Patients presenting with diffuse large B cell lymphoma (DLBCL) are treated with a standard anthracycline-based chemotherapeutic mixture consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Half of DLBCL patients will develop chemo-refractory tumors due to the emergence of CHOP-resistant DLBCL cells. We isolated DLBCL cells that were resistant to CHOP as a model system to investigate the molecular basis of CHOP resistance. Resistant cells emerged from CHOP-sensitive DLBCL populations after repeated cycles of on-off exposure to stepwise increased dosages of CHOP. A proteomic analysis of CHOP-sensitive and -resistant DLBCL cells identified the isoform of the 14-3-3 family as a differentially expressed protein. CHOP-sensitive cells showed reduced expression of 14-3-3 protein in the presence of high-dose CHOP relative to control cells. In contrast, CHOP-resistant cells expressed markedly higher levels of 14-3-3 regardless the presence of high-dose CHOP. Because 14-3-3 is known to exert anti-apoptotic influences and chemoresistance in lung, colon, and prostate carcinoma, we hypothesized that 14-3-3 promotes survival of DLBCL cells in CHOP. In support of our hypothesis, knockdown of 14-3-3 by small interfering RNA restored the sensitivity of resistant DLBCL to CHOP-induce apoptosis. In addition, 14-3-3 expression was highly up-regulated in a resected DLBCL lymph node relative to a normal lymph node by Western blot analysis. Furthermore, more than half of 35 DLBCL tissues showed elevated 14-3-3 expression relative to normal lymph tissue by immunohistochemical analysis. Our study implicates 14-3-3 in the pathogenesis of DLBCL and suggests a promising combination strategy with a 14-3-3 inhibitor for the treatment of refractory DLBCL.
Background: There is currently a lack of evidence-based guidelines regarding postoperative opioids after thyroid and parathyroid surgery. This study aimed to objectively characterize contemporary postoperative pain management practices via a national survey of head and neck endocrine surgeons. Methods: A standardized electronic survey was distributed to the membership of the American Head and Neck Society's Endocrine section. Results: A total of 102 surgeons completed the survey representing a 34% response rate. In all, 65.7% of respondents utilize opioids with wide variations in the total morphine equivalents prescribed. Practice environment (χ 2 = 10.0; P = 0.04) and performing preoperative pain counseling (χ 2 = 9.7; P = 0.002) were significantly associated with a decreased likelihood of prescribing postoperative opioids. Utilization of non-opioid pain management strategies was common and significantly associated with performing outpatient surgery (χ 2 = 6.2; P = 0.013) and preoperative pain counseling (χ 2 = 4.5; P = 0.034). Conclusions: Pain management practice patterns vary significantly among head and neck endocrine surgeons which further emphasize the need for evidence-based guidelines.
K E Y W O R D Shead and neck endocrine surgery, opioid prescribing, parathyroid surgery, postoperative pain, thyroid surgery
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