分化簇24(cluster of differentiation 24,CD24)是一种小分子量、高度糖基化的细胞膜上表达的蛋白质,通过糖基磷脂酰肌醇锚点与质膜相连。正常情况下,CD24主要在人体的免疫细胞上表达,但在70%以上的恶性肿瘤细胞包括肝癌、肺癌及膀胱癌...分化簇24(cluster of differentiation 24,CD24)是一种小分子量、高度糖基化的细胞膜上表达的蛋白质,通过糖基磷脂酰肌醇锚点与质膜相连。正常情况下,CD24主要在人体的免疫细胞上表达,但在70%以上的恶性肿瘤细胞包括肝癌、肺癌及膀胱癌等中也发现其过度表达。CD24往往通过参与介导肿瘤发生发展的相关信号转导通路调节肿瘤细胞的生长增殖、转移及侵袭,包括和配体P-选择素结合促进肿瘤细胞转移,通过激活Wnt信号通路和MAPK信号通路促进肿瘤生长增殖等。因此,利用靶向CD24的siRNA或抗体等阻断其与相关信号通路的联系,将会成为潜在的抗肿瘤治疗方案之一。目前,包括抗体治疗、基因治疗及免疫治疗等方式在内的多项以CD24为靶点的抗肿瘤治疗药物,正处于临床前研究阶段。最新研究显示,CD24可通过与巨噬细胞上的配体-唾液酸结合Ig样凝集素10(sialic-acid-binding Ig-like lectin 10,Siglec-10)结合,释放抑制巨噬细胞对肿瘤细胞吞噬的“别吃我”信号,进而导致肿瘤细胞逃避免疫监视。利用靶向CD24的抗体或CD24受体融合蛋白封闭CD24和Siglec-10的结合,将有助于巨噬细胞等免疫效应细胞识别肿瘤细胞,因此,CD24有望成为新的抗肿瘤免疫治疗靶点。本文将主要介绍CD24分子的结构、生物学功能及其在肿瘤发生、发展与抗肿瘤免疫中的作用,并系统总结以CD24为靶点的抗肿瘤药物和治疗手段的研发现状及最新进展。展开更多
Objective： Airway inflammation and airway hyper-responsiveness（AHR） are principle pathological manifestations of asthma. Cluster of differentiation 69（CD69） is a well-known co-stimulatory factor associated with t...Objective： Airway inflammation and airway hyper-responsiveness（AHR） are principle pathological manifestations of asthma. Cluster of differentiation 69（CD69） is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody（m Ab） on the pathophysiology of a mouse model of asthma. Methods： A murine model of ovalbumin（OVA）-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 μg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1%（0.01 g/ml） OVA on Days 24, 25, and 26. Anti-CD69 m Ab or isotype Ig G was injected intraperitoneally after OVA challenge; dexamethasone（DXM） was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor（GM-CSF） and interleukin-5（IL-5） in bronchoalveolar lavage fluid（BALF） were also assayed as indices of airway inflammation on Day 28 following OVA injection. Results： Pretreatment with DXM together with anti-CD69 m Ab treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti-CD69 m Ab did not alter the concentration of BALF GM-CSF. Conclusions： Anti-CD69 m Ab treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation.展开更多
We report that a 63-year-old Chinese female had acute myeloblastic leukemia （AML） in which trisomy 21 （＋21） was found as the sole acquired karyotypic abnormality. The blasts were positive for rnyeloperoxidase, an...We report that a 63-year-old Chinese female had acute myeloblastic leukemia （AML） in which trisomy 21 （＋21） was found as the sole acquired karyotypic abnormality. The blasts were positive for rnyeloperoxidase, and the immunophenotype was positive for cluster of differentiation 19 （CD19）, CD33, CD34, and human leukocyte antigens （HLA）-DR. The chromosomal analysis of bone marrow showed 47,XX,＋21 [2]/46,XX[ 18]. Fluorescent in situ hybridization （FISH） showed that three copies of AML1 were situated in separate chromosomes, and that t（8;21） was negative. The patient did not have any features of Down syndrome. A diagnosis of CD 19-positive AML-M5 was established with trisomy 21 as a sole acquired karyotypic abnormality. The patient did not respond well to chemotherapy and died three months after the diagnosis. This is the first reported case of CD19-positive AML with trisomy 21 as the sole cytogenetie abnormality. The possible prognostic significance of the finding in AML with ＋21 as the sole acquired karyotypic abnormality was discussed.展开更多
Synchrotron radiation(SR) X-ray has significant potential for medical applications. However, the mechanisms underlying the effects of SR X-ray on biological tissues remain unclear. Because increasing evidence has indi...Synchrotron radiation(SR) X-ray has significant potential for medical applications. However, the mechanisms underlying the effects of SR X-ray on biological tissues remain unclear. Because increasing evidence has indicated critical roles of cluster of differentiation 38(CD38) in various cellular functions and cell survival, in this study we used rodent testes as a model to determine the effects of SR X-ray irradiation on the CD38 level of the testes. We found that SR X-ray irradiation led to a significant increase in the CD38 level of rodent testes one day after the irradiation. In contrast, the SR X-ray irradiation did not produce a significant increase in the CD38 level of the testes from the