References

1. Hanif, F.; Muzaffar, K.; Perveen, K.; Malhi, S.M.; Simjee, S.U. Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment. Asian Pac. J. Cancer Prev. 2017, 18, 3–9.
2. Ostrom, Q.T.; Cioffi, G.; Gittleman, H.; Patil, N.; Waite, K.; Kruchko, C. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012–2016. Neuro Oncol. 2019, 21, v1–v100.
3. Louis, D.N.; Perry, A.; Reifenberger, G.; Von Deimling, A.; Figarella-Branger, D.; Cavenee, W.K. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A summary. Acta Neuropathol. 2016, 131, 803–820.
4. Fernandes, C.; Costa, A.; Osório, L. Current Standards of Care in Glioblastoma Therapy. In Glioblastoma [Internet]; De Vleeschouwer, S., Ed.; Codon Publications: Brisbane, AU, USA, 27 September 2017; Chapter 11. Available online: (accessed on 10 February 2021).
5. Roy, S.; Lahiri, D.; Maji, T.; Biswas, J. Recurrent Glioblastoma: Where we stand. South Asian J. Cancer 2015, 4, 163–173.
6. Wilson, T.A.; Karajannis, M.A.; Harter, D.H. Glioblastoma multiforme: State of the art and future therapeutics. Surg. Neurol. Int. 2014, 5, 64.
7. Davis, M.E. Glioblastoma: Overview of Disease and Treatment. Clin. J. Oncol. Nurs. 2016, 20, S2–S8.
8. Lee, S.Y. Temozolomide resistance in glioblastoma multiforme. Genes Dis. 2016, 3, 198–210.
9. Gilbert, M.R.; Dignam, J.J.; Armstrong, T.S.; Wefel, J.S.; Blumenthal, D.T.; Vogelbaum, M.A. A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma. N. Engl. J. Med. 2014, 370, 699–708.
10. Poulsen, H.S.; Urup, T.; Michaelsen, S.R.; Staberg, M.; Villingshøj, M.; Lassen, U. The impact of bevacizumab treatment on survival and quality of life in newly diagnosed glioblastoma patients. Cancer Manag. Res. 2014, 6, 373–387.
11. Chahar, M.K.; Sharma, N.; Dobhal, M.P.; Joshi, Y.C. Flavonoids: A versatile source of anticancer drugs. Pharmacogn. Rev. 2011, 5, 1–12.
12. Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci. 2016, 5, e47.
13. Hewlings, S.J.; Kalman, D.S. Curcumin: A Review of Its Effects on Human Health. Foods 2017, 6, 92.
14. Gupta, S.C.; Patchva, S.; Aggarwal, B.B. Therapeutic roles of curcumin: Lessons learned from clinical trials. AAPS J. 2013, 15, 195–218.
15. Maugeri, A.; Mazzone, M.G.; Giuliano, F.; Vinciguerra, M.; Basile, G.; Barchitta, M. Curcumin Modulates DNA Methyltransferase Functions in a Cellular Model of Diabetic Retinopathy. Oxid. Med. Cell. Longev. 2018, 2018, 5407482.
16. Ma, Z.; Wang, N.; He, H.; Tang, X. Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application. J. Control. Release 2019, 316, 359–380.
17. Aggarwal, B.B.; Harikumar, K.B. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int. J. Biochem. Cell Biol. 2009, 41, 40–59.
18. Barchitta, M.; Maugeri, A.; Favara, G.; Magnano San Lio, R.; Evola, G.; Agodi, A. Nutrition and Wound Healing: An Overview Focusing on the Beneficial Effects of Curcumin. Int. J. Mol. Sci. 2019, 20, 1119.
19. Sharma, R.A.; McLelland, H.R.; Hill, K.A.; Ireson, C.R.; Euden, S.A.; Manson, M.M. Pharmacodynamic and Pharmacokinetic Study of Oral Curcuma Extract in Patients with Colorectal Cancer. Clin. Cancer Res. 2001, 7, 1894.
