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991.
H.S. Ciftci M.S. Karadeniz T. Tefik Y. Caliskan H. Yazıcı E. Demir A. Turkmen I. Nane F.S. Oguz F. Aydin 《Transplantation proceedings》2017,49(3):490-496
Background
Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression. Clinically relevant drug-drug interactions have been described between immunosuppressive drugs. In the present study, we investigated the drug interaction between MPA and lansoparazole or rabeprazole and the impact of CYP2C19 polymorphisms on these drug interactions after renal transplantation.Materials and Methods
A total of 125 renal transplant patients taking MPA derivatives between 2012 and 2016 were included in this study. The 125 patients were divided into 6 groups: MMF/tacrolimus/steroid together with lansoprazole or rabeprazole; MYF/tacrolimus/steroid together with lansoprazole or rabeprazole and without PPI. The single nucleotide polymorphisms of CYP2C19 were determined by the polymerase chain reaction-restriction fragment length polymorphism. Plasma concentrations of MPA were measured by cloned enzyme donor immunoassay. Clinical parameters such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine, toxicity, and gastrointestinal adverse effects were analyzed retrospectively.Results
The mean concentrations of MPA in the MYF group were higher than those in the MMF group. The mean dose-adjusted blood concentration of MPA coadministered with lansoprazole was lower than that of MPA with rabeprazole or without PPI in MMF and MYF groups (P < .05). In patients with the CYP2C19*2/*2 genotype, the mean concentrations of MMF with lansoprazole were significantly lower than those with rabeprazole with MMF or without PPI (P < .05). Gastrointestinal side effects were significantly higher in MMF with lansoprazole group than in MYF with lansoprazole group (P < .05). However, no differences were found according to genotype distribution in all groups (P > .05).Conclusion
Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. Both genetic and clinical factors in pharmacokinetics may help to make further progress toward individualized therapy to yield maximum efficacy with minimal side effects. 相似文献992.
冯道夫|何向辉|章志翔 《中国普通外科杂志》2017,26(4):468-472
目的:探讨与进展期胃癌对替吉奥胶囊联合奥沙利铂(SOX)新辅助化疗敏感性有关的基因及信号通路。方法:收集15例III期胃癌患者术后标本,其中6例SOX新辅助化疗后缓解(缓解组)、6例SOX新辅助化疗后未缓解(未缓解组),3例未行新辅助化疗(未化疗组),在用高通量基因芯片法检测各组标本基因表达谱后,以DNA损伤修复和叶酸代谢方面为重点分析对象,用系统性生物信息学技术筛选出差异基因,并通过KEGG来解释每个差异表达基因所在通路。结果:3组标本的基因表达谱存在明显差异。缓解组与未缓解组间的差异基因主要集中在细胞因子相互作用和NK细胞介导的细胞毒性作用通路上。与未缓解组比较,缓解组与DNA损伤修复相关的3个基因(HUS1、RECQL5、XRCC4)明显上调和1个基因(GADD45G)明显下调;3组间在叶酸代谢方面未找到任何差异基因。结论:影响进展期胃癌SOX新辅助化疗敏感性的基因可能与免疫信号传导有关,相关的基因检测对评估胃癌SOX新辅助化疗效果有一定的意义。 相似文献
993.
Ilaria Giusti Marianna Di Francesco Sandra D'Ascenzo Maria Grazia Palmerini Guido Macchiarelli Gaspare Carta 《Cancer biology & therapy》2018,19(8):722-734
It has become clear that non-tumor cells in the microenvironment, especially fibroblasts, actively participate in tumor progression. Fibroblasts conditioned by tumor cells become “activated” and, as such, are identified as CAFs (cancer-associated fibroblasts). These CAFs remodel the tumor stroma to make it more favourable for cancer progression. The aim of this work was to verify whether EVs (extracellular vesicles - whose role as mediators of information between tumor and stromal cells is well known) released from human ovarian cancer cells were able to activate fibroblasts. EVs isolated from SKOV3 (more aggressive) and CABA I (less aggressive) cells were administered to fibroblasts. The consequent activation was supported by morphological and molecular changes in treated fibroblasts; XTT assays, zymographies, wound healing tests and invasion assays also highlighted higher proliferation, motility, invasiveness and enzyme expression. The secretome of these “activated” fibroblasts was, in turn, able to modulate the responses (proliferation, motility and invasion) of fibroblasts, and of tumor and endothelial cells. These findings support the idea that ovarian cancer cells can modulate fibroblast behaviour through the release of EVs, activating them to a CAFs-like state; the latter are able, in turn, to stimulate the surrounding cells. EVs from SKOV3 rather than from CABA I seem to be more efficient in some processes. 相似文献
994.
