[Expression and Clinical Significance of MiR-146a and MiR-221 in Childhood Acute T Lymphoblastic Leukemia].

OBJECTIVE: To investigate the expression of miR-146a and miR-211 in peripheral blood mononuclear cells (PBMNC) of children with acute T-lymphoblastic leukemia (T-ALL) and their clinical significance. METHODS: One hundred and thirty newly diagnosed children with T-ALL from Hainan Third People's Hospital (T-ALL group) and 50 healthy persons (control group) were selected. The newly diagnosed T-ALL patients before treatment were taken as initial group, the patients reachived complete remission after induction therapy for 33 days were taken as remission group (n=98), the patients not reachived complete remission after induction therapy fore 33 days were taken as rafractory group (n=32). The expression levels of miR-146a and miR-221 in PBMNC were detected by real-time fluorescence quantitative PCR. ROC curve analysis was used to evaluate the diagnostic value of miR-146a and miR-221 for T-ALL, Pearson correlation analysis was used to estimate the correlation of miR-146a and miR-221 expression with white blood cell count in children with T-ALL. RESULTS: The expression levels of miR-146a and miR-221 of PBMNC in T-ALL group were significantly higher than those in control group (5.83±1.54 vs 0.96±0.17) (7.13±2.60 vs 1.64±0.51) (P＜0.01). The expression levels of miR-146a and miR-221 in refractory group were significantly higher than those in remission group and initial group (8.74±2.35 vs 1.70±0.63 and 5.83±1.54) (11.316±4.83 vs 2.62±0.85 and 7.13±2.60) (P＜0.01). The expression levels of miR-146a and miR-221 correlated with white blood cell count, risk typing and MRD (P＜0.05). ROC curve analysis showed that the best cutoff values of miR-146a and miR-221 for diagnosing childhood T-ALL were 3.90 and 5.28, resoectively. While the AUC (95% CI) of the T-ALL jointy diagnosed by miR-146a and miR-221 was 0.835 (0.764-0.892), and it's sensitivity and specificity were 85.0% and 77.2%, respectively. The correlation analysis showed that the expression levels of miR-146a and miR-221 in PBMNC of children with T-ALL positively correlated with the white blood cell count (r=0.705, r=0.653, P＜0.01), and that of miR-146a positively correlated with miR-221 (r=0.784, P＜0.01). CONCLUSION: The expression of miR-146a and miR-221 is up-regulated in children with T-ALL and closely relates with the prognosis of children with T-ALL. The combined detection of miR-146a and miR-221 is certain value for diagnosis of T-ALL.

[Evaluation of ivermectin's reproductive toxicity to male Carassius auratus].

As a new type of antiparasitic drugs, ivermectin (IVM) has been widely applied in agriculture, stock raising and aquaculture in China because of its broad spectrum and high efficiency. In order to evaluate the IVM' s reproductive toxicity to male Crucian carp (Carassius auratus), IVM was orally given to the experimental fish with different dosages and the gonadosomatic index (GSI), sexual hormone contents (including testosterone and estradiol) in serum and testis, γ-aminobutyric acid content in serum and brain tissues, ultra-structure of spermatozoa and gonadal tissue in fish were determined in this study. The experimental fish were classified into A, B, C and D groups corresponding to the different dosages of IVM (0, 0.3, 0.9 and 1.5 mg . kg-1, respectively once a day for 3 days continuously). Several indices in fish were detected after 8 days self-purification. The results indicated that GSI gradually decreased with the increase of drug dosage, and GSI in groups C and D was significantly lower than that in group A. The contents of testosterone, estradiol and y-aminobutyric acid exhibited a trend of first increasing and then decreasing and reached the peak at group B. Sperm longevity gradually decreased and the motion time also decreased in II, III and IV level sperms with the increasing dosage of IVM, which appeared to be especially obvious in group C and D. No obvious differences were found in the ultra-structure of spermatozoa and gonadal tissues. In conclusion, this study suggested that IVM had no obvious reproductive toxicity to male Crucian carp at the normal therapeutic dosage but could cause serious potential reproductive toxicity to fish at a high concentration.

Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas depends on IDH1 mutation.

Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.

Relationship between magnetic resonance imaging features and miRNA gene expression in patients with glioblastoma multiforme.

