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Ming-Chun Ma, Yi-Ju Chen, Tai-Jan Chiu, Jui Lan, Chien-Ting Liu, Yi-Ching Chen, Hsin-Ho Tien, Yen-Yang Chen
BACKGROUND: Post-surgical prognosis is usually poor for combined hepatocellular cholangiocarcinoma (CHCC-CC), a rare primary liver cancer. Although midkine (MK) is a prognostic biomarker for several known cancers, it is not known whether it can be used as such in resectable CHCC-CC. This study examined whether MK expression can predict recurrence and survival in patients with resectable CHCC-CC. METHODS: We retrospectively enrolled 52 patients with resectable CHCC-CC who had received curative hepatic resections...
February 27, 2018: BMC Cancer
Susana Maza, Noel Gandia-Aguado, José L de Paz, Pedro M Nieto
Here, we present the preparation of a sulfated, fully protected tetrasaccharide derivative following the glycosaminoglycan (GAG)-related sequence GlcNAc-β(1 → 4)-Glc-β(1 → 3). The tetramer was efficiently assembled via an iterative glycosylation strategy using monosaccharide building blocks. A fluorous tag was attached at position 6 of the reducing end unit enabling the purification of reaction intermediates by simple fluorous solid phase extraction. Fluorescence polarization competition experiments revealed that the synthesized tetrasaccharide strongly interacts with two heparin-binding growth factors, midkine and FGF-2 (IC50 of 270 nM and 2...
February 3, 2018: Bioorganic & Medicinal Chemistry
Naghmeh Jeiroodi, Mahshid Bagherpour, Razieh Zare, Shima Torabi-Ardakani, Azadeh Andisheh-Tadbir
OBJECTIVE: Midkine is a heparin-binding growth factor whose expression is increased in most tumors, namely ameloblastomas. This study aimed to compare Midkine expression in different odontogenic lesions. MATERIAL AND METHOD: This analytical cross-sectional study was performed on 52 definitely diagnosed odontogenic lesions including 15 dentigerous cysts, 13 odontogenic keratocysts, and 17 unicystic and 5 multicystic ameloblastomas archived from 1997 to 2015. Midkine expression was examined in tissue samples through immunohistochemistry...
January 31, 2018: Türk Patoloji Dergisi
Christian Albert, Annemarie Albert, Johanna Kube, Rinaldo Bellomo, Nicholas Wettersten, Hermann Kuppe, Sabine Westphal, Michael Haase, Anja Haase-Fielitz
OBJECTIVE: This study aimed to determine the biomarker-specific outcome patterns and short-and long-term prognosis of cardiac surgery-asoociated acute kidney injury (AKI) identified by standard criteria and/or urinary kidney biomarkers. METHODS: Patients enrolled (N = 200), originated a German multicenter study (NCT00672334). Standard risk injury, failure, loss, and end-stage renal disease classification (RIFLE) criteria (including serum creatinine and urine output) and urinary kidney biomarker test result (neutrophil gelatinase-associated lipocalin, midkine, interleukin 6, and proteinuria) were used for diagnosis of postoperative AKI...
December 22, 2017: Journal of Thoracic and Cardiovascular Surgery
Katharina Grupp, Nathaniel Melling, Valentina Bogoevska, Matthias Reeh, Faik Güntac Uzunoglu, Alexander Tarek El Gammal, Michael Fabian Nentwich, Jakob Robert Izbicki, Dean Bogoevski
Development and progression of malignant tumors is in part characterized by the ability of a tumor cell to overcome cell-cell and cell-matrix adhesion and to disseminate in organs distinct from that in which they originated. This study was undertaken to analyze the clinical significance of the expression of the following cell-cell and cell-matrix adhesion molecules in pancreatic ductal adenocarcinomas (PDACs) and synchronous liver metastases: intercellular adhesion molecule 1 (ICAM-1), E-cadherin, periostin, and midkine (MK)...
January 17, 2018: Experimental and Molecular Pathology
Yongliang Lu, Bing Yan, Huihui Guo, Li Qiu, Xinrong Sun, Xiang Wang, Qian Shi, Ying Bao
Gemcitabine‑based chemotherapy is one of the most effective and commonly used chemotherapeutic regimens for biliary tract cancer (BTC). However, development of resistance to this drug limits its efficacy. The present study aimed to explore the effects of midkine (MDK) on the resistance of BTC cells to gemcitabine. Cell viability and proliferation were measured by a Cell Counting Kit‑8 assay and 5‑ethynyl‑2'‑deoxyuridine staining, respectively. Western blot analysis was used to detect the expression of E‑cadherin and vimentin...
