Brief communication: heat-induced accumulation of p53 and hsp72 is suppressed in lung fibroblasts from the SCID mouse

PURPOSE: To investigate how DNA-dependent protein kinase (DNA-PK) contributes to p53-dependent signal transduction after heat shock, thermosensitivity and accumulation of p53 and hsp72 after heat shock in lung fibroblasts derived from the SCID mouse were analysed. MATERIALS AND METHODS: Thermosensitivity at 44 degrees C in colony-forming units and Western blot analysis of p53 and hsp72 were analysed. RESULTS: The results indicated that (1) the thermosensitivity at 44 degrees C of SCID cells was higher than that of parental cells and (2) heat-induced accumulation of p53 and hsp72 was abolished and suppressed in SCID cells as compared with that in parental cells respectively. CONCLUSIONS: The findings suggest that the catalytic subunit of DNA-PK may play an important role upstream of p53 and hsp72, which are possible determinants of cellular thermosensitivity.     

Definitive chemoradiotherapy of limited-disease small cell lung cancer: Retrospective analysis of new predictive factors affecting treatment results

The aim of this study was to evaluate potential predictive factors in the treatment of limited-disease small cell lung cancer (LD-SCLC). A total of 33 patients with LD-SCLC who underwent definitive chemoradiotherapy at our institute between April 1996 and May 2007 were enrolled in our retrospective study. The relationship between a range of potential predictive factors and the initial response, time to progression and pattern of failure was analyzed. The factors evaluated included the tumor markers Pro-gastrin-releasing peptide (Pro-GRP) and neuron-specific enolase; net tumor size (sum of each lesion mass on computed tomography at 1-cm intervals); total radiation dose; biological effective dose (BED); overall treatment time (OTT); time between the start of any type of treatment and the end of radiation therapy (SER). In addition, the novel factors of radiation dose-intensity (RDI = BED/OTT) and RDI/NTS (= RDI/net tumor size) were defined. Of the 33 patients evaluated in our study, 22 (67%) achieved a complete response (CR) and 27 (82%) experienced treatment failure or recurrence. High RDI/NTS values showed a significant correlation with CR (P=0.043). Prolonged OTT and lower values of RDI and RDI/NTS showed a significant correlation with recurrence within 12 months (P=0.022, 0.033 and 0.015, respectively). The lower values of RDI and RDI/NTS showed a significant correlation with distant metastasis as a first failure site (P=0.038 and 0.044, respectively). Patients with RDI/NTS ≥0.08 had a more favorable prognosis (P=0.045). Thus, RDI and RDI/NTS may become beneficial predictive factors in the treatment of LD-SCLC. However, further studies are required to confirm our preliminary results.     

A nonfunctioning islet cell carcinoma with tumor thrombus in both the portal and splenic veins — a case report of successful resection

A rare case of nonfunctioning islet cell carcinoma associated with tumor thrombi in both the portal and splenic veins is reported. The patient, a 49-year-old male, had a 2-year history of occasional abdominal pain. Computed tomography (CT) disclosed a huge mass in the body of the pancreas, and celiac arteriogram showed a tumor stain in the body and tail of the pancreas. Percutaneous transhepatic portography (PTP) demonstrated an irregular filling defect, indicating intraportal tumor growth. Curative surgery, which included total pancreatectomy with combined resection (50 mm in length) and reconstruction of the portal vein, distal gastrectomy, and partial resection of the transverse colon, was performed. Histological examination of the surgical specimen led to a diagnosis of nonfunctioning islet cell carcinoma with a negative immunohistochemical stain for insulin, glucagon, somatostatin, and adrenocorticotropic hormone. The patient has been well for 38 months to date without any sign of tumor recurrence. Our experience with this case has introduced a radical resection for islet cell tumor of the pancreas, even if the tumor has extended into the portal vein.     

Radial augmentation index is related to cardiovascular risk in hemodialysis patients

Cardiovascular accidents related to atherosclerosis are the leading cause of death among hemodialysis patients, which makes continuous monitoring of their cardiovascular status crucial. Recently, a handy device for monitoring the augmentation index (AIx) in the radial artery was introduced in Japan, enabling the use of the AIx in addition to pulse wave velocity (PWV) in the management of hemodialysis patients. In this study the AIx, PWV, abdominal aortic calcification index (ACI), and left ventricular mass index (LVMI) were serially assessed in 108 hemodialysis patients. The radial AIx was monitored using a newly introduced tonometer (HEM-9010AI), and the interrelationships among the measured parameters and their contributions to the risk of cardiovascular accidents were evaluated. The radial AIx was significantly higher in hemodialysis patients than in healthy subjects (N = 50) and was well correlated with risk markers such as LVMI (r = 0.30, P = 0.019) and ACI (r = 0.38, P < 0.001), but not with PWV. Multiregression analysis showed that radial AIx was also significantly associated with LVMI, ACI and blood pressure; PWV was associated with other parameters such as age, blood pressure, and ACI. The AIx and ACI were both significantly increased in patients with cardiovascular complications. Although PWV was strongly increased in the hemodialysis patients, it failed to discriminate between these subgroups of high-risk patients. The radial AIx is closely associated with aortic calcification, cardiac hypertrophy, and a history of cardiovascular accidents in hemodialysis patients, and could be a useful marker for management of these patients.     

Efficacy of amiodarone for preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation after cardioversion.

BACKGROUND: It has been previously reported that the efficacy of class I antiarrhythmics in preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation (AF) is limited when AF lasts for 48 h or more. However, it is unclear whether the efficacy of amiodarone, a class III drug, is superior to class I antiarrhythmics in patients with long-lasting AF. METHOD AND RESULTS: The relationship between the duration of tachycardia and the efficacy of amiodarone in preventing recurrence of tachycardia was examined in 55 patients (37 men, 18 women, mean age 68+/-9 years) to whom amiodarone was administered after electrical or pharmacological cardioversion for paroxysmal and persistent AF. In 26 patients, paroxysmal and persistent AF ceased within 48 h after onset (Group A), and in the other 29 patients, it ceased after 48 h (Group B). Patient characteristics and actuarial recurrence-free rates were compared between the 2 groups. The mean follow-up period was 30+/-11 months. No statistically significant difference between the groups was found in patient characteristics. Actuarial recurrence-free rates in Group A and B at 1, 3, 6, 9, and 12 months were 100%, 81%, 69%, 62%, and 54%, and 93%, 79%, 66%, 52%, and 48%, respectively (p=NS at 12 months). The period of maintenance of sinus rhythm was 14.7+/-3.2 months in group A and 13.3+/-3.3 months in group B (mean+/-SE, p=NS). CONCLUSION: In the case of amiodarone, efficacy for maintaining sinus rhythm after cardioversion of AF was not biased by the duration of arrhythmia. This observation suggests amiodarone is effective in maintaining normal sinus rhythm after cardioversion, even in patients with long-lasting AF and electrical atrial remodeling.