Effects of the Quinone Analog Ubiquinone-5 on Murine Mitochondria and Hypnosis.

Background: A functional anesthetic target has long been suspected to reside within mitochondria, and disruption of bioenergetic capacity is believed to play a role in the anesthetic response. Unfortunately, the exact mechanism by which changes in mitochondrial target activity result in clinically relevant anesthetic endpoints remains unknown. Here, the authors leveraged knowledge of propofol toxicity to guide drug discovery and uncover a previously unknown pharmacologic target within mitochondria.

Altered brown adipose tissue mitochondrial function in newborn fragile X syndrome mice.

Brown adipose tissue (BAT) mitochondria generate heat via uncoupled respiration due to excessive proton leak through uncoupling proteins (UCPs). We previously found hyperthermia in a newborn mouse model of fragile X syndrome and excessive leak in Fmr1 KO forebrain mitochondria caused by CoQ deficiency. The inefficient thermogenic nature of Fmr1 mutant forebrain mitochondria was reminiscent of BAT metabolic features.

Improving diagnostic recognition of primary hyperparathyroidism with machine learning.

Background: Parathyroidectomy offers the only cure for primary hyperparathyroidism, but today only 50% of primary hyperparathyroidism patients are referred for operation, in large part, because the condition is widely under-recognized. The diagnosis of primary hyperparathyroidism can be especially challenging with mild biochemical indices. Machine learning is a collection of methods in which computers build predictive algorithms based on labeled examples.

Notch3 expression correlates with thyroid cancer differentiation, induces apoptosis, and predicts disease prognosis.

Background: Thyroid tumorigenesis is characterized by a progressive loss of differentiation exhibited by a range of disease variants. The Notch receptor family (1-4) regulates developmental progression in both normal and cancerous tissues. This study sought to characterize the third Notch isoform (Notch3) across the various differentiated states of thyroid cancer, and determine its clinical impact.

Notch1 Signaling Regulates the Aggressiveness of Differentiated Thyroid Cancer and Inhibits SERPINE1 Expression.

Purpose: Notch1, a transmembrane receptor, has been recently shown to aid in the determination of thyroid cell fate associated with tumorigenesis. This study aimed to investigate the clinical relevance of Notch1 and its role in the regulation of differentiated thyroid cancer (DTC) behavior.

Experimental Design: We examined Notch1 expression level and its relationship with clinicopathologic features and outcomes of DTC.

Radioguided parathyroidectomy for tertiary hyperparathyroidism.

Background: Tertiary hyperparathyroidism (3HPT) is defined as the persistent hyperproduction of parathyroid hormone and resulting hypercalcemia after renal transplantation. Here, we examine the utility of radioguided parathyroidectomy (RGP) in patients with 3HPT.

Materials And Methods: We reviewed a prospective surgery database containing 80 3HPT patients who underwent RGP from January 2001-July 2014 at our institution.

The effect of cinacalcet on intraoperative findings in tertiary hyperparathyroidism patients undergoing parathyroidectomy.

Introduction: Tertiary hyperparathyroidism (3HPTH) patients who undergo parathyroidectomy (PTX) are often managed with calcium lowering medications such as cinacalcet (Sensipar) before surgery. Here, we assess how cinacalcet treatment influences intraoperative parathyroid hormone (IOPTH) kinetics and surgical findings in 3HPTH patients undergoing PTX.

Methods: We reviewed retrospectively 113 patients 3HPTH who underwent PTX, 14 of whom were taking cinacalcet and 112 who were not taking the drug.

Thyroid: Medullary Carcinoma.

Medullary thyroid cancers (MTC) are rare neuroendocrine tumors arising from the parafollicular C-cells of the thyroid. In this review, we provide a general overview of the classification, pathology, and clinical management of MTC. In the latter half, we survey the underlying genetic framework of MTC and its potential implications within a diagnostic and therapeutic context.

The Phosphatidylinositol 3-kinase/Akt Signaling Pathway in Neuroendocrine Tumors.

The phosphatidylinositol 3-kinase (PI3K)-Akt pathway is often aberrantly activated in neuroendocrine-derived cancers. Therefore, selectively targeting this pathway using small-molecule inhibitors may reduce neuroendocrine tumor burden, potentiate adjunct therapies, and achieve symptomatic control for patients with hormonally active and inoperable disease. Here, we discuss the role of the PI3K-Akt pathway in the malignant transformation of neuroendocrine tumors, specifically carcinoids and small cell lung cancers.

Inhibition of mTOR radiosensitizes soft tissue sarcoma and tumor vasculature.

Purpose: The PI3K/Akt/mTOR prosurvival pathway is frequently up-regulated in soft tissue sarcoma. Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin, have recently shown clinical benefit in soft tissue sarcoma, and mTOR inhibition has also been associated with radiosensitization of carcinoma and endothelial cells. This study tested the hypothesis that rapamycin radiosensitizes soft tissue sarcoma and endothelial cells in vitro and in vivo through the inhibition of mTOR.

Gemcitabine-mediated radiosensitization of human soft tissue sarcoma.

Background/purpose: Local and systemic control of soft tissue sarcoma (STS) remains a clinical challenge, particularly for retroperitoneal, deep truncal, or advanced extremity disease. 2',2'-Difluoro-2'-deoxycytidine (gemcitabine) is a potent radiosensitizer in many tumor types, but it has not been studied in human STS. The purpose of this study was to determine the radiosensitizing potential of gemcitabine in preclinical models of human STS.