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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
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
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
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
Pei Hu, Bin Cheng, Yulin He, Zhiqiang Wei, Dongfang Wu, Zhongji Meng
Introduction: Autophagy plays an important role in the growth and survival of hepatocellular carcinoma (HCC) cells through several target proteins or signaling pathways. Glypican-3 (GPC3) is a new reliable HCC marker, which is involved in tumor growth in HCC, primarily mediated by wnt/β-catenin signaling. Objective: The present study aimed to identify the role of autophagy in the proliferation of HepG2 cells through GPC3/wnt/β-catenin signaling. Results and discussion: Results demonstrated that induction of autophagy by nutrition starvation and rapamycin treatment led to the downregulation of GPC3 expression in HepG2 cells, accompanied by the decreased expression of wnt downstream target genes (β-catenin, c-myc and cyclin D1)...
2018: OncoTargets and Therapy
Hong Liu, Chunmei Yang, Wenzhu Lu, Yong Zeng
BACKGROUND: In recent years, an increasing number of studies has been published analyzing the possible prognostic utility of glypican-3 (GPC3) in hepatocellular carcinoma (HCC), but the results are still controversial. The aim of this meta-analysis was to evaluate possible association between GPC3 expression and patients' survival. METHODS: Relevant publications which assessed GPC3 expression with survival outcome in HCC patients were searched from Pubmed, Embase, Web of Science, and the Cochrane library...
January 2018: Medicine (Baltimore)
Ahmad Saad, Benjamin Liet, Gilles Joucla, Xavier Santarelli, Justine Charpentier, Stéphane Claverol, Christophe F Grosset, Véronique Trézéguet
Glypican 3 (GPC3) is a complex heparan sulfate proteoglycan associated with the outer surface of the plasma membrane by a glycosyl-phosphatidylinositol anchor (GPI). It is also N-glycosylated and processed by a furine-like convertase. GPC3 has numerous biological functions. While undetectable in normal liver tissue, it is abnormally and highly overexpressed in hepatocellular carcinoma (HCC). Interestingly, proliferation of HCC cells such as HepG2 and HuH7 is inhibited when they express a soluble form of GPC3 after lentiviral transduction...
January 18, 2018: Biochemistry
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
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
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
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
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
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)
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) and18 F-fluoride. Cell binding tests were performed to identify the binding specificity of FAM-L5 and18 F radiolabeled peptide...
February 2018: Amino Acids
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
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