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https://www.readbyqxmd.com/read/29683256/the-immunoglobulin-like-domain-of-neuregulins-potentiates-erbb3-her3-activation-and-cellular-proliferation
#1
Ariana Centa, Ruth Rodríguez-Barrueco, Juan Carlos Montero, Atanasio Pandiella
The Neuregulins (NRGs) represent a large family of membrane-anchored growth factors, whose deregulation may contribute to the pathogenesis of several tumours. In fact, targeting of NRG-activated pathways has demonstrated clinical benefit. To improve the efficacy of anti-NRG therapies, it is essential to gain insights into the regions of NRGs that favour their pro-oncogenic properties. Here we have addressed the protumorigenic impact of different NRG domains. To do this, deletion mutants affecting different NRG domains were expressed in 293 and MCF7 cells...
April 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29662620/promotion-of-malignant-phenotype-after-disruption-of-the-three-dimensional-structure-of-cultured-spheroids-from-colorectal-cancer
#2
Jose M Piulats, Jumpei Kondo, Hiroko Endo, Hiromasa Ono, Takeshi Hagihara, Hiroaki Okuyama, Yasuko Nishizawa, Yasuhiko Tomita, Masayuki Ohue, Kouki Okita, Hidejiro Oyama, Hidemasa Bono, Takashi Masuko, Masahiro Inoue
Individual and small clusters of cancer cells may detach from the edges of a main tumor and invade vessels, which can act as the origin of metastasis; however, the mechanism for this phenomenon is not well understood. Using cancer tissue-originated spheroids, we studied whether disturbing the 3D architecture of cancer spheroids can provoke the reformation process and progression of malignancy. We developed a mechanical disruption method to achieve homogenous disruption of the spheroids while maintaining cell-cell contact...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29608843/localized-visualization-and-autonomous-detection-of-cell-surface-receptor-clusters-using-dna-proximity-circuit
#3
Yan Shan Ang, Jia'En Jasmine Li, Pei-Jou Chua, Cheng Teng Ng, Boon-Huat Bay, Lin-Yue Lanry Yung
Cell surface receptor plays an important role in mediating cell communication and is used as disease biomarkers and therapeutic targets. We present a one-pot molecular toolbox, which we term the split proximity circuit (SPC), for the autonomous detection and visualization of cell surface receptor clusters. Detection was powered by antibody recognition and a series of autonomous DNA hybridization to achieve localized, enzyme-free signal amplification. The system under study was the human epidermal growth factor receptor (HER) family, i...
April 2, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29603584/simultaneous-targeting-of-egfr-her2-and-her4-by-afatinib-overcomes-intrinsic-and-acquired-cetuximab-resistance-in-head-and-neck-squamous-cell-carcinoma-cell-lines
#4
Ines De Pauw, Filip Lardon, Jolien Van den Bossche, Hasan Baysal, Erik Fransen, Vanessa Deschoolmeester, Patrick Pauwels, Marc Peeters, Jan Baptist Vermorken, An Wouters
The epidermal growth factor receptor (EGFR, HER1) is a therapeutic target in head and neck squamous cell carcinoma (HNSCC). After initial promising results with EGFR-targeted therapies such as cetuximab, therapeutic resistance has become a major clinical problem, and new treatment options are therefore necessary. Moreover, the relationship between HER receptors, anti-EGFR therapies and the human papillomavirus (HPV) status in HNSCC is not fully understood. In contrast to first generation EGFR inhibitors, afatinib irreversibly inhibits multiple HER receptors simultaneously...
March 30, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29599351/analysis-of-her-family-her1-4-expression-as-a-biomarker-in-combination-therapy-with-pertuzumab-trastuzumab-and-docetaxel-for-advanced-her2-positive-breast-cancer
#5
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Chemotherapy with trastuzumab, pertuzumab and docetaxel (TPD regimen) is now strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER)2-positive breast cancer. In this study, we analyzed the expression of HER 1-4 proteins, and investigated whether or not their expression was predictive of the response of advanced HER2-positive breast cancer to chemotherapy with the TPD regimen. PATIENTS AND METHODS: The study consisted of 29 cases in which TPD regimen chemotherapy was carried out from September 2013 to November 2015...
