Prediction of 1p/19q codeletion status in diffuse lower-grade glioma using multimodal MRI radiomics / 南方医科大学学报

OBJECTIVE@#To develop a noninvasive method for prediction of 1p/19q codeletion in diffuse lower-grade glioma (DLGG) based on multimodal magnetic resonance imaging (MRI) radiomics.@*METHODS@#We collected MRI data from 104 patients with pathologically confirmed DLGG between October, 2015 and September, 2022. A total of 535 radiomics features were extracted from T2WI, T1WI, FLAIR, CE-T1WI and DWI, including 70 morphological features, 90 first order features, and 375 texture features. We constructed logistic regression (LR), logistic regression least absolute shrinkage and selection operator (LRlasso), support vector machine (SVM) and Linear Discriminant Analysis (LDA) radiomics models and compared their predictive performance after 10-fold cross validation. The MRI images were reviewed by two radiologists independently for predicting the 1p/19q status. Receiver operating characteristic curves were used to evaluate classification performance of the radiomics models and the radiologists.@*RESULTS@#The 4 radiomics models (LR, LRlasso, SVM and LDA) achieved similar area under the curve (AUC) in the validation dataset (0.833, 0.819, 0.824 and 0.819, respectively; P>0.1), and their predictive performance was all superior to that of resident physicians of radiology (AUC=0.645, P=0.011, 0.022, 0.016, 0.030, respectively) and similar to that of attending physicians of radiology (AUC=0.838, P>0.05).@*CONCLUSION@#Multiparametric MRI radiomics models show good performance for noninvasive prediction of 1p/19q codeletion status in patients with in diffuse lower-grade glioma.

Correlation Between Apparent Diffusion Coefficient and IDH-1/1p19q Genotype of Glioma / 肿瘤防治研究

Objective To investigate the correlation between ADC value and glioma IDH-1/1p19q genotype. Methods The MRI features and molecular pathological results of 69 patients with pathologically confirmed diagnosis of WHO grade Ⅱ/Ⅲ glioma between March 2013 and December 2020 were retrospectively analyzed. The diagnostic performance of ADC values on glioma genotypes (IDH-1, 1p19q) was evaluated using the ROC curve of the subjects' working characteristics. Results The ADCmean, ADCmin, rADCmean, and rADCmin in the IDH-1 mutation group were significantly higher than those in the IDH-1 wild group (P < 0.05, P < 0.01, P < 0.05, P < 0.01). The use of the rADCmin threshold (0.979×103mm2/s) had the highest efficacy (AUC=0.770) for diagnosis of IDH-1 mutant and IDH-1 wild-type gliomas as well as sensitivity and specificity of 84.61% and 59.09%, respectively. Conclusion ADC can be used as an imaging biomarker for noninvasive prediction of IDH-1 mutant and wild-type Ⅱ /Ⅲ gliomas.

Pleomorphic Xanthoastrocytoma with Oligodendroglioma-Like Areas with Negative 1p19q Co-Deletion

The most common mixed glioma encountered in routine surgical practice is oligoastrocytoma (OA); however, its is currently considered a vanishing entity. The 2016 classification of the World Health Organization (WHO) discourages the diagnosis of tumors as mixed glioma. The recommendations are that diffuse gliomas, including those withmixed or ambiguous histological features, should be subjected tomolecular testing. Dual-genotype OAs are not yet a distinct entity or variant in the classification. We report a case ofmixed glioma: a pleomorphic xanthoastrocytoma (PXA)mixed with an oligodendroglioma. The immunohistochemistry (IHC) pattern of isocitrate dehydrogenase 1 (IDH1) negativity with retained nuclear expression of the alpha-thalassemia x-linked intellectual disability syndrome (ATRX) protein, and 1p19q co-deletion negativity in both the components enabled its identification as a mixed glioma rather than a collision tumor. To the best of our knowledge, the case herein presented is the fourth case of PXA with oligodendroglioma. Out of the other three reported cases, only one was of a collision tumor with a dual genotype, and the other two showed similar molecular signatures in both components. The present article discusses the histological, immunohistochemical and molecular features of the aforementioned case.

