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1.
Theranostics ; 10(1): 179-200, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903114

RESUMO

Background: Alzheimer's disease (AD) currently lacks a cure. Because substantial neuronal damage usually occurs before AD is advanced enough for diagnosis, the best hope for disease-modifying AD therapies likely relies on early intervention or even prevention, and targeting multiple pathways implicated in early AD pathogenesis rather than focusing exclusively on excessive production of ß-amyloid (Aß) species. Methods: Coniferaldehyde (CFA), a food flavoring and agonist of NF-E2-related factor 2 (Nrf2), was selected by multimodal in vitro screening, followed by investigation of several downstream effects potentially involved. Furthermore, in the APP/PS1 AD mouse model, the therapeutic effects of CFA (0.2 mmol kg-1d-1) were tested beginning at 3 months of age. Behavioral phenotypes related to learning and memory capacity, brain pathology and biochemistry, including Aß transport, were assessed at different time intervals. Results: CFA promoted neuron viability and showed potent neuroprotective effects, especially on mitochondrial structure and functions. In addition, CFA greatly enhanced the brain clearance of Aß in both free and extracellular vesicle (EV)-contained Aß forms. In the APP/PS1 mouse model, CFA effectively abolished brain Aß deposits and reduced the level of toxic soluble Aß peptides, thus eliminating AD-like pathological changes in the hippocampus and cerebral cortex and preserving learning and memory capacity of the mice. Conclusion: The experimental evidence overall indicated that Nrf2 activation may contribute to the potent anti-AD effects of CFA. With an excellent safety profile, further clinical investigation of coniferaldehyde might bring hope for AD prevention/therapy.

2.
J Cell Physiol ; 235(3): 2183-2194, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31489631

RESUMO

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is aberrantly expressed in multiple myeloma (MM) patients, however, its role remains largely unknown. The present study aimed to investigate the effect of NY-ESO-1 knockdown on MM impact and provide evidence for targeting treatment of MM. Human MM U266 cells were infected with lentivirus-based small hairpin RNA-targeting NY-ESO-1 (LV-shNY-ESO-1). Cellular proliferation, colony-forming, migration, and invasion assays were employed. The expressions of cell cycle and epithelial-mesenchymal transition (EMT)-related molecules, MM growth, and mouse osteolytic lesions were evaluated. The results showed that the LV-shNY-ESO-1-U266 cells had a lower expression of NY-ESO-1 and a higher expressions of p21 and E-cadherin, and a weaker abilities of colony formation, drug-resistant to adriamycin, migration, and invasion than those of the control cells. Importantly, the knockdown of NY-ESO-1 inhibited significantly the U266 cell-induced MM growth and osteolytic lesions along with increasing the expressions of E-cadherin, p21, and p53 in mice challenged with LV-shNY-ESO-1-U266 cells. Collectively, our findings demonstrate that knockdown of NY-ESO-1 suppressed the U266 cell-induced MM growth and osteolytic lesions by inhibition of the MMs cell cycle and EMT. The NY-ESO-1 knockdown may be considered for future clinical trials in MM.

