Therapeutic targeting of integrin αvβ6 in breast cancer

BACKGROUND: Integrin ?v?6 promotes migration, invasion, and survival of cancer cells; however, the relevance and role of ?v?6 has yet to be elucidated in breast cancer.METHODS: Protein expression of integrin subunit beta6 (?6) was measured in breast cancers by immunohistochemistry (n &gt; 2000) and ITGB6 mRNA expression measured in the Molecular Taxonomy of Breast Cancer International Consortium dataset. Overall survival was assessed using Kaplan Meier curves, and bioinformatics statistical analyses were performed (Cox proportional hazards model, Wald test, and Chi-square test of association). Using antibody (264RAD) blockade and siRNA knockdown of ?6 in breast cell lines, the role of ?v?6 in Human Epidermal Growth Factor Receptor 2 (HER2) biology (expression, proliferation, invasion, growth in vivo) was assessed by flow cytometry, MTT, Transwell invasion, proximity ligation assay, and xenografts (n ? 3), respectively. A student's t-test was used for two variables; three-plus variables used one-way analysis of variance with Bonferroni's Multiple Comparison Test. Xenograft growth was analyzed using linear mixed model analysis, followed by Wald testing and survival, analyzed using the Log-Rank test. All statistical tests were two sided.RESULTS: High expression of either the mRNA or protein for the integrin subunit ?6 was associated with very poor survival (HR = 1.60, 95% CI = 1.19 to 2.15, P = .002) and increased metastases to distant sites. Co-expression of ?6 and HER2 was associated with worse prognosis (HR = 1.97, 95% CI = 1.16 to 3.35, P = .01). Monotherapy with 264RAD or trastuzumab slowed growth of MCF-7/HER2-18 and BT-474 xenografts similarly (P &lt; .001), but combining 264RAD with trastuzumab effectively stopped tumor growth, even in trastuzumab-resistant MCF-7/HER2-18 xenografts.CONCLUSIONS: Targeting ?v?6 with 264RAD alone or in combination with trastuzumab may provide a novel therapy for treating high-risk and trastuzumab-resistant breast cancer patients.<br/

Spectroscopic time series performance of the Mid-Infrared Instrument on the JWST

We present here the first ever mid-infrared spectroscopic time series observation of the transiting exoplanet \object{L 168-9 b} with the Mid-Infrared Instrument (MIRI) on the James Webb Space Telescope. The data were obtained as part of the MIRI commissioning activities, to characterize the performance of the Low Resolution Spectroscopy (LRS) mode for these challenging observations. To assess the MIRI LRS performance, we performed two independent analyses of the data. We find that with a single transit observation we reached a spectro-photometric precision of $\sim$50 ppm in the 7-8 \micron range at R=50, consistent with $\sim$25 ppm systematic noise. The derived band averaged transit depth is 524 $\pm$ 15 ppm and 547 $\pm$ 13 ppm for the two applied analysis methods, respectively, recovering the known transit depth to within 1 $\sigma$. The measured noise in the planet's transmission spectrum is approximately 15-20 \% higher than random noise simulations over wavelengths $6.8 \lesssim \lambda \lesssim 11$ $\mu$m. \added{We observed an larger excess noise at the shortest wavelengths of up to a factor of two, for which possible causes are discussed.} This performance was achieved with limited in-flight calibration data, demonstrating the future potential of MIRI for the characterization of exoplanet atmospheres.Comment: Accepted for publishing in PASP, 21 pages, 10 figure

The Mid-infrared Instrument for JWST and Its In-flight Performance

The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Spectroscopic Time Series Performance of the Mid-infrared Instrument on the JWST

We present here the first ever mid-infrared spectroscopic time series observation of the transiting exoplanet L 168-9 b with the Mid-Infrared Instrument (MIRI) on the James Webb Space Telescope. The data were obtained as part of the MIRI commissioning activities, to characterize the performance of the Low Resolution Spectroscopy (LRS) mode for these challenging observations. To assess the MIRI LRS performance, we performed two independent analyses of the data. We find that with a single transit observation we reached a spectro-photometric precision of ∼50 ppm in the 7-8 μm range at R = 50, consistent with ∼25 ppm systematic noise. The derived band averaged transit depth is 524 ± 15 ppm and 547 ± 13 ppm for the two applied analysis methods, respectively, recovering the known transit depth to within 1σ. The measured noise in the planet’s transmission spectrum is approximately 15%-20% higher than random noise simulations over wavelengths 6.8 ≲ λ ≲ 11 μm. We observed an larger excess noise at the shortest wavelengths of up to a factor of two, for which possible causes are discussed. This performance was achieved with limited in-flight calibration data, demonstrating the future potential of MIRI for the characterization of exoplanet atmospheres.</p