Epigallocatechin gallate induces gene demethylation to promote acute myeloid leukemia cell apoptosis by regulating p19-p53-p21 signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism by which epigallocatechin gallate (EGCG) induces gene demethylation and promotes the apoptosis of acute myeloid leukemia KG-1 and THP-1 cell lines.@*METHODS@#KG-1 and THP-1 cells treated with 25, 50, 75, 100 or 150 μg/mL EGCG for 48 h were examined for gene methylation using MSP and for cell proliferation using MTT assay. The changes in cell cycle and apoptosis of the two cell lines after treatment with EGCG for 48 h were detected using flow cytometry. The mRNA and protein expressions of DNMT1, CHD5, p19, p53 and p21 in the cells were detected using RT-quantitative PCR and Western blot.@*RESULTS@#EGCG dose-dependently reversed hypermethylation of gene and reduced the cell viability in both KG-1 and THP-1 cells ( < 0.05). EGCG treatment caused obvious cell cycle arrest in G1 phase, significantly increased cell apoptosis, downregulated the expression of DNMT1 and upregulated the expressions of CHD5, p19, p53 and p21 in KG-1 and THP-1 cells ( < 0.05).@*CONCLUSIONS@#EGCG reduces hypermethylation of gene in KG-1 and THP-1 cells by downregulating DNMT1 to restore its expression, which results in upregulated expressions of p19, p53 and p21 and induces cell apoptosis.

FISHing for 1p19q codel in oligodendroglioma

@#Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.

Oligodendroglioma with Sarcomatous Transformation: Case Report and Literature Review

Oligodendrogliomas are infiltrative tumors of the central nervous systemconsidered to be morphologically stable and to offer a better prognosis. Here, we describe the case of a 36- year-old man with an initial diagnosis of oligodendroglioma, World Health Organization (WHO) grade II, who presented transformation to a sarcomatous form, while maintaining the oligodendroglial component as well as the genetic characteristics of the initial tumor without having undergone any complementary treatments previously. Despite the favorable genetic characteristics, the tumor presented poor response to complementary treatments, and rapid progression, including spinal metastasis.

Effect of Raldh2 silence on the differentiation of P19 cells into cardiomyocyte-like cells / 复旦学报（医学版）

Objective To study the effect of retinaldehyde dehydrogenase 2 (Raldh2) on the differentiation of P19 cell to cardiomyocyte-like cells and explore the potential mechanism.Methods A miRNA expression plasmid specific to Raldh2 was packaged and constructed by RNA interference (RNAi) method.The P19 stable cell line carried Raldh2 miRNA expression was selected by adding blasticidin and induced to differentiate towards cardiomyocyte-like cells.The mRNA levels of myocardium development-related markers were determined by qPCR at different stages during the differentiation process.Results The miRNA expression plasmid specific to Raldh2 could effectively suppress Raldh2 expression,and the MiRaldh2 group,a P19 stable cell line was established successfully in which the knockdown efficiency on Raldh2 was 91％ (t =25.52,P＜0.000 1,95％ CI:0.81-1.01).When compared with P19 group,the mRNA levels of cardiac transcription factors were generally decreased in the MiRaldh2 group during the whole differentiation process.In detail,on the 7th day,the relatively low expression rates of these cardiac markers including Gata4,Tef-1,N-myc,α-mhc and Ctnt was0.16±0.01 (t=17.29,P＜0.000 1),0.51 ±0.02 (t=3.564,P=0.023 5),0.23 ±0.01 (t=13.17,P =0.000 2),0.20 ± 0.02 (t=17.76,P＜0.000 1) and 0.59 ± 0.06 (t =3.642,P =0.021 9) in MiRaldh2 group when compared with the P19 group.Conversely,the mRNA levels of Nkx2.5 and Hand2 were dramatically increased in MiRaldh2 group on day 2 to 7 and the expression rates on the 7th day was 2.25 ± 0.35 (t =3.526,P =0.024 3) compared with the P19 group while Hand2 was 3.58 ± 0.20 (t =9.214,P =0.011 6).Conclusions Knockdown of Raldh2 inhibits the P19 cells differentiated into cardiomyocyte-like cells,which suggests that Raldh2 may play a potential role in early development of heart.The low expression of Raldh2 might be an explanation of the cardiac malformations associated with retinoic acid deficiency.

