Treatment results of neoadjuvant chemoradiotherapy followed by radical esophagectomy in patients with initially inoperable thoracic esophageal cancer.

Purpose: We evaluated the effectiveness of neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy for cT4 esophageal cancer or lymph node metastases (LNM) invading adjacent structures.

Materials And Methods: We retrospectively evaluated 42 consecutive patients with thoracic esophageal cancer who underwent CRT followed by esophagectomy between 2008 and 2013. All were initially considered to be unresectable because of cT4 (n = 32) disease or LN invasion (n = 10).

Results of surgery plus postoperative radiotherapy for patients with malignant parotid tumor.

Purpose: The latest version of the World Health Organization (WHO) histologic classification of salivary gland malignancies was published in 2005. To contribute to data accumulation on the basis of this latest version, a retrospective study was performed.

Materials And Methods: Participants comprised 27 patients who underwent postoperative radiotherapy between 2000 and 2013.

Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice.

Aims/hypothesis: Obesity is associated with ageing and increased energy intake, while restriction of energy intake improves health and longevity in multiple organisms; the NAD(+)-dependent deacetylase sirtuin 1 (SIRT1) is implicated in this process. Pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in the arcuate nucleus (ARC) of the hypothalamus are critical for energy balance regulation, and the level of SIRT1 protein decreases with age in the ARC. In the current study we tested whether conditional Sirt1 overexpression in mouse POMC or AgRP neurons prevents age-associated weight gain and diet-induced obesity.

FoxO1 gain of function in the pancreas causes glucose intolerance, polycystic pancreas, and islet hypervascularization.

Genetic studies revealed that the ablation of insulin/IGF-1 signaling in the pancreas causes diabetes. FoxO1 is a downstream transcription factor of insulin/IGF-1 signaling. We previously reported that FoxO1 haploinsufficiency restored β cell mass and rescued diabetes in IRS2 knockout mice.

FoxO1 as a double-edged sword in the pancreas: analysis of pancreas- and β-cell-specific FoxO1 knockout mice.

Diabetes is characterized by an absolute or relative deficiency of pancreatic β-cells. New strategies to accelerate β-cell neogenesis or maintain existing β-cells are desired for future therapies against diabetes. We previously reported that forkhead box O1 (FoxO1) inhibits β-cell growth through a Pdx1-mediated mechanism.

Overexpression of FoxO1 in the hypothalamus and pancreas causes obesity and glucose intolerance.

Recent studies have revealed that insulin signaling in pancreatic β-cells and the hypothalamus is critical for maintaining nutrient and energy homeostasis, the failure of which are hallmarks of metabolic syndrome. We previously reported that forkhead transcription factor forkhead box-containing protein of the O subfamily (FoxO)1, a downstream effector of insulin signaling, plays important roles in β-cells and the hypothalamus when we investigated the roles of FoxO1 independently in the pancreas and hypothalamus. However, because metabolic syndrome is caused by the combined disorders in hypothalamus and pancreas, to elucidate the combined implications of FoxO1 in these organs, we generated constitutively active FoxO1 knockin (KI) mice with specific activation in both the hypothalamus and pancreas.