Pathological and molecular biological approaches to early mesothelioma

Malignant mesothelioma is an asbestos-related malignancy that arises primarily from mesothelial cells on the serosal surfaces of the pleural, peritoneal, and pericardial cavities. Malignant pleural mesothelioma (MPM) is most common, and its incidence is dramatically increasing worldwide as a result of widespread use of asbestos. Morphological discrimination between MPM and reactive mesothelial hyperplasia is difficult, and the most reliable pathological criterion for malignancy is mesothelial proliferation invading deeply into subpleural adipose tissues. To establish radical cure of MPM, it is crucial to find early-stage MPM of epithelial type, in which mesothelial proliferation is localized on the serosal surface of parietal pleura or limited within the submesothelial fibrous tissues of parietal pleura. The initial clinical presentation for patients with MPM is frequently dyspnea and/or chest pain due to large pleural effusion, and cytological analysis of pleural effusions is valuable to find patients with early-stage MPM of epithelial type. Recently, cytological features of MPM in pleural effusion, molecular markers for MPM, and genetic alternations of MPM have been reported. In this review, we discuss major issues on pathological and molecular biological approaches for diagnosis of early-stage MPM of epithelial type.     

Effects of ginseng rhizome and ginsenoside Ro on testosterone 5α-reductase and hair re-growth in testosterone-treated mice

This research program on the novel functions of Panax ginseng C. A. Meyer focused on the effects of ginseng rhizome on hair re‐growth in androgenetic alopecia. Extracts of red ginseng rhizome showed greater dose‐dependent inhibitory effects against testosterone 5α‐reductase (5αR) when compared with extracts of the main root. Ginsenoside Ro, the predominant ginsenoside in the rhizome, and ginsenoside Rg₃, a unique ginsenoside in red ginseng, showed inhibitory activity against 5αR with IC₅₀ values of 259.4 and 86.1 µm , respectively. The rhizome of P. japonicus, which contains larger amounts of ginsenoside Ro, also inhibited 5αR. Topical administration of extracts of red ginseng rhizomes (2 mg/mouse) and ginsenoside Ro (0.2 mg/mouse) to shaved skin inhibited hair re‐growth suppression after shaving in the testosterone‐treated C57BL/6 mice. These results suggest that red ginseng rhizomes containing both oleanane‐ and dammarane‐type ginsenosides are a promising raw material for cosmetic use. This is the first report that ginsenoside Ro enhances in vivo hair re‐growth based on their inhibitory activity against 5αR in the androgenetic alopecia model. Copyright © 2011 John Wiley & Sons, Ltd.     

Hepatocellular adenoma in a male with familial adenomatous polyposis coli

Hepatocellular adenoma (HA) is a benign liver tumor most frequently occurring in young women using oral contraceptives. We report a rare case of HA in a 27-year-old male patient with familial adenomatous polyposis (FAP). The patient underwent a total colectomy and ileo-rectal anastomosis for FAP in 2003. A preoperative computed tomography scan of the abdomen disclosed a tumor in the left-lobe of the liver, 5.8 cm in diameter. Pathologic examination of a needle biopsy disclosed HA, but he had never used anabolic steroids or other known inducers of HA. The size of the liver mass gradually increased to 8.5 cm during a follow-up period of 38 months, and a left hepatectomy was performed in 2006. Pathology of the resected specimen confirmed the diagnosis of HA. Although FAP is known to be complicated with neoplasia in various extracolonic organs, only five reported cases of HA have developed in patients with FAP, including this case. This is the first report of HA to develop in a male FAP patient.     

A case of pancreatic carcinoma with suspected autoimmune pancreatitis

We present a case of pancreatic carcinoma with strongly suspected coexisting autoimmune pancreatitis (AIP). The patient presented with a chief complaint of icterus and weight loss, and was referred to our institution after a pancreatic lesion was found. Blood test showed elevation of serum bilirubin, hepato-biliary enzyme, glucose and tumor markers, and also high levels of serum IgG4 (344 mg/dl, normal 4.8–105 mg/dl) and anti-DNA antibody (14 IU/ml, normal <6.0 IU/ml). Ultrasonography demonstrated an enlarged pancreas with smooth borders and low internal echo density. Enhanced computed tomography (CT) showed a sausage-shaped pancreas without definitive metastasis to the surrounding lymph nodes and liver. Imaging of the pancreatic duct, including endoscopic retrograde pancreatography (ERP) and magnetic resonance cholangiopancreatography (MRCP), showed stenosis of the main pancreatic duct at the pancreatic head as well as a long segment of narrowing at the body and no dilatation at the tail. Tissues from these stenotic sites and open biopsy from pancreatic body showed infiltrating adenocarcinoma and dense fibrosis. To date, only a small number of reports have described pancreatic carcinoma accompanied with AIP. It is important to confirm diagnosis with histology in cases of suspicious autoimmune pancreatitis, even when the clinical images are compatible with AIP.     

