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Mahsa Bagherpour, Kamelia Gharibzad, Hossein Rassi
Breast cancer (BC) is a multistep disease that is thought to result from an interaction between genetic background and environmental factors. In Iran, one of the strongest risk factors for developing BC is a positive family history of the disease. Recently, various polymorphisms of E-cadherin (CDH1) and TERT have been found to be associated with increased BC risk worldwide. This study aimed to analyze the association of CDH1 and TERT single-nucleotide polymorphisms with susceptibility to familial BC (FBC) risk in the Iranian patients...
December 11, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Taro Funakoshi, Shin'ichi Miyamoto, Nobuyuki Kakiuchi, Mitsuhiro Nikaido, Takeshi Setoyama, Akira Yokoyama, Takahiro Horimatsu, Atsushi Yamada, Masako Torishima, Shinji Kosugi, Hidetaka Yamada, Haruhiko Sugimura, Hironori Haga, Yoshiharu Sakai, Seishi Ogawa, Hiroshi Seno, Manabu Muto, Tsutomu Chiba
Germline mutations in CDH1, encoding E-cadherin, are known to be the causative mechanism of hereditary diffuse gastric cancer (HDGC). We encountered two cases of gastric cancer in a Japanese family with HDGC. A 28-year-old man (Case 1) died of advanced gastric cancer. His younger sister aged 27 (Case 2) was diagnosed with intramucosal signet ring cell carcinoma (SRCC). Both had identical germline CDH1 mutations, but Case 1 was positive for Helicobacter pylori infection, whereas Case 2 was negative. Case 2 underwent total gastrectomy...
December 12, 2018: Gastric Cancer
Patrick R Benusiglio, Chrystelle Colas, Erell Guillerm, Axelle Canard, Hélène Delhomelle, Mathilde Warcoin, Jérôme Bellanger, Mélanie Eyries, Mohamed Zizi, Jeanne Netter, Florent Soubrier, Yann Parc, Anne Mourregot, Aurélie Maran Gonzalez, Veronica Cusin, Jérôme A Denis, Isabelle Coupier, Magali Svrcek, Florence Coulet
In 2017, we implemented CTNNA1 germline analysis in probands suspected of having hereditary diffuse gastric cancer. Here, we report the results from a retrospective series of 41 cases, including the identification of a new family with a CTNNA1 mutation and the first prophylactic total gastrectomy in an asymptomatic carrier after a normal upper endoscopy. Diffuse gastric cancer foci with loss of catenin alpha-1 expression were seen in the resected tissue, suggesting that CTNNA1 and CDH1 germline mutations behave in a similar manner...
December 4, 2018: Gastric Cancer
Wittaya Suwakulsiri, Alin Rai, Rong Xu, Maoshan Chen, David W Greening, Richard J Simpson
Extracellular vesicles can be classified into two main classes - exosomes and shed microvesicles (sMVs). Whilst much is known about exosome cargo and functionality, sMVs are poorly understood. Here, we describe the large-scale purification of sMVs released from primary (SW480) and metastatic (SW620) human isogenic colorectal cancer (CRC) cell lines using a combination of differential ultracentrifugation and isopycnic iodixanol density centrifugation. The yield of SW480-sMVs and SW620-sMVs was 0.75 mg and 0...
November 28, 2018: Biochimica et biophysica acta. Proteins and proteomics
Bo Xu, Rui Ma, Luke Russell, Ji Young Yoo, Jianfeng Han, Hanwei Cui, Ping Yi, Jianying Zhang, Hiroshi Nakashima, Hongsheng Dai, E Antonio Chiocca, Balveen Kaur, Michael A Caligiuri, Jianhua Yu
The efficacy of oncolytic herpes simplex virus (oHSV) is limited by rapid viral clearance by innate immune effector cells and poor intratumoral viral spread. We combine two approaches to overcome these barriers: inhibition of natural killer (NK) cells and enhancement of intratumoral viral spread. We engineered an oHSV to express CDH1, encoding E-cadherin, an adherent molecule and a ligand for KLRG1, an inhibitory receptor expressed on NK cells. In vitro, infection with this engineered virus, named OV-CDH1, induced high surface E-cadherin expression on infected glioblastoma (GBM) cells, which typically lack endogenous E-cadherin...
