keyword
MENU ▼
Read by QxMD icon Read
search

HER2 amplification

keyword
https://www.readbyqxmd.com/read/29786108/mir%C3%A2-494-inhibits-cancer%C3%A2-initiating-cell-phenotypes-and-reverses-resistance-to-lapatinib-by-downregulating-fgfr2-in-her2%C3%A2-positive-gastric-cancer
#1
Yanxia Yu, Xuejuan Yu, Hong Liu, Qingxun Song, Yongmei Yang
In gastric cancer, >15% of cases are associated with the amplification of human epidermal growth factor receptor 2 (HER2), which leads to poor clinical outcomes. Lapatinib, a potent ATP‑competitive inhibitor, is a small, orally active molecule, which inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1. The activation of receptor tyrosine kinases can contribute to lapatinib resistance in HER2‑positive gastric cancer. The aim of the present study was to explore the effects of miR‑494 and FGFR2 in regulation of cancer‑initiating cell phenotypes and therapeutic efficiency of lapatinib in HER2‑positive gastric cancer...
May 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29765551/functional-significance-of-co-occurring-mutations-in-pik3ca-and-map3k1-in-breast-cancer
#2
Alvaro Avivar-Valderas, Robert McEwen, Amir Taheri-Ghahfarokhi, Larissa S Carnevalli, Elizabeth L Hardaker, Marcello Maresca, Kevin Hudson, Elizabeth A Harrington, Francisco Cruzalegui
The PI3Kα signaling pathway is frequently hyper-activated in breast cancer (BrCa), as a result of mutations/amplifications in oncogenes (e.g. HER2 ), decreased function in tumor suppressors (e.g. PTEN ) or activating mutations in key components of the pathway. In particular, activating mutations of PIK3CA (~45%) are frequently found in luminal A BrCa samples. Genomic studies have uncovered inactivating mutations in MAP3K1 (13-20%) and MAP2K4 (~8%), two upstream kinases of the JNK apoptotic pathway in luminal A BrCa samples...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29760043/her2-amplification-in-tumors-activates-pi3k-akt-signaling-independent-of-her3
#3
Ana Ruiz-Saenz, Courtney Dreyer, Marcia R Campbell, Veronica Steri, Nathaniel P Gulizia, Mark M Moasser
Current evidence suggests that HER2-driven tumorigenesis requires HER3. This is likely due to the unique ability of HER3 to activate PI3K/Akt pathway signaling, which is not directly accessible to HER2. By genetic elimination of HER3 or shRNA knockdown of HER3 in HER2-amplified cancer cells, we find residual HER2-driven activation of PI3K/Akt pathway signaling that is driven by HER2 through direct and indirect mechanisms. Indirect mechanisms involved second messenger pathways including Ras or Grb2. Direct binding of HER2 to PI3K occurred through p-Tyr1139, which has a weak affinity for PI3K but becomes significant at very high expression and phosphorylation...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29755676/genetic-heterogeneity-and-actionable-mutations-in-her2-positive-primary-breast-cancers-and-their-brain-metastases
#4
Leticia De Mattos-Arruda, Charlotte K Y Ng, Salvatore Piscuoglio, Maria Gonzalez-Cao, Raymond S Lim, Maria R De Filippo, Nicola Fusco, Anne M Schultheis, Carolina Ortiz, Santiago Viteri, Alexandra Arias, Gabriel S Macedo, Mafalda Oliveira, Patricia Gomez, Cristina Teixidó, Paolo Nuciforo, Vicente Peg, Cristina Saura, Santiago Ramon Y Cajal, Francesc Tresserra Casas, Britta Weigelt, Javier Cortes, Joan Seoane, Jorge S Reis-Filho
Brain metastases constitute a challenge in the management of patients with HER2-positive breast cancer treated with anti-HER2 systemic therapies. Here we sought to define the repertoire of mutations private to or enriched for in HER2-positive brain metastases. Massively parallel sequencing targeting all exons of 254 genes frequently mutated in breast cancers and/or related to DNA repair was used to characterize the spatial and temporal heterogeneity of HER2-positive breast cancers and their brain metastases in six patients...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29754608/multiplex-polymerase-chain-reaction-in-combination-with-gel-electrophoresis-inductively-coupled-plasma-mass-spectrometry-a-powerful-tool-for-the-determination-of-gene-copy-number-variations-and-gene-expression-changes
#5
A Fernández Asensio, T Iglesias, A Cotarelo, M Espina, E Blanco-González, L M Sierra, M Montes-Bayón
During the last few years multiplex real-time or quantitative polymerase chain reaction PCR (qPCR) has become the method of choice for multiplex gene expression changes and gene copy number variations (CNVs) analysis. However, such determinations require the use of different fluorescent labels for the different amplified sequences, which increases significantly the costs of the analysis and limits the applicability of the technique for simultaneous amplification of many targets of interest in a single reaction...
