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Abstract. To investigate the role of ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, in diabetic gastroparesis, we evaluated the plasma ghrelin profile during the oral glucose tolerance test in 55 patients with diabetes (men/women: 36/19, mean ± SE of age: 55.1 ± 1.7 years) with or without gastroparesis (diagnosed by the 13 Cacetate breath test). We also further examined cardiac autonomic neuropathy by assessing 24-hour variation of the R-R interval in randomly selected 32 patients with diabetes (men/women: 23/9, mean ± SE of age: 54.2 ± 2.5 years), and evaluated the influence of autonomic neuropathy on ghrelin. The fasting plasma ghrelin level was significantly lower in diabetes mellitus with gastroparesis than in healthy controls (7.9 ± 0.7 fmol/ml versus 16.6 ± 5.3 fmol/ml, p = 0.006). Patients with diabetes with gastroparesis showed no decrease of plasma ghrelin after glucose loading, unlike patients without gastroparesis or healthy controls. Diabetes mellitus with autonomic neuropathy, but not those without it, also showed no decrease of plasma ghrelin after glucose loading. Diabetic gastroparesis may be related to ghrelin-associated neurohormonal abnormalities, but the pathophysiological meaning of this abnormal ghrelin response needs further clarification.

Background Photodynamic therapy (PDT) is a cancer‐targeted treatment that uses a photosensitizer (PS) and laser irradiation. The effectiveness of current PDT using red light for advanced cancers is limited, because red light can only reach depths within a few millimeters. To enhance the antitumor effect for lung cancers, we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin and a PS, mono‐L‐aspartyl chlorin e6 (NPe6). Methods We examined whether cetuximab encapsulated in endosomes was released into the cytosol by PS in PDT under light irradiation. A431 cells were treated with fluorescein isothiocyanate‐labeled cetuximab, NPe6, and light irradiation and were observed with fluorescence microscopy. We analyzed the cytotoxicity of saporin‐conjugated cetuximab (IT‐cetuximab) in A431, A549, and MCF7 cells and the antitumor effect in model A549‐bearing mice in vivo using the iTAP method. Results Fluorescent microscopy analysis showed that the photodynamic effect of NPe6 (20 μM) and light irradiation (37.6 J/cm 2 ) caused the release of cetuximab from the endosome into the cytosol. In vitro analysis demonstrated that the iTAP method enhanced the cytotoxicity of IT‐cetuximab by the photodynamic effect. In in vivo experiments, compared with IT‐cetuximab alone or PDT alone, the iTAP method using a low dose of IT‐cetuximab showed the greatest enhancement of the antitumor effect. Conclusions Our study is the first report of the iTAP method using NPe6 for lung cancer cells. The iTAP method may become a new, minimally invasive treatment superior to current PDT methods.

Vascular endothelial growth factor (VEGF) has an ability to induce the migration of human umbilical vein endothelial cells (HUVEC). The objective of this study is to prepare several patterns of gelatin hydrogels for VEGF release and evaluate the 3-dimensional pattern of HUVEC migration in Matrigel by VEGF release. VEGF was incorporated into the gelatin hydrogel sheet to achieve the sustained release and generate the concentration gradient of VEGF. When Matrigel was put on the gelatin hydrogel sheet incorporating VEGF, the VEGF was released into the Matrigel to form a gradient pattern of VEGF concentration in the Matrigel with time and the area of VEGF released by the Matrigel depended upon the position of gelatin hydrogel sheet put on. In addition, HUVEC were seeded on the surface of Matrigel to evaluate the ability of VEGF released to enhance the cell migration into the Matrigel. HUVEC were migrated with time into the Matrigel to the direction and the position of VEGF released. It is concluded that the VEGF release induces the migration of HUVEC in Matrigel based on the concentration gradient and the position of VEGF formed in Matrigel.

Abstract. a 73-year-old woman was admitted to our department for treatment of diabetes (plasma glucose 289 mg/dl, hba 1C 7.1%, and glycated albumin 34.9%). she displayed the signs and symptoms of glucagonoma syndrome, including necrolytic migratory erythema (Nme), low aminoacidemia, and a marked increase of the serum glucagon level (4,940 pg/ ml). Thus, we suspected a glucagonoma causing secondary diabetes. however, we could not detect any mass in the pancreas or the gastrointestinal tract, and only found a liver lesion resembling a hemangioma. her Nme improved markedly after intravenous infusion of amino acids, and her plasma glucose was controlled reasonably well by intensive insulin therapy. however, her general condition deteriorated and she died on day 57 after hospitalization. at autopsy, the only tumor detected was the liver mass. This was a large solid tumor (8×6×5 cm) with a pattern of white and dark brown stripes located in the left lobe, while two white nodules were also found in the right lobe. based on the histopathological and immunohistochemical findings, the liver lesion was shown to be a malignant glucagonoma with intrahepatic metastases. since primary malignant hepatic glucagonoma has not been reported before, we present this extremely rare case of primary malignant glucagonoma of the liver. Correspondence to: Takuyuki kaTabami, m.d., division of metabolism and endocrinology, department of medicine, st. marianna university school of medicine, 2-16-1 sugao, miyamaeku, kawasaki 216-8511, Japan. e-mail: t2kataba@marianna-u.ac.jp NEUROENDOCRINE tumors (NeTs) are diagnosed on the basis of typical histological findings and the diagnosis is confirmed by diffuse positive staining for neuroendocrine cell markers [1]. NeTs are not only found in endocrine glands, but can occur throughout the body, including the gastrointestinal tract, lungs, and liver. Glucagonoma is one of the NeTs, and it almost always arises from the islets of the pancreas, with extrapancreatic tumors accounting for less than 1% of all cases [2]. Primary hepatic glucagonoma has not been reported before. here we present an extremely rare case of primary malignant hepatic glucagonoma that was confirmed at autopsy. Case ReportThe patient was a 73-year-old woman. at the age of 63 years, distal gastrectomy (billroth ii) was performed at another hospital, but we could not obtain any information with regard to the underlying disease. she had a history of heart failure at the age of 64 years. since then, a liver mass had been found (suspected hemangioma) and myelodysplastic syndrome had occurred at 71 years of age. diabetes mellitus had been diagnosed at our hospital when she was aged 69 years, but she had been followed without any anti-diabetic therapy. since her postprandial glucose level increased to 379 mg/dl, she was admitted to our ward for the treatment of diabetes when she was 73 years old.Physical examination on admission, she was very lean (bmi 12.0 kg/m 2 ). blood pressure was normal (116/89 mmhg), heart rate NOTE

A 28-year-old woman with severe ketoacidosis was admitted to our hospital on day 11 after giving birth. However, her HbA1C level was normal (5.2%) and both GAD and anti-insulin autoantibody were negative, and the WBC count was extremely high (57,500/ml)

The cover image, by Naoko Obi et al., is based on the Research Article Development of Drug Discovery Screening System by Molecular Interaction Kinetics Mass Spectrometry, DOI: .