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Caroline Brammer, Sundus Yahya, Dawn Dawson, Carol Glaister, Susan B Merrick
OBJECTIVES: The aim of this feasibility study is to define the resource effectiveness of Cetuximab versus cisplatin given concomitantly with radiotherapy for squamous cell carcinoma within a NHS clinical oncology unit. METHODS: 20 Patients with stage 3 or 4 head and neck squamous cell cancers were randomised to receive either Cetuximab with radiotherapy (ERT) or cisplatin with radiotherapy (CRT) concurrent with external beam radiotherapy 70 Gy in 35 fractions on a 1:1 basis over a 12-month duration...
October 13, 2016: British Journal of Radiology
S Marcatili, A Pichard, A Courteau, R Ladjohounlou, I Navarro-Teulon, A Repetto-Llamazares, H Heyerdahl, J Dahle, J P Pouget, M Bardiès
Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose...
October 7, 2016: Physics in Medicine and Biology
Shi Hu, Haibin Dai, Tian Li, Ying Tang, Wenyan Fu, Qingning Yuan, Feifei Wang, Gaojian Lv, Yuanyuan Lv, Xiaoyan Fan, Sheng Zhang, Ruobing Jin, Yafeng Shen, Fangxing Lin, Xuting Ye, Min Ding, Yongji Yang, Changhai Lei
The human epidermal growth factor receptor (EGFR) targeting chimeric monoclonal antibody, cetuximab (Erbitux®), is a widely used drug in the treatment of metastatic colorectal cancer. However, the activation of the extensive crosstalk among the EGFR family receptors as well as other tyrosine kinase receptors (RTKs) impairs the efficacy of the drug by fueling acquired resistance. To identify the responsible potential activation pathway underlying cetuximab resistance and generate novel treatment strategies, cetuximab-resistant colorectal cancer cell lines were generated and validated and a functional RNAi screen targeting human RTKs was used to identify extensive receptor tyrosine kinase signaling networks established in resistant cancer cells...
November 1, 2016: Cancer Letters
Alexander Ewe, Sabrina Höbel, Claudia Heine, Lea Merz, Sonja Kallendrusch, Ingo Bechmann, Felicitas Merz, Heike Franke, Achim Aigner
The non-viral delivery of small RNA molecules like siRNAs still poses a major bottleneck for their successful application in vivo. This is particularly true with regard to crossing physiological barriers upon systemic administration. We have previously established polyethylenimine (PEI)-based complexes for therapeutic RNA formulation. These nanoplexes mediate full RNA protection against nucleolytic degradation, delivery to target tissues as well as cellular uptake, intracellular release and therapeutic efficacy in preclinical in vivo models...
June 22, 2016: Drug Delivery and Translational Research
Yordan Benhamou, Vincent Picco, Hélène Raybaud, Anne Sudaka, Emmanuel Chamorey, Sanja Brolih, Martino Monteverde, Marco Merlano, Cristiana Lo Nigro, Damien Ambrosetti, Gilles Pagès
Oral Squamous Cell Carcinoma (OSCC) is the most common oral cancer worldwide. Treatments including surgery, radio- and chemo-therapies mostly result in debilitating side effects. Thus, a more accurate evaluation of patients at risk of recurrence after radio/chemo treatment is important for preserving their quality of life. We assessed whether the Telomeric Repeat-binding Factor 2 (TERF2) influences tumor aggressiveness and treatment response. TERF2 is over-expressed in many cancers but its correlation to patient outcome remains controversial in OSCC...
June 14, 2016: Oncotarget
S Cox, C Powell, B Carter, C Hurt, Somnath Mukherjee, Thomas David Lewis Crosby
BACKGROUND: Malnutrition is common in oesophageal cancer. We aimed to identify nutritional prognostic factors and survival outcomes associated with nutritional intervention in the SCOPE1 (Study of Chemoradiotherapy in OesoPhageal Cancer with or without Erbitux) trial. METHODS: Two hundred and fifty eight patients were randomly allocated to definitive chemoradiotherapy (dCRT) +/- cetuximab. Nutritional Risk Index (NRI) scores were calculated; NRI<100 identified patients at risk of malnutrition...
July 12, 2016: British Journal of Cancer
S Laban, J Kimmeyer, R Knecht, T K Hoffmann, C-J Busch, J A Veit, N Möckelmann, T Kurzweg
BACKGROUND: The EXTREME (Erbitux in First-Line Treatment of Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma) protocol is generally considered the gold standard in palliative first-line treatment. However, there is some disagreement about its effectivity, toxicity, and applicability in daily clinical routine. The purpose of this cross-sectional survey was to describe the palliative treatment offered in German-speaking countries. METHODS: From November 2013 to July 2014, 204 departments of otorhinolaryngology (ORL) in Germany, Austria, and the German-speaking parts of Switzerland were contacted and invited to take part in a web-based survey on the treatment of HNSCC...
