Fundamental study of radiogallium-labeled aspartic acid peptides introducing octreotate derivatives

Annals of Nuclear Medicine - Somatostatin receptors are highly expressed in neuroendocrine tumors, and many radiolabeled somatostatin analogs for diagnosis and treatment have been developed. To...     

Tonsillectomy reduces recurrence of IgA nephropathy in mesangial hypercellularity type categorized by the Oxford classification

Background

In patients with IgA nephropathy (IgAN), recurrence after steroid pulse therapy is associated with reduced renal survival. However, the predictors of recurrence have not yet been clarified.

Methods

All patients who received 6-month steroid pulse therapy from 2004 to 2010 in our four affiliated hospitals and achieved a reduction of proteinuria to <0.4 g/day 1 year after treatment were retrospectively evaluated. The primary outcome was proteinuria ≥1.0 g/day during follow-up or additional antiproteinuric therapy. Two histological classifications were evaluated, the Oxford Classification with a split system and Japanese histological grades (HGs) with a lumped system.

Results

During a median follow-up of 3.4 years, 27 (26.7 %) of the 101 patients showed recurrence. Multivariate analysis showed that HG was the only significant predictor of recurrence, with HG 2+3+4 vs HG 1 having a hazard ratio of 7.38 (95 % confidence interval 1.52–133). Furthermore, in patients with mesangial hypercellularity according to the Oxford Classification, cumulative rate of recurrence-free survival was greater in patients with steroid therapy plus tonsillectomy compared with those who received steroid therapy alone (Log-rank test, P = 0.022). However, this association was not observed in patients without mesangial hypercellularity.

Conclusions

HG is a novel predictor of recurrence after steroid pulse therapy in patients with IgAN. Moreover, the combination of steroid pulse therapy plus tonsillectomy may indicate a lower risk of recurrence in patients with mesangial hypercellularity, as defined by the Oxford Classification.

     

The genotype of the transporter associated with antigen processing gene affects susceptibility to colorectal cancer in Japanese

Objective

Although colorectal cancer (CRC) is one of the most frequent malignancies in Japan, the associated genetic factors remain to be elucidated. Functional loss of the transporter associated with antigen processing (TAP) 1 gene induces carcinogenesis. We investigated whether single nucleotide polymorphisms (SNPs) in the TAP1 gene (rs735883) are associated with susceptibility to CRC in a Japanese population.

Methods

The study participants were 143 cases and 243 clinical controls. After extracting DNA from their peripheral blood cells, genotyping was conducted by the polymerase chain reaction–restriction fragment length polymorphism method.

Results

Participants with a mutated allele had an increased risk for CRC. The adjusted odds ratios for the C/T, T/T, and the mutation type (C/T + T/T) compared to that of wild type (C/C) were 2.27 [95 % confidence interval (CI), 1.43–3.67], 1.95 (95 % CI, 0.88–4.30), and 2.22 (95 % CI, 1.42–3.55), respectively. Furthermore, a significant trend in the rate of cases was observed with an increasing number of mutated alleles (P for trend = 0.0068).

Conclusions

The genotype of the TAP1 gene is associated with susceptibility to CRC.     

Diagnosis of bladder cancer using 18F-labeled α-methyl-phenylalanine tracers in a mouse model

Annals of Nuclear Medicine - Although 2-18F-fluoro-2-deoxy-glucose (18F-FDG) has established roles in the diagnosis of a variety of cancers, it has limited value in the detection of...     

Urinary 1-hydroxypyrene as a comprehensive carcinogenic biomarker of exposure to polycyclic aromatic hydrocarbons: a cross-sectional study of coke oven workers in China

Purpose

Polycyclic aromatic hydrocarbons (PAHs) are multiple compounds that include many carcinogens. We conducted a cross-sectional study in steel plant workers in Anshan, China, to identify biomarkers that reflect the carcinogenicity of PAHs.

Methods

Subjects were 57 workers and 20 controls. Level of personal exposure to PAHs was measured using GC–MS. In accordance with the assessment methods defined by the United States Environmental Protection Agency (US EPA), 15 PAHs were selected for the analysis. For the measurement of urinary metabolites, urine samples were treated with β-glucuronidase and analyzed using HPLC with a fluorescence detector.