rats that were administered with the antioxidant N-acetyl cysteine, thus suggesting that oxidative stress plays a significant role in the SR X-ray irradiation-induced increase in the CD38 levels. Our study has also provided evidence suggesting that poly(ADP-ribose) polymerase(PARP) activity is not involved in the SR X-ray irradiation-produced effect on the CD38 levels. Collectively, this study has provided first in vivo evidence indicating that CD38 levels can be increased by ionizing radiation, in which oxidative stress plays an important role. Because oxidative stress occurs in ionizing radiation as well as such diseases as cerebral ischemia and Parkinson's disease, oxidative stress may produce pathological effects by inducing increased CD38 levels.展开更多
Serum biomarkers in the form of proteins （e.g. cluster of differentiation-44 （CD44）） have been demonstrated to have high clinical sensitivity and specificity for disease diagnosis and prognosis. Owing to the high ...Serum biomarkers in the form of proteins （e.g. cluster of differentiation-44 （CD44）） have been demonstrated to have high clinical sensitivity and specificity for disease diagnosis and prognosis. Owing to the high sample complexity and low molecular abundance in serum, the detection and profiling of biomarkers rely on efficient extraction by materials and devices, mostly using immunoassays via antibody-antigen recognition. Antibody-free approaches are promising and need to be developed for real-case applications in serum to address the limitations of antibody-based techniques in terms of robustness, expense, and throughput. In this work, we demonstrated a novel approach using hyaluronic acid （HA）-modified materials/devices for the extraction, detection, and profiling of serum biomarkers via ligand-protein interactions. We constructed Fe304@SiOa@HA particles with different sizes through layer-by-layer assembly and for the first time applied HA-functionalized particles in the facile extraction and sequence identification of CD44 in serum by mass spectrometry. We also first validated HA-CD44 binding through electrochemical sensing using HA- modified electrodes in both standard solutions and diluted serum samples, achieving a detection limit of -0.6 ng/mL and a linear response range from I ng/mL to 10 ~tg/mL. Furthermore, we performed profiling of HA-binding serum proteome, providing a new preliminary benchmark for the construction of future databases, and we investigated selected surface chemistries of particles for the capture of proteins in serum. Our work not only resulted in the development of a platform technology for CD44 extraction/detection and HA-binding proteome identification, but also guided the design of ligand affinity-based approaches for antibody-free analysis of serum biomarkers towards diagnostic applications.展开更多
基金Project supported by the National Natural Science Foundation of China(No.30600266)the Zhejiang Provincial Science and Technology Project(No.2011C37073)+2 种基金the Zhejiang Provincial Natural Science Foundation(No.LQ12H16012)the National Key Clinical Project of Allergy of Chinathe National Key Clinical Specialist Construction Programs of China
文摘Objective： Airway inflammation and airway hyper-responsiveness（AHR） are principle pathological manifestations of asthma. Cluster of differentiation 69（CD69） is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody（m Ab） on the pathophysiology of a mouse model of asthma. Methods： A murine model of ovalbumin（OVA）-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 μg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1%（0.01 g/ml） OVA on Days 24, 25, and 26. Anti-CD69 m Ab or isotype Ig G was injected intraperitoneally after OVA challenge; dexamethasone（DXM） was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor（GM-CSF） and interleukin-5（IL-5） in bronchoalveolar lavage fluid（BALF） were also assayed as indices of airway inflammation on Day 28 following OVA injection. Results： Pretreatment with DXM together with anti-CD69 m Ab treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti-CD69 m Ab did not alter the concentration of BALF GM-CSF. Conclusions： Anti-CD69 m Ab treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation.
