Alsbeih G.A.,Biomedical Physics |
Al-Harbi N.M.,Biomedical Physics |
Bin Judia S.S.,Biomedical Physics |
Khoja H.A.,Pathology and Laboratory Medicine |
And 2 more authors.
Cancer | Year: 2017
BACKGROUND: Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. METHODS: Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. RESULTS: The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P=.016). Furthermore, the variant C allele was significantly overtransmitted in the population (P<.0003). CONCLUSION: Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. © 2017 American Cancer Society.
Velroyen A.,Biomedical Physics |
Bech M.,Biomedical Physics |
Bech M.,Lund University |
Zanette I.,Biomedical Physics |
And 12 more authors.
PLoS ONE | Year: 2011
Purpose: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation.Material and Methods: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 μm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed.Results: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders.Conclusion: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney. © 2014 Velroyen et al.
News Article | December 4, 2015
Oxygen plays a surprisingly large role in tumour evolution and treatment; it is vital for growth and replication of cells. While this might tempt one to think that one can simply starve a tumour of oxygen, this is not the case – oxygen deficient tumours create chaotic networks of blood vessels to sustain themselves, and too frequently acquire a suite of dangerous skills in a low oxygen environment, such as the capacity for metastasis; the spreading of cancer to other parts of the body. Consequently, tumours bereft of oxygen have a markedly worse prognosis, a fact known since the 1950s through research by pioneering medical physicist Hal Gray (see sidebar). Oxygen plays a substantial role in radiotherapy too, with well oxygenated regions of tumour responding by up to a factor of three better than those segments bereft of oxygen. This effect is known clinically as the Oxygen Enhancement Ratio (OER), and oxygenated tumours prove much easier to treat than their anoxic counterparts. The OER curve (below) is unusual in several respects; instead of increasing linearly, the curve rapidly saturates, obtaining half maximum radio-sensitivity somewhere around an oxygen partial pressure of 3 mmHg with maximum OER typically achieved at partial pressures p > 20 mmHg with subsequent increases not significantly modifying the curve. This distinct curve is seen across all sorts of cells lines with huge variation in biology, from human to yeast and bacteria – suggesting perhaps a chemical culprit behind this useful boost. One idea posited to explain this curious result is the oxygen fixation hypothesis. In X-ray therapy, particles of high frequency light are directed at a tumour site. Most of these photons pass through the patient unperturbed, but a significant amount interact with particles in the patient. When a photon does interact, it can create high energy electrons which might impinge upon a target such as the water molecules we contain in abundance. An impacted water molecule loses a proton and becomes a hydroxyl radical. Radicals are highly chemically unstable and extremely reactive - when they encounter DNA, they have the tendency to damage it. This kind of damage is common, and is in general readily chemically repairable, allowing damaged DNA to be restored and cell kill averted. This acts to make radiotherapy less effective, as tumour cells could recover from radiation damage and survive. However, if the radical reacts with oxygen prior to the collision, if forms a new type of radical called a peroxy radical that is difficult or impossible to chemically repair, 'fixing' DNA into a permanent irreparable state. As a consequence, the theory suggests that oxygen is a potent way to make cancers more sensitive to radiotherapy because radical species formed with oxygen are far more difficult for DNA to chemically repair, increasing the lethality of interactions. This concept is illustrated below. While oxygen fixation is commonly accepted as the mechanism behind the oxygen effect, there has been relatively little work on the fundamental physics underpinning oxygen interaction, nor on the physical parameters that might allow modification of this effect. Up until now, mathematical descriptions of OER have tended to be phenomenological and empirical, capturing the gross behaviour of the curve but not the underlying mechanisms that make it so. This is of course useful, but leaves much unanswered. This curious unknown captured the attention of my colleague Dr Mike Partridge and myself. Indeed, it seemed especially relevant to us, as physicists at Oxford have been working on ways to improve the effectiveness of radiotherapy through a wide variety of methods, including studying the role of oxygen in both cancer prognosis and treatment. We ourselves have published quite a bit on oxygen dynamics before, and given the importance of radiotherapy in modern cancer treatment, we were intrigued by not only what factors influence OER but also what parameters might be varied to better understand this oxygen boost to treatment efficacy. In our new paper published in the Institute of Physics journal Biomedical Physics and Engineering Express, we explore the origins of the oxygen effect , describing and predicting the OER curve from first principles. This work establishes a mechanistic explanation of the OER curve from physical first principle, and helps shed light on all the fascinating processes that lead to this marked effect. Our model combines a range of physical considerations from statistical mechanics and kinetic theory, from the thermal velocity and mean-free path length of oxygen molecules to the interaction probability of radicals and DNA. This model was compared to classic experiments on the oxygen enhancement effects, and the results found to agree well with observed experimental