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Sample records for brain cancer combination

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

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    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.

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

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

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    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.

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

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    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

  5. A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases.

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    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.

  6. Enhancement of apoptotic activities on brain cancer cells via the combination of γ-tocotrienol and jerantinine A.

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    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

  7. Brain cancer spreads

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    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)....

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

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    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.

  9. 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.

  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. 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. 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.

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    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.

  13. Brain metastases from colorectal cancer

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    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....

  14. 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

  15. 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.

  16. Non-invasive Photodynamic Therapy in Brain Cancer by Use of Tb3+-Doped LaF3 Nanoparticles in Combination with Photosensitizer Through X-ray Irradiation: A Proof-of-Concept Study

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    Chen, Min-Hua; Jenh, Yi-Jhen; Wu, Sheng-Kai; Chen, Yo-Shen; Hanagata, Nobutaka; Lin, Feng-Huei

    2017-01-01

    The use of photodynamic therapy (PDT) in the treatment of brain cancer has produced exciting results in clinical trials over the past decade. PDT is based on the concept that a photosensitizer exposed to a specific light wavelength produces the predominant cytotoxic agent, to destroy tumor cells. However, delivering an efficient light source to the brain tumor site is still a challenge. The light source should be delivered by placing external optical fibers into the brain at the time of surgical debulking of the tumor. Consequently, there exists the need for a minimally invasive treatment for brain cancer PDT. In this study, we investigated an attractive non-invasive option on glioma cell line by using Tb3+-doped LaF3 scintillating nanoparticles (LaF3:Tb) in combination with photosensitizer, meso-tetra(4-carboxyphenyl)porphyrin (MTCP), followed by activation with soft X-ray (80 kVp). Scintillating LaF3:Tb nanoparticles, with sizes of approximately 25 nm, were fabricated. The particles have a good dispersibility in aqueous solution and possess high biocompatibility. However, significant cytotoxicity was observed in the glioma cells while the LaF3:Tb nanoparticles with MTCP were exposed under X-ray irradiation. The study has demonstrated a proof of concept as a non-invasive way to treat brain cancer in the future.

  17. Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with brain metastases.

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    Subbiah, Vivek; Berry, Jenny; Roxas, Michael; Guha-Thakurta, Nandita; Subbiah, Ishwaria Mohan; Ali, Siraj M; McMahon, Caitlin; Miller, Vincent; Cascone, Tina; Pai, Shobha; Tang, Zhenya; Heymach, John V

    2015-07-01

    In-frame fusion KIF5B (the-kinesin-family-5B-gene)-RET transcripts have been characterized in 1-2% of non-small cell lung cancers and are known oncogenic drivers. The RET tyrosine kinase inhibitor, vandetanib, suppresses fusion-induced, anchorage-independent growth activity. In vitro studies have shown that vandetanib is a high-affinity substrate of breast cancer resistance protein (Bcrp1/Abcg2) but is not transported by P-glycoprotein (P-gp), limiting its blood-brain barrier penetration. A co-administration strategy to enhance the brain accumulation of vandetanib by modulating P-gp/Abcb1- and Bcrp1/Abcg2-mediated efflux with mTOR inhibitors, specifically everolimus, was shown to increase the blood-brain barrier penetration. We report the first bench-to-bedside evidence that RET inhibitor combined with an mTOR inhibitor is active against brain-metastatic RET-rearranged lung cancer and the first evidence of blood-brain barrier penetration. A 74-year-old female with progressive adenocarcinoma of the lung (wild-type EGFR and no ALK rearrangement) presented for therapy options. A deletion of 5'RET was revealed by FISH assay, indicating RET-gene rearrangement. Because of progressive disease in the brain, she was enrolled in a clinical trial with vandetanib and everolimus (NCT01582191). Comprehensive genomic profiling revealed fusion of KIF5B (the-kinesin-family-5B-gene) and RET, in addition to AKT2 gene amplification. After two cycles of therapy a repeat MRI brain showed a decrease in the intracranial disease burden and PET/CT showed systemic response as well. Interestingly, AKT2 amplification seen is a critical component of the PI3K/mTOR pathway, alterations of which has been associated with both de novo and acquired resistance to targeted therapy. The addition of everolimus may have both overcome the AKT2 amplification to produce a response in addition to its direct effects on the RET gene. Our case report forms the first evidence of blood-brain barrier penetration by

  18. 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.

  19. Curcumin in combined cancer therapy.

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    Troselj, Koraljka Gall; Kujundzic, Renata Novak

    2014-01-01

    The mechanisms of beneficial preventive and therapeutic effects achieved by traditional and complementary medicine are currently being deciphered in molecular medicine. Curcumin, a yellow-colored polyphenol derived from the rhizome of turmeric (Curcuma longa), influences a wide variety of cellular processes through the reshaping of many molecular targets. One of them, nuclear factor kappa B (NF-κB), represents a strong mediator of inflammation and, in a majority of systems, supports the pro-proliferative features of cancer cells. The application of various anticancer drugs, cytostatics, triggers signals which lead to an increase in cellular NF-κB activity. As a consequence, cancer cells often reshape their survival signaling pathways and, over time, become resistant to applied therapy. Curcumin was shown to be a strong inhibitor of NF-κB activity and its inhibitory effect on NF-κB related pathways often leads to cellular apoptotic response. All these facts, tested and confirmed in many different biological systems, have paved the way for research aimed to elucidate the potential beneficial effects of combining curcumin and various anti-cancer drugs in order to establish more efficient and less toxic cancer treatment modalities. This review addresses certain aspects of NF-κB-related inflammatory response, its role in carcinogenesis and therapy benefits that may be gained through silencing NF-κB by selectively combining curcumin and various anticancer drugs.

  20. A brain cancer pathway in clinical practice

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    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....

  1. Management of lung cancer brain metastasis: An overview

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    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.

  2. Fighting liver cancer with combination immunotherapies | Center for Cancer Research

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    A new clinical trial testing the effectiveness of immunotherapy treatment combinations against liver cancer is enrolling patients at the NIH Clinical Center in Bethesda, Maryland. Individually, immunotherapy drugs harness the power of the human immune system to better identify and kill cancer cells. Now, researchers at the NIH’s Center for Cancer Research have begun to find evidence that the drugs may work far more effectively when taken in combination with other therapies and with each other than when taken alone.

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

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    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.

  4. 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.

  5. Combined radiotherapy and chemotherapy for high-grade brain tumours

    Science.gov (United States)

    Barazzuol, Lara

    Glioblastoma (GBM) is the most common primary brain tumour in adults and among the most aggressive of all tumours. For several decades, the standard care of GBM was surgical resection followed by radiotherapy alone. In 2005, a landmark phase III clinical trial coordinated by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) demonstrated the benefit of radiotherapy with concomitant and adjuvant temozolomide (TMZ) chemotherapy. With TMZ, the median life expectancy in optimally managed patients is still only 12-14 months, with only 25% surviving 24 months. There is an urgent need for new therapies in particular in those patients whose tumour has an unmethylated methylguanine methyltransferase gene (MGMT) promoter, which is a predictive factor of benefit from TMZ. In this dissertation, the nature of the interaction between TMZ and radiation is investigated using both a mathematical model, based on in vivo population statistics of survival, and in vitro experimentation on a panel of human GBM cell lines. The results show that TMZ has an additive effect in vitro and that the population-based model may be insufficient in predicting TMZ response. The combination of TMZ with particle therapy is also investigated. Very little preclinical data exists on the effects of charged particles on GBM cell lines as well as on the concomitant application of chemotherapy. In this study, human GBM cells are exposed to 3 MeV protons and 6 MeV alpha particles in concomitance with TMZ. The results suggest that the radiation quality does not affect the nature of the interaction between TMZ and radiation, showing reproducible additive cytotoxicity. Since TMZ and radiation cause DNA damage in cancer cells, there has been increased attention to the use of poly(ADP-ribose) polymerase (PARP) inhibitors. PARP is a family of enzymes that play a key role in the repair of DNA breaks. In this study, a novel PARP inhibitor, ABT-888

  6. 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....

  7. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection....... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

  8. 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.

  9. 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.

  10. 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.

  11. 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.

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

    DEFF Research Database (Denmark)

    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...

  13. Novel Nanotechnologies for Brain Cancer Therapeutics and Imaging.

    Science.gov (United States)

    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.

  14. 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.

  15. Brain MRI tumor image fusion combined with Shearlet and wavelet

    Science.gov (United States)

    Zhang, Changjiang; Fang, Mingchao

    2017-11-01

    In order to extract the effective information in different modalities of the tumor region in brain Magnetic resonance imaging (MRI) images, we propose a brain MRI tumor image fusion method combined with Shearlet and wavelet transform. First, the source images are transformed into Shearlet domain and wavelet domain. Second, the low frequency component of Shearlet domain is fused by Laplace pyramid decomposition. Then the low-frequency fusion image is obtained through inverse Shearlet transform. Third, the high frequency subimages in wavelet domain are fused. Then the high-frequency fusion image is obtained through inverse wavelet transform. Finally, the low-frequency fusion image and high-frequency fusion image are summated to get the final fusion image. Through experiments conducted on 10 brain MRI tumor images, the result shown that the proposed fusion algorithm has the best fusion effect in the evaluation indexes of spatial frequency, edge strength and average gradient. The main spatial frequency of 10 images is 29.22, and the mean edge strength and average gradient is 103.77 and 10.42. Compared with different fusion methods, we find that the proposed method effectively fuses the information of multimodal brain MRI tumor images and improves the clarity of the tumor area well.

  16. 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  19. 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.

  20. 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.

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

    Science.gov (United States)

    Abramczyk, Halina; Imiela, Anna

    2018-01-01

    Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n = 5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm- 1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99 ± 0.026) than that found in non-tumor brain tissue, which is 1.456 ± 0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7 kPa, and the mean of 27.16 kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92

  2. Combining Drugs to Treat Ovarian Cancer - Annual Plan

    Science.gov (United States)

    Approximately 70 percent of women diagnosed with ovarian cancer will die from the disease. Read about the NCI-funded combination drug trial that has successfully treated Betsy Brauser's recurrent cancer.

  3. 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 ...

  4. 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.  

  5. 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 ...

  6. 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.

  7. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, Niels; Ellebaek, Eva

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  8. Combinations of genetic data in a study of oral cancer

    DEFF Research Database (Denmark)

    Mellerup, Erling Thyge; Møller, Gert Lykke; Mondal, Pinaki

    2015-01-01

    for a polygenic disorder will not occur in in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented...... with an analysis of combinations of two SNP genotypes from among the 325 SNPs. Two clusters of combinations containing 95 patient specific combinations were significantly associated with oral cancer or leukoplakia. Of 373 patients with oral cancer 205 patients had a number of these 95 combinations in their genome...

  9. 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.

  10. 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

  11. 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.

  12. Development of Combination Therapy with Anti-Cancer Drugs

    NARCIS (Netherlands)

    Leijen, S.

    2013-01-01

    This thesis describes early clinical trials with anti-cancer drugs in combination with commonly applied and registered chemotherapy and single agent studies with compounds that are intended for use in combination with registered or other targeted anti-cancer drugs. Gemcitabine is a prodrug that

  13. 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.

  14. 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.

  15. 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...

  16. 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...

  17. 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

  18. 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.

  19. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype...... can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma....

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. 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).

  10. 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

  11. Predicting the Toxicity of Adjuvant Breast Cancer Drug Combination Therapy

    Science.gov (United States)

    2013-03-01

    Combination With Trastuzumab in Patients With HER2-Positive, Metastatic Breast Cancer Recruiting No Results Available NO Drug: Lapatinib|Drug: Herceptin ...Trastuzumab ( Herceptin ) -Refractory, Metastatic Breast Cancer Active, not recruiting No Results Available NO Drug: Capecitabine|Drug: Lapatinib Lapatinib...Lapatinib Plus Herceptin With or Without Endocrine Therapy Recruiting No Results Available NO Drug: Herceptin |Drug: Lapatinib|Drug: Letrozole

  12. 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

  13. 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.

  14. Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury

    DEFF Research Database (Denmark)

    Jin, Guang; Duggan, Michael; Imam, Ayesha

    2012-01-01

    We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival after hemorrhagic shock (HS), protect neurons from hypoxia-induced apoptosis, and attenuate the inflammatory response. We have also shown that administration of 6% hetastarch (Hextend [...... [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to Hex would decrease the lesion size in a clinically relevant large animal model of TBI + HS....

  15. [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.

  16. 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

  17. 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

  18. Drug combination may be highly effective in recurrent ovarian cancer

    Science.gov (United States)

    Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru

  19. Immunotherapy Combined with Large Fractions of Radiotherapy: Stereotactic Radiosurgery for Brain Metastases—Implications for Intraoperative Radiotherapy after Resection

    Directory of Open Access Journals (Sweden)

    Carsten Herskind

    2017-07-01

    Full Text Available Brain metastases (BM affect approximately a third of all cancer patients with systemic disease. Treatment options include surgery, whole-brain radiotherapy, or stereotactic radiosurgery (SRS while chemotherapy has only limited activity. In cases where patients undergo resection before irradiation, intraoperative radiotherapy (IORT to the tumor bed may be an alternative modality, which would eliminate the repopulation of residual tumor cells between surgery and postoperative radiotherapy. Accumulating evidence has shown that high single doses of ionizing radiation can be highly efficient in eliciting a broad spectrum of local, regional, and systemic tumor-directed immune reactions. Furthermore, immune checkpoint blockade (ICB has proven effective in treating antigenic BM and, thus, combining IORT with ICB might be a promising approach. However, it is not known if a low number of residual tumor cells in the tumor bed after resection is sufficient to act as an immunizing event opening the gate for ICB therapies in the brain. Because immunological data on tumor bed irradiation after resection are lacking, a rationale for combining IORT with ICB must be based on mechanistic insight from experimental models and clinical studies on unresected tumors. The purpose of the present review is to examine the mechanisms by which large radiation doses as applied in SRS and IORT enhance antitumor immune activity. Clinical studies on IORT for brain tumors, and on combined treatment of SRS and ICB for unresected BM, are used to assess the safety, efficacy, and immunogenicity of IORT plus ICB and to suggest an optimal treatment sequence.

  20. 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.

  1. Cancer treatment: the combination of vaccination with other therapies

    DEFF Research Database (Denmark)

    Andersen, M.H.; Sorensen, R.B.; Schrama, D.

    2008-01-01

    approach to fight cancer, the combination with additional therapy could create a number of synergistic effects. Herein we discuss the possibilities and prospects of vaccination when combined with other treatments. In this regard, cell death upon drug exposure may be immunogenic or non-immunogenic depending...... and endothelial cells. The efficacy of therapeutic vaccination against cancer will over the next few years be studied in settings taking advantage of strategies in which vaccination is combined with other treatment modalities. These combinations should be based on current knowledge not only regarding the biology...... of the cancer cell per se, but also considering how treatment may influence the malignant cell population as well as the immune system Udgivelsesdato: 2008/11...

  2. 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.

  3. 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.

  4. 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

  5. Vitamin D in combination cancer treatment

    Directory of Open Access Journals (Sweden)

    Yingyu Ma, Donald L. Trump, Candace S. Johnson

    2010-01-01

    Full Text Available As a steroid hormone that regulates mineral homeostasis and bone metabolism, 1α, 25-dihydroxycholecalciferol (calcitriol also has broad spectrum anti-tumor activities as supported by numerous epidemiological and experimental studies. Calcitriol potentiates the anti-tumor activities of multiple chemotherapeutics agents including DNA-damaging agents cisplatin, carboplatin and doxorubicin; antimetabolites 5-fluorouracil, cytarabine, hydroxyurea, cytarabine and gemcitabine; and microtubule-disturbing agents paclitaxel and docetaxel. Calcitriol elicits anti-tumor effects mainly through the induction of cancer cell apoptosis, cell cycle arrest, differentiation, angiogenesis and the inhibition of cell invasiveness by a number of mechanisms. Calcitriol enhances the cytotoxic effects of gamma irradiation and certain antioxidants and naturally derived compounds. Inhibition of calcitriol metabolism by 24-hydroxylase promotes growth inhibition effect of calcitriol. Calcitriol has been used in a number of clinical trials and it is important to note that sufficient dose and exposure to calcitriol is critical to achieve anti-tumor effect. Several trials have demonstrated that safe and feasible to administer high doses of calcitriol through intermittent regimen. Further well designed clinical trials should be conducted to better understand the role of calcitriol in cancer therapy.

  6. 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.

  7. Two is More Than One: How to Combine Brain Stimulation Rehabilitative Training for Functional Recovery?

    Science.gov (United States)

    Koganemaru, Satoko; Fukuyama, Hidenao; Mima, Tatsuya

    2015-01-01

    A number of studies have shown that non-invasive brain stimulation has an additional effect in combination with rehabilitative therapy to enhance functional recovery than either therapy alone. The combination enhances use-dependent plasticity induced by repetitive training. The neurophysiological mechanism of the effects of this combination is based on associative plasticity. However, these effects were not reported in all cases. We propose a list of possible strategies to achieve an effective association between rehabilitative training with brain stimulation for plasticity: (1) control of temporal aspect between stimulation and task execution; (2) the use of a shaped task for the combination; (3) the appropriate stimulation of neuronal circuits where use-dependent plastic changes occur; and (4) phase synchronization between rhythmically patterned brain stimulation and task-related patterned activities of neurons. To better utilize brain stimulation in neuro-rehabilitation, it is important to develop more effective techniques to combine them. PMID:26617497

  8. Impact of combined hospice care on terminal cancer patients.

    Science.gov (United States)

    Loke, Song-Seng; Rau, Kung-Ming; Huang, Chih-Fang

    2011-06-01

    Many patients with advanced cancer will develop physical and psychological symptoms related to their disease. These symptoms are infrequently treated by conventional care. Palliative care programs have been developed to fill this gap in care. However, there are limited beds in hospice units. To allow more terminal cancer patients to receive care from a hospice team, a combined hospice care system was recently developed in Taiwan. This study is a report of our experiences with this system. From January to December 2009, terminal cancer patients who accepted consultation from a hospice team for combined hospice care were enrolled in the study. Demographic data, clinical symptoms, referring department, type of cancer, and outcome were analyzed. A total of 354 terminal cancer patients in acute wards were referred to a hospice consulting team. The mean patient age was 61 years, and the proportion of males was 63.28%. After combined hospice care, there was a significant improvement in the sign rate of do-not-resuscitate (DNR) orders from 41.53% to 71.47% (p care also enabled 64.21% of terminal cancer patients who were not transferred to hospice ward to receive combined care by a hospice consulting team while in acute wards, thus increasing the hospice utilization of terminal cancer patients. The major symptoms presented by the patients were pain (58%), dyspnea (52%), constipation (45%), and fatigue (23%). Through the hospice consulting system, hospice combined care has a positive effect on the utilization of hospice care, rate of DNR signing and quality of end-of-life care for terminal cancer patients.

  9. 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.

  10. 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.

  11. Oxaliplatin and Infliximab Combination Synergizes in Inducing Colon Cancer Regression.

    Science.gov (United States)

    Li, Wenya; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-02-12

    BACKGROUND Colon cancer is one of the most common malignant cancers and causes millions of deaths each year. There are still no effective treatments for colon cancer patients who are at advanced stage. Tumor necrosis factor-alpha (TNF-α) might be a good therapy target due to its widely-accepted roles in regulating multiple important biological processes, especially in promoting inflammation. MATERIAL AND METHODS We evaluated the expression of TNF-α in 108 human colon cancer tissue samples and 2 colon cancer cell lines (CT26 and HCT116), and analyzed its prognostic values. Further, we explored the roles and mechanism of anti-TNF-α treatment in combination with chemotherapy in vitro and in vivo. RESULTS We found that TNF-α was highly expressed in colon cancer cell lines. The survival analysis and Cox regression analysis indicated that high TNF-α was an independent adverse prognosticator of colon cancer. In addition, anti-TNF-α treatment enhanced the effects of chemotherapy in the xenograft mouse model through inducing ADCC and CDC effects. CONCLUSIONS We conclude that TNF-α is an independent adverse prognosticator of colon cancer, and anti-TNF-α might benefit colon cancer 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. Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation.

    Directory of Open Access Journals (Sweden)

    Navjot Shah

    Full Text Available Ashwagandha, a traditional Indian herb, has been known for its variety of therapeutic activities. We earlier demonstrated anticancer activities in the alcoholic and water extracts of the leaves that were mediated by activation of tumor suppressor functions and oxidative stress in cancer cells. Low doses of these extracts were shown to possess neuroprotective activities in vitro and in vivo assays.We used cultured glioblastoma and neuroblastoma cells to examine the effect of extracts (alcoholic and water as well as their bioactive components for neuroprotective activities against oxidative stress. Various biochemical and imaging assays on the marker proteins of glial and neuronal cells were performed along with their survival profiles in control, stressed and recovered conditions. We found that the extracts and one of the purified components, withanone, when used at a low dose, protected the glial and neuronal cells from oxidative as well as glutamate insult, and induced their differentiation per se. Furthermore, the combinations of extracts and active component were highly potent endorsing the therapeutic merit of the combinational approach.Ashwagandha leaf derived bioactive compounds have neuroprotective potential and may serve as supplement for brain health.

  14. Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation.

    Science.gov (United States)

    Shah, Navjot; Singh, Rumani; Sarangi, Upasana; Saxena, Nishant; Chaudhary, Anupama; Kaur, Gurcharan; Kaul, Sunil C; Wadhwa, Renu

    2015-01-01

    Ashwagandha, a traditional Indian herb, has been known for its variety of therapeutic activities. We earlier demonstrated anticancer activities in the alcoholic and water extracts of the leaves that were mediated by activation of tumor suppressor functions and oxidative stress in cancer cells. Low doses of these extracts were shown to possess neuroprotective activities in vitro and in vivo assays. We used cultured glioblastoma and neuroblastoma cells to examine the effect of extracts (alcoholic and water) as well as their bioactive components for neuroprotective activities against oxidative stress. Various biochemical and imaging assays on the marker proteins of glial and neuronal cells were performed along with their survival profiles in control, stressed and recovered conditions. We found that the extracts and one of the purified components, withanone, when used at a low dose, protected the glial and neuronal cells from oxidative as well as glutamate insult, and induced their differentiation per se. Furthermore, the combinations of extracts and active component were highly potent endorsing the therapeutic merit of the combinational approach. Ashwagandha leaf derived bioactive compounds have neuroprotective potential and may serve as supplement for brain health.

  15. TREATMENT OF SINGLE BRAIN METASTASIS - RADIOTHERAPY ALONE OR COMBINED WITH NEUROSURGERY

    NARCIS (Netherlands)

    VECHT, CJ; HAAXMAREICHE, H; NOORDIJK, EM; PADBERG, GW; VOORMOLEN, JHC; HOEKSTRA, FH; TANS, JTJ; LAMBOOIJ, N; METSAARS, JAL; WATTENDORFF, AR; BRAND, R; HERMANS, J

    Most patients treated for single or multiple brain metastases die from progression of extracranial tumor activity. This makes it uncertain whether the combination of neurosurgery and radiotherapy for treatment of single brain metastasis will lead to better results than less invasive treatment with

  16. Micro-device combining electrophysiology and optical imaging for functional brain monitoring in freely moving animals

    Science.gov (United States)

    Miao, Peng; Wang, Qihong; Zhang, Lingke; Li, Miao; Thakor, Nitish V.

    2017-02-01

    Monitoring brain activities in awake and freely moving status is very important in physiological and pathological studies of brain functions. In this study, we developed a new standalone micro-device combining electrophysiology and optical imaging for monitoring the cerebral blood flow and neural activities with more feasibility for freely moving animals.

  17. Combining HDAC inhibitors with oncolytic virotherapy for cancer therapy

    Directory of Open Access Journals (Sweden)

    Nakashima H

    2015-11-01

    Full Text Available Hiroshi Nakashima, Tran Nguyen, Ennio Antonio ChioccaDepartment of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USAAbstract: Histone deacetylase (HDAC enzymes play a critical role in the epigenetic regulation of cellular functions and signaling pathways in many cancers. HDAC inhibitors (HDACi have been validated for single use or in combination with other drugs in oncologic therapeutics. An even more novel combination therapy with HDACi is to use them with an oncolytic virus. HDACi may lead to an amplification of tumor-specific lytic effects by facilitating increased cycles of viral replication, but there may also be direct anticancer effects of the drug by itself. Here, we review the molecular mechanisms of anti-cancer effects of the combination of oncolytic viruses with HDACi.Keywords: epigenetics, glioma, oncolytic virus, HDAC inhibitor, HSV-1, cancer

  18. 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

  19. 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.

  20. 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.

  1. Pancreatic cancer: systemic combination therapies for a heterogeneous disease.

    Science.gov (United States)

    Melisi, Davide; Calvetti, Lorenzo; Frizziero, Melissa; Tortora, Giampaolo

    2014-01-01

    Pancreatic cancer is the only human malignancy for which patients' survival has not improved substantially during the past 30 years. Despite advances in the comprehension of the molecular mechanisms underlying pancreatic carcinogenesis, current systemic treatments offer only a modest benefit in tumor-related symptoms and survival. Over the past decades, gemcitabine and its combination with other standard cytotoxic agents have been the reference treatments for advanced pancreatic cancer patients. The recent introduction of the three-drug combination regimen FOLFIRINOX or the new taxane nab-paclitaxel represent key advances for a better control of the disease. Novel agents targeting molecular mechanisms involved in cancer development and maintenance are currently under clinical investigation. This review describes the most important findings in the field of systemic combination therapies for the treatment of pancreatic cancer. We discuss the emerging evidences for the clinical activity of combination treatments with standard chemotherapy plus novel agents targeting tumor cell-autonomous and tumor microenvironment signaling pathways. We present some of the most important advances in the comprehension of the molecular mechanisms responsible for the chemoresistance of pancreatic cancer and the emerging therapeutic targets to overcome this resistance.

  2. 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.

  3. Precision medicine and personalized breast cancer: combination pertuzumab therapy

    Directory of Open Access Journals (Sweden)

    Reynolds K

    2014-03-01

    Full Text Available Kerry Reynolds, Sasmit Sarangi, Aditya Bardia, Don S Dizon Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA Abstract: Trastuzumab (Herceptin, a monoclonal antibody directed against the human epidermal growth-factor receptor 2 (HER2, is the poster child for antibody-based targeted therapy in breast cancer. Pertuzumab, another humanized monoclonal antibody, binds to a different domain of HER2 and prevents the formation of HER2:HER3 dimers, which is the most potent heterodimer in the HER family. The combination of trastuzumab and pertuzumab has synergistic activity, and is associated with improved clinical outcomes. The US Food and Drug Administration (FDA approved pertuzumab in combination with trastuzumab-based chemotherapy originally as first-line therapy for metastatic HER2-positive breast cancer in 2012, and more recently as neoadjuvant therapy for localized disease in 2013. Pertuzumab is the first neoadjuvant drug to receive accelerated approval by the FDA based on pathological complete response as the primary end point. In this article, we review the mechanism of action, pharmacokinetics, clinical efficacy, safety, and current role of pertuzumab in the management of breast cancer, as well as ongoing clinical trials and future directions regarding the utility of pertuzumab as a personalized therapeutic option for HER2-positive breast cancer. In the coming years, we anticipate increased utilization of neoadjuvant trials for drug development, biomarker discovery, and validation, and envision conduct of personalized breast cancer clinics in which therapies will be routinely selected based on genetic alterations in the tumor. Regardless of the targeted therapy combinations employed based on tumor genomic profile, trastuzumab and pertuzumab will likely continue to form the backbone of the personalized regimen for HER2-positive breast cancer. Keywords: pertuzumab, HER2 breast cancer, personalized therapy

  4. A model for evaluating therapeutic response of combined cancer treatment modalities: applied to treatment of subcutaneously implanted brain tumors (N32 and N29) in Fischer rats with pulsed electric fields (PEF) and 60Co-gamma radiation (RT).