随着围生医学的不断发展,早产低出生体重儿成活率显著提高,而其脑损伤的发病率亦逐年增加。早产儿脑损伤以脑室内出血及脑白质损伤为主,是早产儿神经系统后遗症的主要原因,已成为影响早产儿生存质量的严重问题。早产儿脑损伤病因复杂,难以避免,早期诊断与及时合理的干预尤为重要。由于早产儿脑损伤早期缺乏特异性的临床表现,目前诊断有赖于影像学检查。脑损伤生物学标记物,如:髓鞘碱性蛋白、S100B、激活素 A、脑红蛋白、基质金属蛋白酶、细胞因子 IL-6、IL-10、IL-11、神经元特异性烯醇化酶、肾上腺髓质素、胶质纤维酸性蛋白等,近年来引起了国内外学者的极大关注。该文对上述相关生物标志物进行综述。 相似文献
995.
椎间盘退变所致的颈肩腰腿痛严重影响许多患者的生活及工作,目前的治疗方法主要侧重于缓解疼痛症状或神经受压症状,而无法阻止椎间盘退变的进程,导致疾病具有高复发率。近年来学者们开始广泛研究椎间盘退变的生物学治疗方法,即通过生物分子治疗、基因治疗、细胞治疗和组织工程等方法来修复和重塑椎间盘,以期从根本上解决椎间盘退变的问题,而上述方法大多处于动物实验或体外实验阶段,临床应用尚存在诸多挑战。 相似文献
996.
The endoplasmic reticulum aminopeptidases (ERAPs), ERAP1 and ERAP2, makes a role in shaping the HLA class I peptidome by trimming peptides to the optimal size in MHC-class I-mediated antigen presentation and educating the immune system to differentiate between self-derived and foreign antigens. Association studies have shown that genetic variations in ERAP1 and ERAP2 genes increase susceptibility to autoimmune diseases, infectious diseases, and cancers. Both ERAP1 and ERAP2 genes exhibit diverse polymorphisms in different populations, which may influence their susceptibly to the aforementioned diseases. In this article, we review the distribution of ERAP1 and ERAP2 gene polymorphisms in various populations; discuss the risk or protective influence of these gene polymorphisms in autoimmune diseases, infectious diseases, and cancers; and highlight how ERAP genetic variations can influence disease associations. 相似文献
997.
Sandip Basu Ayse Mavi Tevfik Cermik Mohamed Houseni Abass Alavi 《Molecular imaging and biology》2008,10(1):62-66
Objectives Tumor glycolytic activity as determined by 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography (FDG-PET) imaging is an important marker of tumor biology and provides critical information
about the behavior of most malignancies at different stages of the disease. This study was undertaken to determine whether
the degree of FDG uptake differs between the primary breast lesions with varying disease burden at diagnosis in proven cases
of breast carcinoma.
Materials and Methods Among 250 patients enrolled for this prospective study, 174 patients with newly diagnosed breast carcinoma at different disease
stages who had undergone dual time point FDG-PET before any therapeutic or surgical interventions were considered for inclusion
in this analysis. These patients prospectively underwent multimodality imaging techniques, such as magnetic resonance imaging
(MRI), ultrasonography, digital mammography, computed tomography (CT), and dual time point FDG-PET, as a component of a National
Institutes of Health-funded project for characterizing primary breast lesions and local–regional staging. The slice with maximum
FDG uptake in the region of interest (ROI) was chosen for the first time point and the second time point images for quantitative
measurement of the metabolic activity of the tracer (SUVmax1 and SUVmax2, respectively). Furthermore, the percent change in
SUVmax (%ΔSUVmax) between SUVmax1 and SUVmax2 was calculated.