G26P[19] rotavirus A strain causing acute gastroenteritis in the American continent

In Brazil, the rotavirus A genotype G26 was first identified in suckling piglets, while the P[19] genotype has not been identified in any animal species so far. This report details the genetic characterisation of a G26P[19] RVA strain detected from an eight year-old child, vaccinated with Rotarix®, hospitalised with acute diarrhoeal disease in Rio de Janeiro in 2015. Most likely, the genome constellation (I5-R1-C1-M1-A8-N1-T1-E1-H1) observed in the G26P[19] Brazilian strain was a result of interspecies transmission events between humans and pigs. In addition, a rearrangement in the NSP5 gene was observed downstream of the 3' non-coding region.

NgR1 Expressed in P19 Embryonal Carcinoma Cells Differentiated by Retinoic Acid Can Activate STAT3

NgR1, a Nogo receptor, is involved in inhibition of neurite outgrowth and axonal regeneration and regulation of synaptic plasticity. P19 embryonal carcinoma cells were induced to differentiate into neuron-like cells using all trans-retinoic acid and the presence and/or function of cellular molecules, such as NgR1, NMDA receptors and STAT3, were examined. Neuronally differentiated P19 cells expressed the mRNA and protein of NgR1, which could stimulate the phosphorylation of STAT3 when activated by Nogo-P4 peptide, an active segment of Nogo-66. During the whole period of differentiation, mRNAs of all of the NMDA receptor subtypes tested (NR1, NR2A-2D) were consistently expressed, which meant that neuronally differentiated P19 cells maintained some characteristics of neurons, especially central nervous system neurons. Our results suggests that neuronally differentiated P19 cells expressing NgR1 may be an efficient and convenient in vitro model for studying the molecular mechanism of cellular events that involve NgR1 and its binding partners, and for screening compounds that activate or inhibit NgR1.

Primary Spinal Cord Oligodendroglioma with Postoperative Adjuvant Radiotherapy: A Case Report

Primary spinal cord oligodendrogliomas are rare tumors comprising two percent of all spinal cord tumors. Although a treatment guideline has yet to be established, maximal surgical resection is primary in the treatment of spinal cord oligodendrogliomas. Adjuvant radiotherapy has remained controversial, and it is unclear whether chemotherapy adds any benefit. In this case report, the authors present a 24-year-old male who had a seven-year history of left leg weakness and a radiating pain in both legs. Magnetic resonance image (MRI) showed an intramedullary mass at the T4-T8 level. He underwent subtotal removal of the tumor and pathologic diagnosis revealed a WHO grade II oligodendroglioma. The patient was treated with radiotherapy postoperatively and followed up with MRI annually. Clinical and radiological status of the patient had been stationary for four years after the surgery. The five-year follow-up MRI showed an increase in the size and extent of the residual tumor. Despite radiological progression, considering that symptoms and the performance status of the patient had remained unchanged, further treatment has not been performed. Given the clinical outcome of this patient, close observation after subtotal removal with adjuvant radiotherapy is one of the acceptable treatment options for WHO grade II spinal cord oligodendrogliomas.

