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Felix C F Schmitt, Eduardo Salgado, Janina Friebe, Thomas Schmoch, Florian Uhle, Thomas Fleming, Johanna Zemva, Lars Kihm, Christian Nusshag, Christian Morath, Martin Zeier, Thomas Bruckner, Arianeb Mehrabi, Peter P Nawroth, Markus A Weigand, Stefan Hofer, Thorsten Brenner
BACKGROUND: A prolonged cold ischemia time (CIT) is suspected to be associated with an increased ischemia and reperfusion injury (IRI) resulting in an increased damage to the graft. METHODS: In total, 91 patients were evaluated for a delayed graft function within 7 days after kidney transplantation (48 deceased, 43 living donors). Blood and urine samples were collected before, immediately after the operation, and 1, 3, 5, 7 and 10 days later. Plasma and/or urine levels of total keratin 18 (total K18), caspase-cleaved keratin 18 (cc K18), the soluble receptor for advanced glycation end-products (sRAGE), tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein-7 ([TIMP-2]×[IGFBP7]) were measured...
March 5, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Donghai Xiong, Jing Pan, Yuxin Yin, Hui Jiang, Eva Szabo, Ronald A Lubet, Yian Wang, Ming You
Lung squamous cell carcinoma (LUSC) is a major subtype of Non-Small Cell Lung Cancer. To increase our understanding of the LUSC pathobiology, we performed exome sequencing and RNA-seq in 16 murine carcinogen-induced LUSC tumors and 8 normal murine lung tissue samples. Additionally, we conducted single-cell RNA-seq on two independent tumors from the same murine model. We identified a list of 59 cancer genes recurrently mutated in the mice LUSC tumors, 47 (80%) of which were also mutated in human LUSCs. At the single cell level, we detected unique clonal mutation patterns for each of the two LUSC tumors, being initiated from clones carrying the mutant Igfbp7 and Trp53 genes, respectively...
January 26, 2018: Oncotarget
Laura Di Leo, Federico Nalesso, Francesco Garzotto, Yun Xie, Bo Yang, Grazia Maria Virzì, Alberto Passannante, Raffaele Bonato, Mariarosa Carta, Davide Giavarina, Dario Gregori, Alessandra Brendolan, Fiorenza Ferrari, Claudio Ronco
BACKGROUND: Acute kidney injury (AKI) diagnosis is based on a rise in serum creatinine and/or fall in urine output. It has been shown that there are patients that fulfill AKI definition but do not have AKI, and there are also patients with evidence of renal injury who do not meet any criteria for AKI. Recently the innovative and emerging proteomic technology has enabled the identification of novel biomarkers that allow improved risk stratification. METHODS: Tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7) were measured to a cohort of 719 consecutive patients admitted to Intensive Care Unit (ICU)...
January 26, 2018: Blood Purification
Takahiro Yoshioka, Kazuhiko Shien, Kei Namba, Hidejiro Torigoe, Hiroki Sato, Shuta Tomida, Hiromasa Yamamoto, Hiroaki Asano, Junichi Soh, Kazunori Tsukuda, Takeshi Nagasaka, Toshiyoshi Fujiwara, Shinichi Toyooka
Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-HER2 drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. At first, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs...
February 21, 2018: Cancer Science
Feng Li, Chen-Yang Qiao, Shuai Gao, Yu-Chen Fan, Long-Yan Chen, Kai Wang
BACKGROUND AND AIM: The initiation and progression of hepatocellular carcinoma (HCC) is a multistage process involving a variety of changes at the gene level. Insulin-like growth factor binding protein 7 (IGFBP7) methylation plays a crucial role in HCC development. The main purpose of this study was to investigate the relationship between oxidative stress, DNA methyltransferases (DNMTs) expression and IGFBP7 methylation, and to evaluate the prognostic value of serum IGFBP7 methylation status in patients with HCC after hepatectomy...
February 20, 2018: Free Radical Research
Zhenzhu Song, Zhongchao Ma, Kai Qu, Sinan Liu, Wenquan Niu, Ting Lin
Acute kidney injury (AKI) most commonly occurs in critically ill and postoperative patients. Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are two newly-identified urinary biomarkers that can help to detect early AKI, yet their predictive accuracies range widely. Here, we conduct a systematic meta-analysis to evaluate the diagnostic values of [TIMP-2] x [IGFBP7] for AKI at different detection times and cutoff levels. Ten studies were meta-analyzed on 1606 patients...