April 2018: Anticancer Research
https://www.readbyqxmd.com/read/29550255/microenvironment-mediated-mechanisms-of-resistance-to-her2-inhibitors-differ-between-her2-breast-cancer-subtypes
#6
Spencer S Watson, Mark Dane, Koei Chin, Zuzana Tatarova, Moqing Liu, Tiera Liby, Wallace Thompson, Rebecca Smith, Michel Nederlof, Elmar Bucher, David Kilburn, Matthew Whitman, Damir Sudar, Gordon B Mills, Laura M Heiser, Oliver Jonas, Joe W Gray, James E Korkola
Extrinsic signals are implicated in breast cancer resistance to HER2-targeted tyrosine kinase inhibitors (TKIs). To examine how microenvironmental signals influence resistance, we monitored TKI-treated breast cancer cell lines grown on microenvironment microarrays composed of printed extracellular matrix proteins supplemented with soluble proteins. We tested ∼2,500 combinations of 56 soluble and 46 matrix microenvironmental proteins on basal-like HER2+ (HER2E) or luminal-like HER2+ (L-HER2+) cells treated with the TKIs lapatinib or neratinib...
February 21, 2018: Cell Systems
https://www.readbyqxmd.com/read/29546323/tumor-suppressive-effect-of-lrig1-a-negative-regulator-of-erbb-in-non-small-cell-lung-cancer-harboring-mutant-egfr
#7
Hidejiro Torigoe, Hiromasa Yamamoto, Masakiyo Sakaguchi, Chen Youyi, Kei Namba, Hiroki Sato, Kazuhiko Shien, Junichi Soh, Ken Suzawa, Shuta Tomida, Kazunori Tsukuda, Shinichiro Miyoshi, Shinichi Toyooka
Epidermal growth factor receptor (EGFR) is a member of the ErbB (HER) family that is known to play important roles in the pathogenesis of various human cancers. Mutations of the EGFR gene are commonly found as oncogenic driver mutations, and have been targeted for treatment in non-small cell lung cancer (NSCLC). Leucine-rich repeat and immunoglobulin-like domain protein-1 (LRIG1) is a cell-surface protein that is known as a negative regulator of the ErbB (HER) family. In this study, we first confirmed that the expression levels of LRIG1 were much lower in NSCLC than in non-malignant cells or tissues...
March 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29541416/targeting-scfv-fc-sctrail-fusion-proteins-to-tumor-cells
#8
Meike Hutt, Sina Fellermeier-Kopf, Oliver Seifert, Lisa C Schmitt, Klaus Pfizenmaier, Roland E Kontermann
Fusion proteins combining hexavalent TRAIL with antibody fragments allow for a targeted delivery and efficient apoptosis induction in tumor cells. Here, we analyzed scFv-Fc-scTRAIL molecules directed against EGFR, HER2, HER3, and EpCAM as well as an untargeted Fc-scTRAIL fusion protein for their potentials to induce cell death both in vitro and in a xenograft tumor model in vivo . The scFv-Fc-scTRAIL fusion protein directed against EGFR as well as the fusion protein directed against EpCAM showed targeting effects on the two tested colorectal carcinoma cell lines Colo205 and HCT116, while a fusion protein targeting HER3 was more effective than untargeted Fc-scTRAIL only on Colo205 cells...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29506988/phase-ii-study-of-the-dual-egfr-her3-inhibitor-duligotuzumab-mehd7945a-vs-cetuximab-in-combination-with-folfiri-in-ras-wild-type-metastatic-colorectal-cancer
#9
Andrew Graham Hill, Michael Findlay, Matthew Burge, Christopher Jackson, Pilar García Alfonso, Leslie Samuel, Vinod Ganju, Meinolf Karthaus, Alessio Amatu, Mark Jeffery, Maria Di Bartolomeo, John Bridgewater, Andrew L Coveler, Manuel Hidalgo, Amy V Kapp, Roxana Sufan, Bruce McCall, William Hanley, Elicia Penuel, Andrea Pirzkall, Josep Tabernero
PURPOSE: Duligotuzumab is a dual-action antibody directed against EGFR and HER3. EXPERIMENTAL DESIGN: mCRC patients with KRAS ex2 wild-type received duligotuzumab or cetuximab and FOLFIRI until progression or intolerable toxicity. Mandatory tumor samples underwent mutation and biomarker analysis. Efficacy analysis was conducted in patients with RAS exon 2/3 wild-type tumors. RESULTS: Of 134 randomized patients, 98 were RAS ex2/3 wild-type...
March 5, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29501698/heregulin-induced-cell-migration-is-promoted-by-aryl-hydrocarbon-receptor-in-her2-overexpressing-breast-cancer-cells
#10
Naoya Yamashita, Nao Saito, Shuai Zhao, Kensuke Terai, Nobuyuki Hiruta, Youngjin Park, Hideaki Bujo, Kiyomitsu Nemoto, Yuichiro Kanno
HER2 overexpression accounts for approximately 15%-20% of all breast cancers. We have shown that HER2 overexpression leads to elevated expression of the aryl hydrocarbon receptor (AhR) in breast cancer cells. In this study, firstly, we showed that AhR expression was up-regulated by treatment with the HER3 ligand heregulin (HRG) in HER2-overexpressing breast cancer cell lines. Induction of AhR was mediated by transcriptional activation of the region of AhR promoter corresponding to -190 to -100bp. In addition, HRG treatment elicited nuclear translocation of AhR...
