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

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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

Microwave hyperthermia makes use of microwaves to deliver heat to biological tissues. Real time temperature monitoring during treatment is important for efficacy and effectiveness of the treatment. Non-invasive methods such as CT, MR and ultrasound (US) have been actively researched for use in hyperthermia monitoring. US has inherent advantages of real-time imaging, portability and non-ionizing nature. It is also known from the literature that acoustic properties of tissue are sensitive to temperature and this has been harnessed to track the evolution of hotspot and temperature in high temperature zones encountered in ablation treatments. However, their usage in low temperature zones typically observed in hyperthermia appears to be less explored. This study introduces an improved method of regularized Kurtosis imaging (RKI) and compares its performance against regularized log spectral difference (RLSD) and regularized Nakagami imaging methods. The performance of these methods is compared against the ground truth estimated from IR thermal images in an experimental study on tissue-mimicking PAG-agar based phantoms. The error in the area estimated by RKI was 10.6%. The error in the lateral and axial co-ordinate of the centroid was 5.92% and 0.47%, respectively. The structural similarity index was 0.82 for RKI when compared with RLSD and RNI having score of 0.76 and 0.72, respectively. The results are promising and offer an alternative way to track the hotspot during microwave hyperthermia treatment.

Regularized Kurtosis Imaging and its Comparison with Regularized Log Spectral Difference and Regularized Nakagami Imaging for Microwave Hyperthermia Hotspot Monitoring

A fundamental challenge in non-destructive evaluation using ultrasound is to accurately estimate the thicknesses of different layers or cracks present in the object being probed. This inherently corresponds to localizing the point-sources of the reflections from the received signal. Conventional signal processing techniques cannot resolve reflectors whose spacing is below the axial resolution limit, which is of the order of the wavelength of the probing pulse. The objective of this paper is to demonstrate axial super-resolution capability using both simulated and experimental ultrasound data. We show that the ultrasound reflections could be modelled effectively as FRI signals, which can be sampled at sub-Nyquist rates. The FRI sampling method brings the reconstruction problem within a parametric estimation framework, for which efficient high-resolution spectral estimation techniques are available. We experimentally demonstrate that the proposed technique is able to resolve the thicknesses of layers of custom designed Agarose phantoms that are up to 2.25 times below the conventional resolution limit.

Axial Super-Resolution in Ultrasound Imaging

This paper presents a novel hybrid two-element scanner (HyTES) for high-frequency ultrasound imaging. The proposed scanner utilizes a combination of a focused and an unfocused high-frequency transducer elements to improve the quality of reconstructed image. An experimental prototype of the proposed scanner is made to serve as proof-of-concept. The scan data obtained from the proposed scheme is beamformed using the recently proposed non-linear beamformer of F-DewMAS, and the results are compared with state-of-the-art monostatic Delay-And-Sum (DAS) and recently proposed Virtual -source-in-front of the transducer with DAS (VS-DAS) beamforming that uses data from only the focused element. As a minor innovation, Virtual Source beamforming is adapted to Delay-Multiply-And-Sum to develop VS-DMAS, which is utilized to reconstruct two element data and the results are compared with other methods. The proposed scanning technology with F-DewMAS beamforming is able improve the image quality by more than 52 % and 63 % in terms of resolution and by more than 44 % and 57 % in terms of CNR and GCNR compared to the recent VS-DAS and monostatic DAS, respectively. Further, the newly proposed VS-DMAS was able to improve resolution and contrast compared to existing methods. However, the performance in terms of the image quality metrics were not as much as obtained with the proposed HyTES. The proposed technology has the potential to improve the image quality without the need for an array, manufacturing of which is a challenge at High-frequencies.

Arun K. Thittai

Papers

Regularized Kurtosis Imaging and its Comparison with Regularized Log Spectral Difference and Regularized Nakagami Imaging for Microwave Hyperthermia Hotspot Monitoring

Axial Super-Resolution in Ultrasound Imaging

A Novel Two-element Scanner for High-frequency Ultrasound Imaging