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2.  Applications of nanoparticles for diagnosis and therapy of cancer 
The British journal of radiology  2015;88(1054):20150207.
During the last decades, a plethora of nanoparticles have been developed and evaluated and a real hype has been created around their potential application as diagnostic and therapeutic agents. Despite their suggestion as potential diagnostic agents, only a single diagnostic nanoparticle formulation, namely iron oxide nanoparticles, found its way into clinical routine so far. This fact is primarily due to difficulties in achieving appropriate pharmacokinetic properties and a reproducible synthesis of monodispersed nanoparticles. Furthermore, concerns exist about their biodegradation, elimination and toxicity.
The majority of nanoparticle formulations that are currently routinely used in the clinic are employed for therapeutic purposes. These therapeutic nanoparticles aim to more efficiently deliver a (chemo-) therapeutic drug to the pathological site, while avoiding its accumulation in healthy organs and tissues, and are predominately based on the “enhanced permeability and retention” (EPR) effect.
Furthermore, based on their ability to integrate diagnostic as well as therapeutic entities within a single nanoparticle formulation, nanoparticles hold great promise for theranostic purposes, and are considered to be highly useful for personalizing nanomedicine-based treatments.
In this review article, we present applications of diagnostic and therapeutic nanoparticles, summarize frequently used non-invasive imaging techniques, and describe the role of EPR in the accumulation of nanotheranostic formulations. In this context, the clinical potential of nanotheranostics and image-guided drug delivery for individualized and improved (chemo-) therapeutic interventions is addressed.
PMCID: PMC4630860  PMID: 25969868
3.  Neuroimaging findings in sickle cell disease 
The British Journal of Radiology  2014;87(1040):20130699.
At least 25% of individuals with sickle cell disease will have a neurological complication over their lifetime, often as early as in childhood. Neuroradiological findings in patients with sickle cell disease are common and include acute territorial infarction, silent ischaemia and intracranial haemorrhage. Imaging abnormalities are typically, but not always, manifestations of the underlying vasculopathy. Coexisting acute and chronic pathology may pose challenges to interpretation.
PMCID: PMC4112221  PMID: 24847772
4.  Imaging of acute stroke prior to treatment: current practice and evolving techniques 
The British Journal of Radiology  2014;87(1040):20140216.
Standard imaging in acute stroke is undertaken with the aim of diagnosing the underlying cause and excluding stroke mimics. In the presence of ischaemic stroke, imaging is also needed to assess patient suitability for treatment with intravenous thrombolysis. Non-contrast CT is predominantly used, but MRI can also exclude any contraindications to thrombolysis treatment. Advanced stroke imaging such as CT and MR angiography and perfusion imaging are increasingly used in an acute setting. In this review, we discuss the evidence for the application of these advanced techniques in the imaging of acute stroke.
PMCID: PMC4112390  PMID: 24936980
5.  Non-cutaneous melanoma: is there a role for 18F-FDG PET-CT? 
The British Journal of Radiology  2014;87(1040):20140324.
Non-cutaneous melanomas (NCM) are diverse and relatively uncommon. They often differ from cutaneous melanomas in their epidemiology, genetic profile and biological behaviour. Despite the growing body of evidence regarding the utility of positron emission tomography (PET)/CT in cutaneous melanoma, the data on its use in NCM are scarce. In this review, we will summarize the existing literature and present cases from our experience with NCM to illustrate current knowledge on the potential role and limitations of fluorine-18 fludeoxyglucose PET/CT in NCM.
PMCID: PMC4112397  PMID: 24901893
6.  Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions 
The British Journal of Radiology  2014;87(1040):20130832.
The black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade, have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotyping that novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional data sets, that is, multimodal mapping and longitudinal studies spanning the natural history of the disease process. And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterization and prognosis of chronic illness or long-term conditions.
PMCID: PMC4112401  PMID: 24936979
7.  Complications of rotator cuff surgery—the role of post-operative imaging in patient care 
The British Journal of Radiology  2014;87(1039):20130630.
