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1.
Neuropathology ; 41(2): 133-138, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33480048

RESUMO

We report a case of a 26-year-old Chinese man who had experienced three grand mal seizures in the past two months. Magnetic resonance imaging revealed a relatively well-circumscribed lesion in the left frontal lobe. A craniotomy with total excision of the tumor was performed. Histopathological investigations confirmed a grade 2 ependymoma according to the World Health Organization classification. Genetic analysis revealed a tumor harboring FAM118B fusion to YAP1, and no other genetic alterations or methylation of the O6 -methylguanine-DNA methyltransferase gene promoter were detected. This is the second case report of ependymoma with YAP1:FAM118B fusion.


Assuntos
Ependimoma/genética , Ependimoma/patologia , Lobo Frontal/patologia , Neoplasias Supratentoriais/genética , Neoplasias Supratentoriais/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Ependimoma/diagnóstico , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Convulsões/patologia , Neoplasias Supratentoriais/diagnóstico , Fator de Transcrição RelA/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP
2.
Neuropathology ; 38(2): 165-170, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28880421

RESUMO

Diffuse midline glioma with histone H3-K27M mutation is a new tumor entity defined by the 2016 WHO Classification of Tumors of the Central Nervous System. A 51-year-old Chinese woman presented with neck pain for a month. Subsequent MRI revealed an intramedullary neoplasm extending from C5 to C7. Histologically, the cellular area of the tumor was composed of primitive, poorly differentiated, small cells with scant cytoplasm, nuclear molding, and brisk mitotic activity, exhibiting PNET-like appearance, while in the hypocellular area, oligodendroglioma-like cells were observed. More importantly, neuropil-like islands were observed in the cellular area. Microvascular proliferation was noted, with no necrosis. Besides histone H3K27M mutation, immunohistochemical staining also showed that the tumor cells were positive for oligodendrocyte lineage transcription factor 2 and ATRX. The neuropil-like areas were positive for synaptophysin, intermingled with scattered neuronal nuclear antigen positive cells. The Ki-67 proliferation index was about 30%, and tumor cells were highly immunopositive for p53. Sequencing for IDH1 codon 132 and IDH2 codon 172 gene mutations showed negative results. Furthermore, fluorescent analysis revealed 1p deletion in the lesion but no 19q deletion. Based on these findings, the tumor was diagnosed as diffuse midline gliomas with histone H3-K27M mutation in the spinal cord, corresponding to WHO grade IV. After 4 months of remission, the tumor recurred; 2 months later, the patient died. Herein, we report an extremely rare case of diffuse midline glioma with histone H3K27M mutation, which was morphologically characterized simultaneously by primitive neuroectodermal tumor-like appearance and neuropil-like islands.


Assuntos
Glioma/patologia , Histonas/genética , Mutação , Neoplasias da Medula Espinal/patologia , Vértebras Cervicais , Feminino , Glioma/diagnóstico , Glioma/diagnóstico por imagem , Glioma/genética , Humanos , Isocitrato Desidrogenase/genética , Pessoa de Meia-Idade , Tumores Neuroectodérmicos Primitivos/patologia , Neurópilo/patologia , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Oligodendroglioma/patologia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/diagnóstico por imagem , Neoplasias da Medula Espinal/genética , Proteína Supressora de Tumor p53/metabolismo
3.
Tumour Biol ; 39(6): 1010428317691177, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28618971

RESUMO

Inversin, encoded by NPHP2, is one of the 10 NPHP proteins known to be involved in nephronophthisis (an autosomal recessive cystic kidney). Although the previous reports showed that inversin played an important role in embryonic development and renal diseases, its function in cancer was not revealed clearly so far. As measured by immunohistochemical staining, inversin was highly expressed in the cytoplasm of lung cancer samples (63.4%, 161/254) compared with adjacent normal lung tissues (22.0%, 11/50, p < 0.01). Moreover, its expression was positively correlated with differentiation ( p = 0.014), tumor node metastasis staging ( p = 0.007), and lymph node metastasis ( p = 0.020). The overall survival of non-small cell lung cancer patients with inversin positive expression (45.41 ± 1.800 months) was significantly reduced compared with those with inversin negative expression (51.046 ± 2.238 months, p = 0.042). Consistently, we found that the invasion capacity of A549 cells transfected with inversin was significantly stronger than that of control cells ( p < 0.05), while inversin siRNA-treatment significantly reduced cell invasion in H1299 cells ( p < 0.05). Additionally, we demonstrated that inversin could upregulate the expression of N-cadherin, Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-9. Collectively, these results indicated that inversin might promote the tumorigenicity of lung cancer cells and serve as a novel therapeutic target of non-small cell lung cancer.


Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma Pulmonar de Células não Pequenas/genética , Prognóstico , Fatores de Transcrição/biossíntese , Células A549 , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/biossíntese , Biomarcadores Tumorais/genética , Caderinas/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Fatores de Transcrição/genética , Vimentina/biossíntese
4.
Neuropathology ; 37(2): 105-109, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28217890

RESUMO

Hemangioblastoma is a well-circumscribed, highly vascular, lipid-rich and low-grade tumor of uncertain histogenesis. Its histopathological features have been well established. Herein, we present a case of cerebellar hemangioblastoma in a 43-year-old woman. Histologically, the tumor was predominantly composed of cellular areas showing eosinophilic or vacuolated stromal cells arranged in nests and sheets. Focally, conventional reticular areas could be seen. Additionally, in some areas, the stromal cells were arranged radially around blood vessels, exhibiting perivascular pseudorosette structures, which were similar mostly to those of ependymomas. Immunohistochemically, the stromal cells markedly showed diffused staining for Vimentin, S-100, CD56, NSE, inhibin-a, podoplanin, alpha-Thalassemia/mental retardation syndrome X and carbonic anhydrase IX, and were negative for cytokeratin, epithelial membrane antigen, oligodendrocyte transcription factor 2, neuronal nuclear antigen, synaptophysin, isocitrate dehydrogenase 1 (R132H), P53 and CD34. Interestingly, the reticular and cellular areas either showed no or individual scattering of the GFAP-positive cells, respectively, while, the perivascular pseudorosette areas strongly and diffusely expressed GFAP. Nuclear mitosis and necrosis were not observed. The MIB-1 antibody labeling index was especially low (about 3%). Based on these findings, the patient was diagnosed with cerebellar hemangioblastoma. In the present case, we documented a distinctive histological appearance of perivascular pseudorosettes in hemangioblastoma and provided the evidence for stromal cells with glial differentiation.


Assuntos
Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/patologia , Hemangioblastoma/diagnóstico , Hemangioblastoma/patologia , Neuroglia/patologia , Adulto , Diferenciação Celular , Neoplasias Cerebelares/irrigação sanguínea , Feminino , Hemangioblastoma/irrigação sanguínea , Humanos , Células Estromais/patologia
5.
Tumour Biol ; 37(10): 14311-14319, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27596142

RESUMO

FBXO25 is a recently discovered protein that belongs to the Fbx class of the F-box family of proteins, and F-box proteins play a crucial role in tumorigenesis. However, the function of FBXO25 in cancer was not revealed so far. As measured by immunohistochemical staining, FBXO25 was highly expressed in the cytoplasm and nucleus of lung cancer samples (64.2 %, 136/212), compared with adjacent normal lung tissues (23.3 %, 7/30, p < 0.01). In addition, its expression was positively correlated with TNM staging (p < 0.001) and lymph node metastasis (p = 0.017). The overall survival of non-small-cell lung cancer (NSCLC) patients with FBXO25-positive expression (40.646 ± 1.745 months) was significantly reduced compared with those with FBXO25-negative expression (46.548 ± 2.176 months, p = 0.023). Consistently, we found that the proliferation, invasion, and migration capacity of A549 cells transfected with FBXO25 were significantly greater than those of control cells, while interference of FBXO25 could significantly inhibit cell proliferation, invasion, and migration in H1299 cells. Furthermore, we demonstrated that FBXO25 could regulate the expression of ß-catenin, YAP, some cyclins, and matrix metalloproteinases (MMPs). Collectively, these results indicate that FBXO25 may promote the tumorigenicity of lung cancer cells and might serve as a novel therapeutic target of NSCLC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Proliferação de Células , Proteínas F-Box/metabolismo , Neoplasias Pulmonares/patologia , Proteínas do Tecido Nervoso/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Apoptose , Western Blotting , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/secundário , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Cicatrização
6.
Tumour Biol ; 34(3): 1641-50, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23423709

