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https://www.readbyqxmd.com/read/28646172/dacomitinib-a-pan-inhibitor-of-erbb-receptors-suppresses-growth-and-invasive-capacity-of-chemoresistant-ovarian-carcinoma-cells
#1
Majid Momeny, Ghazaleh Zarrinrad, Farima Moghaddaskho, Arash Poursheikhani, Ghazaleh Sankanian, Azam Zaghal, Shahab Mirshahvaladi, Fatemeh Esmaeili, Haniyeh Eyvani, Farinaz Barghi, Zahra Sabourinejad, Zivar Alishahi, Hassan Yousefi, Reza Ghasemi, Leila Dardaei, Davood Bashash, Bahram Chahardouli, Ahmad R Dehpour, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28643125/the-role-of-prmt1-in-egfr-methylation-and-signaling-in-mda-mb-468-triple-negative-breast-cancer-cells
#2
Katsuya Nakai, Weiya Xia, Hsin-Wei Liao, Mitsue Saito, Mien-Chie Hung, Hirohito Yamaguchi
BACKGROUND: Epidermal growth factor receptor (EGFR) is often overexpressed in triple-negative breast cancer (TNBC). However, clinical studies have shown that therapies against EGFR are not effective in patients with TNBC. Recently, it has been reported that arginine 198/200 in EGFR extracellular domain is methylated by PRMT1 and that the methylation confers resistance to EGFR monoclonal antibody cetuximab in colorectal cancer cells. To explore a potential mechanism underlying intrinsic resistance to anti-EGFR therapy in TNBC, we investigated the role of PRMT1 in EGFR methylation and signaling in MDA-MB-468 (468) TNBC cells...
June 22, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28641461/the-impact-of-data-errors-on-the-outcome-of-randomized-clinical-trials
#3
Marc Buyse, Pierre Squifflet, Elisabeth Coart, Emmanuel Quinaux, Cornelis Ja Punt, Everardo D Saad
Background/aims Considerable human and financial resources are typically spent to ensure that data collected for clinical trials are free from errors. We investigated the impact of random and systematic errors on the outcome of randomized clinical trials. Methods We used individual patient data relating to response endpoints of interest in two published randomized clinical trials, one in ophthalmology and one in oncology. These randomized clinical trials enrolled 1186 patients with age-related macular degeneration and 736 patients with metastatic colorectal cancer...
June 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28638777/heterobifunctional-dyes-highly-fluorescent-linkers-based-on-cyanine-dyes
#4
Virginia Wycisk, Katharina Achazi, Ole Hirsch, Christian Kuehne, Jens Dernedde, Rainer Haag, Kai Licha
Herein, we present a new synthetic route to cyanine-based heterobifunctional dyes and their application as fluorescent linkers between polymers and biomolecules. The synthesized compounds, designed in the visible spectral range, are equipped with two different reactive groups for highly selective conjugation under physiological conditions. By applying indolenine precursors with functionalized benzenes, we achieved water-soluble asymmetric cyanine dyes bearing maleimido and N-hydroxysuccinimidyl functionalities in a three-step synthesis...
June 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28637013/akt-can-modulate-the-in-vitro-response-of-hnscc-cells-to-irreversible-egfr-inhibitors
#5
Renato José Silva-Oliveira, Matias Melendez, Olga Martinho, Maicon F Zanon, Luciano de Souza Viana, André Lopes Carvalho, Rui Manuel Reis
Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635183/cetuximab-conjugated-nanodiamonds-drug-delivery-system-for-enhanced-targeting-therapy-and-3d-raman-imaging
#6
Dandan Li, Xin Chen, Hong Wang, Jie Liu, Meiling Zheng, Yang Fu, Yuan Yu, Jinfang Zhi
In this study, a multicomponent nanodiamonds (NDs)-based targeting drug delivery system, cetuximab-NDs-cisplatin bioconjugate, combining both specific targeting and enhanced therapeutic efficacy capabilities, is developed and characterized. The specific targeting ability of cetuximab-NDs-cisplatin system on human liver hepatocellular carcinoma (HepG2) cells is evaluated through epidermal growth factor receptor (EGFR) blocking experiments, since EGFR is over-expressed on HepG2 cell membrane. Besides, cytotoxic evaluation confirms that cetuximab-NDs-cisplatin system could significantly inhibit the growth of HepG2 cells, and the therapeutic activity of this system is proven to be better than that of both nonspecific NDs-cisplatin conjugate and specific EGF-NDs-cisplatin conjugate...