20. He, Z.-Y.; Shi, C.-B.; Wen, H.; Li, F.-L.; Wang, B.-L.; Wang, J. Upregulation of p53 Expression in Patients with Colorectal Cancer by Administration of Curcumin. Cancer Investig. 2011, 29, 208–213.
21. Kanai, M.; Yoshimura, K.; Asada, M.; Imaizumi, A.; Suzuki, C.; Matsumoto, S. A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother. Pharmacol. 2011, 68, 157–164.
22. Polasa, K.; Raghuram, T.C.; Krishna, T.P.; Krishnaswamy, K. Effect of turmeric on urinary mutagens in smokers. Mutagenesis 1992, 7, 107–109.
23. Dützmann, S.; Schiborr, C.; Kocher, A.; Pilatus, U.; Hattingen, E.; Weissenberger, J. Intratumoral Concentrations and Effects of Orally Administered Micellar Curcuminoids in Glioblastoma Patients. Nutr. Cancer 2016, 68, 943–948.
24. Giordano, A.; Tommonaro, G. Curcumin and Cancer. Nutrients 2019, 11, 2376.
25. Barati, N.; Momtazi-Borojeni, A.A.; Majeed, M.; Sahebkar, A. Potential therapeutic effects of curcumin in gastric cancer. J. Cell. Physiol. 2019, 234, 2317–2328.
26. Hesari, A.; Azizian, M.; Sheikhi, A.; Nesaei, A.; Sanaei, S.; Mahinparvar, N. Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status. Int. J. Cancer 2019, 144, 1215–1226.
27. Jalili-Nik, M.; Soltani, A.; Moussavi, S.; Ghayour-Mobarhan, M.; Ferns, G.A.; Hassanian, S.M. Current status and future prospective of Curcumin as a potential therapeutic agent in the treatment of colorectal cancer. J. Cell. Physiol. 2018, 233, 6337–6345.
28. Su, C.-C.; Wang, M.-J.; Chiu, T.-L. The anti-cancer efficacy of curcumin scrutinized through core signaling pathways in glioblastoma. Int. J. Mol. Med. 2010, 26, 217–224.
29. Weissenberger, J.; Priester, M.; Bernreuther, C.; Rakel, S.; Glatzel, M.; Seifert, V. Dietary Curcumin Attenuates Glioma Growth in a Syngeneic Mouse Model by Inhibition of the JAK1,2/STAT3 Signaling Pathway. Clin. Cancer Res. 2010, 16, 5781.
30. Gersey, Z.C.; Rodriguez, G.A.; Barbarite, E.; Sanchez, A.; Walters, W.M.; Ohaeto, K.C. Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species. BMC Cancer 2017, 17, 99.
31. Wang, Z.; Liu, F.; Liao, W.; Yu, L.; Hu, Z.; Li, M. Curcumin suppresses glioblastoma cell proliferation by p-AKT/mTOR pathway and increases the PTEN expression. Arch. Biochem. Biophys. 2020, 689, 108412.
32. Du, W.-Z.; Feng, Y.; Wang, X.-F.; Piao, X.-Y.; Cui, Y.-Q.; Chen, L.-C. Curcumin suppresses malignant glioma cells growth and induces apoptosis by inhibition of SHH/GLI1 signaling pathway in vitro and vivo. CNS Neurosci. Ther. 2013, 19, 926–936.
33. Zanotto-Filho, A.; Braganhol, E.; Edelweiss, M.I.; Behr, G.A.; Zanin, R.; Schröder, R.; Simões-Pires, A.; Battastini, A.M.O.; Moreira, J.C.F. The curry spice curcumin selectively inhibits cancer cells growth in vitro and in preclinical model of glioblastoma. J. Nutr. Biochem. 2012, 23, 591–601.