July 2016: HNO
Inmaculada Suárez, Antonio Salmerón-García, José Cabeza, Luis Fermín Capitán-Vallvey, Natalia Navas
Bevacizumab (BVZ), cetuximab (CTX) and trastuzumab (TTZ) are monoclonal antibodies (mAbs) used worldwide for the treatment of several widespread kinds of cancer. They are marketed as medicines under their respective tradenames: Avastin(®), Erbitux(®) and Herceptin(®). The aim of this research was to develop in-house specific enzyme-linked immunosorbent assays (ELISA) to assess the long-term stability of these three mabs. These assays assess the biological functionality of the mAbs by quantifying their biological activity...
October 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Rolf F Barth, Gong Wu, W Hans Meisen, Robin J Nakkula, Weilian Yang, Tianyao Huo, David A Kellough, Pravin Kaumaya, Claudia Turro, Lawrence M Agius, Balveen Kaur
The aim of this study was to evaluate four different platinated bioconjugates containing a cisplatin (cis-diamminedichloroplatinum [cis-DDP]) fragment and epidermal growth factor receptor (EGFR)-targeting moieties as potential therapeutic agents for the treatment of brain tumors using a human EGFR-expressing transfectant of the F98 rat glioma (F98EGFR) to assess their efficacy. The first two bioconjugates employed the monoclonal antibody cetuximab (C225 or Erbitux(®)) as the targeting moiety, and the second two used genetically engineered EGF peptides...
2016: OncoTargets and Therapy
Sijia Wang, Gereon Hüttmann, Thomas Scholzen, Zhenxi Zhang, Alfred Vogel, Tayyaba Hasan, Ramtin Rahmanzadeh
Using nanotechnology for optical manipulation of molecular processes in cells with high spatial and temporal precision promises new therapeutic options. Especially tumor therapy may profit as it requires a combination of both selectivity and an effective cell killing mechanism. Here we show a dual targeting approach for selective and efficient light-controlled killing of cells which are positive for epidermal growth factor receptor (EGFR) and Ki-67. Liposomes with the covalently linked EGFR antibody Erbitux enabled selective uptake of FITC-labeled Ki-67 antibody TuBB-9 in EGFR-positive cells pre-loaded with the photoactive dye BPD...
2016: Scientific Reports
Seza A Gulec
At present, the systemic treatment of unresectable colorectal cancer liver metastases involves oxaliplatin and irinotecan-based chemotherapy regimens combined with targeted therapies such as bevacizumab (Avastin) and cetuximab (Erbitux). Radiation therapy, traditionally, is not considered a viable treatment modality owing to its unacceptably high hepatic toxicity, and still steering traditional wisdom or dogma that chemoradiation cannot be an oncological strategy for a stage IV disease. Selective internal radiation treatment with yttrium-90 (Y-90) radiomicrospheres has emerged as an effective liver-directed therapy with a favorable therapeutic ratio...
March 2016: Seminars in Nuclear Medicine
Khurum Khan, David Cunningham, Clare Peckitt, Sarah Barton, Diana Tait, Maria Hawkins, David Watkins, Naureen Starling, Sheela Rao, Ruwaida Begum, Janet Thomas, Jacqui Oates, Vincenza Guzzardo, Matteo Fassan, Chiara Braconi, Ian Chau
BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with high mortality, and biomarker-driven treatment approach is currently lacking. This study evaluated safety and efficacy of a combination approach of chemotherapy followed by chemo-radiotherapy (CRT) +/- cetuximab, and the prognostic role of miR-21 in patients with LAPC treated with a multimodality approach. PATIENTS AND METHODS: This was a randomised phase II trial in which patients with inoperable LAPC were offered gemcitabine and capecitabine (GEM-CAP) for 16 weeks...
March 15, 2016: Oncotarget
Hitoshi Soda, Hiromichi Maeda, Junichi Hasegawa, Takao Takahashi, Shoichi Hazama, Mutsumi Fukunaga, Emiko Kono, Masahito Kotaka, Junichi Sakamoto, Naoki Nagata, Koji Oba, Hideyuki Mishima
BACKGROUND: The clinical benefit of cetuximab combined with oxaliplatin-based chemotherapy remains under debate. The aim of the present multicenter open-label Phase II study was to explore the efficacy and safety of biweekly administration of cetuximab and mFOLFOX-6 or XELOX as first-line chemotherapy in patients with metastatic colorectal cancer. METHODS: Sixty-two patients with previously untreated KRAS/BRAF wild-type metastatic colorectal cancer were recruited to the study between April 2010 and May 2011...
