The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform

Raymond Sawaya - One of the best experts on this subject based on the ideXlab platform.

  • Neurosurgical Management of Patients With Brain Metastasis
    Neurosurgical review, 2018
    Co-Authors: Mustafa Aziz Hatiboglu, Kerime Akdur, Raymond Sawaya
    Abstract:

    Brain Metastasis is a serious complication in patients with systemic cancer. The main goal of the treatment in patients with Brain Metastasis is to control the disease in the Brain, to prevent death from neurological disease and provide a satisfactory quality of life. Management of a patient with Brain Metastasis is important and sometimes demanding, and several factors such as tumor histology, status of primary disease, number of Brain lesions, size of lesions, and performance status may influence the decision making process. We reviewed the neurosurgical treatment modalities in patients with metastatic Brain tumor and suggested a treatment paradigm for different clinical conditions. The PubMed database was searched using combinations of search terms and synonyms for "management of Brain Metastasis," "stereotactic radiosurgery for Brain Metastasis," and "surgery for Brain Metastasis" between January 1, 1990, and January 1, 2018. This review would guide physicians to solve challenging problems in the treatment of patients with Brain Metastasis. In summary, local aggressive treatments such as surgical resection and stereotactic radiosurgery are reasonable in patients with limited intracranial disease, controlled primary disease, and high performance status. Besides, WBRT is still the standard treatment in patients with low performance score and leptomeningeal dissemination of cancer.

  • Activation of stat3 in human melanoma promotes Brain Metastasis.
    Cancer research, 2006
    Co-Authors: Tongxin Xie, Raymond Sawaya, Feng Ju Huang, Kenneth Aldape, Shin Hyuk Kang, Mingguang Liu, Jeffrey E. Gershenwald, Keping Xie, Suyun Huang
    Abstract:

    Brain Metastasis is a major cause of morbidity and mortality in patients with melanoma. The molecular changes that lead to Brain Metastasis remain poorly understood. In this study, we developed a model to study human melanoma Brain Metastasis and found that Stat3 activity was increased in human Brain metastatic melanoma cells when compared with that in cutaneous melanoma cells. The expression of activated Stat3 is also increased in human Brain Metastasis specimens when compared with that in the primary melanoma specimens. Increased Stat3 activation by transfection with a constitutively activated Stat3 enhanced Brain Metastasis, whereas blockade of Stat3 activation by transfection with a dominant-negative Stat3 suppressed Brain Metastasis of human melanoma cells in animal models. Furthermore, altered Stat3 activity profoundly affected melanoma angiogenesis in vivo and melanoma cell invasion in vitro and significantly affected the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) in vivo and in vitro. Finally, Stat3 activity transcriptionally regulated the promoter activity of bFGF in addition to VEGF and MMP-2 in human melanoma cells. These results indicated that Stat3 activation plays an important role in dysregulated expression of bFGF, VEGF, and MMP-2 as well as angiogenesis and invasion of melanoma cells and contributes to Brain Metastasis of melanoma. Therefore, Stat3 activation might be a new potential target for therapy of human melanoma Brain metastases.

  • Surgery versus radiosurgery in the treatment of Brain Metastasis
    Journal of neurosurgery, 1996
    Co-Authors: Ajay K. Bindal, Rajesh K. Bindal, Kenneth R. Hess, Almon S. Shiu, Samuel J. Hassenbusch, Weiming Shi, Raymond Sawaya
    Abstract:

    Surgery and radiosurgery are effective treatment modalities for Brain Metastasis. To compare the results of these treatment modalities, the authors followed 13 patients treated by radiosurgery and 62 patients treated by surgery who were retrospectively matched. Patients were matched according to the following criteria: histological characteristics of the primary tumor, extent of systemic disease, preoperative Karnofsky Performance Scale score, time to Brain Metastasis, number of Brain metastases, and patient age and sex. For patients treated by radiosurgery, the median size of the treated lesion was 1.96 cm3 (range 0.41-8.25 cm3) and the median dose was 20 Gy (range 12-22 Gy). The median survival was 7.5 months for patients treated by radiosurgery and 16.4 months for those treated by surgery; this difference was found to be statistically significant using both univariate (p = 0.0018) and multivariate (p = 0.0009) analyses. The difference in survival was due to a higher rate of mortality from Brain Metastasis in the radiosurgery group than in the surgery group (p < 0.0001) and not due to a difference in the rate of death from systemic disease (p = 0.28). Log-rank analysis showed that the higher mortality rate found in the radiosurgery group was due to a greater progression rate of the radiosurgically treated lesions (p = 0.0001) and not due to the development of new Brain Metastasis (p = 0.75). On the basis of their data, the authors conclude that surgery is superior to radiosurgery in the treatment of Brain Metastasis. Patients who undergo surgical treatment survive longer and have a better local control. The data lead the authors to suggest that the indications for radiosurgery should be limited to surgically inaccessible metastatic tumors or patients in poor medical condition. Surgery should remain the treatment of choice whenever possible.

