The interplay mechanism between IDH mutation, MGMT-promoter methylation, and PRMT5 activity in the progression of grade 4 astrocytoma: unraveling the complex triad theory

Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.

Pilomyxoid Astrocytoma in Cerebellum

Pilomyxoid astrocytoma is a new identified variant type of pilocytic astrocytoma,and typically locates in the hypothalamic and chiasmatic region.Herein,we reported a nine-year-old boy with pilomyxoid astrocytoma in the cerebellum.MRI scanning showed a tumor involved the cerebellar vermis,tonsil,the forth ventricle and brainstem.It was homogeneous isointensity on T1WI,relative hyper-intensity on T2WI,hyper-intensity on fluid attenuated inversion recovery （FLAIR） images,and uniform enhancement on contrast T1WI.The tumor was sub-totally removed and was proved histologically to be pilomyxoid astrocytoma.Follow-up at the 5th month,MRI showed the residual tumor enlarged at the brainstem.The patient survived 10 months after the operation,and finally died of respiration failure resulting from brainstem dysfunction.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Low-Grade Astrocytomas—Final Report (Protocol BT-13)

Nonresectable Low-Grade Astrocytomas (LGA) can compromise function and threaten life. For the majority of patients, the most appropriate strategy is initial chemotherapy followed by Radiation Therapy (RT). Since curative treatment is not available for most of these patients, it is reasonable to conduct clinical studies to evaluate new agents. This Phase II study evaluates efficacy and safety of Antineoplastons A10 and AS2-1 (ANP) in LGA. Sixteen children diagnosed with LGA were treated. They included 12 males and 4 females, ages 1.6 - 17.4 years (median 10.6). Efficacy was evaluated in 16 patients. The majority of patients were previously treated, but 1 patient had stereotactic biopsy only. Out of the remaining 15 patients, 6 patients received chemotherapy, and 7 patients had surgery, and 2 patients received RT and chemotherapy after surgery. The patients received treatment with ANP administered daily every 4 hours (median dose of A10 was 7.71 g/kg/d and AS2-1 was 0.26 g/kg/d) until objective response or stable disease was documented and for 8 months thereafter. The duration of ANP IV ranged from 1.4 to 286 weeks with a median of 83 weeks. A complete response was documented in 25.0%, partial response in 12.5%, and stable disease in 37.5%. Overall survival was 67.7% at 5 years, and 54.2% at 10 and 15 years. Progression-free survival was 48.1%, 34.4% and 34.4% at 5, 10, and 15 years respectively. The treatment was associated with grade 3 or grade 4 Adverse Drug Experiences (ADE) in 6 patients. There were two hypernatremias of grade 4 (12%). Grade 3 ADE included urinary frequency (6%), fatigue (6%) and hypernatremia (6%). There were no chronic toxicities, and there was a high quality of survival. ANP shows efficacy with a very good toxicity profile in this cohort of children with low-grade astrocytoma.

Screening of differentially expressed genes related to differentiation and proliferation by gene expression profiling of different grade astrocytoma cell lines