RESUMO

The objective of the current study was to investigate the expression pattern and clinicopathological significance of differentiated embryo-chondrocyte-expressed gene 1 (DEC1) in patients with non-small-cell lung cancer (NSCLC). In 118 archived NSCLC tissues, the positive rate of DEC1 was reduced in human lung cancer samples (36/118, 30.5 %) compared with adjacent normal lung tissues (106/118, 89.8 %), as measured by immunohistochemical staining. Loss of DEC1 was correlated with poor differentiation (p=0.005) and high p-TNM stage (p=0.002). Consistently, downregulation of DEC1 by siRNA knockdown promoted the growth and colony formation in the A549 lung cancer cell line, and overexpression of DEC1 inhibited the growth and colony formation in the BE1 lung cancer cell line. In addition, a significant negative correlation was found between DEC1 and cyclin D1 (p=0.014) in 118 cases of NSCLC. Knockdown of DEC1 resulted in the upregulation of cyclin D1, and overexpression of DEC1 led to the downregulation of cyclin D1. Together with the observation that DEC1 bound directly to the promoter region of cyclin D1 in A549 cells, these results indicate that loss of DEC1 may promote tumor progression in NSCLC through upregulation of cyclin D1, and DEC1 might serve as a novel therapeutic target of NSCLC.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Pulmão/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Diferenciação Celular , Ciclina D1/genética , Ciclina D1/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Interferente Pequeno/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética
7.
Histopathology ; 61(2): 178-85, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22691172

RESUMO

AIMS: The two major types of cells of pulmonary sclerosing haemangioma (PSH) with the same origin show significant differences in morphological phenotype. Whether these differences are caused by their different differentiation status is still uncertain. The aim of this study was to analyse their differentiation status by detecting the expression of several stem cell markers in PSH. METHODS AND RESULTS: The expression of stem cell markers was examined by using streptavidin peroxidase (SP) immunohistochemisty in 45 PSH specimens. Also, the two types of cells were, respectively, captured by laser capture microdissection (LCM) from 28 PSH specimens, and total RNA was then extracted followed by reverse transcription-polymerase chain reaction (RT-PCR). The results demonstrated that the expression rates of ABCG2, Notch1 and Notch3 in polygonal cells were significantly higher than those in cuboidal cells (P < 0.05), and the expression levels of ABCG2, Notch3 and Jagged1 in polygonal cells were clearly higher than those in cuboidal cells (P < 0.05). CONCLUSION: The data obtained provided evidence that the two types of cells in PSH may be different in differentiation status. The differentiation difference between the two types of cells might lead to variation in their morphological phenotype.


Assuntos
Biomarcadores Tumorais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Hemangioma Esclerosante Pulmonar/metabolismo , Hemangioma Esclerosante Pulmonar/patologia , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Sequência de Bases , Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Diferenciação Celular , Primers do DNA/genética , Feminino , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Células-Tronco Multipotentes/metabolismo , Células-Tronco Multipotentes/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Hemangioma Esclerosante Pulmonar/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Receptor Notch3 , Receptores Notch/genética , Receptores Notch/metabolismo , Proteínas Serrate-Jagged
8.
Tumour Biol ; 33(5): 1437-44, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22528942

RESUMO

Overexpression of frequently rearranged in advanced T-cell lymphomas 1 (Frat1) has been reported in several human malignant tumors, but the relationship between Frat1 and ß-catenin in lung cancer is still unclear. Our goal was to investigate the correlation between Frat1 and ß-catenin in patients with lung cancers. Immunohistochemistry was performed in 110 cases of non-small cell lung cancer (NSCLC) with clinical follow-up. Results showed that both Frat1 and ß-catenin were overexpressed in NSCLC. The expression of Frat1 and ß-catenin was significantly correlated with tumor differentiation, TNM stage, and lymph node metastasis. Interestingly, the overexpression of ß-catenin was positively correlated with the overexpression of Frat1 (correlation coefficient = 0.285; P = 0.003). In addition, overexpression of Frat1 and abnormal expression of ß-catenin were found to represent a poor prognosis for the patients. Furthermore, based on the transfection of Frat1 and ß-catenin, we found that Frat1 can upregulate the expression of ß-catenin in BE1 cells.


