Randomized phase II Trial of combined chemoradiation with Epidermal Growth Factor Receptor (EGFR) antagonist Cetuximab versus combined chemoradiation with EGFR antagonist Cetuximab and sequential Cetuximab for patients with locally advanced pancreatic adenocarcinoma

开始日期2005-01-01

申办/合作机构-

100 项与 EGFR antagonists(University of Parma) 相关的临床结果

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100 项与 EGFR antagonists(University of Parma) 相关的转化医学

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100 项与 EGFR antagonists(University of Parma) 相关的专利（医药）

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项与 EGFR antagonists(University of Parma) 相关的文献（医药）

2024-06-01·Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

[Mechanism of protective effect of n-butanol extract of Pulsatilla Decoction on vaginal epithelial cells under Candida albicans stimulation through EGFR/MAPK pathway based on transcriptomics].

Article

作者: Wu, Hui ; Liu, Ting-Ting ; Wang, Tian-Ming ; Wang, Chang-Zhong ; Wu, Da-Qiang ; Shao, Jing ; Zhang, Ting ; Zhang, Jia-Ping

This study aimed to investigate the protective effect and its underlying mechanism of n-butanol extract of Pulsatilla Decoction(BEPD) containing medicinal serum on vaginal epithelial cells under Candida glabrata stimulation via the epidermal growth factor receptor/mitogen activated protein kinase( EGFR/MAPK) pathway based on transcriptomics. A vulvovaginal candidiasis(VVC) mouse model was established first and transcriptome sequencing was performed for the vaginal mucosa tissues to analyze the gene expression differences among the control, VVC model, and BEPD intervention groups. Simultaneously, BEPD-containing serum and fluconazole-containing serum were prepared. A431 cells were divided into the control, model, blank serum, fluconazole-containing serum, BEPD-containing serum, EGFR agonist and EGFR inhibitor groups. Additionally, in vitro experiments were conducted using BEPD-containing serum, fluconazole-containing serum, and an EGFR agonist and inhibitor to investigate the intervention mechanisms of BEPD on C. glabrata-induced vaginal epithelial cell damage. Cell counting kit-8(CCK-8) assay was utilized to determine the safe concentrations of C. glabrata, drug-containing serum, and compounds on A431 cells. Enzyme-linked immunosorbent assay(ELISA)was employed to measure the expression levels of interleukin(IL)-1β, IL-6, granulocyte-macrophage colony-stimulating factor(GMCSF), granulocyte CSF(G-CSF), chemokine(C-X-C motif) ligand 20(CCL20), and lactate dehydrogenase(LDH). Gram staining was used to evaluate the adhesion of C. glabrata to vaginal epithelial cells. Flow cytometry was utilized to assess the effect of C.glabrata on A431 cell apoptosis. Based on the transcriptomics results, immunofluorescence was performed to measure the expressions of p-EGFR and p-ERK1/2 proteins, while Western blot validated the expressions of p-EGFR, p-ERK1/2, p-C-Fos, p-P38, Bax and Bcl-2 proteins. Sequencing results showed that compared with the VVC model, BEPD treatment up-regulated 1 075 genes and downregulated 927 genes, mainly enriched in immune-inflammatory pathways, including MAPK. Mechanistically, BEPD significantly reduced the expression of p-EGFR, p-ERK1/2, p-C-Fos and p-P38, as well as the secretion of IL-1β, IL-6, GM-CSF, G-CSF and CCL20, LDH release induced by C. glabrata, and the adhesion of C. glabrata to A431 cells, suggesting that BEPD exerts a protective effect on vaginal epithelial cells damaged by C. glabrata infection by modulating the EGFR/MAPK axis. In addition, BEPD downregulated the pro-apoptotic protein Bax expression and up-regulated the anti-apoptotic protein Bcl-2 expression, leading to a reduction in C. glabrata-induced cell apoptosis. In conclusion, this study reveals that the intervention of BEPD in C. glabrata-induced VVC may be attributed to its regulation of the EGFR/MAPK pathway, which protects vaginal epithelial cells.

