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Bijay Dhungel, Slawomir Andrzejewski, Aparna Jayachandran, Ritu Shrestha, Charmaine A Ramlogan-Steel, Christopher J Layton, Jason C Steel
Hepatocellular carcinoma (HCC) is a major health problem as evidenced by its increasing incidence and high morbidity and mortality rates. Most patients with HCC have underlying liver disease and dysfunction which limits the current therapeutic options. Treatments that spare the liver and destroy the HCC are needed. Targeting transcriptional differences between HCC and liver cells may provide this therapeutic window. In this study, we examine the potential of the Glypican 3 (GPC3) promoter as a targeting strategy...
March 21, 2018: Gene Therapy
Shenghao Wang, Muhammad Kalim, Keying Liang, Jinbiao Zhan
Glypican-3 (GPC3) is an integral membrane proteoglycan, which contains a core protein anchored to the cytoplasmic membrane through a glycosyl phosphatidylinositol linkage. The glypican-3 can regulate the signaling pathways, thereby enhances cell division, growth, and apoptosis in certain cell types. It is almost non-existent on the surface of the human normal cell membrane and highly expresses on the membrane of hepatocellular carcinoma (HCC) cells. It has been well established that GPC3 provide a useful diagnostic marker...
March 21, 2018: Preparative Biochemistry & Biotechnology
María Lázaro-Peña, Carlos Díaz-Balzac, Hannes Bülow, Scott Emmons
The nervous system regulates complex behaviors through a network of neurons interconnected by synapses. How specific synaptic connections are genetically determined is still unclear. Male mating is the most complex behavior in C. elegans It is composed of sequential steps that are governed by more than 3,000 chemical connections. Here we show that heparan sulfates (HS) play a role in the formation and function of the male neural network. HS, sulfated in position 3 by the HS modification enzyme HST-3.1 / HS 3- O -sulfotransferase and attached to the HSPG glypicans LON-2/glypican and GPN-1/glypican, functions cell-autonomously and non-autonomously for response to hermaphrodite contact during mating...
March 20, 2018: Genetics
Sandrine Girerd, Lucie Tosca, Olivier Herault, Christine Vignon, Denis Biard, Djamel Aggoune, Fatima Dkhissi, Marie Laure Bonnet, Nathalie Sorel, Christophe Desterke, Annelise Bennaceur-Griscelli, Gerard Tachdjian, François Guilhot, Joelle Guilhot, Jean-Claude Chomel, Ali G Turhan
Manganese Superoxide dismutase 2 (SOD2) plays a crucial role in antioxidant defense but there are no data suggesting its role in genetic instability in CML. We evaluated the effects of SOD2 silencing in human UT7 cell line expressing either non-mutated or T315I-mutated BCR-ABL. Array-CGH experiments detected in BCR-ABL-expressing cells silenced for SOD2 a major genetic instability within several chromosomal loci, especially in regions carrying the glypican family (duplicated) and β-defensin genes (deleted)...
March 16, 2018: Biochemical and Biophysical Research Communications
Steve Taylor, Kimberly Eisenstein, Vanessa Gildenstern, Harper Price, Pooja Hingorani, Apurvi Patel, Nathan Page, Smita Bailey, David Carpentieri
Infantile choriocarcinoma (ICC) is a rare, highly malignant form of gestational trophoblastic neoplasia. Rapid diagnosis and initiation of treatment are paramount in reaching a successful outcome. Patients with these tumors typically present with a triad of anemia, hepatomegaly, and precocious puberty. Cutaneous manifestations of ICC are extraordinarily rare with few documented cases. Here, we describe a male neonate who presented to our Dermatology clinic with a rapidly growing, markedly vascular glabellar mass associated with abnormal laboratory values suggestive of Kasabach-Merritt phenomenon...
January 1, 2018: Pediatric and Developmental Pathology
Gong Chen, Ya-Chi Chen, Bernhard Reis, Anton Belousov, Lori Jukofsky, Christine Rossin, Axel Muehlig, Chao Xu, Laurent Essioux, Toshihiko Ohtomo, Laura Di Laurenzio, Oscar Puig, Ray Lee
Background: Codrituzumab, a monoclonal antibody targeting an oncofetal protein glypican-3 (GPC3) expressed on cell surface of hepatocellular carcinoma (HCC) induces antibody-dependent cellular cytotoxicity (ADCC) and inhibits tumor growth in preclinical studies. Based on this mechanism, tumor GPC3 expression and CD16 expression on NK cells, which are the effector cells of ADCC, were investigated to correlate with codrituzumab's clinical efficacy in patients with advanced HCC. Results: Joint analyses of the two biomarkers revealed that both high levels of GPC3 and CD16 were required for patients to benefit from codrituzumab; lack of either one of them would lead to a loss of the therapeutic effect...