Assuntos
Adenocarcinoma/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Neoplasias de Células Escamosas/genética , Proteínas Proto-Oncogênicas/genética , beta Catenina/genética , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias de Células Escamosas/mortalidade , Neoplasias de Células Escamosas/patologia , Prognóstico
9.
Tumour Biol ; 33(6): 2307-15, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22941467

RESUMO

Accumulating evidence reveals that aberrant expression of claudins manifests in various tumors; however, their biological functions are poorly understood. Here, we report on the elevated expression of claudin-1 in human breast cancer MCF-7 cells under tumor necrosis factor (TNF)-α treatment. Interestingly, the increased expression of claudin-1 contributes to an anti-apoptotic role in TNF-α-induced apoptosis. In line with this, upon TNF-α stimulus, downregulation of claudin-1 by siRNA knockdown results in a significant increase in cleavage of caspase-8 and poly (ADP-ribose) polymerase, a decrease of cyclinD1 expression, and DNA fragmentation. Consistently, TdT-mediated dUTP nick end labeling assay also shows that loss of claudin-1 increases the susceptibility of MCF-7 cells to TNF-α-induced apoptosis. However, there is no obvious effect on the expression of Bax and p53 after the treatment aforementioned. In addition, TNF-α increases the amount of claudin-1 and the cytoplasmic accumulation of ß-catenin, while claudin-1 siRNA increases the amount of ß-catenin in the cell membrane as well as the amount of E-cadherin in the cytoplasm. In conclusion, our data reveal a novel role of claudin-1 in regulating apoptosis in MCF-7 cells.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Claudina-1/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Western Blotting , Neoplasias da Mama/metabolismo , Caderinas/genética , Caderinas/metabolismo , Caspases/genética , Caspases/metabolismo , Membrana Celular , Proliferação de Células/efeitos dos fármacos , Claudina-1/antagonistas & inibidores , Claudina-1/genética , Citoplasma , Feminino , Imunofluorescência , Humanos , Transporte Proteico , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Frações Subcelulares , Células Tumorais Cultivadas , beta Catenina/genética , beta Catenina/metabolismo
10.
Medicine (Baltimore) ; 101(24): e29448, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35713454

RESUMO

INTRODUCTION: Diffuse midline glioma with H3-K27M mutation is an infiltrative high-grade glioma, with predominantly astrocytic differentiation. PATIENT CONCERNS: A 54-year-old Chinese woman presented with memory loss for a month and walking instability for 15 days. DIAGNOSIS: Magnetic resonance imaging showed a mass shadow of isometric T1 and slightly longer T2 with mild mixed signals in the third ventricle of the suprasellar region. Histologically, the tumor was primarily sheet-like, with many "anucleate areas" composed of long and thin fibrillary processes of the bipolar cells, which formed "whorls." The neoplastic nuclei were ovoid and moderate in size. The tumor showed brisk mitotic activity and vascular proliferation, with no necrosis. In addition to histone H3K27M mutation, immunohistochemical staining showed that the tumor cells were positive for glial fibrillary acidic protein, oligodendrocyte transcription factor 2, alpha-thalassemia/mental retardation syndrome X, S-100 and Vimentin. The "anucleate areas" were positive for glial fibrillary acidic protein and negative for synaptophysin. The Ki-67 proliferation index was about 10%. Molecular genetic analyses detected H3F3A K27M mutation, but no mutations in IDH1 or IDH2, TERT promoter mutations, MGMT promoter methylation, KIAA1549-BRAF fusion or deletion of 1p/19q were found. Based on these findings, the patient was diagnosed as diffuse midline glioma with H3-K27M mutation in the third ventricle, corresponding to WHO grade 4. INTERVENTIONS: A craniotomy with total excision of the tumor was performed. OUTCOMES: After surgery, she was routinely treated with temozolomide for chemotherapy and synchronous radiotherapy. It has been 11 months now, and the patient is living well. CONCLUSION: This case report provides information on the microscopic morphological features of diffuse midline glioma with H3K27M mutation, which can help pathologists to make a definitive diagnosis of this tumor.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/patologia , Feminino , Proteína Glial Fibrilar Ácida/genética , Glioma/diagnóstico , Glioma/genética , Glioma/metabolismo , Histonas/genética , Humanos , Mutação
11.
Neurotoxicol Teratol ; 91: 107079, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35202796

