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Lin Mei, Jean-Paul Borg
ERBB2 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2) is an oncogenic tyrosine kinase receptor that is overexpressed in breast cancer. Antibodies and inhibitors targeting ERBB2 are currently available, although therapeutic failures remain frequent. We discuss here recent data showing that the scaffold protein ERBB2IP (ERBB2 interacting protein, best known as ERBIN) regulates ERBB2 stability and may represent a future therapeutic target.
July 2015: Molecular & Cellular Oncology
Drew C Deniger, Anna Pasetto, Eric Tran, Maria R Parkhurst, Cyrille J Cohen, Paul F Robbins, Laurence Jn Cooper, Steven A Rosenberg
Neoantigens unique to each patient's tumor can be recognized by autologous T cells through their T-cell receptor (TCR) but the low frequency and/or terminal differentiation of mutation-specific T cells in tumors can limit their utility as adoptive T-cell therapies. Transfer of TCR genes into younger T cells from peripheral blood with a high proliferative potential could obviate this problem. We generated a rapid, cost-effective strategy to genetically engineer cancer patient T cells with TCRs using the clinical Sleeping Beauty transposon/transposase system...
June 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Satu J Siiskonen, Mingfeng Zhang, Wen-Qing Li, Liming Liang, Peter Kraft, Tamar Nijsten, Jiali Han, Abrar A Qureshi
BACKGROUND: No GWAS on the risk of cutaneous squamous cell carcinoma (SCC) has been published. We conducted a multistage genome-wide association study (GWAS) to identify novel genetic loci for SCC. METHODS: The study included 745 SCC cases and 12,805 controls of European descent in the discovery stage and 531 SCC cases and 551 controls of European ancestry in the replication stage. We selected 64 independent loci that showed the most significant associations with SCC in the discovery stage (linkage disequilibrium r(2) < 0...
April 2016: Cancer Epidemiology, Biomarkers & Prevention
Wanpeng Wang, Shan Mou, Ling Wang, Minfang Zhang, Xinghua Shao, Wei Fang, Renhua Lu, Chaojun Qi, Zhuping Fan, Qin Cao, Qin Wang, Yan Fang, Zhaohui Ni
Systemic lupus erythematosus (SLE) is a common but severe autoimmune systemic inflammatory disease. Lupus nephritis (LN) is a serious complication of SLE,affecting up to 70% of SLE patients. Circulating microRNAs (miRNA) are emerging as biomarkers for pathological conditions and play significant roles in intercellular communication. In present research, serum samples from healthy control, early and late stage LN patients were used to analyze the expression profile of miRNAs by microarray. Subsequent study demonstrated that miR-130b-3p in serum of patients with early stage LN were significantly up-regulated when compared with healthy controls...
2015: Scientific Reports
Chuan-Ming Xie, Dongping Wei, Lili Zhao, Sylvie Marchetto, Lin Mei, Jean-Paul Borg, Yi Sun
SAG/RBX2 is the RING (really interesting new gene) component of Cullin-RING ligase, which is required for its activity. An organ-specific role of SAG in tumorigenesis is unknown. We recently showed that Sag/Rbx2, upon lung-targeted deletion, suppressed Kras(G12D)-induced tumorigenesis via inactivating NF-κB and mammalian target of rapamycin pathways. In contrast, we report here that, upon skin-targeted deletion, Sag significantly accelerated Kras(G12D)-induced papillomagenesis. In Kras(G12D)-expressing primary keratinocytes, Sag deletion promotes proliferation by inhibiting autophagy and senescence, by inactivating the Ras-Erk pathway, and by blocking reactive oxygen species (ROS) generation...
June 8, 2015: Journal of Cell Biology
Maurizio Zanetti
Cellular immune responses that protect against tumors typically have been attributed to CD8 T cells. However, CD4 T cells also play a central role. It was shown recently that, in a patient with metastatic cholangiocarcinoma, CD4 T cells specific for a peptide from a mutated region of ERBB2IP could arrest tumor progression. This and other recent findings highlight new opportunities for CD4 T cells in cancer immunotherapy. In this article, I discuss the role and regulation of CD4 T cells in response to tumor Ags...