    Science.gov (United States)

    Persson, Bertil R R; Bauréus Koch, Calvin; Grafstrom, G; Engstrom, P E; Salford, L G

    2003-10-01

    The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t(1/e)= 1 ms were first applied to the tumors. Then within 5 min radiation therapy with (60)Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively. Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV(0). exp[TGR.t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p PEF alone (p PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p PEF + 4RT was more effective (p PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0

  5. Combination Drug Delivery Approaches in Metastatic Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jun H. Lee

    2012-01-01

    Full Text Available Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms.

  6. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    OpenAIRE

    Mads Hald Andersen; Niels Junker; Eva Ellebaek; Inge Marie Svane; Per thor Straten

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination with chemotherapy may lead to improved clinical efficacy by clearing suppressor cells, reboot of the immune system, by rendering tumor cells more susceptible to immune mediated killing, or by activation o...

  7. 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.

  8. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    Directory of Open Access Journals (Sweden)

    Mads Hald Andersen

    2010-01-01

    Full Text Available The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination with chemotherapy may lead to improved clinical efficacy by clearing suppressor cells, reboot of the immune system, by rendering tumor cells more susceptible to immune mediated killing, or by activation of cells of the immune system. In addition, a range of tumor antigens have been characterized to allow targeting of proteins coupled to intrinsic properties of cancer cells. For example, proteins associated with drug resistance can be targeted, and form ideal target structures for use in combination with chemotherapy for killing of surviving drug resistant cancer cells. Proteins associated with the malignant phenotype can be targeted to specifically target cancer cells, but proteins targeted by immunotherapy may also simultaneously target cancer cells as well as suppressive cells in the tumor stroma.

  9. 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.

  10. Combined Raloxifene and Letrozole for Breast Cancer Patients.

    Science.gov (United States)

    Vohora, Divya; Kalam, Abul; Leekha, Ankita; Talegaonkar, Sushama; Verma, Anita Kamra

    2017-12-08

    Raloxifene, an anti-osteoporotic drug, is recently approved for prevention of breast cancer in postmenopausal women and thus the drug may be employed to combat the bony adverse effects of letrozole, another anticancer drug. However, the cytotoxic effect of their combination on human breast cancer (MCF-7) and human embryonic kidney (HEK) cell lines is not known. MCF-7 and HEK cell lines were treated with different graded doses of letrozole, raloxifene and their combination, then incubated for 24-48 h. MTT assay was performed to check the cytotoxicity of the drugs. The study indicates that the combination of letrozole and raloxifene possess additive effect in terms of cytotoxicity of cancer cell lines (MCF-7) and negligible effects in normal cell lines (HEK). Our study indicates that the addition of raloxifene doesn't interfere with anticancer efficacy of letrozole rather the combination acted additively for the treatment of breast cancer. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

  11. Acquired brain injury: combining social psychological and neuropsychological perspectives.

    Science.gov (United States)

    Walsh, R Stephen; Fortune, Donal G; Gallagher, Stephen; Muldoon, Orla T

    2014-01-01

    This theoretical paper reviews an emerging literature which attempts to bring together an important area of social psychology and neuropsychology. The paper presents a rationale for the integration of the social identity and clinical neuropsychological approaches in the study of acquired brain injury (ABI). The paper begins by reviewing the social and neuropsychological perspectives of ABI. Subsequently, theoretical and empirical studies that demonstrate the social influences on neuropsychology and the inherently social nature of mind are considered. Neuropsychological understandings of social identities and their potential relationships to the variability in ABIs are also discussed. The values of these understandings to ABI rehabilitation are then examined. The paper concludes by suggesting an agenda for future research that integrates the social identity and neuropsychological paradigms so that psychology might grow in its store of applicable knowledge to enhance support and rehabilitation for those with ABI.

  12. Improvement of cancer immunotherapy by combining molecular targeted therapy

    Directory of Open Access Journals (Sweden)

    Yutaka eKawakami

    2013-05-01

    Full Text Available In human cancer cells, a constitutive activation of MAPK, STAT3, β-catenin, and various other signaling pathways triggers multiple immunosuppressive cascades. These cascades result in the production of immunosuppressive molecules (e.g. TGF-β, IL-10, IL-6, VEGF, and CCL2 and induction of immunosuppressive immune cells (e.g. regulatory T cells, tolerogenic dendritic cells, and myeloid derived suppressor cells. Consequently, immunosuppressive conditions are formed in tumor-associated microenvironments, including the tumor and sentinel lymph nodes. Some of these cancer-derived cytokines and chemokines impair immune cells and render them immunosuppressive via the activation of signaling molecules, such as STAT3, in the immune cells. Thus, administration of signal inhibitors may inhibit the multiple immunosuppressive cascades by acting simultaneously on both cancer and immune cells at the key regulatory points in the cancer-immune network. Since common signaling pathways are involved in manifestation of several hallmarks of cancer, including cancer cell proliferation/survival, invasion/metastasis, and immunosuppression, targeting these shared signaling pathways in combination with immunotherapy may be a promising strategy for cancer treatment.

  13. 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.

  14. 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.

  15. Simulated driving and brain imaging: combining behavior, brain activity, and virtual reality.

    Science.gov (United States)

    Carvalho, Kara N; Pearlson, Godfrey D; Astur, Robert S; Calhoun, Vince D

    2006-01-01

    Virtual reality in the form of simulated driving is a useful tool for studying the brain. Various clinical questions can be addressed, including both the role of alcohol as a modulator of brain function and regional brain activation related to elements of driving. We reviewed a study of the neural correlates of alcohol intoxication through the use of a simulated-driving paradigm and wished to demonstrate the utility of recording continuous-driving behavior through a new study using a programmable driving simulator developed at our center. Functional magnetic resonance imaging data was collected from subjects while operating a driving simulator. Independent component analysis (ICA) was used to analyze the data. Specific brain regions modulated by alcohol, and relationships between behavior, brain function, and alcohol blood levels were examined with aggregate behavioral measures. Fifteen driving epochs taken from two subjects while also recording continuously recorded driving variables were analyzed with ICA. Preliminary findings reveal that four independent components correlate with various aspects of behavior. An increase in braking while driving was found to increase activation in motor areas, while cerebellar areas showed signal increases during steering maintenance, yet signal decreases during steering changes. Additional components and significant findings are further outlined. In summary, continuous behavioral variables conjoined with ICA may offer new insight into the neural correlates of complex human behavior.

  16. 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.

  17. 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.

  18. 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

  19. New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness

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    Isabel Corraliza-Gorjón

    2017-12-01

    Full Text Available Antibodies have proven their high value in antitumor therapy over the last two decades. They are currently being used as the first-choice to treat some of the most frequent metastatic cancers, like HER2+ breast cancers or colorectal cancers, currently treated with trastuzumab (Herceptin and bevacizumab (Avastin, respectively. The impressive therapeutic success of antibodies inhibiting immune checkpoints has extended the use of therapeutic antibodies to previously unanticipated tumor types. These anti-immune checkpoint antibodies allowed the cure of patients devoid of other therapeutic options, through the recovery of the patient’s own immune response against the tumor. In this review, we describe how the antibody-based therapies will evolve, including the use of antibodies in combinations, their main characteristics, advantages, and how they could contribute to significantly increase the chances of success in cancer therapy. Indeed, novel combinations will consist of mixtures of antibodies against either different epitopes of the same molecule or different targets on the same tumor cell; bispecific or multispecific antibodies able of simultaneously binding tumor cells, immune cells or extracellular molecules; immunomodulatory antibodies; antibody-based molecules, including fusion proteins between a ligand or a receptor domain and the IgG Fab or Fc fragments; autologous or heterologous cells; and different formats of vaccines. Through complementary mechanisms of action, these combinations could contribute to elude the current limitations of a single antibody which recognizes only one particular epitope. These combinations may allow the simultaneous attack of the cancer cells by using the help of the own immune cells and exerting wider therapeutic effects, based on a more specific, fast, and robust response, trying to mimic the action of the immune system.

  20. COMBINED TREATMENT OF LOCALLY-ADVANCED BLADDER CANCER

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    I. V. Chernyshev

    2015-01-01

    Full Text Available Bladder cancer (BC is an important clinical and scientific challenge. In 2013, in Russia, the absolute number of patients with first-ever diagnosis of bladder cancer was 12 992 people. There is an increasing proportion of detection of bladder cancer stage I–II disease patterns: 2003–50.8% in 2013–69.6%, while the number of newly diagnosed patients in III and IV clinical stages remains at 30%. The proportion of individuals who completed the treatment of the number of newly diagnosed patients with bladder cancer in 2013, was as follows: only surgical method — 65.4%, 33.5% combined. Purpose. Improvement of the results of treatment of patients with locally advanced bladder cancer. Materials and methods. The main treatment for muscle-invasive bladder cancer is radical cystectomy. In the combined treatment of bladder cancer chemotherapy is the component that systemic exposure to the tumor, the way of regional and distant metastases. The study included 132 patients with locally advanced bladder cancer who were treated for 2005–2013, divided into four groups: NACT + CE — 27 people (20.5%, CE + ACT — 21 (15.9%, NACT + CE + ACT — 21 (15.9% only CE — 63 (47.7%. An important component of treatment has been the use of platinum (cisplatin or carboplatin in Schemes M–VAC and GP. An objective response is possible in 44.7%, and the stabilization process in 40.4% of patients.Results. The clinical effect is evaluated in all patients. In the group of NACT 21% of patients survived for more than 4 years, but did not survive the 5‑year mark. In the group of CE + ACT the indicator achieved only 3‑year survival rate, which amounted to 43%. In the group of CE — none of the patients did not live up to 3 years, with 2‑year survival rate was 30%. In the group of ACT + NCT + CE 3 patients (15% were alive at the time, passed the threshold of the 5‑year survival rate, there is no progression of cancer.Conclusion. Combined treatment mode NACT

  1. Combining gene signatures improves prediction of breast cancer survival.

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    Xi Zhao

    Full Text Available BACKGROUND: Several gene sets for prediction of breast cancer survival have been derived from whole-genome mRNA expression profiles. Here, we develop a statistical framework to explore whether combination of the information from such sets may improve prediction of recurrence and breast cancer specific death in early-stage breast cancers. Microarray data from two clinically similar cohorts of breast cancer patients are used as training (n = 123 and test set (n = 81, respectively. Gene sets from eleven previously published gene signatures are included in the study. PRINCIPAL FINDINGS: To investigate the relationship between breast cancer survival and gene expression on a particular gene set, a Cox proportional hazards model is applied using partial likelihood regression with an L2 penalty to avoid overfitting and using cross-validation to determine the penalty weight. The fitted models are applied to an independent test set to obtain a predicted risk for each individual and each gene set. Hierarchical clustering of the test individuals on the basis of the vector of predicted risks results in two clusters with distinct clinical characteristics in terms of the distribution of molecular subtypes, ER, PR status, TP53 mutation status and histological grade category, and associated with significantly different survival probabilities (recurrence: p = 0.005; breast cancer death: p = 0.014. Finally, principal components analysis of the gene signatures is used to derive combined predictors used to fit a new Cox model. This model classifies test individuals into two risk groups with distinct survival characteristics (recurrence: p = 0.003; breast cancer death: p = 0.001. The latter classifier outperforms all the individual gene signatures, as well as Cox models based on traditional clinical parameters and the Adjuvant! Online for survival prediction. CONCLUSION: Combining the predictive strength of multiple gene signatures improves

  2. [Studies on Cancer Diagnosis by Using Spectroscopy Combined with Chemometrics].

    Science.gov (United States)

    Zhang, Zhuo-yong

    2015-09-01

    Studies on cancer diagnosis using various spectroscopic methods combined with chemometrics are briefly reviewed. Elemental contents in serum samples were determined by inductively coupled plasma atomic emission spectroscopy (ICP-AES), bidirectional associative memory (BAM) networks were used to establish diagnosis models for the relationships between elemental contents and lung cancer, liver cancer, and stomach cancer, respectively. Near infrared spectroscopy (NIRS) is a non-destructive detection technology. Near infrared spectra of endometrial carcinoma samples were determined and spectral features were extracted by chemoometric methods, a fuzzy rule-based expert system (FuRES) was used for establishing diagnosis model, satisfactory results were obtained. We also proposed a novel variable selection method based on particle swarm optimization (PSO) for near infrared spectra of endometrial carcinoma samples. Spectra with optimized variable were then modeled by support victor machine (SVM). Terahertz technology is an emerging technology for non-destructive detection, which has some unique characteristics. Terahertz time domain spectroscopy (THz-TDS) was used for cervical carcinoma measurement. Absorption coefficients were calculated from the measured time domain spectra and then processed with derivative, orthogonal signal correction (PC-OSC) to reduce interference components, and then fuzzy rule-based expert system (FuRES), fuzzy optimal associative memory (FOAM), support victor machine (SVM), and partial least squares discriminant analysis (PLS-DA) were used for diagnosis model establishment. The above results provide useful information for cancer occurring and development, and provide novel approaches for early stage diagnosis of various cancers.

  3. 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.

  4. Two is More Than One: How to Combine Brain Stimulation Rehabilitative Training for Functional Recovery?

    OpenAIRE

    Koganemaru, Satoko; Fukuyama, Hidenao; Mima, Tatsuya

    2015-01-01

    A number of studies have shown that non-invasive brain stimulation has an additional effect in combination with rehabilitative therapy to enhance functional recovery than either therapy alone. The combination enhances use-dependent plasticity induced by repetitive training. The neurophysiological mechanism of the effects of this combination is based on associative plasticity. However, these effects were not reported in all cases. We propose a list of possible strategies to achieve an effectiv...

  5. 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.

  6. A Hybrid Hierarchical Approach for Brain Tissue Segmentation by Combining Brain Atlas and Least Square Support Vector Machine

    Science.gov (United States)

    Kasiri, Keyvan; Kazemi, Kamran; Dehghani, Mohammad Javad; Helfroush, Mohammad Sadegh

    2013-01-01

    In this paper, we present a new semi-automatic brain tissue segmentation method based on a hybrid hierarchical approach that combines a brain atlas as a priori information and a least-square support vector machine (LS-SVM). The method consists of three steps. In the first two steps, the skull is removed and the cerebrospinal fluid (CSF) is extracted. These two steps are performed using the toolbox FMRIB's automated segmentation tool integrated in the FSL software (FSL-FAST) developed in Oxford Centre for functional MRI of the brain (FMRIB). Then, in the third step, the LS-SVM is used to segment grey matter (GM) and white matter (WM). The training samples for LS-SVM are selected from the registered brain atlas. The voxel intensities and spatial positions are selected as the two feature groups for training and test. SVM as a powerful discriminator is able to handle nonlinear classification problems; however, it cannot provide posterior probability. Thus, we use a sigmoid function to map the SVM output into probabilities. The proposed method is used to segment CSF, GM and WM from the simulated magnetic resonance imaging (MRI) using Brainweb MRI simulator and real data provided by Internet Brain Segmentation Repository. The semi-automatically segmented brain tissues were evaluated by comparing to the corresponding ground truth. The Dice and Jaccard similarity coefficients, sensitivity and specificity were calculated for the quantitative validation of the results. The quantitative results show that the proposed method segments brain tissues accurately with respect to corresponding ground truth. PMID:24696800

  7. Cancer nanomedicine: from targeted delivery to combination therapy.

    Science.gov (United States)

    Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

    2015-04-01

    The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of various diseases, including cancer. The unique properties of nanoparticles (NPs), such as large surface-to-volume ratio, small size, the ability to encapsulate various drugs, and tunable surface chemistry, give them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make NPs a mode of treatment potentially superior to conventional cancer therapies. This review highlights the most recent developments in cancer treatment using NPs as drug delivery vehicles, including promising opportunities in targeted and combination therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 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...

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

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    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.

  10. 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

  11. 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

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

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    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

  13. Histomorphological features of combined forms of tuberculosis and lung cancer

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    Savenkov Y.F.

    2017-04-01

    Full Text Available The were studied pathological features of combined forms of tuberculosis and non-small cell lung cancer in 72 patients who underwent radical surgical resection interventions from transsternal access with mediastinal lymph node dissection, with predominance of pneumonectomy - 63.9%. There were identified three main categories of pathological changes: cancer on the background of post-tuberculosis changes, cancer in tuberculoma, cancer in the wall of the active cavity. Post-tuberculosis changes were presented by dense centers, fibrosis, cirrhosis areas, sanitized cavities with histological predominance of coarse fiber connective tissue with giant cell granulomas, with areas characterized by the appearance of the lung tissue with atypical proliferation and metaplasia of bronchopulmonary epithelium, which is a precancerous condition. This malignant tumor process was presented mainly by adenocarcinomas and squamous cell cancer and differred by polymorphic macro- and microscopic picture. Cancer in tuberculoma and fibrous wall cavity differed by pronounced activity of tuberculosis process in the form of lymphohistiocytic infiltration, foci of caseous necrosis and presence of expressed granulation layer of Pirogov-Langhans’ cells. The basic morphological causes of carcinogenesis due to secondary changes of lung tissue in patients with tuberculosis were determined. The features of metastasis of malignant tumors on the background of specific tuberculous and post-tuberculosis changes in regional lymph nodes and the interrelation between the frequency of metastatic lesions with severity of tuberculosis and post-tuberculosis changes in them were studied; this has clinical significance in the surgical treatment of patients with concomitant forms of tuberculosis and lung cancer.

  14. Combined clinical and genetic testing algorithm for cervical cancer diagnosis.

    Science.gov (United States)

    Liou, Yu-Ligh; Zhang, Tao-Lan; Yan, Tian; Yeh, Ching-Tung; Kang, Ya-Nan; Cao, Lanqin; Wu, Nayiyuan; Chang, Chi-Feng; Wang, Huei-Jen; Yen, Carolyn; Chu, Tang-Yuan; Zhang, Yi; Zhang, Yu; Zhou, Honghao

    2016-01-01

    Opportunistic screening in hospitals is widely used to effectively reduce the incidence rate of cervical cancer in China and other developing countries. This study aimed to identify clinical risk factor algorithms that combine gynecologic examination and molecular testing (paired box gene 1 (PAX1) or zinc finger protein 582 (ZNF582) methylation or HPV16/18) results to improve diagnostic accuracy. The delta Cp of methylated PAX1 and ZNF582 was obtained via quantitative methylation-specific PCR in a training set (57 CIN2- and 43 cervical intraepithelial neoplasia ≥grade 3 (CIN3+) women), and the individual and combination gene sensitivities and specificities were determined. The detection accuracy of three algorithms combining gynecologic findings and genetic test results was then compared in a randomized case-control study comprising 449 women referred for colposcopic examination by gynecologists in the outpatient department of Xiangya Hospital between November 2011 and March 2013. Significant association was observed between CIN3+ and methylated PAX1 or ZNF582 in combination with HPV16/18 (OR:15.52, 95 % CI:7.73-31.18). The sensitivities and specificities of methylated PAX1 or ZNF582 combined with HPV16/18 for CIN3+ women were 89.2 and 76.0 %, or 85.4 and 80.1 %, respectively. Of the three algorithms applied to cohort data and validated in the study, two indicated 100 % sensitivity in detecting cervical cancer and a low rate of referrals for colposcopy. These algorithms might contribute to precise and objective cervical cancer diagnostics in the outpatient departments of hospitals in countries with high mortality and low screening rates or areas with uneven resource distribution.

  15. [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.

  16. 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.

  17. 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.

  18. Targeting Neuronal Networks with Combined Drug and Stimulation Paradigms Guided by Neuroimaging to Treat Brain Disorders.

    Science.gov (United States)

    Faingold, Carl L; Blumenfeld, Hal

    2015-10-01

    Improved therapy of brain disorders can be achieved by focusing on neuronal networks, utilizing combined pharmacological and stimulation paradigms guided by neuroimaging. Neuronal networks that mediate normal brain functions, such as hearing, interact with other networks, which is important but commonly neglected. Network interaction changes often underlie brain disorders, including epilepsy. "Conditional multireceptive" (CMR) brain areas (e.g., brainstem reticular formation and amygdala) are critical in mediating neuroplastic changes that facilitate network interactions. CMR neurons receive multiple inputs but exhibit extensive response variability due to milieu and behavioral state changes and are exquisitely sensitive to agents that increase or inhibit GABA-mediated inhibition. Enhanced CMR neuronal responsiveness leads to expression of emergent properties--nonlinear events--resulting from network self-organization. Determining brain disorder mechanisms requires animals that model behaviors and neuroanatomical substrates of human disorders identified by neuroimaging. However, not all sites activated during network operation are requisite for that operation. Other active sites are ancillary, because their blockade does not alter network function. Requisite network sites exhibit emergent properties that are critical targets for pharmacological and stimulation therapies. Improved treatment of brain disorders should involve combined pharmacological and stimulation therapies, guided by neuroimaging, to correct network malfunctions by targeting specific network neurons. © The Author(s) 2015.

  19. Better Together: Targeted Combination Therapies in Breast Cancer.

    Science.gov (United States)

    Zanardi, Elisa; Bregni, Giacomo; de Braud, Filippo; Di Cosimo, Serena

    2015-12-01

    Recent discoveries both in cell proliferation and survival mechanisms and new antineoplastic agents have led to deep change in the breast cancer treatment paradigm. Nonetheless, all of the progress in knowledge and strategy has not been enough to overcome mechanisms of escape and resistance put in place by the tumor cells. New targeted agents mean new possibilities for combinations, a viable option to try to stop compensatory pathways of tumor growth activated in response to therapeutics. The main challenges in designing a combined therapy come from the variety of subtypes of breast cancer (luminal A, luminal B, HER2-enriched, and basal-like) and from the multitude of pathways each subtype can exploit. Recent research has focused on dual blockade of HER2 (trastuzumab-lapatinib; trastuzumab-pertuzumab) and concomitant blockade of the endocrine driver and other pathways such as the PI3K/AKT/mTOR pathway (everolimus-exemestane), HER2 (trastuzumab/lapatinib-endocrine therapy) and the cell cycle through cyclin-dependent kinase inhibition (letrozole-palbociclib). This combined and personalized approach to treatment needs a profound knowledge of the mechanisms leading to proliferation in each tumor subtype. Deepening our understanding of tumor growth is mandatory to keep improving the efficacy of combination therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Combination treatment of tamoxifen with risperidone in breast cancer.

    Directory of Open Access Journals (Sweden)

    Wei-Lan Yeh

    Full Text Available Tamoxifen has long been used and still is the most commonly used endocrine therapy for treatment of both early and advanced estrogen receptor-positive breast cancer in pre- and post-menopause women. Tamoxifen exerts its cytotoxic effect primarily through cytostasis which is associated with the accumulation of cells in the G0/G1 phase of the cell cycle. Apoptotic activity can also be exerted by tamoxifen which involves cleavage of caspase 9, caspase 7, caspase 3, and poly-ADP-ribose polymerase (PARP. Down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulation of pro-apoptotic proteins Bax and Bak have also been observed. In addition, stress response protein of GRP 94 and GRP 78 have also been induced by tamoxifen in our study. However, side effects occur during tamoxifen treatment in breast cancer patients. Researching into combination regimen of tamoxifen and drug(s that relieves tamoxifen-induced hot flushes is important, because drug interactions may decrease tamoxifen efficacy. Risperidone has been shown to be effective in reducing or eliminating hot flushes on women with hormonal variations. In this present study, we demonstrated that combination of tamoxifen with risperidone did not interfered tamoxifen-induced cytotoxic effects in both in vitro and in vivo models, while fluoxetine abrogated the effects of tamoxifen. This is the first paper suggesting the possibility of combination treatment of tamoxifen with risperidone in breast cancer patients, providing a conceivable resolution of tamoxifen-induced side effects without interfering the efficacy of tamoxifen against breast cancer.

  1. Combination Treatment of Tamoxifen with Risperidone in Breast Cancer

    Science.gov (United States)

    Yeh, Wei-Lan; Lin, Hui-Yi; Wu, Hung-Ming; Chen, Dar-Ren

    2014-01-01

    Tamoxifen has long been used and still is the most commonly used endocrine therapy for treatment of both early and advanced estrogen receptor-positive breast cancer in pre- and post-menopause women. Tamoxifen exerts its cytotoxic effect primarily through cytostasis which is associated with the accumulation of cells in the G0/G1 phase of the cell cycle. Apoptotic activity can also be exerted by tamoxifen which involves cleavage of caspase 9, caspase 7, caspase 3, and poly-ADP-ribose polymerase (PARP). Down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-xL and up-regulation of pro-apoptotic proteins Bax and Bak have also been observed. In addition, stress response protein of GRP 94 and GRP 78 have also been induced by tamoxifen in our study. However, side effects occur during tamoxifen treatment in breast cancer patients. Researching into combination regimen of tamoxifen and drug(s) that relieves tamoxifen-induced hot flushes is important, because drug interactions may decrease tamoxifen efficacy. Risperidone has been shown to be effective in reducing or eliminating hot flushes on women with hormonal variations. In this present study, we demonstrated that combination of tamoxifen with risperidone did not interfered tamoxifen-induced cytotoxic effects in both in vitro and in vivo models, while fluoxetine abrogated the effects of tamoxifen. This is the first paper suggesting the possibility of combination treatment of tamoxifen with risperidone in breast cancer patients, providing a conceivable resolution of tamoxifen-induced side effects without interfering the efficacy of tamoxifen against breast cancer. PMID:24886861

  2. 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...

  3. Combined cognitive-psychological-physical intervention induces reorganization of intrinsic functional brain architecture in older adults.

    Science.gov (United States)

    Zheng, Zhiwei; Zhu, Xinyi; Yin, Shufei; Wang, Baoxi; Niu, Yanan; Huang, Xin; Li, Rui; Li, Juan

    2015-01-01

    Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

  4. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

    Directory of Open Access Journals (Sweden)

    Zhiwei Zheng

    2015-01-01

    Full Text Available Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

  5. Response of breast cancer cells and cancer stem cells to metformin and hyperthermia alone or combined.

    Directory of Open Access Journals (Sweden)

    Hyemi Lee

    Full Text Available Metformin, the most widely prescribed drug for treatment of type 2 diabetes, has been shown to exert significant anticancer effects. Hyperthermia has been known to kill cancer cells and enhance the efficacy of various anti-cancer drugs and radiotherapy. We investigated the combined effects of metformin and hyperthermia against MCF-7 and MDA-MB-231 human breast cancer cell, and MIA PaCa-2 human pancreatic cancer cells. Incubation of breast cancer cells with 0.5-10 mM metformin for 48 h caused significant clonogenic cell death. Culturing breast cancer cells with 30 µM metformin, clinically relevant plasma concentration of metformin, significantly reduced the survival of cancer cells. Importantly, metformin was preferentially cytotoxic to CD44(high/CD24(low cells of MCF-7 cells and, CD44(high/CD24(high cells of MIA PaCa-2 cells, which are known to be cancer stem cells (CSCs of MCF-7 cells and MIA PaCa-2 cells, respectively. Heating at 42°C for 1 h was slightly toxic to both cancer cells and CSCs, and it markedly enhanced the efficacy of metformin to kill cancer cells and CSCs. Metformin has been reported to activate AMPK, thereby suppressing mTOR, which plays an important role for protein synthesis, cell cycle progression, and cell survival. For the first time, we show that hyperthermia activates AMPK and inactivates mTOR and its downstream effector S6K. Furthermore, hyperthermia potentiated the effect of metformin to activate AMPK and inactivate mTOR and S6K. Cell proliferation was markedly suppressed by metformin or combination of metformin and hyperthermia, which could be attributed to activation of AMPK leading to inactivation of mTOR. It is conclude that the effects of metformin against cancer cells including CSCs can be markedly enhanced by hyperthermia.

  6. 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.