Results

The mean range of personal exposure to 15 PAHs (total PAHs) was 178.85, 47.08–1,329.45 (geometric mean, 5th and 95th percentile) μg/m³. Ten known urinary metabolites (1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 3-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene, 3-hydroxybenz[a]anthracene, 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene) and four unknown peaks were detected. The highest correlation was between total PAHs and urinary 2-hydroxynaphthalene (Spearman r = 0.716, P < 0.01). Among the detected urinary metabolites, 2-hydroxyfluorene, 1-hydroxyphenanthrene, 3-hydroxyphenanthrene, and 1-hydroxypyrene were found to correlate significantly with the “Σ carcinogenic potency of PAHs” (sum of seven carcinogenic PAHs calculated from the levels of personal PAHs and relative potency factors), and with the greatest correlation found for 1-hydroxypyrene (Spearman r = 0.630, P < 0.01).

Conclusions

The analysis of personal exposure to 15 PAHs and 10 urinary metabolites, and calculation of Σ carcinogenic potency, indicated that urinary 1-hydroxypyrene was the most comprehensive carcinogenic biomarker of exposure to PAHs.     

Prevalence of fatty liver in Japanese children and relationship to obesity

The prevalence of fatty liver in children is unknown and its relationship to obesity is poorly defined. The present study of 810 northern Japanese children (4–12 years old) determined the prevalence of fatty liver in the pediatric population and its relationship to obesity. Diagnosis of fatty liver was based on established real-time ultrasonographic criteria. The overall prevalence of fatty liver was 2.6% and was higher for boys (3.4%) than for girls (1.8%), although not statistically significant (P=0.15). Fatty liver was found in children as young as 6 years of age. There was no significant association between the prevalence of fatty liver and height (physical growth). There was a strong positive correlation between fatty liver prevalence and established obesity indices: Rohrer's index-² linear trend =59.2,P<0.0001; body mass index-² linear trend =91.6,P<0.0001; and age-gender-adjusted Japanese standard index of weight for height-² linear trend =93.2,P<0.0001. However, direct measurement of abdominal subcutaneous fat thickness by ultrasonography was the best predictor of fatty liver: ² linear trend =159,P<0.0001. These results indicate that fatty liver may develop very early in life, and there is a direct relationship between degree of obesity and fatty liver in children.     

Prognostic significance of p53 status in non-small cell lung cancer in correlation with postoperative adjuvant therapy

BACKGROUND AND OBJECTIVE: Significant factors in the prognosis of p53 status in non-small cell lung cancer (NSCLC) remain controversial; some clinical studies have documented that p53 abnormality is a significant factor in predicting poor prognosis, and others failed. In the present study, we examined whether or not adjuvant therapy may influence the prognostic significance. METHODS: 217 patients with pathologic stage I disease were reviewed. As postoperative adjuvant therapy, UFT, an oral 5-fluorouracil derivative, was administered to 73 patients; p53 status was determined immunohistochemically. RESULTS: The 5-year survival rate for tumor with aberrant p53 expression was 66.4 %--significantly lower than that for tumor without aberrant p53 expression (79.7%, p = 0.023). The prognostic significance of p53 status was enhanced in patients who received UFT; 5-year survival rates for tumor with and without aberrant p53 expression were 68.8 and 94.7%, respectively (p = 0.002). In patients who did not receive UFT, the difference did not reach statistical significance (5-year survival rates: 65.5 and 71.5%, respectively; p = 0.267). CONCLUSIONS: This study demonstrates that postoperative survival is improved by UFT administration in patients with normal p53 function, but not in those without normal p53 function.     

Vagal stimulation prior to atrial rapid pacing protects the atrium from electrical remodeling in anesthetized dogs.

Atrial electrical remodeling is thought to be the cause of the maintenance of atrial fibrillation (AF). Although the initiation and maintenance of AF is partially associated with autonomic nervous tone, vagally mediated AF does not tend to become permanent. Therefore, the effects of preceding vagal stimulation (VS) on the atrial effective refractory period (ERP) under electrical remodeling conditions were investigated in anesthetized dogs. Atrial ERPs were measured at 5 sites before and after a 7-h period of atrial rapid pacing in the control group. In the VS group, the vagus nerve was stimulated for 20 min before a period of atrial rapid pacing. Atrial rapid pacing shortened the ERP at each site in the control group (electrical remodeling). On the other hand, atrial rapid pacing after VS did not shorten the ERP at any site in the VS group. Tetrodotoxin, which was administered into the fatty tissue overlying the right atrial side of the right pulmonary vein junctions, blocked the protective effect of VS against the shortening of the ERP induced by atrial rapid pacing. In contrast, atropine did not interfere with such protective effects. These results suggest that VS prior to atrial rapid pacing protects the atrium from atrial electrical remodeling.