Opa Interacting Protein 5 (OIP5) Is a Novel Cancer-testis Specific Gene in Gastric Cancer

Background Identification of novel cancer-specific antigens is important for the advancement of immunotherapy. Our aim was to identify cancer-specific genes in gastric cancer. Methods Using cDNA microarray analysis, we detected genes overexpressed specifically in gastric cancer cells. The expression levels of selected genes, including OIP5, was confirmed by real time RT-PCR analysis in tumor/normal paired bulk samples of 58 clinical cases. The expression levels of selected genes in normal tissues were also determined with a human total RNA master panel. We also compared the expression status of OIP5 with that of the other known cancer-testis specific genes. Results Twenty-two genes were determined to be upregulated in gastric cancer cells. Among these, three genes (CDC6, Exo1, and OIP5) were selected and confirmed to be upregulated in the tumor tissue compared to normal tissue. A human total RNA master panel demonstrated that OIP5, but not Exo1 or CDC6, showed high specificity in testis. Thus OIP5 may be considered a cancer-testis specific gene. In 58 clinical cases of gastric cancer examined, we found OIP5 gene expression in 27 cases (47%). Thirteen of these 27 cases showed no expression of the known cancer specific genes such as MAGE-1, MAGE-3 or NY-ESO-1. Conclusions Using a combination of LMD and microarray, we identified OIP5 as a cancer-testis specific gene. Further expression analysis in a set of clinical cases revealed that OIP5 may be a novel immunotherapy target for patients with gastric cancer. Grant sponsors: CREST, JST; Uehara Memorial Foundation; Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research, grant numbers 17015032, 17109013, 17591411, 17591413, and 16390381; Health and Labour Sciences Research Grants; Third Term Comprehensive Control Research for Cancer, 16271201.     

胰激肽原酶肠溶片对早期糖尿病肾病36例疗效观察

目的观察胰激肽原酶肠溶片(TPK)治疗糖尿病早期肾病,减少尿微量白蛋白的作用。方法36例早期2型糖尿病肾病患者,随机分组,连续三个月给予胰激肽原酶肠溶片治疗,比较治疗前后患者尿微量清蛋白排出量。结果胰激肽原酶肠溶片对早期糖尿病肾病尿微量清蛋白明显减少。结论胰激肽原酶肠溶片对减少早期糖尿病肾病微量清蛋白尿有明显效果。     

人参细粉与超微颗粒的急性毒性实验——半数致死量（LD50）与最大耐受量（MTD）的测定

目的：评价人参细粉与人参超微颗粒的急性毒性。方法：对小鼠1日3次分别灌胃人参细粉和人参超微颗粒,观察7d内小鼠的毒性反应及死亡情况。结果：小鼠的人参细粉和人参超微颗粒的半数致死量（LD50）未测得,最大耐受量（MTD）是7.38g/kg。结论：人参细粉和人参超微颗粒在临床常用剂量口服给药是安全的。     

Relevance of microRNAs in normal and malignant development, including human testicular germ cell tumours

The dogma of genome functionality has recently been challenged by identification of non-protein-encoding RNAs, including mi(cro)RNAs. These relatively small sequences interact with mRNA and in the mammalian system, are involved in fine-tuning the process of translation. miRNAs have been found to be of crucial importance for normal development, including stem cell formation. Recent interesting fundamental observations will be discussed in this paper, as well as their impact on the genesis of human germ cell tumours (GCTs), in particular those of the adult testis, seminomas and non-seminomas (type II), and spermatocytic seminomas (type III). miRNA cluster 371-373 is specifically involved in inhibition of cellular senescence induced by oncogenic stress in the type II GCTs. This explains the unusual presence of wild type P53, characteristic of this type of solid cancer. Specific sets of differentiating miRNA were found to characterize the various differentiation lineages within the GCTs, which simulate normal embryonic development.     

Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis

The EGF/IGF growth factors are potent mitogens that regulate cell proliferation and cell survival and are involved in prostate cancer development. Using laser microdissection technology and real-time PCR, together with immunohistochemistry, we have explored the growth factor and integrin dependent PI3-kinase/PTEN/Akt signalling pathway in prostate cell lines and tumour samples by analysing EGF-R, IGF1-R, ILK, beta3 integrin, PTEN and p-Akt protein expression. We provide evidence that loss of PTEN expression rather than upregulated EGF/IGF1 receptor expression was responsible for increased p-Akt in neoplastic prostate cells. We therefore compared PTEN expression in patient biopsies at first time diagnosis recruited prospectively (Study I, 112 patients) and patients with confirmed metastasis recruited retrospectively from the Luxembourg cancer registry (Study II, 42 patients). In Study I, loss of PTEN expression at first time diagnosis was found in 26 of 112 patients (23%). In Study II, 25 of the 42 patients (59%) with lymph node metastasis had complete loss of PTEN expression in both the neoplastic glands of the prostate and the invasive prostate cancer cells in the lymph node, and of these 13 (52%) exhibited already loss of PTEN expression at first diagnosis. These findings demonstrate that loss of PTEN expression is an important factor in progression towards metastatic disease and could potentially serve as an early prognostic marker for prostate cancer metastasis.     

Rabbit pilot study on the resorbability of three-dimensional bioactive glass fibre scaffolds

Bioactive glass composed of Na2O-K2O-MgO-CaO-B2O3-P2O5-SiO2 is used in this study to manufacture three-dimensional glass fibre scaffolds for a synthetic bone filler material for the treatment of bone defects. The glass is characterized by a large working range, which is the temperature interval at which forming of glass can take place. A preliminary in vivo study on New Zealand skeletally mature rabbit's tibia is reported here. Bone defects were prepared in the medial surfaces of the diaphyses of the tibia. For the first time melt derived three-dimensional bioactive glass fibre constructs were used to fill the cavities. The different implants investigated here were a scaffold with a porosity of 45-50%, scaffold with a porosity of 55-60% and morsels with a porosity of 55-60%. The implanted bone substitutes were dissected after 6 months and evaluated by histological and synchrotron radiation micro tomography analysis. PerioGlas and empty defects were used as positive and negative controls, respectively. The result was that the surgically created tibial defects were healed and new bone formation was found in the medullary cavities. Despite the intrinsic limitations of a pilot study, the preliminary results indicate that in 6 months the glass fibre scaffolds are completely resorbed and that the osteoconductive properties of the filling material are strictly correlated with the structural and morphological characteristics of the bone substitute.     

基于显微图像的血虚证大鼠肠系膜微循环变化研究

目的:观察血虚证大鼠肠系膜微循环变化,并测量其血液流速.方法:通过皮下注射乙酰苯肼( APH)制备血虚证大鼠模型,运用BI-2000医学图像分析系统观测血虚大鼠肠系膜微循环损伤的变化,采集微循环显微图像,并利用LabVIEWIMAQ VISION平台进行图像处理分析,提供一种跟踪白细胞团的微循环血液流速测量方法.结果:①血虚大鼠肠系膜微循环血色暗淡,微血管变形,管壁受损;②测得的大鼠肠系膜微循环血液流速与现代文献研究十分吻合,精确度提高,再现性良好.③血虚模型组大鼠肠系膜微循环血液流态呈粒线流甚至聚集流改变,且血液流速较正常组明显减慢,具有显著性差异(P＜0.05).结论:血虚大鼠微循环存在供血不足、血流瘀滞、管壁损伤和渗出出血等多重病理改变;运用LabVIEW图像处理方法测量血液流速,客观地反映了血虚大鼠微循环的病理改变,表明显微医学图像分析技术在中医血虚证研究中具有良好的应用前景.     