March 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Qun Wang, Hongchao Lv, Wenhua Lv, Miao Shi, Mingming Zhang, Meiwei Luan, Hongjie Zhu, Ruijie Zhang, Yongshuai Jiang
Prostate cancer (PC) is a common malignant tumor that occurs in the prostate epithelial cells. It is generally considered to be caused by both genetic and environmental factors. To identify the genetic risk factors of PC in Chinese population, we carried out a genome-wide haplotype-based association study. The 33 Chinese PC cases were from the public GEO database (GSE18333), and the 139 Chinese controls (CHB) were from the HapMap project. Our analysis included three stages: (1) identifying the linkage disequilibrium (LD) blocks and performing genome-wide haplotype association scan, (2) mapping PC-risk haplotypes to PC candidate genes, and (3) prioritizing PC candidate genes based on their similarity to known PC susceptibility genes...
April 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Eric Tran, Simon Turcotte, Alena Gros, Paul F Robbins, Yong-Chen Lu, Mark E Dudley, John R Wunderlich, Robert P Somerville, Katherine Hogan, Christian S Hinrichs, Maria R Parkhurst, James C Yang, Steven A Rosenberg
Limited evidence exists that humans mount a mutation-specific T cell response to epithelial cancers. We used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (T(H)1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional T(H)1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease...
May 9, 2014: Science
Hiroki Murakami, Seiji Ito, Harunari Tanaka, Eisaku Kondo, Yasuhiro Kodera, Hayao Nakanishi
BACKGROUND: Intraperitoneal (i.p.) chemotherapy with paclitaxel is a potential therapeutic modality for patients with peritoneal metastasis of gastric cancer. To overcome paclitaxel resistance, which is a major clinical problem with this modality, prediction of i.p. paclitaxel resistance is critically important. MATERIALS AND METHODS: We developed three new i.p. paclitaxel-resistant cell lines from parental gastric cancer cell lines by an in vivo selection method using i...
October 2013: Anticancer Research
Robert M Harmon, Cory L Simpson, Jodi L Johnson, Jennifer L Koetsier, Adi D Dubash, Nicole A Najor, Ofer Sarig, Eli Sprecher, Kathleen J Green
Genetic disorders of the Ras/MAPK pathway, termed RASopathies, produce numerous abnormalities, including cutaneous keratodermas. The desmosomal cadherin, desmoglein-1 (DSG1), promotes keratinocyte differentiation by attenuating MAPK/ERK signaling and is linked to striate palmoplantar keratoderma (SPPK). This raises the possibility that cutaneous defects associated with SPPK and RASopathies share certain molecular faults. To identify intermediates responsible for executing the inhibition of ERK by DSG1, we conducted a yeast 2-hybrid screen...
April 2013: Journal of Clinical Investigation
Simone Lipinski, Nils Grabe, Gunnar Jacobs, Susanne Billmann-Born, Andreas Till, Robert Häsler, Konrad Aden, Maren Paulsen, Alexander Arlt, Lars Kraemer, Nina Hagemann, Kai Sven Erdmann, Stefan Schreiber, Philip Rosenstiel
The intracellular nucleotide-binding oligomerization domain-2 (NOD2) receptor detects bacteria-derived muramyl dipeptide (MDP) and activates the transcription factor NF-κB. Here we describe the regulatome of NOD2 signaling using a systematic RNAi screen. Using three consecutive screens, we identified a set of 20 positive NF-κB regulators including the known pathway members RIPK2, RELA, and BIRC4 (XIAP) as well as FRMPD2 (FERM and PDZ domain-containing 2). FRMPD2 interacts with NOD2 via leucine-rich repeats and forms a complex with the membrane-associated protein ERBB2IP...
