Lack of EGFR mutations benefiting gefitinib treatment in adenocarcinoma of esophagogastric junction

<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) inhibitor, gefitinib, has been reported to successfully treat advanced non-small cell lung cancer patients with genetic mutations in EGFR. The aim of this study was to investigate the existence of EGFR mutations in carcinoma of esophagogastric junction, and also to explore the possibility of treating carcinoma of esophagogastric junction using gefitinib.</p> <p>Methods</p> <p>From Aug. 2009 to Jun. 2010, 65 patients with carcinoma of esophagogastric junction underwent surgical resection. The tumor tissue and corresponding blood specimens were collected from all cases. The DNA was extracted and PCR amplification was accomplished based on designed primers for exons 18, 19, 20, and 21. EGFR exons 18, 19, 20 and 21 of both cancer cell and white blood cell were finally successfully sequenced.</p> <p>Results</p> <p>In exon 20, a variant from CAG to CAA at codon 787 (2361G-> A) was identified in 19 patients, which was a genomic variation of EGFR since it was found in both cancer tissue and white blood cells. This EGFR alteration was a synonymous single nucleotide polymorphism (SNP) since CAA and CAG were encoding the same amino-acid of Glutamine (Q787Q, NCBI database 162093G > A, SNP ID: rs10251977). No genetic alteration was found in exons 18, 19 or 21.</p> <p>Conclusions</p> <p>Adenocarcinoma of esophagogastric junction rarely presents EGFR mutation, especially gefitinib-associated mutations such as L858R, or delE746-A750. This means that the gefitinib-based gene target therapy should not be recommended for treating carcinoma of esophagogastric junction.</p

Electroacupuncture could influence the expression of IL-1 β and NLRP3 inflammasome in hippocampus of Alzheimer's disease animal model

Background. Effective therapies for Alzheimer's disease (AD) are still being explored. Electroacupuncture with traditional Chinese medicine theory may improve spatial learning and memory abilities and glucose metabolism rates in an animal model of AD. However, the mechanism of electroacupuncture in intervention of AD is still unclear. According to recent studies of AD mechanisms, the NLRP3 inflammasome regulated the expression of IL-1β in the brain which may mediate AD related processes. Therefore, in our study, we intend to explore the possible relation between electroacupuncture and the expression of NLRP 3 inflammasome in the hippocampus of an AD animal model. Method. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an AD animal model, which were randomly divided into two groups: Alzheimer's disease model group (AD group) and electroacupuncture group (EA group). In the control paradigm, 7.5-month-old male SAMR1 mice were used as the normal control group (N group). DU20, DU26, and EX-HN3 were selected as the acupuncture points, and after a 15-day treatment of electroacupuncture, we used immunohistochemistry and Western blotting to examine the expression of IL-1β and NLRP3, ASC, and Caspase-1 in the hippocampus of the AD animal model. Results. Compared with N group, IL-1β, NLRP3, ASC, and Caspase-1 positive cells in AD group were increased, and the relative expression of all above proteins significantly increased (P < 0.01). Compared with AD group, the expression of IL-1β, NLRP3, ASC, and Caspase-1 in EA group was significantly decreased (P < 0.01). Conclusion. Electroacupuncture treatment could inhibit the inflammation reaction in the hippocampus of SAMP8 mice. What is more, the possible mechanism of electroacupuncture reduced the expression of IL-1β and NLRP3 inflammasome relative protein

Modulatory Function of Invariant Natural Killer T Cells in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with complex immunological and clinical manifestations. Multiple organ failure in SLE can be caused by immune dysfunction and deposition of autoantibodies. Studies of SLE-susceptible loci and the cellular and humoral immune responses reveal variable aberrations associated with this systemic disease. Invariant natural killer T (iNKT) cells are a unique subset of lymphocytes that control peripheral tolerance. Mounting evidence showing reductions in the proportion and activity of iNKT cells in SLE patients suggests the suppressive role of iNKT cells. Studies using murine lupus models demonstrate that iNKT cells participate in SLE progression by sensing apoptotic cells, regulating immunoglobulin production, and altering the cytokine profile upon activation. However, the dichotomy of iNKT cell actions in murine models implies complicated interactions within the body's milieu. Therefore, application of potential therapy for SLE using glycolipids to regulate iNKT cells should be undertaken cautiously