文摘We report that a 63-year-old Chinese female had acute myeloblastic leukemia （AML） in which trisomy 21 （＋21） was found as the sole acquired karyotypic abnormality. The blasts were positive for rnyeloperoxidase, and the immunophenotype was positive for cluster of differentiation 19 （CD19）, CD33, CD34, and human leukocyte antigens （HLA）-DR. The chromosomal analysis of bone marrow showed 47,XX,＋21 [2]/46,XX[ 18]. Fluorescent in situ hybridization （FISH） showed that three copies of AML1 were situated in separate chromosomes, and that t（8;21） was negative. The patient did not have any features of Down syndrome. A diagnosis of CD 19-positive AML-M5 was established with trisomy 21 as a sole acquired karyotypic abnormality. The patient did not respond well to chemotherapy and died three months after the diagnosis. This is the first reported case of CD19-positive AML with trisomy 21 as the sole cytogenetie abnormality. The possible prognostic significance of the finding in AML with ＋21 as the sole acquired karyotypic abnormality was discussed.
基金the National Basic Research Program (973) of China(No.2010CB834306)the National Natural Science Foundation of China(No.81171098)
文摘Synchrotron radiation(SR) X-ray has significant potential for medical applications. However, the mechanisms underlying the effects of SR X-ray on biological tissues remain unclear. Because increasing evidence has indicated critical roles of cluster of differentiation 38(CD38) in various cellular functions and cell survival, in this study we used rodent testes as a model to determine the effects of SR X-ray irradiation on the CD38 level of the testes. We found that SR X-ray irradiation led to a significant increase in the CD38 level of rodent testes one day after the irradiation. In contrast, the SR X-ray irradiation did not produce a significant increase in the CD38 level of the testes from the rats that were administered with the antioxidant N-acetyl cysteine, thus suggesting that oxidative stress plays a significant role in the SR X-ray irradiation-induced increase in the CD38 levels. Our study has also provided evidence suggesting that poly(ADP-ribose) polymerase(PARP) activity is not involved in the SR X-ray irradiation-produced effect on the CD38 levels. Collectively, this study has provided first in vivo evidence indicating that CD38 levels can be increased by ionizing radiation, in which oxidative stress plays an important role. Because oxidative stress occurs in ionizing radiation as well as such diseases as cerebral ischemia and Parkinson's disease, oxidative stress may produce pathological effects by inducing increased CD38 levels.
文摘Serum biomarkers in the form of proteins （e.g. cluster of differentiation-44 （CD44）） have been demonstrated to have high clinical sensitivity and specificity for disease diagnosis and prognosis. Owing to the high sample complexity and low molecular abundance in serum, the detection and profiling of biomarkers rely on efficient extraction by materials and devices, mostly using immunoassays via antibody-antigen recognition. Antibody-free approaches are promising and need to be developed for real-case applications in serum to address the limitations of antibody-based techniques in terms of robustness, expense, and throughput. In this work, we demonstrated a novel approach using hyaluronic acid （HA）-modified materials/devices for the extraction, detection, and profiling of serum biomarkers via ligand-protein interactions. We constructed Fe304@SiOa@HA particles with different sizes through layer-by-layer assembly and for the first time applied HA-functionalized particles in the facile extraction and sequence identification of CD44 in serum by mass spectrometry. We also first validated HA-CD44 binding through electrochemical sensing using HA- modified electrodes in both standard solutions and diluted serum samples, achieving a detection limit of -0.6 ng/mL and a linear response range from I ng/mL to 10 ~tg/mL. Furthermore, we performed profiling of HA-binding serum proteome, providing a new preliminary benchmark for the construction of future databases, and we investigated selected surface chemistries of particles for the capture of proteins in serum. Our work not only resulted in the development of a platform technology for CD44 extraction/detection and HA-binding proteome identification, but also guided the design of ligand affinity-based approaches for antibody-free analysis of serum biomarkers towards diagnostic applications.
