scholarly journals The microenvironment of brain metastases from solid tumors

2021 ◽  
Vol 3 (Supplement_5) ◽  
pp. v121-v132
Author(s):  
Ethan S Srinivasan ◽  
Krutika Deshpande ◽  
Josh Neman ◽  
Frank Winkler ◽  
Mustafa Khasraw
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Intracranial Tumor ◽  
Malignant Cells ◽  
Complex Interplay ◽  
Dismal Prognosis ◽  
Medical Need ◽  
Metabolic Conditions ◽  
The Central Nervous System

Abstract Brain metastasis (BrM) is an area of unmet medical need that poses unique therapeutic challenges and heralds a dismal prognosis. The intracranial tumor microenvironment (TME) presents several challenges, including the therapy-resistant blood–brain barrier, a unique immune milieu, distinct intercellular interactions, and specific metabolic conditions, that are responsible for treatment failures and poor clinical outcomes. There is a complex interplay between malignant cells that metastasize to the central nervous system (CNS) and the native TME. Cancer cells take advantage of vascular, neuronal, immune, and anatomical vulnerabilities to proliferate with mechanisms specific to the CNS. In this review, we discuss unique aspects of the TME in the context of brain metastases and pathways through which the TME may hold the key to the discovery of new and effective therapies for patients with BrM.

scholarly journals Current management of brain metastases

2014 ◽  
Vol 33 (04) ◽  
pp. 347-351
Author(s):  
Pedro Tadao Hamamoto Filho ◽  
Vitor César Machado ◽  
Flávio Ramalho Romero ◽  
Luis Gustavo Ducati ◽  
Marco Antônio Zanini ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Treatment Modalities ◽  
Current Management ◽  
Brain Radiotherapy ◽  
Recent Advances ◽  
The Central Nervous System ◽  
Treatment Surgery

AbstractBrain metastases are the most common tumors within the central nervous system. Recent advances on diagnosis and treatment modalities have allowed for longer survival. In this paper we review the indication of each modality of treatment: surgery, whole brain radiotherapy and stereotactic radiosurgery, as also recent advances on the knowledge of brain metastases biology that may improve the use of medical treatment and chemotherapy.

Long Latency Reflexes and the Silent Period

2009 ◽  
pp. 543-550
Author(s):  
John N. Caviness
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Motor Control ◽  
Brain Stem ◽  
Silent Period ◽  
Complex Interplay ◽  
Long Latency ◽  
System P ◽  
The Central Nervous System ◽  
Long Latency Reflexes

LLRs and the silent period are EMG phenomena that reflect the complex interplay of spinal, brain stem, and cortical influences in motor control. These techniques have been applied to the study of disorders of motor control such as Parkinson’s disease, Huntington’s disease, and dystonia. Abnormalities of these reflexes may help to detect lesions of the central nervous system.

scholarly journals The Biology of Brain Metastasis

2013 ◽  
Vol 59 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Robert R Langley ◽  
Isaiah J Fidler
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Disease Progression ◽  
Microvascular Endothelial Cells ◽  
Number Of Patients ◽  
The Central Nervous System ◽  
Microvascular Endothelial

BACKGROUND It is estimated that at least 200 000 cases of brain metastases occur each year in the US, which is 10 times the number of patients diagnosed with primary brain tumors. Brain metastasis is associated with poor prognosis, neurological deterioration, diminished quality of life, and extremely short survival. Favorable interactions between tumor cells and cerebral microvascular endothelial cells encourage tumor growth in the central nervous system, while tumor cell interactions with astrocytes protect brain metastases from the cytotoxic effects of chemotherapy. CONTENT We review the pathogenesis of brain metastasis and emphasize the contributions of microvascular endothelial cells and astrocytes to disease progression and therapeutic resistance. Animal models used to study brain metastasis are also discussed. SUMMARY Brain metastasis has many unmet clinical needs. There are few clinically relevant tumor models and no targeted therapies specific for brain metastases, and the mean survival for untreated patients is 5 weeks. Improved clinical outcomes are dependent on an enhanced understanding of the metastasis-initiating population of cells and the identification of microenvironmental factors that encourage disease progression in the central nervous system.

Modern Management of Central Nervous System Metastases in the Era of Targeted Therapy and Immune Oncology

2019 ◽  
pp. e59-e69 ◽  
Author(s):  
Priscilla Brastianos ◽  
Michael A. Davies ◽  
Kim Margolin ◽  
Helena A. Yu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
New Era ◽  
Patients With Cancer ◽  
Whole Brain Radiation ◽  
The Central Nervous System ◽  
Considerable Morbidity ◽  
Immune Oncology

Metastases to the central nervous system (CNS) are associated with considerable morbidity and mortality in patients with cancer. Historically, very few systemic therapies have shown efficacy in this patient population. Emerging data are now demonstrating that whole-brain radiation therapy, previously considered the mainstay of treatment of brain metastases, is associated with high rates of neurotoxicity. In this new era of targeted therapy and immunotherapy, clinical outcomes are improving, and patients are living longer. Despite these improvements, there is an urgent need to design central nervous system–penetrant compounds that target the genetic mutations enriched in brain metastases and to bring these to clinical trials.

