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Kévin Ly, Rachid Essalmani, Roxane Desjardins, Nabil G Seidah, Robert Day
The mechanism of LDL receptor (LDLR) degradation mediated by the proprotein convertase subtilisin/kexin type 9 (PCSK9) has been extensively studied, however many steps within this process remain unclear and still require characterization. Recent studies have shown that PCSK9 lacking its Cys/His-rich domain can still promote LDLR internalization, but the complex does not reach the lysosome suggesting the presence of an additional interaction partner(s). In the present study we carried out an unbiased screening approach to identify PCSK9 interacting proteins in the HepG2 cells' secretome using co-immunoprecipitation combined with mass spectrometry analyses...
October 7, 2016: Journal of Biological Chemistry
Natali Abeywickrama-Samarakoon, Jean-Claude Cortay, Paul Dény
PURPOSE OF REVIEW: To highlight new concepts and therapeutic approaches concerning hepatitis D virus (HDV) infection. RECENT FINDINGS: Common receptor for hepatitis B virus (HBV) and HDV has been elucidated, deciphering of HDV replication is still in progress, preliminary results of phase II proof-of-concept clinical assays for entry inhibitors and cellular farnesyl transferase inhibitors are now available. SUMMARY: Hepatitis D infection remains a severe acute and chronic liver illness with the only currently approved therapy (Peg-αIFN) achieving disappointingly low rates of sustained viral response and clinical improvement...
October 7, 2016: Current Opinion in Infectious Diseases
Hanaa H Ahmed, Wafaa Gh Shousha, Hatem A El-Mezayen, Sayed A El-Toumy, Alaa H Sayed, Aesha R Ramadan
Hepatocellular carcinoma (HCC) is one of the deadliest primary cancers, with a 5-year survival rate of 10% or less. This study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favor of N-nitrosodiethylamine-induced hepatocellular carcinoma. Furthermore, the aim of this work was extended to explore the efficacy of Ginkgo biloba leaves extract in deterioration of HCC in rats. In the current study, HCC group experienced significant downregulation of ING-3 gene expression and upregulation of Foxp-1 gene expression in liver...
October 14, 2016: Acta Biochimica Polonica
Alessandro Vaisfeld, Maria Grazia Pomponi, Roberta Pietrobono, Elisabetta Tabolacci, Giovanni Neri
Simpson-Golabi-Behmel syndrome is an X-linked recessive overgrowth condition caused by alterations in GPC3 gene, encoding for the cell surface receptor glypican 3, whose clinical manifestations in affected males are well known. Conversely, there is little information regarding affected females, with very few reported cases, and a clinical definition of this phenotype is still lacking. In the present report we describe an additional case, the first to receive a primary molecular diagnosis based on strong clinical suspicion...
October 14, 2016: American Journal of Medical Genetics. Part A
Yejoo Jeon, Eun Sun Jang, Yun Suk Choi, Jin-Wook Kim, Sook-Hyang Jeong
BACKGROUND/AIMS: Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. METHODS: We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group...
September 2016: Clinical and Molecular Hepatology
Sang Ah Lee, Gwanpyo Koh, Suk Ju Cho, So Yeon Yoo, Sang Ouk Chin
BACKGROUND: Previous studies have reported that glypican-4 (GPC4) regulates insulin signaling by interacting with insulin receptor and through adipocyte differentiation. However, GPC4 has not been studied with regard to its effects on clinical factors in patients with type 2 diabetes mellitus (T2DM). We aimed to identify factors associated with GPC4 level in T2DM. METHODS: Between January 2010 and December 2013, we selected 152 subjects with T2DM and collected serum and plasma into tubes pretreated with aprotinin and dipeptidyl peptidase-4 inhibitor to preserve active gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)...
September 2016: Endocrinology and Metabolism
Elisa Matas-Rico, Michiel van Veen, Daniela Leyton-Puig, Jeroen van den Berg, Jan Koster, Katarzyna M Kedziora, Bas Molenaar, Marjolein J A Weerts, Iris de Rink, René H Medema, Ben N G Giepmans, Anastassis Perrakis, Kees Jalink, Rogier Versteeg, Wouter H Moolenaar
Neuroblastoma is a pediatric embryonal malignancy characterized by impaired neuronal differentiation. A better understanding of neuroblastoma differentiation is essential for developing new therapeutic approaches. GDE2 (encoded by GDPD5) is a six-transmembrane-domain glycerophosphodiesterase that promotes embryonic neurogenesis. We find that high GDPD5 expression is strongly associated with favorable outcome in neuroblastoma. GDE2 induces differentiation of neuroblastoma cells, suppresses cell motility, and opposes RhoA-driven neurite retraction...
