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https://www.readbyqxmd.com/read/29337052/sweet-yet-underappreciated-proteoglycans-and-extracellular-matrix-remodeling-in-heart-disease
#1
REVIEW
Geir Christensen, Kate M Herum, Ida G Lunde
Extracellular matrix remodeling is extensive in several heart diseases and hampers cardiac filling, often leading to heart failure. Proteoglycans have over the last two decades emerged as molecules with important roles in matrix remodeling and fibrosis in the heart. Here we discuss and review current literature on proteoglycans that have been studied in cardiac remodeling. The small leucine rich proteoglycans (SLRPs) are located within the extracellular matrix and are organizers of the matrix structure. Membrane-bound proteoglycans, such as syndecans and glypicans, act as receptors and direct cardiac fibroblast signaling...
January 11, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29327712/glypican-1-immunohistochemistry-is-a-novel-marker-to-differentiate-epithelioid-mesothelioma-from-lung-adenocarcinoma
#2
Vishwa Jeet Amatya, Kei Kushitani, Yuichiro Kai, Rui Suzuki, Yoshihiro Miyata, Morihito Okada, Yukio Takeshima
Histological morphology alone is not sufficient for the pathological diagnosis of malignant mesothelioma. Positive and negative immunohistochemical markers are necessary to differentiate it from lung adenocarcinoma. As calretinin and D2-40, the recognized positive markers of mesothelioma, are expressed in lung adenocarcinoma to some extent, novel markers with high specificity are desirable. In this study, we investigated the applicability of glypican-1 immunohistochemistry to differentiate epithelioid mesothelioma from lung adenocarcinoma...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29322326/heparan-sulfate-accumulation-and-perlecan-hspg2-up-regulation-in-tumour-tissue-predict-low-relapse-free-survival-for-patients-with-glioblastoma
#3
Galina M Kazanskaya, Alexandra Y Tsidulko, Alexander M Volkov, Roman S Kiselev, Anastasia V Suhovskih, Vyacheslav V Kobozev, Alexei S Gaytan, Svetlana V Aidagulova, Alexei L Krivoshapkin, Elvira V Grigorieva
Glycosaminoglycans are major components of brain extracellular matrix (ECM), although heparan sulfate (HS) contribution in brain physiology and carcinogenesis remains underinvestigated. This study examined HS content and distribution in glioblastoma multiforme (GBM) tissues in the context of potential molecular mechanisms underlying its deregulation in brain tumours. Totally, 42 tissue samples and paraffin-embedded tissues for 31 patients with different prognosis were investigated. HS expression was demonstrated in 50-55% of the GBM tumours by immunohistochemistry (IHC), while almost no HS content was detected in the surrounding paratumourous brain tissues...
January 10, 2018: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/29305518/her2-is-frequently-overexpressed-in-hepatoid-adenocarcinoma-and-gastric-carcinoma-with-enteroblastic-differentiation-a-comparison-of-35-cases-to-334-gastric-carcinomas-of-other-histological-types
#4
Masakazu Fujimoto, Ibu Matsuzaki, Masaru Nishino, Yoshifumi Iwahashi, Kenji Warigaya, Fumiyoshi Kojima, Kazuo Ono, Shin-Ichi Murata
AIMS: α-Fetoprotein (AFP)-producing gastric carcinoma (AFPGC) is one of the most aggressive GC subtypes. Frequent expression of human epidermal growth factor receptor 2 (HER2) has previously been reported in hepatoid adenocarcinoma (HAC), a major histological subtype of AFPGC originating from common-type GC (CGC). However, HER2 expression levels in other AFPGC histological subtypes are unknown. In this study, we analysed HER2 expression in GCs with primitive phenotypes in addition to HAC...
January 5, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29285841/cancer-immunotherapy-targeted-glypican-3-or-neoantigens
#5
REVIEW
Yasuhiro Shimizu, Toshihiro Suzuki, Toshiaki Yoshikawa, Nobuhiro Tsuchiya, Yu Sawada, Itaru Endo, Tetsuya Nakatsura
Immune checkpoint inhibitors have ushered a new era in cancer therapy, although other therapies or combinations thereof are still needed for the many patients for whom these drugs are ineffective. In this light, we have identified in glypican-3 an HLA-24, HLA-A2 restriction peptide with extreme cancer specificity. In this paper, we summarize results from a number of related clinical trials demonstrating that glypican-3 peptide vaccines induce specific cytotoxic T lymphocytes in most patients (UMIN Clinical Trials Registry: UMIN000001395, UMIN000005093, UMIN000002614, UMN000003696, UMIN000006357,)...