  7. Combined liquid and solid-phase extraction improves quantification of brain estrogen content

    Directory of Open Access Journals (Sweden)

    Andrew eChao

    2011-09-01

    Full Text Available Accuracy in quantifying brain-derived steroid hormones (‘neurosteroids’ has become increasingly important for understanding the modulation of neuronal activity, development, and physiology. Relative to other neuroactive compounds and classical neurotransmitters, steroids pose particular challenges with regard to isolation and analysis, owing to their lipid solubility. Consequently, anatomical studies of the distribution of neurosteroids have relied primarily on the expression of neurosteroid synthesis enzymes. To evaluate the distribution of synthesis enzymes vis-à-vis the actual steroids themselves, traditional steroid quantification assays, including radioimmunoassays (RIA, have successfully employed liquid extraction methods (e.g., ether, dichloromethane or methanol to isolate steroids from microdissected brain tissue. Due to their sensitivity, safety and reliability, the use of commercial enzyme immunoassays (EIA for laboratory quantification of steroids in plasma and brain has become increasingly widespread. However, EIAs rely on enzymatic reactions in vitro, making them sensitive to interfering substances in brain tissue and thus producing unreliable results. Here, we evaluate the effectiveness of a protocol for combined, two-stage liquid/solid phase extraction as compared to conventional liquid extraction alone for the isolation of estradiol (E2 from brain tissue. We employ the songbird model system, in which brain steroid production is pronounced and linked to neural mechanisms of learning and plasticity. This study outlines a combined liquid-solid phase extraction protocol that improves the performance of a commercial EIA for the quantification of brain E2 content. We demonstrate the effectiveness of our optimized method for evaluating the region specificity of brain E2 content, compare these results to established anatomy of the estrogen synthesis enzyme and estrogen receptor, and discuss the nature of potential EIA interfering

  8. 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

  9. 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

  10. Combining intraoperative ultrasound brain shift correction and augmented reality visualizations: a pilot study of eight cases.

    Science.gov (United States)

    Gerard, Ian J; Kersten-Oertel, Marta; Drouin, Simon; Hall, Jeffery A; Petrecca, Kevin; De Nigris, Dante; Di Giovanni, Daniel A; Arbel, Tal; Collins, D Louis

    2018-04-01

    We present our work investigating the feasibility of combining intraoperative ultrasound for brain shift correction and augmented reality (AR) visualization for intraoperative interpretation of patient-specific models in image-guided neurosurgery (IGNS) of brain tumors. We combine two imaging technologies for image-guided brain tumor neurosurgery. Throughout surgical interventions, AR was used to assess different surgical strategies using three-dimensional (3-D) patient-specific models of the patient's cortex, vasculature, and lesion. Ultrasound imaging was acquired intraoperatively, and preoperative images and models were registered to the intraoperative data. The quality and reliability of the AR views were evaluated with both qualitative and quantitative metrics. A pilot study of eight patients demonstrates the feasible combination of these two technologies and their complementary features. In each case, the AR visualizations enabled the surgeon to accurately visualize the anatomy and pathology of interest for an extended period of the intervention. Inaccuracies associated with misregistration, brain shift, and AR were improved in all cases. These results demonstrate the potential of combining ultrasound-based registration with AR to become a useful tool for neurosurgeons to improve intraoperative patient-specific planning by improving the understanding of complex 3-D medical imaging data and prolonging the reliable use of IGNS.

  11. 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.

  12. 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

  13. 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

  14. Improvements in Attention and Decision-Making Following Combined Behavioral Training and Brain Stimulation.

    Science.gov (United States)

    Filmer, Hannah L; Varghese, Elizabeth; Hawkins, Guy E; Mattingley, Jason B; Dux, Paul E

    2017-07-01

    In recent years there has been a significant commercial interest in 'brain training' - massed or spaced practice on a small set of tasks to boost cognitive performance. Recently, researchers have combined cognitive training regimes with brain stimulation to try and maximize training benefits, leading to task-specific cognitive enhancement. It remains unclear, however, whether the performance gains afforded by such regimes can transfer to untrained tasks, or how training and stimulation affect the brain's latent information processing dynamics. To examine these issues, we applied transcranial direct current stimulation (tDCS) over the prefrontal cortex while participants undertook decision-making training over several days. Anodal, relative to cathodal/sham tDCS, increased performance gains from training. Critically, these gains were reliable for both trained and untrained tasks. The benefit of anodal tDCS occurred for left, but not right, prefrontal stimulation, and was absent for stimulation delivered without concurrent training. Modeling revealed left anodal stimulation combined with training caused an increase in the brain's rate of evidence accumulation for both tasks. Thus tDCS applied during training has the potential to modulate training gains and give rise to transferable performance benefits for distinct cognitive operations through an increase in the rate at which the brain acquires information. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. 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

  16. 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)....

  17. Preoperative staging of lung cancer with combined PET-CT

    DEFF Research Database (Denmark)

    Fischer, Barbara; Lassen, Ulrik; Mortensen, Jann

    2009-01-01

    BACKGROUND: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC...... one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause...

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Long non-coding RNAs may serve as biomarkers in breast cancer combined with primary lung cancer

    Science.gov (United States)

    Mao, Weimin; Chen, Bo; Yang, Shifeng; Ding, Xiaowen; Zou, Dehong; Mo, Wenju; He, Xiangming; Zhang, Xiping

    2017-01-01

    Long non-coding RNAs (lncRNAs) have been shown to play important regulatory role in certain type of cancers biology, including breast and lung cancers. However, the lncRNA expression in breast cancer combined with primary lung cancer remains unknown. In this study, databases of the Cancer Genome Atlas (TCGA) and the lncRNA profiler of contained candidate 192 lncRNAs were utilized. 11 lncRNAs were differentially expressed in breast cancer, 9 candidate lncRNAs were differentially expressed in lung cancer. In order to find the aberrant expression of lncRNAs in breast cancer combined with primary lung cancer, seven samples of primary breast cancer and lung cancer were studied for the expression of selected lncRNAs. The results showed that SNHG6 and NEAT1 were reversely expressed in breast cancer combined with primary lung cancer compared with primary breast or lung cancer. In addition, a significant correlation of lncRNAs was found in the patients whose age was above 56 in breast cancer. What's more, PVT1 expression was negatively correlated with the pathological stage, and the level of ER, PR, HER2, p53 in breast cancer. Furthermore, lncRNA expression did not have significant relationship with the 5-year survival of patients with breast cancer combined with primary lung cancer. The findings revealed that PVT1, SNHG6, NEAT1 may serve as a prognostic marker for breast cancer combined with primary lung cancer. Therefore, these lncRNAs are potential molecular indicators in the diagnosis and prognosis of cancer in the future. PMID:28938549

  4. Raltitrexed combined with bevacizumab in heavily pretreated metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ke Cheng

    2013-01-01

    Full Text Available No standard chemotherapy regimen has been established for metastatic colorectal cancer (mCRC after progression on 5-fluorouracil, oxaliplatin, and irinotecan. Here, we report the combination of raltitrexed and bevacizumab as a salvage regimen for the treatment of three heavily pretreated patients with KRAS mutant mCRC. All three patients had stable disease (SD according to response evaluation criteria in solid tumors (RECIST criteria, progression free survival (PFS were 3.0, 3.2 months for the first two patients and have not been reached for over 5 months for the third patient and no severe adverse effect was observed. The combination of raltitrexed plus bevacizumab in mCRC seems worthy of further investigation.

  5. Callus formation in bone fractures combined with brain injury in rat

    Directory of Open Access Journals (Sweden)

    Yu-Ping Chen

    2017-01-01

    Full Text Available Objective: The objective of this study was to determine the speed of bony union and the serum levels of biomarkers in the setting of bone fractures combined with brain injury. Materials and Methods: In this study, Sprague–Dawley rats were randomized into four groups: sham, brain injury, bone fracture, and bone fracture plus brain injury groups. The serum levels of biochemical markers, namely, nerve growth factor (NGF, Wnt-3a, Dickkopf-related protein-1, receptor-activator of NF-κB ligand, and adrenocorticotropic hormone (ACTH, were measured on the days 1, 3, 7, and 14 following injury. Bony union was evaluated using radiographs every week for 6 weeks. Results: Compared with the brain injury group and bone fracture group, the radiographs of the bone fracture plus brain injury group revealed enhanced callus formations in week 2. From week 3, the callus formation did not differ significantly among the groups. The serum levels of the biomarkers varied at different time points. The serum levels of NGF on days 1 and 3, Wnt-3a on days 3 and 14, and ACTH on days 1, 3, and 7 were significantly higher in the bone fracture plus brain injury group than in the bone fracture group. Conclusions: Brain injury increases callus formation in simultaneous bone fracture. Considering the time point, early NGF, Wnt-3a, and ACTH elevation might be associated with early callus formation enhancement. The results indicate that these brain injury-induced biomarkers might play crucial role in accelerating bone healing.

  6. Combined SPECT and Multidetector CT for Prostate Cancer Evaluations.

    Science.gov (United States)

    Aparici, Carina Mari; Carlson, David; Nguyen, Nhan; Hawkins, Randall A; Seo, Youngho

    2012-01-01

    (111)In-capromab pendetide is an imaging probe for noninvasive detection of prostate cancer dissemination, and can be difficult to interpret because of low photon statistics resulting in noisy images with limited anatomical precision. We examined if a 16-slice multidetector computed tomography (MDCT) combined with single photon emission computed tomography (SPECT) could increase the impact on the clinical management and improve confidence in SPECT image interpretations in comparison to a relatively low-mA (limited resolution) CT. 17 scans were reviewed from a SPECT combined with low-mA CT scanner; 21 scans were reviewed from a SPECT combined with 16-slice MDCT scanner. Reports of the clinical interpretations from the imaging studies, additional examinations performed by referring physicians as a follow-up to the imaging results, and long-term clinical and laboratory follow-ups were used to define confidence of the SPECT/CT readings and impact of the readings on the patient management. The impact was defined as: the occurrence of the (111)In-capromab pendetide interpretation resulted in additional imaging studies or biopsies. MDCT improved the quality and confidence in the characterization of small lymph nodes with or without uptake of (111)In-capromab pendetide. The increased confidence with MDCT in SPECT/CT readings was evident in all cases reviewed in this study, and the impact on the clinical management was higher (8 out of 21) using SPECT/MDCT than the impact using SPECT combined with low-mA CT (2 out of 17). The dual-modality SPECT/CT provides a quantifiable benefit when MDCT is used instead of low-mA CT, particularly for prostate cancer evaluations using (111)In-capromab pendetide.

  7. 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

  8. Combined androgen blockade in the treatment of advanced prostate cancer--an overview. The Scandinavian Prostatic Cancer Group

    DEFF Research Database (Denmark)

    Iversen, P

    1997-01-01

    The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed.......The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed....

  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. Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives

    DEFF Research Database (Denmark)

    Bergmann, Til Ole; Karabanov, Anke; Hartwigsen, Gesa

    2016-01-01

    Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures...... are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS...... experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation...

  12. Drastic therapy for listerial brain abscess involving combined hyperbaric oxygen therapy and antimicrobial agents.

    Science.gov (United States)

    Nakahara, Keiichi; Yamashita, Satoshi; Ideo, Katsumasa; Shindo, Seigo; Suga, Tomohiro; Ueda, Akihiko; Honda, Shoji; Hirahara, Tomoo; Watanabe, Masaki; Yamashita, Taro; Maeda, Yasushi; Yonemochi, Yasuhiro; Takita, Tomohiro; Ando, Yukio

    2014-10-01

    Listeria monocytogenes (L. monocytogenes) is a rare causative pathogen of brain abscess that is often found in immunocompromised patients. Although patients with supratentorial listerial abscesses showed a longer survival with surgical drainage, the standard therapy for patients with subtentorial lesions has not been established. We report herein a patient with supra- and subtentorial brain abscesses caused by L. monocytogenes infection. These abscesses did not respond to antibiotics, and his symptoms gradually worsened. Drainage was not indicated for subtentorial lesions, and the patient was additionally treated with hyperbaric oxygen therapy, which dramatically reduced the volume of abscesses and improved the symptoms. This is the first report of drastic therapy for a patient with listerial brain abscesses involving combined antibiotics and hyperbaric oxygen therapy. The findings suggest that hyperbaric oxygen therapy is a good option for treating patients with deep-seated listerial abscesses and for who surgical drainage is not indicated.

  13. 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.

  14. Targeting Cancer using Polymeric Nanoparticle mediated Combination Chemotherapy

    Science.gov (United States)

    Gad, Aniket; Kydd, Janel; Piel, Brandon; Rai, Prakash

    2016-01-01

    Cancer forms exhibiting poor prognosis have been extensively researched for therapeutic solutions. One of the conventional modes of treatment, chemotherapy shows inadequacy in its methodology due to imminent side-effects and acquired drug-resistance by cancer cells. However, advancements in nanotechnology have opened new frontiers to significantly alleviate collateral damage caused by current treatments via innovative delivery techniques, eliminating pitfalls encountered in conventional treatments. Properties like reduced drug-clearance and increased dose efficacy by the enhanced permeability and retention effect deem nanoparticles suitable for this application. Optimization of size, surface charge and surface modifications have provided nanoparticles with stealth properties capable of evading immune responses, thus deeming them as excellent carriers of chemotherapeutic agents. Biocompatible and biodegradable forms of polymers enhance the bioavailability of chemotherapeutic agents, and permit a sustained and time-dependent release of drugs which is a characteristic of their composition, thereby providing a controlled therapeutic approach. Studies conducted in vitro and animal models have also demonstrated a synergism in cytotoxicity given the mechanism of action of anticancer drugs when administered in combination providing promising results. Combination therapy has also shown implications in overcoming multiple-drug resistance, which can however be subdued by the adaptable nature of tumor microenvironment. Surface modifications with targeting moieties can therefore feasibly increase nanoparticle uptake by specific receptor-ligand interactions, increasing dose efficacy which can seemingly overcome drug-resistance. This article reviews recent trends and investigations in employing polymeric nanoparticles for effectively delivering combination chemotherapy, and modifications in delivery parameters enhancing dose efficacy, thus validating the potential in this

  15. Natural compounds and combination therapy in colorectal cancer treatment.

    Science.gov (United States)

    Rejhová, A; Opattová, A; Čumová, A; Slíva, D; Vodička, P

    2018-01-20

    Colorectal cancer (CRC) therapy using conventional chemotherapeutics represents a considerable burden for the patient's organism because of high toxicity while the response is relatively low. Our review summarizes the findings about natural compounds as chemoprotective agents for decreasing risk of CRC. It also identifies natural compounds which possess anti-tumor effects of various characteristics, mainly in vitro on colorectal cell lines or in vivo studies on experimental models, but also in a few clinical trials. Many of natural compounds suppress proliferation by inducing cell cycle arrest or induce apoptosis of CRC cells resulting in the inhibition of tumor growth. A novel employment of natural substances is a so-called combination therapy - administration of two or more substances - conventional chemotherapeutics and a natural compound or more natural compounds at a time. Some natural compounds may sensitize to conventional cytotoxic therapy, reinforce the drug effective concentration, intensify the combined effect of both administered therapeutics or exert cytotoxic effects specifically on tumor cells. Moreover, combined therapy by targeting multiple signaling pathways, uses various mechanisms to reduce the development of resistance to antitumor drugs. The desired effect could be to diminish burden on the patient's organism by replacing part of the dose of a conventional chemotherapeutic with a natural substance with a defined effect. Many natural compounds are well tolerated by the patients and do not cause toxic effects even at high doses. Interaction of conventional chemotherapeutics with natural compounds introduces a new aspect in the research and therapy of cancer. It could be a promising approach to potentially achieve improvements, while minimizing of adverse effects associated with conventional chemotherapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Classification of MR brain images by combination of multi-CNNs for AD diagnosis

    Science.gov (United States)

    Cheng, Danni; Liu, Manhua; Fu, Jianliang; Wang, Yaping

    2017-07-01

    Alzheimer's disease (AD) is an irreversible neurodegenerative disorder with progressive impairment of memory and cognitive functions. Its early diagnosis is crucial for development of future treatment. Magnetic resonance images (MRI) play important role to help understand the brain anatomical changes related to AD. Conventional methods extract the hand-crafted features such as gray matter volumes and cortical thickness and train a classifier to distinguish AD from other groups. Different from these methods, this paper proposes to construct multiple deep 3D convolutional neural networks (3D-CNNs) to learn the various features from local brain images which are combined to make the final classification for AD diagnosis. First, a number of local image patches are extracted from the whole brain image and a 3D-CNN is built upon each local patch to transform the local image into more compact high-level features. Then, the upper convolution and fully connected layers are fine-tuned to combine the multiple 3D-CNNs for image classification. The proposed method can automatically learn the generic features from imaging data for classification. Our method is evaluated using T1-weighted structural MR brain images on 428 subjects including 199 AD patients and 229 normal controls (NC) from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Experimental results show that the proposed method achieves an accuracy of 87.15% and an AUC (area under the ROC curve) of 92.26% for AD classification, demonstrating the promising classification performances.

  17. 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.

  18. 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.

  19. 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

  20. Regional brain network organization distinguishes the combined and inattentive subtypes of Attention Deficit Hyperactivity Disorder

    OpenAIRE

    Jacqueline F. Saad; Kristi R. Griffiths; Michael R. Kohn; Simon Clarke; Leanne M. Williams; Mayuresh S. Korgaonkar

    2017-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is characterized clinically by hyperactive/impulsive and/or inattentive symptoms which determine diagnostic subtypes as Predominantly Hyperactive-Impulsive (ADHD-HI), Predominantly Inattentive (ADHD-I), and Combined (ADHD-C). Neuroanatomically though we do not yet know if these clinical subtypes reflect distinct aberrations in underlying brain organization. We imaged 34 ADHD participants defined using DSM-IV criteria as ADHD-I (n?=?16) or as ADH...

  1. 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.

  2. 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.

  3. 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.

  4. Combined thalamic and subthalamic deep brain stimulation for tremor-dominant Parkinson's disease.

    Science.gov (United States)

    Oertel, Markus F; Schüpbach, W Michael M; Ghika, Joseph-André; Stieglitz, Lennart H; Fiechter, Michael; Kaelin-Lang, Alain; Raabe, Andreas; Pollo, Claudio

    2017-02-01

    Deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) or the subthalamic nucleus (STN) reportedly improves medication-refractory Parkinson's disease (PD) tremor. However, little is known about the potential synergic effects of combined Vim and STN DBS. We describe a 79-year-old man with medication-refractory tremor-dominant PD. Bilateral Vim DBS electrode implantation produced insufficient improvement. Therefore, the patient underwent additional unilateral left-sided STN DBS. Whereas Vim or STN stimulation alone led to partial improvement, persisting tremor resolution occurred after simultaneous stimulation. The combination of both targets may have a synergic effect and is an alternative option in suitable cases.

  5. BRAF inhibitors and radiotherapy for melanoma brain metastases: potential advantages and disadvantages of combination therapy.

    Science.gov (United States)

    Chowdhary, Mudit; Patel, Kirtesh R; Danish, Hasan H; Lawson, David H; Khan, Mohammad K

    2016-01-01

    Melanoma is an aggressive malignancy that frequently spreads to the brain, resulting in rapid deterioration in both quality and quantity of life. Historically, treatment options for melanoma brain metastases (MBM) have predominantly consisted of surgery and radiotherapy. While these options can help provide local control, the majority of patients still develop intracranial progression. Indeed, novel therapeutic options, including molecularly targeted agents and immunotherapy, have improved outcomes and are now changing the role of radiotherapy. Up to 50% of melanomas contain an activating BRAF mutation, resulting in hyperactive cellular proliferation and survival. Drugs that target BRAF have been introduced for the treatment of metastatic melanoma and offer hope in improving disease outcomes; however, many of these trials either excluded or had a limited amount of patients with MBM. Recent studies have revealed that melanoma cell lines become more radiosensitive following BRAF inhibition, thus providing a potential synergistic mechanism when combining BRAF inhibitor (BRAFi) and radiotherapy. However, neurotoxicity concerns also exist with this combination. This article reviews the efficacy and limitations of BRAFi therapy for MBM, describes current evidence for combining BRAFis with radiation, discusses the rationale and evidence for combination modalities, and highlights emerging clinical trials specifically investigating this combination in MBM.

  6. Cancers in Australia in 2010 attributable to and prevented by the use of combined oral contraceptives.

    Science.gov (United States)

    Jordan, Susan J; Wilson, Louise F; Nagle, Christina M; Green, Adele C; Olsen, Catherine M; Bain, Christopher J; Pandeya, Nirmala; Whiteman, David C; Webb, Penelope M

    2015-10-01

    To estimate the proportion and number of cancers occurring in Australia in 2010 attributable to combined oral contraceptive pill (OCP) use. We estimated the population attributable fraction (PAF) for cancers causally associated with combined OCP use (breast, cervix), and the proportion of endometrial and ovarian cancers prevented (prevented fraction [PF]). We used standard formulae incorporating prevalence of combined OCP use in the Australian population, relative risks of cancer associated with this exposure and cancer incidence. An estimated 105 breast and 52 cervical cancers (0.7% and 6.4% of each cancer, respectively) in Australia in 2010 were attributable to current use of combined OCP. Past combined OCP use was estimated to have prevented 1,032 endometrial and 308 ovarian cancers in 2010, reducing the number of cancers that would otherwise have occurred by 31% and 19%, respectively. A small proportion of breast and cervical cancers is attributable to combined OCP use; OCP use is likely to have prevented larger numbers of endometrial and ovarian cancers. Women seeking contraceptive advice should be told of potential adverse effects, but should also be told that - along with reproductive health benefits - combined OCP use can reduce long-term risks of ovarian and endometrial cancers. © 2015 The Authors.

  7. 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...

  8. 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

  9. Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia.

    Science.gov (United States)

    Gu, Fangyi; Zhang, Han; Hyland, Paula L; Berndt, Sonja; Gapstur, Susan M; Wheeler, William; Ellipse Consortium, The; Amos, Christopher I; Bezieau, Stephane; Bickeböller, Heike; Brenner, Hermann; Brennan, Paul; Chang-Claude, Jenny; Conti, David V; Doherty, Jennifer Anne; Gruber, Stephen B; Harrison, Tabitha A; Hayes, Richard B; Hoffmeister, Michael; Houlston, Richard S; Hung, Rayjean J; Jenkins, Mark A; Kraft, Peter; Lawrenson, Kate; McKay, James; Markt, Sarah; Mucci, Lorelei; Phelan, Catherine M; Qu, Conghui; Risch, Angela; Rossing, Mary Anne; Wichmann, H-Erich; Shi, Jianxin; Schernhammer, Eva; Yu, Kai; Landi, Maria Teresa; Caporaso, Neil E

    2017-11-01

    Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME-ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site, we conducted gene-based and pathway-based analyses by applying the summary-based Adaptive Rank Truncated Product method (sARTP) on the summary association statistics for each SNP within the candidate gene regions. Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME-ON and PLCO, after Bonferroni correction (ppathway  circadian rhythm pathway in GAME-ON (ppathway  = 0.021); this association was not confirmed in GECCO (ppathway  = 0.76) or the combined data (ppathway  = 0.17). No significant association was observed for ovarian and lung cancer. These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms. © 2017 UICC.

  10. Brain morphometry predicts individual creative potential and the ability to combine remote ideas.

    Science.gov (United States)

    Bendetowicz, David; Urbanski, Marika; Aichelburg, Clarisse; Levy, Richard; Volle, Emmanuelle

    2017-01-01

    For complex mental functions such as creative thinking, inter-individual variability is useful to better understand the underlying cognitive components and brain anatomy. Associative theories propose that creative individuals have flexible semantic associations, which allows remote elements to be formed into new combinations. However, the structural brain variability associated with the ability to combine remote associates has not been explored. To address this question, we performed a voxel-based morphometry (VBM) study and explored the anatomical connectivity of significant regions. We developed a Remote Combination Association Task adapted from Mednick's test, in which subjects had to find a solution word related to three cue words presented to them. In our adaptation of the task, we used free association norms to quantify the associative distance between the cue words and solution words, and we varied this distance. The tendency to solve the task with insight and the ability to evaluate the appropriateness of a proposed solution were also analysed. Fifty-four healthy volunteers performed this task and underwent a structural MRI. Structure-function relationships were analysed using regression models between grey matter (GM) volume and task performance. Significant clusters were mapped onto an atlas of white matter (WM) tracts. The ability to solve the task, which depended on the associative distance of the solution word, was associated with structural variation in the left rostrolateral prefrontal and posterior parietal regions; the left rostral prefrontal region was connected to distant regions through long-range pathways. By using a creative combination task in which the semantic distance between words varied, we revealed a brain network centred on the left frontal pole that appears to support the ability to combine information in new ways by bridging the semantic distance between pieces of information. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. 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

  12. 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...

  13. [Median nerve constrictive operation combined with tendon transfer to treat brain paralysis convulsive deformity of hand].

    Science.gov (United States)

    Ma, Shanjun; Zhou, Tianjian

    2014-05-01

    To evaluate the effectiveness of the median nerve constrictive operation combined with tendon transfer to treat the brain paralysis convulsive deformity of the hand. The clinical data from 21 cases with brain paralysis convulsive deformity of the hand were analyzed retrospectively between August 2009 and April 2012. Of them, there were 13 males and 8 females with an average age of 15 years (range, 10-29 years). The causes of the convulsive cerebral palsy included preterm deliveries in 11 cases, hypoxia asphyxia in 7, traumatic brain injury in 2, and encephalitis sequela in 1. The disease duration was 2-26 years (mean, 10.6 years). All the 21 patients had cock waists, crooking fingers, and contracture of adductors pollicis, 12 had the forearm pronation deformity. According to Ashworth criteria, there were 2 cases at level I, 5 cases at level II, 8 cases at level III, 4 cases at level IV, and 2 cases at level V. All patients had no intelligence disturbances. The forearm X-ray film showed no bone architectural changes before operation. The contraction of muscle and innervation was analyzed before operation. The median nerve constrictive operation combined with tendon transfer was performed. The functional activities and deformity improvement were evaluated during follow-up. After operation, all the patients' incision healed by first intension, without muscle atrophy and ischemic spasm. All the 21 cases were followed up 1.5-4.5 years (mean, 2.3 years). No superficial sensory loss occurred. The effectiveness was excellent in 13 cases, good in 6 cases, and poor in 2 cases, with an excellent and good rate of 90.4% at last follow-up. The median nerve constrictive operation combined with tendon transfer to treat brain paralysis convulsive deformity of the hand can remove and prevent the recurrence of spasm, achieve the orthopedic goals, to assure the restoration of motor function and the improvement of the life quality.

  14. 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.

  15. Improving breast cancer outcome prediction by combining multiple data sources

    NARCIS (Netherlands)

    Van Vliet, M.H.

    2010-01-01

    Cancer has recently become the number one cause of death in The Netherlands. Breast cancer is the most prevalent form of cancer among females, with a lifetime risk of 12.8% (i.e. the 1 in 8 rule). As a result, more and more research is devoted to getting a better insight into cancer, and to further

  16. Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes.