March 1, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29499944/targeting-egfr-her2-her3-with-a-three-in-one-aptamer-sirna-chimera-confers-superior-activity-against-her2-breast-cancer
#11
Xiaolin Yu, Sharad Ghamande, Haitao Liu, Lu Xue, Shuhua Zhao, Wenxi Tan, Lijing Zhao, Shou-Ching Tang, Daqing Wu, Hasan Korkaya, Nita J Maihle, Hong Yan Liu
HER family members are interdependent and functionally compensatory. Simultaneously targeting EGFR/HER2/HER3 by antibody combinations has demonstrated superior treatment efficacy over targeting one HER receptor. However, antibody combinations have their limitations, with high immunogenicity and high cost. In this study, we have developed a three-in-one nucleic acid aptamer-small interfering RNA (siRNA) chimera, which targets EGFR/HER2/HER3 in one molecule. This inhibitory molecule was constructed such that a single EGFR siRNA is positioned between the HER2 and HER3 aptamers to create a HER2 aptamer-EGFR siRNA-HER3 aptamer chimera (H2EH3)...
March 2, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/29490608/the-effects-of-trastuzumab-on-her2-mediated-cell-signaling-in-cho-cells-expressing-human-her2
#12
Hamid Maadi, Babak Nami, Junfeng Tong, Gina Li, Zhixiang Wang
BACKGROUND: Targeted therapy with trastuzumab has become a mainstay for HER2-positive breast cancer without a clear understanding of the mechanism of its action. While many mechanisms have been suggested for the action of trastuzumab, most of them are not substantiated by experimental data. It has been suggested that trastuzumab functions by inhibiting intracellular signaling initiated by HER2, however, the data are very controversial. A major issue is the different cellular background of various breast cancer cells lines used in these studies...
March 1, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29473311/her3-expression-is-enhanced-during-progression-of-lung-adenocarcinoma-without-egfr-mutation-from-stage-0-to-ia1
#13
Toru Kumagai, Yasuhiko Tomita, Shin-Ichi Nakatsuka, Madoka Kimura, Kei Kunimasa, Takako Inoue, Motohiro Tamiya, Kazumi Nishino, Yoshiyuki Susaki, Takashi Kusu, Toshiteru Tokunaga, Jiro Okami, Masahiko Higashiyama, Fumio Imamura
BACKGROUND: Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood. In this paper, we focused on which receptor is correlated with lung adenocarcinoma progression in the presence or absence of EGFR mutation from stage 0 to IA1. METHODS: HER2 and HER3 expression and activating EGFR mutations in surgically resected lung adenocarcinoma exhibiting ground glass nodules on chest computed tomography and re-classified to stage 0 and IA1 were examined by immunohistochemistry and peptide nucleic acid-locked nucleic acid PCR clamp method, respectively...
April 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29440899/aptamer-drug-conjugate-targeted-delivery-of-doxorubicin-in-a-her3-aptamer-functionalized-liposomal-delivery-system-reduces-cardiotoxicity
#14
Xiao-Qian Dou, Hua Wang, Jing Zhang, Fang Wang, Gui-Li Xu, Cheng-Cheng Xu, Huan-Hua Xu, Shen-Si Xiang, Jie Fu, Hai-Feng Song
Introduction: The toxic side effects of doxorubicin (DOX) have limited its use in chemotherapy. Neither liposomal DOX nor pegylated liposomal DOX are able to completely resolve this issue. This is a proof-of-concept study testing aptamer-drug conjugate (ApDC) targeted delivery systems for chemotherapeutic drugs. Methods: Aptamer library targeting human epidermal growth factor receptor 3 (HER3) was screened and affinity was determined by enzyme-linked immunosorbent assay...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29440293/a-correlative-analysis-of-pd-l1-pd-1-pd-l2-egfr-her2-and-her3-expression-in-oropharyngeal-squamous-cell-carcinoma
#15
Conor E Steuer, Christopher C Griffith, Sreenivas Nannapaneni, Mihir R Patel, Yuan Liu, Kelly R Magliocca, Mark W El-Deiry, Cynthia Cohen, Taofeek K Owonikoko, Dong M Shin, Zhuo Georgia Chen, Nabil F Saba
We explored potential associations of the PD-1/PD-L1/PD-L2 pathway with clinical characteristics, outcome, and expression of EGFR, HER2, HER3 in oropharyngeal squamous cell carcinoma (OPSCC) using an institutional database. Protein expression was assessed by immunohistochemistry on tissue microarray sections (EGFR, HER2, HER3) or whole tissue sections (PD-1/PD-L1/PD-L2). Expression of EGFR, HER2, HER3, PD-L1, and PD-L2 was quantified on tumor cells. Maximum density of PD-1 positive lymphocytes was measured on a scale of 0-4 within the tumor mass and peritumoral stroma...
