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Sample records for brain cancer propagating

  1. Brain cancer spreads

    DEFF Research Database (Denmark)

    Perryman, Lara; Erler, Janine Terra

    2014-01-01

    The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue).......The discovery that ~20% of patients with brain cancer have circulating tumor cells breaks the dogma that these cells are confined to the brain and has important clinical implications (Müller et al., this issue)....

  2. Cube propagation for focal brain atrophy estimation

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru; Sørensen, Lauge; Darkner, Sune

    2013-01-01

    Precise and robust whole brain, ventricle, and hippocampal atrophy measurements are important as they serve as biomarkers for Alzheimer’s disease. They are used as secondary outcomes in drug trials, and they correlate with the cognitive scores. When two successive scans are non-linearly aligned...

  3. Individual brain structure and modelling predict seizure propagation.

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    Proix, Timothée; Bartolomei, Fabrice; Guye, Maxime; Jirsa, Viktor K

    2017-03-01

    See Lytton (doi:10.1093/awx018) for a scientific commentary on this article.Neural network oscillations are a fundamental mechanism for cognition, perception and consciousness. Consequently, perturbations of network activity play an important role in the pathophysiology of brain disorders. When structural information from non-invasive brain imaging is merged with mathematical modelling, then generative brain network models constitute personalized in silico platforms for the exploration of causal mechanisms of brain function and clinical hypothesis testing. We here demonstrate with the example of drug-resistant epilepsy that patient-specific virtual brain models derived from diffusion magnetic resonance imaging have sufficient predictive power to improve diagnosis and surgery outcome. In partial epilepsy, seizures originate in a local network, the so-called epileptogenic zone, before recruiting other close or distant brain regions. We create personalized large-scale brain networks for 15 patients and simulate the individual seizure propagation patterns. Model validation is performed against the presurgical stereotactic electroencephalography data and the standard-of-care clinical evaluation. We demonstrate that the individual brain models account for the patient seizure propagation patterns, explain the variability in postsurgical success, but do not reliably augment with the use of patient-specific connectivity. Our results show that connectome-based brain network models have the capacity to explain changes in the organization of brain activity as observed in some brain disorders, thus opening up avenues towards discovery of novel clinical interventions. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  4. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

    Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

  5. Cancer around the brain

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    Grisold, Wolfgang; Grisold, Anna

    2014-01-01

    Background Neuro-oncologists are familiar with primary brain tumors, intracerebral metastases meningeal carcinomatosis and extracerebral intracranial tumors as meningeoma. For these conditions, and also some other rare tumor entities several treatment options exist. Cancer can also involve structures around the brain as the dura, the base of the skull, the cavities of the skull and tissue around the bony skull, the skin, the tissue of the neck. and either compress, invade or spread in the central or peripheral nervous system. Methods A systematic literature research was conducted determining symptoms and signs, tumor sites of nerve invasion, tumor types, diagnostic techniques, mechanisms of nerve invasion, and important differential diagnosis. Additional cases from own experience were added for illustration. Results The mechanisms of tumor invasion of cranial nerves is heterogenous and not only involves several types of invasion, but also spread along the cranial nerves in antero- and retrograde fashion and even spread into different nerve territories via anastomosis. In addition the concept of angiosomas may have an influence on the spread of metastases. Conclusion In addition to the well described tumor spread in meningeal carcinomatosis and base of the skull metastases, dural spread, lesions of the bony skull, the cavities of the skull and skin of the face and tissue of the neck region need to be considered, and have an impact on therapeutic decisions. PMID:26034610

  6. Brain metastasization of breast cancer.

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    Custódio-Santos, Tânia; Videira, Mafalda; Brito, Maria Alexandra

    2017-08-01

    Central nervous system metastases have been reported in 15-25% of breast cancer patients, and the incidence is increasing. Moreover, the survival of these patients is generally poor, with reports of a 1-year survival rate of 20%. Therefore, a better knowledge about the determinants of brain metastasization is essential for the improvement of the clinical outcomes. Here, we summarize the current data about the metastatic cascade, ranging from the output of cancer cells from the primary tumour to their colonization in the brain, which involves the epithelial-mesenchymal transition, invasion of mammary tissue, intravasation into circulation, and homing into and extravasation towards the brain. The phenotypic change in malignant cells, and the importance of the microenvironment in the formation of brain metastases are also inspected. Finally, the importance of genetic and epigenetic changes, and the recently disclosed effects of microRNAs in brain metastasization of breast cancer are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Interrogating Metabolism in Brain Cancer.

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    Salzillo, Travis C; Hu, Jingzhe; Nguyen, Linda; Whiting, Nicholas; Lee, Jaehyuk; Weygand, Joseph; Dutta, Prasanta; Pudakalakatti, Shivanand; Millward, Niki Zacharias; Gammon, Seth T; Lang, Frederick F; Heimberger, Amy B; Bhattacharya, Pratip K

    2016-11-01

    This article reviews existing and emerging techniques of interrogating metabolism in brain cancer from well-established proton magnetic resonance spectroscopy to the promising hyperpolarized metabolic imaging and chemical exchange saturation transfer and emerging techniques of imaging inflammation. Some of these techniques are at an early stage of development and clinical trials are in progress in patients to establish the clinical efficacy. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy; with the combined knowledge of genomics and proteomics a complete understanding of tumorigenesis in brain might be achieved. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Metabolomic signature of brain cancer.

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    Pandey, Renu; Caflisch, Laura; Lodi, Alessia; Brenner, Andrew J; Tiziani, Stefano

    2017-11-01

    Despite advances in surgery and adjuvant therapy, brain tumors represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumors, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which charact erizes the phenotype of an individual. This emerging "omics" science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumor biology. Metabolites are highly informative as a direct signature of biochemical activity; therefore, metabolite profiling has become a promising approach for clinical diagnostics and prognostics. The metabolic alterations are well-recognized as one of the key hallmarks in monitoring disease progression, therapy, and revealing new molecular targets for effective therapeutic intervention. Taking advantage of the latest high-throughput analytical technologies, that is, nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), metabolomics is now a promising field for precision medicine and drug discovery. In the present report, we review the application of metabolomics and in vivo metabolic profiling in the context of adult gliomas and paediatric brain tumors. Analytical platforms such as high-resolution (HR) NMR, in vivo magnetic resonance spectroscopic imaging and high- and low-resolution MS are discussed. Moreover, the relevance of metabolic studies in the development of new therapeutic strategies for treatment of gliomas are reviewed. © 2017 Wiley Periodicals, Inc.

  9. A brain cancer pathway in clinical practice

    DEFF Research Database (Denmark)

    Laursen, Emilie Lund; Rasmussen, Birthe Krogh

    2012-01-01

    Danish healthcare seeks to improve cancer survival through improved diagnostics, rapid treatment and increased focus on cancer prevention and early help-seeking. In neuro-oncology, this has resulted in the Integrated Brain Cancer Pathway (IBCP). The paper explores how the pathway works in the ini...... in the initial phase in a clinical setting with emphasis on pathway criteria....

  10. Propagated infra-slow intrinsic brain activity reorganizes across wake and slow wave sleep.

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    Mitra, Anish; Snyder, Abraham Z; Tagliazucchi, Enzo; Laufs, Helmut; Raichle, Marcus E

    2015-11-09

    Propagation of slow intrinsic brain activity has been widely observed in electrophysiogical studies of slow wave sleep (SWS). However, in human resting state fMRI (rs-fMRI), intrinsic activity has been understood predominantly in terms of zero-lag temporal synchrony (functional connectivity) within systems known as resting state networks (RSNs). Prior rs-fMRI studies have found that RSNs are generally preserved across wake and sleep. Here, we use a recently developed analysis technique to study propagation of infra-slow intrinsic blood oxygen level dependent (BOLD) signals in normal adults during wake and SWS. This analysis reveals marked changes in propagation patterns in SWS vs. wake. Broadly, ordered propagation is preserved within traditionally defined RSNs but lost between RSNs. Additionally, propagation between cerebral cortex and subcortical structures reverses directions, and intra-cortical propagation becomes reorganized, especially in visual and sensorimotor cortices. These findings show that propagated rs-fMRI activity informs theoretical accounts of the neural functions of sleep.

  11. Treatment of Brain Metastasis from Lung Cancer

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    Chi, Alexander [Department of Radiation Oncology, University of Arizona, 1501 N Campbell Ave., Tucson, AZ 85724 (United States); Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States)

    2010-12-15

    Brain metastases are not only the most common intracranial neoplasm in adults but also very prevalent in patients with lung cancer. Patients have been grouped into different classes based on the presence of prognostic factors such as control of the primary tumor, functional performance status, age, and number of brain metastases. Patients with good prognosis may benefit from more aggressive treatment because of the potential for prolonged survival for some of them. In this review, we will comprehensively discuss the therapeutic options for treating brain metastases, which arise mostly from a lung cancer primary. In particular, we will focus on the patient selection for combined modality treatment of brain metastases, such as surgical resection or stereotactic radiosurgery (SRS) combined with whole brain irradiation; the use of radiosensitizers; and the neurocognitive deficits after whole brain irradiation with or without SRS. The benefit of prophylactic cranial irradiation (PCI) and its potentially associated neuro-toxicity for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are also discussed, along with the combined treatment of intrathoracic primary disease and solitary brain metastasis. The roles of SRS to the surgical bed, fractionated stereotactic radiotherapy, WBRT with an integrated boost to the gross brain metastases, as well as combining WBRT with epidermal growth factor receptor (EGFR) inhibitors, are explored as well.

  12. Skull and cerebrospinal fluid effects on microwave radiation propagation in human brain

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    Ansari, M. A.; Zarei, M.; Akhlaghipour, N.; Niknam, A. R.

    2017-12-01

    The determination of microwave absorption distribution in the human brain is necessary for the detection of brain tumors using thermo-acoustic imaging and for removing them using hyperthermia treatment. In contrast to ionizing radiation, hyperthermia treatment can be applied to remove tumors inside the brain without the concern of including secondary malignancies, which typically form from the neuronal cells of the septum pellucidum. The aim of this study is to determine the microwave absorption distribution in an adult human brain and to study the effects of skull and cerebrospinal fluid on the propagation of microwave radiation inside the brain. To this end, we simulate the microwave absorption distribution in a realistic adult brain model (Colin 27) using the mesh-based Monte Carlo (MMC) method. This is because in spite of there being other numerical methods, the MMC does not require a large memory, even for complicated geometries, and its algorithm is simple and easy to implement with low computational cost. The brain model is constructed using high-resolution (1 mm isotropic voxel) and low noise magnetic resonance imaging (MRI) scans and its volume contains 181×217×181 voxels, covering the brain completely. Using the MMC method, the radiative transport equation is solved and the absorbed microwave energy distribution in different brain regions is obtained without any fracture or anomaly. The simulation results show that the skull and cerebrospinal fluid guide the microwave radiation and suppress its penetration through deep brain compartments as a shielding factor. These results reveal that the MMC can be used to predict the amount of required energy to increase the temperature inside the tumour during hyperthermia treatment. Our results also show why a deep tumour inside an adult human brain cannot be efficiently treated using hyperthermia treatment. Finally, the accuracy of the presented numerical method is verified using the signal flow graph technique.

  13. Analysis of sports related mTBI injuries caused by elastic wave propagation through brain tissue

    Directory of Open Access Journals (Sweden)

    D Case

    2016-10-01

    Full Text Available Repetitive concussions and sub-concussions suffered by athletes have been linked to a series of sequelae ranging from traumatic encephalopathy to dementia pugilistica. A detailed finite element model of the human head was developed based on standard libraries of medical imaging. The model includes realistic material properties for the brain tissue, bone, soft tissue, and CSF, as well as the structure and properties of a protective helmet. Various impact scenarios were studied, with a focus on the strains/stresses and pressure gradients and concentrations created in the brain tissue due to propagation of waves produced by the impact through the complex internal structure of the human head. This approach has the potential to expand our understanding of the mechanism of brain injury, and to better assess the risk of delayed neurological disorders for tens of thousands of young athletes throughout the world.

  14. Evaluation of seizure propagation on ictal brain SPECT using statistical parametric mapping in temporal lobe epilepsy

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    Jeon, Tae Joo; Lee, Jong Doo; Kim, Hee Joung; Lee, Byung In; Kim, Ok Joon; Kim, Min Jung [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of); Jeon, Jeong Dong [College of Medicine, Inje Univ., Pusan (Korea, Republic of)

    1999-07-01

    Ictal brain SPECT has a high diagnostic sensitivity exceeding 90 % in the localization of seizure focus, however, it often shows increased uptake within the extratemporal areas due to early propagation of seizure discharge. This study aimed to evaluate seizure propagation on ictal brian SPECT in patients with temporal lobe epilepsy (TLE) by statistical parametric mapping (SPM). Twenty-one patients (age 27.14 5.79 y) with temporal lobe epilepsy (right in 8, left in 13) who had successful seizure outcome after surgery and nine normal control were included. The data of ictal and interictal brain SPECT of the patients and baseline SPECT of normal control group were analyzed using automatic image registration and SPM96 softwares. The statistical analysis was performed to compare the mean SPECT image of normal group with individual ictal SPECT, and each mean image of the interictal groups of the right or left TLE with individual ictal scans. The t statistic SPM [t] was transformed to SPM [Z] with a threshold of 1.64. The statistical results were displayed and rendered on the reference 3 dimensional MRI images with P value of 0.05 and uncorrected extent threshold p value of 0.5 for SPM [Z]. SPM data demonstrated increased uptake within the epileptic lesion in 19 patients (90.4 %), among them, localized increased uptake confined to the epileptogenic lesion was seen in only 4 (19%) but 15 patients (71.4%) showed hyperperfusion within propagation sites. Bi-temporal hyperperfusion was observed in 11 out of 19 patients (57.9%, 5 in the right and 6 in the left); higher uptake within the lesion than contralateral side in 9, similar activity in 1 and higher uptake within contralateral lobe in one. Extra-temporal hyperperfusion was observed in 8 (2 in the right, 3 in the left, 3 in bilateral); unilateral hyperperfusion within the epileptogenic temporal lobe and extra-temporal area in 4, bi-temporal with extra-temporal hyperperfusion in remaining 4. Ictal brain SPECT is highly

  15. Amplification and propagation of interleukin-1β signaling by murine brain endothelial and glial cells.

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    Krasnow, Stephanie M; Knoll, J Gabriel; Verghese, Santhosh Chakkaramakkil; Levasseur, Peter R; Marks, Daniel L

    2017-07-01

    During acute infections and chronic illnesses, the pro-inflammatory cytokine interleukin-1β (IL-1β) acts within the brain to elicit metabolic derangements and sickness behaviors. It is unknown which cells in the brain are the proximal targets for IL-1β with respect to the generation of these illness responses. We performed a series of in vitro experiments to (1) investigate which brain cell populations exhibit inflammatory responses to IL-1β and (2) examine the interactions between different IL-1β-responsive cell types in various co-culture combinations. We treated primary cultures of murine brain microvessel endothelial cells (BMEC), astrocytes, and microglia with PBS or IL-1β, and then performed qPCR to measure inflammatory gene expression or immunocytochemistry to evaluate nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. To evaluate whether astrocytes and/or BMEC propagate inflammatory signals to microglia, we exposed microglia to astrocyte-conditioned media and co-cultured endothelial cells and glia in transwells. Treatment groups were compared by Student's t tests or by ANOVA followed by Bonferroni-corrected t tests. IL-1β increased inflammatory gene expression and NF-κB activation in primary murine-mixed glia, enriched astrocyte, and BMEC cultures. Although IL-1β elicited minimal changes in inflammatory gene expression and did not induce the nuclear translocation of NF-κB in isolated microglia, these cells were more robustly activated by IL-1β when co-cultured with astrocytes and/or BMEC. We observed a polarized endothelial response to IL-1β, because the application of IL-1β to the abluminal endothelial surface produced a more complex microglial inflammatory response than that which occurred following luminal IL-1β exposure. Inflammatory signals are detected, amplified, and propagated through the CNS via a sequential and reverberating signaling cascade involving communication between brain endothelial cells and

  16. Simultaneously Propagating Voltage and Pressure Pulses in Lipid Monolayers of pork brain and synthetic lipids

    CERN Document Server

    Griesbauer, J; Wixforth, A; Schneider, M F

    2012-01-01

    Hydrated interfaces are ubiquitous in biology and appear on all length scales from ions, individual molecules to membranes and cellular networks. In vivo, they comprise a high degree of self-organization and complex entanglement, which limits their experimental accessibility by smearing out the individual phenomenology. The Langmuir technique, however, allows the examination of defined interfaces, whose controllable thermodynamic state enables one to explore the proper state diagrams. Here we demonstrate that voltage and pressure pulses simultaneously propagate along monolayers comprised of either native pork brain or synthetic lipids. The excitation of pulses is conducted by the application of small droplets of acetic acid and monitored subsequently employing timeresolved Wilhelmy plate and Kelvin probe measurements. The isothermal state diagrams of the monolayers for both lateral pressure and surface potential are experimentally recorded, enabling us to predict dynamic voltage pulse amplitudes of 0,1 to 3mV...

  17. Inter-hemispheric wave propagation failures in traumatic brain injury are indicative of callosal damage.

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    Spiegel, Daniel P; Laguë-Beauvais, Maude; Sharma, Gaurav; Farivar, Reza

    2015-04-01

    Approximately 3.2-5.3 million Americans live with the consequences of a traumatic brain injury (TBI), making TBI one of the most common causes of disability in the world. Visual deficits often accompany TBI but physiological and anatomical evidence for injury in mild TBI is lacking. Axons traversing the corpus callosum are particularly vulnerable to TBI. Hemifield representations of early visual areas are linked by bundles of fibers that together cross the corpus callosum while maintaining their topographic relations. Given the increased vulnerability of the long visual axons traversing the corpus callosum, we hypothesized that inter-hemispheric transmission for vision will be impaired following mild TBI. Using the travelling wave paradigm (Wilson, Blake, & Lee 2001), we measured inter-hemispheric transmission in terms of both speed and propagation failures in 14 mild TBI patients and 14 age-matched controls. We found that relative to intra-hemispheric waves, inter-hemispheric waves were faster and that the inter-hemispheric propagation failures were more common in TBI patients. Furthermore, the transmission failures were topographically distributed, with a bias towards greater failures for transmission across the upper visual field. We discuss the results in terms of increased local inhibition and topographically-selective axonal injury in mild TBI. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

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    Eisele, Yvonne S; Duyckaerts, Charles

    2016-01-01

    In brains of patients with Alzheimer's disease (AD), Aβ peptides accumulate in parenchyma and, almost invariably, also in the vascular walls. Although Aβ aggregation is, by definition, present in AD, its impact is only incompletely understood. It occurs in a stereotypical spatiotemporal distribution within neuronal networks in the course of the disease. This suggests a role for synaptic connections in propagating Aβ pathology, and possibly of axonal transport in an antero- or retrograde way-although, there is also evidence for passive, extracellular diffusion. Striking, in AD, is the conjunction of tau and Aβ pathology. Tau pathology in the cell body of neurons precedes Aβ deposition in their synaptic endings in several circuits such as the entorhino-dentate, cortico-striatal or subiculo-mammillary connections. However, genetic evidence suggests that Aβ accumulation is the first step in AD pathogenesis. To model the complexity and consequences of Aβ aggregation in vivo, various transgenic (tg) rodents have been generated. In rodents tg for the human Aβ precursor protein, focal injections of preformed Aβ aggregates can induce Aβ deposits in the vicinity of the injection site, and over time in more distant regions of the brain. This suggests that Aβ shares with α-synuclein, tau and other proteins the property to misfold and aggregate homotypic molecules. We propose to group those proteins under the term "propagons". Propagons may lack the infectivity of prions. We review findings from neuropathological examinations of human brains in different stages of AD and from studies in rodent models of Aβ aggregation and discuss putative mechanisms underlying the initiation and spread of Aβ pathology.

  19. Propagation of tau pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    Science.gov (United States)

    Lewis, Jada; Dickson, Dennis W

    2016-01-01

    Tau is a microtubule-associated protein and a key regulator of microtubule stabilization as well as the main component of neurofibrillary tangles-a principle neuropathological hallmark of Alzheimer's disease (AD)-as well as pleomorphic neuronal and glial inclusions in neurodegenerative tauopathies. Cross-sectional studies of neurofibrillary pathology in AD reveal a stereotypic spatiotemporal pattern of neuronal vulnerability that correlates with disease severity; however, the relationship of this pattern to disease progression is less certain and exceptions to the typical pattern have been described in a subset of AD patients. The basis for the selective vulnerability of specific populations of neurons to tau pathology and cell death is largely unknown, although there have been a number of hypotheses based upon shared properties of vulnerable neurons (e.g., degree of axonal myelination or synaptic plasticity). A recent hypothesis for selective vulnerability takes into account the emerging science of functional connectivity based upon resting state functional magnetic resonance imaging, where subsets of neurons that fire synchronously define patterns of degeneration similar to specific neurodegenerative disorders, including various tauopathies. In the past 6 years, the concept of tau propagation has emerged from numerous studies in cell and animal models suggesting that tau moves from cell-to-cell and that this may trigger aggregation and region-to-region spread of tau pathology within the brain. How the spread of tau pathology relates to functional connectivity is an area of active investigation. Observations of templated folding and propagation of tau have prompted comparisons of tau to prions, the pathogenic proteins in transmissible spongiform encephalopathies. In this review, we discuss the most compelling studies in the field, discuss their shortcomings and consider their implications with respect to human tauopathies as well as the controversy that

  20. Proteoglycans and their roles in brain cancer.

    Science.gov (United States)

    Wade, Anna; Robinson, Aaron E; Engler, Jane R; Petritsch, Claudia; James, C David; Phillips, Joanna J

    2013-05-01

    Glioblastoma, a malignant brain cancer, is characterized by abnormal activation of receptor tyrosine kinase signalling pathways and a poor prognosis. Extracellular proteoglycans, including heparan sulfate and chondroitin sulfate, play critical roles in the regulation of cell signalling and migration via interactions with extracellular ligands, growth factor receptors and extracellular matrix components, as well as intracellular enzymes and structural proteins. In cancer, proteoglycans help drive multiple oncogenic pathways in tumour cells and promote critical tumour-microenvironment interactions. In the present review, we summarize the evidence for proteoglycan function in gliomagenesis and examine the expression of proteoglycans and their modifying enzymes in human glioblastoma using data obtained from The Cancer Genome Atlas (http://cancergenome.nih.gov/). Furthermore, we demonstrate an association between specific proteoglycan alterations and changes in receptor tyrosine kinases. Based on these data, we propose a model in which proteoglycans and their modifying enzymes promote receptor tyrosine kinase signalling and progression in glioblastoma, and we suggest that cancer-associated proteoglycans are promising biomarkers for disease and therapeutic targets. © 2013 The Authors Journal compilation © 2013 FEBS.

  1. Brain Cancer in Workers Employed at a Laboratory Research Facility.

    Directory of Open Access Journals (Sweden)

    James J Collins

    Full Text Available An earlier study of research facility workers found more brain cancer deaths than expected, but no workplace exposures were implicated.Adding four additional years of vital-status follow-up, we reassessed the risk of death from brain cancer in the same workforce, including 5,284 workers employed between 1963, when the facility opened, and 2007. We compared the work histories of the brain cancer decedents in relationship to when they died and their ages at death.As in most other studies of laboratory and research workers, we found low rates of total mortality, total cancers, accidents, suicides, and chronic conditions such as heart disease and diabetes. We found no new brain cancer deaths in the four years of additional follow-up. Our best estimate of the brain cancer standardized mortality ratio (SMR was 1.32 (95% confidence interval [95% CI] 0.66-2.37, but the SMR might have been as high as 1.69. Deaths from benign brain tumors and other non-malignant diseases of the nervous system were at or below expected levels.With the addition of four more years of follow-up and in the absence of any new brain cancers, the updated estimate of the risk of brain cancer death is smaller than in the original study. There was no consistent pattern among the work histories of decedents that indicated a common causative exposure.

  2. Work-up times in an integrated brain cancer pathway

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    Lund Laursen, Emilie; Rasmussen, Birthe Krogh

    2012-01-01

    The integrated brain cancer pathway (IBCP) aims to ensure fast-track diagnostics and treatment for brain cancers in Denmark. This paper focuses on the referral pattern and the time frame of key pathway elements during the first two years following implementation of the IBCP in a regional neurology...

  3. Novel Nanotechnologies for Brain Cancer Therapeutics and Imaging.

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    Ferroni, Letizia; Gardin, Chiara; Della Puppa, Alessandro; Sivolella, Stefano; Brunello, Giulia; Scienza, Renato; Bressan, Eriberto; D'Avella, Domenico; Zavan, Barbara

    2015-11-01

    Despite progress in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of brain cancer, specifically malignant gliomas, does not yet exist. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood-brain barrier. Nanotechnology today offers a unique opportunity to develop more effective brain cancer imaging and therapeutics. In particular, the development of nanocarriers that can be conjugated with several functional molecules including tumor-specific ligands, anticancer drugs, and imaging probes, can provide new devices which are able to overcome the difficulties of the classical strategies. Nanotechnology-based approaches hold great promise for revolutionizing brain cancer medical treatments, imaging, and diagnosis.

  4. Attributes of brain metastases from breast and lung cancer.

    Science.gov (United States)

    Hengel, Kyle; Sidhu, Gurinder; Choi, Jai; Weedon, Jeremy; Nwokedi, Emmanuel; Axiotis, Constantine A; Song, Xianyuan; Braverman, Albert S

    2013-06-01

    Most brain metastases arise from breast and lung cancers. Few studies compare the brain regions they involve, their numbers and intrinsic attributes. Records of all patients referred to Radiation Oncology for treatment of symptomatic brain metastases were obtained. Computed tomography (n = 56) or magnetic resonance imaging (n = 72) brain scans were reviewed. Data from 68 breast and 62 lung cancer patients were compared. Brain metastases presented earlier in the course of the lung than of the breast cancer patients (p = 0.001). There were more metastases in the cerebral hemispheres of the breast than of the lung cancer patients (p = 0.014). More breast than lung cancer patients had cerebellar metastases (p = 0.001). The number of cerebral hemisphere metastases and presence of cerebellar metastases were positively correlated (p = 0.001). The prevalence of at least one metastasis surrounded with >2 cm of edema was greater for the lung than for the breast patients (p = 0.019). The primary tumor type, rather than the scanning method, correlated with differences between these variables. Brain metastases from lung occur earlier, are more edematous, but fewer in number than those from breast cancers. Cerebellar brain metastases are more frequent in breast cancer.

  5. Capturing Changes in the Brain Microenvironment during Initial Steps of Breast Cancer Brain Metastasis

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    Lorger, Mihaela; Felding-Habermann, Brunhilde

    2010-01-01

    Brain metastases are difficult to treat and mostly develop late during progressive metastatic disease. Patients at risk would benefit from the development of prevention and improved treatments. This requires knowledge of the initial events that lead to brain metastasis. The present study reveals cellular events during the initiation of brain metastasis by breast cancer cells and documents the earliest host responses to incoming cancer cells after carotid artery injection in immunodeficient and immunocompetent mouse models. Our findings capture and characterize heterogeneous astrocytic and microglial reactions to the arrest and extravasation of cancer cells in the brain, showing immediate and drastic changes in the brain microenvironment on arrival of individual cancer cells. We identified reactive astrocytes as the most active host cell population that immediately localizes to individual invading tumor cells and continuously associates with growing metastatic lesions. Up-regulation of matrix metalloproteinase-9 associated with astrocyte activation in the immediate vicinity of extravasating cancer cells might support their progression. Early involvement of different host cell types indicates environmental clues that might codetermine whether a single cancer cell progresses to macrometastasis or remains dormant. Thus, information on the initial interplay between brain homing tumor cells and reactive host cells may help develop strategies for prevention and treatment of symptomatic breast cancer brain metastases. PMID:20382702

  6. Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer.

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    Matsunaga, Shigeo; Shuto, Takashi; Sato, Mitsuru

    2016-05-01

    The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Cyclohexylmethyl Flavonoids Suppress Propagation of Breast Cancer Stem Cells via Downregulation of NANOG

    Directory of Open Access Journals (Sweden)

    Wen-Ying Liao

    2013-01-01

    Full Text Available Breast cancer stem cells (CSCs are highly tumorigenic and possess the capacity to self-renew. Recent studies indicated that pluripotent gene NANOG involves in regulating self-renewal of breast CSCs, and expression of NANOG is correlated with aggressiveness of poorly differentiated breast cancer. We initially confirmed that breast cancer MCF-7 cells expressed NANOG, and overexpression of NANOG enhanced the tumorigenicity of MCF-7 cells and promoted the self-renewal expansion of CD24−/lowCD44+ CSC subpopulation. In contrast, knockdown of NANOG significantly affected the growth of breast CSCs. Utilizing flow cytometry, we identified five cyclohexylmethyl flavonoids that can inhibit propagation of NANOG-positive cells in both breast cancer MCF-7 and MDA-MB231 cells. Among these flavonoids, ugonins J and K were found to be able to induce apoptosis in non-CSC populations and to reduce self-renewal growth of CD24−/lowCD44+ CSC population. Treatment with ugonin J significantly reduced the tumorigenicity of MCF-7 cells and efficiently suppressed formation of mammospheres. This suppression was possibly due to p53 activation and NANOG reduction as either addition of p53 inhibitor or overexpression of NANOG can counteract the suppressive effect of ugonin J. We therefore conclude that cyclohexylmethyl flavonoids can possibly be utilized to suppress the propagation of breast CSCs via reduction of NANOG.

  8. Non-coding RNAs in cancer brain metastasis.

    Science.gov (United States)

    Wu, Kerui; Sharma, Sambad; Venkat, Suresh; Liu, Keqin; Zhou, Xiaobo; Watabe, Kounosuke

    2016-01-01

    More than 90% of cancer death is attributed to metastatic disease, and the brain is one of the major metastatic sites of melanoma, colon, renal, lung and breast cancers. Despite the recent advancement of targeted therapy for cancer, the incidence of brain metastasis is increasing. One reason is that most therapeutic drugs can't penetrate blood-brain-barrier and tumor cells find the brain as sanctuary site. In this review, we describe the pathophysiology of brain metastases to introduce the latest understandings of metastatic brain malignancies. This review also particularly focuses on non-coding RNAs and their roles in cancer brain metastasis. Furthermore, we discuss the roles of the extracellular vesicles as they are known to transport information between cells to initiate cancer cell-microenvironment communication. The potential clinical translation of non-coding RNAs as a tool for diagnosis and for treatment is also discussed in this review. At the end, the computational aspects of non-coding RNA detection, the sequence and structure calculation and epigenetic regulation of non-coding RNA in brain metastasis are discussed.

  9. Brain metastasis from male breast cancer treated 12 years ago ...

    African Journals Online (AJOL)

    The brain MRI showed a huge right temporal process with a shift of the midline structures (figure). A biopsy was also performed and demonstrated a cerebral relapsed breast primitive with the same disease profile (HR positive and HER2 negative). Brain metastases traditionally occur in 10-16% of metastatic breast cancer ...

  10. Ganging Up on Brain Metastases | Center for Cancer Research

    Science.gov (United States)

    When primary tumors metastasize to the brain, the prognosis for patients is poor. The currently accepted treatment is whole-brain radiation therapy, and the median survival time is several months. Since these types of tumors form in 10 to 30 percent of adult cancer patients, improvements in treatment methods are a necessity.  

  11. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  12. Brain metastasis from ovarian cancer: a systematic review.

    Science.gov (United States)

    Pakneshan, Shabnam; Safarpour, Damoun; Tavassoli, Fattaneh; Jabbari, Bahman

    2014-08-01

    To review the existing literature on brain metastasis (BM) from ovarian cancer and to assess the frequency, anatomical, clinical and paraclinical information and factors associated with prognosis. Ovarian cancer is a rare cause of brain metastasis with a recently reported increasing prevalence. Progressive neurologic disability and poor prognosis is common. A comprehensive review on this subject has not been published previously. This systematic literature search used the Pubmed and Yale library. A total of 66 publications were found, 57 of which were used representing 591 patients with BM from ovarian cancer. The median age of the patients was 54.3 years (range 20-81). A majority of patients (57.3 %) had multiple brain lesions. The location of the lesion was cerebellar (30 %), frontal (20 %), parietal (18 %) and occipital (11 %). Extracranial metastasis was present in 49.8 % of cases involving liver (20.7 %), lung (20.4 %), lymph nodes (12.6 %), bones (6.6 %) and pelvic organs (4.3 %). The most common symptoms were weakness (16 %), seizures (11 %), altered mentality (11 %) visual disturbances (9 %) and dizziness (8 %). The interval from diagnosis of breast cancer to BM ranged from 0 to 133 months (median 24 months) and median survival was 8.2 months. Local radiation, surgical resection, stereotactic radiosurgery and medical therapy were used. Factors that significantly increased the survival were younger age at the time of ovarian cancer diagnosis and brain metastasis diagnosis, lower grade of the primary tumor, higher KPS score and multimodality treatment for the brain metastases. Ovarian cancer is a rare cause of brain metastasis. Development of brain metastasis among older patients and lower KPS score correlate with less favorable prognosis. The more prolonged survival after using multimodality treatment for brain metastasis is important due to potential impact on management of brain metastasis in future.

  13. Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer.

    Science.gov (United States)

    Zhao, Ren; Kong, Wei; Shang, Jun; Zhe, Hong; Wang, Yan-Yang

    2017-03-01

    Brain metastases occur in 20% to 40% of lung cancer patients. Whole-brain radiotherapy (WBRT) has long been considered the treatment of choice for many patients with lung cancer, because of its wide availability, ease of delivery, and effectiveness in prolonging survival. However, WBRT is also associated with several side effects, such as decline in memory and other cognitive functions. There exists significant preclinical and clinical evidence that radiation-induced injury to the hippocampus correlates with neurocognitive decline of patients who receive WBRT. Technological advances in treatment planning and delivery facilitate the use of hippocampal-sparing (HS) WBRT as prophylactic cranial irradiation or the primary treatment modality for lung cancer patients with brain metastases. In this review, we provide a detailed and comprehensive discussion of the safety profile, techniques for hippocampus-sparing, and the clinical evidence of HS-WBRT for lung cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Comparison of Back propagation neural network and Back propagation neural network Based Particle Swarm intelligence in Diagnostic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Farahnaz SADOUGHI

    2014-03-01

    Full Text Available Breast cancer is the most commonly diagnosed cancer and the most common cause of death in women all over the world. Use of computer technology supporting breast cancer diagnosing is now widespread and pervasive across a broad range of medical areas. Early diagnosis of this disease can greatly enhance the chances of long-term survival of breast cancer victims. Artificial Neural Networks (ANN as mainly method play important role in early diagnoses breast cancer. This paper studies Levenberg Marquardet Backpropagation (LMBP neural network and Levenberg Marquardet Backpropagation based Particle Swarm Optimization(LMBP-PSO for the diagnosis of breast cancer. The obtained results show that LMBP and LMBP based PSO system provides higher classification efficiency. But LMBP based PSO needs minimum training and testing time. It helps in developing Medical Decision System (MDS for breast cancer diagnosing. It can also be used as secondary observer in clinical decision making.

  15. Breast Cancer Resistance Protein and P-glycoprotein in Brain Cancer: Two Gatekeepers Team Up

    Science.gov (United States)

    Agarwal, Sagar; Hartz, Anika M.S.; Elmquist, William F.; Bauer, Björn

    2012-01-01

    Brain cancer is a devastating disease. Despite extensive research, treatment of brain tumors has been largely ineffective and the diagnosis of brain cancer remains uniformly fatal. Failure of brain cancer treatment may be in part due to limitations in drug delivery, influenced by the ABC drug efflux transporters P-gp and BCRP at the blood-brain and blood-tumor barriers, in brain tumor cells, as well as in brain tumor stem-like cells. P-gp and BCRP limit various anti-cancer drugs from entering the brain and tumor tissues, thus rendering chemotherapy ineffective. To overcome this obstacle, two strategies – targeting transporter regulation and direct transporter inhibition – have been proposed. In this review, we focus on these strategies. We first introduce the latest findings on signaling pathways that could potentially be targeted to down-regulate P-gp and BCRP expression and/or transport activity. We then highlight in detail the new paradigm of P-gp and BCRP working as a “cooperative team of gatekeepers” at the blood-brain barrier, discuss its ramifications for brain cancer therapy, and summarize the latest findings on dual P-gp/BCRP inhibitors. Finally, we provide a brief summary with conclusions and outline the perspectives for future research endeavors in this field. PMID:21827403

  16. Plumes of neuronal activity propagate in three dimensions through the nuclear avian brain

    NARCIS (Netherlands)

    Beckers, Gabriël J L; van der Meij, Jacqueline; Lesku, John A.; Rattenborg, Niels C.

    2014-01-01

    Background: In mammals, the slow-oscillations of neuronal membrane potentials (reflected in the electroencephalogram as high-amplitude, slow-waves), which occur during non-rapid eye movement sleep and anesthesia, propagate across the neocortex largely as two-dimensional traveling waves. However, it

  17. Targeted Therapies for Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Vyshak Alva Venur

    2016-09-01

    Full Text Available The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2 and epidermal growth factor receptor (EGFR, vascular endothelial growth factor (VEGF receptor, mechanistic target of rapamycin (mTOR pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6 pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%–30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  18. Targeted Therapies for Brain Metastases from Breast Cancer.

    Science.gov (United States)

    Venur, Vyshak Alva; Leone, José Pablo

    2016-09-13

    The discovery of various driver pathways and targeted small molecule agents/antibodies have revolutionized the management of metastatic breast cancer. Currently, the major targets of clinical utility in breast cancer include the human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) receptor, mechanistic target of rapamycin (mTOR) pathway, and the cyclin-dependent kinase 4/6 (CDK-4/6) pathway. Brain metastasis, however, remains a thorn in the flesh, leading to morbidity, neuro-cognitive decline, and interruptions in the management of systemic disease. Approximately 20%-30% of patients with metastatic breast cancer develop brain metastases. Surgery, whole brain radiation therapy, and stereotactic radiosurgery are the traditional treatment options for patients with brain metastases. The therapeutic paradigm is changing due to better understanding of the blood brain barrier and the advent of tyrosine kinase inhibitors and monoclonal antibodies. Several of these agents are in clinical practice and several others are in early stage clinical trials. In this article, we will review the common targetable pathways in the management of breast cancer patients with brain metastases, and the current state of the clinical development of drugs against these pathways.

  19. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid......Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

  20. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

  1. Brain-only metastases of small cell lung cancer; efficacy of whole brain radiotherapy. An EORTC phase II study

    NARCIS (Netherlands)

    Postmus, PE; Haaxma-Reiche, H; Gregor, A; Groen, HJM; Lewinski, T; Scolard, T; Kirkpatrick, A; Curran, D; Sahmoud, T; Giaccone, G

    Background and purpose: To evaluate the efficacy of WBRT as a single treatment modality in patients with brain metastases of small cell lung cancer. Patients and methods: The patients had brain metastases of small cell lung cancer without any sign of tumour outside the brain and were treated with 10

  2. Transferrin liposomes of docetaxel for brain-targeted cancer applications: formulation and brain theranostics.

    Science.gov (United States)

    Sonali; Singh, Rahul Pratap; Singh, Nitesh; Sharma, Gunjan; Vijayakumar, Mahalingam R; Koch, Biplob; Singh, Sanjay; Singh, Usha; Dash, Debabrata; Pandey, Bajarangprasad L; Muthu, Madaswamy S

    2016-05-01

    Diagnosis and therapy of brain cancer was often limited due to low permeability of delivery materials across the blood-brain barrier (BBB) and their poor penetration into the brain tissue. This study explored the possibility of utilizing theranostic d-alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) liposomes as nanocarriers for minimally invasive brain-targeted imaging and therapy (brain theranostics). The aim of this work was to formulate transferrin conjugated TPGS coated theranostic liposomes, which contain both docetaxel and quantum dots (QDs) for imaging and therapy of brain cancer. The theranostic liposomes with and without transferrin decoration were prepared and characterized for their particle size, polydispersity, morphology, drug encapsulation efficiency, in-vitro release study and brain theranostics. The particle sizes of the non-targeted and targeted theranostic liposomes were found below 200 nm. Nearly, 71% of drug encapsulation efficiency was achieved with liposomes. The drug release from transferrin conjugated theranostic liposomes was sustained for more than 72 h with 70% of drug release. The in-vivo results indicated that transferrin receptor-targeted theranostic liposomes could be a promising carrier for brain theranostics due to nano-sized delivery and its permeability which provided an improved and prolonged brain targeting of docetaxel and QDs in comparison to the non-targeted preparations.

  3. Is myelin basic protein a potential biomarker of brain cancer?

    Science.gov (United States)

    Zavialova, M G; Shevchenko, V E; Nikolaev, E N; Zgoda, V G

    2017-08-01

    Myelin basic protein is a potential biomarker for the central nervous system diseases in which the myelin sheath is destroyed. Using pseudo-selected reaction monitoring and the method of standard additions, we have measured the myelin basic protein level in the cerebrospinal fluid of patients with neurotrauma (n = 6), chronic neurodegenerative diseases (n = 2) and brain cancer (n = 5). Myelin basic protein was detected only in four out of five cerebrospinal fluid samples of patients with brain cancer. The cerebrospinal fluid myelin basic protein level ranged from 3.7 to 8.8 ng ml-1. We suggest that monitoring of myelin basic protein in cerebrospinal fluid can serve as a diagnostic test for the brain cancer.

  4. Rethinking Brain Cancer Therapy: Tumor Enzyme Activatable Theranostic Nanoparticles.

    Science.gov (United States)

    Daldrup-Link, Heike E

    2017-01-01

    This invited commentary discusses a recent article by Mohanty et al in Molecular Cancer Therapeutics about significant therapeutic efficacies of novel theranostic nanoparticles (TNPs) for the treatment of human brain cancers in mouse models. The TNPs were cleaved by enzymes in the tumor tissue, matrix metalloproteinase (MMP-14), which lead to release of a highly potent therapeutic drug, azademethylcolchicine. Data showed that the TNPs caused selective toxic effects in MMP-14-expressing glioblastoma and not normal brain. In addition, the iron oxide nanoparticle backbone enabled in vivo drug tracking with magnetic resonance imaging (MRI). This commentary discusses previous efforts of MMP-targeted therapeutics as well as opportunities for further refinements of tumor enzyme-activatable TNPs. If successfully translated to clinical applications, the TNPs might hold substantial potential to improving cytotoxic indexes and long-term outcomes of patients with brain cancer compared to standard therapy.

  5. Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis

    Science.gov (United States)

    Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T. D.; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N.; DiPerna, Danielle M.; Paquette, Kimberly M.; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F.; Liotta, Lance A.; Ramanathan, Ramesh K.; Berens, Michael E.; Tran, Nhan L.

    2014-01-01

    The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. PMID:24489661

  6. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio.

    Science.gov (United States)

    Yang, Tianzhi; Martin, Paige; Fogarty, Brittany; Brown, Alison; Schurman, Kayla; Phipps, Roger; Yin, Viravuth P; Lockman, Paul; Bai, Shuhua

    2015-06-01

    The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. Four types of exosomes were isolated from brain cell culture media and characterized by particle size, morphology, total protein, and transmembrane protein markers. Transport mechanism, cell uptake, and cytotoxicity of optimized exosome delivery system were tested. Brain distribution of exosome delivered anticancer drugs was evaluated using transgenic zebrafish TG (fli1: GFP) embryos and efficacies of optimized formations were examined in a xenotransplanted zebrafish model of brain cancer model. Four exosomes in 30-100 diameters showed different morphologies and exosomes derived from brain endothelial cells expressed more CD63 tetraspanins transmembrane proteins. Optimized exosomes increased the uptake of fluorescent marker via receptor mediated endocytosis and cytotoxicity of anticancer drugs in cancer cells. Images of the zebrafish showed exosome delivered anticancer drugs crossed the BBB and entered into the brain. In the brain cancer model, exosome delivered anticancer drugs significantly decreased fluorescent intensity of xenotransplanted cancer cells and tumor growth marker. Brain endothelial cell derived exosomes could be potentially used as a carrier for brain delivery of anticancer drug for the treatment of brain cancer.

  7. Optimization of propagation-based x-ray phase-contrast tomography for breast cancer imaging.

    Science.gov (United States)

    Baran, P; Pacile, S; Nesterets, Y I; Mayo, S C; Dullin, C; Dreossi, D; Arfelli, F; Thompson, D; Lockie, D; McCormack, M; Taba, S T; Brun, F; Pinamonti, M; Nickson, C; Hall, C; Dimmock, M; Zanconati, F; Cholewa, M; Quiney, H; Brennan, P C; Tromba, G; Gureyev, T E

    2017-03-21

    The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.

  8. Optimization of propagation-based x-ray phase-contrast tomography for breast cancer imaging

    Science.gov (United States)

    Baran, P.; Pacile, S.; Nesterets, Y. I.; Mayo, S. C.; Dullin, C.; Dreossi, D.; Arfelli, F.; Thompson, D.; Lockie, D.; McCormack, M.; Taba, S. T.; Brun, F.; Pinamonti, M.; Nickson, C.; Hall, C.; Dimmock, M.; Zanconati, F.; Cholewa, M.; Quiney, H.; Brennan, P. C.; Tromba, G.; Gureyev, T. E.

    2017-03-01

    The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.

  9. Propagation of registration uncertainty during multi-fraction cervical cancer brachytherapy

    Science.gov (United States)

    Amir-Khalili, A.; Hamarneh, G.; Zakariaee, R.; Spadinger, I.; Abugharbieh, R.

    2017-10-01

    Multi-fraction cervical cancer brachytherapy is a form of image-guided radiotherapy that heavily relies on 3D imaging during treatment planning, delivery, and quality control. In this context, deformable image registration can increase the accuracy of dosimetric evaluations, provided that one can account for the uncertainties associated with the registration process. To enable such capability, we propose a mathematical framework that first estimates the registration uncertainty and subsequently propagates the effects of the computed uncertainties from the registration stage through to the visualizations, organ segmentations, and dosimetric evaluations. To ensure the practicality of our proposed framework in real world image-guided radiotherapy contexts, we implemented our technique via a computationally efficient and generalizable algorithm that is compatible with existing deformable image registration software. In our clinical context of fractionated cervical cancer brachytherapy, we perform a retrospective analysis on 37 patients and present evidence that our proposed methodology for computing and propagating registration uncertainties may be beneficial during therapy planning and quality control. Specifically, we quantify and visualize the influence of registration uncertainty on dosimetric analysis during the computation of the total accumulated radiation dose on the bladder wall. We further show how registration uncertainty may be leveraged into enhanced visualizations that depict the quality of the registration and highlight potential deviations from the treatment plan prior to the delivery of radiation treatment. Finally, we show that we can improve the transfer of delineated volumetric organ segmentation labels from one fraction to the next by encoding the computed registration uncertainties into the segmentation labels.

  10. Management of lung cancer brain metastasis: An overview

    Directory of Open Access Journals (Sweden)

    Himanshu Srivastava

    2017-01-01

    Full Text Available With the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

  11. EGFR and HER2 signaling in breast cancer brain metastasis

    Science.gov (United States)

    Sirkisoon, Sherona R.; Carpenter, Richard L.; Rimkus, Tadas; Miller, Lance; Metheny-Barlow, Linda; Lo, Hui-Wen

    2016-01-01

    Breast cancer occurs in approximately 1 in 8 women and 1 in 37 women with breast cancer succumbed to the disease. Over the past decades, new diagnostic tools and treatments have substantially improved the prognosis of women with local diseases. However, women with metastatic disease still have a dismal prognosis without effective treatments. Among different molecular subtypes of breast cancer, the HER2-enriched and basal-like subtypes typically have higher rates of metastasis to the brain. Basal-like metastatic breast tumors frequently express EGFR. Consequently, HER2- and EGFR-targeted therapies are being used in the clinic and/or evaluated in clinical trials for treating breast cancer patients with brain metastases. In this review, we will first provide an overview of the HER2 and EGFR signaling pathways. The roles that EGFR and HER2 play in breast cancer metastasis to the brain will then be discussed. Finally, we will summarize the preclinical and clinical effects of EGFR- and HER2-targeted therapies on breast cancer metastasis. PMID:26709660

  12. Significance of Primary Tumor Location and Histology for Brain Metastasis Development and Peritumoral Brain Edema in Lung Cancer

    DEFF Research Database (Denmark)

    Fabian, Katalin; Gyulai, Marton; Furak, Jozsef

    2016-01-01

    of peritumoral brain edema (p development of brain metastasis was shorter in central than in peripheral lung cancer (5.3 vs. 9.0 months, p = 0.035). Early brain...... metastasis was characteristic for adenocarcinomas. A total of 135 patients had brain only metastases (N0 disease) characterized by peripheral lung cancer predominance (p development of brain metastasis (9.2 vs. 4.4 months, p ... in patients with N1-3 diseases (p development and radiographic features of brain metastases. Our results might be helpful in selecting patients who might benefit from prophylactic cranial irradiation. (C) 2016 S...

  13. Analysis of sports related mTBI injuries caused by elastic wave propagation through brain tissue

    OpenAIRE

    Case, D.; Richer, E.

    2016-01-01

    Repetitive concussions and sub-concussions suffered by athletes have been linked to a series of sequelae ranging from traumatic encephalopathy to dementia pugilistica. A detailed finite element model of the human head was developed based on standard libraries of medical imaging. The model includes realistic material properties for the brain tissue, bone, soft tissue, and CSF, as well as the structure and properties of a protective helmet. Various impact scenarios were studied, with a focus on...

  14. Brain cancer probed by native fluorescence and stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-hui; He, Yong; Pu, Yang; Li, Qingbo; Wang, Wei; Alfano, Robert R.

    2012-12-01

    Optical biopsy spectroscopy was applied to diagnosis human brain cancer in vitro. The spectra of native fluorescence, Stokes shift and excitation spectra were obtained from malignant meningioma, benign, normal meningeal tissues and acoustic neuroma benign tissues. The wide excitation wavelength ranges were used to establish the criterion for distinguishing brain diseases. The alteration of fluorescence spectra between normal and abnormal brain tissues were identified by the characteristic fluorophores under the excitation with UV to visible wavelength range. It was found that the ratios of the peak intensities and peak position in both spectra of fluorescence and Stokes shift may be used to diagnose human brain meninges diseases. The preliminary analysis of fluorescence spectral data from cancer and normal meningeal tissues by basic biochemical component analysis model (BBCA) and Bayes classification model based on statistical methods revealed the changes of components, and classified the difference between cancer and normal human brain meningeal tissues in a predictions accuracy rate is 0.93 in comparison with histopathology and immunohistochemistry reports (gold standard).

  15. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2013-10-01

    antibodies to the endothelial marker, CD31 (Serotec, Raleigh, NC) followed by Cy3-conjugated secondary antibody ( Jackson Immunoresearch Laboratories...in the brain. Cancer Res 67, 4190-4198, doi:67/9/4190 [pii] 10.1158/0008-5472.CAN-06- 3316 (2007). 7 Percy , D. B. et al. In vivo characterization of

  16. Serpins Promote Cancer Cell Survival and Vascular Cooption in Brain Metastasis

    Science.gov (United States)

    Valiente, Manuel; Obenauf, Anna C.; Jin, Xin; Chen, Qing; Zhang, Xiang H.-F.; Lee, Derek J.; Chaft, Jamie E.; Kris, Mark G.; Huse, Jason T.; Brogi, Edi; Massagué, Joan

    2014-01-01

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM that metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its deleterious consequences. By protecting cancer cells from death signals and fostering vascular cooption, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. PMID:24581498

  17. Targeting energy metabolism in brain cancer: review and hypothesis

    Directory of Open Access Journals (Sweden)

    Mukherjee Purna

    2005-10-01

    Full Text Available Abstract Malignant brain tumors are a significant health problem in children and adults and are often unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration, malignant brain cancer is potentially manageable through changes in metabolic environment. A radically different approach to brain cancer management is proposed that combines metabolic control analysis with the evolutionarily conserved capacity of normal cells to survive extreme shifts in physiological environment. In contrast to malignant brain tumors that are largely dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The bioenergetic transition from glucose to ketone bodies metabolically targets brain tumors through integrated anti-inflammatory, anti-angiogenic, and pro-apoptotic mechanisms. The approach focuses more on the genomic flexibility of normal cells than on the genomic defects of tumor cells and is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with dietary energy restriction and the ketogenic diet.

  18. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Facchino, Sabrina; Abdouh, Mohamed [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Bernier, Gilbert, E-mail: gbernier.hmr@ssss.gouv.qc.ca [Developmental Biology Laboratory, Hopital Maisonneuve-Rosemont, 5415 Boul. l' Assomption, Montreal, H1T 2M4 (Canada); Faculté de Médecine, Université de Montréal, Montréal, H3T 1J4 (Canada)

    2011-03-30

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cell self-renewal mechanism. GBM tumors are also notorious for their resistance to radiation therapy. Notably, GBM “cancer stem cells” were also found to be responsible for this radioresistance. Herein, we will analyze the data supporting or not the cancer stem cell model in GBM, overview the current knowledge regarding GBM stem cell self-renewal and radioresistance molecular mechanisms, and discuss the potential therapeutic application of these findings.

  19. [Robo1 expression in non-small cell lung cancer and its brain metastasis].

    Science.gov (United States)

    Li, Xiao-xia; Jin, Ling; Sun, Zeng-feng; Gu, Feng; Li, Wen-liang; Ma, Yong-jie

    2013-03-01

    To detect the expression of Robo1 in lung cancer tissues, adjacent non-cancerous tissues as well as lung cancer brain metastasis, and explore the correlation of Robo1 expression to lung cancer brain metastasis. SP (streptavidin-peroxidase) staining method was used to examine the Robo1 expression in specimens from 80 cases of NSCLC, 52 cases of adjacent non-cancerous tissues and 72 cases of lung cancer with single brain metastasis (without metastasis in other organs). The Robo1 expression was further examined in 17 self control cases with lung cancer tissues and their brain metastasis tissues. The results were assessed by Kaplan-Meier analysis and log-rank test. The positive expression rate of Robo1 among adjacent non-cancerous tissues, lung cancers tissues and the lung cancer brain metastasis tissues were 1.9% (1/52), 13.8% (11/80) and 40.3% (29/72), respectively, and significant differences were detected among them (P Robo1 in lung cancer tissue and their brain metastasis tissues were 17.6% and 64.7%, respectively, with a significant difference between them (P cancer brain metastasis, the median survival time of cases with positive Robo1 expression was 10 months, significantly shorter than that of cases with negative expression of Robo1 (17 months, P Robo1 was increased in sequence from the lowest in adjacent non-cancerous tissues, intermediate in the lung cancer tissues to highest in the lung cancer brain metastasis tissues. The expression of Robo1 in lung cancer brain metastasis is negatively correlated with the prognosis of patients with lung cancer brain metastasis. Robo1 may promote the genesis and progression of lung cancer and lung cancer brain metastasis as a cancer-promoting oncogene.

  20. No increase in brain cancer rates during period of expanding cell phone use

    Science.gov (United States)

    In a new examination of United States cancer incidence data, investigators at the National Cancer Institute (NCI) reported that incidence trends have remained roughly constant for glioma, the main type of brain cancer hypothesized to be related to cell ph

  1. Dietary acrylamide intake and brain cancer risk

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2009-01-01

    Background: Acrylamide is a probable human carcinogen, which is present in several heat-treatedfood s. In epidemiologic studies, positive associations with endometrial, ovarian, and renal cell cancer risk have been observed. The incidence of central nervous system tumors was increased upon

  2. Do patients with very few brain metastases from breast cancer benefit from whole-brain radiotherapy in addition to radiosurgery?

    Science.gov (United States)

    Rades, Dirk; Huttenlocher, Stefan; Hornung, Dagmar; Blanck, Oliver; Schild, Steven E; Fischer, Dorothea

    2014-12-04

    An important issue in palliative radiation oncology is the whether whole-brain radiotherapy should be added to radiosurgery when treating a limited number of brain metastases. To optimize personalized treatment of cancer patients with brain metastases, the value of whole-brain radiotherapy should be described separately for each tumor entity. This study investigated the role of whole-brain radiotherapy added to radiosurgery in breast cancer patients. Fifty-eight patients with 1-3 brain metastases from breast cancer were included in this retrospective study. Of these patients, 30 were treated with radiosurgery alone and 28 with radiosurgery plus whole-brain radiotherapy. Both groups were compared for local control of the irradiated metastases, freedom from new brain metastases and survival. Furthermore, eight additional factors were analyzed including dose of radiosurgery, age at radiotherapy, Eastern Cooperative Oncology Group (ECOG) performance score, number of brain metastases, maximum diameter of all brain metastases, site of brain metastases, extra-cranial metastases and the time from breast cancer diagnosis to radiotherapy. The treatment regimen had no significant impact on local control in the univariate analysis (p=0.59). Age ≤59 years showed a trend towards improved local control on univariate (p=0.066) and multivariate analysis (p=0.07). On univariate analysis, radiosurgery plus whole-brain radiotherapy (p=0.040) and ECOG 0-1 (p=0.012) showed positive associations with freedom from new brain metastases. Both treatment regimen (p=0.039) and performance status (p=0.028) maintained significance on multivariate analysis. ECOG 0-1 was positively correlated with survival on univariate analysis (pbreast cancer patients with few brain metastases, radiosurgery plus whole-brain radiotherapy resulted in significantly better freedom from new brain metastases than radiosurgery alone. However, this advantage did not lead to significantly better survival.

  3. Rationale for the Use of Upfront Whole Brain Irradiation in Patients with Brain Metastases from Breast Cancer

    Directory of Open Access Journals (Sweden)

    Agnes V. Tallet

    2014-05-01

    Full Text Available Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  4. Rationale for the use of upfront whole brain irradiation in patients with brain metastases from breast cancer.

    Science.gov (United States)

    Tallet, Agnes V; Azria, David; Le Rhun, Emilie; Barlesi, Fabrice; Carpentier, Antoine F; Gonçalves, Antony; Taillibert, Sophie; Dhermain, Frédéric; Spano, Jean-Philippe; Metellus, Philippe

    2014-05-08

    Breast cancer is the second most common cause of brain metastases and deserves particular attention in relation to current prolonged survival of patients with metastatic disease. Advances in both systemic therapies and brain local treatments (surgery and stereotactic radiosurgery) have led to a reappraisal of brain metastases management. With respect to this, the literature review presented here was conducted in an attempt to collect medical evidence-based data on the use of whole-brain radiotherapy for the treatment of brain metastases from breast cancer. In addition, this study discusses here the potential differences in outcomes between patients with brain metastases from breast cancer and those with brain metastases from other primary malignancies and the potential implications within a treatment strategy.

  5. Brain imaging before primary lung cancer resection: a controversial topic.

    Science.gov (United States)

    Hudson, Zoe; Internullo, Eveline; Edey, Anthony; Laurence, Isabel; Bianchi, Davide; Addeo, Alfredo

    2017-01-01

    International and national recommendations for brain imaging in patients planned to undergo potentially curative resection of non-small-cell lung cancer (NSCLC) are variably implemented throughout the United Kingdom [Hudson BJ, Crawford MB, and Curtin J et al (2015) Brain imaging in lung cancer patients without symptoms of brain metastases: a national survey of current practice in England Clin Radiol https://doi.org/10.1016/j.crad.2015.02.007]. However, the recommendations are not based on high-quality evidence and do not take into account cost implications and local resources. Our aim was to determine local practice based on historic outcomes in this patient cohort. This retrospective study took place in a regional thoracic surgical centre in the United Kingdom. Pathology records for all patients who had undergone lung resection with curative intent during the time period January 2012-December 2014 were analysed in October 2015. Electronic pathology and radiology reports were accessed for each patient and data collected about their histological findings, TNM stage, resection margins, and the presence of brain metastases on either pre-operative or post-operative imaging. From the dates given on imaging, we calculated the number of days post-resection that the brain metastases were detected. 585 patients were identified who had undergone resection of their lung cancer. Of these, 471 had accessible electronic radiology records to assess for the radiological evidence of brain metastases. When their electronic records were evaluated, 25/471 (5.3%) patients had radiological evidence of brain metastasis. Of these, five patients had been diagnosed with a brain metastasis at initial presentation and had undergone primary resection of the brain metastasis followed by resection of the lung primary. One patient had been diagnosed with both a primary lung and a primary bowel adenocarcinoma; on review of the case, it was felt that the brain metastasis was more likely to have

  6. [Synchronization and propagation of electrical potentials in neural networks of the brain cortex].

    Science.gov (United States)

    Marchenko, V G; Zaĭchenko, M I

    2014-01-01

    On the basis of the published data the scheme is proposed which explains the spread and synhronization of oscillatory activity in cortex. The main property of the neocortex is the existence of vertically oriented functional columns. Within and between the neuronal columns exist a feedforward and feedback morphological and functional connections. At the certain conditions inside the single module temporal windows are created using inhibitory process, and a synchronized activity can be generated of variable frequency (oscillations). The activity in the columns is enhanced by the synchronous involvement of great amount of neurons which is expressed in the form of local field potentials of high amplitude. Further the information about arisen in a single generator activity is transmitted through direct links to the nearby generator or to the group of such generators. In the nearby generator the activity increases and is transferred to the next generator. At the same time the signal is transmitted through feedback to the primary generator, and the activity is terminated until the next cycle will be initiated and so on along the cortex. The most important notion is that in the transfer of activity from one generator to another is involved a small number of elements. The major part of recorded oscillations of different frequency or epileptiform discharges, is not transmitted via the brain, but is generated in each module according to the characteristics transferred to it. The generation of epileptiform spikes occurs in cases when balance of inhibition determined by GABA A and GABA B receptors is disturbed.

