吉西他滨联合西妥昔单抗对三阴乳腺癌细胞转移相关基质金属蛋白酶-9(MMP-9)活性的影响

目的：探讨吉西他滨联合西妥昔单抗对三阴乳腺癌细胞增殖、迁移、侵袭的影响，并对可能的机制进行初步的探究。方法：将实验分为西妥昔单抗组（150 μg · mL^-1）、吉西他滨联合用药组（西妥昔单抗150 μg · mL^-1，吉西他滨2.8 μg·mL^-1）。通过MTT、Transwell实验检测联合用药对MDA-MB-231细胞增殖、迁移、侵袭能力的影响，Western blotting实验检测合用药对MDA-MB-231细胞MMP-9、TIMP-1、p-IkB、NF-kB-p65表达水平的影响。结果：吉西他滨联合西妥昔单抗作用MDA-MB-231细胞后，其生长被不同程度的抑制，抑制率随吉西他滨浓度的增加而增高（P<0.05）；联合用药组MDA-MB-231细胞迁移、侵袭数目明显减少（P<0.05），同时MMP-9、p-IkB、NF-kB-p65的表达含量降低，TIMP-1表达含量增加。结论：吉西他滨联合西妥昔单抗对三阴乳腺癌细胞增殖、侵袭、迁移具有抑制作用，并明显抑制MMP-9的表达，其机制可能是通过抑制NF-kB通路实现。     

Biological interaction between anti-epidermal growth factor receptor agent cetuximab and magnesium

Background: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab, by the inhibition of epidermal growth factor (EGR), is able to induce hypomagnesaemia by interfering with magnesium transport in the kidney. Objective: To investigate the interactions between magnesium homeostasis and EGF receptor (EGFR) inhibition. Methods: We performed an updated literature search using the MEDLINE database for articles published from 1 January 1966 to 15 February 2008. We comprehensively reviewed all the data published in abstract form during the most significant international meetings (American Society of Clinical Oncology, American Association for Cancer Research, European Society for Medical Oncology and European Cancer Organisation). Results/conclusion: We propose that EGFR inhibition may reduce cancer proliferation and also decrease magnesium levels. These reduced magnesium levels in turn contribute to the inhibition of angiogenesis by directly acting on endothelial cells and indirectly affecting EGFR signalling and the production of angiogenic molecules.     

Targeting epidermal growth factor receptor signaling in the treatment of head and neck cancer

In this review, key aspects of epidermal growth factor receptor (EGFR) biology and the fruitful translation of these fundamental findings into recent treatment advances in head and neck squamous cell cancer (HNSCC) are highlighted. In contrast to a number of contemporary reviews of the EGFR, many of which focus on colorectal and nonsmall cell lung cancer, this review discusses the EGFR as a validated therapeutic target in HNSCC. Recent data confirm a survival advantage for the addition of the anti-EGFR monoclonal antibody cetuximab to definitive radiation therapy in locoregionally advanced HNSCC patients, as well as palliative benefits for patients with incurable recurrent and metastatic HNSCC. Small-molecule EGFR tyrosine kinase inhibitors also show considerable promise in this disease, both alone and in combination with radiation and chemotherapy. Both classes of anti-EGFR agent are generally well tolerated, with side effects (notably skin rash) that are distinct from the toxicities of conventional chemotherapy. Ongoing clinical trials will more clearly define the role for EGFR inhibitors in all treatment phases of HNSCC.     

The developing trend of monoclonal antibodies in the treatment of colorectal cancer

Monoclonal antibodies (mAbs) against growth factors, receptors and tumor-specific/tumor-selective antigens represent a rapidly growing class of pharmaceutical agents which are poised to make a major impact on the treatment of colorectal cancer. mAbs targeting the epidermal growth factor receptor and the vascular endothelial growth factor have already been approved for the treatment of metastatic colorectal cancer. Other antibodies to the same and other molecular targets implicated in tumor growth and metastasis are undergoing intense preclinical and clinical evaluation. In both the neoadjuvant and adjuvant clinical settings, although mAbs are typically administered in combination with established cytotoxic chemotherapy regimens given their synergistic effect, several agents have demonstrated efficacy when given as monotherapy. At the same time, combination therapies with multiple targeted biological agents are actively being investigated. Existing clinical data and recent progress in preclinical and clinical studies of mAbs are reviewed.     

Recent developments in colorectal cancer treatment by monoclonal antibodies

A growing understanding of the molecular mechanisms involved in cancer biology and continuous refinement of available technologies for drug discovery have prompted the development of new therapeutic tools targeting specific cancer-associated molecular pathways. Among these so-called biological therapies, monoclonal antibodies have now reached the time of clinical application. Besides initial development of the murine antibody edrecolomab, the impact of monoclonal antibodies on cancer therapy has recently been clearly demonstrated in colorectal cancer by targeting two major pathways critical to tumourigenesis: the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) signalling pathways. These antibodies showed significant clinical activity in advanced colorectal cancer, especially when combined with chemotherapy. This paper reviews the status of the monoclonal chimeric antibody cetuximab (Erbitux^®) and other anti-EGFR antibodies, and of bevacizumab (Avastin^®; an anti-VEGF humanised monoclonal antibody), in colorectal cancer treatment.     

西妥昔单抗联合IMRT同步化疗治疗晚期鼻咽癌的疗效观察

目的 观察西妥昔单抗联合调强适形放疗(IMRT)同步顺铂化疗治疗晚期鼻咽癌的临床疗效及不良反应.方法 选取2010年1月～2013年1月我科收治的64例晚期鼻咽癌患者随机分为实验组和对照组,每组32例.实试组给予西妥昔单抗联合适形放疗同步顺铂化疗,对照组给予适形放疗同步顺铂化疗,观察比较两组的临床疗效及不良反应.结果 治疗后近期疗效,室验组和对照组的总有效率分别为90.6％和68.8％,疾病控制率分别为100.0％和81.3％;远期疗效,实验组和对照组的总有效率分别为78.1％和53.1％,疾病控制率分别为96.9％和75.0％.实验组的近、远期疗效均优于对照组(P＜0.05),两组不良反应发生情况未见明显差异(P＞0.05).结论 西妥昔单抗联合适形放疗同步顺铂化疗治疗晚期鼻咽癌具有较好的临床疗效和安全性,值得临床推广.     

Human epidermal growth factor receptor 3 in head and neck squamous cell carcinomas

Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptor (HER) family. The main characteristic of HER3 is that it does not possess tyrosine kinase activity, unlike other HERs. The role of HER3 in tumorigenesis has now been recognized, particularly in head and neck squamous cell carcinomas (HNSCCs). Despite conflicting studies, HER3 was found to be overexpressed in HNSCC samples, and correlates with disease progression and poor survival, especially when it is coexpressed with other HERs. HER3 is a significant factor in HNSCC treatment resistance. Indeed, HER3 is a major mechanism described for cetuximab resistance because of modification of epidermal growth factor receptor (EGFR) internalization and by phosphotidylinositol‐3‐kinase (PI3K)/AKT signaling pathway activation. HER3 also affects resistance to tyrosine kinase inhibitors (TKIs) and thereby promotes treatment escape and radiotherapy resistance by activation of the survival signaling pathway. To counteract this, pharmacologic inhibitors of HER3 are currently in development and could significantly improve HNSCC treatment. © 2016 Wiley Periodicals, Inc. Head Neck 38 : E2412–E2418, 2016