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https://www.readbyqxmd.com/read/28821955/targeted-next-generation-sequencing-for-analyzing-the-genetic-alterations-in-atypical-adenomatous-hyperplasia-and-adenocarcinoma-in-situ
#1
Xuan Xu, Na Li, Ruiying Zhao, Lei Zhu, Jinchen Shao, Jie Zhang
PURPOSE: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) have been defined as preinvasive pulmonary adenocarcinoma lesions according to the 2015 World Health Organization lung adenocarcinoma classification. We aimed to search for the most common gene mutations in patients with AAH and AIS and investigate the distinctions between the two groups at the molecular level. METHODS: We performed targeted next-generation sequencing on 18 cases with AAH and 28 cases with AIS to screen for mutations with the Ion Torrent Oncomine Solid Tumor DNA panel...
August 18, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28817097/bloch-surface-waves-biosensors-for-high-sensitivity-detection-of-soluble-erbb2-in-a-complex-biological-environment
#2
Alberto Sinibaldi, Camilla Sampaoli, Norbert Danz, Peter Munzert, Frank Sonntag, Fabio Centola, Agostino Occhicone, Elisa Tremante, Patrizio Giacomini, Francesco Michelotti
We report on the use of one-dimensional photonic crystals to detect clinically relevant concentrations of the cancer biomarker ERBB2 in cell lysates. Overexpression of the ERBB2 protein is associated with aggressive breast cancer subtypes. To detect soluble ERBB2, we developed an optical set-up which operates in both label-free and fluorescence modes. The detection approach makes use of a sandwich assay, in which the one-dimensional photonic crystals sustaining Bloch surface waves are modified with monoclonal antibodies, in order to guarantee high specificity during the biological recognition...
August 17, 2017: Biosensors
https://www.readbyqxmd.com/read/28816616/transfer-rna-mediated-enhancement-of-ribosomal-proteins-s6-kinases-signalling-for-cell-proliferation
#3
Nam Hoon Kwon, Mi Ran Lee, Jiwon Kong, Seung Kyun Park, Byung Joon Hwang, Byung Gyu Kim, Eun-Shin Lee, Hyeong-Gon Moon, Sunghoon Kim
While transfer RNAs (tRNAs) are known to transport amino acids to ribosome, new functions are being unveiled from tRNAs and their fragments beyond protein synthesis. Here we show that phosphorylation of 90-kDa RPS6K (ribosomal proteins S6 kinase) was enhanced by tRNA(Leu) overexpression under amino acids starvation condition. The phosphorylation of 90-kDa RPS6K was decreased by siRNA specific to tRNA(Leu) and was independent to mTOR (mammalian target of rapamycin) signalling. Among the 90-kDa RPS6K family, RSK1 (ribosomal S6 kinase 1) and MSK2 (mitogen-and stress-activated protein kinase 2) were the major kinases phosphorylated by tRNA(Leu) overexpression...
August 17, 2017: RNA Biology
https://www.readbyqxmd.com/read/28815047/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#4
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28811376/in-vivo-loss-of-function-screens-identify-kpnb1-as-a-new-druggable-oncogene-in-epithelial-ovarian-cancer
#5
Michiko Kodama, Takahiro Kodama, Justin Y Newberg, Hiroyuki Katayama, Makoto Kobayashi, Samir M Hanash, Kosuke Yoshihara, Zhubo Wei, Jean C Tien, Roberto Rangel, Kae Hashimoto, Seiji Mabuchi, Kenjiro Sawada, Tadashi Kimura, Neal G Copeland, Nancy A Jenkins
Epithelial ovarian cancer (EOC) is a deadly cancer, and its prognosis has not been changed significantly during several decades. To seek new therapeutic targets for EOC, we performed an in vivo dropout screen in human tumor xenografts using a pooled shRNA library targeting thousands of druggable genes. Then, in follow-up studies, we performed a second screen using a genome-wide CRISPR/Cas9 library. These screens identified 10 high-confidence drug targets that included well-known oncogenes such as ERBB2 and RAF1, and novel oncogenes, notably KPNB1, which we investigated further...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807052/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#6
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28805349/crispr-assisted-receptor-deletion-reveals-distinct-roles-for-erbb2-and-erbb3-in-skin-keratinocytes
#7
Maik Dahlhoff, Nadege Gaborit, Sebastian Bultmann, Heinrich Leonhardt, Yosef Yarden, Marlon R Schneider
While the epidermal growth factor receptor (EGFR) is an established regulator of skin development and homeostasis, the functions of the related tyrosine kinase receptors ERBB2 and ERBB3 in this tissue have only recently been examined. Previously reported, skin-specific deletion of each of these receptors in mice resulted in similar defects in keratinocyte proliferation and migration, resulting in impaired wound healing and tumorigenesis. Because both ERBB2 and ERBB3 are targets for treating an array of cancer types, it is important to examine the consequences of receptor inhibition in human keratinocytes...