Screening of natural compounds with neuronal differentiation promoting effects in a cell-based model / 中国天然药物

The purpose of this study was to establish a drug screening method for small molecules extracted from traditional Chinese medicines (TCM) that have neuronal differentiation promoting effects, using P19 embryonic carcinoma cell as a cell-based model. First, the constructed plasmid (pTα1-Luc) was transfected into P19 cells to establish a screening model. Second, several TCMs were screened using the established model and all-trans-retinoic acid as a positive control. Finally, the underlying molecular mechanism was explored using immunofluorescence staining, qT-PCR, and Western blot analysis. Our results indicated that the drug screen model was established successfully and that both honokiol and hyperoside induced P19 differentiation into neurons, with the possible molecular mechanism being modulating the Wnt signaling pathway. In conclusion, the drug screening model developed in the present study provides a rapid, cell-based screening platform for identifying natural compounds with neuronal differentiation effects.

Effects of microRNA -30c knockdown on proliferation and differentiation of P19 cells / 中华实用儿科临床杂志

Objective To explore the effects of microRNA(miRNA)- 30c knockdown on proliferation,diffe-rentiation of P19 cells. Methods miRNA - 30c knockdown plasmid(miRNA - 30c knockdown group)or no - load vector(negative control group)was transfected into P19 cells by lipo2000 and stable cell lines were selected by Blastici-din;Dual luciferase reporter gene system was used to confirm miRNA - 30c knockdown. Cell counting kit - 8(CCK - 8) assay was adopted to detect cell proliferation activity. An inverted microscope was used to observe morphological chan-ges of P19 cell differentiation. Cells were induced to differentiated to myocardiocyte with dimethyl sulfoxide(DMSO). Differentiation marker genes including cTnT,NKX2. 5,GATA4 relative mRNA expression levels were detected with real - time quantitative polymerase chain reaction,respectively. Results Observation of green fluorescent protein ex-pression under a fluorescence microscope indicated similar transfection efficiencies,and miRNA - 30c knockdown re-leased the activity of target gene Gli2. As a result,miRNA - 30c knockdown vector was constructed successfully(P ﹤0. 001). During differentiation of mouse P19 cells into myocardial cells,the beating cell clusters in miRNA - 30c knockdown cells were much lower than those in the control cells,and cTnT,NKX2. 5,GATA4 in miRNA - 30c knock-down cells showed significantly lower expression than those in the control cells( all P ﹤ 0. 05). Conclusions miRNA - 30c inhibits the P19 cell proliferation and differentiation. This study gives us a new insight of heart develop-ment and we need more efforts on exploring the deep function of heart diseases.

Gliomas triple negativo / Triple-negative gliomas

Los gliomas son los tumores más comunes entre las neoplasias primarias del Sistema Nervioso Central. LaOrganización Mundial de la Salud propone un sistema para su clasificación en cuatro grados crecientes demalignidad, teniendo en cuenta algunos rasgos histológicos. Sin embargo, esta clasificación supone varias limitacionesque afectan la conducta terapéutica y dificultan la predicción pronóstica. Estudios recientes han confirmadoel valor pronóstico de alteraciones moleculares específicas, demostrando que la clasificación molecularpredice la supervivencia de forma más precisa que el estudio histológico. De estas, las más emblemáticas sonla deleción 1p19q y las mutaciones en los genes que codifican para IDH1 y TP53. Las mutaciones en los genesIDH1/2 (80% de los gliomas difusos de grado II), la codeleción 1p19q (70% de los oligodendrogliomas) y lasmutaciones en TP53 (60% de astrocitomas difusos) constituyen marcadores de mayor supervivencia, por locual deben comprobarse rutinariamente en los pacientes con estos tumores como marcadores de pronóstico...

Among the primary neoplasms of the central nervous system, gliomas are the most common. The tumourclassification system proposed by the World Health Organization assigned four grades of increasing malignancyto gliomas based on some histological features. However, this classification has several limitations, one ofwhich is the poor prognostic prediction which affects the therapeutic approach. Recent studies have shown theprognostic value of specific molecular alterations. The most representative of these are the 1p19q deletion andmutations of the genes encoding IDH and TP53. Mutations of IDH1/2 (80% of low-grade diffuse gliomas,grade II), the 1p19q deletion (70% of oligodendrogliomas) and mutations of TP53 (60% diffuse astrocytomas)are associated with better survival. These three immunohistochemical markers greatly contribute to theclassification of gliomas and must be checked routinely as prognostic markers...