3.
J Hepatol ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31813573

RESUMO

BACKGROUND & AIMS: C-C motif chemokine receptor 2 (CCR2) has been recognized as a promising target for the treatment of liver fibrosis. PC3-secreted microprotein (PSMP)/microseminoprotein (MSMP) is a novel chemotactic cytokine and its receptor is CCR2. In the present study we investigated the expression and role of PSMP in liver fibrosis/cirrhosis. METHODS: PSMP expression was studied in patients with fibrosis/cirrhosis and in 3 murine models of liver fibrosis, including mice treated with carbon tetrachloride (CCl4), bile-duct ligation, or a 5-diethoxycarbonyl-1,4-dihydrocollidine diet. The role of PSMP was evaluated in Psmp-/- mice and after treatment with a PSMP antibody in wild-type mice. The direct effects of PSMP on macrophages and hepatic stellate cells were studied in vitro. RESULTS: In this study, we found that PSMP was highly expressed in fibrotic/cirrhotic tissues from patients with different etiologies of liver disease and in the 3 experimental mouse models of fibrosis. Damage-associated molecular pattern molecules HMGB-1 and IL-33 induced hepatocytes to produce PSMP. PSMP deficiency resulted in a marked amelioration of hepatic injury and fibrosis. In CCl4-induced hepatic injury, the infiltration of macrophages and CCR2+ monocytes into the liver was significantly decreased in Psmp-/- mice. Consistent with the decreased levels of intrahepatic macrophages, proinflammatory cytokines were significantly reduced. Moreover, adeno-associated virus-8 vectors successfully overexpressing human PSMP in Psmp-/- mouse livers could reverse the attenuation of liver injury and fibrosis induced by CCl4 in a CCR2-dependent manner. Treatment with a specific PSMP-neutralizing antibody, 3D5, prevented liver injury and fibrosis induced by CCl4 in mice. At the cellular level, PSMP directly promoted M1 polarization of macrophages and activation of LX-2 cells. CONCLUSION: PSMP enhances liver fibrosis through its receptor, CCR2. PSMP is a potentially attractive therapeutic target for the treatment of patients with liver fibrosis. LAY SUMMARY: Our present study identifies the essential role of the protein PSMP for the development and progression of liver fibrosis in humans and mice. PSMP promotes liver fibrosis through inflammatory macrophage infiltration, polarization and production of proinflammatory cytokines, as well as direct activation of hepatic stellate cells via its receptor CCR2. A PSMP antibody can significantly reduce liver fibrosis development in vivo. These findings indicate that PSMP is a potential therapeutic target and its antibody is a potential therapeutic agent for the treatment of liver fibrosis.

4.
Front Oncol ; 9: 724, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31555577

RESUMO

Prostate cancer (PCa), especially metastatic PCa, is one of the main cancer types accounting for male mortality worldwide. Over decades, researchers have tried to search for effective curative methods for PCa, but many attempts have failed. The therapeutic failure of PCa is usually due to off-target or side effects; thus, finding a key molecule that could prevent PCa metastatic progression has become the most important goal for curing aggressive PCa. In this study, we collected hundreds of PCa tissues and serum and urine samples from patients to verify the upregulated expression of PC3-secreted microprotein (PSMP) in PCa tumor tissues with high Gleason scores. According to biopsy results, PSMP expression was found related to extraprostatic extension (EPE), contributing to PCa metastasis. Mechanistically, recombinant PSMP protein could promote the proliferation both in vitro and in vivo, and rhPSMP could promote epithelial-mesenchymal transition (EMT) of PC3 in vitro. Additionally, PSMP could also influence cytokine production in the xenograft model and monocyte migration and macrophage polarization in vitro. Our most important finding was that neutralizing antibodies against PSMP could suppress xenograft PC3 growth and promote the survival of PC3 metastatic mice model, providing an effective option to cure human PCa.

6.
FASEB J ; : fj201800020RRR, 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29799787

RESUMO

FAM19A1 is a member of the family with sequence similarity 19 with unknown function. FAM19A1 mRNA expression is restricted to the CNS. Here, we report that FAM19A1 is a classic secretory protein, and expression levels correlate with brain development, increasing from embryonic d 12.5, peaking between postnatal d (P)1 and P7 and decreasing at wk 8. The adult hippocampus is a region of FAM19A1 high expression. Recombinant FAM19A1 suppressed the proliferation and self-renewal of neural stem cells (NSCs) and altered the lineage progression of NSCs with promoted neuron differentiation and suppressed astrocyte differentiation. Although GPCR 1 (GPR1) has been reported to be expressed in the CNS, its functions in the brain remain unclear. We identified GPR1 to be a functional receptor for FAM19A1. FAM19A1 interacted with GPR1 via the N-terminal domain (GPR1-ND), and its NSC modulatory functions required the Rho-associated protein kinase (ROCK) /ERK1/2 and ROCK/signal transducer and activator of transcription 3 signaling pathways. GPR1-ND that selectively bound to FAM19A1 neutralized the effects of FAM19A1 on NSC functions. Taken together, our results show, for the first time to our knowledge, that FAM19A1 is a novel regulatory factor of the proliferation and differentiation of NSCs, and identified a novel mechanism by which GPCR mediates the effects of FAM19A1 on NSC functions that may be important for brain development and neurogenesis. Additional exploration of the functions of FAM19A1 and GPR1 in the CNS may broaden the range of therapeutic options available for major brain disorders.-Zheng, C., Chen, D., Zhang, Y., Bai, Y., Huang, S., Zheng, D., Liang, W., She, S., Peng, X., Wang, P., Mo, X., Song, Q., Lv, P., Huang, J., Ye, R. D., Wang, Y. FAM19A1 is a new ligand for GPR1 that modulates neural stem-cell proliferation and differentiation.

