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HER2 amplification

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https://www.readbyqxmd.com/read/28930447/ultra-sensitive-quantitation-of-plasma-membrane-proteins-via-isrta
#1
Tao Gao, Bei Wang, Liu Shi, Xiaoli Zhu, Yang Xiang, Jun-Ichi Anzai, Genxi Li
Quantitation of plasma membrane proteins (PMPs) are fundamental and frequently performed in the daily lab-work. However, challenged by inherent/interacted hetero-structures and complex surroundings of the PMPs in lipid membrane, quantitative techniques for PMP often require complex treatments (e.g. labelling, isolation, purification, and determination), and the sensitivity is usually not satisfactory. To address the problem, we have proposed a novel method that enables quantitation of PMPs with extremely high sensitivity, in an easier-to-manipulate and more streamlined way...
September 20, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28913947/extreme-chromosome-17-copy-number-instability-is-a-prognostic-factor-in-patients-with-gastroesophageal-adenocarcinoma-a-retrospective-cohort-study
#2
Jacqueline E Birkness, Neal G Spada, Caitlyn Miller, James D Luketich, Katie S Nason, Weijing Sun, Jon M Davison
Gastric and esophageal cancers frequently show genomic instability and aneuploidy. Chromosomal copy number instability (CIN) is a form of genomic instability that exerts pleiotropic effects on cellular biology and is a source of genetic heterogeneity in a population of cells. CIN results in cell-to-cell variation in chromosome copy number which can be detected and quantified by fluorescence in situ hybridization (FISH). CIN is a biomarker associated with differential response to a number of chemotherapy compounds...
September 14, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28902361/cooperative-oncogenic-effect-and-cell-signaling-crosstalk-of-co%C3%A2-occurring-her2-and-mutant-pik3ca-in-mammary-epithelial-cells
#3
Lun Dong, Fanyan Meng, Ling Wu, Allison V Mitchell, C James Block, Bin Zhang, Douglas B Craig, Hyejeong Jang, Wei Chen, Qifeng Yang, Guojun Wu
Though incidence of PI3K oncogenic mutation is prominent in breast cancer (20-30%), pharmacological targeting of this signaling pathway alone has failed to provide meaningful clinical benefit. To better understand and address this problem, we conducted genome-wide analysis to study the association of mutant PI3K with other gene amplification events. One of the most significant copy number gain events associated with PIK3CA mutation was the region within chromosome 17 containing HER2. To investigate the oncogenic effect and cell signaling regulation of co-occurring PIK3CA-H1047R and or HER2 gene, we generated cell models ectopically expressing mutant PIK3CA, HER2 or both genetic alterations...
August 30, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28901323/human-epidermal-growth-factor-receptor-2-amplification-detection-by-droplet-digital-polymerase-chain-reaction-in-formalin-fixed-paraffin-embedded-breast-and-gastric-cancer-samples
#4
Xingwen Wang, Yunyan Wu, Xueling Song, Chengtao Sun, Changshun Wu, Hong Feng
OBJECTIVE: Human epidermal growth factor receptor 2 (HER2) is an important biomarker for the precise individualized treatment including trastuzumab of HER2-positive breast and gastric cancer. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the routine analyses for formalin-fixed paraffin-embedded (FFPE) samples. However, IHC is variable and depends on the evaluator, and FISH is a labor intensive and expensive method. We evaluated the feasibility of droplet digital polymerase chain reaction (ddPCR) as a precise and quantitative method for HER2 amplification test...
2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28882552/prognostic-and-predictive-biomarkers-in-breast-cancer-past-present-and-future
#5
REVIEW
Andrea Nicolini, Paola Ferrari, Michael J Duffy
Following a diagnosis of breast cancer, the most immediate challenges in patient management are the determination of prognosis and identification of the most appropriate adjuvant systemic therapy. Determining prognosis can best be addressed with a combination of traditional clinicopathological prognostic factors, biomarkers such as HER2/neu and specific multigene genes tests. Amongst the best validated prognostic multigene tests are uPA/PAI1, Oncotype DX and MammaPrint. Oncotype DX and MammaPrint, may be used for predicting outcome and aiding adjunct therapy decision making in patients with ER-positive, HER2-negative breast cancers that are either lymph node-negative or node positive (1-3 metastatic nodes), while uPA/PAI-1 may be similarly used in ER-positive, lymph node-negative patients...
