Cytoplasmic expression of aquaporin-1 in breast cancer cells and its relationship with clinicopathological characteristics and prognosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of aquaporin 1 (AQP1) in breast cancer tissues, and to analyze its relationship with clinicopathological characteristics and prognosis of breast cancer patients.</p><p><b>METHODS</b>Histochemical SP staining was used to assess the AQP1 expression in 30 cases of lobular hyperplasia of mammary gland, 16 cases of ductal carcinoma in situ (DCIS), and 78 cases of invasive ductal carcinoma-not otherwise specified (IDC-NOS), and to analyze the relationship between cytoplasmic expression of AQP1 in IDC-NOS and clinical pathological characteristics and prognosis of the patients.</p><p><b>RESULTS</b>Positive AQP1 immunolabelling appeared as brown deposit over the membrane of myoepithelial cells in all cases of lobular hyperplasia of mammary gland, but only 10.0% of cases showed cytoplasmic staining in glandular epithelial cells. In the ductal carcinoma in situ, brown deposit of AQP1 immunolabelling appeared over the myoepithelial cell membrane in all cases, but only 12.5% of cases were accompanied with cytoplasmic staining in glandular epithelial cells. In the invasive ductal carcinoma not otherwise specified, 35.9% of the cases showed cytoplasmic AQP1 immunoreactivity, but only 3.8% of cases showed positive membrane staining of the tumor cells. There were highly positive AQP1 expression in 14 cases, weakly positive in 14 cases, and negative in 50 cases. Cytoplasmic AQP1 expression in the IDC-NOS cases was significantly correlated with pathologic stage, PR, HER-2, lymph node status, Nottingham prognostic index (NPI) and metastasis or recurrence (all P < 0.05). The 5-year progression-free survival (PFS) rates were 16.8% in the patients with strong positive AQP1 expression, 90.9% in the cases with weakly positive AQP1 expression and 94.9% in the AQP1-negative cases, showing a significant difference (P < 0.05). Multivariate analysis indicated that the lymph node status and cytoplasmic expression of AQP1 were independent factors for PFS (both P < 0.05). The 5-year overall survival (OS) rates were 45.6% in the AQP1- strong positive cases, 90.0% in the AQP1-weakly positive cases and 97.7% in the AQP1-negative cases, showing a significant difference (P < 0.05). Multivariate analysis indicated that the lymph node status and cytoplasmic expression of AQP1 were independent factors affecting the overall survival and progression-free survival (both P < 0.05).</p><p><b>CONCLUSION</b>AQP1 is mainly expressed on the membrane of myoepithelial cells in the benign breast lesions, but in the cytoplasm of breast cancer cells, and its expression is an independent factor affecting prognosis of breast cancer patients.</p>

Robo1 expression in non-small cell lung cancer and its brain metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of Robo1 in lung cancer tissues, adjacent non-cancerous tissues as well as lung cancer brain metastasis, and explore the correlation of Robo1 expression to lung cancer brain metastasis.</p><p><b>METHODS</b>SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC, 52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs). The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues. The results were assessed by Kaplan-Meier analysis and log-rank test.</p><p><b>RESULTS</b>The positive expression rate of Robo1 among adjacent non-cancerous tissues, lung cancers tissues and the lung cancer brain metastasis tissues were 1.9% (1/52), 13.8% (11/80) and 40.3% (29/72), respectively, and significant differences were detected among them (P < 0.05). During the 17 self control cases, the positive expression rate of Robo1 in lung cancer tissue and their brain metastasis tissues were 17.6% and 64.7%, respectively, with a significant difference between them (P < 0.01). Among the 72 cases of lung cancer brain metastasis, the median survival time of cases with positive Robo1 expression was 10 months, significantly shorter than that of cases with negative expression of Robo1 (17 months, P < 0.05).</p><p><b>CONCLUSIONS</b>The positive expression rate of Robo1 was increased in sequence from the lowest in adjacent non-cancerous tissues, intermediate in the lung cancer tissues to highest in the lung cancer brain metastasis tissues. The expression of Robo1 in lung cancer brain metastasis is negatively correlated with the prognosis of patients with lung cancer brain metastasis. Robo1 may promote the genesis and progression of lung cancer and lung cancer brain metastasis as a cancer-promoting oncogene.</p>