November 26, 2018: Nature Biotechnology
Elham Orangi, Majid Motovali-Bashi
PURPOSE: MicroRNAs are involved in diverse biological processes and their dysregulation is a common event in various diseases including breast cancer. Breast cancer is a major threat to women's health. This study was designed to examine the expression levels of miR-9 and miR-34a in breast tumor tissue samples and plasma of breast cancer patients, compare their expression pattern between tissue samples and plasma samples of patients and analyze their relationship with tumor clinical features...
November 20, 2018: Gene
Vicente Munitiz Ruiz, Pilar Jimeno, David Ruiz de Angulo, Ángeles Ortiz, Luisa F Martínez de Haro, Miguel Marín, Pedro Cascales, Gema Ruiz García, Eduardo Ortiz Ruiz, Pascual Parrilla
INTRODUCTION: hereditary diffuse gastric cancer (HDGC) is a recently reported hereditary cancer syndrome. Patients with suspected HDGC must be under surveillance via endoscopy and multiple biopsies. As an alternative, some studies suggest prophylactic gastrectomy (PG) for disease carriers. The goal of this article was to report our experience with a CDH1 mutation positive family who underwent PG. PATIENTS AND METHODS: the index case was a 34-year-old female diagnosed with diffuse gastric adenocarcinoma and massive carcinomatosis...
November 23, 2018: Revista Española de Enfermedades Digestivas
Zuofan Li, Bo Zhang, Wenlong Yao, Chuanhan Zhang, Li Wan, Yue Zhang
Anaphase-promoting complex (APC) with its coactivator Cdh1 is required to maintain the postmitotic state of neurons via degradation of Cyclin B1, which aims to prevent aberrant cell cycle entry that causes neuronal apoptosis. Interestingly, evidence is accumulating that apart from the cell cycle, APC-Cdh1 also involves in neuronal metabolism via modulating the glycolysis promoting enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3). Here, we showed that under oxygen-glucose deprivation and reperfusion (OGD/R), APC-Cdh1 was decreased in primary cortical neurons...
November 20, 2018: Cellular and Molecular Neurobiology
Xiaoqin Zhu, Mohammed Salhab, Keith Tomaszewicz, Xiuling Meng, Carol Mathew, Venu Bathini, Bradley Switzer, Otto Walter, Ediz F Cosar, Xiaofei Wang, Laura A Lambert, Lloyd M Hutchinson
The 8th edition of American Joint Committee on Cancer (AJCC) advocates a three-tier grading system for appendiceal mucinous tumors. The mutational profile for each tumor grade and the impact of TP53 mutation on survival is unknown.We classified appendiceal mucinous tumors into 3 grades based on the 8th edition of AJCC: 21G1 low-grade mucinous neoplasms, 21G2 appendiceal adenocarcinomas, and 26G3 signet ring cell carcinomas (SRC). Mutation profiles were obtained using next generation sequencing (NGS). The impact of TP53 on prognosis was investigated by multivariable analysis...
November 17, 2018: Human Pathology
C van Marcke, A Collard, M Vikkula, F P Duhoux
BACKGROUND: Gene-panels are used to assess predisposition to breast cancer by simultaneous testing of multiple susceptibility genes. This approach increases the identification of variants of unknown significance (VUS) that cannot be used in clinical decision-making. We performed a systematic review of published studies to calculate the prevalence of VUS and pathogenic variants (PV) in routinely tested breast cancer susceptibility genes in patients at high risk of breast cancer. METHODS: We comprehensively searched the literature using Medline through May 23, 2017 for studies conducting gene-panel testing on germline DNA of women with familial breast cancer and reporting on both PVs and VUSs...
