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https://www.readbyqxmd.com/read/28214620/water-soluble-multifunctional-antibody-porphyrin-gold-nanoparticles-for-targeted-photodynamic-therapy
#1
Oriol Penon, María J Marín, David A Russell, Lluïsa Pérez-García
Photodynamic therapy (PDT) is a treatment of cancer by which tumour cells are destroyed using reactive oxygen species produced by photosensitizers following activation with visible or near infrared light. Successful PDT depends on the solubility and the targeting ability of the photosensitizers. In this work, the synthesis of a porphyrin-based water soluble nanoparticle conjugate containing a targeting agent that recognizes the erbB2 receptor overexpressed on the surface of particular cancer cells is reported...
February 8, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28211519/palindromic-amplification-of-the-erbb2-oncogene-in-primary-her2-positive-breast-tumors
#2
Michael Marotta, Taku Onodera, Jeffrey Johnson, G Thomas Budd, Takaaki Watanabe, Xiaojiang Cui, Armando E Giuliano, Atsushi Niida, Hisashi Tanaka
Oncogene amplification confers a growth advantage to tumor cells for clonal expansion. There are several, recurrently amplified oncogenes throughout the human genome. However, it remains unclear whether this recurrent amplification is solely a manifestation of increased fitness resulting from random amplification mechanisms, or if a genomic locus-specific amplification mechanism plays a role. Here we show that the ERBB2 oncogene at 17q12 is susceptible to palindromic gene amplification, a mechanism characterized by the inverted (palindromic) duplication of genomic segments, in HER2-positive breast tumors...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209619/lapatinib-resistance-in-breast-cancer-cells-is-accompanied-by-phosphorylation-mediated-reprogramming-of-glycolysis
#3
Benjamin Ruprecht, Esther A Zaal, Jana Zecha, Wei Wu, Celia R Berkers, Bernhard Kuster, Simone Lemeer
HER2/ERBB2-overexpressing breast cancers targeted effectively by the small molecule kinase inhibitor lapatinib frequently acquire resistance to this drug. In this study, we employed explorative mass spectrometry to profile proteomic, kinomic, and phosphoproteomic changes in an established model of lapatinib resistance to systematically investigate initial inhibitor response and subsequent reprogramming in resistance. The resulting dataset, which collectively contains quantitative data for >7,800 proteins, >300 protein kinases and >15,000 phosphopeptides, enabled deep insight into signaling recovery and molecular reprogramming upon resistance...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209555/detection-of-soluble-erbb2-in-breast-cancer-cell-lysates-using-a-combined-label-free-fluorescence-platform-based-on-bloch-surface-waves
#4
Alberto Sinibaldi, Camilla Sampaoli, Norbert Danz, Peter Munzert, Leonardo Sibilio, Frank Sonntag, Agostino Occhicone, Elisabetta Falvo, Elisa Tremante, Patrizio Giacomini, Francesco Michelotti
We report on the use of one-dimensional photonic crystals to detect clinically relevant concentrations of ERBB2/neu/Her2 in cell lysates. ERBB2 is a pivotal breast cancer biomarker and targetable oncogenic driver associated with aggressive breast cancer subtypes. To quantitate soluble ERBB2, we developed an optical platform that combines label-free and fluorescence detection modes. Such platform makes use of a sandwich assay in which the one-dimensional photonic crystals sustaining Bloch surface waves are tailored with a monoclonal antibody for highly specific biological recognition (BSW biochip)...
