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EGFR and colorectal cancer

Shingo Kishi, Rina Fujiwara-Tani, Yi Luo, Isao Kawahara, Kei Goto, Kiyomu Fujii, Hitoshi Ohmori, Chie Nakashima, Takamitsu Sasaki, Hiroki Kuniyasu
Trans fatty acids (TFAs) are risk factors for cardiovascular disorders, and the cancer-promoting effects of TFAs have been previously reported. The present study examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA was found to increase metastasis of HT29 human CRC cells. Results indicated that, in the plasma membrane, EA was integrated into cholesterol rafts, which contain epidermal growth factor receptors (EGFR). EA increased nanog and c-myc, and decreased PGC-1A through lipid raft-associated EGFR signaling in HT29 cells...
April 2018: Oncology Letters
Anna Mouzakiti, Constantinos Nastos, Dimitrios Vlachodimitropoulos, Constantinos Gennatas, Agathi Kondi-Pafiti, Dionisios Voros
PURPOSE: Colon cancer is one of the most common malignancies. Various prognostic markers have been proposed and individualized treatment strategies have been adapted according to tumor molecular and genetic characteristics. The purpose of the present study was to retrospectively analyze a possible association between the expression of COX- 2 and EGFR and clinical and histopathological factors of patients undergoing colon surgery in a Greek population. METHODS: Data from our department's prospectively collected database were retrieved for a total of 100 consecutive colectomies that were performed in our department...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Xuzhi He, Jazmina L Cruz, Shannon Joseph, Nicola Pett, Hui Yi Chew, Zewen K Tuong, Satomi Okano, Gabrielle Kelly, Margaret Veitch, Fiona Simpson, James W Wells
The Epidermal Growth Factor Receptor (EGFR) is selectively expressed on the surface of numerous tumours, such as non-small cell lung, ovarian, colorectal and head and neck carcinomas. EGFR has therefore become a target for cancer therapy. Cetuximab is a chimeric human/mouse monoclonal antibody (mAb) that binds to EGFR, where it both inhibits signaling and induces cell death by antibody-dependent cell mediated cytotoxicity (ADCC). Cetuximab has been approved for clinical use in patients with head and neck squamous cell carcinoma (HNSCC) and colorectal cancer...
February 23, 2018: Oncotarget
Shaimaa A Abdelatef, Mohammed T El-Saadi, Noha H Amin, Ahmed H Abdelazeem, Hany A Omar, Khaled R A Abdellatif
A novel series of spirobenzo[h]chromene and spirochromane derivatives was designed, synthesized and evaluated as potential anticancer agents against MCF-7 (human breast carcinoma), HT-29 (human colorectal adenocarcinoma) and A549 (human lung carcinoma) cell lines using MTT assay. Eight compounds 7, 8e, 13a-e and 16 showed a better anticancer activity than that of sorafenib, the multi-kinase inhibitor with IC50 values between 1.78 and 5.47 μM or erlotinib with IC50 values over 20 μM. Representative compounds 8e, 13c and 16 were selected for further mechanistic investigation via EGFR, B-RAF and tubulin polymerization assays...
March 5, 2018: European Journal of Medicinal Chemistry
Leena Chularojanamontri, Papapit Tuchinda, Chayanee Likitwattananurak, Kamolwan Pongparit, Chuda Rujitharanawong, Suthinee Ithimakin, Kanokvalai Kulthanan
BACKGROUND: Several prospective studies have been conducted in epidermal growth factor receptor (EGFR) inhibitor-related cutaneous reactions in Caucasian patients, but prospective studies in Asian populations are scarce. OBJECTIVE: To investigate the cutaneous side effects of EGFR inhibitors in Asian cancer patients and to assess tumor response to dermatologic manifestations. METHODS: Sixty patients with lung or colorectal cancer who were receiving EGFR inhibitors were prospectively followed for at least one year by oncologists and dermatologists...
March 12, 2018: Asian Pacific Journal of Allergy and Immunology
Kaixuan Zeng, Xiaoxiang Chen, Mu Xu, Xiangxiang Liu, Xiuxiu Hu, Tao Xu, Huiling Sun, Yuqin Pan, Bangshun He, Shukui Wang
Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] = 2...
March 16, 2018: Cell Death & Disease
Luca Mazzarella, Alessandro Guida, Giuseppe Curigliano
Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials...
