Most studies of idiopathic nonspecific interstitial pneumonia (NSIP) have primarily studied mortality. In order to clarify the detailed outcome and prognostic markers in idiopathic NSIP, the clinical course with initial radiological and clinical features was analysed.The clinical course of 83 patients who were classified with idiopathic NSIP (72 fibrotic, 11 cellular; 27 males and 56 females; mean¡SD age 54.4¡10.1 yrs) was retrospectively analysed.In fibrotic NSIP, 16 (22%) patients died of NSIP-related causes with a median (range) follow-up of 53 (0.3-181) months. Despite the favourable survival (5-yr 74%), patients with fibrotic NSIP were frequently hospitalised with recurrence rate of 36%. Reduced forced vital capacity at 12 months was a predictor of mortality. On follow-up, lung function was improved or stable in ,80% of the patients. The extent of consolidation and ground-glass opacity on initial highresolution computed tomography correlated significantly with serial changes of lung function, and the presence of honeycombing was a predictor of poor prognosis. During follow-up, eight (10%) patients developed collagen vascular disease.In conclusion, the overall prognosis of fibrotic nonspecific interstitial pneumonia was good; however, there were significant recurrences despite initial improvement and a subset of the patients did not respond to therapy. Some patients developed collagen vascular diseases at a later date.
In the effort to develop an efficient chemotherapy drug for the treatment of non-small-cell lung cancer (NSCLC), we analyzed the anti-tumorigenic effects of a novel small molecule targeting the inhibitor of apoptosis (IAPs), HM90822B, on NSCLC cells. HM90822B efficiently decreased IAP expression, especially that of XIAP and survivin, in several NSCLC cells. Interestingly, cells overexpressing epidermal growth factor receptor (EGFR) due to the mutations were more sensitive to HM90822B, undergoing cell cycle arrest and apoptosis when treated. In xenograft experiments, inoculated EGFR-overexpressing NSCLC cells showed tumor regression when treated with the inhibitor, demonstrating the chemotherapeutic potential of this agent. Mechanistically, decreased levels of EGFR, Akt and phospho-MAPKs were observed in inhibitor-treated PC-9 cells on phosphorylation array and western blotting analysis, indicating that the reagent inhibited cell growth by preventing critical cell survival signaling pathways. In addition, gene-specific knockdown studies against XIAP and/or EGFR further uncovered the involvement of Akt and MAPK pathways in HM90822B-mediated downregulation of NSCLC cell growth. Together, these results support that HM90822B is a promising candidate to be developed as lung tumor chemotherapeutics by targeting oncogenic activities of IAP together with inhibiting cell survival signaling pathways.
ABSTRACT. The purpose of this study was to evaluate intratumoral cystic lesions of pancreatic ductal adenocarcinoma (PDAC) depicted on MRI, and to correlate these cystic lesions with their histopathological findings. This study included 12 patients (7 males and 5 females; mean age, 59 years) with intratumoral cystic lesions of PDAC detected on a retrospective MRI review. We reviewed the histopathological findings of the cystic lesions within PDACs and analysed the MRI findings, focusing on the appearance of the intratumoral cystic lesions, i.e. the size, number, margin and intratumoral location, and on the ancillary findings of PDAC, i.e. peripancreatic infiltration, upstream pancreatic duct dilatation and distal parenchymal atrophy. Intratumoral cystic lesions were classified as neoplastic mucin cysts (n57, 58%) or cystic necrosis (n55, 42%) according to the histopathological findings; they ranged in greatest dimension from 0.5 cm to 3.4 cm (mean, 1.7 cm). Seven patients had only one cystic lesion each, while the remaining five had multiple cystic lesions. Most of the neoplastic mucin cysts had smooth margins (n56, 86%) and eccentric locations (n56), whereas most cystic necroses had irregular margins (n54, 80%) and centric locations (n54). The most common ancillary findings of PDAC were peripancreatic infiltration, distal pancreatic atrophy and upstream pancreatic duct dilatation (92%, 75% and 58%, respectively). The intratumoral cystic lesions of PDACs on MRI were classified as either neoplastic mucin cysts with smooth margins and eccentric locations or cystic necroses with irregular margins and centric locations. Pancreatic cancer is the fifth leading cause of cancerrelated death in both men and women and is responsible for 5% of all cancer-related deaths in the United States [1]. Despite the advances in surgical techniques, as well as the major improvements in chemotherapy and radiotherapy protocols, the prognosis of pancreatic ductal adenocarcinoma (PDAC) usually implies a 1-year survival rate of ,20% and a 5-year survival rate of ,5% [2].PDAC typically presents as an irregular solid tumour with a scirrhous character resulting from a prominent desmoplastic reaction. However, recent studies have shown that PDAC may be accompanied by cystic changes within or adjacent to the mass, and that the incidence of PDAC with cystic changes ranges from ,1% to 8% [3,4]. Radiologists should be familiar with PDACs with cystic changes as they may resemble more common cystic pancreatic lesions, such as pseudocysts, intraductal papillary mucinous neoplasms (IPMNs), solid pseudopapillary tumours and non-functioning islet cell tumours, all of which are managed differently and usually have better patient survival rates [5][6][7].Many studies have discussed the radiological appearance of PDAC accompanied by cystic lesions [6][7][8][9][10][11].Most of these studies have discussed pseudocysts or retention cysts depicted adjacent to the PDAC or in the extrapancreatic area in the clinical setting of pancreatitis [8][9][10][11], where...
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