RESUMO
Upregulation of the Big mitogenactivated protein kinase (BMK)1 has been reported in glioma and other epithelial tumors. In addition, the decreased expression of BMK1 inhibits tumorigenesis, leading to the broad consensus that it functions as cellautonomous epithelial tumor promoter. Using two online miRNA target prediction databases, microRNA (miR)143 was predicted as the potential miRNA regulator of BMK1. RNA immunoprecipitation analysis and Luciferase reporter assay showed that miR143 binds to the 3' untranslated region of BMK1. Notably, the expression of miR143 has a strong association with the World Health Organization grade and survival rates in patients with glioma by statistical analysis. Furthermore, miR143 inhibited glioma cells migration and invasion through cytoskeletal rearrangement in vitro and in vivo through matrigel invasion assay, scratch assay, cellular Factin measurement, chemotaxis assay and intracranial brain tumor xenografts. Finally, DNA methylation assay showed that the downregulation of miR143 was due to hypermethylation of its promoter region. These results reveal that miR143 represents a potential therapeutic target in glioma by modulating BMK1.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , MicroRNAs/genética , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Adulto , Idoso , Animais , Apoptose , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Movimento Celular , Proliferação de Células , Metilação de DNA , Feminino , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Quinase 7 Ativada por Mitógeno/genética , Invasividade Neoplásica , Prognóstico , Ratos , Ratos Sprague-Dawley , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: The association of positive margin and local recurrence after nephron-sparing surgery (NSS) remains a notably controversial issue. The aim of the present study was to investigate the relationship between classification of positive surgical margins (PSMs) and tumor recurrence based pathological findings. METHODS: Clinical, pathological, and follow-up data of 600 small renal cancer patients who underwent NSS between November 2007 and November 2017 at four hospitals in China were analyzed retrospectively. RESULTS: Of the 600 reviewed patients, 20 had positive margins. During the follow-up period of 56 months, only three cases of tumor recurrence were identified. Pathological examination was performed, and subsequently a new classification criteria were proposed: 1) False PSMs, which could be further divided into three subtypes: i) no standard processing performed on pathological specimens (seven patients); ii) incidental incision into the tumor during operation, with the tumor bed free of tumor residues (four patients); iii) part of the tumor pseudocapsule was noted to be remained in the tumor bed, with no signs of tumor residue (four patients). 2) True PSMs with two subtypes: i) a large number of residual tumor cells at the surgical margin (three patients); ii) incision of satellite tumor nodules detected around a large tumor (two patients). CONCLUSION: Taken together, PSMs in NSS were rarely found. Based on the pathological examination findings, PSMs can be divided into false positive and true positive. This being said, PSMs were determined to be poor predictors for local recurrence, with no predominant association with true tumor remnants in the majority of our evaluated cases. Through the key findings of our study, we concluded that PSMs should be carefully analyzed and treated on a case-by-case basis.
RESUMO
Endoplasmic reticulum (ER) stress is a critical molecular mechanism involved in the pathogenesis of sepsis. Hence, strategies for alleviating this stress may be essential for preventing cardiovascular injuries under sepsis. Adiponectin is secreted by adipocytes and its levels are decreased in sepsis. The purpose of this study was to investigate the protective effects of adiponectin treatment on endothelial cells and its mechanism. Male Wistar rats underwent cecal ligation and puncture (CLP) before being treated with adiponectin (72 and 120 μg/kg). The levels of malondialdehyde (MDA) in plasma, histological structure, and apoptosis of endothelial cells were evaluated. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with adiponectin at 10 and 20 μg/mL for 24 h after stimulation by lipopolysaccharide (LPS). The levels of reactive oxygen species (ROS), ultrastructure, rate of apoptosis, the expression of inositol-requiring enzyme 1α (IRE1α) protein, and its downstream molecules (78 kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and caspase-12) were detected. The results showed that the levels of MDA and ROS induced by CLP or LPS stimulation were increased. Furthermore, endothelial cell apoptosis was increased under sepsis. The IRE1α pathway was initiated, as evidenced by activated IRE1α, increased GRP78, and up-regulated CHOP and caspase-12 in HUVECs. Following treatment with adiponectin, the number of apoptotic endothelial cells was markedly decreased. These findings demonstrated that treatment with adiponectin decreased apoptosis of endothelial cells caused by sepsis by attenuating the ER stress IRE1α pathway activated by oxidative stress.