7.
Cancer Sci ; 109(4): 1263-1275, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29369502

RESUMO

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. It contains at least four distinct molecular subgroups. The aim of this study is to explore novel diagnostic and potential therapeutic markers within each subgroup of MB, in particular within Group 4, the largest subgroup, to facilitate diagnosis together with gene therapy. One hundred and six MB samples were examined. Tumor subtype was evaluated with the NanoString assay. Several novel tumor related genes were shown to have high subgroup sensitivity and specificity, including PDGFRA, FGFR1, and ALK in the WNT group, CCND1 in the SHH group, and α-synuclein (SNCA) in Group 4. Knockdown and overexpression assays of SNCA revealed the ability of this gene to inhibit tumor invasion and induce apoptosis. Methylation-specific PCR and pyrosequencing analysis showed that epigenetic mechanisms, rather than DNA hypermethylation, might play the key role in the regulation of SNCA expression in MB tumors. In conclusion, we identify SNCA as a novel diagnostic biomarker for Group 4 MB. Some other subgroup signature genes have also been found as candidate therapeutic targets for this tumor.


Assuntos
Apoptose/genética , Biomarcadores Tumorais/genética , Meduloblastoma/genética , Invasividade Neoplásica/genética , alfa-Sinucleína/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Metilação de DNA/genética , Epigênese Genética/genética , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Humanos , Lactente , Masculino , Meduloblastoma/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Sensibilidade e Especificidade , Adulto Jovem
8.
Appl Immunohistochem Mol Morphol ; 26(2): 101-107, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-27258564

RESUMO

BACKGROUND: Isocitrate dehydrogenase (IDH) mutations have been reported as biomarkers associated with tumorigenesis and prognosis in gliomas. However, genes affected by these mutations are still under investigation. The purpose of this study is to identify new molecular biomarkers associated with IDH mutation and prognosis in astrocytic tumors, which account for the largest proportion of gliomas. MATERIALS AND METHODS: NanoString analysis was conducted on 40 astrocytic tumors. In total, 69 genes and 6 fusion genes were selected for screening. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to validate the selected discriminatory genes. Kaplan-Meier survival curves and log-rank test were used to analyze the overall survival and progression-free survival. RESULTS: mRNA levels of NTRK3, ERCC1, JAK2, AXL, BCL2, ESR1, HSP90AB1, TUBB3, RET, and ABCG2 were elevated in the IDH mutant group, whereas levels of POSTN and ERBB2 were elevated in the IDH wild-type group. Genes more highly expressed in the better prognosis group included NTRK3, ERCC1, ROS1, ERBB4, BCL2, CDKN2A, AXL, PI3KCA, HSP90AB1, ABCG2, JAK2, and RET. In the worse prognosis group, TIMP1, POSTN, and ERBB2 showed increased expressions. The elevated expression of HSP90AB1 was correlated with IDH mutation, long survival, and secondary glioblastomas. Elevated TIMP1 expression was related to high tumor grade and short patient survival. The results of NanoString were confirmed with quantitative real-time polymerase chain reaction and immunohistochemistry. CONCLUSIONS: HSP90AB1 is related to IDH mutation and the expressions of HSP90AB1 and TIMP1 can predict prognosis in astrocytic tumors. The NanoString analysis system is a precise and reliable method to detect mRNA expression in formalin-fixed paraffin-embedded samples.


