Regression of Intracranial Meningioma during Treatment with α1-Adrenoceptor Blocker.
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ABSTRACT:
SUBMITTER: Hoegestoel EA
PROVIDER: S-EPMC4863873 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
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Project description:Recurrent meningiomas remain a substantial treatment challenge given the lack of effective therapeutic options aside from surgery and radiation therapy, which yield limited results in the retreatment situation. Systemic therapies have little effect, and responses are rare; the search for effective systemic therapeutics remains elusive. In this case report, we provide data regarding significant responses in two radiographically diagnosed intracranial meningiomas in a patient with concurrent thyroid carcinoma treated with cabozantinib, an oral multitarget tyrosine kinase inhibitor with potent activity against MET and VEGF receptor 2. Given the clinical experience supporting the role of VEGF agents as experimental therapeutics in meningioma and the current understanding of the biological pathways underlying meningioma growth, this may represent a new oral therapeutic alternative, warranting prospective evaluation.
| S-EPMC8167720 | biostudies-literature
Project description:Protein kinase C (PKC) plays key roles in the regulation of signal transduction and cellular function in various cell types. At least ten PKC isoforms have been identified and intracellular localization and trafficking of these individual isoforms are important for regulation of enzyme activity and substrate specificity. PKC can be activated downstream of Gq-protein coupled receptor (GqPCR) signaling and translocate to various cellular compartments including plasma membrane (PM). Recent reports suggested that different types of GqPCRs would activate different PKC isoforms (classic, novel and atypical PKCs) with different trafficking patterns. However, the knowledge of isoform-specific activation of PKC by each GqPCR is limited. α1-Adrenoceptor (α1-AR) is one of the GqPCRs highly expressed in the cardiovascular system. In this study, we examined the isoform-specific dynamic translocation of PKC in living HEK293T cells by α1-AR stimulation (α1-ARS). Rat PKCα, βI, βII, δ, ε and ζ fused with GFP at C-term were co-transfected with human α1A-AR into HEK293T cells. The isoform-specific dynamic translocation of PKC in living HEK293T cells by α1-ARS using phenylephrine was measured by confocal microscopy. Before stimulation, GFP-PKCs were localized at cytosolic region. α1-ARS strongly and rapidly translocated a classical PKC (cPKC), PKCα, (<30 s) to PM, with PKCα returning diffusively into the cytosol within 5 min. α1-ARS rapidly translocated other cPKCs, PKCβI and PKCβII, to the PM (<30 s), with sustained membrane localization. One novel PKC (nPKC), PKCε, but not another nPKC, PKCδ, was translocated by α1-AR stimulation to the PM (<30 s) and its membrane localization was also sustained. Finally, α1-AR stimulation did not cause a diacylglycerol-insensitive atypical PKC, PKCζ translocation. Our data suggest that PKCα, β and ε activation may underlie physiological and pathophysiological responses of α1-AR signaling for the phosphorylation of membrane-associated substrates including ion-channel and transporter proteins in the cardiovascular system.
| S-EPMC4564329 | biostudies-literature
Project description:BACKGROUND:Single session radiosurgery represents a widely accepted treatment for intracranial meningiomas. However, this approach could involve a high risk of treatment-related complications when applied to large volume lesions. In these cases and for those not suitable for surgical resection, radiosurgery in multisession setting could represents a viable option. The literature results are reassuring in terms of correlated adverse events as well as in terms of tumor control. However, no prospective long-term results are available. In this scenario, we design a prospective monocentric phase II study, in order to verify the safety of a multisession radiosurgery schedule delivering 25?Gy in 5 daily fractions. METHODS:Patients diagnosed with large and/or near to critical structures, intracranial meningiomas have been treated by means of multisession radiosurgery in both exclusive and postoperative settings. The primary study aim is safety that has been being prospectively scored based on international scales, including NCI Common Toxicity criteria, version 4.03, Barrow Neurological Institute pain intensity score, Barrow Neurological Institute facial numbness score and House-Brackmann Facial Nerve Grading System for qualitative analysis. Secondary aim is treatment efficacy in terms of local control that has been being assessed on volumetric analysis. DISCUSSION:This is the first prospective phase II trial on multisession radiosurgery for large and/or near to critical structures intracranial meningiomas. If positive results will be found, this study could represent the starting point for a phase III trial exploring the role of multisession radiosurgery in the exclusive and postoperative radiation therapy treatment of intracranial meningiomas. TRIAL REGISTRATION:Trial registration: clinicaltrials.gov platform (Multisession Radiosurgery in Large Meningiomas -MuRaLM- identifier NCT02974127). Registered: November 28, 2016. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02974127?term=radiosurgery&cond=Intracranial+Meningioma&draw=2&rank=1.