February 9, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28205537/her2-alterations-in-muscle-invasive-bladder-cancer-patient-selection-beyond-protein-expression-for-targeted-therapy
#5
Bernhard Kiss, Alexander W Wyatt, James Douglas, Veronika Skuginna, Fan Mo, Shawn Anderson, Diana Rotzer, Achim Fleischmann, Vera Genitsch, Tetsutaro Hayashi, Maja Neuenschwander, Christine Buerki, Elai Davicioni, Colin Collins, George N Thalmann, Peter C Black, Roland Seiler
Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205231/analysis-of-ctdna-to-predict-prognosis-and-monitor-treatment-responses-in-metastatic-pancreatic-cancer-patients
#6
He Cheng, Chen Liu, Jiahao Jiang, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Zhenzhen Zhang, Jin Xu, Liang Liu, Quanxing Ni, Xianjun Yu
Cell-free circulating tumor DNA (ctDNA) in plasma has been used as a potential noninvasive biomarker for various tumors. The current study was performed to evaluate the clinical implications of ctDNA detection in patients with metastatic pancreatic cancer. Firstly, we attempted to prospectively screen a panel of 60 genes in cell-free DNA (cfDNA) from ten metastatic pancreatic cancer patients via exome sequencing. Secondly, droplet digital PCR (ddPCR) was used to identify potential mutations in a cohort of 188 patients with metastatic pancreatic cancer...
February 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28199989/presence-of-cancer-associated-mutations-in-exhaled-breath-condensates-of-healthy-individuals-by-next-generation-sequencing
#7
Omar Youssef, Aija Knuuttila, Päivi Piirilä, Tom Böhling, Virinder Sarhadi, Sakari Knuutila
Exhaled breath condensate (EBC) is a non-invasive source that can be used for studying different genetic alterations occurring in lung tissue. However, the low yield of DNA available from EBC has hampered the more detailed mutation analysis by conventional methods. We applied the more sensitive amplicon-based next generation sequencing (NGS) to identify cancer related mutations in DNA isolated from EBC. In order to apply any method for the purpose of mutation screening in cancer patients, it is important to clarify the incidence of these mutations in healthy individuals...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28191772/human-induced-pluripotent-cell-derived-sensory-neurons-for-fate-commitment-of-bone-marrow-derived-schwann-cells-implications-for-remyelination-therapy
#8
Sa Cai, Lei Han, Qiang Ao, Ying-Shing Chan, Daisy Kwok-Yan Shum
Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins. Continuing culture in maintenance medium resulted in neuronal networks immunopositive for synaptic vesicle markers and vesicular glutamate transporters suggestive of excitatory neurotransmission...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28187448/impact-of-country-of-birth-on-genetic-testing-of-metastatic-lung-adenocarcinomas-in-france-african-women-exhibit-a-mutational-spectrum-more-similar-to-asians-than-to-caucasians
#9
Raphael Saffroy, Jean-François Morère, Nelly Bosselut, Pasquale F Innominato, Jocelyne Hamelin, Jean Trédaniel, Sophie Masse, Véronique Dussaule-Duchatelle, André Balaton, Pierre Validire, Catherine Guettier, Mohamed Bouchahda, Antoinette Lemoine
BACKGROUND: Limited data are available on the prevalence of oncogenic driver mutations in Caucasian populations, and especially in Europeans. AIM: To evaluate the targetable mutational spectra in unselected patients with lung adenocarcinoma in routine clinical practice from several French hospitals, using the same molecular platform. PATIENTS AND METHODS: Samples from 2,219 consecutive patients with histologically-proven advanced lung adenocarcinoma were centrally analysed at a referenced and certified diagnostic platform in order to test for activating and resistance mutations in EGFR, KRAS, BRAF, ERBB2 and PI3KCA...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186982/avidinox-anchored-biotinylated-trastuzumab-and-pertuzumab-induce-down-modulation-of-erbb2-and-tumor-cell-death-at-concentrations-order-of-magnitude-lower-than-not-anchored-antibodies
#10
Ferdinando Maria Milazzo, Anna Maria Anastasi, Caterina Chiapparino, Antonio Rosi, Barbara Leoni, Loredana Vesci, Fiorella Petronzelli, Rita De Santis
The oxidized version of Avidin, known as AvidinOX, was previously shown to link to tissue proteins upon injection or nebulization, thus becoming a stable receptor for biotinylated therapeutics. AvidinOX is currently under clinical investigation to target radioactive biotin to inoperable tumor lesions (ClinicalTrials.gov NCT02053324). Presently, we show that the anti-ErbB2 monoclonal antibodies Trastuzumab and Pertuzumab can be chemically biotinylated while maintaining their biochemical and biological properties...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178722/differential-gene-expression-in-ductal-carcinoma-in-situ-of-the-breast-based-on-erbb2-status