  7. Gum chewing inhibits the sensory processing and the propagation of stress-related information in a brain network.

    Directory of Open Access Journals (Sweden)

    Hongbo Yu

    Full Text Available Stress is prevalent in human life and threatens both physical and mental health; stress coping is thus of adaptive value for individual's survival and well-being. Although there has been extensive research on how the neural and physiological systems respond to stressful stimulation, relatively little is known about how the brain dynamically copes with stress evoked by this stimulation. Here we investigated how stress is relieved by a popular coping behavior, namely, gum chewing. In an fMRI study, we used loud noise as an acute stressor and asked participants to rate their feeling of stress in gum-chewing and no-chewing conditions. The participants generally felt more stressful when hearing noise, but less so when they were simultaneously chewing gum. The bilateral superior temporal sulcus (STS and the left anterior insula (AI were activated by noise, and their activations showed a positive correlation with the self-reported feeling of stress. Critically, gum chewing significantly reduced the noise-induced activation in these areas. Psychophysiological interaction (PPI analysis showed that the functional connectivity between the left AI and the dorsal anterior cingulate cortex (dACC was increased by noise to a lesser extent when the participants were chewing gum than when not chewing gum. Dynamic causality modeling (DCM demonstrated that gum chewing inhibited the connectivity from the STS to the left AI. These findings demonstrate that gum chewing relieves stress by attenuating the sensory processing of external stressor and by inhibiting the propagation of stress-related information in the brain stress network.

  8. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images.

    Science.gov (United States)

    Gupta, Suneet; Porwal, Rabins

    2016-01-01

    Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images.

  9. Appropriate Contrast Enhancement Measures for Brain and Breast Cancer Images

    Directory of Open Access Journals (Sweden)

    Suneet Gupta

    2016-01-01

    Full Text Available Medical imaging systems often produce images that require enhancement, such as improving the image contrast as they are poor in contrast. Therefore, they must be enhanced before they are examined by medical professionals. This is necessary for proper diagnosis and subsequent treatment. We do have various enhancement algorithms which enhance the medical images to different extents. We also have various quantitative metrics or measures which evaluate the quality of an image. This paper suggests the most appropriate measures for two of the medical images, namely, brain cancer images and breast cancer images.

  10. A mathematical theory of shape and neuro-fuzzy methodology-based diagnostic analysis: a comparative study on early detection and treatment planning of brain cancer.

    Science.gov (United States)

    Kar, Subrata; Majumder, D Dutta

    2017-08-01

    Investigation of brain cancer can detect the abnormal growth of tissue in the brain using computed tomography (CT) scans and magnetic resonance (MR) images of patients. The proposed method classifies brain cancer on shape-based feature extraction as either benign or malignant. The authors used input variables such as shape distance (SD) and shape similarity measure (SSM) in fuzzy tools, and used fuzzy rules to evaluate the risk status as an output variable. We presented a classifier neural network system (NNS), namely Levenberg-Marquardt (LM), which is a feed-forward back-propagation learning algorithm used to train the NN for the status of brain cancer, if any, and which achieved satisfactory performance with 100% accuracy. The proposed methodology is divided into three phases. First, we find the region of interest (ROI) in the brain to detect the tumors using CT and MR images. Second, we extract the shape-based features, like SD and SSM, and grade the brain tumors as benign or malignant with the concept of SD function and SSM as shape-based parameters. Third, we classify the brain cancers using neuro-fuzzy tools. In this experiment, we used a 16-sample database with SSM (μ) values and classified the benignancy or malignancy of the brain tumor lesions using the neuro-fuzzy system (NFS). We have developed a fuzzy expert system (FES) and NFS for early detection of brain cancer from CT and MR images. In this experiment, shape-based features, such as SD and SSM, were extracted from the ROI of brain tumor lesions. These shape-based features were considered as input variables and, using fuzzy rules, we were able to evaluate brain cancer risk values for each case. We used an NNS with LM, a feed-forward back-propagation learning algorithm, as a classifier for the diagnosis of brain cancer and achieved satisfactory performance with 100% accuracy. The proposed network was trained with MR image datasets of 16 cases. The 16 cases were fed to the ANN with 2 input neurons, one

  11. Lung cancer brain metastases – the role of neurosurgery

    Directory of Open Access Journals (Sweden)

    V. A. Aleshin

    2016-01-01

    Full Text Available Lung cancer is mostly common occurring oncological disease in the developed countries. Currently lung cancers are subdivided into nonsmall-cell (adenocarcinoma, large-cell, squamous cell and small-cell. The difference in the clinical and morphological picture leads to the necessity of choosing therapeutic approaches to patients of various groups.Lung cancer should be referred to encephalotropic diseases since metastatic lesion of the central nervous system is sufficiently common complication. Successes of complex treatment of primary tumor result in increase of total longlivety currently ther is ageing of patients suffering lung cancer. These factors increase the risk of metastatic lesions of the brain.Interest to the problem of neurosurgical treatment of patients suffering lung cancer is determined by frequency of lesion, varicosity of morphological variants of the disease, requiring various algorithms of treatment and diagnosis.The main role of neurosurgical intervention in cerebral metastases of lung cancer consist in creation of the paled of carrying out combined therapy. Ideally, a neurosurgical operation should be carried out with clearcut observance of oncological principles of ablasty.Adequate comprehensive approach to treatment or patients with cerebral metastases of various forms of lung cancer with the developed of optimal tactics of and stages of treatment would make it possible to increase duration and quality of life of patients.

  12. Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases

    Directory of Open Access Journals (Sweden)

    Liyan QU

    2016-08-01

    Full Text Available Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized.

  13. Radiological Patterns of Brain Metastases in Breast Cancer Patients : A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry

    NARCIS (Netherlands)

    Laakmann, Elena; Witzel, Isabell; Scriba, Verena; Grzyska, Ulrich; zu Eulenburg, Christine; Burchardi, Nicole; Hesse, Tobias; Wuerschmidt, Florian; Fehm, Tanja; Moebus, Volker; von Minckwitz, Gunter; Loibl, Sibylle; Park-Simon, Tjoung-Won; Mueller, Volkmar

    2016-01-01

    Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT) and magnetic resonance imaging (MRI) scans of 300 breast cancer patients with brain

  14. Metabolic therapy: a new paradigm for managing malignant brain cancer.

    Science.gov (United States)

    Seyfried, Thomas N; Flores, Roberto; Poff, Angela M; D'Agostino, Dominic P; Mukherjee, Purna

    2015-01-28

    Little progress has been made in the long-term management of glioblastoma multiforme (GBM), considered among the most lethal of brain cancers. Cytotoxic chemotherapy, steroids, and high-dose radiation are generally used as the standard of care for GBM. These procedures can create a tumor microenvironment rich in glucose and glutamine. Glucose and glutamine are suggested to facilitate tumor progression. Recent evidence suggests that many GBMs are infected with cytomegalovirus, which could further enhance glucose and glutamine metabolism in the tumor cells. Emerging evidence also suggests that neoplastic macrophages/microglia, arising through possible fusion hybridization, can comprise an invasive cell subpopulation within GBM. Glucose and glutamine are major fuels for myeloid cells, as well as for the more rapidly proliferating cancer stem cells. Therapies that increase inflammation and energy metabolites in the GBM microenvironment can enhance tumor progression. In contrast to current GBM therapies, metabolic therapy is designed to target the metabolic malady common to all tumor cells (aerobic fermentation), while enhancing the health and vitality of normal brain cells and the entire body. The calorie restricted ketogenic diet (KD-R) is an anti-angiogenic, anti-inflammatory and pro-apoptotic metabolic therapy that also reduces fermentable fuels in the tumor microenvironment. Metabolic therapy, as an alternative to the standard of care, has the potential to improve outcome for patients with GBM and other malignant brain cancers. Copyright © 2014. Published by Elsevier Ireland Ltd.

  15. Brain microvascular endothelium induced-annexin A1 secretion contributes to small cell lung cancer brain metastasis.

    Science.gov (United States)

    Liu, Yi; Liu, Yong-Shuo; Wu, Peng-Fei; Li, Qiang; Dai, Wu-Min; Yuan, Shuai; Xu, Zhi-Hua; Liu, Ting-Ting; Miao, Zi-Wei; Fang, Wen-Gang; Chen, Yu-Hua; Li, Bo

    2015-09-01

    Small cell lung cancer is the most aggressive histologic subtype of lung cancer, with a strong predilection for metastasizing to brain early. However, the cellular and molecular basis is poorly known. Here, we provided evidence to reveal the role of annexin A1 in small cell lung cancer metastasis to brain. Firstly, the elevated annexin A1 serum levels in small cell lung cancer patients were associated with brain metastasis. The levels of annexin A1 were also upregulated in NCI-H446 cells, a small cell lung cancer cell line, upon migration into the mice brain. More interestingly, annexin A1 was secreted by NCI-H446 cells in a time-dependent manner when co-culturing with human brain microvascular endothelial cells, which was identified with the detections of annexin A1 in the co-cultured cellular supernatants by ELISA and western blot. Further results showed that blockage of annexin A1 in the co-cultured cellular supernatants using a neutralized antibody significantly inhibited NCI-H446 cells adhesion to brain endothelium and its transendothelial migration. Conversely, the addition of Ac2-26, an annexin A1 mimic peptide, enhanced these effects. Furthermore, knockdown of annexin A1 in NCI-H446 cells prevented its transendothelial migration in vitro and metastasis to mice brain in vivo. Our data showed that small cell lung cancer cell in brain microvasculature microenvironment could express much more annexin A1 and release it outside, which facilitated small cell lung cancer cell to gain malignant properties of entry into brain. These findings provided a potential target for the management of SCLC brain metastasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. βIII-Tubulin Regulates Breast Cancer Metastases to the Brain.

    Science.gov (United States)

    Kanojia, Deepak; Morshed, Ramin A; Zhang, Lingjiao; Miska, Jason M; Qiao, Jian; Kim, Julius W; Pytel, Peter; Balyasnikova, Irina V; Lesniak, Maciej S; Ahmed, Atique U

    2015-05-01

    Brain metastases occur in about 10% to 30% of breast cancer patients, which culminates in a poor prognosis. It is, therefore, critical to understand the molecular mechanisms underlying brain metastatic processes to identify relevant targets. We hypothesized that breast cancer cells must express brain-associated markers that would enable their invasion and survival in the brain microenvironment. We assessed a panel of brain-predominant markers and found an elevation of several neuronal markers (βIII-tubulin, Nestin, and AchE) in brain metastatic breast cancer cells. Among these neuronal predominant markers, in silico analysis revealed overexpression of βIII-tubulin (TUBB3) in breast cancer brain metastases (BCBM) and its expression was significantly associated with distant metastases. TUBB3 knockdown studies were conducted in breast cancer models (MDA-Br, GLIM2, and MDA-MB-468), which revealed significant reduction in their invasive capabilities. MDA-Br cells with suppressed TUBB3 also demonstrated loss of key signaling molecules such as β3 integrin, pFAK, and pSrc in vitro. Furthermore, TUBB3 knockdown in a brain metastatic breast cancer cell line compromised its metastatic ability in vivo, and significantly improved survival in a brain metastasis model. These results implicate a critical role of TUBB3 in conferring brain metastatic potential to breast cancer cells. ©2015 American Association for Cancer Research.

  17. Extracellular Tau Paired Helical Filaments Differentially Affect Tau Pathogenic Mechanisms in Mitotic and Post-Mitotic Cells: Implications for Mechanisms of Tau Propagation in the Brain.

    Science.gov (United States)

    Varghese, Merina; Santa-Maria, Ismael; Ho, Lap; Ward, Libby; Yemul, Shrishailam; Dubner, Lauren; Księżak-Reding, Hanna; Pasinetti, Giulio Maria

    2016-09-06

    The release of paired helical filaments (PHFs) from neurons into the extracellular space may contribute to the propagation of tau pathology across brain regions in Alzheimer's disease (AD) and other tauopathies. The majority of available mechanistic studies exploring the pathologic role of extracellular PHFs are conducted in proliferating cell lines. Here, we compare how extracellular PHFs induce tauopathy in mitotic cells and in post-mitotic brain neurons. In a mitotic cell line (HEK 293T), extracellular exposure to AD PHFs leads to an intracellular "aggresomal" type deposition of tau, coincidental with redistribution of dynein, a retrograde motor protein. We also observed that PHFs impaired proteasome degradation, but not autophagy. Exposure of cells to proteasome inhibitors was sufficient to induce intracellular tau aggregate formation as well as reorganization of dynein and the intermediate filament protein, vimentin. Thus, in mitotic cells, extracellular PHFs promote cellular tau aggregation, in part, by interfering with cellular proteasome degradation processes. In contrast with our observations with proliferating cells, exposure of post-mitotic primary neuronal cultures to AD PHFs did not promote "aggresomal" tau deposition, but instead resulted in a widespread accumulation of phosphorylated tau-immunoreactive swellings in neuritic processes, characterized by disturbed cytoskeletal organization of dynein and vimentin. Collectively, our observations suggest that extracellular PHFs may contribute to the propagation of tau pathology by independent mechanisms in post-mitotic and mitotic brain cells. These outcomes indicate that in addition to post-mitotic brain neurons, mitotic brain cells should also be considered as targets for therapeutic interventions to attenuate propagation of tauopathy.

  18. Monocarboxylate transporters in the brain and in cancer.

    Science.gov (United States)

    Pérez-Escuredo, Jhudit; Van Hée, Vincent F; Sboarina, Martina; Falces, Jorge; Payen, Valéry L; Pellerin, Luc; Sonveaux, Pierre

    2016-10-01

    Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Current challenges in the management of breast cancer brain metastases.

    Science.gov (United States)

    O'Sullivan, Ciara C; Davarpanah, Nicole N; Abraham, Jame; Bates, Susan E

    2017-04-01

    Approximately 50% of patients with advanced human epidermal growth factor 2 (HER2)-positive breast cancer and triple-negative breast cancer (TNBC) ultimately develop breast cancer brain metastases (BCBM), which are associated with significant morbidity and mortality. The advent of HER2-directed therapy resulted in greatly improved survival outcomes, but unfortunately at the price of an increased cumulative incidence of BCBM. We review challenges in the management of BCBM, and potential treatment strategies, including novel agents such as poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors (olaparib, veliparib), cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib, abemaciclib), and taxane derivatives (eg, ANG1005 and TPI-287). The utility of human epidermal growth factor 2 (HER2)-directed therapies-lapatinib, ado-trastuzumab emtansine (T-DM1), neratinib and tucatinib-is also being studied in this setting. We address the need for improved imaging techniques and innovation in clinical trial design. For example, the current practice is to initially administer whole-brain radiotherapy (WBRT) as treatment for patients with multiple BCBM. However, in selected circumstances, first-line systemic treatment may be more appropriate in order to avoid neurocognitive toxicities, and potential options should be evaluated in window of opportunity trials. Other strategies that may aid development of more effective clinical trials and expedite the development of promising agents include the use of different clinical endpoints and different imaging tools. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-12-01

    autoradiograph film . After 12 hr incubation, autoradiograph images showed multiple hot spots on the tumor brain, while clean background signal observed on the...Contents …………………………………………………………….……...3 Introduction…………………………………………………………….…………....4 Body …………………………………………………………………………………….4 Key Research...treatment for breast cancer brain metastasis. Body : The Statement of Work in this period had two major tasks: Task 1. To study phosphatidylserine

  1. Lung cancer-associated brain metastasis: Molecular mechanisms and therapeutic options.

    Science.gov (United States)

    Yousefi, Meysam; Bahrami, Tayyeb; Salmaninejad, Arash; Nosrati, Rahim; Ghaffari, Parisa; Ghaffari, Seyed H

    2017-10-01

    Lung cancer is the most common cause of cancer-related mortality in humans. There are several reasons for this high rate of mortality, including metastasis to several organs, especially the brain. In fact, lung cancer is responsible for approximately 50% of all brain metastases, which are very difficult to manage. Understanding the cellular and molecular mechanisms underlying lung cancer-associated brain metastasis brings up novel therapeutic promises with the hope to ameliorate the severity of the disease. Here, we provide an overview of the molecular mechanisms underlying the pathogenesis of lung cancer dissemination and metastasis to the brain, as well as promising horizons for impeding lung cancer brain metastasis, including the role of cancer stem cells, the blood-brain barrier, interactions of lung cancer cells with the brain microenvironment and lung cancer-driven systemic processes, as well as the role of growth factor/receptor tyrosine kinases, cell adhesion molecules and non-coding RNAs. In addition, we provide an overview of current and novel therapeutic approaches, including radiotherapy, surgery and stereotactic radiosurgery, chemotherapy, as also targeted cancer stem cell and epithelial-mesenchymal transition (EMT)-based therapies, micro-RNA-based therapies and other small molecule or antibody-based therapies. We will also discuss the daunting potential of some combined therapies. The identification of molecular mechanisms underlying lung cancer metastasis has opened up new avenues towards their eradication and provides interesting opportunities for future research aimed at the development of novel targeted therapies.

  2. Headache Caused by Brain Metastases of Castration-resistant Prostate Cancer during Cabazitaxel Therapy.

    Science.gov (United States)

    Watanabe, Keitaro; Kosaka, Takeo; Hongo, Hiroshi; Tamaki, Satoshi; Oya, Mototsugu

    2017-04-07

    We describe the case of a 55-year-old man who underwent four cycles of cabazitaxel therapy for castration-resistant prostate cancer (CRPC). After the fourth cycle of cabazitaxel, the patient experienced severe headaches. Brain gadolinium (Gd) contrast-enhanced magnetic resonance imaging (MRI) revealed multiple brain metastases. A few days later, the patient suffered impaired consciousness that progressed rapidly. The patient was treated for the symptoms of increased intracranial pressure and underwent whole-brain radiation. One month later, the patient's consciousness level and headache had improved. Although brain metastases of prostate cancer are rare, the possibility of brain metastases should be considered for prostate cancer patients, especially when a CRPC patient complains of headache. Additionally, even if major conditions such as cerebral hemorrhage are excluded by the use of non-contrast-enhanced computed tomography, brain Gd contrast-enhanced MRI should be performed in consideration of the possibility of brain metastases of prostate cancer.

  3. Models of logistic regression analysis, support vector machine, and back-propagation neural network based on serum tumor markers in colorectal cancer diagnosis.

    Science.gov (United States)

    Zhang, B; Liang, X L; Gao, H Y; Ye, L S; Wang, Y G

    2016-05-13

    We evaluated the application of three machine learning algorithms, including logistic regression, support vector machine and back-propagation neural network, for diagnosing congenital heart disease and colorectal cancer. By inspecting related serum tumor marker levels in colorectal cancer patients and healthy subjects, early diagnosis models for colorectal cancer were built using three machine learning algorithms to assess their corresponding diagnostic values. Except for serum alpha-fetoprotein, the levels of 11 other serum markers of patients in the colorectal cancer group were higher than those in the benign colorectal cancer group (P model and back-propagation, a neural network diagnosis model was built with diagnostic accuracies of 82 and 75%, sensitivities of 85 and 80%, and specificities of 80 and 70%, respectively. Colorectal cancer diagnosis models based on the three machine learning algorithms showed high diagnostic value and can help obtain evidence for the early diagnosis of colorectal cancer.

  4. Comparative membrane proteomics analyses of breast cancer cell lines to understand the molecular mechanism of breast cancer brain metastasis.

    Science.gov (United States)

    Peng, Wenjing; Zhang, Yu; Zhu, Rui; Mechref, Yehia

    2017-09-01

    Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from five different breast cancer and a brain cancer cell lines. Quantitative proteomic data of all cell lines were compared with MDA-MB-231BR which is a brain seeking breast cancer cell line, thus representing brain metastasis characteristics. Label-free proteomics of the six cell lines facilitates the identification of 1238 proteins and the quantification of 899 proteins of which more than 70% were membrane proteins. Unsupervised principal component analysis (PCA) of the label-free proteomics data resulted in a distinct clustering of cell lines, suggesting quantitative differences in the expression of several proteins among the different cell lines. Unique protein expressions in 231BR were observed for 28 proteins. The up-regulation of STAU1, AT1B3, NPM1, hnRNP Q, and hnRNP K and the down-regulation of TUBB4B and TUBB5 were noted in 231BR relative to 231 (precursor cell lines from which 231BR is derived). These proteins might contribute to the breast cancer brain metastasis. Ingenuity pathway analysis (IPA) supported the great brain metastatic propensity of 231BR and suggested the importance of the up-regulation of integrin proteins and down-regulation of EPHA2 in brain metastasis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Evaluation of health-related quality of life in Lithuanian brain tumor patients using the EORTC brain cancer module

    OpenAIRE

    Bunevičius, Adomas; Tamašauskas, Šarūnas; Tamašauskas, Arimantas; Deltuva, Vytenis Pranas

    2012-01-01

    Background and Objective. Health-related quality of life (HRQoL) is considered an important outcome measure in neuro-oncology. The aim of this study was to evaluate the psychometric properties of the brain cancer-specific Quality of Life Questionnaire (QLQ-BN20) of the European Organization for Research and Treatment of Cancer (EORTC) in Lithuanian brain tumor patients. Material and Methods. One hundred consecutive patients (71% of women; mean age, 58±14 years) admitted for elective brain tum...

  6. The biochemical, nanomechanical and chemometric signatures of brain cancer

    Science.gov (United States)

    Abramczyk, Halina; Imiela, Anna

    2018-01-01

    % for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

  7. Altered resting brain connectivity in persistent cancer related fatigue

    Science.gov (United States)

    Hampson, Johnson P.; Zick, Suzanna M.; Khabir, Tohfa; Wright, Benjamin D.; Harris, Richard E.

    2015-01-01

    There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF) disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued) who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI). Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P fatigue (P = 0.04, r = 0.52) and poor sleep quality (P = 0.04, r = 0.52) in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P fatigue scores were associated with greater default mode network (DMN) connectivity to the superior frontal gyrus (P = 0.05 FDR corrected) among fatigued subjects (r = 0.82) and less connectivity in the non-fatigued group (r = −0.88). These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent fatigue. As the DMN is a network involved in self-referential thinking we speculate that enhanced connectivity between the DMN and

  8. Altered resting brain connectivity in persistent cancer related fatigue

    Directory of Open Access Journals (Sweden)

    Johnson P. Hampson

    2015-01-01

    Full Text Available There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI. Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected. This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52 and poor sleep quality (P = 0.04, r = 0.52 in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected. Mental fatigue scores were associated with greater default mode network (DMN connectivity to the superior frontal gyrus (P = 0.05 FDR corrected among fatigued subjects (r = 0.82 and less connectivity in the non-fatigued group (r = −0.88. These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent

  9. Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

    Directory of Open Access Journals (Sweden)

    Thirugnanam Sivasakthivel

    2013-02-01

    Full Text Available Abstract Background The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs, which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and

  10. [Establish and analyze the predictive model of early stage brain metastases in patients with breast cancer].

    Science.gov (United States)

    Wang, Qiusheng; Wu, Shikai; Sun, Bing; Huang, Zhou; Meng, Xiangying; Huang, Yan

    2015-12-19

    To investigate the risk factors of cerebral metastasis of breast cancer and to provide guidance for the early diagnosis and treatment of brain metastases. Clinical data of postoperative patients with breast cancer were collected in our hospital from 2005 to 2009. All the patients were divided into two groups, with or without brain metastasis. The risk factors of brain metastases of patients with breast cancer were analyzed by the logistic regression. Eight hundred and twenty four early postoperative patients with breast cancer were enrolled. The median follow-up time was 68 months and 199 cases had brain metastasis. The univariate logistic regression results showed that higher grade of tumor, metastases. This model has the predictive value for the occurrence of brain metastases from breast cancer.

  11. A Case of Lung Cancer with Brain Metastases Diagnosed After Epileptic Seizure

    Directory of Open Access Journals (Sweden)

    Murat Eroglu

    2014-03-01

    Full Text Available    Epileptic seizures can accompany benign diseases, also can be the first sign of malign tumors. In brain metastasis, epileptic seizures can be seen before the symptoms of the primary lesion. Brain metastasis is bad prognostic factor in all malignancies and it is determined that lung cancers are the most metastatic tumors to the brain. Especially in new onset epileptic seizures in elderly patients, metastatic brain tumors are frequent in etiology. We aimed to present a lung cancer patient with brain metastasis who admitted emergency department with first epileptic seizure.

  12. Nanotheranostics: Emerging Strategies for Early Diagnosis and Therapy of Brain Cancer

    OpenAIRE

    Sonali,; Viswanadh, Matte Kasi; Singh, Rahul Pratap; Agrawal, Poornima; Mehata, Abhishesh Kumar; Pawde, Datta Maroti; Narendra,; Sonkar, Roshan; Muthu, Madaswamy Sona

    2018-01-01

    Nanotheranostics have demonstrated the development of advanced platforms that can diagnose brain cancer at early stages, initiate first-line therapy, monitor it, and if needed, rapidly start subsequent treatments. In brain nanotheranostics, therapeutic as well as diagnostic entities are loaded in a single nanoplatform, which can be further developed as a clinical formulation for targeting various modes of brain cancer. In the present review, we concerned about theranostic nanosystems establis...

  13. Investigating key genes associated with ovarian cancer by integrating affinity propagation clustering and mutual information network analysis.

    Science.gov (United States)

    Wang, J; Chen, C; Li, H-F; Jiang, X-L; Zhang, L

    2016-06-01

    The objective of the present work was to investigate key genes in ovarian cancer based on mAP-KL method which comprised the maxT multiple hypothesis (m), Krzanowski and Lai (KL) cluster quality index, and affinity propagation (AP) clustering algorithm, and mutual information network (MIN) constructed by the context likelihood of relatedness (CLR) algorithm. MAP-KL method was employed to identify exemplars in ovarian cancer, of which the maxT function ranked the genes of train set and test set and obtained top 200 genes; KL cluster index was utilized to determine the quantity of clusters; and then AP clustering algorithm was conducted to identify the clusters and their exemplars. Also, we assessed the classification performance of mAP-KL by support vector machines (SVM) model. Subsequently, the MIN for exemplars and cluster genes was constructed according to CLR algorithm. Finally, topological centrality properties of exemplars in MIN were assessed to investigate key genes for ovarian cancer. SVM model validated that the classification between normal controls and ovarian cancer patients by mAP-KL had a good performance. A total of 22 clusters and exemplars were detected by performing the mAP-KL method. Based on the topological centrality analyses for exemplars in MIN, we considered the C9orf16, COX5B and ACTB to be key genes in the progress of ovarian cancer. We have obtained three key genes (C9orf16, COX5B and ACTB) for ovarian cancer on the basis of mAP-KL method and MIN analysis. These genes might be potential biomarkers for treatment of ovarian cancer, and give insight for revealing the underlying mechanism of this tumor.

  14. Extremely low frequency electromagnetic fields (EMF) and brain cancer in adults and children: review and comment.

    Science.gov (United States)

    Gurney, J G; van Wijngaarden, E

    1999-07-01

    Epidemiologic and experimental research on the potential carcinogenic effects of extremely low frequency electromagnetic fields (EMF) has now been conducted for over two decades. Cancer epidemiology studies in relation to EMF have focused primarily on brain cancer and leukemia, both from residential sources of exposure in children and adults and from occupational exposure in adult men. Because genotoxic effects of EMF have not been shown, most recent laboratory research has attempted to show biological effects that could be related to cancer promotion. In this report, we briefly review residential and occupational EMF studies on brain cancer. We also provide a general review of experimental studies as they relate both to the biological plausibility of an EMF-brain cancer relation and to the insufficiency of such research to help guide exposure assessment in epidemiologic studies. We conclude from our review that no recent research, either epidemiologic or experimental, has emerged to provide reasonable support for a causal role of EMF on brain cancer.

  15. miR-20b is up-regulated in brain metastases from primary breast cancers

    Science.gov (United States)

    Ahmad, Aamir; Ginnebaugh, Kevin R.; Sethi, Seema; Chen, Wei; Ali, Rouba; Mittal, Sandeep; Sarkar, Fazlul H.

    2015-01-01

    Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target. PMID:25893380

  16. Serpins promote cancer cell survival and vascular co-option in brain metastasis.

    Science.gov (United States)

    Valiente, Manuel; Obenauf, Anna C; Jin, Xin; Chen, Qing; Zhang, Xiang H-F; Lee, Derek J; Chaft, Jamie E; Kris, Mark G; Huse, Jason T; Brogi, Edi; Massagué, Joan

    2014-02-27

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Brain Metastases in Gastrointestinal Cancers: Is there a Role for Surgery?

    Science.gov (United States)

    Lemke, Johannes; Scheele, Jan; Kapapa, Thomas; von Karstedt, Silvia; Wirtz, Christian Rainer; Henne-Bruns, Doris; Kornmann, Marko

    2014-01-01

    About 10% of all cancer patients will develop brain metastases during advanced disease progression. Interestingly, the vast majority of brain metastases occur in only three types of cancer: Melanoma, lung and breast cancer. In this review, we focus on summarizing the prognosis and impact of surgical resection of brain metastases originating from gastrointestinal cancers such as esophageal, gastric, pancreatic and colorectal cancer. The incidence of brain metastases is cancer and cancer. Overall, prognosis of these patients is very poor with a median survival in the range of only months. Interestingly, a substantial number of patients who had received surgical resection of brain metastases showed prolonged survival. However, it should be taken into account that all these studies were not randomized and it is likely that patients selected for surgical treatment presented with other important prognostic factors such as solitary brain metastases and exclusion of extra-cranial disease. Nevertheless, other reports have demonstrated long-term survival of patients upon resection of brain metastases originating from gastrointestinal cancers. Thus, it appears to be justified to consider aggressive surgical approaches for these patients. PMID:25247579

  18. Targeting cancer stem cell propagation with palbociclib, a CDK4/6 inhibitor: Telomerase drives tumor cell heterogeneity.

    Science.gov (United States)

    Bonuccelli, Gloria; Peiris-Pages, Maria; Ozsvari, Bela; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2017-02-07

    In this report, we systematically examined the role of telomerase activity in lung and ovarian cancer stem cell (CSC) propagation. For this purpose, we indirectly gauged telomerase activity, by linking the hTERT-promoter to eGFP. Using lung (A549) and ovarian (SKOV3) cancer cells, transduced with the hTERT-GFP reporter, we then employed GFP-expression levels to fractionate these cell lines into GFP-high and GFP-low populations. We functionally compared the phenotype of these GFP-high and GFP-low populations. More specifically, we now show that the cancer cells with higher telomerase activity (GFP-high) are more energetically activated, with increased mitochondrial mass and function, as well as increased glycolytic activity. This was further validated and confirmed by unbiased proteomics analysis. Cells with high telomerase activity also showed an increased capacity for stem cell activity (as measured using the 3D-spheroid assay) and cell migration (as measured using a Boyden chamber approach). These enhanced biological phenotypes were effectively inhibited by classical modulators of energy metabolism, which target either i) mitochondrial metabolism (i.e., oligomycin) or ii) glycolysis (i.e., 2-deoxy-glucose), or iii) by using the FDA-approved antibiotic doxycycline, which inhibits mitochondrial biogenesis. Finally, the level of telomerase activity also determined the ability of hTERT-high cells to proliferate, as assessed by measuring DNA synthesis via EdU incorporation. Consistent with these observations, treatment with an FDA-approved CDK4/6 inhibitor (PD-0332991/palbociclib) specifically blocked the propagation of both lung and ovarian CSCs. Virtually identical results were obtained with breast CSCs, which were also highly sensitive to palbociclib at concentrations in the nanomolar range. In summary, CSCs with high telomerase activity are among the most energetically activated, migratory and proliferative cell sub-populations. These observations may provide a

  19. Application of machine learning on brain cancer multiclass classification

    Science.gov (United States)

    Panca, V.; Rustam, Z.

    2017-07-01

    Classification of brain cancer is a problem of multiclass classification. One approach to solve this problem is by first transforming it into several binary problems. The microarray gene expression dataset has the two main characteristics of medical data: extremely many features (genes) and only a few number of samples. The application of machine learning on microarray gene expression dataset mainly consists of two steps: feature selection and classification. In this paper, the features are selected using a method based on support vector machine recursive feature elimination (SVM-RFE) principle which is improved to solve multiclass classification, called multiple multiclass SVM-RFE. Instead of using only the selected features on a single classifier, this method combines the result of multiple classifiers. The features are divided into subsets and SVM-RFE is used on each subset. Then, the selected features on each subset are put on separate classifiers. This method enhances the feature selection ability of each single SVM-RFE. Twin support vector machine (TWSVM) is used as the method of the classifier to reduce computational complexity. While ordinary SVM finds single optimum hyperplane, the main objective Twin SVM is to find two non-parallel optimum hyperplanes. The experiment on the brain cancer microarray gene expression dataset shows this method could classify 71,4% of the overall test data correctly, using 100 and 1000 genes selected from multiple multiclass SVM-RFE feature selection method. Furthermore, the per class results show that this method could classify data of normal and MD class with 100% accuracy.

  20. The risk of brain tumours in hereditary non-polyposis colorectal cancer (HNPCC)

    NARCIS (Netherlands)

    Vasen, HFA; Sanders, EACM; Taal, BG; Nagengast, FM; Griffioen, G; Menko, FH; Kleibeuker, JH; HouwingDuistermaat, JJ; Khan, PM

    1996-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) is known to be associated with several extracolonic cancers, e.g., cancers of the endometrium, stomach, urinary tract, small bowel and ovary. An association between HNPCC and brain tumours has also been reported, although previous risk analysis did

  1. A placebo-controlled, randomized phase II study of maintenance enzastaurin following whole brain radiation therapy in the treatment of brain metastases from lung cancer

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Ciuleanu, Tudor; Fløtten, Øystein

    2012-01-01

    Enzastaurin is a protein kinase C inhibitor with anti-tumor activity. This study was designed to determine if maintenance enzastaurin improved the outcome of whole brain radiotherapy (WBRT) in lung cancer (LC) patients with brain metastases (BMs)....

  2. Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France

    Science.gov (United States)

    Vittecoq, Marion; Elguero, Eric; Lafferty, Kevin D.; Roche, Benjamin; Brodeur, Jacques; Gauthier-Clerc, Michel; Missé, Dorothée; Thomas, Frédéric

    2012-01-01

    The incidence of adult brain cancer was previously shown to be higher in countries where the parasite Toxoplasma gondii is common, suggesting that this brain protozoan could potentially increase the risk of tumor formation. Using countries as replicates has, however, several potential confounding factors, particularly because detection rates vary with country wealth. Using an independent dataset entirely within France, we further establish the significance of the association between T. gondii and brain cancer and find additional demographic resolution. In adult age classes 55 years and older, regional mortality rates due to brain cancer correlated positively with the local seroprevalence of T. gondii. This effect was particularly strong for men. While this novel evidence of a significant statistical association between T. gondii infection and brain cancer does not demonstrate causation, these results suggest that investigations at the scale of the individual are merited.

  3. Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center.

    Science.gov (United States)

    Suki, Dima; Khoury Abdulla, Rami; Ding, Minming; Khatua, Soumen; Sawaya, Raymond

    2014-10-01

    Metastasis to the brain is frequent in adult cancer patients but rare among children. Advances in primary tumor treatment and the associated prolonged survival are said to have increased the frequency of brain metastasis in children. The authors present a series of cases of brain metastases in children diagnosed with a solid primary cancer, evaluate brain metastasis trends, and describe tumor type, patterns of occurrence, and prognosis. Patients with brain metastases whose primary cancer was diagnosed during childhood were identified in the 1990-2012 Tumor Registry at The University of Texas M.D. Anderson Cancer Center. A review of their hospital records provided demographic data, history, and clinical data, including primary cancer sites, number and location of brain metastases, sites of extracranial metastases, treatments, and outcomes. Fifty-four pediatric patients (1.4%) had a brain metastasis from a solid primary tumor. Sarcomas were the most common (54%), followed by melanoma (15%). The patients' median ages at diagnosis of the primary cancer and the brain metastasis were 11.37 years and 15.03 years, respectively. The primary cancer was localized at diagnosis in 48% of patients and disseminated regionally in only 14%. The primary tumor and brain metastasis presented synchronously in 15% of patients, and other extracranial metastases were present when the primary cancer was diagnosed. The remaining patients were diagnosed with brain metastasis after initiation of primary cancer treatment, with a median presentation interval of 17 months after primary cancer diagnosis (range 2-77 months). At the time of diagnosis, the brain metastasis was the first site of systemic metastasis in only 4 (8%) of the 51 patients for whom data were available. Up to 70% of patients had lung metastases when brain metastases were found. Symptoms led to the brain metastasis diagnosis in 65% of cases. Brain metastases were single in 60% of cases and multiple in 35%; 6% had only

  4. Neural networks improve brain cancer detection with Raman spectroscopy in the presence of light artifacts

    Science.gov (United States)

    Jermyn, Michael; Desroches, Joannie; Mercier, Jeanne; St-Arnaud, Karl; Guiot, Marie-Christine; Petrecca, Kevin; Leblond, Frederic

    2016-03-01

    It is often difficult to identify cancer tissue during brain cancer (glioma) surgery. Gliomas invade into areas of normal brain, and this cancer invasion is frequently not detected using standard preoperative magnetic resonance imaging (MRI). This results in enduring invasive cancer following surgery and leads to recurrence. A hand-held Raman spectroscopy is able to rapidly detect cancer invasion in patients with grade 2-4 gliomas. However, ambient light sources can produce spectral artifacts which inhibit the ability to distinguish between cancer and normal tissue using the spectral information available. To address this issue, we have demonstrated that artificial neural networks (ANN) can accurately classify invasive cancer versus normal brain tissue, even when including measurements with significant spectral artifacts from external light sources. The non-parametric and adaptive model used by ANN makes it suitable for detecting complex non-linear spectral characteristics associated with different tissues and the confounding presence of light artifacts. The use of ANN for brain cancer detection with Raman spectroscopy, in the presence of light artifacts, improves the robustness and clinical translation potential for intraoperative use. Integration with the neurosurgical workflow is facilitated by accounting for the effect of light artifacts which may occur, due to operating room lights, neuronavigation systems, windows, or other light sources. The ability to rapidly detect invasive brain cancer under these conditions may reduce residual cancer remaining after surgery, and thereby improve patient survival.

  5. SRC family kinases as novel therapeutic targets to treat breast cancer brain metastases.

    Science.gov (United States)

    Zhang, Siyuan; Huang, Wen-Chien; Zhang, Lin; Zhang, Chenyu; Lowery, Frank J; Ding, Zhaoxi; Guo, Hua; Wang, Hai; Huang, Suyun; Sahin, Aysegul A; Aldape, Kenneth D; Steeg, Patricia S; Yu, Dihua

    2013-09-15

    Despite better control of early-stage disease and improved overall survival of patients with breast cancer, the incidence of life-threatening brain metastases continues to increase in some of these patients. Unfortunately, other than palliative treatments there is no effective therapy for this condition. In this study, we reveal a critical role for Src activation in promoting brain metastasis in a preclinical model of breast cancer and we show how Src-targeting combinatorial regimens can treat HER2(+) brain metastases in this model. We found that Src was hyperactivated in brain-seeking breast cancer cells derived from human cell lines or from patients' brain metastases. Mechanistically, Src activation promoted tumor cell extravasation into the brain parenchyma via permeabilization of the blood-brain barrier. When combined with the EGFR/HER2 dual-targeting drug lapatinib, an Src-targeting combinatorial regimen prevented outgrowth of disseminated breast cancer cells through the induction of cell-cycle arrest. More importantly, this combinatorial regimen inhibited the outgrowth of established experimental brain metastases, prolonging the survival of metastases-bearing mice. Our results provide a rationale for clinical evaluation of Src-targeting regimens to treat patients with breast cancer suffering from brain metastasis. ©2013 AACR.

  6. Identifying risk factors for brain metastasis in breast cancer patients: Implication for a vigorous surveillance program.

    Science.gov (United States)

    Chow, Lorraine; Suen, Dacita; Ma, Kwok Kuen; Kwong, Ava

    2015-10-01

    Brain metastasis occurs in 10-15% of metastatic breast cancer patients and is associated with poor prognosis. This study aims to identify tumor characteristics of primary breast cancer, which are related to brain metastases in Hong Kong Chinese patients. A retrospective study of patients with invasive breast cancer receiving treatment in a university hospital from January 2001 to December 2008 was performed. The clinicopathological factors of patients with brain metastases were analyzed and compared with those who had no brain metastasis. Risk factors for brain metastasis were identified by univariate analysis first and then by multivariate analysis. A total of 912 patients with invasive breast cancer were treated during the study period. Of these, 30 patients were found to have distant metastases to brain. Patients with brain metastases had more breast tumors of higher histological grade (Grade III, 78.9% vs. 30.2%; p = 0.001). Their tumors also had a significantly higher rate of negative estrogen receptors (78.9% vs. 30.2%, p = 0.001). On multivariate analysis, only high tumor grading was found to be predictive of developing brain metastasis. Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients. Copyright © 2015. Published by Elsevier Taiwan.

  7. Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

    Science.gov (United States)

    Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

    2017-06-01

    Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Treatment of brain metastases of small-cell lung cancer : Comparing teniposide and teniposide with whole-brain radiotherapy - A phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

    NARCIS (Netherlands)

    Postmus, PE; Haaxma-Reiche, H; Smit, EF; Groen, HJM; Karnicka, H; Lewinski, T; van Meerbeeck, J; Clerico, M; Gregor, A; Curran, D; Sahmoud, T; Kirkpatrick, A; Giaccone, G

    2000-01-01

    Purpose: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases, Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be

  9. Roles of the Cyclooxygenase 2 Matrix Metalloproteinase 1 Pathway in Brain Metastasis of Breast Cancer*

    Science.gov (United States)

    Wu, Kerui; Fukuda, Koji; Xing, Fei; Zhang, Yingyu; Sharma, Sambad; Liu, Yin; Chan, Michael D.; Zhou, Xiaobo; Qasem, Shadi A.; Pochampally, Radhika; Mo, Yin-Yuan; Watabe, Kounosuke

    2015-01-01

    Brain is one of the major sites of metastasis in breast cancer; however, the pathological mechanism of brain metastasis is poorly understood. One of the critical rate-limiting steps of brain metastasis is the breaching of blood-brain barrier, which acts as a selective interface between the circulation and the central nervous system, and this process is considered to involve tumor-secreted proteinases. We analyzed clinical significance of 21 matrix metalloproteinases on brain metastasis-free survival of breast cancer followed by verification in brain metastatic cell lines and found that only matrix metalloproteinase 1 (MMP1) is significantly correlated with brain metastasis. We have shown that MMP1 is highly expressed in brain metastatic cells and is capable of degrading Claudin and Occludin but not Zo-1, which are key components of blood-brain barrier. Knockdown of MMP1 in brain metastatic cells significantly suppressed their ability of brain metastasis in vivo, whereas ectopic expression of MMP1 significantly increased the brain metastatic ability of the cells that are not brain metastatic. We also found that COX2 was highly up-regulated in brain metastatic cells and that COX2-induced prostaglandins were directly able to promote the expression of MMP1 followed by augmenting brain metastasis. Furthermore, we found that COX2 and prostaglandin were able to activate astrocytes to release chemokine (C-C motif) ligand 7 (CCL7), which in turn promoted self-renewal of tumor-initiating cells in the brain and that knockdown of COX2 significantly reduced the brain metastatic ability of tumor cells. Our results suggest the COX2-MMP1/CCL7 axis as a novel therapeutic target for brain metastasis. PMID:25691572

  10. Roles of the cyclooxygenase 2 matrix metalloproteinase 1 pathway in brain metastasis of breast cancer.

    Science.gov (United States)

    Wu, Kerui; Fukuda, Koji; Xing, Fei; Zhang, Yingyu; Sharma, Sambad; Liu, Yin; Chan, Michael D; Zhou, Xiaobo; Qasem, Shadi A; Pochampally, Radhika; Mo, Yin-Yuan; Watabe, Kounosuke

    2015-04-10

    Brain is one of the major sites of metastasis in breast cancer; however, the pathological mechanism of brain metastasis is poorly understood. One of the critical rate-limiting steps of brain metastasis is the breaching of blood-brain barrier, which acts as a selective interface between the circulation and the central nervous system, and this process is considered to involve tumor-secreted proteinases. We analyzed clinical significance of 21 matrix metalloproteinases on brain metastasis-free survival of breast cancer followed by verification in brain metastatic cell lines and found that only matrix metalloproteinase 1 (MMP1) is significantly correlated with brain metastasis. We have shown that MMP1 is highly expressed in brain metastatic cells and is capable of degrading Claudin and Occludin but not Zo-1, which are key components of blood-brain barrier. Knockdown of MMP1 in brain metastatic cells significantly suppressed their ability of brain metastasis in vivo, whereas ectopic expression of MMP1 significantly increased the brain metastatic ability of the cells that are not brain metastatic. We also found that COX2 was highly up-regulated in brain metastatic cells and that COX2-induced prostaglandins were directly able to promote the expression of MMP1 followed by augmenting brain metastasis. Furthermore, we found that COX2 and prostaglandin were able to activate astrocytes to release chemokine (C-C motif) ligand 7 (CCL7), which in turn promoted self-renewal of tumor-initiating cells in the brain and that knockdown of COX2 significantly reduced the brain metastatic ability of tumor cells. Our results suggest the COX2-MMP1/CCL7 axis as a novel therapeutic target for brain metastasis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Modeling of light propagation in the human neck for diagnoses of thyroid cancers by diffuse optical tomography.

    Science.gov (United States)

    Fujii, H; Yamada, Y; Kobayashi, K; Watanabe, M; Hoshi, Y

    2017-05-01

    Diffuse optical tomography using near-infrared light in a wavelength range from 700 to 1000 nm has the potential to enable non-invasive diagnoses of thyroid cancers; some of which are difficult to detect by conventional methods such as ultrasound tomography. Diffuse optical tomography needs to be based on a physically accurate model of light propagation in the neck, because it reconstructs tomographic images of the optical properties in the human neck by inverse analysis. Our objective here was to investigate the effects of three factors on light propagation in the neck using the 2D time-dependent radiative transfer equation: (1) the presence of the trachea, (2) the refractive-index mismatch at the trachea-tissue interface, and (3) the effect of neck organs other than the trachea (spine, spinal cord, and blood vessels). There was a significant influence of reflection and refraction at the trachea-tissue interface on the light intensities in the region between the trachea and the front of the neck surface. Organs other than the trachea showed little effect on the light intensities measured at the front of the neck surface although these organs affected the light intensities locally. These results indicated the necessity of modeling the refractive-index mismatch at the trachea-tissue interface and the possibility of modeling other neck organs simply as a homogeneous medium when the source and detectors were far from large blood vessels. Copyright © 2016 John Wiley & Sons, Ltd.

  12. T lymphocytes facilitate brain metastasis of breast cancer by inducing Guanylate-Binding Protein 1 expression.

    Science.gov (United States)

    Mustafa, Dana A M; Pedrosa, Rute M S M; Smid, Marcel; van der Weiden, Marcel; de Weerd, Vanja; Nigg, Alex L; Berrevoets, Cor; Zeneyedpour, Lona; Priego, Neibla; Valiente, Manuel; Luider, Theo M; Debets, Reno; Martens, John W M; Foekens, John A; Sieuwerts, Anieta M; Kros, Johan M

    2018-01-19

    The discovery of genes and molecular pathways involved in the formation of brain metastasis would direct the development of therapeutic strategies to prevent this deadly complication of cancer. By comparing gene expression profiles of Estrogen Receptor negative (ER-) primary breast tumors between patients who developed metastasis to brain and to organs other than brain, we found that T lymphocytes promote the formation of brain metastases. To functionally test the ability of T cells to promote brain metastasis, we used an in vitro blood-brain barrier (BBB) model. By co-culturing T lymphocytes with breast cancer cells, we confirmed that T cells increase the ability of breast cancer cells to cross the BBB. Proteomics analysis of the tumor cells revealed Guanylate-Binding Protein 1 (GBP1) as a key T lymphocyte-induced protein that enables breast cancer cells to cross the BBB. The GBP1 gene appeared to be up-regulated in breast cancer of patients who developed brain metastasis. Silencing of GBP1 reduced the ability of breast cancer cells to cross the in vitro BBB model. In addition, the findings were confirmed in vivo in an immunocompetent syngeneic mouse model. Co-culturing of ErbB2 tumor cells with activated T cells induced a significant increase in Gbp1 expression by the cancer cells. Intracardial inoculation of the co-cultured tumor cells resulted in preferential seeding to brain. Moreover, intracerebral outgrowth of the tumor cells was demonstrated. The findings point to a role of T cells in the formation of brain metastases in ER- breast cancers, and provide potential targets for intervention to prevent the development of cerebral metastases.

  13. Surgical Treatment for Non-small Cell Lung Cancer Patients with Synchronous Solitary Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Hao BAI

    2013-12-01

    Full Text Available Background and objective Brain metastases are common in non-small cell lung cancer. Usual treatments include radiotherapy and chemotherapy. However, these methods result in poor patient prognosis. The aim of this study is to assess the effectiveness of surgical resection in the multimodality management of non-small cell lung cancer patients with synchronous solitary brain metastasis. Methods The clinical data of 46 non-small cell lung cancer patients with synchronous solitary brain metastasis were retrospectively reviewed. All patients underwent surgical resection of primary lung tumor, followed by whole brain radiotherapy and chemotherapy. In addition, 13 out of the 46 patients underwent resection of brain metastasis, whereas the remaining 33 patients received stereotactic radiosurgery. Results The median survival time of the enrolled patients was 16.8 months. The 1-, 2-, and 3-year survival rates were 76.1%, 20.9%, and 4.7%, respectively. The median survival times of the patients with brain metastasis resection or stereotactic radiosurgery were 18.3 and 15.8 months, respectively (P=0.091,2. Conclusion Surgical resection of primary lung tumor and brain metastasis may improve prognosis of non-small cell lung cancer patients with synchronous solitary brain metastasis. However, the survival benefit of surgical resection over brain metastasis resection or stereotactic radiosurgery is uncertain.

  14. Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain.

    Science.gov (United States)

    Chen, Jinyu; Lee, Ho-Jeong; Wu, Xuefeng; Huo, Lei; Kim, Sun-Jin; Xu, Lei; Wang, Yan; He, Junqing; Bollu, Lakshmi R; Gao, Guang; Su, Fei; Briggs, James; Liu, Xiaojing; Melman, Tamar; Asara, John M; Fidler, Isaiah J; Cantley, Lewis C; Locasale, Jason W; Weihua, Zhang

    2015-02-01

    Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells, but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the nonoxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBP) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. ©2014 American Association for Cancer Research.

  15. Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

    DEFF Research Database (Denmark)

    Dewhurst, Sally M.; McGranahan, Nicholas; Burrell, Rebecca A.

    2014-01-01

    The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells ...... [discovery data: hazard ratio (HR), 4.70, 95% confidence interval (CI), 1.04–21.37; validation data: HR, 1.59, 95% CI, 1.05–2.42]. These data highlight an important role for the tolerance of genome doubling in driving cancer genome evolution.......The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells...

  16. Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics.

    Science.gov (United States)

    Bollig-Fischer, Aliccia; Michelhaugh, Sharon K; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

    2015-06-10

    Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n = 4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments.

  17. Identifying risk factors for brain metastasis in breast cancer patients: Implication for a vigorous surveillance program

    Directory of Open Access Journals (Sweden)

    Lorraine Chow

    2015-10-01

    Conclusion: Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients.

  18. Application of wavelet transformation and adaptive neighborhood based modified backpropagation (ANMBP) for classification of brain cancer

    Science.gov (United States)

    Werdiningsih, Indah; Zaman, Badrus; Nuqoba, Barry

    2017-08-01

    This paper presents classification of brain cancer using wavelet transformation and Adaptive Neighborhood Based Modified Backpropagation (ANMBP). Three stages of the processes, namely features extraction, features reduction, and classification process. Wavelet transformation is used for feature extraction and ANMBP is used for classification process. The result of features extraction is feature vectors. Features reduction used 100 energy values per feature and 10 energy values per feature. Classifications of brain cancer are normal, alzheimer, glioma, and carcinoma. Based on simulation results, 10 energy values per feature can be used to classify brain cancer correctly. The correct classification rate of proposed system is 95 %. This research demonstrated that wavelet transformation can be used for features extraction and ANMBP can be used for classification of brain cancer.

  19. Combining Self-Organizing Mapping and Supervised Affinity Propagation Clustering Approach to Investigate Functional Brain Networks Involved in Motor Imagery and Execution with fMRI Measurements

    Directory of Open Access Journals (Sweden)

    Jiang eZhang

    2015-07-01

    Full Text Available AbstractClustering analysis methods have been widely applied to identifying the functional brain networks of a multitask paradigm. However, the previously used clustering analysis techniques are computationally expensive and thus impractical for clinical applications. In this study a novel method, called SOM-SAPC that combines self-organizing mapping (SOM and supervised affinity propagation clustering (SAPC, is proposed and implemented to identify the motor execution (ME and motor imagery (MI networks. In SOM-SAPC, SOM was first performed to process fMRI data and SAPC is further utilized for clustering the patterns of functional networks. As a result, SOM-SAPC is able to significantly reduce the computational cost for brain network analysis. Simulation and clinical tests involving ME and MI were conducted based on SOM-SAPC, and the analysis results indicated that functional brain networks were clearly identified with different response patterns and reduced computational cost. In particular, three activation clusters were clearly revealed, which include parts of the visual, ME and MI functional networks. These findings validated that SOM-SAPC is an effective and robust method to analyze the fMRI data with multitasks.

  20. Combining self-organizing mapping and supervised affinity propagation clustering approach to investigate functional brain networks involved in motor imagery and execution with fMRI measurements.

    Science.gov (United States)

    Zhang, Jiang; Liu, Qi; Chen, Huafu; Yuan, Zhen; Huang, Jin; Deng, Lihua; Lu, Fengmei; Zhang, Junpeng; Wang, Yuqing; Wang, Mingwen; Chen, Liangyin

    2015-01-01

    Clustering analysis methods have been widely applied to identifying the functional brain networks of a multitask paradigm. However, the previously used clustering analysis techniques are computationally expensive and thus impractical for clinical applications. In this study a novel method, called SOM-SAPC that combines self-organizing mapping (SOM) and supervised affinity propagation clustering (SAPC), is proposed and implemented to identify the motor execution (ME) and motor imagery (MI) networks. In SOM-SAPC, SOM was first performed to process fMRI data and SAPC is further utilized for clustering the patterns of functional networks. As a result, SOM-SAPC is able to significantly reduce the computational cost for brain network analysis. Simulation and clinical tests involving ME and MI were conducted based on SOM-SAPC, and the analysis results indicated that functional brain networks were clearly identified with different response patterns and reduced computational cost. In particular, three activation clusters were clearly revealed, which include parts of the visual, ME and MI functional networks. These findings validated that SOM-SAPC is an effective and robust method to analyze the fMRI data with multitasks.

  1. Residential radon exposure and brain cancer: an ecological study in a radon prone area (Galicia, Spain)

    OpenAIRE

    Ruano-Ravina, Alberto; Aragon?s, Nuria; Kelsey, Karl T.; P?rez-R?os, M?nica; Pi?eiro-Lamas, Mar?a; L?pez-Abente, Gonzalo; Juan M. Barros-Dios

    2017-01-01

    We aimed to know if radon concentration is associated with municipal mortality due to brain cancer in Galicia, Spain. We designed an ecological study taking as study unit Galician municipalities. To be included, municipalities had to have at least three radon measurements. We correlated radon concentrations with municipal mortality due to these malignant tumors during the period 1999?2008. We calculated the relative risk of dying of brain cancers for each municipality and correlated this valu...

  2. A Case of Brain Metastases from Breast Cancer Treated with Whole-Brain Radiotherapy and Eribulin Mesylate

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2012-01-01

    Full Text Available Patients with triple receptor-negative breast cancer often develop aggressive metastatic disease, which also might involve the brain. In many cases, systemic and local treatment is needed. It is important to consider the toxicity of chemo- and radiotherapy, especially when newly approved drugs become available. Randomised studies leading to drug approval often exclude patients with newly diagnosed brain metastases. Here we report our initial experience with eribulin mesylate and whole-brain radiotherapy (WBRT in a heavily pretreated patient with multiple brain, lung, and bone metastases from triple receptor-negative breast cancer. Eribulin mesylate was given after 4 previous lines for metastatic disease. Two weeks after the initial dose, that is, during the first cycle, the patient was diagnosed with 5 brain metastases with a maximum size of approximately 4.5 cm. She continued chemotherapy and received concomitant WBRT with 10 fractions of 3 Gy. After 3 cycles of eribulin mesylate, treatment was discontinued because of newly diagnosed liver metastases and progression in the lungs. No unexpected acute toxicity was observed. The only relevant adverse reactions were haematological events after the third cycle (haemoglobin 9.5 g/dL, leukocytes 3.1×109/L. The patient died from respiratory failure 18.5 months from diagnosis of metastatic disease, and 2.7 months from diagnosis of brain metastases. To the best of our knowledge, this is the first report on combined WBRT and eribulin mesylate.

  3. TENIPOSIDE FOR BRAIN METASTASES OF SMALL-CELL LUNG-CANCER - A PHASE-II STUDY

    NARCIS (Netherlands)

    POSTMUS, PE; SMIT, EF; HAAXMAREICHE, H; VANZANDWIJK, N; ARDIZZONI, A; QUOIX, E; KIRKPATRICK, A; SAHMOUD, T; GIACCONE, G

    Purpose: Here we report the results of a phase II study of teniposide, one of the most active drugs against small-cell lung cancer (SCLC), in patients with brain metastases. Patients and Methods: Patients with SCLC who presented with brain metastases at diagnosis (n = 11) or during follow-up

  4. Brain Connectivity and Neuropsychological Functioning in Recently Treated Testicular Cancer Patients

    DEFF Research Database (Denmark)

    Amidi, Ali; Agerbæk, Mads; Leemans, Alexander

    Objective Treatment with the combined cytostatic regimens of bleomycin, etoposide, and cisplatin (BEP) has dramatically reduced the mortality rate in testicular cancer (TC). However, evidence suggests that the use of chemotherapy (CT) may be associated with reduced brain connectivity and impaired...... the possible adverse effects of BEP on brain white matter connectivity and neuropsychological functioning in recently treated men with TC....

  5. Admission criteria to the Danish Brain Cancer Program are moderately associated with magnetic resonance imaging findings

    DEFF Research Database (Denmark)

    Hill, Thomas Winther; Nielsen, Mie Kiszka; Nepper-Rasmussen, Jørgen

    2013-01-01

    The objective of this study was to evaluate the Danish Brain Cancer Program by examining the criteria for admission to the program and the results of magnetic resonance imaging (MRI) of the brain in 359 patients referred to the program at the Odense University Hospital during one year...

  6. [Influence of the brain functional state evoked by spreading depression wave propagation on the recurrent waves properties].

    Science.gov (United States)

    Roshchina, G Ia; Koroleva, V I; Davydov, V I

    2012-01-01

    EEG aftereffects of spreading depression waves were studied in waking rabbits in chronic experiments by spectral coherence analysis. Experiments were divided in two groups: early (from the first to the third-fourth experiments) and late (fifth-tenth experiments). During the early experimental series, unilateral persistent EEG changes consisting in an increase in the delta- and beta-band power with a simultaneous depression of the gamma-band activity were observed in the ipsilateral to SD hemisphere. In addition, interhemispheric coherence between symmetrical cortical points decreased. During the late experimental series, a generalized bilateral increase in the power of the delta and beta activity was demonstrated with a rise in coherence in the beta band. This generalized activity occurred cyclically and was distinct during a long period of time (2-3 hours) after propagation of a single SD wave. Such kind of cyclical activity blocked the propagation of subsequent SD waves in the neocortex of a waking rabbit and decreased the probability of recurrent wave origin up to a complete cessation of wave generation. Thus, a cortical SD wave provoked the appearance of synchronized beta oscillations in the EEG, which in turn actively influenced the properties of recurrent waves.

  7. SPECIFIC CHARACTERISTICS OF BRAIN METASTASIZING IN PATIENTS WITH LUMINAL SUBTYPE OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Balkanov

    2016-01-01

    Full Text Available Background: More than half of female patients with breast cancer are diagnosed with a  luminal subtype of the disease; however, specific characteristics of its metastases to the brain have been not well studied, unlike those of HER2 positive and triple negative subtypes. Aim: A  comparative analysis of characteristics of metastatic brain lesions in patients with luminal breast cancer. Materials and methods: The time from surgery for breast cancer to the first recurrence and to metastatic brain lesions (assessed by contrast-enhanced MRI imaging was measured in 41 patients with luminal subtype of breast cancer (median age, 49.5±9.6  years, depending on a  diameter of the primary tumor and numbers of involved axillary lymph nodes. Results: The time interval to occurrence of brain metastases in luminal subtype of breast cancer is not associated with the size of the tumor. If≥4  axillary lymph nodes are involved (N2–3, brain metastases are identified much earlier (p<0.05 than in patients with N0–1 (34.5±23.9 months and 62.7±50 months, respectively. Neither the size nor the involvement of axillary lymph nodes has any impact on the rates of metastatic lesion to the brain during the first recurrence. Conclusion: Brain metastases occur at a much shorter time in those patients of luminal subtype of breast cancer who have metastases in≥4  axillary lymph nodes. Brain metastases develop in 50% of patients with the first recurrence of the luminal subtype of breast cancer.

