腦膠質瘤是位於中樞神經系統(CNS)的腫瘤，許多研究發現微膠細胞會大量累積於腦膠質瘤中。微膠細胞與巨噬細胞有相同的功能，具有吞噬與產生發炎因子的能力。腫瘤壞死因子第二型受體(TNFR2)具有調控微膠細胞的活化與釋放抗發炎因子的能力。先前研究發現在患腦膠質瘤的病人其體內單核球的TNFR2的表現較為低下且有文獻指出微膠細胞在發炎時，會大量表現TNFR2。許多研究指出微膠細胞會抑制腦膠質瘤的成長，但近期研究卻發現微膠細胞會促進腦膠質瘤的惡化，因此微膠細胞在腦膠質瘤生長所扮演的角色一直受到爭議。在我們的細胞實驗中發現，在TNFR2缺陷微膠細胞與腦膠質瘤共培養的情況下，TNFR2缺陷微膠細胞與腦膠質瘤的增生都有顯著性的增加，且也增加微膠細胞的遷移能力。在動物實驗中，發現以LPS連續七天的腹腔注射於小鼠中(0.5 mg/kg/day)，發現其大腦皮質的TNFR2 mRNA的表現有顯著性的上升。同一處理下，發現TNFR2+/-與TNFR2-/-小鼠的大腦皮質的TNFa mRNA的表現有顯著性的增加，並且發現Iba1+微膠細胞數量有顯著性的增加。小鼠在以LPS注射7天後，再將腦膠質瘤細胞植入野生型、TNFR2皮質+/-或TNFR2-/-小鼠皮質後（LPS前處理），發現TNFR2-/-小鼠中的腦膠質瘤明顯大於野生型和TNFR2+/-小鼠。腦膠質瘤植入7天後，再注射LPS後（LPS後處理），發現TNFR2-/-小鼠的皮質中有較大的腦膠質瘤生成。此外，有大量的Ki67+細胞被發現在LPS前處理與後處理TNFR2-/-小鼠的腦膠質瘤中。LPS前處理或後處理的TNFR2-/-小鼠的腫瘤中亦發現有大量Iba1+-微膠細胞和單核球化學趨化蛋白-1（MCP-1+）細胞累積。根據我們的研究結果，我們得出這樣的結論，在大腦發炎時，在TNFR2功能缺陷的微膠細胞，不僅增加了微膠細胞的活化，還可以促進腦膠質瘤生長。也就是說TNFR2功能缺陷導致微膠細胞活化更甚，進而促進腦膠質瘤的惡化。

Gliomas are tumor of the central nerve system (CNS). Abundant amounts of microglia are accumulated in glioma. Microglia are resident macrophages and serve as the phagocytes and produce proinflammatory mediators upon stimulation in the CNS. Tumor necrosis factor receptor type II (TNFR2) can regulate activation and ability of release anti-inflammatory factor in microglia. Previous findings showed that analysis of monocyte receptor expression demonstrated significantly reduced TNFR2 in patients with glioblastoma and TNFR2 was the only receptor type detectable on the microglial in inflammation. Yet, microglia function in glioma growth is still arguable, although the recent findings indicated that activated microglia can promote glioma progression. In vitro study showed that C6 glioma cells increased in number when those cells were cocultured with BV2-microglia with TNFR2 gene knockdown. Moreover, the migration of BV2-microglia was improved when TNFR2 gene expression was suppressed. Our findings showed that intraperitoneal (ip) injection with lipopolysaccharide (LPS) into C57BL/6 mice (0.5 mg/kg/day) for 7 days significantly increased mRNA expression of TNFR2 in the cortex. Furthermore, a 7-day injection with LPS into mice with heterogeneous or homogeneous TNFR2 gene knockout (TNFR2+/- or TNFR2-/-) upregulated the expression of TNFa mRNA and induced an increase in Iba1+-microglia when compared to those observed in vehicle-treated groups. In vivo study also indicated that mice receiving vehicle or LPS at 7 day after C6 glioma implantation (LPS post-treatment), C6 glioma tumor size was larger in the cortex of TNFR2-/- mice. LPS injection for 7 days (LPS pre-treatment) following C6 glioma cell implantation in the cortex of wild type, TNFR2+/- or TNFR2-/- mice, C6-formed tumor size in TNFR2-/- mice brain was significantly larger when compared to that observed in wild type and TNFR2+/- mice. Moreover, the profound amount of Ki67+-cells was found in tumor of TNFR2-/- mice with LPS pre-treatment and post-treatment. The extensive accumulation of Iba1+-microglia and monocyte chemotactic protein-1 (MCP-1)+-cells was found in tumor formed in TNFR2-/- mice receiving pre-treatment or post-treatment with LPS. Based on our findings, we conclude that loss of TNFR2 function not only increases microglia activation in the inflamed brain, but also promote glioma progression. In addition, activation of microglia increases glioma growth in brain.