Expression pattern of microRNA-379 during the embryo heart development and differentiation of P19 cells / 中华实用儿科临床杂志

Objective To observe the expression changes in microRNA (miR)-379 in the developmental process of the mouse heart and during the differentiation of P19 cells into cardiac myocytes,and to explore the possible relationship between miR-379 and the differentiation of cardiacmyocytes.Methods Heart tissues were collected from fetal mice in pregnant ones at their gestational age (8.5,11.5,14.5 and 18.5 days) respectively.Heart tissue sections of the fatal mice were obtained to observe the heart development process.Then total RNA was isolated from heart tissues by using the TRIzol method.Complementary DNA was synthesized from 1 μg total RNA by using a Reverse Transcriptase Kit.Finally,real-time PCR (RT-PCR) was employed to detect the expression of miR-379.At the same time,P19 cells were cultured with 10 mL/L Dimethyl sulfoxide in suspension for 4 days to form cell aggregation,and these aggregations were transferred into 6-wells plate for culturing by adherence.Beating cells were detected with microscopy on the 10th day after induction.Afterwards,total RNA was extracted from cultured P19 cells at different time points.Reverse transcription was executed to get DNA.At last,RT-PCR was used to explore the expression of miR-379 on 0,4,6,10 days after aggregation.Results The expression level of miR-379 was down-regulated gradually in the developing heart (at gestational age of 8.5,11.5,14.5,16.5 days,respectively),and there were significant differences on the different days (F =21.13,P ＜ 0.05).On the other hand,myocardial markers of troponin T represented an increasing trend during the process of P19 cells induction,which demonstrated that P19 cells were successfully induced into cardiomyocyte-like cells.Meanwhile,miR-379 showed a low expression on day 0 of P19 cells aggregation.On day 4,miR-379 demonstrated a higher level.Afterwards,miR-379 proved to be down-regulated gradually.Conclusions miR-379 plays a role in the process of the heart development,but the specific mechanisms need further research.

Alpha Internexin Expression Related with Molecular Characteristics in Adult Glioblastoma and Oligodendroglioma

Alpha-internexin (INA) is a proneuronal gene-encoding neurofilament interacting protein. INA is overexpressed mostly in oligodendroglial phenotype gliomas, is related to 1p/19q codeletion, and is a favorable prognostic marker. We studied INA expression in oligodendrogliomas (ODGs) and glioblastomas (GBMs) to verify its association with several molecular phenotypes, 1p/19q codeletion, and epidermal growth-factor-receptor (EGFR) amplification. A total of 230 low- and high-grade ODG and GBM cases was analyzed for INA expression by immunohistochemical staining; and 1p/19q and EGFR gene status was examined by fluorescence in-situ hybridization. INA was positive in 80.3% of ODGs and in 34.3% of GBMs. 1p/19q codeletion was detected in 77.0% of ODGs and 5.5% of GBMs. INA and 1p/19q codeletion were strongly correlated (P < 0.001). The specificity of INA expression for 1p/19q codeletion was 70.8%, while sensitivity was 100%; positive predictive value was 72.5%, and negative predictive value was 29.2% in all 228 tumors. INA expression was correlated with better progression-free survival (PFS) and overall survival (OS) (P = 0.001). In conclusion, INA expression has high specificity and sensitivity to predict 1p/19q codeletion, and it is well correlated with PFS of both ODGs and GBMs. Therefore, INA expression could be a simple, reliable, and favorable prognostic and surrogate marker for 1p/19q codeletion and long term survival.