When pain or disability occurs after rotator cuff surgery, post-operative imaging is frequently performed. Post-operative complications and expected post-operative imaging findings in the shoulder are presented, with a focus on MRI, MR arthrography (MRA) and CT arthrography. MR and CT techniques are available to reduce image degradation secondary to surgical distortions of native anatomy and implant-related artefacts and to define complications after rotator cuff surgery. A useful approach to image the shoulder after surgery is the standard radiography, followed by MRI/MRA for patients with low “metal presence” and CT for patients who have a higher metal presence. However, for the assessment of patients who have undergone surgery for rotator cuff injuries, imaging findings should always be correlated with the clinical presentation because post-operative imaging abnormalities do not necessarily correlate with symptoms.
PMCID: PMC4075575  PMID: 24734935
8.  Image-guided high-dose-rate brachytherapy in inoperable endometrial cancer 
The British Journal of Radiology  2014;87(1039):20140018.
Inoperable endometrial cancer may be treated with curative aim using radical radiotherapy alone. The radiation techniques are external beam radiotherapy (EBRT) alone, EBRT plus brachytherapy and brachytherapy alone. Recently, high-dose-rate brachytherapy has been used instead of low-dose-rate brachytherapy. Image-guided brachytherapy enables sufficient coverage of tumour and reduction of dose to the organs at risk, thus increasing the therapeutic ratio of treatment. Local control rates with three-dimensional brachytherapy appear better than with conventional techniques (about 90–100% and 70–90%, respectively).
PMCID: PMC4075585  PMID: 24807067
9.  Structural MRI connectome in development: challenges of the changing brain 
The British Journal of Radiology  2014;87(1039):20140086.
MRI connectomics is an emerging approach to study the brain as a network of interconnected brain regions. Understanding and mapping the development of the MRI connectome may offer new insights into the development of brain connectivity and plasticity, ultimately leading to improved understanding of normal development and to more effective diagnosis and treatment of developmental disorders. In this review, we describe the attempts made to date to map the whole-brain structural MRI connectome in the developing brain and pay a special attention to the challenges associated with the rapid changes that the brain is undergoing during maturation. The two main steps in constructing a structural brain network are (i) choosing connectivity measures that will serve as the network “edges” and (ii) finding an appropriate way to divide the brain into regions that will serve as the network “nodes”. We will discuss how these two steps are usually performed in developmental studies and the rationale behind different strategies. Changes in local and global network properties that have been described during maturation in neonates and children will be reviewed, along with differences in network topology between typically and atypically developing subjects, for example, owing to pre-mature birth or hypoxic ischaemic encephalopathy. Finally, future directions of connectomics will be discussed, addressing important steps necessary to advance the study of the structural MRI connectome in development.
PMCID: PMC4075590  PMID: 24827379
10.  Resistive intrarenal index: myth or reality? 
The British Journal of Radiology  2014;87(1038):20140004.
In renal diagnosis, the B-mode ultrasound is used to provide an accurate study of the renal morphology, whereas the colour and power Doppler are of strategic importance in providing qualitative and quantitative information about the renal vasculature, which can also be obtained through the assessment of the resistive index (RI). To date, this is one of the most sensitive parameters in the study of kidney diseases and allows us to quantify the changes in renal plasma flow. If a proper Doppler ultrasound examination is carried out and a critical analysis of the values obtained is performed, the RI measurement at the interlobar artery level has been suggested in the differential diagnosis between nephropathies. The aim of this review is to highlight the pathological conditions in which the study of intrarenal RI provides useful information about the pathophysiology of renal diseases in both the native and the transplanted kidneys.
PMCID: PMC4075561  PMID: 24734937
11.  The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis 
The British Journal of Radiology  2014;87(1038):20140065.
Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm.
PMCID: PMC4075563  PMID: 24597512
12.  Prostate cancer and its mimics at multiparametric prostate MRI 
The British Journal of Radiology  2014;87(1037):20130659.