Abounader, R., and J. Laterra. 2005. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro-oncology. 7:436-451.
Acharyya, S., M.E. Butchbach, Z. Sahenk, H. Wang, M. Saji, M. Carathers, M.D. Ringel, R.J. Skipworth, K.C. Fearon, M.A. Hollingsworth, P. Muscarella, A.H. Burghes, J.A. Rafael-Fortney, and D.C. Guttridge. 2005. Dystrophin glycoprotein complex dysfunction: a regulatory link between muscular dystrophy and cancer cachexia. Cancer cell. 8:421-432.
Aloisi, F. 2001. Immune function of microglia. Glia. 36:165-179.
Alterman, R.L., and E.R. Stanley. 1994. Colony stimulating factor-1 expression in human glioma. Molecular and chemical neuropathology / sponsored by the International Society for Neurochemistry and the World Federation of Neurology and research groups on neurochemistry and cerebrospinal fluid. 21:177-188.
Arnett, H.A., J. Mason, M. Marino, K. Suzuki, G.K. Matsushima, and J.P. Ting. 2001. TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nature neuroscience. 4:1116-1122.
Auvergne, R.M., F.J. Sim, S. Wang, D. Chandler-Militello, J. Burch, Y. Al Fanek, D. Davis, A. Benraiss, K. Walter, P. Achanta, M. Johnson, A. Quinones-Hinojosa, S. Natesan, H.L. Ford, and S.A. Goldman. 2013. Transcriptional Differences between Normal and Glioma-Derived Glial Progenitor Cells Identify a Core Set of Dysregulated Genes. Cell reports.
Badie, B., and J. Schartner. 2001. Role of microglia in glioma biology. Microscopy research and technique. 54:106-113.
Badie, B., and J.M. Schartner. 2000. Flow cytometric characterization of tumor-associated macrophages in experimental gliomas. Neurosurgery. 46:957-961; discussion 961-952.
Bechmann, I., J. Goldmann, A.D. Kovac, E. Kwidzinski, E. Simburger, F. Naftolin, U. Dirnagl, R. Nitsch, and J. Priller. 2005. Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 19:647-649.
Black, R.A., C.T. Rauch, C.J. Kozlosky, J.J. Peschon, J.L. Slack, M.F. Wolfson, B.J. Castner, K.L. Stocking, P. Reddy, S. Srinivasan, N. Nelson, N. Boiani, K.A. Schooley, M. Gerhart, R. Davis, J.N. Fitzner, R.S. Johnson, R.J. Paxton, C.J. March, and D.P. Cerretti. 1997. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature. 385:729-733.
Block, M.L., and J.S. Hong. 2005. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Progress in neurobiology. 76:77-98.
Bonizzi, G., and M. Karin. 2004. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends in immunology. 25:280-288.
Britschgi, M., and T. Wyss-Coray. 2007. Immune cells may fend off Alzheimer disease. Nature medicine. 13:408-409.
Cahill, J., G. LoBiondo-Wood, N. Bergstrom, and T. Armstrong. 2012. Brain tumor symptoms as antecedents to uncertainty: an integrative review. Journal of nursing scholarship : an official publication of Sigma Theta Tau International Honor Society of Nursing / Sigma Theta Tau. 44:145-155.
Cairncross, J.G., K. Ueki, M.C. Zlatescu, D.K. Lisle, D.M. Finkelstein, R.R. Hammond, J.S. Silver, P.C. Stark, D.R. Macdonald, Y. Ino, D.A. Ramsay, and D.N. Louis. 1998. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. Journal of the National Cancer Institute. 90:1473-1479.
Canoll, P., and J.E. Goldman. 2008. The interface between glial progenitors and gliomas. Acta neuropathologica. 116:465-477.
