Hypermethylation of the Promoter of miR-338-5p Mediates Aberrant Expression of ETS-1 and Is Correlated With Disease Severity Of Astrocytoma Patients

The pro-oncogene ETS-1 (E26 transformation-specific sequence 1) is a key regulator of the proliferation and invasion of cancer cells. The present work examined the correlation of the aberrant expression of ETS-1 with histological or clinical classification of astrocytoma: grade I (pilocytic astrocytoma), grade II (diffuse astrocytoma), grade III (anaplastic astrocytoma), and grade IV (glioblastoma multiforme). MicroRNA, miR-338-5p, was predicted by an online tool (miRDB) to potentially target the 3’ untranslated region of ETS-1; this was confirmed by multi-assays, including western blot experiments or the point mutation of the targeting sites of miR-338-5p in ETS-1’s 3’untralation region (3’UTR). The expression of miR-338-5p was negatively associated with that of ETS-1 in astrocytoma, and deficiency of miR-338-5p would mediate aberrant expression of ETS-1 in astrocytoma. Mechanistically, hypermethylation of miR-338-5p by DNA methyltransferase 1 (DNMT1) resulted in repression of miR-338-5p expression and the aberrant expression of ETS-1. Knockdown or deactivation of DNMT1 decreased the methylation rate of the miR-338-5p promoter, increased the expression of miR-338-5p, and repressed the expression of ETS-1 in astrocytoma cell lines U251 and U87. These results indicate that hypermethylation of the miR-338-5p promoter by DNMT1 mediates the aberrant expression of ETS-1 related to disease severity of patients with astrocytoma.

Slow Off-Rate Modified Aptamer (SOMAmer) Proteomic Analysis of Patient-Derived Malignant Glioma Identifies Distinct Cellular Proteomes

Malignant gliomas derive from brain glial cells and represent >75% of primary brain tumors. This includes anaplastic astrocytoma (grade III; AS), the most common and fatal glioblastoma multiforme (grade IV; GBM), and oligodendroglioma (ODG). We have generated patient-derived AS, GBM, and ODG cell models to study disease mechanisms and test patient-centered therapeutic strategies. We have used an aptamer-based high-throughput SOMAscan® 1.3K assay to determine the proteomic profiles of 1307 different analytes. SOMAscan® proteomes of AS and GBM self-organized into closely adjacent proteomes which were clearly distinct from ODG proteomes. GBM self-organized into four proteomic clusters of which SOMAscan® cluster 4 proteome predicted a highly inter-connected proteomic network. Several up- and down-regulated proteins relevant to glioma were successfully validated in GBM cell isolates across different SOMAscan® clusters and in corresponding GBM tissues. Slow off-rate modified aptamer proteomics is an attractive analytical tool for rapid proteomic stratification of different malignant gliomas and identified cluster-specific SOMAscan® signatures and functionalities in patient GBM cells.

Nocardia farcinica meningitis in a patient with high-grade astrocytoma

We describe a case of 91-year-old male with astrocytoma who developed meningitis caused by Nocardia farcinica. He had a past medical history of anaplastic astrocytoma grade III. Endocranial computed tomography (CT) scan revealed mass lesion in the left occipital region associated with perilesional edema, without evidence of midline shift issue. The analyses of cerebrospinal fluid (CSF) revealed neutrophilic pleocytosis, hyperproteinorrachia and hypoglycorrhachia. Combined antimicrobial therapy was initiated (vancomycin, meropenem, acyclovir). CSF culture revealed Nocardia farcinica. Susceptibility testing revealed intermediate sensitivity to meropenem and antibiotic treatment was switched to trimethoprim-sulfamethoxazole and imipenem. After 7 days of treatment the patient developed progressive dyspnea. The chest CT scan revealed bilateral pleural effusion and alveolar infiltrate mostly in the right lobe. Ceftriaxone was added to the therapy, but the outcome was lethal. Nocardia spp. should be considered as differential diagnosis in the patients with brain tumor or meningitis in the setting of immune suppression and corticosteroid use. CSF cultures should be incubated longer with aim to allow fastidious organisms to grow, such as Nocardia spp.