October 10, 2016: Cancer Cell
Aixian Zheng, Xiaolong Zhang, Ju Gao, Xiaolong Liu, Jingfeng Liu
Glypican-3 (GPC3) might be used as new biomarker of liver cancer for the development of new diagnostic methods. The most commonly used methods for protein detection are based on natural enzymes, which are easily affected by environmental conditions and suffer from the rigorous preparation conditions. Thus, the development of new enzyme mimetics with high and stable catalytic activity is of great significance in diagnostic applications. In this paper, copper ions (Cu(2+)) was found to possess the peroxidase-like catalytic activity, which can catalyze H2O2-mediated oxidation of peroxidase substrate and obtain the oxidation product with color change...
October 19, 2016: Analytica Chimica Acta
Hongliang Yao, Zhulin Yang, Ziru Liu, Xiongying Miao, Leping Yang, Daiqiang Li, Qiong Zou, Yuan Yuan
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with metastasis in most patients at diagnosis. The molecular mechanisms associated with its high malignancy have not been fully elucidated. This study investigated the clinicopathological significances of GPC3 and KRT19 expression in PDAC. METHODS: GPC3, KRT19, and CA19-9 protein expression were measured by immunohistochemistry. RESULTS: GPC3 and KRT19 protein levels were overexpressed in PDAC tumors compared to normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P< 0...
September 22, 2016: Cancer Biomarkers: Section A of Disease Markers
Kohei Matsumoto, Hiroya Ueyama, Kenshi Matsumoto, Yoichi Akazawa, Hiroyuki Komori, Tsutomu Takeda, Takashi Murakami, Daisuke Asaoka, Mariko Hojo, Natsumi Tomita, Akihito Nagahara, Yoshiaki Kajiyama, Takashi Yao, Sumio Watanabe
AIM: To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation (GCED). METHODS: We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer (CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital. GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4...
September 28, 2016: World Journal of Gastroenterology: WJG
Ye Zeng, Jingxia Liu
Blood flow patterns in proatherogenic and antiatherogenic regions are rather different. We hypothesize that the laminar flow with steady shear stress increased nitric oxide (NO) bioavailability while disturbed flow with low shear stress reduced it, which is mediating by glypican-1. Thus, we detected the expression of glypican-1 under different shear stress magnitudes, and tested whether the magnitude of shear stress determines the level of endothelial NO synthase (eNOS) via glypican-1 by using phosphatidylinositol phospholipase C (PI-PLC)...
September 26, 2016: Experimental Cell Research
Mikhail Paveliev, Keith K Fenrich, Mikhail Kislin, Juha Kuja-Panula, Evgeny Kulesskiy, Markku Varjosalo, Tommi Kajander, Ekaterina Mugantseva, Anni Ahonen-Bishopp, Leonard Khiroug, Natalia Kulesskaya, Geneviève Rougon, Heikki Rauvala
Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma)...
September 27, 2016: Scientific Reports
Bryan D Fleming, Mitchell Ho
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, yet no effective therapeutics exist. This review provides an overview of the recent development of recombinant immunotoxins for the treatment of glypican-3 (GPC3) expressing HCC. GPC3 is a cell surface heparan sulfate proteoglycan that is overexpressed in HCC, but is absent from normal adult human tissues. Treatment of HCC with anti-GPC3 immunotoxins represents a new therapeutic option. Using phage display and hybridoma technologies, three high affinity antibodies (HN3, HS20 and YP7) have been generated against GPC3...
2016: Toxins
Yi-Fan Zhang, Mitchell Ho
Glypican-3 (GPC3) is a cell-surface heparan sulfate proteoglycan highly expressed in hepatocellular carcinoma (HCC). We have generated a group of high-affinity mouse monoclonal antibodies targeting GPC3. Here, we report the humanization and testing of these antibodies for clinical development. We compared the affinity and cytotoxicity of recombinant immunotoxins containing mouse single-chain variable regions fused with a Pseudomonas toxin. To humanize the mouse Fvs, we grafted the combined KABAT/IMGT complementarity determining regions (CDR) into a human IgG germline framework...
