Objective
Growing evidence suggests that a phenotypic switch converting pancreatic acinar cells to duct-like cells can lead to pancreatic intraepithelial neoplasia (PanIN) and eventually to invasive pancreatic ductal adenocarcinoma. Histologically, the onset of this switch is characterised by the co-expression of acinar and ductal markers in acini, a lesion called acinar-to-ductal metaplasia (ADM). Transcriptional regulators required to initiate ADM still remain unknown, yet need to be identified to characterise the regulatory networks that drive ADM. Here we investigate the role of the ductal transcription factors Hepatocyte Nuclear Factor 6 (HNF6, also known as Onecut1)and SRY-related HMG box factor 9 (Sox9) in ADM.
Design
Expression of HNF6 and Sox9 is measured by immunostaining in normal and diseased human pancreas. The function of the factors is tested in cultured cells and in mouse models of ADM by a combination of gain- and loss-of-function experiments.
Results
Expression of HNF6 and Sox9 is ectopically induced in acinar cells in human ADM, as well as in mouse models of ADM. We show that these factors are required for repression of acinar genes, for modulation of ADM-associated changes in cell polarity, and for activation of ductal genes in metaplastic acinar cells.
Conclusions
HNF6 and Sox9 are new biomarkers of ADM and constitute candidate targets for preventive therapy in cases when ADM may lead to cancer. Our work also highlights that ectopic activation of transcription factors may underlie metaplastic processes occurring in other organs.
Cardiovascular diseases are still the primary causes of mortality in the United States and in Western Europe. Arterial thrombosis is triggered by a ruptured atherosclerotic plaque and precipitates an acute vascular event, which is responsible for the high mortality rate. These rupture-prone plaques are called "vulnerable plaques." During the past decades, much effort has been put toward accurately detecting the presence of vulnerable plaques with different imaging techniques. In this review, we provide an overview of the currently available invasive and noninvasive imaging modalities used to detect vulnerable plaques. We will discuss the upcoming challenges in translating these techniques into clinical practice and in assigning them their exact place in the decision-making process.
Planar pulmonary scintigraphy is still regularly performed for the evaluation of pulmonary embolism (PE). However, only about 50-80% of cases can be resolved by this approach. This study evaluates the ability of tomographic acquisition (single photon emission computed tomography, SPECT) of the perfusion scan to improve the radionuclide diagnosis of PE. One hundred and fourteen consecutive patients with a suspicion of PE underwent planar and SPECT lung perfusion scans as well as planar ventilation scans. The final diagnosis was obtained by using an algorithm, including D-dimer measurement, leg ultrasonography, a V/Q scan and chest spiral computed tomography, as well as the patient outcome. A planar perfusion scan was considered positive for PE in the presence of one or more wedge shaped defect, while SPECT was considered positive with one or more wedge shaped defect with sharp borders, three-plane visualization, whatever the photopenia. A definite diagnosis was achieved in 70 patients. After exclusion of four 'non-diagnostic' SPECT images, the prevalence of PE was 23% (n =15). Intraobserver and interobserver reproducibilities were 91%/94% and 79%/88% for planar/SPECT images, respectively. The sensitivities for PE diagnosis were similar for planar and SPECT perfusion scans (80%), whereas SPECT had a higher specificity (96% vs 78%; P =0.01). SPECT correctly classified 8/9 intermediate and 31/32 low probability V/Q scans as negative. It is concluded that lung perfusion SPECT is readily performed and reproducible. A negative study eliminates the need for a combined V/Q study and most of the 'non-diagnostic' V/Q probabilities can be solved with a perfusion image obtained by using tomography.
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