BACKGROUND： The detection of differential gene expression in brain is possible by cDNA microarray technology, and the screening of differentially expressed genes might provide a biological basis for gene-targeted therapy for tumors. OBJECTIVE： To detect the differential expression of genes among astrocytoma SHG-44 （WHO grade Ⅳ）, CHG-5 （WHO grade Ⅱ）, and ATRA-treated SHG-44 cell lines by cDNA microarray. DESIGN： Laboratory experiments in vitro. SETTING： Department of Neurobiology, the Third Military Medical University. MATERIALS： The experiment was performed at the Department of Neurobiology in the Third Military Medical University of the Chinese PLA from January to October 2007. The SHG-44 cell line （WHO grade Ⅳ） was established by Prof. Ziwei Du, and the CHG-5 cell line （WHO grade Ⅱ） was set up by Prof. Xiuwu Bian from the Third Military Medical University of the Chinese PLA. The cDNA microarray containing 9182 known genes was prepared and provided by Dr. Yang Zhong at the City University of Hong Kong. METHODS： To screen differentially expressed genes from the gene expression profiles detected by cDNA microarray comparisons were made between CHG-5 and SHG-44 cells and between SHG-44 cells with or without treatment with 10 μmol/L ATRA. Some differentially expressed genes were selected randomly for Northern Blot analysis to confirm the results of the microarray. The determination criteria for differential gene expression were as follows. ① The ratio of Cy5 signal to Cy3 was greater than 2.0 or less than 0.5. ② The results of the triplicate microarray hybridizations showed the same trend in three experiments. ③ A gene appeared at least two times on the triplicate microarray hybridizations, and the 3^rd value did not show a contradictory trend. A normalized ratio of Cy5 intensity to Cy3 greater than 2.0 or less than 0.5 was considered to represent up-regulated or down-regulated gene expression, respectively. MAIN OUTCOME MEASURES： The identification of genes that were similarly regulated （overlapping） during tumor progression and differentiation, by comparison of gene expression profiles between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. RESULTS： Thirty-one overlapping genes were found to have similar regulatory effects on astrocytomas; among them, twenty genes were up-regulated and eleven were down-regulated in both comparisons between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. The four reported genes, SERPINFI, MAPKI 1, HIFIA and SOD2, were up-regulated in this study. CONCLUSION： The differentially expressed genes in different grade astrocytoma cell lines were revealed primarily by cDNA microarray; among them, five identified overlapping genes, SERPINF1, MAPK11, DCTN2, HIF1 A and SOD2, were related to the malignant progression of astrocytoma cells.

Magnetic resonance diffusion tensor imaging and fibertracking diffusion tensor tractography in the management of spinal astrocytomas

Some specially imaging of magnetic resonance imaging,the diffusion-weighted imaging(DWI),the diffusion tensor imaging and fractional anisotropy(FA),are useful to described,detect,and map the extent of spinal cord lesions.FA measurements may are used to predicting the outcome of patients who have spinal cord lesions.Fiber tracking enable to visualizing the integrity of white matter tracts surrounding some lesions,and this information could be used to formulating a differential diagnosis and planning biopsies or resection.In this article,we will describe the current uses for DWI and fiber tracking and speculate on others in which we believe these techniques will be useful in the future.

Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

This study was designed to investigate whether the Notch pathway is involved in the develop-ment of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133＋and CD133？ cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7–11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133＋ cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133？ cell suspension, and Notch-immunopositive expres-sion was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133＋ astro-cytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However,it should be emphasized that the sub-cortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133？ astrocytoma cells. However, these ifndings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treat-ment target for diffuse spinal cord astrocytoma.

Concise review of radiosurgery for contemporary management of pilocytic astrocytomas in children and adults

Pilocytic astrocytoma(PA)may be seen in both adults and children as a distinct histologic and biologic subset of low-grade glioma.Surgery is the principal treatment for the management of PAs;however,selected patients may benefit from irradiation particularly in the setting of inoperability,incomplete resection,or recurrent disease.While conventionally fractionated radiation therapy has been traditionally utilized for radiotherapeutic management,stereotactic irradiation strategies have been introduced more recently to improve the toxicity profile of radiation delivery without compromising tumor control.PAs may be suitable for radiosurgical management due to their typical appearance as well circumscribed lesions.Focused and precise targeting of these well-defined lesions under stereotactic immobilization and image guidance may offer great potential for achieving an improved therapeutic ratio by virtue of radiosurgical techniques.Given the high conformality along with steep dose gradients around the target volume allowing for reduced normal tissue exposure,radiosurgery may be considered a viable modality of radiotherapeutic management.Another advantage of radiosurgery may be the completion of therapy in a usually shorter overall treatment time,which may be particularly well suited for children with requirement of anesthesia during irradiation.Several studies have addressed the utility of radiosurgery particularly as an adjuvant or salvage treatment modality for PA.Nevertheless,despite the growing body of evidence supporting the use of radiosurgery,there is need for a high level of evidence to dictate treatment decisions and establish its optimal role in the management of PA.Herein,we provide a concise review of radiosurgery for PA in light of the literature.

