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71.
Liu WF Ji SR Sun JJ Zhang Y Liu ZY Liang AB Zeng HZ 《International journal of molecular sciences》2012,13(5):6399-6406
CD146 has been regarded as a novel potential therapeutic target for multiple cancers. The aim of the study was to investigate the expression of CD146 in gastric cancer and evaluate its clinical-pathological and prognostic significance. The expression of CD146 and three epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, β-catenin and vimentin) was examined in 144 gastric cancers by immunohistochemistry. Fifty-nine cases (41.0%) were defined as positive for CD146 expression. We found that CD146 expression correlated positively with lymph node involvement and a poor prognosis, and retained an independent prognostic factor for gastric cancer patients. Furthermore, positive expression of CD146 was strongly associated with loss of the epithelial marker E-cadherin and acquisition of the expression of the mesenchymal markers nuclear β-catenin and vimentin. These findings suggest that CD146 might promote EMT and progression in gastric cancer, and thus may be a potential therapeutic target for patients with gastric cancers. 相似文献
72.
Prof. Dr. Zhiqing Zhang Dr. Mark A. Eckert Dr. M. Monsur Ali Linan Liu Dr. Dong‐Ku Kang Elizabeth Chang Dr. Egest J. Pone Prof. Dr. Leonard S. Sender Prof. Dr. David A. Fruman Prof. Dr. Weian Zhao 《Chembiochem : a European journal of chemical biology》2014,15(9):1268-1273
We report a simple, versatile, multivalent ligand system that is capable of specifically and efficiently modulating cell‐surface receptor clustering and function. The multivalent ligand is made of a polymeric DNA scaffold decorated with biorecognition ligands (i.e., antibodies) to interrogate and modulate cell receptor signaling and function. Using CD20 clustering‐mediated apoptosis in B‐cell cancer cells as a model system, we demonstrated that our multivalent ligand is significantly more effective at inducing apoptosis of target cancer cells than its monovalent counterpart. This multivalent DNA material approach represents a new chemical biology tool to interrogate cell receptor signaling and functions and to potentially manipulate such functions for the development of therapeutics. 相似文献
73.
采用^99Tc^m直接标记法标记抗CD44的单克隆抗体,并对标记抗体的特性进行鉴定;利用^99Tc^m-CD44-McAb对荷人肺腺癌裸鼠进行放射免疫显像及体内分布研究。结果显示,^99Tc^m-CD44-McAb的标记率为92.3%±4.1%,比活度为2.9±0.5TBq/g,放化纯度为96.2%±3.1%。放射免疫显像结果显示,肿瘤组织对^99Tc^m~CD44-McAb有较高的摄取,通过感兴趣区(Regional Interest,ROD技术测得肿瘤部位与对侧相应部位的放射性摄取比(T/NT)为2.29±0.56,明显高于对照组(P〈0.05)。标记抗体的小鼠体内分布结果与显像结果基本一致。以上研究结果说明,^99Tc^m-CD44-McAb用于荷人肺腺癌裸鼠的放射免疫显像能得到较理想的T/NT,CD44是肺腺癌放射免疫显像研究值得推荐的目标抗原之一。 相似文献
74.
EH36高强度船板钢奥氏体连续冷却的转变行为 总被引:1,自引:0,他引:1
利用Gleeble2000型热模拟试验机对EH36船板钢连续冷却相变行为以及在增速冷却和减速冷却条件下的相变行为进行了研究。结果表明:在连续冷却条件下,在400-650℃范围内,冷却速率在4~16℃/s时,相变组织以贝氏体组织为主且随着冷速的增大贝氏体的体积分数增加;在冷却速率≥1℃/s时,先以一定速率冷却至600℃,然后将冷速减半时,其显微组织与半速恒速冷却组织相近;而先以一定速率冷却至600℃,然后将冷速加倍时,其显微组织与两倍速恒速冷却的显微组织相近。 相似文献
75.
76.
