排序方式: 共有49条查询结果,搜索用时 15 毫秒
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Haiman CA Chen GK Vachon CM Canzian F Dunning A Millikan RC Wang X Ademuyiwa F Ahmed S Ambrosone CB Baglietto L Balleine R Bandera EV Beckmann MW Berg CD Bernstein L Blomqvist C Blot WJ Brauch H Buring JE Carey LA Carpenter JE Chang-Claude J Chanock SJ Chasman DI Clarke CL Cox A Cross SS Deming SL Diasio RB Dimopoulos AM Driver WR Dünnebier T Durcan L Eccles D Edlund CK Ekici AB Fasching PA Feigelson HS Flesch-Janys D Fostira F Försti A Fountzilas G 《Nature genetics》2011,43(12):1210-1214
Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. 相似文献
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Valente EM Silhavy JL Brancati F Barrano G Krishnaswami SR Castori M Lancaster MA Boltshauser E Boccone L Al-Gazali L Fazzi E Signorini S Louie CM Bellacchio E;International Joubert Syndrome Related Disorders Study Group Bertini E Dallapiccola B Gleeson JG 《Nature genetics》2006,38(6):623-625
Joubert syndrome-related disorders (JSRD) are a group of syndromes sharing the neuroradiological features of cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the 'molar tooth sign'. We identified mutations in the CEP290 gene in five families with variable neurological, retinal and renal manifestations. CEP290 expression was detected mostly in proliferating cerebellar granule neuron populations and showed centrosome and ciliary localization, linking JSRDs to other human ciliopathies. 相似文献
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Comino-Méndez I Gracia-Aznárez FJ Schiavi F Landa I Leandro-García LJ Letón R Honrado E Ramos-Medina R Caronia D Pita G Gómez-Graña A de Cubas AA Inglada-Pérez L Maliszewska A Taschin E Bobisse S Pica G Loli P Hernández-Lavado R Díaz JA Gómez-Morales M González-Neira A Roncador G Rodríguez-Antona C Benítez J Mannelli M Opocher G Robledo M Cascón A 《Nature genetics》2011,43(7):663-667
Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential. 相似文献
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Elisa Rossi Christilla Bachelot-Loza Dominique Pidard Pascale Gaussem Sonia Poirault-Chassac Francisco J. Blanco Carmen Langa Consuelo González-Manchón Jose M. Lopez Novoa David M. Smadja Carmelo Bernabeu 《Cellular and molecular life sciences : CMLS》2018,75(7):1269-1284
Complex interactions between platelets and activated endothelium occur during the thrombo-inflammatory reaction at sites of vascular injuries and during vascular hemostasis. The endothelial receptor endoglin is involved in inflammation through integrin-mediated leukocyte adhesion and transmigration; and heterozygous mutations in the endoglin gene cause hereditary hemorrhagic telangiectasia type 1. This vascular disease is characterized by a bleeding tendency that is postulated to be a consequence of telangiectasia fragility rather than a platelet defect, since platelets display normal functions in vitro in this condition. Here, we hypothesize that endoglin may act as an adhesion molecule involved in the interaction between endothelial cells and platelets through integrin recognition. We find that the extracellular domain of human endoglin promotes specific platelet adhesion under static conditions and confers resistance of adherent platelets to detachment upon exposure to flow. Also, platelets adhere to confluent endothelial cells in an endoglin-mediated process. Remarkably, Chinese hamster ovary cells ectopically expressing the human αIIbβ3 integrin acquire the capacity to adhere to myoblast transfectants expressing human endoglin, whereas platelets from Glanzmann’s thrombasthenia patients lacking the αIIbβ3 integrin are defective for endoglin-dependent adhesion to endothelial cells. Furthermore, the bleeding time, but not the prothrombin time, is significantly prolonged in endoglin-haplodeficient (Eng +/?) mice compared to Eng +/+ animals. These results suggest a new role for endoglin in αIIbβ3 integrin-mediated adhesion of platelets to the endothelium, and may provide a better understanding on the basic cellular mechanisms involved in hemostasis and thrombo-inflammatory events. 相似文献
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Morgado M Cairrão E Santos-Silva AJ Verde I 《Cellular and molecular life sciences : CMLS》2012,69(2):247-266
Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation
of force (vasoconstriction) and release of force (vasodilation). The initiation of force is associated with increases in intracellular
calcium concentrations, activation of myosin light-chain kinase, increases in the phosphorylation of the regulatory myosin
light chains, and actin-myosin crossbridge cycling. There are, however, several signaling pathways modulating Ca2+ mobilization and Ca2+ sensitivity of the contractile machinery that secondarily regulate the contractile response of vascular smooth muscle to
receptor agonists. Among these regulatory mechanisms involved in the physiological regulation of vascular tone are the cyclic
nucleotides (cAMP and cGMP), which are considered the main messengers that mediate vasodilation under physiological conditions.