34. Mao, H.; Lebrun, D.G.; Yang, J.; Zhu, V.F.; Li, M. Deregulated signaling pathways in glioblastoma multiforme: Molecular mechanisms and therapeutic targets. Cancer Investig. 2012, 30, 48–56.
35. Chiu, S.S.; Lui, E.; Majeed, M.; Vishwanatha, J.K.; Ranjan, A.P.; Maitra, A. Differential Distribution of Intravenous Curcumin Formulations in the Rat Brain. Anticancer Res. 2011, 31, 907.
36. Priyadarsini, K.I. The chemistry of curcumin: From extraction to therapeutic agent. Molecules 2014, 19, 20091–20112.
37. Liu, E.; Wu, J.; Cao, W.; Zhang, J.; Liu, W.; Jiang, X. Curcumin induces G2/M cell cycle arrest in a p53-dependent manner and upregulates ING4 expression in human glioma. J. Neuro-Oncol. 2007, 85, 263–270.
38. Fratantonio, D.; Molonia, M.S.; Bashllari, R.; Muscarà, C.; Ferlazzo, G.; Costa, G. Curcumin potentiates the antitumor activity of Paclitaxel in rat glioma C6 cells. Phytomedicine 2019, 55, 23–30.
39. Ramachandran, C.; Nair, S.M.; Escalon, E.; Melnick, S.J. Potentiation of Etoposide and Temozolomide Cytotoxicity by Curcumin and Turmeric Force in Brain Tumor Cell Lines. J. Complementary Integr. Med. 2012, 9.
40. Garrido-Armas, M.; Corona, J.C.; Escobar, M.L.; Torres, L.; Ordóñez-Romero, F.; Hernández-Hernández, A. Paraptosis in human glioblastoma cell line induced by curcumin. Toxicol. In Vitro 2018, 51, 63–73.
41. Khaw, A.K.; Hande, M.P.; Kalthur, G.; Hande, M.P. Curcumin inhibits telomerase and induces telomere shortening and apoptosis in brain tumour cells. J. Cell. Biochem. 2013, 114, 1257–1270.
42. Karmakar, S.; Banik, N.L.; Ray, S.K. Curcumin Suppressed Anti-apoptotic Signals and Activated Cysteine Proteases for Apoptosis in Human Malignant Glioblastoma U87MG Cells. Neurochem. Res. 2007, 32, 2103–2113.
43. Senft, C.; Polacin, M.; Priester, M.; Seifert, V.; Kögel, D.; Weissenberger, J. The nontoxic natural compound Curcumin exerts anti-proliferative, anti-migratory, and anti-invasive properties against malignant gliomas. BMC Cancer 2010, 10, 491.
44. Wu, B.; Yao, X.; Nie, X.; Xu, R. Epigenetic reactivation of RANK in glioblastoma cells by curcumin: Involvement of STAT3 inhibition. DNA Cell Biol. 2013, 32, 292–297.
45. Kim, S.-Y.; Jung, S.-H.; Kim, H.-S. Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochem. Biophys. Res. Commun. 2005, 337, 510–516.
46. Woo, M.-S.; Jung, S.-H.; Kim, S.-Y.; Hyun, J.-W.; Ko, K.-H.; Kim, W.-K. Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells. Biochem. Biophys. Res. Commun. 2005, 335, 1017–1025.
47. Choi, B.H.; Kim, C.G.; Bae, Y.-S.; Lim, Y.; Lee, Y.H.; Shin, S.Y. p21Waf1/Cip1 Expression by Curcumin in U-87MG Human Glioma Cells: Role of Early Growth Response-1 Expression. Cancer Res. 2008, 68, 1369.
48. Aoki, H.; Takada, Y.; Kondo, S.; Sawaya, R.; Aggarwal, B.B.; Kondo, Y. Evidence That Curcumin Suppresses the Growth of Malignant Gliomas in Vitro and in Vivo through Induction of Autophagy: Role of Akt and Extracellular Signal-Regulated Kinase Signaling Pathways. Mol. Pharmacol. 2007, 72, 29.