2021-08-01·CANCER SCIENCE

Enhancement of epidermal growth factor receptor antibody tumor immunotherapy by glutaminyl cyclase inhibition to interfere with CD47/signal regulatory protein alpha interactions.

Article

作者: Marie Eichholz, Klara ; Valerius, Thomas ; Winterberg, Dorothee ; Müller, Kristina ; Klausz, Katja ; Peipp, Matthias ; Kellner, Christian ; Schewe, Denis M ; Leusen, Jeanette H W ; Burger, Renate ; Chan, Chilam ; Humpe, Andreas ; Jansen, J H Marco ; Rösner, Thies ; Baumann, Niklas

Integrin associated protein (CD47) is an important target in immunotherapy, as it is expressed as a "don't eat me" signal on many tumor cells. Interference with its counter molecule signal regulatory protein alpha (SIRPα), expressed on myeloid cells, can be achieved with blocking Abs, but also by inhibiting the enzyme glutaminyl cyclase (QC) with small molecules. Glutaminyl cyclase inhibition reduces N-terminal pyro-glutamate formation of CD47 at the SIRPα binding site. Here, we investigated the impact of QC inhibition on myeloid effector cell-mediated tumor cell killing by epidermal growth factor receptor (EGFR) Abs and the influence of Ab isotypes. SEN177 is a QC inhibitor and did not interfere with EGFR Ab-mediated direct growth inhibition, complement-dependent cytotoxicity, or Ab-dependent cell-mediated cytotoxicity (ADCC) by mononuclear cells. However, binding of a human soluble SIRPα-Fc fusion protein to SEN177 treated cancer cells was significantly reduced in a dose-dependent manner, suggesting that pyro-glutamate formation of CD47 was affected. Glutaminyl cyclase inhibition in tumor cells translated into enhanced Ab-dependent cellular phagocytosis by macrophages and enhanced ADCC by polymorphonuclear neutrophilic granulocytes. Polymorphonuclear neutrophilic granulocyte-mediated ADCC was significantly more effective with EGFR Abs of human IgG2 or IgA2 isotypes than with IgG1 Abs, proposing that the selection of Ab isotypes could critically affect the efficacy of Ab therapy in the presence of QC inhibition. Importantly, QC inhibition also enhanced the therapeutic efficacy of EGFR Abs in vivo. Together, these results suggest a novel approach to specifically enhance myeloid effector cell-mediated efficacy of EGFR Abs by orally applicable small molecule QC inhibitors.

2007-01-01·The International journal of biological markers4区 · 医学

The Rationale for the Combination of Selective EGFR Inhibitors with Cytotoxic Drugs and Radiotherapy

4区 · 医学

Review

作者: Tortora, G. ; Ciardiello, F. ; Gelardi, T. ; Bianco, R.

The epidermal growth factor receptor (EGFR) is frequently overexpressed in a wide range of human tumors; such overexpression often correlates with poor prognosis and worse clinical outcome. It has been demonstrated that the EGFR autocrine pathway plays a crucial role in human cancer since it contributes to a number of highly relevant processes in tumor development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis and metastatic spread. For these reasons EGFR is one of the most studied and exploited targets for molecular cancer therapy. Two classes of anti-EGFR agents have entered clinical practice: monoclonal antibodies and small molecules targeting receptor tyrosine kinases. The possibility of combining conventional cytotoxic drugs with agents that specifically interfere with key pathways controlling cancer cell survival, proliferation, invasion and/or metastatic spread has generated wide interest. This could be a promising therapeutic approach for several reasons. First, the occurrence of cross-resistance is infrequent since the cellular targets and mechanisms of action of cytotoxic drugs and EGFR antagonists are different. Second, alterations in the expression and/or activity of genes that regulate mitogenic signals may either cause perturbation of cell growth or affect the sensitivity of cancer cells to conventional chemotherapy and radiotherapy. In fact, EGFR inhibitors have shown activity alone and/or in combination with conventional antitumor treatments.

100 项与 EGFR antagonists(University of Parma) 相关的药物交易

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