Receptor-interacting protein kinase-3 (RIP3 or RIPK3) is an essential part of the cellular machinery that executes "programmed" or "regulated" necrosis. Here we show that programmed necrosis is activated in response to many chemotherapeutic agents and contributes to chemotherapy-induced cell death. However, we show that RIP3 expression is often silenced in cancer cells due to genomic methylation near its transcriptional start site, thus RIP3-dependent activation of MLKL and downstream programmed necrosis during chemotherapeutic death is largely repressed. Nevertheless, treatment with hypomethylating agents restores RIP3 expression, and thereby promotes sensitivity to chemotherapeutics in a RIP3-dependent manner. RIP3 expression is reduced in tumors compared to normal tissue in 85% of breast cancer patients, suggesting that RIP3 deficiency is positively selected during tumor growth/development. Since hypomethylating agents are reasonably well-tolerated in patients, we propose that RIP3-deficient cancer patients may benefit from receiving hypomethylating agents to induce RIP3 expression prior to treatment with conventional chemotherapeutics.
Serum TgAb levels measured at 6-12 months after remnant ablation could predict recurrence in patients with undetectable Tg values. In patients with undetectable Tg and positive TgAb values, a change in TgAb concentration during the early postoperative period may be a prognostic indicator of recurrence.
Surgery for thyroid disease requires skin incisions that can result in postsurgical problems such as prominent scars, adhesions, hypesthesia, and paresthesia in the neck. To overcome these problems we performed gasless endoscopic thyroidectomy via an axillary approach. Between May 2004 and April 2005, 30 patients underwent gasless endoscopic thyroidectomy via an axillary approach. The mean operating time was 126.8+/-32.4 minutes, and the mean length of hospital stay was 4.3+/-1.1 days. No cases required conversion to open surgery and none involved significant intraoperative complications. Three patients (10.0%) complained of slight hypesthesia or paresthesia in the anterior chest wall, and only 2 patients (6.7%) complained of discomfort while swallowing 4 months after surgery. All patients were satisfied with the cosmetic results. Gasless endoscopic thyroidectomy via an axillary approach is feasible and safe and provides excellent cosmetic results with a minimal degree of postoperative complaints.
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