RESUMO

The abnormal expression of the dopamine D1 receptor (DRD1) may be associated with schizophrenia. MicroRNAs (miRNAs) can post-transcriptionally regulate DRD1 expression. Here, we established a ketamine-induced schizophrenia-like behavior mouse model and investigated the changes in miR-15a-3p, miR-15b-3p, miR-16-1-3p, and DRD1 in response to ketamine. Administration of high-dose ketamine for seven consecutive days to mice simulated the main symptoms of schizophrenia. The mice exhibited increasing excitability and autonomous activity and reduced learning and memory, including spatial memory. Moreover, ketamine decreased miR-15a-3p, miR-15b-3p, and miR-16-1-3p expression levels in the prefrontal cortex (PFC) and miR-16-1-3p expression in the hippocampus, whereas DRD1 expression increased in these brain regions. In HT22 mouse hippocampal neuronal cells, ketamine induced a dose-dependent increase of endogenous DRD1, which was partially attenuated by a combination of miR-15b-3p and miR-16-1-3p mimics. Indeed, the miR-15b-3p and miR-16-1-3p mimics could significantly inhibit endogenous DRD1expression. We identified +72 to +78 bp (TGCTGCT) of the DRD1 3'UTR as the core regulatory region recognized by the target miRNAs. In summary, we developed a ketamine-induced schizophrenia-like behavior mouse model and found that ketamine inhibited the levels of miR-15a-3p, miR-15b-3p, miR-16-1-3p and increased DRD1 expression in mice.


Assuntos
Ketamina , MicroRNAs , Esquizofrenia , Regiões 3' não Traduzidas , Animais , Modelos Animais de Doenças , Ketamina/toxicidade , Camundongos , MicroRNAs/genética , Receptores de Dopamina D1/genética , Esquizofrenia/induzido quimicamente , Esquizofrenia/genética
12.
World J Clin Cases ; 10(13): 4249-4263, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35665119

RESUMO

BACKGROUND: The coexistence of meningioma and other intracranial primary benign tumors is rare, especially in non-neurofibromatosis type 2, and there is limited guidance for the management of such patients. Here, we report a series of 5 patients with concomitant meningioma and other intracranial benign tumors, including subependymoma and pituitary adenoma. CASE SUMMARY: Five non-neurofibromatosis type 2 patients with simultaneous occurrence of meningioma and other intracranial benign tumors were retrospectively reviewed. The patients had no history of previous irradiation. The clinical features, pre- and postoperative imaging, surgical procedure and pathological findings were extracted from electronic medical records. There were 4 female patients (80%) and 1 male patient (20%). The mean age was 42.8 years (range: 29-52 years). The coexisting tumors included subependymoma in 1 case (20%) and pituitary adenoma in 4 cases (80%). The most common clinical symptom was headache (3/5, 60%). Four patients (80%) underwent craniotomy. One patient (20%) underwent transsphenoidal surgery followed by transcranial operation. All tumor diagnoses were confirmed by histopathological examination. The mean follow-up was 38.8 mo (range: 23-96 mo), and all 5 patients were in a stable condition at the last follow-up. CONCLUSION: The simultaneous occurrence of meningioma and other intracranial benign tumors is a rare clinical event. Histological examination is necessary for the accurate diagnosis. Neurosurgeons should select the appropriate surgical strategy according to the clinical features of each patient, which may provide a more favorable prognosis for individual patients.