February 13, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29440171/crosstalk-signaling-between-her3-and-hpv16-e6-and-e7-mediates-resistance-to-pi3k-inhibitors-in-head-and-neck-cancer
#16
Toni M Brand, Stefan Hartmann, Neil E Bhola, Hua Li, Yan Zang, Rachel A O'Keefe, Max V Ranall, Sourav Bandyopadhyay, Margaret Soucheray, Nevan J Krogan, Carolyn Kemp, Umamaheswar Duvvuri, Theresa LaVallee, Daniel E Johnson, Michelle A Ozbun, Julie E Bauman, Jennifer R Grandis
Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise in the oropharynx, where viral expression of the E6 and E7 oncoproteins promote cellular transformation, tumor growth, and maintenance. An important oncogenic signaling pathway activated by E6 and E7 is the phosphatidylinositol 3-kinase (PI3K) pathway, a key driver of carcinogenesis. The PI3K pathway is also activated by mutation or amplification of PIK3CA in over half of HPV(+) HNSCC...
February 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29437790/her3-mediated-resistance-to-hsp90-inhibition-detected-in-breast-cancer-xenografts-by-affibody-based-pet-imaging
#17
Carlos Daniel Martins, Chiara Da Pieve, Thomas A Burley, Rhodri Smith, Daniela M Ciobota, Louis Allott, Kevin Harrington, Wim J G Oyen, Graham Smith, Gabriela Kramer-Marek
PURPOSE: Recent studies have highlighted a role of human epidermal growth factor receptor 3 (HER3) in HER2-driven cancers (e.g. breast cancer) implicating the up-regulation of the receptor in resistance to HER-targeted therapies and Hsp90 inhibitors (e.g. AUY922). Therefore, we have developed an affibody-based PET radioconjugate that quantitatively assesses HER3 changes induced by Hsp90 inhibition in vivo Experimental Design: Z HER3:8698 affibody molecules were conjugated via the C-terminus cysteine to DFO-maleimide for 89 Zr radiolabeling...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29436155/design-of-cyclic-and-d-amino-acids-containing-peptidomimetics-for-inhibition-of-protein-protein-interactions-of-her2-her3
#18
Sandeep Pallerla, Himgauri Naik, Sitanshu Singh, Ted Gauthier, Rushikesh Sable, Seetharama D Jois
HER2 receptors are surface proteins belonging to the epidermal growth factor family of receptors. Their numbers are elevated in breast, lung, and ovarian cancers. HER2-positive cancers are aggressive, have higher mortality rate, and have a poor prognosis. We have designed peptidomimetics that bind to HER2 and block the HER2-mediated dimerization of epidermal growth factor family of receptors. Among these, a symmetrical cyclic peptidomimetic (compound 18) exhibited antiproliferative activity in HER2-overexpressing lung cancer cell lines with IC50 values in the nanomolar concentration range...
February 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/29434878/progesterone-impairs-herceptin-effect-on-breast-cancer-cells
#19
Kamila Kitowska, Agnieszka Kowalska, Magdalena Mieszkowska, Dominika Piasecka, Andrzej C Skladanowski, Hanna M Romanska, Rafal Sadej
Breast cancer (BCa) is the most common cancer affecting women worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in ~20-25% of invasive ductal breast carcinomas and is associated with the more aggressive phenotype. Herceptin, a humanized antibody against HER2, is a standard therapy in HER2-overexpressing cases. Approximately one-third of patients relapse despite treatment. Therefore numerous studies have investigated the molecular mechanisms associated with Herceptin resistance...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434875/soluble-her3-predicts-survival-in-bladder-cancer-patients
#20
Ashfaque A Memon, Stephen C Gilliver, Michael Borre, Jan Sundquist, Kristina Sundquist, Ebba Nexo, Boe S Sorensen
The role of soluble human epidermal growth factor receptor (sHER3) in bladder cancer remains unclear. In the present study, an ELISA was developed for the quantification of sHER3 and its role was investigated in patients with bladder cancer (n=82) followed for 10 years. Furthermore, the effects of sHER3 on bladder cancer cell growth and migration were also investigated. The results demonstrated that plasma sHER3 levels were significantly higher in non-invasive tumours (Ta) compared with muscle-invasive tumours (T2-T4)...
February 2018: Oncology Letters
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