One in six males will develop prostate cancer during their lifetime. Prostate cancer is the second leading cause of cancer death in American males, behind only lung cancer. Unfortunately, even though this disease is so common, clinical screening methods such as prostate-specific antigen test and transrectal ultrasound-guided prostate biopsy lack sensitivity and specificity in diagnosing prostate cancer. In recent years, multiparametric prostate MRI has emerged as a very important tool in the diagnosis of prostate carcinoma with a high accuracy. However, diagnostic difficulty is often encountered even with an experienced abdominal radiologist. That is mainly because many normal and abnormal entities can mimic prostate carcinoma at multiparametric MRI. Therefore, the purpose of this pictorial review is to discuss the usefulness of multiparametric prostate MRI in the diagnosis of prostate carcinoma, emphasizing the key MRI features that help to make a distinction of prostate carcinoma from its mimics.
PMCID: PMC4075530  PMID: 24646125
13.  Radiologist's perspective for the Meckel's diverticulum and its complications 
The British Journal of Radiology  2014;87(1037):20130743.
The Meckel's diverticulum is the commonest congenital anomaly of the gastrointestinal tract, often presenting with complications such as gastrointestinal bleeding, intussusception, bowel obstruction and diverticulitis, which are often misdiagnosed. Imaging plays an important role in the early diagnosis and characterization of these conditions and is very helpful in decision making. The Meckel's diverticulum and its complications have myriad presentations and appearances on various imaging modalities. Thus, sound knowledge of the anatomy, embryology, clinical presentation, imaging characteristics and complications is crucial to the practice of abdominal imaging. We present a review of the literature and current radiological practices in the diagnosis and management of the Meckel's diverticulum and its various complications with special emphasis on the imaging of various complications, mimickers and pathological correlation.
PMCID: PMC4075535  PMID: 24611767
14.  Post-mortem MRI as an alternative to non-forensic autopsy in foetuses and children: from research into clinical practice 
The British Journal of Radiology  2014;87(1036):20130621.
Although post-mortem MRI (PMMR) was proposed as an alternative to conventional autopsy more than a decade ago, the lack of systematic validation has limited its clinical uptake. Minimally invasive autopsy (MIA) using PMMR together with ancillary investigations has now been shown to be as accurate as conventional autopsy in foetuses, newborns and infants and is particularly useful for cerebral, cardiac and genitourinary imaging. Unlike conventional autopsy, PMMR provides a permanent three-dimensional auditable record, with accurate estimation of internal organ volumes. MIA is becoming highly acceptable to parents and professionals, and there is widespread political support and public interest in its clinical implementation in the UK. In the short to medium term, it is desirable that a supraregional network of specialist centres should be established to provide this service within the current National Health Service framework.
PMCID: PMC4067011  PMID: 24288400
15.  Essentials of forensic post-mortem MR imaging in adults 
The British Journal of Radiology  2014;87(1036):20130567.
Post-mortem MR (PMMR) imaging is a powerful diagnostic tool with a wide scope in forensic radiology. In the past 20 years, PMMR has been used as both an adjunct and an alternative to autopsy. The role of PMMR in forensic death investigations largely depends on the rules and habits of local jurisdictions, availability of experts, financial resources, and individual case circumstances. PMMR images are affected by post-mortem changes, including position-dependent sedimentation, variable body temperature and decomposition. Investigators must be familiar with the appearance of normal findings on PMMR to distinguish them from disease or injury. Coronal whole-body images provide a comprehensive overview. Notably, short tau inversion–recovery (STIR) images enable investigators to screen for pathological fluid accumulation, to which we refer as “forensic sentinel sign”. If scan time is short, subsequent PMMR imaging may be focussed on regions with a positive forensic sentinel sign. PMMR offers excellent anatomical detail and is especially useful to visualize pathologies of the brain, heart, subcutaneous fat tissue and abdominal organs. PMMR may also be used to document skeletal injury. Cardiovascular imaging is a core area of PMMR imaging and growing evidence indicates that PMMR is able to detect ischaemic injury at an earlier stage than traditional autopsy and routine histology. The aim of this review is to present an overview of normal findings on forensic PMMR, provide general advice on the application of PMMR and summarise the current literature on PMMR imaging of the head and neck, cardiovascular system, abdomen and musculoskeletal system.
