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Participation of hypoxia-inducible factor-1α in the pathogenesis of preeclampsia-related placental ischemia and its potential as a marker for preeclampsia 缺氧诱导因子-1α参与子痫前期相关胎盘缺血的发病机制及其作为子痫前期标志物的潜力
Pub Date : 2014-09-01 DOI: 10.1016/j.bgm.2014.04.002
Meenakshi Akhilesh , Vivekananda Mahalingam , Sivalingam Nalliah , Rosalina Mohd Ali , Murali Ganesalingam , Nagaraja Haleagrahara

Hypoxia-inducible factor-1α (HIF-1α) is important for placental development. This study aims to determine whether the increased level and expression of HIF could be used to demonstrate failed placentation in women with preeclampsia. The study included 20 pregnant females [10 with and 10 without preeclampsia (the control group)]. Placental tissues were collected and stained with hematoxylin and eosin. Immunohistochemical studies for evaluating the expression of HIF-1α by these tissues were then performed. The results demonstrated that placental tissues collected from mothers with preeclampsia showed a variety of histomorphological changes. All the cytotrophoblasts rimming the placental villi in mothers with preeclampsia demonstrated a strong and uniform nuclear staining with HIF-1α. The study results indicated that cytotrophoblasts respond to an ischemic environment by their nuclear expression of HIF-1α, and thus we conclude that this transcription factor has a significant potential as a marker for preeclampsia.

缺氧诱导因子-1α (HIF-1α)在胎盘发育中起重要作用。本研究旨在确定HIF水平和表达的增加是否可以用来证明先兆子痫妇女的胎盘失败。本研究纳入20例孕妇[10例有先兆子痫,10例无先兆子痫(对照组)]。收集胎盘组织并用苏木精和伊红染色。然后进行免疫组织化学研究,以评估这些组织中HIF-1α的表达。结果表明,从先兆子痫母亲收集的胎盘组织显示出多种组织形态学变化。所有子痫前期母亲胎盘绒毛周围的细胞滋养细胞均表现出强烈而均匀的HIF-1α染色。研究结果表明,细胞滋养细胞通过其核表达HIF-1α来响应缺血环境,因此我们认为该转录因子具有作为子痫前期标记物的重要潜力。
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引用次数: 7
Polyclonal antibody from 47 kDa protein of bladder cancer is sensitive and specific for detection of bladder cancer 膀胱癌47 kDa蛋白多克隆抗体对膀胱癌的检测具有敏感性和特异性
Pub Date : 2014-09-01 DOI: 10.1016/j.bgm.2014.06.003
Heru Prasetya , Basuki Bambang Purnomo , I. Ketut Gede Muliartha , Sumarno Reto Prawiro

This study aims to investigate whether the protein isolated from bladder cancer in an Indonesian population can produce the polyclonal antibody for clinical markers of bladder cancer. The participants in this study are bladder cancer patients and healthy persons who were approved for midstream portion urine collection. The inclusion criteria included bladder cancer patients who obtained hematuria examination, urine cytology, and initial therapy with transurethral resection of the bladder; a healthy volunteer who was approved for midstream portion urine collection but without hematuria history, bladder stones, and signs or symptoms of tractus urinarius infection. The procedure consisted of tissue preparation, tissue processing, isolation of membrane cell protein, monitoring of protein in membrane cell, production of polyclonal antibodies, and dot blot technique. A protein with 122 kDa molecular weight is present in epithelial cells of bladder cancer and the normal bladder. A protein with 69 kDa molecular weight is only present in the epithelial cell bladder of normal individuals. In addition, a protein with molecular weight of 47 kDa is only present in epithelial cells of bladder cancer. The minimal ratio of polyclonal antibody with antigen is 1:6400 of the antibody and 1:40 of antigen. Subsequently, this concentration was applied to detect proteins with 47 kDa only in several cancer tissues. Positive results in bladder cancer, but negative results in prostate cancer, rectal cancer, and breast cancer were found. The polyclonal antibody produced from 47 kDa protein subunit is sensitive and specific to detect bladder cancer and become an alternative biomarker for diagnosis and surveillance of bladder cancer.