February 13, 2018: Oncotarget
Jorge A Carrasquillo, Joseph A O'Donoghue, Volkan Beylergil, Shutian Ruan, Neeta Pandit-Taskar, Steven M Larson, Peter M Smith-Jones, Serge K Lyashchenko, Norihisa Ohishi, Toshihiko Ohtomo, Ghassan K Abou-Alfa
BACKGROUND: I-124 codrituzumab (aka GC33), an antibody directed at Glypican 3, was evaluated in patients with hepatocellular carcinoma (HCC). Fourteen patients with HCC underwent baseline imaging with I-124 codrituzumab (~ 185 MBq, 10 mg). Seven of these patients undergoing sorafenib/immunotherapy with 2.5 or 5 mg/kg of cold codrituzumab had repeat imaging, with co-infusion of I-124 codrituzumab, as part of their immunotherapy treatment. Three patients who progressed while on sorafenib/immunotherapy were re-imaged after a 4-week washout period to assess for the presence of antigen...
March 5, 2018: EJNMMI Research
Maristela P Rangel, Vanessa K de Sá, Tabatha Prieto, João Roberto M Martins, Eloísa R Olivieri, Dirce Carraro, Teresa Takagaki, Vera Luiza Capelozzi
Matrix proteoglycans (PGs) have shown promise as biomarker in malignancies. We employed agarose gel eletrophoresis, quantitative real- time reverse transcription-polymerase chain reaction and immunohistochemistry to evaluate the content of sulfated glicosaminoglycans (chondroitin sulfate and heparan sulfate) and expression of PG (biglycan, glypican, perlecan, syndecan e versican) in patient-matched normal and tumor tissues obtained from resected specimens of lung cancer. A significant increase of heparan sulfate (HS) and chondroitin sulfate (CS) concentrations was found in tumor tissue samples when compared to normal lung tissue samples...
March 3, 2018: Glycoconjugate Journal
Vitor H Pomin, Barbara Mulloy
In this editorial to MDPI Pharmaceuticals special issue " Glycosaminoglycans and Proteoglycans " we describe in outline the common structural features of glycosaminoglycans and the characteristics of proteoglycans, including the intracellular proteoglycan, serglycin, cell-surface proteoglycans, like syndecans and glypicans, and the extracellular matrix proteoglycans, like aggrecan, perlecan, and small leucine-rich proteoglycans. The context in which the pharmaceutical uses of glycosaminoglycans and proteoglycans are presented in this special issue is given at the very end...
February 27, 2018: Pharmaceuticals
Asmaa M Zaazaa, Maha S Lokman, Aziza B Shalby, Hanaa H Ahmed, Sayed A El-Toumy
This research work was initiated to explore the efficacy of ellagic acid in mitigation of hepatocarcinogenesis in rats. Rats were distributed into 4 groups; negative control, hepatocellular carcinoma (HCC), doxorubicin and ellagic acid. Serum alpha-fetoprotein (AFP), glypican-3 (GPC-3), signal transducer and activator of transcription 3 (STAT3) and suppressors of cytokine signaling 3 (SOCS3) levels were assayed by ELISA. Immunohistochemical examination of hepatic VEGF expression was also conducted, along with histological procedures for examination of liver tissue sections...
February 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
O Sulaieva, Y Chereshneva, N Kartashkina, M Ivanova, D Tsomartova
In addition to accumulation and metabolism of triglycerides, white adipose tissue is recognized as the active endocrine organ, whose dysfunction is associated with the development of a wide range of diseases. The secretome of adipocytes is represented by a wide range of adipokines, which vary in depot and sex-specific manner. In addition, adipokines have diverse biological effects, correlations with different metabolic features and functions. In this review, the data on biological effects, origin and the clinical significance of adipokines are discussed...
January 2018: Georgian Medical News
Rania Naiem Sherif, Hussein Abdellatif, Noha Hazem, Neven A Ebrahim, Dalia Saleh, Gamal Shiha, Huda Eltahry, Kamal G Botros, Omar M Gabr
BACKGROUND AND AIM OF THE WORK: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy. Chronic liver injuries as chronic hepatitis C and hepatitis B viruses, aflatoxins consumption and nonalcoholic fatty liver disease are well-established causes of HCC. HCC is associated with a series of molecular changes, as alternation in glypican-3, P53 expression and Wnt/β-catenin pathway. Hepatic cancer progenitor cells could contribute to HCC development. This research aimed to study the effectiveness of human CD34+ hematopoietic stem cell on Wnt4 and P53 genes expression, histopathological grading and hepatic progenitor cells percentage in HCC rat model...
February 2018: Tissue & Cell
M Herman Chui, Cherry Have, Lien N Hoang, Patricia Shaw, Cheng-Han Lee, Blaise A Clarke
Uterine carcinosarcoma, also known as Malignant Mixed Müllerian Tumour, is a high-grade biphasic neoplasm composed of sarcomatous elements thought to originate via transdifferentiation from high-grade endometrial carcinoma. To identify molecular factors contributing to the histogenesis of this tumour, we analyzed DNA extracted from matched carcinoma and sarcoma components from 12 cases of carcinosarcoma by a molecular inversion probe microarray to assess genomic copy number alterations (CNAs) and allelic imbalances...
