Tumor Growth in the Brain: Complexity and Fractality

2016 ◽  
pp. 351-369 ◽  
Author(s):  
Miguel Martín-Landrove ◽  
Antonio Brú ◽  
Antonio Rueda-Toicen ◽  
Francisco Torres-Hoyos
Keyword(s):  
Tumor Growth ◽  
The Brain

Comorbidity: Chronic neurogenic pain affects malignant growth and changes balance of neurosteroids in brain of rats.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23516-e23516
Author(s):  
Yulia A. Pogorelova ◽  
Ekaterina I. Surikova ◽  
Elena M. Frantsiyants ◽  
Valeria A. Bandovkina ◽  
Irina V. Kaplieva ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Subclavian Vein ◽  
Tumor Development ◽  
Stress Factors ◽  
Male Rats ◽  
Control Group ◽  
Malignant Growth ◽  
Neurogenic Pain ◽  
Pulmonary Tissue ◽  
The Brain

e23516 Background: Sex steroids in the brain regulate neurogenesis and the body's response to stress. Chronic neurogenic pain (CNP) and the tumor growth are stress factors that often accompany each other. The purpose of the study was to analyze levels of sex steroid hormones in white matter of the brain of rats with tumor development in presence of CNP. Methods: The study included white outbred male rats (n = 74). In the main groups, a CNP model was created by bilateral sciatic nerve ligation, and after 45 days, M1 sarcoma was transplanted subcutaneously (n = 11) or into the subclavian vein (n = 11). Two comparison groups (each n = 13) included sham operated animals with M1 sarcoma transplanted subcutaneously or into the subclavian vein. Control groups (each n = 13) included animals with CNP or sham operated rats. Levels of testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) were measured by ELISA (Cusabio, China) in the brain tissues obtained on day 21 of the tumor growth. Results: Tumors transplanted subcutaneously with and without CNP grew in 100% of animals. Tumor volumes were 1.5 times (p<0.05) greater in animals with CNP, compared with rats without CNP, while the survival in the groups was similar. Levels of all studied hormones, except for E1, in the brain tissue in subcutaneous sarcoma growth were lower in presence of CNP than without it: T and E3–on average by 1.4 times (p<0.05), E2 and P4–by 3.5 times (p<0.05). In rats with intravenous transplantation of M1, tumor nodes in the lungs were registered only in rats with CNP, and the survival of animals was 36 days shorter (p<0.05) than in rats of the corresponding control group. Such specificity of selective neoplastic growth in the pulmonary tissue was combined with lower cerebral T and E3 levels than in the corresponding control–on average by 1.4 times (p<0.05), E2–by 7.2 times, and higher levels of E1–by 1.3 (p<0.05) and P4–by 2.0 times, compared to animals which did not develop the neoplastic process in the lungs without pain. Conclusions: The presence of CNP stimulates the growth of M1 sarcoma in standard subcutaneous inoculation and allows the development of tumors in the lung in intravenous inoculation. The specificity of malignant growth in presence of CNP is accompanied by changes in the brain levels of neurosteroids in rats.

Mathematical Modeling of Substrates Fluxes and Tumor Growth in the Brain

2019 ◽  
Vol 67 (2) ◽  
pp. 149-175 ◽  
Author(s):  
Angélique Perrillat-Mercerot ◽  
Nicolas Bourmeyster ◽  
Carole Guillevin ◽  
Alain Miranville ◽  
Rémy Guillevin
Keyword(s):  
Mathematical Modeling ◽  
Tumor Growth ◽  
The Brain

scholarly journals HIF1A signaling selectively supports proliferation of breast cancer in the brain

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Richard Y. Ebright ◽  
Marcus A. Zachariah ◽  
Douglas S. Micalizzi ◽  
Ben S. Wittner ◽  
Kira L. Niederhoffer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Tumor Growth ◽  
Hypoxia Inducible Factor ◽  
Metastatic Breast ◽  
Major Complication ◽  
Proliferative Potential ◽  
Therapeutic Implications ◽  
Drug Inhibition ◽  
The Brain