Carpenter, A., T.J. Evans, W.A. Buurman, M.H. Bemelmans, D. Moyes, and J. Cohen. 1995. Differences in the shedding of soluble TNF receptors between endotoxin-sensitive and endotoxin-resistant mice in response to lipopolysaccharide or live bacterial challenge. Journal of immunology. 155:2005-2012.
Chakravarty, S., and M. Herkenham. 2005. Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines. The Journal of neuroscience : the official journal of the Society for Neuroscience. 25:1788-1796.
Choi, D.K., S. Koppula, and K. Suk. 2011. Inhibitors of microglial neurotoxicity: focus on natural products. Molecules. 16:1021-1043.
Clarke, I.D., and P.B. Dirks. 2003. A human brain tumor-derived PDGFR-alpha deletion mutant is transforming. Oncogene. 22:722-733.
D'Mello, C., T. Le, and M.G. Swain. 2009. Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 29:2089-2102.
Desbaillets, I., M. Tada, N. de Tribolet, A.C. Diserens, M.F. Hamou, and E.G. Van Meir. 1994. Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro. International journal of cancer. Journal international du cancer. 58:240-247.
Di Rocco, F., R.S. Carroll, J. Zhang, and P.M. Black. 1998. Platelet-derived growth factor and its receptor expression in human oligodendrogliomas. Neurosurgery. 42:341-346.
Dil, N., and A.J. Marshall. 2009. Role of phosphoinositide 3-kinase p110 delta in TLR4- and TLR9-mediated B cell cytokine production and differentiation. Molecular immunology. 46:1970-1978.
Dopp, J.M., A. Mackenzie-Graham, G.C. Otero, and J.E. Merrill. 1997. Differential expression, cytokine modulation, and specific functions of type-1 and type-2 tumor necrosis factor receptors in rat glia. Journal of neuroimmunology. 75:104-112.
Dopp, J.M., T.A. Sarafian, F.M. Spinella, M.A. Kahn, H. Shau, and J. de Vellis. 2002. Expression of the p75 TNF receptor is linked to TNF-induced NFkappaB translocation and oxyradical neutralization in glial cells. Neurochemical research. 27:1535-1542.
Englot, D.J., M.S. Berger, E.F. Chang, and P.A. Garcia. 2012. Characteristics and treatment of seizures in patients with high-grade glioma: a review. Neurosurgery clinics of North America. 23:227-235, vii-viii.
Fang, K.M., Y.L. Wang, M.C. Huang, S.H. Sun, H. Cheng, and S.F. Tzeng. 2011. Expression of macrophage inflammatory protein-1alpha and monocyte chemoattractant protein-1 in glioma-infiltrating microglia: involvement of ATP and P2X(7) receptor. Journal of neuroscience research. 89:199-211.
Fearon, K.C. 2008. Cancer cachexia: developing multimodal therapy for a multidimensional problem. European journal of cancer (Oxford, England : 1990). 44:1124-1132.
Feinstein, D.L., E. Galea, S. Roberts, H. Berquist, H. Wang, and D.J. Reis. 1994. Induction of nitric oxide synthase in rat C6 glioma cells. Journal of neurochemistry. 62:315-321.
Frederick, L., X.Y. Wang, G. Eley, and C.D. James. 2000. Diversity and frequency of epidermal growth factor receptor mutations in human glioblastomas. Cancer research. 60:1383-1387.
Ghosh, A., J. Mukherjee, M. Bhattacharjee, P. Sarkar, S. Acharya, S. Chaudhuri, and S. Chaudhuri. 2007. The other side of the coin: beneficiary effect of 'oxidative burst' upsurge with T11TS facilitates the elimination of glioma cells. Cellular and molecular biology (Noisy-le-Grand, France). 53:53-62.
Goralski, K.B., D. Abdulla, C.J. Sinal, A. Arsenault, and K.W. Renton. 2005. Toll-like receptor-4 regulation of hepatic Cyp3a11 metabolism in a mouse model of LPS-induced CNS inflammation. American journal of physiology. Gastrointestinal and liver physiology. 289:G434-443.
Graeber, M.B., B.W. Scheithauer, and G.W. Kreutzberg. 2002. Microglia in brain tumors. Glia. 40:252-259.
Guha, M., and N. Mackman. 2001. LPS induction of gene expression in human monocytes. Cellular signalling. 13:85-94.
Hanisch, U.K., and H. Kettenmann. 2007. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature neuroscience. 10:1387-1394.