BACKGROUND: Magnetic resonance imaging (MRI) is commonly utilized as part of the diagnostic workup for the clinical diagnosis of glioblastoma multiforme (GBM), further guiding the clinical treatment of this aggressive cancer. Recent research has shown that microRNAs (miRNAs) may act as oncogenes, or in some cases, tumor suppressor genes that in turn may reflect the genotypic features of GBM. This study aimed to investigate the relationship between MRI features and miRNA gene expression in patients with glioblastoma multiforme. METHODS: In order to identify the relationship between the radiographic findings of MRI and those identified changes in miRNA gene expression of GBM, we reviewed the MRI images of GBM patients and compared them with the identified miRNA expression profiles utilizing microarray analysis of paired GBM tumor samples. We chose five MRI imaging features: (1) contrast tumor enhanced/necrosis ratio, (2) contrast tumor enhanced/T2 ratio, (3) multiple lesions, (4) hemorrhage, and (5) necrotic volume. The relationship between these five imaging features and miRNA expression was studied using significance analysis of microarrays analysis. RESULTS: We found that the expression of miRNAs such as hsa-miR-892b, hsa-miR-892a, and hsa-miR-888 was inversely correlated with an enhanced/necrosis ratio ≥ 1. The miRNAs such as hsa-miR-95, hsa-miR-498, and hsa-miR-1300 were associated with a contrast tumor enhanced/T2 ratio ≥1. The miRNAs such as hsa-miR-612, hsa-miR-524-3, and hsamiR-1282 were associated with multiple lesions identified on MRI and the expression of miR-221 was associated with hemorrhage by GBM. The expression of miR-let-7, including miR-let-7f, miR-let-7i, and miR-let-7f-1*, was downregulated in the hemorrhage group. The gene expression of miRNAs such as hsa-miR-140-5p, hsa-miR-30e, and hsa-miR-301a was relatively low when compared with the larger necrotic volume group as identified by MRI. CONCLUSIONS: The miRNA gene expression profiles correlate with several selected MRI features of patients with GBM. Further analysis of key imaging features of MRI with correlation with miRNA gene expression patterns may help to guide treatment decisions based on these unique correlative profiles of GBM.

BCL2A1 is a potential biomarker for postoperative seizure control in patients with low-grade gliomas.

AIMS: To identify molecular genetic factors that influence preoperative seizure occurrence and postoperative seizure control in patients with low-grade gliomas (LGGs). METHODS: Fifty-four WHO grade II astrocytomas were used for microarray analysis under strict inclusion criteria. The primary endpoint was seizure control at 12 months after surgery. Biological processes were investigated by gene ontology (GO) analysis. Quantitative RT-PCR and immunohistochemistry were used to validate key genes. RESULTS: Differentially expressed genes correlated with seizure occurrence failed to significantly distinguish patients with and without a history of seizures. With respect to postoperative seizure control, a transcript profile of 92 genes was identified, which successfully separated patients with good and poor seizure prognosis. GO analysis revealed that the most striking overrepresentation of genes was found in a category of anti-apoptotic genes and their regulation. Increased expression was also observed for genes involved in immune and inflammatory responses. BCL2A1 was proven to be a novel marker associated with seizure prognosis. CONCLUSION: Increased anti-apoptotic activity of tumor cells appears to contribute to seizure recurrence after surgery in patients with LGGs. These findings provide insights that may lead to the development of effective treatment strategies for prolonging the survival of patients with LGG in the future.

Proton magnetic resonance spectroscopy predicts radiotherapy response and time-to-progression in high-grade gliomas after surgery.