Manuel Valiente - One of the best experts on this subject based on the ideXlab platform.

  • Preclinical Models of Brain Metastasis
    Central Nervous System Metastases, 2020
    Co-Authors: Lucía Zhu, Manuel Valiente
    Abstract:

    Brain metastases have received limited attention in spite of representing a major clinical problem. Difficulties to model this progression of cancer are partially responsible for the limited knowledge of the underlying biology. However, in recent years multiple experimental models have been developed representing the main types of cancer that generate Brain Metastasis. Although most studies have used non-spontaneous and untreated Brain Metastasis, more refined versions do exist. We provide an updated review of available and emerging models as well as a discussion regarding their advantages and disadvantages for Brain Metastasis research.

  • Vascular co-option in Brain Metastasis.
    Angiogenesis, 2019
    Co-Authors: Pedro García-gómez, Manuel Valiente
    Abstract:

    Vascular co-option by Brain Metastasis-initiating cells has been demonstrated as a critical step in organ colonization. The physical interaction between the cancer cell and the endothelial cell is mediated by integrins and L1CAM and could be involved in aggressive growth but also latency and immune evasion. The key involvement of vascular co-option in Brain Metastasis has created an emerging field that aims to identify critical targets as well as effective inhibitors with the goal of preventing Brain metastases.

  • Reactive Astrocytes in Brain Metastasis.
    Frontiers in oncology, 2017
    Co-Authors: David Wasilewski, Neibla Priego, Coral Fustero-torre, Manuel Valiente
    Abstract:

    Brain Metastasis, the secondary growth of malignant cells within the central nervous system (CNS), exceeds the incidence of primary Brain tumors (i.e., gliomas) by tenfold and are seemingly on the rise owing to the emergence of novel targeted therapies that are more effective in controlling extracranial disease relatively to intracranial lesions. Despite the fact that Metastasis to the Brain poses a unmet clinical problem, with afflicted patients carrying significant morbidity and a fatal prognosis, our knowledge as to how metastatic cells manage to adapt to the tissue environment of the CNS remains limited. Answering this question could pave the way for novel and more specific therapeutic modalities in Brain Metastasis by targeting the specific makeup of the Brain metastatic niche. In regard to this, astrocytes have emerged as the major host cell type that cancer cells encounter and interact with during Brain Metastasis formation. Similarly to other CNS disorders, astrocytes become reactive and respond to the presence of cancer cells by changing their phenotype and significantly influencing the outcome of disseminated cancer cells within the CNS. Here, we summarize the current knowledge on the contribution of reactive astrocytes in Brain Metastasis by focusing on the signaling pathways and types of interactions that play a crucial part in the communication with cancer cells and how these could be translated into innovative therapies.

Yibin Kang - One of the best experts on this subject based on the ideXlab platform.

Sébastien Serres - One of the best experts on this subject based on the ideXlab platform.

  • STAT3-mediated astrocyte reactivity associated with Brain Metastasis contributes to neurovascular dysfunction.
    Cancer Research, 2020
    Co-Authors: Manuel Sarmiento Soto, James Larkin, Chris Martin, Alexandre Khrapitchev, Melissa Maczka, Vasiliki Economopoulos, Helen Scott, Carole Escartin, Gilles Bonvento, Sébastien Serres
    Abstract:

    Astrocytes are thought to play a pivotal role in coupling neural activity and cerebral blood flow. However, it has been shown that astrocytes undergo morphological changes in response to Brain Metastasis, switching to a reactive phenotype which has the potential to significantly compromise cerebrovascular function and contribute to the neurological sequelae associated with Brain Metastasis. Given that signal transducer and activator of transcription 3 (STAT3) is a key regulator of astrocyte reactivity, we aimed here to determine the impact of STAT3-mediated astrocyte reactivity on neurovascular function in Brain Metastasis. Rat models of Brain Metastasis and ciliary neurotrophic factor (CNTF) were used to induce astrocyte reactivity. Multimodal imaging, electrophysiology, and immunohistochemistry were performed to determine the relationship between reactive astrocytes and changes in the cerebrovascular response to electrical and physiological stimuli. Subsequently, the STAT3 pathway in astrocytes was inhibited with WP1066 to determine the role of STAT3-mediated astrocyte reactivity, specifically, in Brain Metastasis. Astrocyte reactivity associated with Brain metastases impaired cerebrovascular responses to stimuli at both the cellular and functional level and disrupted astrocyte-endothelial interactions in both animal models and human Brain Metastasis samples. Inhibition of STAT3-mediated astrocyte reactivity in rats with Brain metastases restored cerebrovascular function, as shown by in vivo imaging, and limited cerebrovascular changes associated with tumor growth. Together these findings suggest that inhibiting STAT3-mediated astrocyte reactivity may confer significant improvements in neurological outcome for patients with Brain metastases and could potentially be tested in other Brain tumors.

Minhong Shen - One of the best experts on this subject based on the ideXlab platform.