AbstractBlood-borne metastasis to the brain is a major complication of breast cancer, but cellular pathways that enable cancer cells to selectively grow in the brain microenvironment are poorly understood. We find that cultured circulating tumor cells (CTCs), derived from blood samples of women with advanced breast cancer and directly inoculated into the mouse frontal lobe, exhibit striking differences in proliferative potential in the brain. Derivative cell lines generated by serial intracranial injections acquire selectively increased proliferative competency in the brain, with reduced orthotopic tumor growth. Increased Hypoxia Inducible Factor 1A (HIF1A)-associated signaling correlates with enhanced proliferation in the brain, and shRNA-mediated suppression of HIF1A or drug inhibition of HIF-associated glycolytic pathways selectively impairs brain tumor growth while minimally impacting mammary tumor growth. In clinical specimens, brain metastases have elevated HIF1A protein expression, compared with matched primary breast tumors, and in patients with brain metastases, hypoxic signaling within CTCs predicts decreased overall survival. The selective activation of hypoxic signaling by metastatic breast cancer in the brain may have therapeutic implications.

Site-specific immune response to implanted gliomas

2001 ◽  
Vol 95 (6) ◽  
pp. 1012-1019 ◽  
Author(s):  
Martin A. Proescholdt ◽  
Marsha J. Merrill ◽  
Barbara Ikejiri ◽  
Stuart Walbridge ◽  
Aytac Akbasak ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Tumor Growth ◽  
Mhc Class Ii ◽  
Lymphocytic Infiltration ◽  
Class Ii ◽  
Content Type ◽  
Time Points ◽  
Early Tumor ◽  
The Brain ◽  
Fine Print

Object. Immunotherapy for glioblastoma has been uniformly ineffective. The immunological environment of the brain, with its low expression of major histocompatibility complex (MHC) molecules and limited access for inflammatory cells and humoral immune effectors due to the blood—brain barrier (BBB), may contribute to the failure of immunotherapy. The authors hypothesize that brain tumors are protected from immune surveillance by an intact BBB at early stages of development. To investigate the immunological characteristics of early tumor growth, the authors compared the host response to a glioma implanted into the brain and into subcutaneous tissue. Methods. Samples of tumors growing in the brain or subcutaneously in rats were obtained for 7 consecutive days and were examined immunohistochemically for MHC Class I & II molecules, and for CD4 and CD8 lymphocyte markers. Additionally, B7-1 costimulatory molecule expression and lymphocyte-specific apoptosis were examined. Conclusions. On Days 3 and 4 after implantation, brain tumors displayed significantly lower MHC Class II expression and lymphocytic infiltration (p < 0.05). After Day 5, however, no differences were detected. The MHC Class II expressing cells within the brain tumors appeared to be infiltrating microglia. Minimal B7-1 expression combined with lymphocyte-specific apoptosis were detected in both brain and subcutaneous tumors. Low MHC Class II expression and low lymphocytic infiltration at early time points indicate the importance of the immunologically privileged status of the brain during early tumor growth. These characteristics disappeared at later time points, possibly because the increasing perturbation of the BBB alters the specific immunological environment of the brain. The lack of B7-1 expression combined with lymphocyte apoptosis indicates clonal anergy of glioma-infiltrating lymphocytes regardless of implantation site.

scholarly journals Computational Modeling of the Effect of Sulci during Tumor Growth and Cerebral Edema

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Dan Peng ◽  
Zhiheng Zhou ◽  
Yin Liu ◽  
Tianfu Guo ◽  
Ying Li ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cerebral Edema ◽  
Volume Expansion ◽  
Maximum Stress ◽  
Nonlinear Finite Element ◽  
Nonlinear Finite Element Method ◽  
Future Studies ◽  
Brain Modeling ◽  
The Brain ◽  
Brain Tissues

This paper aims at studying the effect of sulci structures during tumor growth and cerebral edema in brain tissues. Motivated by the Intracranial Cerebral Pressure (ICP) monitoring during the brain surgery, a computational model has been created to study macroscopic behaviors of brain tissues with local volume expansion introduced by the tumor growth and cerebral edema. To consider the extra-large deformation during the tumor growth, a nonlinear finite element method has been adopted. Numerical simulation results reveal that sulci structures play significant roles in macroscopic volume expansion and maximum stress of brain tissues. Without considering the sulci structures, predictions on the ICP will be dramatically different from those including sulci structure. Therefore, it is strongly suggested that the sulci structure should be included in future studies on the brain modeling for investigating the space-occupying lesions.