BACKGROUND: Reliable early prediction response to therapy and time-to-progression (TTP) remain an important goal of high-grade gliomas (HGGs) research. Proton magnetic resonance spectroscopy ((1)H-MRS) has been applied with variable success in clinical application, and we hypothesize that (1)H-MRS in predictive value should perform well as a marker of TTP in patients treated with radiotherapy (RT) after surgery. METHODS: (1)H-MRS was performed before surgery on 25 patients who had undergone resection of HGGs; then the ratios of lipid/creatine (Lip/Cr) and myo-inositol/creatine (mI/Cr) were determined in the solid tumor. RT response was classified as follows: complete resolution (CR), partial response (PR), stable disease (SD), and progressive disease (PD) by comparison of pre-treatment and post-radiotherapy scans. TTP was defined at the time to radiographic progression by MacDonald criteria. Correlation was evaluated between the ratios of Lip/Cr, mI/Cr and treatment response, TTP. The chi-square test and Pearson correlation test were used for data analyses. RESULTS: Multivariate analysis revealed that the prognostic value of spectroscopic variables was independent of age, sex, WHO histologic grade, extent of surgery, and Karnofsky score (KPS). The correlation between the ratios of lipid/Cr and TTP was significant (r = 0.894, P = 0.000), and between the ratios of mI/Cr and TTP was also significant (r = 0.891, P = 0.000). As predicted, RT response correlated significantly with TTP (r = 0.59, P = 0.002): median TTP was 49.9 days for patients with PD compared with 202.7 days for SD, 208.0 days for PR, and 234.5 days for CR. CONCLUSION: The ratios of Lip/Cr and mI/Cr of the solid tumor region before surgery could provide important information in predicting RT response and TTP in patients with HGGs treated by radiation alone after surgery.

Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of low-grade gliomas: a clinicopathological study.

Seizure is a common presenting manifestation and plays an important role in the clinical presentation and quality of life for patients with low-grade gliomas (LGGs). The authors set out to identify factors that influence preoperative seizure characteristics and postoperative seizure control. Cases involving adult patients who had undergone initial surgery for LGGs in a single institution between 2005 and 2009 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures and postoperative seizure control. Of the 508 patients in the series, 350 (68.9%) presented with seizures. Age less than 38 years and cortical involvement of tumor were more likely to be associated with seizures (P = .003 and .001, respectively, multivariate logistic analysis). For the cohort of 350 patients with seizures, Engel classification was used to evaluate 6- and 12-month outcome after surgery: completely seizure free (Engel class I), 65.3% and 62.5%; not seizure free (Engel classes II, III, IV), 34.7% and 37.5%. After multivariate logistic analysis, favorable seizure prognosis was more common in patients with secondary generalized seizure (P = .006) and with calcification on MRI (.031). With respect to treatment-related variables, patients achieved much better seizure control after gross total resection than after subtotal resection (P < .0001). Ki67 was an independent molecular marker predicting poor seizure control in the patients with a history of seizure if overexpressed but was not a predictor for those without preoperative seizures. These factors may provide insight into developing effective treatment strategies aimed at prolonging patients' survival.

MRI manifestions correlate with survival of glioblastoma multiforme patients.

OBJECTIVE: To identify the correlation between magnetic resonance manifestation and survival of patients with glioblastoma multiforme (GBM). METHODS: The magnetic resonance imaging (MRI) images of 30 glioblastoma patients were collected. Imaging features including degrees of contrasted area, edema surrounding the tumor, and intensity in T2-weighted imaging were selected to determine their correlation with patient survival. The relationship between imaging and survival time was studied using SPSS 19.0 software. Kaplan-Meier survival analysis and log-rank test were used to compare the survival curves. RESULTS: Patients with ≤5% contrasted enhancement area of tumor had longer overall survival (OS) than those with >5% contrasted enhancement area of tumor. Patients without edema surrounding the tumor had longer OS than those with edema. Patients with tumor of hyperintensity and/or isointensity in T2-weighted imaging had longer OS than those with hyperintensity and/or isointensity and hypointensity. CONCLUSIONS: Some MR imaging features including degrees of contrasted area, edema surrounding the tumor, and intensity in T2-weighted imaging are correlated with the survival of patients with GBM. These features can serve as prognostic indicators for GBM patients.

Relationship between magnetic resonance imaging and molecular pathology in patients with glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor in adults. Magnetic resonance imaging (MRI) is routinely used in the diagnosis, characterization and clinical management of GBM. The diagnosis and treatment of GBM is largely guided by histopathology and immunohistochemistry. This study aimed to identify the relationship between magnetic resonance features and molecular pathology of GBM. METHODS: MRI images of 43 glioblastoma patients were collected. Four imaging features, degree of edema, contrast tumor enhanced/T2 ratio, multiple lesions and tumor across the midline, were selected to identify their relationship with P53, Ki-67 and O(6)-methylguanine-DNA methyltransferase (MGMT) expression in patients with GBM. The relationship between imaging features and molecular pathology was studied by chi-square test using the software SPSS 13.0. RESULTS: High expression of P53 was found correlated with low contrast tumor enhanced/T2 ratio, low expression of Ki-67 was correlated with multiple lesions and high expression of KI-67 may be related with tumor across the midline, low expression of MGMT was correlated with edema. CONCLUSION: Some MRI features such as the degree of edema, contrast tumor enhanced/T2 ratio, multiple lesions and tumor acrossing the midline are correlated with P53, Ki-67 and MGMT of GBM.