Identification of tumor invasion-related differentially expressed genes in different grades and all-trans retinoic acid-treated astrocytoma cell lines

BACKGROUND： Although several genetic aberrations and gene expressional changes have been shown to exist in tumors and different grades of astrocytomas, as well as in normal tissues, the gene profiling and genetic pathways associated with malignant transformation and progression remain unclear. OBJECTIVE： To identify differentially expressed genes related to tumor invasion from various grades and all-trans retinoic acid （ATRA）-treated astrocytoma cell lines by cDNA microarray. DESIGN, TIME AND SETTING： In vitro gene experiment was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA from January to October 2007. MATERIALS： Two different grades of astrocytoma cell lines CHG-5 （WHO grade II ） and SHG-44 （WHO grade IV） were developed by our laboratory; a cell differentiation-inducing agent ATRA and a human cDNA microarray technology were used to determine differentially expressed genes （City University of Hong Kong）. METHODS： Total RNA was extracted using the Trizol test kit. Reverse transcription was performed using Superscript 11 reverse transcriptase. The cDNA product （target DNA） was marked with fluorochromes Cy3 （normal SHG-44） and Cy5 （CHG-5 or ATRA-treated SHG-44）, followed by chip hybridization. MAIN OUTCOME MEASURES： Gene expression profiles of CHG-5 vs. SHG-44 and ATRA-treated vs. normal SHG-44 were performed to identify differentially expressed genes. Several of these genes were randomly selected for Northern Blot analysis. The identification of genes that were similarly regulated （overlapping） was performed by comparing gene expression profiles between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. RESULTS： No significant differences were observed between CHG5 and SHG-44 cell line morphology. Under confocal microscopy, GFAP staining intensity of CHG5 cells was greater than SHG-44 cells （t = 6.078 P = 0.004）. Growth curve analysis demonstrated that the speed of SHG-44 cell growth was greater than CHG5 cells. Flow cytometry analysis showed that the number of ATRA-treated SHG-44 cells at G0/G1 stage increased by 15%, compared with normal SHG-44 cells （P 〈 0.05）. A total of 31 known genes with altered expression were identified in this study. Among them, 20 genes were upregulated and 11 were downregulated in CHG-5 compared with SHG-44 cells, and ATRA-treated SHG-44 compared with untreated SHG-44 ceils. Four of these reported genes （CD151, G3BP, UGB, and CSTB） were shown to be involved in tumor invasion. Validation of a selection of differentially expressed genes was perfonlaed by Northern blot. CONCLUSION： A total of 31 known genes were demonstrated by cDNA microarray to relate to the malignant progression of astrocytomas, and four differentially expressed genes （CD151, G3BP, UGB, and CSTB） were shown to relate to tumor invasion.

Differential protein expression in low-grade astrocytomas and peritumoral human brain tissues

Differential protein expression between various pathological grades of glioma has been shown in studies of glioma proteomics. However, very little data is available regarding normal brain tissues and glioma differential protein expression, because normal human brain tissues are difficult to harvest. The present study selected samples from low-grade astrocytomas and peritumoral brain tissues to analyze differential protein expression by two-dimensional （2D） electrophoresis and mass spectrometry techniques. Results revealing 36 protein spots by 2D electrophoresis, including 23 spots revealing increased expression and 13 spots revealing decreased expression. However, 25 differential proteins were identified by mass spectrometry, including 16 proteins with increased expression and 9 with decreased expression. Western blot analysis confirmed the mass spectrometry results, i.e., heat shock protein 70 （HSP70） and human transthyretin （TTR） expressions were increased, but glial fibrillary acidic protein （GFAP） was decreased, in astrocytomas. The present study constructed a 2D electrophoresis pattern between low-grade astrocytomas in the human brain and peritumoral tissues. Results demonstrated that a majority of differential proteins, such as HSP70, TTR, and GFAP, participate in malignant progression of gliomas.