Hao, C., I.F. Parney, W.H. Roa, J. Turner, K.C. Petruk, and D.A. Ramsay. 2002. Cytokine and cytokine receptor mRNA expression in human glioblastomas: evidence of Th1, Th2 and Th3 cytokine dysregulation. Acta neuropathologica. 103:171-178.
Hardbower, D.M., T. de Sablet, R. Chaturvedi, and K.T. Wilson. 2013. Chronic inflammation and oxidative stress: The smoking gun for Helicobacter pylori-induced gastric cancer? Gut microbes. 4.
Hauss-Wegrzyniak, B., L.B. Willard, P. Del Soldato, G. Pepeu, and G.L. Wenk. 1999. Peripheral administration of novel anti-inflammatories can attenuate the effects of chronic inflammation within the CNS. Brain research. 815:36-43.
He, P., Z. Zhong, K. Lindholm, L. Berning, W. Lee, C. Lemere, M. Staufenbiel, R. Li, and Y. Shen. 2007. Deletion of tumor necrosis factor death receptor inhibits amyloid beta generation and prevents learning and memory deficits in Alzheimer's mice. The Journal of cell biology. 178:829-841.
Huang, H., H.L. Lung, K.N. Leung, and D. Tsang. 1998. Selective induction of tumor necrosis factor receptor type II gene expression by tumor necrosis factor-alpha in C6 glioma cells. Life sciences. 62:889-896.
Hwang, S.Y., B.C. Yoo, J.W. Jung, E.S. Oh, J.S. Hwang, J.A. Shin, S.Y. Kim, S.H. Cha, and I.O. Han. 2009. Induction of glioma apoptosis by microglia-secreted molecules: The role of nitric oxide and cathepsin B. Biochimica et biophysica acta. 1793:1656-1668.
Inoue, K. 2008. Purinergic systems in microglia. Cellular and molecular life sciences : CMLS. 65:3074-3080.
Ishii, N., M. Tada, S. Sakuma, Y. Sawamura, Y. Shinohe, and H. Abe. 1998. Human astrocytoma cells are capable of producing macrophage inflammatory protein-1beta. Journal of neuro-oncology. 37:17-23.
Ito, D., Y. Imai, K. Ohsawa, K. Nakajima, Y. Fukuuchi, and S. Kohsaka. 1998. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain research. Molecular brain research. 57:1-9.
James, C.D., E. Carlbom, J.P. Dumanski, M. Hansen, M. Nordenskjold, V.P. Collins, and W.K. Cavenee. 1988. Clonal genomic alterations in glioma malignancy stages. Cancer research. 48:5546-5551.
Johnson, D.R., P.D. Brown, E. Galanis, and J.E. Hammack. 2012. Pilocytic astrocytoma survival in adults: analysis of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Journal of neuro-oncology. 108:187-193.
Kettenmann, H. 2006. Triggering the brain's pathology sensor. Nature neuroscience. 9:1463-1464.
Kim, S.U., and J. de Vellis. 2005. Microglia in health and disease. Journal of neuroscience research. 81:302-313.
Klein, R., and W. Roggendorf. 2001. Increased microglia proliferation separates pilocytic astrocytomas from diffuse astrocytomas: a double labeling study. Acta neuropathologica. 101:245-248.
Koul, D. 2008. PTEN signaling pathways in glioblastoma. Cancer biology & therapy. 7:1321-1325.
Kremlev, S.G., R.L. Roberts, and C. Palmer. 2004. Differential expression of chemokines and chemokine receptors during microglial activation and inhibition. Journal of neuroimmunology. 149:1-9.
Kreth, F.W., P.C. Warnke, R. Scheremet, and C.B. Ostertag. 1993. Surgical resection and radiation therapy versus biopsy and radiation therapy in the treatment of glioblastoma multiforme. Journal of neurosurgery. 78:762-766.
Kreutzberg, G.W. 1995. Microglia, the first line of defence in brain pathologies. Arzneimittel-Forschung. 45:357-360.
Lee, J.Y., B.S. Jhun, Y.T. Oh, J.H. Lee, W. Choe, H.H. Baik, J. Ha, K.S. Yoon, S.S. Kim, and I. Kang. 2006. Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Neuroscience letters. 396:1-6.
Lee, S.M., T.Y. Yune, S.J. Kim, Y.C. Kim, Y.J. Oh, G.J. Markelonis, and T.H. Oh. 2004. Minocycline inhibits apoptotic cell death via attenuation of TNF-alpha expression following iNOS/NO induction by lipopolysaccharide in neuron/glia co-cultures. Journal of neurochemistry. 91:568-578.