March 14, 2018: Expert Opinion on Biological Therapy
Zhenhua Wu, Mingzhu Huang, Yiwei Gong, Chen Lin, Weijian Guo
Mutations in the oncogene BRAF(V600E) are found in ~10% of colorectal cancers (CRCs) and are associated with poor prognosis. However, BRAF(V600E) has a limited response to the small-molecule drug, vemurafenib, a BRAF inhibitor, and BRAF inhibition is thought to cause a feedback activation of EGFR signaling that supports continued proliferation. In this study, we explored the effect of combined use of dabrafenib, a BRAF inhibitor, and cetuximab, an EGFR inhibitor, on BRAF(V600E)-mutant CRC stem cells and its possible mechanisms...
March 9, 2018: Acta Biochimica et Biophysica Sinica
Datian Chen, Li Li, Xiang Zhang, Guangyi Gao, Lili Shen, Jing Hu, Mi Yang, Baorui Liu, Xiaoping Qian
BACKGROUND: The efficacy of oxaliplatin-based chemotherapy combined with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) remains controversial in metastatic colorectal cancer (mCRC). This meta-analysis aims to estimate the effect of adding panitumumab or cetuximab to oxaliplatin-based chemotherapy in RAS wild type mCRC patients for the first-line treatment. The primary tumor location is also considered into this meta-analysis. METHODS: RCT studies were identified by a search of MEDLINE, EMBASE, Cochrane library to October 2017, supplemented by manually retrieving ASCO, ESMO conference abstracts...
March 2018: Medicine (Baltimore)
Chao Qi, Yuanlei Chen, Yixuan Zhou, Xucheng Huang, Guoli Li, Jin Zeng, Zhi Ruan, Xinyou Xie, Jun Zhang
Colorectal cancer (CRC) is considered the world's fourth most deadly cancer. Its metastasis is associated with poor prognosis and weakens the effects of treatment. However, the potential molecular mechanisms and key genes involved in CRC metastasis have remained to be comprehensively elucidated. The objective of the present study was to identify the key genes and molecular pathways underlying CRC metastasis. Differentially expressed genes (DEGs) between primary CRC tissues and metastatic CRC were identified by analyzing the GSE2509 dataset from the Gene Expression Omnibus database...
March 8, 2018: Oncology Reports
Witold Owczarek, Monika Słowińska, Aleksandra Lesiak, Magdalena Ciążyńska, Aldona Maciąg, Elwira Paluchowska, Luiza Marek-Józefowicz, Rafał Czajkowski
Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them...
October 2017: Postȩpy Dermatologii i Alergologii
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
Rosa Falcone, Michela Roberto, Marco Filetti, Elisabetta Anselmi, Paolo Marchetti
RATIONALE: Small bowel adenocarcinoma (SBA) is an uncommon gastrointestinal cancer, thus limited data about treatment for advanced disease are available. The lack of specific guidelines has justified the use of therapeutic protocols usually applied in advanced colorectal cancer. Few and preliminary data have suggested possible clinical benefit from the use of target therapy such as bevacizumab and cetuximab. PATIENT CONCERNS: We present the case of a young woman who was admitted to the emergency department for acute abdominal pain, nausea, and vomiting related to a jejunal stenosis...
January 2018: Medicine (Baltimore)
J Zhang, X L Lu, G Zhao, H T Shi, Y Geng, W T Zhong, L Dong
Objective: To explore relationships between the enrichment of ETBF, Fn, Hp in feces, tissues and colorectal cancer. Methods: Feces, lesion tissue and adjacent tissue from 24 patients with colorectal cancer and 31 patients with adenomas were collected, and we collected Feces and tissue of 20 healthy control persons. Then the copy numbers of enterotoxigenic B. fragilis (ETBF), Fusobacterium nucleatum (Fn) and Helicobacter pylori (Hp) were determined by quantitative real-time PCR. Immunohistochemical method was used to examine the expression intensity of EGFR and p53, and the relationships between different expression intensity of EGFR, p53 and the numbers of three bacterias...
February 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Xiang Hu, Ya-Qi Li, Qing-Guo Li, Yan-Lei Ma, Jun-Jie Peng, San-Jun Cai
BACKGROUND: Many types of cancers are devoid of the small leucine-rich proteoglycans: osteoglycin (OGN), but its role in tumorigenesis is poorly studied especially in colorectal cancers (CRC). Here we aim to evaluate the relationship between OGN expression patterns and the clinical course of CRC, and the role of OGN in cancer progression. METHODS: The tissue microarray staining was performed and the relevance between OGN expression and oncologic outcomes was performed using Cox regression analysis...
