Soluble HLA class I molecules: biological significance and clinical implications

Soluble class I human leukocyte antigens (sHLAs) have been detected in serum, sweat, lymphatic fluid, urine and cerebrospinal fluid. Their biological function has, however, remained a puzzle. The physiological concentration of sHLA varies more than tenfold depending on the phenotype of the individual, and is significantly upregulated in various diseases and during inflammation. This suggests that sHLAs might serve as a marker of pathological changes. Recent experiments have shown that, in vitro, sHLAs can modulate T-cell reactivity and induce cell-activated apoptosis, implicating sHLAs in the induction and maintenance of peripheral tolerance. Therefore, sHLAs have the therapeutic potential to induce tolerance to transplants.     

Regulation, clinical and biological significance of cathepsin D in breast cancer

The lysosomal protease, pro-cathepsin D, is overexpressed and secreted by human breast cancers. In estrogen-responsive breast cancer cell lines, estrogens and growth factors stimulate cathepsin D expression through distinct mechanisms. Clinical studies indicate that high cathepsin D concentration in primary breast cancers is correlated with an increased risk of metastasis and particularly useful to orientate node-negative tumors towards an adjuvant therapy.     

Measuring Soluble ICAM-1 in African Populations

The level of plasma soluble ICAM-1 (sICAM-1) has been associated with the pathogenesis of several diseases. Previously, a commercial antibody was reported not to recognize an ICAM-1 allele known as ICAM-1^kilifi prevalent among African populations. However, that study was based on 19 samples from African Americans of whom 13 had the wild type allele, five heterozygotes and one homozygote. Here, we compare plasma sICAM-1 measures using three different commercial antibodies in samples from Kenyan children genotyped for ICAM-1^kilifi allele. We show that two of these antibodies have some degree of deficiency in detecting the ICAM-1^kilifi allele. Consideration of the antibody used to measure sICAM-1 is important as up to 30% of the populations in Africa harbour this allele.     

Manganese superoxide dismutase in breast cancer: From molecular mechanisms of gene regulation to biological and clinical significance

Breast cancer is one of the most common malignancies of all cancers in women worldwide. Many difficulties reside in the prediction of tumor metastatic progression because of the lack of sufficiently reliable predictive biological markers, and this is a permanent preoccupation for clinicians. Manganese superoxide dismutase (MnSOD) may represent a rational candidate as a predictive biomarker of breast tumor metastatic progression, because its gene expression is profoundly altered between early and advanced breast cancer, in contrast to expression in the normal mammary gland. In this review, we report the characterization of some gene polymorphisms and molecular mechanisms of SOD2 gene regulation, which allows a better understanding of how MnSOD is decreased in early breast cancer and increased in advanced breast cancer. Several studies display the biological significance of MnSOD level in proliferation as well as in invasive and angiogenic abilities of breast tumor cells by controlling superoxide anion radical (O₂^•−) and hydrogen peroxide (H₂O₂). Particularly, they report how these reactive oxygen species may activate some signaling pathways involved in breast tumor growth. Emerging understanding of these findings provides an interesting framework for guiding translational research and suggests a way to define precisely the clinical interest of MnSOD as a prognostic and/or predicting marker in breast cancer, by associating with some regulators involved in SOD2 gene regulation and other well-known biomarkers, in addition to the typical clinical parameters.     

Soluble metals in the atmosphere and their biological implications

Multivariate statistical analysis has been applied to time series measurements of aerosol elemental composition from PIXE analysis of filter samples, and principal components have been resolved that represent distinct particle types in an external mixture in the atmosphere. In this study, it is argued that a combination of chemical and statistical analyses of the data may be more powerful in determining chemical species in atmospheric aerosols than studies that employ mainly direct chemical analysis of chemical species in unresolved mixtures of aerosol particle samples. Sulfur is generally associated with mineral dust elements. It is reasoned that the association may represent sulfuric acid coatings on particles that can lead to mineral dissolution and solubilization of significant amounts of aluminum, iron, and other metals. Upon wet or dry deposition to the surface, the fluxes of these metals in biologically-available form may be sufficient to affect primary productivity in the world ocean and cause ecological damage in lakes. As a consequence, the fluxes of biogenic trace gases to the atmosphere may be changed, possibly leading to changes in the tropospheric concentration of ozone. The inputs to lakes of soluble aluminum, which is toxic to fish, may be partly by deposition directly from the atmosphere, thus not limited to leaching of soils by acid deposition. Human inhalation of soluble aluminum and other solulilized mineral metals may account, in part, for the observed geographic pattern of deaths attributed to chronic obstructive pulmonary disease (COPD) that show high rates in cities of the Western US and the southeast region, but low in most of the midwest and northeast.     

