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

Weighted non-linear beamformers for low cost 2-element receive ultrasound imaging system.

Rotation Elastogram Estimation Using Synthetic Transmit-aperture Technique: A Feasibility Study.

In elastography, conventional linear array (CLA)-based RF data acquisition provides more accurate displacement measurements in the direction of beam propagation (axial direction) when compared to the perpendicular direction (lateral). Obtaining good quality lateral displacement estimates in ultrasound (US) elastography will lead to several benefits such as obtaining accurate inverse solutions, improving shear strain elastogram quality, getting good quality poroelastograms, and obtaining reliable rotation elastograms. For accomplishing high-precision lateral displacement estimation (LDE), one of the popular methods is by interpolating additional A-lines in between neighboring RF A-lines. We describe a method wherein true RF A-lines (not interpolated) are acquired and augmented at subpitch locations using CLA transducer, instead of interpolating the data, and using this new frame data for further image formation and/or processing to yield better lateral resolution and LDE. We demonstrate the proposed method by translating the US beam of CLA transducer in subpitch range by the following two approaches: 1) actuator-assisted beam translation and 2) electronic translation of subaperture of a CLA by activating odd and even number of consecutive elements sequentially, referred to as electronic beam translation. The performances of the different methods were studied through simulations and experiments on phantoms. The results demonstrate that these methods yield better quality LDE compared to those obtained from interpolation of RF A-lines. These methods may provide affordable ways to obtain subpitch precision LDE using CLA.

Strategies to Obtain Subpitch Precision in Lateral Motion Estimation in Ultrasound Elastography

Photoacoustic imaging is a molecular cum functional imaging modality based on differential optical absorption of the incident laser pulse by the endogeneous tissue chromophores. Several numerical simulations and finite element models have been developed in the past to describe and study Photoacoustic (PA) signal generation principles and study the effect of variation in PA parameters. Most of these simulation work concentrate on analyzing extracted 1D PA signals and each of them mostly describe only few of the building blocks of a Photoacoustic Tomography (PAT) imaging system. Papers describing simulation of the entire PAT system in one simulation platform, along with reconstruction is seemingly rare. This study attempts to describe how a commercially available Finite Element software (COMSOL(R)), can serve as a single platform for simulating PAT that couples the electromagnetic, thermodynamic and acoustic pressure physics involved in PA phenomena. Further, an array of detector elements placed at the boundary in the FE model can provide acoustic pressure data that can be exported to Matlab(R) to perform tomographic image reconstruction. The performance of two most commonly used image reconstruction techniques; namely, Filtered Backprojection (FBP) and Synthetic Aperture (SA) beamforming are compared. Results obtained showed that the lateral resolution obtained using FBP vs. SA largely depends on the aperture parameters. FBP reconstruction was able to provide a slightly better lateral resolution for smaller aperture while SA worked better for larger aperture. This interesting effect is currently being investigated further. Computationally FBP was faster, but it had artifacts along the spherical shell on which the data is projected.

Simulation of photoacoustic tomography (PAT) system in COMSOL and comparison of two popular reconstruction techniques

Breast cancers that are found and confirmed because they are causing symptoms tend to be larger and are more likely to have already spread to the lymph nodes and beyond. Thus, early detection and confirmation are of paramount importance. The normalized axial–shear strain area (NASSA) feature from the axial-shear strain elastogram (ASSE) has been shown to be a feature that can identify the boundary-bonding conditions that are indicative of the presence of cancer. Recently, we investigated and reported on the potential of the NASSA feature for breast lesion classification into fibroadenomas and cancers. In this article, we investigate the size distribution of the lesions that were part of the previous study and analyze classification performance specifically on small lesions ( p 10 mm had a difference of 0.52 ± 0.24 ( p 10 mm). These results suggest that the ASSE feature can work equally well, even on small lesions, to improve the standard ultrasound BIRADS–based breast lesion classification of fibroadenoma and malignant tumors.

/pdf/small-breast-lesion-classification-performance-using-the-1p4k7xmk12.pdf

Arun K. Thittai

Papers

Weighted non-linear beamformers for low cost 2-element receive ultrasound imaging system.

Rotation Elastogram Estimation Using Synthetic Transmit-aperture Technique: A Feasibility Study.

Strategies to Obtain Subpitch Precision in Lateral Motion Estimation in Ultrasound Elastography

Simulation of photoacoustic tomography (PAT) system in COMSOL and comparison of two popular reconstruction techniques

Small breast lesion classification performance using the normalized axial-shear strain area feature.