13.
Int J Oncol ; 56(5): 1175-1185, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32319569

RESUMO

The ankyrin repeat and KH domain­containing 1 (ANKHD1) protein was recently reported to be a potential member of the Hippo signaling pathway. However, its role in human non­small­cell lung cancer (NSCLC) has not been extensively investigated. The aim of the present study was to examine the expression of ANKHD1 in primary human tissues and cells and determine whether it is correlated with the clinical characteristics of tumor growth. The biological functions of ANKHD1 were evaluated in vitro and in vivo. Yes­associated protein (YAP) expression and phosphorylation induced by ANKHD1 were evaluated by western blotting and immunoprecipitation. Marked upregulation of ANKHD1 protein expression was observed in NSCLC cells and tissues, which was associated with advanced pathological tumor­node­metastasis stage, lymph node metastasis and poor prognosis in patients with NSCLC. ANKHD1 overexpression also promoted the proliferation and invasion of NSCLC cells. ANKHD1 upregulation inactivated Hippo signaling via increasing YAP protein levels, as well as inhibiting YAP protein phosphorylation, whereas depletion of YAP abolished the effects of ANKHD1 on cell proliferation and invasion. Therefore, ANKHD1 may play an important role in NSCLC through regulating the YAP­dependent Hippo signaling pathway.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Hippo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Metástase Linfática , Masculino , Camundongos , Invasividade Neoplásica , Estadiamento de Neoplasias , Transplante de Neoplasias , Fosforilação , Prognóstico , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Proteínas de Sinalização YAP
14.
Curr Cancer Drug Targets ; 19(8): 674-680, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30451112

RESUMO

BACKGROUND: Nemo-like kinase (NLK) is an evolutionarily conserved MAP kinaserelated kinase involved in the pathogenesis of several human cancers. OBJECTIVE: The aim of this study was to investigate the expression and role of NLK in lung cancers, and its underlying mechanisms. METHODS: We examined the expression of NLK in lung cancer tissues through western blot analysis. We enhanced or knocked down NLK expression by gene transfection or RNA interference, respectively, in lung cancer cells, and examined expression alterations of key proteins in the Wnt signaling pathway and in epithelial-mesenchymal transition (EMT). We also examined the roles of NLK in the proliferation and invasiveness of lung cancer cells by cell proliferation, colony formation, and Matrigel invasion assays. RESULTS: NLK expression was found to be significantly higher in lung cancer tissue samples than in corresponding healthy lung tissue samples. Overexpression of NLK correlated with poor prognosis of patients with lung cancer. Overexpression of NLK upregulated ß-catenin, TCF4, and Wnt target genes such as cyclin D1, c-Myc, and MMP7. N-cadherin and TWIST, the key proteins in EMT, were upregulated, while E-cadherin expression was reduced. Additionally, proliferation, colony formation, and invasion turned out to be enhanced in NLK-overexpressing cells. After NLK knockdown in lung cancer cells, we obtained the opposite results. CONCLUSION: NLK is overexpressed in lung cancers and indicates poor prognosis. Overexpression of NLK activates the Wnt signaling pathway and EMT and promotes the proliferation and invasiveness of lung cancer cells.


Assuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Invasividade Neoplásica , Prognóstico , Proteínas Serina-Treonina Quinases/genética , Células Tumorais Cultivadas , Via de Sinalização Wnt
15.
Ann Surg Oncol ; 14(11): 3251-9, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17768662

RESUMO

BACKGROUND: T cell factor 4 (TCF-4) mediates a nuclear response to wingless/int (Wnt) signals by interacting with beta-catenin. Axis inhibition protein (axin) is an important negative regulator of the Wnt signaling pathway. Our aims were to examine the relationship between axin and TCF-4 and to explore the effects of axin on the development of lung cancer. METHODS: Expression levels of axin and TCF-4 were examined in 107 lung cancer specimens by immunohistochemistry. The axin gene was transfected into lung cancer BE1 cells. The expression levels of axin, beta-catenin, and TCF-4 were detected with immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR) experiments. Apoptosis, proliferation, and the invasive ability of lung cancer cells were examined using flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), and Matrigel invasive assays. RESULTS: Preserved axin expression correlated negatively with TCF-4 expression (P = .031). Axin expression differed with respect to degree of differentiation (P = .025) and histological tumor type (P = .031). TCF-4 expression differed relative to tumor, node metastasis (TNM) stage (P = .024). BE1 cells transfected with axin (BE1-axin cells) exhibited a significant decrease in TCF-4 expression. The level of apoptosis in BE1-axin cells was significantly increased, while the proliferative and invasive abilities of BE1-axin cells were decreased. CONCLUSION: These results suggest that reduced expression of axin or augmented expression of TCF-4 is associated with the malignant behavior of lung cancers. Overexpression of axin can downregulate expression of TCF-4 and can inhibit the ability of lung cancer cells to proliferate and invade.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Repressoras/metabolismo , Fatores de Transcrição TCF/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Proteína Axina , Carcinoma de Células Gigantes/genética , Carcinoma de Células Gigantes/metabolismo , Carcinoma de Células Gigantes/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Diferenciação Celular , Movimento Celular , Proliferação de Células , Feminino , Imunofluorescência , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Fatores de Transcrição TCF/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição , Transcrição Gênica , Células Tumorais Cultivadas , beta Catenina/metabolismo
16.
Medicine (Baltimore) ; 96(49): e9049, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29245307

