex (celecoxib) with Temodar (temozolomide) or Lomustine (CCNU) is effective in the treatment of recurrent or progressive anaplastic glioma or glioblastoma multiforme in patients who have failed previous treatments. The safety of these combination treatment will also be studied.. Objectives:. 1.1 To determine the efficacy, as measured by 12 month progression-free survival, of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in the treatment of patients with recurrent and/or progressive anaplastic gliomas or glioblastoma multiforme.. 1.2 To determine the long-term toxicity of TEMOZOLOMIDE or CCNU with 6-THIOGUANINE followed by CAPECITABINE and CELECOXIB in recurrent anaplastic glioma or glioblastoma multiforme patients treated in this manner.. 1.3 To determine the clinical relevance of genetic subtyping tumors ...https://clinicaltrials.gov/ct2/show/NCT00504660?term=glioblastoma&rank=6
Potentiation of radiation therapy by the oncolytic adenovirus dl1520 (ONYX-015) in human malignant glioma xenografts.
In spite of aggressive surgery, irradiation and/or chemotherapy, treatment of malignant gliomas remains a major challenge in adults and children due to high treatment failure. We have demonstrated significant cell lysis and antitumour activity of the E1B-55 kDa-gene-deleted adenovirus ONYX-015 (dl1520, CI-1042; ONYX Pharmaceuticals) in subcutaneous human malignant glioma xenografts deriving from primary tumours. Here, we show the combined efficacy of this oncolytic therapy with radiation therapy. Total body irradiation (5 Gy) of athymic nude mice prior to intratumoral injections of ONYX-015 1 x 10(8) PFU daily for 5 consecutive days yielded additive tumour growth delays in the p53 mutant xenograft IGRG88. Radiation therapy was potentiated in the p53 functional tumour IGRG121 with a 'subtherapeutic' dose of 1 x 10(7) PFU daily for 5 consecutive days, inducing significant tumour growth delay, 90% tumour regression and 50% tumour-free survivors 4 months after treatment. These ...http://dare.ubvu.vu.nl/handle/1871/20739
Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: targeting PI3K-AKT-mTOR signaling, HSP90 and...
The current standard of care for malignant glioma is initial treatment with radiation therapy combined with TMZ; however, malignant gliomas usually recur with a median time to progression of approximately 7 months . Two decades of molecular studies have identified important genetic events such as dysregulation of growth factor signaling via amplification or mutation of receptor tyrosine kinase genes; activation of PI3K pathway; and inactivation of p53 and Rb tumor suppressor pathways . In this study, we tried to identify the potential targets for counteracting the pro-survival signaling implicated in radioresistance of malignant glioma cells and to get insight into potential strategies to improve the therapeutic outcome of radiotherapy and TMZ in the management of GBM.. Inhibition of signal transduction pathways may provide the basis for a new paradigm of GBM therapy, based on the fact that most human gliomas exhibit aberrant ...https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-14-17
A glioma is a type of tumor that starts in the brain or spine. Gliomas arise from glial cells, which act as a supportive cell in the central nervous system. Gliomas are the second most common type of tumor after meningiomas.. There are three types of normal glial cells that can produce tumors. An astrocyte will produce astrocytomas (including glioblastomas), an oligodendrocyte will produce oligodendrogliomas, and ependymomas come from ependymal cells. Tumors that display a mixture of these different cells are called mixed gliomas. Tumors are also commonly identified by their specific locations (such as brain stem gliomas), not the tissue type from which they originate.. Gliomas are also categorized by grade, determined by pathologic evaluation of the tumor. Of numerous grading systems in use, the most common is the World Health Organization (WHO) grading system for astrocytoma, under which ...https://www.brainsciencefoundation.org/brain-tumor-resources/glioma/
Study of glioma susceptibility in dogs may yield insights for humans | Veterinary Sciences Tomorrow
by Vetscite. A new study of the genetic factors underlying glioma formation in dogs may hold clues to how these common and often untreatable tumors form in humans. The genome study, which was conducted across 25 dog breeds, identified three genes associated with the tumor. The results from this research, led by Katarina Truvé of the Swedish University of Agricultural Sciences and Kerstin Lindblad-Toh of Uppsala University, were published on May 12 in PLOS Genetics.. Gliomas are the most common form of malignant primary brain tumors in humans and the second most common in dogs. Several dog breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, while certain related breeds do not, suggesting that a mix of genes may impact glioma formation. Dr Truvé says: "Researchers in the consortium are now continuing the analysis of the genes identified, and their functional roles in development and progression of ...http://vetscite.org/2016/06/study-of-glioma-susceptibility-in-dogs-may-yield-insights-for-humans/
The Presence of IL-17A and T Helper 17 Cells in Experimental Mouse Brain Tumors and Human Glioma
Background Recently, CD4+IL-17A+ T helper 17 (Th17) cells were identified and reported in several diseased states, including autoimmunity, infection and various peripheral nervous system tumors. However, the presence of Th17 in glia-derived tumors of the central nervous system has not been studied. Methodology/Principal Findings In this report, we demonstrate that mRNA expression for the Th17 cell cytokine IL-17A, as well as Th17 cells, are present in human glioma. The mRNA expression for IL-17A in glioma was recapitulated in an immunocompetent mouse model of malignant glioma. Furthermore, the presence of Th17 cells was confirmed in both human and mouse glioma. Interestingly, some Th17 cells present in mouse glioma co-expressed the Th1 and Th2 lineage markers, IFN-γ and IL-4, respectively, but predominantly co-expressed the Treg lineage marker FoxP3. Conclusions These data confirm the presence of Th17 cells in ...http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0015390
GDF-15 contributes to proliferation and immune escape of malignant gliomas - Zurich Open Repository and Archive
PURPOSE: Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-beta family. GDF-15 is necessary for the maintenance of pregnancy but has also been linked to other physiological and pathological conditions. EXPERIMENTAL DESIGN: The expression of GDF-15 in glioma cell lines was assessed by qRT-PCR and immunoblot. GDF-15 levels in situ and in peripheral blood of glioma patients were examined by immunohistochemistry and ELISA, respectively. Effects of shRNA-mediated GDF-15 inhibition on proliferation and immunogenicity of SMA-560 glioma cells were investigated by [methyl-3H]thymidine incorporation and immune-mediated target cell lysis. The impact of GDF-15 on glioma growth in vivo was assessed in syngeneic mice.RESULTS: GDF-15 is expressed by gliomas of different WHO grades as assessed by immunohistochemistry. The high expression of GDF-15 in tumor tissue translates into elevated GDF-15 ...http://www.zora.uzh.ch/id/eprint/34877/