Protease-activated receptor 2 signaling upregulates angiogenic growth factors in renal cell carcinoma

Renal cell carcinoma (RCC) is a highly vascular tumor associated with expression of various angiogenic growth factors. The precise process of how these growth factors are regulated in RCC is not fully understood. Recent evidence suggests that protease activated receptors (PARs), a new family of G-protein coupled receptors, play a crucial role in vascular development and tumor progression through a variety of mechanisms. However, the nature of PAR expression in human RCC tissues and its function in regulating angiogenesis in RCC are largely unknown. In this study, we investigated the expression and function of PAR-2 in RCC. RT-PCR and immunohistochemistry assays show that PAR-2 expression is significantly increased in human RCC tissue compared with the adjacent non-neoplastic kidney tissue. In RCC derived cells, PAR-2 is functional as evidenced by robust signaling through MAP kinases including ERK1/2 and JNK. Furthermore, activation of PAR-2 significantly upregulates several angiogenic cytokines, including interleukin-6 (IL-6), IL-8, monocytes chemotactic protein-1 (MCP-1) and growth-related oncogene (GRO). To our knowledge, this is the first report that characterized PAR-2 expression in RCC tissue and further demonstrated that PAR-2 has a critical role in regulating angiogenesis in RCC.     

Acoustic radiation force impulse under clinical conditions with single infusion of ultrasound contrast agent evoking arrhythmias in rabbit heart

Journal of Medical Ultrasonics - We previously reported that acoustic radiation force impulse (ARFI) with concomitant administration of perfluorobutane as an ultrasound contrast agent (UCA)-induced...     

Assessing Blood Flow in an Intracranial Stent: A Feasibility Study of MR Angiography Using a Silent Scan after Stent-Assisted Coil Embolization for Anterior Circulation Aneurysms

BACKGROUND AND PURPOSE:Blood flow in an intracranial stent cannot be visualized with 3D time-of-flight MR angiography owing to magnetic susceptibility and radiofrequency shielding. As a novel follow-up tool after stent-assisted coil embolization, we applied MRA by using a Silent Scan algorithm that contains an ultrashort TE combined with an arterial spin-labeling technique (Silent MRA). The purpose of this study was to determine whether Silent MRA could visualize flow in an intracranial stent placed in the anterior circulation.MATERIALS AND METHODS:Nine patients treated with stent-assisted coil embolization for anterior circulation aneurysms underwent MRAs (Silent MRA and TOF MRA) and x-ray digital subtraction angiography. MRAs were performed in the same session on a 3T unit. Two neuroradiologists independently reviewed the MRA images and subjectively scored flow in a stent as 1 (not visible) to 4 (excellent) by referring to the latest x-ray digital subtraction angiography image as a criterion standard.RESULTS:Both observers gave MRA higher scores than TOF MRA for flow in a stent in all cases. The mean score for Silent MRA was 3.44 ± 0.53, and for TOF MRA, it was 1.44 ± 0.46 (P < .001).CONCLUSIONS:Silent MRA was able to visualize flow in an intracranial stent more effectively than TOF MRA. Silent MRA might be useful for follow-up imaging after stent-assisted coil embolization, though these study results may be only preliminary due to some limitations.

Endovascular therapy for intracranial aneurysms has been widely used since the International Subarachnoid Aneurysm Trial.¹ The number of cases of coil embolization for aneurysms is increasing, and the stent-protection technique has widened the applicability to cases that had been otherwise difficult to treat with conventional coil embolization.² Nevertheless, there is a risk of coil compaction or in-stent restenosis after stent-assisted coil embolization. X-ray digital subtraction angiography is the optimal technique used to examine these adverse events, and it is commonly used as a follow-up tool after using an intracranial stent. However, DSA presents some unavoidable risks related to the catheter procedure, radiation, and contrast media.^3–53D time-of-flight MR angiography is widely used for the assessment of cerebral vascular diseases and has also been examined as a noninvasive substitute for DSA.^6–9 These studies generally reported difficulty in visualizing flow in a stent with TOF MRA because of magnetic susceptibility and radiofrequency shielding, though some beneficial aspects were observed in assessing the residual lumen of aneurysms. As a novel follow-up tool after stent-assisted coil embolization, we applied MRA by using a Silent Scan algorithm (GE Healthcare, Milwaukee, Wisconsin) that contains an ultrashort TE combined with an arterial spin-labeling technique (Silent MRA). In this situation, visualizing flow means visualizing arterial geometry and patency. It does not mean directly visualizing blood flow rate. The purpose of this study was to determine whether Silent MRA can visualize flow in an intracranial stent placed at the anterior circulation.     

A case of extrapleural empyema

A 49-year-old man with diabetes mellitus and alcoholic liver cirrhosis presented with dyspnoea and fever. A chest computed tomography scan revealed three areas of loculated pleural effusion. Initially, the patient was thought to have an intrapleural empyema and was treated with intravenous antibiotics and closed drainage. However, as he did not improve, he was then treated with open drainage. During open drainage, the patient was diagnosed to have an extrapleural empyema and improved following open drainage treatment.     