September 26, 2016: Scientific Reports
Giuliana Cassinelli, Nadia Zaffaroni, Cinzia Lanzi
Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression...
September 22, 2016: Cancer Letters
Théophile Vissiennon, Markus Freick, Ergin Kilic, Thomas Schmidt, Sven Dänicke, Marion Schmicke, Eckard Schneider
Congenital testicular tumours are seldom reported in bovine species. This case report describes the clinical, sonographical, haematological, pathomorphological and immunohistological features of a Sertoli cell tumour in a neonatal German Holstein calf. Microscopically, the enlarged testicle was composed of neoplastic cells, which were packed in well-formed tubules. The mostly polygonal shaped cells had round to elongated nuclei and a scanty eosinophilic cytoplasm. Some cells were arranged perpendicularly to the light PAS-positive basement membrane...
September 21, 2016: Tierärztliche Praxis. Ausgabe G, Grosstiere/Nutztiere
Ramon Barreto Mendes, Rosane Borges Dias, Andreia Leal Figueiredo, Clarissa Araújo Gurgel, Manoel Santana Filho, Leonardo Araújo Melo, Marília Trierveiler, Patrícia Ramos Cury, Rosalia Leonardi, Jean Nunes Dos Santos
BACKGROUND: Glypican-3 is a cell surface proteoglycan that is found in embrionary tissues, and there are no studies investigating this protein in odontogenic tumor. Thus, the aim of this study was to investigate glypican-3 in a series of aggressive and non-aggressive odontogenic tumors. METHODS: Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, 28 KOTs including five associated with Gorlin-Goltz syndrome) and non-aggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic tumors) and analyzed for glypican-3 using immunohistochemistry...
September 20, 2016: Journal of Oral Pathology & Medicine
Annikka Weissferdt, Neda Kalhor, Jaime Rodriguez Canales, Junya Fujimoto, Ignacio I Wistuba, Cesar A Moran
Primary mediastinal germ cell tumors are uncommon tumors that can pose diagnostic difficulties due to their morphologic spectrum and unusual site. Immunohistochemistry plays an increasing role in the diagnosis of these tumors. Whereas the immunophenotype of testicular yolk sac tumors (YST) is rather well known, the opposite is true for primary mediastinal YST leading us to investigate the immunohistochemical features of 14 such neoplasms. Fourteen cases of primary mediastinal YST were reviewed and representative whole tissue sections were selected for immunohistochemical analysis using antibodies directed against CAM5...
September 16, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Chang-Jiang Lei, Chun Yao, De-Ke Li, Zhi-Xiong Long, Yuan Li, Dan Tao, Yan-Ping Liou, Jiang-Zhou Zhang, Ning Liu
OBJECTIVE: To investigate the effects of co-transfection of miR-520c-3p and miR-132 on proliferation and apoptosis of hepatocellular carcinoma Huh7. METHODS: Hepatocellular carcinoma Huh7 was cultured in vitro and lipidosome was used to transfect miR-520c-3p and miR-132, respectively or together. The effects of transfection of miR-520c-3p and miR-132 on proliferation and apoptosis of Huh7 were detected by CCK8 and Annexin V staining and flow cytometry, and the expression level of the targeted gene of over-expressed miR-520c-3p and miR-132 was determined by Western blot and realtime PCR...
September 2016: Asian Pacific Journal of Tropical Medicine
Sanjita Ravishankar, Anais Malpica, Preetha Ramalingam, Elizabeth D Euscher
We present the clinicopathologic features of 15 cases of extragonadal yolk sac tumor (EGYST) detected in female patients and reviewed at our institution from 1988 to 2016. We recorded: patient age, clinical presentation, tumor location, FIGO stage (where applicable), histologic patterns including presence/absence of Schiller-Duval bodies, other germ cell or somatic components, immunoperoxidase results, treatment, and outcome. Patients' ages ranged from 17 to 87 (median, 62) years and presentation included: abnormal uterine bleeding, 12; hematuria, 1; labial mass, 1; abdominal pain, 1...
September 14, 2016: American Journal of Surgical Pathology
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