    Science.gov (United States)

    Mohamed, Tarek Mostafa; Ghaffar, Hamdy M Abdel; El Husseiny, Rabee M R

    2015-12-01

    The present study is an unsubstantiated qualitative assessment of the abused drugs-tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively. © The Author(s) 2012.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. Study on diffusion tensor imaging combined with electrophysiological monitoring in brain stem cavernous hemangioma resection

    Directory of Open Access Journals (Sweden)

    Dong-sheng KONG

    2017-07-01

    Full Text Available Objective To evaluate the clinical application value of diffusion tensor imaging (DTI combined with electrophysiological monitoring in the resection of brain stem cavernous hemangioma (CM.    Methods There were 39 patients with brain stem cavernous hemangioma. DTI was performed before and during the operation. Diffusion tensor tractography (DTT was used to track fiber and reconstruct pyramidal tract. Intraoperative neurobehavioral monitoring was used to detect the changes of somatosensory-evoked potentials (SEP, motor - evoked potentials (MEP and brain stem auditory - evoked potentials (BAEP.    Results Of all the 39 patients, there was no significant change of BAEP during the operation, 5 patients (12.82% had abnormal SEP, 6 cases (15.38% had abnormalities in MEP monitoring, 2 cases (5.13% had reduced volumes of pyramidal tract proved by DTI. Intraoperative MRI confirmed 36 cases (92.31% had complete removal of lesions, and 3 cases (7.69% had subtotal resection. There were improvement of clinical symptoms in 29 cases (74.36% , no obvious changes in 4 cases (10.26% , postoperative facial paralysis in 3 cases (7.69%, worsened movement disorder in 2 cases (5.13%, death due to disorder of consciousness and pulmonary infection in one case (2.56% . Postoperative follow - up was 30 months in average. Glasgow Outcome Scale (GOS showed 27 cases (69.23% of Grade 5, 7 cases (17.95% of Grade 4, 4 cases (10.26% of Grade 3, and one case (2.56% of Grade 1.    Conclusions Combined use of intraoperative DTI and electrophysiological monitoring can safely and effectively remove brain stem cavernous hemangioma. DOI: 10.3969/j.issn.1672-6731.2017.05.010

  5. Use of Ultrasound Pulses Combined with Definity for Targeted Blood-Brain Barrier Disruption

    Science.gov (United States)

    McDannold, Nathan; Vykhodtseva, Natalia; Hynynen, Kullervo

    2007-05-01

    We have developed a method to combine an ultrasound contrast agent (USCA) with low-intensity focused ultrasound pulses combined to produce temporary blood-brain barrier disruption (BBBD), a potential non-invasive means for targeted drug delivery in the brain. All of our previous work used the USCA Optison. The purpose of this work was to test the feasibility of using the USCA Definity for BBBD. Thirty-six non-overlapping locations were sonicated through a craniotomy in experiments in the brains of nine rabbits (4 locations per rabbit; US frequency: 0.69MHz, burst: 10ms, PRF: 1Hz, duration: 20s; pressure amplitude: 0.2-1.5 MPa). Eleven locations were sonicated using Optison at 0.5 MPa. For both agents, the probability for BBBD was estimated to be 50% at 0.4 MPa using probit regression. In histology, small isolated areas of extravasated erythrocytes were observed in some locations. At 0.8 MPa and above, this extravasation was sometimes accompanied by tiny (dimensions of 100 μm or less) regions of damaged brain parenchyma. The magnitude of the BBBD was larger with Optison than with Definity at 0.5 MPa (P=0.04), and more areas with extravasated erythrocytes were observed (P=0.03). We conclude that BBBD is possible using Definity for the dosage of USCA and the acoustic parameters tested in this study. While the probability for BBBD as a function of pressure amplitude and the type of acute tissue effects was similar to findings with Optison, under these experimental conditions, Optison produced a larger effect.

  6. 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.

  7. 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

  8. 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.

  9. Label-free imaging of brain and brain tumor specimens with combined two-photon excited fluorescence and second harmonic generation microscopy

    Science.gov (United States)

    Jiang, Liwei; Wang, Xingfu; Wu, Zanyi; Du, Huiping; Wang, Shu; Li, Lianhuang; Fang, Na; Lin, Peihua; Chen, Jianxin; Kang, Dezhi; Zhuo, Shuangmu

    2017-10-01

    Label-free imaging techniques are gaining acceptance within the medical imaging field, including brain imaging, because they have the potential to be applied to intraoperative in situ identifications of pathological conditions. In this paper, we describe the use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) microscopy in combination for the label-free detection of brain and brain tumor specimens; gliomas. Two independently detecting channels were chosen to subsequently collect TPEF/SHG signals from the specimen to increase TPEF/SHG image contrasts. Our results indicate that the combined TPEF/SHG microscopic techniques can provide similar rat brain structural information and produce a similar resolution like conventional H&E staining in neuropathology; including meninges, cerebral cortex, white-matter structure corpus callosum, choroid plexus, hippocampus, striatum, and cerebellar cortex. It can simultaneously detect infiltrating human brain tumor cells, the extracellular matrix collagen fiber of connective stroma within brain vessels and collagen depostion in tumor microenvironments. The nuclear-to-cytoplasmic ratio and collagen content can be extracted as quantitative indicators for differentiating brain gliomas from healthy brain tissues. With the development of two-photon fiberscopes and microendoscope probes and their clinical applications, the combined TPEF and SHG microcopy may become an important multimodal, nonlinear optical imaging approach for real-time intraoperative histological diagnostics of residual brain tumors. These occur in various brain regions during ongoing surgeries through the method of simultaneously identifying tumor cells, and the change of tumor microenvironments, without the need for the removal biopsies and without the need for tissue labelling or fluorescent markers.

  10. 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.

  11. 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

  12. 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

  13. 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)

  14. 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.

  15. 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

  16. 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

  17. NCI ALMANAC Tool for Research on Cancer Drug Combinations

    Science.gov (United States)

    A Cancer Currents blog post on the NCI ALMANAC, a new resource that provides data showing how well pairs of FDA-approved cancer drugs performed in killing tumor cells from NCI-60 Human Tumor Cell Lines.

  18. Oxaliplatin and Infliximab Combination Synergizes in Inducing Colon Cancer Regression

    OpenAIRE

    Li, Wenya; Xu, Jian; Zhao, Jian; ZHANG, Rui

    2017-01-01

    Background Colon cancer is one of the most common malignant cancers and causes millions of deaths each year. There are still no effective treatments for colon cancer patients who are at advanced stage. Tumor necrosis factor-alpha (TNF-?) might be a good therapy target due to its widely-accepted roles in regulating multiple important biological processes, especially in promoting inflammation. Material/Methods We evaluated the expression of TNF-? in 108 human colon cancer tissue samples and 2 c...

  19. 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.)

  20. Combined effects of smoking and HPV16 in oropharyngeal cancer

    NARCIS (Netherlands)

    Anantharaman, Devasena; Muller, David C; Lagiou, Pagona; Ahrens, Wolfgang; Holcátová, Ivana; Merletti, Franco; Kjærheim, Kristina; Polesel, Jerry; Simonato, Lorenzo; Canova, Cristina; Castellsague, Xavier; Macfarlane, Tatiana V; Znaor, Ariana; Thomson, Peter; Robinson, Max; Conway, David I; Healy, Claire M; Tjønneland, Anne; Westin, Ulla; Ekström, Johanna; Chang-Claude, Jenny; Kaaks, Rudolf; Overvad, Kim; Drogan, Dagmar; Hallmans, Göran; Laurell, Göran; Bueno-de-Mesquita, H B; Peeters, Petra H; Agudo, Antonio; Larrañaga, Nerea; Travis, Ruth C; Palli, Domenico; Barricarte, Aurelio; Trichopoulou, Antonia; George, Saitakis; Trichopoulos, Dimitrios; Quirós, J Ramón; Grioni, Sara; Sacerdote, Carlotta; Navarro, Carmen; Sánchez, María-José; Tumino, Rosario; Severi, Gianluca; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Panico, Salvatore; Weiderpass, Elisabete; Lund, Eiliv; Gram, Inger T; Riboli, Elio; Pawlita, Michael; Waterboer, Tim; Kreimer, Aimée R; Johansson, Mattias; Brennan, Paul

    BACKGROUND: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not

  1. Combination of axitinib and dasatinib for anti-cancer activities in two prostate cancer cell lines

    Directory of Open Access Journals (Sweden)

    Nai-Xiong Peng

    2016-03-01

    Full Text Available Prostate cancer is major cause of cancer related deaths worldwide in men. There are new treatment methods and drugs are being developed with promising results in two of the prostate cancer cell lines (PPC-1 and TSU-Pr1. These two cells were treated with 20 uM of axitinib combined with dasatinib for 6-72 hours. The cell viability assessed by the cytotoxicity assay. Various regulatory genes such as c-KIT, cell cycle and apoptosis and angiogenic factors were also studied. The enzyme activity of apoptosis efector caspase-3 was colorimetrically determined. Axitinib and dasatinib combination lowered the survival rate of PPC-1 cells but enhanced the survival rate of TSU-Pr1 cells. The protein expression levels in apoptosis and angiogenesis factors were also found to be in contrast between the two cell lines. PPC-1 and TSU-Pr1 cells displayed a different response to axitinib with dasatinib, which explains different expression levels of regulators of cell-cycle, apoptosis and angiogenesis.

  2. Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock

    DEFF Research Database (Denmark)

    Imam, Ayesha M; Jin, Guang; Sillesen, Martin

    2013-01-01

    Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the assoc......Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well...... as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP....

  3. The combined effect of cancer and chronic diseases on general practitioner consultation rates.

    NARCIS (Netherlands)

    Heins, M.J.; Korevaar, J.C.; Donker, G.A.; Rijken, P.M.; Schellevis, F.G.

    2015-01-01

    Aim: More than two-thirds of cancer patients have one or more chronic diseases besides cancer. The purpose of this study was to get detailed insight into the combined effect of cancer and chronic diseases on general practitioner (GP) consultation rates. Methods: From the NIVEL Primary Care Database

  4. The combined effect of cancer and chronic diseases on general practitioner consultation rates

    NARCIS (Netherlands)

    Heins, M.J.; Korevaar, J.C.; Donker, G.A.; Rijken, P.M.; Schellevis, F.G.

    2015-01-01

    Aim: More than two-thirds of cancer patients have one or more chronic diseases besides cancer. The purpose of this study was to get detailed insight into the combined effect of cancer and chronic diseases on general practitioner (GP) consultation rates. Methods: From the NIVEL Primary Care Database

  5. Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography

    Directory of Open Access Journals (Sweden)

    Faranak Farzan

    2016-09-01

    Full Text Available The concurrent combination of transcranial magnetic stimulation (TMS with electroencephalography (TMS-EEG is a powerful technology for characterizing and modulating brain networks across developmental, behavioral and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research.

  6. Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography.

    Science.gov (United States)

    Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M D; Rotenberg, Alexander; Daskalakis, Zafiris J; Pascual-Leone, Alvaro

    2016-01-01

    The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research.

  7. 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

  8. 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.

  9. 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.

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. [Diagnosis of Vater's papilla cancer and its combination treatment and radiotherapy].

    Science.gov (United States)

    Kharchenko, V P; Liutfaliev, T A; Khmelevskiĭ, E V; Kunda, M A; Zapirov, G M; Eptyshev, N A

    2008-01-01

    The paper considers the problems of enhancing the efficiency of diagnosis and treatment of Vater's papilla cancer complicated by jaundice, by maximally realizing the capacities of instrumental studies and by improving the procedures of combination treatment and radiotherapy for this disease. The achieved treatment results show it expedient to use combination treatment and, if radical surgery is contraindicated, radiotherapy for Vater's papilla cancer.

  13. Combining multiple features for error detection and its application in brain-computer interface.

    Science.gov (United States)

    Tong, Jijun; Lin, Qinguang; Xiao, Ran; Ding, Lei

    2016-02-04

    Brain-computer interface (BCI) is an assistive technology that conveys users' intentions by decoding various brain activities and translating them into control commands, without the need of verbal instructions and/or physical interactions. However, errors existing in BCI systems affect their performance greatly, which in turn confines the development and application of BCI technology. It has been demonstrated viable to extract error potential from electroencephalography recordings. This study proposed a new approach of fusing multiple-channel features from temporal, spectral, and spatial domains through two times of dimensionality reduction based on neural network. 26 participants (13 males, mean age = 28.8 ± 5.4, range 20-37) took part in the study, who engaged in a P300 speller task spelling cued words from a 36-character matrix. In order to evaluate the generalization ability across subjects, the data from 16 participants were used for training and the rest for testing. The total classification accuracy with combination of features is 76.7 %. The receiver operating characteristic (ROC) curve and area under ROC curve (AUC) further indicate the superior performance of the combination of features over any single features in error detection. The average AUC reaches 0.7818 with combined features, while 0.7270, 0.6376, 0.7330 with single temporal, spectral, and spatial features respectively. The proposed method combining multiple-channel features from temporal, spectral, and spatial domain has better classification performance than any individual feature alone. It has good generalization ability across subject and provides a way of improving error detection, which could serve as promising feedbacks to promote the performance of BCI systems.

  14. PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy

    Energy Technology Data Exchange (ETDEWEB)

    Vera, Jaime H. [Brighton and Sussex Medical School, Department of Infection and Global Health, Brighton (United Kingdom); Brighton and Sussex University Hospitals NHS Trust, HIV Department, Brighton (United Kingdom); Ridha, Basil [Brighton and Sussex University Hospitals NHS Trust, Neurology Department, Brighton (United Kingdom); Gilleece, Yvonne; Amlani, Aliza [Brighton and Sussex University Hospitals NHS Trust, HIV Department, Brighton (United Kingdom); Thorburn, Patrick; Dizdarevic, Sabina [Brighton and Sussex University Hospitals NHS Trust, Imaging and Nuclear Medicine Department, Brighton (United Kingdom); Brighton and Sussex Medical School, Clinical Imaging Science Centre, Brighton (United Kingdom)

    2017-05-15

    Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV. (orig.)

  15. Combined Hyperthermia and Radiotherapy for the Treatment of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Punit [Department of Pathology, Scott & White Hospital and the Texas A& M Health Science Center, College of Medicine, Temple, TX 76504 (United States); Hurwitz, Mark D. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center and Harvard Medical School, Boston, MA 02115 (United States); Krishnan, Sunil [Department of Radiation Oncology, The University of Texas MD Anderson Medical Center, Houston, TX 77030 (United States); Asea, Alexzander, E-mail: asea@medicine.tamhsc.edu [Department of Pathology, Scott & White Hospital and the Texas A& M Health Science Center, College of Medicine, Temple, TX 76504 (United States)

    2011-09-30

    Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an integral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, cardiac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threatening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic

  16. Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors.

    Science.gov (United States)

    Thomas, Diana L; Doty, Rosalinda; Tosic, Vesna; Liu, Jia; Kranz, David M; McFadden, Grant; Macneill, Amy L; Roy, Edward J

    2011-10-01

    Adoptive transfer of tumor-specific T cells has shown some success for treating metastatic melanoma. We evaluated a novel strategy to improve adoptive therapy by administering both T cells and oncolytic myxoma virus to mice with syngeneic B16.SIY melanoma brain tumors. Adoptive transfer of activated CD8(+) 2C T cells that recognize SIY peptide doubled survival time, but SIY-negative tumors recurred. Myxoma virus killed B16.SIY cells in vitro, and intratumoral injection of virus led to selective and transient infection of the tumor. Virus treatment recruited innate immune cells to the tumor and induced IFNβ production in the brain, resulting in limited oncolytic effects in vivo. To counter this, we evaluated the safety and efficacy of co-administering 2C T cells, myxoma virus, and either rapamycin or neutralizing antibodies against IFNβ. Mice that received either triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Importantly, rapamycin treatment did not impair T cell-mediated tumor destruction, supporting the feasibility of combining adoptive immunotherapy and rapamycin-enhanced virotherapy. Myxoma virus may be a useful vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses.

  17. Feasibility of approaches combining sensor and source features in brain-computer interface.

    Science.gov (United States)

    Ahn, Minkyu; Hong, Jun Hee; Jun, Sung Chan

    2012-02-15

    Brain-computer interface (BCI) provides a new channel for communication between brain and computers through brain signals. Cost-effective EEG provides good temporal resolution, but its spatial resolution is poor and sensor information is blurred by inherent noise. To overcome these issues, spatial filtering and feature extraction techniques have been developed. Source imaging, transformation of sensor signals into the source space through source localizer, has gained attention as a new approach for BCI. It has been reported that the source imaging yields some improvement of BCI performance. However, there exists no thorough investigation on how source imaging information overlaps with, and is complementary to, sensor information. Information (visible information) from the source space may overlap as well as be exclusive to information from the sensor space is hypothesized. Therefore, we can extract more information from the sensor and source spaces if our hypothesis is true, thereby contributing to more accurate BCI systems. In this work, features from each space (sensor or source), and two strategies combining sensor and source features are assessed. The information distribution among the sensor, source, and combined spaces is discussed through a Venn diagram for 18 motor imagery datasets. Additional 5 motor imagery datasets from the BCI Competition III site were examined. The results showed that the addition of source information yielded about 3.8% classification improvement for 18 motor imagery datasets and showed an average accuracy of 75.56% for BCI Competition data. Our proposed approach is promising, and improved performance may be possible with better head model. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Combined MRI and MRS improves pre-therapeutic diagnoses of pediatric brain tumors over MRI alone

    Energy Technology Data Exchange (ETDEWEB)

    Shiroishi, Mark S.; Nelson, Marvin D. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Pediatric Radiology, Pittsburgh, PA (United States); Moore, Kevin R. [Primary Children' s Medical Center, Department of Radiology, Salt Lake City, UT (United States); Gilles, Floyd H. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Pathology, Los Angeles, CA (United States); Gonzalez-Gomez, Ignacio [All Children' s Hospital, Department of Pathology, St. Petersburg, FL (United States); Blueml, Stefan [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States)

    2015-09-15

    The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre-surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10 % the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27 % of cases the reports were wrong. For group B, the diagnoses were correct in 87 %, partially correct in 5 %, and incorrect in 8 % of the cases, which is a significant improvement (p < 0.005). Re-review of combined MRI and MRS of group A resulted 87 % correct, 7 % partially correct, and 7 % incorrect diagnoses, which is a significant improvement over the original diagnoses (p < 0.05). Adding MRS to conventional MRI significantly improved diagnostic accuracy in preoperative pediatric patients with untreated brain tumors. (orig.)

  19. Combined effects of smoking and HPV16 in oropharyngeal cancer

    DEFF Research Database (Denmark)

    Anantharaman, Devasena; Muller, David C; Lagiou, Pagona

    2016-01-01

    is not understood. METHODS: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multi-centre studies. Odds ratios and credible...... intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression. RESULTS: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association......BACKGROUND: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer...

  20. 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.

  1. 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.

  2. MaLT - Combined Motor and Language Therapy Tool for Brain Injury Patients Using Kinect.

    Science.gov (United States)

    Wairagkar, Maitreyee; McCrindle, Rachel; Robson, Holly; Meteyard, Lotte; Sperrin, Malcom; Smith, Andy; Pugh, Moyra

    2017-03-23

    The functional connectivity and structural proximity of elements of the language and motor systems result in frequent co-morbidity post brain injury. Although rehabilitation services are becoming increasingly multidisciplinary and "integrated", treatment for language and motor functions often occurs in isolation. Thus, behavioural therapies which promote neural reorganisation do not reflect the high intersystem connectivity of the neurologically intact brain. As such, there is a pressing need for rehabilitation tools which better reflect and target the impaired cognitive networks. The objective of this research is to develop a combined high dosage therapy tool for language and motor rehabilitation. The rehabilitation therapy tool developed, MaLT (Motor and Language Therapy), comprises a suite of computer games targeting both language and motor therapy that use the Kinect sensor as an interaction device. The games developed are intended for use in the home environment over prolonged periods of time. In order to track patients' engagement with the games and their rehabilitation progress, the game records patient performance data for the therapist to interrogate. MaLT incorporates Kinect-based games, a database of objects and language parameters, and a reporting tool for therapists. Games have been developed that target four major language therapy tasks involving single word comprehension, initial phoneme identification, rhyme identification and a naming task. These tasks have 8 levels each increasing in difficulty. A database of 750 objects is used to programmatically generate appropriate questions for the game, providing both targeted therapy and unique gameplay every time. The design of the games has been informed by therapists and by discussions with a Public Patient Involvement (PPI) group. Pilot MaLT trials have been conducted with three stroke survivors for the duration of 6 to 8 weeks. Patients' performance is monitored through MaLT's reporting facility

  3. Combined administration of D-galactose and aluminium induces Alzheimer-like lesions in brain.

    Science.gov (United States)

    Xiao, Fei; Li, Xiao-Guang; Zhang, Xiao-Yu; Hou, Jun-Dai; Lin, Lian-Feng; Gao, Qin; Luo, Huan-Min

    2011-06-01

    It has been reported that D-galactose (D-gal) can model subacute aging, and aluminum (Al) acts as a neurotoxin, but combined effects of them have not been reported. The present work aimed to reveal the effect of combined administration of D-gal and Al in mice and compare the effect of D-gal treatment with that of Al treatment. Al was intragastrically administered and D-gal was subcutaneously injected into Kunming mice for 10 consecutive weeks. Learning and memory, cholinergic systems, as well as protein levels of amyloid β (Aβ) and hyperphosphorylated tau were determined using Morri water maze test, biochemical assays and immunohistochemical staining, respectively. The mice with combined treatment had obvious learning and memory deficits, and showed decreases in brain acetylcholine (ACh) level and in activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). Formation of senile plaque (SP)-like and neurofibrillary tangle (NFT)-like structures was also observed. The behavioral and pathological changes persisted for at least 6 weeks after withdrawal of D-gal and Al. Combined use of D-gal and Al is an effective way to establish the non-transgenic Alzheimer's disease (AD) animal model, and is useful for studies of AD pathogenesis and therapeutic evaluation.

  4. Combined chemotherapy and radiation therapy in limited disease small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Moon Kyung; Ahn, Yong Chan; Park, Keun Chil; Lim Do Hoon; Huh, Seung Jae; Kim, Dae Yong; Shin, Kyung Hwan; Lee, Kyu Chan; Kwon, O Jung [College of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

    1999-03-01

    This is a retrospective study to evaluate the response rate, acute toxicity, and survival rate of a combined chemotherapy and radiation therapy in limited disease small cell lung cancer. Forty six patients with limited disease small-cell lung cancer who underwent combined chemotherapy and radiation therapy between October 1994 and April 1998 were evaluated. Six cycles of chemotherapy were planned either using a VIP regimen (etoposide, ifosfamide, and cis-platin) or a EP regimen (etoposide and cis-platin). Thoracic radiation therapy was planned to deliver 44 Gy using 10MV X-ray, starting concurrently with chemotherapy. Response was evaluated 4 weeks after the completion of the planned chemotherapy and radiation therapy, and the prophylactic cranial irradiation was planned only for the patients with complete responses. Acute toxicity was evaluated using the SWOG toxicity criteria, and the overall survival and disease-free survival were calculated using the Kaplan-Meier Method. The median follow-up period was 16 months (range:2 to 41 months). Complete response was achieved in 30 (65%) patients, of which 22 patients received prophylactic cranial irradiations. Acute toxicities over grade III were granulocytopenia in 23 (50%), anemia in 17 (37%), thrombo-cytopenia in nine (20%), alopecia in nine (20%), nausea/vomiting in five (11%), and peripheral neuropathy in one (2%). Chemotherapy was delayed in one patient, and the chemotherapy doses were reduced in 58 (24%) out of the total 246 cycles. No radiation esophagitis over grade III was observed, while interruption during radiation therapy for a mean of 8.3 days occurred in 21 patients. The local recurrences were observed in 8 patients and local progressions were in 6 patients, and the distant metastases in 17 patients. Among these, four patients had both the local relapse and the distant metastasis. Brain was the most common metastatic site (10 patients), followed by the liver as the next common site (4 patients). The

  5. 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 ...

  6. 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.

  7. 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

  8. Exploring combinations of auditory and visual stimuli for gaze-independent brain-computer interfaces.

    Directory of Open Access Journals (Sweden)

    Xingwei An

    Full Text Available For Brain-Computer Interface (BCI systems that are designed for users with severe impairments of the oculomotor system, an appropriate mode of presenting stimuli to the user is crucial. To investigate whether multi-sensory integration can be exploited in the gaze-independent event-related potentials (ERP speller and to enhance BCI performance, we designed a visual-auditory speller. We investigate the possibility to enhance stimulus presentation by combining visual and auditory stimuli within gaze-independent spellers. In this study with N = 15 healthy users, two different ways of combining the two sensory modalities are proposed: simultaneous redundant streams (Combined-Speller and interleaved independent streams (Parallel-Speller. Unimodal stimuli were applied as control conditions. The workload, ERP components, classification accuracy and resulting spelling speed were analyzed for each condition. The Combined-speller showed a lower workload than uni-modal paradigms, without the sacrifice of spelling performance. Besides, shorter latencies, lower amplitudes, as well as a shift of the temporal and spatial distribution of discriminative information were observed for Combined-speller. These results are important and are inspirations for future studies to search the reason for these differences. For the more innovative and demanding Parallel-Speller, where the auditory and visual domains are independent from each other, a proof of concept was obtained: fifteen users could spell online with a mean accuracy of 87.7% (chance level <3% showing a competitive average speed of 1.65 symbols per minute. The fact that it requires only one selection period per symbol makes it a good candidate for a fast communication channel. It brings a new insight into the true multisensory stimuli paradigms. Novel approaches for combining two sensory modalities were designed here, which are valuable for the development of ERP-based BCI paradigms.

  9. Intracavitary moderator balloon combined with (252)Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations.

    Science.gov (United States)

    Brandão, S F; Campos, T P R

    2015-07-01

    This article proposes a combination of californium-252 ((252)Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Dosimetric evaluations were performed on three protocol set-ups: (252)Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0-5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the (252)Cf source, sparing the normal brain tissue. Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis.

  10. Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

    Science.gov (United States)

    Brandão, S F

    2015-01-01

    Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

  11. 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.

  12. 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.

  13. Combination of capecitabine and ludartin inhibits colon cancer ...

    African Journals Online (AJOL)

    Purpose: To investigate the efficacy of capecitabine and ludartin in the treatment of colon cancer in mice. Methods: Mice model of colon cancer was used in this study. Quantitative real-time polymerase chain reaction (Qrt-PCR) was used to quantify the expression of vascular endothelial growth factor (VEGF) mRNA.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Combining ICA and Granger causality: a novel tool for investigation of brain dynamics and brain oscillations using fNIRS measurements

    Science.gov (United States)

    Yuan, Zhen

    2014-03-01

    Identifying directional influences in neural circuits from functional near infrared spectroscopy (fNIRS) recordings presents one of the main challenges for understanding brain dynamics. In this study a new strategy that combines Granger causality mapping (GCM) and independent component analysis (ICA) is proposed to reveal complex neural network dynamics underlying cognitive processes with fNIRS measurements. The GCM-ICA algorithm implements the following two procedures: (i) extraction of the region of interests (ROIs) of cortical activations by ICA, and (ii) estimation of the direct causal influences in local brain networks using Granger causality among voxels of ROIs. Our results show the use of GCM in conjunction with ICA is able to effectively capture the brain network dynamics in time-frequency domain with significantly reduced computational cost. We thus suggest that the GCM-ICA technique is a potentially valuable tool that could be used for the investigation of directional causality influences of brain network dynamics in biophotonics fields.

  2. Explorations of combinational therapy in cancer : targeting the tumor and its microenvironment by combining chemotherapy with chemopreventive approaches

    NARCIS (Netherlands)

    Wijngaarden, Johannes Willem van

    2011-01-01

    One of the most effective anticancer therapy still remains chemotherapy, however, both used as single agent as in combinational regimens, chemotherapy still encounters the problem of therapeutic resistance. Limitations of chemotherapy have led to the exploration of alternative anti-cancer approaches

  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. Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer.