RESUMO

RATIONALE: Chondromyxoid fibroma (CMF) is a rare benign bone neoplasm which often occurs in the lower extremities. Little is known about the radiological and histological presentation of CMF in the sellar region. PATIENT CONCERNS: A 16-year-old Asian male presented to the hospital 12 months ago with bilateral diplopia involving right visual fields, intermittent headaches, and dizziness. INTERVENTIONS: After the patient underwent enough examinations, the lesion was surgically removed by curettage. DIAGNOSIS: Postoperatively, the lesion was pathologically confirmed to be CMF. OUTCOMES: There was no recurrence at the 12-month follow-up. LESSONS: To the best of our knowledge, this is the second reported case of CMF in the sellar region which was clinically suspected to be a pituitary macroadenoma, craniopharyngioma, or schwannoma due to its location and radiographic features. We reviewed the morbidity, symptoms, radiographic features, pathological findings, and differential diagnosis of CMF. Because of its rarity, attention should be paid to avoid misdiagnosis of this lesion.


Assuntos
Fibroma/diagnóstico por imagem , Radiografia/métodos , Sela Túrcica/diagnóstico por imagem , Neoplasias Cranianas/diagnóstico por imagem , Adolescente , Humanos , Masculino
17.
Medicine (Baltimore) ; 96(47): e8851, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29381996

RESUMO

RATIONALE: Primary thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare malignant nasopharyngeal tumor with features resembling papillary thyroid carcinoma including nuclear positive expression of thyroid transcription factor-1 (TTF-1). PATIENT CONCERNS: A 64-year-old male presented with nasal bleeding and a foreign body sensation of the nasopharynx. Laryngoscopy revealed a 2.0-cm broad-based mass with a smooth surface on the posterior wall of the nasopharynx. A biopsy was obtained. DIAGNOSES: Histopathologic examination demonstrated tumor cells arranged in both papillary and glandular architecture. The tumor cells express nuclear immunoreactivity for TTF-1. The diagnosis of TL-LGNPPA was made. INTERVENTIONS: After the patient was diagnosed with TL-LGNPPA, he underwent complete surgical resection. OUTCOMES: There was no recurrence or evidence of metastatic disease at the 12-month follow-up. LESSONS: TL-LGNPPA is easy to misdiagnose as metastatic papillary thyroid carcinoma or other relative primary adenocarcinomas. It is important to have a broad differential diagnosis and know the key features of each entity because the prognosis and clinical treatment of each may differ.


Assuntos
Adenocarcinoma Papilar/patologia , Neoplasias Nasofaríngeas/patologia , Adenocarcinoma Papilar/diagnóstico , Carcinoma Papilar/diagnóstico , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico , Nasofaringe/patologia , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico , Fator Nuclear 1 de Tireoide/metabolismo
18.
Zhonghua Bing Li Xue Za Zhi ; 35(11): 664-8, 2006 Nov.
Artigo em Zh | MEDLINE | ID: mdl-17374210

