Adhesion G-protein-coupled receptors (GPCR), which contain adhesion domains in their extracellular region, have been found to play important roles in cell adhesion, motility, embryonic development, and immune response. Because most adhesion molecules with adhesion domains have vital roles in cancer metastasis, we speculated that adhesion GPCRs are potentially involved in cancer metastasis. In this study, we identified GPR116 as a novel regulator of breast cancer metastasis through expression and functional screening of the adhesion GPCR family. We found that knockdown of GPR116 in highly metastatic (MDA-MB-231) breast cancer cells suppressed cell migration and invasion. Conversely, ectopic GPR116 expression in poorly metastatic (MCF-7 and Hs578T) cells promoted cell invasion. We further showed that knockdown of GPR116 inhibited breast cancer cell metastasis in two mammary tumor metastasis mouse models. Moreover, GPR116 modulated the formation of lamellipodia and actin stress fibers in cells in a RhoA-and Rac1-dependent manner. At a molecular level, GPR116 regulated cell motility and morphology through the Gaq-p63RhoGEF-RhoA/Rac1 pathway. The biologic significance of GPR116 in breast cancer is substantiated in human patient samples, where GPR116 expression is significantly correlated with breast tumor progression, recurrence, and poor prognosis. These findings show that GPR116 is crucial for the metastasis of breast cancer and support GPR116 as a potential prognostic marker and drug target against metastatic human breast cancer. Cancer Res; 73(20); 6206-18. Ó2013 AACR.
A total of 100 osteoarthritis patients undergoing unilateral total knee arthroplasty were randomly assigned to receive either a multimodal analgesia protocol, comprising oral celecoxib and tramadol before and after surgery and intra-articular injection of large doses of morphine, ropivacaine, adrenaline and betamethasone during surgery (trial group), or oral and intra-articular placebo (control group). All patients received patient-controlled analgesia for 48 h after surgery. Morphine consumption up to 48 h after surgery was significantly lower in the trial than in the control group. Compared with the control group, the trial group had significantly lower visual analogue scale (VAS) scores for pain at rest from 6 h to 7 days after surgery and significantly lower VAS scores during activity from 24 h to 7 days after surgery. Active straight leg raise and active 90 degrees knee flexion were achieved sooner and range of knee movement at postoperative days 1 - 15 were significantly greater in the trial group. Postoperative wound healing, infection, blood pressure, heart rate, rash, respiratory depression, urinary retention and deep vein thrombosis were similar in the two groups, but nausea and vomiting were significantly less frequent in the trial group.
We believe that the need for single stage 360° fusion of hangman's fractures can be somewhat predicted by a combination of high resolution imaging. For hangman's fractures with significant deformity and gapping, it is our experience that immediate single-stage anterior-posterior reduction, instrumentation, and arthrodesis achieve superior postoperative reduction and long-term functional outcomes.
GCT of the cervical spine easily onsets between 20 and 40 years of age. As a kind of benign but local aggressive or low potential malignancy tumor, we should take an aggressive attitude to excise the tumor as much as possible while reserving the neural function as a precondition. Unlike in the thoracic and lumbar spine, a strictly "en bloc" resection is often not a feasible option because of the involvement of critical neurovascular structures. Total spondylectomy (even intralesional) with radiation therapy as an adjunctive treatment has significantly lowered the local recurrence rate of the GCT in the special segments.
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