The micro‐Ames test: A direct comparison of the performance and sensitivities of the standard and 24‐well plate versions of the bacterial mutation test

“Ames” bacterial mutation tests are widely performed for evaluation and registration of new materials including industrial chemicals, agrochemicals, medical devices, pharmaceuticals, pharmaceutical impurities and other materials. Tests are used to predict their potential long‐term adverse health effects (including carcinogenicity). Given their importance, pre‐screening ‘miniaturized’ versions have been developed which allow higher throughput and use less test material, including the widely‐employed 24‐well micro‐Ames (µAmes) test which uses 20 times less material. However, little quantitative information has been published on the methodology or sensitivity of this system. We describe methods and results used in direct comparisons of the sensitivity of micro and standard systems using the same cultures, formulations, etc. Initial testing utilized the plate incorporation method and, later, the pre‐incubation method. In a subsequent phase of testing, a four‐way direct comparison was made between the pre‐incubation and plate incorporation methods in both systems using some direct‐acting mutagens. Tests used only those strain/S9/chemical combinations where a response was expected. Historical control results accumulated during testing are also presented. Spontaneous and induced revertant colony counts for the µAmes system were consistently proportionate and approximately 1/20th those for the standard Ames test. Sensitivities of the two systems were found to be nearly identical in almost all cases for a wide variety of weak and strong inorganic and organic mutagens. Standardized procedures and increased reliability of the estimate of the background revertant frequency in the µAmes system means that the two systems give equivalent results and are expected to be highly predictive of one another. Environ. Mol. Mutagen. 57:687–705, 2016. © 2016 Wiley Periodicals, Inc.     

A potential mechanism for allometric trabecular bone scaling in terrestrial mammals

Trabecular bone microstructural parameters, including trabecular thickness, spacing, and number, have been reported to scale with animal size with negative allometry, whereas bone volume fraction is animal size‐invariant in terrestrial mammals. As for the majority of scaling patterns described in animals, its underlying mechanism is unknown. However, it has also been found that osteocyte density is inversely related to animal size, possibly adapted to metabolic rate, which shows a negative relationship as well. In addition, the signalling reach of osteocytes is limited by the extent of the lacuno‐canalicular network, depending on trabecular dimensions and thus also on animal size. Here we propose animal size‐dependent variations in osteocyte density and their signalling influence distance as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. Using an established and tested computational model of bone modelling and remodelling, we run simulations with different osteocyte densities and influence distances mimicking six terrestrial mammals covering a large range of body masses. Simulated trabecular structures revealed negative allometric scaling for trabecular thickness, spacing, and number, constant bone volume fraction, and bone turnover rates inversely related to animal size. These results are in agreement with previous observations supporting our proposal of osteocyte density and influence distance variation as a potential mechanism for negative allometric trabecular bone scaling in terrestrial mammals. The inverse relationship between bone turnover rates and animal size further indicates that trabecular bone scaling may be linked to metabolic rather than mechanical adaptations.     

Membrane lipid interactions in intestinal ischemia/reperfusion-induced Injury

Ischemia, lack of blood flow, and reperfusion, return of blood flow, are a common phenomenon affecting millions of Americans each year. Roughly 30,000 Americans per year experience intestinal ischemia-reperfusion (IR), which is associated with a high mortality rate. Previous studies of the intestine established a role for neutrophils, eicosanoids, the complement system and naturally occurring antibodies in IR-induced pathology. Furthermore, data indicate involvement of a lipid or lipid-like moiety in mediating IR-induced damage. It has been proposed that antibodies recognize exposure of neo-antigens, triggering action of the complement cascade. While it is evident that the pathophysiology of IR-induced injury is complex and multi-factorial, we focus this review on the involvement of eicosanoids, phospholipids and neo-antigens in the early pathogenesis. Lipid changes occurring in response to IR, neo-antigens exposed and the role of a phospholipid transporter, phospholipid scramblase 1 will be discussed.