Leon, L.R., W. Kozak, J. Peschon, and M.J. Kluger. 1997. Exacerbated febrile responses to LPS, but not turpentine, in TNF double receptor-knockout mice. The American journal of physiology. 272:R563-569.
Lesniak, M.S., and H. Brem. 2004. Targeted therapy for brain tumours. Nature reviews. Drug discovery. 3:499-508.
Loughlin, A.J., M.N. Woodroofe, and M.L. Cuzner. 1992. Regulation of Fc receptor and major histocompatibility complex antigen expression on isolated rat microglia by tumour necrosis factor, interleukin-1 and lipopolysaccharide: effects on interferon-gamma induced activation. Immunology. 75:170-175.
Mackaness, G.B. 1964. THE IMMUNOLOGICAL BASIS OF ACQUIRED CELLULAR RESISTANCE. The Journal of experimental medicine. 120:105-120.
Malkin, D., F.P. Li, L.C. Strong, J.F. Fraumeni, Jr., C.E. Nelson, D.H. Kim, J. Kassel, M.A. Gryka, F.Z. Bischoff, M.A. Tainsky, and et al. 1990. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science (New York, N.Y.). 250:1233-1238.
Mantovani, A., A. Sica, S. Sozzani, P. Allavena, A. Vecchi, and M. Locati. 2004. The chemokine system in diverse forms of macrophage activation and polarization. Trends in immunology. 25:677-686.
Marchetti, L., M. Klein, K. Schlett, K. Pfizenmaier, and U.L. Eisel. 2004. Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation. Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kappa B pathway. The Journal of biological chemistry. 279:32869-32881.
Massey, S.C., M.C. Assanah, K.A. Lopez, P. Canoll, and K.R. Swanson. 2012. Glial progenitor cell recruitment drives aggressive glioma growth: mathematical and experimental modelling. Journal of the Royal Society, Interface / the Royal Society. 9:1757-1766.
Mishima, K., S. Higashiyama, A. Asai, K. Yamaoka, Y. Nagashima, N. Taniguchi, C. Kitanaka, T. Kirino, and Y. Kuchino. 1998. Heparin-binding epidermal growth factor-like growth factor stimulates mitogenic signaling and is highly expressed in human malignant gliomas. Acta neuropathologica. 96:322-328.
Misra, A., S. Ganesh, A. Shahiwala, and S.P. Shah. 2003. Drug delivery to the central nervous system: a review. Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques. 6:252-273.
Mrak, R.E., and W.S. Griffin. 2005. Glia and their cytokines in progression of neurodegeneration. Neurobiology of aging. 26:349-354.
Nadeau, S., and S. Rivest. 1999a. Effects of circulating tumor necrosis factor on the neuronal activity and expression of the genes encoding the tumor necrosis factor receptors (p55 and p75) in the rat brain: a view from the blood-brain barrier. Neuroscience. 93:1449-1464.
Nadeau, S., and S. Rivest. 1999b. Regulation of the gene encoding tumor necrosis factor alpha (TNF-alpha) in the rat brain and pituitary in response in different models of systemic immune challenge. Journal of neuropathology and experimental neurology. 58:61-77.
Neumark, E., R. Anavi, I.P. Witz, and A. Ben-Baruch. 1999. MCP-1 expression as a potential contributor to the high malignancy phenotype of murine mammary adenocarcinoma cells. Immunology letters. 68:141-146.
Norden, D.M., and J.P. Godbout. 2013. Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathology and applied neurobiology. 39:19-34.
Ogden, A.T., D. Horgan, A. Waziri, D. Anderson, J. Louca, G.M. McKhann, M.B. Sisti, A.T. Parsa, and J.N. Bruce. 2006. Defective receptor expression and dendritic cell differentiation of monocytes in glioblastomas. Neurosurgery. 59:902-909; discussion 909-910.
Onizawa, M., T. Nagaishi, T. Kanai, K. Nagano, S. Oshima, Y. Nemoto, A. Yoshioka, T. Totsuka, R. Okamoto, T. Nakamura, N. Sakamoto, K. Tsuchiya, K. Aoki, K. Ohya, H. Yagita, and M. Watanabe. 2009. Signaling pathway via TNF-alpha/NF-kappaB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis. American journal of physiology. Gastrointestinal and liver physiology. 296:G850-859.
