Temozolomide (TMZ) is widely used to treat glioblastoma multiforme (GBM). Although the MGMT gene methylation status is postulated to correlate with TMZ response, some patients with a methylated MGMT gene still do not benefit from TMZ therapy. Cancer stem cells (CSCs) may be one of the causes of therapeutic resistance, but the molecular mechanism underlying this resistance is unclear. microRNA (miRNA) deregulation has been recognized as another chemoresistance modulating mechanism. Thus, we aimed to evaluate the miRNA expression patterns associated with chemoresistance that is dependent on the CSC status in GBM tumors to identify therapeutic biomarkers. CSCs were identified in 5 of 20 patients' tumor tissues using magnetic separation. CSC (+) tumors displayed a significant induction of CpG island methylation in the MGMT gene promoter (p = 0.009). Using real-time reverse transcription polymerase chain reaction (qRT-PCR), 9 miRNAs related to GBM (mir-181b, miR-153, miR-137, miR-145, miR-10a, miR-10b, let-7d, miR-9, and miR-455-3p), which are associated with cell cycle and invasion was analyzed in tumor samples. Low miR-181b and high miR-455-3p expression levels were detected (p = 0.053, p = 0.004; respectively) in CSC (+) tumors. Analysis revealed a significant correlation between miR-455-3p expression and Smad2 protein levels as analyzed by immunohistochemistry in CSC (+) tumors (p = 0.002). Thus, miR-455-3p may be involved in TMZ resistance in MGMT methylated CSC (+) GBM patients. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for GBM treatment and new directions for the development of anticancer drugs.
Glioblastoma represents extreme anaplasia in astrocytic tumors. In spite of this aggressiveness, extracranial metastasis of glioblastoma is very rare and has been documented in only a few patients in the literature. In this article, a 30-year-old woman with secondary glioblastoma associated with extracranial distant metastasis was presented. In September 2008, an intracranial lesion in the left frontal region was diagnosed by magnetic resonance imaging (MRI) after admission to the hospital by headache and seizure and subsequently resected. The histology of the lesion revealed an anaplastic astrocytoma (grade III). Upon recurrence of the tumor 7 months later, the patient underwent a second craniotomy for recurrence tumor resection. The histological diagnosis was glioblastoma. After radiotherapy and chemotherapy, cranial computerized tomography (CT) and whole body scintigraphy revealed metastatic lesions in the right cervical lymph nodes and the left ischium. A neck dissection and parathyroidectomy on the right side was performed. The cytomorphological and histological features of the tumor supported the diagnosis of metastatic glioblastoma.
KeywOrds: Glioblastoma, Extracranial metastasis, Secondary glioblastoma, Prognosis
ÖZGlioblastom astrositik tümörler içerisinde en fazla anaplaziyi gösterenidir. Bu agresif davranışı yanında ekstrakraniyal metastazları oldukça nadirdir ve literatürde çok az hastada bildirilmiştir. Bu makalede, 30 yaşında sekonder glioblastoma bağlı ekstrakraniyal uzak metastazları bulunan bir bayan hasta sunulmuştur. Eylül 2008 tarihinde baş ağrısı ve nöbet şikayeti ile hastaneye başvuran hastanın çekilen kraniyal manyetik rezonans görüntülemesinde sol frontal bölgede intrakraniyal kitle saptanmıştı. Hasta opere edildi. Patoloji tanısı anaplastik astrositom (grade III)olarak raporlandı. 7 ay sonra rekürrens nedeniyle hasta tekrar opere edildi. Histolojik tanısı glioblastom olarak raporlandı. Radyoterapi ve kemoterapiden sonra çektirilen bilgisayarlı tomografi ve tüm vücut sintigrafisinde sağ servikal lenf nodları ve sol iskiumda metastatik lezyonlar saptandı. Sağ taraflı boyun diseksiyonu ve paratiroidektomi uygulandı. Sitomorfolojik ve histolojik çalışmalar metastatik glioblastomla uyumlu olarak bildirildi.
Glioblastoma multiforme (GBM) is one of the deadliest human malignancies. A cure for GBM remains elusive, and the overall survival time is less than 1 year. Thus, the development of more efficient therapeutic approaches for the treatment of these patients is required. Induction of tumor cell death by certain phytochemicals derived from medicinal herbs and dietary plants has become a new frontier for cancer therapy research. Although the cancer suppressive effect of Ficus carica (fig) latex (FCL) has been determined in a few cancer types, the effect of this latex on GBM tumors has not been investigated. Therefore, in the current study, the anti-proliferative activity of FCL and the effect of the FCL-temozolomide (TMZ) combination were tested in the T98G, U-138 MG, and U-87 MG GBM cell lines using the WST-1 assay. The mechanism of cell death was analyzed using Annexin-V/FITC and TUNEL assays, and the effect of FCL on invasion was tested using the chick chorioallantoic membrane assay. To determine the effect of FCL on GBM progression, the expression levels of 40 GBM associated miRNAs were analyzed in T98G cells using RT-qPCR. According to the obtained data, FCL causes cell death in GBM cells with different responses to TMZ, and this effect is synergistically increased in combination with TMZ. In addition, the current study is the first to demonstrate the effect of FCL on modulation of let-7d expression, which may be an important underlying mechanism of the anti-invasive effect of this extract.
Aim: To evaluate the clinical outcome in a 13-year consecutive series of children operated for pituitary adenomas with transnasal transsphenoidal surgery. Methods: All patients <18 years who were operated on at our center by transsphenoidal surgery for pediatric pituitary adenomas were included in the study. Clinical features, hormonal profile, radiology, surgical approach, results and complications were analyzed. Results: Eighteen patients (90%) had functional pituitary adenomas and 2 (10%) patients had nonfunctional pituitary adenoma. The most common type was prolactin-secreting adenoma (n = 12), followed by corticotropinoma (n = 4), growth hormone-secreting adenoma (n = 2), and nonfunctioning adenoma (n = 2). Prolactin-secreting adenomas in children occurred more commonly with suprasellar expansion than did other adenomas. Conclusion: Transsphenoidal surgery was effective for decompression of suprasellar extension and relieved the chiasmal compression immediately. Prolactin-secreting tumors required postoperative medical therapy for persistently elevated prolactin levels.
AIm:The aim of this study was to investigate the dose dependence of citicoline's previously-reported effects on recovery of peripheral nerve injury. mAterIAl and methOds: Right sciatic nerves of sixty adult female Wistar Albino rats were incised and primary anastomosis was performed. Rats were then divided into four groups: Control group received 2 ml of saline intraperitoneally, while rats in C-300, C-600 and C-900 groups received 300 μmol/kg, 600 μmol/kg and 900 μmol/kg citicoline dissolved in 2 ml saline, respectively. Rats were tested for sciatic functional index (SFI) on the 4th, 8th and 12th weeks and electrophysiological recordings were obtained on the 12th week. Rats were then sacrificed to investigate nerve adhesions and perform histomorphological examinations.
results:Our results showed that rats in C-600 and C-900 groups had significantly lesser neural adhesion and greater SFI and electrophysiological score than those in the Control and C-300 groups (p<0.05). Mean density and total number of functionally myelinated axons were significantly increased in C-900 group, while perineural scar tissue formation was reduced in all citicoline-treated groups.
COnClusIOn:We conclude that citicoline exhibits dose-dependent effects on axonal regeneration and recovery without scar formation in a rat model of peripheral nerve incision and primary anastomosis.
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