Assuntos
Astrocitoma/genética , Biomarcadores Tumorais/genética , Proteínas de Choque Térmico HSP90/genética , Isocitrato Desidrogenase/genética , Mutação/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/diagnóstico , Astrocitoma/mortalidade , Carcinogênese , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanotecnologia , Prognóstico , Análise de Sobrevida , Adulto Jovem
9.
Sci Rep ; 7(1): 5107, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28698550

RESUMO

Monocytes/macrophages have been found to be an important component of colitis. However, the key chemokine that initiates the CCR2+ monocytes migration from circulation to colitis tissue remains to be undiscovered. PC3-secreted microprotein (PSMP) is a novel chemokine whose receptor is CCR2. The physiological and pathological functions of PSMP have not yet been reported. In this study, PSMP was found to be expressed in colitis and colonic tumor tissues from patients and significantly up-regulated in mouse DSS-induced colitis tissues. PSMP overexpression in the colon aggravated the DSS-induced colitis and the anti-PSMP neutralizing antibody mollified the colitis by reducing macrophage infiltration and inhibiting the expression of IL-6, TNF-α and CCL2. Furthermore, we demonstrated that lipopolysaccharide and muramyl dipeptide induced PSMP expression in the colonic epithelial cells. PSMP was up-regulated in the initial stage prior to IL-6, TNF-α and CCL2 up-regulated expression in DSS colitis and promoted the M1 macrophages to produce CCL2. PSMP chemo-attracted Ly6Chi monocytes in a CCR2 dependent manner via in situ chemotaxis and adoptive transfer assays. Our data identify PSMP as a key molecule in ulcerative colitis, which provides a novel mechanism of monocyte/macrophage migration that affects gut innate immunity and makes PSMP a potential target for controlling colitis.


Assuntos
Colite/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Secretadas pela Próstata/metabolismo , Receptores CCR2/metabolismo , Animais , Movimento Celular , Quimiocina CCL2/metabolismo , Colite/induzido quimicamente , Sulfato de Dextrana , Modelos Animais de Doenças , Humanos , Interleucina-6/metabolismo , Masculino , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
10.
Alzheimers Dement ; 12(11): 1125-1131, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27234211

RESUMO

INTRODUCTION: Alzheimer's disease (AD) and Parkinson's disease (PD) involve tau pathology. Tau is detectable in blood, but its clearance from neuronal cells and the brain is poorly understood. METHODS: Tau efflux from the brain to the blood was evaluated by administering radioactively labeled and unlabeled tau intracerebroventricularly in wild-type and tau knock-out mice, respectively. Central nervous system (CNS)-derived tau in L1CAM-containing exosomes was further characterized extensively in human plasma, including by single molecule array technology with 303 subjects. RESULTS: The efflux of Tau, including a fraction via CNS-derived L1CAM exosomes, was observed in mice. In human plasma, tau was explicitly identified within L1CAM exosomes. In contrast to AD patients, L1CAM exosomal tau was significantly higher in PD patients than controls and correlated with cerebrospinal fluid tau. CONCLUSIONS: Tau is readily transported from the brain to the blood. The mechanisms of CNS tau efflux are likely different between AD and PD.


Assuntos
Doença de Alzheimer/metabolismo , Exossomos/metabolismo , Doença de Parkinson/metabolismo , Proteínas tau/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Transporte Biológico/fisiologia , Barreira Hematoencefálica/metabolismo , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Proteínas tau/genética
11.
J Cell Sci ; 129(9): 1831-42, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-26966188