At least four distinct mechanisms are currently thought to be involved in the vasodilator effect of cyclic nucleotides and
their dependent protein kinases: (1) the decrease in cytosolic calcium concentration ([Ca2+]c), (2) the hyperpolarization of the smooth muscle cell membrane potential, (3) the reduction in the sensitivity of the contractile
machinery by decreasing the [Ca2+]c sensitivity of myosin light-chain phosphorylation, and (4) the reduction in the sensitivity of the contractile machinery
by uncoupling contraction from myosin light-chain phosphorylation. This review focuses on each of these mechanisms involved
in cyclic nucleotide-dependent relaxation of vascular smooth muscle under physiological conditions. 相似文献
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Federica Corallini Paola Secchiero Antonio Paolo Beltrami Daniela Cesselli Elisa Puppato Roberto Ferrari Carlo Alberto Beltrami Giorgio Zauli 《Cellular and molecular life sciences : CMLS》2010,67(8):1307-1314
The number of circulating mesenchymal stem cells (MSC), analyzed after acute myocardial infarction (AMI), was lower in AMI
patients who developed heart failure (HF) in the follow-up. Conversely, the circulating levels of tumor necrosis factor (TNF)-α,
and osteoprotegerin (OPG) were higher in AMI patients who developed HF with respect to the patients who did not develop HF.
In vitro exposure to TNF-α enhanced the migration of MSC in response to TNF-related apoptosis-inducing ligand (TRAIL) and
significantly increased the release of OPG by endothelial cells. On the contrary, OPG dose-dependently neutralized the in
vitro pro-migratory activity of TRAIL. Thus, TNF-α exhibits opposite effects on MSC migration driven by TRAIL: it is capable
of potentiating MSC migration as well as of inhibiting MSC migration as an indirect consequence of OPG induction, which might
result in a suboptimal recruitment of circulating MSC after AMI in those patients who develop HF in the follow-up. 相似文献
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Endoglin regulates mural cell adhesion in the circulatory system 总被引:1,自引:1,他引:0
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Elisa Tomellini Chann Lagadec Renata Polakowska Xuefen Le Bourhis 《Cellular and molecular life sciences : CMLS》2014,71(13):2467-2481
p75NTR, the common receptor for both neurotrophins and proneurotrophins, has been widely studied because of its role in many tissues, including the nervous system. More recently, a close relationship between p75NTR expression and pluripotency has been described. p75NTR was shown to be expressed in various types of stem cells and has been used to prospectively isolate stem cells with different degrees of potency. Here, we give an overview of the current knowledge on p75NTR in stem cells, ranging from embryonic to adult stem cells, and cancer stem cells. In an attempt to address its potential role in the control of stem cell biology, the molecular mechanisms underlying p75NTR signaling in different models are also highlighted. p75NTR-mediated functions include survival, apoptosis, migration, and differentiation, and depend on cell type, (pro)neurotrophin binding, interacting transmembrane co-receptors expression, intracellular adaptor molecule availability, and post-translational modifications, such as regulated proteolytic processing. It is therefore conceivable that p75NTR can modulate cell-fate decisions through its highly ramified signaling pathways. Thus, elucidating the potential implications of p75NTR activity as well as the underlying molecular mechanisms of p75NTR will shed new light on the biology of both normal and cancer stem cells. 相似文献