  8. Activity-dependent neuroprotective protein (ADNP): a case study for highly conserved chordata-specific genes shaping the brain and mutated in cancer.

    Science.gov (United States)

    Gozes, Illana; Yeheskel, Adva; Pasmanik-Chor, Metsada

    2015-01-01

    The recent finding of activity-dependent neuroprotective protein (ADNP) as a protein decreased in serum of patients with Alzheimer's disease (AD) compared to controls, alongside with the discovery of ADNP mutations in autism and coupled with the original description of cancer mutations, ignited an interest for a comparative analysis of ADNP with other AD/autism/cancer-associated genes. We strive toward a better understanding of the molecular structure of key players in psychiatric/neurodegenerative diseases including autism, schizophrenia, and AD. This article includes data mining and bioinformatics analysis on the ADNP gene and protein, in addition to other related genes, with emphasis on recent literature. ADNP is discovered here as unique to chordata with specific autism mutations different from cancer-associated mutation. Furthermore, ADNP exhibits similarities to other cancer/autism-associated genes. We suggest that key genes, which shape and maintain our brain and are prone to mutations, are by in large unique to chordata. Furthermore, these brain-controlling genes, like ADNP, are linked to cell growth and differentiation, and under different stress conditions may mutate or exhibit expression changes leading to cancer propagation. Better understanding of these genes could lead to better therapeutics.

  9. Integrin Alpha-v and HER2 in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    ZOOM live cell imaging machine (ESSEN Bioscience; Figure 2). c. Interactions of αv integrin and HER2 in breast cancer brain metastases. We found...HCC1954 breast cancer cells. C) Real time live cell imaging of MM2BH cells treated with cilengitide (0, .3, 1, 3, and 10 µg/mL) using IncuCyte ZOOM

  10. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

    Directory of Open Access Journals (Sweden)

    Couraud Pierre-Olivier

    2009-07-01

    Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

  11. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain.

    Science.gov (United States)

    Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

    2009-07-29

    The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming alpha-subunit of BKCa channels in breast cancer metastasis and invasion. We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX). The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BKCa channel expression in breast cancer metastatic to brain and the mechanism of its action in

  12. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC Registry

    Directory of Open Access Journals (Sweden)

    Elena Laakmann

    2016-09-01

    Full Text Available Evidence about distribution patterns of brain metastases with regard to breast cancer subtypes and its influence on the prognosis of patients is insufficient. Clinical data, cranial computed tomography (CT and magnetic resonance imaging (MRI scans of 300 breast cancer patients with brain metastases (BMs were collected retrospectively in four centers participating in the Brain Metastases in Breast Cancer Registry (BMBC in Germany. Patients with positive estrogen (ER, progesterone (PR, or human epidermal growth factor receptor 2 (HER2 statuses, had a significantly lower number of BMs at diagnosis. Concerning the treatment mode, HER2-positive patients treated with trastuzumab before the diagnosis of BMs showed a lower number of intracranial metastases (p < 0.001. Patients with a HER2-positive tumor-subtype developed cerebellar metastases more often compared with HER2-negative patients (59.8% vs. 44.5%, p = 0.021, whereas patients with triple-negative primary tumors had leptomeningeal disease more often (31.4% vs. 18.3%, p = 0.038. The localization of Brain metastases (BMs was associated with prognosis: patients with leptomeningeal disease had shorter survival compared with patients without signs of leptomeningeal disease (median survival 3 vs. 5 months, p = 0.025. A shorter survival could also be observed in the patients with metastases in the occipital lobe (median survival 3 vs. 5 months, p = 0.012. Our findings suggest a different tumor cell homing to different brain regions depending on subtype and treatment.

  13. Family history of cancer in benign brain tumor subtypes versus gliomas

    Directory of Open Access Journals (Sweden)

    Quinn eOstrom

    2012-02-01

    Full Text Available Purpose: Family history is associated with gliomas, but this association has not ben established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study (OBTS. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%, 78 meningioma (65%, 49 pituitary adenoma (73.1% and 152 glioma patients (58.2%. The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs and 95% confidence intervals (95% CI. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusions: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases.

  14. Family History of Cancer in Benign Brain Tumor Subtypes Versus Gliomas

    Science.gov (United States)

    Ostrom, Quinn T.; McCulloh, Christopher; Chen, Yanwen; Devine, Karen; Wolinsky, Yingli; Davitkov, Perica; Robbins, Sarah; Cherukuri, Rajesh; Patel, Ashokkumar; Gupta, Rajnish; Cohen, Mark; Barrios, Jaime Vengoechea; Brewer, Cathy; Schilero, Cathy; Smolenski, Kathy; McGraw, Mary; Denk, Barbara; Naska, Theresa; Laube, Frances; Steele, Ruth; Greene, Dale; Kastl, Alison; Bell, Susan; Aziz, Dina; Chiocca, E. A.; McPherson, Christopher; Warnick, Ronald; Barnett, Gene H.; Sloan, Andrew E.; Barnholtz-Sloan, Jill S.

    2012-01-01

    Purpose: Family history is associated with gliomas, but this association has not been established for benign brain tumors. Using information from newly diagnosed primary brain tumor patients, we describe patterns of family cancer histories in patients with benign brain tumors and compare those to patients with gliomas. Methods: Newly diagnosed primary brain tumor patients were identified as part of the Ohio Brain Tumor Study. Each patient was asked to participate in a telephone interview about personal medical history, family history of cancer, and other exposures. Information was available from 33 acoustic neuroma (65%), 78 meningioma (65%), 49 pituitary adenoma (73.1%), and 152 glioma patients (58.2%). The association between family history of cancer and each subtype was compared with gliomas using unconditional logistic regression models generating odds ratios (ORs) and 95% confidence intervals. Results: There was no significant difference in family history of cancer between patients with glioma and benign subtypes. Conclusion: The results suggest that benign brain tumor may have an association with family history of cancer. More studies are warranted to disentangle the potential genetic and/or environmental causes for these diseases. PMID:22649779

  15. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  16. The factors that have an impact on the development of brain metastasis in the patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Adem Dayan

    2012-01-01

    Conclusions: As the prognostic and predictive factors showing the development of brain metastasis in breast cancer patients may be identified, follow-up also including the brain is important in order to take preventive measures.

  17. αB-crystallin: a Novel Regulator of Breast Cancer Metastasis to the Brain

    Science.gov (United States)

    Malin, Dmitry; Strekalova, Elena; Petrovic, Vladimir; Deal, Allison M.; Ahmad, Abraham Al; Adamo, Barbara; Miller, C. Ryan; Ugolkov, Andrey; Livasy, Chad; Fritchie, Karen; Hamilton, Erika; Blackwell, Kimberly; Geradts, Joseph; Ewend, Matt; Carey, Lisa; Shusta, Eric V.; Anders, Carey K.; Cryns, Vincent L.

    2013-01-01

    Purpose Basal-like breast tumors are typically (ER/PR/HER2) triple-negative and are associated with a high incidence of brain metastases and poor clinical outcomes. The molecular chaperone αB-crystallin is predominantly expressed in triple-negative breast cancer (TNBC) and contributes to an aggressive tumor phenotype in preclinical models. We investigated the potential role of αB-crystallin in brain metastasis in TNBC. Experimental Design αB-crystallin expression in primary breast carcinomas and brain metastases was analyzed by immunohistochemistry among breast cancer patients with brain metastases. αB-crystallin was overexpressed or silenced in two different TNBC cell lines. The effects on cell adhesion to human brain microvascular endothelial cells (HBMECs) or extracellular matrix proteins, transendothelial migration, and transmigration across a HBMEC/astrocyte co-culture blood-brain barrier (BBB) model were examined. Additionally, the effects of overexpressing or silencing αB-crystallin on brain metastasis in vivo were investigated using orthotopic TNBC models. Results In a cohort of women with breast cancer brain metastasis, αB-crystallin expression in primary breast carcinomas was associated with poor overall survival and poor survival after brain metastasis, even among TNBC patients. Stable overexpression of αB-crystallin in TNBC cells enhanced adhesion to HBMECs, transendothelial migration, and BBB transmigration in vitro, while silencing αB-crystallin inhibited these events. αB-crystallin promoted adhesion of TNBC cells to HBMECs at least in part through an α3β1 integrin-dependent mechanism. αB-crystallin overexpression promoted brain metastasis, while silencing αB-crystallin inhibited brain metastasis in orthotopic TNBC models. Conclusion αB-crystallin is a novel regulator of brain metastasis in TNBC and represents a potential biomarker and drug target for this aggressive disease. PMID:24132917

  18. Propagation of alpha-synuclein pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    Science.gov (United States)

    Uchihara, Toshiki; Giasson, Benoit I

    2016-01-01

    Progressive aggregation of alpha-synuclein (αS) through formation of amorphous pale bodies to mature Lewy bodies or in neuronal processes as Lewy neurites may be the consequence of conformational protein changes and accumulations, which structurally represents "molecular template". Focal initiation and subsequent spread along anatomically connected structures embody "structural template". To investigate the hypothesis that both processes might be closely associated and involved in the progression of αS pathology, which can be observed in human brains, αS amyloidogenic precursors termed "seeds" were experimentally injected into the brain or peripheral nervous system of animals. Although these studies showed that αS amyloidogenic seeds can induce αS pathology, which can spread in the nervous system, the findings are still not unequivocal in demonstrating predominant transsynaptic or intraneuronal spreads either in anterograde or retrograde directions. Interpretation of some of these studies is further complicated by other concurrent aberrant processes including neuroimmune activation, injury responses and/or general perturbation of proteostasis. In human brain, αS deposition and neuronal degeneration are accentuated in distal axon/synapse. Hyperbranching of axons is an anatomical commonality of Lewy-prone systems, providing a structural basis for abundance in distal axons and synaptic terminals. This neuroanatomical feature also can contribute to such distal accentuation of vulnerability in neuronal demise and the formation of αS inclusion pathology. Although retrograde progression of αS aggregation in hyperbranching axons may be a consistent feature of Lewy pathology, the regional distribution and gradient of Lewy pathology are not necessarily compatible with a predictable pattern such as upward progression from lower brainstem to cerebral cortex. Furthermore, "focal Lewy body disease" with the specific isolated involvement of autonomic, olfactory or cardiac

  19. Brain Metastases in Newly Diagnosed Breast Cancer: A Population-Based Study.

    Science.gov (United States)

    Martin, Allison M; Cagney, Daniel N; Catalano, Paul J; Warren, Laura E; Bellon, Jennifer R; Punglia, Rinaa S; Claus, Elizabeth B; Lee, Eudocia Q; Wen, Patrick Y; Haas-Kogan, Daphne A; Alexander, Brian M; Lin, Nancy U; Aizer, Ayal A

    2017-08-01

    Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking. To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis. Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Data were stratified by subtype, age, sex, and race. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and factors associated with all-cause mortality, respectively. For incidence, we identified a population-based sample of 238 726 adult patients diagnosed as having invasive breast cancer between 2010 and 2013 for whom the presence or absence of brain metastases at diagnosis was known. Patients diagnosed at autopsy or with an unknown follow-up were excluded from the survival analysis, leaving 231 684 patients in this cohort. Incidence proportion and median survival of patients with brain metastases and newly diagnosed breast cancer. We identified 968 patients with brain metastases at the time of diagnosis of breast cancer, representing 0.41% of the entire cohort and 7.56% of the subset with metastatic disease to any site. A total of 57 were 18 to 40 years old, 423 were 41 to 60 years old, 425 were 61-80 years old, and 63 were older than 80 years. Ten were male and 958 were female. Incidence proportions were highest among patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive (1.1% among entire cohort, 11.5% among patients with metastatic disease to any distant site) and triple-negative (0.7% among entire cohort, 11.4% among patients with metastatic disease to any distant site) subtypes. Median survival among the entire cohort with brain metastases was 10.0 months. Patients with HR

  20. A case of leukoencephalopathy caused by radiation and chemotherapy for brain metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Shigeru; Sonoo, Hiroshi; Nomura, Tsunehisa; Ohkubo, Sumiko; Yamamoto, Yutaka; Tanaka, Katsuhiro; Kurebayashi, Junichi; Hiratsuka, Junichi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    2002-08-01

    A case of treatment-related leukoencephalopathy is presented. A patient with breast cancer metastasis to the brain, liver, bone and distant lymph nodes was treated with whole brain radiation and docetaxcel. Eleven months after radiation, magnetic resonance imaging showed diffuse leukoencephalopathy. Twenty-two months after radiation, the patient had gait disturbance, parkinsonism, dementia and urinary incontinence. From this experience, stereotactic radiosurgery such as cyber knife and gamma knife therapy, representing a new modality for delivering intense focal radiation, should be come preferred techniques for treating patients with brain metastases, to avoid the potential cognitive side effects of fractionated whole-brain radiotherapy. (author)

  1. Global Analysis of miRNA-mRNA Interaction Network in Breast Cancer with Brain Metastasis.

    Science.gov (United States)

    Li, Zhixin; Peng, Zhiqiang; Gu, Siyu; Zheng, Junfang; Feng, Duiping; Qin, Qiong; He, Junqi

    2017-08-01

    MicroRNAs (miRNAs) have been linked to a number of cancer types including breast cancer. The rate of brain metastases is 10-30% in patients with advanced breast cancer which is associated with poor prognosis. The potential application of miRNAs in the diagnostics and therapeutics of breast cancer with brain metastasis is an area of intense interest. In an initial effort to systematically address the differential expression of miRNAs and mRNAs in primary breast cancer which may provide clues for early detection of brain metastasis, we analyzed the consequent changes in global patterns of gene expression in Gene Expression Omnibus (GEO) data set obtained by microarray from patients with in situ carcinoma and patients with brain metastasis. The miRNA-pathway regulatory network and miRNA-mRNA regulatory network were investigated in breast cancer specimens from patients with brain metastasis to screen for significantly dysregulated miRNAs followed by prediction of their target genes and pathways by Gene Ontology (GO) analysis. Functional coordination of the changes of gene expression can be modulated by individual miRNAs. Two miRNAs, hsa-miR-17-5p and hsa-miR-16-5p, were identified as having the highest associations with targeted mRNAs [such as B-cell lymphoma 2 (BCL2), small body size/mothers against decapentaplegic 3 (SMAD3) and suppressor of cytokine signaling 1 (SOCS1)] and pathways associated with epithelial-mesenchymal transitions and other processes linked with cancer metastasis (including cell cycle, adherence junctions and extracellular matrix-receptor interaction). mRNAs for two genes [HECT, UBA and WWE domain containing 1 (HUWE1) and BCL2] were found to have the highest associations with miRNAs, which were down-regulated in brain metastasis specimens of breast cancer. The change of 11 selected miRNAs was verified in The Cancer Genome Atlas (TCGA) breast cancer dataset. Up-regulation of hsa-miR-17-5p was detected in triple-negative breast cancer tissues in

  2. Clinical features of brain metastases in breast cancer: an implication for hippocampal-sparing whole-brain radiation therapy

    Directory of Open Access Journals (Sweden)

    Wu S

    2016-12-01

    Full Text Available San-Gang Wu,1,* Jia-Yuan Sun,2,* Qin Tong,3 Feng-Yan Li,2 Zhen-Yu He2 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, 2Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 3Department of Radiation Oncology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China *These authors contributed equally to this work Objective: The objectives of this study were to describe the distribution of brain metastases (BM in breast cancer patients and investigate the risk factors for perihippocampal metastases (PHM. Patients and methods: Retrospective analysis of the clinicopathological characteristics and patterns of BM was performed. Associations between clinicopathological characteristics and PHM (the hippocampus plus 5 mm margin were evaluated using logistic regression analyses. Results: A total of 1,356 brain metastatic lesions were identified in 192 patients. Patients with 1–3 BM, 4–9 BM, and ≥10 BM accounted for 63.0%, 18.8%, and 18.2%, respectively. There were only 7 (3.6% patients with hippocampal metastases (HM and 14 (7.3% patients with PHM. On logistic regression, the number of BM was an independent risk factor for PHM. Patients with ≥10 BM had a significantly higher risk of PHM compared with those with <10 BM. Breast cancer subtype (BCS was not associated with PHM. The number of BM was significantly correlated with various BCSs. Patients with hormone receptor (HR+/human epidermal growth factor receptor 2 (HER2+, HR-/HER2+, and HR-/HER2- subtypes had a higher probability of ≥10 BM, relative to patients with an HR+/HER2- subtype. Conclusion: Our study suggests that a low incidence of PHM may be acceptable to perform hippocampal-sparing whole-brain radiation therapy for breast cancer patients

  3. A clinical analysis of brain metastasis in gynecologic cancer: a retrospective multi-institute analysis.

    Science.gov (United States)

    Kim, Young Zoon; Kwon, Jae Hyun; Lim, Soyi

    2015-01-01

    This study analyzes the clinical characteristics of the brain metastasis (BM) of gynecologic cancer based on the type of cancer. In addition, the study examines the factors influencing the survival. Total 61 BM patients of gynecologic cancer were analyzed retrospectively from January 2000 to December 2012 in terms of clinical and radiological characteristics by using medical and radiological records from three university hospitals. There were 19 (31.1%) uterine cancers, 32 (52.5%) ovarian cancers, and 10 (16.4%) cervical cancers. The mean interval to BM was 25.4 months (21.6 months in ovarian cancer, 27.8 months in uterine cancer, and 33.1 months in cervical cancer). The mean survival from BM was 16.7 months (14.1 months in ovarian cancer, 23.3 months in uterine cancer, and 8.8 months in cervical cancer). According to a multivariate analysis of factors influencing survival, type of primary cancer, Karnofsky performance score, status of primary cancer, recursive partitioning analysis class, and treatment modality, particularly combined therapies, were significantly related to the overall survival. These results suggest that, in addition to traditional prognostic factors in BM, multiple treatment methods such as neurosurgery and combined chemoradiotherapy may play an important role in prolonging the survival for BM patients of gynecologic cancer.

  4. Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data

    Science.gov (United States)

    Davis, Faith G.; Dolecek, Therese A.; McCarthy, Bridget J.; Villano, John L.

    2012-01-01

    Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Disease Control and Prevention (CDC Wonder) and Surveillance, Epidemiology, and End Results (SEER) Program Web sites. Incidence proportions were identified for cancer sites, reflecting 80% of all cancers. It was conservatively estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis in 2007 of primary invasive cancer in the United States. That is, 6% of newly diagnosed cases of cancer during 2007 would be expected to develop brain metastasis as a progression of their original cancer diagnosis; the most frequent sites for metastases being lung and bronchus and breast cancers. The estimated numbers of brain metastasis will be expected to be higher among white individuals, female individuals, and older age groups. Changing patterns in the occurrence of primary cancers, trends in populations at risk, effectiveness of treatments on survival, and access to those treatments will influence the extent of brain tumor metastasis at the population level. These findings provide insight on the patterns of brain tumor metastasis and the future burden of this condition in the United States. PMID:22898372

  5. Prolonged survival after diagnosis of brain metastasis from breast cancer: contributing factors and treatment implications.

    Science.gov (United States)

    Honda, Yayoi; Aruga, Tomoyuki; Yamashita, Toshinari; Miyamoto, Hiromi; Horiguchi, Kazumi; Kitagawa, Dai; Idera, Nami; Goto, Risa; Kuroi, Katsumasa

    2015-08-01

    The prognosis of breast cancer-derived brain metastasis is poor, but new drugs and recent therapeutic strategies have helped extend survival in patients. Prediction of therapeutic responses and outcomes is not yet possible, however. In a retrospective study, we examined prognostic factors in patients with breast cancer-derived brain metastasis, and we tested the prognostic utility of a breast cancer-specific Graded Prognostic Assessment in these patients. Sixty-three patients diagnosed with brain metastasis from breast cancer treated surgically and adjuvantly were included. We examined clinical variables per primary tumor subtype: ER+/HER2- (luminal), HER2+ (human epidermal growth factor receptor type 2-enriched) or ER-/PR-/HER2- (triple negative). We also categorized patients' breast cancer-specific Graded Prognostic Assessment scores and analyzed post-brain metastasis survival time in relation to these categories. The breast cancers comprised the following subtypes: luminal, n = 18; human epidermal growth factor receptor type 2-enriched, n = 27 and triple-negative, n = 18; median survival per subtype was 11, 37 and 3 months, respectively. Survival of human epidermal growth factor receptor type 2-enriched patients was longer, though not significantly (P = 0.188), than that of luminal patients. Survival of triple-negative patients was significantly short (vs. human epidermal growth factor receptor type 2-enriched patients, P cancer-specific Graded Prognostic Assessment scores reflected disease-free intervals and survival times. Our data indicate that breast cancer-specific Graded Prognostic Assessment-based prediction will be helpful in determining appropriate therapeutic strategies for patients with brain metastasis from breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Insights into brain metastasis in patients with ALK+ lung cancer: is the brain truly a sanctuary?

    Science.gov (United States)

    Toyokawa, Gouji; Seto, Takashi; Takenoyama, Mitsuhiro; Ichinose, Yukito

    2015-12-01

    Anaplastic lymphoma kinase (ALK) has been identified to exert a potent transforming activity through its rearrangement in non-small cell lung cancer (NSCLC), and patients (pts) with ALK rearrangement can be treated more successfully with ALK inhibitors, such as crizotinib, alectinib, and ceritinib, than with chemotherapy. Despite the excellent efficacy of ALK inhibitors, resistance to these drugs is inevitably encountered in most ALK-rearranged pts. Cases of resistance are subtyped into three groups, i.e., systemic, oligo, and central nervous system (CNS) types, with the CNS being used to be considered a sanctuary. With regard to the management of CNS lesions in pts with ALK+ NSCLC, a growing body of evidence has gradually demonstrated the intracranial (IC) efficacy of ALK inhibitor (ALKi) in ALK+ NSCLC pts with brain metastases (BMs). Although the efficacy of crizotinib for the CNS lesions remains controversial, a recent retrospective investigation of ALK+ pts with BM enrolled in PROFILE 1005 and PROFILE 1007 demonstrated that crizotinib is associated with a high disease control rate for BM. However, BM comprises the most common site of progressive disease in pts with or without baseline BMs, which is a serious problem for crizotinib. Furthermore, alectinib can be used to achieve strong and long-lasting inhibitory effects on BM. In addition to alectinib, the IC efficacy of other next-generation ALK inhibitors, such as ceritinib, AP26113 and PF-06463922, has been demonstrated. In this article, we review the latest evidence regarding the BM and IC efficacy of ALK inhibitors in pts with ALK+ NSCLC.

  7. Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes.

    Science.gov (United States)

    Ebben, Johnathan D; You, Ming

    2016-09-01

    Lung cancer is a clinically difficult disease with rising disease burden around the world. Unfortunately, most lung cancers present at a clinically advanced stage. Of these cancers, many also present with brain metastasis which complicates the clinical picture. This review summarizes current knowledge on the molecular basis of lung cancer brain metastases. We start from the clinical perspective, aiming to provide a clinical context for a significant problem that requires much deeper scientific investigation. We review new research governing the metastatic process, including tumor cell signaling, establishment of a receptive tumor niches in the brain and evaluate potential new therapeutic options that take advantage of these new scientific advances. Lung cancer remains the largest single cause of cancer mortality in the United States (Siegel et al., 2015). This continues to be the clinical picture despite significant advances in therapy, including the advent of targeted molecular therapies and newly adopted immunotherapies for certain subtypes of lung cancer. In the vast majority of cases, lung cancer presents as advanced disease; in many instances, this advanced disease state is intimately associated with micro and macrometastatic disease (Goldberg et al., 2015). For both non-small cell lung cancer and small cell lung cancer patients, the predominant metastatic site is the brain, with up to 68% of patients with mediastinal lymph node metastasis eventually demonstrating brain metastasis (Wang et al., 2009).The frequency (incidence) of brain metastasis is highest in lung cancers, relative to other common epithelial malignancies (Schouten et al., 2002). Other studies have attempted to predict the risk of brain metastasis in the setting of previously non-metastatic disease. One of the largest studies to do this, analyzing historical data from 1973 to 2011 using the SEER database revealed a 9% risk of patients with previously non-metastatic NSCLC developing brain

  8. Brain Tumor Trials Collaborative | Center for Cancer Research

    Science.gov (United States)

    Brain Tumor Trials Collaborative In Pursuit of a Cure The mission of the BTTC is to develop and perform state-of-the-art clinical trials in a collaborative and collegial environment, advancing treatments for patients with brain tumors, merging good scientific method with concern for patient well-being and outcome.

  9. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jacob; Fathallan-Shaykh, Hassan

    2006-09-22

    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  10. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  11. Salmonella as a biological "Trojan horse" for neoplasia: future possibilities including brain cancer.

    Science.gov (United States)

    Mlynarczyk, Gregory S A; Berg, Carrie A; Withrock, Isabelle C; Fick, Meghan E; Anderson, Stephen J; Laboissonniere, Lauren A; Jefferson, Matthew A; Brewer, Matthew T; Stock, Matthew L; Lange, Jennifer K; Luna, K C; Acharya, Sreemoyee; Kanuri, Sriharsha; Sharma, Shaunik; Kondru, Naveen C; McCormack, Garrett R; Carlson, Steve A

    2014-09-01

    This manuscript considers available evidence that a specific Salmonella strain could be used as an effective orally-administered option for cancer therapy involving the brain. It has been established that Salmonella preferentially colonizes neoplastic tissue and thrives as a facultative anaerobe in the intra-tumor environment. Although Salmonella accumulates in tumors by passive processes, it is still possible for lipopolysaccharide to cause sepsis and endotoxic shock during the migration of bacteria to the tumor site. An LPS-free version of a recently identified Salmonella isolate may have the capability to circumvent the blood brain barrier and provide a safer method of reaching brain tumors. This isolate merits further research as a "Trojan horse" for future oral biotherapy of brain cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

    DEFF Research Database (Denmark)

    Lassen, U; Andersen, P; Daugaard, G

    1998-01-01

    Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors...... for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor r......CMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P

  13. Stereotactic radiation therapy of brain metastases from colorectal cancer: A single institution cohort.

    Science.gov (United States)

    Paix, A; Antoni, D; Adeduntan, R; Noël, G

    2017-05-01

    The brain remains an uncommon site of colorectal cancer metastases. Due to the improvement of overall colorectal cancer patient survival, the incidence of brain metastases will likely rise. We report the efficacy and safety of hypofractionnated stereotactic radiation therapy and stereotactic radiosurgery, and its role in colorectal cancer brain metastasis management. Between June 2010 and December 2014, fifteen consecutive patients received hypofractionnated stereotactic radiation therapy or stereotactic radiosurgery as first local therapy or following surgical removal for colorectal cancer brain metastases. The primary endpoint was overall survival. Secondary endpoints were brain progression free survival, in field control rates and safety. Median follow-up was 41 months (95% confidence interval [CI]: [8.9-73.1 months]), median overall survival was 8 months (95% CI [4.7-11.3 months]), and median brain progression-free survival was 5 months (95% CI [3.9-6.1 months]). Five in field recurrences were observed, which makes a control rate per metastases at 6 and 12 months of 77.8% (95% CI [74.34%-81.26%]), 51.9% (95% CI [44.21%-59.59%]) respectively. Over the 19 treatment sequences, five in field recurences were observed: 6, 12 and 18 months control rate per treatment sequence were 93.3% (95% CI [90.42%-96.18%]), 68.1% (95% CI [62.03%-74.17%]) and 45.4% (95% CI [36.14%-54.66%]) respectively. Immediate tolerance was good with no toxicity grade III or more. Long-term toxicity included two radionecrosis among which, one was symptomatic. The results of this retrospective analysis suggest that hypofractionnated stereotactic radiation therapy and stereotactic radiosurgery are effective and safe treatment modalities for single and multiple small brain metastases from colorectal cancer. However, results need to be confirmed by multicenter, collected data. Copyright © 2017. Published by Elsevier SAS.

  14. Cancer and non-cancer brain and eye effects of chronic low-dose ionizing radiation exposure

    Directory of Open Access Journals (Sweden)

    Picano Eugenio

    2012-04-01

    Full Text Available Abstract Background According to a fundamental law of radiobiology (“Law of Bergonié and Tribondeau”, 1906, the brain is a paradigm of a highly differentiated organ with low mitotic activity, and is thus radio-resistant. This assumption has been challenged by recent evidence discussed in the present review. Results Ionizing radiation is an established environmental cause of brain cancer. Although direct evidence is lacking in contemporary fluoroscopy due to obvious sample size limitation, limited follow-up time and lack of focused research, anecdotal reports of clusters have appeared in the literature, raising the suspicion that brain cancer may be a professional disease of interventional cardiologists. In addition, although terminally differentiated neurons have reduced or mild proliferative capacity, and are therefore not regarded as critical radiation targets, adult neurogenesis occurs in the dentate gyrus of the hippocampus and the olfactory bulb, and is important for mood, learning/memory and normal olfactory function, whose impairment is a recognized early biomarker of neurodegenerative diseases. The head doses involved in radiotherapy are high, usually above 2 Sv, whereas the low-dose range of professional exposure typically involves lifetime cumulative whole-body exposure in the low-dose range of Conclusions At this point, a systematic assessment of brain (cancer and non-cancer effects of chronic low-dose radiation exposure in interventional cardiologists and staff is needed.

  15. The Effects of smoking status and smoking history on patients with brain metastases from lung cancer.

    Science.gov (United States)

    Shenker, Rachel F; McTyre, Emory R; Ruiz, Jimmy; Weaver, Kathryn E; Cramer, Christina; Alphonse-Sullivan, Natalie K; Farris, Michael; Petty, William J; Bonomi, Marcelo R; Watabe, Kounosuke; Laxton, Adrian W; Tatter, Stephen B; Warren, Graham W; Chan, Michael D

    2017-05-01

    There is limited data on the effects of smoking on lung cancer patients with brain metastases. This single institution retrospective study of patients with brain metastases from lung cancer who received stereotactic radiosurgery assessed whether smoking history is associated with overall survival, local control, rate of new brain metastases (brain metastasis velocity), and likelihood of neurologic death after brain metastases. Patients were stratified by adenocarcinoma versus nonadenocarcinoma histologies. Kaplan-Meier analysis was performed for survival endpoints. Competing risk analysis was performed for neurologic death analysis to account for risk of nonneurologic death. Separate linear regression and multivariate analyses were performed to estimate the brain metastasis velocity. Of 366 patients included in the analysis, the median age was 63, 54% were male and, 60% were diagnosed with adenocarcinoma. Current smoking was reported by 37% and 91% had a smoking history. Current smoking status and pack-year history of smoking had no effect on overall survival. There was a trend for an increased risk of neurologic death in nonadenocarcinoma patients who continued to smoke (14%, 35%, and 46% at 6/12/24 months) compared with patients who did not smoke (12%, 23%, and 30%, P = 0.053). Cumulative pack years smoking was associated with an increase in neurologic death for nonadenocarcinoma patients (HR = 1.01, CI: 1.00-1.02, P = 0.046). Increased pack-year history increased brain metastasis velocity in multivariate analysis for overall patients (P = 0.026). Current smokers with nonadenocarcinoma lung cancers had a trend toward greater neurologic death than nonsmokers. Cumulative pack years smoking is associated with a greater brain metastasis velocity. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  16. Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.

    Science.gov (United States)

    Rahman, Ruman; Heath, Rachel; Grundy, Richard

    2009-04-01

    Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in approximately 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.

  17. NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer.

    Science.gov (United States)

    Adkins, Chris E; Nounou, Mohamed I; Hye, Tanvirul; Mohammad, Afroz S; Terrell-Hall, Tori; Mohan, Neel K; Eldon, Michael A; Hoch, Ute; Lockman, Paul R

    2015-10-13

    Brain metastases are an increasing problem in women with invasive breast cancer. Strategies designed to treat brain metastases of breast cancer, particularly chemotherapeutics such as irinotecan, demonstrate limited efficacy. Conventional irinotecan distributes poorly to brain metastases; therefore, NKTR-102, a PEGylated irinotecan conjugate should enhance irinotecan and its active metabolite SN38 exposure in brain metastases leading to brain tumor cytotoxicity. Female nude mice were intracranially or intracardially implanted with human brain seeking breast cancer cells (MDA-MB-231Br) and dosed with irinotecan or NKTR-102 to determine plasma and tumor pharmacokinetics of irinotecan and SN38. Tumor burden and survival were evaluated in mice treated with vehicle, irinotecan (50 mg/kg), or NKTR-102 low and high doses (10 mg/kg, 50 mg/kg respectively). NKTR-102 penetrates the blood-tumor barrier and distributes to brain metastases. NKTR-102 increased and prolonged SN38 exposure (>20 ng/g for 168 h) versus conventional irinotecan (>1 ng/g for 4 h). Treatment with NKTR-102 extended survival time (from 35 days to 74 days) and increased overall survival for NKTR-102 low dose (30 % mice) and NKTR-102 high dose (50 % mice). Tumor burden decreased (37 % with 10 mg/kg NKTR-102 and 96 % with 50 mg/kg) and lesion sizes decreased (33 % with 10 mg/kg NKTR-102 and 83 % with 50 mg/kg NKTR-102) compared to conventional irinotecan treated animals. Elevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m(2) NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results.

  18. Three-Dimensional Magnetic Resonance Spectroscopic Imaging of Brain and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    John Kurhanewicz

    2000-01-01

    Full Text Available Clinical applications of magnetic resonance spectroscopic imaging (MRSI for the study of brain and prostate cancer have expanded significantly over the past 10 years. Proton MRSI studies of the brain and prostate have demonstrated the feasibility of noninvasively assessing human cancers based on metabolite levels before and after therapy in a clinically reasonable amount of time. MRSI provides a unique biochemical “window” to study cellular metabolism noninvasively. MRSI studies have demonstrated dramatic spectral differences between normal brain tissue (low choline and high N-acetyl aspartate, NAA and prostate (low choline and high citrate compared to brain (low NAA, high choline and prostate (low citrate, high choline tumors. The presence of edema and necrosis in both the prostate and brain was reflected by a reduction of the intensity of all resonances due to reduced cell density. MRSI was able to discriminate necrosis (absence of all metabolites, except lipids and lactate from viable normal tissue and cancer following therapy. The results of current MRSI studies also provide evidence that the magnitude of metabolic changes in regions of cancer before therapy as well as the magnitude and time course of metabolic changes after therapy can improve our understanding of cancer aggressiveness and mechanisms of therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the potential for improved diagnosis, staging and treatment planning of brain and prostate cancer. Additionally, studies are under way to determine the accuracy of anatomic and metabolic parameters in providing an objective quantitative basis for assessing disease progression and response to therapy.

  19. High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats.

    Science.gov (United States)

    Wu, Yingjen Jeffrey; Pagel, Michael A; Muldoon, Leslie L; Fu, Rongwei; Neuwelt, Edward A

    2017-08-01

    Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-αv integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. The number of brain metastases and the rate of occurrence were positively correlated with cancer cell αv integrin levels. High αv integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low αv integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of αv integrin expression level. Overexpression of αv integrin in cancer cells with low αv integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. αv integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting αv integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet

    Directory of Open Access Journals (Sweden)

    Seyfried B

    2009-09-01

    Full Text Available Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect, malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  1. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet.

    Science.gov (United States)

    Seyfried, B Thomas N; Kiebish, Michael; Marsh, Jeremy; Mukherjee, Purna

    2009-09-01

    Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect), malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (beta-hydroxybutyrate) for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  2. In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer.

    Science.gov (United States)

    Hamilton, Amanda M; Foster, Paula J

    2017-02-01

    Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

  3. Translation and validation of the EORTC brain cancer module (EORTC QLQ-BN20) for use in Iran

    NARCIS (Netherlands)

    Khoshnevisan, A.; Yekaninejad, M.S.; Ardakani, S.K.; Pakpour, A.H.; Mardani, A.; Aaronson, N.K.

    2012-01-01

    Background The aim of this study was to translate the EORTC quality of life questionnaire for brain cancer, the QLQ-BN20, into Persian, and to evaluate its psychometric properties when used among brain cancer patients in Iran. Methods A standard backward and forward translation procedure was used to

  4. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

    Science.gov (United States)

    Seyfried, Thomas N; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy

    2008-11-01

    Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

  5. Role of infectious agents in the carcinogenesis of brain and head and neck cancers

    Directory of Open Access Journals (Sweden)

    Alibek Kenneth

    2013-02-01

    Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

  6. Extremely low frequency electromagnetic fields (EMF) and brain cancer in adults and children: review and comment.

    OpenAIRE

    Gurney, J G; van Wijngaarden, E

    1999-01-01

    Epidemiologic and experimental research on the potential carcinogenic effects of extremely low frequency electromagnetic fields (EMF) has now been conducted for over two decades. Cancer epidemiology studies in relation to EMF have focused primarily on brain cancer and leukemia, both from residential sources of exposure in children and adults and from occupational exposure in adult men. Because genotoxic effects of EMF have not been shown, most recent laboratory research has attempted to show ...

  7. Targeting Phosphatidylserine for Radioimmunotherapy of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2013-10-01

    Phosphatidylserine-targeted bimodal liposomal nanoparticles for in vivo imaging of breast cancer in mice. J. Controlled Release 2014 epub ahead of...Immunol 2005;174: 4880–91. 12. Troy A, Davidson P, AtkinsonC,Hart D. Phenotypic characterisation of the dendritic cell infiltrate in prostate cancer

  8. Contour propagation in MRI-guided radiotherapy treatment of cervical cancer: the accuracy of rigid, non-rigid and semi-automatic registrations

    Science.gov (United States)

    van der Put, R. W.; Kerkhof, E. M.; Raaymakers, B. W.; Jürgenliemk-Schulz, I. M.; Lagendijk, J. J. W.

    2009-12-01

    External beam radiation treatment for patients with cervical cancer is hindered by the relatively large motion of the target volume. A hybrid MRI-accelerator system makes it possible to acquire online MR images during treatment in order to correct for motion and deformation. To fully benefit from such a system, online delineation of the target volumes is necessary. The aim of this study is to investigate the accuracy of rigid, non-rigid and semi-automatic registrations of MR images for interfractional contour propagation in patients with cervical cancer. Registration using mutual information was performed on both bony anatomy and soft tissue. A B-spline transform was used for the non-rigid method. Semi-automatic registration was implemented with a point set registration algorithm on a small set of manual landmarks. Online registration was simulated by application of each method to four weekly MRI scans for each of 33 cervical cancer patients. Evaluation was performed by distance analysis with respect to manual delineations. The results show that soft-tissue registration significantly (P cervical cancer, online MRI imaging will allow target localization based on soft tissue visualization, which provides a significantly higher accuracy than localization based on bony anatomy. The use of limited user input to guide the registration increases overall accuracy. Additional non-rigid registration further reduces the propagation error and negates errors caused by small observer variations.

  9. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier.

    Science.gov (United States)

    Tominaga, Naoomi; Kosaka, Nobuyoshi; Ono, Makiko; Katsuda, Takeshi; Yoshioka, Yusuke; Tamura, Kenji; Lötvall, Jan; Nakagama, Hitoshi; Ochiya, Takahiro

    2015-04-01

    Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood-brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell-cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the destruction of BBB through the abnormal localization of actin via the downregulation of its target gene, PDPK1. PDPK1 degradation by miR-181c leads to the downregulation of phosphorylated cofilin and the resultant activated cofilin-induced modulation of actin dynamics. Furthermore, we demonstrate that systemic injection of brain metastatic cancer cell-derived EVs promoted brain metastasis of breast cancer cell lines and are preferentially incorporated into the brain in vivo. Taken together, these results indicate a novel mechanism of brain metastasis mediated by EVs that triggers the destruction of BBB.

  10. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier

    Science.gov (United States)

    Tominaga, Naoomi; Kosaka, Nobuyoshi; Ono, Makiko; Katsuda, Takeshi; Yoshioka, Yusuke; Tamura, Kenji; Lötvall, Jan; Nakagama, Hitoshi; Ochiya, Takahiro

    2015-01-01

    Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood–brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell–cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the destruction of BBB through the abnormal localization of actin via the downregulation of its target gene, PDPK1. PDPK1 degradation by miR-181c leads to the downregulation of phosphorylated cofilin and the resultant activated cofilin-induced modulation of actin dynamics. Furthermore, we demonstrate that systemic injection of brain metastatic cancer cell-derived EVs promoted brain metastasis of breast cancer cell lines and are preferentially incorporated into the brain in vivo. Taken together, these results indicate a novel mechanism of brain metastasis mediated by EVs that triggers the destruction of BBB. PMID:25828099

  11. Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer.

    Science.gov (United States)

    Halasz, Lia M; Uno, Hajime; Hughes, Melissa; D'Amico, Thomas; Dexter, Elisabeth U; Edge, Stephen B; Hayman, James A; Niland, Joyce C; Otterson, Gregory A; Pisters, Katherine M W; Theriault, Richard; Weeks, Jane C; Punglia, Rinaa S

    2016-07-01

    The optimal treatment for patients with brain metastases remains controversial as the use of stereotactic radiosurgery (SRS) alone, replacing whole-brain radiation therapy (WBRT), has increased. This study determined the patterns of care at multiple institutions before 2010 and examined whether or not survival was different between patients treated with SRS and patients treated with WBRT. This study examined the overall survival of patients treated with radiation therapy for brain metastases from non-small cell lung cancer (NSCLC; initially diagnosed in 2007-2009) or breast cancer (initially diagnosed in 1997-2009) at 5 centers. Propensity score analyses were performed to adjust for confounding factors such as the number of metastases, the extent of extracranial metastases, and the treatment center. Overall, 27.8% of 400 NSCLC patients and 13.4% of 387 breast cancer patients underwent SRS alone for the treatment of brain metastases. Few patients with more than 3 brain metastases or lesions ≥ 4 cm in size underwent SRS. Patients with fewer than 4 brain metastases less than 4 cm in size (n = 189 for NSCLC and n = 117 for breast cancer) who were treated with SRS had longer survival (adjusted hazard ratio [HR] for NSCLC, 0.58; 95% confidence Interval [CI], 0.38-0.87; P = .01; adjusted HR for breast cancer, 0.54; 95% CI, 0.33-0.91; P = .02) than those treated with WBRT. Patients treated for fewer than 4 brain metastases from NSCLC or breast cancer with SRS alone had longer survival than those treated with WBRT in this multi-institutional, retrospective study, even after adjustments for the propensity to undergo SRS. Cancer 2016;122:2091-100. © 2016 American Cancer Society. © 2016 American Cancer Society.

  12. An active treatment of lung adenocarcinoma cancer with brain metastases: icotinib

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-06-01

    Full Text Available Ying Zhang, Huaping Tang, Jun Li, Meng Li Department of Respiration Medicine, Municipal Hospital, Qingdao, People’s Republic of China Abstract: Lung cancer has the highest mortality rate of all cancers world­wide. A total of 70%–75% of all lung cancers are non-small cell lung cancer (NSCLC with two-thirds presenting with locally advanced or metastatic disease at diagnosis. Brain metastasis is one of the most common problems in the management of NSCLC, worsening the prognosis and quality of life of NSCLC patients. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs gefitinib and erlotinib have been tested in patients with NSCLC and brain metastasis. Icotinib is a new type of oral EGFR-TKI. In this report, we describe a patient with lung adenocarcinoma cancer with brain metastases who received icotinib treatment and kept satisfactory health-related quality of life for 1 year. Keywords: EGFR, non-small cell lung cancer, tyrosine kinase inhibitor

  13. [Breast cancer brain metastases: clinical and prognostic characteristics of different biological subtypes].

    Science.gov (United States)

    Zhang, Tongtong; Li, Qing; Xu, Binghe; Zhang, Pin; Yuan, Peng; Ma, Fei; Wang, Jiayu; Fan, Ying

    2014-09-01

    To analyze the clinical characteristics and survival depending on biological subtypes in breast cancer patients with brain metastases (BM). A retrospective analysis was performed on 152 breast cancer patients with BM admitted to the Cancer Institute & Hospital, Chinese Academy of Medical Sciences from January 2003 to December 2012. Depending on the biological characteristics, these patients were divided into three subtypes: Luminal, human epidermal growth factor receptor 2 (HER-2)-overexpressing, and triple-negative subtypes. The clinicopathological characteristics, recurrence status, and prognostic factors were analyzed at the initial diagnosis. The systemic therapy after BM was further studied. Among the 152 patients, the number of Luminal, HER-2-overexpressing, and triple-negative breast cancer (TNBC) subtypes were 60, 53, and 39 cases, respectively. The median time from first recurrence to BM of all patients was 7.3 months, the median time of Luminal, HER-2-overexpressing, and TNBC subtypes was 11.0 months, 9.6 months, and 5.5 months, respectively (P cancer patients (17.1 vs. 1.7 months, P brain meatastases occurr earlier in HER-2-overexpressing and TNBC subtypes. Trastuzumab can delay the occurrence of BM from advanced breast cancer, and systemic therapy can improve the survival of patients after brain metastasis.

  14. Treatment of brain metastases of renal cell cancer with combined hypofractionated stereotactic radiotherapy and whole brain radiotherapy with hippocampal sparing.

    Science.gov (United States)

    Vrána, David; Študentová, Hana; Matzenauer, Marcel; Vlachová, Zuzana; Cwiertka, Karel; Gremlica, David; Kalita, Ondřej

    2016-06-01

    Renal cell cancer patients with brain metastatic disease generally have poor prognosis. Treatment options include surgery, radiotherapy, targeted therapy or best supportive care with respect to disease burden, patient preference and performance status. In the present case report the radiotherapy technique combining whole brain radiotherapy with hippocampal sparing (hippocampal avoidance whole brain radiotherapy HA-WBRT) and hypofractionated stereotactic radiotherapy (SRT) of the brain metastases is performed in a patient with metastatic renal cell carcinoma. HA-WBRT was administered to 30 Gy in 10 fractions with sparing of the hippocampal structures and SRT of 21 Gy in 3 fractions to brain metastases which has preceded the HA-WBRT. Two single arc volumetric modulated arc radiotherapy (VMAT) plans were prepared using Monaco planning software. The HA-WBRT treatment plan achieved the following results: D2=33.91 Gy, D98=25.20 Gy, D100=14.18 Gy, D50=31.26 Gy. The homogeneity index was calculated as a deduction of the minimum dose in 2% and 98% of the planning target volume (PTV), divided by the minimum dose in 50% of the PTV. The maximum dose to the hippocampus was 17.50 Gy and mean dose was 11.59 Gy. The following doses to organs at risk (OAR) were achieved: Right opticus Dmax, 31.96 Gy; left opticus Dmax, 30.96 Gy; chiasma D max, 32,76 Gy. The volume of PTV for stereotactic radiotherapy was 3,736 cm3, with coverage D100=20.95 Gy and with only 0.11% of the PTV being irradiated to dose below the prescribed dose. HA-WBRT with SRT represents a feasible technique for radiotherapy of brain metastatic disease, however this technique is considerably demanding on departmental equipment and staff time/experience.

  15. Multi-study integration of brain cancer transcriptomes reveals organ-level molecular signatures.

    Directory of Open Access Journals (Sweden)

    Jaeyun Sung

    Full Text Available We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein--Identification of Structured Signatures and Classifiers (ISSAC--that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood.

  16. Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Man-Hsin Hung

    Full Text Available BACKGROUND: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. PATIENTS AND METHODS: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. RESULTS: Of the 2248 eligible patients, 164 (7.3% developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507. Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. CONCLUSIONS: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

  17. Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

    Science.gov (United States)

    Hung, Man-Hsin; Liu, Chun-Yu; Shiau, Cheng-Ying; Hsu, Chin-Yi; Tsai, Yi-Fang; Wang, Yu-Ling; Tai, Ling-Chen; King, Kuang-Liang; Chao, Ta-Chung; Chiu, Jen-Hwey; Su, Cheng-Hsi; Lo, Su-Shun; Tzeng, Cheng-Hwai; Shyr, Yi-Ming; Tseng, Ling-Ming

    2014-01-01

    Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

  18. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.

    Science.gov (United States)

    Sato, Ryo; Nakano, Teppei; Hosonaga, Mari; Sampetrean, Oltea; Harigai, Ritsuko; Sasaki, Takashi; Koya, Ikuko; Okano, Hideyuki; Kudoh, Jun; Saya, Hideyuki; Arima, Yoshimi

    2017-01-01

    Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non-small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  19. RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis

    Directory of Open Access Journals (Sweden)

    Ryo Sato

    2017-01-01

    Full Text Available Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.

  20. Deciphering the Finger Prints of Brain Cancer Glioblastoma Multiforme from Four Different Patients by Using Near Infrared Raman Spectroscopy.

    Science.gov (United States)

    Banerjee, Hirendra Nath; Banerji, Arnold; Banerjee, Arunendra Nath; Riddick, Eilena; Petis, Jenae; Evans, Shavonda; Patel, Megha; Parson, Carl; Smith, Valerie; Gwebu, E; Voisin, Sarah

    2015-02-03

    To explore the effectiveness of Raman spectra to diagnose brain cancer glioblastoma multiforme (GBM), we investigated the Raman spectra of single cell from four different GBM cell lines developed from four different patients and analyzed the spectra. The Raman spectra of brain cancer (GBM) cells were similar in all these cell lines. The results indicate that Raman spectra can offer the experimental basis for the cancer diagnosis and treatment.

  1. Deciphering the Finger Prints of Brain Cancer Glioblastoma Multiforme from Four Different Patients by Using Near Infrared Raman Spectroscopy

    OpenAIRE

    Banerjee, Hirendra Nath; Banerji, Arnold; Banerjee, Arunendra Nath; Riddick, Eilena; Petis, Jenae; Evans, Shavonda; Patel, Megha; Parson, Carl; Smith, Valerie; Gwebu, E; Voisin, Sarah

    2015-01-01

    To explore the effectiveness of Raman spectra to diagnose brain cancer glioblastoma multiforme (GBM), we investigated the Raman spectra of single cell from four different GBM cell lines developed from four different patients and analyzed the spectra. The Raman spectra of brain cancer (GBM) cells were similar in all these cell lines. The results indicate that Raman spectra can offer the experimental basis for the cancer diagnosis and treatment.

  2. Brain cancer incidence trends in relation to cellular telephone use in the United States

    Science.gov (United States)

    Inskip, Peter D.; Hoover, Robert N.; Devesa, Susan S.

    2010-01-01

    The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users. To address this issue, we examined temporal trends in brain cancer incidence rates in the United States, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. Log-linear models were used to estimate the annual percent change in rates among whites. With the exception of the 20–29-year age group, the trends for 1992–2006 were downward or flat. Among those aged 20–29 years, there was a statistically significant increasing trend between 1992 and 2006 among females but not among males. The recent trend in 20–29-year-old women was driven by a rising incidence of frontal lobe cancers. No increases were apparent for temporal or parietal lobe cancers, or cancers of the cerebellum, which involve the parts of the brain that would be more highly exposed to radiofrequency radiation from cellular phones. Frontal lobe cancer rates also rose among 20–29-year-old males, but the increase began earlier than among females and before cell phone use was highly prevalent. Overall, these incidence data do not provide support to the view that cellular phone use causes brain cancer. PMID:20639214

  3. Novel Treatment Strategies for Brain Metastases in Non-small-cell Lung Cancer.

    Science.gov (United States)

    Bui, Nam; Woodward, Brian; Johnson, Anna; Husain, Hatim

    2016-05-01

    Brain metastases are common in patients with non-small cell lung cancer (NSCLC), and due to associated poor prognosis, this field is an important area of need for the development of innovative medical therapies. Therapies including local approaches through surgical intervention and/or radiation and evolving systemic therapies have led to improvements in the treatment of brain metastases in patients with lung cancer. Strategies that consider applying advanced radiation techniques to minimize toxicity, intervening early with effective systemic therapies to spare radiation/surgery, testing radiosensitization combinations, and developing drug penetrant molecules have and will continue to define new practice patterns. We believe that in carefully considered asymptomatic patients, first-line systemic therapy may be considered before radiation therapy and small-molecule targeted therapy may provide an opportunity to defer radiation therapy for recurrence or progression of disease. The next several years in oncology drug development will see the reporting on of brain penetrant molecules in oncogene-defined non-small cell lung cancer. Ongoing studies will evaluate immunotherapies in patients with brain metastases with associated endpoints. We hope that continued drug development and carefully designed clinical trials may afford an opportunity to improve the lives of patients with brain metastases.

  4. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Koo, Tae Ryool [Dept. of Radiation Oncology, Hallym University Chuncheon Sacred Heart Hospital, Chuncheon (Korea, Republic of); Kim, In Ah [Dept. of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2016-03-15

    Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

  5. Exercise Improves Physical Function and Mental Health of Brain Cancer Survivors: Two Exploratory Case Studies.

    Science.gov (United States)

    Levin, Gregory T; Greenwood, Kenneth M; Singh, Favil; Tsoi, Daphne; Newton, Robert U

    2016-06-01

    Background Malignant brain tumors are unpredictable and incurable, with 5-year survival rates less than 30%. The poor prognosis combined with intensive treatment necessitates the inclusion of complementary and supportive therapies that optimize quality of life and reduce treatment-related declines in health. Exercise therapy has been shown to be beneficial in other cancer populations, but no evidence is available for brain cancer survivors. Therefore, we report results from 2 preliminary cases. Methods Two female patients diagnosed with glioblastoma multiforme and oligodendroglioma participated in a structured and supervised 12-week exercise program. The program consisted of two 1-hour resistance and aerobic exercise sessions per week and additional self-managed aerobic sessions. Outcome measures of strength, cardiovascular fitness, and several psychological indicators (depression, anxiety, and quality of life) were recorded at baseline, after 6 weeks and at the conclusion of the intervention. Results Exercise was well tolerated; both participants completed all 24 sessions and the home-based component with no adverse effects. Objective outcome measures displayed positive responses relating to reduced morbidity. Similar positive responses were found for psychological outcomes. Scores on the Hospital Anxiety and Depression Scale showed clinically meaningful improvements in depression and total distress. Conclusion These findings provide initial evidence that, despite the difficulties associated with brain cancer treatment and survivorship, exercise may be safe and beneficial and should be considered in the overall management of patients with brain cancer. © The Author(s) 2015.

  6. Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review.

    Science.gov (United States)

    Ghidini, Michele; Petrelli, Fausto; Hahne, Jens Claus; De Giorgi, Annamaria; Toppo, Laura; Pizzo, Claudio; Ratti, Margherita; Barni, Sandro; Passalacqua, Rodolfo; Tomasello, Gianluca

    2017-04-01

    The aim of the study was to collect the available data on central nervous system (CNS) metastases from esophageal and gastric cancer. A PubMed, EMBASE, SCOPUS, Web of Science, LILACS, Ovid and Cochrane Library search was performed. Thirty-seven studies including 779 patients were considered. Among the data extracted, treatment of tumor and brain metastases (BMs), time to BMs development, number and subsite, extracerebral metastases rate, median overall survival (OS) and prognostic factors were included. For esophageal cancer, the median OS from diagnosis of BMs was 4.2 months. Prognostic factors for OS included: performance status, multimodal therapy, adjuvant chemotherapy, single BM, brain only disease and surgery. For gastric cancer, median OS was 2.4 months. Prognostic factors for OS included: recursive partitioning analysis class 2, stereotactic radiosurgery (SRT) and use of intrathecal therapy. HER2-positive gastric cancer was shown to be associated with a higher risk and shorter time to CNS relapse. Patients harboring BMs from gastric and esophageal tumors, except cases with single lesions that are treated aggressively, have a poor prognosis. SRT (plus or minus surgery and whole brain radiotherapy) seems to give better results in terms of longer OS after brain relapse.

  7. Residential radon exposure and brain cancer: an ecological study in a radon prone area (Galicia, Spain).

    Science.gov (United States)

    Ruano-Ravina, Alberto; Aragonés, Nuria; Kelsey, Karl T; Pérez-Ríos, Mónica; Piñeiro-Lamas, María; López-Abente, Gonzalo; Barros-Dios, Juan M

    2017-06-15

    We aimed to know if radon concentration is associated with municipal mortality due to brain cancer in Galicia, Spain. We designed an ecological study taking as study unit Galician municipalities. To be included, municipalities had to have at least three radon measurements. We correlated radon concentrations with municipal mortality due to these malignant tumors during the period 1999-2008. We calculated the relative risk of dying of brain cancers for each municipality and correlated this value with municipal radon concentration using Spearman's Rho. 251 municipalities were included, with close to 3,500 radon measurements and an average of 14 radon measurements at each municipality. We observed a significant correlation between residential radon with brain cancer mortality for males and females and the intensity of the correlation was higher for females. These results were reinforced when the analysis was restricted to municipalities with more than 5 radon measurements: Spearman's Rho 0.286 (p-value < 0.001) and Spearman's Rho 0.509 (p-value < 0.001) for males and females, respectively. These results suggest an association between residential radon and brain cancer mortality. More research using more robust epidemiological designs is needed to confirm these findings.

  8. Have Changes in Systemic Treatment Improved Survival in Patients with Breast Cancer Metastatic to the Brain?

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2008-01-01

    Full Text Available Newly developed systemic treatment regimens might lead to improved survival also in the subgroup of breast cancer patients that harbour brain metastases. In order to examine this hypothesis, a matched pairs analysis was performed that involved one group of patients, which were treated after these new drugs were introduced, and one group of patients, which were treated approximately 10 years earlier. The two groups were well balanced for the known prognostic factors age, KPS, extracranial disease status, and recursive partitioning analysis class, as well as for the extent of brain treatment. The results show that the use of systemic chemotherapy has increased over time, both before and after the diagnosis of brain metastases. However, such treatment was performed nearly exclusively in those patients with brain metastases that belonged to the prognostically more favourable groups. Survival after whole-brain radiotherapy has remained unchanged in patients without further active treatment. It has improved in prognostically better patients and especially patients that received active treatment, where the 1-year survival rates have almost doubled. As these patient groups were small, confirmation of the results in other series should be attempted. Nevertheless, the present results are compatible with the hypothesis that improved systemic therapy might contribute to prolonged survival in patients with brain metastases from breast cancer.

  9. Task Specific Cognitive Challenges in Brain Cancer Survivors at Work

    Science.gov (United States)

    2013-03-25

    Cronbach α = 0.86), working memory ( Cronbach α = 0.93), and executive function ( Cronbach α = 0.91) (12). Identification of brain tumor-specific cognitive...model described above, 32 of the 59 specific work tasks differed significantly between the two groups based on a Bonferroni adjusted alpha level of .001

  10. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    ... 26-70 years) who were operated for brain astrocytomas. Immunohistochemical staining for Nestin, TP53, and Ki 67 was carried out on paraffin embedded tissue samples from the resected gliomas. Scores for markers' expression were statistically correlated with patients' age and gender, tumor grade, and patients' survival ...

  11. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  12. Transmigration characteristics of breast cancer and melanoma cells through the brain endothelium: Role of Rac and PI3K.

    Science.gov (United States)

    Molnár, Judit; Fazakas, Csilla; Haskó, János; Sipos, Orsolya; Nagy, Krisztina; Nyúl-Tóth, Ádám; Farkas, Attila E; Végh, Attila G; Váró, György; Galajda, Péter; Krizbai, István A; Wilhelm, Imola

    2016-05-03

    Brain metastases are common and devastating complications of both breast cancer and melanoma. Although mammary carcinoma brain metastases are more frequent than those originating from melanoma, this latter has the highest tropism to the brain. Using static and dynamic in vitro approaches, here we show that melanoma cells have increased adhesion to the brain endothelium in comparison to breast cancer cells. Moreover, melanoma cells can transmigrate more rapidly and in a higher number through brain endothelial monolayers than breast cancer cells. In addition, melanoma cells have increased ability to impair tight junctions of cerebral endothelial cells. We also show that inhibition of Rac or PI3K impedes adhesion of breast cancer cells and melanoma cells to the brain endothelium. In addition, inhibition of Rac or PI3K inhibits the late phase of transmigration of breast cancer cells and the early phase of transmigration of melanoma cells. On the other hand, the Rac inhibitor EHT1864 impairs the junctional integrity of the brain endothelium, while the PI3K inhibitor LY294002 has no damaging effect on interendothelial junctions. We suggest that targeting the PI3K/Akt pathway may represent a novel opportunity in preventing the formation of brain metastases of melanoma and breast cancer.

  13. Resonance Raman Spectroscopy of human brain metastasis of lung cancer analyzed by blind source separation

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-Hui; Pu, Yang; Cheng, Gangge; Yu, Xinguang; Zhou, Lixin; Lin, Dongmei; Zhu, Ke; Alfano, Robert R.