RESUMO

The family with sequence similarity 3 (FAM3) gene family is a cytokine-like gene family with four members FAM3A, FAM3B, FAM3C and FAM3D. In this study, we found that FAM3D strongly chemoattracted human peripheral blood neutrophils and monocytes. To identify the FAM3D receptor, we used chemotaxis, receptor internalization, Ca(2+) flux and radioligand-binding assays in FAM3D-stimulated HEK293 cells that transiently expressed formyl peptide receptor (FPR)1 or FPR2 to show that FAM3D was a high affinity ligand of these receptors, both of which were highly expressed on the surface of neutrophils, and monocytes and macrophages. After being injected into the mouse peritoneal cavity, FAM3D chemoattracted CD11b+ Ly6G+ neutrophils in a short time. In response to FAM3D stimulation, phosphorylated ERK1/2 and phosphorylated p38 MAPK family proteins were upregulated in the mouse neutrophils, and this increase was inhibited upon treatment with an inhibitor of FPR1 or FPR2. FAM3D has been reported to be constitutively expressed in the gastrointestinal tract. We found that FAM3D expression increased significantly during colitis induced by dextran sulfate sodium. Taken together, we propose that FAM3D plays a role in gastrointestinal homeostasis and inflammation through its receptors FPR1 and FPR2.


Assuntos
Quimiotaxia , Colite/metabolismo , Citocinas/metabolismo , Sistema de Sinalização das MAP Quinases , Monócitos/metabolismo , Neutrófilos/metabolismo , Receptores de Formil Peptídeo , Receptores de Lipoxinas , Animais , Colite/genética , Colite/patologia , Citocinas/genética , Sulfato de Dextrana/toxicidade , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HEK293 , Humanos , Camundongos , Monócitos/patologia , Neutrófilos/patologia , Receptores de Formil Peptídeo/agonistas , Receptores de Formil Peptídeo/genética , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/agonistas , Receptores de Lipoxinas/genética , Receptores de Lipoxinas/metabolismo
12.
Int J Clin Exp Pathol ; 7(6): 3347-54, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25031759

RESUMO

Intraneural perineurioma is a neoplasm of perineurial cells, corresponding to WHO grade I. We present a case of intraneural perineurioma affecting multiple nerves, which usually involved one or two of major nerve trunks in one patient. We describe the clinical presentation, magnetic resonance (MR) neurography characteristics, and pathological characteristics. The differential diagnosis with other diseases, such as neurofibroma, Schwannomatosis and HNPP, will also be discussed. We also review the literature in efforts to highlight recent studies on intraneural perineurioma and heighten and awareness for the possible presentations of this disorder.


Assuntos
Neoplasias da Bainha Neural/patologia , Neoplasias do Sistema Nervoso Periférico/patologia , Artrogripose/diagnóstico , Diagnóstico Diferencial , Feminino , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Humanos , Neurilemoma/diagnóstico , Neurofibroma/diagnóstico , Neurofibromatoses/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto Jovem
13.
Neurosurgery ; 75(1): 10-22, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24662504

RESUMO

BACKGROUND: The development of an hourglass-like constriction in the nerve is rare, and its origin is unknown. Its clinical manifestations are not well documented, and the treatment protocol has not been established. OBJECTIVE: To identify the cause, presentation, and possible treatment for patients with nerve palsies secondary to an hourglass-like constriction in the affected nerves. METHODS: Patients presenting with peripheral nerve palsy caused by an hourglass-like constriction of nerves were retrospectively investigated in 2 hand centers. The patients' presentation and neurological findings were reviewed, and the immunohistochemistry of excised specimens was studied. RESULTS: Forty-two patients who presented with 47 nerve palsies were examined. Forty-one patients experienced a sudden onset of pain in the upper limb, followed by flaccid paralysis in the affected muscles. Ten patients had multiple nerve involvement. Surgical exploration found 1 or more hourglass-like constrictions in the nerve. The treatments included internal neurolysis, neurorrhaphy, and nerve grafting. Thirty-one of 42 patients (36 nerves) were followed up for a mean of 48 months (range, 8-157 months). Fifteen of 16 nerves treated by neurolysis, 10 of 13 nerves treated by neurorrhaphy, and 4 of 7 nerves treated by nerve grafting had good recovery. CD8-positive T-lymphocyte infiltration was observed in all the excised specimens. CONCLUSION: The clinical presentation of patients with hourglass-like constrictions in their nerves is similar to that of patients with neuralgic amyotrophy. Histochemical analysis suggests that the pathogenesis may be immunological in origin. The role of surgery in this condition is uncertain.