49. Zhang, Z.-J.; Zhao, L.-X.; Cao, D.-L.; Zhang, X.; Gao, Y.-J.; Xia, C. Curcumin Inhibits LPS-Induced CCL2 Expression via JNK Pathway in C6 Rat Astrocytoma Cells. Cell. Mol. Neurobiol. 2012, 32, 1003–1010.
50. Maiti, P.; Scott, J.; Sengupta, D.; Al-Gharaibeh, A.; Dunbar, G.L. Curcumin and Solid Lipid Curcumin Particles Induce Autophagy, but Inhibit Mitophagy and the PI3K-Akt/mTOR Pathway in Cultured Glioblastoma Cells. Int. J. Mol. Sci. 2019, 20, 399.
51. Zhao, J.; Zhu, J.; Lv, X.; Xing, J.; Liu, S.; Chen, C. Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma by suppressing the PI3K/AKT and NF-κB/COX-2 signaling pathways. OncoTargets Ther. 2017, 10, 5471–5482.
52. Yin, S.; Du, W.; Wang, F.; Han, B.; Cui, Y.; Yang, D. MicroRNA-326 sensitizes human glioblastoma cells to curcumin via the SHH/GLI1 signaling pathway. Cancer Biol. Ther. 2018, 19, 260–270.
53. Karmakar, S.; Banik, N.L.; Patel, S.J.; Ray, S.K. Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic pathways for apoptosis in human glioblastoma T98G cells. Neurosci. Lett. 2006, 407, 53–58.
54. Nagai, S.; Kurimoto, M.; Washiyama, K.; Hirashima, Y.; Kumanishi, T.; Endo, S. Inhibition of Cellular Proliferation and Induction of Apoptosis by Curcumin in Human Malignant Astrocytoma Cell Lines. J. Neuro-Oncol. 2005, 74, 105–111.
55. Huang, T.-Y.; Tsai, T.-H.; Hsu, C.-W.; Hsu, Y.-C. Curcuminoids Suppress the Growth and Induce Apoptosis through Caspase-3-Dependent Pathways in Glioblastoma Multiforme (GBM) 8401 Cells. J. Agric. Food Chem. 2010, 58, 10639–10645.
56. Giacinti, C.; Giordano, A. RB and cell cycle progression. Oncogene 2006, 25, 5220–5227.
57. Knudsen, E.S.; Wang, J.Y.J. Targeting the RB-pathway in cancer therapy. Clin. Cancer Res. 2010, 16, 1094–1099.
58. Nakada, M.; Kita, D.; Watanabe, T.; Hayashi, Y.; Teng, L.; Pyko, I.V. Aberrant Signaling Pathways in Glioma. Cancers 2011, 3, 3242–3278.
59. Biernat, W.; Tohma, Y.; Yonekawa, Y.; Kleihues, P.; Ohgaki, H. Alterations of cell cycle regulatory genes in primary (de novo) and secondary glioblastomas. Acta Neuropathol. 1997, 94, 303–309.
60. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008, 455, 1061–1068.
61. Grzmil, M.; Hemmings, B.A. Deregulated signalling networks in human brain tumours. Biochim. Biophys. Acta BBA Proteins Proteom. 2010, 1804, 476–483.
62. Biasoli, D.; Kahn, S.A.; Cornélio, T.A.; Furtado, M.; Campanati, L.; Chneiweiss, H. Retinoblastoma protein regulates the crosstalk between autophagy and apoptosis, and favors glioblastoma resistance to etoposide. Cell Death Dis. 2013, 4, e767.
63. Zhang, D.; Dai, D.; Zhou, M.; Li, Z.; Wang, C.; Lu, Y. Inhibition of Cyclin D1 Expression in Human Glioblastoma Cells is Associated with Increased Temozolomide Chemosensitivity. Cell. Physiol. Biochem. 2018, 51, 2496–2508.
