Comparison of single versus fractionated dose of stereotactic radiotherapy for salvaging local failures of nasopharyngeal carcinoma: a matched-cohort analysis

BACKGROUND: Local failure is an important cause of morbidity and mortality in nasopharyngeal carcinoma (NPC). Although surgery or brachytherapy may be feasible in selected cases, most patients with local failure require external beam re-irradiation. Stereotactic radiation using single or multiple fractions have been employed in re-irradiation of NPC, but the optimal fractionation scheme and dose are not clear. METHODS: Records of 125 NPC patients who received salvage stereotactic radiation were reviewed. A matched-pair design was used to select patients with similar prognostic factors who received stereotactic re-irradiation using single fraction (SRS) or multiple fractions (SRM). Eighty-six patients were selected with equal number in SRS and SRM groups. All patients were individually matched for failure type (persistent or recurrent), rT stage (rT1-2 or rT3-4), and tumor volume (5-10 cc, or >10 cc). Median dose was 12.5 Gy in single fraction by SRS, and 34 Gy in 2-6 fractions by SRM. RESULTS: Local control rate was better in SRM group although overall survival rates were similar. One- and 3-year local failure-free rates were 70% and 51% in SRS group compared with 91% and 83% in SRM group (p = 0.003). One- and 3-year overall survival rates were 98% and 66% in SRS group compared with 78% and 61% in SRM group (p = 0.31). The differences in local control were mainly observed in recurrent or rT2-4 disease. Incidence of severe late complications was 33% in SRS group vs. 21% in SRM group, including brain necrosis (16% vs. 12%) and hemorrhage (5% vs. 2%). CONCLUSION: Our study showed that SRM was superior to SRS in salvaging local failures of NPC, especially in the treatment of recurrent and rT2-4 disease. In patient with local failure of NPC suitable for stereotactic re-irradiation, use of fractionated treatment is preferred.link_to_subscribed_fulltex

Plasmodium berghei Hsp90 contains a natural immunogenic I-A^b-restricted antigen common to rodent and human Plasmodium species

Thorough understanding of the role of CD4 T cells in immunity can be greatly assisted by the study of responses to defined specificities. This requires knowledge of Plasmodium-derived immunogenic epitopes, of which only a few have been identified, especially for the mouse C57BL/6 background. We recently developed a TCR transgenic mouse line, termed PbT-II, that produces CD4+ T cells specific for an MHC class II (I-Ab)-restricted Plasmodium epitope and is responsive to both sporozoites and blood-stage P. berghei. Here, we identify a peptide within the P. berghei heat shock protein 90 as the cognate epitope recognised by PbT-II cells. We show that C57BL/6 mice infected with P. berghei blood-stage induce an endogenous CD4 T cell response specific for this epitope, indicating cells of similar specificity to PbT-II cells are present in the naïve repertoire. Adoptive transfer of in vitro activated TH1-, or particularly TH2-polarised PbT-II cells improved control of P. berghei parasitemia in C57BL/6 mice and drastically reduced the onset of experimental cerebral malaria. Our results identify a versatile, potentially protective MHC-II restricted epitope useful for exploration of CD4 T cell-mediated immunity and vaccination strategies against malaria

Characterization of Novel and Uncharacterized p53 SNPs in the Chinese Population – Intron 2 SNP Co-Segregates with the Common Codon 72 Polymorphism

Multiple single nucleotide polymorphisms (SNPs) have been identified in the tumor suppressor gene p53, though the relevance of many of them is unclear. Some of them are also differentially distributed in various ethnic populations, suggesting selective functionality. We have therefore sequenced all exons and flanking regions of p53 from the Singaporean Chinese population and report here the characterization of some novel and uncharacterized SNPs - four in intron 1 (nucleotide positions 8759/10361/10506/11130), three in intron 3 (11968/11969/11974) and two in the 3′UTR (19168/19514). Allelic frequencies were determined for all these and some known SNPs, and were compared in a limited scale to leukemia and lung cancer patient samples. Intron 2 (11827) and 7 (14181/14201) SNPs were found to have a high minor allele frequency of between 26–47%, in contrast to the lower frequencies found in the US population, but similar in trend to the codon 72 polymorphism (SNP12139) that shows a distribution pattern correlative with latitude. Several of the SNPs were linked, such as those in introns 1, 3 and 7. Most interestingly, we noticed the co-segregation of the intron 2 and the codon 72 SNPs, the latter which has been shown to be expressed in an allele-specific manner, suggesting possible regulatory cross-talk. Association analysis indicated that the T/G alleles in both the co-segregating intron 7 SNPs and a 4tagSNP haplotype was strongly associated increased susceptibility to lung cancer in non-smoker females [OR: 1.97 (1.32, 3.394)]. These data together demonstrate high SNP diversity in p53 gene between different populations, highlighting ethnicity-based differences, and their association with cancer risk

Investigation of Semiconductor Quantum Dots for Waveguide Electroabsorption Modulator

In this work, we investigated the use of 10-layer InAs quantum dot (QD) as active region of an electroabsorption modulator (EAM). The QD-EAM is a p-i-n ridge waveguide structure with intrinsic layer thickness of 0.4 μm, width of 10 μm, and length of 1.0 mm. Photocurrent measurement reveals a Stark shift of ~5 meV (~7 nm) at reverse bias of 3 V (75 kV/cm) and broadening of the resonance peak due to field ionization of electrons and holes was observed for E-field larger than 25 kV/cm. Investigation at wavelength range of 1,300–1320 nm reveals that the largest absorption change occurs at 1317 nm. Optical transmission measurement at this wavelength shows insertion loss of ~8 dB, and extinction ratio of ~5 dB at reverse bias of 5 V. Consequently, methods to improve the performance of the QD-EAM are proposed. We believe that QDs are promising for EAM and the performance of QD-EAM will improve with increasing research efforts