Misdiagnosed Angioimmunoblastic T-cell Lymphoma Secondary to Cranial Astrocytoma

A case of angioimmunoblastic T-cell lymphoma （AITL） which was misdiagnosed as adult Still＇s disease was presented. The clinical and laboratory characteristics of this case and related literatures were analyzed and reviewed. The patient was finally diagnosed as AITL （Ann Arbor classification： Stage IIIB） secondary to cranial astrocytoma （WHO classification： Stage III）, complicated with severe pulmonary infection because of long time treatment of corticosteroid and misdiagnosis （about one and a half year）. It is concluded that AITL is a rare disease which was easily misdiagnosed. The diagnosis of AITL should combine the clinical manifestation with pathological biopsy as well as corresponding immunohistochemical tests.

STUDY OF DELETION OF P16 GENE IN THE PROGRESSION OF BRAIN ASTROCYTOMAS

Objective: To study the relationship between deletion of P16 gene and occurrence and progression of astrocytomas Methods: The techniques of polymerase chain reaction (PCR) and immunohistochemistry were used to detect the deletion of exon2 of P16 gene and expression of P16 gene in 52 cases of Brain astrocytoma Results: The deletion rate of exon2 of P16 gene in the tumors analyzed was 34 6% Most of them with deletion of exon2 of p16 gene were high grade astrocytomas (grade III 42%, grade IV 50%) 61 5% of the tumors were absent from expression of p16 and the deletion rate of p16 protein increased with the grade of astrocytoma (X 2=10 83, P <0 005) Conclusion: Deletion of p16 gene and protein may correlate with the malignant progression of astrocytoma

Case Report: Anaplastic Astrocytoma Treated with Postoperative Radiotherapy Using Flattening Filter-Free Volumetric Arc Therapy (FFF-VMAT) during Pregnancy—Acceptable Fetal Dosimetry

Background: Postoperative irradiation for brain tumor in pregnant women is a matter of concern. Aim: We aimed to assess the safety of radiotherapy for brain tumors in pregnancy. We here report a successful treatment for anaplastic astrocytoma during pregnancy: surgery + postoperative irradiation. We wish to emphasize how we devised irradiation procedure to achieve both therapeutic effectiveness and safety to the fetus/infant. Case Presentation: A 34-year-old pregnant woman suffered with brain anaplastic astrocytoma. Tumor resection under craniotomy was performed with success. We decided to conduct postoperative radiotherapy at 25 weeks of gestation to reduce the risk of recurrence. We used a flattening filter-free volumetric arc therapy (FFF-VMAT) technique, which can achieve lower out-of-field dose than VMAT with a flattening filter or helical tomotherapy. We prescribed 60 Gy over 30 fractions. During actual beam delivery, surface and rectal dose to the patient (mother) were measured. The total fetal dose was estimated at 0.006 - 0.018 Gy, which is under the threshold set by the ICRP. A male healthy infant was born vaginally at the 37th week of pregnancy. The patient (mother) and the infant are healthy at the time of writing. Conclusion: FFF-VMAT is a good choice for brain tumors during pregnancy.

Synthesis of Amine Terminated Pegylated Iron Oxide Nanoparticles for Prospective Astrocytoma Resection Grade Improvement