August 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28802750/para-sulfonatocalix-4-arene-stabilized-gold-nanoparticles-multilayers-interfaced-to-electrodes-through-host-guest-interaction-for-sensitive-erbb2-detection
#8
Xingxin Wang, Dongshu Du, Haibin Dong, Sunfengda Song, Kwangnak Koh, Hongxia Chen
Nanoparticle (NP) structure, compositing and the nature of the NP-functionalized electrode interface have a strong influence upon electrochemical properties that are critical in applications such as sensing, photocatalysis and electrocatalysis. Existing methods to fabricate NP-functionalized electrodes do not allow or precise control over all these variables, especially the NP-electrode interface, making it difficult to understand and predict how structural changes influence electrode activity and consequently limit the application...
August 8, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28802642/prognostic-value-of-tert-alterations-and-mutational-and-copy-number-alteration-burden-in-urothelial-carcinoma
#9
Sumit Isharwal, François Audenet, Esther Drill, Eugene J Pietzak, Gopa Iyer, Irina Ostrovnaya, Eugene Cha, Timothy Donahue, Maria Arcila, Gowtham Jayakumaran, Michael F Berger, Jonathan E Rosenberg, Dean F Bajorin, Jonathan Coleman, Guido Dalbagni, Victor E Reuter, Bernard H Bochner, David B Solit, Hikmat A Al-Ahmadie
Missense mutations in the TERT gene promoter occur at high frequency in multiple cancers, including urothelial carcinoma (UC). However, the relationship between TERT promoter mutations and UC patient outcomes is unclear due to conflicting reports in the literature. In this study, we examined the association of TERT alterations, tumor mutational burden per megabase (Mb), and copy number alteration (CNA) burden with clinical parameters and their prognostic value in a cohort of 398 urothelial tumors. The majority of TERT mutations were located at two promoter region hotspots (chromosome 5, 1 295 228 C>T and 1 295 250 C>T)...
August 9, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28802177/dna-biosensors-based-on-gold-nanoparticles-modified-graphene-oxide-for-the-detection-of-breast-cancer-biomarkers-for-early-diagnosis
#10
Ayman Ali Saeed, Josep Lluís Acero Sánchez, Ciara K O'Sullivan, Mohammed Nooredeen Abbas
Two different DNA (ERBB2c and CD24c) modified gold nanoparticles and graphene oxide loaded on glassy carbon electrodes were prepared for early detection of breast cancer markers by electrochemical detection of HER2. Comparative study of ERBB2c and CD24c for the detection was carried out. A "sandwich-type" detection strategy was employed in this electrochemical DNA biosensor and its response was measured by amperometric detection. The electrochemical signal enhancement achieved via gold nanoparticles and grapheme oxide system allowed for sensitive detection of the breast cancer biomarker ERBB2 and the control marker CD24...