    2017-02-01

    Resonance Raman (RR) spectroscopy offers a novel Optical Biopsy method in cancer discrimination by a means of enhancement in Raman scattering. It is widely acknowledged that the RR spectrum of tissue is a superposition of spectra of various key building block molecules. In this study, the Resonance Raman (RR) spectra of human metastasis of lung cancerous and normal brain tissues excited by a visible selected wavelength at 532 nm are used to explore spectral changes caused by the tumor evolution. The potential application of RR spectra human brain metastasis of lung cancer was investigated by Blind Source Separation such as Principal Component Analysis (PCA). PCA is a statistical procedure that uses an orthogonal transformation to convert a set of observations of possibly correlated variables into a set of values of linearly uncorrelated variables called principal components (PCs). The results show significant RR spectra difference between human metastasis of lung cancerous and normal brain tissues analyzed by PCA. To evaluate the efficacy of for cancer detection, a linear discriminant analysis (LDA) classifier is utilized to calculate the sensitivity, and specificity and the receiver operating characteristic (ROC) curves are used to evaluate the performance of this criterion. Excellent sensitivity of 0.97, specificity (close to 1.00) and the Area Under ROC Curve (AUC) of 0.99 values are achieved under best optimal circumstance. This research demonstrates that RR spectroscopy is effective for detecting changes of tissues due to the development of brain metastasis of lung cancer. RR spectroscopy analyzed by blind source separation may have potential to be a new armamentarium.

  14. Pathogenesis and Blood-Brain Barrier Heterogeneity of Breast Cancer Brain Metastasis

    Science.gov (United States)

    2005-07-01

    fluorescence microscope . Serendipitous observations indicate that our current concepts about pathogenesis and BBB function of brain metastasis (Fenner and...GFP expression under a fluorescence microscope . Those colonies with robust GFP expression were picked, pooled, and expanded for further experiments...days. In our system, both vasculature and tumor cells were clearly visible under fluorescence microscope . The results suggest that the intravascular

  15. Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

    Science.gov (United States)

    Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

  16. Geostatistical analysis of disease data: visualization and propagation of spatial uncertainty in cancer mortality risk using Poisson kriging and p-field simulation

    Directory of Open Access Journals (Sweden)

    Goovaerts Pierre

    2006-02-01

    Full Text Available Abstract Background Smoothing methods have been developed to improve the reliability of risk cancer estimates from sparsely populated geographical entities. Filtering local details of the spatial variation of the risk leads however to the detection of larger clusters of low or high cancer risk while most spatial outliers are filtered out. Static maps of risk estimates and the associated prediction variance also fail to depict the uncertainty attached to the spatial distribution of risk values and does not allow its propagation through local cluster analysis. This paper presents a geostatistical methodology to generate multiple realizations of the spatial distribution of risk values. These maps are then fed into spatial operators, such as in local cluster analysis, allowing one to assess how risk spatial uncertainty translates into uncertainty about the location of spatial clusters and outliers. This novel approach is applied to age-adjusted breast and pancreatic cancer mortality rates recorded for white females in 295 US counties of the Northeast (1970–1994. A public-domain executable with example datasets is provided. Results Geostatistical simulation generates risk maps that are more variable than the smooth risk map estimated by Poisson kriging and reproduce better the spatial pattern captured by the risk semivariogram model. Local cluster analysis of the set of simulated risk maps leads to a clear visualization of the lower reliability of the classification obtained for pancreatic cancer versus breast cancer: only a few counties in the large cluster of low risk detected in West Virginia and Southern Pennsylvania are significant over 90% of all simulations. On the other hand, the cluster of high breast cancer mortality in Niagara county, detected after application of Poisson kriging, appears on 60% of simulated risk maps. Sensitivity analysis shows that 500 realizations are needed to achieve a stable classification for pancreatic cancer

  17. Comprehensive Clinical Staging for Resectable Lung Cancer: Clinicopathological Correlations and the Role of Brain MRI.

    Science.gov (United States)

    Vernon, Jordyn; Andruszkiewicz, Nicole; Schneider, Laura; Schieman, Colin; Finley, Christian J; Shargall, Yaron; Fahim, Christine; Farrokhyar, Forough; Hanna, Waël C

    2016-11-01

    In our model of comprehensive clinical staging (CCS) for lung cancer, patients with a computerized tomography scan of the chest and upper abdomen not showing distant metastases will then routinely undergo whole body positron emission tomography/computerized tomography and magnetic resonance imaging (MRI) of the brain before any therapeutic decision. Our aim was to determine the accuracy of CCS and the value of brain MRI in this population. A retrospective analysis of a prospectively entered database was performed for all patients who underwent lung cancer resection from January 2012 to June 2014. Demographics, clinical and pathological stage (seventh edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, and metastasis staging manual), and costs of staging were collected. Correlation between clinical and pathological stage was determined. Of 315 patients with primary lung cancer, 55.6% were female and the mean age was 70 ± 9.6 years. When correlation was analyzed without consideration for substages A and B, 49.8% of patients (158 of 315) were staged accurately, 39.7% (125 of 315) were overstaged, and 10.5% (32 of 315) were understaged. Only 4.7% of patients (15 of 315) underwent surgery without appropriate neoadjuvant treatment. Preoperative brain MRI detected asymptomatic metastases in four of 315 patients (1.3%). At a median postoperative follow-up of 19 months (range 6-43), symptomatic brain metastases developed in seven additional patients. The total cost of CCS in Canadian dollars was $367,292 over the study period, with $117,272 (31.9%) going toward brain MRI. CCS is effective for patients with resectable lung cancer, with less than 5% of patients being denied appropriate systemic treatment before surgery. Brain MRI is a low-yield and high-cost intervention in this population, and its routine use should be questioned. Copyright © 2016 International Association for the Study of Lung Cancer. Published by

  18. Androgen receptor status predicts development of brain metastases in ovarian cancers.

    Science.gov (United States)

    Mittica, Gloria; Senetta, Rebecca; Scotto, Giulia; Aglietta, Massimo; Maggiorotto, Furio; Ghisoni, Eleonora; Genta, Sofia; Boldorini, Renzo; Manini, Claudia; Morra, Isabella; Buosi, Roberta; Sapino, Anna; Cassoni, Paola; Valabrega, Giorgio

    2017-06-20

    Brain metastases are uncommon localizations in epithelial ovarian cancer (EOC), their reported incidence is increasing and no predictive biomarkers have been identified yet. Goals of this study were: i) to define a possible association between Estrogen Receptor (ER), Progesterone Receptor (PR), Androgen Receptor (AR),human EGF receptor 2 (HER2) and brain progression in EOC patients, and ii) to identify differences in ER, PR, AR and HER2 protein expression from primary EOC and its matched resected brain metastasis. A retrospective series of 11 EOC with matched brain metastasis surgically removed was collected. For comparison, a "Control dataset" of 22 patients, without evidence of brain involvement after an adequate follow up was matched. ER, PR, AR and HER2 status were analyzed by means of immunohistochemistry forCases (both primary and metastatic lesions) and Controls.Univariate analysis showed that AR status was significantly associated with brain localization, both considered as discrete variable (cut-off: 10%, p=0.013) and as continuous one (p=0.035). Multivariate analysis confirmed this trend (p=0.053). When considered as continuous variables, ER and AR showed greater expression in primary tumors in comparison with brain metastases (p=0.013 and p=0.032, respectively).In our series, AR predicts brain involvement, with a 9.5 times higher propensity for AR-negative EOC. Moreover, brain dissemination is probably the result of progressive dedifferentiation of primary tumor, shown by reduction of ER and AR expression in metastases. Further studies are required, in order to anticipate and improve multimodal treatment of brain metastases.

  19. Evaluation of health-related quality of life in Lithuanian brain tumor patients using the EORTC brain cancer module.

    Science.gov (United States)

    Bunevičius, Adomas; Tamašauskas, Šarūnas; Tamašauskas, Arimantas; Deltuva, Vytenis

    2012-01-01

    BACKGROUND AND OBJECTIVE. Health-related quality of life (HRQoL) is considered an important outcome measure in neuro-oncology. The aim of this study was to evaluate the psychometric properties of the brain cancer-specific Quality of Life Questionnaire (QLQ-BN20) of the European Organization for Research and Treatment of Cancer (EORTC) in Lithuanian brain tumor patients. MATERIAL AND METHODS. One hundred consecutive patients (71% of women; mean age, 58 ± 14 years) admitted for elective brain tumor surgery were evaluated for HRQoL using the QLQ-BN20, QLQ-C30 (a core EORTC questionnaire for cancer patients), and SF-36 scale; for motor dysfunction (clinical examination); for cognitive dysfunction (Mini-Mental State Examination); and for disability (Barthel Index). RESULTS. The QLQ-BN20 subscales had an adequate internal consistency (Cronbach α, 0.75-0.90). Motor dysfunction on neurological examination was associated with greater motor dysfunction on the QLQ-BN20; greater disability, with greater future uncertainty, motor dysfunction, communication deficits, headaches, seizures, drowsiness, itchy skin, weakness of legs, and poor bladder control on the QLQ-BN20; and cognitive dysfunction, with greater future uncertainty, visual deficits, motor dysfunction, communication deficits, headaches, drowsiness, and weakness of legs symptoms on the QLQ-BN20, suggesting an adequate clinical validity of the QLQ-BN20. A score for motor dysfunction on the QLQ-BN20 correlated with a score for motor dysfunction on the QLQ-C30 and SF-36 scales; a score for headache on the QLQ-BN20, with a score for pain on the QLQ-C30 and SF-36 scales; and a score for drowsiness symptoms on the QLQ-BN20, with a score for fatigue on the QLQ-C30. CONCLUSIONS. The Lithuanian version of the EORTC-QLQ-BN20 scale has acceptable psychometric properties and can be reliably used for the assessment of HRQoL in brain tumor patients.

  20. [Robo1 expression in breast cancer and its relationship to brain metastasis].

    Science.gov (United States)

    Wang, Jing; Wang, Le; Liu, Fang-fang; Ma, Yong-jie; Fu, Li; Li, Wen-liang; Gu, Feng

    2011-06-01

    To detect the expression of Robo1 in different breast tumors and its association with the breast cancer brain metastasis. Labelled streptavidin-biotin (LSAB) staining was used to examine the Robo1 expression in specimens from 24 cases of invasive ductal carcinoma (IDC) with brain metastasis, 71 cases of IDC without brain metastasis, 22 cases of ductal carcinoma in situ (DCIS) and 23 cases of fibroadenoma. The expression pattern of Robo1 in DCIS (59.1%) and IDC (45.3%) was significantly lower than that in adenofibroma (87.0%, P Robo1 in IDC with brain metastasis (12.5%) was significantly lower than that in IDC without brain metastasis (56.3%, P Robo1 was much higher in more than 50 year-old-group (57.8%) than that in less than 50 year-old-group (34.0%) of IDC patients. The overall survival time in patients with the Robo1 negative expression was significantly shorter than those with positive expression (P Robo1 expression and the tumor size, lymph node metastasis, pathologic stage, histological grade and clinical stage (P > 0.05). The Robo1 expression correlates negatively with IDC brain metastasis, and correlates positively with the age and prognosis of IDC patients. Robo1 may be applied as a marker in evaluation of the IDC prognosis and brain metastasis.

  1. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    bioinformatics.istge.it/ clima /) and from each other (Fig. 2b). Third, we interrogated CTC subsets by their abilities to be viable and expand in vitro. We...employing cancer cell lines from available databases (http://bioinfor- matics.istge.it/ clima /) and from each other (Fig. 2b). Third, we interrogated CTC

  2. Nano-enabled drug delivery systems for brain cancer and Alzheimer's disease: research patterns and opportunities.

    Science.gov (United States)

    Ma, Jing; Porter, Alan L; Aminabhavi, Tejraj M; Zhu, Donghua

    2015-10-01

    "Tech mining" applies bibliometric and text analytic methods to scientific literature of a target field. In this study, we compare the evolution of nano-enabled drug delivery (NEDD) systems for two different applications - viz., brain cancer (BC) and Alzheimer's disease (AD) - using this approach. In this process, we derive research intelligence from papers indexed in MEDLINE. Review by domain specialists helps understand the macro-level disease problems and pathologies to identify commonalities and differences between BC and AD. Results provide a fresh perspective on the developmental pathways for NEDD approaches that have been used in the treatment of BC and AD. Results also point toward finding future solutions to drug delivery issues that are critical to medical practitioners and pharmaceutical scientists addressing the brain. Drug delivery to brain cells has been very challenging due to the presence of the blood-brain barrier (BBB). Suitable and effective nano-enabled drug delivery (NEDD) system is urgently needed. In this study, the authors utilized "tech-mining" tools to describe and compare various choices of delivery system available for the diagnosis, as well as treatment, of brain cancer and Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Predicting brain metastases of breast cancer based on serum S100B and serum HER2

    DEFF Research Database (Denmark)

    Bechmann, Troels; Madsen, Jonna Skov; Brandslund, Ivan

    2013-01-01

    Brain metastases are a major cause of morbidity and mortality in breast cancer. The aim of the current study was to evaluate the prediction of brain metastases based on serum S100B and human epidermal growth factor receptor 2 (HER2). A total of 107 breast cancer patients were included...... in the current study from two prospective cohort studies with either elevated serum HER2 levels >15 ng/ml or brain metastases verified by magnetic resonance imaging (MRI) or computer tomography (CT). Following the exclusion of six patients, the remaining 101 patients were divided into two groups: Group 0 (n=55......), patients with normal MRI results; and group 1 (n=46), patients with brain metastases. The levels of serum S100B and HER2 in the two groups were analyzed prior to MRI or CT of the brain, and no significant differences were identified in the serum HER2 (P=0.060) or S100B levels (P=0.623) between the groups...

  4. Deciphering the finger prints of brain cancer astrocytoma in comparison to astrocytes by using near infrared Raman spectroscopy.

    Science.gov (United States)

    Banerjee, Hirendra Nath; Zhang, L

    2007-01-01

    To explore the biochemical differences between brain cancer cells Astrocytoma and normal cells Astrocyte, we investigated the Raman spectra of single cell from these two cell types and analyzed the difference in spectra and intensity. Raman spectrum shows the banding pattern of different compounds as detected by the laser. Raman intensity measures the intensity of these individual bands. The Raman spectra of brain cancer cells was similar to those of normal cells, but the Raman intensity of cancer cells was much higher than that of normal cells. The Raman spectra of brain cancer Astrocytoma shows that the structural changes of cancer cells happen so that many biological functions of these cells are lost. The results indicate that Raman spectra can offer the experimental basis for the cancer diagnosis and treatment.

  5. Systematic review of wireless phone use and brain cancer and other head tumors.

    Science.gov (United States)

    Repacholi, Michael H; Lerchl, Alexander; Röösli, Martin; Sienkiewicz, Zenon; Auvinen, Anssi; Breckenkamp, Jürgen; d'Inzeo, Guglielmo; Elliott, Paul; Frei, Patrizia; Heinrich, Sabine; Lagroye, Isabelle; Lahkola, Anna; McCormick, David L; Thomas, Silke; Vecchia, Paolo

    2012-04-01

    We conducted a systematic review of scientific studies to evaluate whether the use of wireless phones is linked to an increased incidence of the brain cancer glioma or other tumors of the head (meningioma, acoustic neuroma, and parotid gland), originating in the areas of the head that most absorb radiofrequency (RF) energy from wireless phones. Epidemiology and in vivo studies were evaluated according to an agreed protocol; quality criteria were used to evaluate the studies for narrative synthesis but not for meta-analyses or pooling of results. The epidemiology study results were heterogeneous, with sparse data on long-term use (≥ 10 years). Meta-analyses of the epidemiology studies showed no statistically significant increase in risk (defined as P cancer or other head tumors from wireless phone use. Analyses of the in vivo oncogenicity, tumor promotion, and genotoxicity studies also showed no statistically significant relationship between exposure to RF fields and genotoxic damage to brain cells, or the incidence of brain cancers or other tumors of the head. Assessment of the review results using the Hill criteria did not support a causal relationship between wireless phone use and the incidence of adult cancers in the areas of the head that most absorb RF energy from the use of wireless phones. There are insufficient data to make any determinations about longer-term use (≥ 10 years). © 2011 Wiley Periodicals, Inc.

  6. A Multidisciplinary Breast Cancer Brain Metastases Clinic: The University of North Carolina Experience.

    Science.gov (United States)

    McKee, Megan J; Keith, Kevin; Deal, Allison M; Garrett, Amy L; Wheless, Amy A; Green, Rebecca L; Benbow, Julie M; Dees, E Claire; Carey, Lisa A; Ewend, Matthew G; Anders, Carey K; Zagar, Timothy M

    2016-01-01

    Breast cancer brain metastasis (BCBM) confers a poor prognosis and is unusual in requiring multidisciplinary care in the metastatic setting. The University of North Carolina at Chapel Hill (UNC-CH) has created a BCBM clinic to provide medical and radiation oncology, neurosurgical, and supportive services to this complex patient population. We describe organization and design of the clinic as well as characteristics, treatments, and outcomes of the patients seen in its first 3 years. Clinical and demographic data were collected from patients in a prospectively maintained database. Descriptive statistics are reported as percentages and means. The Kaplan-Meier method was used to estimate time-to-event outcomes. Sixty-five patients were seen between January 2012 and January 2015. At the time of presentation to the BCBM clinic, most patients (74%) had multiple (≥2) brain metastases and had received prior systemic (77%) and whole-brain radiation therapy and/or central nervous system stereotactic radiosurgery (65%) in the metastatic setting. Seventy-eight percent returned for a follow-up visit; 32% were enrolled in a clinical trial. Median time from diagnosis of brain metastasis to death was 2.11 years (95% confidence interval [CI] 1.31-2.47) for all patients, 1.15 years (95% CI 0.4-2.43) for triple-negative breast cancer, 1.31 years (95% CI 0.51-2.52) for hormone receptor-positive/HER2- breast cancer, and 3.03 years (95% CI lower limit 1.94, upper limit not estimable) for HER2+ breast cancer (p = .0037). Patients with BCBM have unique and complex needs that require input from several oncologic disciplines. The development of the UNC-CH multidisciplinary BCBM clinic is a model that can be adapted at other centers to provide coordinated care for patients with a challenging and complex disease. Patients with breast cancer brain metastases often require unique multidisciplinary care to meet the numerous and uncommon challenges associated with their conditions. Here, the

  7. Metastatic brain tumor

    Science.gov (United States)

    ... JavaScript. A metastatic brain tumor is cancer that started in another part of the body ... of cancer rarely spread to the brain, such as colon cancer and prostate cancer. In other rare cases, a tumor can ...

  8. Changes in brain activation in breast cancer patients depend on cognitive domain and treatment type.

    Science.gov (United States)

    Menning, Sanne; de Ruiter, Michiel B; Veltman, Dick J; Boogerd, Willem; Oldenburg, Hester S A; Reneman, Liesbeth; Schagen, Sanne B

    2017-01-01

    Cognitive problems in breast cancer patients are common after systemic treatment, particularly chemotherapy. An increasing number of fMRI studies show altered brain activation in breast cancer patients after treatment, suggestive of neurotoxicity. Previous prospective fMRI studies administered a single cognitive task. The current study employed two task paradigms to evaluate whether treatment-induced changes depend on the probed cognitive domain. Participants were breast cancer patients scheduled to receive systemic treatment (anthracycline-based chemotherapy +/- endocrine treatment, n = 28), or no systemic treatment (n = 24) and no-cancer controls (n = 31). Assessment took place before adjuvant treatment and six months after chemotherapy, or at similar intervals. Blood oxygen level dependent (BOLD) activation and performance were measured during an executive functioning task and an episodic memory task. Group-by-time interactions were analyzed using a flexible factorial design. Task performance did not differ between patient groups and did not change over time. Breast cancer patients who received systemic treatment, however, showed increased parietal activation compared to baseline with increasing executive functioning task load compared to breast cancer patients who did not receive systemic treatment. This hyperactivation was accompanied by worse physical functioning, higher levels of fatigue and more cognitive complaints. In contrast, in breast cancer patients who did not receive systemic treatment, parietal activation normalized over time compared to the other two groups. Parietal hyperactivation after systemic treatment in the context of stable levels of executive task performance is compatible with a compensatory processing account of hyperactivation or maintain adequate performance levels. This over-recruitment of brain regions depends on the probed cognitive domain and may represent a response to decreased neural integrity after systemic treatment. Overall

  9. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

    Directory of Open Access Journals (Sweden)

    Zhou Weihua

    2007-02-01

    Full Text Available Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal®, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A and a human malignant glioma (U87-MG. Methods Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal® was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal® on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet. Results KetoCal® administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal® diet reduced plasma glucose levels while elevating plasma ketone body (β-hydroxybutyrate levels. Tumor microvessel density was less in the calorically restricted KetoCal® groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, β-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid Co

  10. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer.

    Science.gov (United States)

    Zhou, Weihua; Mukherjee, Purna; Kiebish, Michael A; Markis, William T; Mantis, John G; Seyfried, Thomas N

    2007-02-21

    Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A) and a human malignant glioma (U87-MG). Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet. KetoCal administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal diet reduced plasma glucose levels while elevating plasma ketone body (beta-hydroxybutyrate) levels. Tumor microvessel density was less in the calorically restricted KetoCal groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, beta-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, was lower in the tumors than in the contralateral normal

  11. Time trends (1998-2007) in brain cancer incidence rates in relation to mobile phone use in England.

    Science.gov (United States)

    de Vocht, Frank; Burstyn, Igor; Cherrie, John W

    2011-07-01

    Mobile phone use in the United Kingdom and other countries has risen steeply since the early 1990's when the first digital mobile phones were introduced. There is an ongoing controversy about whether radio frequency (RF) exposure from mobile phones increases the risk of brain cancer. However, given the widespread use and nearly two decades elapsing since mobile phones were introduced, an association should have produced a noticeable increase in the incidence of brain cancer by now. Trends in rates of newly diagnosed brain cancer cases in England between 1998 and 2007 were examined. There were no time trends in overall incidence of brain cancers for either gender, or any specific age group. Systematic increases in rates for cancers of the temporal lobe in men (0.04 new cases/year) and women (0.02/year) were observed, along with decreases in the rates of cancers of the parietal lobe (-0.03/year), cerebrum (-0.02/year) and cerebellum (-0.01/year) in men only. The increased use of mobile phones between 1985 and 2003 has not led to a noticeable change in the incidence of brain cancer in England between 1998 and 2007. The observed increase in the rate of cancers in the temporal lobe, if caused by mobile phone use, would constitute phones. Copyright © 2011 Wiley-Liss, Inc.

  12. Topological Organization of Metabolic Brain Networks in Pre-Chemotherapy Cancer with Depression: A Resting-State PET Study.

    Science.gov (United States)

    Fang, Lei; Yao, Zhijun; An, Jianping; Chen, Xuejiao; Xie, Yuanwei; Zhao, Hui; Mao, Junfeng; Liang, Wangsheng; Ma, Xiangxing

    2016-01-01

    This study aimed to investigate the metabolic brain network and its relationship with depression symptoms using 18F-fluorodeoxyglucose positron emission tomography data in 78 pre-chemotherapy cancer patients with depression and 80 matched healthy subjects. Functional and structural imbalance or disruption of brain networks frequently occur following chemotherapy in cancer patients. However, few studies have focused on the topological organization of the metabolic brain network in cancer with depression, especially those without chemotherapy. The nodal and global parameters of the metabolic brain network were computed for cancer patients and healthy subjects. Significant decreases in metabolism were found in the frontal and temporal gyri in cancer patients compared with healthy subjects. Negative correlations between depression and metabolism were found predominantly in the inferior frontal and cuneus regions, whereas positive correlations were observed in several regions, primarily including the insula, hippocampus, amygdala, and middle temporal gyri. Furthermore, a higher clustering efficiency, longer path length, and fewer hubs were found in cancer patients compared with healthy subjects. The topological organization of the whole-brain metabolic networks may be disrupted in cancer. Finally, the present findings may provide a new avenue for exploring the neurobiological mechanism, which plays a key role in lessening the depression effects in pre-chemotherapy cancer patients.

  13. Nitrates in drinking water and the risk of death from brain cancer: does hardness in drinking water matter?

    Science.gov (United States)

    Ho, Chi-Kung; Yang, Ya-Hui; Yang, Chun-Yuh

    2011-01-01

    The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and risk of death from brain cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the influence of nitrates on development of brain cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death from brain cancer and exposure to nitrates in drinking water in Taiwan. All brain cancer deaths of Taiwan residents from 2003 through 2008 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO₃-N), Ca, and Mg in drinking water was obtained from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO₃-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO₃-N exposure level was water with a NO₃-N exposure ≥ 0.38 ppm. No marked effect modification was observed due to Ca and Mg intake via drinking water on brain cancer occurrence.

  14. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  15. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer-brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  16. Selection of Brain Metastasis-Initiating Breast Cancer Cells Determined by Growth on Hard Agar

    Science.gov (United States)

    Guo, Lixia; Fan, Dominic; Zhang, Fahao; Price, Janet E.; Lee, Ju-Seog; Marchetti, Dario; Fidler, Isaiah J.; Langley, Robert R.

    2011-01-01

    An approach that facilitates rapid isolation and characterization of tumor cells with enhanced metastatic potential is highly desirable. Here, we demonstrate that plating GI-101A human breast cancer cells on hard (0.9%) agar selects for the subpopulation of metastasis-initiating cells. The agar-selected cells, designated GI-AGR, were homogeneous for CD44+ and CD133+ and five times more invasive than the parental GI-101A cells. Moreover, mice injected with GI-AGR cells had significantly more experimental brain metastases and shorter overall survival than did mice injected with GI-101A cells. Comparative gene expression analysis revealed that GI-AGR cells were markedly distinct from the parental cells but shared an overlapping pattern of gene expression with the GI-101A subline GI-BRN, which was generated by repeated in vivo recycling of GI-101A cells in an experimental brain metastasis model. Data mining on 216 genes shared between GI-AGR and GI-BRN breast cancer cells suggested that the molecular phenotype of these cells is consistent with that of cancer stem cells and the aggressive basal subtype of breast cancer. Collectively, these results demonstrate that analysis of cell growth in a hard agar assay is a powerful tool for selecting metastasis-initiating cells in a heterogeneous population of breast cancer cells, and that such selected cells have properties similar to those of tumor cells that are selected based on their potential to form metastases in mice. PMID:21514446

  17. Exposure to magnetic field and brain cancer among child; Exposition au champ magnetique et cancer du cerveau chez l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Mir, L

    2008-09-15

    The risk of childhood brain cancer as a function of magnetic field exposure has been studied less than the risk of leukemia. this updated meta-analysis of thirteen epidemiologic studies thus provides an important contribution to the literature. No increased risk of brain cancer was found, and there were no differences by method of exposure assessment. Doubt remains only for the highest exposure levels, for which very limited data are available. (author)

  18. Management of breast cancer brain metastases: Focus on human epidermal growth factor receptor 2-positive breast cancer.

    Science.gov (United States)

    Yuan, Peng; Gao, Song-Lin

    2017-03-25

    After the introduction of trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2), the overall survival (OS) among patients with HER2-positive breast cancer has been substantially improved. However, among these patients, the incidence of brain metastases (BM) has been increasing and an increased proportion of them have died of intracranial progression, which makes HER2-positive breast cancer brain metastases (BCBM) a critical issue of concern. For local control of limited BM, stereotactic radiosurgery (SRS) and surgical resection are available modalities with different clinical indications. Postoperative or preoperative radiation is usually delivered in conjunction with surgical resection to boost local control. Adjuvant whole-brain radiotherapy (WBRT) should be deferred for limited BM because of its impairment of neurocognitive function while having no benefit for OS. Although WBRT is still the standard treatment for local control of diffuse BM, SRS is a promising treatment for diffuse BM as the technique continues to improve. Although large molecules have difficulty crossing the blood brain barrier, trastuzumab-containing regimens are critical for treating HER2-positive BCBM patients because they significantly prolong OS. Tyrosine kinase inhibitors are more capable of crossing into the brain and they have been shown to be beneficial for treating BM in HER2-positive patients, especially lapatinib combined with capecitabine. The antiangiogenic agent, bevacizumab, can be applied in the HER2-positive BCBM scenario as well. In this review, we also discuss several strategies for delivering drugs into the central nervous system and several microRNAs that have the potential to become biomarkers of BCBM.

  19. Comparison of the molecular profile of brain metastases from colorectal cancer and corresponding primary tumors.

    Science.gov (United States)

    Aprile, Giuseppe; Casagrande, Mariaelena; De Maglio, Giovanna; Fontanella, Caterina; Rihawi, Karim; Bonotto, Marta; Pisa, Federica E; Tuniz, Francesco; Pizzolitto, Stefano; Fasola, Gianpiero

    2017-01-01

    Little is known about molecular biology of brain metastasis (BM) from colorectal cancer and its concordance with matched primary tumors. We identified 56 consecutive colorectal cancer patients who underwent neurosurgical resection of BM. Tumor samples were tested for KRAS, NRAS, BRAF and PIK3CA. The molecular profile of the brain lesion was compared with the corresponding primary tumor. The molecular profile concordance rate was 95.1%. Median survival after neurosurgery was 5.5 months (95% CI: 4.7-6.3); median overall survival was 24.0 months (95% CI: 15.6-32.4). In this cohort, we report a high frequency of KRAS mutations and a very high concordance rate between the molecular status of BM and that of matched primary tumors.

  20. Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor.

    Science.gov (United States)

    Takano, Koji; Kinoshita, Manabu; Takagaki, Masatoshi; Sakai, Mio; Tateishi, Souichirou; Achiha, Takamune; Hirayama, Ryuichi; Nishino, Kazumi; Uchida, Junji; Kumagai, Toru; Okami, Jiro; Kawaguchi, Atsushi; Hashimoto, Naoya; Nakanishi, Katsuyuki; Imamura, Fumio; Higashiyama, Masahiko; Yoshimine, Toshiki

    2016-05-01

    The purpose of this study was to test the hypothesis that the genetic backgrounds of lung cancers could affect the spatial distribution of brain metastases. CT or MR images of 200 patients with a total of 1033 treatment-naive brain metastases from lung cancer were retrospectively reviewed (23 by CT and 177 by MRI). All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. Locations, depths from the brain surface, and sizes of the lesions after image standardization were analyzed. The posterior fossa, the anatomic "watershed areas," and the gray-white matter junction were confirmed to be more commonly affected by lung cancer brain metastases, and brain metastases with epidermal growth factor receptor (EGFR) L858R mutation occurred more often in the caudate, cerebellum, and temporal lobe than those with exon 19 deletion of EGFR. Median depths of the lesions from the brain surface were 13.7 mm (range, 8.6-21.9) for exon 19 deleted EGFR, 11.5 mm (6.6-16.8) for L858R mutated, and 15.0 mm (10.0-20.7) for wild-type EGFR. Lesions with L858R mutated EGFR were located significantly closer to the brain surface than lesions with exon 19 deleted or wild-type EGFR (P = .0032 and P < .0001, respectively). Furthermore, brain metastases of adenocarcinoma lung cancer patients with a history of chemotherapy but not molecular targeted therapy were located significantly deeper from the brain surface (P = .0002). This analysis is the first to reveal the relationship between EGFR mutation status and the spatial distribution of brain metastases of lung cancer. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. The views of patients with brain cancer about palliative care: a qualitative study

    Science.gov (United States)

    Vierhout, M.; Daniels, M.; Mazzotta, P.; Vlahos, J.; Mason, W.P.; Bernstein, M.

    2017-01-01

    Background Palliative care, a specialty aimed at providing optimal care to patients with life-limiting and chronic conditions, has several benefits. Although palliative care is appropriate for neurosurgical conditions, including brain cancer, few studies have examined the views of brain cancer patients about palliative care. We aimed to explore the thoughts of brain cancer patients about palliative care, their opinions about early palliative care, and their preferred care setting. Methods Semi-structured interviews and the qualitative research methodologies of grounded theory were used to explore perceptions of palliative care on the part of 39 brain cancer outpatients. Results Seven overarching actions emerged: ■Patients would prefer to receive palliative care in the home.■Increased time with caregivers and family are the main appeals of home care.■Patients express dissatisfaction with brief and superficial interactions with health care providers.■Patients believe that palliative care can contribute to their emotional well-being.■Patients are open to palliative care if they believe that it will not diminish optimism.■There is a preconceived idea that palliative care is directly linked to active dying, and that supposed link generates fear in some patients.■Patients prefer to be educated about palliative care as an option early in their illness, even if they are fearful of it. Conclusions Overall, when educated about the true meaning of palliative care, most patients express interest in accessing palliative care services. Although the level of fear concerning palliative care varies in patients, most recognize the associated benefits. PMID:29270049

  2. Role of KCNMA1 gene in breast cancer invasion and metastasis to brain.

    OpenAIRE

    Khaitan, Divya; Sankpal, Umesh; Weksler, Babette; Meister, Edward; Romero, Ignacio; Couraud, Pierre-Olivier; Ningaraj, Nagendra

    2009-01-01

    Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa) channels are significantly upregulated in breast cancer cells. In this study we investigated the role ...

  3. The views of patients with brain cancer about palliative care: a qualitative study.

    Science.gov (United States)

    Vierhout, M; Daniels, M; Mazzotta, P; Vlahos, J; Mason, W P; Bernstein, M

    2017-12-01

    Palliative care, a specialty aimed at providing optimal care to patients with life-limiting and chronic conditions, has several benefits. Although palliative care is appropriate for neurosurgical conditions, including brain cancer, few studies have examined the views of brain cancer patients about palliative care. We aimed to explore the thoughts of brain cancer patients about palliative care, their opinions about early palliative care, and their preferred care setting. Semi-structured interviews and the qualitative research methodologies of grounded theory were used to explore perceptions of palliative care on the part of 39 brain cancer outpatients. Seven overarching actions emerged: ■Patients would prefer to receive palliative care in the home.■Increased time with caregivers and family are the main appeals of home care.■Patients express dissatisfaction with brief and superficial interactions with health care providers.■Patients believe that palliative care can contribute to their emotional well-being.■Patients are open to palliative care if they believe that it will not diminish optimism.■There is a preconceived idea that palliative care is directly linked to active dying, and that supposed link generates fear in some patients.■Patients prefer to be educated about palliative care as an option early in their illness, even if they are fearful of it. Overall, when educated about the true meaning of palliative care, most patients express interest in accessing palliative care services. Although the level of fear concerning palliative care varies in patients, most recognize the associated benefits.

  4. The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer.

    Science.gov (United States)

    Meidenbauer, Joshua J; Mukherjee, Purna; Seyfried, Thomas N

    2015-01-01

    Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg effect), which is the common metabolic malady of most cancers including brain tumors. The KD targets tumor energy metabolism by lowering blood glucose and elevating blood ketones (β-hydroxybutyrate). Brain tumor cells, unlike normal brain cells, cannot use ketone bodies effectively for energy when glucose becomes limiting. Although plasma levels of glucose and ketone bodies have been used separately to predict the therapeutic success of metabolic therapy, daily glucose levels can fluctuate widely in brain cancer patients. This can create difficulty in linking changes in blood glucose and ketones to efficacy of metabolic therapy. A program was developed (Glucose Ketone Index Calculator, GKIC) that tracks the ratio of blood glucose to ketones as a single value. We have termed this ratio the Glucose Ketone Index (GKI). The GKIC was used to compute the GKI for data published on blood glucose and ketone levels in humans and mice with brain tumors. The results showed a clear relationship between the GKI and therapeutic efficacy using ketogenic diets and calorie restriction. The GKIC is a simple tool that can help monitor the efficacy of metabolic therapy in preclinical animal models and in clinical trials for malignant brain cancer and possibly other cancers that express aerobic fermentation.

  5. Cancer-associated fibroblast promote transmigration through endothelial brain cells in three-dimensional in vitro models.

    Science.gov (United States)

    Choi, Yoon Pyo; Lee, Joo Hyun; Gao, Ming-Qing; Kim, Baek Gil; Kang, Suki; Kim, Se Hoon; Cho, Nam Hoon

    2014-11-01

    Brain metastases are associated with high morbidity as well as with poor prognosis and survival in breast cancer patients. Despite its clinical importance, metastasis of breast cancer cells through the blood-brain barrier (BBB) is poorly understood. The objective of our study was to investigate whether cancer-associated fibroblasts (CAFs) play crucial roles in breast cancer brain metastasis. Using a cell adhesion assays, in vitro BBB permeability and transmigration assays and soft agar colony formation assays, we investigated the physical roles of CAFs in breast cancer brain metastasis. We also performed immunofluorescence, flow cytometric analysis, Droplet Digital PCR and Simon™ Simple Western System to confirm changes in expression levels. We established two novel three-dimensional (3D) culture systems using a perpendicular slide chamber and applying 3D embedded culture method to reflect brain metastasis conditions. With a newly developed device, CAFs was proven to promote cell adhesion to human brain microvascular endothelial cells, in vitro BBB permeability and transmigration and colony formation of breast cancer cells. Furthermore, CAFs enhanced the invasive migration of breast cancer cells in two kinds of 3D cultures. These 3D models also reliably recapitulate the initial steps of BBB transmigration, micro-metastasis and colonization. Expression of integrin α5β1 and αvβ3, c-MET and α2,6-siayltransferase was increased in breast cancer cells that migrated through the BBB. In conclusion, based on our in vitro BBB and co-culture models, our data suggest that CAFs may play a role in breast cancer brain metastasis. © 2014 UICC.

  6. Brain metastases as site of first and isolated recurrence of breast cancer: the role of systemic therapy after local treatment.

    Science.gov (United States)

    Niwińska, Anna

    2016-10-01

    The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p brain metastasis in patients with solitary brain metastasis, with and without systemic treatment after local therapy, was respectively 22 and 7 months (p = 0.003). Cox multivariate analysis demonstrated that good performance status, solitary brain metastasis and systemic therapy undertaken after local treatment were factors which prolonged survival. However patient survival was adversely affected by those having leptomeningeal metastasis associated with brain parenchymal lesions. Systemic therapy, undertaken after local treatment improved survival in those patients with breast cancer and brain metastases as the site of first and isolated recurrence. Further study is required in order to fully establish the role of systemic treatment for this patient group.

  7. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

    Science.gov (United States)

    Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

    2012-01-01

    We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations. Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

  8. The attitudes of brain cancer patients and their caregivers towards death and dying: a qualitative study

    Directory of Open Access Journals (Sweden)

    Kimmelman Jonathan

    2007-11-01

    Full Text Available Abstract Background Much money and energy has been spent on the study of the molecular biology of malignant brain tumours. However, little attention has been paid to the wishes of patients afflicted with these incurable tumours, and how this might influence treatment considerations. Methods We interviewed 29 individuals – 7 patients dying of a malignant brain tumor and 22 loved ones. One-on-one interviews were conducted according to a pre-designed interview guide. A combination of open-ended questions, as well as clinical scenarios was presented to participants in order to understand what is meaningful and valuable to them when determining treatment options and management approaches. The results were analyzed, coded, and interpreted using qualitative analytic techniques in order to arrive at several common overarching themes. Results Seven major themes were identified. In general, respondents were united in viewing brain cancer as unique amongst malignancies, due in large part to the premium placed on mental competence and cognitive functioning. Importantly, participants found their experiences, however difficult, led to the discovery of inner strength and resilience. Responses were usually framed within an interpersonal context, and participants were generally grateful for the opportunity to speak about their experiences. Attitudes towards religion, spirituality, and euthanasia were also probed. Conclusion Several important themes underlie the experiences of brain cancer patients and their caregivers. It is important to consider these when managing these patients and to respect not only their autonomy but also the complex interpersonal toll that a malignant diagnosis can have.

  9. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-01

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  10. Examination of the predictive factors of the response to whole brain radiotherapy for brain metastases from lung cancer using MRI.

    Science.gov (United States)

    Aoki, Shuri; Kanda, Tomonori; Matsutani, Noriyuki; Seki, Nobuhiko; Kawamura, Masafumi; Furui, Shigeru; Yamashita, Hideomi

    2017-07-01

    Previous studies have been conducted on the prognostic factors for overall survival in patients with brain metastases (BMs) following whole brain radiotherapy (WBRT). However, there have been a small number of studies regarding the prognostic factors for the response of tumor to WBRT. The aim of the present study was to identify the predictive factors for the response to WBRT from the point of view of reduction of tumor using magnetic resonance imaging. A retrospective analysis of 62 patients with BMs from primary lung cancer treated with WBRT was undertaken. The effects of the following factors on the response to WBRT were evaluated: Age; sex; performance status; lactate dehydrogenase; pathology; existence of extracranial metastases; activity of extracranial disease; chemo-history; chest radiotherapy history; treatment term; γ-knife radiotherapy; diffusion weighted image signal intensity; tumor diameter; extent of edema and the edema/tumor (E/T) ratio. The association between the reduction of tumors and clinical factors was evaluated using logistic regression analysis. Ppredictive factors for the reduction of tumor. The following 3 factors were significantly associated with the response of tumors to WBRT: The presence of SCLC; an E/T ratio of ≥1.5; and the presence of extracranial metastases. The E/T ratio is a novel index that provides a simple and easy predictive method for use in a clinical setting.

  11. Prognostic factors in patients with brain metastasis from non-small cell lung cancer treated with whole-brain radiotherapy.

    Science.gov (United States)

    Harada, Hideyuki; Asakura, Hirofumi; Ogawa, Hirofumi; Mori, Keita; Takahashi, Toshiaki; Nakasu, Yoko; Nishimura, Tetsuo

    2016-01-01

    The purpose of this study was to evaluate the prognostic factors associated with overall survival (OS) in nonsmall cell lung cancer (NSCLC) patients with brain metastasis who received whole-brain radiotherapy (WBRT). This study included 264 consecutive NSCLC patients with brain metastasis who received WBRT. Patients with leptomeningeal metastasis and those who underwent craniotomy or stereotactic radiotherapy before WBRT were excluded. The evaluated prognostic factors for OS included gender, neurological deficit, histology, epidermal growth factor receptor (EGFR) mutation status, previous cytotoxic chemotherapy, previous EGFR-tyrosine kinase inhibitor treatment, recursive partitioning analysis (RPA) class, and diagnosis-specific graded prognostic assessment (DS-GPA) score. All factors with a P < 0.05 in univariate analysis were entered into multivariate analysis using Cox regression and a confidence interval of 99%. Two hundred thirty patients had died, 14 patients were alive, and 20 patients were lost to follow-up. The median follow-up time was 20.9 months. The median survival time was 5.5 months (95% confidence interval; 4.8-6.3). Univariate analysis showed that gender, neurological deficit, histology, EGFR mutation status, RPA class, and DS-GPA score were significant prognostic factors for OS. In multivariate analysis, RPA class and histology were found to be significant prognostic factors for OS, with P values of 0.0039 and 0.0014, respectively. RPA Class I or II (Karnofsky Performance Status ≥70) and adenocarcinoma histology were associated with longer OS. These factors should be taken into account when considering indication for WBRT.

  12. Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel.

    Science.gov (United States)

    Lee, Ho Jeong; Hanibuchi, Masaki; Kim, Sun-Jin; Yu, Hyunkyung; Kim, Mark Seungwook; He, Junqin; Langley, Robert R; Lehembre, François; Regenass, Urs; Fidler, Isaiah J

    2016-04-01

    We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved

  13. Delivery of Small Interfering RNA to Inhibit Vascular Endothelial Growth Factor in Zebrafish Using Natural Brain Endothelia Cell-Secreted Exosome Nanovesicles for the Treatment of Brain Cancer.

    Science.gov (United States)

    Yang, Tianzhi; Fogarty, Brittany; LaForge, Bret; Aziz, Salma; Pham, Thuy; Lai, Leanne; Bai, Shuhua

    2017-03-01

    Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p brain endothelial bEND.3 cell and astrocyte. Inhibition at the expression of VEGF RNA and protein levels was observed in glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs. Imaging results showed that exosome delivered more siRNAs across the BBB in Tg(fli1:GFP) zebrafish. In a xenotransplanted brain tumor model, exosome-delivered VEGF siRNAs decreased the fluorescence intensity of labeled cancer cells in the brain of zebrafish. Brain endothelial cell-derived exosomes could be potentially used as a natural carrier for the brain delivery of exogenous siRNA.

  14. Systemic treatments for brain metastases from breast cancer, non-small cell lung cancer, melanoma and renal cell carcinoma: an overview of the literature.

    Science.gov (United States)

    Lombardi, Giuseppe; Di Stefano, Anna Luisa; Farina, Patrizia; Zagonel, Vittorina; Tabouret, Emeline

    2014-09-01

    The frequency of metastatic brain tumors has increased over recent years; the primary tumors most involved are breast cancer, lung cancer, melanoma and renal cell carcinoma. While radiation therapy and surgery remain the mainstay treatment in selected patients, new molecular drugs have been developed for brain metastases. Studies so far report interesting results. This review focuses on systemic cytotoxic drugs and, in particular, on new targeted therapies and their clinically relevant activities in brain metastases from solid tumors in adults. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model.

    Science.gov (United States)

    Liu, Hui; Kato, Yukinari; Erzinger, Stephanie A; Kiriakova, Galina M; Qian, Yongzhen; Palmieri, Diane; Steeg, Patricia S; Price, Janet E

    2012-12-07

    Brain metastasis is an increasingly common complication for breast cancer patients; approximately 15- 30% of breast cancer patients develop brain metastasis. However, relatively little is known about how these metastases form, and what phenotypes are characteristic of cells with brain metastasizing potential. In this study, we show that the targeted knockdown of MMP-1 in breast cancer cells with enhanced brain metastatic ability not only reduced primary tumor growth, but also significantly inhibited brain metastasis. Two variants of the MDA-MB-231 human breast cancer cell line selected for enhanced ability to form brain metastases in nude mice (231-BR and 231-BR3 cells) were found to express high levels of matrix metalloproteinase-1 (MMP-1). Short hairpin RNA-mediated stable knockdown of MMP-1 in 231-BR and 231-BR3 cells were established to analyze tumorigenic ability and metastatic ability. Short hairpin RNA-mediated stable knockdown of MMP-1 inhibited the invasive ability of MDA-MB 231 variant cells in vitro, and inhibited breast cancer growth when the cells were injected into the mammary fat pad of nude mice. Reduction of MMP-1 expression significantly attenuated brain metastasis and lung metastasis formation following injection of cells into the left ventricle of the heart and tail vein, respectively. There were significantly fewer proliferating cells in brain metastases of cells with reduced MMP-1 expression. Furthermore, reduced MMP-1 expression was associated with decreased TGFα release and phospho-EGFR expression in 231-BR and BR3 cells. Our results show that elevated expression of MMP-1 can promote the local growth and the formation of brain metastases by breast cancer cells.

  16. Impact of Triple-Negative Phenotype on Prognosis of Patients With Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Xu Zhiyuan [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Schlesinger, David [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Toulmin, Sushila [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States); Rich, Tyvin [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Sheehan, Jason, E-mail: jps2f@virginia.edu [Department of Neurosurgery, University of Virginia, Charlottesville, Virginia (United States)

    2012-11-01

    Purpose: To elucidate survival times and identify potential prognostic factors in patients with triple-negative (TN) phenotype who harbored brain metastases arising from breast cancer and who underwent stereotactic radiosurgery (SRS). Methods and Materials: A total of 103 breast cancer patients with brain metastases were treated with SRS and then studied retrospectively. Twenty-four patients (23.3%) were TN. Survival times were estimated using the Kaplan-Meier method, with a log-rank test computing the survival time difference between groups. Univariate and multivariate analyses to predict potential prognostic factors were performed using a Cox proportional hazard regression model. Results: The presence of TN phenotype was associated with worse survival times, including overall survival after the diagnosis of primary breast cancer (43 months vs. 82 months), neurologic survival after the diagnosis of intracranial metastases, and radiosurgical survival after SRS, with median survival times being 13 months vs. 25 months and 6 months vs. 16 months, respectively (p < 0.002 in all three comparisons). On multivariate analysis, radiosurgical survival benefit was associated with non-TN status and lower recursive partitioning analysis class at the initial SRS. Conclusion: The TN phenotype represents a significant adverse prognostic factor with respect to overall survival, neurologic survival, and radiosurgical survival in breast cancer patients with intracranial metastasis. Recursive partitioning analysis class also served as an important and independent prognostic factor.

  17. miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF-α.

    Science.gov (United States)

    Xing, F; Sharma, S; Liu, Y; Mo, Y-Y; Wu, K; Zhang, Y-Y; Pochampally, R; Martinez, L A; Lo, H-W; Watabe, K

    2015-09-10

    The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective owing to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of the brain metastasis is poorly understood. In this study, we have isolated RNA from samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling analysis. Our results revealed that the miR-509 is highly expressed in the primary tumors, whereas the expression of this microRNA is significantly decreased in the brain metastatic lesions. MicroRNA target prediction and the analysis of cytokine array for the cells ectopically expressed with miR-509 demonstrated that this microRNA was capable of modulating the two genes essential for brain invasion, RhoC and TNF-α that affect the invasion of cancer cells and permeability of BBB, respectively. Importantly, high levels of TNF-α and RhoC-induced MMP9 were significantly correlated with brain metastasis-free survival of breast cancer patients. Furthermore, the results of our in vivo experiments indicate that miR-509 significantly suppressed the ability of cancer cells to metastasize to the brain. These findings suggest that miR-509 has a critical role in brain metastasis of breast cancer by modulating the RhoC-TNF-α network and that this miR-509 axis may represent a potential therapeutic target or serve as a prognostic tool for brain metastasis.

  18. Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Xinhong Wu

    2013-01-01

    Conclusion: After whole brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor.

  19. Brain and central nervous system cancer incidence in navarre (Spain), 1973-2008 and projections for 2014.

    Science.gov (United States)

    Etxeberria, J; Román, E San; Burgui, R; Guevara, M; Moreno-Iribas, C; Urbina, M J; Ardanaz, E

    2015-01-01

    Different studies have pointed out Navarre as one of the regions of Spain with the highest incidence rates of brain and other central nervous system (CNS) cancer. Trend analysis for cancer incidence rates for long periods of time, might help determining risk factors as well as, assessing prevention actions involved in this disease. The objective of this study was to describe the incidence of brain and CNS cancer using data from the population-based cancer registry of Navarre, (Spain) during the period 1973-2008 and provide forecast figures up to-2014. Crude and age-standardized (world population) incidence rates of brain cancer per 100,000 person-years were calculated by the direct method separately by gender, area (Pamplona and others), and age-groups. Penalized splines for smoothing rates in the temporal dimensions were applied in order to estimate and forecast cancer incidence rates. Age-adjusted incidence rates showed an increase over the study and forecast periods in both sexes more marked in women than in men. Higher incidence rates were observed in men compared with women but the differences became smaller with time. The increase was due to the rise of rates in the oldest age groups since the rates for younger age groups remained stable or decreased over time. As the entire aetiology of brain and other CNS cancer is not still clear, keep promoting healthful lifestyles for cancer primary prevention among the whole population is necessary.

  20. Longitudinal Brain Changes Associated with Prophylactic Cranial Irradiation in Lung Cancer.

    Science.gov (United States)

    Simó, Marta; Vaquero, Lucía; Ripollés, Pablo; Gurtubay-Antolin, Ane; Jové, Josep; Navarro, Arturo; Cardenal, Felipe; Bruna, Jordi; Rodríguez-Fornells, Antoni

    2016-04-01

    The toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. Twenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire was also completed. Patients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GM over time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. This longitudinal

  1. Challenges in the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer with brain metastases.

    Science.gov (United States)

    Liu, Minetta C; Cortés, Javier; O'Shaughnessy, Joyce

    2016-06-01

    Brain metastases are a major cause of morbidity and mortality for women with hormone receptor (HR)-positive breast cancer, yet little is known about the optimal treatment of brain disease in this group of patients. Although these patients are at lower risk for brain metastases relative to those with HER2-positive and triple-negative disease, they comprise the majority of women diagnosed with breast cancer. Surgery and radiation continue to have a role in the treatment of brain metastases, but there is a dearth of effective systemic therapies due to the poor penetrability of many systemic drugs across the blood-brain barrier (BBB). Additionally, patients with brain metastases have long been excluded from clinical trials, and few studies have been conducted to evaluate the safety and effectiveness of systemic therapies specifically for the treatment of HER2-negative breast cancer brain metastases. New approaches are on the horizon, such as nanoparticle-based cytotoxic drugs that have the potential to cross the BBB and provide clinically meaningful benefits to patients with this life-threatening consequence of HR-positive breast cancer.

  2. Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

    2016-03-01

    Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

  3. Wave Propagation

    CERN Document Server

    Ferrarese, Giorgio

    2011-01-01

    Lectures: A. Jeffrey: Lectures on nonlinear wave propagation.- Y. Choquet-Bruhat: Ondes asymptotiques.- G. Boillat: Urti.- Seminars: D. Graffi: Sulla teoria dell'ottica non-lineare.- G. Grioli: Sulla propagazione del calore nei mezzi continui.- T. Manacorda: Onde nei solidi con vincoli interni.- T. Ruggeri: "Entropy principle" and main field for a non linear covariant system.- B. Straughan: Singular surfaces in dipolar materials and possible consequences for continuum mechanics

  4. The Molecular Mechanisms of Plant-Derived Compounds Targeting Brain Cancer

    Directory of Open Access Journals (Sweden)

    Hueng-Chuen Fan

    2018-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most aggressive and malignant forms of brain tumors. Despite recent advances in operative and postoperative treatments, it is almost impossible to perform complete resection of these tumors owing to their invasive and diffuse nature. Several natural plant-derived products, however, have been demonstrated to have promising therapeutic effects, such that they may serve as resources for anticancer drug discovery. The therapeutic effects of one such plant product, n-butylidenephthalide (BP, are wide-ranging in nature, including impacts on cancer cell apoptosis, cell cycle arrest, and cancer cell senescence. The compound also exhibits a relatively high level of penetration through the blood-brain barrier (BBB. Taken together, its actions have been shown to have anti-proliferative, anti-chemoresistance, anti-invasion, anti-migration, and anti-dissemination effects against GBM. In addition, a local drug delivery system for the subcutaneous and intracranial implantation of BP wafers that significantly reduce tumor size in xenograft models, as well as orthotopic and spontaneous brain tumors in animal models, has been developed. Isochaihulactone (ICL, another kind of plant product, possesses a broad spectrum of pharmacological activities, including impacts on cancer cell apoptosis and cell cycle arrest, as well as anti-proliferative and anti-chemoresistance effects. Furthermore, these actions have been specifically shown to have cancer-fighting effects on GBM. In short, the results of various studies reviewed herein have provided substantial evidence indicating that BP and ICH are promising novel anticancer compounds with good potential for clinical applications.

  5. Evaluation of non-rigid constrained CT/CBCT registration algorithms for delineation propagation in the context of prostate cancer radiotherapy

    Science.gov (United States)

    Rubeaux, Mathieu; Simon, Antoine; Gnep, Khemara; Colliaux, Jérémy; Acosta, Oscar; de Crevoisier, Renaud; Haigron, Pascal

    2013-03-01

    Image-Guided Radiation Therapy (IGRT) aims at increasing the precision of radiation dose delivery. In the context of prostate cancer, a planning Computed Tomography (CT) image with manually defined prostate and organs at risk (OAR) delineations is usually associated with daily Cone Beam Computed Tomography (CBCT) follow-up images. The CBCT images allow to visualize the prostate position and to reposition the patient accordingly. They also should be used to evaluate the dose received by the organs at each fraction of the treatment. To do so, the first step is a prostate and OAR segmentation on the daily CBCTs, which is very timeconsuming. To simplify this task, CT to CBCT non-rigid registration could be used in order to propagate the original CT delineations in the CBCT images. For this aim, we compared several non-rigid registration methods. They are all based on the Mutual Information (MI) similarity measure, and use a BSpline transformation model. But we add different constraints to this global scheme in order to evaluate their impact on the final results. These algorithms are investigated on two real datasets, representing a total of 70 CBCT on which a reference delineation has been realized. The evaluation is led using the Dice Similarity Coefficient (DSC) as a quality criteria. The experiments show that a rigid penalty term on the bones improves the final registration result, providing high quality propagated delineations.

  6. Uterine cervical cancer with brain metastasis as the initial site of presentation.

    Science.gov (United States)

    Sato, Yumi; Tanaka, Kei; Kobayashi, Yoichi; Shibuya, Hiromi; Nishigaya, Yoshiko; Momomura, Mai; Matsumoto, Hironori; Iwashita, Mitsutoshi

    2015-07-01

    Brain metastasis from uterine cervical cancer is rare, with an incidence of 0.5%, and usually occurs late in the course of the disease. We report a case of uterine cervical cancer with brain metastasis as the initial site of presentation. A 50-year-old woman with headache, vertigo, amnesia and loss of appetite was admitted for persistent vomiting. Contrast enhanced computed tomography showed a solitary right frontal cerebral lesion with ring enhancement and uterine cervical tumor. She was diagnosed with uterine cervical squamous cell carcinoma with parametrium invasion and no other distant affected organs were detected. The cerebral lesion was surgically removed and pathologically proved to be metastasis of uterine cervical squamous cell carcinoma. The patient underwent concurrent chemoradiotherapy, followed by cerebral radiation therapy, but multiple metastases to the liver and lung developed and the patient died 7 months after diagnosis of brain metastasis. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

  7. Correlation of neurocognitive function and brain parenchyma volumes in children surviving cancer

    Science.gov (United States)

    Reddick, Wilburn E.; White, Holly A.; Glass, John O.; Mulhern, Raymond K.

    2002-04-01

    This research builds on our hypothesis that white matter damage and associated neurocognitive symptoms, in children treated for cancer with cranial spinal irradiation, spans a continuum of severity that can be reliably probed using non-invasive MR technology. Quantitative volumetric assessments of MR imaging and psychological assessments were obtained in 40 long-term survivors of malignant brain tumors treated with cranial irradiation. Neurocognitive assessments included a test of intellect (Wechsler Intelligence Test for Children, Wechsler Adult Intelligence Scale), attention (Conner's Continuous Performance Test), and memory (California Verbal Learning Test). One-sample t-tests were conducted to evaluate test performance of survivors against age-adjusted scores from the test norms; these analyses revealed significant impairments in all apriori selected measures of intelligence, attention, and memory. Partial correlation analyses were performed to assess the relationships between brain tissues volumes (normal appearing white matter (NAWM), gray matter, and CSF) and neurocognitive function. Global intelligence (r = 0.32, p = 0.05) and global attentional (r = 0.49, p < 0.01) were significantly positively correlated with NAWM volumes, whereas global memory was significantly positively correlated with overall brain parenchyma (r = 0.38, p = 0.04). We conclude that quantitative assessment of MR examinations in survivors of childhood cancer treated with cranial irradiation reveal that loss of NAWM is associated with decreased intellectual and attentional deficits, whereas overall parenchyma loss, as reflected by increased CSF and decreased white matter, is associated with memory-related deficits.

  8. Gene set based integrated data analysis reveals phenotypic differences in a brain cancer model.

    Directory of Open Access Journals (Sweden)

    Kjell Petersen

    Full Text Available A key challenge in the data analysis of biological high-throughput experiments is to handle the often low number of samples in the experiments compared to the number of biomolecules that are simultaneously measured. Combining experimental data using independent technologies to illuminate the same biological trends, as well as complementing each other in a larger perspective, is one natural way to overcome this challenge. In this work we investigated if integrating proteomics and transcriptomics data from a brain cancer animal model using gene set based analysis methodology, could enhance the biological interpretation of the data relative to more traditional analysis of the two datasets individually. The brain cancer model used is based on serial passaging of transplanted human brain tumor material (glioblastoma--GBM through several generations in rats. These serial transplantations lead over time to genotypic and phenotypic changes in the tumors and represent a medically relevant model with a rare access to samples and where consequent analyses of individual datasets have revealed relatively few significant findings on their own. We found that the integrated analysis both performed better in terms of significance measure of its findings compared to individual analyses, as well as providing independent verification of the individual results. Thus a better context for overall biological interpretation of the data can be achieved.

  9. Multiscale biomechanics of brain tumours favours cancer invasion by cell softening and tissue stiffening

    Science.gov (United States)

    Kas, Josef; Fritsch, Anatol; Grosser, Steffen; Friebe, Sabrina; Reiss-Zimmermann, Martin; Müller, Wolf; Hoffmann, Karl-Titus; Sack, Ingolf

    Cancer progression needs two contradictory mechanical prerequisites. For metastasis individual cancer cells or small clusters have to flow through the microenvironment by overcoming the yield stress exerted by the surrounding. On the other hand a tumour has to behave as a solid to permit cell proliferation and spreading of the tumour mass against its surrounding. We determine that the high mechanical adaptability of cancer cells and the scale controlled viscoelastic properties of tissues reconcile both conflicting properties, fluid and solid, simultaneously in brain tumours. We resolve why different techniques that assess cell and tissue mechanics have produced apparently conflicting results by our finding that tumours generate different viscoelastic behaviours on different length scales, which are in concert optimal for tumour spreading and metastasis. Single cancer cells become very soft in their elastic behavior which promotes cell unjamming. On the level of direct cell-to-cell interactions cells feel their micro-environment as rigid elastic substrate that stimulates cancer on the molecular level. All over a tumour has predominately a stiff elastic character in terms of viscoelastic behaviour caused by a solid backbone. Simultaneously, the tumour mass is characterized by a large local variability in the storage and loss modulus that is caused by areas of a more fluid nature.