December 29, 2017: Cancer Science
https://www.readbyqxmd.com/read/29277631/a-proteomic-clock-of-human-pregnancy
#6
Nima Aghaeepour, Benoit Lehallier, Quentin Baca, Ed A Ganio, Ronald J Wong, Mohammad S Ghaemi, Anthony Culos, Yasser Y El-Sayed, Yair J Blumenfeld, Maurice L Druzin, Virginia D Winn, Ronald S Gibbs, Rob Tibshirani, Gary M Shaw, David K Stevenson, Brice Gaudilliere, Martin S Angst
BACKGROUND: Early detection of maladaptive processes underlying pregnancy-related pathologies is desirable, as it will enable targeted interventions ahead of clinical manifestations. The quantitative analysis of plasma proteins features prominently among molecular approaches used to detect deviations from normal pregnancy. However, derivation of proteomic signatures sufficiently predictive of pregnancy-related outcomes has been challenging. An important obstacle hindering such efforts were limitations in assay technology, which prevented the broad examination of the plasma proteome...
December 22, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29259231/a-novel-cell-line-based-orthotopic-xenograft-mouse-model-that-recapitulates-human-hepatoblastoma
#7
Sarah E Woodfield, Yan Shi, Roma H Patel, Jingling Jin, Angela Major, Stephen F Sarabia, Zbigniew Starosolski, Barry Zorman, Siddharth S Gupta, Zhenghu Chen, Aryana M Ibarra, Karl-Dimiter Bissig, Ketan B Ghaghada, Pavel Sumazin, Dolores López-Terrada, Sanjeev A Vasudevan
Currently, preclinical testing of therapies for hepatoblastoma (HB) is limited to subcutaneous and intrasplenic xenograft models that do not recapitulate the hepatic tumors seen in patients. We hypothesized that injection of HB cell lines into the livers of mice would result in liver tumors that resemble their clinical counterparts. HepG2 and Huh-6 HB cell lines were injected, and tumor growth was monitored with bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). Levels of human α-fetoprotein (AFP) were monitored in the serum of animals...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29245923/evi1-modulates-oncogenic-role-of-gpc1-in-pancreatic-carcinogenesis
#8
Mariko Tanaka, Shumpei Ishikawa, Tetsuo Ushiku, Teppei Morikawa, Takayuki Isagawa, Makoto Yamagishi, Hiroyuki Yamamoto, Hiroto Katoh, Kimiko Takeshita, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Masashi Fukayama
Glypican-1 (GPC1) protein in exosomes was recently identified as a biomarker for the early detection of pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analyses and in vitro assays were conducted to assess the usefulness of GPC1 as a PDAC biomarker, to reveal the biological role of GPC1 in pancreatic carcinogenesis, and to ascertain the regulation mechanism of GPC1. An aberrant overexpression of GPC1 protein which is usually absent in normal pancreatic duct, was a widespread marker across the full spectrum of human PDAC precursors, PDAC, and pancreatic cancerous stroma...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226636/the-value-of-gpc3-and-gp73-in-clinical-diagnosis-of-hepatocellular-carcinoma
#9
Ji-Sheng Jing, Wei Ye, Ying-Kui Jiang, Jie Ma, Meng-Qi Zhu, Jiu-Ming Ma, Hua Zhou, La-Qing Yu, Yong-Feng Yang, Shun-Cai Wang
BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has increased over the past decades in China. Current screening methods of HCC such as detection of α-fetoprotein (AFP) combined with liver ultrasonography remain unsatisfactory. Many HCC patients have already missed the optimal treatment period when diagnosed. Our study aimed to evaluate the value of Glypican 3 (GPC3) and Golgi protein 73 (GP73) in the detection of HCC. METHODS: Thirty-nine patients with HCC and 31 patients with liver cirrhosis were enrolled...