September 6, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29753009/the-implications-of-trka-and-met-aberrations-in-de-novo-salivary-duct-carcinoma
#6
Hyang Joo Ryu, Yoon Woo Koh, Sun Och Yoon
Salivary duct carcinoma (SDC) is an aggressive carcinoma with poor prognosis. Although anti-HER2 therapy is a potential treatment option for HER2-positive SDC, other potential therapeutic targets are not known, in particular for HER2-negative cases. In this study, the recently identified receptor tyrosine kinases MET and tropomyosin-receptor kinase (Trk) were investigated as potential therapeutic targets. A total of 28 consecutive, surgically resected, de novo SDC cases were selected after evaluating histology and immunohistochemical expression of androgen receptor...
May 9, 2018: Human Pathology
https://www.readbyqxmd.com/read/29751042/next-generation-sequencing-analysis-for-gastric-adenocarcinoma-with-enteroblastic-differentiation-emphasis-on-the-relationship-with-hepatoid-adenocarcinoma
#7
Yoichi Akazawa, Tsuyoshi Saito, Takuo Hayashi, Yuka Yanai, Sho Tsuyama, Keisuke Akaike, Yoshiyuki Suehara, Fumiyuki Takahashi, Kazuya Takamochi, Hiroya Ueyama, Takashi Murakami, Sumio Watanabe, Akihito Nagahara, Takashi Yao
Histologically tubulo-papillary structures with glycogen-rich clear cytoplasm in gastric adenocarcinoma with enteroblastic differentiation (GAED) are well-known, but a solid growth pattern can also be observed as a minor component. In contrast, hepatoid adenocarcinoma (HAC) of the stomach shows many overlapping features, including solid pattern and alpha-fetoprotein expression. In this study, we employed next-generation sequencing (NGS) to establish a molecular/clinicopathological concept of GAED and clarify whether these two tumors should be grouped together in one category...
May 8, 2018: Human Pathology
https://www.readbyqxmd.com/read/29739401/limited-utility-of-tissue-micro-arrays-in-detecting-intra-tumoral-heterogeneity-in-stem-cell-characteristics-and-tumor-progression-markers-in-breast-cancer
#8
Pascale Kündig, Charlotte Giesen, Hartland Jackson, Bernd Bodenmiller, Bärbel Papassotirolopus, Sandra Nicole Freiberger, Catharine Aquino, Lennart Opitz, Zsuzsanna Varga
BACKGROUND: Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas...
May 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29734245/human-epidermal-growth-factor-receptor-2-promotes-invasion-and-metastasis-in-gastric-cancer-by-activating-mitogen-activated-protein-kinase-signaling
#9
Feng Hou, Duan-Bo Shi, Yun-Qing Chen, Peng Gao
Increasing evidence supports an important role for the human epidermal growth factor receptor-2 (HER2) gene and mitogen-activated protein kinase (MAPK) signaling pathways in the progression of human cancers by enhancing cancer cell metastasis and proliferation. However, the relationship between HER2 and MAPK signaling pathways in gastric cancer (GC) remains unclear. In the present study, dual in situ hybridization was performed to detect HER2 gene amplification and reverse transcription-quantitative polymerase chain reaction was used to investigate the mRNA expression of members of the MAPK signaling pathway, including rapidly accelerated fibrosarcoma (RAF), extracellular regulated signal-activated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), in 112 primary GC tissue samples...
May 4, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29733681/comparative-performance-of-breast-cancer-human-epidermal-growth-factor-receptor-2-fluorescence-in-situ-hybridization-and-brightfield-in-situ-hybridization-on-college-of-american-pathologists-proficiency-tests
#10
Katherine B Geiersbach, Julia A Bridge, Michelle Dolan, Lawrence J Jennings, Diane L Persons, Rhona J Souers, Karen D Tsuchiya, Patricia H Vasalos, Joel T Moncur
CONTEXT: - Fluorescence in situ hybridization (FISH) and brightfield in situ hybridization (ISH) are 2 clinically approved laboratory methods for detecting ERBB2 (HER2) amplification in breast cancer. OBJECTIVE: - To compare the performance of FISH and brightfield ISH on proficiency testing administered by the College of American Pathologists Laboratory Accreditation Program Design.- Retrospective review was performed on 70 tissue core samples in 7 separate proficiency testing surveys conducted between 2009 and 2013...
