Citations

ABSTRACT We present a case of tenosynovitis caused by a novel, slowly growing, nonchromogenic, nontuberculous mycobacterium (NTM). Originally misidentified as Mycobacterium tuberculosis complex, the NTM cross-reacts with the M. tuberculosis complex nucleic acid hybridization probe, a M. tuberculosis gamma interferon release assay, and is closely related to M. tuberculosis by 16S rRNA gene sequencing.

A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes‐type shrinkage estimator. Six SNPs showed interactions with associated p ‐values ( p int ) <1.1 × 10 −3 . None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER‐negative BC risk in women ≥170 cm (OR = 1.22, p = 0.017), but inversely associated with ER‐negative BC risk in women <160 cm (OR = 0.83, p = 0.039, p int = 1.9 × 10 −4 ). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10 −4 ), and absent in women who had had just one (OR = 0.96, p = 0.19, p int = 6.1 × 10 −4 ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10 −5 ), but no association was observed in current smokers (OR = 1.07, p = 0.14, p int = 3.4 × 10 −4 ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.

Abstract The serine/cysteine protease inhibitor SCCA1 (SERPINB3) is upregulated in many advanced cancers with poor prognosis, but there is limited information about whether it makes functional contributions to malignancy. Here, we show that SCCA1 expression promoted oncogenic transformation and epithelial–mesenchymal transition (EMT) in mammary epithelial cells, and that SCCA1 silencing in breast cancer cells halted their proliferation. SCCA1 overexpression in neu+ mammary tumors increased the unfolded protein response (UPR), IL6 expression, and inflammatory phenotypes. Mechanistically, SCCA1 induced a prolonged nonlethal increase in the UPR that was sufficient to activate NF-κB and expression of the protumorigenic cytokine IL6. Overall, our findings established that SCCA1 contributes to tumorigenesis by promoting EMT and a UPR-dependent induction of NF-κB and IL6 autocrine signaling that promotes a protumorigenic inflammation. Cancer Res; 74(21); 6318–29. ©2014 AACR.

Abstract Background Scientists working in the field of xenotransplantation do not employ a uniform method to measure and report natural and induced antibody responses to non‐ G alα(1,3) G al (non‐ G al) epitopes. Such humoral responses are thought to be particularly pathogenic after transplantation of vascularized Gal TKO pig organs and having a more uniform assay and reporting format would greatly facilitate comparisons between laboratories. Methods Flow cytometry allows examination of antibody reactivity to intact antigens in their natural location and conformation on cell membranes. We have established a simple and reproducible flow cytometric assay to detect antibodies specific for non‐ G al pig antigens using primary porcine aortic endothelial cells ( pAEC s) and cell culture‐adapted pAEC cell lines generated from wild type and α1,3galactosyl transferase knockout (Gal TKO ) swine. Results The consensus protocol we propose here is based on procedures routinely used in four xenotransplantation centers and was independently evaluated at three sites using shared cells and serum samples. Our observation support use of the cell culture‐adapted Gal TKO pAEC KO :15502 cells as a routine method to determine the reactivity of anti‐non‐ G al antibodies in human and baboon serum. Conclusions We have developed an assay that allows the detection of natural and induced non‐Gal xenoreactive antibodies present in human or baboon serum in a reliable and consistent manner. This consensus assay and format for reporting the data should be accessible to laboratories and will be useful for assessing experimental results between multiple research centers. Adopting this assay and format for reporting the data should facilitate the detection, monitoring, and detailed characterization of non‐ G al antibody responses.

Background Chronic migraine (CM) is a disabling disorder characterized by ≥15 headache days per month that has been shown to significantly reduce quality of life. Migraine-prevention guidelines recommend preventive medications as the standard of care for patients with frequent migraine. The aim of this study was to assess adherence to 14 commonly prescribed oral migraine-preventive medications (OMPMs) among patients with CM. Methods Retrospective claims analysis of a US claim database (Truven MarketScan® Databases) was queried to identify patients who were at least 18 years old, diagnosed with CM, and initiated an OMPM (antidepressants, beta blockers, or anticonvulsants) between January 1, 2008 and September 30, 2012. Medication possession ratios (MPR) and proportion of days covered (PDC) were calculated for each patient. A cutoff of ≥80% was used to classify adherence. The odds of adherence between OMPMs were compared using logistic regression models. Results Of the 75,870 patients identified with CM, 8688 met the inclusion/exclusion criteria. Adherence ranged between 26% to 29% at six months and 17% to 20% at 12 months depending on the calculation used to classify adherence (PDC and MPR, respectively). Adherence among the 14 OMPMs was similar except for amitriptyline, nortriptyline, gabapentin, and divalproex, which had significantly lower odds of adherence when compared to topiramate. Conclusion Adherence to OMPMs is low among the US CM population at six months and worsens by 12 months.