本研究旨在探讨从印度尼西亚人群中分离的膀胱癌蛋白能否产生膀胱癌临床标志物的多克隆抗体。本研究的参与者是膀胱癌患者和健康的人,他们被批准进行中游部分尿液收集。入选标准包括接受血尿检查、尿细胞学检查和经尿道膀胱切除术的膀胱癌患者;健康志愿者,经批准进行中游部分尿液采集,但无血尿史、膀胱结石、尿路感染体征或症状。实验过程包括组织制备、组织处理、膜细胞蛋白分离、膜细胞蛋白监测、多克隆抗体的制备和点印迹技术。一种分子量为122kda的蛋白存在于膀胱癌和正常膀胱上皮细胞中。分子量为69 kDa的蛋白仅存在于正常人的上皮细胞膀胱中。此外,分子量为47 kDa的蛋白仅存在于膀胱癌上皮细胞中。多克隆抗体与抗原的最小比值为抗体的1:6400和抗原的1:40。随后,该浓度仅用于检测几种癌组织中含有47 kDa的蛋白。膀胱癌呈阳性,但前列腺癌、直肠癌和乳腺癌呈阴性。由47 kDa蛋白亚基制备的多克隆抗体对膀胱癌的检测具有敏感性和特异性,成为膀胱癌诊断和监测的替代生物标志物。
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引用次数: 3
Subchronic inhalation of particulate matter 10 coal dust induces atherosclerosis in the aorta of diabetic and nondiabetic rats 亚慢性吸入颗粒物10煤尘可诱导糖尿病和非糖尿病大鼠主动脉动脉粥样硬化
Pub Date : 2014-06-01 DOI: 10.1016/j.bgm.2014.03.002
Bambang Setiawan , Nia Kania , Dian Nugrahenny , Nurdiana Nurdiana , Moch. Aris Widodo

This study aimed to elucidate whether subchronic inhalation of particulate matter (PM10) coal dust induces atherosclerosis in diabetic rats. A total of 32 male Wistar rats, were randomly divided into eight groups including four nondiabetic groups and four groups of diabetic rats. These rats were exposed to doses of coal dust equal to 0 mg/m3, 6.25 mg/m3, 12.5 mg/m3, or 25 mg/m3 for 1 hour/day for 28 days. Plasma levels of lipid peroxides were determined as thiobarbituric acid reactive substance. The levels of circulating endothelial cells were analyzed histologically. Foam cells formation was analyzed in aorta and tail artery with Oil Red O staining. Analysis of variance test was used to compare all parameters. Nondiabetic rats exposed to coal dust had significantly increased oxidative stress compared to the control group (p < 0.05). Diabetic rats exposed to coal dust at dose of 25 mg/m3 had significantly increased oxidative stress compared to that of control diabetic rats (p < 0.05). The levels of endothelial damage were significantly increased in diabetic rats exposed to coal dust at doses of 6.25 mg/m3 and 12.5 mg/m3 (p < 0.05) compared to control diabetic rats. The foam cell counts were significantly increased in the aorta of nondiabetic rats exposed to coal dust at doses of 6.25 mg/m3 and 25 mg/m3 compared to control rats (p < 0.05), also in the tail artery at dose of 25 mg/m3. The foam cell counts were significantly increased in the aorta of diabetic rats exposed to coal dust at doses of 6.25 mg/m3 and 12.5 mg/m3 than that in control diabetic rats (p < 0.05). Subchronic inhalation of PM10 coal dust induces atherosclerosis through oxidative stress and endothelial damage in aorta of nondiabetic and diabetic rats.