Soluble ICAM-1: a marker of vascular inflammation and lifestyle

The circulating form of a membrane-bound intercellular adhesion molecule-1 (ICAM-1), has been the source of recent debate as a candidate marker of vascular inflammation in atherosclerosis and myocardial infarction, although its increased levels were also observed in other diseases affecting the cardiovascular system, such as myocarditis, inflammatory cardiomyopathy and heart failure per se. Faulty dietary habits, a sedentary mode of life, smoking, and alcohol abuse, are factors which at least in part contribute to atherosclerosis. This paper describes the responses of sICAM-1 levels to nutrients, physical activity, smoke exposure and alcohol consumption.     

Clinicopathological and biological significance of human voltage-gated proton channel Hv1 protein overexpression in breast cancer

In our previous work, we showed for the first time that the voltage-gated proton channel Hv1 is specifically expressed in highly metastatic human breast tumor tissues and cell lines. However, the contribution of Hv1 to breast carcinogenesis is not well known. In this study, we showed that Hv1 expression was significantly correlated with the tumor size (p = 0.001), tumor classification (p = 0.000), lymph node status (p = 0.000), clinical stage (p = 0.000), and Her-2 status (p = 0.045). High Hv1 expression was associated significantly with shorter overall (p = 0.000) and recurrence-free survival (p = 0.000). In vitro, knockdown of Hv1 expression in the highly metastatic MDA-MB-231 cells decreased the cell proliferation and invasiveness, inhibited the cell proton secretion and intracellular pH recovery, and blocked the cell capacity of acidifying extracellular milieu. Furthermore, the gelatinase activity in MDA-MB-231 cells that suppressed Hv1 was reduced. In vivo, the breast tumor size of the implantation of the MDA-MB-231 xenografts in nude mice that were knocked down by Hv1 was dramatically smaller than that in the control groups. The results demonstrated that the inhibition of Hv1 function via knockdown of Hv1 expression can effectively retard the cancer growth and suppress the cancer metastasis by the decrease of proton extrusion and the down-regulation of gelatinase activity. Based on these results, we came to the conclusion that Hv1 is a potential biomarker for prognosis of breast cancer and a potential target for anticancer drugs in breast cancer therapy.     

Ambra1 in cancer: implications for clinical oncology

Apoptosis - Activating molecule in Beclin-1-regulated autophagy protein 1 (Ambra1) is well known to mediate the autophagy process and promote the formation of autophagosomes. In addition, Ambra1 is...     

可溶性细胞间粘附分子-1在新生儿缺氧缺血性脑病血清中的表达及临床意义

目的:探讨可溶性细胞间粘附分子-1(ICAM-1)在新生儿缺氧缺血性脑病(HIE)血清中的表达及其与病情严重程度的关系。方法:采用酶联免疫吸附双抗体夹心法(ELISA)检测45例HIE新生儿和50例健康新生儿血清中可溶性ICAM-1水平。结果:HIE组血清可溶性ICAM-1浓度为(159.25±25.62)ng/ml,对照组血清可溶性ICAM-1浓度为(53.35±12.42)ng/ml,两组相比较有显著性并差异(P<0.05);轻、中、重度HIE患儿血清可溶性ICAM-1浓度与对照组比较显著升高(P<0.05),在HIE各组中可溶性ICAM-1浓度为重度>中度>轻度,各组相比较有显著性差异(P<0.05);HIE患儿血清可溶性ICAM-1水平与临床分度呈正相关相关(r=0.652,P<0.01)。结论:可溶性ICAM-1在HIE新生儿血清中呈高表达,可溶性ICAM-1的水平与病情严重程度密切相关。可溶性ICAM-l在新生儿缺氧缺血性脑损伤中起着重要作用。     

