No abstract

Although bladder cancer is commonly chemosensitive to standard first-line therapy, the acquisition of the resistance to cisplatin (DDP)-based therapeutic regimens remains a huge challenge. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs, have been reported to play a critical role in cancer resistance to DDP.Here, we attempted to provide a novel mechanism by which the resistance of bladder cancer to DDP treatment could be modulated from the perspective of ncRNA regulation.We demonstrated that lncRNA MST1P2 (lnc-MST1P2) expression was dramatically upregulated, whereas miR-133b expression was downregulated in DDP-resistant bladder cancer cell lines, SW 780/DDP and RT4/DDP. Lnc-MST1P2 and miR-133b negatively regulated each other via targeting miR-133b. Both lnc-MST1P2 silence and miR-133b overexpression could resensitize DDP-resistant bladder cancer cells to DDP treatment. More important, miR-133b could directly target the Sirt1 3′-untranslated region to inhibit its expression. Inc-MST1P2/miR-133b axis affected the resistance of bladder cancer cells to DDP via Sirt1/p53 signaling. In conclusion, MST1P2 serves as a competing endogenous RNA for miR-133b to counteract miR-133b-induced suppression on Sirt1, therefore enhancing the resistance of bladder cancer cells to DDP. MST1P2/miR-133b axis affects the resistance of bladder cancer cells to DDP via downstream Sirt1/p53 signaling. K E Y W O R D S bladder cancer, chemoresistance, cisplatin, miR-133b, MST1P2, Sirt1/p53 signaling

A high frame-rate near-infrared (NIR) tomography system was created to allow transmission imaging of thick tissues with spectral encoding for parallel source implementation. The design was created to maximize tissue penetration through up to 10 cm of tissue, allowing eventual use in human imaging. Eight temperature-controlled laser diodes (LD) are used in parallel with 1.5 nm shifts in their lasing wavelengths. Simultaneous detection is achieved with eight high-resolution, CCD-based spectrometers that were synchronized to detect the intensities and decode their source locations from the spectrum. Static and dynamic imaging is demonstrated through a 64 mm tissueequivalent phantom, with acquisition rates up to 20 frames per second. Imaging of pulsatile absorption changes through a 72 mm phantom was demonstrated with a 0.5 Hz varying object having only 1% effect upon the transmitted signal. This subtle signal change was used to show that while reconstructing the signal changes in a tissue may not be possible, image-guided recovery of the pulsatile change in broad regions of tissue was possible. The ability to image thick tissue and the capacity to image periodic changes in absorption makes this design well suited for tracking thick tissue hemodynamics in vivo during MR or CT imaging.

A near-IR (NIR) tomography system with spectral-encoded sources was built to quantify the temporal contrast in human breast tissue using guidance from magnetic resonance imaging. The systems were integrated with a custom breast coil interface to provide simultaneous acquisition. The NIR signal was synchronized to simultaneous finger pulse oximeter plethysmogram, which offered a frequency reference. A 0:1 s temporal delay of the absorption pulse within adipose tissue relative to fibroglandular tissue was found, in an initial human study, showing the potential for novel contrast imaging of fast flow signals in deep tissue.

Maintaining a sharp lateral dose falloff in pencil beam scanning (PBS) proton therapy is crucial for sparing organs at risk (OARs), especially when they are in close proximity to the target volume. The most common approach to improve lateral dose falloff is through the use of physical beam shaping devices, such as brass apertures or collimator based systems. A recently proposed approach focuses on proton beam spot placements, moving away from traditional grid-based placements to concentric-contours based schemes. This improves lateral dose falloff in two ways: (1) by better conforming all spots to the tumor boundary and (2) allowing for ‘edge enhancement’, where boundary spots deliver higher fluence than more central spots, thereby creating a steeper lateral dose falloff. However, these benefits come at the expense of maintaining uniformity of spot distribution inside the target volume. In this work we have developed a new optimized spot placement scheme that provides robust spot distributions inside the target. This approach achieves the boundary conformity of a concentric-contours based approach and uses a fast-iterative method to distribute the interior spots in a highly uniform fashion in an attempt to improve both the lateral dose falloff and uniformity. Furthermore, we quantified the impact of this new approach through direct comparison with grid, contour, and hybrid spot placements schemes, showing improvements for this new approach. The results were validated in homogeneous medium for two different target shapes having concave and convex geometry.