本研究旨在阐明亚慢性吸入颗粒物(PM10)煤尘是否诱导糖尿病大鼠动脉粥样硬化。将32只雄性Wistar大鼠随机分为8组,其中4组为非糖尿病大鼠,4组为糖尿病大鼠。这些大鼠分别暴露于0 mg/m3、6.25 mg/m3、12.5 mg/m3或25 mg/m3剂量的煤尘中,每天1小时,持续28天。血浆脂质过氧化物水平测定为硫代巴比妥酸活性物质。组织学分析循环内皮细胞水平。油红O染色观察主动脉和尾动脉泡沫细胞形成情况。采用方差分析检验对各参数进行比较。与对照组相比,暴露于煤尘的非糖尿病大鼠氧化应激显著增加(p <0.05)。25 mg/m3剂量的煤尘对糖尿病大鼠氧化应激的影响显著高于对照组(p <0.05)。暴露于6.25 mg/m3和12.5 mg/m3剂量煤尘的糖尿病大鼠内皮损伤水平显著增加(p <0.05)。与对照大鼠相比,暴露于6.25 mg/m3和25 mg/m3剂量煤尘的非糖尿病大鼠主动脉泡沫细胞计数显著增加(p <0.05),在25 mg/m3剂量下尾动脉中也有。暴露于6.25 mg/m3和12.5 mg/m3剂量下的糖尿病大鼠主动脉泡沫细胞计数明显高于对照组(p <0.05)。亚慢性吸入PM10煤尘可通过氧化应激和主动脉内皮损伤诱导非糖尿病和糖尿病大鼠动脉粥样硬化。
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引用次数: 9
The female-specific effect of 5-hydroxytryptamine receptor 3A gene on postoperative vomiting in Taiwan 台湾5-羟色胺受体3A基因对术后呕吐的女性特异性影响
Pub Date : 2014-06-01 DOI: 10.1016/j.bgm.2014.02.003
Yi-Mei Joy Lin , Cheng-Da Hsu , Hsiao-Yen Hsieh , Chia-Chih Alex Tseng

Postoperative vomiting (POV) is a common complication after general anesthesia. Clarifying the genetic factors that affect POV are important for evaluating a patient's susceptibility to the condition. Although evidence suggests that the 5-hydroxytryptamine (serotonin) receptor 3A (HTR3A) gene may be important in the occurrence of POV, associations for HTR3A polymorphisms with POV have not been investigated in a Taiwanese population. Three single nucleotide polymorphisms (SNPs) of the HTR3A gene were used to study the genetic association with POV in 369 postoperative Taiwanese adults who underwent general anesthesia. Although no significant differences were found at the single-locus level for HTR3A polymorphisms, a significant haplotype-based association was found between HTR3A and POV. In addition, because female sex is associated with a higher risk of PONV (postoperative nausea and vomiting), we separately analyzed the haplotypic associations for both sexes to test whether HTR3A genetic factors interact with female sex and specifically contribute to the etiology of POV. We found that a significant haplotype effect was identified only for females. The CTT haplotype, the most common, showed a significant protective effect (odds ratio: 0.68), and the CTG haplotype was associated with a significantly higher risk (odds ratio: 2.08) for POV in females. Furthermore, p values from an overall comparison of all haplotypes and from permutation tests were still significant. These data suggest that the HTR3A gene may have a sex-specific effect on the etiology of POV in Taiwan. The effects and the biological causal variants related to POV are worth additional investigation.

术后呕吐(POV)是全身麻醉后常见的并发症。明确影响POV的遗传因素对于评估患者对该病的易感性非常重要。虽然有证据表明5-羟色胺(5-羟色胺)受体3A (HTR3A)基因可能在POV的发生中起重要作用,但尚未在台湾人群中调查HTR3A多态性与POV的关系。本研究利用3个HTR3A基因单核苷酸多态性(SNPs)研究369例台湾成人全身麻醉术后POV的遗传关系。尽管在单位点水平上没有发现HTR3A多态性的显著差异,但在HTR3A和POV之间发现了基于单倍型的显著关联。此外,由于女性与PONV(术后恶心和呕吐)的风险较高,我们分别分析了两性的单倍型相关性,以检测HTR3A遗传因子是否与女性相互作用,并特异性地促进了POV的病因学。我们发现,单倍型效应仅在雌性中存在。最常见的CTT单倍型显示出显著的保护作用(比值比:0.68),而CTG单倍型与女性患POV的风险显著升高(比值比:2.08)相关。此外,所有单倍型的总体比较和排列测试的p值仍然显著。这些数据提示HTR3A基因可能对台湾地区POV的病因有性别特异性影响。与POV相关的效应和生物学上的因果变异值得进一步研究。
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引用次数: 1
Detection and characterization of class 1 integron-associated gene cassettes from Pseudomonas aeruginosa isolates in southern Taiwan 台湾南部铜绿假单胞菌1类整合子相关基因盒的检测与鉴定
Pub Date : 2014-06-01 DOI: 10.1016/j.bgm.2014.02.004
Ke-Yu Hsiao, Mei-Feng Lee, Chien-Fang Peng