国家税收电子化正在不断深入发展,税控收款机和税控器是解决税收电子化的两类产品,税控收款机系统的设计一般采用嵌入式系统结构.嵌入式系统的开发首先选取合适的微处理器和嵌入式操作系统,根据税控收款机对软硬件的要求,选取W90N740CD微处理器和uClinux操作系统,提出了一种税控收款机系统的设计方案,并就软硬件关键技术的实现进行了论述.该方案已成功的开发为产品,功能、性能优于国标. 相似文献
77.
Cynthia M. Simbulan-Rosenthal Yogameenakshi Haribabu Sahar Vakili Li-Wei Kuo Havens Clark Ryan Dougherty Ryyan Alobaidi Bonnie Carney Peter Sykora Dean S. Rosenthal 《International journal of molecular sciences》2022,23(4)
Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC) implicated in tumorigenesis, invasion, and drug resistance, and is characterized by the elevated expression of stem cell markers, including CD133. The siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133’s anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRASQ61K and NRASQ61R drivers, after CRISPR-Cas9 CD133 knockout or Dox-inducible expression of CD133. MACS-sorted CD133(+) BAKP cells were conditionally reprogrammed to derive BAKR cells with sustained CD133 expression and MIC features. Compared to BAKP, CD133(+) BAKR exhibit increased cell survival and reduced apoptosis in response to trametinib or the chemotherapeutic dacarbazine (DTIC). CRISPR-Cas9-mediated CD133 knockout in BAKR cells (BAKR-KO) re-sensitized cells to trametinib. CD133 knockout in BAKP and POT cells increased trametinib-induced apoptosis by reducing anti-apoptotic BCL-xL, p-AKT, and p-BAD and increasing pro-apoptotic BAX. Conversely, Dox-induced CD133 expression diminished apoptosis in both trametinib-treated cell lines, coincident with elevated p-AKT, p-BAD, BCL-2, and BCL-xL and decreased activation of BAX and caspases-3 and -9. AKT1/2 siRNA knockdown or inhibition of BCL-2 family members with navitoclax (ABT-263) in BAKP-KO cells further enhanced caspase-mediated apoptotic PARP cleavage. CD133 may therefore activate a survival pathway where (1) increased AKT phosphorylation and activation induces (2) BAD phosphorylation and inactivation, (3) decreases BAX activation, and (4) reduces caspases-3 and -9 activity and caspase-mediated PARP cleavage, leading to apoptosis suppression and drug resistance in melanoma. Targeting nodes of the CD133, AKT, or BCL-2 survival pathways with trametinib highlights the potential for combination therapies for NRAS-mutant melanoma stem cells for the development of more effective treatments for patients with high-risk melanoma. 相似文献
78.
Luis Gonzlez-Osuna Alfredo Sierra-Cristancho Emilio A. Cafferata Samanta Melgar-Rodríguez Carolina Rojas Paola Carvajal Cristian Cortez Rolando Vernal 《International journal of molecular sciences》2022,23(5)
Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4+ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28− Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4+CD28− T lymphocytes in periodontitis. 相似文献
79.
80.
Ozlem Yildiz Johannes Schroth Vittoria Lombardi Valentina Pucino Yoana Bobeva Ping Kei Yip Klaus Schmierer Claudio Mauro Timothy Tree Sian Mari Henson Andrea Malaspina 《International journal of molecular sciences》2022,23(6)
Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis. Active CD11b+ CM frequencies increased steeply between the baseline and V3 (ANOVA repeated measurement, p < 0.001), and the V2/V1 ratio negatively correlated with the disease progression rate, similar to higher frequencies of active CD11b+ NCM at the baseline (R = −0.6567; p = 0.0031 and R = 0.3862; p = 0.0168, respectively). CD11b NCM, clinical covariates and neurofilament light-chain plasma concentration at the baseline predicted shorter survival in a multivariable and univariate analysis (CD11b NCM—HR: 1.05, CI: 1.01–1.11, p = 0.013. Log rank: above median: 43 months and below median: 21.22 months; p = 0.0022). Blood samples with the highest frequencies of active CD11b+ IM and NCM contained the lowest concentrations of soluble CD11b. Our preliminary data suggest that the levels of active CD11b+ monocytes and NCM in the blood predict different clinical outcomes in ALS. 相似文献