Expressions of interleukin (IL)-22 and related cytokines in the sera and peripheral blood mononuclear cells (PBMCs) of patients with psoriasis / 中华皮肤科杂志

Objective To investigate the expressions and significance of IL-22 and related cytokines (IL-23pl9 and IL-6) in sera and PBMCs of patients with psoriasis. Methods Sera and PBMCs were obtained from the venous blood samples from 58 patients with psoriasis vulgaris and 20 normal human controls. The PBMCs were subjected to culture for 5 hours followed by the collection of cells and culture supernatant. Then,quantitative real-time RT-PCR was used to examine the mRNA expressions of IL-22, IL-23pl9 and IL-6 in PBMCs, enzyme-linked immunosorbent assay (ELJSA) to detect the level of IL-22 protein in the sera and culture supernatant of PBMCs. Results In the patients with psoriasis and controls, the relative expression level in PBMCs was 4.48 ± 2.64 and 2.35 ± 0.91 respectively for IL-22 mRNA, 6.07 ± 4.09 and 2.61 ± 1.46 respectively for IL-23pl9 mRNA, 3.87 ± 1.49 and 1.48 ± 0.62 respectively for IL-6 mRNA; significant differences were observed between the two groups in all the above parameters (all P < 0.01). ELISA revealed that the level of IL-22 protein in the patients and controls was (86.23 ± 25.58) ng/L and (43.67 ± 14.82) ng/L respectively in the sera (P< 0.01), (119.11 ± 21.51) ng/L and (57.70 ± 13.17) ng/L respectively in the culture supernatant of PBMCs (P< 0.01). Conclusion There is an overexpression of IL-22 in the PBMCs and sera of patients with psoriasis, implying that IL-22 is involved in the pathogenesis of psoriasis.

Expression and significance of CDK4,p18,p19 in canceration of esophageal epithelium / 肿瘤研究与临床

Objective To investigate the role of cell cycle regulatory protein CDK4,p18,p19 in the genesis and development of esophageal squamous cell carcinoma (SCC).Methods Tissue microarray and immunohistochemical method (Envision) were used to detect the protein expression of CDK4,p18,p19 in 120 cases of esophageal tissues.The results were statistically analyzed.Results The positive rate of CDK4 protein expression in normal esophageal epithelium was low [28.3 % (34/120)],it increased in esophageal intraepithelial neoplasia [32.5 % (39/120)],and it was high in esophageal SCC [84.2 % (101/120)],which increased with the degree of SCC differentiation decreasing gradually.There was significant differences between the SCC and normal esophageal epithelium or esophageal intraepithelial neoplasia (x2= 76.004,P ＜0.05; x 2= 65.897,P ＜ 0.05).The expression of CDK4 in group with lymphatic metastasis [93.88 % (46/49)]was higher than without it [71.43 % (55/71)] (x2= 5.860,P ＜ 0.05).The positive rates of p18,p19 protein expression in normal esophageal epithelium were high [34.2 % (41/120),29.2 % (35/120)],it decreased in esophageal intraepithelial neoplasia [19.2 % (23/120),15.0 % (1 8/120)] (x 2= 134.481,P ＜ 0.05; x 2 = 141.376,P ＜ 0.05),but it were high in esophageal SCC [63.3 % (76/120) and 61.7 % (74/120)] which decreased with the degree of SCC differentiation gradually increased.There were significant differences between the normal esophageal epithelium and esophageal intraepithelial neoplasia,esophegeal intraepithelial neoplasia and SCC,normal esophageal epithelium and SCC (p 18:x 2 = 6.903,48.296,20.429,P ＜ 0.05; p1 9:x2 = 6.998,55.276,25.565,P＜ 0.05).CDK4 protein expression was correlated with both p18 and p19 (r =0.696,0.630,P ＜0.05),and there was significant positive correlation between the protein expression of p18 and p19 (r =0.833,P ＜0.05).Conclusion Cell cycle regulatory gene CDK4,p18,p19 get involved in the genesis and development of esophageal squamous cell carcinoma.Their protein expressions are closely related to canceration of esophageal epithelium.