January 2018: Journal of Pathology. Clinical Research
Katie L Davis-Anderson, Hendrik Wesseling, Lara M Siebert, Emilie R Lunde-Young, Vishal D Naik, Hanno Steen, Jayanth Ramadoss
Fetal alcohol spectrum disorders (FASD) describe neurodevelopmental deficits in children exposed to alcohol in utero. We hypothesized that gestational alcohol significantly alters fetal brain regional protein signature. Pregnant rats were binge-treated with alcohol or pair-fed and nutritionally-controlled. Mass spectrometry identified 1,806, 2,077, and 1,456 quantifiable proteins in the fetal hippocampus, cortex, and cerebellum, respectively. A stronger effect of alcohol exposure on the hippocampal proteome was noted: over 600 hippocampal proteins were significantly (P < 0...
January 31, 2018: Reproductive Toxicology
Fang Cheng, Lars-Åke Fransson, Katrin Mani
Import of the polyamine spermine from the extracellular environment depends on the presence of cell surface heparan sulfate proteoglycans, such as glypican-1. This proteoglycan is internalized by endocytosis, releases its heparan sulfate chains in endosomes by a nitric oxide-, copper- and amyloid precursor protein-dependent mechanism, then penetrates the membrane and is transported to the nucleus and then to autophagosomes. This process is spontaneous or induced by ascorbate depending on the growth-state of the cell...
February 2, 2018: Experimental Cell Research
Qinggong Yuan, Yan Zhang, Junhui Li, Gang Cao, Wenbin Yang
A growing amount of evidence has documented that Glypican-5 (GPC5) is an important regulator of tumor progression. However, little is known about the role of GPC5 in pancreatic ductal adenocarcinoma (PDAC). In this study, we aimed to investigate the potential function and regulatory mechanism of GPC5 in PDAC. We found that GPC5 expression was significantly down-regulated in PDAC cell lines. The overexpression of GPC5 inhibited cell proliferation and the invasion of PDAC cells. In addition, the overexpression of GPC5 suppressed Wnt/β-catenin signaling in PDAC cells...
February 3, 2018: Biochemical and Biophysical Research Communications
You-Cai Li, Chuan-Sheng Yang, Wen-Lan Zhou, Hong-Sheng Li, Yan-Jiang Han, Quan-Shi Wang, Hu-Bing Wu
AIM: To investigate the relationship between glucose metabolism and glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC). METHODS: Immunohistochemical staining of pathological samples for GPC3 and glucose transporter 1 (GLUT1), and whole-body 18F-FDG PET/CT for measuring tumour glucose uptake were performed in 55 newly diagnosed HCC patients. The maximum standard uptake value (SUVmax) and tumour-to-non-tumourous liver uptake (T/NT) ratio were used to quantify 18F-FDG uptake...
January 28, 2018: World Journal of Gastroenterology: WJG
Jun-Ke Wang, Yan-Wen Jin, Hai-Jie Hu, Parbatraj Regmi, Wen-Jie Ma, Qin Yang, Fei Liu, Cong-Dun Ran, Fei Su, Er-Liang Zheng, Fu-Yu Li
RATIONAL: Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a rare variant of hepatocellular carcinoma (HCC). To date, few cases have been reported in the literature, and almost no report in analyzing the different features of LEL-HCC. PATIENT CONCERNS: We describe a 37-year-old female patient with a 32 × 30 mm mass in the right liver. INTERVENTIONS: Complete surgical resection of the lesion was performed. DIAGNOSES: Histopathological examination of the resected tumor revealed undifferentiated HCC cells with significant lymphocytes infiltration...
December 2017: Medicine (Baltimore)
Julia Esperanza Torres-Mena, Karla Noemí Salazar-Villegas, Ricardo Sánchez-Rodríguez, Belém López-Gabiño, Luis Del Pozo-Yauner, Jaime Arellanes-Robledo, Saúl Villa-Treviño, María Angélica Gutiérrez-Nava, Julio Isael Pérez-Carreón
BACKGROUND: The intrinsic heterogeneity of hepatocellular carcinoma (HCC) represents a great challenge for its molecular classification and for detecting predictive biomarkers. Aldo-keto reductase (Akr) family members have shown differential expression in human HCC, while AKR1B10 overexpression is considered a biomarker; AKR7A3 expression is frequently reduced in HCC. AIMS: To investigate the time-course expression of Akr members in the experimental hepatocarcinogenesis...
January 30, 2018: Digestive Diseases and Sciences
Mikiko Nakamura, Chao Xu, Cheikh Diack, Norihisa Ohishi, Ruey-Min Lee, Satofumi Lida, Takehiko Kawanishi, Toshihiko Ohtomo, Ghassan K Abou-Alfa, Ya-Chi Chen
AIMS: Codrituzumab (GC33) is a recombinant, humanized mAb that binds to glypican-3 (GPC3), an oncofoetal protein highly expressed in hepatocellular carcinoma (HCC). This investigation aimed to identify clinically relevant factors that may affect the overall survival (OS) in HCC patients treated with codrituzumab and to quantitatively annotate their effects. METHODS: Codrituzumab exposure was estimated by a population pharmacokinetics model with a non-linear elimination pathway...
January 30, 2018: British Journal of Clinical Pharmacology
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