In this study, detection and characterization of class 1 integron-associated gene cassettes from Pseudomonas aeruginosa isolates in southern Taiwan were investigated. The study focused on the association between integron-associated resistance gene cassettes and multidrug resistance in P. aeruginosa isolates. Using polymerase chain reaction amplification, DNA sequencing, and basic local alignment search tool analysis, a total of 22 different types of gene cassette arrays were detected in 162 class 1 integron-positive P. aeruginosa isolates. We first identified 11 different types of new gene cassette arrays within class 1 integron in P. aeruginosa isolates, including aac(6)-II-catB2-aadA2, aac(6)-II-aadA2, aac(6)-II-catB2, aacA4-aadA15, aacC1-orfA-orfB-aadA1, cm1A-aadA1, catB3-blaOxA-10-aadA15, aacA4-catB8-aadA1, aadB-orfF1-aadA11, dfrB1, and dfrB4a-aacA4-aacA4-aadA1. Of these, aac(6)-II-catB2-aadA2 was the most frequently found gene cassette. Twenty-one (21/162, 12.9%) strains carrying two different types of gene cassette arrays of catB3-blaOxA-10-aadA15 and aac(6)-II-catB2-aadA2 were also simultaneously present in the P. aeruginosa isolates. A novel dfrB4a gene, different from the dfrB4 gene detected in the gene cassette array of dfrB4a-aacA4-aacA4-aadA, was characterized. A metallo-β-lactamaseo gene was also found to be carried on the gene cassette of blaVIM-3-orf2a-aacA4-aadB-aacA4 inserted in a class 1 integron obtained from meropenem-resistant P. aeruginosa isolates.

本研究对台湾南部铜绿假单胞菌1类整合子相关基因盒的检测与鉴定进行了研究。本研究的重点是铜绿假单胞菌整合子相关耐药基因盒与多药耐药的关系。利用聚合酶链反应扩增、DNA测序和基本局部比对搜索工具分析,在162株1类整合子阳性铜绿假单胞菌中共检测到22种不同类型的基因盒阵列。首先在铜绿假单胞菌1类整合子中鉴定出11种不同类型的新基因盒阵列,包括aac(6’)-II-catB2- aada2, aac(6’)-II-aadA2, aac(6’)-II-aadA2, aac(6’)-II-catB2, aacA4-aadA15, aacC1-orfA-orfB-aadA1, cm1A-aadA1, catB3-blaOxA-10-aadA15, aacA4-catB8-aadA1, aadB-orfF1-aadA11, dfrB1和dfrb4a - aaca4 - aaca4 - aaca4 - aada1。其中,aac(6’)-II-catB2-aadA2是最常见的基因盒。在铜绿假单胞菌分离株中同时存在21株(21/162,12.9%)携带catB3-blaOxA-10-aadA15和aac(6’)-II-catB2-aadA2两种不同类型基因盒阵列的菌株。鉴定了一个不同于dfrB4a- aaca4 - aaca4 - aada基因盒阵列中检测到的dfrB4a基因。从耐美洛培尼铜绿假单胞菌分离株中获得的1类整合子中插入的blaVIM-3-orf2a-aacA4-aadB-aacA4基因盒上也发现了一个金属β-内酰胺酶基因。
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引用次数: 8
Molecular markers and their applications in cattle genetic research: A review 分子标记及其在牛遗传研究中的应用综述
Pub Date : 2014-06-01 DOI: 10.1016/j.bgm.2014.03.001
Umesh Singh , Rajib Deb , Rafeeque Rahman Alyethodi , Rani Alex , Sushil Kumar , Sandip Chakraborty , Kuldeep Dhama , Arjava Sharma