    Science.gov (United States)

    Jang, Na Young; Kim, Dan Hyo; Cho, Bong Jun; Choi, Eun Jung; Lee, Jong-Soo; Wu, Hong-Gyun; Chie, Eui Kyu; Kim, In Ah

    2015-03-03

    Triple-negative breast cancer (TNBC) shows aggressive clinical behavior, but the treatment options are limited due to lack of a specific target. TNBC shares many clinical and pathological similarities with BRCA-deficient breast cancer, for which poly(ADP-ribose) polymerase (PARP) inhibitor is effective, but PARP inhibitor alone failed to show clinical effects in patients with sporadic TNBC. Radiation induces DNA double-strand breaks, and the phosphoinositide 3-kinase (PI3K) signaling pathway has been known to regulate steady-state levels of homologous recombination. A recent preclinical study showed that PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient TNBC to PARP inhibition. Therefore, we assessed the radiosensitizing effect, and the underlying mechanism of combination treatment with PARP inhibitor olaparib and PI3K inhibitor PI-103 in BRCA-proficient TNBC cells. MDA-MB-435S cells were divided into four treatment groups, irradiation (IR) alone, olaparib plus IR, PI-103 plus IR, and olaparib plus PI-103 plus IR. Cells were exposed to the drugs for 2 hours prior to irradiation, and the cell survival curve was obtained using a clonogenic assay. Western blotting and immunofluorescent detection of γH2AX foci were performed. Xenograft and bioluminescence imaging were carried out to assess in vivo radiosensitivity. Combined use of olaparib and PI-103 enhanced radiation-induced death of MDA-MB-435S (sensitizer enhancement ratio[SER]0.05,1.7) and MDA-MB-231-BR (SER0.05,2.1) cells and significantly reduced tumor volume in a xenograft models (P < 0.001). Treatment with PI-103 showed persistent γH2AX foci, indicating delayed repair of DNA strand breaks. PI-103 alone increased levels of poly(ADP-ribose) and phosphorylated extracellular signal-regulated kinase, and downregulated BRCA1. Combined use of olaparib and PI-103 enhanced radiation-induced cell death in BRCA-proficient MDA-MB-435S and MDA-MB-231-BR cells and xenografts. TNBC patients

  5. Subject Combination and Electrode Selection in Cooperative Brain-Computer Interface Based on Event Related Potentials

    Directory of Open Access Journals (Sweden)

    Hubert Cecotti

    2014-04-01

    Full Text Available New paradigms are required in Brain-Computer Interface (BCI systems for the needs and expectations of healthy people. To solve this issue, we explore the emerging field of cooperative BCIs, which involves several users in a single BCI system. Contrary to classical BCIs that are dependent on the unique subject’s will, cooperative BCIs are used for problem solving tasks where several people shall be engaged by sharing a common goal. Similarly as combining trials over time improves performance, combining trials across subjects can significantly improve performance compared with when only a single user is involved. Yet, cooperative BCIs may only be used in particular settings, and new paradigms must be proposed to efficiently use this approach. The possible benefits of using several subjects are addressed, and compared with current single-subject BCI paradigms. To show the advantages of a cooperative BCI, we evaluate the performance of combining decisions across subjects with data from an event-related potentials (ERP based experiment where each subject observed the same sequence of visual stimuli. Furthermore, we show that it is possible to achieve a mean AUC superior to 0.95 with 10 subjects and 3 electrodes on each subject, or with 4 subjects and 6 electrodes on each subject. Several emerging challenges and possible applications are proposed to highlight how cooperative BCIs could be efficiently used with current technologies and leverage BCI applications.

  6. Contrast enhancement by combining T1- and T2-weighted structural brain MR Images.

    Science.gov (United States)

    Misaki, Masaya; Savitz, Jonathan; Zotev, Vadim; Phillips, Raquel; Yuan, Han; Young, Kymberly D; Drevets, Wayne C; Bodurka, Jerzy

    2015-12-01

    In order to more precisely differentiate cerebral structures in neuroimaging studies, a novel technique for enhancing the tissue contrast based on a combination of T1-weighted (T1w) and T2-weighted (T2w) MRI images was developed. The combined image (CI) was calculated as CI = (T1w - sT2w)/(T1w + sT2w), where sT2w is the scaled T2-weighted image. The scaling factor was calculated to adjust the gray- matter (GM) voxel intensities in the T2w image so that their median value equaled that of the GM voxel intensities in the T1w image. The image intensity homogeneity within a tissue and the discriminability between tissues in the CI versus the separate T1w and T2w images were evaluated using the segmentation by the FMRIB Software Library (FSL) and FreeSurfer (Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, Boston, MA) software. The combined image significantly improved homogeneity in the white matter (WM) and GM compared to the T1w images alone. The discriminability between WM and GM also improved significantly by applying the CI approach. Significant enhancements to the homogeneity and discriminability also were achieved in most subcortical nuclei tested, with the exception of the amygdala and the thalamus. The tissue discriminability enhancement offered by the CI potentially enables more accurate neuromorphometric analyses of brain structures. © 2014 Wiley Periodicals, Inc.

  7. Combination Therapy for Multi-Target Manipulation of Secondary Brain Injury Mechanisms.

    Science.gov (United States)

    Somayaji, Mahadevabharath R; Mahadevabharath, R; Przekwas; Andrzej, J; Gupta; Raj, K

    2017-08-28

    Traumatic brain injury (TBI) is a major healthcare problem that affects millions of people worldwide. Despite advances in understanding and developing preventative and treatment strategies using preclinical animal models, clinical trials to date have failed, and a "magic bullet" for effectively treating TBI-induced damage does not exist. Thus, novel pharmacological strategies to effectively manipulate the complex and heterogeneous pathophysiology of secondary injury mechanisms are needed. Given that goal, this paper discusses the relevance and advantages of combination therapies (COMTs) for "multi-target manipulation" of the injury cascade by administering multiple drugs to achieve an optimal therapeutic window of opportunity (e.g., temporally broad window) and compares these regimens to monotherapies that manipulate a single target with a single drug at a time. Furthermore, we posit that integrated mechanistic multiscale models that combine primary biomechanics, secondary injury mechano-/neurobiology, pharmacology and mathematical programming techniques could account for vast differences in the biological space and time scales and help to accelerate drug development, optimize combination pharmacotherapy protocols and improve treatment outcomes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Treating brain tumor-initiating cells using a combination of myxoma virus and rapamycin.

    Science.gov (United States)

    Zemp, Franz J; Lun, Xueqing; McKenzie, Brienne A; Zhou, Hongyuan; Maxwell, Lori; Sun, Beichen; Kelly, John J P; Stechishin, Owen; Luchman, Artee; Weiss, Samuel; Cairncross, J Gregory; Hamilton, Mark G; Rabinovich, Brian A; Rahman, Masmudur M; Mohamed, Mohamed R; Smallwood, Sherin; Senger, Donna L; Bell, John; McFadden, Grant; Forsyth, Peter A

    2013-07-01

    Intratumoral heterogeneity in glioblastoma multiforme (GBM) poses a significant barrier to therapy in certain subpopulation such as the tumor-initiating cell population, being shown to be refractory to conventional therapies. Oncolytic virotherapy has the potential to target multiple compartments within the tumor and thus circumvent some of the barriers facing conventional therapies. In this study, we investigate the oncolytic potential of myxoma virus (MYXV) alone and in combination with rapamycin in vitro and in vivo using human brain tumor-initiating cells (BTICs). We cultured fresh GBM specimens as neurospheres and assayed their growth characteristics in vivo. We then tested the susceptibility of BTICs to MYXV infection with or without rapamycin in vitro and assessed viral biodistribution/survival in vivo in orthotopic xenografts. The cultured neurospheres were found to retain stem cell markers in vivo, and they closely resembled human infiltrative GBM. In this study we determined that (i) all patient-derived BTICs tested, including those resistant to temozolomide, were susceptible to MYXV replication and killing in vitro; (ii) MYXV replicated within BTICs in vivo, and intratumoral administration of MYXV significantly prolonged survival of BTIC-bearing mice; (iii) combination therapy with MYXV and rapamycin improved antitumor activity, even in mice bearing "advanced" BTIC tumors; (iv) MYXV treatment decreased expression of stem cell markers in vitro and in vivo. Our study suggests that MYXV in combination with rapamycin infects and kills both the BTICs and the differentiated compartments of GBM and may be an effective treatment even in TMZ-resistant patients.

  9. 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.

  10. 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.

  11. Combining Brain-Computer Interfaces and Assistive Technologies: State-of-the-Art and Challenges.

    Science.gov (United States)

    Millán, J D R; Rupp, R; Müller-Putz, G R; Murray-Smith, R; Giugliemma, C; Tangermann, M; Vidaurre, C; Cincotti, F; Kübler, A; Leeb, R; Neuper, C; Müller, K-R; Mattia, D

    2010-01-01

    In recent years, new research has brought the field of electroencephalogram (EEG)-based brain-computer interfacing (BCI) out of its infancy and into a phase of relative maturity through many demonstrated prototypes such as brain-controlled wheelchairs, keyboards, and computer games. With this proof-of-concept phase in the past, the time is now ripe to focus on the development of practical BCI technologies that can be brought out of the lab and into real-world applications. In particular, we focus on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT). In pursuit of more practical BCIs for use outside of the lab, in this paper, we identify four application areas where disabled individuals could greatly benefit from advancements in BCI technology, namely, "Communication and Control", "Motor Substitution", "Entertainment", and "Motor Recovery". We review the current state of the art and possible future developments, while discussing the main research issues in these four areas. In particular, we expect the most progress in the development of technologies such as hybrid BCI architectures, user-machine adaptation algorithms, the exploitation of users' mental states for BCI reliability and confidence measures, the incorporation of principles in human-computer interaction (HCI) to improve BCI usability, and the development of novel BCI technology including better EEG devices.

  12. Combining Brain-Computer Interfaces and Assistive Technologies: State-of-the-Art and Challenges

    Directory of Open Access Journals (Sweden)

    José del R. Millán

    2010-09-01

    Full Text Available In recent years, new research has brought the field of EEG-based Brain-Computer Interfacing (BCI out of its infancy and into a phase of relative maturity through many demonstrated prototypes such as brain-controlled wheelchairs, keyboards, and computer games. With this proof-of-concept phase in the past, the time is now ripe to focus on the development of practical BCI technologies that can be brought out of the lab and into real-world applications. In particular, we focus on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT. In pursuit of more practical BCIs for use outside of the lab, in this paper, we identify four application areas where disabled individuals could greatly benefit from advancements in BCI technology, namely,“Communication & Control”, “Motor Substitution”, “Entertainment”, and “Motor Recovery”. We review the current state of the art and possible future developments, while discussing the main research issues in these four areas. In particular, we expect the most progress in the development of technologies such as hybrid BCI architectures, user-machine adaptation algorithms, the exploitation of users’ mental states for BCI reliability and confidence measures, the incorporation of principles in human-computer interaction (HCI to improve BCI usability, and the development of novel BCI technology including better EEG devices.

  13. Enhancement of Combined Umami and Salty Taste by Glutathione in the Human Tongue and Brain.

    Science.gov (United States)

    Goto, Tazuko K; Yeung, Andy Wai Kan; Tanabe, Hiroki C; Ito, Yuki; Jung, Han-Sung; Ninomiya, Yuzo

    2016-09-01

    Glutathione, a natural substance, acts on calcium receptors on the tongue and is known to enhance basic taste sensations. However, the effects of glutathione on brain activity associated with taste sensation on the tongue have not been determined under standardized taste delivery conditions. In this study, we investigated the sensory effect of glutathione on taste with no effect of the smell when glutathione added to a combined umami and salty taste stimulus. Twenty-six volunteers (12 women and 14 men; age 19-27 years) performed a sensory evaluation of taste of a solution of monosodium L-glutamate and sodium chloride, with and without glutathione. The addition of glutathione changed taste qualities and significantly increased taste intensity ratings under standardized taste delivery conditions (P umami and salty mixture. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Combined Treatment of Residual, Recurrent and Unresectable Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Hoon Sik [Maryknoll Hospital, Pusan (Korea, Republic of)

    1990-06-15

    A series of 25 patients with residual, recurrent, and unresectable gastric cancer received various combination of surgery, radiotherapy (RT), chemotherapy (CT), and hyperthermia (HT). They were placed INTO 7 categories; 1) CT and HT-14 patients; 2) RT and HT-15 patients; 3) surgery, RT and HT-2 patients; 4) surgery, RT, HT and CT-1 patient; 5) RT, HT and CT-1 patient; 6) RT and CT-1 patient; 7) RT alone-1 patient. Three patients had curative resection. 21 patients received irradiation with tightly contoured portals to spare as much small bowel, kidney and marrow as possible. Hyperthermia was applied regionally once or twice a week for 23 patients using 8 MHz radiofrequency capacitive heating device (Thermotron RF-8). HT was given approximately 30 min after RT. 7 patients were treated with CT: 4 patients received HT and concomitant Mitomycin-C; 3 patients received HT and sequential 5-FU+Adriamycin+Mitomycin-C. There was not any treatment related deaths. There was also no evidence of treatment related problems with liver, kidney, stomach, or spinal cord except only one case of transient diabetic ketoacidosis. The tumor response was evaluable in 22 patients. None achieved complete remission. 11(50%) achieved partial remission. The response rate was correlated with total radiation dose and achieved maximum temperature. 9 of 14 (64%) received more than 4000 cGy showed partial remission; especially, all 3 patients received more than 5500 cGy achieved partial response. 8 of the 12 patients (67%) who achieved maximal temperature more than 41 .deg. C showed partial response in comparing with 25% (2 of 8 patients, below 41 .deg. C). The numbers of HT, however, was not correlated with the response. 3 of the 25 patients (12%) remain alive. The one who was surgically unresectable and underwent irradiation alone is in progression of the disease with distant metastases. The remaining two patients with curative resection are alive with free of disease, 24 and 35 months

  15. 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

  16. 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 ...

  17. 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

  18. 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.

  19. Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

    Science.gov (United States)

    Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

  20. A Selective Ensemble Classification Method Combining Mammography Images with Ultrasound Images for Breast Cancer Diagnosis

    Directory of Open Access Journals (Sweden)

    Jinyu Cong

    2017-01-01

    Full Text Available Breast cancer has been one of the main diseases that threatens women’s life. Early detection and diagnosis of breast cancer play an important role in reducing mortality of breast cancer. In this paper, we propose a selective ensemble method integrated with the KNN, SVM, and Naive Bayes to diagnose the breast cancer combining ultrasound images with mammography images. Our experimental results have shown that the selective classification method with an accuracy of 88.73% and sensitivity of 97.06% is efficient for breast cancer diagnosis. And indicator R presents a new way to choose the base classifier for ensemble learning.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. [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.

  6. Partial volume correction of brain PET studies using iterative deconvolution in combination with HYPR denoising.

    Science.gov (United States)

    Golla, Sandeep S V; Lubberink, Mark; van Berckel, Bart N M; Lammertsma, Adriaan A; Boellaard, Ronald

    2017-12-01

    Accurate quantification of PET studies depends on the spatial resolution of the PET data. The commonly limited PET resolution results in partial volume effects (PVE). Iterative deconvolution methods (IDM) have been proposed as a means to correct for PVE. IDM improves spatial resolution of PET studies without the need for structural information (e.g. MR scans). On the other hand, deconvolution also increases noise, which results in lower signal-to-noise ratios (SNR). The aim of this study was to implement IDM in combination with HighlY constrained back-PRojection (HYPR) denoising to mitigate poor SNR properties of conventional IDM. An anthropomorphic Hoffman brain phantom was filled with an [ 18 F]FDG solution of ~25 kBq mL -1 and scanned for 30 min on a Philips Ingenuity TF PET/CT scanner (Philips, Cleveland, USA) using a dynamic brain protocol with various frame durations ranging from 10 to 300 s. Van Cittert IDM was used for PVC of the scans. In addition, HYPR was used to improve SNR of the dynamic PET images, applying it both before and/or after IDM. The Hoffman phantom dataset was used to optimise IDM parameters (number of iterations, type of algorithm, with/without HYPR) and the order of HYPR implementation based on the best average agreement of measured and actual activity concentrations in the regions. Next, dynamic [ 11 C]flumazenil (five healthy subjects) and [ 11 C]PIB (four healthy subjects and four patients with Alzheimer's disease) scans were used to assess the impact of IDM with and without HYPR on plasma input-derived distribution volumes (V T ) across various regions of the brain. In the case of [ 11 C]flumazenil scans, Hypr-IDM-Hypr showed an increase of 5 to 20% in the regional V T whereas a 0 to 10% increase or decrease was seen in the case of [ 11 C]PIB depending on the volume of interest or type of subject (healthy or patient). References for these comparisons were the V T s from the PVE-uncorrected scans. IDM improved quantitative accuracy

  7. Propranolol and Mesenchymal Stromal Cells Combine to Treat Traumatic Brain Injury.

    Science.gov (United States)

    Kota, Daniel J; Prabhakara, Karthik S; van Brummen, Alexandra J; Bedi, Supinder; Xue, Hasen; DiCarlo, Bryan; Cox, Charles S; Olson, Scott D

    2016-01-01

    More than 6.5 million patients are burdened by the physical, cognitive, and psychosocial deficits associated with traumatic brain injury (TBI) in the U.S. Despite extensive efforts to develop neuroprotective therapies for this devastating disorder, there have been no successful outcomes in human clinical trials to date. Retrospective studies have shown that β-adrenergic receptor blockers, specifically propranolol, significantly decrease mortality of TBI through mechanisms not yet fully elucidated but are thought to counterbalance a hyperadrenergic state resulting from a TBI. Conversely, cellular therapies have been shown to improve long-term behavior following TBI, likely by reducing inflammation. Given the nonredundancy in their therapeutic mechanisms, we hypothesized that a combination of acute propranolol followed by mesenchymal stem cells (MSCs) isolated from human bone marrow would have additive effects in treating a rodent model of TBI. We have found that the treatments are well-tolerated individually and in combination with no adverse events. MSCs decrease BBB permeability at 96 hours after injury, inhibit a significant accumulation of activated microglia/macrophage in the thalamic region of the brain both short and long term, and enhance neurogenesis short term. Propranolol decreases edema and reduces the number of fully activated microglia at 7 days and the number of semiactivated microglia at 120 days. Combinatory treatment improved cognitive and memory functions 120 days following TBI. Therefore, the results here suggest a new, efficacious sequential treatment for TBI may be achieved using the β-blocker propranolol followed by MSC treatment. Despite continuous efforts, traumatic brain injury (TBI) remains the leading cause of death and disability worldwide in patients under the age of 44. In this study, an animal model of moderate-severe TBI was treated with an acute dose of propranolol followed by a delayed dose of human mesenchymal stem cells (MSCs

  8. 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.

  9. Combination of Aβ Suppression and Innate Immune Activation in the Brain Significantly Attenuates Amyloid Plaque Deposition.

    Science.gov (United States)

    Verbeeck, Christophe; Carrano, Anna; Chakrabarty, Paramita; Jankowsky, Joanna L; Das, Pritam

    2017-12-01

    Anti-Aβ clinical trials are currently under way to determine whether preventing amyloid deposition will be beneficial in arresting progression of Alzheimer disease. Both clinical and preclinical studies suggest that antiamyloid strategies are only effective if started at early stages of the disease process in a primary prevention strategy. Because this approach will be difficult to deploy, strategies for secondary prevention aimed at later stages of disease are also needed. In this study, we asked whether combining innate immune activation in the brain with concurrent Aβ suppression could enhance plaque clearance and could improve pathologic outcomes in mice with moderate amyloid pathologic disorder. Starting at 5 months of age, tet-off amyloid precursor protein transgenic mice were treated with doxycycline (dox) to suppress further amyloid precursor protein/Aβ production, and at the same time mice were intracranially injected with adeno-associated virus 1 expressing murine IL-6 (AAV1-mIL-6). Three months later, mice treated with the combination of Aβ suppression and AAV1-mIL-6 showed significantly less plaque pathologic disorder than dox or AAV1-mIL-6 only groups. The combination of AAV1-mIL-6 + dox treatment lowered total plaque burden by >60% versus untreated controls. Treatment with either dox or AAV1-mIL-6 alone was less effective than the combination. Our results suggest a synergistic mechanism by which the up-regulation of mIL-6 was able to improve plaque clearance in the setting of Aβ suppression. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. MAP training: combining meditation and aerobic exercise reduces depression and rumination while enhancing synchronized brain activity

    Science.gov (United States)

    Alderman, B L; Olson, R L; Brush, C J; Shors, T J

    2016-01-01

    Mental and physical (MAP) training is a novel clinical intervention that combines mental training through meditation and physical training through aerobic exercise. The intervention was translated from neuroscientific studies indicating that MAP training increases neurogenesis in the adult brain. Each session consisted of 30 min of focused-attention (FA) meditation and 30 min of moderate-intensity aerobic exercise. Fifty-two participants completed the 8-week intervention, which consisted of two sessions per week. Following the intervention, individuals with major depressive disorder (MDD; n=22) reported significantly less depressive symptoms and ruminative thoughts. Typical healthy individuals (n=30) also reported less depressive symptoms at follow-up. Behavioral and event-related potential indices of cognitive control were collected at baseline and follow-up during a modified flanker task. Following MAP training, N2 and P3 component amplitudes increased relative to baseline, especially among individuals with MDD. These data indicate enhanced neural responses during the detection and resolution of conflicting stimuli. Although previous research has supported the individual beneficial effects of aerobic exercise and meditation for depression, these findings indicate that a combination of the two may be particularly effective in increasing cognitive control processes and decreasing ruminative thought patterns. PMID:26836414

  20. Two critical brain networks for generation and combination of remote associations.

    Science.gov (United States)

    Bendetowicz, David; Urbanski, Marika; Garcin, Béatrice; Foulon, Chris; Levy, Richard; Bréchemier, Marie-Laure; Rosso, Charlotte; Thiebaut de Schotten, Michel; Volle, Emmanuelle

    2018-01-01

    Recent functional imaging findings in humans indicate that creativity relies on spontaneous and controlled processes, possibly supported by the default mode and the fronto-parietal control networks, respectively. Here, we examined the ability to generate and combine remote semantic associations, in relation to creative abilities, in patients with focal frontal lesions. Voxel-based lesion-deficit mapping, disconnection-deficit mapping and network-based lesion-deficit approaches revealed critical prefrontal nodes and connections for distinct mechanisms related to creative cognition. Damage to the right medial prefrontal region, or its potential disrupting effect on the default mode network, affected the ability to generate remote ideas, likely by altering the organization of semantic associations. Damage to the left rostrolateral prefrontal region and its connections, or its potential disrupting effect on the left fronto-parietal control network, spared the ability to generate remote ideas but impaired the ability to appropriately combine remote ideas. Hence, the current findings suggest that damage to specific nodes within the default mode and fronto-parietal control networks led to a critical loss of verbal creative abilities by altering distinct cognitive mechanisms. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. A Combined Intensity and Gradient-Based Similarity Criterion for Interindividual SPECT Brain Scan Registration

    Directory of Open Access Journals (Sweden)

    Bengtsson Ewert

    2003-01-01

    Full Text Available An evaluation of a new similarity criterion for interindividual image registration is presented. The proposed criterion combines intensity and gradient information from the images to achieve a more robust and accurate registration. It builds on a combination of the normalised mutual information (NMI cost function and a gradient-weighting function, calculated from gradient magnitude and relative gradient angle values from the images. An investigation was made to determine the best settings for the number of bins in the NMI joint histograms, subsampling, and smoothing of the images prior to the registration. The new method was compared with the NMI and correlation-coefficient (CC criterions for interindividual SPECT image registration. Two different validation tests were performed, based on the displacement of voxels inside the brain relative to their estimated true positions after registration. The results show that the registration quality was improved when compared with the NMI and CC measures. The actual improvements, in one of the tests, were in the order of 30-40% for the mean voxel displacement error measured within 20 different SPECT images. A conclusion from the studies is that the new similarity measure significantly improves the registration quality, compared with the NMI and CC similarity measures.

  2. Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

    Science.gov (United States)

    Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

    2015-12-01

    It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,pmusic induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01). Copyright © 2015 Elsevier Inc. All rights reserved.

  3. 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.

  4. 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.

  5. Adjuvant chemoradiotherapy combined with cisplatin, 5-fluorouracil and folinic acid for locally advanced gastric cancer

    Directory of Open Access Journals (Sweden)

    Muharrem Kocar

    2016-04-01

    Conclusion: The addition of combination chemotherapy with cisplatin, infusional 5-fluorouracil and folinic acid before and after chemoradiotherapy was found to be safe and effective in patients with operated gastric cancer.

  6. Advances in combination therapy of lung cancer: Rationales, delivery technologies and dosage regimens

    DEFF Research Database (Denmark)

    Wu, Lan; Leng, Donglei; Cun, Dongmei

    2017-01-01

    Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy...... using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given...... for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials....

  7. 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.

  8. 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

  9. 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 ...

  10. A Novel Combination of Thermal Ablation and Heat-Inducible Gene therapy for Breast Cancer Treatment

    Science.gov (United States)

    2009-04-01

    intensity focused ultrasound ( HIFU ) has been developed as an emerging non-invasive strategy for cancer treatment by thermal ablation of tumor tissue. The...feasibility of synergistic combination of HIFU thermal ablation and HIFU -induced gene therapy is interpreted both in vitro and in vivo using cancer...distribution. This work opens up a new paradigm for synergistic combination of HIFU thermal ablation with heat-induced gene therapy to improve the overall

  11. Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, Sanne; Fredslund, Rikke; Lindebjerg, Jan

    2012-01-01

    To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.......To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients....

  12. Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer

    Science.gov (United States)

    2015-10-01

    1 AWARD NUMBER: W81XWH-14-1-0109 TITLE: Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer PRINCIPAL...Report 3. DATES COVERED 4. TITLE AND SUBTITLE Combination Immunotherapy for the Treatment of High-Risk HER2Positive Breast Cancer 5a. CONTRACT NUMBER...HER2-positive, immunotherapy , vaccines, NeuVax, clinical trial 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a

  13. Combined therapy of iron chelator and antioxidant completely restores brain dysfunction induced by iron toxicity

    National Research Council Canada - National Science Library

    Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

    2014-01-01

    .... We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine...

  14. Combination of capecitabine and ludartin inhibits colon cancer ...

    African Journals Online (AJOL)

    increase in white blood cell (WBC) count, and increased median survival time of colon cancer mice from. 38 to 55 days. Expression of VEGF in ... pathway and mutation of cell cycle components. [3-6]. It has also been observed that ..... Angew Chem Int Ed. Eng1985; 24: 94. 9. Rodriguez E, Towers GHN, Mitchell JC.

  15. Cardiotoxicity from intensive chemotherapy combined with radiotherapy in breast cancer

    NARCIS (Netherlands)

    deGraaf, H; Dolsma, WV; Willemse, PHB; vanderGraaf, WTA; Sleijfer, DT; deVries, EGE; Mulder, NH

    1997-01-01

    Cardiac function was evaluated in 86 breast cancer patients after standard chemotherapy, followed by ablative chemotherapy and chest irradiation. One patient died of subacute heart failure 3 months after ablative chemotherapy. At a minimum of 1 year's follow-up (range 1-11 years) left vertricular

  16. 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 ...

  17. 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.

  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. 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.

  1. 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

  2. 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.

  3. Tissue distribution of crizotinib and gemcitabine combination in a patient-derived orthotopic mouse model of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Richard J. Honeywell

    2016-12-01

    Full Text Available Pharmacokinetics focuses on the question whether a drug actually reaches its target in therapeutic concentrations or accumulates elsewhere, potentially causing toxicological or unpredictable side effects. We determined tissue distribution of gemcitabine, an antimetabolite, and crizotinib, a tyrosine-kinase inhibitor targeted against the anaplastic lymphoma kinase (ALK and mesenchymal-epithelial transition factor (c-Met receptors, in a validated orthotopic mouse model for pancreatic cancer. Mice with pancreatic cancer were treated with either oral crizotinib at 25 mg/kg, gemcitabine at 100 mg/kg or with their combination. Two hours after the last gemcitabine dose mice were sacrificed and all available blood/organs/tissues were sampled. Tissue was subsequently analyzed for drug concentrations using a validated liquid chromatography-mass spectrometry (LC-MS/MS technique. In whole blood gemcitabine was about 1.0 µM and crizotinib 2.4 µM in the single treatment, whereas in the combination crizotinib increased the levels of gemcitabine. Crizotinib was found in all major tissues, being highest in the intestine. Comparison of crizotinib alone to the gemcitabine-crizotinib combination showed that crizotinib tissue concentrations were 3-6 fold lower in liver, lung, kidney and spleen, 30-fold lower in the skin, heart and pancreas and 200-fold lower in the brain. Tissue gemcitabine was highest in spleen and skin, being about 5-10 fold higher than in the other tissues, including brain, which still had a relatively high accumulation. In conclusion, both gemcitabine and crizotinib accumulate at clinically active but variable levels in tissues, possibly relating to the effects exerted by these drugs.