64. Fry, D.W.; Harvey, P.J.; Keller, P.R.; Elliott, W.L.; Meade, M.; Trachet, E. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol. Cancer Ther. 2004, 3, 1427.
65. Michaud, K.; Solomon, D.A.; Oermann, E.; Kim, J.-S.; Zhong, W.-Z.; Prados, M.D. Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts. Cancer Res. 2010, 70, 3228–3238.
66. Chen, J. The Cell-Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression. Cold Spring Harb. Perspect. Med. 2016, 6, a026104.
67. Shangary, S.; Wang, S. Small-Molecule Inhibitors of the MDM2-p53 Protein-Protein Interaction to Reactivate p53 Function: A Novel Approach for Cancer Therapy. Annu. Rev. Pharmacol. Toxicol. 2009, 49, 223–241.
68. Kubbutat, M.H.G.; Jones, S.N.; Vousden, K.H. Regulation of p53 stability by Mdm2. Nature 1997, 387, 299–303.
69. Hemann, M.T.; Lowe, S.W. The p53-Bcl-2 connection. Cell Death Differ. 2006, 13, 1256–1259.
70. Zawlik, I.; Kita, D.; Vaccarella, S.; Mittelbronn, M.; Franceschi, S.; Ohgaki, H. Common Polymorphisms in the MDM2 and TP53 Genes and the Relationship between TP53 Mutations and Patient Outcomes in Glioblastomas. Brain Pathol. 2009, 19, 188–194.
71. Fels, C.; Schäfer, C.; Hüppe, B.; Bahn, H.; Heidecke, V.; Kramm, C.M. Bcl-2 Expression in Higher-grade Human Glioma: A Clinical and Experimental Study. J. Neuro-Oncol. 2000, 48, 207–216.
72. Zhang, Y.; Dube, C.; Gibert, M., Jr.; Cruickshanks, N.; Wang, B.; Coughlan, M. The p53 Pathway in Glioblastoma. Cancers 2018, 10, 297.
73. Ghaemi, S.; Arefian, E.; Rezazadeh Valojerdi, R.; Soleimani, M.; Moradimotlagh, A.; Jamshidi Adegani, F. Inhibiting the expression of anti-apoptotic genes BCL2L1 and MCL1, and apoptosis induction in glioblastoma cells by microRNA-342. Biomed. Pharmacother. 2020, 121, 109641.
74. Pareja, F.; Macleod, D.; Shu, C.; Crary, J.F.; Canoll, P.D.; Ross, A.H. PI3K and Bcl-2 Inhibition Primes Glioblastoma Cells to Apoptosis through Downregulation of Mcl-1 and Phospho-BAD. Mol. Cancer Res. 2014, 12, 987.
75. Doyon, Y.; Cayrou, C.; Ullah, M.; Landry, A.-J.; Côté, V.; Selleck, W. ING Tumor Suppressor Proteins Are Critical Regulators of Chromatin Acetylation Required for Genome Expression and Perpetuation. Mol. Cell 2006, 21, 51–64.
76. Kim, S. HuntING4 New Tumor Suppressors. Cell Cycle 2005, 4, 516–517.
77. Yamaoka, K.; Saharinen, P.; Pesu, M.; Holt, V.E.T., 3rd; Silvennoinen, O.; O’Shea, J.J. The Janus kinases (Jaks). Genome Biol. 2004, 5, 253.
78. Zhou, Y.-J.; Chen, M.; Cusack, N.A.; Kimmel, L.H.; Magnuson, K.S.; Boyd, J.G. Unexpected Effects of FERM Domain Mutations on Catalytic Activity of Jak3: Structural Implication for Janus Kinases. Mol. Cell 2001, 8, 959–969.