November 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29215008/roles-of-two-types-of-heparan-sulfate-clusters-in-wnt-distribution-and-signaling-in-xenopus
#10
Yusuke Mii, Takayoshi Yamamoto, Ritsuko Takada, Shuji Mizumoto, Makoto Matsuyama, Shuhei Yamada, Shinji Takada, Masanori Taira
Wnt proteins direct embryonic patterning, but the regulatory basis of their distribution and signal reception remain unclear. Here, we show that endogenous Wnt8 protein is distributed in a graded manner in Xenopus embryo and accumulated on the cell surface in a punctate manner in association with "N-sulfo-rich heparan sulfate (HS)," not with "N-acetyl-rich HS". These two types of HS are differentially clustered by attaching to different glypicans as core proteins. N-sulfo-rich HS is frequently internalized and associated with the signaling vesicle, known as the Frizzled/Wnt/LRP6 signalosome, in the presence of Wnt8...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29204978/role-of-glypican-3-in-the-growth-migration-and-invasion-of-primary-hepatocytes-isolated-from-patients-with-hepatocellular-carcinoma
#11
Mauro Montalbano, Cristiana Rastellini, Joshua T McGuire, Janika Prajapati, Ali Shirafkan, Renza Vento, Luca Cicalese
BACKGROUND: Recently, Glypican-3 (GPC3) has been identified as a potential hepatocellular carcinoma (HCC) diagnostic and/or therapeutic target. GPC3 has been found to be up-regulated in HCC and to be absent in normal and cirrhotic liver. As yet, however, the molecular characteristics of GPC3 and its role in HCC cell physiology and development are still undefined. METHODS: Human hepatocyte cultures were established from 10 HCC patients. Additional liver samples were obtained from 5 patients without cirrhosis and/or HCC...
December 4, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29204748/imaging-the-expression-of-glypican-3-in-hepatocellular-carcinoma-by-pet
#12
Zhen Wang, Yan-Jiang Han, Shun Huang, Meng Wang, Wen-Lan Zhou, Hong-Sheng Li, Quan-Shi Wang, Hu-Bing Wu
The glypican-3 (GPC3) receptor is overexpressed in hepatocellular carcinoma (HCC) and is a potential diagnostic and therapeutic target. GPC3-targeted molecular imaging will be helpful to differentiate diagnosis and guide therapy. In the present study, we will develop a novel PET probe for imaging the expression of GPC-3. L5 (sequence: RLNVGGTYFLTTRQ), a GPC3 targeting peptide, was labeled with 5-carboxyfluorescein (FAM) and 18F-fluoride. Cell binding tests were performed to identify the binding specificity of FAM-L5 and 18F radiolabeled peptide...
December 4, 2017: Amino Acids
https://www.readbyqxmd.com/read/29203107/glypican-3-specific-cytotoxic-t-lymphocytes-induced-by-human-leucocyte-antigen-a-0201-restricted-peptide-effectively-kill-hepatocellular-carcinoma-cells-in%C3%A2-vitro
#13
Jiang-Zheng Zeng, Yu Liu, Fen Huang, Zhi-Hui He, Huamao Sun, Yan-Da Lu, Jun-Hua Lei, Rong-Cheng Luo
OBJECTIVE: To investigate potential human leucocyte antigen (HLA)-A2-restricted epitope peptides of glypican-3 (GPC3) and determine the cytotoxicity of peptide-specific cytotoxic T lymphocytes (CTLs) against hepatocellular carcinoma (HCC) cells. METHODS: The potential HLA-A*0201-restricted GPC3 peptides were screened using computer algorithms, T2 cell-binding affinity and stability of peptide/HLA-A*0201 complex assay. The peptide-specific CTLs were generated and their cytotoxicity against GPC3+ SMMC 7721 and HepG2 cells was detected using IFN-γ based enzyme-linked immunospot and lactate dehydrogenase release assays in vitro...
November 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/29168748/variety-and-dynamics-of-proteoforms-in-the-human-proteome-aspects-of-markers-for-hepatocellular-carcinoma
#14
Stanislav Naryzhny, Victor Zgoda, Artur Kopylov, Elena Petrenko, Olga Kleist, Аlexander Archakov
We have previously developed an approach, where two-dimensional gel electrophoresis (2DE) was used, followed by sectional analysis of the whole gel using high-resolution nano-liquid chromatography-mass spectrometry (ESI LC-MS/MS). In this study, we applied this approach on the panoramic analysis of proteins and their proteoforms from normal (liver) and cancer (HepG2) cells. This allowed us to detect, in a single proteome, about 20,000 proteoforms coded by more than 4000 genes. A set of 3D-graphs showing distribution of these proteoforms in 2DE maps (profiles) was generated...