September 4, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28882180/high-performance-of-targeted-next-generation-sequencing-on-variance-detection-in-clinical-tumor-specimens-in-comparison-with-current-conventional-methods
#6
Dan Su, Dadong Zhang, Kaiyan Chen, Jing Lu, Junzhou Wu, Xinkai Cao, Lisha Ying, Qihuang Jin, Yizhou Ye, Zhenghua Xie, Lei Xiong, Weimin Mao, Fugen Li
BACKGROUND: Next generation sequencing (NGS) is being increasingly applied for assisting cancer molecular diagnosis. However, it is still needed to validate NGS accuracy on detection of DNA alternations based on a large number of clinical samples, especially for DNA rearrangements and copy number variations (CNVs). This study is to set up basic parameters of targeted NGS for clinical diagnosis and to understand advantage of targeted NGS in comparison with the conventional methods of molecular diagnosis...
September 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28870915/critical-overview-of-her2-assessement-in-bladder-cancer-what-is-missing-for-a-better-therapeutic-approach
#7
Anca Maria Cimpean, Valeria Tarlui, Alin Adrian Cumpănaş, Sorin Bolintineanu, Andrei Cumpănaş, Marius Raica
BACKGROUND/AIM: To assess the concordance between IHC and FISH and its influence on tumor type, grade and lympho-vascular invasion (LVI). MATERIALS AND METHODS: HER2 immunohistochemistry (IHC) to 45 cases of bladder carcinoma, followed by fluorescent in situ hybridization (FISH) were applied. RESULTS: 31.12% cases were IHC positive. Less than 35% of HER2-negative cases presented LVI and this percent increased to 54.54% for +1 HER2 cases. LVI increases up to 57...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28859480/self-assembled-dna-generated-electric-current-biosensor-for-her2-analysis
#8
Congcong Shen, Ke Zeng, Junjun Luo, Xiaoqing Li, Minghui Yang, Avraham Rasooly
We have developed a new DNA self-assembly amplification technology that generates electric current to power electrochemical biosensing. The new technology was used for detection of human epidermal growth factor receptor 2 (HER2). In our technology, an aptamer was utilized both as a ligand for recognition and as a signal generating reporter. The aptasensor is based on a sandwich format: a DNA primer on a HER2 aptamer initiates auxiliary DNA self-assembly on the electrode to form a long one-dimensional DNA. The resulting DNA is then reacted with molybdate to generate electrochemical current...
September 1, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28859471/phase-1-studies-of-poziotinib-an-irreversible-pan-her-tyrosine-kinase-inhibitor-in-patients-with-advanced-solid-tumors
#9
Tae Min Kim, Keun-Wook Lee, Do-Youn Oh, Jong-Seok Lee, Seock-Ah Im, Dong-Wan Kim, Sae-Won Han, Yu Jung Kim, Tae-You Kim, Jee Hyun Kim, Hyesun Han, Woo Ho Kim, Yung-Jue Bang
Purpose: Poziotinib, a pan-HER tyrosine kinase inhibitor (TKI), has shown potent activity against wild type of epidermal growth factor receptor (EGFR) family kinases including EGFR, HER-2 and HER-4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety and antitumor activity against advanced solid tumors. Materials and Methods: Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on and 7-day off (intermittent schedule); and once daily continuous dosing with food effect...