| S-EPMC6993396 | biostudies-literature
Project description:The outcomes following re-operation for meningioma are poorly described. The aim of this study was to identify risk factors for a performance status outcome following a second operation for a recurrent meningioma. A retrospective, comparative cohort study was conducted. The primary outcome measure was World Health Organization performance. Secondary outcomes were complications, and overall and progression free survival (OS and PFS respectively). Baseline clinical characteristics, tumor details, and operation details were collected. Multivariable binary logistic regression was used to identify risk factors for performance status outcome following a second operation. Between 1988 and 2018, 712 patients had surgery for intracranial meningiomas, 56 (7.9%) of which underwent a second operation for recurrence. Fifteen patients (26.8%) had worsened performance status after the second operation compared to three (5.4%) after the primary procedure (p = 0.002). An increased number of post-operative complications following the second operation was associated with a poorer performance status following that procedure (odds ratio 2.2 [95% CI 1.1-4.6]). The second operation complication rates were higher than after the first surgery (46.4%, n = 26 versus 32.1%, n = 18, p = 0.069). The median OS was 312.0 months (95% CI 257.8-366.2). The median PFS following the first operation was 35.0 months (95% CI 28.9-41.1). Following the second operation, the median PFS was 68.0 months (95% CI 49.1-86.9). The patients undergoing a second operation for meningioma had higher rates of post-operative complications, which is associated with poorer clinical outcomes. The decisions surrounding second operations must be balanced against the surgical risks and should take patient goals into consideration.
| S-EPMC8507983 | biostudies-literature
Project description:ObjectiveAnticoagulation (AC) is a critical topic in perioperative and post-bleeding management. Nevertheless, there is a lack of data about the safe, judicious use of prophylactic and therapeutic anticoagulation with regard to risk factors and the cause and modality of brain tissue damage as well as unfavorable outcomes such as postoperative hemorrhage (PH) and thromboembolic events (TE) in neurosurgical patients. We therefore present retrospective data on perioperative anticoagulation in meningioma surgery.MethodsData of 286 patients undergoing meningioma surgery between 2006 and 2018 were analyzed. We followed up on anticoagulation management, doses and time points of first application, laboratory values, and adverse events such as PH and TE. Pre-existing medication and hemostatic conditions were evaluated. The time course of patients was measured as overall survival, readmission within 30 days after surgery, as well as Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS). Statistical analysis was performed using multivariate regression.ResultsWe carried out AC with Fraxiparin and, starting in 2015, Tinzaparin in weight-adapted recommended prophylactic doses. Delayed (216 ± 228h) AC was associated with a significantly increased rate of TE (p = 0.026). Early (29 ± 21.9h) prophylactic AC, on the other hand, did not increase the risk of PH. We identified additional risk factors for PH, such as blood pressure maxima, steroid treatment, and increased white blood cell count. Patients' outcome was affected more adversely by TE than PH (+3 points in modified Rankin Scale in TE vs. +1 point in PH, p = 0.001).ConclusionEarly prophylactic AC is not associated with an increased rate of PH. The risks of TE seem to outweigh those of PH. Early postoperative prophylactic AC in patients undergoing intracranial meningioma resection should be considered.
| S-EPMC7462284 | biostudies-literature
Project description:Background:The availability of image guidance and intensity modulation has led to the increasing use of hypofractionated stereotactic radiotherapy (hSRT) as an alternative to conventionally fractionated radiotherapy or radiosurgery for intracranial meningiomas (ICMs). As the safety and efficacy of this approach is not well characterized, we conducted a systematic review of the literature to assess the clinical outcomes of hSRT in the setting of ICMs. Methods:A systematic review of Medline and EMBASE databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies were retrospective or prospective series that examined an ICM population of ?10 patients, delivered >1 fraction of photon hSRT (?2.5 Gy per fraction), and had a median follow-up of ?2 years. Descriptive statistics were generated for included studies. Results:Of 1480 initial studies, 14 met eligibility criteria for inclusion, reporting on 630 patients (age range, 18-90) treated for 638 tumors. Primary radiotherapy was delivered in 37% of patients, 36% had radiation following surgery, and surgical details were unavailable for 27%. In 474 tumors assessed for radiologic response, 78% remained stable, 18% decreased in size, and 4% increased in size. Crude local control was 90%-100% as reported in 10 studies. The median late toxicity rate was 10%. The most common significant late toxicities were decreased visual acuity and new cranial neuropathy. Conclusions:With limited follow-up, the available literature suggests hSRT for ICMs has local control and toxicity profiles comparable to other radiotherapy approaches. Confirmation in larger patient cohorts with a longer duration of follow-up is required.
| S-EPMC6753355 | biostudies-literature
Project description:BackgroundRecent comprehensive studies have revealed several molecular alterations that are frequently found in meningiomas. However, effective treatment reagents targeting specific molecular alterations have not yet been identified because of the limited number of representative research models of meningiomas.MethodsWe performed organoid cultures using meningioma cells and meningioma tumor tissues. Using immunohistochemistry and molecular analyses consisting of whole-exome sequencing, RNA-seq, and DNA methylation analyses, we compared the histological findings and molecular profiling of organoid models with those of parental tumors. Further, using these organoid models together with a public database of meningiomas, we explored molecular alterations, which are a potent treatment target for meningioma.ResultsWe established 18 organoid models comprising of two malignant meningioma cells (HKBMM and IOMM-Lee), 10 benign meningiomas, four malignant meningiomas, and two solitary fibrous tumors (SFTs). The organoids exhibited consistent histological features and molecular profiles with those of the parental tumors. Using a public database, we identified that upregulated forkhead box M1 (FOXM1) was correlated with increased tumor proliferation. Overexpression of FOXM1 in benign meningioma organoids increased organoid proliferation; depletion of FOXM1 in malignant organoids decreased proliferation. Additionally, thiostrepton, a FOXM1 inhibitor combined with radiation therapy, significantly inhibited the proliferation of malignant meningioma organoid models.ConclusionsAn organoid model for meningioma enabled us to elucidate the tumor biology of meningioma along with potent treatment targets for meningioma.