Expression of Notch1, MMP-2 and MMP-9 and their significance in glioma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression of Notch1, MMP-2 and MMP-9 in glioma patients and their relationship with progression and prognosis of gliomas.</p><p><b>METHODS</b>Sixty-four cases of glioma were included in this study. There were four cases of grade 1 tumor, twenty-five cases of grade 2, nine cases of grade 3, and twenty-six cases of grade 4. Immunohistochemistry (SP staining method) was used to detect the expression of Notch1, MMP-2 and MMP-9 in glioma tissues and adjacent non-tumor tissues, and the patients were followed up.</p><p><b>RESULTS</b>Notch1, MMP-2 and MMP-9 were detected in glioma tissues but not in adjacent non-tumor tissues. The expression of Notch1 was increased with the pathological grade of the gliomas (r = 0.262, P < 0.05). The survival time of patients with strong expression of Notch1 was 31.0 months, significantly shorter than that of patients with non-strong positive (negative, weak and moderately) Notch1 expression (53.0 months, P < 0.05). Significant difference in survival time was observed between patients with negative and positive expression of MMP-9 (P < 0.05).</p><p><b>CONCLUSIONS</b>Notch1, MMP-2 and MMP-9 are closely correlated with the progression and prognosis of malignant gliomas. Notch1 may participate in the expression regulation of MMP-2 and MMP-9. Compared with MMP-2, MMP-9 may play a more important role in determining the prognosis of malignant glioma. Notch1 and MMP-9 may become new biological markers for prognosis of patients with malignant glioma.</p>

Expression and significance of phosphorylated Girdin in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of phosphorylated girdin (p-girdin) in breast cancer and its association with pathological characteristics and molecular subtypes of breast cancer.</p><p><b>METHODS</b>Immunohistochemical SP staining was used to investigate the expression of p-girdin in 27 cases of lobular hyperplasia of mammary gland, 61 cases of ductal carcinoma in situ (DCIS), and 94 cases of non-special type invasive carcinoma (IDC-NOS) of breast.</p><p><b>RESULTS</b>p-girdin was located in the cell cytoplasm and (or) nuclei in breast cancer. There was statistically a very significant difference among lobular hyperplasia, DCIS and IDC-NOS (χ2=26.724, P<0.001). Its cytoplasmic and nuclear reactivity were 25.9% (7/27), 39.3% (24/61), and 66.0% (62/94), respectively. The expression of p-girdin was positively associated with pathologic stage (r=0.204, P=0.049), lymph node metastasis (r=0.212, P=0.041) and HER2/neu (r=0.248, P=0.016). But no significant association was identified between p-girdin expression and histological grade (r=-0.015, P=0.918), age of patients (r=-0.011, P=0.918), tumor size (r=0.075, P=0.471), ER(r=0.071, P=0.498), PR (r=-0.050, P=0.634). Mann-Whitney test showed that p-girdin expression in luminal A, luminal B, triple negative and HER-2(+) type was significantly different (χ2=14.017, P=0.003). Among the four types, its positive rate was 55.8% (24/43), 95.8% (23/24), 66.7% (10/15), and 41.7% (5/12), respectively.</p><p><b>CONCLUSIONS</b>p-Girdin expression is closely correlated with the malignant progression of breast cancer. Its expression may have clinical value as a new target for the treatment of breast cancer.</p>

Function of intersectin in endocytosis and exocytosis / 生理学报

Intersectin is an evolutionarily conserved multifunctional adaptor protein with multifunctional domains. These domains interact with components of the endocytic and exocytic pathways, such as the clathrin mediating synaptic vesicle recycling, the protein related to endocytosis via caveolae, the with-no-lysine kinases related to the regulation of renal outer medullar potassium, and the Cdc42 mediating exocytic pathway. Recently, the understanding of intersectin function in the pathogenesis of endocrine tumor and many neurodegenerative diseases such as Down syndrome, Alzheimer disease has been deepened. This article reviewed the structure and roles in endocytosis/exocytosis and diseases of intersectin.

