SUMMARY Exosomes are secreted by all cell types and contain proteins and nucleic acids. Here, we report that breast cancer associated exosomes contain microRNAs (miRNAs) associated with the RISC Loading Complex (RLC) and display cell-independent capacity to process precursor microRNAs (pre-miRNAs) into mature miRNAs. Pre-miRNAs, along with Dicer, AGO2, and TRBP, are present in exosomes of cancer cells. CD43 mediates the accumulation of Dicer specifically in cancer exosomes. Cancer exosomes mediate an efficient and rapid silencing of mRNAs to reprogram the target cell transcriptome. Exosomes derived from cells and sera of patients with breast cancer instigate non-tumorigenic epithelial cells to form tumors in a Dicer-dependent manner. These findings offer opportunities for the development of exosomes based biomarkers and therapies.

This article reports the development of an optical imaging technique, confocal light absorption and scattering spectroscopic (CLASS) microscopy, capable of noninvasively determining the dimensions and other physical properties of single subcellular organelles. CLASS microscopy combines the principles of lightscattering spectroscopy (LSS) with confocal microscopy. LSS is an optical technique that relates the spectroscopic properties of light elastically scattered by small particles to their size, refractive index, and shape. The multispectral nature of LSS enables it to measure internal cell structures much smaller than the diffraction limit without damaging the cell or requiring exogenous markers, which could affect cell function. Scanning the confocal volume across the sample creates an image. CLASS microscopy approaches the accuracy of electron microscopy but is nondestructive and does not require the contrast agents common to optical microscopy. It provides unique capabilities to study functions of viable cells, which are beyond the capabilities of other techniques.light-scattering spectroscopy ͉ submicrometer ͉ native contrast ͉ imaging ͉ refractive index

Esophageal cancer is increasing in frequency in the United States faster than any other cancer. Barrett's esophagus, an otherwise benign complication of esophageal reflux, affects approximately three million Americans and precedes almost all cases of esophageal cancer. If detected as highgrade dysplasia (HGD), most esophageal cancers can be prevented. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is highly focal and visually indistinguishable. We developed a system called endoscopic polarized scanning spectroscopy (EPSS), which performs rapid optical scanning and multispectral imaging of the entire esophageal surface and provides diagnoses in near real time. By detecting and mapping suspicious sites, guided biopsy of invisible, precancerous dysplasia becomes practicable. Here we report the development of EPSS and its application in several clinical cases, one of which merits special consideration.Previously we demonstrated that spectroscopic information in light scattered by nuclei could reveal precancer cellular changes 1 . The first application of light-scattering spectroscopy successfully detected dysplasia in Barrett's esophagus 1-5 using a fiber optic probe that illuminated 1 mm 2 of tissue. Searching the entire area of a diseased esophagus with a singlepoint probe is clinically impractical.Correspondence should be addressed to L.T.P. (ltperel@bidmc.harvard.edu). Note: Supplementary information is available on the Nature Medicine website. AUTHOR CONTRIBUTIONSL.Q., E.V., M.D.M., E.B.H., I.I. and L.T.P. developed and evaluated the method; S.I., L.Q. and E.V. contributed codes for instrument control; D.K.P., R.C., J.D.G., J.L., N.O., L.G., L.Q. and A.S. performed clinical procedures; L.Q., D.K.P., R.C., E.B.H., I.I. and L.T.P. contributed to the writing of the manuscript; E.B.H., I.I., D.K.P., R.C. and L.T.P. designed and planned the project. COMPETING FINANCIAL INTERESTSThe authors declare no competing financial interests.Reprints and permissions information is available online at http://npg.nature.com/reprintsandpermissions/. Since then, several new approaches have been explored using high-resolution endoscopy (HRE) combined with narrow band imaging (NBI) 6 , autofluorescence imaging (AFI) 7 , trimodal imaging 8 , which is a combination of the previous three, and confocal laser endomicroscopy 9 . These techniques showed promise in increased detection of dysplasia in Barrett's esophagus, although none has as yet achieved clinical acceptance. NIH Public AccessA clinically useful technique in the detection of dysplasia in Barrett's esophagus must rapidly survey a comparatively large area while simultaneously detecting changes on a cellular scale. We felt we could achieve both goals by combining an endoscopically compatible scanning instrument with polarized light-scattering spectroscopy (PLSS) 5...