Toxoplasma pericarditis without immunosuppressant disorder detected by polymerase chain reaction of pericardial fluid: a case report

There have been several case reports, a total of 22 up to the present, of toxoplasma pericarditis. Out of them, in only a few cases the diagnosis was properly made with a proof of the microscopic presence of Toxoplasma gondii. This is the first report of toxoplasma pericarditis in which the presence of Toxoplasma gondii was detected by polymerase chain reaction of pericardial effusion. In addition, the previous reports will be reviewed, and compared to this present case. A 29-year-old woman, without immunosuppressant disorder, suffering from fever and orthopnea was admitted to our hospital. Blood chemistry findings indicated mild liver dysfunction and inflammation. Chest radiography showed cardiac enlargement. Electrocardiography showed sinus tachycardia and ST elevation. Echocardiography revealed a massive pericardial effusion. Pericardiocentesis demonstrated 638 ml of bloody fluid. Cytologic study of the fluid was class II for malignancy, and polymerase chain reaction to tuberculosis was negative. However, a high titer of the anti-toxoplasma antibody of 1: 20,480 (passive hemagglutination) indicated pericarditis caused by Toxoplasma gondii. Subsequently, Toxoplasma gondii was identified in the pericardial effusion by polymerase chain reaction. Clinical symptoms improved after pericardiocentesis, but 2 months later pericarditis recurred. Treatment was started with 800 mg acetylspiramycin daily but failed to improve the symptoms. Because of the development of pleuritis, treatment was changed to sulfadoxine 1,000 mg/pyrimethamine 50 mg. After the treatment with them, her symptoms improved. Only 22 cases of toxoplasma pericarditis have been reported worldwide and 15 of those cases were without immunosuppressant disorder. The usual symptoms at the onset of pericarditis without immunosuppressant disorder are fever, dyspnea and chest pain. Seven patients developed cardiac tamponade. Pericardiocentesis was performed in 8 cases and the pericardial fluid was hemorrhagic in 6. Pericardial thickening was detected in 5 cases. The diagnosis of toxoplasma infection is very difficult, because asymptomatic infection of Toxoplasma gondii is very common. Pericarditis is a disease difficult to confirm the etiology. Detection of Toxoplasma gondii in pericardial effusion by the polymerase chain reaction is very useful for its diagnosis.     

Deregulation of G1/S transition is a common event in carcinoma of the ampulla of vater

BACKGROUND/AIMS: Aberrant expression of cell cycle regulators and subsequent deregulation of G1/S transition is one of the most important characteristics of human cancer. The aim of this study was to determine the overall pattern of deranged expression of the cell cycle regulators involved in the G1/S transition in ampullary carcinoma. METHODOLOGY: Using immunohistochemistry, we investigated the expression of p21WAF1/CIP1, p27Kip1, p16INK4, cyclin D1, cyclin E, pRb and p53 in 14 resected specimens of ampullary carcinoma and defined the proliferative activity of each tumor by quantifying Ki-67 antigen. RESULTS: Decreased expression of p21WAF1/CIP1, p27Kip1, and p16INK4 was detected in 6 (43%), 11 (79%), and 4 (29%) tumors, respectively. Four tumors (29%) overexpressed cyclin D1 and 8 (57%) overexpressed cyclin E. Eight tumors (57%) overexpressed pRb. Aberrant accumulation of p53 was observed in 10 (71%) of the tumors. Overall, the expression of two or more of these cell cycle regulators was altered in all of the 14 tumors. Decreased p21WAF1/CIP1 expression was related to higher TMN stage (P = 0.04) and lymphatic invasion (P = 0.04). The proliferative index was higher in tumors with decreased p27Kip expression (P = 0.005), and in tumors with cyclin E overexpression (P = 0.06). CONCLUSIONS: Our observations suggest that deregulation of G1/S transition is a very common event in ampullary carcinoma, and that altered expression of cell cycle regulators is associated with the aggressive behavior of this tumor. Correcting the G1/S transition regulatory machinery may provide a novel therapy for this malignancy.     

Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid

BACKGROUND & AIMS: Aberrant crypt foci, precursors of colonic adenoma, are frequently positive for glutathione-S-transferase P1-1. Because deoxycholic acid is an apoptosis-inducing xenobiotic in the colon, we examined the possibility that aberrant crypt foci, through the cytoprotecting function of glutathione-S-transferase P1-1, resist deoxycholic acid-induced apoptosis, thereby surviving to become adenomas and subsequently cancer. METHODS: Glutathione-S-transferase P1-1 or cyclooxygenase-2 expression and the percentage of apoptotic cells in aberrant crypt foci were examined by immunohistochemistry and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively. Glutathione-S-transferase P1-1 was transfected into colon cancer cells (M7609) and human lung fibroblasts, and deoxycholic acid-induced apoptosis was evaluated by a dye-uptake assay and flow cytometry. Binding of deoxycholic acid to glutathione-S-transferase P1-1 was analyzed by circular dichroism and immunoprecipitation. Caspase activities were determined by colorimetric protease assay, and sulindac binding to glutathione-S-transferase P1-1 was determined by inhibition assay of glutathione-S-transferase P1-1 activity. RESULTS: Aberrant crypt foci showed positive immunostaining for glutathione-S-transferase P1-1 but negative staining for cyclooxygenase-2. The percentage of apoptotic cells in aberrant crypt foci was significantly lower than in healthy epithelium, and the difference became more apparent with deoxycholic acid treatment. The impaired sensitivity of aberrant crypt foci to deoxycholic acid was restored by the glutathione-S-transferase P1-1-specific inhibitor gamma-glutamyl-S-(benzyl)cysteinyl-R-phenylglycine diethylester. By transfection of glutathione-S-transferase P1-1, M7609 cells became more resistant to deoxycholic acid-induced apoptosis than mock transfectants. Direct binding of glutathione-S-transferase P1-1 to deoxycholic acid was proven by circular dichroism and by immunoprecipitation. The aberrant crypt foci in adenoma patients treated with sulindac, which was shown to bind to glutathione-S-transferase P1-1, underwent apoptosis in 4 days and mostly regressed in 2-3 months. CONCLUSIONS: Glutathione-S-transferase P1-1 protects aberrant crypt foci from deoxycholic acid-induced apoptosis and may play a pivotal role in early colon carcinogenesis.