December 2018: Critical Reviews in Oncology/hematology
Doreen N Palsgrove, Diana Taheri, Simeon U Springer, Morgan Cowan, Gunes Guner, Maria A Mendoza Rodriguez, Maria Del Carmen Rodriguez Pena, Yuxuan Wang, Isaac Kinde, Bernardo F P Ricardo, Isabela Cunha, Kazutoshi Fujita, Dilek Ertoy, Kenneth W Kinzler, Trinity J Bivalacqua, Nickolas Papadopoulos, Bert Vogelstein, George J Netto
Activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. While the cadherin 1 (CDH1) gene is commonly mutated in the clinically aggressive plasmacytoid variant of urothelial carcinoma (PUC), little is known about their TERT promoter mutation status. A retrospective search of our archives for PUC and UC with plasmacytoid and/or signet ring cell features (2007-2014) was performed...
November 14, 2018: Human Pathology
Rong Wang, Jinbin Li, Chunyu Yin, Di Zhao, Ling Yin
BACKGROUND: This study aimed to identify the differentially expressed genes (DEGs) and the typical fusion genes in different types of breast cancers using RNA-seq. METHODS: GSE52643 was downloaded from Gene Expression Omnibus, which included 1 normal sample (MCF10A) and 7 breast cancer samples (BT-474, BT-20, MCF7, MDA-MB-231, MDA-MB-468, T47D, and ZR-75-1). The transcript abundance and the DEGs screening were performed by Cufflinks. The functional and pathway enrichment was analyzed by Gostats...
November 16, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Nicolas Skrypek, Kenneth Bruneel, Cindy Vandewalle, Eva De Smedt, Bieke Soen, Nele Loret, Joachim Taminau, Steven Goossens, Niels Vandamme, Geert Berx
BACKGROUND: Epithelial mesenchymal transition (EMT) is tightly regulated by a network of transcription factors (EMT-TFs). Among them is the nuclear factor ZEB2, a member of the zinc-finger E-box binding homeobox family. ZEB2 nuclear localization has been identified in several cancer types, and its overexpression is correlated with the malignant progression. ZEB2 transcriptionally represses epithelial genes, such as E-cadherin (CDH1), by directly binding to the promoter of the genes it regulates and activating mesenchymal genes by a mechanism in which there is no full agreement...
November 16, 2018: Epigenetics & Chromatin
Stephanie Schubert, Jana L van Luttikhuizen, Bernd Auber, Gunnar Schmidt, Winfried Hofmann, Judith Penkert, Colin F Davenport, Ursula Hille-Betz, Lena Wendeburg, Janin Bublitz, Marcel Tauscher, Karl Hackmann, Evelin Schroeck, Caroline Scholz, Hannah Wallaschek, Brigitte Schlegelberger, Thomas Illig, Doris Steinemann
NGS-based multiple gene panel resequencing in combination with a high resolution CGH-array was used to identify genetic risk factors for hereditary breast and/or ovarian cancer in 237 high risk patients who were previously tested negative for pathogenic BRCA1/2 variants. All patients were screened for pathogenic variants in 94 different cancer predisposing genes. We identified 32 pathogenic variants in 14 different genes (ATM, BLM, BRCA1, CDH1, CHEK2, FANCG, FANCM, FH, HRAS, PALB2, PMS2, PTEN, RAD51C and NBN) in 30 patients (12...
November 13, 2018: International Journal of Cancer. Journal International du Cancer
Taiki Hashimoto, Reiko Ogawa, Tzu-Yin Tang, Hiroshi Yoshida, Hirokazu Taniguchi, Hitoshi Katai, Ichiro Oda, Shigeki Sekine
A subtype of intestinal-type adenocarcinoma of the stomach, characterized by low-grade cytological atypia and anastomosing glands, has been described in several reports under different names. One of the remarkable features of these lesions, herein referred to as intestinal-type adenocarcinoma with anastomosing glands, is the frequent association of poorly differentiated adenocarcinoma components. Here we analyzed 44 intestinal-type adenocarcinomas with anastomosing glands focusing on the molecular abnormalities that are common in diffuse-type gastric cancers...