July 14, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/28791647/analysis-of-epithelial-mesenchymal-transition-induced-by-overexpression-of-twist
#11
Jing-Wen Bai, Yong-Qu Zhang, Yao-Chen Li, Guo-Jun Zhang
Breast cancer, the most common malignancy among women worldwide, is a heterogeneous disease, and it therefore has remarkably different biological characteristics and clinical behavior. Breast cancer has been divided into several different molecular subtypes based on the status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2, also named as ErbB2) status. Her2 is a member of EGFR family of transmembrane tyrosine kinase-type receptors, and is involved in the activation of its downstream signaling cascades, which could promote cell proliferation, metastasis, and angiogenesis in tumors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791631/erbb-receptors-and-cancer
#12
Zhixiang Wang
The ErbB receptor family, also known as the EGF receptor family or type I receptor family, includes the epidermal growth factor (EGF) receptor (EGFR) or ErbB1/Her1, ErbB2/Her2, ErbB3/Her3, and ErbB4/Her4. Among all RTKs, EGFR was the first RTK identified and the first one linked to cancer. Thus, EGFR has also been the most intensively studied among all RTKs. ErbB receptors are activated after homodimerization or heterodimerization. The ErbB family is unique among the various groups of receptor tyrosine kinases (RTKs) in that ErbB3 has impaired kinase activity, while ErbB2 does not have a direct ligand...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28791339/identification-of-novel-genetic-etiology-and-key-molecular-pathways-for-seminoma-via-network-based-studies
#13
Yuanlei Chen, Chao Qi, Liqun Xia, Gonghui Li
Seminoma is the most common testicular malignant germ cell tumor which severely threaten male reproductive health. However, the pathogenesis and progression mechanisms are still unclear and little research is carried out to uncover the mechanism of this cancer. To identify gene signatures that are expected to converge on particular molecular pathways may drive the development of the core cancer characteristics in seminoma. We downloaded the gene expression profiles GSE18155 from GEO database and obtained the differentially expressed genes (DEGs)...
August 4, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28789929/commentary-on-comprehensive-transcriptional-analysis-of-early-stage-urothelial-carcinoma-hedegaard-j-lamy-p-nordentoft-i-algaba-f-h%C3%A3-yer-s-ulh%C3%A3-i-bp-vang-s-reinert-t-hermann-gg-mogensen-k-thomsen-mb-nielsen-mm-marquez-m-segersten-u-aine-m-h%C3%A3-glund-m-birkenkamp
#14
Byron H Lee
Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into 3 major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions...
August 5, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28783168/erbb2-positive-mammary-tumors-can-escape-pi3k-p110%C3%AE-loss-through-downregulation-of-the-pten-tumor-suppressor
#15
A M Simond, T Rao, D Zuo, J J Zhao, W J Muller
Breast cancer is the most common cancer among women and 30% of patients will be diagnosed with an ErbB2-positive tumor. Forty percent of ErbB2-positive breast tumors have an activating mutation in p110α, a catalytic subunit of phosphoinositide 3-kinase. Clinical and experimental data show that breast tumors treated with a p110α-specific inhibitor often circumvent inhibition and resume growth. To understand this mechanism of resistance, we crossed a p110α conditional (p110α(flx/flx)) mouse model with mice that overexpress the ErbB2/Neu-IRES-Cre transgene (NIC) specifically in the mammary epithelium...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28782986/her2-heterogeneity-in-gastroesophageal-cancer-detected-by-testing-biopsy-and-resection-specimens
#16
Ladan Fazlollahi, Helen E Remotti, Alina Iuga, Hui-Min Yang, Stephen M Lagana, Antonia R Sepulveda
CONTEXT: - In advanced gastric, esophageal, and gastroesophageal junction adenocarcinomas (GE-GEJ-AC) that overexpress ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2), anti-HER2 monoclonal antibody therapy confers survival benefit. To select patients for treatment, HER2 expression and gene amplification are evaluated by immunohistochemistry (IHC) and in situ hybridization. OBJECTIVE: - To determine whether GE-GEJ-AC tested for HER2 on biopsy specimens of a primary tumor show different IHC scores and/or HER2 amplification by in situ hybridization in matched resection specimens, potentially changing therapy eligibility...