India is one the world's five largest producers of livestock and poultry meat. The livestock sector contributes 28% of the country's agriculture gross domestic product and about 5% of the country's overall gross domestic product. Genetic improvement of livestock has been mainly dependent on the selective breeding with superior phenotypes. The use of molecular genetics techniques in association with conventional animal breeding tools are important to balance the process of selection and thus to optimize the animal breeding program. In this regard, the use of molecular markers is significantly important and it certainly has added advantages over conventional breeding techniques. On the basis of techniques used for the detection of molecular markers, two major categories have been identified: hybridization-based and polymerase chain reaction-based markers. Identification and use of markers for milk quality and production traits, disease resistance, and thermo-tolerance will ensure better health and productivity. Also, markers for fertility and carcass quality traits ensure faster and preferred growth in cattle. Apart from these, the use of different markers such as microsatellites for assessment of biodiversity will help the conservation of our indigenous germplasm. The present review deals with molecular markers and their application in versatile aspects that will prove beneficial for researchers and scientists to undertake further research to improve cattle health and production.

印度是世界五大畜禽肉类生产国之一。畜牧业占该国农业国内生产总值的28%,约占该国整体国内生产总值的5%。家畜遗传改良主要依赖于具有优良表型的选择性育种。分子遗传学技术与传统动物育种工具的结合使用对于平衡选择过程和优化动物育种计划非常重要。在这方面,分子标记的使用是非常重要的,它当然比传统育种技术有更多的优势。基于检测分子标记的技术,已经确定了两大类:基于杂交的标记和基于聚合酶链反应的标记。鉴定和使用牛奶品质和生产性状、抗病性和耐热性标记将确保更好的健康和生产力。此外,肥力和胴体品质性状的标记确保了牛的更快和更好的生长。除此之外,利用微卫星等不同的标记来评估生物多样性将有助于保护我们的本土种质资源。目前的综述涉及分子标记及其在多方面的应用,这将证明有利于研究人员和科学家进行进一步的研究,以改善牛的健康和生产。
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引用次数: 78
Primary aortojejunal fistula manifested as herald gastrointestinal hemorrhage 原发性主动脉空肠瘘表现为胃肠道出血的先兆
Pub Date : 2014-06-01 DOI: 10.1016/j.bgm.2014.04.001
Chih-Pin Chien , Yung-Sung Yeh , Chong-Chao Hsieh , Chao-Wen Chen , Chau-Yun Chen , Jaw-Yuan Wang

Aortoenteric fistulas (AEFs) are a rare but fatal cause of massive, life-threatening gastrointestinal bleeding and require emergent intervention. The clinical signs of AEF are nonspecific and non-prevalent. The classic triad of AEF (abdominal pain, gastrointestinal hemorrhage, and a pulsatile abdominal mass) exhibit only in 23% of patients with AEF, which makes diagnosis of AEF difficult. Gastroduodenoscopy and abdominal computed tomography are the mainstay studies for AEF in the emergency setting. However, proving the existence of the AEF remains a difficult issue. AEF could be managed either by endovascular stent or open surgery. Herein, we report a case of primary aortojejunal fistula on which a successful surgical aortic reconstruction was performed.

主动脉肠瘘(AEFs)是一种罕见但致命的原因,大量的,危及生命的胃肠道出血,需要紧急干预。AEF的临床症状是非特异性和不普遍的。AEF的典型三联征(腹痛、胃肠出血和搏动性腹部肿块)仅在23%的AEF患者中表现出来,这使得AEF的诊断变得困难。胃十二指肠镜检查和腹部计算机断层扫描是急诊AEF的主要研究方法。然而,证明AEF的存在仍然是一个困难的问题。AEF可以通过血管内支架或开放手术治疗。在此,我们报告一例原发性主动脉空肠瘘,成功的手术主动脉重建进行。
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引用次数: 0
Mutations in the quinolone resistance-determining regions associated with ciprofloxacin resistance in Pseudomonas aeruginosa isolates from Southern Taiwan 台湾南部铜绿假单胞菌环丙沙星耐药相关的喹诺酮类耐药区突变
Pub Date : 2014-06-01 DOI: 10.1016/j.bgm.2014.03.003
Yung-Ting Wang, Mei-Feng Lee, Chien-Fang Peng