CSF tau protein is a useful marker for effective treatment of superficial siderosis of the central nervous system: Two case reports

We report two cases of superficial siderosis (SS) of the central nervous system (CNS), which is caused by chronic haemorrhaging into the subarachnoid space with haemosiderin deposition in the superficial portion of the CNS. Patient 1 had fluid collection in the spinal canal, which was reported as the source of the chronic bleeding. Patient 2 was bleeding from thickened dura at the level of the sacral vertebrae. Both of the patients had xanthochromic cerebrospinal fluid. We surgically repaired the sources of bleeding. Subsequently the cerebrospinal fluid (CSF) cleared and their symptoms were not aggravated for about 1 year. We measured several CSF markers of SS before and after surgery. Total tau protein (CSF-t-tau), phosphorylated tau protein (CSF-p-tau), iron (CSF-iron) and ferritin (CSF-ferritin) in the CSF were highly elevated at diagnosis. After surgery, the levels of CSF-t-tau and CSF-p-tau were markedly reduced while CSF-iron and CSF-ferritin had not decreased. It is suggested that CSF-t-tau and CSF-p-tau reflected the neural damage in SS and were useful to evaluate the effectiveness of SS therapies.     

Effect of mood stabilizers on gene expression in lymphoblastoid cells

Lithium and valproate are widely used as effective mood stabilizers for the treatment of bipolar disorder. To elucidate the common molecular effect of these drugs on non-neuronal cells, we studied the gene expression changes induced by these drugs. Lymphoblastoid cell cultures derived from lymphocytes harvested from three healthy subjects were incubated in medium containing therapeutic concentrations of lithium (0.75 mM) or valproate (100 μg ml⁻¹) for 7 days. Gene expression profiling was performed using an Affymetrix HGU95Av2 array containing approximately 12,000 probe sets. We identified 44 and 416 genes that were regulated by lithium and valproate, respectively. Most of the genes were not commonly affected by the two drugs. Among the 18 genes commonly altered by both drugs, vascular endothelial growth factor A (VEGFA), which is one of the VEGF gene isoforms, showed the largest downregulation. Our findings indicate that these two structurally dissimilar mood stabilizers, lithium, and valproate, alter VEGFA expression. VEGFA might be a useful biomarker of their effects on peripheral tissue.     

Reevaluation of trkA expression as a biological marker of neuroblastoma by high-sensitivity expression analysis--a study of 106 primary neuroblastomas treated in a single institute

Background/Purpose

It has previously been shown that neuroblastomas with favorable prognosis often express a high level of nerve growth factor receptor trkA. We performed an expression analysis of trkA in 106 NB samples based on the quantitative real-time polymerase chain reaction (PCR) and reevaluated the prognostic power of trkA.

Materials and methods

A total of 106 primary tumors from NB patients treated from 1988 to 2009 were analyzed. MYCN was amplified in 13 cases. TaqMan probe method was used for quantitative PCR. Primers and probes were designed to detect trkA I and trkA II, but not the oncogenic splice variant trkA III.

Results

Expression analysis by real-time PCR revealed a wide range of expression levels of trkA within neuroblastoma tissues. Extremely low levels of trkA that were undetectable by semiquantitative PCR were able to be quantified by this method. trkA was predominantly expressed in tumors with favorable outcome. Further analysis of trkA expression was performed in a cohort excluding mass-screened neuroblastomas. Strikingly, multivariate analysis containing age, MYCN status, and trkA expression identified trkA as the only variable that independently predicts the prognosis of the 44 patients who presented clinically.

Conclusion

High-resolution expression analysis targeting trkA and trkA II may add more statistical power on trkA as a biological marker.