可溶性细胞间粘附分子-1在新生儿缺氧缺血性脑病血清中的表达及临床意义

目的：探讨可溶性细胞间粘附分子-1（ICAM-1）在新生儿缺氧缺血性脑病（HIE）血清中的表达及其与病情严重程度的关系。方法：采用酶联免疫吸附双抗体夹心法（ELISA）检测45例HIE新生儿和50例健康新生儿血清中可溶性ICAM-1水平。结果：HIE组血清可溶性ICAM-1浓度为（159．25±25．62）ng／ml,对照组血清可溶性ICAM-1浓度为（53．35±12．42）ng／ml,两组相比较有显著性并差异（P〈0．05）;轻、中、重度HIE患儿血清可溶性ICAM-1浓度与对照组比较显著升高（P〈0．05）,在HIE各组中可溶性ICAM-1浓度为重度〉中度〉轻度,各组相比较有显著性差异（P〈0．05）;HIE患儿血清可溶性ICAM-1水平与临床分度呈正相关相关（r=0．652,P〈0．01）。结论：可溶性ICAM-1在HIE新生儿血清中呈高表达,可溶性ICAM-1的水平与病情严重程度密切相关。可溶性ICAM-1在新生儿缺氧缺血性脑损伤中起着重要作用：     

EZH2在乳腺癌中的表达及其临床意义

目的 探讨EZH2在乳腺癌中的表达及其临床意义.方法 用免疫组化的方法研究105例乳腺癌中EZH2蛋白表达情况,并进一步探讨其与乳腺癌临床病理因素及其预后的关系.结果 EZH2蛋白在乳腺癌组织中表达明显高于乳腺良性疾病,其表达与患者年龄、肿瘤大小、TNM分期、PR和c-erbB-2表达无关(P＞0.05),与淋巴结转移、病理组织学分级、ER表达及乳腺癌预后相关(P＜0.05).EZH2蛋白表达在三阴性乳腺癌中表达明显高于非三阴性乳腺癌(P＜0.05).结论 EZH2在乳腺癌淋巴结转移及侵袭中扮演一定的角色,其与乳腺癌预后相关,与ER阴性的乳腺癌发生发展有关.     

Genetic characterization of breast cancer and implications for clinical management

Breast cancer is a genetic disease caused by the accumulation of mutations in neoplastic cells. In the last few years, high-throughput microarray-based molecular analysis has provided increasingly more coherent information about the genetic aberrations in breast cancer. New biomarkers and molecular techniques are slowly becoming part of the diagnostic and prognostic armamentarium available for pathologists and oncologists to tailor the therapy for breast cancer patients. In this review, we will focus on the contribution of breast cancer somatic genetics to our understanding of breast cancer biology and its impact on breast cancer patient management.     

Osteopontin overexpression in breast cancer: knowledge gained and possible implications for clinical management

Osteopontin (OPN) is a secreted protein that is overexpressed in a number of human cancers, and has been associated with increased metastatic burden and poor prognosis in breast cancer patients. The OPN protein contains several conserved structural elements including heparin- and calcium-binding domains, a thrombin-cleavage site, a CD44 binding site, and two integrin-binding sites. Experimental studies have shown that the ability of OPN to interact with a diverse range of factors, including cell surface receptors (integrins, CD44), secreted proteases (matrix metalloproteinases, urokinase plasminogen activator), and growth factor/receptor pathways (TGFalpha/EGFR, HGF/Met) is central to its role in malignancy. These complex signaling interactions can result in changes in gene expression, which ultimately lead to alterations in cell properties involved in malignancy such as adhesion, migration, invasion, enhanced tumor cell survival, tumor angiogenesis, and metastasis. Therefore, OPN is not merely associated with cancer, but rather it plays a multi-faceted functional role via complex molecular cross-talk with other factors. This review will focus on the role of OPN in breast cancer, in particular on the malignancy-promoting aspects of OPN that may reveal opportunities for new approaches to the clinical management of breast cancer.     

Interleukin-18: biological properties and clinical implications

IL-18, originally identified as interferon-gamma inducing factor (IGIF), is related to the IL-1 family in terms of its structure, processing, receptor, signal transduction pathway and pro-inflammatory properties. IL-18 is also functionally related to IL-12, as it induces the production of Th1 cytokines and participates in cell-mediated immune cytotoxicity. This review summarizes the recent advances in the understanding of IL-18 structure, processing, receptor expression and immunoregulatory functions, and focuses on the role of IL-18 modulation in tumours, infections, and autoimmune and inflammatory diseases.     

