Xinying Li

The Nuclear Factor Kappa-B Signaling Pathway as a Therapeutic Target Against Thyroid Cancers.

BACKGROUNDnThe nuclear factor kappa-B (NF-κB) proteins, a family of transcription factors found virtually in all cells, are known to play crucial roles in the growth of a number of human malignancies. The ability of NF-κB to target a large number of genes that regulate cell proliferation, differentiation, survival, and apoptosis, provides clues toward its deregulation during the process of tumorigenesis, metastatic progression, and therapeutic resistance of tumors.nnnSUMMARYnIn addition to the signaling pathways known to be involved in thyroid tumorigenesis, such as the mitogen-activated protein kinase and janus kinase cascades, studies implicate the NF-κB pathway in the development of both less aggressive thyroid cancers, papillary and follicular adenocarcinomas, and progression to aggressive thyroid cancers, such as anaplastic adenocarcinomas. A constitutively activated NF-κB pathway also closely links Hashimotos thyroiditis with increased incidence of thyroid cancers. The NF-κB pathway is becoming one of the major targets for drug development, and a number of compounds have been developed to inhibit this pathway at different levels in cancer cells. Some of these targets have shown promising outcomes in both in vitro and in vivo investigations and a handful of them have shown efficacy in the clinical setting.nnnCONCLUSIONSnThis review discusses the recent findings that demonstrate that the inhibition of NF-κB, alone or with other signaling pathway inhibitors may be of significant therapeutic benefits against aggressive thyroid cancers.

Synergistic inhibition of thyroid cancer by suppressing MAPK/PI3K/AKT pathways.

BACKGROUNDnAlthough a wide spectrum of inhibitors of the MEK/ERK and PI3K/AKT pathways have been discovered and entered clinical trials, the effects of their individual use in thyroid cancer were often disappointing. We hypothesized that dual targeting of these two pathways would be a safe and effective strategy against aggressive thyroid cancers.nnnMETHODSnWe examined the antiproliferative effects of the MEK/ERK inhibitor AZD6244 and the PI3K/AKT inhibitor GDC0941, individually or in combination, on thyroid cancer cells harboring both the BRAF(V600E) and PIK3CA mutations. The effects of drug exposure on both total and phosphorylated (p-) forms of AKT and ERK were monitored by Western blotting analysis. Effects of these inhibitors on cell-cycle progression and apoptosis were measured by flow cytometry and DNA-fragmentation analyses, respectively.nnnRESULTSnWe observed significant toxicities to viability of cells with low concentrations of AZD6244 or GDC0941, which were synergistic when the two inhibitors were used in combination (P < 0.01). AZD6244 abrogated p-ERK and GDC0941 abrogated p-AKT levels, confirming their expected target effects. Unexpectedly, monotherapy with AZD6244 resulted in activation of the PI3K signaling pathway in some cancer cell lines and co-exposure to AZD6244 and GDC0941 was necessary to suppress both pathways. Flow cytometry showed G1 arrest. DNA fragmentation analysis showed an increased apoptosis of cells dually treated with the two inhibitors.nnnCONCLUSIONnConcomitant suppression of MEK/ERK and PI3K/AKT pathways by AZD6244 and GDC0941 abrogates compensatory mechanisms of tumor survival and causes synergistic cytotoxicity in thyroid cancer cells.

Single incision robotic transaxillary approach to perform parathyroidectomy

The recent development of robotic systems provided a safe, precise, 3D magnified dissection without the need for CO 2 insufflation and has a better cosmetic result due to the invisible axillary scar in the neutral position (1). In the past two decades, significant improvements in the accuracy and reliability of preoperative localization studies have facilitated further evolution in surgical management of primary hyperparathyroidism (2). Targeted parathyroidectomy is the current preferred procedure for PHPT by most endocrine surgeons (3,4).

Different surgical approaches in parathyroid adenoma resections

Three patients were referred to our clinic for the management of a persistent symptomatic primary hyperparathyroidism. Pre-operative imageological localization revealed evidence of an adenoma. Here we are presenting three videos demonstrating the different surgical approaches of parathyroid adenoma resection, with the use of an intraoperative gamma probe and nerve monitoring.

Robotic clipless transperitoneal adrenalectomy.

Robotic adrenalectomy is a minimally invasive alternative to traditional laparoscopic adrenalectomy. In addition to the benefits of decreased postoperative pain and shortened recovery time represented by laparoscopic adrenalectomy, robotic technology adds to the advantages of laparoscopy the benefits of a 3-dimensional display that enhances depth perception. Robotic approach enables the surgeon to operate in a comfortable, seated position in which the eye, hand, and target are in line; and has instruments that contain a “wrist” joint to improve dexterity (1-3).