| 10551. |
- Wee, Shimei, et al.
(författare)
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Selective Calcium Sensitivity in Immature Glioma Cancer Stem Cells
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-initiating cells are a subpopulation in aggressive cancers that exhibit traits shared with stem cells, including the ability to self-renew and differentiate, commonly referred to as stemness. In addition, such cells are resistant to chemo- and radiation therapy posing a therapeutic challenge. To uncover stemness-associated functions in glioma-initiating cells (GICs), transcriptome profiles were compared to neural stem cells (NSCs) and gene ontology analysis identified an enrichment of Ca2+ signaling genes in NSCs and the more stem-like (NSC-proximal) GICs. Functional analysis in a set of different GIC lines regarding sensitivity to disturbed homeostasis using A23187 and Thapsigargin, revealed that NSC-proximal GICs were more sensitive, corroborating the transcriptome data. Furthermore, Ca2+ drug sensitivity was reduced in GICs after differentiation, with most potent effect in the NSC-proximal GIC, supporting a stemness-associated Ca2+ sensitivity. NSCs and the NSC-proximal GIC line expressed a larger number of ion channels permeable to potassium, sodium and Ca2+. Conversely, a higher number of and higher expression levels of Ca2+ binding genes that may buffer Ca2+, were expressed in NSC-distal GICs. In particular, expression of the AMPA glutamate receptor subunit GRIA1, was found to associate with Ca2+ sensitive NSC-proximal GICs, and decreased as GICs differentiated along with reduced Ca2+ drug sensitivity. The correlation between high expression of Ca2+ channels (such as GRIA1) and sensitivity to Ca2+ drugs was confirmed in an additional nine novel GIC lines. Calcium drug sensitivity also correlated with expression of the NSC markers nestin (NES) and FABP7 (BLBP, brain lipid-binding protein) in this extended analysis. In summary, NSC-associated NES+/FABP7(+)/GRIA1(+) GICs were selectively sensitive to disturbances in Ca2+ homeostasis, providing a potential target mechanism for eradication of an immature population of malignant cells.
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| 10552. |
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| 10553. |
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| 10554. |
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| 10555. |
- Öhrvik, Helena, et al.
(författare)
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Mast cells promote melanoma colonization of lungs
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:42, s. 68990-69001
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells have been implicated in malignant processes, mainly through clinical correlative studies and by experiments performed using animals lacking mast cells due to defective c-kit signaling. However, mast cell-deficient mouse models based on c-kit defects have recently been questioned for their relevance. Here we addressed the effect of mast cells in a tumor setting by using transgenic Mcpt5-Cre(+) R-DTA(+) mice, in which the deficiency of mast cells is independent of c-kit defects. Melanoma cells (B16.F10) were administered either subcutaneously or intravenously into Mcpt5-Cre(+) R-DTA(+) mice or Mcpt5-Cre(-) R-DTA(+) littermate controls, followed by the assessment of formed tumors. In the subcutaneous model, mast cells were abundant in the tumor stroma of control mice but were absent in Mcpt5-Cre(+) R-DTA(+) mice. However, the absence of mast cells did not affect tumor size. In contrast, after intravenous administration of B16.F10 cells, melanoma colonization of the lungs was markedly reduced in Mcpt5-Cre(+) R-DTA(+) vs. Mcpt5-Cre(-) R-DTA(+) animals. Decreased melanoma colonization of the lungs in Mcpt5-Cre(+) R-DTA(+) animals was accompanied by increased inflammatory cell recruitment into the bronchoalveolar lavage fluid, suggesting that mast cells suppress inflammation in this setting. Further, qPCR analysis revealed significant alterations in the expression of Twist and E-cadherin in lungs of Mcpt5-Cre(+) R-DTA(+) vs. control Mcpt5-Cre(-) R-DTA(+) animals, suggesting an impact of mast cells on epithelial-mesenchymal transition. In conclusion, this study reveals that mast cells promote melanoma colonization of the lung.
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| 10556. |
- Zätterström, U K, et al.
(författare)
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Tumor angiogenesis and prognosis in squamous cell carcinoma of the head and neck
- 1995
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Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 17:4, s. 8-312
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The progression of tumor growth requires the recruitment of new blood vessels. It has been suggested that the degree of neovascularization would correlate with clinical prognosis. The purpose of the present study was to ascertain whether tumor vascularization correlated with clinical outcome in cases of primary squamous cell carcinoma of the head and neck (SCCHN).METHODS: In tumor biopsies from 48 patients, microvessel density was determined by immunohistochemistry based on polyclonal antibodies against factor VIII related endothelial antigen. Computerized image analysis was used to evaluate the staining intensity per histologic area. The degree of staining was quantitated and expressed as microvessel density, low and high microvessel density subgroups being compared with regard to survival.RESULTS: Median survival was 10 months in the subgroup with very low microvessel density scores, as contrasted to 69 months in the remainder with high scores (p = 0.08). Neither the patient's age, TNM status, clinical stage, nor histologic grade was related to microvessel density. Among the patients who eventually died of SCCHN (n = 23), there was a subgroup of patients with complete response to radiotherapy. This subgroup had significantly higher microvessel density and longer survival than did the patients who responded poorly or not at all to radiotherapy.CONCLUSION: The findings suggest that in SCCHN the degree of vascularization might be used as a predictor of response to radiotherapy.