May 7, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29731265/mir-21-up-regulation-in-ampullary-adenocarcinoma-and-its-pre-invasive-lesions
#11
Deborah Saraggi, Francesca Galuppini, Giuseppe N Fanelli, Andrea Remo, Emanuele D L Urso, Ricardo Q Bao, Deborah Bacchin, Vincenza Guzzardo, Claudio Luchini, Chiara Braconi, Fabio Farinati, Massimo Rugge, Matteo Fassan
Poor information is available on the molecular landscape characterizing the carcinogenetic process leading to ampullary carcinoma. MiR-21 is one of the most frequently up-regulated miRNAs in pancreatic adenocarcinoma, a tumor sharing similar molecular features with ampullary adenocarcinomas (AVCs), above all with the pancreatic-biliary type. We profiled, by in situ hybridization (ISH), miR-21 expression in a series of 26 AVCs, 50 ampullary dysplastic lesions (35 low-grade [LG-IEN] and 15 high-grade [HG-IEN]) and 10 normal duodenal mucosa samples...
May 1, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29717443/assessing-her2-amplification-in-plasma-cfdna
#12
Isaac Garcia-Murillas, Nicholas C Turner
Digital PCR (dPCR) is a highly accurate method to determine DNA concentration. In dPCR, DNA is portioned into many discrete single entities, and these are analyzed individually for the presence or absence of a target molecule of interest. Here we describe how digital PCR can be employed to determine the presence of oncogenic amplification through noninvasive analysis of circulating free DNA (cfDNA), and exemplify this approach by developing a plasma circulating free DNA dPCR assay for HER2 copy number.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29715436/detection-of-her2-amplification-in-formalin-fixed-paraffin-embedded-breast-carcinoma-tissue-with-digital-pcr-using-two-tff3-sequences-as-internal-reference
#13
Runliu Yu, Wenjing Xuan, Lei Zhou, Ying Luo, Xinyang Liu, Peiwu Xiong, Xuyi Ren
PURPOSE: Droplet digital PCR (ddPCR) is a highly accurate method to determine DNA concentration and detect copy number variations. We developed an approach to assess HER2 gene amplification status using ddPCR with two sequences of TFF3 as reference probes. EXPERIMENTAL DESIGN: 76 templates of carcinoma DNA were prepared from formalin-fixed paraffin-embedded (FFPE) tissues. Digital PCR assay of the copy number of HER2 and TFF3 DNA was performed on the samples. The results were compared to prior fluorescent in-situ hybridation (FISH) assays performed on the same samples...
April 28, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29715106/3d-culture-represents-apoptosis-induced-by-trastuzumab-better-than-2d-monolayer-culture
#14
Takashi Tatara, Toru Mukohara, Rina Tanaka, Yohei Shimono, Yohei Funakoshi, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Midori Hirai, Yoshihiro Kakeji, Hironobu Minami
BACKGROUND: Our hypothesis was that three-dimensional (3D) culture better represents differential in vivo responses to trastuzumab between PIK3CA-wild-type (wt) and mutant (mt) cell lines than does two-dimensional (2D) culture. MATERIALS AND METHODS: Apoptosis and cell signaling proteins were evaluated in response to trastuzumab with and without BKM120, a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, using western blot analysis of four breast cancer cell lines with human epidermal growth factor receptor 2 (HER2) amplification...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29714649/personalized-therapy-based-on-sequential-molecular-analysis-leads-to-30-months-of-survival-in-a-patient-with-diffuse-unresectable-gastric-linitis-plastica
#15
Linda Mahjoubi, Fabiola Cecchi, Christophe Massard, Fabio Calabro, Anas Gazzah, Rastislav Bahleda, Philippe Jamme, Maximiliano Gelli, Diane Goere, Ludovic Lacroix, Julien Adam, Lukas Heukamp, Patrizia Trenta, Todd Hembrough, Jean-Charles Soria, Cora Sternberg, Michel Ducreux
INTRODUCTION: Diffuse gastric cancer is associated with poor prognosis. We report a patient with metastatic gastric linitis plastica harboring human epidermal growth factor receptor 2 ( HER2) activating mutation and HER2 amplification. CASE DESCRIPTION: The patient received 5-fluorouracil/folinic acid and oxaliplatin combined with trastuzumab/pertuzumab, resulting in disease control for 8 months. Second-line therapy with nivolumab and trastuzumab/pertuzumab was well-tolerated, with macroscopic peritoneal response...