December 26, 2012: Proceedings of the National Academy of Sciences of the United States of America
Mijke W Vogels, Bas W M van Balkom, Albert J R Heck, Cornelis A M de Haan, Peter J M Rottier, Joseph J Batenburg, Dora V Kaloyanova, J Bernd Helms
To identify host factors involved in Salmonella replication, SILAC-based quantitative proteomics was used to investigate the interactions of Salmonella typhimurium with the secretory pathway in human epithelial cells. Protein profiles of Golgi-enriched fractions isolated from S. typhimurium-infected cells were compared with those of mock-infected cells, revealing significant depletion or enrichment of 105 proteins. Proteins annotated to play a role in membrane traffic were overrepresented among the depleted proteins whereas proteins annotated to the cytoskeleton showed a diverse behavior with some proteins being enriched, others being depleted from the Golgi fraction upon Salmonella infection...
December 2011: Proteomics
Elena Zaslavsky, Philip Bradley, Chen Yanover
Many important cellular protein interactions are mediated by peptide recognition domains. The ability to predict a domain's binding specificity directly from its primary sequence is essential to understanding the complexity of protein-protein interaction networks. One such recognition domain is the PDZ domain, functioning in scaffold proteins that facilitate formation of signaling networks. Predicting the PDZ domain's binding specificity was a part of the DREAM4 Peptide Recognition Domain challenge, the goal of which was to describe, as position weight matrices, the specificity profiles of five multi-mutant ERBB2IP-1 domains...
2010: PloS One
Masahiro Oikawa, Hideo Kuniba, Tatsuro Kondoh, Akira Kinoshita, Takeshi Nagayasu, Norio Niikawa, Koh-ichiro Yoshiura
Familial arteriovenous malformations (AVM) in the brain is a very rare disease. It is defined as its occurrence in two or more relatives (up to third-degree relatives) in a family without any associated disorders, such as hereditary hemorrhagic telangiectasia. We encountered a Japanese family with brain AVM in which four affected members in four successive generations were observed. One DNA sample extracted from leukocytes of the proband and ten DNA samples from clipped finger nails of other members were available...
September 2010: European Journal of Medical Genetics
A Spötter, H Hamann, S Müller, O Distl
We carried out an SNP discovery project in pigs for candidate genes playing potentially important roles in embryonic development. Using eight pigs one each from eight breeds (Meishan, Mangalitza, Duroc, Pietrain, German Landrace, Hampshire, Husum Red Pied, German Large White), 36 SNPs were identified in intronic sequences of 21 porcine candidate genes based on sequencing of PCR products. The primer pairs were designed using porcine EST sequences allowing amplification of introns. These SNPs were tested for their association with the number of piglets born alive in German Large White sows using a discordant approach...
August 2010: Reproduction in Domestic Animals, Zuchthygiene
Margarita Stefanova, Katrin Zemke, Boyan Dimitrov, Christina Has, Johannes S Kern, Leena Bruckner-Tuderman, Kerstin Kutsche
Mutations in the type VII collagen gene (COL7A1) cause autosomal recessive and autosomal dominant inherited dystrophic epidermolysis bullosa (DEB). We report a family with three individuals who present blistering, scarring, hypo- and hyperpigmentation, and nail dystrophy suggestive for DEB. Whereas father and son carry a 5;13 translocation, the daughter shows a normal karyotype. Segregation analysis revealed that all affected family members inherited the same COL7A1 allele. Mutation analysis disclosed a heterozygous missense mutation, c...
October 2005: Journal of Investigative Dermatology
Masuko Katoh, Masaru Katoh
Drosophila Guanylate-kinase holder (Gukh) is an adaptor molecule bridging Discs large (Dlg) and Scribble (Scrib), which are implicated in the establishment and maintenance of epithelial polarity. Here, we searched for human homologs of Drosophila gukh by using bioinformatics, and identified GUKH1 and GUKH2 genes. GUKH1 was identical to Nance-Horan syndrome (NHS) gene, while GUKH2 was a novel gene. FLJ35425 (AK092744.1), DKFZp686P1949 (BX647246.1) and KIAA1357 (AB037778.1) cDNAs were derived from human GUKH2 gene...
April 2004: International Journal of Oncology
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