Robo1 expression in breast cancer and its relationship to brain metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of Robo1 in different breast tumors and its association with the breast cancer brain metastasis.</p><p><b>METHODS</b>Labelled streptavidin-biotin (LSAB) staining was used to examine the Robo1 expression in specimens from 24 cases of invasive ductal carcinoma (IDC) with brain metastasis, 71 cases of IDC without brain metastasis, 22 cases of ductal carcinoma in situ (DCIS) and 23 cases of fibroadenoma.</p><p><b>RESULTS</b>The expression pattern of Robo1 in DCIS (59.1%) and IDC (45.3%) was significantly lower than that in adenofibroma (87.0%, P < 0.05). The expression of Robo1 in IDC with brain metastasis (12.5%) was significantly lower than that in IDC without brain metastasis (56.3%, P < 0.05). The expression of Robo1 was much higher in more than 50 year-old-group (57.8%) than that in less than 50 year-old-group (34.0%) of IDC patients. The overall survival time in patients with the Robo1 negative expression was significantly shorter than those with positive expression (P < 0.05). No correlation was found between the Robo1 expression and the tumor size, lymph node metastasis, pathologic stage, histological grade and clinical stage (P > 0.05).</p><p><b>CONCLUSIONS</b>The Robo1 expression correlates negatively with IDC brain metastasis, and correlates positively with the age and prognosis of IDC patients. Robo1 may be applied as a marker in evaluation of the IDC prognosis and brain metastasis.</p>

Co-culture with microglia promotes neural stem cells differentiation into astrocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neural stem cells (NSCs) are a self-renewing and multipotent population of the central nervous system (CNS), which are active during development and maintain homeostasis and tissue integrity throughout life. Microglias are an immune cell population resident in the CNS, which have crucial physiological functions in the developing and adult CNS. This study aimed to investigate that whether microglia co-cultured with NSCs could promote astrogliogenesis from NSCs.</p><p><b>METHODS</b>Microglia and NSCs were co-cultured in 24-well insert plates. NSCs were plated in the bottom of the well and microglia in the insert. Fluorescent staining, Western blotting and RT-PCR were used to determine the effect of microglia on NSCs differentiation.</p><p><b>RESULTS</b>Co-culture of microglia and NSCs promoted astrogliogenesis from NSCs. Several key genes, such as Notch 1, Notch 2, Notch 3, Hes 5, and NRSF were downregulated, while the critical genes Id1 and Id2 were upregulated. BMP2 and FGF2 were upregulated.</p><p><b>CONCLUSION</b>Microglias act as a regulator of NSCs astrogliogenesis.</p>

Intersectin 1: a molecular linker in the central nervous system / 神经科学通报·英文版

Down syndrome (DS) is the most common cause of cognitive impairment associated with a congenital chromosomal abnormality, trisomy of chromosome 21. Mental retardation and congenital heart defects are key features of DS. All DS individuals develop early-onset Alzheimer's disease-like neuropathology. Intersectin 1 gene is localized on human chromosome 21, the critical region of DS, and it has higher expression in the brain of DS patients than in normal individuals. So fully understanding functions of intersectin 1 is critical for revealing the pathogenesis of DS. Intersectin 1 protein has two isoforms: intersectin 1-L and intersectin 1-S. This review will focus on the distribution, expression characters and functions of intersectin 1 in the central nervous system.

Effects of rotation on osteonectin and osteopontin mRNA level of cultured osteoblasts in rats / 生理学报

Conditions of disuse such as bed rest, space flight, and immobilization result in decreased mechanical loading of bone, which is associated with reduced bone mineral density and increased fracture risk. Mechanisms involved in this process are not well understood except the suppression of osteoblast function. To investigate the effect of simulated weightlessness on mRNA level of extracellular matrix proteins, osteoblasts were rotated in horizontal plane as a model of simulated microgravity. Primordial osteoblasts of rats were grown for 2 d and then rotated for 24, 48 and 72 h, respectively. After isolating total RNA in cells, reverse transcription polymerase chain reaction (PT-PCR) was made to examine the mRNA level of osteopontin (OPN) and osteonectin (ON). Meanwhile, the levels of alkaline phosphatase (ALP) and osteocalcin (BGP) in the cultured medium were measured to evaluate the calcific function of cell. The expression of OPN and ON mRNA fell significantly after rotating for 24, 48 and 72 h, respectively. The contents of BGP descended significantly, meanwhile, the activity of ALP also showed a degressive tendency. Horizontal rotation decreased the expression of ON and OPN as well as diminished the secretion of BGP and ALP, which affected the calcific function of osteoblast. The results obtained suggest that depression of extracellular matrix proteins expression plays a key role in bone loss during weightlessness.