#11
Emmanuel Agosto-Arroyo, Tatyana Isayeva, Shi Wei, Jonas S Almeida, Shuko Harada
BACKGROUND: The molecular signature of ductal carcinoma in situ (DCIS) in the breast is not well understood. Erb-b2 receptor tyrosine kinase 2 (ERBB2 [formerly known as HER2/neu]) positivity in DCIS is predictive of coexistent early invasive breast carcinoma. The aim of this study is to identify the gene-expression signature profiles of estrogen receptor (ER)/progesterone receptor (PR)-positive, ERBB2, and triple-negative subtypes of DCIS. METHODS: Based on ER, PR, and ERBB2 status, a total of 18 high nuclear grade DCIS cases with no evidence of invasive breast carcinoma were selected along with 6 non-neoplastic controls...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28178681/molecular-profiling-of-metastatic-colorectal-tumors-using-next-generation-sequencing-a-single-institution-experience
#12
Jun Gong, May Cho, Marvin Sy, Ravi Salgia, Marwan Fakih
BACKGROUND: Recent molecular characterization of colorectal tumors has identified several molecular alterations of interest that are considered targetable in metastatic colorectal cancer (mCRC). METHODS: We conducted a single-institution, retrospective study based on comprehensive genomic profiling of tumors from 138 patients with mCRC using next-generation sequencing (NGS) via FoundationOne. RESULTS: Overall, RAS mutations were present in 51...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177558/tmem16a-ano1-suppression-improves-response-to-antibody-mediated-targeted-therapy-of-egfr-and-her2-erbb2
#13
Sucheta Kulkarni, Anke Bill, Neal R Godse, Nayel I Khan, Jason I Kass, Kevin Steehler, Carolyn Kemp, Kara Davis, Carol A Bertrand, Avani R Vyas, Douglas E Holt, Jennifer R Grandis, L Alex Gaither, Umamaheswar Duvvuri
TMEM16A, a Ca(2+) -activated Cl(-) channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl(-) channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl(-) channel inhibition...
February 8, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28174229/effects-of-erbb2-overexpression-on-the-proteome-and-erbb-ligand-specific-phosphosignalling-in-mammary-luminal-epithelial-cells
#14
Jenny Worthington, Georgia Spain, John F Timms
Most breast cancers arise from luminal epithelial cells and 25-30% of these tumours overexpress the ErbB2/HER2 receptor which correlates with disease progression and poor prognosis. The mechanisms of ErbB2 signalling and the effects of its overexpression are not fully understood. Herein, SILAC expression profiling and phosphopeptide enrichment of a relevant, non-transformed, immortalized human mammary luminal epithelial cell model were used to profile ErbB2-dependent differences in protein expression and phosphorylation events triggered via EGFR (EGF treatment) and ErbB3 (HRG1β treatment) in the context of ErbB2 overexpression...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28169993/the-evolving-genomic-landscape-of-urothelial-carcinoma
#15
REVIEW
Alexander P Glaser, Damiano Fantini, Ali Shilatifard, Edward M Schaeffer, Joshua J Meeks
Survival of patients with urothelial carcinoma (including bladder cancer and upper tract urothelial carcinoma) is limited by our current approaches to staging, surgery, and chemotherapy. Large-scale, next-generation sequencing collaborations, such as The Cancer Genome Atlas, have already identified drivers and vulnerabilities of urothelial carcinoma. This disease has a high degree of mutational heterogeneity and a high frequency of somatic mutations compared with other solid tumours, potentially resulting in an increased neoantigen burden...
February 7, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28167203/erbb2-mutated-metastatic-non-small-cell-lung-cancer-response-and-resistance-to-targeted-therapies
#16
Jody C Chuang, Henning Stehr, Ying Liang, Millie Das, Jane Huang, Maximilian Diehn, Heather A Wakelee, Joel W Neal
ERBB2/HER2 has long been recognized as an oncogenic driver in some breast and gastro-esophageal cancers, in which amplification of this gene confers sensitivity to treatment with ERBB2 directed agents. More recently, somatic mutations in ERBB2 have been reported in 1-2% of patients with lung adenocarcinoma. Previous case series have suggested clinical tumor responses using anti-ERBB2 small molecules and antibody therapies. Here we report the outcomes of nine patients with metastatic lung adenocarcinoma with ERBB2 mutations being treated with ERBB2 targeted therapies...