PMCID: PMC4067017  PMID: 24191122
16.  Virtual anthropology and forensic identification using multidetector CT 
The British Journal of Radiology  2014;87(1036):20130468.
Virtual anthropology is made possible by modern cross-sectional imaging. Multislice CT (MSCT) can be used for comparative bone and dental identification, reconstructive identification and lesion identification. Comparative identification, the comparison of ante- and post-mortem imaging data, can be performed on both teeth and bones. Reconstructive identification, a considerable challenge for the radiologist, identifies the deceased by determining sex, geographical origin, stature and age at death. Lesion identification combines virtual autopsy and virtual anthropology. MSCT can be useful in palaeopathology, seeking arthropathy, infection, oral pathology, trauma, tumours, haematological disorders, stress indicators or occupational stress in bones and teeth. We examine some of the possibilities offered by this new radiological subspeciality that adds a new dimension to the work of the forensic radiologist. A multidisciplinary approach is crucial and involves communication and data exchange between radiologists, forensic pathologists, anthropologists and radiographers.
PMCID: PMC4067023  PMID: 24234584
17.  Adult post-mortem imaging in traumatic and cardiorespiratory death and its relation to clinical radiological imaging 
The British Journal of Radiology  2014;87(1036):20130662.
The use of post-mortem imaging is expanding throughout the world with increasing use of advanced imaging techniques, such as contrast-enhanced CT and MRI. The questions asked of post-mortem imaging are complex and can be very different, for example for natural sudden death investigation will focus on the cause, whereas for trauma the cause of death is often clear, but injury patterns may be very revealing in investigating the background to the incident. Post-mortem imaging is different to clinical imaging regarding both the appearance of pathology and the information required, but there is much to learn from many years of clinical research in the use of these techniques. Furthermore, it is possible that post-mortem imaging research could be used not only for investigating the cause of death but also as a model to conduct clinically relevant research. This article reviews challenges to the development of post-mortem imaging for trauma, identification and cardiorespiratory death, and how they may be influenced by current clinical thinking and practice.
PMCID: PMC4067026  PMID: 24338941
18.  Advances in post-mortem CT-angiography 
The British Journal of Radiology  2014;87(1036):20130488.
Performing a post-mortem multidetector CT (MDCT) scan has already become routine in some institutes of forensic medicine. To better visualize the vascular system, different techniques of post-mortem CT-angiography have been explored, which can essentially be divided into partial- and whole-body angiography techniques. Probably the most frequently applied technique today is the so-called multiphase post-mortem CT-angiography (MPMCTA) a standardized method for investigating the vessels of the head, thorax and abdomen. Different studies exist, describing its use for medicolegal investigations, and its advantages as well as its artefacts and pitfalls. With the aim to investigate the performance of PMCTA and to develop and validate techniques, an international working group was created in 2012 called the “Technical Working Group Post-mortem Angiography Methods” (TWGPAM). Beyond its primary perspective, the goals of this group include creating recommendations for the indication of the investigation and for the interpretation of the images and to distribute knowledge about PMCTA. This article provides an overview about the different approaches that have been developed and tested in recent years and an update about ongoing research in this field. It will explain the technique of MPMCTA in detail and give an outline of its indications, application, advantages and limitations.
PMCID: PMC4067028  PMID: 24234582
19.  Imaging in head and neck squamous cell carcinoma: the potential role of PET/MRI 
The British Journal of Radiology  2014;87(1036):20130677.