  10. Predicting the presence of extracranial metastases in patients with brain metastases upon first diagnosis of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Arizona (United States); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Khoa, M.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam)

    2014-04-15

    This study aimed to determine factors allowing the prediction of extracranial metastases in patients presenting with brain metastases at the first diagnosis of cancer. Data from 659 patients with brain metastases upon first diagnosis of cancer were retrospectively analyzed. The parameters age, gender, Karnofsky performance score (KPS), primary tumor type and number of brain metastases were compared between 359 patients with extracranial metastases and 300 patients without extracranial metastases. Additional analyses were performed for patients with the most unfavorable and those with the most favorable characteristics. The comparison of patients with versus without extracranial metastases revealed significant differences between the groups in terms of KPS (p < 0.001) and number of brain metastases (p < 0.001). Of the study patients, 113 had both most unfavorable characteristics, i.e. KPS ≤ 50 and ≥ 4 brain metastases. The sensitivity for identifying patients with extracranial metastases was 82 %; specificity was 51 %. A total of 50 patients had KPS ≥ 90 and only one brain metastasis. The sensitivity for identifying patients without extracranial metastases was 86 %; specificity was 58 %. The combination of KPS and the number of brain metastases can help to predict the presence or absence of extracranial metastases. (orig.) [German] Diese Studie soll zur Abschaetzung des Vorliegens extrakranieller Metastasen bei Patienten mit primaer zerebral metastasierter Tumorerkrankung beitragen. Daten von 659 Patienten mit primaer zerebral metastasierter Tumorerkrankung wurden retrospektiv analysiert. Insgesamt 359 Patienten mit extrakraniellen Metastasen wurden mit 300 Patienten ohne extrakranielle Metastasierung hinsichtlich Alter, Geschlecht, Karnofsky-Performance-Score (KPS), Art des Primaertumors und der Anzahl der Hirnmetastasen miteinander verglichen. Weitere Analysen erfolgten bei Patienten mit den unguenstigsten und bei Patienten mit den guenstigsten

  11. Metachronous brain and intramedullary spinal cord metastases from nonsmall-cell lung cancer: A case report

    Directory of Open Access Journals (Sweden)

    Wen-Chih Liu

    2012-05-01

    Full Text Available A 44-year-old man had a brain tumor secondary to lung adenocarcinoma and underwent craniectomy to remove the brain tumor. After postoperative whole-brain radiation therapy, he underwent pneumonectomy followed by chemotherapy, mediastinal radiotherapy, and target therapy for lung cancer. Thirty-six months after the initial brain surgery, he suffered from neck pain and right upper limb numbness that rapidly progressed to upper extremity weakness and paralysis in 2 months. Magnetic resonance imaging demonstrated an intramedullary spinal cord lesion at the C4 level. Laminectomy and gross intramedullary tumor removal were performed. The patient’s neurological function improved after the operation. Nevertheless, 4 months after the intramedullary tumor removal, he began to show multiple metastases. Unfortunately, the patient died from respiratory failure 8 months after diagnosis with intramedullary spinal cord metastasis. In this case, early diagnosis and aggressive surgical treatment combined with postoperative radiotherapy and chemotherapy might have provided this patient with a prolonged survival and better quality of life.

  12. Functional Assessment of Cancer Therapy-Brain questionnaire: translation and linguistic adaptation to Brazilian Portuguese

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    Mariana Rodrigues Gazzotti

    Full Text Available CONTEXT AND OBJECTIVE: Quality of life assessment among patients with brain tumors is important, given that new treatments have increased patient survival. The aim of this study was to translate the Functional Assessment of Cancer Therapy-Brain (FACT-Br questionnaire (version 4 into Portuguese, carry out cross-cultural adaptation and assess its reproducibility. DESIGN AND SETTING: Cohort at the Universidade Federal de São Paulo (Unifesp. METHODS: Forty patients with a brain tumor seen at the neuro-oncology outpatient clinic participated in the study. The process of translation and back-translation was carried out, along with adaptation to the Portuguese language and Brazilian culture. The intraclass correlation coefficient (ICC was used to test the reproducibility of the FACT-Br (version 4. RESULTS: The reproducibility of the questionnaire was excellent (ICC = 0.95; 95% confidence interval, CI: 0.89-0.97. The ICC with a mean interval of 15 days between applications of the questionnaire was very good in all domains (ICC = 0.87 to 0.95. The mean time taken to answer the questionnaire was 6.27 ± 2.26 minutes, ranging from 3 to 11 minutes. CONCLUSION: The translated version of the FACT-Br questionnaire (version 4 adapted to the Portuguese language and Brazilian culture proved to be easily understood and achieved very good reproducibility among patients with diagnoses of brain tumors.

  13. Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer?

    Science.gov (United States)

    Seyfried, Thomas N; Marsh, Jeremy; Shelton, Laura M; Huysentruyt, Leanne C; Mukherjee, Purna

    2012-07-01

    Malignant brain cancer persists as a major disease of morbidity and mortality. The failure to recognize brain cancer as a disease of energy metabolism has contributed in large part to the failure in management. As long as brain tumor cells have access to glucose and glutamine, the disease will progress. The current standard of care provides brain tumors with access to glucose and glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose availability and possibly that of glutamine when administered in carefully restricted amounts to reduce total caloric intake and circulating levels of glucose. The restricted KD (RKD) targets major signaling pathways associated with glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when evaluated in mice with malignant brain cancer. The therapeutic efficacy of the restricted KD can be enhanced when combined with drugs that also target glucose and glutamine. Therapeutic efficacy of the RKD was also seen against malignant gliomas in human case reports. Hence, the RKD can be an effective non-toxic therapeutic option to the current standard of care for inhibiting the growth and invasive properties of malignant brain cancer. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Neural networks improve brain cancer detection with Raman spectroscopy in the presence of operating room light artifacts

    Science.gov (United States)

    Jermyn, Michael; Desroches, Joannie; Mercier, Jeanne; Tremblay, Marie-Andrée; St-Arnaud, Karl; Guiot, Marie-Christine; Petrecca, Kevin; Leblond, Frederic

    2016-09-01

    Invasive brain cancer cells cannot be visualized during surgery and so they are often not removed. These residual cancer cells give rise to recurrences. In vivo Raman spectroscopy can detect these invasive cancer cells in patients with grade 2 to 4 gliomas. The robustness of this Raman signal can be dampened by spectral artifacts generated by lights in the operating room. We found that artificial neural networks (ANNs) can overcome these spectral artifacts using nonparametric and adaptive models to detect complex nonlinear spectral characteristics. Coupling ANN with Raman spectroscopy simplifies the intraoperative use of Raman spectroscopy by limiting changes required to the standard neurosurgical workflow. The ability to detect invasive brain cancer under these conditions may reduce residual cancer remaining after surgery and improve patient survival.

  15. Leptomeningeal disease following stereotactic radiosurgery for brain metastases from breast cancer.

    Science.gov (United States)

    Trifiletti, Daniel M; Romano, Kara D; Xu, Zhiyuan; Reardon, Kelli A; Sheehan, Jason

    2015-09-01

    Leptomeningeal disease (LMD) is a highly aggressive and usually rapidly fatal condition. The purpose of this study is to identify clinical factors that can serve to predict for LMD at the time of stereotactic radiosurgery (SRS) for brain metastases from breast carcinoma. We conducted a retrospective review of patients with brain metastases from breast cancer treated with SRS from 1995 to 2014 at our institution. Clinical, radiographic, and dosimetric data were collected. LMD was diagnosed by cerebrospinal fluid (CSF) cytology or MRI demonstrating CSF seeding. Comparative statistical analyses were conducted using Cox proportional hazards regression, binary logistic regression, and/or log-rank test. 126 patients met inclusion criteria. Eighteen patients (14 %) developed LMD following SRS. From the time of SRS, the actuarial rate of LMD at 12 months from diagnosis of brain metastasis was 9 % (11 patients). Active disease in the chest at the time of SRS was associated with development of LMD (p = 0.038). Factors including receptor status, tumor size, number of intra-axial tumors, cystic tumor morphology, prior WBRT, active bone metastases, and active liver metastases were not significantly associated with the development of LMD. In patients with brain metastasis from breast cancer that undergo SRS, there is a relatively low rate of LMD. We found that while tumor hormonal status, bone metastases, and hepatic metastases were not associated with the development of LMD, active lung metastases at SRS was associated with LMD. Further research may help to delineate a causative relationship between metastatic lung disease and LMD.

  16. Risk factors for brain metastases in patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Christensen, Troels Dreier; Palshof, Jesper Andreas; Larsen, Finn Ole

    2017-01-01

    Background: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict...... patients had previously progression on 5-FU, irinotecan and oxaliplatin containing regimens and received CetIri treatment independent of RAS mutations status. We subsequently performed KRAS, NRAS, BRAF, PIK3CA, PTEN, ERBB2 and EGFR sequencing of DNA extracted from primary tumor tissue. Results: Totally...

  17. Brain metastases in patients with epithelial ovarian cancer: report of two cases and literature review

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    Vieira, Leonardo Jose; Alves, Christiane Maria Meurer [Servico de Cirurgia Oncologica do Hospital ASCOMCER, Juiz de Fora, MG (Brazil); Oliveira, Alexandre Ferreira; Nascimento, Antonio Carlos Rodrigues do, E-mail: ljvieira@terra.com.br [Universidade Federal de Juiz de Fora, MG (Brazil)

    2011-07-01

    Brain metastasis from primary ovarian cancer is rare. We report two patients diagnosed with FIGO stage IIIc ovarian carcinoma. After primary diagnosis, the two patients underwent six cycles of neoadjuvant paclitaxel plus carboplatin chemotherapy, followed by optimum debulking surgery and three additional cycles of adjuvant chemotherapy. Patient 1 developed several supratentorial lesions twenty months after initial diagnosis and subsequently was treated with intrathecal chemotherapy, cranial radiotherapy and intravenous chemotherapy. Patient 2 developed an isolated cerebellar metastasis ten months after initial diagnosis and subsequently was treated with surgical resection, cranial radiotherapy and intravenous chemotherapy. (author)

  18. Risk of intracranial hemorrhage and cerebrovascular accidents in non-small cell lung cancer brain metastasis patients.

    Science.gov (United States)

    Srivastava, Geetika; Rana, Vishal; Wallace, Suzy; Taylor, Sarah; Debnam, Matthew; Feng, Lei; Suki, Dima; Karp, Daniel; Stewart, David; Oh, Yun

    2009-03-01

    Brain metastases confer significant morbidity and a poorer survival in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor-targeted antiangiogenic therapies (AAT) have demonstrated benefit for patients with metastatic NSCLC and are expected to directly inhibit the pathophysiology and morbidity of brain metastases, yet patients with brain metastases have been excluded from most clinical trials of AAT for fear of intracranial hemorrhage (ICH). The underlying risk of ICH from NSCLC brain metastases is low, but needs to be quantitated to plan clinical trials of AAT for NSCLC brain metastases. Data from MD Anderson Cancer Center Tumor Registry and electronic medical records from January 1998 to March 2006 was interrogated. Two thousand one hundred forty-three patients with metastatic NSCLC registering from January 1998 to September 2005 were followed till March 2006. Seven hundred seventy-six patients with and 1,367 patients without brain metastases were followed till death, date of ICH, or last date of study, whichever occurred first. The incidence of ICH seemed to be higher in those with brain metastasis compared with those without brain metastases, in whom they occurred as result of cerebrovascular accidents. However, the rates of symptomatic ICH were not significantly different. All ICH patients with brain metastasis had received radiation therapy for them and had been free of anticoagulation. Most of the brain metastasis-associated ICH's were asymptomatic, detected during increased radiologic surveillance. The rates of symptomatic ICH, or other cerebrovascular accidents in general were similar and not significantly different between the two groups. In metastatic NSCLC patients, the incidence of spontaneous ICH appeared to be higher in those with brain metastases compared with those without, but was very low in both groups without a statistically significant difference. These data suggest a minimal risk of clinically significant ICH for NSCLC

  19. MGMT promoter methylation status in brain metastases from colorectal cancer and corresponding primary tumors.

    Science.gov (United States)

    De Maglio, Giovanna; Casagrande, Mariaelena; Guardascione, Michela; Fontanella, Caterina; Lutrino, Stefania Eufemia; Rihawi, Karim; Pisa, Federica Edith; Tuniz, Francesco; Fasola, Gianpiero; Pizzolitto, Stefano; Aprile, Giuseppe

    2015-01-01

    Brain metastases (BM) from colorectal cancer are usually associated with poor prognosis. The aim of this retrospective study is to evaluate MGMT promoter methylation in BM and their corresponding primary colorectal cancer tumors. MGMT promoter methylation status was assessed by pyrosequencing in 53 consecutive patients resected for BM. A concordance analysis between BM and matched primary tumor was performed in 39 cases. MGMT methylation was found in 34 (64.2%) BM and in 25 corresponding primary tumors (64.1%). Median survival after neurosurgery was independent from MGMT promoter methylation (163 days for those with methylated MGMT versus 193 days for the unmethylated). Epigenetic MGMT promoter methylation was common and the concordance between primary and secondary lesions was high.

  20. mTORC2 activity in brain cancer: Extracellular nutrients are required to maintain oncogenic signaling.

    Science.gov (United States)

    Masui, Kenta; Shibata, Noriyuki; Cavenee, Webster K; Mischel, Paul S

    2016-09-01

    Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro-environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin complex 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. © 2016 WILEY Periodicals, Inc.

  1. Neuro emotional technique effects on brain physiology in cancer patients with traumatic stress symptoms: preliminary findings.

    Science.gov (United States)

    Monti, Daniel A; Tobia, Anna; Stoner, Marie; Wintering, Nancy; Matthews, Michael; He, Xiao-Song; Doucet, Gaelle; Chervoneva, Inna; Tracy, Joseph I; Newberg, Andrew B

    2017-08-01

    The purpose of this study was to characterize the neurophysiological and clinical effects that may result from the neuro emotional technique (NET) in patients with traumatic stress symptoms associated with a cancer-related event. We hypothesized that self-regulatory processing of traumatic memories would be observable as physiological changes in key brain areas after undergoing the NET intervention and that these changes would be associated with improvement of traumatic stress symptoms. We enrolled 23 participants with a prior cancer diagnosis who expressed a distressing cancer-related memory that was associated with traumatic stress symptoms of at least 6 months in duration. Participants were randomized to either the NET intervention or a waitlist control condition. To evaluate the primary outcome of neurophysiological effects, all participants received functional magnetic resonance imaging (fMRI) during the auditory presentation of both a neutral stimulus and a description of the specific traumatic event. Pre/post-comparisons were performed between the traumatic and neutral condition, within and between groups. Psychological measures included the Impact of Event Scale (IES), State Trait Anxiety Index (STAI), Brief Symptom Inventory (BSI)-18, and Posttraumatic Cognitions Inventory (PTCI). The initial fMRI scans in both groups showed significant increases in the bilateral parahippocampus and brainstem. After NET, reactivity in the parahippocampus, brainstem, anterior cingulate, and insula was significantly decreased during the traumatic stimulus. Likewise, participants receiving the NET intervention had significant reductions (p brain regions involved with traumatic memories and distress such as the brainstem, insula, anterior cingulate gyrus, and parahippocampus had significantly reduced activity after the NET intervention and were associated with clinical improvement of symptoms associated with distressing recollections. This preliminary study suggests that the

  2. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  3. Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

    Directory of Open Access Journals (Sweden)

    M. Suzuki

    2014-01-01

    Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

  4. The SOX2-interactome in brain cancer cells identifies the requirement of MSI2 and USP9X for the growth of brain tumor cells.

    Directory of Open Access Journals (Sweden)

    Jesse L Cox

    Full Text Available Medulloblastomas and glioblastomas, the most common primary brain tumors in children and adults, respectively, are extremely difficult to treat. Efforts to identify novel proteins essential for the growth of these tumors may help to further our understanding of the biology of these tumors, as well as, identify targets for future therapies. The recent identification of multiple transcription factor-centric protein interaction landscapes in embryonic stem cells has identified numerous understudied proteins that are essential for the self-renewal of these stem cells. To identify novel proteins essential for the fate of brain tumor cells, we examined the protein interaction network of the transcription factor, SOX2, in medulloblastoma cells. For this purpose, Multidimensional Protein Identification Technology (MudPIT identified >280 SOX2-associated proteins in the medulloblastoma cell line DAOY. To begin to understand the roles of SOX2-associated proteins in brain cancer, we focused on two SOX2-associated proteins, Musashi 2 (MSI2 and Ubiquitin Specific Protease 9x (USP9X. Recent studies have implicated MSI2, a putative RNA binding protein, and USP9X, a deubiquitinating enzyme, in several cancers, but not brain tumors. We demonstrate that knockdown of MSI2 significantly reduces the growth of DAOY cells as well as U87 and U118 glioblastoma cells. We also demonstrate that the knockdown of USP9X in DAOY, U87 and U118 brain tumor cells strongly reduces their growth. Together, our studies identify a large set of SOX2-associated proteins in DAOY medulloblastoma cells and identify two proteins, MSI2 and USP9X, that warrant further investigation to determine whether they are potential therapeutic targets for brain cancer.

  5. Epidural Brain Metastases in a Patient with Early Onset Pancreatic Cancer: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Aibek E. Mirrakhimov

    2012-01-01

    Full Text Available We present a case of early onset pancreatic cancer related extra-axial brain metastases. A 46-year-old Caucasian non-Jewish nonobese male with a history of PC diagnosed 3 months ago with metastases to the liver, omentum, malignant ascites, and a history of a pulmonary embolism was admitted to the hospital because of a new onset headache, nausea, and vomiting which started 2 days prior to the encounter. Brain MRI was ordered, which showed acute bihemispheric subdural hematomas and left hemispheric extra-axial heterogeneously enhancing lesions consisting with metastatic disease. The patient was started on ondansentron, metoclopramide, and dexamethasone. The cranial irradiation was started, and the patient’s headache and nausea significantly improved. There are only 9 published reports of extra-axial brain metastases related to the pancreatic cancer, whereas our paper is the first such case reported on a patient with epidural metastases and early onset pancreatic cancer.

  6. Quantitative T2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T.

    Science.gov (United States)

    Song, Ho-Taek; Jordan, Elaine K; Lewis, Bobbi K; Gold, Eric; Liu, Wei; Frank, Joseph A

    2011-04-01

    This study uses quantitative T(2)* imaging to track ferumoxides--protamine sulfate (FEPro)-labeled MDA-MB-231BR-Luc (231BRL) human breast cancer cells that metastasize to the nude rat brain. Four cohorts of nude rats were injected intracardially with FEPro-labeled, unlabeled or tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-treated (to induce apoptosis) 231BRL cells, or saline, in order to develop metastatic breast cancer in the brain. The heads of the rats were imaged serially over 3-4 weeks using gradient multi-echo and turbo spin-echo pulse sequences at 3 T with a solenoid receive-only 4-cm-diameter coil. Quantitative T(2)* maps of the whole brain were obtained by the application of single-exponential fitting to the signal intensity of T(2)* images, and the distribution of T(2)* values in brain voxels was calculated. MRI findings were correlated with Prussian blue staining and immunohistochemical staining for iron in breast cancer and macrophages. Quantitative analysis of T(2)* from brain voxels demonstrated a significant shift to lower values following the intracardiac injection of FEPro-labeled 231BRL cells, relative to animals receiving unlabeled cells, apoptotic cells or saline. Quartile analysis based on the T(2)* distribution obtained from brain voxels demonstrated significant differences (p TRAIL-treated cells or saline. Histologic analysis demonstrated isolated Prussian blue-positive breast cancer cells scattered in the brains of rats receiving labeled cells, relative to animals receiving unlabeled or apoptotic cells. Quantitative T(2)* analysis of FEPro-labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T(2)*-weighted images. This article is a U.S. Government work and is in the public domain in the U.S.A. Published in 2010 by John Wiley & Sons, Ltd.

  7. Exploring the Support Needs of Family Caregivers of Patients with Brain Cancer Using the CSNAT: A Comparative Study with Other Cancer Groups

    Science.gov (United States)

    Aoun, Samar M.; Deas, Kathleen; Howting, Denise; Lee, Gabriel

    2015-01-01

    A substantial burden is placed on family caregivers of patients diagnosed with brain cancers. Despite this, the support needs of the caregivers are often under-recognised and not addressed adequately in current routine and patient centred clinical care. The Care Support Needs Assessment Tool (CSNAT) is a validated instrument designed to systematically identify and address caregiver needs. It has been trialled in an Australian palliative care community setting using a stepped wedge cluster design involving 322 family carers of terminally ill patients. The current article reports on a subset from this trial, 29 caregivers of patients with primary brain cancer, and compares their profile and outcomes to those of other cancer groups. Caregiver strain was assessed using the Family Appraisal of Caregiving Questionnaire, caregiver physical and mental wellbeing using SF12 and caregiver workload using a questionnaire on support with activities of daily living (ADL). In comparison to caregivers of patients with all other cancers, the primary brain cancer group had significantly higher levels of caregiver strain, lower levels of mental wellbeing and a higher level of ADL workload. Their physical wellness also deteriorated significantly over time. An action plan approach led to practical solutions for addressing highlighted concerns. Four themes evolved from the family caregivers’ feedback interviews: The extremely challenging caregiver experience with brain cancer; the systematic and practical approach of the CSNAT during rapid changes; connection with health professionals, feeling acknowledged and empowered; and timely advice and assurance of support during the caregiving journey. This preliminary study has demonstrated that the CSNAT provides a practical and useful tool for assessing the support needs of family caregivers of patients with brain cancer and has provided the basis for a larger scale, longitudinal study that allows a more detailed characterisation of the

  8. The Vitamin D Receptor (VDR Gene Polymorphisms in Turkish Brain Cancer Patients

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    Bahar Toptaş

    2013-01-01

    Full Text Available Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR gene polymorphisms and the risk of glioma and meningioma. Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP. Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9% compared with controls (2.5%, and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles. Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.

  9. The number of involved extracranial organs: a new predictor of survival in breast cancer patients with brain metastasis.

    Science.gov (United States)

    Gerdan, Lavinia; Segedin, Barbara; Nagy, Viorica; Khoa, Mai T; Trang, Ngo T; Schild, Steven E; Rades, Dirk

    2013-10-01

    This study was performed to investigate the potential impact of the number of involved extracranial organs on survival in patients with brain metastasis from breast cancer. The data of 196 patients treated with whole-brain radiotherapy (WBRT) alone for brain metastases from breast cancer were retrospectively analyzed. Six potential prognostic factors were evaluated for associations with survival. These factors included WBRT regimen, age, Karnofsky performance score (KPS), number of brain metastases, interval from breast cancer diagnosis to WBRT, and the number of involved extracranial organs. The 6-month survival rates of patients with involvement of 0, 1, 2, 3 and ≥4 extracranial organs were 59%, 49%, 26%, 26% and 13%, respectively, and the 12-month survival rates were 45%, 36%, 17%, 17% and 13%, respectively (pnumber of involved extracranial organs (risk ratio 1.17; 95%-confidence interval 1.02-1.35; p=0.028) maintained significance, as did KPS (pnumber of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from breast cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Stereotactic Radiosurgery Alone for One to Two Brain Metastases from Cancer of Unknown Primary.

    Science.gov (United States)

    Dziggel, Liesa; Bajrovic, Amira; Schild, Steven E; Rades, Dirk

    2018-01-01

    The use of stereotactic radiosurgery (SRS) alone has become popular for treating patients with a limited number of brain metastases. In very few patients, the primary tumor leading to cerebral spread is unknown. This study investigated the role of SRS for this rare situation. Eight patients with 1-2 brain metastases from cancer of unknown primary (CUP) received SRS alone (median dose 20 Gy). Five clinical factors were evaluated for association with local control of the irradiated lesions, freedom from new cerebral lesions and survival. Six-month and 12-month survival rates were 63% and 63%, respectively. Improved survival was associated with male gender and only one cerebral lesion. Local control rates at 6 and 12 months were 100%. Six-month rate of freedom from new cerebral lesions was 86%. SRS appeared effective and resulted in promising local control and survival rates in patients with 1-2 brain metastases from CUP. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

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    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  12. RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer.

    Science.gov (United States)

    Yaeger, Rona; Cowell, Elizabeth; Chou, Joanne F; Gewirtz, Alexandra N; Borsu, Laetitia; Vakiani, Efsevia; Solit, David B; Rosen, Neal; Capanu, Marinela; Ladanyi, Marc; Kemeny, Nancy

    2015-04-15

    RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site-specific metastasis. Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site-specific pattern of metastatic spread. The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site-specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. © 2014 American Cancer Society.

  13. The extracellular matrix niche microenvironment of neural and cancer stem cells in the brain.

    Science.gov (United States)

    Reinhard, Jacqueline; Brösicke, Nicole; Theocharidis, Ursula; Faissner, Andreas

    2016-12-01

    Numerous studies demonstrated that neural stem cells and cancer stem cells (NSCs/CSCs) share several overlapping characteristics such as self-renewal, multipotency and a comparable molecular repertoire. In addition to the intrinsic cellular properties, NSCs/CSCs favor a similar environment to acquire and maintain their characteristics. In the present review, we highlight the shared properties of NSCs and CSCs in regard to their extracellular microenvironment called the NSC/CSC niche. Moreover, we point out that extracellular matrix (ECM) molecules and their complementary receptors influence the behavior of NSCs/CSCs as well as brain tumor progression. Here, we focus on the expression profile and functional importance of the ECM glycoprotein tenascin-C, the chondroitin sulfate proteoglycan DSD-1-PG/phosphacan but also on other important glycoprotein/proteoglycan constituents. Within this review, we specifically concentrate on glioblastoma multiforme (GBM). GBM is the most common malignant brain tumor in adults and is associated with poor prognosis despite intense and aggressive surgical and therapeutic treatment. Recent studies indicate that GBM onset is driven by a subpopulation of CSCs that display self-renewal and recapitulate tumor heterogeneity. Based on the CSC hypothesis the cancer arises just from a small subpopulation of self-sustaining cancer cells with the exclusive ability to self-renew and maintain the tumor. Besides the fundamental stem cell properties of self-renewal and multipotency, GBM stem cells share further molecular characteristics with NSCs, which we would like to review in this article. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. A nomogram to predict brain metastasis as the first relapse in curatively resected non-small cell lung cancer patients.

    Science.gov (United States)

    Won, Young-Woong; Joo, Jungnam; Yun, Tak; Lee, Geon-Kook; Han, Ji-Youn; Kim, Heung Tae; Lee, Jin Soo; Kim, Moon Soo; Lee, Jong Mog; Lee, Hyun-Sung; Zo, Jae Ill; Kim, Sohee

    2015-05-01

    Development of brain metastasis results in a significant reduction in overall survival. However, there is no an effective tool to predict brain metastasis in non-small cell lung cancer (NSCLC) patients. We conducted this study to develop a feasible nomogram that can predict metastasis to the brain as the first relapse site in patients with curatively resected NSCLC. A retrospective review of NSCLC patients who had received curative surgery at National Cancer Center (Goyang, South Korea) between 2001 and 2008 was performed. We chose metastasis to the brain as the first relapse site after curative surgery as the primary endpoint of the study. A nomogram was modeled using logistic regression. Among 1218 patients, brain metastasis as the first relapse developed in 87 patients (7.14%) during the median follow-up of 43.6 months. Occurrence rates of brain metastasis were higher in patients with adenocarcinoma or those with a high pT and pN stage. Younger age appeared to be associated with brain metastasis, but this result was not statistically significant. The final prediction model included histology, smoking status, pT stage, and the interaction between adenocarcinoma and pN stage. The model showed fairly good discriminatory ability with a C-statistic of 69.3% and 69.8% for predicting brain metastasis within 2 years and 5 years, respectively. Internal validation using 2000 bootstrap samples resulted in C-statistics of 67.0% and 67.4% which still indicated good discriminatory performances. The nomogram presented here provides the individual risk estimate of developing metastasis to the brain as the first relapse site in patients with NSCLC who have undergone curative surgery. Surveillance programs or preventive treatment strategies for brain metastasis could be established based on this nomogram. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Predicting brain metastases for non-small cell lung cancer based on magnetic resonance imaging.

    Science.gov (United States)

    Yin, Gang; Li, Churong; Chen, Heng; Luo, Yangkun; Orlandini, Lucia Clara; Wang, Pei; Lang, Jinyi

    2017-02-01

    In this study the relationship between brain structure and brain metastases (BM) occurrence was analyzed. A model for predicting the time of BM onset in patients with non-small cell lung cancer (NSCLC) was proposed. Twenty patients were used to develop the model, whereas the remaining 69 were used for independent validation and verification of the model. Magnetic resonance images were segmented into cerebrospinal fluid, gray matter (GM), and white matter using voxel-based morphometry. Automatic anatomic labeling template was used to extract 116 brain regions from the GM volume. The elapsed time between the MRI acquisitions and BM diagnosed was analyzed using the least absolute shrinkage and selection operator method. The model was validated using the leave-one-out cross validation (LOOCV) and permutation test. The GM volume of the extracted 11 regions of interest increased with the progression of BM from NSCLC. LOOCV test on the model indicated that the measured and predicted BM onset were highly correlated (r = 0.834, P = 0.0000). For the 69 independent validating patients, accuracy, sensitivity, and specificity of the model for predicting BM occurrence were 70, 75, and 66%, respectively, in 6 months and 74, 82, and 60%, respectively, in 1 year. The extracted brain GM volumes and interval times for BM occurrence were correlated. The established model based on MRI data may reliably predict BM in 6 months or 1 year. Further studies with larger sample size are needed to validate the findings in a clinical setting.

  16. Prostate cancer identification: quantitative analysis of T2-weighted MR images based on a back propagation artificial neural network model.

    Science.gov (United States)

    Zhao, Kai; Wang, ChengYan; Hu, Juan; Yang, XueDong; Wang, He; Li, FeiYu; Zhang, XiaoDong; Zhang, Jue; Wang, XiaoYing

    2015-07-01

    Computer-aided diagnosis (CAD) systems have been proposed to assist radiologists in making diagnostic decisions by providing helpful information. As one of the most important sequences in prostate magnetic resonance imaging (MRI), image features from T2-weighted images (T2WI) were extracted and evaluated for the diagnostic performances by using CAD. We extracted 12 quantitative image features from prostate T2-weighted MR images. The importance of each feature in cancer identification was compared in the peripheral zone (PZ) and central gland (CG), respectively. The performance of the computer-aided diagnosis system supported by an artificial neural network was tested. With computer-aided analysis of T2-weighted images, many characteristic features with different diagnostic capabilities can be extracted. We discovered most of the features (10/12) had significant difference (Pimages can reach high accuracy and specificity while maintaining acceptable sensitivity. The outcome is convictive and helpful in medical diagnosis.

  17. An international validation study of the EORTC brain cancer module (EORTC QLQ-BN20) for assessing health-related quality of life and symptoms in brain cancer patients

    NARCIS (Netherlands)

    Taphoorn, M.J.B.; Claassens, L.; Aaronson, N.K.; Coens, C.; Mauer, M.; Osoba, D.; Stupp, R.; Mirimanoff, R.O.; van den Bent, M.J.; Bottomley, A.

    2010-01-01

    Aims The psychometric properties of the EORTC QLQ-BN20, a brain cancer-specific HRQOL questionnaire, have been previously determined in an English-speaking sample of patients. This study examined the validity and reliability of the questionnaire in a multi-national, multi-lingual study. Methods

  18. Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.

    Science.gov (United States)

    Rades, Dirk; Dziggel, Liesa; Veninga, Theo; Bajrovic, Amira; Schild, Steven E

    2016-09-01

    To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Influence of handling conditions on the establishment and propagation of head and neck cancer patient derived xenografts.

    Directory of Open Access Journals (Sweden)

    Andrew P Stein

    Full Text Available Patient derived xenografts (PDXs for head and neck cancer (HNC and other cancers represent powerful research platforms. Most groups implant patient tissue into immunodeficient mice immediately although the significance of this time interval is anecdotal. We tested the hypothesis that the time from tumor excision to implantation is crucial for PDX passaging and establishment.We examined whether time or storage medium affected PDX viability for passaging two established HNC PDXs (UW-SCC34, UW-SCC52. Tumors were harvested, stored in ice-cold media or saline for 0-48 hours, and implanted into new mice. Tumor growth was compared by two-way ANOVA with respect to time and storage condition. Three new HNC PDXs (UW-SCC63-65 were generated by implanting patient tissue into mice immediately (Time 0 and 24 hours after receiving tissue from the operating room.Similar quantities of tumor were implanted into each mouse. At the end of the experiment, no significant difference was seen in mean tumor weight between the media and saline storage conditions for UW-SCC34 or UW-SCC52 (p = 0.650 and p = 0.177, respectively. No difference in tumor formation prevalence was seen on the basis of time from harvest to implantation (≥13 of 16 tumors grew at every time point. Histological analysis showed strong similarity to the initial tumor across all groups. Tumors developed at both Time 0 and 24 hours for UW-SCC63 and UW-SCC64.We demonstrated that neither storage medium nor time from tumor excision to implantation (up to 48 hours affected viability or histological differentiation in a subsequent passage for two HNC PDXs. Moreover, we revealed that fresh patient tissue is viable up to 24 hours post-resection. This information is important as it applies to the development and sharing of PDXs.

  20. Subjective cognitive impairment and brain structural networks in Chinese gynaecological cancer survivors compared with age-matched controls: a cross-sectional study.

    Science.gov (United States)

    Zeng, Yingchun; Cheng, Andy S K; Song, Ting; Sheng, Xiujie; Zhang, Yang; Liu, Xiangyu; Chan, Chetwyn C H

    2017-11-28

    Subjective cognitive impairment can be a significant and prevalent problem for gynaecological cancer survivors. The aims of this study were to assess subjective cognitive functioning in gynaecological cancer survivors after primary cancer treatment, and to investigate the impact of cancer treatment on brain structural networks and its association with subjective cognitive impairment. This was a cross-sectional survey using a self-reported questionnaire by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to assess subjective cognitive functioning, and applying DTI (diffusion tensor imaging) and graph theoretical analyses to investigate brain structural networks after primary cancer treatment. A total of 158 patients with gynaecological cancer (mean age, 45.86 years) and 130 age-matched non-cancer controls (mean age, 44.55 years) were assessed. Patients reported significantly greater subjective cognitive functioning on the FACT-Cog total score and two subscales of perceived cognitive impairment and perceived cognitive ability (all p values impairment (r = -0.388, p = 0.034). When compared with non-cancer controls, a considerable proportion of gynaecological cancer survivors may exhibit subjective cognitive impairment. This study provides the first evidence of brain structural network alteration in gynaecological cancer patients at post-treatment, and offers novel insights regarding the possible neurobiological mechanism of cancer-related cognitive impairment (CRCI) in gynaecological cancer patients. As primary cancer treatment can result in a more random organisation of structural brain networks, this may reduce brain functional specificity and segregation, and have implications for cognitive impairment. Future prospective and longitudinal studies are needed to build upon the study findings in order to assess potentially relevant clinical and psychosocial variables and brain network measures, so as to more accurately understand the

  1. Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report

    Directory of Open Access Journals (Sweden)

    Ameer L. Elaimy

    2012-01-01

    Full Text Available Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient’s primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival.

  2. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients.

    Science.gov (United States)

    Qin, Fengxia; Zhang, Huikun; Ma, Li; Liu, Xiaoli; Dai, Kun; Li, Wenliang; Gu, Feng; Fu, Li; Ma, Yongjie

    2015-09-24

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast cancer brain metastasis for the first time. Our results demonstrated that (1) Invasive ductal carcinoma patients with low expression of Slit2 or Robo1 exhibited worse prognosis and brain-specific metastasis, but not liver, bone or lung. (2) Lower expression of Slit2 and Robo1 were observed in patients with brain metastasis, especially in their brain metastasis tumors, compared with patients without brain metastasis. (3) The interval from diagnosis of breast cancer to brain metastasis and brain metastasis to death were both much shorter in patients with low expression of Slit2 or Robo1 compared with the high expression group. Overall, our findings indicated that Slit2/Robo1 axis possibly be regarded as a significant clinical parameter for predicting brain metastasis in breast cancer patients.

  3. Brain responses to erotic and other emotional stimuli in breast cancer survivors with and without distress about low sexual desire: a preliminary fMRI study.

    Science.gov (United States)

    Versace, Francesco; Engelmann, Jeffrey M; Jackson, Edward F; Slapin, Aurelija; Cortese, Kristin M; Bevers, Therese B; Schover, Leslie R

    2013-12-01

    Many breast cancer survivors report a loss of sexual desire and arousability, consonant with the new DSM-V category of female sexual interest/arousal disorder. The cause of decreased sexual desire and pleasure after treatment for cancer is unknown. One possibility is that cancer, or treatment for cancer, damages brain circuits that are involved in reward-seeking. To test the hypothesis that brain reward systems are involved in decreased sexual desire in breast cancer survivors, we used functional magnetic resonance imaging (fMRI) to compare brain responses to erotica and other emotional stimuli in two groups of women previously treated for breast cancer with chemotherapy: those who were distressed about a perceived loss of sexual desire and those who may have had low desire, but were not distressed about it. Women distressed about their desire had reduced brain responses to erotica in the anterior cingulate and dorsolateral prefrontal cortex, which are part of the brain reward system. This study is the first to demonstrate, in cancer survivors, that problems with sexual desire/arousability are associated with blunted brain responses to erotica in reward systems. Future research is necessary to determine whether brain responses differ as a result of chemotherapy, hormone therapy, and menopausal status. This may contribute to the development of new, evidence-based interventions for one of the most prevalent and enduring side effects of cancer treatment.

  4. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Freund, Derek; Zhang, Rui, E-mail: rzhang@marybird.com [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States); Sanders, Mary [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Newhauser, Wayne [Department of Radiation Oncology, Mary Bird Perkins Cancer Center, 4950 Essen Ln., Baton Rouge, LA 70809 (United States); Department of Physics and Astronomy, Louisiana State University, Nicholson Hall, Tower Dr., Baton Rouge, LA 70810 (United States)

    2015-04-13

    Cancer of the brain and central nervous system (CNS) is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN) can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT) compared to passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT). Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV) and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

  5. Predictive Risk of Radiation Induced Cerebral Necrosis in Pediatric Brain Cancer Patients after VMAT Versus Proton Therapy

    Directory of Open Access Journals (Sweden)

    Derek Freund

    2015-04-01

    Full Text Available Cancer of the brain and central nervous system (CNS is the second most common of all pediatric cancers. Treatment of many of these cancers includes radiation therapy of which radiation induced cerebral necrosis (RICN can be a severe and potentially devastating side effect. Risk factors for RICN include brain volume irradiated, the dose given per fraction and total dose. Thirteen pediatric patients were selected for this study to determine the difference in predicted risk of RICN when treating with volumetric modulated arc therapy (VMAT compared to passively scattered proton therapy (PSPT and intensity modulated proton therapy (IMPT. Plans were compared on the basis of dosimetric endpoints in the planned treatment volume (PTV and brain and a radiobiological endpoint of RICN calculated using the Lyman-Kutcher-Burman probit model. Uncertainty tests were performed to determine if the predicted risk of necrosis was sensitive to positional errors, proton range errors and selection of risk models. Both PSPT and IMPT plans resulted in a significant increase in the maximum dose to the brain, a significant reduction in the total brain volume irradiated to low doses, and a significant lower predicted risk of necrosis compared with the VMAT plans. The findings of this study were upheld by the uncertainty analysis.

  6. CARBOPLATIN AS 2ND LINE TREATMENT FOR RECURRENT OR PROGRESSIVE BRAIN METASTASES FROM SMALL-CELL LUNG-CANCER

    NARCIS (Netherlands)

    GROEN, HJM; SMIT, EF; HAAXMAREICHE, H; POSTMUS, PE

    1993-01-01

    Patients with brain metastases from small cell lung cancer (SCLC) have a poor prognosis. Although most patients die from metastatic disease outside the central nervous system, this disabling metastatic site often needs treatment to mitigate the signs and symptoms of intracranial disease. The effect

  7. Cell-Penetrating Peptide-Modified Gold Nanoparticles for the Delivery of Doxorubicin to Brain Metastatic Breast Cancer.

    Science.gov (United States)

    Morshed, Ramin A; Muroski, Megan E; Dai, Qing; Wegscheid, Michelle L; Auffinger, Brenda; Yu, Dou; Han, Yu; Zhang, Lingjiao; Wu, Meijing; Cheng, Yu; Lesniak, Maciej S

    2016-06-06

    As therapies continue to increase the lifespan of patients with breast cancer, the incidence of brain metastases has steadily increased, affecting a significant number of patients with metastatic disease. However, a major barrier toward treating these lesions is the inability of therapeutics to penetrate into the central nervous system and accumulate within intracranial tumor sites. In this study, we designed a cell-penetrating gold nanoparticle platform to increase drug delivery to brain metastatic breast cancer cells. TAT peptide-modified gold nanoparticles carrying doxorubicin led to improved cytotoxicity toward two brain metastatic breast cancer cell lines with a decrease in the IC50 of at least 80% compared to free drug. Intravenous administration of these particles led to extensive accumulation of particles throughout diffuse intracranial metastatic microsatellites with cleaved caspase-3 activity corresponding to tumor foci. Furthermore, intratumoral administration of these particles improved survival in an intracranial MDA-MB-231-Br xenograft mouse model. Our results demonstrate the promising application of gold nanoparticles for improving drug delivery in the context of brain metastatic breast cancer.

  8. Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy

    NARCIS (Netherlands)

    Amidi, Ali; Hosseini, S. M.Hadi; Leemans, Alexander; Kesler, Shelli R.; Agerbæk, Mads; Wu, Lisa M.; Zachariae, Robert

    2017-01-01

    Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore

  9. Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer.

    Science.gov (United States)

    Wu, Xinhong; Luo, Bo; Wei, Shaozhong; Luo, Yan; Feng, Yaojun; Xu, Juan; Wei, Wei

    2013-11-01

    To investigate the treatment efficiency of whole brain irradiation combined with precise radiotherapy on triple-negative (TN) phenotype breast cancer patients with brain metastases and their survival times. A total of 112 metastatic breast cancer patients treated with whole brain irradiation and intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT) were analyzed. Thirty-seven patients were of TN phenotype. Objective response rates were compared. Survival times were estimated by using the Kaplan-Meier method. Log-rank test was used to compare the survival time difference between the TN and non-TN groups. Potential prognostic factors were determined by using a Cox proportional hazard regression model. The efficiency of radiotherapy treatment on TN and non-TN phenotypes was 96.2% and 97%, respectively. TN phenotype was associated with worse survival times than non-TN phenotype after radiotherapy (6.9 months vs. 17 months) (P brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor.

  10. Germ cell cancer presenting as gastrointestinal bleeding and developing brain metastases: case report and review of the literature.

    Science.gov (United States)

    Fu, Shuang; Avezbakiyev, Boris; Zhi, Wanqing; Kodali, Sreenath; Rizvon, Kaleem; Alaverdian, Artur; Freedman, Lester; Mejia, Jose; Shahzad, Ghulamullah; Gotlieb, Vladimir

    2012-11-01

    This paper describes a rare case of germ cell cancer with duodenum, brain and lung metastases. The patient presented with melena and left testicle enlargement. Orchiectomy revealed mixed germ cell cancer, enteroscopy revealed duodenal choriocarcinoma, and chest x-ray and computed tomography (CT) showed bilateral lung metastases. The patient received and tolerated cisplatinum-based chemotherapy, and responded well. However, he developed seizures 3 months later. MRI showed brain metastases and he was treated with whole-brain radiation. One month later, he developed progressive dyspnea. Chest CT showed worsening lung metastases. He received second-line chemotherapy, but died due to multiorgan failure. Germ cell cancer with nonpulmonary metastases has poor prognosis and the management of these patients requires a multimodal approach. Head CT should be considered as routine screening for all germ cell cancer patients on initial diagnosis and brain MRI should be considered for high-risk patients (with an embryo- or choriocarcinoma histology, dramatically elevated β-human chorionic gonadotropin and lung involvement).

  11. Activation of the c-Met pathway mobilizes an inflammatory network in the brain microenvironment to promote brain metastasis of breast cancer

    Science.gov (United States)

    Xing, Fei; Liu, Yin; Sharma, Sambad; Wu, Kerui; Chan, Michael D.; Lo, Hui-Wen; Carpenter, Richard L.; Metheny-Barlow, Linda J.; Zhou, Xiaobo; Qasem, Shadi A.; Pasche, Boris; Watabe, Kounosuke

    2016-01-01

    Brain metastasis is one of the chief causes of mortality in breast cancer patients, but the mechanisms that drive this process remains poorly understood. Here we report that brain metastatic cells expressing high levels of c-Met promote the metastatic process via inflammatory cytokine upregulation and vascular reprogramming. Activated c-Met signaling promoted adhesion of tumor cells to brain endothelial cells and enhanced neovascularization by inducing the secretion of IL-8 and CXCL1. Additionally, stimulation of IL1β secretion by activation of c-Met induced tumor-associated astrocytes to secrete the c-Met ligand HGF. Thus, a feed-forward mechanism of cytokine release initiated and sustained by c-Met fed a vicious cycle which generated a favorable microenvironment for metastatic cells. Reinforcing our results, we found that pterostilbene, a compound that penetrates the blood-brain barrier, could suppress brain metastasis by targeting c-Met signaling. These findings suggest a potential utility of this natural compound for chemoprevention. PMID:27364556

  12. Metastatic brain cancer: prediction of response to whole-brain helical tomotherapy with simultaneous intralesional boost for metastatic disease using quantitative MR imaging features

    Science.gov (United States)

    Sharma, Harish; Bauman, Glenn; Rodrigues, George; Bartha, Robert; Ward, Aaron

    2014-03-01

    The sequential application of whole brain radiotherapy (WBRT) and more targeted stereotactic radiosurgery (SRS) is frequently used to treat metastatic brain tumors. However, SRS has side effects related to necrosis and edema, and requires separate and relatively invasive localization procedures. Helical tomotherapy (HT) allows for a SRS-type simultaneous infield boost (SIB) of multiple brain metastases, synchronously with WBRT and without separate stereotactic procedures. However, some patients' tumors may not respond to HT+SIB, and would be more appropriately treated with radiosurgery or conventional surgery despite the additional risks and side effects. As a first step toward a broader objective of developing a means for response prediction to HT+SIB, the goal of this study was to investigate whether quantitative measurements of tumor size and appearance (including first- and second-order texture features) on a magnetic resonance imaging (MRI) scan acquired prior to treatment could be used to differentiate responder and nonresponder patient groups after HT+SIB treatment of metastatic disease of the brain. Our results demonstrated that smaller lesions may respond better to this form of therapy; measures of appearance provided limited added value over measures of size for response prediction. With further validation on a larger data set, this approach may lead to a means for prediction of individual patient response based on pre-treatment MRI, supporting appropriate therapy selection for patients with metastatic brain cancer.

  13. Brain Functional Connectivity in Small Cell Lung Cancer Population after Chemotherapy Treatment: an ICA fMRI Study

    Science.gov (United States)

    Bromis, K.; Kakkos, I.; Gkiatis, K.; Karanasiou, I. S.; Matsopoulos, G. K.

    2017-11-01

    Previous neurocognitive assessments in Small Cell Lung Cancer (SCLC) population, highlight the presence of neurocognitive impairments (mainly in attention processing and executive functioning) in this type of cancer. The majority of these studies, associate these deficits with the Prophylactic Cranial Irradiation (PCI) that patients undergo in order to avoid brain metastasis. However, there is not much evidence exploring cognitive impairments induced by chemotherapy in SCLC patients. For this reason, we aimed to investigate the underlying processes that may potentially affect cognition by examining brain functional connectivity in nineteen SCLC patients after chemotherapy treatment, while additionally including fourteen healthy participants as control group. Independent Component Analysis (ICA) is a functional connectivity measure aiming to unravel the temporal correlation between brain regions, which are called brain networks. We focused on two brain networks related to the aforementioned cognitive functions, the Default Mode Network (DMN) and the Task-Positive Network (TPN). Permutation tests were performed between the two groups to assess the differences and control for familywise errors in the statistical parametric maps. ICA analysis showed functional connectivity disruptions within both of the investigated networks. These results, propose a detrimental effect of chemotherapy on brain functioning in the SCLC population.

  14. Brain Tumor’s Radioresistance: The Neighborhood Helps | Center for Cancer Research

    Science.gov (United States)

    Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. The primary treatment for GBM is radiation therapy. Unfortunately, while some patients initially respond, the vast majority of GBM patients fail radiotherapy, and the tumor usually grows back within two years. To gain a better understanding of the biological basis for GBM resistance to radiation, researchers initially studied GBM cell lines in vitro. In recent years, the focus has been on so-called tumor stem-like cells (TSCs), which are thought to be responsible for driving and maintaining tumor growth. To the researchers’ surprise, TSCs grown in vitro did not have the same ability to resist radiation as TSCs in the GBM tumors.

  15. Reenlargement of radiation necrosis after stereotactic radiotherapy for brain metastasis from lung cancer during bevacizumab treatment.

    Science.gov (United States)

    Furuuchi, Koji; Nishiyama, Akihiro; Yoshioka, Hiroshige; Yokoyama, Toshihide; Ishida, Tadashi

    2017-03-01

    We describe a 55-year-old man who received stereotactic radiotherapy (SRT) for the treatment of brain metastasis from lung adenocarcinoma. Fourteen months after SRT, right-sided hemiparesis developed, and magnetic resonance imaging revealed progression of perifocal edema and an enhanced lesion. Cerebral radiation necrosis was diagnosed, and treatment with bevacizumab was initiated. The lesion clearly responded to bevacizumab therapy, but reenlarged 8 months later and was surgically resected. Histopathological analysis of the resected specimen revealed large areas of necrosis; however, viable tumor cells were detected in the necrotic areas. Reenlargement of the necrotic lesion was attributed to the recurrence of lung cancer. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  16. Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer

    Science.gov (United States)

    Wu, Sheng-Kai; Chiang, Chi-Feng; Hsu, Yu-Hone; Lin, Tzu-Hung; Liou, Houng-Chi; Fu, Wen-Mei; Lin, Win-Li

    2014-01-01

    The blood–brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers. PMID:25278753

  17. Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

    Science.gov (United States)

    Miller, Jacob A; Kotecha, Rupesh; Ahluwalia, Manmeet S; Mohammadi, Alireza M; Chao, Samuel T; Barnett, Gene H; Murphy, Erin S; Vogelbaum, Michael A; Angelov, Lilyana; Peereboom, David M; Suh, John H

    2017-06-15

    The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (Pbrain radiotherapy for salvage. Cancer 2017;123:2283-2293. © 2017 American Cancer Society. © 2017 American Cancer Society.

  18. Detection of brain-directed autoantibodies in the serum of non-small cell lung cancer patients.

    Science.gov (United States)

    Banjara, Manoj; Ghosh, Chaitali; Dadas, Aaron; Mazzone, Peter; Janigro, Damir

    2017-01-01

    Antibodies against brain proteins were identified in the plasma of cancer patients and are defined to cause paraneoplastic neurological syndromes. The profiles of brain-directed antibodies in non-small cell lung cancer (NSCLC) are largely unknown. Here, for the first time, we compared autoantibodies against brain proteins in NSCLC (n = 18) against those present in age-matched non-cancer control subjects (n = 18) with a similar life-style, habit, and medical history. Self-recognizing immunoglobulin (IgG) are primarily directed against cells in the cortex (P = 0.008), hippocampus (P = 0.003-0.05), and cerebellum (P = 0.02). More specifically, IgG targets were prominent in the pyramidal, Purkinje, and granule cell layers. Furthermore, autoimmune IgG signals were localized to neurons (81%), astrocytes (48%), and endothelial (29%) cells. While cancer sera yielded overall higher intensity signals, autoantigens of 100, 65, 45, 37, and 30 kDa molecular weights were the most represented. Additionally, a group of 100 kDa proteins seem more prevalent in female adenocarcinoma patients (4/5, 80%). In conclusion, our results revealed autoantigen specificity in NSCLC, which implicitly depends on patient's demographics and disease history. Patients at risk for lung cancer but with no active disease revealed that the immune profile in NSCLC is disease-dependent.

  19. Detection of brain-directed autoantibodies in the serum of non-small cell lung cancer patients.

    Directory of Open Access Journals (Sweden)

    Manoj Banjara

    Full Text Available Antibodies against brain proteins were identified in the plasma of cancer patients and are defined to cause paraneoplastic neurological syndromes. The profiles of brain-directed antibodies in non-small cell lung cancer (NSCLC are largely unknown. Here, for the first time, we compared autoantibodies against brain proteins in NSCLC (n = 18 against those present in age-matched non-cancer control subjects (n = 18 with a similar life-style, habit, and medical history. Self-recognizing immunoglobulin (IgG are primarily directed against cells in the cortex (P = 0.008, hippocampus (P = 0.003-0.05, and cerebellum (P = 0.02. More specifically, IgG targets were prominent in the pyramidal, Purkinje, and granule cell layers. Furthermore, autoimmune IgG signals were localized to neurons (81%, astrocytes (48%, and endothelial (29% cells. While cancer sera yielded overall higher intensity signals, autoantigens of 100, 65, 45, 37, and 30 kDa molecular weights were the most represented. Additionally, a group of 100 kDa proteins seem more prevalent in female adenocarcinoma patients (4/5, 80%. In conclusion, our results revealed autoantigen specificity in NSCLC, which implicitly depends on patient's demographics and disease history. Patients at risk for lung cancer but with no active disease revealed that the immune profile in NSCLC is disease-dependent.

  20. Accuracy of UTE-MRI-based patient setup for brain cancer radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yingli; Cao, Minsong; Kaprealian, Tania; Sheng, Ke; Gao, Yu; Gomez, Caitlin; Santhanam, Anand; Tenn, Stephen; Agazaryan, Nzhde; Low, Daniel A. [Department of Radiation Oncology, University of California, Los Angeles, California 90095 (United States); Han, Fei; Hu, Peng, E-mail: penghu@mednet.ucla.edu [Department of Radiological Sciences, University of California, Los Angeles, California 90095 (United States)

    2016-01-15

    Purpose: Radiation therapy simulations solely based on MRI have advantages compared to CT-based approaches. One feature readily available from computed tomography (CT) that would need to be reproduced with MR is the ability to compute digitally reconstructed radiographs (DRRs) for comparison against on-board radiographs commonly used for patient positioning. In this study, the authors generate MR-based bone images using a single ultrashort echo time (UTE) pulse sequence and quantify their 3D and 2D image registration accuracy to CT and radiographic images for treatments in the cranium. Methods: Seven brain cancer patients were scanned at 1.5 T using a radial UTE sequence. The sequence acquired two images at two different echo times. The two images were processed using an in-house software to generate the UTE bone images. The resultant bone images were rigidly registered to simulation CT data and the registration error was determined using manually annotated landmarks as references. DRRs were created based on UTE-MRI and registered to simulated on-board images (OBIs) and actual clinical 2D oblique images from ExacTrac™. Results: UTE-MRI resulted in well visualized cranial, facial, and vertebral bones that quantitatively matched the bones in the CT images with geometric measurement errors of less than 1 mm. The registration error between DRRs generated from 3D UTE-MRI and the simulated 2D OBIs or the clinical oblique x-ray images was also less than 1 mm for all patients. Conclusions: UTE-MRI-based DRRs appear to be promising for daily patient setup of brain cancer radiotherapy with kV on-board imaging.

  1. Chemotherapy and biological treatment options in breast cancer patients with brain metastasis: an update.

    Science.gov (United States)

    Arslan, Cagatay; Dizdar, Omer; Altundag, Kadri

    2014-08-01

    Breast cancer (BC) is the second most common cause of CNS metastasis. Ten to 20% of all, and 38% of human epidermal growth factor-2(+), metastatic BC patients experience brain metastasis (BM). Prolonged survival with better control of systemic disease and limited penetration of drugs to CNS increased the probability of CNS metastasis as a sanctuary site of relapse. Treatment of CNS disease has become an important component of overall disease control and quality of life. Current standard therapy for BM is whole-brain radiotherapy, surgery, stereotactic body radiation therapy for selected cases, corticosteroids and systemic chemotherapy. Little progress has been made in chemotherapy for the treatment of BM in patients with BC. Nevertheless, new treatment choices have emerged. In this review, we aimed to update current and future treatment options in systemic treatment for BM of BC. Cornerstone local treatment options for BM of BC are radiotherapy and surgery in selected cases. Efficacy of cytotoxic chemotherapeutics is limited. Among targeted therapies, lapatinib has activity in systemic treatment of BM particularly when used in combination with capecitabine. Novel agents are currently investigated.

  2. Optimal dose and volume for postoperative radiotherapy in brain oligometastases from lung cancer: a retrospective study

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    Chung, Seung Yeun; Kim, Hye Ryun; Cho, Byoung Chul; Lee, Chang Geol; Suh, Chang Ok [Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chang, Jong Hee [Dept. of Neurosurgery, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2017-06-15

    To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ± boost (WBRT ± boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). The WBRT ± boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ± boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ≥42.3 Gy compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option.

  3. A systematic review of trastuzumab and lapatinib in the treatment of women with brain metastases from HER2-positive breast cancer

    DEFF Research Database (Denmark)

    Larsen, Pia Bükmann; Kümler, Iben; Nielsen, Dorte Lisbet

    2013-01-01

    Patients with HER2-positive breast cancer are living still longer and increasingly experiencing brain metastases. Current HER2-targeted therapies have limited potential to cross the blood-brain-barrier. We performed a systematic review to investigate data on HER2-targeting therapies...... in the treatment of brain metastases in breast cancer. We searched PUBMED for all human studies published 1998-2012 using the following search terms: breast neoplasm/cancer, human epidermal growth factor receptor 2/HER2, ErbB2, trastuzumab, lapatinib, brain/cerebral neoplasm/metastases and blood-brain barrier. We...... retrospective thus possibly biasing data. Only three studies were identified comparing trastuzumab to lapatinib. Conclusively, no solid data exist on how to treat patients with HER2-positive disease and brain metastases. Although continuous HER2-blockade is recommended by international consensus guidelines...

  4. Socioeconomic Disparities in the Quality of Life in Children with Cancer or Brain Tumors: The Mediating Role of Family Factors

    Science.gov (United States)

    Litzelman, Kristin; Barker, Emily; Catrine, Kristine; Puccetti, Diane; Possin, Peggy; Witt, Whitney P

    2012-01-01

    Objective This study aimed to determine if and to what extent: (1) socioeconomic disparities exist in the health-related quality of life (QOL) of children with cancer or brain tumors and healthy children; and (2) family functioning and burden mediate the relationship between socioeconomic status and children’s QOL. Methods In this cross-sectional study, parents of children ages 2–18 with (n=71) and without (n=135) cancer or brain tumors completed in-person interviewer-assisted surveys assessing sociodemographics (including income and parental education), child QOL (measure: PedsQL), family functioning (measure: FACES IV) and burden (measure: Impact on the Family Scale). For children with cancer, clinical characteristics were captured through medical record abstraction. Multiple linear regression was used to determine the relationship between income and child QOL; the interaction between group status and income was assessed. Staged multivariate regression models were used to assess the role of family factors in this relationship among children with cancer. Results In multivariate analyses, the effect of income differed by cancer status; lower income was associated with worse QOL in children with cancer, but not among healthy children. Among children with cancer, this relationship was significantly attenuated by family burden. Conclusions Significant socioeconomic disparities exist in the QOL of children with cancer. Family factors partially explain the relationship between low income and poor QOL outcomes among these children. Lower income families may have fewer resources to cope with their child’s cancer. Increased support, monitoring, and referrals to reduce burden for these families may lead to improved QOL in children with cancer. PMID:22645071

  5. Socioeconomic disparities in the quality of life in children with cancer or brain tumors: the mediating role of family factors.

    Science.gov (United States)

    Litzelman, Kristin; Barker, Emily; Catrine, Kristine; Puccetti, Diane; Possin, Peggy; Witt, Whitney P

    2013-05-01

    This study aimed to determine if and to what extent (i) socioeconomic disparities exist in the health-related quality of life (QOL) of children with cancer or brain tumors and healthy children; and (ii) family functioning and burden mediate the relationship between socioeconomic status and children's QOL. In this cross-sectional study, parents of children ages 2-18 with (n = 71) and without (n = 135) cancer or brain tumors completed in-person interviewer-assisted surveys assessing sociodemographics (including income and parental education), child QOL (measure: PedsQL), family functioning (measure: Family Adaptability and Cohesion Evaluation Scale IV) and burden (measure: Impact on the Family Scale). For children with cancer, clinical characteristics were captured through medical record abstraction. Multiple linear regression was used to determine the relationship between income and child QOL; the interaction between group status and income was assessed. Staged multivariate regression models were used to assess the role of family factors in this relationship among children with cancer. In multivariate analyses, the effect of income differed by cancer status; lower income was associated with worse QOL in children with cancer but not among healthy children. Among children with cancer, this relationship was significantly attenuated by family burden. Significant socioeconomic disparities exist in the QOL of children with cancer. Family factors partially explain the relationship between low income and poor QOL outcomes among these children. Lower-income families may have fewer resources to cope with their child's cancer. Increased support, monitoring, and referrals to reduce burden for these families may lead to improved QOL in children with cancer. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Brain metastases in metastatic breast cancer patients receiving trastuzumab-based therapies.

