Metastatic prostate cancer continues to pose a difficult therapeutic challenge. Prostate cancer progression is associated with aberrant O-glycosylation of cancer cell surface receptors, but the functional impact of such events is uncertain. Here we report spontaneous metastasis of human prostate cancer xenografts that express high levels of galectin-4 along with genetic signatures of EGFR-HER2 signaling and O-glycosylation. Galectin-4 expression in clinical specimens of prostate cancer correlated with poor patient survival. Galectin-4 binding to multiple receptor tyrosine kinases stimulated their autophosphorylation, activated expression of pERK, pAkt, fibronectin, and Twist1, and lowered expression of E-cadherin, thereby facilitating epithelial-mesenchymal transition, invasion, and metastasis. In vivo investigations established that galectin-4 expression enabled prostate cancer cells to repopulate tumors in orthotopic and heterotopic tissues. Notably, these effects of galectin-4 relied upon O-glycosylation mediated by C1GALT1, a galactosyltransferase implicated in other cancers. Parallel changes in galectin-4 and O-glycosylation triggered aberrant receptor signaling and more aggressive invasive character in prostate cancer cells, which through better survival in the circulation also contributed to the bulk cell progeny of distal tumors. Our findings establish galectin-4 and C1GALT1-mediated glycosylation in a signaling axis that is activated during prostate cancer progression, with implications for therapeutic targeting of advanced metastatic disease. Cancer Res; 76(19); 5756-67. ©2016 AACR.

Preparation of a high-concentration Au nanoring (NR) water solution and its applications to the enhancement of image contrast in optical coherence tomography (OCT) and the generation of the photothermal effect in a bio-sample through localized surface plasmon (LSP) resonance are demonstrated. Au NRs are first fabricated on a sapphire substrate with colloidal lithography and secondary sputtering of Au, and then transferred into a water solution through a liftoff process. By controlling the NR geometry, the LSP dipole resonance wavelength in tissue can cover a spectral range of 1300 nm for OCT scanning of deep tissue penetration. The extinction cross sections of the fabricated Au NRs in water are estimated to give levels of 10(-10)-10(-9) cm(2) near their LSP resonance wavelengths. The fabricated Au NRs are then delivered into pig adipose samples for OCT scanning. It is observed that, when resonant Au NRs are delivered into such a sample, LSP resonance-induced Au NR absorption results in a photothermal effect, making the opaque pig adipose cells transparent. Also, the delivered Au NRs in the intercellular substance enhance the image contrast of OCT scanning through LSP resonance-enhanced scattering. By continuously OCT scanning a sample, both photothermal and image contrast enhancement effects are observed. However, by continually scanning a sample with a low scan frequency, only the image contrast enhancement effect is observed.

Abstract:Fractional photothermolysis induced by non-ablative fractional lasers (NAFLs) or ablative fractional lasers (AFLs) can remodel the skin, regenerate collagen, and remove tumor tissue. However, fractional laser treatments may result in severe side effects, and multiple treatments are required to achieve the expected outcome. Thus, the treatment outcome and downtime after fractional laser treatments are key issues to determine the following treatment strategy. In this study, an optical coherence tomography (OCT) system was implemented for in vivo studies of wound healing after NAFL and AFL treatments. According to the OCT scanning results, the laser-induced photothermolysis including volatilization and coagulation could be morphologically identified. To continue monitoring the wound healing process, the treated regions were scanned with OCT at different time points, and the en-face images at various tissue depths were extracted from three-dimensional OCT images. Furthermore, to quantitatively evaluate the morphological changes at different tissue depths during wound healing, an algorithm was developed to distinguish the backscattering properties of untreated and treated tissues. The results showed that the coagulation damage induced by the NAFLs could be rapidly healed in 6 days. In contrast, the tissue volatilization induced by AFLs required a longer recovery time of 14 days. In conclusion, this study establishes the feasibility of this methodology as a means of clinically monitoring treatment outcomes and wound healing after fractional laser treatments. References and links 1. T. S. Alster and S. Garg, "Treatment of facial rhytides with a high-energy pulsed carbon dioxide laser," Plast. ©2013 Optical Society of AmericaReconstr. Surg. 98(5), 791-794 (1996). 2. C. B. Zachary, "Modulating the Er:YAG laser," Lasers Surg. Med. 26(2), 223-226 (2000).

We report the first experimental demonstration of curvature-tunable random lasers to control the transport mean free path of emitted photons.