Platten, M., A. Kretz, U. Naumann, S. Aulwurm, K. Egashira, S. Isenmann, and M. Weller. 2003. Monocyte chemoattractant protein-1 increases microglial infiltration and aggressiveness of gliomas. Annals of neurology. 54:388-392.
Qin, L., X. Wu, M.L. Block, Y. Liu, G.R. Breese, J.S. Hong, D.J. Knapp, and F.T. Crews. 2007. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 55:453-462.
Ramos-Nino, M.E. 2013. The role of chronic inflammation in obesity-associated cancers. ISRN oncology. 2013:697521.
Ransohoff, R.M., and V.H. Perry. 2009. Microglial physiology: unique stimuli, specialized responses. Annual review of immunology. 27:119-145.
Reclawowicz, D., M. Stempniewicz, W. Biernat, and P. Sloniewski. 2008. [Modern approach to WHO grade II glioma classification and treatment--review of the literature]. Neurologia i neurochirurgia polska. 42:536-545.
Reifenberger, J., G. Reifenberger, L. Liu, C.D. James, W. Wechsler, and V.P. Collins. 1994. Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. The American journal of pathology. 145:1175-1190.
Rietschel, E.T., T. Kirikae, F.U. Schade, U. Mamat, G. Schmidt, H. Loppnow, A.J. Ulmer, U. Zahringer, U. Seydel, F. Di Padova, and et al. 1994. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 8:217-225.
Roggendorf, W., S. Strupp, and W. Paulus. 1996. Distribution and characterization of microglia/macrophages in human brain tumors. Acta neuropathologica. 92:288-293.
Schartner, J.M., A.R. Hagar, M. Van Handel, L. Zhang, N. Nadkarni, and B. Badie. 2005. Impaired capacity for upregulation of MHC class II in tumor-associated microglia. Glia. 51:279-285.
Schneider-Brachert, W., V. Tchikov, J. Neumeyer, M. Jakob, S. Winoto-Morbach, J. Held-Feindt, M. Heinrich, O. Merkel, M. Ehrenschwender, D. Adam, R. Mentlein, D. Kabelitz, and S. Schutze. 2004. Compartmentalization of TNF receptor 1 signaling: internalized TNF receptosomes as death signaling vesicles. Immunity. 21:415-428.
Sizoo, E.M., L. Braam, T.J. Postma, H.R. Pasman, J.J. Heimans, M. Klein, J.C. Reijneveld, and M.J. Taphoorn. 2010. Symptoms and problems in the end-of-life phase of high-grade glioma patients. Neuro-oncology. 12:1162-1166.
Smith, C.A., T. Farrah, and R.G. Goodwin. 1994. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell. 76:959-962.
Smith, J.S., B. Alderete, Y. Minn, T.J. Borell, A. Perry, G. Mohapatra, S.M. Hosek, D. Kimmel, J. O'Fallon, A. Yates, B.G. Feuerstein, P.C. Burger, B.W. Scheithauer, and R.B. Jenkins. 1999. Localization of common deletion regions on 1p and 19q in human gliomas and their association with histological subtype. Oncogene. 18:4144-4152.
Srivastava, S., Z.Q. Zou, K. Pirollo, W. Blattner, and E.H. Chang. 1990. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 348:747-749.
Stupp, R., M.E. Hegi, W.P. Mason, M.J. van den Bent, M.J. Taphoorn, R.C. Janzer, S.K. Ludwin, A. Allgeier, B. Fisher, K. Belanger, P. Hau, A.A. Brandes, J. Gijtenbeek, C. Marosi, C.J. Vecht, K. Mokhtari, P. Wesseling, S. Villa, E. Eisenhauer, T. Gorlia, M. Weller, D. Lacombe, J.G. Cairncross, and R.O. Mirimanoff. 2009. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. The lancet oncology. 10:459-466.
Stupp, R., M. Reni, G. Gatta, E. Mazza, and C. Vecht. 2007. Anaplastic astrocytoma in adults. Critical reviews in oncology/hematology. 63:72-80.
Sugawa, N., A.J. Ekstrand, C.D. James, and V.P. Collins. 1990. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proceedings of the National Academy of Sciences of the United States of America. 87:8602-8606.
Takeuchi, H., T. Kubota, R. Kitai, T. Nakagawa, and N. Hashimoto. 2008. CD98 immunoreactivity in multinucleated giant cells of glioblastomas: an immunohistochemical double labeling study. Neuropathology : official journal of the Japanese Society of Neuropathology. 28:127-131.