August 7, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28782530/chemotherapeutics-resistance-arms-race-an-update-on-mechanisms-involved-in-resistance-limiting-egfr-inhibitors-in-lung-cancer
#17
REVIEW
Pankaj Kumar Singh, Om Silakari
Clinical reports suggest that EGFR-mutated lung cancer usually respond significantly towards small molecule tyrosine kinase inhibitors. Same studies also report the eventual development of acquired resistance within a median time interval of 9 to 14months. One of the major mechanisms involved in this acquired resistance was found to be a secondary point mutation at gate-keeper residue, EGFR T790M. However, there are other recent studies which disclose the role of few other novel key players such as, ZEB1, TOPK etc...
August 4, 2017: Life Sciences
https://www.readbyqxmd.com/read/28781955/erbb2-signaling-epigenetically-suppresses-microrna-205-transcription-via-ras-raf-mek-erk-pathway-in-breast-cancer
#18
Takuya Hasegawa, Ryohei Adachi, Hitoshi Iwakata, Takayoshi Takeno, Koji Sato, Toshiyuki Sakamaki
We previously reported that microRNA-205 (miR-205) is downregulated by overexpression of the receptor tyrosine kinase ErbB2 and that ectopic transfection of miR-205 precursor decreases ErbB2 tumorigenicity in soft agar. In this study, we further analyzed the regulatory mechanisms linking ErbB2 overexpression and miR-205 downregulation. In ErbB2-overexpressing breast epithelial cells, miR-205 expression was significantly increased by treatment with MEK inhibitor U0126 or PD98059, Raf-1 inhibitor ZM-336372, and ERK inhibitor SCH772984, but PI3K inhibitor LY294002 and p38 MAPK inhibitor SB203580 had no effect...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28775148/the-tumor-suppressor-protein-opcml-potentiates-anti-egfr-and-anti-her2-targeted-therapy-in-her2-positive-ovarian-and-breast-cancer
#19
Elisa Zanini, Louay S Louis, Jane Antony, Evdoxia Karali, Imoh S Okon, Arthur B McKie, Sebastian Vaughan, Mona El-Bahrawy, Justin Stebbing, Chiara Recchi, Hani Gabra
OPCML is a tumor suppressor gene that is frequently inactivated in ovarian cancer and many other cancers by somatic methylation. We have previously shown that OPCML exerts its suppressor function by negatively regulating a spectrum of receptor tyrosine kinases (RTKs), such as ErbB2/HER2, FGFR1 and EphA2, thus attenuating their related downstream signaling. The physical interaction of OPCML with this defined group of RTKs is a prerequisite for their downregulation. Overexpression/gene amplification of EGFR and HER2 is a frequent event in multiple cancers including ovarian and breast cancers...
August 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28766916/interleukin-18-il-18-is-equally-expressed-in-inflammatory-breast-cancer-and-noninflammatory-locally-advanced-breast-cancer-a-possible-association-with-chemotherapy-response
#20
Marco Antonio Nasser Aguiar, Carlos Wagner S Wanderley, Lívia Maria Soares Nobre, Mateus Rolim Mendes Alencar, Maria do Perpétuo Socorro Saldanha, Alceu Machado Souza, Deysi Viviana Tenazoa Wong, Paulo Goberlânio Barros, Paulo Roberto Carvalho Almeida, Roberto Cesar Pereira Lima-Júnior, Ronaldo Albuquerque Ribeiro
AIM: Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer. The signs of inflammation such as hyperemia and hyperthermia might suggest the possible participation of inflammatory mediators. This study investigates stromal and tumor expression of nuclear factor-kappa B (NF-κB) and interleukin-18 (IL-18) in samples obtained from IBC and noninflammatory locally advanced breast cancer (LABC) and the influence of these markers on patients' prognosis...
August 2, 2017: Asia-Pacific Journal of Clinical Oncology
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