Assuntos
Nervos Periféricos/patologia , Adolescente , Adulto , Criança , Constrição Patológica/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Paralisia/cirurgia , Nervos Periféricos/cirurgia , Estudos Retrospectivos , Extremidade Superior/inervação , Adulto Jovem
14.
Zhonghua Bing Li Xue Za Zhi ; 42(5): 292-8, 2013 May.
Artigo em Chinês | MEDLINE | ID: mdl-24004584

RESUMO

OBJECTIVE: To investigate mutation status of isocitrate dehydrogenase (IDH) 1 and IDH2 genes in Chinese patients with gliomas in correlation with clinicopathological characteristics. METHODS: 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. RESULTS: (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. CONCLUSIONS: 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.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/genética , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Criança , Ependimoma/genética , Ependimoma/metabolismo , Receptores ErbB/metabolismo , Feminino , Glioblastoma/genética , Glioblastoma/metabolismo , Glioma/metabolismo , Humanos , Isocitrato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/genética , Oligodendroglioma/metabolismo , Mutação Puntual , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
15.
Exp Ther Med ; 3(2): 309-313, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22969887

RESUMO

In this study, we aimed to explore the correlation between solute carrier family 38 member 4 (SLC38A4) and system A activity in human placentas from pregnancies with abnormal fetal birth weight. We collected placentas from consenting women immediately after their full-term babies were born, with normal, low birth weight or macrosomia, and used real-time PCR and Western blot analysis to detect the levels of SLC38A4 mRNA and protein [also known as sodium-coupled neutral amino acid transport protein 4 (SNAT4)]. Isotope incorporation assay was applied to measure system A activity in the placentas. Compared to the normal birth weight (NBW) group, placentas from the fetal macrosomia (FM) group had significantly increased levels of SLC38A4 mRNA and SNAT4 (both were increased by almost 2-fold; P<0.05), while no significant changes were detected in the placentas from the low birth weight (LBW) group. In addition, system A activity in the placentas from the FM and LBW groups was significantly different from that in the NBW group (1.2±0.20, 0.6±0.14 vs. 1.0±0.18, P<0.05). The data suggest that SNAT4 and system A have a strong association with abnormal fetal birth weight and that they may play a crucial role in fetal growth and development.

16.
Beijing Da Xue Xue Bao Yi Xue Ban ; 41(4): 459-62, 2009 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-19727239

RESUMO

OBJECTIVE: To summarize the improvement of various muscle staining techniques and discuss their application in diagnosis of neuromuscular diseases. METHODS: Three hundred cases of skeletal muscle biopsy samples were examined by histopathological methods. The flash-freezing techniques were used for the preparation of frozen section, which were stained with HE, Gomori trichromic (GMR), glycogen (PAS), and fat acid (oil red O); the enzyme histochemical staining with myosin adenosine triphosphatase (ATPase), and NADH-TR. Those stained methods had been improved. The immunohistochemical staining with dystrophin; and transmission electronic microscopy were used. RESULTS: Deepfreeze with heteropentane-liquid nitrogen and flash-freezing techniques could avoid artifacts of ice crystal vacuolation. GMR staining mainly showed the degenerative and necrotic lesions of mitochondria and muscle fibers. Oil red O staining showed the increase of lipid in muscle fibers. PAS staining mainly showed glycogen and glycoprotein. Application of frozen sections in muscular tissue was better than that of paraffin sections. NADH-TR staining and ATPase staining could distinguish the two types of muscle fibers, and show the changes of inner structure of muscle fibers and mitochondria enzymes. CONCLUSION: The distribution and characteristic pathological changes of the two types of muscle fibers can be showed clearly by enzyme and non-enzyme histochemical staining techniques of the skeletal muscle. These methods can compliment with each other. Only after understanding the technical principles can we master and apply these methods.


Assuntos
Biópsia , Crioultramicrotomia/métodos , Músculo Esquelético/patologia , Coloração e Rotulagem/métodos , Humanos , Doenças Neuromusculares/patologia
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