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Abstract Background Gastric cancer presents a major health burden worldwide. Therefore, many molecular targeting agents have been evaluated for treatment of gastric cancer. Gefitinib has shown anticancer activity against gastric cancer which work through inhibiting epidermal growth factor receptor (EGFR). However, the effect of gefitinib is limited due to its resistance. Therefore, understanding the mechanisms of gefitinib resistance is desperately needed to formulate novel strategies against gastric cancer. Here, we analyzed resistance mechanism from the crosstalk between EGFR and integrin β4. Methods Integrin β4-expression vector or siRNA were used to analyze the functional effects of integrin β4 on chemoresistance of gastric cancer cells to gefitinib. EGFR and integrin β4 expression, proliferation and apoptosis of gastric cancer cells were assayed by indirect immunofluorescence, western blot, MTT and flow cytometry respectively. EGFR and integrin β4 expression were also assayed on patient samples. Results It was found that the integrin β4 expression was increased in gefitinib-resistant gastric cell line. The upregulated integrin β4 expression was identified to promote gefitinib resistance and proliferation, and inhibit apoptosis, while downregulation of integrin β4 was to inhibit gefitinib resistance and proliferation, and induce apoptosis. Moreover, the overexpression of integrin β4 in SGC7901 cells resulted in the down-regulation of p-EGFR protein levels while down-regulation of integrin β4, significantly resulted in overexpression of p-EGFR. The results of western blot from patients also showed there was obvious negative correlation between p-EGFR and integrin β4 in gastric cancer patients. Conclusion Considering the above results, it is concluded that the interaction of EGFR and integrin β4 may change the sensitivity of gefitinib treatment.

Objective: To explore the mechanism of the aging deformity of tear trough through the anatomic study of the tear trough region., Methods: 13 adult cadaveric heads (26 sides), including 9 male heads (18 sides) and 4 female heads (8 sides), aged 22-78 years old, were used. Anatomic study was performed around the orbital, especially tear trough region, with microsurgery instrument under microscope( x 10 times). The lower orbicularis retaining ligament was dissected and exposed. The anatomic location was recorded and photographed., Results: (1) The anatomic layers of the tear trough region contains skin, subcutaneous tissue, orbicularis oculi muscle, periosteal membrane. There is no subcutaneous fat above the tear trough, while it exists below the tear trough, called malar fat pad. (2) There is a natural boundary between the septal and the orbital portions of the orbicularis oculi muscle of lower eyelid at surface of the orbital bone. The natural boundary, projected on the body surface corresponds to tear trough. The width of boundary is (2.06 +/- 0.15) mm on the vertical line through inner canthus and (3.25 +/- 0.12) mm on the vertical line through the lateral margin of the ala. The septal portion and the orbital portion of the orbicularis oculi muscle began to merge in (16.56 +/- 0.51) mm to inner canthus. (3) There is ligament attachment in the medial, upper and lower orbital and no ligament attachment in the lateral orbital. Orbicularis retaining ligament of lower eyelid is divided into two layers. (4) The medial of the upper layer of the orbicularis retaining ligament in lower eyelid originates from orbital margin and from preorbital walls laterally in (16.10 +/- 0.43) mm to the medial of lateral orbital margin, through orbicularis oculi muscle and ends at the skin. The lower layer of the orbicularis retaining ligament of lower eyelid originates from preorbital walls through orbicularis oculi muscle and its superficial fat, then ends at the skin., Conclusions: The length of tear trough is (16.56 +/- 0.51) mm, the width of tear trough is (2.06 +/- 0.15) mm and (3.25 +/- 0.12) mm on the vertical line through inner canthus and the lateral margin of the ala nasi respectively. The main reason of the aging deformity of tear trough attributes to the increased distance between the upper and lower layers of the orbicularis retaining ligament in lower eyelid, which is caused by loose of the orbicularis retaining ligament and its underlying fat atrophy or decline.