Presentation of central nervous system sarcoidosis as intracranial tumors

1985 ◽  
Vol 63 (6) ◽  
pp. 851-856 ◽  
Author(s):  
W. Craig Clark ◽  
James D. Acker ◽  
F. Curtis Dohan ◽  
Jon H. Robertson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Pulmonary Involvement ◽  
Intracranial Tumor ◽  
Intracranial Tumors ◽  
Serum Angiotensin Converting Enzyme ◽  
Content Type ◽  
The Central Nervous System ◽  
A Site

✓ Five cases of sarcoid presenting as an intracranial tumor are reported. In one instance, the lesion presented as a tumor in the cerebellopontine angle, a site not previously reported for the initial presentation of sarcoid isolated to the central nervous system. The role of computerized tomography, surgery, and steroid therapy is discussed. In the absence of pulmonary involvement, serum angiotensin-converting enzyme levels do not appear to be helpful in predicting steroid response.

Predictive factors for oligometastatic versus non-oligometastatic involvement of the central nervous system by brain metastases from breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 123-123 ◽  
Author(s):  
S. Garg ◽  
J. C. Marsh ◽  
R. D. Rao ◽  
K. L. Griem
Keyword(s):  
Breast Cancer ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Metastases ◽  
Initial Diagnosis ◽  
Breast Cancer Patients ◽  
Cns Involvement ◽  
Cancer Subtypes ◽  
Oligometastatic Disease ◽  
The Central Nervous System

123 Background: To assess rates of oligometastatic (1-3 metastases) versus non-oligometastatic (4 or more) involvement of the central nervous system (CNS) from breast cancer and determine whether rates vary for different breast cancer subtypes. Methods: We reviewed records of 65 patients with brain metastases from breast cancer. Fisher’s Exact Test compared incidence of oligometastatic versus nonoligometastatic CNS involvement and presence of visceral metastatic disease between groups. Paired Student's t test compared mean age and interval from initial diagnosis to development of brain metastases. Results: 25 patients (38.5%) developed oligometastatic and 40 (61.5%) developed non-oligometastatic CNS disease. Subtypes predictive of oligometastatic disease included ER+ (p .04) and PR+ (p .008). Subtypes predictive of non-oligometastatic disease included HER2+ (p .05). HER2+ patients trended toward a lower incidence of visceral metastases compared to ER+ or PR+ patients (p .07). Non-oligometastatic and HER2+ patients developed brain metastases sooner after initial diagnosis (p .046 and .03, respectively). Conclusions: ER+ breast cancer patients are more likely to develop oligometastatic CNS involvement and may be excellent candidates for stereotactic radiosurgery (SRS) alone. HER+ patients are likely to develop non-oligometastatic CNS involvement and may be better treated initially with whole brain radiotherapy (WBRT) even with apparent initial oligometastatic CNS involvement.

Episodic release of insulin by rat pancreas: effects of CNS and state of satiety

1988 ◽  
Vol 254 (3) ◽  
pp. E384-E388
Author(s):  
R. H. Safarik ◽  
R. M. Joy ◽  
D. L. Curry
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Insulin Release ◽  
Cycle Length ◽  
Sprague Dawley ◽  
Rat Pancreas ◽  
Sprague Dawley Rats ◽  
Metabolic Conditions ◽  
The Central Nervous System

This study reports that insulin is secreted in an episodic manner in rats and that the characteristics of its release can be modified by the central nervous system (CNS) and state of satiety. The pancreata of male Sprague-Dawley rats were perfused using the in situ brain-pancreas technique under urethan anesthesia. Episodic insulin release under non-fasted conditions was not altered by the presence or absence of CNS innervation to the pancreas. Under these conditions the interpeak period was 5.9 and 6 min, respectively, and cycle length was 3.7 and 4 min. However, perfusions that were performed following an overnight fast demonstrated that the CNS is capable of modulating episodic insulin release. After fasting, when comparing CNS-ablated with -intact preparations, the period was shortened from 5.2 to 4.1 min (P less than 0.05), and the number of episodes per 90-min perfusion increased from 16.0 to 19.0 (P less than 0.05) when the pancreas was innervated by the CNS. Additionally, the effect of fasting on denervated pancreata resulted in a shortening of the cycle length, which was prevented when the CNS was functional. These results demonstrate that episodic insulin release can be modified by metabolic conditions and are subject to mediation by the CNS.

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