Takeuchi, H., K. Sato, K. Ido, and T. Kubota. 2006. Mitotic activity of multinucleated giant cells with glial fibrillary acidic protein immunoreactivity in glioblastomas: an immunohistochemical double labeling study. Journal of neuro-oncology. 78:15-18.
Tanabe, K., R. Matsushima-Nishiwaki, S. Yamaguchi, H. Iida, S. Dohi, and O. Kozawa. 2010. Mechanisms of tumor necrosis factor-alpha-induced interleukin-6 synthesis in glioma cells. Journal of neuroinflammation. 7:16.
Tisdale, M.J. 2009. Mechanisms of cancer cachexia. Physiological reviews. 89:381-410.
Tremblay, M.E., B. Stevens, A. Sierra, H. Wake, A. Bessis, and A. Nimmerjahn. 2011. The role of microglia in the healthy brain. The Journal of neuroscience : the official journal of the Society for Neuroscience. 31:16064-16069.
Tsakiri, N., D. Papadopoulos, M.C. Denis, D.D. Mitsikostas, and G. Kollias. 2012. TNFR2 on non-haematopoietic cells is required for Foxp3+ Treg-cell function and disease suppression in EAE. European journal of immunology. 42:403-412.
van Mierlo, G.J., H.U. Scherer, M. Hameetman, M.E. Morgan, R. Flierman, T.W. Huizinga, and R.E. Toes. 2008. Cutting edge: TNFR-shedding by CD4+CD25+ regulatory T cells inhibits the induction of inflammatory mediators. Journal of immunology. 180:2747-2751.
Vercammen, D., P. Vandenabeele, W. Declercq, M. Van de Craen, J. Grooten, and W. Fiers. 1995. Cytotoxicity in L929 murine fibrosarcoma cells after triggering of transfected human p75 tumour necrosis factor (TNF) receptor is mediated by endogenous murine TNF. Cytokine. 7:463-470.
Veroni, C., L. Gabriele, I. Canini, L. Castiello, E. Coccia, M.E. Remoli, S. Columba-Cabezas, E. Arico, F. Aloisi, and C. Agresti. 2010. Activation of TNF receptor 2 in microglia promotes induction of anti-inflammatory pathways. Molecular and cellular neurosciences. 45:234-244.
Watters, J.J., J.M. Schartner, and B. Badie. 2005. Microglia function in brain tumors. Journal of neuroscience research. 81:447-455.
Wessels, P.H., W.E. Weber, G. Raven, F.C. Ramaekers, A.H. Hopman, and A. Twijnstra. 2003. Supratentorial grade II astrocytoma: biological features and clinical course. Lancet neurology. 2:395-403.
Westermark, B., C.H. Heldin, and M. Nister. 1995. Platelet-derived growth factor in human glioma. Glia. 15:257-263.
Wideheim, A.K., T. Edvardsson, A. Pahlson, and G. Ahlstrom. 2002. A family's perspective on living with a highly malignant brain tumor. Cancer nursing. 25:236-244.
Wilson, E.H., W. Weninger, and C.A. Hunter. 2010. Trafficking of immune cells in the central nervous system. The Journal of clinical investigation. 120:1368-1379.
Zhai, H., F.L. Heppner, and S.E. Tsirka. 2011. Microglia/macrophages promote glioma progression. Glia. 59:472-485.
Zhang, J., S. Sarkar, R. Cua, Y. Zhou, W. Hader, and V.W. Yong. 2012. A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis. Carcinogenesis. 33:312-319.
Zheng, H., H. Ying, H. Yan, A.C. Kimmelman, D.J. Hiller, A.J. Chen, S.R. Perry, G. Tonon, G.C. Chu, Z. Ding, J.M. Stommel, K.L. Dunn, R. Wiedemeyer, M.J. You, C. Brennan, Y.A. Wang, K.L. Ligon, W.H. Wong, L. Chin, and R.A. DePinho. 2008. p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature. 455:1129-1133.
Zhou, X., J.L. Wang, J. Lu, Y. Song, K.S. Kwak, Q. Jiao, R. Rosenfeld, Q. Chen, T. Boone, W.S. Simonet, D.L. Lacey, A.L. Goldberg, and H.Q. Han. 2010. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell. 142:531-543.