Jian Yang

© 2015 Macmillan Publishers Limited. Matrix stiffness potently regulates cellular behaviour in various biological contexts. In breast tumours, the presence of dense clusters of collagen fibrils indicates increased matrix stiffness and correlates with poor survival. It is unclear how mechanical inputs are transduced into transcriptional outputs to drive tumour progression. Here we report that TWIST1 is an essential mechanomediator that promotes epithelial-mesenchymal transition in response to increasing matrix stiffness. High matrix stiffness promotes nuclear translocation of TWIST1 by releasing TWIST1 from its cytoplasmic binding partner G3BP2. Loss of G3BP2 leads to constitutive TWIST1 nuclear localization and synergizes with increasing matrix stiffness to induce EMT and promote tumour invasion and metastasis. In human breast tumours, collagen fibre alignment, a marker of increasing matrix stiffness, and reduced expression of G3BP2 together predict poor survival. Our findings reveal a TWIST1-G3BP2 mechanotransduction pathway that responds to biomechanical signals from the tumour microenvironment to drive EMT, invasion and metastasis.

© 2017 American Chemical Society.Linoleic acid and a-linolenic acid in plant or algae oils are precursors to oxidized fatty acid metabolites known as oxylipins. Liquid chromatography tandem mass spectrometry was used to quantify oxylipins in soybean, corn, olive, canola, and four high-oleic acid algae oils at room temperature or after heating for 10 min at 100 °C. Flaxseed oil oxylipin concentrations were determined in a follow-up experiment that compared it to soybean, canola, corn, and olive oil. Published consumption data for soybean, canola, corn, and olive oil were used to estimate daily oxylipin intake. The LA and ALA fatty acid composition of the oils was generally related to their respective oxylipin metabolites, except for olive and flaxseed oil, which had higher LA derived monohydroxy and ketone oxylipins than other oils, despite their low LA content. Algae oils had the least amount of oxylipins. The change in oxylipin concentrations was not significantly different among the oils after short-term heating. The estimated oxylipin intake from nonheated soybean, canola, corn, and olive oil was 1.1 mg per person per day. These findings suggest that oils represent a dietary source of LA and ALA derived oxylipins and that the response of oils to short-term heating does not differ among the various oils.

Background: Research is limited on the independent and joint effects of individual- and neighborhood-level socioeconomic status on breast cancer survival across different racial/ethnic groups. Methods: We studied individual-level SES, measured by self-reported education, and a composite neighborhood SES measure in females, ages 18 to 79 years and diagnosed 1995 to 2008, in the San Francisco Bay Area. We evaluated all-cause and breast cancer-specific survival using stage-stratified Cox proportional hazards models with cluster adjustment for census block groups. Results: In models adjusting for education and nSES, lower nSES was associated with worse all-cause survival among African-Americans, Hispanics, and Asian-Americans. Education was not associated with all-cause survival. For breast cancer-specific survival, lower nSES was associated with poorer survival only among Asian-Americans. When nSES and education were jointly considered, women with low education and low nSES had 1.4 to 2.7 times worse all-cause survival than women with high education and high nSES across all races/ethnicities. Among African-Americans and Asian- Americans, women with high education and low nSES had 1.6 to 1.9 times worse survival, respectively. For breast cancer-specific survival, joint associations were found only among Asian-Americans with worse survival for those with low nSES regardless of education. Conclusions: Both neighborhood and individual SES are associated with survival after breast cancer diagnosis, but these relationships vary by race/ethnicity. Impact: A better understanding of the relative contributions and interactions of SES with other factors will inform targeted interventions toward reducing long-standing disparities in breast cancer survival. © 2014 American Association for Cancer Research.

IMPORTANCE: Mycosis fungoides and Sézary syndrome are rare in children and young adults, and thus the incidence and outcomes in this patient population are not well studied. OBJECTIVE: To assess the incidence and outcomes of MF/SS in patients diagnosed before 30 years of age. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of 2 population-based cancer registries - the California Cancer Registry and 9 US cancer registries of the Surveillance, Epidemiology, and End Results program - for patients diagnosed with MF/SS before 30 years of age. MAIN OUTCOMES AND MEASURES Overall survivalwas calculated by the Kaplan-Meier method. The risk of a second cancer was assessed by calculating the standard incidence ratio comparing observed cancer incidence in patients with MF/SS with the expected incidence in the age-, sex-, and race-standardized general population. RESULTS: The incidence of MF/SS is rare before 30 years of age, with an incidence rate of 0.05 per 100 000 persons per year before age 20 years and 0.12 per 100 000 persons per year between ages 20 and 29 years in the California Cancer Registry. At 10 years, patients with MF/SS had an overall survival of 94.3% in the California Cancer Registry and 88.9% in SEER 9. In SEER 9, there was a significant excess risk of all types of second cancers combined, particularly lymphoma and melanoma. In the California Cancer Registry, the SIR for risk of all types of second cancers was similar to that in SEER 9, although not statistically significant. CONCLUSIONS AND RELEVANCE: Young patients with MF/SS have a favorable outcome, despite a strong suggestion of an increased risk of second primary cancers. Prolonged follow-up is warranted to definitively assess their risk of developing second cancers in a lifetime. Copyright 2014 American Medical Association. All rights reserved.