  4. 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

  5. Simvastatin Combined with Antioxidant Attenuates the Cerebral Vascular Endothelial Inflammatory Response in a Rat Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Kuo-Wei Wang

    2014-01-01

    Full Text Available Traumatic brain injury (TBI leads to important and deleterious neuroinflammation, as evidenced by indicators such as edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In our previous study, we proved that simvastatin could attenuate cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat. In our study, cortical contusions were induced, and the effect of acute and continuous treatment of simvastatin and vitamin C on behavior and inflammation in adult rats following experimental TBI was evaluated. The results demonstrated that simvastatin combined with an antioxidant could provide neuroprotection and it may be attributed to a dampening of cerebral vascular endothelial inflammatory response.

  6. 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.

  7. 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.

  8. NMR with Combined Antiangiogenic and Radiation Therapies - Breast Cancer

    National Research Council Canada - National Science Library

    Brown, Stephen

    2000-01-01

    The original goal of the present study was to determine optimal strategies for combining radiation and antiangiogenic therapies in spontaneous murine tumors and to evaluate the potential of Nuclear Magnetic Resonance (NMR...

  9. Schiff base-Poloxamer P85 combination demonstrates chemotherapeutic effect on prostate cancer cells in vitro.

    Science.gov (United States)

    Demirci, Selami; Doğan, Ayşegül; Türkmen, Neşe Başak; Telci, Dilek; Rizvanov, Albert A; Şahin, Fikrettin

    2017-02-01

    Prostate cancer is a multistep and complicated cancer type that is regulated by androgens at the cellular level and remains the second commonest cause of death among men. Discovery and development of novel chemotherapeutic agents enabling rapid tumor cell death with minimal toxic effects to healthy tissues might greatly improve the safety of chemotherapy. The present study evaluates the anti-cancer activity of a novel heterodinuclear copper(II)Mn(II) complex (Schiff base) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (Pluronic) P85. We used assays for cell proliferation, apoptosis, cell migration and invasion, DNA binding and cleavage to elucidate the molecular mechanisms of action, in addition to the anti-inflammatory potency of the new combination. The combined treatment of Schiff base and P85 lead to a remarkable anti-cancer effect on prostate cancer cell lines. Cell proliferation was inhibited in Schiff base-P85 treatment. The activity of this formulation is on DNA binding and cleavage and prevents inflammation in in vitro conditions. This is the first study presenting the anti-cancer activity of the present Schiff base derivative and its combination with P85 to treat prostate cancer in vitro. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. [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.

  11. 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

  12. Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures

    Directory of Open Access Journals (Sweden)

    Chan Daniel K

    2012-07-01

    Full Text Available Abstract Background High mortality rates in ovarian cancer are largely a result of resistance to currently used chemotherapies. Expanding therapies with a variety of drugs has the potential to reduce this high mortality rate. Metformin and phenethyl isothiocyanate (PEITC are both potentially useful in ovarian cancer, and they are particularly attractive because of their safety. Methods Cell proliferation of each drug and drug combination was evaluated by hemacytometry with Trypan blue exclusion or Sytox green staining for cell death. Levels of total and cleaved PARP were measured by Western blot. General cellular and mitochondrial reactive oxygen species were measured by flow cytometry and live cell confocal microscopy with the fluorescent dyes dihydroethidine and MitoSOX. Results Individually, metformin and PEITC each show inhibition of cell growth in multiple ovarian cancer cell lines. Alone, PEITC was also able to induce apoptosis, whereas metformin was primarily growth inhibitory. Both total cellular and mitochondrial reactive oxygen species were increased when treated with either metformin or PEITC. The growth inhibitory effects of metformin were reversed by methyl succinate supplementation, suggesting complex I plays a role in metformin's anti-cancer mechanism. PEITC's anti-cancer effect was reversed by N-acetyl-cysteine supplementation, suggesting PEITC relies on reactive oxygen species generation to induce apoptosis. Metformin and PEITC together showed a synergistic effect on ovarian cancer cell lines, including the cisplatin resistant A2780cis. Conclusions Here we show that when used in combination, these drugs are effective in both slowing cancer cell growth and killing ovarian cancer cells in vitro. Furthermore, the combination of these drugs remains effective in cisplatin resistant cell lines. Novel combinations such as metformin and PEITC show promise in expanding ovarian cancer therapies and overcoming the high incidence of

  13. Meta-analysis of gemcitabine and cisplatin combination chemotherapy versus gemcitabine alone for pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Diyu Huang

    2016-01-01

    Conclusions: Overall response rate, stable disease, and progressive disease, as well as 1-year survival rate in patients who received GEM + CIS, were superior to those treated with GEM alone. Combination chemotherapy with GEM and CIS may offer greater benefits in the treatment of pancreatic cancer than that of GEM alone although the combination group had higher hematological toxicities.

  14. 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.

  15. 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...

  16. 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.

  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. 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.

  20. Effects of Physical Exercise Combined with Nutritional Supplements on Aging Brain Related Structures and Functions: A Systematic Review.

    Science.gov (United States)

    Schättin, Alexandra; Baur, Kilian; Stutz, Jan; Wolf, Peter; de Bruin, Eling D

    2016-01-01

    Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: "Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?" Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods with

  1. Imaging nonmelanoma skin cancers with combined ultrasound-photoacoustic microscopy

    Science.gov (United States)

    Sunar, Ulas; Rohrbach, Daniel J.; Morgan, Janet; Zeitouni, Natalie

    2013-03-01

    PDT has become a treatment of choice especially for the cases with multiple sites and large areas. However, the efficacy of PDT is limited for thicker and deeper tumors. Depth and size information as well as vascularity can provide useful information to clinicians for planning and evaluating PDT. High-resolution ultrasound and photoacoustic imaging can provide information regarding skin structure and vascularity. We utilized combined ultrasound-photoacoustic microscopy for imaging a basal cell carcinoma (BCC) tumor pre-PDT and the results indicate that combined ultrasound-photoacoustic imaging can be useful tool for PDT planning by providing both structural and functional contrasts.

  2. 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

  3. The Impact of Combined Prehospital Hypotension and Hypoxia on Mortality in Major Traumatic Brain Injury

    Science.gov (United States)

    Spaite, Daniel W.; Hu, Chengcheng; Bobrow, Bentley J.; Chikani, Vatsal; Barnhart, Bruce; Gaither, Joshua B.; Denninghoff, Kurt R.; Adelson, P. David; Keim, Samuel M.; Viscusi, Chad; Mullins, Terry; Sherrill, Duane

    2016-01-01

    BACKGROUND Survival is significantly reduced by either hypotension or hypoxia during the prehospital management of major traumatic brain injury (TBI). However, only a handful of small studies have investigated the influence of the combination of both hypotension and hypoxia occurring together. Objective: In patients with major TBI, we evaluated the associations between mortality and prehospital hypotension and hypoxia, both separately and in combination. METHODS All moderate/severe TBI cases in the pre-implementation cohort of the Excellence in Prehospital Injury Care (EPIC) Study (a statewide, before/after, controlled study of the impact of implementing the prehospital TBI treatment guidelines) from 1/1/07–3/31/14 were evaluated [exclusions: age200mmHg]. The relationship between mortality and hypotension (SBP controlling for Injury Severity Score, head region severity, injury type (blunt versus penetrating), age, sex, race, ethnicity, payer, inter-hospital transfer, and trauma center. RESULTS Among the 13,151 cases that met inclusion criteria [Median age: 45; Male: 68.6%], 11,545 (87.8%) had neither hypotension nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and 212 (1.6%) had both hypotension and hypoxia. Mortality for the four study cohorts was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds ratios (cOR/aOR) for death within the cohorts, utilizing the patients with neither hypotension nor hypoxia as the reference, were 4.4/2.5, 6.6/3.0, and 13.2/6.1, respectively. Evaluation for an interaction between hypotension and hypoxia revealed that the effects are additive on the log odds of death. CONCLUSION In this statewide analysis of major TBI, combined prehospital hypotension/hypoxia were associated with dramatically increased mortality. This effect on survival persisted even after controlling for multiple potential confounders. In fact, the adjusted odds of death in patients with both hypotension and hypoxia was

  4. 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

  5. Combined doxorubicin and paclitaxel in advanced breast cancer

    DEFF Research Database (Denmark)

    Gehl, J; Boesgaard, M; Paaske, T

    1996-01-01

    -550). The main toxicities were neutropenia, parestesia, nausea/vomiting, alopecia, myalgia and cardiotoxicity. Fifteen patients (50%) had reductions of left ventricular ejection fraction of below normal levels and 6 of these patients (20%) developed congestive heart failure. CONCLUSION: The combination...

  6. 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 ...

  7. Mechanistic overview of immune checkpoints to support the rational design of their combinations in cancer immunotherapy.

    Science.gov (United States)

    Rotte, A; Jin, J Y; Lemaire, V

    2017-10-24

    Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy. Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab), and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hogdkins lymphoma. The main problem with checkpoint blockers is that only a fraction of patients respond to the therapy. Insufficient immune activation is considered as one of the main reason for low response rates and combination of checkpoint blockers has been proposed to increase the response rates. The combination of checkpoint blockers was successful in melanoma but had significant adverse events. A combination that is selected based on the mechanistic differences between checkpoints and the differences in expression of checkpoints and their ligands in the tumor microenvironment (TME) could have a synergistic effect in a given cancer subtype and also have a manageable safety profile. This review aims to help in design of optimal checkpoint blocker combinations by discussing the mechanistic details and outlining the subtle differences between major checkpoints targeted for cancer immunotherapy. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. [br]All rights reserved. For

  8. A combined registration and finite element analysis method for fast estimation of intraoperative brain shift; phantom and animal model study.

    Science.gov (United States)

    Mohammadi, Amrollah; Ahmadian, Alireza; Rabbani, Shahram; Fattahi, Ehsan; Shirani, Shapour

    2017-12-01

    Finite element models for estimation of intraoperative brain shift suffer from huge computational cost. In these models, image registration and finite element analysis are two time-consuming processes. The proposed method is an improved version of our previously developed Finite Element Drift (FED) registration algorithm. In this work the registration process is combined with the finite element analysis. In the Combined FED (CFED), the deformation of whole brain mesh is iteratively calculated by geometrical extension of a local load vector which is computed by FED. While the processing time of the FED-based method including registration and finite element analysis was about 70 s, the computation time of the CFED was about 3.2 s. The computational cost of CFED is almost 50% less than similar state of the art brain shift estimators based on finite element models. The proposed combination of registration and structural analysis can make the calculation of brain deformation much faster. Copyright © 2016 John Wiley & Sons, Ltd.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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, ...

  16. 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 ...

  17. 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

  18. Combination of TB lymphadenitis and metastatic LAP in breast cancer

    Directory of Open Access Journals (Sweden)

    Abdolhassan Talaiezadeh

    2015-06-01

    Full Text Available Tuberculosis (TB may present as pulmonary and extra-pulmonary. TB lymphadenitis is the most common presentation of extra-pulmonary TB. TB lymphadenitis should be taken into account in the differential diagnosis of different disorders such as metastatic lymphadenopathy. The reported patient was a 65-year-old lady with breast cancer and conglomerated and matted axillary lymphadenopathy who received chemotherapy. She presented with more extensive axillary LAP contrary to our expectation. Modified radical mastectomy was done and pathology analysis reported TB lymphadenitis associated with metastatic LAP. Under cover of anti-TB therapy adjuvant chemoradiation therapy was started. Accordingly, we recommend TB be ruled out in every patient who needs chemotherapy in the endemic region because chemotherapy may cause the extension of TB in the body.

  19. 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)

  20. The Timing and Quality of Early Experiences Combine to Shape Brain Architecture. Working Paper #5

    Science.gov (United States)

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    The foundations of brain architecture are established early in life through a continuous series of dynamic interactions in which environmental conditions and personal experiences have a significant impact on how genetic predispositions are expressed. Because specific experiences affect specific brain circuits during specific developmental…

  1. Minocycline and N-acetylcysteine: A Synergistic Drug Combination to Treat Traumatic Brain Injury

    Science.gov (United States)

    2013-10-01

    TBI (“Multidrug treatment of traumatic brain injury”, PT073028) from the Fiscal Year 2007 CDMRP program for Psychological Health/Traumatic Brain...ncbi.nlm.nih.gov/pubmed/20166806). Inman, C.F., et al., 2005. Validation of computer-assisted, pixel-based analysis of multiple- colour immunofluorescence

  2. 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.

  3. ViRPET--combination of virtual reality and PET brain imaging

    Energy Technology Data Exchange (ETDEWEB)

    Majewski, Stanislaw; Brefczynski-Lewis, Julie

    2017-05-23

    Various methods, systems and apparatus are provided for brain imaging during virtual reality stimulation. In one example, among others, a system for virtual ambulatory environment brain imaging includes a mobile brain imager configured to obtain positron emission tomography (PET) scans of a subject in motion, and a virtual reality (VR) system configured to provide one or more stimuli to the subject during the PET scans. In another example, a method for virtual ambulatory environment brain imaging includes providing stimulation to a subject through a virtual reality (VR) system; and obtaining a positron emission tomography (PET) scan of the subject while moving in response to the stimulation from the VR system. The mobile brain imager can be positioned on the subject with an array of imaging photodetector modules distributed about the head of the subject.

  4. 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.

  5. 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

  6. 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 ...

  7. 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.

  8. Targeted Therapy Combined with Immune Modulation Using Gold Nanoparticles for Treating Metastatic Colorectal Cancer

    Science.gov (United States)

    2017-09-01

    stimulate the body’s immune system to target and attack cancer cells. Another part of our research includes coating these gold nanoparticles with...AWARD NUMBER: W81XWH-16-1-0427 TITLE: Targeted Therapy Combined with Immune Modulation Using Gold Nanoparticles for Treating Metastatic Colorectal... Nanoparticles for Treating Metastatic Colorectal Cancer 5b. GRANT NUMBER W81XWH-16-1-0427 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Branden Moriarity, Tim

  9. Novel anesthetic technique for combined intracavitary and interstitial brachytherapy for cervix cancer in an outpatient setting

    OpenAIRE

    Yiat Horng Leong; Kenneth Hock Soon Tan; Bok Ai Choo; Vicky Yaling Koh; Johann I-Hsiung Tang

    2017-01-01

    Purpose : To determine the feasibility and safety of outpatient combined intracavitary and interstitial brachytherapy for cervix cancer with sedation and local anesthesia. Material and methods : We included patients diagnosed with non-metastatic cervix cancer and have completed brachytherapy between December 2015 and December 2016. Moderate to deep sedation was achieved using intravenous midazolam, propofol, fentanyl, and oxycodone. Local anesthesia was achieved with 2% lignocaine gel a...

  10. Combining polarimetry and spectropolarimetry techniques in diagnostics of cancer changes in biological tissues

    Science.gov (United States)

    Yermolenko, Sergey; Ivashko, Pavlo; Gruia, Ion; Gruia, Maria; Peresunko, Olexander; Zelinska, Natalia; Voloshynskyi, Dmytro; Fedoruk, Olexander; Zimnyakov, Dmitry; Alonova, Marina

    2015-02-01

    The aim of the study is combining polarimetry and spectropolarimetry techniques for identifying the changes of opticalgeometrical structure in different kinds of biotissues with solid tumours. It is researched that a linear dichroism appears in biotissues (human esophagus, muscle tissue of rats, human prostate tissue, cervical smear) with cancer diseases, magnitude of which depends on the type of the tissue and on the time of cancer process development.

  11. 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.

  12. Combination approaches with immune checkpoint blockade in cancer therapy

    Directory of Open Access Journals (Sweden)

    Maarten Swart

    2016-11-01

    Full Text Available In healthy individuals, immune checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune checkpoint blockade of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 (PD-1 emerged as promising strategies to activate anti-tumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune checkpoint blockade, aimed at increasing response-rates to the single treatments.

  13. 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.

  14. 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.

  15. 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.

  16. Current status of transcatheter arterial chemoembolization combined with radiofrequency ablation in treatment of primary liver cancer

    Directory of Open Access Journals (Sweden)

    LYU Tianshi

    2016-01-01

    Full Text Available In recent years, more and more therapeutic methods have been applied for the treatment of primary liver cancer; however, since most lesions develop from progressive liver disease or liver cirrhosis, primary liver cancer is still a refractory malignant tumor. Although surgical resection and liver transplantation are radical therapeutic methods, they are not applicable to most patients due to complex issues related to transplantation and insidious onset of such disease. With the improvement in equipment and technology, the interventional therapies for primary liver cancer have been taken more seriously, especially transcatheter arterial chemoembolization and percutaneous radiofrequency ablation. This article investigates the effect and feasibility of the combination of these two therapies for primary liver cancer and introduces the research advances in interventional therapy for primary liver cancer.

  17. Combined preoperative therapy for oral cancer with nedaplatin and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Masatoshi; Shibata, Akihiko; Hayashi, Munehiro [Nippon Dental Univ., Tokyo (Japan). Hospital] (and others)

    2002-03-01

    We performed preoperative combined therapy using nedaplatin (CDGP) and radiation in 12 patients with squamous cell carcinoma originating from the oral cavity and maxillary sinus, and examined for any adverse events that may have occurred during this therapeutic regimen. Regarding the irradiation, external irradiation utilizing a 6 MV linac (linear accelerator) at a dose of 2.0 Gy/day was performed 5 times a week, with the target total radiation dose set at 40 Gy. In addition, CDGP was intravenously administered 30 minutes before irradiation at a dose of 5 mg/m{sup 2}/day. Mucositis was observed in all 12 subjects, however, the severity was observed to be grade 1-2 with no major differences in comparison to the patients given standard radiation monotherapy. Two subjects developed grade 3 leucopenia and were thus given granulocyte colony stimulating factor (G-CSF). In addition, grade 2 and grade 3 thrombocytopenia were both observed in one subject each. The subject with grade 3 thrombocytopenia required a platelet transfusion during surgery. No marked changes in serum creatinine levels were noted. These findings are therefore considered to provide evidence supporting the safety of this combination therapy. (author)

  18. A combined MR and CT study for precise quantitative analysis of the avian brain

    Science.gov (United States)

    Jirak, Daniel; Janacek, Jiri; Kear, Benjamin P.

    2015-10-01

    Brain size is widely used as a measure of behavioural complexity and sensory-locomotive capacity in avians but has largely relied upon laborious dissections, endoneurocranial tissue displacement, and physical measurement to derive comparative volumes. As an alternative, we present a new precise calculation method based upon coupled magnetic resonance (MR) imaging and computed tomography (CT). Our approach utilizes a novel interactive Fakir probe cross-referenced with an automated CT protocol to efficiently generate total volumes and surface areas of the brain tissue and endoneurocranial space, as well as the discrete cephalic compartments. We also complemented our procedures by using sodium polytungstate (SPT) as a contrast agent. This greatly enhanced CT applications but did not degrade MR quality and is therefore practical for virtual brain tissue reconstructions employing multiple imaging modalities. To demonstrate our technique, we visualized sex-based brain size differentiation in a sample set of Ring-necked pheasants (Phasianus colchicus). This revealed no significant variance in relative volume or surface areas of the primary brain regions. Rather, a trend towards isometric enlargement of the total brain and endoneurocranial space was evidenced in males versus females, thus advocating a non-differential sexually dimorphic pattern of brain size increase amongst these facultatively flying birds.

  19. The Toxic Effect of Silibinin and Paclitaxel Combination on Endometrial Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Ameneh Basiri

    2016-10-01

    Full Text Available Background & objectives: Among gynecologic malignancies, endometrial cancer is the fourth most frequent cause of cancer death all over the world. Paclitaxel is one of the chemotherapy regimens that is used against this cancer. Treatment of tumor with Paclitaxel induces apoptosis, but it is also associated with serious side effects. Thus, it is imperative to search for more effective and safer chemotherapeutic regimens. Silibinin is a milk thistle plant extract that its antioxidant effects against some cancers have been studied. The aim of this study was to examine the effect of Paclitaxel and Silibinin combination on endometrial cancer cell line (Hela. Methods: Hela cell line was cultured in 25cm2 flask in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS. Then the numbers of live cells were calculated with trypan blue staining method and then the cells were seeded in to 96-well flat-bottomed culture plates and treated with Silibilin, Paclitaxel and Paclitaxel plus Silibilin together with the control without treatment. MTT assay was used to evaluate cytotoxicity of different treatments. Results: After 48 hours of treatment, Paclitaxel and Silibilin combination inhibited cell growth significantly compared with the other groups (p<0.05. Conclusions: It is indicated that combination of Paclitaxel and Silibilin can affect the growth arrest of Hela cancer cell line more  effective than other treatments and is needed to be examined in vitro.

  20. 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.

  1. 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.

  2. A combined healthy lifestyle score and risk of pancreatic cancer in a large cohort study.

    Science.gov (United States)

    Jiao, Li; Mitrou, Panagiota N; Reedy, Jill; Graubard, Barry I; Hollenbeck, Albert R; Schatzkin, Arthur; Stolzenberg-Solomon, Rachael

    2009-04-27

    Smoking, alcohol use, diet, body mass index (calculated as weight in kilograms divided by height in meters squared), and physical activity have been studied independently in relation to pancreatic cancer. We generated a healthy lifestyle score to investigate their joint effect on risk of pancreatic cancer. In the prospective National Institutes of Health-AARP Diet and Health Study, a total of 450 416 participants aged 50 to 71 years completed the baseline food frequency questionnaire (1995-1996) eliciting diet and lifestyle information and were followed up through December 31, 2003. We identified 1057 eligible incident pancreatic cancer cases. Participants were scored on 5 modifiable lifestyle factors as unhealthy (0 points) or healthy (1 point) on the basis of current epidemiologic evidence. Participants received 1 point for each respective lifestyle factor: nonsmoking, limited alcohol use, adherence to the Mediterranean dietary pattern, body mass index (> or =18 and pancreatic cancer. Compared with the lowest combined score (0 points), the highest score (5 points) was associated with a 58% reduction in risk of developing pancreatic cancer in all participants (relative risk, 0.42; 95% confidence interval, 0.26-0.66; P(trend) pancreatic cancer cases in our population. Findings from this large study suggest that having a high score, as opposed to a low score, on an index combining 5 modifiable lifestyle factors substantially reduces the risk of developing pancreatic cancer.

  3. The Effect of Combined Aspirin and Clopidogrel Treatment on Cancer Incidence.

    Science.gov (United States)

    Leader, Avi; Zelikson-Saporta, Ravit; Pereg, David; Spectre, Galia; Rozovski, Uri; Raanani, Pia; Hermoni, Doron; Lishner, Michael

    2017-07-01

    Multiple studies have shown an association between aspirin treatment and a reduction in newly diagnosed cancer. Conversely, there are conflicting clinical and laboratory data on the effect of combined clopidogrel and aspirin therapy on cancer incidence, including analyses suggesting an increased cancer risk. No large-scale cohort study has been performed to address this issue in a heterogeneous real-world scenario. We investigated the effect of clopidogrel and aspirin on cancer incidence compared with aspirin alone and no antiplatelet therapy. A population-based historical cohort study of subjects aged ≥50 years covered by Clalit Health Services, an Israeli health maintenance organization, was performed. Patients treated with the newer antiplatelet drugs, prasugrel or ticagrelor, which, like clopidogrel, inhibit adenosine diphosphate receptors, and those with prior cancer were excluded. Prescription records of antiplatelet medication were retrieved. The cohort included 183,912 subjects diagnosed with 21,974 cancer cases based upon the International Classification of Diseases, Ninth Revision. Dual aspirin and clopidogrel was prescribed in 9.6%, while 49% received aspirin alone and 41% used neither. Compared with nonusers, there was a lower risk of cancer in subjects exposed to aspirin with (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.44-0.49) or without clopidogrel (HR 0.54; 95% CI, 0.52-0.56), on long-term follow-up. Combined treatment was associated with a lower cancer risk than the aspirin-only group (HR 0.92; 95% CI, 0.86-0.97). Dual clopidogrel and aspirin treatment is safe regarding the cancer risk. This study generates the hypothesis that clopidogrel may reduce cancer incidence. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Diagnosis and Management of Combined Central Diabetes Insipidus and Cerebral Salt Wasting Syndrome After Traumatic Brain Injury.

    Science.gov (United States)

    Wu, Xuehai; Zhou, Xiaolan; Gao, Liang; Wu, Xing; Fei, Li; Mao, Ying; Hu, Jin; Zhou, Liangfu

    2016-04-01

    Combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury (TBI) is rare, is characterized by massive polyuria leading to severe water and electrolyte disturbances, and usually is associated with very high mortality mainly as a result of delayed diagnosis and improper management. We retrospectively reviewed the clinical presentation, management, and outcomes of 11 patients who developed combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury to define distinctive features for timely diagnosis and proper management. The most typical clinical presentation was massive polyuria (10,000 mL/24 hours or >1000 mL/hour) refractory to vasopressin alone but responsive to vasopressin plus cortisone acetate. Other characteristic presentations included low central venous pressure, high brain natriuretic peptide precursor level without cardiac dysfunction, high 24-hour urine sodium excretion and hypovolemia, and much higher urine than serum osmolarity; normal serum sodium level and urine specific gravity can also be present. Timely and adequate infusion of sodium chloride was key in treatment. Of 11 patients, 5 had a good prognosis 3 months later (Extended Glasgow Outcome Scale score ≥6), 1 had an Extended Glasgow Outcome Scale score of 4, 2 died in the hospital of brain hernia, and 3 developed a vegetative state. For combined diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury, massive polyuria is a major typical presentation, and intensive monitoring of fluid and sodium status is key for timely diagnosis. To achieve a favorable outcome, proper sodium chloride supplementation and cortisone acetate and vasopressin coadministration are key. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Combination of brain-computer interface training and goal-directed physical therapy in chronic stroke: a case report.

    Science.gov (United States)

    Broetz, Doris; Braun, Christoph; Weber, Cornelia; Soekadar, Surjo R; Caria, Andrea; Birbaumer, Niels

    2010-09-01

    There is no accepted and efficient rehabilitation strategy to reduce focal impairments for patients with chronic stroke who lack residual movements. A 67-year-old hemiplegic patient with no active finger extension was trained with a brain-computer interface (BCI) combined with a specific daily life-oriented physiotherapy. The BCI used electrical brain activity (EEG) and magnetic brain activity (MEG) to drive an orthosis and a robot affixed to the patient's affected upper extremity, which enabled him to move the paralyzed arm and hand driven by voluntary modulation of micro-rhythm activity. In addition, the patient practiced goal-directed physiotherapy training. Over 1 year, he completed 3 training blocks. Arm motor function, gait capacities (using Fugl-Meyer Assessment, Wolf Motor Function Test, Modified Ashworth Scale, 10-m walk speed, and goal attainment score), and brain reorganization (functional MRI, MEG) were repeatedly assessed. The ability of hand and arm movements as well as speed and safety of gait improved significantly (mean 46.6%). Improvement of motor function was associated with increased micro-oscillations in the ipsilesional motor cortex. This proof-of-principle study suggests that the combination of BCI training with goal-directed, active physical therapy may improve the motor abilities of chronic stroke patients despite apparent initial paralysis.

  6. Combining electroencephalographic activity and instantaneous heart rate for assessing brain-heart dynamics during visual emotional elicitation in healthy subjects.