November 21, 2017: Oncotarget
Wei Zhang, Erman Chen, Mo Chen, Chenyi Ye, Yiying Qi, Qianhai Ding, Hang Li, Deting Xue, Xiang Gao, Zhijun Pan
Insulin-like growth factor-binding protein 7 (IGFBP7), a low-affinity IGF binder, may play an important role in bone metabolism. However, its function in osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we investigated its effects on osteogenic differentiation. Overexpression of IGFBP7 enhanced the expression of osteo-specific genes and proteins, and IGFBP7 knockdown decreased osteogenesis-specific markers. More mineral deposits and higher alkaline phosphatase activity were observed after the up-regulation of IGFBP7 Moreover, β-catenin levels were up-regulated by the overexpression of IGFBP7 or the addition of extracellular IGFBP7 protein and were reduced by the depletion of IGFBP7 The increase in osteogenic differentiation due to the overexpression of IGFBP7 was partially decreased by specific Wnt/β-catenin signaling inhibitors...
December 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
J Yang, S Y Lim, M-G Kim, C-W Jung, W-Y Cho, S-K Jo
BACKGROUND: Recently, urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-7 (IGFBP-7), markers for G1 cell cycle arrest, have been identified and validated in predicting the development of acute kidney injury in critically ill patients. It is unknown, however, whether these two biomarkers could predict the development of delayed graft function (DGF) after kidney transplantation (KT). METHODS: This is a single-center, prospective, observational study...
November 2017: Transplantation Proceedings
Chiara Levante, Fiorenza Ferrari, Chiara Manenti, Faeq Husain-Syed, Marta Scarpa, Tommaso Hinna Danesi, Massimo De Cal, Valentina Corradi, Grazia M Virzì, Alessandra Brendolan, Federico Nalesso, Pércia Bezerra, Salvador Lopez-Giacoman, Sara Samoni, Mara Senzolo, Davide Giavarina, Loris Salvador, Raffaele Bonato, Silvia De Rosa, Enrico Rettore, Claudio Ronco
BACKGROUND AND PURPOSE: Acute Kidney Injury (AKI) is a severe complication affecting many hospitalized patients after cardiac surgery, with negative impacts on short- and long-term clinical outcomes and on healthcare costs. Recently, clinical interest has been aimed at defining and classifying AKI, identifying risk factors and developing diagnostic strategies to identify patients at risk early on. Achieving an early and accurate diagnosis of AKI is a crucial issue, because prevention and timely detection may help to prevent negative clinical outcomes and avoid AKI-associated costs...
November 24, 2017: International Journal of Artificial Organs
Cédrick Zaouter, Frédérique Priem, Lionel Leroux, Guillaume Bonnet, Marie-Lise Bats, Marie-Christine Beauvieux, Alain Rémy, Alexandre Ouattara
BACKGROUND: Acute kidney injury (AKI) is a frequent complication after a transcatheter aortic valve implantation (TAVI). Biomarkers such as urinary G1 cell cycle arrest proteins (TIMP-2 and IGFBP7) and sonographic evaluation (Doppler Renal Resistive Index [RRI]) have been advocated to predict AKI at an early stage after a TAVI-procedure. The primary aim was to determine the predictive value of these markers to detect AKI after a TAVI-procedure at an early phase. PATIENTS AND METHODS: In a prospective observational study, 62 consecutive patients were scheduled for a TAVI...
November 13, 2017: Anaesthesia, Critical Care & Pain Medicine
Daniela Knafl, Markus Müller, Sahra Pajenda, Zeynep Genc, Manfred Hecking, Ludwig Wagner
BACKGROUND: Acute kidney injury (AKI) is frequently observed in serious infections, following nephrotoxic medication, surgery and trauma. Here we tested whether the detection of two recently identified biomarkers for AKI, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding Protein 7 (IGFBP7), depends on the expression of these proteins in cells of the urinary sediment. METHOD: We collected urine samples of 33 kidney transplant recipients and 14 non-transplanted patients who all had AKI (stages 1-3 according to KDIGO), and measured [IGFBP7]x[TIMP-2] using the NephroCheck® Astute1 40 ™ meter...
2017: PloS One
Xiaokai Li, Rui Su, Wenting Wan, Wenguang Zhang, Huaizhi Jiang, Xian Qiao, Yixing Fan, Yanjun Zhang, Ruijun Wang, Zhihong Liu, Zhiying Wang, Bin Liu, Yuehui Ma, Hongping Zhang, Qianjun Zhao, Tao Zhong, Ran Di, Yu Jiang, Wei Chen, Wen Wang, Yang Dong, Jinquan Li
Inner Mongolia and Liaoning cashmere goats are two outstanding Chinese multipurpose breeds that adapt well to the semi-arid temperate grassland. These two breeds are characterized by their soft cashmere fibers, thus making them great models to identify genomic regions that are associated with cashmere fiber traits. Whole-genome sequencing of 70 cashmere goats produced more than 5.52 million single-nucleotide polymorphisms and 710,600 short insertions and deletions. Further analysis of these genetic variants showed some population-specific molecular markers for the two cashmere goat breeds that are otherwise phenotypically similar...
