Effects of two varieties of Bacillus thuringiensis maize on the biology of Plodia interpunctella

On the market since 1996, genetically modified plants expressing an insecticidal toxin (Cry toxin stemmed from Bacillus thuringiensis) target several lepidopteran and coleopteran pests. In this study, we assessed the impact of two varieties of Bt maize producing different toxins (Cry1Ab or Cry1Fa, respectively) on the biology of a storage pest: Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae). The Indianmeal moths were susceptible to both toxins but showed an escape behavior only from Cry1Fa. The weight of females issued from larvae reared on Cry1Ab increased with increasing toxin concentration, but adults of both sexes reared on Cry1Fa had decreased weight. Both toxins increased development time from egg to adult regardless of sex and had no impact on the male adult lifespan. Finally, we recorded a time lag between metamorphosis from the non-Bt and the Bt diets, which increased proportionally to Cry concentration in the Bt diet.     

Profile of inflammatory mediators in tonsils of patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome

The purpose of this study was to analyze the levels of white blood cells and profile of proinflammatory Th1, Th2, Th17, and T regulatory tissue cytokines in the tonsils of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) patients to contribute to the pathophysiological understanding of the PFAPA syndrome. A cohort of PFAPA patients who had tonsillectomy during 2010 and 2011 was included and compared to control patients who had tonsillectomy for tonsillar hypertrophy. White blood cell counts were measured during flares in PFAPA patients and before tonsillectomy in the control group. Cytokine gene expression was analyzed in removed tonsils by real-time PCR. Nine PFAPA patients with a median age of 5.3 years (1.7–8 years) and 17 hypertrophic tonsils of patients with a median age of 4.8 years (2.3–8.4 years) participated in this study. Tonsillectomy was performed during afebrile period between PFAPA flares. Three of the nine patients had recurrent episodes of aphthous stomatitis without fever after tonsillectomy. Leukocyte and neutrophil counts were higher in PFAPA patients compared to controls (p?<?0.05). Eosinophil counts were lower in PFAPA patients during flares (p?=?0.006). IL-1β, TNF-α, TGF-β, IL-17, and IFN-γ levels were similar in the tonsils of patients and controls. IL-4 gene expression in the tonsils was lower in PFAPA patients compared to those of the controls (p?=?0.04). Proinflammatory, effector, and regulatory cytokine gene expression in tonsil tissue of PFAPA children removed in a noninflammatory asymptomatic interval and in control patients were similar. However, IL-4 cytokine gene expression in the tonsils and peripheral blood eosinophils were lower in the PFAPA patients suggesting a potential pathogenesis pathway based on an inhibition of Th2 responses.     

A retrospective comparison of proton therapy and carbon ion therapy for stage I non-small cell lung cancer

Background and purpose

This retrospective study aimed to compare the clinical outcomes and late toxicities of proton therapy (PT) with those of carbon ion therapy (CIT) for stage I non-small cell lung cancer (NSCLC).

Material and methods

A total of 111 patients who underwent particle therapy for stage I NSCLC between April 2003 and December 2009 were enrolled in this study. PT (n = 70) and CIT (n = 41) were delivered to total doses of 52.8–80 GyE in 4–26 fractions and 52.8–70.2 GyE in 4–26 fractions, respectively. The median follow-up time was 41 months.

Results

Differences in outcome between the PT and CIT groups regarding 3-year overall survival (72% and 76%, respectively), progression-free survival (44% and 53%, respectively), and local control (81% and 78%, respectively) were not statistically significant. In multivariate analysis, the type of treatment beam did not correlate with overall survival. The severity of late toxicities was comparable between the two groups.

Conclusions

Clinical results in the PT group were comparable to those in the CIT group. However, this study was a retrospective analysis of a highly heterogeneous population. Consequently, more homogeneous prospective data, large multicentric databases and, ideally, randomized trials are warranted.     

Biological evaluation of 3-[18F]fluoro-α-methyl-d-tyrosine (d-[18F]FAMT) as a novel amino acid tracer for positron emission tomography

Objective

3-[¹⁸F]Fluoro-α-methyl-l-tyrosine (l-[¹⁸F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. Because d-amino acids are not well distributed in non-target organs and are rapidly excreted in urine, the d-isomer of [¹⁸F]FAMT could allow clear PET imaging of tumors early after administration. In this study, we prepared 3-[¹⁸F]fluoro-α-methyl-d-tyrosine (d-[¹⁸F]FAMT) and evaluated its usefulness.

Methods

d-[¹⁸F]FAMT was synthesized according to the method for preparation of l-[¹⁸F]FAMT. The in vitro and in vivo stability of [¹⁸F]FAMT were evaluated by high-performance liquid chromatography. Cellular uptake of [¹⁸F]FAMT was evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in LS180 tumor-bearing mice, and the tumors were imaged using a small-animal PET scanner.

Results

The radiolabeling yield of d-[¹⁸F]FAMT was approximately 10 %, similar to that of l-[¹⁸F]FAMT. Over 95 % of d-[¹⁸F]FAMT remained intact in mice until 60 min after administration. d-[¹⁸F]FAMT was gradually taken up by the LS180 cells. Tumor uptake of d-[¹⁸F]FAMT was competitively inhibited by pretreatment with α-methyl-l-tyrosine, a selective substrate for the system l-amino acid transporter 1 (LAT1), suggesting the involvement of LAT1 in tumor uptake of d-[¹⁸F]FAMT. In biodistribution studies, d-[¹⁸F]FAMT showed rapid clearance from the blood, marked accumulation and retention in the tumor, and lower accumulation in non-target organs, especially kidney and pancreas, compared to l-[¹⁸F]FAMT. The amount of d-[¹⁸F]FAMT in the tumor was also reduced, and tumor-to-blood ratio and tumor-to-muscle ratio of d-[¹⁸F]FAMT were similar to those of l-[¹⁸F]FAMT at every time point. PET imaging with d-[¹⁸F]FAMT did not provide a clear image of the tumor early after administration. However, d-[¹⁸F]FAMT provided higher tumor-to-background contrast than l-[¹⁸F]FAMT.

Conclusions

d-[¹⁸F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective imaging compared with l-[¹⁸F]FAMT. Thus, d-[¹⁸F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.