Results The patient population (n = 174) were divided into three groups for the purposes of this study. Sixty-four patients with primary and metastatic axillary
lymphadenopathy (designated as group I) and 18 patients with both axillary and distant metastases (designated as group II)
met the inclusion criteria for this analysis. The third group (group III) comprised of a population of 92 patients without
any metastasis either at the lymph nodes or at distant sites. The mean SUVmax1, SUVmax2, and the %ΔSUVmax in the early and
delayed FDG-PET in group I (n = 64) patients were as follows: primary lesion 4.8 ± 3.9, 5.3 ± 4.5, and 9.4 ± 12.8%, respectively, and axillary lesions
3 ± 2.6, 3 ± 2.7, and 1.1 ± 21.3%, respectively. Among the group II patients (n = 18), the mean values of the primary lesion with regard to the SUVmax1, SUVmax2, and the %ΔSUVmax were 7.7 ± 6.2, 8.9 ± 7.1,
and 15.7 ± 10.8%, respectively. The corresponding figures for the axillary lesions were 3.5 ± 3.1, 3.7 ± 3.1, and 6.3 ± 20.9%,
respectively, and those for the distant metastatic lesions were 3 ± 1.4, 3.1 ± 1.2, and 8.5 ± 21.2%, respectively. The mean
SUVmax1, SUVmax2, and the %ΔSUVmax of the primary lesion of group III patients (n = 92) without any metastasis were 2.9 ± 2.7, 3.4 ± 2.4, and 4.5 ± 4.2%, respectively. Unifactorial ANOVA of the three parameters
among the primary lesions of these three groups were statistically significant with regard to the mean SUVmax1 (p = 0.01) and SUVmax2 (p = 0.01). These values in the primary lesions were highest in group II (those with both axillary and distant metastases),
followed by group I (those with only metastatic axillary adenopathy) and group III (patients without any metastasis), and
could be related to the more aggressive tumor biology in group II.
Conclusion The findings provide evidence that among the lesions with varying disease burden at diagnosis, the FDG uptake is highest in
cases with both axillary and distant metastasis, followed by those with axillary metastasis and then by those with no metastatic
disease. These provide in vivo insight into tumor biology as FDG uptake is regarded as a surrogate marker of the same. 相似文献
998.
Molecular,structural, and biological characteristics of the tumor necrosis factor ligand superfamily 总被引:7,自引:0,他引:7
H. -J. Gruss 《International Journal of Clinical & Laboratory Research》1996,26(3):143-159
The tumor necrosis factor receptor superfamily at present consists of ten different transmembrane (type I) glycoproteins with
characteristic limited sequence homology for the cysteine-rich repeats in the extracellular domain. In parallel the tumor
necrosis factor ligand superfamily has been recognized by discovery of ligands for all members of the receptor superfamily.
These molecules are also transmembrane (type II) glycoproteins, with the exception of lymphotoxin-α which is the only entirely
secreted protein of the tumor necrosis factor-like proteins. Several members of the ligand superfamily, including tumor necrosis
factor and CD95L also exist in a biologically active soluble form. The tumor necrosis factor ligand superfamily contains at
present ten different proteins. In addition, NGFR p75 binds to a second family of proteins (neurotrophins). These nerve growth
factor-like dimeric soluble molecules are basic neurotrophic factors and the five members (NGF, BDNF, NT-3, NT-4, NT-5) are
not related to the tumor necrosis factor superfamily ligands. The members of the tumor necrosis factor ligand superfamily
(TNF, LT-α, LT-β, CD27L, CD30L, CD40L, CD95L, 4-1BB, OX40L, TRAIL) share common biological activities, but some properties
are shared by only some ligands, while others are unique. The diverse biological activities but some properties are shared
by only some ligands, while others are unique. The diverse biological activities triggered through tumor necrosis factor receptors
have been linked to the regulation of cellular activation, including immune responses and inflammatory reactions, but also
with the pathology of a series of human diseases. 相似文献
999.
1000.