Withdrawn: Intraoperative Sono-photodynamic Therapy for Anaplastic Astrocytoma Grade III With Transformation in Glioblastoma Grade IV

The following article has been withdrawn on the request of the editor of the journal Clinical Cancer Drugs: Title: Intraoperative Sono-photodynamic Therapy for Anaplastic Astrocytoma Grade III with Transformation in Glioblastoma Grade IV Authors: Dmitry Tzerkovsky*, Fedor Borichevsky, Yuri Grachev, Yuri Istomin Bentham Science apologizes to the readers of the journal for any inconvenience this may cause Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Aquaporin Positron Emission Tomography Differentiates Between Grade III and IV Human Astrocytoma

BACKGROUND Aquaporin (AQP) water channels play a significant role in mesenchymal microvascular proliferation and infiltrative growth. AQPs are highly expressed in malignant astrocytomas, and a positive correlation is observed between their expression levels and histological tumor grade. OBJECTIVE To examine the utility of aquaporin positron emission tomography (PET) for differentiating between astrocytoma grade III and grade IV using the AQP radioligand [11C]TGN-020. METHODS Fifteen astrocytoma patients, grade III (n = 7) and grade IV (n = 8), and 10 healthy volunteers underwent [11C]TGN-020 aquaporin PET imaging. Surgical tissues of astrocytoma patients were examined for histopathological grading using the WHO classification standard and expression of AQP1 and AQP4 immunohistochemically. RESULTS Mean standardized uptake values of astrocytoma grade III and IV (0.51 ± 0.11 vs 1.50 ± 0.44, respectively) were higher than normal white matter (0.17 ± 0.02, P < .001) for both tumor grades. Importantly, mean standardized uptake values of astrocytoma grade IV were significantly higher than grade III (P < .01). CONCLUSION Our study demonstrated that [11C]TGN-020 aquaporin PET imaging differentiated between astrocytoma grades III and IV. We suggest its clinical application as a noninvasive diagnostic tool would lead to advancements in the management of these malignant brain tumors.

Bilateral Thalamic Glioma –A Rare Tumour

We report a case of 48-year old woman who presented with dementia, progressive mental decline, personality change, paresis of the right lower extremity, and gait ataxia. Magnetic resonance imaging (MRI) T1-weighted image revealed bilateral thalamic swelling with homogenous low signal intensity and mild contrast enhancement with gadolinium. The T2- weighted image showed high intensity lesions in the bilateral thalamus, septum pellucidum and fornix. A CT-guided stereotactic biopsy of the lesion revealed fibrillary astrocytoma grade III as per WHO classification. Bilateral thalamic gliomas are very rare tumours and when present may resemble other benign diseases having similar clinical presentations DOI: http://dx.doi.org/10.3126/jonmc.v3i1.10059 Journal of Nobel Medical College Vol.3(1) 2014; 71-73

Progesterone Induces the Growth and Infiltration of Human Astrocytoma Cells Implanted in the Cerebral Cortex of the Rat

Progesterone (P4) promotes cell proliferation in several types of cancer, including brain tumors such as astrocytomas, the most common and aggressive primary intracerebral neoplasm in humans. In this work, we studied the effects of P4and its intracellular receptor antagonist, RU486, on growth and infiltration of U373 cells derived from a human astrocytoma grade III, implanted in the motor cortex of adult male rats, using two treatment schemes. In the first one, fifteen days after cells implantation, rats were daily subcutaneously treated with vehicle (propylene glycol, 160 μL), P4(1 mg), RU486 (5 mg), or P4+ RU486 (1 mg and 5 mg, resp.) for 21 days. In the second one, treatments started 8 weeks after cells implantation and lasted for 14 days. In both schemes we found that P4significantly increased the tumor area as compared with the rest of the treatments, whereas RU486 blocked P4effects. All rats treated with P4showed tumor infiltration, while 28.6% and 42.9% of the animals treated with RU486 and P4+ RU486, respectively, presented it. Our data suggest that P4promotes growth and migration of human astrocytoma cells implanted in the motor cortex of the rat through the interaction with its intracellular receptor.

The evaluation of malignant astrocytoma score (MAS)

Background/Aim. At the moment there are few scoring systems for malignant astrocytoma but they are not widely accepted. The aim of this study was to evaluate malignant astrocytoma score (MAS) on a new group of patients with malignant astrocytoma, to compare MAS with other prognostic tools and to describe the use of MAS in everyday practice in neurooncology. Methods. The study was performed on 124 patients with supratentorial malignant astrocytoma grade III or IV. They were operated on and subsequently irradiated with 50-60 Gy. Results. The mean age of the patients was 57.3 years. The mean Karnofski performance status (KPS) of the functional inpairment was 54. The removal of the tumor > 90% was done in 59.7% of patients. The mean survival was 9.1 months, and 27.4% of patients had a 12-month survival. The area under receiver operating characteristic (ROC) curve (AUC) of the MAS for predicting 6-, 12- and 18-month survival was 0.754, 0.783 and 0.882, respectively. We compared the MAS with the two mostly cited scoring systems. The AUC for the same prediction for medical research council (MRC) was 0.601, 0.693, 0.772 respectively. For the Radiation Therapy Oncology Group (RTOG) the AUC was 0.732, 0.765, 0.827, respectively. Conclusion. MAS represents a useful scoring system for determining illness severity and prognosis in patients with malignant supratentorial astrocytoma. It can be helpful in comparing single patients or groups of patients, as well as results of different treatments and in controlling the quality of hospital treatment and so on.