Aminergic status in the brain of urokinase gene-deficient mice with malignant tumors growing in presence of chronic neurogenic pain.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21582-e21582
Author(s):  
Yulia A. Pogorelova ◽  
Irina V. Kaplieva ◽  
Elena M. Frantsiyants ◽  
Ekaterina I. Surikova ◽  
Valeria A. Bandovkina ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Tumor Growth ◽  
Biogenic Amines ◽  
Malignant Tumors ◽  
Gene Knockout ◽  
Significant Inhibition ◽  
Mouse Strains ◽  
Neurogenic Pain ◽  
The Brain ◽  
Melanoma Growth

e21582 Background: The fibrinolytic system of the brain is important for its normal functioning and participation in processes that are significant in various stressful influences, including tumor growth and chronic neurogenic pain (CNP). These pathological conditions change the activity of the brain neurotransmitter system. On the other hand, urokinase deficiency is associated with significant inhibition of tumor growth, while CNP – with its stimulation. The purpose of the study was to analyze the effect of CNP on the levels of biogenic amines in the brain of mice with urokinase deficiency (uPA-/-) with transplanted B16/F10 melanoma. Methods: The study included male and female mice: С57ВL/6 (uPA+/+, n = 48) and C57BL/6-Plautm1.1Bug-ThisPlauGFDhu/GFDhu (urokinase gene-knockout - uPA-/-, n = 48). Mouse strains were divided into subgroups (each n = 6): intact; with CNP (bilateral sciatic nerve ligation); 21 days after subcutaneous transplantation of B16/F10 melanoma; 21 days of B16/F10 melanoma growth in presence of CNP (B16/F10+CNP), with tumor transplantation 2 weeks after the sciatic nerve ligation. Levels of adrenaline (A), noradrenaline (NA), dopamine (DA), histamine, serotonin (5HT), and 5-hydroxyindoleacetic acid (5OHIA) were determined in the brain by ELISA (Cusabio, China). Statistical processing - Statistica 10.0. Results: Levels of NA, DA and 5HT in the brain of intact uPA-/- mice were 3.5, 2.1 and 1.9 times higher (p < 0.05), respectively, than in intact uPA+/+ animals, while histamine and 5OHIA were on average 2.0 times lower. The dynamics of cerebral levels of biogenic amines in uPA-/- mice with pathological factors, alone or combined, had practically no gender specificity, with rare exceptions. So, 5HT levels increased up to 4.5 times in uPA-/- mice of both sexes in response to CNP or B16/F10 growth. Melanoma growth in presence of CNP, on the contrary, decreased 5HT by 3-10 times and DA by 1.6 times (p < 0.05) both in males and females, and decreased NA by 1.6 times (p < 0.05) in females. Conclusions: CNP together with melanoma inhibits the initial activation of the HA-, DA- and 5HT-ergic systems in the brain of uPA-/- mice, which may be an important pathogenetic mechanism of the cancellation of genetically determined inhibition of subcutaneous B16/F10 melanoma growth in urokinase deficiency.

Neurotrophins in the brain of C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice with B16/F10 melanoma growing with comorbid pathology.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21557-e21557
Author(s):  
Elena M. Frantsiyants ◽  
Irina V. Kaplieva ◽  
Valeria A. Bandovkina ◽  
Ekaterina I. Surikova ◽  
Irina V. Neskubina ◽  
...  
Keyword(s):  
White Matter ◽  
Tumor Growth ◽  
Tumor Volume ◽  
Gene Knockout ◽  
Chronic Neuropathic Pain ◽  
Inhibition Of Tumor Growth ◽  
Growth Changes ◽  
The Brain ◽  
Melanoma Growth ◽  
Stimulation Of

