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BACKGROUND@#Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lower-grade gliomas that carry IDH2 mutations.@*METHODS@#Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test.@*RESULTS@#Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively).@*CONCLUSIONS@#IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.
ABSTRACT
Objective To study the role of interleukin-22 (IL-22) in murine asthmatic airway inflammation and airway models, and explore the mechanism of astragaioside (AS) Ⅳin the treatment of asthma.Methods Ovalbumin(OVA) was used as an allergen to sensitize and challenge the mice .Thirty-two female specific-free ( SPF) four-week BALB/c mice were randomly divided into 4 groups:control group , asthma group , budesonide treatment group ( BUD group ) and AS-Ⅳgroup.HE staining and AB-PAS were used to measure the inflammation scores and goblet cells hyperplasia , enzyme-linked immunosorbent assay(ELISA) was used to analyze IL-22 levels in bronchoalveolar lavage fluid (BALF), flow cytometry was performed to analyze the proportion of Th22 cells in spleen single cell suspension , and realtime-PCR was performed to analyze the IL-22 mRNA levels in lung tissue .Results The inflammation scores of asthma group were elevated compared with the control group(P<0.05).An overall reduction of asthmatic airway inflammation was observed in the BUD group and AS-Ⅳgroup by the end of the trial .IL-22 levels in BALF and the proportion of Th22 cells in spleen single cell suspension were significantly increased after treatment in BUD and AS-Ⅳ groups(P<0.01), while the mRNA levels of IL-22 were obviously decreased(P<0.01).Conclusion The increase of IL-22 can induce airway inflammation of asthma . AS-Ⅳcan reduce Th22 cell differentiation and the expression of IL-22, thereby inhibiting the development of airway inflammation of asthma.
ABSTRACT
Objective To study the role of interleukin-22 (IL-22) in murine asthmatic airway inflammation and airway models, and explore the mechanism of astragaioside (AS) Ⅳin the treatment of asthma.Methods Ovalbumin(OVA) was used as an allergen to sensitize and challenge the mice .Thirty-two female specific-free ( SPF) four-week BALB/c mice were randomly divided into 4 groups:control group , asthma group , budesonide treatment group ( BUD group ) and AS-Ⅳgroup.HE staining and AB-PAS were used to measure the inflammation scores and goblet cells hyperplasia , enzyme-linked immunosorbent assay(ELISA) was used to analyze IL-22 levels in bronchoalveolar lavage fluid (BALF), flow cytometry was performed to analyze the proportion of Th22 cells in spleen single cell suspension , and realtime-PCR was performed to analyze the IL-22 mRNA levels in lung tissue .Results The inflammation scores of asthma group were elevated compared with the control group(P<0.05).An overall reduction of asthmatic airway inflammation was observed in the BUD group and AS-Ⅳgroup by the end of the trial .IL-22 levels in BALF and the proportion of Th22 cells in spleen single cell suspension were significantly increased after treatment in BUD and AS-Ⅳ groups(P<0.01), while the mRNA levels of IL-22 were obviously decreased(P<0.01).Conclusion The increase of IL-22 can induce airway inflammation of asthma . AS-Ⅳcan reduce Th22 cell differentiation and the expression of IL-22, thereby inhibiting the development of airway inflammation of asthma.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate mutation status of isocitrate dehydrogenase (IDH) 1 and IDH2 genes in Chinese patients with gliomas in correlation with clinicopathological characteristics.</p><p><b>METHODS</b>Formalin-fixed and paraffin-embedded (FFPE) tissue samples of 234 gliomas were collected including the matched blood samples in 30 patients. DNA was extracted, followed by PCR-Sanger sequencing to detect IDH1 and IDH2 gene mutations. Immunohistochemistry was performed using mutation-specific antibody recognizing IDH1R132H mutation. Immunostains for p53 and epidermal growth factor receptor (EGFR) were also performed. Oligodendroglial tumors with IDH mutation were double stained with IDH1R132H and GFAP by immunofluorescence to investigate the location of IDH1R132H expression.</p><p><b>RESULTS</b>(1) By IDH1 heterozygous somatic mutation analysis, Arg132His (c: G395A) was found in 31.6% (74 of 234) of the cases. IDH mutations were more frequent in oligoastrocytomas (9/13), anaplastic oligoastrocytomas (7/11), oligodendrogliomas(18/26, 69.2%), anaplastic oligodendrogliomas (8/10), and less frequent in diffuse astrocytomas (17/47, 36.2%), anaplastic astrocytomas (5/18), and glioblastomas (10/69, 14.5%). The mutation rate inversely correlated with the tumor grade in a linear fashion in astrocytic tumors (P = 0.007). Primary glioblastomas were characterized by a lower frequency of mutations than secondary glioblastomas (5/55 vs. 5/14, P = 0.036); IDH mutation was not detected in pilocytic astrocytoma and ependymoma. No IDH2 mutation was identified in this study cohort. (2) Immunohistochemistry of IDH1R132H demonstrated a strong cytoplasmic staining in 80 cases, which was highly correlated with IDH mutation status (P = 0.001). IDH1R132H was highly specific to tumor cells. (3) p53 immunostain was significantly correlated the IDH mutation in diffuse astrocytoma, anaplastic astrocytoma and secondary glioblastomas (P = 0.007, 0.026, 0.038 respectively). (4) No correlation between EGFR and IDH mutation was found.</p><p><b>CONCLUSIONS</b>High prevalence of IDH heterozygous somatic mutation occurs in the earlier stage of gliomas, which can be detected by mutation-specific antibody IDH1R132H. Furthermore, evaluation of p53 and EGFR expression combined with IDH mutation analysis may significantly aid in the diagnosis and differential diagnoses of gliomas in Chinese patients.</p>