Avances en el tratamiento del glioblastoma multiforme: [revisión] / Advances in the treatment of glioblastoma multiforme: [review]

El glioblastoma multiforme es el tumor primario del sistema nervioso central más frecuente en hombres. Su incidencia en Europa oscila entre 3 y 4 casos por 100.000 habitantes, y representa el 25% de todos los tumores de sistema nervioso central y el 50% de los tumores primarios. Menos del 3% de todos los pacientes con diagnóstico de glioblastoma sobreviven más de cuatro años y la supervivencia promedio es de seis meses. En la actualidad, se están adelantando estudios que tienen como objetivo lograr una mayor supervivencia y aumentar los periodos asintomáticos. Esta revisión tiene como objetivo principal hacer un breve recuento de los avances en el tratamiento del glioblastoma multiforme, haciendo énfasis en la terapia génica. En la literatura revisada se encontró que, en la actualidad, sólo hay dos tipos de mutaciones capaces de definir el pronóstico de la enfermedad; la presencia de la metilguanina-ADN metiltransferasa (MGMT) y la deleción 1p/19q, en las cuales se hará hincapié en el transcurso del documento.

Glioblastoma multiforme is the most common central nervous system (CNS) primary tumor in men. Its incidence in Europe lies between 3 to 4 cases per 100,000 inhabitants and it represents 25% of all the CNS tumors and 50% of the primary tumors. Less than 3% of all patients diagnosed with glioblastoma multiforme survive more than 4 years and the average survival is of 6 months. Studies aiming to increase the survival rate, as well as to achieve longer asymptomatic periods are being carried out at present. The main goal of this review is to offer a brief recount on the progress in the treatment of glioblastoma multiforme, focusing on genetic therapy. The consulted literature showed, that there are only two types of mutations capable of defining the prognosis of this disease at this point; one is the presence of O6-methylguanine-DNA methyltransferase protein expression (MGMT) and the 1p/ 19q deletion on which we will emphasize in the course of this document.

Influence of Mycobacterium tuberculosis 19-kDa lipoprotein on function and phenotype of macrophage / 中国人兽共患病学报

To observe the influence of Mycobacterium tuberculosis 19-kDa lipoprotein (Mtb P19) on function and phenotype of macrophage,the Mtb P19 was prepared from cultured Mtb H37Ra and the phorbol myristate acetate-differentiated THP-1 cells were incubated with P19 at the concentration of 10 μg/mL with 5% CO_2 at 37℃ for up to 48 hours.Supernatants were collected for TNF-α and IL-6 detection by ELISA,then the phenotype fluorescent antibodies were stained to analyze HLA-DR expression changes between control group and experimental group.Flow cytometry and microscopy was used to assay the phagocytosis in macrophages stimulated by Mtb P19.IL-6 and TNF-α in collected supernatants were detected.Results indicated that both were found significant increases and their phagocytosis were enhanced.Comparing to the control group,the mean fluorescence intensity showed a significant increase 24hs after stimulation.It presents that Mtb P19 could be able to induce macrophages activation,and it would be significantly important for protection during infection period.

Cardiomyocyte Differentiation from P19 Cells Induced by NKX2-5 / 中国医科大学学报

Objective To identify the rale of NKX2-5 gene in cardiomyocyte differentiation and its mechanism.Methods P19 cells were divided into transfected and non-transfected groups.In the transfected group,P19 cells were with stable expression of NKX2-5 gene.The P19 cells were cultured in suspension for 4 days,and the formed aggregates were transferred to Petri dish for adherent culture.On days 4,8,12,and 16 of the adherent culture,the expressions of ct-saicomeric actin(α-SA)and cardiac troponin T(cTnT)were detected with double-labeling immunofluorescence and Western blot.The ultrastruetural changes were observed on day 16.Results In the transfected group,no expression of α-SA and cTnT was found on day 4,and the expression of these 2 proteins or co-expression existed on days 8,12,and 16.There were early cell junction and myofilament-like structure in the cytoplasm of some cells in the transfected group.In the non-transfected group,these 2 proteins were negative,and no differentiated cell was found.Conclusion Stable expression of NKX2-5 gene can induce cardiomyocyte differentiation from P19 cells,but the P19 cells with stable expression of JVKX2-5 gene is not suitable to be an in vitro model of cardiac development.