Racial Variation in Breast Tumor Promoter Methylation in the Carolina Breast Cancer Study

African American (AA) women are diagnosed with more advanced breast cancers and have worse survival than white women, but a comprehensive understanding of the basis for this disparity remains unclear. Analysis of DNA methylation, an epigenetic mechanism that can regulate gene expression, could help to explain racial differences in breast tumor clinical biology and outcomes

DNA methylation profiling in the Carolina Breast Cancer Study defines cancer subclasses differing in clinicopathologic characteristics and survival

Abstract Introduction Breast cancer is a heterogeneous disease, with several intrinsic subtypes differing by hormone receptor (HR) status, molecular profiles, and prognosis. However, the role of DNA methylation in breast cancer development and progression and its relationship with the intrinsic tumor subtypes are not fully understood. Methods A microarray targeting promoters of cancer-related genes was used to evaluate DNA methylation at 935 CpG sites in 517 breast tumors from the Carolina Breast Cancer Study, a population-based study of invasive breast cancer. Results Consensus clustering using methylation (β) values for the 167 most variant CpG loci defined four clusters differing most distinctly in HR status, intrinsic subtype (luminal versus basal-like), and p53 mutation status. Supervised analyses for HR status, subtype, and p53 status identified 266 differentially methylated CpG loci with considerable overlap. Genes relatively hypermethylated in HR+, luminal A, or p53 wild-type breast cancers included FABP3, FGF2, FZD9, GAS7, HDAC9, HOXA11, MME, PAX6, POMC, PTGS2, RASSF1, RBP1, and SCGB3A1, whereas those more highly methylated in HR-, basal-like, or p53 mutant tumors included BCR, C4B, DAB2IP, MEST, RARA, SEPT5, TFF1, THY1, and SERPINA5. Clustering also defined a hypermethylated luminal-enriched tumor cluster 3 that gene ontology analysis revealed to be enriched for homeobox and other developmental genes (ASCL2, DLK1, EYA4, GAS7, HOXA5, HOXA9, HOXB13, IHH, IPF1, ISL1, PAX6, TBX1, SOX1, and SOX17). Although basal-enriched cluster 2 showed worse short-term survival, the luminal-enriched cluster 3 showed worse long-term survival but was not independently prognostic in multivariate Cox proportional hazard analysis, likely due to the mostly early stage cases in this dataset. Conclusions This study demonstrates that epigenetic patterns are strongly associated with HR status, subtype, and p53 mutation status and may show heterogeneity within tumor subclass. Among HR+ breast tumors, a subset exhibiting a gene signature characterized by hypermethylation of developmental genes and poorer clinicopathologic features may have prognostic value and requires further study. Genes differentially methylated between clinically important tumor subsets have roles in differentiation, development, and tumor growth and may be critical to establishing and maintaining tumor phenotypes and clinical outcomes

Telling partners about chlamydia: how acceptable are the new technologies?

<p>Abstract</p> <p>Background</p> <p>Partner notification is accepted as a vital component in the control of chlamydia. However, in reality, many sexual partners of individuals diagnosed with chlamydia are never informed of their risk. The newer technologies of email and SMS have been used as a means of improving partner notification rates. This study explored the use and acceptability of different partner notification methods to help inform the development of strategies and resources to increase the number of partners notified.</p> <p>Methods</p> <p>Semi-structured telephone interviews were conducted with 40 people who were recently diagnosed with chlamydia from three sexual health centres and two general practices across three Australian jurisdictions.</p> <p>Results</p> <p>Most participants chose to contact their partners either in person (56%) or by phone (44%). Only 17% chose email or SMS. Participants viewed face-to-face as the "gold standard" in partner notification because it demonstrated caring, respect and courage. Telephone contact, while considered insensitive by some, was often valued because it was quick, convenient and less confronting. Email was often seen as less personal while SMS was generally considered the least acceptable method for telling partners. There was also concern that emails and SMS could be misunderstood, not taken seriously or shown to others. Despite these, email and SMS were seen to be appropriate and useful in some circumstances. Letters, both from the patients or from their doctor, were viewed more favourably but were seldom used.</p> <p>Conclusion</p> <p>These findings suggest that many people diagnosed with chlamydia are reluctant to use the new technologies for partner notification, except in specific circumstances, and our efforts in developing partner notification resources may best be focused on giving patients the skills and confidence for personal interaction.</p

InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma

We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids’ quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium.Medicin