The use of massive allograft with intramedullary fibular graft for intercalary reconstruction after resection of tibial malignancy.

Reconstruction after intercalary excision of tibia malignancy is challenging. The combined use of a vascularized fibular flap and allograft can provide a reliable reconstructive option. Eight patients underwent reconstruction with an allograft and vascularized fibula following tibia malignancy resection. Patients were examined clinically and radiographically. The average age of patients was 16.5 years. The mean follow-up time was 38.4 months. Contralateral free fibula flap was used in three patients and ipsilateral pedicle fibula in five. The average length of defect was 11.8 cm and of fibula flap was 15.9 cm. Primary union was achieved in seven patients. The average time for bone union was 5.8 months at fibula-tibia junction and 14.1 months at allograft-tibia junction. Five patients had 10 complications. The Musculoskeletal Tumor Society average score was 90.8% at final follow-up. Intramedullary fibular flap in combination with massive allografts provide an excellent option for reconstruction of large bony defects after tibial malignancy extirpation. Ipsilateral pedicle fibula transportation had the advantages of short operation time and avoidance of donor site complications compared with the contralateral free fibula transfer.

Preoperative 3T high field blood oxygen level dependent functional magnetic resonance imaging for glioma involving sensory cortical areas.

BACKGROUND: Localization of sensory cortical areas during the operation is essential to preserve the sensory function. Intraoperative direct electrostimulation under awake anesthesia is the golden standard but time-consuming. We applied 3T high field blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to identify the relationship between glioma and cortical sensory areas preoperatively and to guide intraoperative direct electrostimulation for quick and precise localization. METHODS: Five glioma patients with sensory cortex involvement by or next to the lesion had preoperative BOLD fMRI to determine the spatial relationship of cortical sensory areas to the tumours. Bilateral hand opposite movement was performed by these patients for fMRI. Precentral and postcentral gyri were identified by electrical stimulation during the operation. Karnofsky Performance Status scores of the patients' pre- and postoperative and the role of BOLD fMRI were evaluated. RESULTS: The cortical sensory areas were all activated in five glioma patients involving postcentral gyrus areas by BOLD fMRI with bilateral hand opposite movement. The detected activation areas corresponded with the results from cortical electrical stimulation. CONCLUSIONS: The relationship between cortical sensory areas and tumour can be accurately shown by BOLD fMRI before operation. And the information used to make the tumour resection could obtain good clinical results.

[Upper limbs motor maps in cortex and plasticity after the anatomical hemispherectomy].

OBJECTIVE: To locate motor functional area of patients who undergone modified anatomical hemispherectomy in order to analysis the plasticity of upper limbs motor. METHODS: The patients who undergone modified anatomical hemispherectomy were performed BOLD sequences, to locate functional cortical areas in their residual brain. RESULTS: 6 patients have performed examination of BOLD sequences by 3.0-T MRI.5 of them obtained contralateral upper limb motor areas in their residual brain, and 3 of them obtained ipsilateral and contralateral upper limb motor area map in cortex. The ipsilateral upper limb motor areas in the M1, SMA and posterior parietal cortex. CONCLUSIONS: The patients who undergone modified anatomical hemispherectomy is an excellent model to investigate mechanism of plasticity in the developing brain. Functional magnetic resonance (fMRI) provided fine spatial detail of brain responses, would describe the motor functional area of cortical maps. These patients exist ipsilateral motor areas in their residual mono hemisphere. The study indicated there maybe have somewhat extent of correlation between the surgical procedure and the outcome of neuroplasticity.

Tumefactive demyelinating lesions: nine cases and a review of the literature.