Validation of a new prognostic index score for disseminated nasopharyngeal carcinoma

Patients with metastatic nasopharyngeal carcinoma have variable survival outcomes. We previously designed a scoring system to better prognosticate these patients. Here, we report results on validation of this new prognostic index score in a separate cohort of patients. Clinical features and laboratory parameters were examined in 172 patients with univariate and multivariate analyses and a numerical score was derived for each independent prognostic variable. Significant independent prognostic variables and their scores assigned included poor performance status (score 5), haemoglobin <12 g dl−1 (score 4) and disease-free interval (DFI) (DFI⩽6 months (score 10) or metastases at initial diagnosis (score 1)). Maximum score was 19 and patients stratified into three prognostic groups: good, 0–3; intermediate, 4–8; poor, ⩾9. When applied to a separate cohort of 120 patients, 59 patients were good, 43 intermediate and 18 poor prognosis, with median survivals of 19.6 (95% CI 16.1, 23.1), 14.3 (95% CI 12.3, 16.2) and 7.9 (95% CI 6.6, 9.2) months, respectively. (logrank test: P=0.003). We have validated a new prognostic score with factors readily available in the clinics. This simple score will prove useful as a method to prognosticate and stratify patients as well as to promote consistent reporting among clinical trials

Heat shock proteins in stabilization of spontaneously restored sinus rhythm in permanent atrial fibrillation patients after mitral valve surgery

A spontaneously restored sinus rhythm in permanent atrial fibrillation patients has been often observed after mitral valve (MV) surgery, but persisting duration in sinus rhythm varies from patient to patient. Heat shock proteins (Hsps) may be involved in pathogenesis of atrial fibrillation. We hypothesized that stabilization of restored sinus rhythm is associated with expression of Hsps in the atria. To test this hypothesis, clinical data, biopsies of right atrial appendage, and blood samples were collected from 135 atrial fibrillation patients who spontaneously restored sinus rhythm after conventional isolated MV replacement. Comparison was made between patients who had recurrence of atrial fibrillation within 7 days (AF) vs. patients with persisted sinus rhythm for more than 7 days (SR). Results showed that SR patients had higher activity of heat shock transcription factor 1 (HSF1) as well as upregulated expressions of heat shock cognate 70, Hsp70, and Hsp27 in the tissues. The activation of HSF1–Hsps pathway was associated with less-aggressive pathogenesis as reflected by lower rates of myolysis, apoptosis, interstitial fibrosis, and inflammation in SR patients. However, Hsp60 was lower in both tissue and plasma in SR patients, and was positively correlated with apoptosis, interstitial fibrosis, and inflammation. These findings suggest that the Hsps play important roles in stabilization of restored sinus rhythm after MV surgery by inhibiting AF-related atrial remodeling and arrhythmogenic substrates in atrial fibrillation patients. Low circulating Hsp60 levels preoperatively might predict a stable spontaneously restored sinus rhythm postoperatively

Judgment of Learning Accuracy in High-functioning Adolescents and Adults with Autism Spectrum Disorder

This study explored whether adults and adolescents with autism spectrum disorder (ASD) demonstrate difficulties making metacognitive judgments, specifically judgments of learning. Across two experiments, the study examined whether individuals with ASD could accurately judge whether they had learnt a piece of information (in this case word pairs). In Experiment 1, adults with ASD demonstrated typical accuracy on a standard ‘cue-alone’ judgment of learning (JOL) task, compared to age- and IQmatched neurotypical adults. Additionally, in Experiment 2, adolescents with ASD demonstrated typical accuracy on both a standard ‘cue-alone’ JOL task, and a ‘cue-target’ JOL task. These results suggest that JOL accuracy is unimpaired in ASD. These results have important implications for both theories of metacognition in ASD and educational practise

Effects of edible bird's nest (EBN) on cultured rabbit corneal keratocytes

<p>Abstract</p> <p>Background</p> <p>There has been no effective treatment or agent that is available for corneal injury in promoting corneal wound healing. Previous studies on edible bird's nest extract (EBN) had reported the presence of hormone-like substance; avian epidermal growth factor that could stimulate cell division and enhance regeneration. This study aimed to investigate the effects of EBN on corneal keratocytes proliferative capacity and phenotypical changes.</p> <p>Methods</p> <p>Corneal keratocytes from six New Zealand White Rabbits were isolated and cultured until Passage 1. The proliferative effects of EBN on corneal keratocytes were determined by MTT assay in serum-containing medium (FDS) and serum-free medium (FD). Keratocytes phenotypical changes were morphologically assessed and gene expression of aldehyde dehydrogenase (ALDH), collagen type 1 and lumican were determined through RT-PCR.</p> <p>Results</p> <p>The highest cell proliferation was observed when both media were supplemented with 0.05% and 0.1% EBN. Cell proliferation was also consistently higher in FDS compared to FD. Both phase contrast micrographs and gene expression analysis confirmed the corneal keratocytes retained their phenotypes with the addition of EBN.</p> <p>Conclusions</p> <p>These results suggested that low concentration of EBN could synergistically induce cell proliferation, especially in serum-containing medium. This could be a novel breakthrough as both cell proliferation and functional maintenance are important during corneal wound healing. The in vitro test is considered as a crucial first step for nutri-pharmaceutical formation of EBN-based eye drops before in vivo application.</p