Evaluation of Bacterial Glycocalyx Preservation and Staining by Ruthenium Red, Ruthenium Red-Lysine and Alcian Blue for Several Methanotroph and Staphylococcal Species

The cationic reagents, ruthenium red (RR), alcian blue (AB) and ruthenium red -lysine were compared for ultrastructural preservation and staining of the bacterial glycocalyx. En bloc RR, AB and RR-lysine procedures, and a glutaraldehyde/OsO4 fixation withou t cationic reagent, were evaluated by transmission electron microscopy (TEM) for several methanotroph and staphylococcal species. The glutaraldehyde/OsO4 fixation was totally ineffective in preserving or staining the glycocalyx material in all species studied. The RR procedure was more effective than the glutaraldehyde/OsO4 fixation but was generally less so than the RR-lysine procedure. By the RR-lysine procedure, extensive layers that were often filamentous or fibrous were observed in the methanotrophs, and extended fibrous elaborations were seen in the staphylococci. By the AB procedure, staphylococci glycocalyx material consisted of condensed curved structures or net-like features not directly comparable to the RR-lysine images. In the methanotrophs, filamentous or fibrous layers were often comparable between AB and RR-lysine. Thus, ultrastructural observation of the bacterial glycocalyx in all species studied was improved by use of RR-lysine, whereas the use of AB showed species variation

Assessing Occurrence and Biological Consequences of Contaminants of Emerging Concern on Oceanic Islands

Freshwater streams on oceanic islands serve critical ecological and economic functions. However, these are underrepresented in assessments of pollution from contaminants of emerging concern (CEC). Furthermore, freshwater streams and their endemic fauna often have characteristics that are distinct from those of continental streams and model species, calling extrapolations from studies of such systems into question for island streams. In the current study, we assessed the presence of CEC across three sampling events and five freshwater streams on the Island of Hawai&rsquo;i. We also exposed juveniles of the native fish species Sicyopterus stimpsoni to a mixture of commonly co-occurring CEC for 96 h in static renewal experiments, testing for impacts of CEC in two ecologically relevant assays of functional performance. CEC from multiple sources were ubiquitous in Hawaiian streams, including human-use pharmaceuticals, agricultural herbicides, and industrial runoff. Concentrations of CEC were comparable to published studies from continental streams, exceeding total concentrations of 1000 ng/L for the eight quantified CEC in four samples, and approaching 2500 ng/L in one sample. Effects on exposed fish were subtle and limited to treatments with higher CEC concentrations but indicated potential impacts of CEC on locomotor performance. These results indicate that Hawaiian streams follow a global trend of widespread freshwater pollution by CEC that are accompanied by subtle effects on native fish species and highlight the need for the inclusion of endemic species and ecologically relevant assays when assessing the effects of contaminants in island habitats

Dryad_CharacterizationData

The file contains imager characterization data, such as quantum efficiency, fixed pattern noise, concentration detection, filter optical density, filter transmission data

Bio-inspired imager improves sensitivity in near-infrared fluorescence image-guided surgery

Image-guided surgery can enhance cancer treatment by decreasing, and ideally eliminating, positive tumor margins and iatrogenic damage to healthy tissue. Current state-of-the-art near-infrared fluorescence imaging systems are bulky and costly, lack sensitivity under surgical illumination, and lack co-registration accuracy between multimodal images. As a result, an overwhelming majority of physicians still rely on their unaided eyes and palpation as the primary sensing modalities for distinguishing cancerous from healthy tissue. Here we introduce an innovative design, comprising an artificial multispectral sensor inspired by the Morpho butterfly's compound eye, which can significantly improve image-guided surgery. By monolithically integrating spectral tapetal filters with photodetectors, we have realized a single-chip multispectral imager with 1000 x higher sensitivity and 7 x better spatial co-registration accuracy compared to clinical imaging systems in current use. Preclinical and clinical data demonstrate that this technology seamlessly integrates into the surgical workflow while providing surgeons with real-time information on the location of cancerous tissue and sentinel lymph nodes. Due to its low manufacturing cost, our bio-inspired sensor will provide resource-limited hospitals with much-needed technology to enable more accurate value-based health care. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing AgreementAir Force Office of Scientific Research (AFOSR) [FA9550-12-1-0321]; National Institutes of Health (NIH) [NCI R01 CA171651]; National Science Foundation (NSF) [1724615, 1740737]Open access journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]