RESUMO

OBJECTIVE: To study the expression of caveolin-1 in primary lung cancer and its relationship with microvessel density and clinicopathologic parameters. METHODS: Immunohistochemical study for caveolin-1 and CD34 was performed on paraffin sections of 154 cases of primary lung cancer and adjacent non-neoplastic lung parenchymal tissue, as well as 36 cases with nodal metastasis. Microvessel density was analyzed by CD34 immunostaining. Western blot assay was also employed in tumor and non-neoplastic lung tissues of the 50 cases (25 cases of pulmonary squamous cell carcinoma and 25 cases of pulmonary adenocarcinoma) with fresh specimens available. RESULTS: Immunohistochemical study showed that non-neoplastic bronchial and alveolar epithelium was positive for caveolin-1 (membranous and cytoplasmic). The expression rate of caveolin-1 in lung cancer was 59.1%, which was significantly lower than that in normal lung tissues (P < 0.01). Western blot assay confirmed that the expression of caveolin-1 in pulmonary squamous cell carcinoma and adenocarcinoma was lower than in surrounding non-neoplastic lung tissues (P < 0.01). Caveolin-1 expression in pulmonary small cell carcinoma (7.1%) was significantly lower than that in non-small cell carcinoma (64.3%) (P < 0.01). Within the group of non-small cell carcinoma, the expression of caveolin-1 was much higher in patients with lymph node metastasis (P = 0.005). The expression was also higher in stage III and IV than in stage I and II disease (P = 0.042). CONCLUSIONS: The expression of caveolin-1 is lower in lung cancer tissues than that in non-small cell carcinoma, it is also significantly correlated with tumor stage and lymph node metastasis. Caveolin-1 may play some role in the progression of pulmonary non-small cell carcinoma.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Caveolina 1/biossíntese , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Imuno-Histoquímica , Pulmão/química , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Microvasos/química , Microvasos/metabolismo , Microvasos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia
19.
J Clin Neurosci ; 33: 228-231, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27452134

RESUMO

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic neoplasm that usually arises in children and young adults. Typically, lesions of PXA are superficially located in the cerebral hemispheres. Herein, we report two extremely rare patients with PXA arising from suprasellar regions. One of the patients is a 29-year-old man admitted to our hospital with a history of progressive headache for 1month. The patient's brain MRI revealed a large tumor arising from the suprasellar cistern of the third ventricle. The second patient, a 52-year-old woman, presented with progressive dizziness and visual disturbance that had developed over the course of 1year. The MRI revealed a well-enhanced suprasellar solid mass measuring 1.4×1.2×1.4cm. Both patients underwent surgical removal of their tumors, and both patients showed similar microscopic structures and immunohistochemical phenotypes: the tumor cells were pleomorphic with mixtures of spindle-shaped, and multinuclear giant cells. In addition, eosinophilic granular bodies and xanthomatous cells were seen on section. Immunohistochemistry was positive for GFAP, S-100, and CD34, and was negative for IDH 1, CK, and Syn. The Ki-67 proliferation index was less than 1%. Silver impregnation revealed reticulin fibers surrounding the individual tumor cells, and small cell groups. Based on these findings, the two patients were diagnosed with PXA in the suprasellar region. To date, only five such patients have been reported in the literature. PXA should be included in the differential diagnosis for tumors arising in the sellar region.


Assuntos
Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Adulto , Feminino , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Sela Túrcica/patologia , Terceiro Ventrículo/patologia
20.
Diagn Pathol ; 10: 171, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26376790

RESUMO

Central neurocytoma/extraventricular neurocytoma is a central nervous system (CNS) tumor composed of uniform round cells with neuronal differentiation. The typical lesions of central neurocytoma/extraventricular neurocytoma are at the interventricular foramen of the lateral ventricles (central neurocytoma) or brain parenchyma (extraventricular neurocytoma). Mature teratoma is a benign germ cell tumor commonly found in young women. Herein, we report a 24-year-old female with neurocytoma in a mature teratoma of the right ovary. The histological examinations showed mature epidermis, skin appendages, adipose and bone tissues in the tumor; microscopic foci of immature cartilage tissues were also found in some parts. In addition, massive solid sheets and uniform round tumor cells were found in the neuroectodermal tissues, with the formation of neuropil-like islands. Immunohistochemical examinations showed that the tumor cells were synaptophysin- and NeuN-positive but GFAP-negative. Based on these findings, the woman was diagnosed with neurocytoma arising from mature ovary teratoma, with microscopic foci of immature cartilage tissues. This is the fourth case report of neurocytoma outside the CNS to date.


Assuntos
Neoplasias Complexas Mistas/patologia , Neurocitoma/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Biomarcadores Tumorais/análise , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/cirurgia , Neurocitoma/química , Neurocitoma/cirurgia , Neoplasias Ovarianas/química , Neoplasias Ovarianas/cirurgia , Teratoma/química , Teratoma/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
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