June 21, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28632865/effect-of-first-line-chemotherapy-combined-with-cetuximab-or-bevacizumab-on-overall-survival-in-patients-with-kras-wild-type-advanced-or-metastatic-colorectal-cancer-a-randomized-clinical-trial
#7
Alan P Venook, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Briant Fruth, Jeffrey A Meyerhardt, Deborah Schrag, Claire Greene, Bert H O'Neil, James Norman Atkins, Scott Berry, Blase N Polite, Eileen M O'Reilly, Richard M Goldberg, Howard S Hochster, Richard L Schilsky, Monica M Bertagnolli, Anthony B El-Khoueiry, Peter Watson, Al B Benson, Daniel L Mulkerin, Robert J Mayer, Charles Blanke
Importance: Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. Objective: To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer...
June 20, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28632850/cetuximab-or-bevacizumab-with-first-line-chemotherapy-in-advanced-kras-wild-type-colorectal-cancer-no-difference-but-not-the-same
#8
Christopher H Lieu, Wells A Messersmith
No abstract text is available yet for this article.
June 20, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28632725/the-role-of-primary-tumour-sidedness-egfr-gene-copy-number-and-egfr-promoter-methylation-in-ras-braf-wild-type-colorectal-cancer-patients-receiving-irinotecan-cetuximab
#9
Laura Demurtas, Marco Puzzoni, Riccardo Giampieri, Pina Ziranu, Valeria Pusceddu, Alessandra Mandolesi, Chiara Cremolini, Gianluca Masi, Fabio Gelsomino, Carlotta Antoniotti, Cristian Loretelli, Fausto Meriggi, Alberto Zaniboni, Alfredo Falcone, Stefano Cascinu, Mario Scartozzi
BACKGROUND: The data from randomised trials suggested that primary tumour sidedness could represent a prognostic and predictive factor in colorectal cancer (CRC) patients, particularly during treatment with anti-epidermal growth factor receptor (EGFR) therapy. However, an in-deep molecular selection might overcome the predictive role of primary tumour location in this setting. METHODS: We conducted a retrospective analysis in which tumour samples from RAS/BRAF wild-type (WT) metastatic CRC patients treated with second-third-line irinotecan/cetuximab were analysed for EGFR gene copy number (GCN) and promoter methylation...
June 20, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28628728/characterizing-the-detection-threshold-for-optical-imaging-in-surgical-oncology
#10
Andrew C Prince, Aditi Jani, Melissa Korb, Kiranya E Tipirneni, Benjamin B Kasten, Eben L Rosenthal, Jason M Warram
BACKGROUND AND OBJECTIVES: Optical imaging to guide cancer resections is rapidly transitioning into the operating room. However, the sensitivity of this technique to detect subclinical disease is yet characterized. The purpose of this study was to determine the minimum range of cancer cells that can be detected by antibody-based fluorescence imaging. METHODS: 2LMP (breast), COLO-205 (colon), MiaPaca-2 (pancreas), and SCC-1 (head and neck) cells incubated in vitro with cetuximab-IRDye800CW (dose range 8...
June 19, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28622036/molecular-targeted-drugs-and-treatment-of-colorectal-cancer-recent-progress-and-future-perspectives
#11
Fang Geng, Zheng Wang, Hang Yin, Junxian Yu, Bangwei Cao
Nowadays, colorectal cancer is the fourth most common type of tumor all over the world. When diagnosed, ∼50%-60% of tumors have metastasized, thus resulting in a grim prognosis. Chemotherapy is regarded as standard treatment for patients with colorectal cancer, however, limitations of chemotherapy cannot be ignored, such as low selectivity, insufficient concentrations in tumor tissues, and systemic toxicity. Recently, six targeted drugs have been approved by the U.S. Food and Drug Administration (FDA) for treatment of metastatic colorectal cancer (mCRC), including bevacizumab, aflibercept, regorafenib, cetuximab, and panitumumab...
