https://www.cell.com/trends/pharmacological-sciences/pdf/S0165-6147(12)00017-X.pdf

Hypoxia-inducible factors: Mediators of cancer progression and targets for cancer therapy

Photoacoustic imaging is a promising method for visualizing biological tissues with optical absorbers. This article provides an overview of the rapidly developing field of photoacoustic imaging. Photoacoustics, the physical basis of photoacoustic imaging, is analyzed briefly. The merits of photoacoustic technology, compared with optical imaging and ultrasonic imaging, are described. Various imaging techniques are also discussed, including scanning tomography, computed tomography and original detection of photoacoustic imaging. Finally, some biomedical applications of photoacoustic imaging are summarized.

Photoacoustic imaging in biomedicine

/pdf/cancer-stem-cells-and-drug-resistance-the-potential-of-2yhm8xdpth.pdf

Cancer stem cells and drug resistance: the potential of nanomedicine.

Radiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia–telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (poly[ADP-ribose] polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.

/pdf/dna-damage-response-signaling-pathways-and-targets-for-4c7h0c5hhc.pdf

DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer.

Pancreatic ductal adenocarcinoma is one of the most intractable and fatal cancer. The decreased blood vessel density displayed by this tumor not only favors its resistance to chemotherapy but also participates in its aggressiveness due to the consequent high degree of hypoxia. It is indeed clear that hypoxia promotes selective pressure on malignant cells that must develop adaptive metabolic responses to reach their energetic and biosynthetic demands. Here, using a well-defined mouse model of pancreatic cancer, we report that hypoxic areas from pancreatic ductal adenocarcinoma are mainly composed of epithelial cells harboring epithelial-mesenchymal transition features and expressing glycolytic markers, two characteristics associated with tumor aggressiveness. We also show that hypoxia increases the "glycolytic" switch of pancreatic cancer cells from oxydative phosphorylation to lactate production and we demonstrate that increased lactate efflux from hypoxic cancer cells favors the growth of normoxic cancer cells. In addition, we show that glutamine metabolization by hypoxic pancreatic tumor cells is necessary for their survival. Metabolized glucose and glutamine converge toward a common pathway, termed hexosamine biosynthetic pathway, which allows O-linked N-acetylglucosamine modifications of proteins. Here, we report that hypoxia increases transcription of hexosamine biosynthetic pathway genes as well as levels of O-glycosylated proteins and that O-linked N-acetylglucosaminylation of proteins is a process required for hypoxic pancreatic cancer cell survival. Our results demonstrate that hypoxia-driven metabolic adaptive processes, such as high glycolytic rate and hexosamine biosynthetic pathway activation, favor hypoxic and normoxic cancer cell survival and correlate with pancreatic ductal adenocarcinoma aggressiveness.

https://www.pnas.org/content/pnas/110/10/3919.full.pdf

Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma

In this paper, the development of weighted nonlinear beamformer, called as Filtered Delay Weighted Multiply and Sum (F-DwMAS) is reported. This method was investigated on Synthetic Transmit Aperture (STA) technique. The performance of the developed F-DwMAS method was compared with Delay and Sum (DAS) and recently introduced F-DMAS beamforming methods. Importantly, in the method proposed, an extra window stage is added after the delay stage in the F-DMAS method. The different methods of DAS, F-DMAS and F-DwMAS were compared in terms of the resulting image quality metrics, Lateral Resolution (LR), Axial Resolution (AR), Contrast Ratio (CR) and contrast-to-noise ratio (CNR), in experiments on tissue-mimicking phantoms. Experimental results show that, for STA technique, F-DwMAS resulted in improvements of AR by 46.91% and 30.19%, LR by 61.35% and 52.48%, CR by 84.68% and 27.51%, and CNR by 5.45% and 34.4% compared to those obtained using DAS and F-DMAS, respectively. Hence, it can be concluded that the image quality is improved by F-DwMAS compared to DAS and F-DMAS.

A Weighted Non-Linear Beamformer for Synthetic Aperture Ultrasound Imaging

Importance of Axial Compression Verification to Correct Interpretation of Axial-Shear Strain Elastograms in Breast Lesions

Novel spatio-temporal non-linear beamformers for sparse synthetic aperture ultrasound imaging.

In this paper, a new method inspired by the synthetic aperture approach is proposed that aims at reducing the system's complexity (only 8 or 16 active elements) without compromising the image quality, and at frame rates comparable to or higher than conventional focused linear array technique. The novel method has been investigated in simulations using Field II software and experiments performed on a wire phantom using an ultrasound scanner. Results show that the proposed method provides better Lateral Resolution (LR) to that obtained when conventional focused linear array technique is used. The estimated LR at the focal point was 1.09 mm and 0.29 mm for conventional and the proposed method, respectively, in simulations. These were estimated to be 1.03 mm and 0.38 mm, respectively, in experiments. The image quality is shown to improve further when sign coherence factor weighting is incorporated during beamforming.

Design of a low cost ultrasound system using diverging beams and synthetic aperture approach: Preliminary study

This work reports a modified nonlinear beamforming method, named as, Spatio-Temporal Delay Multiply and Sum (ST-DMAS). The developed ST-DMAS method was investigated on a sparse-transmit Synthetic Transmit Aperture technique (sparse-STA) that used just 8 transmits to form the final Ultrasound (US) image. This method allows for achieving high-quality imaging with improved frame rates. The different methods of Delay and Sum (DAS), Filtered Delay Multiply and Sum (F-DMAS) and ST-DMAS were compared in terms of Lateral Resolution (LR), Axial Resolution (AR), Contrast Ratio (CR) and contrast-to-noise ratio (CNR) in experimental studies. Experimental results show that ST-DMAS resulted in improvements of AR by 57 % and 49 %, LR by 61 % and 55 %, CR by 74 % and 43 %, and CNR by 45 % and 32 % in comparison to images reconstructed using DAS and F-DMAS, respectively. Hence, a conclusion can be drawn that both the image quality and frame rate of an US system can be improved by ST-DMAS compared to DAS and F-DMAS.

Arun K. Thittai

Papers

A Weighted Non-Linear Beamformer for Synthetic Aperture Ultrasound Imaging

Importance of Axial Compression Verification to Correct Interpretation of Axial-Shear Strain Elastograms in Breast Lesions

Novel spatio-temporal non-linear beamformers for sparse synthetic aperture ultrasound imaging.

Design of a low cost ultrasound system using diverging beams and synthetic aperture approach: Preliminary study

A Novel Spatio-Temporal DMAS (ST-DMAS) Beamforming for Sparse Synthetic Aperture Ultrasound Imaging: Initial Results