Mutations in the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE have been characterized among the 232 isolates of ciprofloxacin (CIP)-resistant Pseudomonas aeruginosa. As expected, no mutations in the QRDRs of four target genes were detected in the CIP-susceptible isolates of P. aeruginosa. It was noted that P. aeruginosa showing no mutation in the QRDRs of target genes were frequently found in isolates with a CIP in minimal inhibitory concentration (MIC) = 2 μg/mL than those of isolates with a CIP in MIC ≥4 μg/mL. The prevalence of P. aeruginosa with no mutations in the QRDRs of target genes is higher in isolates only resistant to CIP than in isolates resistant to CIP and other drugs. Double mutations occurring in gyrA and parC genes associated with a high-level resistance to CIP in MICs ≥4 μg/mL were found in 101 out of 176 isolates. Furthermore, mutations in parC and parE joined with mutation in gyrA were commonly found in P. aeruginosa highly resistant to CIP.

在232株环丙沙星(CIP)耐药铜绿假单胞菌中发现了gyrA、gyrB、parC和parE的喹诺酮类耐药决定区(QRDRs)突变。正如预期的那样,在铜绿假单胞菌对cip敏感的分离株中未检测到4个靶基因的qrdr突变。结果表明,最低抑制浓度(MIC)为2 μg/mL的铜绿假单胞菌比最低抑制浓度(MIC)≥4 μg/mL的铜绿假单胞菌的QRDRs无突变。靶基因qrdr无突变的铜绿假单胞菌在仅耐CIP的分离株中的流行率高于耐CIP和其他药物的分离株。176个分离株中有101个存在与mic≥4 μg/mL时高水平CIP耐药相关的gyrA和parC基因双突变。此外,在耐CIP的铜绿假单胞菌中,parC和parE突变与gyrA突变共同存在。
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引用次数: 12
Impacts of protease inhibitors on clathrin and fibronectin in cancer metastasis 蛋白酶抑制剂对癌转移中网格蛋白和纤维连接蛋白的影响
Pub Date : 2014-03-01 DOI: 10.1016/j.bgm.2014.02.002
Chih-I Wu , Ming-Min Chang , Chun-Li Su , Pin Ling , Wen-Tsan Chang , Hung-Chi Cheng

Metastasis is a major cause of cancer deaths. Seeking alternative prognostic biomarkers may enable oncologists to make accurate therapeutic decisions to benefit cancer patients. Cumulated evidence reveals that fibronectin (FN) is highly correlated with cancer metastasis but has not been deemed as a prognostic biomarker due to its broad tissue distribution patterns and complicated physiological and pathological functionalities that significantly interfere with the judgmental accuracy. Combining other FN-related factors may make FN possible as a useful prognostic biomarker. Clathrin, a highly protease-susceptible cytoplasmic molecule, is known to affect pericellular FN (periFN) assembly via regulating cell surface FN receptors or FN matrix turnover by coating the endocytic vesicles. Researching our previously published proteomics database of 660 differential secretome proteins expressed in human lung adenocarcinoma cell lines and performing double immunofluorescent staining for periFN and clathrin, we recognized an inverse relationship between them. However, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) data contradicted this relationship, which could be corrected by the addition of a mixture of protease inhibitors into nonmetastatic cancer cell lysates. These results suggested that nonmetastatic cells express either higher levels of cellular proteases or less amounts of protease inhibitors. By examining our proteomic database and reviewing the literature, we conclude that clathrin expression and assembly is inversely correlated with metastatic potential of FNhigh cancer cells mainly related to the expression of protease inhibitors, instead of proteases. It is worth investigating whether such an inverse relationship between FN/protease inhibitors and clathrin in human cancers could clinically be incorporated into the prognostic strategy for various cancer types.