November 9, 2017: Scientific Reports
Li-Ping Tao, Xiao-Peng Fan, Yu-Chen Fan, Jing Zhao, Shuai Gao, Kai Wang
This study quantitatively assessed serum insulin-like growth factor-binding protein 7 (IGFBP7) promoter methylation in hepatocellular carcinoma (HCC), and explored its clinical value. A total of 80 patients with hepatitis B virus-associated HCC, 35 patients with chronic hepatitis B (CHB), and 20 healthy controls (HC) were enrolled. MethyLight was used to quantitatively assess the methylation levels of serum IGFBP7 promoter. A logistic regression model was established for the combined evaluation of AFP and serum IGFBP7 promoter methylation...
October 9, 2017: Pathology, Research and Practice
Hua Zhang, Yu Shi, Maoxian He
Insulin-like growth factors (IGFs) play critical roles in regulating metabolism, growth, and reproduction in invertebrates. IGF binding proteins (IGFBPs) serve as major regulators of IGF activity and regulate endocrine system. In the present study, the full-length cDNA of an igfbp was identified from the pearl oyster, Pinctada fucata, using expressed sequence tag (EST) sequence. The 1124bp Pfigfbp cDNA contains a 465bp open reading frame (ORF) encoding a putative protein of 154 amino acids, a 5'-untranslated region (UTR) of 238bp, and a 3'-UTR of 394bp (not including polyA+)...
December 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
M Cuartero, J Ballús, J Sabater, X Pérez, N Nin, J Ordonez-Llanos, A J Betbesé
PURPOSE: To analyse the usefulness of the composite index of the tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as urinary biomarkers for the early prediction of AKI in septic and non-septic patients. METHODS: This is a prospective, observational study including patients admitted to ICU from acute care departments and hospital length of stay <48 h. The main exclusion criteria were pre-existing eGFR <30 mL/min/1...
September 7, 2017: Annals of Intensive Care
Tanja Mayer, Daniel Bolliger, Markus Scholz, Oliver Reuthebuch, Michael Gregor, Patrick Meier, Martin Grapow, Manfred D Seeberger, Jens Fassl
OBJECTIVE: To evaluate the perioperative course of urine levels of the renal damage biomarkers tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) and to evaluate the predictive value of elevated TIMP-2 × IGFBP7 concentrations to predict acute kidney injury (AKI) early after cardiac on-pump surgery. DESIGN: Prospective, observational cohort study. SETTING: University hospital. PARTICIPANTS: The study comprised 110 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB) between January and March 2014...
December 2017: Journal of Cardiothoracic and Vascular Anesthesia
M Kimmel, M Schanz, M D Alscher
Acute kidney injury (AKI) is a common syndrome with increased mortality, a heavy burden of illness and high cost. The Kidney Disease Improving Global Outcomes (KDIGO) criteria for staging of AKI have been validated in large patient cohorts and classify AKI into three stages. In order to achieve prevention or early therapy, the focus of scientific interest is early detection and risk prediction of AKI. The combination of the two cell cycle arrest markers [TIMP-2]·[IGFBP7] in the urine shows good results in the risk prediction of AKI in different clinical settings (intensive care medicine, sepsis, cardiac surgery, emergency department)...
June 2017: Drugs of Today
David R Emlet, Xiaoyan Wen, John A Kellum
In March of 2017, Acta Physiologica published a special series on renoprotection, and one of the publications in that series was a review entitled "Biomarkers in acute kidney injury - pathophysiological basis and clinical performance". This review described very well the current understanding of the pathophysiology, cellular localization, and clinical performance of the most important currently proposed biomarkers of AKI, to include insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases 2 (TIMP2)...
August 9, 2017: Acta Physiologica
K Xia, J Zhang, M Ahn, S Jha, J J Crowley, J Szatkiewicz, T Li, F Zou, H Zhu, D Hibar, P Thompson, P F Sullivan, M Styner, J H Gilmore, R C Knickmeyer
Genome-wide association studies (GWAS) of adolescents and adults are transforming our understanding of how genetic variants impact brain structure and psychiatric risk, but cannot address the reality that psychiatric disorders are unfolding developmental processes with origins in fetal life. To investigate how genetic variation impacts prenatal brain development, we conducted a GWAS of global brain tissue volumes in 561 infants. An intronic single-nucleotide polymorphism (SNP) in IGFBP7 (rs114518130) achieved genome-wide significance for gray matter volume (P=4...
August 1, 2017: Translational Psychiatry
Liqun Dong, Qing Ma, Michael Bennett, Prasad Devarajan
BACKGROUND: Several novel biomarkers that predict acute kidney injury (AKI) have recently been proposed. We have evaluated the sequential patterns of biomarker elevation after pediatric cardiopulmonary bypass (CPB) and determined their diagnostic accuracy. METHODS: We measured the ability of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), liver type fatty-acid binding protein (L-FABP), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein 7 (IGFBP7), to predict AKI (≥50% increase in serum creatinine from baseline)...
December 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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