June 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28619608/real-world-direct-health-care-costs-for-metastatic-colorectal-cancer-patients-treated-with-cetuximab-or-bevacizumab-containing-regimens-in-first-line-or-first-line-through-second-line-therapy
#12
Stephen Johnston, Kathleen Wilson, Helen Varker, Elisabetta Malangone-Monaco, Paul Juneau, Ellen Riehle, Sacha Satram-Hoang, Nicolas Sommer, Sarika Ogale
BACKGROUND: The present study examined real-world direct health care costs for metastatic colorectal cancer (mCRC) patients initiating first-line (1L) bevacizumab (BEV)- or cetuximab (CET)-containing regimen in 1L or 1L-through-second-line (1L-2L) therapy. PATIENTS AND METHODS: Using a large US insurance claims database, patients with mCRC initiating 1L BEV- or 1L CET-containing regimen from January 1, 2008 to September 30, 2014 were identified. The per-patient per-month (PPPM) all-cause health care costs (2014 US dollars) were measured during 1L therapy and, for patients continuing to a 2L biologic-containing regimen, 1L-2L therapy...
March 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28618305/phase-i-study-of-temsirolimus-in-combination-with-cetuximab-in-patients-with-advanced-solid-tumours
#13
A Hollebecque, R Bahleda, L Faivre, J Adam, V Poinsignon, A Paci, C Gomez-Roca, J C Thery, M C Le Deley, A Varga, A Gazzah, E Ileana, M Gharib, E Angevin, K Malekzadeh, C Massard, J C Soria, J P Spano
BACKGROUND: Preclinical studies suggest synergistic antitumour effects of mammalian target of rapamycin (mTOR) inhibitor such as temsirolimus combined with anti-EGFR monoclonal antibody such as cetuximab. METHODS: Temsirolimus (T) and cetuximab (C) were combined and escalated in cohorts of patients with advanced or metastatic solid tumours, respectively from 15 to 25 mg and 150-250 mg/m(2), until the maximum tolerated dose (MTD) was determined. Effort was made in the expansion cohort to enrol patients harbouring a molecular aberration in the human epidermal growth factor receptor (EGFR) and/or phosphoinositide 3-kinase (PI3K) pathways...
June 12, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28611205/mouse-pdx-trial-suggests-synergy-of-concurrent-inhibition-of-raf-and-egfr-in-colorectal-cancer-with-braf-or-kras-mutations
#14
Yung-Mae M Yao, Gregory P Donoho, Philip Iversen, Youyan Zhang, Robert D Van Horn, Amelie Forest, Ruslan Novosiadly, Yue Webster, Ebert J Philip, Steven M Bray, Jason C Ting, Amit Aggarwal, James R Henry, Ramon V Tiu, Gregory D Plowman, Sheng-Bin Peng
Purpose: It is to evaluate the anti-tumor efficacy of cetuximab in combination with LSN3074753, an analogue of LY3009120 and pan-RAF inhibitor in 79 colorectal cancer (CRC) patient derived xenograft (PDX) models.<br />Experimental Design: 79 well characterized CRC PDX models were employed to conduct a single mouse per treatment group (n=1) trial.<br />Results: Consistent with clinical results, cetuximab was efficacious in wild type KRAS and BRAF PDX models, with an overall response rate (ORR) of 6...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28606015/retrospective-analysis-of-premedication-glucocorticosteroids-and-h1-antihistamines-for-preventing-infusion-reactions-associated-with-cetuximab-treatment-of-patients-with-head-and-neck-cancer
#15
Kiwako Ikegawa, Shinya Suzuki, Hisanaga Nomura, Tomohiro Enokida, Tomoko Yamazaki, Susumu Okano, Kazushi Endo, Shinichiro Saito, Masakazu Yamaguchi, Makoto Tahara
Objectives We evaluated infusion-related reactions associated with cetuximab combination chemotherapy comprising an H1-receptor antagonist plus dexamethasone as anti-allergy premedications for patients with head and neck cancer. Methods We retrospectively evaluated 248 patients who received a cetuximab combination regimen between December 2012 and August 2015. All patients received 5 mg intravenous dichlorpheniramine (H1-receptor antagonist), and dexamethasone (DEX) was adjusted from 6.6 mg to 13.2 mg according to the emetogenic risk...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28602170/treatment-options-for-metastatic-colorectal-cancer-in-patients-with-liver-dysfunction-due-to-malignancy
#16
REVIEW
L Faugeras, A Dili, A Druez, B Krug, C Decoster, L D'Hondt
BACKGROUND: The survival of colorectal cancer patients is frequently determined by the extent of metastatic invasion to the liver; in cases of major involvement, therapeutic strategies are limited because the liver is necessary for drug metabolism. MATERIAL AND METHODS: We have reviewed articles about the pharmacokinetic profiles of each drug used in colorectal cancer patients with hepatic dysfunction to determine which of these treatments are most feasible. RESULTS: Some drugs appear to be feasible options for patients with hepatic insufficiency...