IL-20: biological functions and clinical implications

Summary IL-20 belongs to the IL-10 family and plays a role in skin inflammation and the development of hematopoietic cells. Little is known about its other biological functions and clinical implications, however. Updated information about IL-20, such as its identification, expression, receptors, signaling, biological activities, and potential clinical implications, is illustrated in this review based on our research and on data available in the literature. Our studies of IL-20 show that it is a pleiotropic cytokine with potent inflammatory, angiogenic, and chemoattractive characteristics. Inflammation and angiogenesis are essential for the pathogenesis of rheumatoid arthritis and atherosclerosis. Based on in vitro data and clinical samples, we demonstrated that IL-20 is involved in the diseases of rheumatoid arthritis and atherosclerosis. In addition, we found in our studies that IL-20 signaled through different molecules in several cells. The present review presents the clinical implications of IL-20 in rheumatoid arthritis and atherosclerosis. It may provide new therapeutic options in the future.This work was supported by a grant from Chi-Mei Medical Center, Tainan, Taiwan.     

ICAM-1和CD44v6在结、直肠癌中的表达及临床意义

目的:了解ICAM-1和CD44v6在结、直肠癌中的表达,探讨它们与结直肠癌侵袭与转移的关系.方法:应用免疫组织化学pv-9000二步法检测ICAM-1和CD44v6在40例结直肠癌和30例大肠良性腺瘤组织中的表达情况,并分析其与结直肠癌临床病理特征的关系.结果:40例结、直肠癌和30例大肠良性腺瘤中,ICAM-1的表达阳性率分别是72.5%(29/40)、33.3%(10/30),CD44v6的表达阳性率分别是88.9%(27/40)、26.7%(8/30). ICAM-1和CD44v6的表达与年龄、性别、肿瘤细胞分化程度无关,但与淋巴结转移、Dukes分期具有相关性(p<0.05).有淋巴结转移、Dukes分期在C+D期者,ICAM-1和CD44v6的表达阳性率均明显升高.ICAM-1和CD44v6在大肠良性腺瘤中呈低表达或不表达.ICAM-1和CD44v6两者均阳性表达时,其预测结、直肠癌淋巴结转移的特异性升高,有一定的临床意义.结论:CD44v6和ICAM-1的阳性表达预示结直肠癌具有较强的侵袭转移能力,可作为预测结直肠癌转移潜能的生物学指标.     

Prognostic significance of CHAC1 expression in breast cancer

Molecular Biology Reports - An emerging component of Unfolded Protein Response (UPR) pathway, cation transport regulator homolog 1 (CHAC1) has been conferred with the ability to degrade...     

Aberrant expression of Arpin in human breast cancer and its clinical significance

Arpin (Arp2/3 complex inhibitor), a novel protein found in 2013, plays a pivotal role in cell motility and migration. However, the precise role of Arpin in cancer is unclear. This study investigated the expression of Arpin in breast cancer and evaluated its correlation with the characteristics of clinical pathology and prognosis of breast cancer patients. Immunohistochemistry (IHC) for Arpin protein was performed on formalin‐fixed, paraffin‐embedded 176 breast cancer tissues and 43 normal breast tissues while qRT‐PCR for Arpin mRNA with 104 paired tumour and paratumoural tissues from breast cancer patients respectively. The association of Arpin expression with clinical pathological features and survival was assessed in a retrospective cohort analysis of patients. The results showed that the expression of Arpin protein in cancer tissues was lower compared to that in normal breast and the expression of Arpin mRNA was also lower in cancer tissues than that in the matched paratumoural tissues. Among the 176 breast cancer patients, the lower expression of Arpin was significantly associated with advanced tumour, nodes and metastasis system stage, and the reduced Arpin expression was strongly associated with axillary lymph node metastasis using univariate and multivariate logistic regression analysis [odds ratio: 3.242; 95% confidence interval (CI): 1.526, 6.888; P < 0.05]. Furthermore, Arpin expression was an independent risk factor for recurrence‐free survival (HR: 0.373; 95% CI: 0.171, 0.813; P < 0.05). As Arpin expression was first examined in human breast cancer tissues with qRT‐PCR and IHC, our results suggest that Arpin downregulation may contribute to the initiation and development of breast cancer metastasis. Therefore, as a potential predictive marker, Arpin deserves future studies.