March 2, 2018: Journal of Experimental & Clinical Cancer Research: CR
Wen-Yu Chu, Ming-Hsien Tsai, Cheng-Liang Peng, Ying-Hsia Shih, Tsai-Yueh Luo, Shu-Jyuan Yang, Ming-Jium Shieh
Photodynamic therapy (PDT) has been shown to kill cancer cells and improve survival and quality of life in cancer patients, and numerous new approaches have been considered for maximizing the efficacy of PDT. In this study, a new multifunctional nanophotosensitizer Ce6/GE11-(pH) micelle was developed to target epidermal growth factor receptor (EGFR) overexpressing colorectal cancer (CRC) cells. This nanophotosensitizer was synthesized using a micelle comprising pH-responsive copolymers (PEGMA-PDPA), biodegradable copolymers (mPEG-PCL), and maleimide-modified biodegradable copolymers (Mal-PEG-PCL) to entrap the potential hydrophobic photosensitizer chlorin e6 (Ce6) and to present EGFR-targeting peptides (GE11) on its surface...
March 2, 2018: Molecular Pharmaceutics
Paul Mésange, Anaïs Bouygues, Nathalie Ferrand, Michèle Sabbah, Alexandre E Escargueil, Ariel Savina, Benoist Chibaudel, Christophe Tournigand, Thierry Andre, Aimery de Gramont, Annette K Larsen
PURPOSE: There is extensive cross-talk between VEGF- and EGFRpathway signaling in colorectal cancer (CRC). However, combinations of VEGF- and EGFR-targeted monoclonal antibodies (mAbs) show disappointing activity, in particular for patients with mutant RAS. Previous results show that tyrosine kinase inhibitors (TKIs) can be active in CRC models resistant to mAbs. This promoted us to examine whether the activity of bevacizumab can be increased by combination with erlotinib. EXPERIMENTAL DESIGN: The antitumor activity of bevacizumab, erlotinib and their combination was determined in CRC models with different RAS status and bevacizumab sensitivity...
February 28, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nicolas Aznar, Jason Ear, Ying Dunkel, Nina Sun, Kendall Satterfield, Fang He, Nicholas A Kalogriopoulos, Inmaculada Lopez-Sanchez, Majid Ghassemian, Debashis Sahoo, Irina Kufareva, Pradipta Ghosh
Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor tyrosine kinases (RTKs), and heterotrimeric G proteins and associated GPCRs. Daple is a guanine nucleotide exchange factor (GEF) for the G protein Gαi Daple also binds to FZD and the Wnt/FZD mediator Dishevelled (Dvl), and it enhances β-catenin-independent Wnt signaling in response to Wnt5a-FZD7 signaling...
February 27, 2018: Science Signaling
Teppei Kono, Hajime Yokomizo, Yuki Yano, Sachiyo Okayama, Masaya Satake, Yasufumi Yamada, Arika Ida, Takebumi Usui, Kentaro Yamaguchi, Shunichi Shiozawa, Kazuhiko Yoshimatsu, Takeshi Shimakawa, Takao Katsube, Hiroyuki Kato, Yoshihiko Naritaka
The patient was 55-year-old woman, undergoing Hartmann operation by the sigmoid colon diverticulum perforation, 2 years later visited our hospital with abdominal pain. Although lower endoscopy and histological examination could not be performed due to stoma stenosis, we diagnosed cecal carcinoma, liver metastasis, distant lymph node metastasis from CT and PET-CT, CapeOX plus Bmabtherapy and IRIS plus Bmabtherapy were performed. After that, repeated intestinal obstruction due to exacerbated stoma stenosis, metastatic lesion increased in CT examination, furthermore the patient had hope of stoma closure, we decided to resect the primacy tumor, performed subtotal colonectomy and stoma closure...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Nicholas Forsythe, Alaa Refaat, Arman Javadi, Hajrah Khawaja, Jessica-Anne Weir, Heba Emam, Wendy L Allen, Frank Burkamp, Vlad Popovici, Puthen V Jithesh, Claudio Isella, Melissa J LaBonte, Ian G Mills, Patrick G Johnston, Sandra Van Schaeybroeck
BRAFV600E mutations occur in 10% of colorectal cancer (CRC) cases, are associated with poor survival and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition. There is an unmet need to understand the biology of poor prognostic BRAFMT CRC. We have used differential gene expression and pathway analyses of untreated stage II and stage III BRAFMT (discovery set: n=31; validation set: n=26) CRC and an siRNA screen to characterize the biology underpinning the BRAFMT subgroup with poorest outcome...
February 26, 2018: Molecular Cancer Therapeutics
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