July 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28602169/toxicities-of-systemic-agents-in-squamous-cell-carcinoma-of-the-head-and-neck-scchn-a-new-perspective-in-the-era-of-immunotherapy
#17
REVIEW
Nabil F Saba, Mayur D Mody, Elaine S Tan, Harpaul S Gill, Alessandra Rinaldo, Robert P Takes, Primož Strojan, Dana M Hartl, Jan B Vermorken, Missak Haigentz, Alfio Ferlito
Squamous cell carcinoma of the head and neck (SCCHN) is a difficult to treat malignancy and represents the seventh most common cancer worldwide. Systemic therapy has a critical role in the treatment of locally advanced and recurrent/metastatic disease. Cytotoxic chemotherapy has been primarily used along with radiation and surgery, with cisplatin being the standard of care choice of therapy. When contraindications to cisplatin exist, other agents such as carboplatin, taxanes, 5-fluorouracil, and cetuximab are used...
July 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28600476/phase-ib-study-of-lumretuzumab-plus-cetuximab-or-erlotinib-in-solid-tumor-patients-and-evaluation-of-her3-and-heregulin-as-potential-biomarkers-of-clinical-activity
#18
Didier Meulendijks, Wolfgang Jacob, Emile E Voest, Morten Mau-Sørensen, Maria Martinez-Garcia, Alvaro Taus, Tania Fleitas, Andres Cervantes, Martijn Lolkema, Marlies Hg Langenberg, Maja J A de Jonge, Stefan Sleijfer, Ji-Youn Han, Antonio Calles, Enriqueta Felip, Sang-We Kim, Jan H M Schellens, Sabine Wilson, Marlene Thomas, Maurizio Ceppi, Georgina Meneses-Lorente, Ian James, Suzana Vega Harring, Rajiv Dua, Maitram Nguyen, Lori Steiner, Celine Adessi, Francesca Michielin, Birgit Bossenmaier, Martin Weisser, Ulrik Lassen
<br /> <p>This study investigated the safety, clinical activity and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.</p> <br />Experimental Design: <br /> <p>The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28599497/monoclonal-antibodies-against-autocrine-motility-factor-suppress-gastric-cancer
#19
Hahn-Sun Jung, Su In Lee, Seung-Hoon Kang, Jin Sang Wang, Eun Hee Yang, Byungwook Jeon, Jayhyuk Myung, Ji Young Baek, Song-Kyu Park
Autocrine motility factor (AMF), which is a secreted form of phosphoglucose isomerase, is mainly secreted by various tumors and has cytokine-like activity. AMF is known to stimulate proliferation, survival and metastasis of cancer cells, and angiogenesis within a tumor. The present study investigated whether inhibition of AMF using targeted-antibodies was able to suppress the growth of cancer. A migration assay using a Boyden chamber was utilized to measure the activity of AMF on the motility of cancer cells...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28598813/identification-of-a-novel-atm-inhibitor-with-cancer-cell-specific-radiosensitization-activity
#20
Amy J C Dohmen, Xiaohang Qiao, Anja Duursma, Ruud H Wijdeven, Cor Lieftink, Floor Hageman, Ben Morris, Pasi Halonen, Conchita Vens, Michiel W M van den Brekel, Huib Ovaa, Jacques Neefjes, Charlotte L Zuur
Treatment of advanced head and neck squamous cell carcinoma (HNSCC) is plagued by low survival and high recurrence rates, despite multimodal therapies. Presently, cisplatin or cetuximab is used in combination with radiotherapy which has resulted in minor survival benefits but increased severe toxicities relative to RT alone. This underscores the urgent need for improved tumor-specific radiosensitizers for better control with lower toxicities. In a small molecule screen targeting kinases, performed on three HNSCC cell lines, we identified GSK635416A as a novel radiosensitizer...
May 19, 2017: Oncotarget
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