    Science.gov (United States)

    Puente Vázquez, Javier; López-Tarruella Cobo, Sara; García-Sáenz, José A; Casado Herráez, Antonio; Moreno Antón, Fernando; Sampedro Gimeno, Teresa; Bueno Muiño, Coralia; Grande Pulido, Enrique; Martín Jiménez, Miguel; Díaz-Rubio, Eduardo

    2006-01-01

    CNS metastases mean a great challenge. It has been suggested that the brain metastases incidence could be high in metastasic breast cancer patients receiving trastuzumab based-therapies. We performed a descriptive analysis of our experience in this setting. 86 patients met the criteria (From Oct/99 to Oct/03). CNS progression occurred in 17 patients (19.5%). Mean age of CNS progression disease patients was 45.4 years while mean age for all the patients was 50.5 years. Response rate for the entire group of patients was: OR 39.7%; CB (OR + SD) 69%. Response rate to trastuzumab based-therapy was OR 82.4% and CB 88.2 at the time of CNS progression. Median time from the start of trastuzumab therapy up to the CNS progression was 10 months. OS was 23.4 weeks. The incidence of CNS involvement is high in young metastasic breast cancer women responding to trastuzumab-based therapies. This may lead to prophylactic cranial irradiation strategies or to the early detection in asymptomatic patients to improve surgery or radiosurgery results in these patients.

  7. Altered intrinsic brain activity after chemotherapy in patients with gastric cancer: A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Gi [Ajou University Medical Center, Department of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); Shin, Na-Young [Ewha Womans University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Bak, Yunjin; Lim, Soo Mee [Ewha Womans University School of Medicine, Department of Radiology, Seoul (Korea, Republic of); Kim, Kyung Ran; Jung, Young-Chul [Yonsei University College of Medicine, Department of Psychiatry, Seoul (Korea, Republic of); Han, Kyunghwa; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of)

    2017-07-15

    To characterize the pattern of altered intrinsic brain activity in gastric cancer patients after chemotherapy (CTx). Patients before and after CTx (n = 14) and control subjects (n = 11) underwent resting-state functional MRI (rsfMRI) at baseline and 3 months after CTx. Regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF) were calculated and compared between the groups using the two-sample t test. Correlation analysis was also performed between rsfMRI values (i.e., ReHo, ALFF, and fALFF) and neuropsychological test results. Patients showed poor performance in verbal memory and executive function and decreased rsfMRI values in the frontal areas even before CTx and showed decreased attention/working memory and executive function after CTx compared to the control subjects. In direct comparison of values before and after CTx, there were no significant differences in neuropsychological test scores, but decreased rsfMRI values were observed at the frontal lobes and right cerebellar region. Among rsfMRI values, lower ALFF in the left inferior frontal gyrus was significantly associated with poor performance of the executive function test. We observed decreased attention/working memory and executive function that corresponded to the decline of frontal region activation in gastric cancer patients who underwent CTx. (orig.)

  8. Has the incidence of brain cancer risen in Australia since the introduction of mobile phones 29 years ago?

    Science.gov (United States)

    Chapman, Simon; Azizi, Lamiae; Luo, Qingwei; Sitas, Freddy

    2016-06-01

    Mobile phone use in Australia has increased rapidly since its introduction in 1987 with whole population usage being 94% by 2014. We explored the popularly hypothesised association between brain cancer incidence and mobile phone use. Using national cancer registration data, we examined age and gender specific incidence rates of 19,858 male and 14,222 females diagnosed with brain cancer in Australia between 1982 and 2012, and mobile phone usage data from 1987 to 2012. We modelled expected age specific rates (20-39, 40-59, 60-69, 70-84 years), based on published reports of relative risks (RR) of 1.5 in ever-users of mobile phones, and RR of 2.5 in a proportion of 'heavy users' (19% of all users), assuming a 10-year lag period between use and incidence. Age adjusted brain cancer incidence rates (20-84 years, per 100,000) have risen slightly in males (p0.05) and are higher in males 8.7 (CI=8.1-9.3) than in females, 5.8 (CI=5.3-6.3). Assuming a causal RR of 1.5 and 10-year lag period, the expected incidence rate in males in 2012 would be 11.7 (11-12.4) and in females 7.7 (CI=7.2-8.3), both pcancer incidence were observed (in keeping with modelled rates) only in those aged ≥70 years (both sexes), but the increase in incidence in this age group began from 1982, before the introduction of mobile phones. Modelled expected incidence rates were higher in all age groups in comparison to what was observed. Assuming a causal RR of 2.5 among 'heavy users' gave 2038 expected cases in all age groups. This is an ecological trends analysis, with no data on individual mobile phone use and outcome. The observed stability of brain cancer incidence in Australia between 1982 and 2012 in all age groups except in those over 70 years compared to increasing modelled expected estimates, suggests that the observed increases in brain cancer incidence in the older age group are unlikely to be related to mobile phone use. Rather, we hypothesize that the observed increases in brain cancer

  9. Longitudinal MRI evaluation of intracranial development and vascular characteristics of breast cancer brain metastases in a mouse model.

    Directory of Open Access Journals (Sweden)

    Heling Zhou

    Full Text Available Longitudinal MRI was applied to monitor intracranial initiation and development of brain metastases and assess tumor vascular volume and permeability in a mouse model of breast cancer brain metastases. Using a 9.4T system, high resolution anatomic MRI and dynamic susceptibility contrast (DSC perfusion MRI were acquired at different time points after an intracardiac injection of brain-tropic breast cancer MDA-MB231BR-EGFP cells. Three weeks post injection, multifocal brain metastases were first observed with hyperintensity on T2-weighted images, but isointensity on T1-weighted post contrast images, indicating that blood-tumor-barrier (BTB at early stage of brain metastases was impermeable. Follow-up MRI revealed intracranial tumor growth and increased number of metastases that distributed throughout the whole brain. At the last scan on week 5, T1-weighted post contrast images detected BTB disruption in 160 (34% of a total of 464 brain metastases. Enhancement in some of the metastases was only seen in partial regions of the tumor, suggesting intratumoral heterogeneity of BTB disruption. DSC MRI measurements of relative cerebral blood volume (rCBV showed that rCBV of brain metastases was significantly lower (mean= 0.89±0.03 than that of contralateral normal brain (mean= 1.00±0.03; p<0.005. Intriguingly, longitudinal measurements revealed that rCBV of individual metastases at early stage was similar to, but became significantly lower than that of contralateral normal brain with tumor growth (p<0.05. The rCBV data were concordant with histological analysis of microvascular density (MVD. Moreover, comprehensive analysis suggested no significant correlation among tumor size, rCBV and BTB permeability. In conclusion, longitudinal MRI provides non-invasive in vivo assessments of spatial and temporal development of brain metastases and their vascular volume and permeability. The characteristic rCBV of brain metastases may have a diagnostic value.

  10. SC1, an immunoglobulin-superfamily cell adhesion molecule, is involved in the brain metastatic activity of lung cancer cells.

    Science.gov (United States)

    Kubota, Yuka; Kirimura, Naoki; Shiba, Hatsuki; Adachi, Kazuhide; Tsukamoto, Yasuhiro

    2015-10-01

    SC1 is a cell adhesion molecule that belongs to the immunoglobulin superfamily; this molecule was initially purified from the chick embryonic nervous system and was reported to exhibit homophilic adhesion activity. SC1 is transiently expressed in various organs during development and has been identified in numerous neoplastic tissues, including lung cancer and colorectal carcinomas. The present study focused on the encephalic metastasis of lung cancer cells with respect to the potential function of SC1, as this molecule is known to be consistently expressed in the central nervous system as well as lung cancers. SC1 complementary DNA was introduced into A549 cells, a human lung cancer-derived cell line. The stable overexpression of the SC1 protein in A549 cells was demonstrated to enhance the self-aggregation of the cells. In addition, the SC1 transfectants enhanced the metastatic and invasive potential to the encephalic parenchyma following implantation into nude mice. In conclusion, the results of the present study demonstrated that cell adhesion due interactions between SC1 on brain tissue and SC1 on lung cancer cells was involved in the malignant aspects of lung cancer, including invasion and metastasis to the brain.

  11. Pharmacologic inhibition of MLK3 kinase activity blocks the in vitro migratory capacity of breast cancer cells but has no effect on breast cancer brain metastasis in a mouse xenograft model.

    Directory of Open Access Journals (Sweden)

    Kun Hyoe Rhoo

    Full Text Available Brain metastasis of breast cancer is an important clinical problem, with few therapeutic options and a poor prognosis. Recent data have implicated mixed lineage kinase 3 (MLK3 in controlling the in vitro migratory capacity of breast cancer cells, as well as the metastasis of MDA-MB-231 breast cancer cells from the mammary fat pad to distant lymph nodes in a mouse xenograft model. We therefore set out to test whether MLK3 plays a role in brain metastasis of breast cancer cells. To address this question, we used a novel, brain penetrant, MLK3 inhibitor, URMC099. URMC099 efficiently inhibited the migration of breast cancer cells in an in vitro cell monolayer wounding assay, and an in vitro transwell migration assay, but had no effect on in vitro cell growth. We also tested the effect of URMC099 on tumor formation in a mouse xenograft model of breast cancer brain metastasis. This analysis showed that URMC099 had no effect on the either the frequency or size of breast cancer brain metastases. We conclude that pharmacologic inhibition of MLK3 by URMC099 can reduce the in vitro migratory capacity of breast cancer cells, but that it has no effect on either the frequency or size of breast cancer brain metastases, in a mouse xenograft model.

  12. Targeting metastatic breast cancer with ANG1005, a novel peptide-paclitaxel conjugate that crosses the blood-brain-barrier (BBB

    Directory of Open Access Journals (Sweden)

    Fei Li

    2017-03-01

    Full Text Available We devoted this short interview piece with Dr Shou-Ching Tang at Augusta University to feature some promising results from a clinical phase II trial on a novel brain-penetrating peptide-paclitaxel-conjugate, ANG1005, in treating brain metastatic breast cancer. These results were presented by Dr. Tang at the recent annual meeting of the European Society for Medical Oncology (ESMO 2016 Congress. This development heralds an important step forward towards the development of effective chemotherapeutic agents, which can cross the blood-brain-barrier and effectively treat and prevent the brain metastatic cancers.

  13. Late effects of adjuvant chemotherapy for adult onset non-CNS cancer; cognitive impairment, brain structure and risk of dementia.

    Science.gov (United States)

    Koppelmans, Vincent; Breteler, Monique M B; Boogerd, Willem; Seynaeve, Caroline; Schagen, Sanne B

    2013-10-01

    Few studies have investigated the late (i.e. ≥ 5 years post-treatment) effects of chemotherapy for non-central nervous system (non-CNS) cancer on the brain. Here we discuss the studies that have investigated the late effects of adjuvant chemotherapy for non-CNS cancer on cognitive function (n=6); brain structure and function (n=5); and incidence of dementia (n=4). The neuropsychological studies showed long-term adverse cognitive problems in chemotherapy-exposed breast cancer survivors. This is in line with results from neuroimaging studies that report long-term brain structural alterations after chemotherapy. The studies exploring the association between chemotherapy and the incidence of dementia were contradictive and showed no clear relationship between the two phenomena. Although several methodological issues limit the validity and interpretation of some of the results of these studies, they suggest that chemotherapy is associated with subtle, yet long-lasting cognitive deficits, possibly related to brain structural and functional differences, but as yet not with an increased risk of dementia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Whole-brain radiation fails to boost intracerebral gefitinib concentration in patients with brain metastatic non-small cell lung cancer: a self-controlled, pilot study.

    Science.gov (United States)

    Fang, Luo; Sun, Xiaojiang; Song, Yu; Zhang, Yiwen; Li, Fanzhu; Xu, Yaping; Ma, Shenglin; Lin, Nengming

    2015-10-01

    Whole-brain radiation therapy (WBRT) is generally considered as an efficient strategy to improve blood-brain barrier (BBB) permeability by damaging BBB structure and is therefore, used as a promising pretreatment of chemotherapy. However, the impact of radiotherapy on leaky BBB is still controversial for the reason that BBB of metastatic brain tumor lesion had been breached by tumor metastasizing. Herein, we conducted a self-controlled study to evaluate the effect of WBRT on the permeability of BBB in non-small cell lung cancer (NSCLC) patients with brain metastases (BM). A prospective self-controlled research was performed. Radiation-naive NSCLC patients with BM were enrolled and treated with gefitinib for 2 weeks, and then concurrently combined with WBRT for 2 weeks. Plasma and cerebrospinal fluid (CSF) before and after WBRT were collected on day 15 and 29 after the initiation of gefitinib treatment. The concentrations of gefitinib in these samples were measured by HPLC. Three patients were enrolled and evaluated. The concentrations of gefitinib in plasma and CSF pre-WBRT were comparable to those of post-WBRT. Consequently, no significant change was noted in the CSF-to-plasma ratios of gefitinib before and after WBRT (2.79 ± 1.47 vs. 2.35 ± 1.74 %, p = 0.123). The WBRT may not affect the BBB permeability by determining the concentration of gefitinib in NSCLC patients with BM.

  15. Importance of Extracranial Disease Status and Tumor Subtype for Patients Undergoing Radiosurgery for Breast Cancer Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Dyer, Michael A.; Kelly, Paul J. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA (United States); Pinnell, Nancy E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Claus, Elizabeth B. [Harvard Medical School, Boston, MA (United States); Department of Neurosurgery, Brigham and Women' s Hospital, Boston, MA (United States); Yale University School of Medicine, New Haven, CT (United States); Lee, Eudocia Q. [Harvard Medical School, Boston, MA (United States); Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Center, Boston, MA (United States); Weiss, Stephanie E. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Arvold, Nils D. [Harvard Radiation Oncology Program, Boston, MA (United States); Lin, Nancy U. [Harvard Medical School, Boston, MA (United States); Department of Medical Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)

    2012-07-15

    Purpose: In this retrospective study, we report on outcomes and prognostic factors for patients treated with stereotactic radiosurgery (SRS) for breast cancer brain metastases. Methods and Materials: We identified 132 consecutive patients with breast cancer who were treated with SRS for brain metastases from January 2000 through June 2010. We retrospectively reviewed records of the 51 patients with adequate follow-up data who received SRS as part of the initial management of their brain metastases. Overall survival (OS) and time to central nervous system (CNS) progression from the date of SRS were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. Results: Triple negative subtype was associated with CNS progression on univariate analysis (hazard ratio [HR] = 5.0, p = 0.008). On multivariate analysis, triple negative subtype (HR = 8.6, p = 0.001), Luminal B subtype (HR = 4.3, p = 0.03), and omission of whole-brain radiation therapy (HR = 3.7, p = 0.02) were associated with CNS progression. With respect to OS, Karnofsky Performance Status (KPS) {<=} 80% (HR = 2.0, p = 0.04) and progressive extracranial disease (HR = 3.1, p = 0.002) were significant on univariate analysis; KPS {<=} 80% (HR = 4.1, p = 0.0004), progressive extracranial disease (HR = 6.4, p < 0.0001), and triple negative subtype (HR = 2.9, p = 0.04) were significant on multivariate analysis. Although median survival times were consistent with those predicted by the breast cancer-specific Graded Prognostic Assessment (Breast-GPA) score, the addition of extracranial disease status further separated patient outcomes. Conclusions: Tumor subtype is associated with risk of CNS progression after SRS for breast cancer brain metastases. In addition to tumor subtype and KPS, which are incorporated into the Breast-GPA, progressive extracranial disease may be an important prognostic factor for OS.

  16. Automatic contour propagation using deformable image registration to determine delivered dose to spinal cord in head-and-neck cancer radiotherapy

    Science.gov (United States)

    Yeap, P. L.; Noble, D. J.; Harrison, K.; Bates, A. M.; Burnet, N. G.; Jena, R.; Romanchikova, M.; Sutcliffe, M. P. F.; Thomas, S. J.; Barnett, G. C.; Benson, R. J.; Jefferies, S. J.; Parker, M. A.

    2017-08-01

    To determine delivered dose to the spinal cord, a technique has been developed to propagate manual contours from kilovoltage computed-tomography (kVCT) scans for treatment planning to megavoltage computed-tomography (MVCT) guidance scans. The technique uses the Elastix software to perform intensity-based deformable image registration of each kVCT scan to the associated MVCT scans. The registration transform is then applied to contours of the spinal cord drawn manually on the kVCT scan, to obtain contour positions on the MVCT scans. Different registration strategies have been investigated, with performance evaluated by comparing the resulting auto-contours with manual contours, drawn by oncologists. The comparison metrics include the conformity index (CI), and the distance between centres (DBC). With optimised registration, auto-contours generally agree well with manual contours. Considering all 30 MVCT scans for each of three patients, the median CI is 0.759 +/- 0.003 , and the median DBC is (0.87 +/- 0.01 ) mm. An intra-observer comparison for the same scans gives a median CI of 0.820 +/- 0.002 and a DBC of (0.64 +/- 0.01 ) mm. Good levels of conformity are also obtained when auto-contours are compared with manual contours from one observer for a single MVCT scan for each of 30 patients, and when they are compared with manual contours from six observers for two MVCT scans for each of three patients. Using the auto-contours to estimate organ position at treatment time, a preliminary study of 33 patients who underwent radiotherapy for head-and-neck cancers indicates good agreement between planned and delivered dose to the spinal cord.

  17. Automatic contour propagation using deformable image registration to determine delivered dose to spinal cord in head-and-neck cancer radiotherapy.

    Science.gov (United States)

    Yeap, P L; Noble, D J; Harrison, K; Bates, A M; Burnet, N G; Jena, R; Romanchikova, M; Sutcliffe, M P F; Thomas, S J; Barnett, G C; Benson, R J; Jefferies, S J; Parker, M A

    2017-07-12

    To determine delivered dose to the spinal cord, a technique has been developed to propagate manual contours from kilovoltage computed-tomography (kVCT) scans for treatment planning to megavoltage computed-tomography (MVCT) guidance scans. The technique uses the Elastix software to perform intensity-based deformable image registration of each kVCT scan to the associated MVCT scans. The registration transform is then applied to contours of the spinal cord drawn manually on the kVCT scan, to obtain contour positions on the MVCT scans. Different registration strategies have been investigated, with performance evaluated by comparing the resulting auto-contours with manual contours, drawn by oncologists. The comparison metrics include the conformity index (CI), and the distance between centres (DBC). With optimised registration, auto-contours generally agree well with manual contours. Considering all 30 MVCT scans for each of three patients, the median CI is [Formula: see text], and the median DBC is ([Formula: see text]) mm. An intra-observer comparison for the same scans gives a median CI of [Formula: see text] and a DBC of ([Formula: see text]) mm. Good levels of conformity are also obtained when auto-contours are compared with manual contours from one observer for a single MVCT scan for each of 30 patients, and when they are compared with manual contours from six observers for two MVCT scans for each of three patients. Using the auto-contours to estimate organ position at treatment time, a preliminary study of 33 patients who underwent radiotherapy for head-and-neck cancers indicates good agreement between planned and delivered dose to the spinal cord.

  18. Stochastic Ca(2+) waves that propagate through the neuroepithelium in limited distances of the brain and retina imaged with GCaMP3 in zebrafish embryos.

    Science.gov (United States)

    Okamoto, Shin-ichi; Nakagawa, Masashi; Hatta, Kohei

    2013-09-01

    Ca(2+) plays important roles in animal development and behavior. Various Ca(2+) transients during development have been reported in non-neuronal tissues, mainly by using synthesized calcium indicators. Here we used GCaMP3, a genetically encoded calcium indicator, to monitor stochastic Ca(2+) waves, in zebrafish embryos. To express GCaMP3 systemically throughout the body, its mRNA was injected into fertilized eggs. In the neuroepithelium of developing anterior brain and retina at 12-20 hours post-fertilization, we found spontaneously occurring stochastic Ca(2+) waves. Each Ca(2+) wave typically appeared in a randomly distributed spot, spread for 5-60 sec to form an area whose position and size varied each time with a diameter ranging from 10 to 160 µm, and then shrank and decreased to 50% brightness in 4-67 sec. A precise examination of the cellular distribution using Nipkow disk multibeam confocal laser scanning indicated that the Ca(2+) waves spread cell by cell. 2-APB, IP3-receptor inhibitor, but not carbenoxolone, a gap junction blocker, inhibit these Ca(2+) waves. Stronger fluorescence was found in the cytoplasm compared to the nuclei in the resting cells, and localized fluorescence was observed at the spindle poles in dividing cells. Ca(2+) waves also spread through the dividing cells. Our results reveal a novel type of cell-to-cell communication through the neuroepithelium in the developing zebrafish brain and retina, distinct from communication through neuron-neuron circuits. Our findings also indicated that GCaMP3 was useful for monitoring both stochastic and behavior-related Ca(2+) waves in the nervous system and skeletal muscles in zebrafish embryos.

  19. Prognostic factors for patients with brain metastasis from gynecological cancer: a significance of treatment-free interval of more than 6 months.

    Science.gov (United States)

    Takeshita, Sho; Todo, Yukiharu; Furuta, Yu; Okamoto, Kazuhira; Minobe, Shinichiro; Yamashiro, Katsushige; Kato, Hidenori

    2017-07-01

    Treatment-free interval has been confirmed as a significant prognostic factor in recurrent gynecological cancers. However, treatment-free interval has not been evaluated in previous studies investigating brain metastasis from gynecological malignancies. The aim of the study was to establish a predictive model of survival period after brain metastasis from gynecological cancer. Of a total of 2848 patients with gynecological cancer, patients with brain metastasis were included in the study. Data at the time of brain metastasis diagnosis, which included primary origin, presence of extracranial metastasis, the Eastern Cooperative Oncology Group (ECOG) performance status, the number of brain metastases, brain-metastasis free-interval, treatment-free interval and treatment for brain metastasis were collected. Survival data were analyzed using Kaplan-Meier methods and Cox proportional hazards models. Incidences of brain metastasis were 1.7% (47/2848). Median survival period after diagnosis of brain metastasis was 20 weeks (4-5 months). The 6-, 12- and 24-month survival rates after brain metastasis were 44.0%, 22.0% and 16.5%, respectively. Cox regression analysis showed that extracranial metastasis (hazard ratio [HR], 5.2; 95% confidence interval [CI]: 1.04-26.3), ECOG performance status of 3-4 (HR, 3.1; 95% CI: 1.20-7.91), treatment-free interval of cancer treatment for brain metastasis (HR, 3.6; 95% CI: 1.34-9.41) were significantly and independently related to poor survival. Treatment-free interval should be assessed in a future study to verify prognostic predictors of brain metastasis from gynecological cancer.

  20. Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer.

    Science.gov (United States)

    Nayak, Lakshmi; DeAngelis, Lisa M; Robins, H Ian; Govindan, Ramaswamy; Gadgeel, Shirish; Kelly, Karen; Rigas, James R; Peereboom, David M; Rosenfeld, Steven S; Muzikansky, Alona; Zheng, Ming; Urban, Patrick; Abrey, Lauren E; Omuro, Antonio; Wen, Patrick Y

    2015-12-01

    Treatment options for patients with non-small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases. Adult patients with NSCLC and confirmed progressive brain metastases received patupilone intravenously at 10 mg/m(2) every 3 weeks. The primary endpoint of this multinomial 2-stage study combined early progression (EP; death or progression within 3 weeks) and progression-free survival at 9 weeks (PFS9w) to determine drug activity. Fifty patients with a median age of 60 years (range, 33-74 years) were enrolled; the majority were men (58%), and most had received prior therapy for brain metastases (98%). The PFS9w rate was 36%, and the EP rate was 26%. Patupilone blood pharmacokinetic analyses showed mean areas under the concentration-time curve from time zero to 504 hours for cycles 1 and 3 of 1544 and 1978 ng h/mL, respectively, and a mean steady state distribution volume of 755 L/m(2) . Grade 3/4 adverse events (AEs), regardless of their relation with the study drug, included diarrhea (24%), pulmonary embolisms (8%), convulsions (4%), and peripheral neuropathy (4%). All patients discontinued the study drug: 31 (62%) for disease progression and 13 (26%) for AEs. Twenty-five of 32 deaths were due to brain metastases. The median time to progression and the overall survival were 3.2 and 8.8 months, respectively. This is the first prospective study of chemotherapy for recurrent brain metastases from NSCLC. In this population, patupilone demonstrated activity in heavily treated patients. © 2015 American Cancer Society.

  1. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  2. Enhanced brain disposition and effects of Δ9-tetrahydrocannabinol in P-glycoprotein and breast cancer resistance protein knockout mice.

    Directory of Open Access Journals (Sweden)

    Adena S Spiro

    Full Text Available The ABC transporters P-glycoprotein (P-gp, Abcb1 and breast cancer resistance protein (Bcrp, Abcg2 regulate the CNS disposition of many drugs. The main psychoactive constituent of cannabis Δ(9-tetrahydrocannabinol (THC has affinity for P-gp and Bcrp, however it is unknown whether these transporters modulate the brain accumulation of THC and its functional effects on the CNS. Here we aim to show that mice devoid of Abcb1 and Abcg2 retain higher brain THC levels and are more sensitive to cannabinoid-induced hypothermia than wild-type (WT mice. Abcb1a/b (-/-, Abcg2 (-/- and wild-type (WT mice were injected with THC before brain and blood were collected and THC concentrations determined. Another cohort of mice was examined for THC-induced hypothermia by measuring rectal body temperature. Brain THC concentrations were higher in both Abcb1a/b (-/- and Abcg2 (-/- mice than WT mice. ABC transporter knockout mice exhibited delayed elimination of THC from the brain with the effect being more prominent in Abcg2 (-/- mice. ABC transporter knockout mice were more sensitive to THC-induced hypothermia compared to WT mice. These results show P-gp and Bcrp prolong the brain disposition and hypothermic effects of THC and offer a novel mechanism for both genetic vulnerability to the psychoactive effects of cannabis and drug interactions between CNS therapies and cannabis.

  3. A New Predictive Tool for Optimization of the Treatment of Brain Metastases from Colorectal Cancer After Stereotactic Radiosurgery.

    Science.gov (United States)

    Rades, Dirk; Dahlke, Markus; Gebauer, Niklas; Bartscht, Tobias; Hornung, Dagmar; Trang, Ngo Thuy; Phuong, Pham Cam; Khoa, Mai Trong; Gliemroth, Jan

    2015-10-01

    To develop a predictive tool for survival after stereotactic radiosurgery of brain metastases from colorectal cancer. Out of nine factors analyzed for survival, those showing significance (pradiosurgery (p=0.026) achieved significance, extracranial metastases showed a trend (p=0.06). These factors were included in the tool. Total scores were 0-3 points. Six-month survival rates were 17% for patients with 0, 25% for those with 1, 67% for those with 2 and 100% for those with 3 points; 12-month rates were 0%, 0%, 33% and 67%, respectively. Two groups were created: 0-1 and 2-3 points. Six- and 12-month survival rates were 20% vs. 78% and 0% vs. 44% (p=0.002), respectively. This tool helps optimize the treatment of patients after stereotactic radiosurgery for brain metastases from colorectal cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial

    OpenAIRE

    Cort?s, Javier; Rugo, Hope S.; Awada, Ahmad; Twelves, Chris; Perez, Edith A.; Im, Seock?Ah; G?mez-Pardo, Patricia; Schwartzberg, Lee S; Di?ras, Veronique; Yardley, Denise A.; Potter, David A.; Mailliez, Audrey; Moreno-Aspitia, Alvaro; Ahn, Jin-Seok; Zhao, Carol

    2017-01-01

    Purpose Conventional chemotherapy has limited activity in patients with breast cancer and brain metastases (BCBM). Etirinotecan pegol (EP), a novel long-acting topoisomerase-1 inhibitor, was designed using advanced polymer technology to preferentially accumulate in tumor tissue including brain metastases, providing sustained cytotoxic SN38 levels. Methods The phase 3 BEACON trial enrolled 852 women with heavily pretreated locally recurrent or metastatic breast cancer between 2011 and 2013. BE...

  5. Low Expression of Slit2 and Robo1 is Associated with Poor Prognosis and Brain-specific Metastasis of Breast Cancer Patients

    OpenAIRE

    Fengxia Qin; Huikun Zhang; Li Ma; Xiaoli Liu; Kun Dai; Wenliang Li; Feng Gu; Li Fu; Yongjie Ma

    2015-01-01

    Brain metastasis is a significant unmet clinical problem in breast cancer treatment. It is always associated with poor prognosis and high morbidity. Recently, Slit2/Robo1 pathway has been demonstrated to be involved in the progression of breast carcinoma. However, until present, there are no convincing reports that suggest whether the Slit2/Robo1 axis has any role in brain metastasis of breast cancer. In this study, we investigated the correlation between Slit2/Robo1 signaling and breast canc...

  6. Correlates of objectively measured sedentary behavior in cancer patients with brain metastases: an application of the theory of planned behavior.

    Science.gov (United States)

    Lowe, Sonya S; Danielson, Brita; Beaumont, Crystal; Watanabe, Sharon M; Baracos, Vickie E; Courneya, Kerry S

    2015-07-01

    The aim of this study is to examine the demographic, medical, and social-cognitive correlates of objectively measured sedentary behavior in advanced cancer patients with brain metastases. Advanced cancer patients diagnosed with brain metastases, aged 18 years or older, cognitively intact, and with palliative performance scale greater than 30%, were recruited from a Rapid Access Palliative Radiotherapy Program multidisciplinary brain metastases clinic. A cross-sectional survey interview assessed the theory of planned behavior variables and medical and demographic information. Participants wore activPAL™ (PAL Technologies Ltd, Glasgow, United Kingdom) accelerometers recording time spent supine, sitting, standing, and stepping during 7 days encompassing palliative whole brain radiotherapy treatments. Thirty-one patients were recruited. Correlates of median time spent supine or sitting in hours per day were instrumental attitude (i.e., perceived benefits) of physical activity (r = -0.42; p = 0.030) and affective attitude (i.e., perceived enjoyment) of physical activity (r = -0.43; p = 0.024). Moreover, participants who sat or were supine for greater than 20.7 h per day reported significantly lower instrumental attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.051) and affective attitude (M = 0.7; 95% CI = 0.0-1.4; p = 0.041). Finally, participants who were older than 60 years of age spent more time sitting or being supine. Instrumental attitude and affective attitude were the strongest correlates of objectively measured sedentary behavior. This information could inform intervention studies to increase physical activity in advanced cancer patients with brain metastases. Copyright © 2014 John Wiley & Sons, Ltd.

  7. P08.23MULTIPLE CALCIFIED BRAIN METASTASES IN A MALE PATIENT WITH INVASIVE DUCTAL BREAST CANCER

    OpenAIRE

    Ressl, N.; Haindl, M.; Schenk, T.; Ungersboeck, K.; Sedivy, R.; Oberndorfer, S.

    2014-01-01

    Breast cancer in men is a rare disease and accounts for 1.6% of all malignancies of the breast. We report a case of a 51-year-old man with invasive ductal carcinoma of the breast with multiple calcified brain metastases. After modified radical mastectomy he received adjuvant chemotherapy with cyclophosphamide and doxorubicin, hormonal therapy and trastuzumab. About one year after initial diagnosis he developed a generalized epileptic seizure. Neuroradiological imaging (MRI) revealed multiple ...

  8. Clinical interrogation and application of super-selective intracranial artery infusion chemotherapy for lung cancer patients with brain metastases.

    Science.gov (United States)

    Rong, J; Chunhua, M; Yuan, L; Ning, M; Jinduo, L; Bin, W; Liwei, S

    2015-11-01

    The purpose of this study was to evaluate the clinical efficacy of super-selective intracranial artery infusion chemotherapy and to determine correlated prognostic parameters for advanced lung cancer patients with brain metastases. Fifty-four lung cancer patients with brain metastasis who had no previous treatment were enrolled for the study. These patients received super-selective intracranial artery infusion chemotherapy, as well as arterial infusion chemotherapy for primary and metastatic lesions. The procedure was performed once every 4 weeks. Patients were monitored to evaluate short-term clinical outcomes 4 weeks after the first 2 treatments, and follow-up visits performed every 4 weeks after the first 4 treatments until the appearance of disease progression or intolerable toxicity. All 54 cases were treated at least 4 times. The overall response rate was 55.56% (30/54), and the disease control rate was 85.19% (46/54). The median overall survival was 7 months, with a 95% confidence interval (CI) of 5.87-8.13 months, and the median progression-free survival was 4 months, with a 95% CI of 3.20-4.80 months. The 6-month survival rate and 1-year survival rate were 81.48% (44/54) and 18.52% (10/54), respectively. Super-selective intracranial artery infusion chemotherapy provides a clinically efficacious avenue of treatment for lung cancer patients with brain metastases. Pathological classification, Karnofsky performance status, and extracranial metastases may serve as reliable prognostic parameters in determining the clinical outcomes for lung cancer patients with brain metastases.

  9. Sequential Change of Hypometabolic Metastasis from Non-small-cell Lung Cancer on Brain FDG-PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Park, Soon Ah; Yang, Sei Hoon; Yang, Chung Yong; Choi, Keum Ha [Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan (Korea, Republic of)

    2009-10-15

    A 60-year-old woman, who had non-small-cell lung cancer (NSCLC) in left lower lobe underwent brain F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for evaluation of cerebral metastasis. On follow-up FDG-PET/CT, only hypometaolic lesion was detected and progressed in right frontal lobe at 6 months and 10 months, later. Hypermetabolic metastasis was not detected even at last scan time of FDG-PET/CT. Brain MRI showed brain metastasis in right frontal lobe. As might be expected, the physician should take cerebral metastasis into consideration even though there is only hypometabolic change on subsequent FDG-PET/CT in patients with NSCLC.

  10. Annual Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System

    Science.gov (United States)

    Ward, Elizabeth; McCarthy, Bridget J.; Schymura, Maria J.; Eheman, Christie; Jemal, Ahmedin; Anderson, Robert N.; Ajani, Umed A.; Edwards, Brenda K.

    2011-01-01

    Background The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year’s report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Methods Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC’s National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992–2007 for incidence; 1975–2007 for mortality) trends and short-term fixed interval (1998–2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980–2007; data on nonmalignant tumors were available for 2004–2007. All statistical tests were two-sided. Results Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003–2007, more than a decade after decreasing in men. During 2004–2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987–2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. Conclusions The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection, and treatment

  11. Brain metastasis from non-small cell lung cancer (NSCLC). Prognostic importance of the number of involved extracranial organs

    Energy Technology Data Exchange (ETDEWEB)

    Gerdan, L. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany); University of Luebeck, Section of Nuclear Medicine, Luebeck (Germany); Segedin, B. [Institute of Oncology, Department of Radiation Oncology, Ljubljana (Slovenia); Nagy, V. [Oncology Institute Ion Ciricuta, Department of Radiotherapy, Cluj-Napoca (Romania); Khoa, M.T. [Hanoi Medical University, Department of Nuclear Medicine, Hanoi (Viet Nam); Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Trang, N.T. [Bach Mai Hospital, Nuclear Medicine and Oncology Center, Hanoi (Viet Nam); Schild, S.E. [Mayo Clinic Scottsdale, Department of Radiation Oncology, Scottsdale, AZ (United States); Rades, D. [University of Luebeck, Department of Radiation Oncology, Luebeck (Germany)

    2014-01-15

    This study investigated the potential prognostic value of the number of involved extracranial organs in patients with brain metastasis from non-small cell lung cancer (NSCLC). A total of 472 patients who received whole-brain radiotherapy (WBRT) alone with 5 x 4 Gy or 10 x 3 Gy for brain metastasis from NSCLC were included in this retrospective study. In addition to the number of involved extracranial organs, 6 further potential prognostic factors were investigated including WBRT regimen, age, gender, Karnofsky Performance Score (KPS), number of brain metastases, and the interval from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung+bone vs. lung+lymph nodes vs. other combinations) extracranial organs. The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3, and ≥4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001). On multivariate analysis, the number of involved extracranial organs remained significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age <65 years (p=0.004), KPS ≥70 (p<0.001), and only 1-3 brain metastases (p=0.022) were also significantly associated with survival in the multivariate analysis. In the separate analyses of patients with involvement of one and two extracranial organs, survival was not significantly different based on the pattern of extracranial organ involvement. The number of involved extracranial organs is an independent prognostic factor of survival in patients with brain metastasis from NSCLC, irrespective of the pattern of extracranial organ involvement. (orig.)

  12. Analyzing collaboration networks and developmental patterns of nano-enabled drug delivery (NEDD for brain cancer

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2015-07-01

    Full Text Available The rapid development of new and emerging science & technologies (NESTs brings unprecedented challenges, but also opportunities. In this paper, we use bibliometric and social network analyses, at country, institution, and individual levels, to explore the patterns of scientific networking for a key nano area – nano-enabled drug delivery (NEDD. NEDD has successfully been used clinically to modulate drug release and to target particular diseased tissues. The data for this research come from a global compilation of research publication information on NEDD directed at brain cancer. We derive a family of indicators that address multiple facets of research collaboration and knowledge transfer patterns. Results show that: (1 international cooperation is increasing, but networking characteristics change over time; (2 highly productive institutions also lead in influence, as measured by citation to their work, with American institutes leading; (3 research collaboration is dominated by local relationships, with interesting information available from authorship patterns that go well beyond journal impact factors. Results offer useful technical intelligence to help researchers identify potential collaborators and to help inform R&D management and science & innovation policy for such nanotechnologies.

  13. Mobile phones, non-ionizing radiofrequency fields and brain cancer: is there an adaptive response?

    Science.gov (United States)

    Vijayalaxmi; Prihoda, Thomas J

    2014-07-01

    There is widespread concern among the general public regarding the ever increasing use of mobile phones. The concern is mainly because the antenna which transmits nonionizing radiofrequency fields is held close to the head during use and thus might cause brain cancer. By far, the largest epidemiological study was conducted by the INTER-PHONE study group and the results were published in 2011. The author's conclusions were (i) no increased risk of meningioma and glioma in mobile phone users and (ii) there were suggestions of an increased risk for glioma at the highest exposure levels but, bias and error prevented a causal interpretation. We have carefully examined all of the odd ratios presented in the INTERPHONE study publication: our results showed 24.3% decreased and 0.7% increased risk for meningioma and 22.1% decreased and 6.6% increased risk for glioma. Hence, we hypothesize that the overwhelming evidence for the decreased risk for both diseases may be due to the induction of 'adaptive response' which is well-documented in scientific literature.

  14. Epileptiform discharge propagation

    DEFF Research Database (Denmark)

    Mălîia, Mihai Dragos; Meritam, Pirgit; Scherg, Michael

    2016-01-01

    propagation was analyzed using sequential voltage-maps of the averaged spikes, and principal components analysis. When propagation was detected, sources were modeled both at onset and peak. RESULTS: Propagation occurred in half of the patients. The median time of propagation between onset and peak was 17 ms......OBJECTIVE: To investigate how often discharge propagation occurs within the spikes recorded in patients evaluated for epilepsy surgery, and to assess its impact on the accuracy of source imaging. METHODS: Data were analyzed from 50 consecutive patients who had presurgical workup. Discharge....... In 60% of the cases with propagation (15/25 patients) this remained in the same sub-lobar area where onset occurred. The accuracy of source imaging in cases of propagating spikes was 67% when only analyzing onset or peak. This was lower as compared to cases without propagation (79%). Combining source...

  15. Viscothermal wave propagation

    NARCIS (Netherlands)

    Nijhof, M.J.J.

    2010-01-01

    In this work, the accuracy, efficiency and range of applicability of various (approximate) models for viscothermal wave propagation are investigated. Models for viscothermal wave propagation describe thewave behavior of fluids including viscous and thermal effects. Cases where viscothermal effects

  16. Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

    2016-09-01

    We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

  17. Inverse spatial distribution of brain metastases and white matter hyperintensities in advanced lung and non-lung cancer patients.

    Science.gov (United States)

    Quattrocchi, Carlo Cosimo; Errante, Yuri; Mallio, Carlo Augusto; Carideo, Luciano; Scarciolla, Laura; Santini, Daniele; Tonini, Giuseppe; Zobel, Bruno Beomonte

    2014-11-01

    The aim of this study was to test by means of a voxel-based approach the hypothesis that there is a different spatial distribution of brain metastases (BM) and white matter hyperintensities (WMH) and that the presence of WMH affects the location of BM in lung and non-lung cancer patients. Two-hundred consecutive cancer patients at first diagnosis of BM were included. Images were acquired using a 1.5 Tesla MRI system (Magnetom Avanto B13, Siemens, Erlangen, Germany). Axial FLAIR T2 weighted images and gadolinium-enhanced T1 weighted images were post-processed for segmentation, co-registration and analysis. Binary lesion masks were created for WMH and BM, using Volumes of Interest. Lesion probability maps were generated and the voxel-based lesion-symptom mapping approach was used to model each voxel and to calculate a non parametric statistics (Brunner-Munzel test) describing the differences between the groups. In the lung cancer group we found higher frequency of BM in WMH- than in WMH+ patients in the occipital lobe and the cerebellum. In contrast, BM were more frequent in the right frontal lobe in WMH+ than in WMH- patients. We suggest that there exists an inverse brain spatial distribution between WMH and BM. In lung cancer patients, the presence of WMH seems to shift the distribution of BM toward locations different than what it is expected based on primary tumor.

  18. Lattice photon propagator

    Energy Technology Data Exchange (ETDEWEB)

    Coddington, P.; Hey, A.; Mandula, J.; Ogilvie, M.

    1987-10-22

    The fermion propagator in the Landau gauge is calculated for a U(1) lattice gauge theory. In the confined, strong coupling phase, the propagator resembles that of a massive particle. In the weak coupling phase, the propagator is that of a massless particle. An abrupt change occurs at the transition point. The results are compared to simulations of the gluon propagator in SU(3) lattice gauge theory.

  19. The lattice photon propagator

    Science.gov (United States)

    Coddington, P.; Hey, A.; Mandula, J.; Ogilvie, M.

    1987-10-01

    The photon propagator in the Landau gauge is calculated for a U(1) lattice gauge theory. In the confined, strong coupling phase, the propagator resembles that of a massive particle. In the weak coupling phase, the propagator is that of a massless particle. An abrupt change occurs at the transition point. The results are compared to simulations of the gluon propagator in SU(3) lattice gauge theory.

  20. Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation

    Directory of Open Access Journals (Sweden)

    Arrieta Oscar

    2011-11-01

    Full Text Available Abstract Background Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients. Methods We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed. Results Median Progression-free survival (PFS and Overall survival (OS were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1- and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038. Conclusions Patients with NSCLC and brain metastasis might benefit from treatment with WBRT and concurrent thoracic chemoradiotherapy. The subgroup of N0-N1 patients appears to achieve the greatest benefit. The result of this study warrants a prospective trial to confirm the benefit of this treatment.

  1. Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation.

    Science.gov (United States)

    Arrieta, Oscar; Villarreal-Garza, Cynthia; Zamora, Jesús; Blake-Cerda, Mónika; de la Mata, María D; Zavala, Diego G; Muñiz-Hernández, Saé; de la Garza, Jaime

    2011-11-25

    Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients. We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed. Median Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1- and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038). Patients with NSCLC and brain metastasis might benefit from treatment with WBRT and concurrent thoracic chemoradiotherapy. The subgroup of N0-N1 patients appears to achieve the greatest benefit. The result of this study warrants a prospective trial to confirm the benefit of this treatment.

  2. Durable brain response with pulse-dose crizotinib and ceritinib in ALK-positive non-small cell lung cancer compared with brain radiotherapy.

    Science.gov (United States)

    Dudnik, Elizabeth; Siegal, Tali; Zach, Leor; Allen, Aaron M; Flex, Dov; Yust-Katz, Shlomit; Limon, Dror; Hirsch, Fred R; Peled, Nir

    2016-04-01

    Crizotinib achieves excellent systemic control in anaplastic lymphoma kinase-rearranged (ALK+) non-small cell lung cancer (NSCLC); however, central nervous system (CNS) metastases frequently occur as an early event. Whole brain irradiation, the standard treatment, results in neurocognitive impairment. We present a case series of three ALK+ NSCLC patients with progressing CNS metastases who were treated with pulse-dose crizotinib followed by ceritinib. Three ALK+ NSCLC patients treated between 2011 and 2014 (two males, two never smokers, age range 20-54years, all echinoderm microtubule-associated protein-like 4/ALK rearrangement), were diagnosed with progressing cerebral disease while receiving crizotinib. Clinico-pathological characteristics, treatments, and outcomes were analyzed. In two patients the progression was limited to the CNS, and radiological evidence of leptomeningeal spread was present in one patient. Sequential use of crizotinib 500mg administered once daily (pulse-dose) followed by ceritinib on progression achieved control of the disease in the CNS for over 18 months and over 7 months in Patient 1 and Patient 2, respectively. This strategy provided durable CNS control after whole-brain radiotherapy failure in Patient 1, and allowed the whole-brain radiotherapy to be deferred in Patient 2. Limited CNS progression was documented in Patient 3 while he was on standard-dose/pulse-dose crizotinib for 15months; durable (over 7 months) complete remission was achieved with stereotactic radiotherapy and ceritinib. Manipulating the crizotinib schedule in ALK+ NSCLC patients with CNS metastases and using a novel ALK-inhibitor at the time of further progression may provide durable CNS control and allow brain radiotherapy to be deferred. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Delivery of Nanotethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

    Science.gov (United States)

    2016-12-01

    traditional Monte Carlo software is computationally expensive as it relies on generating millions of photons and tracking each photon as it propagates...Chen, W.; Bartels, M.; Perez-Torres, C.; Botero, M. F.; McAninch, R. W.; Contreras, A.; Schiff, R.; Pautler, R. G.; Halas, N. J.; et al., “ Tracking of...approximation with diffusion theory and with Monte Carlo calculations of light propagation in a slab geometry,” in SPIE Proceedings on Dosimetry of

  4. Inhibition of β2-adrenergic receptor reduces triple-negative breast cancer brain metastases: The potential benefit of perioperative β-blockade.

    Science.gov (United States)

    Choy, Cecilia; Raytis, John L; Smith, David D; Duenas, Matthew; Neman, Josh; Jandial, Rahul; Lew, Michael W

    2016-06-01

    In response to recent studies, we investigated an association between perioperative β-blockade and breast cancer metastases. First, a retrospective study examining perioperative β-blocker use and cancer recurrence and metastases was conducted on 1,029 patients who underwent breast cancer surgery at the City of Hope Cancer Center between 2000 and 2010. We followed the clinical study and examined proliferation, migration, and invasion in vitro of primary and brain-metastatic breast cancer cells in response to β2-activation and inhibition. We also investigated in vivo the metastatic potential of propranolol-treated metastatic cells. For stage II breast cancer patients, perioperative β-blockade was associated with decreased cancer recurrence using Cox regression analysis (hazard's ratio =0.51; 95% CI: 0.23-0.97; p=0.041). Triple-negative (TN) brain-metastatic cells were found to have increased β2-adrenergic receptor mRNA and protein expression relative to TN primary cells. In response to β2-adrenergic receptor activation, TN brain-metastatic cells also exhibited increased cell proliferation and migration relative to the control. These effects were abrogated by propranolol. Propranolol decreased β2-adrenergic receptor-activated invasion. In vivo, propranolol treatment of TN brain-metastatic cells decreased establishment of brain metastases. Our results suggest that stress and corresponding β2-activation may promote the establishment of brain metastases of TN breast cancer cells. In addition, our data suggest a benefit to perioperative β-blockade during surgery-induced stress with respect to breast cancer recurrence and metastases.

  5. Durable Clinical Benefit of Pertuzumab in a Young Patient with BRCA2 Mutation and HER2-Overexpressing Breast Cancer Involving the Brain

    Directory of Open Access Journals (Sweden)

    Anna Koumarianou

    2016-01-01

    Full Text Available Patients with HER2-positive breast cancer and brain metastases have limited treatment options, and, as a result of their poor performance status and worse prognosis, they are underrepresented in clinical trials. Not surprisingly, these patients may not be fit enough to receive any active treatment and are offered supportive therapy. BRCA2 mutations are reported to be rarely associated with HER2-overexpressing advanced breast cancer and even more rarely with brain metastases at diagnosis. We report on a BRCA2-positive breast cancer patient with metastatic disease in multiple sites, including the brain, and poor performance status who exhibited an extraordinary clinical and imaging response to the novel anti-HER2 therapy pertuzumab after multiple lines of therapy including anti-HER2 targeting. To our knowledge, the clinicopathologic and therapeutic characteristics of this patient point to a unique case and an urgent need for further investigation of pertuzumab in patients with brain metastases.

  6. Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer.

    Science.gov (United States)

    Ogiya, Rin; Niikura, Naoki; Kumaki, Nobue; Yasojima, Hiroyuki; Iwasa, Tsutomu; Kanbayashi, Chizuko; Oshitanai, Risa; Tsuneizumi, Michiko; Watanabe, Ken-Ichi; Matsui, Akira; Fujisawa, Tomomi; Saji, Shigehira; Masuda, Norikazu; Tokuda, Yutaka; Iwata, Hiroji

    2017-11-28

    Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored. The median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1-70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, P L1, PD-L2, and HLA class I was also performed. There are significantly fewer TILs in brain metastases than in primary breast tumors.

  7. [Immunohistochemical hormonal mismatch and human epidermal growth factor type 2 [HER2] phenotype of brain metastases in breast cancer carcinoma compared to primary tumors].

    Science.gov (United States)

    Joubert, C; Boissonneau, S; Fina, F; Figarella-Branger, D; Ouafik, L; Fuentes, S; Dufour, H; Gonçalves, A; Charaffe-Jauffret, E; Metellus, P

    2016-06-01

    Phenotype changes between primary tumor and the corresponding brain metastases are recent reported data. Breast cancer, with biological markers predicting prognosis and guiding therapeutic strategy remains an interesting model to observe and evaluate theses changes. The objective of our study was to compare molecular features (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2, [HER2]) between brain metastases and its primary tumor in patients presenting with pathologically confirmed breast cancer. This retrospective study was based on the immunohistochemical analysis of the brain metastases paraffin embedded samples stored in our institutional tumor bank, after surgical resection. The level of expression of hormonal receptors and HER2 on brain metastases were centrally reviewed and compared to the expression status in primary breast cancer from medical records. Forty-four samples of brain metastases were available for analysis. Hormonal receptor modification status was observed in 11/44 brain metastases (25%) for ER and 6/44 (13.6%) for PR. A modification of HER2 overexpression was observed in brain metastases in 6/44 (13.6%). Molecular subtype modification was shown in 17 cases (38.6%). A significant difference was demonstrated between time to develop brain metastases in cases without status modification (HER2, ER and PR) (med=49.5months [7.8-236.4]) and in cases in which brain metastases status differs from primary tumor (med=27.5months [0-197.3]), (P=0.0244, IC95=3.09-51.62, Mann and Whitney test). the main interest of this study was to focus on the molecular feature changes between primary tumor and their brain metastases. Time to develop brain metastases was correlated to phenotypic changes in brain metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Incidence of Brain Metastases on Follow-up18F-FDG PET/CT Scans of Non-Small Cell Lung Cancer Patients: Should We Include the Brain?

    Science.gov (United States)

    Nia, Emily S; Garland, Linda L; Eshghi, Naghmehossadat; Nia, Benjamin B; Avery, Ryan J; Kuo, Phillip H

    2017-09-01

    The brain is the most common site of distant metastasis from lung cancer. Thus, MRI of the brain at initial staging is routinely performed, but if this examination is negative a follow-up examination is often not performed. This study evaluates the incidence of asymptomatic brain metastases in non-small cell lung cancer patients detected on follow-up 18 F-FDG PET/CT scans. Methods: In this Institutional Review Board-approved retrospective review, all vertex to thigh 18 F-FDG PET/CT scans in patients with all subtypes of lung cancer from August 2014 to August 2016 were reviewed. A total of 1,175 18 F-FDG PET/CT examinations in 363 patients were reviewed. Exclusion criteria included brain metastases on initial staging, histologic subtype of small-cell lung cancer, and no follow-up 18 F-FDG PET/CT examinations. After our exclusion criteria were applied, a total of 809 follow-up 18 F-FDG PET/CT scans in 227 patients were included in the final analysis. The original report of each 18 F-FDG PET/CT study was reviewed for the finding of brain metastasis. The finding of a new brain metastasis prompted a brain MRI, which was reviewed to determine the accuracy of the 18 F-FDG PET/CT. Results: Five of 227 patients with 809 follow-up 18 F-FDG PET/CT scans reviewed were found to have incidental brain metastases. The mean age of the patients with incidental brain metastasis was 68 y (range, 60-77 y). The mean time from initial diagnosis to time of detection of incidental brain metastasis was 36 mo (range, 15-66 mo). When MRI was used as the gold standard, our false-positive rate was zero. Conclusion: By including the entire head during follow-up 18 F-FDG PET/CT scans of patients with non-small cell lung cancer, brain metastases can be detected earlier while still asymptomatic. But, given the additional scan time, radiation, and low incidence of new brain metastases in asymptomatic patients, the cost-to-benefit ratio should be weighed by each institution. © 2017 by the Society of

  9. CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells on Brain Endothelial Cells: Implications for Cerebral Metastasis

    Science.gov (United States)

    Jassam, Samah A.; Maherally, Zaynah; Ashkan, Keyoumars; Roncaroli, Federico; Fillmore, Helen L.; Pilkington, Geoffrey J.

    2017-01-01

    Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections. TNF-α (25 pg/mL) stimulated extracellular expression of CD62E while adhesion assays, under both static and physiological flow live-cell conditions, explored the effect of CD15s-mAb immunoblocking on adhesion of cancer cell–brain endothelium. CD15s was faintly expressed on hCMEC/D3, while high levels were observed on primary NSCLC cells with expression highest on metastatic NSCLC cells (p cells activated with TNF-α, with lower levels on primary and metastatic NSCLC cells. CD15s and CD62E were expressed on lung metastatic brain biopsies. CD15s/CD62E interaction was localised at adhesion sites of cancer cell–brain endothelium. CD15s immunoblocking significantly decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (p brain metastasis. PMID:28698503

  10. A PET/MR Imaging Approach for the Integrated Assessment of Chemotherapy-induced Brain, Heart, and Bone Injuries in Pediatric Cancer Survivors: A Pilot Study.

    Science.gov (United States)

    Theruvath, Ashok J; Ilivitzki, Anat; Muehe, Anne; Theruvath, Johanna; Gulaka, Praveen; Kim, Christine; Luna-Fineman, Sandra; Sakamoto, Kathleen M; Yeom, Kristen W; Yang, Phillip; Moseley, Michael; Chan, Frandics; Daldrup-Link, Heike E

    2017-12-01

    Purpose To develop a positron emission tomography (PET)/magnetic resonance (MR) imaging protocol for evaluation of the brain, heart, and joints of pediatric cancer survivors for chemotherapy-induced injuries in one session. Materials and Methods Three teams of experts in neuroimaging, cardiac imaging, and bone imaging were tasked to develop a 20-30-minute PET/MR imaging protocol for detection of chemotherapy-induced tissue injuries of the brain, heart, and bone. In an institutional review board-approved, HIPAA-compliant, prospective study from April to July 2016, 10 pediatric cancer survivors who completed chemotherapy underwent imaging of the brain, heart, and bone with a 3-T PET/MR imager. Cumulative chemotherapy doses and clinical symptoms were correlated with the severity of MR imaging abnormalities by using linear regression analyses. MR imaging measures of brain perfusion and metabolism were compared among eight patients who were treated with methotrexate and eight untreated age-matched control subjects by using Wilcoxon rank-sum tests. Results Combined brain, heart, and bone examinations were completed within 90 minutes. Eight of 10 cancer survivors had abnormal findings on brain, heart, and bone images, including six patients with and two patients without clinical symptoms. Cumulative chemotherapy doses correlated significantly with MR imaging measures of left ventricular ejection fraction and end-systolic volume, but not with the severity of brain or bone abnormalities. Methotrexate-treated cancer survivors had significantly lower cerebral blood flow and metabolic activity in key brain areas compared with control subjects. Conclusion The feasibility of a single examination for assessment of chemotherapy-induced injuries of the brain, heart, and joints was shown. Earlier detection of tissue injuries may enable initiation of timely interventions and help to preserve long-term health of pediatric cancer survivors. © RSNA, 2017 Online supplemental material is

  11. WITHDRAWN: Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission.

    Science.gov (United States)

    2018-02-06

    Prophylactic cranial irradiation halves the rate of brain metastases in patients with small cell lung cancer. Individual randomized trials conducted on patients in complete remission were unable to clarify whether this treatment improves survival. This study aims to test whether prophylactic cranial irradiation prolongs survival of patients with small cell lung cancer in complete remission. Published and unpublished trials were eligible. Electronic databases (Medline, Cancerlit, Excerpta Medica, Biosis from 1965 to 1998), reference lists of trial publications, review articles and relevant books were used to identify potentially eligible trials. The search was also guided by discussions with investigators and experts, and the examination of meeting proceedings and of the Physician Data Query clinical trial registry. Randomized trials comparing prophylactic cranial irradiation with no prophylactic cranial irradiation in patients with small cell lung cancer in complete remission. Meta-analysis based on updated individual data. The main endpoint was survival. Seven trials with a total of 987 participants were included. The relative risk of death in the treatment group compared to the control group was 0.84 (95% confidence interval=0.73 to 0.97, P=0.01), corresponding to a 5.4 percent increase in the 3-year survival rate (from 15.3 percent in the control group to 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased disease-free survival (relative risk=0.75, 95% confidence interval=0.65 to 0.86, P<0.001) and decreased the risk of brain metastases (relative risk=0.46, 95% confidence interval=0.38 to 0.57, P<0.001). Increasing doses of irradiation decreased the risk of brain metastases when four groups (8 Gy, 24-25 Gy, 30 Gy, 36-40 Gy) were analyzed [trend test, P=0.02], but the effect on survival did not differ significantly according to the dose. We found a trend (P=0.01) for a decrease in the brain metastasis risk in favour of earlier

  12. miRNA-197 and miRNA-184 are associated with brain metastasis in EGFR-mutant lung cancers.

    Science.gov (United States)

    Remon, J; Alvarez-Berdugo, D; Majem, M; Moran, T; Reguart, N; Lianes, P

    2016-02-01

    The prognostic value of EGFR mutation in lung cancer patients with brain metastases is uncertain and therapeutic efficacy with EGFR TKI is limited. Looking for biomarkers closely related with early tumor changes and brain metastases in non-small cell lung cancer is warranted. MicroRNAs (miRNAs) are frequently deregulated in lung cancer. The objective of this study was to investigate whether some miRNAs are related with brain metastasis risk in EGFR-mutant non-small cell lung cancer patients. miRNA quantification was retrospectively performed in formalin-fixed, extracranial paraffin-embedded adenocarcinoma tumor tissue available from 17 human samples of advanced non-small cell lung cancer patients. Samples were classified as brain metastasis group (5 EGFR-mutant patients with initial BM, EGFRm-BM+; and 6 EGFR wild-type patients with initial BM) and the control group (6 EGFR-mutant NSCLC patients without BM). The RNA obtained was preamplified and retro-transcribed, and the miRNA was quantified with the TaqMan OpenArray Human MiRNA Panel in the QuantStudio™ 12 K Flex Real-Time PCR system. miRNA-197 and miRNA-184 showed a significant higher expression in EGFRm-BM+ group than in the control group (p = 0.017 and p = 0.01, for miRNA-197 and miRNA-184, respectively), with a trend toward overexpression in BM group compared with the control group (p = 0.08 and p = 0.065, for miRNA-197 and miRNA-184, respectively), without differences in expression in BM group according to EGFR mutational status (EGFR wild type vs. EGFR-mutant: p = 0.175 and p = 0.117, for miRNA-197, miRNA-184 respectively). miRNA-197 and miRNA-184 are overexpressed in EGFR-mutant patients with BM and they might be a new biomarker for stratifying the risk of BM in this subpopulation.

  13. Robust and fast characterization of OCT-based optical attenuation using a novel frequency-domain algorithm for brain cancer detection

    Science.gov (United States)

    Yuan, Wu; Kut, Carmen; Liang, Wenxuan; Li, Xingde

    2017-03-01

    Cancer is known to alter the local optical properties of tissues. The detection of OCT-based optical attenuation provides a quantitative method to efficiently differentiate cancer from non-cancer tissues. In particular, the intraoperative use of quantitative OCT is able to provide a direct visual guidance in real time for accurate identification of cancer tissues, especially these without any obvious structural layers, such as brain cancer. However, current methods are suboptimal in providing high-speed and accurate OCT attenuation mapping for intraoperative brain cancer detection. In this paper, we report a novel frequency-domain (FD) algorithm to enable robust and fast characterization of optical attenuation as derived from OCT intensity images. The performance of this FD algorithm was compared with traditional fitting methods by analyzing datasets containing images from freshly resected human brain cancer and from a silica phantom acquired by a 1310 nm swept-source OCT (SS-OCT) system. With graphics processing unit (GPU)-based CUDA C/C++ implementation, this new attenuation mapping algorithm can offer robust and accurate quantitative interpretation of OCT images in real time during brain surgery.

  14. Occupational exposure to electromagnetic fields, leukemia and brain cancer: update of two meta-analysis; Exposition professionnelle aux champs electromagnetiques, leucemie et cancer du cerveau: mise a jour de deux meta-analyses

    Energy Technology Data Exchange (ETDEWEB)

    Anon

    2008-11-15

    This new meta-analysis found a slight increase in the risk of brain cancer and of leukemia in populations occupationally exposed to electromagnetic fields. it does not, however, support the hypothesis that electromagnetic fields have an effect on these cancers. (author)

  15. Patient-derived xenografts from non-small cell lung cancer brain metastases are valuable translational platforms for the development of personalized targeted therapy.