data. The conclusions of this work strongly support the idea that oxygen fixation with radicals is indeed the mechanism which gives rise to the observed clinical effect. Our theory also suggests that while most of the vital parameters are fixed constants of nature and impossible to modify, there is a small thermal effect which may exist, though it is not likely to be clinically exploitable. Understanding the mechanisms that affect treatment outcome are of paramount importance in improving patient prognosis, and the better we understand the factors that influence treatment outcome the better we can treat patients and improve lives. More information: David Robert Grimes et al. A mechanistic investigation of the oxygen fixation hypothesis and oxygen enhancement ratio, Biomedical Physics & Engineering Express (2015). DOI: 10.1088/2057-1976/1/4/045209 D. R. Grimes et al. A method for estimating the oxygen consumption rate in multicellular tumour spheroids, Journal of The Royal Society Interface (2014). DOI: 10.1098/rsif.2013.1124
News Article | November 22, 2015
Home > Press > Details from the inner life of a tooth: New X-ray method uses scattering to visualize nanostructures Abstract: Both in materials science and in biomedical research it is important to be able to view minute nanostructures, for example in carbon-fiber materials and bones. A team from the Technical University of Munich (TUM), the University of Lund, Charite hospital in Berlin and the Paul Scherrer Institute (PSI) have now developed a new computed tomography method based on the scattering, rather than on the absorption, of X-rays. The technique makes it possible for the first time to visualize nanostructures in objects measuring just a few millimeters, allowing the researchers to view the precise three-dimensional structure of collagen fibers in a piece of human tooth. In principle, X-ray computed tomography (CT) has been around since the 1960s: X-ray images are taken of an object from various directions, and a computer then uses the individual images to generate a three-dimensional image of the object. Contrast is produced by the differential absorption of X-rays in dissimilar materials. However, the new method, which was developed by Franz Pfeiffer, professor for Biomedical Physics at TUM and his team utilizes the scattering of X-rays rather than their absorption. The results have now been published in the journal Nature. Scattering provides detailed images of nanostructures Theoretically, X-rays act like light with a very short wavelength. This principle lies at the heart of the new method: When a light is shone on a structured object, for example a CD, the reflected light produces a characteristic rainbow pattern. Although the fine grooves in the CD cannot be seen directly, the diffraction of the light rays - known as scattering - indirectly reveals the structure of the object. The same effect can be observed with X-rays, and it is this phenomenon that the researchers take advantage of in their new technique. The advantage of X-rays over visible light is that they are able to penetrate into materials, thus providing detailed information about the internal structure of objects. The researchers have now combined this three-dimensional information from scattered X-rays with computed tomography (CT). Conventional CT methods calculate exactly one value, known as a voxel, for each three-dimensional image point within an object. The new technique assigns multiple values to each voxel, as the scattered light arrives from various directions. "Thanks to this additional information, we're able to learn a great deal more about the nanostructure of an object than with conventional CT methods. By indirectly measuring scattered X-rays, we can now visualize minute structures that are too small for direct spatial resolution," Franz Pfeiffer explains. Internal view of a tooth For demonstration purposes the scientists examined a piece of human tooth measuring around three millimeters. A large part of a human tooth is made from the substance dentin. It consists largely of mineralized collagen fibers whose structure is largely responsible for the mechanical properties of the tooth. The scientists have now visualized these tiny fiber networks. A total of 1.4 million scatter images were taken, with the scattered light arriving from various directions. The individual images were then processed using a specially devised algorithm that builds up a complete reconstruction of the three-dimensional distribution of the scattered rays step by step. "Our algorithm calculates the precise direction of the scatter information for each image and then forms groups having the same scatter direction. This allows internal structures to be precisely reconstructed," says Martin Bech, former postdoc at the TUM and now assistant professor at the University of Lund. Using this method, it was possible to clearly view the three-dimensional orientation of the collagen fibers within a sample of this size for the first time. The results are in agreement with knowledge previously obtained about the structures from thin sections. "A sophisticated CT method is still more suitable for examining large objects. However, our new method makes it possible to visualize structures in the nanometer range in millimeter-sized objects at this level of precision for the first time," says Florian Schaff, lead author of the paper. For more information, please click Contacts: Prof. Dr. Franz Pfeiffer Chair of Biomedical Physics Department of Physics / IMETUM Technical University of Munich Tel.: +49 89 289 12551 (office) +49 89 289 12552 (secretariat) Vera Siegler 49-892-892-2731 If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.
News Article | October 23, 2015
Scientists have developed a hand-held optical scanner with the potential to offer breast cancer imaging in real time. The results are reported today, Oct. 23, 2015, in the journal Biomedical Physics & Engineering Express.