August 29, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28843919/gene-copy-number-variation-and-protein-overexpression-of-egfr-and-her2-in-distal-extrahepatic-cholangiocarcinoma
#10
Min Jung Jung, Chang Gok Woo, Saetbyeol Lee, Susie Chin, Hee Kyung Kim, Jeong Ja Kwak, Eun Suk Koh, Bora Lee, Kee-Taek Jang, Ahrim Moon
EGFR and HER2 are among the most promising therapeutic targets in solid cancers. The expression status of EGFR and HER2 are associated with the prognosis, and with a number of clinicopathological factors, in many cancers. However, few studies have examined this association in distal extrahepatic cholangiocarcinoma (EHCC). Therefore, we investigated EGFR and HER2 protein expression and gene copy number variation (CNV) in distal EHCC. We also studied the association of these factors with clinicopathological parameters and prognosis...
August 24, 2017: Pathology
https://www.readbyqxmd.com/read/28841389/osimertinib-as-first-line-treatment-of-egfr-mutation-positive-advanced-non-small-cell-lung-cancer
#11
Suresh S Ramalingam, James C-H Yang, Chee Khoon Lee, Takayasu Kurata, Dong-Wan Kim, Thomas John, Naoyuki Nogami, Yuichiro Ohe, Helen Mann, Yuri Rukazenkov, Serban Ghiorghiu, Daniel Stetson, Aleksandra Markovets, J Carl Barrett, Kenneth S Thress, Pasi A Jänne
Purpose The Osimertinib First Time in Patients Ascending Dose (AURA) study ( ClinicalTrials.gov identifier: NCT01802632) included two cohorts of treatment-naïve patients to examine clinical activity and safety of osimertinib (an epidermal growth factor receptor [EGFR] -tyrosine kinase inhibitor selective for EGFR-tyrosine kinase inhibitor sensitizing [ EGFRm] and EGFR T790M resistance mutations) as first-line treatment of EGFR-mutated advanced non-small-cell lung cancer (NSCLC). Patients and Methods Sixty treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily (30 patients per cohort)...
August 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28831439/clinical-overestimation-of-her2-positivity-in-early-estrogen-and-progesterone-receptor-positive-breast-cancer-and-the-value-of-molecular-subtyping-using-blueprint
#12
Ettienne J Myburgh, Lizanne Langenhoven, Kathleen A Grant, Lize van der Merwe, Maritha J Kotze
PURPOSE: Human epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm...
August 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28818608/potential-resistance-mechanisms-revealed-by-targeted-sequencing-from-lung-adenocarcinoma-patients-with-primary-resistance-to-epidermal-growth-factor-receptor-egfr-tyrosine-kinase-inhibitors-tkis
#13
Jia Zhong, Lei Li, Zhijie Wang, Hua Bai, Gai Fei, Jian Chunduan, Jun Zhao, Minglei Zhuo, Yuyang Wang, Shuhang Wang, Wanchun Zang, Meina Wu, Tongtong An, Guanhua Rao, Jie Wang
BACKGROUND: EGFR-TKIs have greatly improved the prognosis of lung adenocarcinoma. However, approximately 5%-10% lung adenocarcinoma patients with EGFR sensitive mutations have primary resistance to EGFR-TKIs treatment. The underlying mechanism is unknown. METHODS: This study used next-generation sequencing (NGS) to explore the mechanisms of primary resistance by analyzing 11 patients with primary resistance and 11 patients sensitive to EGFR-TKIs. NGS targeted sequencing was performed on the Illumina X platform for 483 cancer-related genes...
August 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28809762/elucidation-of-novel-chromosomal-abnormalities-in-pancreatic-cancer-conventional-and-molecular-cytogenetic-characterization-of-16-pancreatic-cell-lines
#14
David Shabsovich, Carlos A Tirado
Pancreatic carcinoma is a major cause of cancer-related death in the United States, with a five-year survival rate of approximately 5%. Cytogenetic analysis has identified clinically significant chromosomal abnormalities in numerous malignancies, but it is not utilized in the clinical management of pancreatic carcinoma. We performed conventional and molecular cytogenetic analysis of 16 pancreatic carcinoma cell lines using Giemsa banding and DNA-based fluorescence in situ hybridization (FISH). Conventional cytogenetic analysis revealed a diversity of recurrent and clonal numerical and structural abnormalities in all cell lines analyzed, many of which occurred at loci of genes implicated in pancreatic or related cancers...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/28806950/precision-medicine-approaches-to-lung-adenocarcinoma-with-concomitant-met-and-her2-amplification
#15
Doo-Yi Oh, Kyungsoo Jung, Ji-Young Song, Seokhwi Kim, Sang Shin, Yong-Jun Kwon, Ensel Oh, Woong-Yang Park, Sang Yong Song, Yoon-La Choi
BACKGROUND: Patient-derived xenograft (PDX) models are important tools in precision medicine and for the development of targeted therapies to treat cancer patients. This study aimed to evaluate our precision medicine strategy that integrates genomic profiling and preclinical drug-screening platforms, in order to personalize cancer treatments using PDX models. METHODS: We performed array-comparative genomic hybridization, microarray, and targeted next-generation sequencing analyses, in order to determine the oncogenic driver mutations...