2015: BMC Cancer
Ye-Jin Kim, Jeomil Bae, Tae-Hwan Shin, Se Hun Kang, Moonkyoung Jeong, Yunho Han, Ji-Ho Park, Seok-Ki Kim, Yong-Sung Kim
Neuropilin-1 (NRP1) receptor, involved in vascular endothelial growth factor (VEGF)-mediated vascular permeability and tumor angiogenesis, is targeted by peptides that bind to its VEGF-binding site. However, these peptides also cross-react with the structurally related receptor, NRP2. Here, we describe an immunoglobulin Fc-fused peptide, Fc-TPP11, which specifically binds to the VEGF-binding site of NRP1 with approximately 2nM affinity, but negligibly to that of NRP2. Fc-TPP11 triggered NRP1-dependent signaling, enhanced vascular permeability via vascular endothelial (VE)-cadherin downregulation, and increased paracellular permeability via E-cadherin downregulation in tumor tissues...
October 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Roger Gilabert-Oriol, Alexander Weng, Alexandra Trautner, Christoph Weise, Daniel Schmid, Cheenu Bhargava, Nicole Niesler, Peter J Wookey, Hendrik Fuchs, Mayank Thakur
The therapeutic relevance of immunotoxins is based on the conjugation of monoclonal antibodies to toxins. In cancer therapies, the conjugated antibodies not only direct the binding of immunotoxins to cancer-specific receptors and mediate the elimination of tumor cells through the innate immune system, but also increase target cytotoxicity by the intrinsic toxin activity. In the present study, the therapeutic antibodies Cetuximab (anti-EGFR, Erbitux(®)), Panitumumab (anti-EGFR, Vectibix(®)) and Trastuzumab (anti-HER2, Herceptin(®)) were chemically conjugated to the toxin dianthin...
October 1, 2015: Biochemical Pharmacology
Soudabeh Sabetian, Mohd Shahir Shamsir
BACKGROUND: Sperm-egg interaction defect is a significant cause of in-vitro fertilization failure for infertile cases. Numerous molecular interactions in the form of protein-protein interactions mediate the sperm-egg membrane interaction process. Recent studies have demonstrated that in addition to experimental techniques, computational methods, namely protein interaction network approach, can address protein-protein interactions between human sperm and egg. Up to now, no drugs have been detected to treat sperm-egg interaction disorder, and the initial step in drug discovery research is finding out essential proteins or drug targets for a biological process...
2015: BMC Systems Biology
Andreas Jung
With the advent of targeted therapies-drugs that specifically target molecules of tumor-driving signalling pathways-and the availability of biomarkers that predict the response of an individual patient on such a targeted therapy, the analysis of the status of the biomarker became an integral part of the therapy. For metastatic colorectal cancer, anti-EGFR-targeted antibodies (Cetuximab/Erbitux(®), Panitumumab/Vectibix(®)) fall into this category of drugs as it was shown in several clinical studies that oncogenic mutations in exons 2-4 of the RAS genes KRAS or NRAS result in therapeutic resistance of the metastatic colorectal cancers against the action of both targeted drugs...
2015: Methods in Molecular Biology
Karen M Xu, Kimmen Quan, David A Clump, Robert L Ferris, Dwight E Heron
PURPOSE: Stereotactic ablative radiotherapy (SABR) is an attractive modality to treat malignancies invading the skull base as it can deliver a highly conformal dose with minimal toxicity. However, variation exists in the prescribed dose and fractionation. The purpose of our study is to examine the local control, survival, and toxicities in SABR for the treatment of previously irradiated malignant skull base tumors. MATERIALS AND METHODS: A total of 31 patients and 40 locally advanced or recurrent head and neck malignancies involving the skull base treated with a common SABR regimen, which delivers a radiation dose of 44 Gy in 5 fractions from January 1st, 2004 to December 31st, 2013, were retrospectively reviewed...
2015: Frontiers in Oncology
P Senter
Monoclonal antibodies (mAbs) have played a major role in cancer medicine, with active drugs such as trastuzumab (Herceptin), cetuximab (Erbitux), bevacizumab (Avastin) and rituximab (Rituxan) in a wide range of therapeutic applications. The mechanisms of these agents involve such activities as direct signaling, interactions with Fc□ receptors on effector cells, and complement fixation. Several approaches have been explored to improve antibody-based therapies for cancer treatment by optimizing such activities and by conscripting their selectivity profiles for the delivery of high potency cytotoxic drugs...
March 2015: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Yasunori Hasuike, Ichiro Higuchi, Yosuke Akiyama, Makoto Yamamoto, Takahiko Tanigawa, Atsuya Okada
A 58-year-old woman was suffering from abdominal pain due to large liver metastases(LM)and lung metastasis from sigmoid colon cancer. After laparoscopic sigmoidectomy, three 6 g/wk high dose hepatic arterial infusions(HDHAI)of5 - fluorouracil (5-FU) were administered and the tumor decreased in size. Unfortunately, the patient had an infectious pseudoaneurysm at the site of puncture. She was given a drainage and femoro-femoral(F-F)bypass. At last, a hepatectomy, radiofrequency ablation(RFA), and catheter insertion from gastroepiploic artery, were performed successfully...
November 2014: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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