November 23, 2017: Proteomes
https://www.readbyqxmd.com/read/29166820/sinonasal-smarcb1-ini1-deficient-carcinoma-with-yolk-sac-tumor-differentiation-report-of-a-case-and-comparison-with-ini1-expression-in-gonadal-germ-cell-tumors
#15
Michal Zamecnik, Jiri Rychnovsky, Jakub Syrovatka
SMARCB1 (INI1) deficient sinonasal carcinoma is a recently recognized entity with wide histomorphologic spectrum. We present a case of this carcinoma that contained, in addition to a "common" morphology, scattered foci of yolk sac tumor differentiation. The tumor occurred in paranasal sinuses in a 44-year-old woman. Immunohistochemically, it was diffusely negative for INI1, whereas an expression of yolk sac tumor markers (α-fetoprotein, glypican-3, CDX2) was limited to the yolk sac tumor component. For comparison with the present case, we performed INI1 immunostaining on a series of 11 gonadal germ cell tumors with yolk sac tumor differentiation...
November 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29166241/two-classes-of-secreted-synaptic-organizers-in-the-central-nervous-system
#16
Michisuke Yuzaki
Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of preand/ or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft...
November 20, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/29162835/a-signal-amplifiable-biochip-quantifies-extracellular-vesicle-associated-rnas-for-early-cancer-detection
#17
Jiaming Hu, Yan Sheng, Kwang Joo Kwak, Junfeng Shi, Bohao Yu, L James Lee
Detection of extracellular vesicle (EV)-associated RNAs with low expression levels in early-stage cancer remains a challenge and is highly valuable. Here, we report a nanoparticle-based biochip that could capture circulating EVs without isolation, brighten encapsulated RNAs, and amplify fluorescence signals in situ in a single step. We confine catalyzed hairpin DNA circuit (CHDC) in cationic lipid-polymer hybrid nanoparticles (LPHNs) that are tethered on a chip. LPHN features a core-shell-corona structure that facilitates the transfer and mixing of CHDC with EV-associated RNAs when forming the LPHN-EV nanocomplex...
November 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29152084/the-stromal-morphological-changes-for-differential-diagnosis-of-uninodular-high-grade-dysplastic-nodule-and-well-differentiated-small-hepatocellular-carcinoma
#18
Long-Hai Feng, Han Wang, Hui Dong, Yu-Yao Zhu, Wen-Ming Cong
Aim: The stromal invasion has been regarded as the most valuable clue to distinguish high-grade dysplastic nodules (HGDNs) and well-differentiated small hepatocellular carcinomas (WD-SHCCs). The purposes of this study are to explore the stromal morphological changes for the differential diagnosis of these two equivocal lesions. Results: Based on the systemic studies of histological characteristics of HGDNs and WD-SHCCs, the stromal morphological changes, including sinusoid capillarization, ductular reaction and solitary artery, were performed to make a differential diagnosis between them...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29123959/immunological-efficacy-of-glypican-3-peptide-vaccine-in-patients-with-advanced-hepatocellular-carcinoma
#19
Nobuhiro Tsuchiya, Toshiaki Yoshikawa, Norihiro Fujinami, Keigo Saito, Shoichi Mizuno, Yu Sawada, Itaru Endo, Tetsuya Nakatsura
We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29118993/cellular-characteristics-of-keratin-19-positive-canine-hepatocellular-tumours-explain-its-aggressive-behaviour
#20
Renee G van Sprundel, Ted Sgam van den Ingh, Baukje A Schotanus, Monique E van Wolferen, Louis C Penning, Jan Rothuizen, Bart Spee
The expression of the hepatic progenitor cell marker keratin 19 (K19) in canine hepatocellular carcinomas is linked with a poor prognosis. To better understand this aggressive behaviour, K19-positive hepatocellular carcinomas (n=5) and K19-negative hepatocellular adenomas (n=6) were immunohistochemically stained for proteins involved in malignant tumour development. The K19-positive carcinomas showed marked positivity for platelet-derived growth factor receptor alpha polypeptide (PDGFRα), laminin, integrin beta-1/CD29, B-cell-specific Moloney murine leukaemia virus Integration site 1, glypican-3 (GPC-3) and prominin-1/CD133, in contrast with K19-negative hepatocellular adenomas...
2017: Veterinary Record Open
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