In head and neck oncology, the information provided by positron emission tomography (PET)/CT and MRI is often complementary because both the methods are based on different biophysical foundations. Therefore, combining diagnostic information from both modalities can provide additional diagnostic gain. Debates about integrated PET/MRI systems have become fashionable during the past few years, since the introduction and wide adoption of software-based multimodality image registration and fusion and the hardware implementation of integrated hybrid PET/MRI systems in pre-clinical and clinical settings. However, combining PET with MRI has proven to be technically and clinically more challenging than initially expected and, as such, research into the potential clinical role of PET/MRI in comparison with PET/CT, diffusion-weighted MRI (DW MRI) or the combination thereof is still ongoing. This review focuses on the clinical applications of PET/MRI in head and neck squamous cell carcinoma (HNSCC). We first discuss current evidence about the use of combined PET/CT and DW MRI, and, then, we explain the rationale and principles of PET/MR image fusion before summarizing the state-of-the-art knowledge regarding the diagnostic performance of PET/MRI in HNSCC. Feasibility and quantification issues, diagnostic pitfalls and challenges in clinical settings as well as ongoing research and potential future applications are also discussed.
PMCID: PMC4067029  PMID: 24649835
20.  Multimodality imaging of primary CNS lymphoma in immunocompetent patients 
The British Journal of Radiology  2014;87(1036):20130684.
Primary central nervous system lymphoma (PCNSL) belongs to the group of extranodal non-Hodgkin's lymphoma, and the management of the disease is radically different from other central nervous system neoplasms. Owing to its varied appearance on imaging, diagnosis of PCNSL can be challenging. The purpose of this pictorial review is to depict the brain findings of PCNSL during initial diagnosis in immunocompetent individuals. Multimodal imaging integrating advanced sequences can facilitate differentiation of PCNSL from other CNS neoplasms.
PMCID: PMC4067032  PMID: 24646184
21.  Radiological and practical aspects of body packing 
The British Journal of Radiology  2014;87(1036):20130500.
Body packing represents the concealment of illegal substances in a person's body with the aim of smuggling. “Body packers” either swallow drug-filled packets or introduce drug-filled packets into their bodies rectally or vaginally with the purpose of concealing them. The three main smuggled drugs are cocaine, heroin and cannabis products. Body packing represents a serious risk of acute narcotic toxicity from drug exposure, intestinal obstruction owing to pellet impaction and bowel perforation with consequent abdominal sepsis. A suspected body packer is generally admitted to hospital to perform imaging investigations and confirm the presence of drugs in his/her body. Radiological imaging methods are essential to diagnose body packing and to detect potential complications. Increasing sophistication of traffickers and improvements in packaging add to the detection difficulty. Radiologists should be aware of the appearance of drug packets in a range of imaging modalities. This article informs physicians about the challenging aspects of body packing, its background and medicolegal issues, what imaging methods can be used and what criteria are necessary to perform a correct diagnosis.
PMCID: PMC4067033  PMID: 24472727
22.  DNA DSB repair pathway choice: an orchestrated handover mechanism 
The British Journal of Radiology  2014;87(1035):20130685.
DNA double strand breaks (DSBs) are potential lethal lesions but can also lead to chromosome rearrangements, a step promoting carcinogenesis. DNA non-homologous end-joining (NHEJ) is the major DSB rejoining process and occurs in all cell cycle stages. Homologous recombination (HR) can additionally function to repair irradiation-induced two-ended DSBs in G2 phase. In mammalian cells, HR predominantly uses a sister chromatid as a template for DSB repair; thus HR functions only in late S/G2 phase. Here, we review current insight into the interplay between HR and NHEJ in G2 phase. We argue that NHEJ represents the first choice pathway, repairing approximately 80% of X-ray-induced DSBs with rapid kinetics. However, a subset of DSBs undergoes end resection and repair by HR. 53BP1 restricts resection, thereby promoting NHEJ. During the switch from NHEJ to HR, 53BP1 is repositioned to the periphery of enlarged irradiation-induced foci (IRIF) via a BRCA1-dependent process. K63-linked ubiquitin chains, which also form at IRIF, are also repositioned as well as receptor-associated protein 80 (RAP80), a ubiquitin binding protein. RAP80 repositioning requires POH1, a proteasome component. Thus, the interfacing barriers to HR, 53BP1 and RAP80 are relieved by POH1 and BRCA1, respectively. Removal of RAP80 from the IRIF core is required for loss of the ubiquitin chains and 53BP1, and for efficient replication protein A foci formation. We propose that NHEJ is used preferentially to HR because it is a compact process that does not necessitate extensive chromatin changes in the DSB vicinity.