e21557 Background: 10% of cancer patients have comorbidities accompanied by chronic pain. Neurotrophins and fibrinolytic system are involved in carcinogenesis and pain pathogenesis. The purpose of the study was to measure levels of neurotrophins in white matter of the brain of urokinase-deficient (uPA–) mice with B16/F10 melanoma growing in presence of chronic neuropathic pain (CNP). Methods: The study included female mice С57ВL/6 (normal genome uPA+, n = 40) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu (urokinase gene-knockout uPA–, n = 28) with B16/F10 melanoma (M) implanted subcutaneously 2 weeks after bilateral sciatic nerve ligation (CNP model). Intact mice (I) were controls. Levels of brain-derived neurotrophic factor BDNF, nerve growth factor NGF-β and neurotrophins 3 and 4 (NT3, NT4) were measured by ELISA in white matter of the brain after 3 weeks of tumor growth in presence of CNP. Results: Tumor volume in (uPA–) females by week 3 of carcinogenesis was 0.04 cm3, which was 70 times smaller than in (uPA+) females. Tumor volume in (uPA–) females with CNP was 5.76 cm3, which was 144 times larger than in (uPA–) females without CNP, and in (uPA+) females – 2.5 cm3. The brain of I (uPA–) showed higher levels of NT3 (by 1.3 times, p < 0.05), NT4 (by 2.6 times) and NGF-β (by 1.9 times, p < 0.05) and lower BDNF (by 1.7 times, p < 0.05), compared to I (uPA+). Both strains of mice with M or CNP demonstrated decreased levels of NGF-β, more pronounced in animals with a combination of these factors. (uPA–) females with CNP+M showed a decrease of NT3 and BDNF by 2 times, with NGF-β 2.2 times higher than in (uPA+) mice. Conclusions: The study revealed underlying differences in levels of neurotrophins in the brain of (uPA–) females which could contribute to the creation of conditions for the inhibition of tumor growth. Changes in the levels of NGF-β in mice with melanoma or CNP were nonspecific. Changes in the BDNF, NT3 and NGF-β balance in the brain of (uPA–) mice may be part of the mechanism of greater stimulation of melanoma growth under the influence of CNP.

Targeting Monoacylglycerol Lipase in Triple Negative Breast Cancer Reduced Tumor-Associated Inflammation, Tumor Growth and Tumor Colonization in the Brain

2021 ◽  
Author(s):  
Othman Benchama ◽  
Sergiy Tyukhtenko ◽  
Michael S. Malamas ◽  
Mark K. Williams ◽  
Alexandros Makriyannis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Breast Cancer Metastasis ◽  
Monoacylglycerol Lipase ◽  
Breast Cancers ◽  
Novel Treatments ◽  
The Brain

Abstract While the prevalence of breast cancer metastasis in the brain is significantly higher in triple negative breast cancers (TNBCs), there is a lack of novel and/or improved therapies for these patients. Monoacylglycerol lipase (MAGL) is a hydrolase involved in lipid metabolism that catalyzes the degradation of 2-arachidonoylglycerol (2-AG) linked to generation of pro- and anti-inflammatory molecules. Here, we targeted MAGL in TNBCs, using the selective MAGL inhibitor AM9928 (hMAGL IC50 = 9nM, with prolonged pharmacodynamic effects of 46 hours residence time). AM9928 blocked TNBC cell adhesion and transmigration across human brain microvascular endothelial cells (HBMECs) in 3D co-cultures. In addition, AM9928 inhibited the secretion of IL-6, IL-8, and VEGF-A from TNBC cells. TNBC-derived exosomes activated HBMECs resulting in secretion of elevated levels of IL-8 and VEGF, which were inhibited by AM9928. Knockdown of MAGL by siRNA or treatment with AM9928 increased the expression of the adherent junction E-cadherin, known to be regulated by MAGL. Using in vivo studies of syngeneic GFP-4T1-BrM5 mammary tumor cells, AM9928 inhibited tumor growth in the mammary fat pads and attenuated blood brain barrier (BBB) permeability changes, resulting in reduced TNBC colonization in brain. Together, these results support the potential clinical application of MAGL inhibitors as novel treatments for TNBC.

Abstract 5546: UVC irradiation inhibits superficial tumor growth in the brain of nude mice

2012 ◽  
Author(s):  
Masashi Momiyama ◽  
Yukihiko Hiroshima ◽  
Atsushi Suetsugu ◽  
Yasunori Tome ◽  
Sumiyuki Mii ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Nude Mice ◽  
The Brain ◽  
Superficial Tumor

scholarly journals Late Effects of Radiation Prime the Brain Microenvironment for Accelerated Tumor Growth

2019 ◽  
Vol 103 (1) ◽  
pp. 190-194 ◽  
Author(s):  
Chong Duan ◽  
Ruimeng Yang ◽  
Liya Yuan ◽  
John A. Engelbach ◽  
Christina I. Tsien ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Late Effects ◽  
Effects Of Radiation ◽  
The Brain
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