    Science.gov (United States)

    Valenza, G; Greco, A; Gentili, C; Lanata, A; Sebastiani, L; Menicucci, D; Gemignani, A; Scilingo, E P

    2016-05-13

    Emotion perception, occurring in brain areas such as the prefrontal cortex and amygdala, involves autonomic responses affecting cardiovascular dynamics. However, how such brain-heart dynamics is further modulated by emotional valence (pleasantness/unpleasantness), also considering different arousing levels (the intensity of the emotional stimuli), is still unknown. To this extent, we combined electroencephalographic (EEG) dynamics and instantaneous heart rate estimates to study emotional processing in healthy subjects. Twenty-two healthy volunteers were elicited through affective pictures gathered from the International Affective Picture System. The experimental protocol foresaw 110 pictures, each of which lasted 10 s, associated to 25 different combinations of arousal and valence levels, including neutral elicitations. EEG data were processed using short-time Fourier transforms to obtain time-varying maps of cortical activation, whereas the associated instantaneous cardiovascular dynamics was estimated in the time and frequency domains through inhomogeneous point-process models. Brain-heart linear and nonlinear coupling was estimated through the maximal information coefficient (MIC). Considering EEG oscillations in theθband (4-8 Hz), MIC highlighted significant arousal-dependent changes between positive and negative stimuli, especially occurring at intermediate arousing levels through the prefrontal cortex interplay. Moreover, high arousing elicitations seem to mitigate changes in brain-heart dynamics in response to pleasant/unpleasant visual elicitation. © 2016 The Author(s).

  7. MYC RNAi-Pt Combination Nanotherapy for Metastatic Prostate Cancer Treatment

    Science.gov (United States)

    2017-10-01

    4b and 4c). We further harvested the tumors and major organs at 24 h post injection (Figure 4d and 4e) and the quantification of BioD is shown in...AWARD NUMBER: W81XWH-15-1-0728 TITLE: MYC RNAi-PT Combination Nanotherapy for Metastatic Prostate Cancer Treatment PRINCIPAL INVESTIGATOR: Omid C...MYC RNAi-Pt Combination Nanotherapy for Metastatic Prostate Cancer Treatment 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0728 5c. PROGRAM

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Combined effects of caffeine and zinc in the maternal diet on fetal brains

    Energy Technology Data Exchange (ETDEWEB)

    Nakamoto, T.; Gottschalk, S.B.; Yazdani, M.; Joseph, F. Jr. (Louisiana State Univ., New Orleans (United States))

    1991-03-15

    The authors have reported that caffeine (C) intake during the lactational period by dams decreases the Zn content of the brain in their offspring. The objective of the present study is to determine how C plus Zn supplementation to the maternal diet during gestation affects the fetal brains. Timed-pregnant rats at day 3 of gestation were randomly divided into 4 groups (G). G1 was fed a 20% protein diet as a control, G2 was fed a diet supplemented with Zn, G3 was fed a diet with C and G4 was fed a diet with C and Zn. At day 22 of gestation, fetuses were taken out surgically. Fetal brains were removed. Their weights, DNA, Zn, protein, cholesterol, caffeine concentration, and alkaline phosphatase activity were determined. Body and brain weights and cholesterol contents in G4 were greater than in G1, whereas Zn concentration and alkaline phosphatase activity were less. Zn concentration and Zn/DNA in G2 were greater than in G1. Cholesterol content in G4 was higher than in G3. Although mean caffeine concentration in brain and plasma in G4 was greater than in G3, there was no statistical significance between the G due to the wide fluctuation among the pups. It is concluded that supplementation of C and Zn in the maternal diet during gestation could influence fetal brain composition differently than C supplementation alone. Supplementation of Zn alone showed minor effects.

  14. PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy

    OpenAIRE

    Vera, Jaime H.; Ridha, Basil; Gilleece, Yvonne; Amlani, Aliza; Thorburn, Patrick; Dizdarevic, Sabina

    2017-01-01

    Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence sugge...

  15. Repositioning FDA-Approved Drugs in Combination with Epigenetic Drugs to Reprogram Colon Cancer Epigenome.

    Science.gov (United States)

    Raynal, Noël J-M; Da Costa, Elodie M; Lee, Justin T; Gharibyan, Vazganush; Ahmed, Saira; Zhang, Hanghang; Sato, Takahiro; Malouf, Gabriel G; Issa, Jean-Pierre J

    2017-02-01

    Epigenetic drugs, such as DNA methylation inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi), are approved in monotherapy for cancer treatment. These drugs reprogram gene expression profiles, reactivate tumor suppressor genes (TSG) producing cancer cell differentiation and apoptosis. Epigenetic drugs have been shown to synergize with other epigenetic drugs or various anticancer drugs. To discover new molecular entities that enhance epigenetic therapy, we performed a high-throughput screening using FDA-approved libraries in combination with DNMTi or HDACi. As a screening model, we used YB5 system, a human colon cancer cell line, which contains an epigenetically silenced CMV-GFP locus, mimicking TSG silencing in cancer. CMV-GFP reactivation is triggered by DNMTi or HDACi and responds synergistically to DNMTi/HDACi combination, which phenocopies TSG reactivation upon epigenetic therapy. GFP fluorescence was used as a quantitative readout for epigenetic activity. We discovered that 45 FDA-approved drugs (4% of all drugs tested) in our FDA-approved libraries enhanced DNMTi and HDACi activity, mainly belonging to anticancer and antiarrhythmic drug classes. Transcriptome analysis revealed that combination of decitabine (DNMTi) with the antiarrhythmic proscillaridin A produced profound gene expression reprogramming, which was associated with downregulation of 153 epigenetic regulators, including two known oncogenes in colon cancer (SYMD3 and KDM8). Also, we identified about 85 FDA-approved drugs that antagonized DNMTi and HDACi activity through cytotoxic mechanisms, suggesting detrimental drug interactions for patients undergoing epigenetic therapy. Overall, our drug screening identified new combinations of epigenetic and FDA-approved drugs, which can be rapidly implemented into clinical trials. Mol Cancer Ther; 16(2); 397-407. ©2016 AACR. ©2016 American Association for Cancer Research.

  16. Pharmacokinetics and Drug Interactions Determine Optimum Combination Strategies in Computational Models of Cancer Evolution.

    Science.gov (United States)

    Chakrabarti, Shaon; Michor, Franziska

    2017-07-15

    The identification of optimal drug administration schedules to battle the emergence of resistance is a major challenge in cancer research. The existence of a multitude of resistance mechanisms necessitates administering drugs in combination, significantly complicating the endeavor of predicting the evolutionary dynamics of cancers and optimal intervention strategies. A thorough understanding of the important determinants of cancer evolution under combination therapies is therefore crucial for correctly predicting treatment outcomes. Here we developed the first computational strategy to explore pharmacokinetic and drug interaction effects in evolutionary models of cancer progression, a crucial step towards making clinically relevant predictions. We found that incorporating these phenomena into our multiscale stochastic modeling framework significantly changes the optimum drug administration schedules identified, often predicting nonintuitive strategies for combination therapies. We applied our approach to an ongoing phase Ib clinical trial (TATTON) administering AZD9291 and selumetinib to EGFR-mutant lung cancer patients. Our results suggest that the schedules used in the three trial arms have almost identical efficacies, but slight modifications in the dosing frequencies of the two drugs can significantly increase tumor cell eradication. Interestingly, we also predict that drug concentrations lower than the MTD are as efficacious, suggesting that lowering the total amount of drug administered could lower toxicities while not compromising on the effectiveness of the drugs. Our approach highlights the fact that quantitative knowledge of pharmacokinetic, drug interaction, and evolutionary processes is essential for identifying best intervention strategies. Our method is applicable to diverse cancer and treatment types and allows for a rational design of clinical trials. Cancer Res; 77(14); 3908-21. ©2017 AACR. ©2017 American Association for Cancer Research.

  17. Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers.

    Science.gov (United States)

    Van Roosbroeck, Katrien; Fanini, Francesca; Setoyama, Tetsuro; Ivan, Cristina; Rodriguez-Aguayo, Cristian; Fuentes-Mattei, Enrique; Xiao, Lianchun; Vannini, Ivan; Redis, Roxana S; D'Abundo, Lucilla; Zhang, Xinna; Nicoloso, Milena S; Rossi, Simona; Gonzalez-Villasana, Vianey; Rupaimoole, Rajesha; Ferracin, Manuela; Morabito, Fortunato; Neri, Antonino; Ruvolo, Peter P; Ruvolo, Vivian R; Pecot, Chad V; Amadori, Dino; Abruzzo, Lynne; Calin, Steliana; Wang, Xuemei; You, M James; Ferrajoli, Alessandra; Orlowski, Robert; Plunkett, William; Lichtenberg, Tara M; Davuluri, Ramana V; Berindan-Neagoe, Ioana; Negrini, Massimo; Wistuba, Ignacio I; Kantarjian, Hagop M; Sood, Anil K; Lopez-Berestein, Gabriel; Keating, Michael J; Fabbri, Muller; Calin, George A

    2017-06-01

    Purpose: The oncogenic miR-155 is upregulated in many human cancers, and its expression is increased in more aggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors.Experimental Design: We performed in vitro studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an in vivo orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and TP53 expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia, and acute lymphoblastic leukemia.Results: We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents in vitro, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy in vivo We show that anti-miR-155-DOPC can be considered non-toxic in vivo We further demonstrate that miR-155 and TP53 are linked in a negative feedback mechanism and that a combination of high expression of miR-155 and low expression of TP53 is significantly associated with shorter survival in lung cancer.Conclusions: Our findings support the existence of an miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, an important cause of cancer-related death. Clin Cancer Res; 23(11); 2891-904. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Synergistic enhancement of breast cancer cell death using ultrasound-microbubbles in combination with cisplatin

    Science.gov (United States)

    Jetha, Sheliza; Karshafian, Raffi

    2017-03-01

    Cisplatin (CDDP), an anti-cancer agent, can effectively treat several cancerous tumourstumors such as testicular, bladder, and ovarian cancers. CDDP binds to specific DNA bases causing 1,2-intrastrand cross-links, single strand and double strand breaks inducing apoptosis. However, the effectiveness of CDDP is limited in tumourtumors such as breast cancer due to drug resistance. In this study, the application of ultrasound-microbubble (USMB) in improving the therapeutic effect of CDDP in breast cancer cell line is investigated. Human breast cancer (MDA-MB-231) cells in suspension (2×106 cells/mL concentration and 0.6 mL volume) were treated with CDDP (3 µM, 30 µM and 300 µM) and USMB at 0.5 MHz pulse centered frequency, 60 s insonation time, 16 µs pulse duration, 1 kHz pulse repetition frequency, and 1.7% v/v (volume concentration) of Definity microbubble agent. Following USMB treatment, cells were plated in 96-well plates for 24 and 48-hour incubation, after which cell viability was measured using MTT assay (VMTT). Cell viability decreased significantly with the combined treatment of CDDP and USMB compared to CDDP alone (pcisplatin synergistically enhances chemotherapeutic effectiveness in breast cancer cells. However, this enhanced effectiveness, in breast cancer cells (MDA-MB-231), is dependent on incubation time and cisplatin (CDDP) concentration.

  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. Prostate cancer immunotherapy, particularly in combination with androgen deprivation or radiation treatment. Customized pharmacogenomic approaches to overcome immunotherapy cancer resistance.

    Science.gov (United States)

    Alberti, C

    2017-01-01

    Conventional therapeutic approaches for advanced prostate cancer - such as androgen deprivation, chemotherapy, radiation - come up often against lack of effectiveness because of possible arising of correlative cancer cell resistance and/or inadequate anti-tumor immune conditions. Whence the timeliness of resorting to immune-based treatment strategies including either therapeutic vaccination-based active immunotherapy or anti-tumor monoclonal antibody-mediated passive immunotherapy. Particularly attractive, as for research studies and clinical applications, results to be the cytotoxic T-lymphocyte check point blockade by the use of anti-CTLA-4 and PD-1 monoclonal antibodies, particularly when combined with androgen deprivation therapy or radiation. Unlike afore said immune check point inhibitors, both cell-based (by the use of prostate specific antigen carriers autologous dendritic cells or even whole cancer cells) and recombinant viral vector vaccines are able to induce immune-mediated focused killing of specific antigen-presenting prostate cancer cells. Such vaccines, either used alone or concurrently/sequentially combined with above-mentioned conventional therapies, led to generally reach, in the field of various clinical trials, reasonable results particularly as regards the patient's overall survival. Adoptive trasferred T-cells, as adoptive T-cell passive immunotherapy, and monoclonal antibodies against specific antigen-endowed prostate cancer cells can improve immune micro-environmental conditions. On the basis of a preliminary survey about various immunotherapy strategies, are here also outlined their effects when combined with androgen deprivation therapy or radiation. What's more, as regard the immune-based treatment effectiveness, it has to be pointed out that suitable personalized epigenetic/gene profile-achieved pharmacogenomic approaches to target identified gene aberrations, may lead to overcome - as well as for conventional therapies - possible

  1. Nanotechnology-based combinational drug delivery: an emerging approach for cancer therapy.

    Science.gov (United States)

    Parhi, Priyambada; Mohanty, Chandana; Sahoo, Sanjeeb Kumar

    2012-09-01

    Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. A study of an effective sunitinib–chemotherapeutic combination regimen for bladder cancer treatment using a mouse model

    Directory of Open Access Journals (Sweden)

    Dah-Shyong Yu

    2014-06-01

    Conclusion: Combination of the tyrosine kinase receptor inhibitor sunitinib with gemcitabine chemotherapy synergistically enhances tumor cytotoxicity and may provide a new treatment modality for advanced bladder cancer.

  3. 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

  4. Combination therapy targeting Raf-1 and MEK causes apoptosis of HCT116 colon cancer cells.

    Science.gov (United States)

    Subramanian, Romesh R; Yamakawa, Akio

    2012-11-01

    Members of the Ras protooncogene family are mutated in approximately 75% of colon cancers. The Raf kinases (Raf-1, b-Raf and a-Raf) directly interact with Ras and serve as mediators of mitogenic signals. Expression of the constitutively active alleles of Raf or Ras gene families results in oncogenesis in a number of model systems. Previous studies emphasized the importance of Raf-1 and b-Raf in preventing apoptosis in addition to their roles in cell growth. In the present study, we examined whether inhibition of the Raf-1 or b-Raf kinase decreases cell growth and increases apoptosis in colon cancer cells. c-Raf and b-Raf were depleted in colon cancer cell lines, such as HCT116, HT29 and Colo205, containing Ras or b-Raf mutations by RNA interference (RNAi). The results showed that colon cancer cells with activating Ras mutations undergo apoptosis following Raf-1 inhibition, as determined by cell cycle analysis and the release of cytochrome c. Moreover, in b-Raf mutant colon cancers, the inhibition of b-Raf as compared to Raf-1 is crucial for cancer cell death. There is increasing evidence for both MEK-independent Raf signaling and Raf-independent MEK signaling. Thus, we investigated whether targeting multiple points of the mitogen-activated protein kinase (MAPK) pathway with a MEK inhibitor and Raf RNAi increases cancer cell death. The results showed that combination therapy, inhibiting Raf and MEK kinases simultaneously, increased apoptosis in colon cancer cells. Taken together, our data demonstrate that combination therapy targeting the MAPK pathway at two distinct points, Raf kinase and MEK, has greater efficacy in increasing cancer cell death and is likely to improve therapeutic outcomes for patients.

  5. Combined Treatment with Exendin-4 and Metformin Attenuates Prostate Cancer Growth.

    Directory of Open Access Journals (Sweden)

    Yoko Tsutsumi

    Full Text Available Recently, the pleiotropic benefits of incretin-based therapy have been reported. We have previously reported that Exendin-4, a glucagon-like peptide-1 (GLP-1 receptor agonist, attenuates prostate cancer growth. Metformin is known for its anti-cancer effect. Here, we examined the anti-cancer effect of Exendin-4 and metformin using a prostate cancer model.Prostate cancer cells were treated with Exendin-4 and/or metformin. Cell proliferation was quantified by growth curves and 5-bromo-2'-deoxyuridine (BrdU assay. TUNEL assay and AMP-activated protein kinase (AMPK phosphorylation were examined in LNCaP cells. For in vivo experiments, LNCaP cells were transplanted subcutaneously into the flank region of athymic mice, which were then treated with Exendin-4 and/or metformin. TUNEL assay and immunohistochemistry were performed on tumors.Exendin-4 and metformin additively decreased the growth curve, but not the migration, of prostate cancer cells. The BrdU assay revealed that both Exendin-4 and metformin significantly decreased prostate cancer cell proliferation. Furthermore, metformin, but not Exendin-4, activated AMPK and induced apoptosis in LNCaP cells. The anti-proliferative effect of metformin was abolished by inhibition or knock down of AMPK. In vivo, Exendin-4 and metformin significantly decreased tumor size, and further significant tumor size reduction was observed after combined treatment. Immunohistochemistry on tumors revealed that the P504S and Ki67 expression decreased by Exendin-4 and/or metformin, and that metformin increased phospho-AMPK expression and the apoptotic cell number.These data suggest that Exendin-4 and metformin attenuated prostate cancer growth by inhibiting proliferation, and that metformin inhibited proliferation by inducing apoptosis. Combined treatment with Exendin-4 and metformin attenuated prostate cancer growth more than separate treatments.

  6. Combined Treatment with Exendin-4 and Metformin Attenuates Prostate Cancer Growth.

    Science.gov (United States)

    Tsutsumi, Yoko; Nomiyama, Takashi; Kawanami, Takako; Hamaguchi, Yuriko; Terawaki, Yuichi; Tanaka, Tomoko; Murase, Kunitaka; Motonaga, Ryoko; Tanabe, Makito; Yanase, Toshihiko

    2015-01-01

    Recently, the pleiotropic benefits of incretin-based therapy have been reported. We have previously reported that Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, attenuates prostate cancer growth. Metformin is known for its anti-cancer effect. Here, we examined the anti-cancer effect of Exendin-4 and metformin using a prostate cancer model. Prostate cancer cells were treated with Exendin-4 and/or metformin. Cell proliferation was quantified by growth curves and 5-bromo-2'-deoxyuridine (BrdU) assay. TUNEL assay and AMP-activated protein kinase (AMPK) phosphorylation were examined in LNCaP cells. For in vivo experiments, LNCaP cells were transplanted subcutaneously into the flank region of athymic mice, which were then treated with Exendin-4 and/or metformin. TUNEL assay and immunohistochemistry were performed on tumors. Exendin-4 and metformin additively decreased the growth curve, but not the migration, of prostate cancer cells. The BrdU assay revealed that both Exendin-4 and metformin significantly decreased prostate cancer cell proliferation. Furthermore, metformin, but not Exendin-4, activated AMPK and induced apoptosis in LNCaP cells. The anti-proliferative effect of metformin was abolished by inhibition or knock down of AMPK. In vivo, Exendin-4 and metformin significantly decreased tumor size, and further significant tumor size reduction was observed after combined treatment. Immunohistochemistry on tumors revealed that the P504S and Ki67 expression decreased by Exendin-4 and/or metformin, and that metformin increased phospho-AMPK expression and the apoptotic cell number. These data suggest that Exendin-4 and metformin attenuated prostate cancer growth by inhibiting proliferation, and that metformin inhibited proliferation by inducing apoptosis. Combined treatment with Exendin-4 and metformin attenuated prostate cancer growth more than separate treatments.

  7. Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer.

    Science.gov (United States)

    Zalazar, Florencia; De Luca, Paola; Gardner, Kevin; Figg, William D; Meiss, Roberto; Spallanzani, Raul G; Vallecorsa, Pablo; Elguero, Belen; Cotignola, Javier; Vazquez, Elba; De Siervi, Adriana

    2015-01-01

    Prostate cancer (PCa) still ranks as the second most frequently diagnosed cancer and metastatic castration resistant prostate cancer (CRPC) is a foremost cause of men cancer death around the world. The aim of this work was to investigate the selectivity and efficacy of new drug combinations for CRPC. We combined three compounds: paclitaxel (PTX: taxane that inhibits microtubule polymerization); 2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole- 1,3(2H)-dione (CPS49; redox-reactive thalidomide analog with anti-angiogenic properties) and flavopiridol (flavo: semisynthetic flavonoid that inhibits cyclin dependent kinases). We assessed CPS49-flavo or -PTX combinations cytotoxicity in a panel of PCa cell lines and PC3 xenografts. We found that CPS49 enhanced flavo or PTX cytotoxicity in human PCa cell lines while showed resistance in a non-tumor cell line. Furthermore, xenografts generated by inoculation of human prostate carcinoma PC3 cells in nu/nu mice showed that CPS49/flavo administration reduced tumor growth both after 2 weeks of co-treatment and after 1 week of pretreatment with a low dose of flavo followed by 2 weeks of co-treatment. PTX and CPS49 combination did not significantly reduce tumor growth in PC3 xenografts. Histological analysis of xenograft PC3 tumor samples from CPS49/flavo combination showed extensive areas of necrosis induced by the treatment. RT-qPCR array containing 23 genes from PC3 cells or PC3 xenografts exposed to CPS49/flavo combination showed that this treatment shut down the expression of several genes involved in adhesion, migration or invasion. In summary, the antitumor activity of CPS49 or flavopiridol was improved by the combination of these compounds and using half dose of that previously reported. Hence, CPS49-flavo combination is a promising new alternative for PCa therapy.

  8. 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.

  9. Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer.

    Directory of Open Access Journals (Sweden)

    Nikita Pozdeyev

    Full Text Available NF-κB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-κB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-κB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-κB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IκBα or pharmacologic (proteasome inhibitor bortezomib and IKKβ inhibitor GO-Y030 inhibition of the NF-κB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-κB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-κB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-κB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic

  10. HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy.

    Science.gov (United States)

    Lin, Tzu-Yin; Guo, Wenchang; Long, Qilai; Ma, Aihong; Liu, Qiangqiang; Zhang, Hongyong; Huang, Yee; Chandrasekaran, Siddarth; Pan, Chongxian; Lam, Kit S; Li, Yuanpei

    2016-01-01

    Photodynamic therapy (PDT) is a promising non-invasive therapeutic modality that has been proposed for treating prostate cancer, but the procedure is associated with limited efficacy, tumor recurrence and photo-toxicity. In the present study, we proposed to develop a novel multifunctional nano-platform for targeted delivery of heat, reactive oxygen species (ROS) and heat shock protein 90 (Hsp90) inhibitor simultaneously for combination therapy against prostate cancer. This new nano-platform combines two newly developed entities: 1) a unique organic and biocompatible nanoporphyrin-based drug delivery system that can generate efficient heat and ROS simultaneously with light activation at the tumor sites for dual-modal photothermal- and photodynamic- therapy (PTT/PDT), and 2) new nano-formulations of Hsp90 inhibitors that can decrease the levels of pro-survival and angiogenic signaling molecules induced by phototherapy, therefore, further sensitizing cancer cells to phototherapy. Furthermore, the nanoparticles have activatable near infrared (NIR) fluorescence for optical imaging to conveniently monitor the real-time drug delivery in both subcutaneous and orthotopic mouse models bearing prostate cancer xenograft. This novel multifunctional nano-platform has great potential to improve the care of prostate cancer patients through targeted combination therapy.

  11. Combined modality treatment of aromatherapy, footsoak, and reflexology relieves fatigue in patients with cancer.

    Science.gov (United States)

    Kohara, Hiroyuki; Miyauchi, Takako; Suehiro, Yoko; Ueoka, Hiroshi; Takeyama, Hiroyasu; Morita, Tatsuya

    2004-12-01

    Fatigue is one of the most distressful symptoms experienced by patients with advanced cancer. Aromatherapy, footsoak, and reflexology are popular health care modality treatments in Japan, however, the effectiveness of each treatment for cancer-related fatigue has not been fully established. To investigate the effectiveness of combined modality treatment consisting of aromatherapy, footsoak, and reflexology against fatigue, an open study was performed in 20 terminally ill patients with cancer. After a patch test was performed, patients received aromatherapy that was accompanied with footsoak in warm water containing lavender essential oil for 3 minutes, followed by reflexology treatment with jojoba oil containing lavender for 10 min. Fatigue was evaluated using the Cancer Fatigue Scale (CFS) before, 1 hour after, and 4 hours after treatment. Total CFS scores improved significantly after this treatment (from 25.6 +/- 11.0 to 18.1 +/- 10.0, p < 0.001). Among three CFS subscales, physical and cognitive subscale scores were reduced significantly (11.3 +/- 6.1 to 6.7 +/- 6.1, p < 0.001; 4.5 +/- 3.2 to 2.4 +/- 2.4, p < 0.001). No adverse effects were experienced. Because all patients desired to continue this treatment, they received treatment eight times on average. Combined modality treatment consisting of aromatherapy, footsoak, and reflexology appears to be effective for alleviating fatigue in terminally ill cancer patients. To confirm safety and effectiveness of this combined modality treatment, further investigation including randomized treatment assignment is warranted.

  12. 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.

  13. Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton

    Science.gov (United States)

    Grimm, Florian; Walter, Armin; Spüler, Martin; Naros, Georgios; Rosenstiel, Wolfgang; Gharabaghi, Alireza

    2016-01-01

    Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation

  14. Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton.

    Science.gov (United States)

    Grimm, Florian; Walter, Armin; Spüler, Martin; Naros, Georgios; Rosenstiel, Wolfgang; Gharabaghi, Alireza

    2016-01-01

    Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation

  15. 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.

  16. Effects of Physical Exercise Combined with Nutritional Supplements on Aging Brain Related Structures and Functions: A Systematic Review

    Science.gov (United States)

    Schättin, Alexandra; Baur, Kilian; Stutz, Jan; Wolf, Peter; de Bruin, Eling D.

    2016-01-01

    Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: “Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?” Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods

  17. Combining dissimilarities in a Hyper Reproducing Kernel Hilbert Space for complex human cancer prediction.

    Science.gov (United States)

    Martín-Merino, Manuel; Blanco, Angela; De Las Rivas, Javier

    2009-01-01

    DNA microarrays provide rich profiles that are used in cancer prediction considering the gene expression levels across a collection of related samples. Support Vector Machines (SVM) have been applied to the classification of cancer samples with encouraging results. However, they rely on Euclidean distances that fail to reflect accurately the proximities among sample profiles. Then, non-Euclidean dissimilarities provide additional information that should be considered to reduce the misclassification errors. In this paper, we incorporate in the nu-SVM algorithm a linear combination of non-Euclidean dissimilarities. The weights of the combination are learnt in a (Hyper Reproducing Kernel Hilbert Space) HRKHS using a Semidefinite Programming algorithm. This approach allows us to incorporate a smoothing term that penalizes the complexity of the family of distances and avoids overfitting. The experimental results suggest that the method proposed helps to reduce the misclassification errors in several human cancer problems.

  18. Chemotherapy by superselective intraarterial infusion of nedaplatin combined with radiotherapy for oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Yoshio; Goto, Masaaki; Katsuki, Takeshi [Saga Medical School (Japan)

    2002-06-01

    Nedaplatin (CDGP), which is a CDDP derivative, has been reported to be an effective anticancer agent for head and neck cancer. This study was performed to assess the feasibility of chemotherapy by superselective intraarterial infusion of nedaplatin (CDGP) in patients with oral cancers. Ten patients were treated with chemotherapy by superselective intraarterial infusion of CDGP combined with radiotherapy. The complete and partial response rates were 7/10 (70%) and 3/10 (30%), respectively. Nine patients showed grade 1-2 hematological toxicity including leukocytopenia and anemia. Thrombocytopenia of grade 4 was seen in only one patient. However, all the patients were free from renal dysfunction. From these results, it is suggested that this combination therapy might be quite effective and safe. Further study will be needed to determine its efficacy against oral cancer. (author)

  19. Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Sachin S Hingmire

    2017-01-01

    Full Text Available Background: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. Methods and Material: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. Results: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months.

  20. Combined endobronchial and oesophageal endosonography for the diagnosis and staging of lung cancer

    DEFF Research Database (Denmark)

    Vilmann, Peter; Clementsen, Paul Frost; Colella, Sara

    2015-01-01

    New guidelines for combined endobronchial and oesophageal mediastinal nodal staging of lung cancer. This is an official guideline of the European Society of Gastrointestinal Endoscopy (ESGE), produced in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic...