79. Rawlings, J.S.; Rosler, K.M.; Harrison, D.A. The JAK/STAT signaling pathway. J. Cell Sci. 2004, 117, 1281.
80. Schaefer, L.K.; Ren, Z.; Fuller, G.N.; Schaefer, T.S. Constitutive activation of Stat3α in brain tumors: Localization to tumor endothelial cells and activation by the endothelial tyrosine kinase receptor (VEGFR-2). Oncogene 2002, 21, 2058–2065.
81. Rahaman, S.O.; Harbor, P.C.; Chernova, O.; Barnett, G.H.; Vogelbaum, M.A.; Haque, S.J. Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene 2002, 21, 8404–8413.
82. Zhang, L.; Alizadeh, D.; Van Handel, M.; Kortylewski, M.; Yu, H.; Badie, B. Stat3 inhibition activates tumor macrophages and abrogates glioma growth in mice. Glia 2009, 57, 1458–1467.
83. Kim, H.Y.; Park, E.J.; Joe, E.-h.; Jou, I. Curcumin Suppresses Janus Kinase-STAT Inflammatory Signaling through Activation of Src Homology 2 Domain-Containing Tyrosine Phosphatase 2 in Brain Microglia. J. Immunol. 2003, 171, 6072.
84. Papanastasiou, A.D.; Sirinian, C.; Kalofonos, H.P. Identification of novel human receptor activator of nuclear factor-kB isoforms generated through alternative splicing: Implications in breast cancer cell survival and migration. Breast Cancer Res. 2012, 14, R112.
85. Von dem Knesebeck, A.; Felsberg, J.; Waha, A.; Hartmann, W.; Scheffler, B.; Glas, M. RANK (TNFRSF11A) is epigenetically inactivated and induces apoptosis in gliomas. Neoplasia 2012, 14, 526–534.
86. Lee, H.; Zhang, P.; Herrmann, A.; Yang, C.; Xin, H.; Wang, Z. Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation. Proc. Natl. Acad. Sci. USA 2012, 109, 7765–7769.
87. Soares-Silva, M.; Diniz, F.F.; Gomes, G.N.; Bahia, D. The Mitogen-Activated Protein Kinase (MAPK) Pathway: Role in Immune Evasion by Trypanosomatids. Front. Microbiol. 2016, 7.
88. Teramoto, H.; Gutkind, J.S. Mitogen-Activated Protein Kinase Family. In Encyclopedia of Biological Chemistry, 2nd ed.; Lennarz, W.J., Lane, M.D., Eds.; Academic Press: Cambridge, MA, USA, 2013; pp. 176–180.
89. Mebratu, Y.; Tesfaigzi, Y. How ERK1/2 activation controls cell proliferation and cell death: Is subcellular localization the answer? Cell Cycle 2009, 8, 1168–1175.
90. Huang, G.; Shi, L.Z.; Chi, H. Regulation of JNK and p38 MAPK in the immune system: Signal integration, propagation and termination. Cytokine 2009, 48, 161–169.
91. Vo, V.A.; Lee, J.-W.; Lee, H.J.; Chun, W.; Lim, S.Y.; Kim, S.-S. Inhibition of JNK Potentiates Temozolomide-induced Cytotoxicity in U87MG Glioblastoma Cells via Suppression of Akt Phosphorylation. Anticancer Res. 2014, 34, 5509.
92. Ramaswamy, P.; Nanjaiah, N.D.; Borkotokey, M. Role of MEK-ERK signaling mediated adhesion of glioma cells to extra-cellular matrix: Possible implication on migration and proliferation. Ann. Neurosci. 2019, 26, 52–56.
93. Lo, H.-W. Targeting Ras-RAF-ERK and its interactive pathways as a novel therapy for malignant gliomas. Curr. Cancer Drug Targets 2010, 10, 840–848.
94. Yang, K.; Liu, Y.; Liu, Z.; Liu, J.; Liu, X.; Chen, X. p38γ overexpression in gliomas and its role in proliferation and apoptosis. Sci. Rep. 2013, 3, 2089.