Having a survival rate to 5 years of only 3%,Glioblastoma’s(GBM)main treatment is surgical excision.Iron oxide nanoparticles have been proved to be a magnetic resonance imaging contrast agent and,if synthesized and tuned correctly,could be used to improve complete GBM resection.In this work monodisperse iron oxide nanoparticles were synthesized using thermal decomposition method,then a ligand exchange reaction with 3-aminopropyl trimethoxysilane(APS)was performed,following Pegylation of the particles using dicarboxylic acid PEG(PEG-diacid)and finally aminating with 2,2’-(ethylenedioxy)bis(ethylamine),last two by amide reactions.STEM and DLS demonstrate monodispersity(log σ<0.2)and desired size range to penetrate the blood-brain barrier(BBB);FT-IR shows the reactions were executed correctly and finally stability in deionized water,0.07 M NaCl and PBS 1X,as a function of 0-30 days,was tested.Results revealed the importance that the oleic acid/iron oleate molar ratio and the growth stage time represents for determining iron oxide nanoparticles’ size;as well as APS concentration and nucleation time influence on silica coating when performing the ligand exchange reaction.The produced iron oxide nanoparticles exhibit stability and proper amine terminated groups which are needed to allow easy incorporation of Chlorotoxin,a 36-amino acid peptide that binds specifically to astrocytoma cells,and a fluorescent molecule,which enables real time visualization of the tumor during surgery.

Volumetric Assessment of Corticospinal Tract Infiltration by Astrocytoma Using Diffusion Tensor Tractography

Objectives: The aim of the study is to assess volumetric Corticospinal Tract infiltration by Astro-cytoma using Diffusion Tensor Tractography. Material and Methods: Preoperative, anatomic (T1- and T2-weighted) and diffusion tensor MRI were performed in 9 patients with supratentorial gliomas (WHO grade II and III). The tumors were manually segmented from the T1- and T2-weighted MRI, and their volume calculated. A three-dimensional tractography was performed in each case. A second segmentation and volume measurement was performed on the tumor regions intersecting adjacent white matter fiber tracts. Results: We identified that white matter tracts were infiltrated by 6 Astrocytoma tumors. The median tumor volume (±standard deviation) in our patient population was 33 ± 26.82 ml. The median tumor volume (±standard deviation) infiltrating white matter fiber tracts was 4.15 ± 9.23 ml. The median fraction of tumor volume infiltrating white matter fiber tracts was 26.3% ± 10.1%. Conclusions: Diffusion tensor MR Tractography is a reliable preoperative assessment tool since it detects extensive white matter infiltration by Astrocytoma irrespective of brain tumors volume. Recommendations: Prospective large population studies are required to clarify how infiltration relates to tumor location.

Solitary Retinal Astrocytoma: A Case Series

Background: Astrocytic tumors of the retina are rare. We report and discuss the clinical features of two cases of retinal astrocytoma along with presenting a current literature review. Case Presentation: Case 1 was a 46-year-old Japanese female who became aware of her decreased visual acuity. A fundus photograph indicated the presence of a 5 mm hemispherical yellow-white tumor, retinal edema and hard exudate around the tumor. In case 2, a 36-year-old Japanese female became aware of her myodesopsia, and presented with a retinal tumor and vitreous hemorrhage in her right eye. Since the tumors occurred in the peripheral retina in both cases, endoresections were performed. Histological examination showed that the tumors were composed of spindle-shaped cells with small nuclei, which was consistent with astrocytes. Conclusion: Pathologically, it can be difficult to differentiate astrocytic tumors. Therefore, when making a diagnosis, it is important that comprehensive examinations be done in conjunction with the clinical findings. Since retinal astrocytoma has a favorable prognosis, provided proper treatment is administered, utilization of endoresection for peripheral astrocytoma may be advantageous in this patient group.

Perioperative Nursing Care Experience of a Case of Postoperative Recurrent Grade Ⅱ-Ⅰ Left Frontal Astrocytoma

Objective:To investigate the effect and value of perioperative nursing intervention on postoperative recurrent grade II-I left frontal astrocytoma.Method:Nursing care procedures:left frontal lobe of the patient was occupied by a large space.Clinical teaching of nursing was strengthened.Preoperative,intraoperative and postoperative care and ward patrol were enhanced.Close attention was paid on consciousness,pupil,vital signs,body temperature,lungs condition,cranial and nerve function of the patient.Extra care was taken in keeping the incision clean and dry.Blood diffusion condition in wound was observed.Active cooperation with doctor was taken to prevent occurrence of pulmonary infection,urinary tract infection,pressure ulcer and other complication.Results:After operation,the patient had stable condition,clear mind and consciousness.There was no occurrence of epilepsy but intracranial hemorrhage.Pneumatosis was relieved.There was no infection and other complication.Conclusion:Application of comprehensive nursing intervention could effectively improve quality of life of patient and reduce incidence of postoperative complication in patients with brain tumor.

Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in association with neovascularization in human primary astrocytoma

Objective: To investigate the relationship between the expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and angiogenesis in primary astrocytoma. Methods: Thirty-seven primary astrocytomas and 4 astrocytic hyperplasia samples were collected and divided into three groups according to histological grade. The expression of eNOS, VEGF and factor Ⅷ related antigen (FVIIIRAg) were assayed by immunohistochemistry. Microvascular density was assessed by FVIIIRAg immunoreactivity. The intensity of immunoreactivity was graded according to the percentage of positive tumor cells. Results: No eNOS and VEGF were expressed in the astrocytes and vascular endothelium in astrocytic hyperplasia.The expression of eNOS or VEGF was light in low-grade astrocytoma and strong in glioblastoma. eNOS expression in astrocytoma was very positively correlated with VEGF. eNOS and VEGF expression in anaplastic astrocytoma was median in contrast to the low grade astrocytoma and glioblastoma. Lower microvascular density was found in low grade astrocytoma than that in higher grade malignant ones. The expressions of eNOS and VEGF were correlated with microvascular density and tumor malignancy.Conclusion: This finding suggests that eNOS and VEGF may have cooperative effect in tumor angiogenesis and play an important role in the pathogenesis of primary astrocytoma.

Long-term molecular changes in WHO grade II astrocytomas following radiotherapy

Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas(LGGs) facilitates the understanding of LGG response to radiotherapy.In this study,we used immunohistochemistry to analyze the expression of Ki-67,tumor protein P53(TP53),P21,and P27 in 8 paired WHO grade II astrocytoma samples.The interval between radiotherapy(RT) and the second surgery was more than 3 months in all cases.The average Ki-67 labeling index(LI) was 5.3% in pre-RT samples and 11.54% in post-RT samples.Ki-67 LI was higher in the primary tumors that underwent malignant transformation observed at the second surgery after radiation.Post-RT Ki-67 LI decreased in 2 cases with an interval of less than 12 months between RT and the second surgery.TP53 expression was found in 3 out of 4 pre-RT samples with malignant transformation and in 1 out of 4 pre-RT samples without malignant transformation.Post-RT TP53 increased in 2 cases in which increased expression of P21 or P27 was also observed.Our study suggests that radiotherapy can inhibit WHO grade II astrocytoma proliferation as reflected by Ki-67 LI,but the effect attenuates with time.In addition,there is a tendency of malignant transformation for WHO grade II astrocytomas with a high Ki-67 level or TP53 expression in initial samples.

Presumed Acquired Retinal Astrocytoma in Association with Anterior Uveitis

Purpose:To report a case of presumed acquired retinal astrocytoma in association with anterior uveitis. Methods:A 29-year-old man presented with mutton fat keratic precipitates in the inferiorlower cornea,with complicated cataract and a circumscribed,solitary,yellowish-white retinal lesion in the right eye.Phacoemulsification with intraocular lens implantation was performed, with election to observeand the lesion was observed periodically. The lesion was followed for over two years without any change in size, shape or, and appearance. The anterior uveitis has not recurred at the time of writing. Results:Systemic medical and laboratory evaluations, including chest computed tomography,cranial magnetic resonance imaging,and serum angiotensin converting enzyme level, were normal. The characteristic fundus, FA,OCT scan, ultrasound scan,and lack of other contributory laboratory findings strongly supported the diagnosis of acquired retinal astrocytoma in this patient. Conclusion:We hypothesized that anterior uveitis may contribute to the growth and maintenance of retinal lesions. (Eye Science 2013; 28:51-54)