Assuntos
Humanos , Animais , Masculino , Veias Umbilicais/citologia , Apoptose/efeitos dos fármacos , Sepse/patologia , Células Endoteliais/efeitos dos fármacos , Adiponectina/farmacologia , Estresse do Retículo Endoplasmático/fisiologia , Valores de Referência , Células Cultivadas , Lipopolissacarídeos , Western Blotting , Espécies Reativas de Oxigênio/análise , Ratos Wistar , Apoptose/fisiologia , Microscopia Confocal , Células Endoteliais/metabolismo , Microscopia Eletrônica de Transmissão , Citometria de Fluxo , Malondialdeído/sangueAssuntos
Pavilhão Auricular/patologia , Neoplasias da Orelha , Melanoma , Criança , Humanos , MasculinoAssuntos
Linfoma Difuso de Grandes Células B/patologia , Neoplasias Vasculares/patologia , Antígenos CD20/metabolismo , Antígenos CD34/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/metabolismo , Vincristina/uso terapêuticoAssuntos
Mama/patologia , Doença da Mama Fibrocística/patologia , Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Mama/metabolismo , Mama/cirurgia , Caderinas/metabolismo , Feminino , Doença da Mama Fibrocística/metabolismo , Doença da Mama Fibrocística/cirurgia , Seguimentos , Humanos , Pessoa de Meia-Idade , Proteínas S100/metabolismoAssuntos
Carcinoma de Células Renais/patologia , Doenças Renais Císticas/patologia , Neoplasias Renais/patologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/cirurgia , Citocinas/metabolismo , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Rim/química , Rim/patologia , Rim/cirurgia , Doenças Renais Císticas/metabolismo , Doenças Renais Císticas/cirurgia , Neoplasias Renais/metabolismo , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Mucina-1/metabolismo , NefrectomiaRESUMO
OBJECTIVE: To investigate the clinicopathologic and immunohistochemical features of secretory meningiomas. METHODS: Nine secretory meningiomas were examined. From each specimen, sections were cut and stained with hematoxylin-eosin, periodic acid-Schiff (PAS) stain, and periodic acid-Schiff stain with diatase(PAS-D ). Immunohistochemical markers including oestrogen receptor (ER), progesterone receptor (PR), carcinoembryonic antigen (CEA), cytokeratin (CK), epithelial membrane antigen (EMA), and MIB-1 were detected with streptavidin peroxidase (SP) immunohistochemical staining methods. One case was observed by electron microscopy (EM). RESULTS: The 9 secretory meningiomas were located at sphenoid ridge, left parietal lobe or frontal lobe. Severe peritumoral edema was observed in 5 cases. Seven cases were followed up for 6 to 88 months; none of them showed evidence of recurrence. Histologically, the conspicuous feature was the eosinophilic inclusions. The finding of pericytic proliferation on examination was helpful to making a diagnosis. In all 9 cases, the tumor cells were positive for PR, but in 6 cases the inclusions were negative. ER was negative in 8 cases. CEA,CK, EMA expressed in the inclusions and the surrounding cells in 7 cases. In 1 case the positive rate for MIB-1 was 5%, but in the other 8 cases the positive rates were not more than 2%. The intercellular lumens and intracellular mucosa were observed under EM. CONCLUSION: Secretory meningioma is a rare subtype of meningioma that shows glandular epithelium differentiation. It is a meningioma of the low-risk type in terms of incidence, recurrence and prognosis.
Assuntos
Neoplasias Meníngeas/patologia , Meningioma/patologia , Receptores de Progesterona/análise , Adulto , Idoso , Antígeno Carcinoembrionário/análise , Feminino , Humanos , Queratinas/análise , Masculino , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the clinical value of HER2 overexpression in breast cancer and its prognostic implication in patients with lymph node negative breast carcinoma. METHODS: The following electronic database were extracted using appropriate inclusive and exclusive standards: Cochrane library, PUBMED, Embase (1984 - 2003), OVID, CMCC and CNKI. Excel and RevMan 4.2 were used for statistical analysis. RESULTS: Fifty-six articles were extracted to calculate the positive rate of HER2 overexpression. The pooled positive rate was 23.14% [19.54%, 26.73%], with positive immunohistochemistry (IHC) rate of 23.13% [19.49%, 26.77%] and positive FISH rate of 20.90% [15.54%, 26.25%]. Seven articles were used to evaluate prognostic predication of HER2 expression. It was concluded that in patients with lymph node negative breast carcinoma, HER2 overexpression (both IHC and FISH) independently predicted a poor prognosis based on disease-free survival (DFS) and overall survival (OS) with a P < 0.05. For DFS, the pooled RR was 1.38 [1.07, 1.80] with 1.16 [1.02, 1.31] for IHC and 1.98 [1.56, 2.52] for FISH. For OS, the pooled RR was 1.58 [1.16, 2.14] with 1.37 [1.14 to 1.64] for IHC and 2.33 [1.45 to 3.75] for FISH. HER2 overexpression effectively predicted DFS/OS of patients without adjuvant therapy and OS of patients with the therapy, but not for DFS, with the pooled RR of 1.46 [1.02, 2.09] and 1.11 [0.95, 1.31] for DFS, respectively and the pooled RR of 1.93 [1.44 to 2.58] and 1.25 [1.01, 1.56] for OS, respectively. CONCLUSIONS: In patients with lymph node negative breast carcinoma, the positive rate of HER2 overexpression is 23.14%. HER2 overexpression indicates a poor prognosis and adjuvant therapy after surgery should be recommended.
Assuntos
Neoplasias da Mama/patologia , Linfonodos/patologia , Receptor ErbB-2/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Genes erbB-2 , Humanos , Mastectomia , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: To evaluate the expression of cytokeratins in intraductal proliferative lesions of breast, including usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), ductal carcinoma-in-situ (DCIS) and its role in differential diagnosis. METHODS: Ninety two cases of paraffin-embedded lesional breast tissue, 30 cases of frozen samples, cell cultures of hyperplastic ductal cells and 2 invasive ductal carcinoma cell lines (T47D and MCF-7) were used for this study. Immunohistochemistry was performed using EnVision method for 34betaE12, CK8 and CK14. RESULTS: The percentage of 34betaE12-positivity in paraffin-embedded samples of UDH, ADH, DCIS and invasive ductal carcinoma (IDC) was found to be 95.2%, 33.3%, 19.2% and 12.5% respectively. In frozen tissues, all UDH cases and 55% of IDC cases expressed 34betaE12. The primary UDH cell cultures and T47D cell line were also 34betaE12-positive, whereas MCF7 cell line showed negative staining. The expression rate of CK8 and CK14 in UDH was also different from that in ADH and DCIS. CONCLUSIONS: 34betaE12 can be useful in differential diagnosis of intraductal proliferative lesions of the breast. However application of this cytokeratin stain in intraoperative frozen sections is relatively limited. The expression patterns of CK8 and CK14 are also helpful in the differential diagnosis of similar lesions.