November 13, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
E S Sokol, Y X Feng, D X Jin, A Basudan, A V Lee, J M Atkinson, J Chen, P J Stephens, G M Frampton, P B Gupta, J S Ross, J Chung, S Oesterreich, S Ali, R J Hartmaier
Background: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations may develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed. Patients and Methods: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 ER-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in 395 cancer-related genes...
November 13, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Bárbara Roberta Ongaratti, Taiana Haag, Marícia Fantinel D'Ávila, Geraldine Trott, Nelson Pires Ferreira, Carolina Garcia Soares Leães Rech, Júlia Fernanda Semmelmman Pereira-Lima, Miriam da Costa Oliveira
Non-functioning pituitary adenomas (NFPA) are classified as benign tumors of slow growth, but 40% of them present local invasion, a characteristic of behavior still unpredictable with the use of current tumor markers. This work aims to evaluate the tissue markers E-cadherin and NCAM, which act on cell adhesion, in tumor tissue samples of NFPA and its relationship with the degree of local invasiveness. Gene expression of E-cadherin (CDH1) and NCAM (NCAM1) was assessed by real-time PCR and tissue expression by immunohistochemistry...
October 9, 2018: Annals of Diagnostic Pathology
Yue-Hang Geng, Zi-Fan Wang, Yu-Mian Jia, Li-Yuan Zheng, Lan Chen, Dong-Ge Liu, Xiang-Hong Li, Xin-Xia Tian, Wei-Gang Fang
The cadherin 1 ( CDH1 ) gene plays critical roles in the epithelial-mesenchymal transition process, potentially offering us a glimpse into the development of endometrial carcinoma (EC). The present study aimed to identify whether genetic variants in CDH1 affect EC susceptibility in Chinese Han women, using a strategy combining haplotype-tagging single nucleotide polymorphisms (htSNPs) association analysis with fine-scale mapping. A total of 9 htSNPs in CDH1 were genotyped among 516 cases and 706 age-matched cancer-free controls...
November 2018: Oncology Letters
Masayoshi Nagai, Atsuko Shibata, Takashi Ushimaru
Cdh1, a substrate-recognition subunit of anaphase-promoting complex/cyclosome (APC/C), is a tumor suppressor, and it is downregulated in various tumor cells in humans. APC/C-Cdh1 is activated from late M phase to G1 phase by antagonizing Cdk1-mediated inhibitory phosphorylation. However, how Cdh1 protein levels are properly regulated is ill-defined. Here we show that Cdh1 is degraded via APC/C-Cdh1 and Skp1-Cullin1-F-box (SCF)-Cdc4 in the budding yeast Saccharomyces cerevisiae. Cdh1 degradation was promoted by forced localization of Cdh1 into the nucleus, where APC/C and SCF are present...
November 2, 2018: Biochemical and Biophysical Research Communications
Maja Životić, Björn Tampe, Gerhard Müller, Claudia Müller, Aleksandar Lipkovski, Xingbo Xu, Gunsmaa Nyamsuren, Michael Zeisberg, Jasmina Marković-Lipkovski
Neural cell adhesion molecule (NCAM) and fibroblast growth factor receptor 1 (FGFR1) cross-talk have been involved in epithelial-to-mesenchymal transition (EMT) process during carcinogenesis. Since EMT also contributes to maladaptive repair and parenchymal damage during renal fibrosis, we became encouraged to explore the role of NCAM/FGFR1 signaling as initiating or driving forces of EMT program in cultured human proximal tubular epithelial cells (TECs). TECs stimulated with TGF-β1 (10ng/mL) was used as an established in vitro EMT model...
2018: PloS One
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