    Science.gov (United States)

    Lee, Hye Won; Lee, Jung-Il; Lee, Se Jeong; Cho, Hyun Jung; Song, Hye Jin; Jeong, Da Eun; Seo, Yun Jee; Shin, Sang; Joung, Je-Gun; Kwon, Yong-Jun; Choi, Yoon-La; Park, Woong-Yang; Lee, Hyun Moo; Seol, Ho Jun; Shim, Young Mog; Joo, Kyeung Min; Nam, Do-Hyun

    2015-03-01

    The increasing prevalence of distant metastases from non-small cell lung cancer (NSCLC) indicates an urgent need for novel therapeutic modalities. Brain metastasis is particularly common in NSCLC, with severe adverse effects on clinical prognosis. Although the molecular heterogeneity of NSCLC and availability of various targeted agents suggest personalized therapeutic approaches for such brain metastases, further development of appropriate preclinical models is needed to validate the strategies. We established patient-derived xenografts (PDX) using NSCLC brain metastasis surgical samples and elucidated their possible preclinical and clinical implications for personalized treatment. NSCLC brain metastases (n = 34) showed a significantly higher successful PDX establishment rate than primary specimens (n = 64; 74% vs. 23%). PDXs derived from NSCLC brain metastases recapitulated the pathologic, genetic, and functional properties of corresponding parental tumors. Furthermore, tumor spheres established in vitro from the xenografts under serum-free conditions maintained their in vivo brain metastatic potential. Differential phenotypic and molecular responses to 20 targeted agents could subsequently be screened in vitro using these NSCLC PDXs derived from brain metastases. Although PDX establishment from primary NSCLCs was significantly influenced by histologic subtype, clinical aggressiveness, and genetic alteration status, the brain metastases exhibited consistently adequate in vivo tumor take rate and in vitro tumor sphere formation capacity, regardless of clinical and molecular conditions. Therefore, PDXs from NSCLC brain metastases may better represent the heterogeneous advanced NSCLC population and could be utilized as preclinical models to meet unmet clinical needs such as drug screening for personalized treatments. ©2014 American Association for Cancer Research.

  16. A multimodality imaging model to track viable breast cancer cells from single arrest to metastasis in the mouse brain

    Science.gov (United States)

    Parkins, Katie M.; Hamilton, Amanda M.; Makela, Ashley V.; Chen, Yuanxin; Foster, Paula J.; Ronald, John A.

    2016-10-01

    Cellular MRI involves sensitive visualization of iron-labeled cells in vivo but cannot differentiate between dead and viable cells. Bioluminescence imaging (BLI) measures cellular viability, and thus we explored combining these tools to provide a more holistic view of metastatic cancer cell fate in mice. Human breast carcinoma cells stably expressing Firefly luciferase were loaded with iron particles, injected into the left ventricle, and BLI and MRI were performed on days 0, 8, 21 and 28. The number of brain MR signal voids (i.e., iron-loaded cells) on day 0 significantly correlated with BLI signal. Both BLI and MRI signals decreased from day 0 to day 8, indicating a loss of viable cells rather than a loss of iron label. Total brain MR tumour volume on day 28 also correlated with BLI signal. Overall, BLI complemented our sensitive cellular MRI technologies well, allowing us for the first time to screen animals for successful injections, and, in addition to MR measures of cell arrest and tumor burden, provided longitudinal measures of cancer cell viability in individual animals. We predict this novel multimodality molecular imaging framework will be useful for evaluating the efficacy of emerging anti-cancer drugs at different stages of the metastatic cascade.

  17. Timing of Whole Brain Radiotherapy on Survival of Patients with EGFR-mutated 
Non-small Cell Lung Cancer and Brain Metastases

    Directory of Open Access Journals (Sweden)

    Guimei LIU

    2016-08-01

    Full Text Available Background and objective There is no high-level evidence for the time of whole brain radiotherapy (WBRT for patients with epidermal growth factor receptor (EGFR-mutated non-small cell lung cancer (NSCLC and brain metastases. The aim of this study is to assess the appropriate timing of WBRT for patients with EGFR-mutated NSCLC and brain metastases (BM. Methods There were 78 patients diagnosed with EGFR-mutated NSCLC and BM in Beijing Chest Hospital between August 2009 and May 2015. 48 untreated patients who received both WBRT and EGFR-tyrosine kinase inhibitors (TKIs therapy. Prognostic factors of intracranial progression-free survival (PFS and overall survival (OS were identified by Cox proportional hazards modeling. Results Intracranial objective response rate was 81.3% and disease control rate was 93.8%. Median intracranial PFS was 10 months. Median OS was 18 months. Multivariate analysis of intracranial PFS revealed that Eastern Cooperative Oncology Group (ECOG performance status (PS 0-1 (HR=30.436, 95%CI: 4.721-196.211, P<0.001 and early WBRT (HR=3.663, 95%CI: 1.657-8.098, P=0.001 had a better intracranial PFS. Multivariate analysis of OS revealed that PS 0-1 (HR=57.607, 95%CI: 6.135-540.953, P<0.001, early WBRT (HR=2.757, 95%CI: 1.140-6.669, P=0.024, and stereotactic radiosurgery (HR=5.964, 95%CI: 1.895-18.767, P=0.002 were independent prognostic factors of OS. Conclusion Early WBRT combined with EGFR-TKIs can improve outcomes of patients with EGFR-mutated NSCLC and BM, but it needs to be confirmed by large-sample-size and multicenter prospective clinical trials.

  18. Whole brain radiotherapy plus concurrent chemotherapy in non-small cell lung cancer patients with brain metastases: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Hong Qin

    Full Text Available The aim of the present meta-analysis is to evaluate the response rate, median survival time (MST and toxicity in patients with brain metastases (BM originating from non-small cell lung cancer (NSCLC and who were treated using either whole brain radiotherapy (WBRT plus concurrent chemotherapy or WBRT alone.PubMed, EMBASE, Web of Science, The Cochrane Library, clinical trials and current controlled trials were searched to identify any relevant publications. After screening the literature and undertaking quality assessment and data extraction, the meta-analysis was performed using Stata11.0 software.In total, six randomized controlled trials (RCT involving 910 participants were included in the meta-analysis. The results of the analysis indicate that WBRT plus concurrent chemotherapy was more effective at improving response rate (RR = 2.06, 95% CI [1.13, 3.77]; P = 0.019 than WBRT alone. However, WBRT plus concurrent chemotherapy did not improve median survival time (MST (HR = 1.09, 95%CI [0.94, 1.26]; P = 0.233 or time of neurological progression (CNS-TTP (HR = 0.93, 95%CI [0.75, 1.16]; P = 0.543, and increased adverse events (Grade≥3 (RR = 2.59, 95% CI [1.88, 3.58]; P = 0.000. There were no significant differences in Grade 3-5 neurological or hematological toxicity between two patient groups (RR = 1.08, 95%CI [0.23, 5.1]; P = 0.92.The combination of chemotherapy plus WBRT in patients with BM originating from NSCLC may increase treatment response rates of brain metastases with limited toxicity. Although the therapy schedule did not prolong MST or CNS-TTP, further assessment is warranted.

  19. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses.

    Science.gov (United States)

    Deeken, John F; Löscher, Wolfgang

    2007-03-15

    Despite scientific advances in understanding the causes and treatment of human malignancy, a persistent challenge facing basic and clinical investigators is how to adequately treat primary and metastatic brain tumors. The blood-brain barrier is a physiologic obstruction to the delivery of systemic chemotherapy to the brain parenchyma and central nervous system (CNS). A number of physiologic properties make the endothelium in the CNS distinct from the vasculature found in the periphery. Recent evidence has shown that a critical aspect of this barrier is composed of xenobiotic transporters which extrude substrates from the brain into the cerebrospinal fluid and systemic circulation. These transporters also extrude drugs and toxins if they gain entry into the cytoplasm of brain endothelial cells before they enter the brain. This review highlights the properties of the blood-brain barrier, including the location, function, and relative importance of the drug transporters that maintain this barrier. Primary and metastatic brain malignancy can compromise this barrier, allowing some access of chemotherapy treatment to reach the tumor. The responsiveness of brain tumors to systemic treatment found in past clinical research is discussed, as are possible explanations as to why CNS tumors are nonetheless able to evade therapy. Finally, strategies to overcome this barrier and better deliver chemotherapy into CNS tumors are presented.

  20. HIF-1α- Targeting Acriflavine Provides Long Term Survival and Radiological Tumor Response in Brain Cancer Therapy.

    Science.gov (United States)

    Mangraviti, Antonella; Raghavan, Tula; Volpin, Francesco; Skuli, Nicolas; Gullotti, David; Zhou, Jinyuan; Asnaghi, Laura; Sankey, Eric; Liu, Ann; Wang, Yuan; Lee, Dong-Hoon; Gorelick, Noah; Serra, Riccardo; Peters, Michael; Schriefer, Destiny; Delaspre, Fabien; Rodriguez, Fausto J; Eberhart, Charles G; Brem, Henry; Olivi, Alessandro; Tyler, Betty

    2017-11-02

    Tumor progression, limited efficacy of current standard treatments, and the rise in patient mortality are associated with gene expression caused by the synergistic action of intratumoral hypoxia and HIF-1α activation. For this reason, recent investigations have focused on HIF-targeting therapeutic agents, with encouraging preclinical and clinical results in solid tumors. Here we describe the efficacy of a HIF-1α inhibitor, Acriflavine, and demonstrate its potency against brain cancer. This safe antibacterial dye induces cell death and apoptosis in several glioma cell lines, targets HIF-1α-mediated pathways, and decreases the level of PGK1, VEGF and HIF-1α in vitro and in vivo. Administered locally via biodegradable polymers, Acriflavine provides significant benefits in survival resulting in nearly 100% long term survival, confirmed by MRI and histological analyses. This study reports preclinical evidence that this safe, small molecule can contribute to brain tumor therapy and highlights the significance of HIF-1α-targeting molecules.

  1. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Directory of Open Access Journals (Sweden)

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  2. Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy

    Directory of Open Access Journals (Sweden)

    Donna H. Murrell

    2015-06-01

    Full Text Available OBJECTIVES: Brain metastases due to breast cancer are increasing, and the prognosis is poor. Lack of effective therapy is attributed to heterogeneity of breast cancers and their resulting metastases, as well as impermeability of the blood–brain barrier (BBB, which hinders delivery of therapeutics to the brain. This work investigates three experimental models of HER2+ breast cancer brain metastasis to better understand the inherent heterogeneity of the disease. We use magnetic resonance imaging (MRI to quantify brain metastatic growth and explore its relationship with BBB permeability. DESIGN: Brain metastases due to breast cancer cells (SUM190-BR3, JIMT-1-BR3, or MDA-MB-231-BR-HER2 were imaged at 3 T using balanced steady-state free precession and contrast-enhanced T1-weighted spin echo sequences. The histology and immunohistochemistry corresponding to MRI were also analyzed. RESULTS: There were differences in metastatic tumor appearance by MRI, histology, and immunohistochemistry (Ki67, CD31, CD105 across the three models. The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05; interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001. Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05 in the MDA-MB-231-BR-HER2 model. CD31 and CD105 staining suggested no difference in new vasculature patterns between permeable and impermeable tumors in any model. CONCLUSION: Significant heterogeneity is present in these models of brain metastases from HER2+ breast cancer. Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery.

  3. Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.

    Science.gov (United States)

    Weitzel, Douglas H; Tovmasyan, Artak; Ashcraft, Kathleen A; Boico, Alina; Birer, Samuel R; Roy Choudhury, Kingshuk; Herndon, James; Rodriguiz, Ramona M; Wetsel, William C; Peters, Katherine B; Spasojevic, Ivan; Batinic-Haberle, Ines; Dewhirst, Mark W

    2016-06-01

    Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE-2-PyP(5+) (Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium -2-yl)porphyrin) rescued RT-induced white matter damage in cranially-irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard-of-care for adult glioblastoma, whereas cisplatin is often used for treatment of pediatric brain tumors. Therefore, we evaluated the brain radiation mitigation ability of MnTnBuOE-2-PyP(5+) after either temozolomide or cisplatin was used singly or in combination with 10 Gy RT. MnTnBuOE-2-PyP(5+) accumulated in brains at low nanomolar levels. Histological and neurobehavioral testing showed a drastic decrease (1) of axon density in the corpus callosum and (2) rotorod and running wheel performance in the RT only treatment group, respectively. MnTnBuOE-2-PyP(5+) completely rescued this phenotype in irradiated animals. In the temozolomide groups, temozolomide/ RT treatment resulted in further decreased rotorod responses over RT alone. Again, MnTnBuOE-2-PyP(5+) treatment rescued the negative effects of both temozolomide ± RT on rotorod performance. While the cisplatin-treated groups did not give similar results as the temozolomide groups, inclusion of MnTnBuOE-2-PyP(5+) did not negatively affect rotorod performance. Additionally, MnTnBuOE-2-PyP(5+) sensitized glioblastomas to either RT ± temozolomide in flank tumor models. Mice treated with both MnTnBuOE-2-PyP(5+) and radio-/chemo-therapy herein demonstrated brain radiation mitigation. MnTnBuOE-2-PyP(5+) may well serve as a normal tissue radio-/chemo-mitigator adjuvant therapy to standard brain cancer treatment regimens. Environ. Mol. Mutagen. 57:372-381, 2016. © 2016 Wiley Periodicals, Inc.

  4. Image Guided Radiation Therapy Using Synthetic Computed Tomography Images in Brain Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Price, Ryan G. [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan (United States); Kim, Joshua P.; Zheng, Weili [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Chetty, Indrin J. [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan (United States); Glide-Hurst, Carri, E-mail: churst2@hfhs.org [Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan (United States); Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, Michigan (United States)

    2016-07-15

    Purpose: The development of synthetic computed tomography (CT) (synCT) derived from magnetic resonance (MR) images supports MR-only treatment planning. We evaluated the accuracy of synCT and synCT-generated digitally reconstructed radiographs (DRRs) relative to CT and determined their performance for image guided radiation therapy (IGRT). Methods and Materials: Magnetic resonance simulation (MR-SIM) and CT simulation (CT-SIM) images were acquired of an anthropomorphic skull phantom and 12 patient brain cancer cases. SynCTs were generated using fluid attenuation inversion recovery, ultrashort echo time, and Dixon data sets through a voxel-based weighted summation of 5 tissue classifications. The DRRs were generated from the phantom synCT, and geometric fidelity was assessed relative to CT-generated DRRs through bounding box and landmark analysis. An offline retrospective analysis was conducted to register cone beam CTs (n=34) to synCTs and CTs using automated rigid registration in the treatment planning system. Planar MV and KV images (n=37) were rigidly registered to synCT and CT DRRs using an in-house script. Planar and volumetric registration reproducibility was assessed and margin differences were characterized by the van Herk formalism. Results: Bounding box and landmark analysis of phantom synCT DRRs were within 1 mm of CT DRRs. Absolute planar registration shift differences ranged from 0.0 to 0.7 mm for phantom DRRs on all treatment platforms and from 0.0 to 0.4 mm for volumetric registrations. For patient planar registrations, the mean shift differences were 0.4 ± 0.5 mm (range, −0.6 to 1.6 mm), 0.0 ± 0.5 mm (range, −0.9 to 1.2 mm), and 0.1 ± 0.3 mm (range, −0.7 to 0.6 mm) for the superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) axes, respectively. The mean shift differences in volumetric registrations were 0.6 ± 0.4 mm (range, −0.2 to 1.6 mm), 0.2 ± 0.4 mm (range, −0.3 to 1.2 mm), and 0.2 ± 0

  5. Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer

    Directory of Open Access Journals (Sweden)

    Mokbel Kefah

    2011-07-01

    Full Text Available Abstract Introduction Brain-derived neurotrophic factor (BDNF has established physiological roles in the development and function of the vertebrate nervous system. BDNF has also been implicated in several human malignancies, including breast cancer (BC. However, the precise biological role of BDNF and its utility as a novel biomarker have yet to be determined. The objective of this study was to determine the mRNA and protein expression of BDNF in a cohort of women with BC. Expression levels were compared with normal background tissues and evaluated against established pathological parameters and clinical outcome over a 10 year follow-up period. Methods BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription, BDNF transcript levels were determined using real-time quantitative PCR. BDNF protein expression in mammary tissues was assessed with standard immuno-histochemical methodology. Expression levels were analyzed against tumour size, grade, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI and clinical outcome over a 10 year follow-up period. Results Immuno-histochemical staining revealed substantially greater BDNF expression within neoplastic cells, compared to normal mammary epithelial cells. Significantly higher mRNA transcript levels were found in the BC specimens compared to background tissues (p = 0.007. The expression of BDNF mRNA was demonstrated to increase with increasing NPI; NPI-1 vs. NPI-2 (p = 0.009. Increased BDNF transcript levels were found to be significantly associated with nodal positivity (p = 0.047. Compared to patients who remained disease free, higher BDNF expression was significantly associated with local recurrence (LR (p = 0.0014, death from BC (p = 0.018 and poor prognosis overall (p = 0.013. After a median follow up of 10 years, higher BDNF expression levels were significantly associated with reduced overall survival (OS (106 vs. 136 months, p = 0.006. BDNF

  6. Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

    Science.gov (United States)

    Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

    2014-01-06

    Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

  7. Brain cortical structural differences between non-central nervous system cancer patients treated with and without chemotherapy compared to non-cancer controls: a cross-sectional pilot MRI study using clinically indicated scans

    Science.gov (United States)

    Shiroishi, Mark S.; Gupta, Vikash; Bigjahan, Bavrina; Cen, Steven Y.; Rashid, Faisal; Hwang, Darryl H.; Lerner, Alexander; Boyko, Orest B.; Liu, Chia-Shang Jason; Law, Meng; Thompson, Paul M.; Jahanshad, Neda

    2017-11-01

    Background: Increases in cancer survival have made understanding the basis of cancer-related cognitive impairment (CRCI) more important. CRCI neuroimaging studies have traditionally used dedicated research brain MRIs in breast cancer survivors with small sample sizes; little is known about other non-CNS cancers. However, there is a wealth of unused data from clinically-indicated MRIs that could be used to study CRCI. Objective: Evaluate brain cortical structural differences in those with non-CNS cancers using clinically-indicated MRIs. Design: Cross-sectional Patients: Adult non-CNS cancer and non-cancer control (C) patients who underwent clinically-indicated MRIs. Methods: Brain cortical surface area and thickness were measured using 3D T1-weighted images. An age-adjusted linear regression model was used and the Benjamini and Hochberg false discovery rate (FDR) corrected for multiple comparisons. Group comparisons were: cancer cases with chemotherapy (Ch+), cancer cases without chemotherapy (Ch-) and subgroup of lung cancer cases with and without chemotherapy vs C. Results: Sixty-four subjects were analyzed: 22 Ch+, 23 Ch- and 19 C patients. Subgroup analysis of 16 LCa was also performed. Statistically significant decreases in either cortical surface area or thickness were found in multiple ROIs primarily within the frontal and temporal lobes for all comparisons. Limitations: Several limitations were apparent including a small sample size that precluded adjustment for other covariates. Conclusions: Our preliminary results suggest that various types of non-CNS cancers, both with and without chemotherapy, may result in brain structural abnormalities. Also, there is a wealth of untapped clinical MRIs that could be used for future CRCI studies.

  8. A NOVEL METHOD FOR ANALYZING ELECTRIC FIELD DISTRIBUTION OF ELECTRO CAPACITIVE CANCER TREATMENT (ECCT USING WIRE MESH ELECTRODES: A CASE STUDY OF BRAIN CANCER THERAPY.

    Directory of Open Access Journals (Sweden)

    Linahtadiya Andiani

    2017-12-01

    Full Text Available Electric field distribution analysis generated by ECCT in a human head model with or without brain cancer using wire mesh electrode has been conductedsuccessfully. The analysis of electric field distribution was done using simulation in a human head model with ECCT Apparel Helmet system type A which is three dimensional model. The electric field distribution was measured with and without a wire mesh electrode which was either passive or active using COMSOL Multiphysics 5.2 software and was then processed using MATLAB R2010a. The aim of the research was to assess the performance of wire mesh electrode in detecting electric field distribution. ECCT which is utilized in brain cancer therapy with input 10 V is able to produce an electric field with an average of 178.8 V/m. The input voltage influences electric field distribution whereas the signal frequency does not affect the electric field distribution. Wire mesh electrode which is either active or passive can measure the electric field distribution generated by ECCT that neither the active nor the passive wire mesh electrode changed the pattern of the electric field distribution and the change in the measured electric field value is not significant.

  9. Association of cancer history with Alzheimer’s disease onset and structural brain changes

    Directory of Open Access Journals (Sweden)

    Kelly Nicole Holohan Nudelman

    2014-10-01

    Full Text Available Epidemiological studies show a reciprocal inverse association between cancer and Alzheimer’s disease (AD. The common mechanistic theory for this effect posits that cells have an innate tendency towards apoptotic or survival pathways, translating to increased risk for either neurodegeneration or cancer. However, it has been shown that cancer patients experience cognitive dysfunction pre- and post-treatment as well as alterations in cerebral gray matter density (GMD on MRI. To further investigate these issues, we analyzed the association between cancer history (CA+/- and age of AD onset, and the relationship between GMD and CA+/- status across diagnostic groups in the Alzheimer’s Disease Neuroimaging Initiative (ADNI cohort study. Data was analyzed from 1609 participants with information on baseline cancer history and AD diagnosis, age of AD onset, and baseline MRI scans. Participants were CA+ (N=503 and CA- (N=1106 diagnosed with AD, mild cognitive impairment, significant memory concerns, and cognitively normal older adults. As in previous studies, CA+ was inversely associated with AD at baseline (P=0.025; interestingly, this effect appears to be driven by non-melanoma skin cancer, the largest cancer category in this study (P=0.001. CA+ was also associated with later age of AD onset (P<0.001, independent of apolipoprotein E (APOE ε4 allele status, and individuals with two prior cancers had later mean age of AD onset than those with one or no prior cancer (P<0.001, suggesting an additive effect. Voxel-based morphometric analysis of GMD showed CA+ had lower GMD in the right superior frontal gyrus compared to CA- across diagnostic groups (Pcrit<0.001, uncorrected; this cluster of lower GMD appeared to be driven by history of invasive cancer types, rather than skin cancer. Thus, while cancer history is associated with a measurable delay in AD onset independent of APOE ε4, the underlying mechanism does not appear to be cancer

  10. Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment.

    Science.gov (United States)

    Kesler, Shelli R; Adams, Marjorie; Packer, Melissa; Rao, Vikram; Henneghan, Ashley M; Blayney, Douglas W; Palesh, Oxana

    2017-03-01

    Several previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non-CNS cancers. Using a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29-65 and 50 frequency-matched healthy female controls who underwent anatomic and resting-state functional MRI as well as cognitive testing. Compared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics (p = .046) and cognitive functioning (p cancer group also showed subtle alterations in structural local clustering and functional local clustering (p cancer may directly and/or indirectly affect the brain via mechanisms such as tumor-induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

  11. P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan.

    Science.gov (United States)

    de Vries, Nienke A; Zhao, Jin; Kroon, Emily; Buckle, Tessa; Beijnen, Jos H; van Tellingen, Olaf

    2007-11-01

    The brain is a pharmacologic sanctuary site, due to the presence of the blood-brain barrier (BBB). Whereas the effect of P-glycoprotein (P-gp) at the BBB is well established, the role of breast cancer resistance protein (BCRP) that is also expressed at the BBB is not. We have studied the effect of BCRP by administering topotecan to wild-type (WT), single Mdr1a/b(-/-) and Bcrp1(-/-), and compound Mdr1a/b(-/-)Bcrp1(-/-) knockout mice. Drug levels in plasma and tissues were determined by high-performance liquid chromatography. The area under the plasma and tissue concentration-time curve (AUC) of topotecan in brains of Mdr1a/b(-/-) and Bcrp1(-/-) mice was only 1.5-fold higher compared with WT mice, but in Mdr1a/b(-/-)Bcrp1(-/-) mice, where both transporters are absent, the AUC increased by 12-fold. The AUC in plasma was approximately 0.75-, 2.4-, and 3.7-fold higher in Mdr1a/b(-/-), Bcrp1(-/-), and Mdr1a/b(-/-)Bcrp1(-/-) mice, respectively, resulting in 2.0-fold (P brain-to-plasma AUC ratios. Results using Mrp4(-/-) mice showed that this transporter had no effect on the brain penetration of topotecan. The P-gp/BCRP inhibitor elacridar fully inhibited P-gp-mediated transport of topotecan, whereas inhibition of Bcrp1-mediated transport by elacridar was minimal. Our results using Mdr1a/b(-/-)Bcrp1(-/-) mice clearly show the effect of Bcrp1 at the BBB and also show how two drug transporters act in concert to limit the brain penetration of topotecan. We expect that this finding will also apply to other drugs that are substrates of both P-gp and BCRP. Consequently, to improve the brain penetration of such compounds for targeting intracranial malignancies in patients, it will be essential to use potent inhibitors of both drug transporters.

  12. Sound propagation in cities

    NARCIS (Netherlands)

    Salomons, E.; Polinder, H.; Lohman, W.; Zhou, H.; Borst, H.

    2009-01-01

    A new engineering model for sound propagation in cities is presented. The model is based on numerical and experimental studies of sound propagation between street canyons. Multiple reflections in the source canyon and the receiver canyon are taken into account in an efficient way, while weak

  13. Spread spectrum propagation prediction

    Science.gov (United States)

    Luebbers, Raymond

    1989-02-01

    In order to efficiently model effects of terrain on wideband radio signals, several basic improvements to the Geometrical Theory of Diffraction (GTD) propagation model were made. As a result of this effort a terrain sensitive propagation model capable of predicting the wideband channel transfer function, including the important channel characterization parameters, has been developed and validated against measurements.

  14. Propagation of Significant Figures.

    Science.gov (United States)

    Schwartz, Lowell M.

    1985-01-01

    Shows that the rules of thumb for propagating significant figures through arithmetic calculations frequently yield misleading results. Also describes two procedures for performing this propagation more reliably than the rules of thumb. However, both require considerably more calculational effort than do the rules. (JN)

  15. A Chaplain-led Spiritual Life Review Pilot Study for Patients with Brain Cancers and Other Degenerative Neurologic Diseases

    Directory of Open Access Journals (Sweden)

    Katherine M. Piderman

    2015-04-01

    Full Text Available Objective: This pilot study was designed to describe changes in spiritual well-being (SWB, spiritual coping, and quality of life (QOL in patients with brain cancer or other neurodegenerative diseases participating in a chaplain-led spiritual life review interview and development of a spiritual legacy document (SLD. Methods: Eligible participants were enrolled and completed baseline questionnaires. They were interviewed by a board-certified chaplain about spiritual influences, beliefs, practices, values, and spiritual struggles. An SLD was prepared for each participant, and one month follow-up questionnaires were completed. Two cases are summarized, and spiritual development themes are illustrated within a spiritual development framework. Results: A total of 27 patients completed baseline questionnaires and the interview; 24 completed the SLD, and 15 completed the follow-up questionnaire. Increases in SWB, religious coping, and QOL were detected. The majority maintained the highest (best scores of negative religious coping, demonstrating minimal spiritual struggle. Conclusions: Despite the challenges of brain cancers and other neurodegenerative diseases, participants demonstrated improvements in SWB, positive religious coping, and QOL. Patient comments indicate that benefit is related to the opportunity to reflect on and integrate spiritual experiences and to preserve them for others. Research with a larger, more diverse sample is needed, as well as clinical applications for those too vulnerable to participate in longitudinal follow-up.

  16. Considerations for developing chronic care system for traumatic brain injury based on comparisons of cancer survivorship and diabetes management care.

    Science.gov (United States)

    Heiden, Siobhan M; Caldwell, Barrett S

    2018-01-01

    Experts in traumatic brain injury (TBI) rehabilitation recently proposed the framing of TBI as a chronic disease rather than a discrete event. Within the framework of the Chronic Care Model (CCM), a systematic comparison of three diseases - cancer survivorship, diabetes management and TBI chronic care - was conducted regarding chronic needs and the management of those needs. In addition, comparisons of these conditions require comparative evaluations of disease management characteristics and the survivor concept. The analysis found diabetes is more established within the CCM, where care is integrated across specialists and primary care providers. No single comparison provides a full analogue for understanding the chronic care health delivery system for TBI, indicating the need for a separate model to address needs and resources for TBI survivors. The findings from this research can provide practitioners with a context to develop a robust continued care health system for TBI. Practitioner Summary: We examine development of a chronic care system for traumatic brain injury. We conducted a systematic comparison of Chronic Care Model elements of decision and information support. Development of capabilities using a benchmark of diabetes care, with additional insights from cancer care, provides insights for implementing TBI chronic care systems.

  17. Ten-Year Survival of a Patient Treated with Stereotactic Gamma Knife Radiosurgery for Brain Metastases from Colon Cancer with Ovarian and Lymph Node Metastases: A Case Report

    Directory of Open Access Journals (Sweden)

    Nobuhiro Morinaga

    2016-05-01

    Full Text Available Brain metastasis from colorectal cancer is infrequent and carries a poor prognosis. Herein, we present a patient alive 10 years after the identification of a first brain metastasis from sigmoid colon cancer. A 39-year-old woman underwent sigmoidectomy for sigmoid colon cancer during an emergency operation for pelvic peritonitis. The pathological finding was moderately differentiated adenocarcinoma. Eleven months after the sigmoidectomy, a metastatic lesion was identified in the left ovary. Despite local radiotherapy followed by chemotherapy, the left ovarian lesion grew, so resection of the uterus and bilateral ovaries was performed. Adjuvant chemotherapy with tegafur-uracil (UFT/calcium folinate (leucovorin, LV was initiated. Seven months after resection of the ovarian lesion, brain metastases appeared in the bilateral frontal lobes and were treated with stereotactic Gamma Knife radiosurgery. Cervical and mediastinal lymph node metastases were also diagnosed, and irradiation of these lesions was performed. After radiotherapy, 10 courses of oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX were administered. During FOLFOX administration, recurrent left frontal lobe brain metastasis was diagnosed and treated with stereotactic Gamma Knife radiosurgery. In this case, the brain metastases were well treated with stereotactic Gamma Knife radiosurgery, and the systemic disease arising from sigmoid colon cancer has been kept under control with chemotherapies, surgical resection, and radiotherapy.

  18. Trajectories of Symptom Clusters, Performance Status, and Quality of Life During Concurrent Chemoradiotherapy in Patients With High-Grade Brain Cancers.

    Science.gov (United States)

    Kim, Sang-Hee; Byun, Youngsoon

    Symptom clusters must be identified in patients with high-grade brain cancers for effective symptom management during cancer-related therapy. The aims of this study were to identify symptom clusters in patients with high-grade brain cancers and to determine the relationship of each cluster with the performance status and quality of life (QOL) during concurrent chemoradiotherapy (CCRT). Symptoms were assessed using the Memorial Symptom Assessment Scale, and the performance status was evaluated using the Karnofsky Performance Scale. Quality of life was assessed using the Functional Assessment of Cancer Therapy-General. This prospective longitudinal survey was conducted before CCRT and at 2 to 3 weeks and 4 to 6 weeks after the initiation of CCRT. A total of 51 patients with newly diagnosed primary malignant brain cancer were included. Six symptom clusters were identified, and 2 symptom clusters were present at each time point (ie, "negative emotion" and "neurocognitive" clusters before CCRT, "negative emotion and decreased vitality" and "gastrointestinal and decreased sensory" clusters at 2-3 weeks, and "body image and decreased vitality" and "gastrointestinal" clusters at 4-6 weeks). The symptom clusters at each time point demonstrated a significant relationship with the performance status or QOL. Differences were observed in symptom clusters in patients with high-grade brain cancers during CCRT. In addition, the symptom clusters were correlated with the performance status and QOL of patients, and these effects could change during CCRT. The results of this study will provide suggestions for interventions to treat or prevent symptom clusters in patients with high-grade brain cancer during CCRT.

  19. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  20. Changes of Brain Glucose Metabolism in the Pretreatment Patients with Non-Small Cell Lung Cancer: A Retrospective PET/CT Study.

    Science.gov (United States)

    Zhang, Weishan; Ning, Ning; Li, Xianjun; Niu, Gang; Bai, Lijun; Guo, Youmin; Yang, Jian

    2016-01-01

    The tumor-to-brain communication has been emphasized by recent converging evidences. This study aimed to compare the difference of brain glucose metabolism between patients with non-small cell lung cancer (NSCLC) and control subjects. NSCLC patients prior to oncotherapy and control subjects without malignancy confirmed by 6 months follow-up were collected and underwent the resting state 18F-fluoro-D-glucose (FDG) PET/CT. Normalized FDG metabolism was calculated by a signal intensity ratio of each brain region to whole brain. Brain glucose metabolism was compared between NSCLC patients and control group using two samples t-test and multivariate test by statistical parametric maps (SPM) software. Compared with the control subjects (n = 76), both brain glucose hyper- and hypometabolism regions with significant statistical differences (Pbrain signal transduction pathways, and the hypometabolism regions (the left superior parietal lobule, bilateral inferior parietal lobule and left fusiform gyrus) lied in dorsal attention network and visuospatial function areas. The changes of brain glucose metabolism exist in NSCLC patients prior to oncotherapy, which might be attributed to lung-cancer related visceral sympathetic activation and decrease of dorsal attention network function.

  1. Prognostic factors for cases with no extracranial metastasis in whom brain metastasis is detected after resection of non-small cell lung cancer.

    Science.gov (United States)

    Bae, Mi Kyung; Yu, Woo Sik; Byun, Go Eun; Lee, Chang Young; Lee, Jin Gu; Kim, Dae Joon; Chung, Kyung Young

    2015-05-01

    This study aimed to determine prognostic factors associated with postrecurrence survival in cases with postoperative brain metastasis but with no extracranial metastasis in non-small cell lung cancer (NSCLC). Between 1992 and 2012, a total of 2832 patients underwent surgical resection for NSCLC. Among those, 86 patients had postoperative brain metastasis as the initial recurrence. Those patients were retrospectively reviewed. The median follow-up time after the initial lung resection was 24.0 months (range, 2.0-126.0 months). The median overall survival after initial lung cancer resection was 25.0 months and the median overall postrecurrence survival was 11 months. An initial lesion of adenocarcinoma (hazard ratio, 0.548; 95% confidence interval, 0.318 to 0.946; p=0.031), non-pneumonectomy, and a disease-free interval longer than 10.0 months (hazard ratio, 0.565; 95% confidence interval, 0.321-0.995; p=0.048) from the initial lung resection to the diagnosis of brain metastasis positively related to a good postrecurrence survival. Solitary brain metastasis and a size of less than 3 cm for the largest brain lesion were also positive factors for postrecurrence survival. Systemic chemotherapy for brain metastasis (hazard ratio, 0.356; 95% confidence interval, 0.189-0.670; p=0.001) and local treatment of surgery and/or stereotactic radiosurgery (SRS) for brain lesions (hazard ratio, 0.321; 95% confidence interval, 0.138-0.747; p=0.008) were positive factors for better postrecurrence survival. In patients with brain metastasis after resection for NSCLC with no extracranial metastasis, adenocarcinoma histologic type, longer disease-free interval, systemic chemotherapy for brain metastasis and local treatment of surgery and/or SRS for brain metastasis are independent positive prognostic factors for postrecurrence survival. Copyright © 2015. Published by Elsevier Ireland Ltd.

  2. Use of Stereotactic Radiosurgery for Brain Metastases From Non-Small Cell Lung Cancer in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Halasz, Lia M., E-mail: lhalasz@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Harvard Radiation Oncology Program, Harvard Medical School, Boston, Massachusetts (United States); Weeks, Jane C.; Neville, Bridget A.; Taback, Nathan [Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Punglia, Rinaa S. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2013-02-01

    Purpose: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. Methods and Materials: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. Results: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. Conclusions: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

  3. P-glycoprotein and breast cancer resistance protein restrict the brain penetration of the CDK4/6 inhibitor palbociclib.

    Science.gov (United States)

    de Gooijer, Mark C; Zhang, Ping; Thota, Nishita; Mayayo-Peralta, Isabel; Buil, Levi C M; Beijnen, Jos H; van Tellingen, Olaf

    2015-10-01

    Palbociclib is a cyclin dependent kinase (CDK) 4/6 inhibitor with nanomolar potency and was recently approved for treatment of breast cancer. The drug may also be useful in glioblastoma (GBM) and diffuse intrinsic pontine gliomas (DIPG), which often have an activated CDK4/6-retinoblastoma signaling pathway. However, GBM and DIPG spread widely into the surrounding brain, which calls for a CDK4/6 inhibitor with sufficient blood-brain barrier penetration. We first performed in vitro transwell assays and demonstrate that palbociclib is a substrate of both P-gp and BCRP. Next, we conducted pharmacokinetic studies using wildtype, Abcg2(-/-), Abcb1a/b(-/-) and Abcg2; Abcb1a/b(-/-) mice. The plasma levels were about 3000 and 500 nM and similar in all genotypes at 1 and 4 h after i.v. administration of 10 mg/kg. At 4 h the brain-to-plasma ratios were 0.3 in WT and Abcg2(-/-) mice versus 5.5 and 15 in Abcb1a/b(-/-) and Abcg2; Abcb1a/b(-/-) mice, respectively. The oral bioavailability of palbociclib was high (63 %) in WT mice and increased only modestly and non-significantly in Abcg2; Abcb1a/b(-/-) mice. The plasma level after oral dosing of 150 mg/kg was already much higher than observed in patients (200-400 nM) and exceeded 2500 nM for up to 24 h. This latter dose is commonly used in preclinical studies, which calls into question their predictive value as they were conducted at dose levels causing a clinically non-relevant systemic drug exposure. Thus, the brain penetration of palbociclib is restricted by P-gp and BCRP, which may restrict the efficacy against GBM and DIPG. Moreover, preclinical studies with this agent should be conducted at a more clinically relevant dose level.

  4. Vector wave propagation method.

    Science.gov (United States)

    Fertig, M; Brenner, K-H

    2010-04-01

    In this paper, we extend the scalar wave propagation method (WPM) to vector fields. The WPM [Appl. Opt.32, 4984 (1993)] was introduced in order to overcome the major limitations of the beam propagation method (BPM). With the WPM, the range of application can be extended from the simulation of waveguides to simulation of other optical elements like lenses, prisms and gratings. In that reference it was demonstrated that the wave propagation scheme provides valid results for propagation angles up to 85 degrees and that it is not limited to small index variations in the axis of propagation. Here, we extend the WPM to three-dimensional vectorial fields (VWPMs) by considering the polarization dependent Fresnel coefficients for transmission in each propagation step. The continuity of the electric field is maintained in all three dimensions by an enhanced propagation vector and the transfer matrix. We verify the validity of the method by transmission through a prism and by comparison with the focal distribution from vectorial Debye theory. Furthermore, a two-dimensional grating is simulated and compared with the results from three-dimensional RCWA. Especially for 3D problems, the runtime of the VWPM exhibits special advantage over the RCWA.

  5. Controlling micro- and nano-environment of tumor and stem cells for novel research and therapy of brain cancer

    Science.gov (United States)

    Smith, Christopher Lloyd

    The use of modern technologies in cancer research has engendered a great deal of excitement. Many of these advanced approaches involve in-depth mathematical analyses of the inner working of cells, via genomic and proteomic analyses. However these techniques may not be ideal for the study of complex cell phenotypes and behaviors. This dissertation explores cancer and potential therapies through phenotypic analysis of cell behaviors, an alternative approach. We employ this experimental framework to study brain cancer (glioma), a particularly formidable example of this diverse ailment. Through the application of micro- and nanotechnology, we carefully control the surrounding environments of cells to understand their responses to various cues and to manipulate their behaviors. Subsequently we obtain clinically relevant information that allows better understanding of glioma, and enhancement of potential therapies. We first aim to address brain tumor dispersal, through analysis of cell migration. Utilizing nanometer-scale topographic models of the extracellular matrix, we study the migratory response of glioma cells to various stimuli in vitro. Second, we implement knowledge gained from these investigations to define characteristics of tumor progression in patients, and to develop treatments inhibiting cell migration. Next we use microfluidic and nanotopographic models to study the behaviors of stem cells in vitro. Here we attempt to improve their abilities to deliver therapeutic proteins to cancer, an innovative treatment approach. We analyze the multi-step process by which adipose-derived stem cells naturally home to tumor sites, and identify numerous environmental perturbations to enhance this behavior. Finally, we attempt to demonstrate that these cell culture-based manipulations can enhance the localization of adipose stem cells to glioma in vivo using animal models. Throughout this work we utilize environmental cues to analyze and induce particular behaviors in

  6. The gluon propagator

    Science.gov (United States)

    Mandula, Jeffrey E.

    1999-07-01

    We discuss the current state of what is known non-perturbatively about the gluon propagator in QCD, with emphasis on the information coming from lattice simulations. We review specification of the lattice Landau gauge and the procedure for calculating the gluon propagator on the lattice. We also discuss some of the difficulties in non-perturbative calculations - especially Gribov copy issues. We trace the evolution of lattice simulations over the past dozen years, emphasizing how the improvement in computations has led not only to more precise determinations of the propagator, but has allowed more detailed information about it to be extracted.

  7. Continuous Time Random Walk and Migration-Proliferation Dichotomy of Brain Cancer

    Science.gov (United States)

    Iomin, A.

    A theory of fractional kinetics of glial cancer cells is presented. A role of the migration-proliferation dichotomy in the fractional cancer cell dynamics in the outer-invasive zone is discussed and explained in the framework of a continuous time random walk. The main suggested model is based on a construction of a 3D comb model, where the migration-proliferation dichotomy becomes naturally apparent and the outer-invasive zone of glioma cancer is considered as a fractal composite with a fractal dimension Dfr < 3.

  8. Bamboo in vitro propagation

    National Research Council Canada - National Science Library

    Yudith García- Ramírez; Marisol Freire-Seijo; Ortelio Hurtado

    2011-01-01

    ... the social problems of the countryside in Cuba. Traditional bamboo propagation is affected by long intervals of flowering, the limited stock of plant material, the low percentages of rooting and the limited existence of propagules...

  9. Neural Stem Cells Secreting Anti-HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases.

    Science.gov (United States)

    Kanojia, Deepak; Balyasnikova, Irina V; Morshed, Ramin A; Frank, Richard T; Yu, Dou; Zhang, Lingjiao; Spencer, Drew A; Kim, Julius W; Han, Yu; Yu, Dihua; Ahmed, Atique U; Aboody, Karen S; Lesniak, Maciej S

    2015-10-01

    The treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been revolutionized by trastuzumab. However, longer survival of these patients now predisposes them to forming HER2 positive brain metastases, as the therapeutic antibodies cannot cross the blood brain barrier. The current oncologic repertoire does not offer a rational, nontoxic targeted therapy for brain metastases. In this study, we used an established human neural stem cell line, HB1.F3 NSCs and generated a stable pool of cells secreting a high amount of functional full-length anti-HER2 antibody, equivalent to trastuzumab. Anti-HER2Ab secreted by the NSCs (HER2Ab-NSCs) specifically binds to HER2 overexpressing human breast cancer cells and inhibits PI3K-Akt signaling. This translates to HER2Ab-NSC inhibition of breast cancer cell growth in vitro. Preclinical in vivo experiments using HER2Ab overexpressing NSCs in a breast cancer brain metastases (BCBM) mouse model demonstrate that intracranial injection of HER2Ab-NSCs significantly improves survival. In effect, these NSCs provide tumor localized production of HER2Ab, minimizing any potential off-target side effects. Our results establish HER2Ab-NSCs as a novel, nontoxic, and rational therapeutic approach for the successful treatment of HER2 overexpressing BCBM, which now warrants further preclinical and clinical investigation. © 2015 AlphaMed Press.

  10. Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) gene dosage on plasma pharmacokinetics and brain accumulation of dasatinib, sorafenib, and sunitinib.

    NARCIS (Netherlands)

    Tang, S.C.; Vries, N. de; Sparidans, R.W.; Wagenaar, E.; Beijnen, J.H.; Schinkel, A.H.

    2013-01-01

    Low brain accumulation of anticancer drugs due to efflux transporters may limit chemotherapeutic efficacy, necessitating a better understanding of the underlying mechanisms. P-glycoprotein (Abcb1a/1b) and breast cancer resistance protein (Abcg2) combination knockout mice often display

  11. Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

    NARCIS (Netherlands)

    A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

    2011-01-01

    textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive

  12. A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases.

    Science.gov (United States)

    Chen, Xilin; Han, Jianfeng; Chu, Jianhong; Zhang, Lingling; Zhang, Jianying; Chen, Charlie; Chen, Luxi; Wang, Youwei; Wang, Hongwei; Yi, Long; Elder, J Bradley; Wang, Qi-En; He, Xiaoming; Kaur, Balveen; Chiocca, E Antonio; Yu, Jianhua

    2016-05-10

    Breast cancer brain metastases (BCBMs) are common in patients with metastatic breast cancer and indicate a poor prognosis. These tumors are especially resistant to currently available treatments due to multiple factors. However, the combination of chimeric antigen receptor (CAR)-modified immune cells and oncolytic herpes simplex virus (oHSV) has not yet been explored in this context. In this study, NK-92 cells and primary NK cells were engineered to express the second generation of EGFR-CAR. The efficacies of anti-BCBMs of EGFR-CAR NK cells, oHSV-1, and their combination were tested in vitro and in a breast cancer intracranial mouse model. In vitro, compared with mock-transduced NK-92 cells or primary NK cells, EGFR-CAR-engineered NK-92 cells and primary NK cells displayed enhanced cytotoxicity and IFN-γ production when co-cultured with breast cancer cell lines MDA-MB-231, MDA-MB-468, and MCF-7. oHSV-1 alone was also capable of lysing and destroying these cells. However, a higher cytolytic effect of EGFR-CAR NK-92 cells was observed when combined with oHSV-1 compared to the monotherapies. In the mice intracranially pre-inoculated with EGFR-expressing MDA-MB-231 cells, intratumoral administration of either EGFR-CAR-transduced NK-92 cells or oHSV-1 mitigated tumor growth. Notably, the combination of EGFR-CAR NK-92 cells with oHSV-1 resulted in more efficient killing of MDA-MB-231 tumor cells and significantly longer survival of tumor-bearing mice when compared to monotherapies. These results demonstrate that regional administration of EGFR-CAR NK-92 cells combined with oHSV-1 therapy is a potentially promising strategy to treat BCBMs.

  13. Outcomes of social support programs in brain cancer survivors in an Australian community cohort: a prospective study

    Directory of Open Access Journals (Sweden)

    Khan F

    2013-03-01

    Full Text Available This study evaluated the impact of social support programs on improving cancer related disability, neuro-cognitive dysfunction and enhancing participation (quality of life (QoL, social reintegration in brain tumour (BT survivors. Participants (n=43 were recruited prospectively following definitive treatment in the community. Each BT survivor received an individualised social support program which comprised: face-to-face interview for education/counselling plus peer support program or community education/counselling sessions. The assessments were at baseline (T1, 6-week (T2 and 6-month (T3 post-intervention using validated questionnaires: depression anxiety stress scale (DASS, functional independence measure (FIM, perceived impact problem profile (PIPP, cancer rehabilitation evaluation system–short form (CARES-SF, a cancer survivor unmet needs measure (CaSUN, McGill quality of life questionnaire (MQOL and Brief COPE. Participants’ mean age was 53 years (range 31–72 years, the majority were female (72%; median time since BT diagnosis was 2.3 years and almost half (47% had high grade tumours. At T2, participants reported higher emotional well-being (DASS ‘anxiety’ and ‘stress’ subscales, p<0.05; FIM ‘cognition’ subscale, p<0.01, improved function (FIM ‘motor’ subscale, p<0.01 and higher QoL (CARES-SF ‘global’ score, p<0.05; MQOL ‘physical symptom’ subscale, p<0.05. At the T3 follow-up, most of these effects were maintained. The intervention effect for BT specific coping strategies emerged for the Brief COPE ‘self-distraction’ and ‘behavioural disengagement’ domains, (p<0.05 for both. There were no adverse effects reported. A post-treatment social support program can improve physical and cognitive function and enhancing overall QoL of BT survivors. Social support programs need further evaluation and should be encouraged by clinicians within cancer rehabilitative services.

  14. The role of brain/behavioural systems in prediction of quality of life and coping strategies in cancer patients

    Directory of Open Access Journals (Sweden)

    Shala Jangi Goujeh Biglou

    2014-03-01

    Full Text Available Background: It seems that individual differences in personality characteristics are implicated in the incidence and progress of physical diseases and socio-psychological consequences. However, there are a few studies about the role of personality in the prediction of socio-psychological consequences of cancer. The aim of this research was to survey the role of personality in the prediction of socio-psychosocial factors: quality of life and coping strategies. Methods: This research was a descriptive-correlational study in which the sample included fifty cancer patients who were selected through convenience sampling method. To assess the personality differences, quality of life and coping strategies, the Carver and White (1994 BIS/BAS Scales, SF-12 Health Survey and Coping Inventory for Stressful Situation (CISS were used, respectively. The data were analysed by SPSS software using Pearson correlation coefficient and stepwise regression. Results: The findings showed that Both BIS and BAS systems could predict the quality of life (P<0.001, BIS system could explain the emotion-oriented coping strategy (P<0.05 and avoidance-oriented coping stratesy (P<0.01 and BAS system could explain the problem-oriented coping strategy (P<0.001. Conclusion: The findings of this study showed that brain/behavioural systems can predict the quality of life and coping strategies in cancer patients. The identification of these systems in cancer patients can help recognize the persons that are under the risk of poor quality of life or have a higher chance of using inconsistent coping strategies, and execute preventive measures about them.

  15. Breast cancer subtype as a predictor for outcomes and control in the setting of brain metastases treated with stereotactic radiosurgery.

    Science.gov (United States)

    Grubb, Christopher S; Jani, Ashish; Wu, Cheng-Chia; Saad, Shumaila; Qureshi, Yasir H; Nanda, Tavish; Yaeh, Andrew; Rozenblat, Tzlil; Sisti, Michael B; Bruce, Jeffrey N; McKhann, Guy M; Sheth, Sameer A; Lesser, Jeraldine; Cheng, Simon K; Isaacson, Steven R; Lassman, Andrew B; Connolly, Eileen P; Wang, Tony J C

    2016-03-01

    We investigated effects of breast cancer subtype on overall survival (OS), local and distant control, and time from initial diagnosis to brain metastases (BM). We also investigated advances in graded prognostic assessment (GPA) scores. A cohort of 72 patients treated for BM from breast cancer with Gamma Knife stereotactic radiosurgery at our institution from 2000 to 2014 had subtyping available and were used for this study. Median follow up for OS was 12 months and for control was 6 months. OS for luminal, HER2, and triple negative subtypes were 26, 20, and 22 months. OS when stratified by Sperduto et al. (J Clin Oncol 30(4):419-425, 2012) and Subbiah et al. (J Clin Oncol 33(20):2239-2245, 2015) GPAs were similar (p = 0.087 and p = 0.063). KPS and treatment modality were significant for OS (p = 0.002; p = 0.034). On univariate analysis, triple negative subtype and >3 BM were trending and significant for decreased OS (p = 0.084; p = 0.047). On multivariable analysis HER2, triple negative, and >3 BM were significant for OS (p = 0.022; p = 0.040; p = 0.009). Subtype was significant for response on a per lesion basis (p = 0.007). Subtype was trending towards significance when analyzing time from initial diagnosis to BM treatment (p = 0.064). Breast cancer subtype is an important prognostic factor when stratifying breast cancer patients with BM. The addition of number of BM to the GPA is a useful addition and should be further investigated. Subtype has an effect on lesion response, and also on rate of development BM after initial diagnosis.

  16. Risk factors of brain metastases in completely resected pathological stage IIIA-N2 non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Ding Xiao

    2012-07-01

    Full Text Available Abstract Background Brain metastases (BM is one of the most common failures of locally advanced non-small cell lung cancer (LA-NSCLC after combined-modality therapy. The outcome of trials on prophylactic cranial irradiation (PCI has prompted us to identify the highest-risk subset most likely to benefit from PCI. Focusing on patients with completely resected pathological stage IIIA-N2 (pIIIA-N2 NSCLC, we aimed to assess risk factors of BM and to define the highest-risk subset. Methods Between 2003 and 2005, the records of 217 consecutive patients with pIIIA-N2 NSCLC in our institution were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method, and differences between the groups were analyzed using log-rank test. Multivariate Cox regression analysis was applied to assess risk factors of BM. Results Fifty-three (24.4 % patients developed BM at some point during their clinical course. On multivariate analysis, non-squamous cell cancer (relative risk [RR]: 4.13, 95 % CI: 1.86–9.19; P = 0.001 and the ratio of metastatic to examined nodes or lymph node ratio (LNR ≥ 30 % (RR: 3.33, 95 % CI: 1.79–6.18; P = 0.000 were found to be associated with an increased risk of BM. In patients with non-squamous cell cancer and LNR ≥ 30 %, the 5-year actuarial risk of BM was 57.3 %. Conclusions In NSCLC, patients with completely resected pIIIA-N2 non-squamous cell cancer and LNR ≥ 30 % are at the highest risk for BM, and are most likely to benefit from PCI. Further studies are warranted to investigate the effect of PCI on this subset of patients.

  17. Analyses of prognostic factors in cases of non-small cell lung cancer with multiple brain metastases

    Directory of Open Access Journals (Sweden)

    Gong X

    2016-03-01

    Full Text Available Xiaomei Gong,1 Daoan Zhou,1 Shixiong Liang,1 Caicun Zhou2 1Department of Radiation Oncology, 2Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Aim: To observe the therapeutic efficacy and prognostic factors that influence survival rates in non-small cell lung cancer (NSCLC patients with multiple brain metastases (BMs, more than three and less than ten. Methods: Retrospective analyses were conducted on the clinical data of 209 NSCLC patients with multiple BMs and were admitted to our hospital between March 2007 and November 2012. All BM patients received whole-brain radiotherapy. Two hundred patients received combined chemotherapy during the treatment process; 99 received targeted drug therapy; and nine got only symptomatic and supportive treatment. Survival time was defined as the period from the start of BM therapy to the patient’s death or end of the follow-up period. The Kaplan–Meier method was used to calculate the median survival time, and the 6-month, 1-, and 2-year cumulative survival rates, as well as to plot the survival curves. The patients’ cultural background included their socioeconomic status, level of education, their understanding of the disease, and the degree of care and support they received from their family members. Log-rank test was employed to test the differences in the survival rates between the subgroups. Cox multivariate regression analyses were used to analyze the various factors influencing the prognoses of NSCLC with multiple BMs. Results: The follow-up duration was between 1 and 87 months. The median survival time for all BM patients was 12.1 months (95% confidence interval 9.37–14.83. The 6-month, 1-, and 2-year cumulative survival rates were 80%, 50.2%, and 10.7%, respectively. Univariate analyses revealed that the independent factors influencing survival prognoses included Karnofsky Performance Status score, control of the

  18. Mobile phones, cordless phones and rates of brain tumors in different age groups in the Swedish National Inpatient Register and the Swedish Cancer Register during 1998-2015.

    Directory of Open Access Journals (Sweden)

    Lennart Hardell

    Full Text Available We used the Swedish Inpatient Register (IPR to analyze rates of brain tumors of unknown type (D43 during 1998-2015. Average Annual Percentage Change (AAPC per 100,000 increased with +2.06%, 95% confidence interval (CI +1.27, +2.86% in both genders combined. A joinpoint was found in 2007 with Annual Percentage Change (APC 1998-2007 of +0.16%, 95% CI -0.94, +1.28%, and 2007-2015 of +4.24%, 95% CI +2.87, +5.63%. Highest AAPC was found in the age group 20-39 years. In the Swedish Cancer Register the age-standardized incidence rate per 100,000 increased for brain tumors, ICD-code 193.0, during 1998-2015 with AAPC in men +0.49%, 95% CI +0.05, +0.94%, and in women +0.33%, 95% CI -0.29, +0.45%. The cases with brain tumor of unknown type lack morphological examination. Brain tumor diagnosis was based on cytology/histopathology in 83% for men and in 87% for women in 1980. This frequency increased to 90% in men and 88% in women in 2015. During the same time period CT and MRI imaging techniques were introduced and morphology is not always necessary for diagnosis. If all brain tumors based on clinical diagnosis with CT or MRI had been reported to the Cancer Register the frequency of diagnoses based on cytology/histology would have decreased in the register. The results indicate underreporting of brain tumor cases to the Cancer Register. The real incidence would be higher. Thus, incidence trends based on the Cancer Register should be used with caution. Use of wireless phones should be considered in relation to the change of incidence rates.

  19. Mobile phones, cordless phones and rates of brain tumors in different age groups in the Swedish National Inpatient Register and the Swedish Cancer Register during 1998-2015.

    Science.gov (United States)

    Hardell, Lennart; Carlberg, Michael

    2017-01-01

    We used the Swedish Inpatient Register (IPR) to analyze rates of brain tumors of unknown type (D43) during 1998-2015. Average Annual Percentage Change (AAPC) per 100,000 increased with +2.06%, 95% confidence interval (CI) +1.27, +2.86% in both genders combined. A joinpoint was found in 2007 with Annual Percentage Change (APC) 1998-2007 of +0.16%, 95% CI -0.94, +1.28%, and 2007-2015 of +4.24%, 95% CI +2.87, +5.63%. Highest AAPC was found in the age group 20-39 years. In the Swedish Cancer Register the age-standardized incidence rate per 100,000 increased for brain tumors, ICD-code 193.0, during 1998-2015 with AAPC in men +0.49%, 95% CI +0.05, +0.94%, and in women +0.33%, 95% CI -0.29, +0.45%. The cases with brain tumor of unknown type lack morphological examination. Brain tumor diagnosis was based on cytology/histopathology in 83% for men and in 87% for women in 1980. This frequency increased to 90% in men and 88% in women in 2015. During the same time period CT and MRI imaging techniques were introduced and morphology is not always necessary for diagnosis. If all brain tumors based on clinical diagnosis with CT or MRI had been reported to the Cancer Register the frequency of diagnoses based on cytology/histology would have decreased in the register. The results indicate underreporting of brain tumor cases to the Cancer Register. The real incidence would be higher. Thus, incidence trends based on the Cancer Register should be used with caution. Use of wireless phones should be considered in relation to the change of incidence rates.

  20. SU-E-J-90: MRI-Based Treatment Simulation and Patient Setup for Radiation Therapy of Brain Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Y [UCLA School of Medicine, Los Angeles, AA (United States); Cao, M; Han, F; Santhanam, A; Neylon, J; Gomez, C; Kaprealian, T; Sheng, K; Agazaryan, N; Low, D; Hu, P

    2014-06-01

    Purpose: Traditional radiation therapy of cancer is heavily dependent on CT. CT provides excellent depiction of the bones but lacks good soft tissue contrast, which makes contouring difficult. Often, MRIs are fused with CT to take advantage of its superior soft tissue contrast. Such an approach has drawbacks. It is desirable to perform treatment simulation entirely based on MRI. To achieve MR-based simulation for radiation therapy, bone imaging is an important challenge because of the low MR signal intensity from bone due to its ultra-short T2 and T1, which presents difficulty for both dose calculation and patient setup in terms of digitally reconstructed radiograph (DRR) generation. Current solutions will either require manual bone contouring or multiple MR scans. We present a technique to generate DRR using MRI with an Ultra Short Echo Time (UTE) sequence which is applicable to both OBI and ExacTrac 2D patient setup. Methods: Seven brain cancer patients were scanned at 1.5 Tesla using a radial UTE sequence. The sequence acquires two images at two different echo times. The two images were processed using in-house software. The resultant bone images were subsequently loaded into commercial systems to generate DRRs. Simulation and patient clinical on-board images were used to evaluate 2D patient setup with MRI-DRRs. Results: The majority bones are well visualized in all patients. The fused image of patient CT with the MR bone image demonstrates the accuracy of automatic bone identification using our technique. The generated DRR is of good quality. Accuracy of 2D patient setup by using MRI-DRR is comparable to CT-based 2D patient setup. Conclusion: This study shows the potential of DRR generation with single MR sequence. Further work will be needed on MR sequence development and post-processing procedure to achieve robust MR bone imaging for other human sites in addition to brain.