Tumefactive demyelinating lesions (TDLs) are misdiagnosed frequently. To investigate the characteristics of TDLs, clinical and radiological data from nine cases with TDLs were analyzed after admission. All cases underwent surgery and pathological examination; some received postoperative steroid therapy. Onsets were mostly within 3 weeks and main presentation included intracranial hypertension, extremity weakness, epilepsy, and visual disturbance. Symptoms in children were acute and severe, frequently including headache, vomiting, and visual disturbance. Most intracephalic lesions were in cerebral hemispheres. All intraspinal lesions were in cervical segments. Radiological features included mass effect, perifocal edema and enhancement (of which open-ring enhancement was diagnostic), and decreased relative cerebral blood volume. Intraoperative frozen section did not confirm the diagnosis, while postoperative paraffin section did confirm it (by evidence of macrophage infiltration). The patients responded well to steroid therapy and no relapse was found during following up. Thus, intensive analysis of both clinical and radiological data may provide some clues for diagnosis. For suspected cases, it is advisable to take steroid therapy or undergo advanced radiological examinations, such as serial magnetic resonance spectroscopy. However, in difficult cases, pathological evidence is beneficial to a final diagnosis.

Dynamic radiological change of gliomas located in the paralimbic system and its clinical significance.

BACKGROUND: The paralimbic system, which is composed of three parts, is an important functional unit. Gliomas located in the region remain a challenge for clinical treatment. However, the dynamic change of gliomas in the area has not been well documented. The purpose of this study was to identify the growth tendency of gliomas located in the paralimbic system and to obtain some suggestions for clinical treatment. METHODS: Eleven cases of gliomas located in the paralimbic system were recruited in the study. All of them were proven by pathology. Analysis of the serial radiological examinations in each patient was performed from the initial to the final examination, taking into consideration the following items: initial tumor location, final location and the growth tendency. RESULTS: In the initial and final examinations the ratios of insula involvement were 64% and 100%, respectively. On the other hand, the ratios of gliomas located in two or more parts of paralimbic system increased from 64% to 100% during the dynamic examination. CONCLUSIONS: Even though the paralimbic system is composed of three independent anatomical parts, gliomas tend to involve all three parts, especially the insula. Therapeutic plans should aim at the whole region of the system, even during the early stages of gliomas.

[Function magnetic resonance imaging and diffusion tensor tractography in patients with brain gliomas involving motor areas: clinical application and outcome].

OBJECTIVE: To explore the role of preoperative blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and diffusion tensor tractography (DTT) to identify the relationship between motor cortical area, pyramidal tracts with brain gliomas in neurosurgical treatment of intraoperative electrical stimulation for gliomas involving motor areas at 3T. METHODS: Twenty-eight patients with brain gliomas involving motor areas were included. They underwent MRI examination, which included conventional T1WI, T2WI, BOLD-fMRI of bilateral hands movement paradigm and diffusion tensor imaging (DTI). The data of BOLD-fMRI and DTI were transferred to the workstation (Leonardo syngo 2003A, Siemens) and analyzed. Activation mapping of hands movement, fractional Anisotropy (FA) Color and three dimensional pyramidal tracts were produced. The relationship between motor cortical area, pyramidal tracts and brain gliomas was demonstrated, which was used to optimize the pre-surgical planning. With guidance of the result of BOLD-fMRI and DTT, all patients received microsurgery under anaesthesia retaining consciousness using intraoperative motor functional brain mapping with the method of direct electrical stimulations. The brain lesions were removed as far as possible in the case of eloquent areas and sub-cortical important white matters preservation. The preoperative and postoperative KPS of all patients were operated to evaluate the state of patients. RESULTS: BOLD-fMRI, DTI were performed successfully in 28 patients. The relationship between the primary motor cortex, premotor area, supplementary motor area, pyramidal tracts and brain gliomas localized by preoperative fMRI and DTI. Under anaesthesia retaining consciousness, the primary motor area was monitored by the method of direct electrical stimulations with the guidance of preoperative BOLD-fMRI. There was good correlation between preoperative fMRI and intraoperative cortical stimulation. Furthermore, the preoperative mappings and DTT could make up for the un-monitored motor areas and pyramidal tracts during operative cortical stimulation. Comparing the preoperative KPS, the postoperative KPS was advanced. CONCLUSIONS: BOLD-fMRI and DTT could non-invasively localize the relationship between brain motor cortex, pyramidal tracts and brain gliomas in vivo to optimize the surgical planning, guide the microsurgery under anaesthesia retaining consciousness using intraoperative motor functional brain mapping with the method of direct electrical stimulations and remove brain tumors as far as possible in the case of eloquent areas and sub-cortical important white matters preservation.