March 1, 2018: Tumori
https://www.readbyqxmd.com/read/29713646/mutational-profiling-of-non-small-cell-lung-cancer-resistant-to-osimertinib-using-next-generation-sequencing-in-chinese-patients
#16
Keke Nie, Haiping Jiang, Chunling Zhang, Chuanxin Geng, Xiajuan Xu, Ling Zhang, Hao Zhang, Zhongfa Zhang, Ketao Lan, Youxin Ji
Purpose: To identify the somatic mutated genes for optimal targets of non-small-cell lung cancer after resistance to osimertinib treatment. Patients and Methods: Study patients all had advanced lung adenocarcinoma and acquired resistance to osimertinib as a second- or third-line treatment. These patients had harboring EGFR T790M mutation before osimertinib treatment, which was confirmed by Amplification Refractory Mutation System (ARMS) PCR or Next-Generation Sequencing (NGS)...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29700710/her2-genomic-amplification-in-circulating-tumor-dna-and-estrogen-receptor-positivity-predict-primary-resistance-to-trastuzumab-emtansine-t-dm1-in-patients-with-her2-positive-metastatic-breast-cancer
#17
Hitomi Sakai, Junji Tsurutani, Tsutomu Iwasa, Yoshifumi Komoike, Kazuko Sakai, Kazuto Nishio, Kazuhiko Nakagawa
BACKGROUND: Trastuzumab emtansine (T-DM1) is approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC), and has high efficacy. However, some patients exhibit primary resistance to T-DM1, and thus methods that can predict resistance in clinical practice are needed. Genomic analysis of circulating tumor DNA (ctDNA) in plasma is a non-invasive and reproducible method. This study aimed to predict primary resistance to T-DM1 by combining genomic analysis of ctDNA and other clinicopathological features of patients with HER2-positive ABC...
April 26, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/29695635/mechanisms-of-acquired-resistance-to-trastuzumab-emtansine-in-breast-cancer-cells
#18
Guangmin Li, Jun Guo, Ben-Quan Shen, Daniela Bumbaca Yadav, Mark X Sliwkowski, Lisa M Crocker, Jennifer A Lacap, Gail D Lewis Phillips
The receptor tyrosine kinase HER2 is overexpressed in approximately 20% of breast cancer, and its amplification is associated with reduced survival. Trastuzumab emtansine (Kadcyla®, T-DM1), an antibody-drug conjugate that is comprised of trastuzumab covalently linked to the anti-mitotic agent DM1 through a stable linker, was designed to selectively deliver DM1 to HER2-overexpressing tumor cells. T-DM1 is approved for the treatment of patients with HER2-positive metastatic breast cancer following progression on trastuzumab and a taxane...
April 25, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29683229/stromal-immunoglobulin-%C3%AE%C2%BAc-expression-is-associated-with-initiation-of-breast-cancer-in-ta2-mice-and-human-breast-cancer
#19
Shiwu Zhang, Fei Fei, Hua Wang, Yanjun Gu, Chunyuan Li, Xinlu Wang, Yongjie Zhao, Yuwei Li
The initiation of spontaneous breast cancer (SBC) in Tientsin Albino 2 (TA2) mice is related to mouse mammary tumor virus (MMTV) infection, and MMTV amplification is hormonally regulated. To explore the insertion site of MMTVLTR in TA2 mouse genome, reverse PCR and nested PCR were used to amplify the unknown sequence on both sides of the MMTV-LTRSAG gene in SBC and normal breast tissue of TA2 mice. Furthermore, the clinicopathological significance of the insertion site was evaluated in 43 samples of normal breast tissue, 46 samples of breast cystic hyperplasia, 54 samples of ductal carcinoma in situ, 142 samples of primary breast cancer, and 47 samples of lymph node metastatic breast cancer by RNA in situ hybridization...
April 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29672836/pathogenic-and-targetable-genetic-alterations-in-70-urachal-adenocarcinomas
#20
Henning Reis, Kristan E van der Vos, Christian Niedworok, Thomas Herold, Orsolya Módos, Attila Szendrői, Thomas Hager, Marc Ingenwerth, Daniël J Vis, Mark A Behrendt, Jeroen de Jong, Michiel S van der Heijden, Benoit Peyronnet, Romain Mathieu, Marcel Wiesweg, Jason Ablat, Krzysztof Okon, Yuri Tolkach, David Keresztes, Nikolett Nagy, Felix Bremmer, Nadine T Gaisa, Piotr Chlosta, Joerg Kriegsmann, Ilona Kovalszky, József Timar, Glen Kristiansen, Heinz-Joachim Radzun, Ruth Knüchel, Martin Schuler, Peter Black, Herbert Rübben, Boris Hadaschik, Kurt Werner Schmid, Bas W G van Rhijn, Péter Nyirády, Tibor Szarvas
Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins (MMR)) and evaluated the microsatellite instability (MSI) status...
April 19, 2018: International Journal of Cancer. Journal International du Cancer
keyword
keyword
59125
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"