  1. Enhancement of apoptotic activities on brain cancer cells via the combination of γ-tocotrienol and jerantinine A.

    Science.gov (United States)

    Abubakar, Ibrahim Babangida; Lim, Kuan-Hon; Kam, Toh-Seok; Loh, Hwei-San

    2017-07-01

    γ-Tocotrienol, a vitamin E isomer possesses pronounced in vitro anticancer activities. However, the in vivo potency has been limited by hardly achievable therapeutic levels owing to inefficient high-dose oral delivery which leads to subsequent metabolic degradation. Jerantinine A, an Aspidosperma alkaloid, originally isolated from Tabernaemontana corymbosa, has proved to possess interesting anticancer activities. However, jerantinine A also induces toxicity to non-cancerous cells. We adopted a combinatorial approach with the joint application of γ-tocotrienol and jerantinine A at lower concentrations in order to minimize toxicity towards non-cancerous cells while improving the potency on brain cancer cells. The antiproliferative potency of individual γ-tocotrienol and jerantinine A as well as combined in low-concentration was firstly evaluated on U87MG cancer and MRC5 normal cells. Morphological changes, DNA damage patterns, cell cycle arrests and the effects of individual and combined low-concentration compounds on microtubules were then investigated. Finally, the potential roles of caspase enzymes and apoptosis-related proteins in mediating the apoptotic mechanisms were investigated using apoptosis antibody array, ELISA and Western blotting analysis. Combinatorial study between γ-tocotrienol at a concentration range (0-24µg/ml) and fixed IC20 concentration of jerantinine A (0.16µg/ml) induced a potent antiproliferative effect on U87MG cells and led to a reduction on the new half maximal inhibitory concentration of γ-tocotrienol (i.e.tIC50=1.29µg/ml) as compared to that of individual γ-tocotrienol (i.e. IC50=3.17µg/ml). A reduction on undesirable toxicity to MRC5 normal cells was also observed. G0/G1 cell cycle arrest was evident on U87MG cells receiving IC50 of individual γ-tocotrienol and combined low-concentration compounds (1.29µg/ml γ-tocotrienol + 0.16µg/ml jerantinine A), whereas, a profound G2/M arrest was evident on cells treated with IC50

  2. A Numerical Investigation of the Time Reversal Mirror Technique for Trans-skull Brain Cancer Ultrasound Surgery

    Directory of Open Access Journals (Sweden)

    H. Zahedmanesh

    2007-06-01

    Full Text Available Introduction: The medical applications of ultrasound on human brain are highly limited by the phase and amplitude aberrations induced by the heterogeneities of the skull. However, it has been shown that time reversing coupled with amplitude compensation can overcome these aberrations. In this work, a model for 2D simulation of the time reversal mirror technique is proposed to study the possibility of targeting any point within the brain without the need for craniotomy and to calculate the acoustic pressure field and the resulting temperature distribution within the skull and brain during a High Intensity Focused Ultrasound (HIFU transcranial therapy. Materials and Methods: To overcome the sensitivity of the wave pattern to the heterogeneous geometry of the skull, a real MRI derived 2D model is constructed. The model should include the real geometry of brain and skull. The model should also include the couplant medium which has the responsibility of coupling the transducer to the skull for the penetration of ultrasound. The clinical substance used as the couplant is water. The acoustic and thermal parameters are derived from the references. Next, the wave propagation through the skull is computed based on the Helmholtz equation, with a 2D finite element analysis. The acoustic simulation is combined with a 2D thermal diffusion analysis based on Pennes Bioheat equation and the temperature elevation inside the skull and brain is computed. The numerical simulations were performed using the FEMLAB 3.2 software on a PC having 8 GB RAM and a 2.4 MHz dual CPU. Results: It is seen that the ultrasonic waves are exactly focalized at the location where the hydrophone has been previously implanted. There is no penetration into the sinuses and the waves are reflected from their surface because of the high discrepancy between the speed of sound in bone and air.  Under the focal pressure of 2.5 MPa and after 4 seconds of sonication the temperature at the focus

  3. Risk factors for brain metastases after definitive chemoradiation for locally advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2009-01-01

    Full Text Available Background/Aim. As therapy for locally advanced nonsmall cell lung carcinoma (NSCLC improves, brain metastases (BM still remain a great problem. The aim of the study was to analyze risk factors for BM in patients with locally advanced NSCLC after chemoradiation therapy. Methods. Records for 150 patients with non-resectable stage IIIA/IIIB NSCLC treated with combined chemoradiation therapy were analyzed. All of them had negative brain metastases imaging result before the treatment. Incidence of BM was examined in relation to age, sex, histological type, stage, performance status scale of wellbeing of cancer patients, weight loss, chemotherapy regimen and chemotherapy timing. Results. One- and 2-year incidence rates of BM were 19 and 31%, respectively. Among pretreatment parameters, stage IIIB was associated with a higher risk of BM (p < 0.004 vs stage IIIA. Histologically, the patients with nonsquamous tumors had an exceptionally high 2-year BM risk rate of 32% (p < 0.02. Examining treatment-related parameters, 1-year and 2-year actuarial risk of BM were 27 and 39%, respectively, in the patients receiving chemotherapy before radiotherapy and 15 and 20%, respectively, when radiotherapy was not delayed (p < 0.03. On multivariate analysis, timing of chemotherapy (p < 0.05 and stage IIIA vs IIIB (p < 0.01 remained statistically significant. Conclusion. Patients with IIIB stage, nonsquamous NSCLC, particularly those receiving sequential chemotherapy, had significantly high BM rates.

  4. Integrating structure to protein-protein interaction networks that drive metastasis to brain and lung in breast cancer.

    Directory of Open Access Journals (Sweden)

    H Billur Engin

    Full Text Available Blocking specific protein interactions can lead to human diseases. Accordingly, protein interactions and the structural knowledge on interacting surfaces of proteins (interfaces have an important role in predicting the genotype-phenotype relationship. We have built the phenotype specific sub-networks of protein-protein interactions (PPIs involving the relevant genes responsible for lung and brain metastasis from primary tumor in breast cancer. First, we selected the PPIs most relevant to metastasis causing genes (seed genes, by using the "guilt-by-association" principle. Then, we modeled structures of the interactions whose complex forms are not available in Protein Databank (PDB. Finally, we mapped mutations to interface structures (real and modeled, in order to spot the interactions that might be manipulated by these mutations. Functional analyses performed on these sub-networks revealed the potential relationship between immune system-infectious diseases and lung metastasis progression, but this connection was not observed significantly in the brain metastasis. Besides, structural analyses showed that some PPI interfaces in both metastasis sub-networks are originating from microbial proteins, which in turn were mostly related with cell adhesion. Cell adhesion is a key mechanism in metastasis, therefore these PPIs may be involved in similar molecular pathways that are shared by infectious disease and metastasis. Finally, by mapping the mutations and amino acid variations on the interface regions of the proteins in the metastasis sub-networks we found evidence for some mutations to be involved in the mechanisms differentiating the type of the metastasis.

  5. Boron neutron capture therapy design calculation of a 3H(p,n reaction based BSA for brain cancer setup

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    Bassem Elshahat

    2015-09-01

    Full Text Available Purpose: Boron neutron capture therapy (BNCT is a promising technique for the treatment of malignant disease targeting organs of the human body. Monte Carlo simulations were carried out to calculate optimum design parameters of an accelerator based beam shaping assembly (BSA for BNCT of brain cancer setup.Methods: Epithermal beam of neutrons were obtained through moderation of fast neutrons from 3H(p,n reaction in a high density polyethylene moderator and a graphite reflector. The dimensions of the moderator and the reflector were optimized through optimization of epithermal / fast neutron intensity ratio as a function of geometric parameters of the setup. Results: The results of our calculation showed the capability of our setup to treat the tumor within 4 cm of the head surface. The calculated peak therapeutic ratio for the setup was found to be 2.15. Conclusion: With further improvement in the polyethylene moderator design and brain phantom irradiation arrangement, the setup capabilities can be improved to reach further deep-seated tumor.

  6. Outcome in patients with small cell lung cancer re-irradiated for brain metastases after prior prophylactic cranial irradiation.

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    Bernhardt, Denise; Bozorgmehr, Farastuk; Adeberg, Sebastian; Opfermann, Nils; von Eiff, Damian; Rieber, Juliane; Kappes, Jutta; Foerster, Robert; König, Laila; Thomas, Michael; Debus, Jürgen; Steins, Martin; Rieken, Stefan

    2016-11-01

    Patients with brain metastases from small-cell lung cancer (SCLC) who underwent prior prophylactic cranial irradiation (PCI) are often treated with a second course of whole brain radiation therapy (Re-WBRT) or stereotactic radiosurgery (SRS) for purposes of palliation in symptomatic patients, hope for increased life expectancy or even as an alternative to untolerated steroids. Up to date there is only limited data available regarding the effect of this treatment. This study examines outcomes in patients in a single institution who underwent cerebral re-irradiation after prior PCI. We examined the medical records of 76 patients with brain metastases who had initially received PCI between 2008 and 2015 and were subsequently irradiated with a second course of cerebral radiotherapy. Patients underwent re-irradiation using either Re-WBRT (88%) or SRS (17%). The outcomes, including symptom palliation, radiation toxicity, and overall survival (OS) following re-irradiation were analyzed. Survival and correlations were calculated using log-rank, univariate, and multivariate Cox proportional hazards-ratio analyses. Treatment-related toxicity was classified according to CTCAE v4.0. Median OS of all patients was 3 months (range 0-12 months). Median OS after Re-WBRT was 3 months (range 0-12 months). Median OS after SRS was 5 months (range 0-12 months). Karnofsky performance status scale (KPS ≥50%) was significantly associated with improved OS in both univariate (HR 2772; p=0,009) and multivariate analyses (HR 2613; p=0,024) for patients receiving Re-WBRT. No unexpected toxicity was observed and the observed toxicity remained consistently low. Symptom palliation was achieved in 40% of symptomatic patients. In conclusion, cerebral re-irradiation after prior PCI is beneficial for symptom palliation and is associated with minimal side effects in patients with SCLC. Our survival data suggests that it is primarily useful in patients with adequate performance status. Copyright

  7. Cancer: brain-regulated biphasic stress response induces cell growth or cell death to adapt to psychological stressors.

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    Thomas, Charles; Bhatia, Shruti

    2014-01-01

    According to Indian Vedic philosophy, a human being contains 3 major bodies: (1) the matter body--brain, organs, and senses; (2) the mental body--mind, individual consciousness, intellect, and ego; and (3) the soul or causal body--universal consciousness. The third, which is located in the heart according to all spiritual traditions and recent scientific literature, can be seen as the information body that contains all memories. The mental body, which can interface with the matter and information bodies, can be seen as a field of immaterial energy that can carry, regulate, and strengthen all information (eg, thoughts or emotions) both positively and negatively. This body of information may store ancestral and/or autobiographical memories: unconscious memories from inner traumas--inner information (Ii) or samskaras in Vedic philosophy--and conscious memories from outer traumas--outer information (Io). These conscious and unconscious memories can be seen as potential psychological stressors. Resonance between Ii and Io may induce active conflicts if resistance occurs in the mental body; this conflict may cause specific metabolic activity in the brain and a stress response in the physical body, which permits adjustment to psychological stressors. The brainregulated stress response may be biphasic: cell death or growth induced by adrenergic molecular pathways during the conflict's unresolved phase and reversion to cell growth or death induced by cholinergic molecular pathways during the conflict's resolved phase. Case studies and data mining from PubMed suggest that this concept complies with the principles of holistic medicine and the scientific literature supporting its benefits. We suggest that the evolution of cancer can be seen as a biphasic stress response regulated by the brain to adapt to psychological stressors, which produce imbalance among the physical, mental, and information bodies.

  8. Cancer

    Science.gov (United States)

    ... Prostate cancer Lung cancer Colorectal cancer In US women, other than skin cancer the three most common cancers are: Breast cancer Lung cancer Colorectal cancer Some cancers are more common in certain parts of the world. For example, in Japan, there are many cases of stomach cancer . But ...

  9. Brain-derived neurotrophic factor (BDNF) -TrKB signaling modulates cancer-endothelial cells interaction and affects the outcomes of triple negative breast cancer.

    Science.gov (United States)

    Tsai, Yi-Fang; Tseng, Ling-Ming; Hsu, Chih-Yi; Yang, Muh-Hwa; Chiu, Jen-Hwey; Shyr, Yi-Ming

    2017-01-01

    There is good evidence that the tumor microenvironment plays an important role in cancer metastasis and progression. Our previous studies have shown that brain-derived neurotrophic factor (BDNF) participates in the process of metastasis and in the migration of cancer cells. The aim of this study was to investigate the role of BDNF on the tumor cell microenvironment, namely, the cancer cell-endothelial cell interaction of TNBC cells. We conducted oligoneucleotide microarray analysis of potential biomarkers that are able to differentiate recurrent TNBC from non-recurrent TNBC. The MDA-MB-231 and human endothelial HUVEC lines were used for this study and our approaches included functional studies, such as migration assay, as well as Western blot and real-time PCR analysis of migration and angiogenic signaling. In addition, we analyzed the survival outcome of TNBC breast cancer patients according to their expression level of BDNF using clinical samples. The results demonstrated that BDNF was able to bring about autocrinal (MDA-MB-231) and paracrinal (HUVECs) regulation of BDNF-TrkB gene expression and this affected cell migratory activity. The BDNF-induced migratory activity was blocked by inhibitors of ERK, PI3K and TrkB when MDA-MB-231 cells were examined, but only an inhibitor of ERK blocked this activity when HUVEC cells were used. Furthermore, decreased migratory activity was found for △BDNF and △TrkB cell lines. Ingenuity pathway analysis (IPA) of MDA-MB-231 cells showed that BDNF is a key factor that is able to regulate a network made up of metalloproteases and calmodulin. Protein expression levels in a tissue array of tumor slices were found to be correlated with patient prognosis and the results showed that there was significant correlation of TrkB expression, but not of BDNF. expressionwith patient DFS and OS. Our study demonstrates that up-regulation of the BDNF signaling pathway seems tobe involved in the mechanism associated with early recurrence in

  10. Carmustine and methotrexate in combination after whole brain radiation therapy in breast cancer patients presenting with brain metastases: a retrospective study

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    Poujol Sylvain

    2010-06-01

    Full Text Available Abstract Background Since 1999, patients presenting with brain metastases (BM from breast cancer (BC are treated in our institution with a carmustine (BCNU - methotrexate (MTX combination. We report here our clinical experience regarding this combination. Patients and Methods Patients were treated by a combination of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 day cycle. Treatment was continued until progression or unacceptable toxicity. Results 50 patients were treated between 1999 and 2007. 94% of the patients presented with concomitant extra-cerebral disease. Median number of previous metastatic setting chemotherapy regimens was 2 (0-5. Median number of cycles was 3 (1-20. There were 11 objective responses (23% [95%CI 12-37] among 48 evaluable patients. Median progression-free survival and overall survival (OS were 4.2 (95%CI: 2.8-5.3 and 6.9 (4.2-10.7 months respectively, with a one-year OS rate of 32% (20-46. Median Relative Dose Intensity for BCNU and MTX were 0.98 (0.31-1.1 and 0.96 (0.57-1.66 respectively. There were 2 presumed treatment-related deaths. One patient developed febrile neutropenia. Performance status, BS-BM score and presence of liver metastases were associated with OS in univariate analysis. Conclusions This combination appears to be effective and well tolerated in good performance status BC patients presenting with BM.

  11. Risk of brain metastases in patients with nonmetastatic lung cancer: Analysis of the Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) data.

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    Goncalves, Priscila H; Peterson, Stephanie L; Vigneau, Fawn D; Shore, Ronald D; Quarshie, William O; Islam, Khairul; Schwartz, Ann G; Wozniak, Antoinette J; Gadgeel, Shirish M

    2016-06-15

    Brain metastases (BM) remain an important cause of morbidity and mortality in patients with lung cancer. The current study evaluated population-based incidence and outcomes of BM in patients with nonmetastatic lung cancer. Patients diagnosed with nonmetastatic first primary lung cancer between 1973 and 2011 in the Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry were used for the current analysis. Age-adjusted odds ratios of developing BM based on various demographic characteristics and histology were calculated with 95% confidence intervals. Adjusted Cox proportional hazard ratios and log-rank tests of Kaplan-Meier survival curves were calculated to evaluate survival differences for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The incidence of BM in patients with nonmetastatic NSCLC and SCLC was 9% and 18%, respectively. There was variation in the incidence of BM according to NCSLC histology. The incidence of BM was higher in patients aged cancer varies according to histology, age, and sex. BM are associated with worse survival for patients with NSCLC but not those with SCLC. Cancer 2016;122:1921-7. © 2016 American Cancer Society. © 2016 American Cancer Society.

  12. Occupational and Environmental Risk Factors of Adult Primary Brain Cancers: A Systematic Review

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    J Gomes

    2011-03-01

    Full Text Available The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and highvoltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary.

  13. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    Science.gov (United States)

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary.

  14. SU-F-303-12: Implementation of MR-Only Simulation for Brain Cancer: A Virtual Clinical Trial

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    Glide-Hurst, C; Zheng, W; Kim, J; Wen, N; Chetty, I J [Henry Ford Health System, Detroit, MI (United States)

    2015-06-15

    Purpose: To perform a retrospective virtual clinical trial using an MR-only workflow for a variety of brain cancer cases by incorporating novel imaging sequences, tissue segmentation using phase images, and an innovative synthetic CT (synCT) solution. Methods: Ten patients (16 lesions) were evaluated using a 1.0T MR-SIM including UTE-DIXON imaging (TE = 0.144/3.4/6.9ms). Bone-enhanced images were generated from DIXON-water/fat and inverted UTE. Automated air segmentation was performed using unwrapped UTE phase maps. Segmentation accuracy was assessed by calculating intersection and Dice similarity coefficients (DSC) using CT-SIM as ground truth. SynCTs were generated using voxel-based weighted summation incorporating T2, FLAIR, UTE1, and bone-enhanced images. Mean absolute error (MAE) characterized HU differences between synCT and CT-SIM. Dose was recalculated on synCTs; differences were quantified using planar gamma analysis (2%/2 mm dose difference/distance to agreement) at isocenter. Digitally reconstructed radiographs (DRRs) were compared. Results: On average, air maps intersected 80.8 ±5.5% (range: 71.8–88.8%) between MR-SIM and CT-SIM yielding DSCs of 0.78 ± 0.04 (range: 0.70–0.83). Whole-brain MAE between synCT and CT-SIM was 160.7±8.8 HU, with the largest uncertainty arising from bone (MAE = 423.3±33.2 HU). Gamma analysis revealed pass rates of 99.4 ± 0.04% between synCT and CT-SIM for the cohort. Dose volume histogram analysis revealed that synCT tended to yield slightly higher doses. Organs at risk such as the chiasm and optic nerves were most sensitive due to their proximities to air/bone interfaces. DRRs generated via synCT and CT-SIM were within clinical tolerances. Conclusion: Our approach for MR-only simulation for brain cancer treatment planning yielded clinically acceptable results relative to the CT-based benchmark. While slight dose differences were observed, reoptimization of treatment plans and improved image registration can address

  15. Motexafin gadolinium combined with prompt whole brain radiotherapy prolongs time to neurologic progression in non-small-cell lung cancer patients with brain metastases: results of a phase III trial.

    Science.gov (United States)

    Mehta, Minesh P; Shapiro, William R; Phan, See C; Gervais, Radj; Carrie, Christian; Chabot, Pierre; Patchell, Roy A; Glantz, Michael J; Recht, Lawrence; Langer, Corey; Sur, Ranjan K; Roa, Wilson H; Mahe, Marc A; Fortin, Andre; Nieder, Carsten; Meyers, Christina A; Smith, Jennifer A; Miller, Richard A; Renschler, Markus F

    2009-03-15

    To determine the efficacy of motexafin gadolinium (MGd) in combination with whole brain radiotherapy (WBRT) for the treatment of brain metastases from non-small-cell lung cancer. In an international, randomized, Phase III study, patients with brain metastases from non-small-cell lung cancer were randomized to WBRT with or without MGd. The primary endpoint was the interval to neurologic progression, determined by a centralized Events Review Committee who was unaware of the treatment the patients had received. Of 554 patients, 275 were randomized to WBRT and 279 to WBRT+MGd. Treatment with MGd was well tolerated, and 92% of the intended doses were administered. The most common MGd-related Grade 3+ adverse events included liver function abnormalities (5.5%), asthenia (4.0%), and hypertension (4%). MGd improved the interval to neurologic progression compared with WBRT alone (15 vs. 10 months; p = 0.12, hazard ratio [HR] = 0.78) and the interval to neurocognitive progression (p = 0.057, HR = 0.78). The WBRT patients required more salvage brain surgery or radiosurgery than did the WBRT+MGd patients (54 vs. 25 salvage procedures, p < 0.001). A statistically significant interaction between the geographic region and MGd treatment effect (which was in the prespecified analysis plan) and between treatment delay and MGd treatment effect was found. In North American patients, where treatment was more prompt, a statistically significant prolongation of the interval to neurologic progression, from 8.8 months for WBRT to 24.2 months for WBRT+MGd (p = 0.004, HR = 0.53), and the interval to neurocognitive progression (p = 0.06, HR = 0.73) were observed. In the intent-to-treat analysis, MGd exhibited a favorable trend in neurologic outcomes. MGd significantly prolonged the interval to neurologic progression in non-small-cell lung cancer patients with brain metastases receiving prompt WBRT. The toxicity was acceptable.

  16. N-Acetylaspartate Metabolism Outside the Brain: Lipogenesis, Histone Acetylation, and Cancer

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    Juliane G. Bogner-Strauss

    2017-09-01

    Full Text Available N-acetylaspartate (NAA is a highly abundant brain metabolite. Aberrant NAA concentrations have been detected in many pathological conditions and although the function of NAA has been extensively investigated in the brain it is still controversial. Only recently, a role of NAA has been reported outside the brain. In brown adipocytes, which show high expression of the NAA-producing and the NAA-cleaving enzyme, the metabolism of NAA has been implicated in lipid synthesis and histone acetylation. Increased expression of N-acetyltransferase 8-like (Nat8l, the gene encoding the NAA synthesizing enzyme induces de novo lipogenesis and the brown adipocyte phenotype. Accordingly silencing of aspartoacylase, the NAA-cleaving enzyme, reduced brown adipocyte differentiation mechanistically by decreasing histone acetylation and gene transcription. Notably, the expression of Nat8l and the amount of NAA were also shown to be increased in several tumors and inversely correlate with patients’ survival. Additionally, Nat8l silencing reduced cell proliferation in tumor and non-tumor cells, while NAA supplementation could rescue it. However, the mechanism behind has not yet been clarified. It remains to be addressed whether NAA per se and/or its catabolism to acetate and aspartate, metabolites that have both been implicated in tumor growth, are valuable targets for future therapies.

  17. Development of a Bifunctional Aptamer Targeting the Transferrin Receptor and Epithelial Cell Adhesion Molecule (EpCAM) for the Treatment of Brain Cancer Metastases.

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    Macdonald, Joanna; Henri, Justin; Goodman, Lynda; Xiang, Dongxi; Duan, Wei; Shigdar, Sarah

    2017-04-19

    The treatment of brain disorders is greatly hindered by the presence of the blood-brain barrier, which restricts the overwhelming majority of small molecules from entering the brain. A novel approach by which to overcome this barrier is to target receptor mediated transport mechanisms present on the endothelial cell membranes. Therefore, we fused an aptamer that binds to epithelial cell adhesion molecule-expressing cancer cells to an aptamer targeting the transferrin receptor. This generated a proof of concept bifunctional aptamer that can overcome the blood-brain barrier and potentially specifically target brain disorders. The initial fusion of the two sequences enhanced the binding affinity of both aptamers while maintaining specificity. Additionally, mutations were introduced into both binding loops to determine their effect on aptamer specificity. The ability of the aptamer to transcytose the blood-brain barrier was then confirmed in vivo following a 1 nmol injection. This study has shown that through the fusion of two aptamer sequences, a bifunctional aptamer can be generated that has the potential to be developed for the specific treatment of brain disorders.

  18. Mapping Circular Current for a Single Brain Cancer Cell’s Spatial-Temporal Orientations Based on a Memristor/Memcapacitor

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    E. T. CHEN

    2014-12-01

    Full Text Available An increasing demand for improving neuronal imaging technologies in spatial- temporal resolution has emphasized in literature. Here we report a nanostructured memrisor/memcapacitor device is able to bio-communicate with the brain cancer cells without using tracers, antibodies and reagent. A “normal neuron” with a biomimetic acetylcholinesterase (ACHE active gorge was made by cross-linked multiple polymers on gold surface as Sensor 1 and an “abnormal neuron” without a hydrophobic ACHE lining as Sensor 2. A cyclic voltammetry (CV method was used. Three types of maps were constructed in light images, contour maps and in 3D dynamic interaction between cross-point location, direct-electron transfer and frequency. The spatial-temporal orientations of the dynamic interaction maps with and without cancer between 10-300 Hz were presented and compared in details regarding how the cancer broken the direct electron-relay circular current, how it changed the brain circuitry structure and its direction. Our results show Sensor 2 without a hydrophobic lining suffered more damage by the cancer than Sensor 1. The cancer’s behaviors toward the neuronal sensors were defined in spatial-temporal fine resolution/orientation in a single cancer concentration and the direction of the synapse network signaling pathway and the trajectory of cancer interaction were identified and mapped.

  19. HER-2 Expression in Brain Metastases from Colorectal Cancer and Corresponding Primary Tumors: A Case Cohort Series

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    Gianpiero Fasola

    2013-01-01

    Full Text Available Brain metastases (BM from colorectal cancer (CRC are a rare but increasing event. Surgical resection of oligometastatic disease, including BM, may produce a survival benefit in selected patients. Previous studies described the HER-2 expression patterns in CRC patients, but its prognostic role still remains controversial. Information on the HER-2 expression in BM from CRC is currently lacking. Among the over 500 patients treated at our Department of Neurosurgery in the last 13 years (1999–2012, we identified a cohort of 50 consecutive CRC patients resected for BM. Clinical data were retrospectively reviewed using electronic hospital charts and surgical notes. Formalin-fixed, paraffin-embedded tissue samples were retrieved and histologically reviewed. HER-2 status was assessed on 4-μm sections by HerceptTest™, and scored by two pathologists according to gastric cancer HER-2 status guidelines. In score 2+ cases HER-2 gene copy number was analyzed by FISH, performed using the PathVysion HER-2 DNA Probe Kit. Median age at time of BM resection was 65 years (35–82; most patients were males (60% with a good performance status. The majority of the BM were single (74% and sited in the supratentorial area (64%; 2–4 lesions were diagnosed in 9 patients (18%, and >4 in 3 patients (6%. The rate of HER-2 positivity (defined as IHC score 3+ or IHC score 2+ and FISH gene amplification was 8.1% for the primary CRC tumors and 12% for their corresponding BM. The concordance rate between primary tumors and matched BM was 89%. Median overall survival after neurosurgery was 6.5 months for HER-2 IHC score 0 vs. 4.6 months for HER-2 IHC score 1+/2+/3+; the difference was statistically significant (p = 0.01, Log-rank test. HER-2 positivity of our case cohort was low but comparable to literature. Concordance rate of HER-2 expression between BM and corresponding primary tumors is high and similar to those reported for breast and gastric cancers. Our data suggest a

  20. Neurocognitive function, brain-derived neurotrophic factor (BDNF) and IL-6 levels in cancer patients with depression.

    Science.gov (United States)

    Jehn, C F; Becker, B; Flath, B; Nogai, H; Vuong, L; Schmid, P; Lüftner, D

    2015-10-15

    Increased IL-6 and decreased brain-derived neurotrophic factor (BDNF) levels have been implicated in the pathophysiology of depression. The objective was to assess the influence of BDNF and IL-6 on cognitive function and depression in patients with cancer. Serum BDNF and plasma IL-6 were measured in patients with metastatic cancer. Diagnosis of depression was established according to DSM-IV criteria. Cognitive function was assessed by the Verbal Learning and Memory Test (VLMT). A total of 59 patients were recruited in this study. Only IL-6 levels were significantly elevated in patients with clinical depression (35.7 vs. 6.9 pg/ml; pBDNF levels (p=0.16). Patients with clinical depression showed significant impairment of short-term memory (STM) (24.4 vs. 37.5; p=0.01), but not of long-term memory (LTM) (3.9 vs. 2.8; p=0.3). STM was dependent on the level of BDNF and younger age (b=0.60; p=0.001; b= -0.63; p=0.003, respectively). IL-6 was not only strongly associated with depression, but was an independent predictor of BDNF level as well (b= -0.50; p=0.01). LTM was associated only with a good KPS (b=0.47; p=0.037). Hemoglobin levels and the prior number of chemotherapy lines were not predictive of memory performance. Low BDNF is associated with cognitive impairment, STM, in patients with cancer, however no influence on depression could be found. IL-6 is strongly associated with depression and an independent predictor of BDNF levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. A Comparative Study of Personality Traits and Brain Behavioral activation Systems and Inhibition in Women with Cancer, Cardiovascular Diseases and Normal Women

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    Sohrab Amiri

    2017-04-01

    Full Text Available Background and Objectives: Chronic diseases are among the most important causes of mortality. The aim of the current study was to compare the Brain/behavioral systems and Dark personality traits of Machiavellianism, narcissism, and psychopathy in cancer, cardiovascular female patients and normal women. Methods: In this study, 60 individuals were selected using available sampling in three groups of 20 cancer patients, cardiovascular patients, and normal subjects. Finally, in order to test the goals and hypotheses of the research, the participants were studied based on Behavioral Activation System and Behavioral Inhibition System, and Dark Triad traits. Data analysis was performed using multivariate ANOVA, univariate ANOVA and post-hoc tests. Results: In this study, there was a significant difference among the three groups in Brain/behavioral systems and traits of Machiavellianism, narcissism, and psychopathy, so that the cancer and cardiovascular patients had higher score in dark triad traits compared to normal individuals. Also, the cancer patients had a higher score in Machiavellianism trait compared to the cardiovascular patients. In the brain/behavioral systems, cardiovascular and cancer patients had higher score in behavioral inhibition system (BIS component compared to the normal individuals in the of behavioral inhibition system (BIS. Also, in the reward seeking subscale of behavioral activation system (BAS-f, cancer patients had a higher score compared to cardiovascular patients, which was significantly different. Conclusion: The results of this study indicated that cancer and cardiovascular patients, have greater extent of social disgusting personality traits as well as behavioral inhibition system as anxiety-predisposing factor.

  2. Metastasis of Pregnancy-Associated Breast Cancer (Suspected to Be Hereditary Breast and Ovarian Cancer to the Brain, Diagnosed at 18 Weeks’ Gestation: A Case Report and Review of the Literature

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    Tomohiro Okuda

    2016-01-01

    Full Text Available We report a case of pregnancy-associated breast cancer with metastasis to the brain, likely resulting from hereditary breast and ovarian cancer (HBOC. A 35-year-old woman (gravida 2, para 0-1-0-1 underwent a right mastectomy and right axillary dissection after a cesarean section at 30 years of age; her mother died at 47 years of age due to breast cancer. Histopathological examination indicated an invasive ductal carcinoma with triple-negative cancer (cancer stage 2B [pT3N0M0]. The patient refused adjuvant therapy because of the risk of infertility. After 4 years, she became pregnant naturally. At 18 weeks’ gestation, she experienced aphasia and dyslexia due to brain metastasis. The pregnancy was terminated at 21 weeks’ gestation after thorough counseling. Her family history, young-onset disease, and histopathological findings suggested HBOC. She declined genetic testing for BRCA1/2, though genetic counseling was provided. In cases of pregnancy-related breast cancer, consideration must be given to whether the pregnancy should be continued and to posttreatment fertility. HBOC should also be considered. Genetic counseling should be provided and the patient should be checked for the BRCA mutation, as it is meaningful for the future of any potential children. Genetic counseling should be provided even if the cancer is advanced or recurrent.

  3. Risk Factors for Brain Metastases in Locally Advanced Non-Small Cell Lung Cancer With Definitive Chest Radiation

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    Ji, Zhe; Bi, Nan; Wang, Jingbo; Hui, Zhouguang; Xiao, Zefen; Feng, Qinfu; Zhou, Zongmei; Chen, Dongfu; Lv, Jima; Liang, Jun; Fan, Chengcheng; Liu, Lipin; Wang, Luhua, E-mail: wlhwq@yahoo.com

    2014-06-01

    Purpose: We intended to identify risk factors that affect brain metastases (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving definitive radiation therapy, which may guide the choice of selective prevention strategies. Methods and Materials: The characteristics of 346 patients with stage III NSCLC treated with thoracic radiation therapy from January 2008 to December 2010 in our institution were retrospectively reviewed. BM rates were analyzed by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to determine independent risk factors for BM. Results: The median follow-up time was 48.3 months in surviving patients. A total of 74 patients (21.4%) experienced BM at the time of analysis, and for 40 (11.7%) of them, the brain was the first site of failure. The 1-year and 3-year brain metastasis rates were 15% and 28.1%, respectively. In univariate analysis, female sex, age ≤60 years, non-squamous cell carcinoma, T3-4, N3, >3 areas of lymph node metastasis, high lactate dehydrogenase and serum levels of tumor markers (CEA, NSE, CA125) before treatment were significantly associated with BM (P<.05). In multivariate analysis, age ≤60 years (P=.004, hazard ratio [HR] = 0.491), non-squamous cell carcinoma (P=.000, HR=3.726), NSE >18 ng/mL (P=.008, HR=1.968) and CA125 ≥ 35 U/mL (P=.002, HR=2.129) were independent risk factors for BM. For patients with 0, 1, 2, and 3 to 4 risk factors, the 3-year BM rates were 7.3%, 18.9%, 35.8%, and 70.3%, respectively (P<.001). Conclusions: Age ≤60 years, non-squamous cell carcinoma, serum NSE >18 ng/mL, and CA125 ≥ 35 U/mL were independent risk factors for brain metastasis. The possibilities of selectively using prophylactic cranial irradiation in higher-risk patients with LA-NSCLC should be further explored in the future.

  4. Turbofan Duct Propagation Model

    Science.gov (United States)

    Lan, Justin H.; Posey, Joe W. (Technical Monitor)

    2001-01-01

    The CDUCT code utilizes a parabolic approximation to the convected Helmholtz equation in order to efficiently model acoustic propagation in acoustically treated, complex shaped ducts. The parabolic approximation solves one-way wave propagation with a marching method which neglects backwards reflected waves. The derivation of the parabolic approximation is presented. Several code validation cases are given. An acoustic lining design process for an example aft fan duct is discussed. It is noted that the method can efficiently model realistic three-dimension effects, acoustic lining, and flow within the computational capabilities of a typical computer workstation.

  5. Propagation of waves

    CERN Document Server

    David, P

    2013-01-01

    Propagation of Waves focuses on the wave propagation around the earth, which is influenced by its curvature, surface irregularities, and by passage through atmospheric layers that may be refracting, absorbing, or ionized. This book begins by outlining the behavior of waves in the various media and at their interfaces, which simplifies the basic phenomena, such as absorption, refraction, reflection, and interference. Applications to the case of the terrestrial sphere are also discussed as a natural generalization. Following the deliberation on the diffraction of the "ground? wave around the ear

  6. Brain activity correlated with food preferences: a functional study comparing advanced non-small cell lung cancer patients with and without anorexia.

    Science.gov (United States)

    Sánchez-Lara, Karla; Arrieta, Oscar; Pasaye, Eric; Laviano, Alessandro; Mercadillo, Roberto E; Sosa-Sánchez, Ricardo; Méndez-Sánchez, Nahum

    2013-01-01

    The aim of this study was to examine the brain activity manifested while non-small cell lung cancer (NSCLC) patients with and without anorexia were exposed to visual food stimuli. We included 26 treatment-naïve patients who had been recently diagnosed with advanced NSCLC. Patients with brain metastasis were excluded. The patients were classified into anorectic and non-anorectic groups. Data from functional magnetic resonance imaging based on blood oxygen level-dependent (BOLD) signals were analyzed while the patients perceived pleasant and unpleasant food pictures. The brain records were analyzed with SPM 5 using a voxelwise multiple regression analysis. The non-anorexic patients demonstrated BOLD activation, comprising frontal brain regions in the premotor and the prefrontal cortices, only while watching unpleasant stimuli. The anorectic patients demonstrated no activation while watching the pleasant and unpleasant food pictures. Anorectic patients with lung cancer present a lack of activation in the brain regions associated with food stimuli processing. These results are consistent with experiences in the clinical environment: Patients describe themselves as not experiencing sensations of hunger or having an appetite. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. In vivo visualization and ex vivo quantification of murine breast cancer cells in the mouse brain using MRI cell tracking and electron paramagnetic resonance.

    Science.gov (United States)

    Danhier, Pierre; Magat, Julie; Levêque, Philippe; De Preter, Géraldine; Porporato, Paolo E; Bouzin, Caroline; Jordan, Bénédicte F; Demeur, Gladys; Haufroid, Vincent; Feron, Olivier; Sonveaux, Pierre; Gallez, Bernard

    2015-03-01

    Cell tracking could be useful to elucidate fundamental processes of cancer biology such as metastasis. The aim of this study was to visualize, using MRI, and to quantify, using electron paramagnetic resonance (EPR), the entrapment of murine breast cancer cells labeled with superparamagnetic iron oxide particles (SPIOs) in the mouse brain after intracardiac injection. For this purpose, luciferase-expressing murine 4 T1-luc breast cancer cells were labeled with fluorescent Molday ION Rhodamine B SPIOs. Following intracardiac injection, SPIO-labeled 4 T1-luc cells were imaged using multiple gradient-echo sequences. Ex vivo iron oxide quantification in the mouse brain was performed using EPR (9 GHz). The long-term fate of 4 T1-luc cells after injection was characterized using bioluminescence imaging (BLI), brain MRI and immunofluorescence. We observed hypointense spots due to SPIO-labeled cells in the mouse brain 4 h after injection on T2 *-weighted images. Histology studies showed that SPIO-labeled cancer cells were localized within blood vessels shortly after delivery. Ex vivo quantification of SPIOs showed that less than 1% of the injected cells were taken up by the mouse brain after injection. MRI experiments did not reveal the development of macrometastases in the mouse brain several days after injection, but immunofluorescence studies demonstrated that these cells found in the brain established micrometastases. Concerning the metastatic patterns of 4 T1-luc cells, an EPR biodistribution study demonstrated that SPIO-labeled 4 T1-luc cells were also entrapped in the lungs of mice after intracardiac injection. BLI performed 6 days after injection of 4 T1-luc cells showed that this cell line formed macrometastases in the lungs and in the bones. Conclusively, EPR and MRI were found to be complementary for cell tracking applications. MRI cell tracking at 11.7 T allowed sensitive detection of isolated SPIO-labeled cells in the mouse brain, whereas EPR

  8. KISS1 tumor suppressor restricts angiogenesis of breast cancer brain metastases and sensitizes them to oncolytic virotherapy in vitro.

    Science.gov (United States)

    Platonov, Mikhail E; Borovjagin, Anton V; Kaverina, Natalya; Xiao, Ting; Kadagidze, Zaira; Lesniak, Maciej; Baryshnikova, Marya; Ulasov, Ilya V

    2018-03-28

    KISS1 tumor suppressor protein regulates cancer cell invasion via MMP9 metalloproteinase. Downregulation of KISS1 gene expression promotes progression of breast cancer and melanoma, resulting in the development of distant metastases. In the current study, we investigated whether restoration of KISS1 expression in KISS1-deficient human metastatic breast cancer cells holds potential as an advanced anticancer strategy. To this end we engineered an infectivity-enhanced conditionally-replicative human adenovirus type 5 encoding KISS1 as an "arming" transgene in the Ad5 E3 region for an ectopic KISS1 expression in transduced cancer cells. The oncolytic potential of the vector was examined using brain-invading metastatic clones of CN34 and MDA-MB-231 breast cancer cells, which supported high levels of AdKISS1 replication, correlating with a robust CRAd-mediated cytotoxicity. Secretion of cellular factors responsible for tumor angiogenesis, cell-to-cell communication and anti-tumoral immune responses upon KISS1 expression in breast cancer cells was analyzed by a RayBiotech Kiloplex Quantibody array. Overall, our results indicate that KISS1 transgene expression provides an important benefit for CRAd-mediated cytotoxicity in breast cancer cells and holds potential as an anticancer treatment in conjunction with oncolytic virotherapy of breast and other metastatic cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Problem Solving and Emotional Distress Among Brain and Breast Cancer Survivors

    Science.gov (United States)

    2007-03-30

    astrocytic tumors, oligodendroglial tumors, mixed gliomas, ependymal tumors, choroids- plexus tumors, neuronal and mixed neuronal-glial tumors, pineal...alongside their medical disease (Bambauer, Locke , Aupont, Mullan, & McLaughlin, 2005). The HADS also appears to be a justified target of...side effect experience in women receiving treatment for breast cancer. Oncology Nursing Forum, 28, 567-574. Bambauer, K. Z., Locke , S. E., Aupont

  10. Mobile phone use and risk of brain neoplasms and other cancers: prospective study.

    Science.gov (United States)

    Benson, Victoria S; Pirie, Kirstin; Schüz, Joachim; Reeves, Gillian K; Beral, Valerie; Green, Jane

    2013-06-01

    Results from some retrospective studies suggest a possible increased risk of glioma and acoustic neuroma in users of mobile phones. The relation between mobile phone use and incidence of intracranial central nervous system (CNS) tumours and other cancers was examined in 791,710 middle-aged women in a UK prospective cohort, the Million Women Study. Cox regression models were used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Women reported mobile phone use in 1999 to 2005 and again in 2009. During 7 years' follow-up, 51,680 incident invasive cancers and 1,261 incident intracranial CNS tumours occurred. Risk among ever vs never users of mobile phones was not increased for all intracranial CNS tumours (RR = 1.01, 95% CI = 0.90-1.14, P = 0.82), for specified CNS tumour types nor for cancer at 18 other specified sites. For long-term users compared with never users, there was no appreciable association for glioma (10+ years: RR = 0.78, 95% CI = 0.55-1.10, P = 0.16) or meningioma (10+ years: RR = 1.10, 95% CI = 0.66-1.84, P = 0.71). For acoustic neuroma, there was an increase in risk with long term use vs never use (10+ years: RR = 2.46, 95% CI = 1.07-5.64, P = 0.03), the risk increasing with duration of use (trend among users, P = 0.03). In this large prospective study, mobile phone use was not associated with increased incidence of glioma, meningioma or non-CNS cancers.

  11. Vascular endothelial growth factor blockade alters magnetic resonance imaging biomarkers of vascular function and decreases barrier permeability in a rat model of lung cancer brain metastasis.

    Science.gov (United States)

    Pishko, Gregory L; Muldoon, Leslie L; Pagel, Michael A; Schwartz, Daniel L; Neuwelt, Edward A

    2015-02-17

    Blockade of vascular endothelial growth factor (VEGF) to promote vascular normalization and inhibit angiogenesis has been proposed for the treatment of brain metastases; however, vascular normalization has not been well-characterized in this disease. We investigated the effect of treatment with bevacizumab anti-VEGF antibody on magnetic resonance imaging (MRI) biomarkers of brain tumor vascular characteristics in comparison to small molecule delivery in a rat model of human lung cancer brain metastasis. Athymic rats with A549 human lung adenocarcinoma intracerebral xenografts underwent MRI at 11.75 T before and one day after treatment with bevacizumab (n = 8) or saline control (n = 8) to evaluate tumor volume, free water content (edema), blood volume and vascular permeability (Ktrans). One day later, permeability to 14C-aminoisobutyric acid (AIB) was measured in tumor and brain to assess the penetration of a small drug-like molecule. In saline control animals, tumor volume, edema and permeability increased over the two day assessment period. Compared to controls, bevacizumab treatment slowed the rate of tumor growth (P = 0.003) and blocked the increase in edema (P = 0.033), but did not alter tumor blood volume. Bevacizumab also significantly reduced Ktrans (P = 0.033) and AIB passive permeability in tumor (P = 0.04), but not to peritumoral tissue or normal brain. Post-treatment Ktrans correlated with AIB levels in the bevacizumab-treated rats but not in the saline controls. The correlation of an MRI biomarker for decreased vascular permeability with decreased AIB concentration in tumor after antiangiogenic treatment suggests that bevacizumab partially restored the normal low permeability characteristics of the blood-brain barrier in a model of human lung cancer brain metastasis.

  12. Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Sunit [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Chan, Michael D., E-mail: mchan@wfubmc.edu [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States); Lovato, James F. [Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University, Winston-Salem, North Carolina (United States); Bourland, J. Daniel; Munley, Michael T.; Guzman, Allan F. de; Shaw, Edward G.; Urbanic, James J.; McMullen, Kevin P. [Department of Radiation Oncology, Wake Forest University, Winston-Salem, North Carolina (United States)

    2012-05-01

    Purpose: Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC). Methods and Materials: Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10-24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival. Results: Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006). Conclusions: GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients' ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to

  13. Flood Wave Propagation

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 5. Flood Wave Propagation-The Saint Venant Equations. P P Mujumdar. General Article Volume 6 Issue 5 May 2001 pp 66-73. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/006/05/0066-0073 ...

  14. Uncertainty Propagation in OMFIT

    Science.gov (United States)

    Smith, Sterling; Meneghini, Orso; Sung, Choongki

    2017-10-01

    A rigorous comparison of power balance fluxes and turbulent model fluxes requires the propagation of uncertainties in the kinetic profiles and their derivatives. Making extensive use of the python uncertainties package, the OMFIT framework has been used to propagate covariant uncertainties to provide an uncertainty in the power balance calculation from the ONETWO code, as well as through the turbulent fluxes calculated by the TGLF code. The covariant uncertainties arise from fitting 1D (constant on flux surface) density and temperature profiles and associated random errors with parameterized functions such as a modified tanh. The power balance and model fluxes can then be compared with quantification of the uncertainties. No effort is made at propagating systematic errors. A case study will be shown for the effects of resonant magnetic perturbations on the kinetic profiles and fluxes at the top of the pedestal. A separate attempt at modeling the random errors with Monte Carlo sampling will be compared to the method of propagating the fitting function parameter covariant uncertainties. Work supported by US DOE under DE-FC02-04ER54698, DE-FG2-95ER-54309, DE-SC 0012656.

  15. Effective treatment of glioblastoma requires crossing the blood-brain barrier and targeting tumors including cancer stem cells: The promise of nanomedicine.

    Science.gov (United States)

    Kim, Sang-Soo; Harford, Joe B; Pirollo, Kathleen F; Chang, Esther H

    2015-12-18

    Glioblastoma multiforme (GBM) is the most aggressive and lethal type of brain tumor. Both therapeutic resistance and restricted permeation of drugs across the blood-brain barrier (BBB) play a major role in the poor prognosis of GBM patients. Accumulated evidence suggests that in many human cancers, including GBM, therapeutic resistance can be attributed to a small fraction of cancer cells known as cancer stem cells (CSCs). CSCs have been shown to have stem cell-like properties that enable them to evade traditional cytotoxic therapies, and so new CSC-directed anti-cancer therapies are needed. Nanoparticles have been designed to selectively deliver payloads to relevant target cells in the body, and there is considerable interest in the use of nanoparticles for CSC-directed anti-cancer therapies. Recent advances in the field of nanomedicine offer new possibilities for overcoming CSC-mediated therapeutic resistance and thus significantly improving management of GBM. In this review, we will examine the current nanomedicine approaches for targeting CSCs and their therapeutic implications. The inhibitory effect of various nanoparticle-based drug delivery system towards CSCs in GBM tumors is the primary focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Interactions between αv-Integrin and HER2 and Their Role in the Invasive Phenotype of Breast Cancer Cells In Vitro and in Rat Brain.

    Science.gov (United States)

    Lal, Sangeet; Kersch, Cymon; Beeson, Kathleen A; Wu, Y Jeffrey; Muldoon, Leslie L; Neuwelt, Edward A

    2015-01-01

    We tested the hypothesis that αv-integrin and the human epidermal growth factor receptor type 2 (HER2) interact with each other in brain trophic metastatic breast cancer cells and influence their invasive phenotype. Clones of MDA-MB231BR human breast cancer cells with stable knock down of αv-integrin in combination with high or low levels of HER2 were created. The interactions of these two proteins and their combined effect on cell migration and invasion were investigated in vitro and in vivo. Knockdown of αv-integrin in MDA-MB231BR clones altered the actin cytoskeleton and cell morphology. HER2 co-precipitated with αv-integrin in three breast cancer cell lines in vitro, suggesting they complex in cells. Knockdown of αv-integrin altered HER2 localization from its normal membrane position to a predominantly lysosomal localization. When αv-integrin expression was decreased by 69-93% in HER2-expressing cells, cellular motility was significantly reduced. Deficiency of both αv-integrin and HER2 decreased cellular migration and invasion by almost 90% compared to cells expressing both proteins (Pcancer cells and may regulate HER2 localization. The combined impacts of αv-integrin and HER2 influence the invasive phenotype of breast cancer cells. Targeting αv-integrin in HER2-positive breast cancer may slow growth and decrease infiltration in the normal brain.

  17. Nausea as a sentinel symptom for cytotoxic chemotherapy effects on the gut-brain axis among women receiving treatment for recurrent ovarian cancer: an exploratory analysis.

    Science.gov (United States)

    Donovan, Heidi S; Hagan, Teresa L; Campbell, Grace B; Boisen, Michelle M; Rosenblum, Leah M; Edwards, Robert P; Bovbjerg, Dana H; Horn, Charles C

    2016-06-01

    Nausea is a common and potentially serious effect of cytotoxic chemotherapy for recurrent ovarian cancer and may function as a sentinel symptom reflecting adverse effects on the gut-brain axis (GBA) more generally, but research is scant. As a first exploratory test of this GBA hypothesis, we compared women reporting nausea to women not reporting nausea with regard to the severity of other commonly reported symptoms in this patient population. A secondary analysis of data systematically collected from women in active chemotherapy treatment for recurrent ovarian cancer (n = 158) was conducted. The Symptom Representation Questionnaire (SRQ) provided severity ratings for 22 common symptoms related to cancer and chemotherapy. Independent sample t tests and regression analyses were used to compare women with and without nausea with regard to their experience of other symptoms. Nausea was reported by 89 (56.2 %) women. Symptoms that were significantly associated with nausea in bivariate and regression analyses included abdominal bloating, bowel disturbances, dizziness, depression, drowsiness, fatigue, headache, lack of appetite, memory problems, mood swings, shortness of breath, pain, sleep disturbance, urinary problems, vomiting, and weight loss. Symptoms that were not associated with nausea included hair loss, numbness and tingling, sexuality concerns, and weight gain. Nausea experienced during chemotherapy for recurrent ovarian cancer may be an indicator of broader effects on the gut-brain axis. A better understanding of the mechanisms underlying these effects could lead to the development of novel supportive therapies to increase the tolerability and effectiveness of cancer treatment.

  18. Risk factors for brain metastasis as a first site of disease recurrence in patients with HER2 positive early stage breast cancer treated with adjuvant trastuzumab.

    Science.gov (United States)

    Tonyali, Onder; Coskun, Ugur; Yuksel, Sinemis; Inanc, Mevlude; Bal, Oznur; Akman, Tulay; Yazilitas, Dogan; Ulas, Arife; Kucukoner, Mehmet; Aksoy, Asude; Demirci, Umut; Uysal, Mukremin; Tanriverdi, Ozgur; Gunaydin, Yusuf; Sumbul, Ahmet Taner; Yildiz, Ramazan; Karaca, Halit; Oksuzoglu, Berna; Ciltas, Aydin; Buyukberber, Suleyman; Benekli, Mustafa

    2016-02-01

    The aim of this study was to determine risk factors for brain metastasis as the first site of disease recurrence in patients with HER2-positive early-stage breast cancer (EBC) who received adjuvant trastuzumab. Medical records of 588 female patients who received 52-week adjuvant trastuzumab from 14 centers were evaluated. Cumulative incidence functions for brain metastasis as the first site of disease recurrence and the effect of covariates on brain metastasis were evaluated in a competing risk analysis and competing risks regression, respectively. Median follow-up time was 36 months. Cumulative incidence of brain metastasis at 12 months and 24 months was 0.6% and 2%, respectively. HER2-enriched subtype (ER- and PR-) tumor (p = 0.001, RR: 3.4, 95% CI: 1.33-8.71) and stage 3 disease (p = 0.0032, RR: 9.39, 95% CI: 1.33-8.71) were significant risk factors for development of brain metastasis as the first site of recurrence. In patients with HER2 positive EBC who received adjuvant trastuzumab, HER2-enriched subtype (ER- and PR-) tumor and stage 3 disease were associated with increased risk of brain metastasis as the first site of disease recurrence. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. A Database for Propagation Models

    Science.gov (United States)

    Kantak, Anil V.; Rucker, James

    1997-01-01

    The Propagation Models Database is designed to allow the scientists and experimenters in the propagation field to process their data through many known and accepted propagation models. The database is an Excel 5.0 based software that houses user-callable propagation models of propagation phenomena. It does not contain a database of propagation data generated out of the experiments. The database not only provides a powerful software tool to process the data generated by the experiments, but is also a time- and energy-saving tool for plotting results, generating tables and producing impressive and crisp hard copy for presentation and filing.

  20. Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

    Science.gov (United States)

    2009-10-01

    conditions is promising ( 1 ) . Furthermore, it has previously 1. Introduction John S. Yu (ed.), Cancer Stem Cells, Methods in Molecular Biology, vol...D, Aucoin R, Blust J, Murry B, Greiter‐ Wilke  A: p75 neurotrophin receptor functions as a survival receptor in brain‐metastatic melanoma cells, J...domains. Nat Biotechnol 23(9): 1126-1136. (39) Colcher D, Pavlinkova G, Beresford G, Booth BJ, Choudhury A, Batra SK (1998) Pharmacokinetics and

  1. Propagating Instabilities in Solids

    Science.gov (United States)

    Kyriakides, Stelios

    1998-03-01

    Instability is one of the factors which limit the extent to which solids can be loaded or deformed and plays a pivotal role in the design of many structures. Such instabilities often result in localized deformation which precipitates catastrophic failure. Some materials have the capacity to recover their stiffness following a certain amount of localized deformation. This local recovery in stiffness arrests further local deformation and spreading of the instability to neighboring material becomes preferred. Under displacement controlled loading the propagation of the transition fronts can be achieved in a steady-state manner at a constant stress level known as the propagation stress. The stresses in the transition fronts joining the highly deformed zone to the intact material overcome the instability nucleation stresses and, as a result, the propagation stress is usually much lower than the stress required to nucleate the instability. The classical example of this class of material instabilities is L/"uders bands which tend to affect mild steels and other metals. Recent work has demonstrated that propagating instabilities occur in several other materials. Experimental and analytical results from four examples will be used to illustrate this point: First the evolution of L=FCders bands in mild steel strips will be revisited. The second example involves the evolution of stress induced phase transformations (austenite to martensite phases and the reverse) in a shape memory alloy under displacement controlled stretching. The third example is the crushing behavior of cellular materials such as honeycombs and foams made from metals and polymers. The fourth example involves the axial broadening/propagation of kink bands in aligned fiber/matrix composites under compression. The microstructure and, as a result, the micromechanisms governing the onset, localization, local arrest and propagation of instabilities in each of the four materials are vastly different. Despite this

  2. Outcomes and Prognostic Factors in Women With 1 to 3 Breast Cancer Brain Metastases Treated With Definitive Stereotactic Radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Yang, T. Jonathan [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Oh, Jung Hun [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Folkert, Michael R.; Gupta, Gaorav [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Shi, Weiji; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Morikawa, Aki; Seidman, Andrew [Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Brennan, Cameron [Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Yamada, Yoshiya; Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Beal, Kathryn, E-mail: BealK@MSKCC.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

    2014-11-01

    Background: With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. Methods and Materials: We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess overall survival (OS), regional failure (RF), and local failure (LF). Associations between clinical factors and outcomes were tested using Cox regression. A point scoring system was used to stratify patients based on OS, and the predictive power was tested with concordance probability estimate (CPE). Results: The median OS was 17.6 months. The 12-month RF and LF rates were 45% and 10%, respectively. On multivariate analysis, >1 lesion (hazard ratio [HR] = 1.6, P=.02), triple-negative (TN) disease (HR=2.0, P=.006), and active extracranial disease (ED) (HR=2.7, P<.0001) were significantly associated with worse OS. The point score system was defined using proportional simplification of the multivariate Cox proportional hazards regression function. The median OS for patients with 3.0-4.0 points (n=37), 4.5-5.5 points (n=28), 6.0-6.5 points (n=37), and 8-8.5 points (n=34) were 9.2, 15.6, 25.1, and 45.1 months, respectively (P<.0001, CPE = 0.72). Active ED (HR=2.4, P=.0007) was significantly associated with RF. Higher risk for LF was significantly associated with larger BM size (HR=3.1, P=.0001). Conclusion: Patients with >1 BM, active ED, and TN had the highest risk of death after SRS. Active ED is an important prognostic factor for OS and intracranial control.

  3. Biological and clinical implications of cancer stem cells in primary brain tumors

    Directory of Open Access Journals (Sweden)

    Marcello eMaugeri-Saccà

    2013-01-01

    Full Text Available Despite therapeutic advances, glioblastoma multiforme (GBM remains a lethal disease. The infiltrative nature of this disease and the presence of a cellular population resistant to current medical treatments account for the poor prognosis of these patients. Growing evidence indicates the existence of a fraction of cancer cells sharing the functional properties of adult stem cells, including self-renewal and a greater ability to escape chemo-radiotherapy-induced death stimuli. Therefore, these cells are commonly defined as cancer stem cells (GBM-SCs. The initial GBM-SC concept has been challenged, and refined according to the emerging molecular taxonomy of GBM. This allowed to postulate the existence of multiple CSC types, each one driving a given molecular entity. Furthermore, it is becoming increasingly clear that GBM-SCs thrive through a dynamic and bidirectional interaction with the surrounding microenvironment. In this article, we discuss recent advances in GBM-SC biology, mechanisms through which these cells adapt to hostile conditions, pharmacological strategies for selectively killing GBM-SCs, and how novel CSC-associated endpoints have been investigated in the clinical setting.

  4. Impact of preexisting tumor necrosis on the efficacy of stereotactic radiosurgery in the treatment of brain metastases in women with breast cancer.

    Science.gov (United States)

    Xu, Zhiyuan; Marko, Nicholas F; Angelov, Lilyana; Barnett, Gene H; Chao, Samuel T; Vogelbaum, Michael A; Suh, John H; Weil, Robert J

    2012-03-01

    Breast cancer is the second most common source of brain metastasis. Stereotactic radiosurgery (SRS) can be an effective treatment for some patients with brain metastasis (BM). Necrosis is a common feature of many brain tumors, including BM; however, the influence of tumor necrosis on treatment efficacy of SRS in women with breast cancer metastatic to the brain is unknown. A cohort of 147 women with breast cancer and BM treated consecutively with SRS over 10 years were studied. Of these, 80 (54.4%) had necrosis identified on pretreatment magnetic resonance images and 67 (46.4%) did not. Survival times were computed using the Kaplan-Meier method. Log-rank tests were used to compare groups with respect to survival times, Cox proportional hazards regression models were used to perform univariate and multivariate analyses, and chi-square and Fisher exact tests were used to compare clinicopathologic covariates. Neurological survival (NS) and survival after SRS were decreased in BM patients with necrosis at the time of SRS compared with patients without necrosis by 32% and 27%, respectively (NS median survival, 25 vs 17 months [log-rank test, P = .006]; SRS median survival, 15 vs 11 months [log-rank test, P = .045]). On multivariate analysis, HER2 amplification status and necrosis influenced NS and SRS after adjusting for standard clinical features, including BM number, size, and volume as well as Karnofsky performance status. Neuroimaging evidence of necrosis at the time of SRS significantly diminished the efficacy of therapy and was a potent prognostic marker. Copyright © 2011 American Cancer Society.

  5. Different early effect of irradiation in brain and small cell lung cancer examined by in vivo 31P-magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Kristjansen, P E; Pedersen, A G; Quistorff, B

    1992-01-01

    Early effects of irradiation were evaluated by non-invasive in vivo 31P-magnetic resonance spectroscopy (31P-MRS) of two small cell lung cancer (SCLC) tumor lines CPH SCCL 54A and 54B, in nude mice. The tumors were originally derived from the same patient and have similar morphology and growth......-MRS. No effect was observed in brain at any dose level. In contrast, 40 Gy induced a statistically significant reduction in ATP/Pi ratio during the 12-h post-irradiation period. This effect was more pronounced in 54A than in 54B. Some reduction was observed following 10 Gy, whereas 2.5 Gy induced no changes...... in ATP/Pi. The differential effect on tumors and brain might be relevant for monitoring irradiation effects by in vivo 31P-MRS in patients with brain metastases....

  6. In vivo evaluation of P-glycoprotein and breast cancer resistance protein modulation in the brain using [{sup 11}C]gefitinib

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Kazunori [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: kawamur@nirs.go.jp; Yamasaki, Tomoteru; Yui, Joji; Hatori, Akiko; Konno, Fujiko; Kumata, Katsushi; Irie, Toshiaki; Fukumura, Toshimitsu; Suzuki, Kazutoshi; Kanno, Iwao; Zhang Mingrong [Department of Molecular Probes, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2009-04-15

    Gefitinib (Iressa) is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. Recent studies confirmed that gefitinib interacted with the breast cancer resistance protein (BCRP) at submicromolar concentrations, whereas other multidrug transporters, including P-glycoprotein (P-gp), showed much lower reactivity toward gefitinib. Recently, many tracers for positron emission tomography (PET) have been prepared to study P-gp function in vivo; however, PET tracers had not been evaluated for both P-gp and BCRP modulation in the brain. Therefore, we evaluated in vivo brain penetration-mediated P-gp and BCRP in mice using [{sup 11}C]gefitinib. Co-injection with gefitinib (over 50 mg/kg), a nonspecific P-gp modul