  1. Personalized drug combinations to overcome trastuzumab resistance in HER2-positive breast cancer

    Science.gov (United States)

    Vu, Thuy; Sliwkowski, Mark X.; Claret, Francois X.

    2014-01-01

    HER2-positive (HER2+) breast cancer accounts for 18%–20% of all breast cancer cases and has the second poorest prognosis among breast cancer subtypes. Trastuzumab, the first Food and Drug Administration-approved targeted therapy for breast cancer, established the era of personalized treatment for HER2+ metastatic disease. It is well tolerated and improves overall survival and time-to-disease progression; with chemotherapy, it is part of the standard of care for patients with HER2+ metastatic disease. However, many patients do not benefit from it because of resistance. Substantial research has been performed to understand the mechanism of trastuzumab resistance and develop combination strategies to overcome the resistance. In this review, we provide insight into the current pipeline of drugs used in combination with trastuzumab and the degree to which these combinations have been evaluated, especially in patients who have experienced disease progression on trastuzumab. We conclude with a discussion of the current challenges and future therapeutic approaches to trastuzumab-based combination therapy. PMID:25065528

  2. Outcome of combination chemotherapy in extensive stage small-cell lung cancer

    DEFF Research Database (Denmark)

    Lassen, U N; Hirsch, F R; Osterlind, K

    1998-01-01

    During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during...

  3. Recent Advances in Upconversion Nanoparticles-Based Multifunctional Nanocomposites for Combined Cancer Therapy.

    Science.gov (United States)

    Tian, Gan; Zhang, Xiao; Gu, Zhanjun; Zhao, Yuliang

    2015-12-16

    Lanthanide-doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous-wave near-infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue-penetration ability and high signal-to-noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging-guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co-delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti-cancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs-based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs-based composites. The future prospects and challenges in this emerging field will be also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. 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 modulator cyclosporin A (50 mg/kg), and the dual P-gp and BCRP modulator GF120918 (over 5 mg/kg) induced an increase in the brain uptake of [{sup 11}C]gefitinib in mice 30 min after injection. In the PET study of mice, the radioactivity level in the brain with co-injection of GF120918 (5 mg/kg) was three- to fourfold higher than that in control after initial uptake. The radioactivity level in the brain in P-gp and Bcrp knockout mice was approximately eightfold higher than that in wild-type mice 60 min after injection. In conclusion, [{sup 11}C]gefitinib is a promising PET tracer to evaluate the penetration of gefitinib into the brain by combined therapy with P-gp or BCRP modulators, and into brain tumors. Furthermore, PET study with GF120918 is a promising approach for evaluating brain penetration-mediated P-gp and BCRP.

  5. 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.

  6. Exploiting Synergy: Immune-Based Combinations in the Treatment of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Mauricio eBurotto

    2014-12-01

    Full Text Available Cancer treatment is being revolutionized by the emergence of immunotherapies such as immune check point inhibitors and therapeutic cancer vaccines. Prostate cancer has is amenable to such therapeutic approaches. The improved understanding of the relationship between the immune system and tumors has allowed therapeutic targeting of immune checkpoints and tumor associated antigens to be developed. Furthermore, interventions used in prostate cancer are capable of impacting the immune system. As demonstrated by preclinical data and emerging clinical data, radiation therapy, anti-androgen therapy and chemotherapy can be used with immunotherapies to obtain synergistic results. Current and future clinical trials will further investigate these principals as immunotherapeutics are combined with each other and standard therapies for optimal clinical utility.

  7. DNA damage in peripheral blood lymphocytes in patients during combined chemotherapy for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Suarez, Patricia [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico); Ostrosky-Wegman, Patricia [Biomedical Research Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Gallegos-Hernandez, Francisco [Department of Clinical Oncology, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City (Mexico); Penarroja-Flores, Rubicelia; Toledo-Garcia, Jorge [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico); Bravo, Jose Luis [Atmospheric Sciences Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Rojas del Castillo, Emilio [Biomedical Research Institute, Universidad Nacional Autonoma de Mexico (UNAM), Mexico City (Mexico); Benitez-Bribiesca, Luis [Oncological Research Unit, Oncology Hospital, National Medical Center S-XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, Col. Doctores, 06725 Mexico, D.F. (Mexico)], E-mail: luisbenbri@mexis.com

    2008-04-02

    Combined chemotherapy is used for the treatment of a number of malignancies such as breast cancer. The target of these antineoplastic agents is nuclear DNA, although it is not restricted to malignant cells. The aim of the present study was to assess DNA damage in peripheral blood lymphocytes (PBLs) of breast cancer patients subjected to combined adjuvant chemotherapy (5-fluorouracil, epirubicin and cyclophosphamide, FEC), using a modified comet assay to detect DNA single-strand breaks (SSB) and double-strand breaks (DSB). Forty-one female patients with advanced breast cancer before and after chemotherapy and 60 healthy females participated in the study. Alkaline and neutral comet assays were performed in PBLs according to a standard protocol, and DNA tail moment was measured by a computer-based image analysis system. Breast cancer patients before treatment had higher increased background levels of SSB and DSB as compared to healthy women. During treatment, a significant increase in DNA damage was observed after the 2nd cycle, which persisted until the end of treatment. Eighty days after the end of treatment the percentage of PBLs with SSB and DSB remained elevated, but the magnitude of DNA damage (tail moment) returned to baseline levels. There was no correlation between PBL DNA damage and response to chemotherapy. DNA-SSB and DSB in PBLs are present in cancer patients before treatment and increase significantly after combined chemotherapy. No correlation with response to adjuvant chemotherapy was found. Biomonitoring DNA damage in PBLs of cancer patients could help prevent secondary effects and the potential risks of developing secondary cancers.

  8. 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.

  9. 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.

  10. [Combining SSH and cDNA microarray for identification of lung cancer related genes].

    Science.gov (United States)

    Fan, Baoxing; Zhang, Kaitai; Da, Jiping; Xie, Ling; Wang, Shengqi; Wu, Dechang

    2003-04-20

    To screen and identify differentially expressed genes among lung cancer tissues, paracancerous pulmonary tissues and some other kinds of tumor tissues using suppression subtractive hybridization (SSH) and cDNA Microarray. One cDNA chip was made by gathering clones of three differentially expressed cDNA libraries which came from BEP2D cell lines during three different malignant transformed phases. Then the clones were hybridizated with cDNA probes which extracted from 15 cases of lung cancer tissues, 5 cases of paracancerous pulmonary tissues and 24 cases of other 8 kinds of tumor tissues respectively. Twenty-six cDNAs were obtained which expressed higher in lung cancer tissues than that in paracancerous pulmonary tissues. Thirty-one cDNAs expressed remarkably higher in paracancerous tissues than those in cancer tissues. Compared with other 8 kinds of tumors, paracancerous tissues had 63 overexpressed cDNAs and lung cancer tissues had 87 overexpressed cDNAs. The combination of SSH and cDNA microarray is rapid and effective for screening and identification of differentially expressed genes in different samples. It may be potentially useful for diagnosis of lung cancer to further study the differentially expressed genes among lung cancer tissues, paracancerous pulmonary tissues and other tumor tissues.

  11. Combined radiotherapy and local external hyperthermia in advanced cancer. Animal experiment and clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Terashima, Hiromi; Ishino, Yohichi; Nakata, Hajime; Norimura, Toshiyuki; Tsuchiya, Takehiko

    1987-06-01

    The response of a mouse's foot to heat was studied. Transplanted syngeneic tumor, C3H mouse mammary carcinoma, was treated with irradiation and hyperthermia in a waterbath. The tumor did not disappear in any of the mice treated with radiotherapy with a dose of 20 Gy alone, but disappearance of the tumor was observed in 11 of 15 and 6 of 8 of the mice treated with combined therapy of irradiation and hyperthermia. There was a significant difference between these two groups. Synergistic effect was confirmed (P < 0.001, P < 0.005). Hyperthermia using Thermotron RF-8 was performed on 19 patients (5 bladder cancers, 3 uterine cancers, 3 rectal cancers, 4 soft tissue tumors, 2 oral cancers, 1 biliary tract cancer, 1 renal cancer) between April, 1986 and December, 1986. They were irradiated with a daily dose of 1.5 - 2.0 Gy, 5 times a week and hyperthermia was performed within 30 minutes after each irradiation once or twice a week. Intratumoral temperature was kept at 43 deg C - 45 deg C. Temperature over 41 deg C was maintained in most patients. Clinical response was assessed by tumor regression rates. Partial response a (PRa), defined as 80 % or more regression in tumor volume, was obtained in 1 bladder cancer patient and PRb, defined as 50 % to less than 80 % regression, was obtained in another 5 patients. Side effects were observed in all patients including mild skin burn, nausea and diarrhea. Rectovaginal fistula developed in 1 patient. Combined radiotherapy and hyperthermia seems to be useful in advanced cancer patients.

  12. The Effect of Combined Out-of-Hospital Hypotension and Hypoxia on Mortality in Major Traumatic Brain Injury.

    Science.gov (United States)

    Spaite, Daniel W; Hu, Chengcheng; Bobrow, Bentley J; Chikani, Vatsal; Barnhart, Bruce; Gaither, Joshua B; Denninghoff, Kurt R; Adelson, P David; Keim, Samuel M; Viscusi, Chad; Mullins, Terry; Sherrill, Duane

    2017-01-01

    Survival is significantly reduced by either hypotension or hypoxia during the out-of-hospital management of major traumatic brain injury. However, only a handful of small studies have investigated the influence of the combination of both hypotension and hypoxia occurring together. In patients with major traumatic brain injury, we evaluate the associations between mortality and out-of-hospital hypotension and hypoxia separately and in combination. All moderate or severe traumatic brain injury cases in the preimplementation cohort of the Excellence in Prehospital Injury Care study (a statewide, before/after, controlled study of the effect of implementing the out-of-hospital traumatic brain injury treatment guidelines) from January 1, 2007, to March 31, 2014, were evaluated (exclusions: 200 mm Hg). The relationship between mortality and hypotension (systolic blood pressure controlling for Injury Severity Score, head region severity, injury type (blunt versus penetrating), age, sex, race, ethnicity, payer, interhospital transfer, and trauma center. Among the 13,151 patients who met inclusion criteria (median age 45 years; 68.6% men), 11,545 (87.8%) had neither hypotension nor hypoxia, 604 (4.6%) had hypotension only, 790 (6.0%) had hypoxia only, and 212 (1.6%) had both hypotension and hypoxia. Mortality for the 4 study cohorts was 5.6%, 20.7%, 28.1%, and 43.9%, respectively. The crude and adjusted odds ratios for death within the cohorts, using the patients with neither hypotension nor hypoxia as the reference, were 4.4 and 2.5, 6.6 and 3.0, and 13.2 and 6.1, respectively. Evaluation for an interaction between hypotension and hypoxia revealed that the effects were additive on the log odds of death. In this statewide analysis of major traumatic brain injury, combined out-of-hospital hypotension and hypoxia were associated with significantly increased mortality. This effect on survival persisted even after controlling for multiple potential confounders. In fact, the

  13. A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly.

    Science.gov (United States)

    Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

    2014-12-02

    Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

  14. The effect of artificial neural network model combined with six tumor markers in auxiliary diagnosis of lung cancer.

    Science.gov (United States)

    Feng, Feifei; Wu, Yiming; Wu, Yongjun; Nie, Guangjin; Ni, Ran

    2012-10-01

    To evaluate the diagnosis potential of artificial neural network (ANN) model combined with six tumor markers in auxiliary diagnosis of lung cancer, to differentiate lung cancer from lung benign disease, normal control, and gastrointestinal cancers. Serum carcino-embryonic antigen (CEA), gastrin, neurone specific enolase (NSE), sialic acid (SA), Cu/Zn, Ca were measured through different experimental procedures in 117 lung cancer patients, 93 lung benign disease patients, 111 normal control, 47 gastric cancer patients, 50 patients with colon cancer and 50 esophagus cancer patients, 19 parameters of basic information were surveyed among lung cancer, lung benign disease and normal control, then developed and evaluated ANN models to distinguish lung cancer. Using the ANN model with the six serum tumor markers and 19 parameters to distinguish lung cancer from benign lung disease and healthy people, the sensitivity was 98.3%, the specificity was 99.5% and the accuracy was 96.9%. Another three ANN models with the six serum tumor markers were employed to differentiate lung cancer from three gastrointestinal cancers, the sensitivity, specificity and accuracy of distinguishing lung cancer from gastric cancer by the ANN model of lung cancer-gastric cancer were 100%, 83.3% and 93.5%, respectively; The sensitivity, specificity and accuracy of discriminating lung cancer by lung cancer-colon cancer ANN model were 90.0%, 90.0%, and 90.0%; And which were 86.7%, 84.6%, and 86.0%, respectively, by lung cancer-esophagus cancer ANN model. ANN model built with the six serum tumor markers could distinguish lung cancer, not only from lung benign disease and normal people, but also from three common gastrointestinal cancers. And our evidence indicates the ANN model maybe is an excellent and intelligent system to discriminate lung cancer.

  15. 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.

  16. Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells.

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M; Vadgama, Jaydutt V

    2015-02-01

    We investigated whether a combination of two promising chemopreventive agents arctigenin (Arc) and quercetin (Q) increases the anticarcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of Arc and Q alone or in combination for 48 h. The antiproliferative activity of Arc was 10- to 20-fold stronger than Q in both cell lines. Their combination synergistically enhanced the antiproliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arc demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. The combination of Arc and Q that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  18. Combined treatment effects of radiation and immunotherapy: studies in an autochthonous prostate cancer model.

    Science.gov (United States)

    Wada, Satoshi; Harris, Timothy J; Tryggestad, Erik; Yoshimura, Kiyoshi; Zeng, Jing; Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F; Bruno, Tullia C; De Marzo, Angelo M; Netto, George J; Pardoll, Drew M; DeWeese, Theodore L; Wong, John; Drake, Charles G

    2013-11-15

    To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

    Energy Technology Data Exchange (ETDEWEB)

    Wada, Satoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Harris, Timothy J.; Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yoshimura, Kiyoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C. [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); De Marzo, Angelo M. [Department of Pathology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); and others

    2013-11-15

    Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.

  20. Radiotherapy combined with hormonal therapy in prostate cancer: the state of the art

    Directory of Open Access Journals (Sweden)

    Piotr Milecki

    2010-10-01

    Full Text Available Piotr Milecki1,2, Piotr Martenka1, Andrzej Antczak3, Zbigniew Kwias31Department of Radiotherapy, Greater Poland Cancer Center, Poznan, Poland; 2Department of Electroradiology, Medical University, Poznan, Poland; 3Chair of Urology, Medical University, Poznan, PolandAbstract: Androgen-deprivation therapy (ADT is used routinely in combination with definitive external beam radiation therapy (EBRT in patients with high-risk clinically localized or locally advanced disease. The combined treatment (ADT–EBRT also seems to play a significant role in improving treatment results in the intermediate-risk group of prostate cancer patients. On the other hand, there is a growing body of evidence that treatment with ADT can be associated with serious and lifelong adverse events including osteoporosis, cardiovascular disease, diabetes, and many others. Almost all ADT adverse events are time dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, it is crucial to clearly state the optimal schedule for ADT in combination with EBRT, that maintaining the positive effect on treatment efficacy would keep the adverse events risk at reasonable level. To achieve this goal, treatment schedule may have to be highly individualized on the basis of the patient-specific potential vulnerability to adverse events. In this study, the concise and evidence-based review of current literature concerning the general rationales for combining radiotherapy and hormonal therapy, its mechanism, treatment results, and toxicity profile is presented.Keywords: prostate cancer, radiotherapy, androgen deprivation, combined treatment

  1. Brain-computer interface game applications for combined neurofeedback and biofeedback treatment for children on the autism spectrum

    Directory of Open Access Journals (Sweden)

    Elisabeth V C Friedrich

    2014-07-01

    Full Text Available Individuals with Autism Spectrum Disorder (ASD show deficits in social and communicative skills, including imitation, empathy, and shared attention, as well as restricted interests and repetitive patterns of behaviors. Evidence for and against the idea that dysfunctions in the mirror neuron system are involved in imitation and could be one underlying cause for ASD is discussed in this review. Neurofeedback interventions have reduced symptoms in children with ASD by self-regulation of brain rhythms. However, cortical deficiencies are not the only cause of these symptoms. Peripheral physiological activity, such as the heart rate, is closely linked to neurophysiological signals and associated with social engagement. Therefore, a combined approach targeting the interplay between brain, body and behavior could be more effective. Brain-computer interface applications for combined neurofeedback and biofeedback treatment for children with ASD are currently nonexistent. To facilitate their use, we have designed an innovative game that includes social interactions and provides neural- and body-based feedback that corresponds directly to the underlying significance of the trained signals as well as to the behavior that is reinforced.

  2. Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neuronal systems in brain

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, M.E.; Khachaturian, H.; Watson, S.J.

    1985-01-01

    Using adjacent section autoradiography-immunocytochemistry, the distribution of (TH)naloxone binding sites was studied in relation to neuronal systems containing (Leu)enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of (TH)naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand (TH)D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between (TH)naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed. Within regions, the relationship was complex. The complexity of the association between (TH)naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.

  3. A combined MR and CT study for precise quantitative analysis of the avian brain

    Czech Academy of Sciences Publication Activity Database

    Jirák, D.; Janáček, Jiří; Kear, B. P.

    2015-01-01

    Roč. 5, Oct 30 (2015), s. 16002 ISSN 2045-2322 R&D Projects: GA ČR(CZ) GAP302/12/1207 Institutional support: RVO:67985823 Keywords : avian brain * magnetic resonance imaging * computed tomography * Fakir probe Subject RIV: EA - Cell Biology Impact factor: 5.228, year: 2015

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Molecular Landscape of Acquired Resistance to Targeted Therapy Combinations in BRAF-Mutant Colorectal Cancer.

    Science.gov (United States)

    Oddo, Daniele; Sennott, Erin M; Barault, Ludovic; Valtorta, Emanuele; Arena, Sabrina; Cassingena, Andrea; Filiciotto, Genny; Marzolla, Giulia; Elez, Elena; van Geel, Robin M J M; Bartolini, Alice; Crisafulli, Giovanni; Boscaro, Valentina; Godfrey, Jason T; Buscarino, Michela; Cancelliere, Carlotta; Linnebacher, Michael; Corti, Giorgio; Truini, Mauro; Siravegna, Giulia; Grasselli, Julieta; Gallicchio, Margherita; Bernards, René; Schellens, Jan H M; Tabernero, Josep; Engelman, Jeffrey A; Sartore-Bianchi, Andrea; Bardelli, Alberto; Siena, Salvatore; Corcoran, Ryan B; Di Nicolantonio, Federica

    2016-08-01

    Although recent clinical trials of BRAF inhibitor combinations have demonstrated improved efficacy in BRAF-mutant colorectal cancer, emergence of acquired resistance limits clinical benefit. Here, we undertook a comprehensive effort to define mechanisms underlying drug resistance with the goal of guiding development of therapeutic strategies to overcome this limitation. We generated a broad panel of BRAF-mutant resistant cell line models across seven different clinically relevant drug combinations. Combinatorial drug treatments were able to abrogate ERK1/2 phosphorylation in parental-sensitive cells, but not in their resistant counterparts, indicating that resistant cells escaped drug treatments through one or more mechanisms leading to biochemical reactivation of the MAPK signaling pathway. Genotyping of resistant cells identified gene amplification of EGFR, KRAS, and mutant BRAF, as well as acquired mutations in KRAS, EGFR, and MAP2K1 These mechanisms were clinically relevant, as we identified emergence of a KRAS G12C mutation and increase of mutant BRAF V600E allele frequency in the circulating tumor DNA of a patient at relapse from combined treatment with BRAF and MEK inhibitors. To identify therapeutic combinations capable of overcoming drug resistance, we performed a systematic assessment of candidate therapies across the panel of resistant cell lines. Independent of the molecular alteration acquired upon drug pressure, most resistant cells retained sensitivity to vertical MAPK pathway suppression when combinations of ERK, BRAF, and EGFR inhibitors were applied. These therapeutic combinations represent promising strategies for future clinical trials in BRAF-mutant colorectal cancer. Cancer Res; 76(15); 4504-15. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Additively Enhanced Antiproliferative Effect of Interferon Combined with Proanthocyanidin on Bladder Cancer Cells

    Directory of Open Access Journals (Sweden)

    Andrew I. Fishman, Blake Johnson, Bobby Alexander, John Won, Muhammad Choudhury, Sensuke Konno

    2012-01-01

    Full Text Available Although interferon (IFN has been often used as immunotherapy for bladder cancer, its efficacy is rather unsatisfactory, demanding further improvement. Combination therapy is one of viable options, and grape seed proanthocyanidin (GSP could be such an agent to be used with IFN because it has been shown to have anticancer activity. We thus investigated whether combination of IFN and GSP might enhance the overall antiproliferative effect on bladder cancer cells in vitro. Human bladder cancer T24 cells were employed and treated with the varying concentrations of recombinant IFN-α2b (0-100,000 IU/ml, GSP (0-100 μg/ml, or their combinations. IFN-α2b alone led to a ~50% growth reduction at 20,000 (20K IU/ml, which further declined to ~67% at ≥50K IU/ml. Similarly, GSP alone induced a ~35% and ~100% growth reduction at 25 and ≥50 μg/ml, respectively. When IFN-α2b and GSP were then combined, combination of 50K IU/ml IFN-α2b and 25 μg/ml GSP resulted in a drastic >95% growth reduction. Cell cycle analysis indicated that such an enhanced growth inhibition was accompanied by a G1 cell cycle arrest. This was further confirmed by Western blot analysis revealing that expressions of G1-specific cell cycle regulators (CDK2, CDK4, cyclin E and p27/Kip1 were distinctly modulated with such IFN-α2b/GSP treatment. Therefore, these findings support the notion that combination of IFN-α2b and GSP is capable of additively enhancing antiproliferative effect on T24 cells with a G1 cell cycle arrest, implying an adjuvant therapeutic modality for superficial bladder cancer.

  7. Combining quantitative and qualitative breast density measures to assess breast cancer risk.

    Science.gov (United States)

    Kerlikowske, Karla; Ma, Lin; Scott, Christopher G; Mahmoudzadeh, Amir P; Jensen, Matthew R; Sprague, Brian L; Henderson, Louise M; Pankratz, V Shane; Cummings, Steven R; Miglioretti, Diana L; Vachon, Celine M; Shepherd, John A

    2017-08-22

    Accurately identifying women with dense breasts (Breast Imaging Reporting and Data System [BI-RADS] heterogeneously or extremely dense) who are at high breast cancer risk will facilitate discussions of supplemental imaging and primary prevention. We examined the independent contribution of dense breast volume and BI-RADS breast density to predict invasive breast cancer and whether dense breast volume combined with Breast Cancer Surveillance Consortium (BCSC) risk model factors (age, race/ethnicity, family history of breast cancer, history of breast biopsy, and BI-RADS breast density) improves identifying women with dense breasts at high breast cancer risk. We conducted a case-control study of 1720 women with invasive cancer and 3686 control subjects. We calculated ORs and 95% CIs for the effect of BI-RADS breast density and Volpara™ automated dense breast volume on invasive cancer risk, adjusting for other BCSC risk model factors plus body mass index (BMI), and we compared C-statistics between models. We calculated BCSC 5-year breast cancer risk, incorporating the adjusted ORs associated with dense breast volume. Compared with women with BI-RADS scattered fibroglandular densities and second-quartile dense breast volume, women with BI-RADS extremely dense breasts and third- or fourth-quartile dense breast volume (75% of women with extremely dense breasts) had high breast cancer risk (OR 2.87, 95% CI 1.84-4.47, and OR 2.56, 95% CI 1.87-3.52, respectively), whereas women with extremely dense breasts and first- or second-quartile dense breast volume were not at significantly increased breast cancer risk (OR 1.53, 95% CI 0.75-3.09, and OR 1.50, 95% CI 0.82-2.73, respectively). Adding continuous dense breast volume to a model with BCSC risk model factors and BMI increased discriminatory accuracy compared with a model with only BCSC risk model factors (C-statistic 0.639, 95% CI 0.623-0.654, vs. C-statistic 0.614, 95% CI 0.598-0.630, respectively; P breasts and fourth

  8. The combination of neuronavigation with transcranial magnetic stimulation for treatment of opercular gliomas of the dominant brain hemisphere.

    Science.gov (United States)

    Shamov, T; Spiriev, T; Tzvetanov, P; Petkov, A

    2010-10-01

    The objective of this study is to investigate the application of transcranial magnetic stimulation combined with neuronavigation for preoperative mapping of the language area in neurosurgical interventions on the opercular area of the dominant hemisphere. Five patients were operated upon gliomas in the opercular area. For localization of the speech area a transcranial magnetic stimulator MEDTRONIC-MagPro was used. BrainLAB-VectorVision Neuronavigation system was utilized for precise planning of the operative approach. Gross total resection was achieved in all patients. Three-month postoperative follow-up was done. Three of the patients had a transient postoperative motor aphasia which resolved within 1 month. This method is useful for preoperative localization of the speech area, as well as preoperative planning of the operative approach and intra-operative planning of the direction of brain retraction and operative corridor. (c) 2010 Elsevier B.V. All rights reserved.

  9. Intrahepatic and systemic therapy with oxaliplatin combined with capecitabine in patients with hepatic metastases from breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D L; Nørgaard, H; Weber Vestermark, Lene

    2012-01-01

    The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease.......The aim was to evaluate activity and toxicity of hepatic arterial infusion of oxaliplatin in combination with capecitabine in patients with metastatic breast cancer with liver metastases and limited extrahepatic disease....

  10. 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.

  11. Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations.

    Directory of Open Access Journals (Sweden)

    Michal Yalon

    Full Text Available Inhibitors of poly[ADP-ribose] polymerase 1 (PARPis show promise for treatment of cancers which lack capacity for homologous recombination repair (HRR. However, new therapeutic strategies are required in order to overcome innate and acquired resistance to these drugs and thus expand the array of cancers that could benefit from them. We show that human cancer cell lines which respond poorly to ABT-888 (a PARPi, become sensitive to it when co-treated with vorinostat (a histone deacetylase inhibitor (HDACi. Vorinostat also sensitized PARPis insensitive cancer cell lines to 6-thioguanine (6-TG-a drug that targets PARPis sensitive cells. The sensitizing effect of vorinostat was associated with increased phosphorylation of eukaryotic initiation factor (eIF 2α which in and of itself increases the sensitivity of cancer cells to ABT-888. Importantly, these drug combinations did not affect survival of normal fibroblasts and breast cells, and significantly increased the inhibition of xenograft tumor growth relative to each drug alone, without affecting the mice weight or their liver and kidney function. Our results show that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. Importantly, drugs which increase phosphorylation of eIF2α may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors.

  12. 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.

  13. Cancer prevention and treatment using combination therapy with plant- and animal-derived compounds.

    Science.gov (United States)

    Uzoigwe, Jacinta; Sauter, Edward R

    2012-11-01

    Compounds naturally occurring in plants and animals play an essential role in the prevention and treatment of various cancers. There are more than 100 plant- and animal-based natural compounds currently in clinical use. Similar to synthetic compounds, these natural compounds are associated with dose-related toxicity that limits efficacy. Scientists have investigated combination therapy with compounds that have different toxicities in order to optimize efficacy. These combination therapies may work additively or synergistically, there may be no effect or they may promote tumor formation. Combination therapy with agents that have similar mechanisms of action may increase toxicity. In this article, combination therapies that have been investigated, their rationale, mechanism of action and findings are reviewed. When the data warrant it, combined (pharmacologic and natural; two or more natural) interventions that appear to increase efficacy (compared with monotherapy) while minimizing toxicity have been highlighted.

  14. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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 mo