August 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28801248/clinical-value-of-ctdna-in-upper-gi-cancers-a-systematic-review-and-meta-analysis
#16
REVIEW
A Creemers, S Krausz, M Strijker, M J van der Wel, E C Soer, R J Reinten, M G Besselink, J W Wilmink, M J van de Vijver, C J M van Noesel, J Verheij, S L Meijer, F Dijk, M F Bijlsma, M G H van Oijen, H W M van Laarhoven
BACKGROUND: The recent expanding technical possibilities to detect tumor derived mutations in blood, so-called circulating tumor DNA (ctDNA), has rapidly increased the interest in liquid biopsies. This review and meta-analysis explores the clinical value of ctDNA in malignancies of the upper gastro-intestinal tract. METHODS: PubMed, Cochrane and Embase databases were searched to identify studies reporting the diagnostic, prognostic or predictive value of ctDNA in patients with esophageal, gastric and pancreatic cancer, until January 2017...
August 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28800870/recent-advances-in-her2-positive-breast-cancer-epigenetics-susceptibility-and-therapeutic-strategies
#17
REVIEW
Heena Singla, Abhilash Ludhiadch, Raman Preet Kaur, Harish Chander, Vinod Kumar, Anjana Munshi
HER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways. Understanding of epigenomic regulation of HER2 overexpression and signaling may help uncover the unmatchable physiology of HER2 gene/protein...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28794806/recent-developments-in-the-treatment-of-metastatic-colorectal-cancer
#18
REVIEW
Jonathan M Loree, Scott Kopetz
Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease...
August 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28794284/genomic-profiling-of-er-breast-cancers-after-short-term-estrogen-suppression-reveals-alterations-associated-with-endocrine-resistance
#19
Jennifer M Giltnane, Katherine E Hutchinson, Thomas P Stricker, Luigi Formisano, Christian D Young, Monica V Estrada, Mellissa J Nixon, Liping Du, Violeta Sanchez, Paula Gonzalez Ericsson, Maria G Kuba, Melinda E Sanders, Xinmeng J Mu, Eliezer M Van Allen, Nikhil Wagle, Ingrid A Mayer, Vandana Abramson, Henry Gόmez, Monica Rizzo, Weiyi Toy, Sarat Chandarlapaty, Erica L Mayer, Jason Christiansen, Danielle Murphy, Kerry Fitzgerald, Kai Wang, Jeffrey S Ross, Vincent A Miller, Phillip J Stephens, Roman Yelensky, Levi Garraway, Yu Shyr, Ingrid Meszoely, Justin M Balko, Carlos L Arteaga
Inhibition of proliferation in estrogen receptor-positive (ER(+)) breast cancers after short-term antiestrogen therapy correlates with long-term patient outcome. We profiled 155 ER(+)/human epidermal growth factor receptor 2-negative (HER2(-)) early breast cancers from 143 patients treated with the aromatase inhibitor letrozole for 10 to 21 days before surgery. Twenty-one percent of tumors remained highly proliferative, suggesting that these tumors harbor alterations associated with intrinsic endocrine therapy resistance...
August 9, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28782986/her2-heterogeneity-in-gastroesophageal-cancer-detected-by-testing-biopsy-and-resection-specimens
#20
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
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