| S-EPMC8563327 | biostudies-literature
Project description:Surgical resection is the main therapeutic option for intracranial meningiomas, but it is not without significant morbidities. The Surgical Apgar Score (SAS), assessed by intraoperative blood pressure, heart rate, and blood loss, was developed for prognostic prediction in general and vascular surgery. We aimed to examine whether the application of SAS in patients undergoing craniotomy for meningioma resection can predict postoperative major complications. We retrospectively enrolled 99 patients that had undergone intracranial meningioma surgery. The patients were subdivided into 2 groups based on whether major complications were present (N = 34) or not (N = 65). We recognized the intergroup differences in SAS and clinical variables. The incidence of 30-day major complications in patients after operation was 34.3%. The lengths of ICU and hospital stay for the morbid cases were prolonged significantly (p = 0.009, p < 0.001, respectively). In the multivariate logistic regression model, SAS was an independent predicting factor of major complications following surgery for intracranial meningiomas (odds ratio, 95% confidence interval = 0.57, 0.38-0.87; p = 0.009), and thus a decrease of one mean SAS increased the rate of major complications by 43%. In conclusions, SAS is an independent predictor of major complications in patients undergoing intracranial meningioma surgery, and provides acceptable risk discrimination. Since this scoring system is relatively simple, objective, and practical, we suggest that SAS be included as an indicator in the guidance for the level of care after craniotomy for meningioma resection.
| S-EPMC5383036 | biostudies-literature
Project description:BACKGROUND:Meningiomas are the most common primary tumors of the central nervous system. In patients with WHO grade I meningiomas no adjuvant therapy is recommended after resection. In case of anaplastic meningiomas (WHO grade III), adjuvant fractionated radiotherapy is generally recommended, regardless of the extent of surgical resection. For atypical meningiomas (WHO grade II) optimal postoperative management has not been clearly defined yet. METHODS:We conducted a retrospective analysis of patients treated for intracranial atypical meningioma at Charité Universitätsmedizin Berlin from March 1999 to October 2018. Considering the individual circumstances (risk of recurrence, anatomical location, etc.), patients were either advised to follow a wait-and-see approach or to undergo adjuvant radiotherapy. Primary endpoint was progression-free survival (PFS). RESULTS:This analysis included 99 patients with atypical meningioma (WHO grade II). Nineteen patients received adjuvant RT after primary tumor resection (intervention group). The remaining 80 patients did not receive any further adjuvant therapy after surgical resection (control group). Median follow-up was 37?months. Median PFS after primary resection was significantly longer in the intervention group than in the control group (64?m vs. 37?m, p?=?0.009, HR?=?0.204, 95% CI?=?0.062-0.668). The influence of adjuvant RT was confirmed in multivariable analysis (p?=?0.041, HR?=?0.192, 95% CI?=?0.039-0.932). CONCLUSIONS:Our study adds to the evidence that RT can improve PFS in patients with atypical meningioma.
| S-EPMC6719347 | biostudies-literature
Project description:BackgroundMeningioma incidence was reported to have risen substantially in the United States during the first decade of the 21st century. There are few reports about subsequent incidence trends. This study provides updated data to investigate trends in meningioma incidence by demographic and tumor characteristics at diagnosis in the United states from 2004 to 2015.MethodsTrends in meningioma incidence were analyzed using data from the Surveillance, Epidemiology, and End Results-18 (SEER-18) registry database of the National Cancer Institute. The joinpoint program was used to calculate annual percent change (APC) in incidence rates.ResultsThe overall incidence of meningioma increased by 4.6% (95% CI, 3.4-5.9) annually in 2004-2009, but remained stable from 2009 to 2015 (APC, 0; 95% CI, -0.8 to 0.8). Females (10.66 per 100 000 person-years) and blacks (9.52 per 100 000 person-years) had significant predominance in meningioma incidence. Incidence in many subgroups increased significantly up to 2009 and then remained stable until 2015. However, meningioma incidence in young and middle-aged people increased significantly throughout the entire time period from 2004 to 2015 (APC: 3.6% for <20-year-olds; 2.5% for 20-39-year-olds; 1.8% for 40-59-year-olds). The incidence of WHO II meningioma increased during 2011-2015 (APC = 5.4%), while the incidence of WHO III meningioma decreased during 2004-2015 (APC = -5.6%).ConclusionIn this study, the incidence of meningioma was found to be stable in recent years. Possible reasons for this finding include changes in population characteristics, the widespread use of diagnostic techniques, and changes in tumor classification and risk factors in the US population.
| S-EPMC6797634 | biostudies-literature