January 18, 2018: International Journal of Molecular Medicine
Ching-Huang Lin, Jun-Yen Pan, Jung-Jui Chang, Hsin-Hung Chen, Pei-Wen Cheng, Ching-Jiunn Tseng
The growth factor midkine has been implicated in various biologic and pathologic events. It has been shown that the peripheral influence of midkine on cardiovascular regulation is due to an influence on the renin-angiotensin system. The nucleus tractus solitarii (NTS) is the primary integrative center for cardiovascular control and other autonomic functions in the central nervous system. However, the signaling mechanisms involved in midkine-mediated cardiovascular effects in the NTS remain unclear. In this study, we investigated whether the renin-angiotensin system and/ or N-methyl-D-aspartate (NMDA) receptor-calmodulin-eNOS signaling pathways were both involved in midkine-mediated blood pressure (BP) regulation in the NTS of Wistar-Kyoto rats...
December 15, 2017: Chinese Journal of Physiology
Thomas Lautz, Manuel Lasch, Julia Borgolte, Kerstin Troidl, Judith-Irina Pagel, Amelia Caballero-Martinez, Eike Christian Kleinert, Barbara Walzog, Elisabeth Deindl
Midkine is a pleiotropic factor, which is involved in angiogenesis. However, its mode of action in this process is still ill defined. The function of midkine in arteriogenesis, the growth of natural bypasses from pre-existing collateral arteries, compensating for the loss of an occluded artery has never been investigated. Arteriogenesis is an inflammatory process, which relies on the proliferation of endothelial cells and smooth muscle cells. We show that midkine deficiency strikingly interferes with the proliferation of endothelial cells in arteriogenesis, thereby interfering with the process of collateral artery growth...
November 26, 2017: EBioMedicine
Yao Li, Yongda Lu, Jiaqing Shen, Chunfang Xu
BACKGROUND: Midkine (MK) is reported to be involved in the pathogenesis of numerous pathologies, but the expression of MK in acute pancreatitis (AP) has not been well studied and documented. METHODS: In this study, the temporal changes of serum MK were assessed in 97 patients with AP by enzyme-linked immunosorbent assay. RESULTS: The concentration of serum MK increased along with the severity of AP. Serum MK level increased more significantly in patients with organ failure than in those without organ failure...
December 2017: American Journal of the Medical Sciences
Dongya Zhang, Liang Ding, Yi Li, Jing Ren, Guoping Shi, Yong Wang, Shuli Zhao, Yanhong Ni, Yayi Hou
Midkine (MK) is a heparin-binding growth factor that promotes carcinogenesis and chemoresistance. The tumour microenvironment (TME) can affect chemotherapy sensitivity. However, the role of stromal-derived MK, especially in cancer-associated fibroblasts (CAFs), is unclear. Here, we confirmed that MK decreased cisplatin-induced cell death in oral squamous cell carcinoma (OSCC) cells, ovarian cancer cells and lung cancer cells. We also isolated primary CAFs (n = 3) from OSCC patients and found that CAFs secreted increased levels of MK, which abrogated cisplatin-induced cell death...
November 24, 2017: Scientific Reports
Erman Esnafoglu, Selma Cirrik
BACKGROUND: Midkine (MK) is a heparin binding growth factor and is involved in neurogenesis, neural development and neuroprotection. Additionally, MK may contribute to cancer development and pathogenesis of neurodegenerative disorders and schizophrenia. Considering these effects of MK, this study researched whether MK is involved in autism spectrum disorders (ASD) pathogenesis. METHODS: We evaluated serum MK levels of 38 patients with ASD and 32 healthy control group...
December 6, 2017: International Journal of Neuroscience
F Torabi, O A Bogle, J M Estanyol, R Oliva, D Miller
STUDY QUESTION: Are there novel hyaladherins in human sperm? SUMMARY ANSWER: Zona pellucida-binding protein 2 (ZPBP2), containing a Link-like hyaluronic acid (HA)-binding domain, and several other proteins containing BX7B motifs, such as ADAM32 and Midkine, may be novel hyaladherins with HA-binding properties. WHAT IS KNOWN ALREADY: HA-binding proteins (hyaladherins), which can bind HA surrounding the cumulus-oophorus complex, are distinct from hyases such as PH 20 (SPAM1) and are expressed by mature spermatozoa...
December 1, 2017: Molecular Human Reproduction
Hyun-Min Kim, Young-Hoon Kang, June-Ho Byun, Si-Jung Jang, Gyu-Jin Rho, Jong-Sil Lee, Bong-Wook Park
To increase the overall survival rate and obtain a better prognosis for oral squamous cell carcinoma (OSCC) patients, the detection of more effective and reliable tumor prognostic markers is needed. This study is focused on the analysis of correlation between the clinicopathological features of OSCCs and the immunohistochemical (IHC) expression patterns of MIDKINE (MK) and NANOG. Sixty-two primary OSCC patients were selected and their pretreatment biopsy specimens were immunohistochemically analyzed for the MK and NANOG proteins...
