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

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.

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

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.

2004-03-01·International Journal of Radiation Oncology*Biology*Physics2区 · 医学

Targeting the EGFR in neoplasia—more questions than answers

2区 · 医学

Article

作者: Ulrich Rodeck ; Adam P Dicker

Forty years ago, the study of retroviral transformation revolutionized our understanding of malignant transformation. The discovery of virally transmitted oncogenes was closely followed by the realization that they were homologues of mammalian genes, thus leading to the term proto-oncogenes. The epidermal growth factor receptor (EGFR; HER1; erbB1) is a prominent example for this sequence of events. First cloned in 1984, it was immediately recognized to be the counterpart of a viral oncogene, v-erbB (1). In keeping with its oncogenic potential, the EGFR is molecularly altered and deregulated in many “spontaneous” tumors with no apparent viral etiology. The EGFR is one of many receptor tyrosine kinases with transforming potential. Yet, it is believed to contribute to the malignant phenotype of a broad spectrum of neoplasms affecting primarily epithelial tissues. Almost 20 years after its discovery, the EGFR has emerged as a prominent target for therapeutic intervention. This supplement to the International Journal of Radiation Oncology, Biology, Physics contains proceedings of the Radiation Therapy Oncology Group symposium “Epidermal Growth Factor Receptor Inhibitors and Cancer Therapeutics” held in Philadelphia in June 2002. It focuses on the preclinical development and clinical evaluation of EGFR antagonists. Meeting participants presented the epidemiologic rationale for targeting the EGFR, highlighted the complexity of signaling events downstream of EGFR activation and relevant to malignant transformation, and delineated strong preclinical evidence that the EGFR is a worthy therapeutic target. Most importantly, the meeting provided a forum to discuss functional roles of the EGFR as they relate to tumor development in vivo and emerging problems in the application of EGFR antagonists to clinical practice. EGFR expression and activation The EGFR is a widely expressed transmembrane protein composed of an extracellular ligand-binding domain, a hydrophobic transmembrane region, and a cytoplasmic domain with intrinsic tyrosine kinase activity, tyrosine residues, and regulatory motifs (2, 3). Activation of EGFR is elicited by the binding of at least 6 ligands, including epidermal growth factor (EGF), transforming growth factor(TGF), and amphiregulin, to its extracellular domain. Ligand binding triggers EGFR dimerization, activation, and autophosphorylation of several tyrosine residues in the carboxy-terminal region of the intracellular domain (4). Subsequently, intracellular substrates with Src-homology 2 and phosphotyrosine-binding domains bind to the phosphorylated tyrosine residues, leading to activation of multiple intracellular signaling pathways, and in turn, to cell proliferation, survival, differentiation, migration, and other cellular responses (Fig. 1) (2–4). In this supplement, Drs. Marmor and Yarden discuss signal transduction and oncogenesis by ErbB receptors. They outline an extraordinary complex system of signaling events triggered by EGFR activation, as well as the contribution of signaling networks at the cell surface capable of amplifying EGFR-dependent signals. The EGFR is expressed or overexpressed in a large number of malignancies, including non–small-cell lung (NSCLC), head-and-neck, esophageal, gastric, colorectal, breast, prostate, bladder, renal, pancreatic, and ovarian cancer (5, 6). EGFR expression is often found in association with increased expression of its ligands, EGF, TGF, or amphiregulin (2). Despite conflicting reports, EGFR expression is generally considered predictive of a poor prognosis, particularly in head-and-neck, ovarian, cervical, bladder, and esophageal cancer (7). Several articles presented here validate the functional relevance of EGFR expression in clinical oncology. Dr. Ang discusses an immunohistochemistry approach used to determine the prognostic significance

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

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