A gain-of-function mutation in head involution defective , Wrinkled, causes precocious cell death of wing epidermal cells in Drosophila.

In Drosophila , wing epidermal cells undergo programmed cell death as the last step of metamorphosis. The aim of this study was to evaluate the role of hid , particularly the Wrinkled mutation ( hid W ), an allele of hid , in the cell death. The wing epithelial cell death is suppressed by loss-of-function mutation of hid , indicating that the death is governed by a cascade involving hid . Examination of the cell death in hid W showed that precocious death started at G stage, 3 h before eclosion. Thus, mutated-HID in the hid W mutant was activated at G stage, supporting the gain-of-function effect of hid W mutation.

Gastric endoscopic submucosal dissection via gastrostoma before the second operation for esophageal perforation: A case report.

A 69-year-old man with advanced esophageal cancer and 2 early gastric cancers received chemoradiotherapy and was scheduled to undergo subtotal esophagectomy after gastric endoscopic submucosal dissection (ESD). However, left lower esophageal perforation induced by vomiting suddenly occurred, and he urgently underwent esophago-proximal gastrectomy and gastrostomy without reconstruction. The resected specimen showed a complete response of pretreatment for the esophageal cancer and radical resection of one gastric cancer. Radical resection of the other gastric lesion was necessary before reconstruction. The fistula of gastrostoma was gradually dilated from 6.7 to 9.3 mm in order to pass the endoscope. At nine months after emergent operation, gastric ESD was performed via only the gastrostoma. A hemoclip with thread was attached to the specimen, and the thread was pulled out of the gastrostoma. The specimen was able to be removed en bloc, resulting in radical resection. Gastric tube reconstruction through the posterior sternal route was performed at six months after the ESD. He has not developed recurrence of the esophageal or gastric cancer in the two years since the emergent operation.

[Clinical evaluation of eribulin mesylate for the treatment of metastatic breast cancer].

BACKGROUND: Eribulin mesylate, a novel non-taxane inhibitor of microtubule dynamics, results in a significant improvement in the overall survival of heavily pretreated patients with metastatic breast cancer(MBC). In the present study, we aimed to clarify the efficacy and safety of eribulin mesylate for the treatment of MBC. PATIENTS AND METHODS: We examined 18 patients with MBC who received eribulin mesylate in our hospital from October 2011 to May 2013. The patients were assessed for therapeutic response and adverse events with this treatment; in addition, these parameters were assessed in patients undergoing a combination treatment of eribulin mesylate and trastuzumab. RESULTS: The mean age of the patients in this study was 68.7 years(range, 60-85 years). All patients exhibited metastases to lymph nodes and distant sites. The mean number of prior regimens was 4.4(range, 2-9). The mean number of cycles of eribulin mesylate treatment administered was 7.2(range, 2- 17). The objective response rate and clinical benefit rate(PR+long SD)were 33.3%(6/18)and 50.0%(9/18), respectively, and the median progression-free survival was 6 months. The Grade 3/4 adverse events occurring in the patients included neutropenia in 13 patients(72.2%), anemia in 1 patient(5.6%), anorexia in 1 patient(5.6%), stomatitis in 1 patient(5.6%), and peripheral neuropathy in 1 patient(5.6%). However, 3 elderly patients who received the combination treatment of trastuzumab and eribulin mesylate experienced no adverse events. CONCLUSIONS: eribulin mesylate appears to demonstrate an acceptable tumor response in patients with MBC, and it can be safely administered to elderly patients if myelosuppression is carefully managed.

Ductal branch-oriented pancreatic resection for an intraductal papillary mucinous neoplasm in the uncinate process that caused recurrent acute pancreatitis: a case report of successful treatment.

Acute pancreatitis reportedly occurs in about 15 % of cases of branch duct (BD)-intraductal papillary mucinous neoplasms (IPMNs), with two-thirds of BD-IPMNs being located in the head or uncinate process of the pancreas. However, the surgical indications and optimal treatment methods for BD-IPMNs have not been established. A 59-year-old Japanese male with epigastralgia was admitted to our hospital. A multidetector row computed tomography (MDCT) scan disclosed grade I acute pancreatitis. Magnetic resonance cholangiopancreatography disclosed a 1.5-cm BD-IPMN in the uncinate process. Two months after discharge, the epigastralgia recurred, and MDCT again revealed grade I pancreatitis. Due to the repeated episodes of pancreatitis, we performed ductal branch-oriented pancreatic resection. To detect the inferior branch of the Wirsung duct and avoid the development of a pancreatic fistula, we injected indigo carmine into the tumor which confirmed ligation of the inferior branch. Histopathologically, the tumor proved to be an adenoma. The postoperative course was uneventful in both the short- and long-term follow-up and, to date, there has been no recurrence of pancreatitis, or diabetes mellitus during the 6 years since pancreatectomy. This procedure is one of the methods that can be used for the successful resection of a BD-IPMN in the uncinate process that caused recurrent acute pancreatitis.

Role of perfusion CT in assessing tumor blood flow and malignancy level of gastric cancer.

BACKGROUND/AIMS: Intratumoral hemodynamics or tumor perfusion is useful in understanding the pathological background of the cancer. A parameter for a non-invasive, preoperative assessment of tumor perfusion has yet to be developed. METHODS: The study included 50 patients who underwent surgery for gastric cancer. Perfusion computed tomography (P-CT) was performed using a 16-row multidetector CT, and tumor blood flow (ml/min/100 g tissue) values were measured. We compared blood flow with histopathological characteristics and evaluated its correlation with microvessel density and tumor stromal density and calculated the ratio of vessels and stromal tissue. RESULTS: There was a significant decrease in blood flow in advanced tumor depth, peritoneal dissemination and undifferentiated subtypes. Cases with Lauren's diffuse type carcinoma were found to have decreased blood flow compared to the mixed or intestinal type. As for the stromal structure, despite the lack of correlation with microvessel density, blood flow significantly decreased with increased stromal density. CONCLUSIONS: Decreased blood flow value acquired from P-CT may reflect a progressive state of gastric cancer. The pathological background for this relation involves the tumor stroma. Tumor perfusion decreased as the stage and malignant character of the tumor advanced, and therefore P-CT could be a better strategy to estimate the malignancy level of cancer.

Activation of the cAMP/PKA signaling pathway is required for post-ecdysial cell death in wing epidermal cells of Drosophila melanogaster.

At the last step of metamorphosis in Drosophila, the wing epidermal cells are removed by programmed cell death during the wing spreading behavior after eclosion. The cell death was accompanied by DNA fragmentation demonstrated by the TUNEL assay. Transmission electron microscopy revealed that this cell death exhibited extensive vacuoles, indicative of autophagy. Ectopic expression of an anti-apoptotic gene, p35, inhibited the cell death, indicating the involvement of caspases. Neck ligation and hemolymph injection experiments demonstrated that the cell death is triggered by a hormonal factor secreted just after eclosion. The timing of the hormonal release implies that the hormone to trigger the death might be the insect tanning hormone, bursicon. This was supported by evidence that wing cell death was inhibited by a mutation of rickets, which encodes a G-protein coupled receptor in the glycoprotein hormone family that is a putative bursicon receptor. Furthermore, stimulation of components downstream of bursicon, such as a membrane permeant analog of cAMP, or ectopic expression of constitutively active forms of G proteins or PKA, induced precocious death. Conversely, cell death was inhibited in wing clones lacking G protein or PKA function. Thus, activation of the cAMP/PKA signaling pathway is required for transduction of the hormonal signal that induces wing epidermal cell death after eclosion.