November 6, 2017: International Journal of Molecular Sciences
Yuki Takakura, Noritaka Yamaguchi, Takuya Honda, Mariko Morii, Ryuzaburo Yuki, Yuji Nakayama, Naoto Yamaguchi
Anaplastic lymphoma kinase (ALK) is a receptor-type tyrosine kinase that promotes cell growth upon stimulation with ligands such as midkine and pleiotrophin. Recently, a truncated isoform of ALK was identified in a variety of tumors. This isoform is expressed from a novel ALK transcript initiated from a de novo alternative transcription initiation (ATI) site in ALK intron 19 (referred to as ALK(ATI)). ALK(ATI), which consists of only the intracellular kinase domain, localizes to the nucleus as well as the cytoplasm...
2017: Biological & Pharmaceutical Bulletin
Rosalía Fernández-Calle, Marta Vicente-Rodríguez, Esther Gramage, Carlos de la Torre-Ortiz, Carmen Pérez-García, María P Ramos, Gonzalo Herradón
Pleiotrophin (PTN) and Midkine (MK) are two growth factors that modulate neuroinflammation. PTN overexpression in the brain prevents LPS-induced astrocytosis in mice but potentiates microglial activation. The modest astrocytic response caused by a low dose of LPS (0.5mg/kg) is blocked in the striatum of MK-/- mice whereas microglial response is unaffected. We have now tested the effects of an intermediate dose of LPS (7.5mg/kg) in glial response in PTN-/- and MK-/- mice. We found that LPS-induced astrocytosis is prevented in prefrontal cortex and striatum of both PTN-/- and MK-/- mice...
October 20, 2017: Neuroscience Letters
Petra Schneiderova, Tomas Pika, Petr Gajdos, Regina Fillerova, Pavel Kromer, Milos Kudelka, Jiri Minarik, Tomas Papajik, Vlastimil Scudla, Eva Kriegova
Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, Pcorr= .0004), Growth differentiation factor 15 (GDF15, Pcorr= .003), and soluble Major histocompatibility complex class I-related chain A (sMICA, Pcorr= .023), all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS...
September 19, 2017: Oncotarget
Victoria K Campbell, Chris M Anstey, Ryan P Gately, Drew C Comeau, Carolyn J Clark, Euan P Noble, Kumar Mahadevan, Peter R Hollett, Andrea J Pollock, Sharron T Hall, Darren R Jones, Dominic Burg, Nicholas A Gray
BACKGROUND AND OBJECTIVES: The cytokine midkine (MK) is pathologically implicated in progressive chronic kidney disease (CKD) and its systemic consequences and has potential as both a biomarker and therapeutic target. To date, there are no published data on MK levels in patients with different stages of CKD. This study aims to quantify MK levels in patients with CKD and to identify any correlation with CKD stage, cause, progression, comorbid disease or prescribed medication. METHODS: In this observational, single-centre study, demographic data were collected, and serum and urine assayed from 197 patients with CKD and 19 healthy volunteers in an outpatient setting...
September 27, 2017: BMJ Open
Nicole M Giamanco, Youn Hee Jee, Anton Wellstein, Craig D Shriver, Thomas A Summers, Jeffrey Baron
BACKGROUND/OBJECTIVE: Midkine (MDK) and pleiotrophin (PTN) are two closely related heparin-binding growth factors which are overexpressed in a wide variety of human cancers. We hypothesized that the concentrations of these factors in washout of biopsy needles would be higher in breast and lung cancer than in benign lesions. METHODS: Seventy subjects underwent pre-operative core needle biopsies of 78 breast masses (16 malignancies). In 11 subjects, fine needle aspiration was performed ex vivo on 7 non-small cell lung cancers and 11 normal lung specimens within surgically excised lung tissue...
September 7, 2017: Cancer Biomarkers: Section A of Disease Markers
Jiaojiao Zhao, Yuchen Pan, Xiujun Li, Xuefang Zhang, Yaxian Xue, Tingting Wang, Shuli Zhao, Yayi Hou
BACKGROUND/AIM: Women with advanced ovarian carcinoma are less likely to receive platinum-based chemotherapy and surgery due to a greater risk of cytotoxicity and poorer outcomes. We attempted to improve a promising therapy against ovarian cancer by using a combination of dihydroartemisinin (DHA) and curcumin (Cur). METHODS: Human ovarian cancer SKOV3 cells were treated with DHA, Cur alone, or a combination of both. The viability of SKOV3 cells was measured by Cell Counting Kit-8 (CCK-8) and a colony formation assay...
2017: Cellular Physiology and Biochemistry
Kathleen C Woulfe, Carmen C Sucharov
Midkine (MDK) is a heparin-binding growth factor that is normally expressed in mid-gestational development mediating mesenchymal and epithelial interactions. As organisms age, expression of MDK diminishes; however, in adults, MDK expression is associated with acute and chronic pathologic conditions such as myocardial infarction and heart failure (HF). The role of MDK is not clear in cardiovascular disease and currently there is no consensus if it plays a beneficial or detrimental role in HF. The lack of clarity in the literature is exacerbated by differing roles that circulating and myocardial MDK play in signaling pathways in cardiomyocytes (some of which have yet to be elucidated)...
September 2017: Journal of Cardiovascular Development and Disease
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