Correlation between PDZK1, Cdc37, Akt and breast cancer malignancy: the role of PDZK1 in cell growth through Akt stabilization by increasing and interacting with Cdc37.

PDZ domain containing 1 (PDZK1) is a scaffold protein that plays a role in the fate of several proteins. Estrogen can induce PDZK1 gene expression; however, our recent report showed that PDZK1 expression in the breast cancer cell line MCF-7 is indirect and involves insulin-like growth factor (IGF)-1 receptor function. Such a relationship was established in cell culture systems and human breast cancer tissues. Here we show that overexpression of PDZK1 promoted an increase in cyclin D1 and enhanced anchorage-independent growth of MCF-7 cells in the absence of 17ß-estradiol, suggesting that PDZK1 harbors oncogenic activity. Indeed, PDKZ1 overexpression enhanced epidermal growth factor receptor (EGFR)-stimulated MEK/ERK1/2 signaling and IGF-induced Akt phosphorylation. PDZK1 appeared to play this role, in part, by stabilizing the integrity of the growth promoting factors Akt, human epidermal growth factor receptor 2 (Her2/Neu) and EGFR. Increased Akt levels occurred via a decrease in the ubiquitination of the kinase. PDZK1 overexpression was associated with resistance to paclitaxel/5-fluorouracil/etoposide only at low concentrations. Although the increased stability of Akt was sensitive to heat shock protein 90 (HSP90) inhibition, increased levels of the cochaperone cell division cycle 37 (Cdc37), as well as its ability to bind PDZK1, appear to play a larger role in kinase stability. Using human tissue microarrays, we show strong positive correlation between PDZK1, Akt and Cdc37 protein levels, and all correlated with human breast malignancy. There were no positive correlations between PDZK1 and Cdc37 at the mRNA levels, confirming our in vitro studies. These results demonstrate a relationship between PDZK1, Akt and Cdc37, and potentially Her2/Neu and EGFR, in breast cancer, representing a new axis that can be targeted therapeutically to reduce the burden of human breast cancer.

Robotic transaxillary thyroidectomy with gasless approach in a girl with goitre.

BACKGROUND: Robotic-assisted transaxillary thyroidectomy is a minimally invasive approach for the removal of the thyroid through the axilla. This technique eliminates a visible scar and affords excellent optics of the cervical anatomy. We sought to describe the technique and outcome for transaxillary gasless subtotal thyroidectomy in the paediatric population. METHODS: A 13 year-old female with an enlarged goitre underwent a transaxillary robot-assisted gasless subtotal thyroidectomy in an academic institution. The main outcome measures were feasibility of the robotic approach, patient and gland characteristics, operative time and complications. RESULTS: There was no conversion to laparoscopic or open surgery. The robotic docking time was 110 min and total operative time was 150 min. The patient tolerated the procedure well. Estimated blood loss was 10 ml. The patient was discharged within 24 h. There were no perioperative or postoperative complications. In addition there was no evidence of postoperative vocal cord palsy or paresis. CONCLUSIONS: This initial experience demonstrates that this technique can be a feasible, safe and effective method for subtotal thyroidectomy in the paediatric population. The use of robotic technology for endoscopic thyroid surgery could overcome the limitations of conventional endoscopic surgeries in the surgical management of thyroid disease.

Preoperative parathyroid needle localization: a minimally invasive novel technique in reoperative settings.

Background. Reoperative parathyroid surgery for primary hyperparathyroidism can be challenging. Numerous preoperative localization techniques have been employed to facilitate a more focused surgical exploration. This paper describes a novel, minimally invasive, and highly successful method of parathyroid localization. Methods. Patients with recurrent or persistent primary hyperparathyroidism underwent parathyroidectomy following CT scan or ultrasound-guided wire localization of the parathyroid. Accurate placement was confirmed by fine-needle aspiration with immunocytochemistry or PTH washout. The guide wire was left in situ to guide surgical excision of the gland. Curative resection was established by monitoring intact serum PTH levels after excision of the adenoma. Results. All ten patients underwent successful redo-targeted parathyroidectomy. Nine of the ten patients were discharged on the day of surgery. One patient was observed overnight due to transient postoperative hypocalcemia, which resolved with calcium supplementation. Conclusion. Placement of a localization wire via preoperative high-resolution ultrasound or CT can expedite reoperative parathyroid surgery. It allows identification of parathyroid adenoma via a minimally invasive approach, especially in cases where a sestamibi scan is inconclusive.