转移是癌症死亡的主要原因。寻找替代的预后生物标志物可能使肿瘤学家做出准确的治疗决定,使癌症患者受益。越来越多的证据表明,纤维连接蛋白(FN)与癌症转移高度相关,但由于其广泛的组织分布模式和复杂的生理和病理功能会显著干扰判断的准确性,因此尚未被视为预后生物标志物。结合其他FN相关因素可能使FN成为一种有用的预后生物标志物。网格蛋白是一种高度蛋白酶敏感的细胞质分子,已知其通过包裹胞吞囊泡来调节细胞表面FN受体或FN基质的转换,从而影响细胞周围FN (periFN)的组装。研究了我们之前发表的660种在人肺腺癌细胞系中表达的差异分泌组蛋白的蛋白质组学数据库,并对periFN和clathrin进行了双重免疫荧光染色,我们发现它们之间存在反比关系。然而,十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)数据与这种关系相矛盾,这可以通过在非转移性癌细胞裂解物中加入蛋白酶抑制剂的混合物来纠正。这些结果表明,非转移性细胞表达较高水平的细胞蛋白酶或较少数量的蛋白酶抑制剂。通过检查我们的蛋白质组学数据库和回顾文献,我们得出结论,网格蛋白的表达和组装与FNhigh癌细胞的转移潜能呈负相关,主要与蛋白酶抑制剂的表达有关,而不是蛋白酶的表达。FN/蛋白酶抑制剂与网格蛋白在人类癌症中的这种反比关系是否可以在临床上纳入各种癌症类型的预后策略值得研究。
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引用次数: 2
Hypoxia-induced tumor malignancy and drug resistance: Role of microRNAs 低氧诱导的肿瘤恶性与耐药:microrna的作用
Pub Date : 2014-03-01 DOI: 10.1016/j.bgm.2014.01.003
Wan-Lin Liao , Shao-Chieh Lin , H. Sunny Sun , Shaw-Jenq Tsai

Hypoxia is an intricate microenvironment associated with aggressiveness and chemoresistance of a variety of solid tumors. Hypoxia-inducible factors (HIFs) regulate downstream target genes that render cancer cells capacity to adapt to the hostile, low-oxygen stress for survival. HIF has been estimated to regulate more than 5% of total human genes. The HIF-regulated gene network has been shown to be associated with resistance to chemotherapy, metastasis, tumor recurrence, and reduced overall survival rate. With the increasing findings that microRNAs (miRNAs) are aberrantly expressed under hypoxia, which participate positively or negatively in regulating hypoxia-related genes, the signaling pathway of hypoxia becomes more and more complicated. Based on the roles of miRNAs in tumor development and drug resistance, the potential of targeting miRNAs as a therapeutic regimen has been emphasized recently. Therefore, understanding the regulation and functions of miRNAs in cancer cells will provide us with useful information for designing more efficacious treatment regimens. In this article, we will review the biological kinship of hypoxia and hypoxia-regulated miRNAs in cancer malignancy and drug resistance.

缺氧是一种复杂的微环境,与多种实体肿瘤的侵袭性和化疗耐药有关。低氧诱导因子(hif)调节下游靶基因,使癌细胞能够适应恶劣的低氧胁迫以生存。据估计,HIF调节了超过5%的人类基因。hif调控的基因网络已被证明与化疗耐药、转移、肿瘤复发和总生存率降低有关。随着越来越多的研究发现microRNAs (miRNAs)在缺氧条件下异常表达,并参与或正或负调节缺氧相关基因,使缺氧的信号通路变得越来越复杂。基于miRNAs在肿瘤发展和耐药中的作用,靶向miRNAs作为一种治疗方案的潜力最近得到了强调。因此,了解mirna在癌细胞中的调控和功能将为我们设计更有效的治疗方案提供有用的信息。在本文中,我们将回顾低氧和低氧调控的mirna在肿瘤恶性和耐药中的生物学亲和关系。
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引用次数: 18
期刊
Biomarkers and Genomic Medicine
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