February 3, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28162790/myocardial-ischemia-reperfusion-upregulates-the-transcription-of-the-neuregulin1-receptor-erbb3-but-only-postconditioning-preserves-protein-translation-role-in-oxidative-stress
#17
Michela Morano, Carmelina Angotti, Francesca Tullio, Giovanna Gambarotta, Claudia Penna, Pasquale Pagliaro, Stefano Geuna
BACKGROUND: Neuregulin1 (Nrg1) and its receptors ErbB are crucial for heart development and for adult heart structural maintenance and function and Nrg1 has been proposed for heart failure treatment. Infarct size is the major determinant of heart failure and the mechanism of action and the role of each ErbB receptor remain obscure, especially in the post-ischemic myocardium. We hypothesized that Nrg1 and ErbB are affected at transcriptional level early after ischemia/reperfusion (I/R) injury, and that the protective postconditioning procedure (PostC, brief cycles of ischemia/reperfusion carried out after a sustained ischemia) can influence this pathway...
January 31, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28161812/tumor-grade-versus-expression-of-invasion-related-molecules-in-astrocytoma
#18
József Virga, László Bognár, Tibor Hortobágyi, Gábor Zahuczky, Éva Csősz, Gergő Kalló, Judit Tóth, Gábor Hutóczki, Judit Reményi-Puskár, László Steiner, Almos Klekner
Peritumoral infiltration is characteristic of astrocytomas even in low-grade tumors. Tumor cells migrate to neighbouring tissue and cause recurrence. The extracellular matrix (ECM) plays a role in tumor invasion; expression levels of its components' have been linked to tumor invasion. This study determines the mRNA and protein expression of 20 invasion-related ECM components by examining non-tumor brain; grade I-II-III astrocytoma and glioblastoma samples. Expression levels were measured by QRT-PCR and mass-spectroscopy...
February 4, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28160563/tumor-suppressor-role-of-mir-3622b-5p-in-erbb2-positive-cancer
#19
Mingjie Lu, Tongshan Wang, Mingfeng He, Wenfang Cheng, Ting Yan, Zebo Huang, Lan Zhang, Huo Zhang, Wei Zhu, Yichao Zhu, Ping Liu
Over-expression or amplification of ERBB2 is observed in multifarious carcinomas. However, the molecular mechanism of ERBB2 downregulation in ERBB2-positive cancers remains obscure. This experiment investigated the suppressive role of miR-3622b-5p in ERBB2-positive breast and gastric cancers. The luciferase activity of ERBB2 3'-untranslated region-based reporters constructed in HEK-293T, SK-BR-3 and MCF-10A cells suggested that ERBB2 was the target gene of miR-3622b-5p. Over-expressed miR-3622b-5p reduced the protein level of ERBB2, weakened the activation of mTORC1/S6, and induced the apoptosis of ERBB2-positive cancer cells...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28154322/non-canonical-activation-of-receptor-tyrosine-kinases-in-cancer-progression
#20
Hiroaki Sakurai
 Receptor tyrosine kinases (RTKs) are known to be key regulators of cancer cell proliferation, migration, invasion and metastatic spread. Ligand-binding to the extracellular domain triggers canonical activation of the intracellular tyrosine kinase domain. In contrast, it has become evident that RTKs are also regulated by non-canonical tyrosine kinase-independent mechanisms via phosphorylation of their serine/threonine residues. In this review, I mainly introduce our recent findings on the non-canonical regulation of epidermal growth factor receptor (EGFR), ErbB2 and erythropoietin-producing hepatocellular receptor A2 (EphA2), and discuss the roles of non-canonical activation of RTKs in cancer progression and resistance to targeted cancer agents...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
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