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| 10557. |
- Bartek, Jiri, Jr, et al.
(författare)
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Neurokirurgin alltjämt kärnan i behandlingen av hjärntumörer : [Neurosurgery still pivotal in the diagnostics and treatment of brain tumor patients]
- 2023
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- Behandling av hjärntumörer görs i samverkan mellan flera medicinska discipliner: neurokirurgi, onkologi, neurologi, neuropatologi, neuroradiologi och rehabiliteringsmedicin.Symtom som talar för förhöjt intrakraniellt tryck, såsom kraftig huvudvärk, illamående, kräkningar och papillödem, bör leda till snabb utredning och kontakt med neurokirurg. Förbättrad preoperativ kartläggning av tumören samt angränsande anatomiska och funktionella hjärnområden tillsammans med avancerad mikrokirurgisk teknik, intraoperativ monitorering och visualisering samt nya minimalinvasiva tekniker gör operationer säkrare, och det är i dag möjligt att utföra ingrepp som tidigare ansågs omöjliga eller alltför riskabla.
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| 10558. |
- Blomstrand, Malin, et al.
(författare)
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Different reactions to irradiation in the juvenile and adult hippocampus
- 2014
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 90:9, s. 807-815
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cranial radiotherapy is an important tool in the cure of primary brain tumors. Unfortunately, it is associated with late-appearing toxicity to the normal brain tissue, including cognitive impairment, particularly in children. The underlying mechanisms are not fully understood but involve changes in hippocampal neurogenesis. Recent studies report essentially different responses in the juvenile and the adult brain after irradiation, but this has never been verified in a comparative study. Materials and methods: We subjected juvenile (9-day-old) and adult (6-month-old) male rats to a single dose of 6 Gray (Gy) whole brain irradiation and euthanized them 6 hours, 7 days or 4 weeks later. Hippocampal lysates were analyzed for caspase-3 activity (apoptosis) and the expression of cytokines, chemokines and growth factors. Four weeks after irradiation, the number of microglia (expressing ionized calcium-binding adapter molecule 1, Iba-1), activated microglia (expressing cluster of differentiation 68 [CD68]), bromodeoxyuridine (BrdU) incorporation and granule cell layer (GCL) volume were assessed. Results: The major findings were (i) higher baseline BrdU incorporation (cell proliferation) in juvenile than in adult controls, which explains the increased susceptibility to irradiation and higher level of acute cell death (caspase activity) in juvenile rats, leading to impaired growth and subsequently a smaller dentate gyrus volume 4 weeks after irradiation, (ii) more activated (CD68-positive) microglia in adult compared to juvenile rats, regardless of irradiation, and (iii) differently expressed cytokines and chemokines after cranial irradiation in the juvenile compared to the adult rat hippocampus, indicating a more pro-inflammatory response in adult brains. Conclusion: We found essentially diverse irradiation reactions in the juvenile compared to the adult hippocampus, indicating different mechanisms involved in degeneration and regeneration after injury. Strategies to ameliorate the cognitive deficits after cranial radiotherapy should therefore likely be adapted to the developmental level of the brain.
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| 10559. |
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| 10560. |
- Burguillos Garcia, Miguel, et al.
(författare)
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Caspase signalling controls microglia activation and neurotoxicity.
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 472, s. 214-319
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Tidskriftsartikel (refereegranskat)abstract
- Activation of microglia and inflammation-mediated neurotoxicity are suggested to play a decisive role in the pathogenesis of several neurodegenerative disorders. Activated microglia release pro-inflammatory factors that may be neurotoxic. Here we show that the orderly activation of caspase-8 and caspase-3/7, known executioners of apoptotic cell death, regulate microglia activation through a protein kinase C (PKC)-δ-dependent pathway. We find that stimulation of microglia with various inflammogens activates caspase-8 and caspase-3/7 in microglia without triggering cell death in vitro and in vivo. Knockdown or chemical inhibition of each of these caspases hindered microglia activation and consequently reduced neurotoxicity. We observe that these caspases are activated in microglia in the ventral mesencephalon of Parkinson's disease (PD) and the frontal cortex of individuals with Alzheimer's disease (AD). Taken together, we show that caspase-8 and caspase-3/7 are involved in regulating microglia activation. We conclude that inhibition of these caspases could be neuroprotective by targeting the microglia rather than the neurons themselves.
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