PMCID: PMC4064598  PMID: 24363387
23.  Vasculogenesis: a crucial player in the resistance of solid tumours to radiotherapy 
The British Journal of Radiology  2014;87(1035):20130686.
Tumours have two main ways to develop a vasculature: by angiogenesis, the sprouting of endothelial cells from nearby blood vessels, and vasculogenesis, the formation of blood vessels from circulating cells. Because tumour irradiation abrogates local angiogenesis, the tumour must rely on the vasculogenesis pathway for regrowth after irradiation. Tumour irradiation produces a marked influx of CD11b+ myeloid cells (macrophages) into the tumours, and these are crucial to the formation of blood vessels in the tumours after irradiation and for the recurrence of the tumours. This process is driven by increased tumour hypoxia, which increases levels of HIF-1 (hypoxia-inducible factor 1), which in turn upregulates SDF-1 (stromal cell-derived factor 1 or CXCL12), the main driver of the vasculogenesis pathway. Inhibition of HIF-1 or of its downstream target SDF-1 prevents the radiation-induced influx of the CD11b+ myeloid cells and delays or prevents the tumours from recurring following irradiation. Others and we have shown that with a variety of tumours in both mice and rats, the inhibition of the SDF-1/CXCR4 pathway delays or prevents the recurrence of implanted or autochthonous tumours following irradiation or following treatment with vascular disrupting agents or some chemotherapeutic drugs such as paclitaxel. In addition to the recruited macrophages, endothelial progenitor cells (EPCs) are also recruited to the irradiated tumours, a process also driven by SDF-1. Together, the recruited proangiogenic macrophages and the EPCs reform the tumour vasculature and allow the tumour to regrow following irradiation. This is a new paradigm with major implications for the treatment of solid tumours by radiotherapy.
PMCID: PMC4064599  PMID: 24338942
24.  Radiation-mediated formation of complex damage to DNA: a chemical aspect overview 
The British Journal of Radiology  2014;87(1035):20130715.
During the last three decades, a considerable amount of work has been undertaken to determine the nature, the mechanism of formation and the biological consequences of radiation-induced DNA lesions. Most of the information was obtained via the development of chemical approaches, including theoretical, analytical and organic synthesis methods. Since it is not possible to present all the results obtained in this review article, we will focus on recent data dealing with the formation of complex DNA lesions produced by a single oxidation event, as these lesions may play a significant role in cellular responses to ionizing radiation and also to other sources of oxidative stress. Through the description of specific results, the contribution of different chemical disciplines in the assessment of the structure, the identification of the mechanism of formation and the biological impacts in terms of repair and mutagenicity of these complex radiation-induced DNA lesions will be highlighted.
PMCID: PMC4064600  PMID: 24472775
25.  Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response 
The British Journal of Radiology  2014;87(1035):20130676.
Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer therapies, as it compromises treatment and drives malignant progression. This review seeks to clarify the oxygen levels that are pertinent to this issue. It is argued that normoxia (20% oxygen) is an extremely poor comparator for “physoxia”, i.e. the much lower levels of oxygen universally found in normal tissues, which averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it should be recognized that the median oxygenation in untreated tumours is significantly much lower, falling between approximately 0.3% and 4.2% oxygen, with most tumours exhibiting median oxygen levels <2%. This is partially dependent on the tissue of origin, and it is notable that many prostate and pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even further, often unrecognized, changes in tumour oxygenation that may vary longitudinally, increasing or decreasing during treatment in ways that are not always predictable. Studies that fail to take cognizance of the actual physiological levels of oxygen in tissues (approximately 5%) and tumours (approximately 1%) may fail to identify the real circumstances driving tumour response to treatment and/or malignant progression. This can be of particular importance in genetic studies in vitro when comparison to human tumours is required.
PMCID: PMC4064601  PMID: 24588669

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