95. Matsuda, K.-I.; Sato, A.; Okada, M.; Shibuya, K.; Seino, S.; Suzuki, K. Targeting JNK for therapeutic depletion of stem-like glioblastoma cells. Sci. Rep. 2012, 2, 516.
96. Ke, X.-X.; Pang, Y.; Chen, K.; Zhang, D.; Wang, F.; Zhu, S. Knockdown of arsenic resistance protein 2 inhibits human glioblastoma cell proliferation through the MAPK/ERK pathway. Oncol. Rep. 2018, 40, 3313–3322.
97. Ouyang, Z.; Xu, G. Antitumor effects of Sweroside in human glioblastoma: Its effects on mitochondrial mediated apoptosis, activation of different caspases, G0/G1 cell cycle arrest and targeting JNK/p38 MAPK signal pathways. J. BUON 2019, 24, 2141–2146.
98. Heiland, D.H.; Haaker, G.; Delev, D.; Mercas, B.; Masalha, W.; Heynckes, S. Comprehensive analysis of PD-L1 expression in glioblastoma multiforme. Oncotarget 2017, 8, 42214–42225.
99. Wurm, J.; Behringer, S.P.; Ravi, V.M.; Joseph, K.; Neidert, N.; Maier, J.P. Astrogliosis Releases Pro-Oncogenic Chitinase 3-Like 1 Causing MAPK Signaling in Glioblastoma. Cancers 2019, 11, 1437.
100. Munaut, C.; Noël, A.; Hougrand, O.; Foidart, J.-M.; Boniver, J.; Deprez, M. Vascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas. Int. J. Cancer 2003, 106, 848–855.
101. Sawaya, R.; Go, Y.; Kyritisis, A.P.; Uhm, J.; Venkaiah, B.; Mohanam, S. Elevated Levels of Mr92,000 Type IV Collagenase during Tumor Growthin Vivo. Biochem. Biophys. Res. Commun. 1998, 251, 632–636.
102. Lorenzl, S.; Albers, D.S.; Chirichigno, J.W.; Augood, S.J.; Beal, M.F. Elevated levels of matrix metalloproteinases-9 and -1 and of tissue inhibitors of MMPs, TIMP-1 and TIMP-2 in postmortem brain tissue of progressive supranuclear palsy. J. Neurol. Sci. 2004, 218, 39–45.
103. Bignami, A.; Hosley, M.; Dahl, D. Hyaluronic acid and hyaluronic acid-binding proteins in brain extracellular matrix. Anat. Embryol. 1993, 188, 419–433.
104. Keshari, R.S.; Verma, A.; Barthwal, M.K.; Dikshit, M. Reactive oxygen species-induced activation of ERK and p38 MAPK mediates PMA-induced NETs release from human neutrophils. J. Cell. Biochem. 2013, 114, 532–540.
105. McCubrey, J.A.; LaHair, M.M.; Franklin, R.A. Reactive Oxygen Species-Induced Activation of the MAP Kinase Signaling Pathways. Antioxid. Redox Signal. 2006, 8, 1775–1789.
106. Escamilla-Ramírez, A.; Castillo-Rodríguez, R.A.; Zavala-Vega, S.; Jimenez-Farfan, D.; Anaya-Rubio, I.; Briseño, E. Autophagy as a Potential Therapy for Malignant Glioma. Pharmaceuticals 2020, 13, 156.
107. Chang, A.L.; Miska, J.; Wainwright, D.A.; Dey, M.; Rivetta, C.V.; Yu, D. CCL2 Produced by the Glioma Microenvironment Is Essential for the Recruitment of Regulatory T Cells and Myeloid-Derived Suppressor Cells. Cancer Res. 2016, 76, 5671–5682.
108. Engelman, J.A.; Luo, J.; Cantley, L.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 2006, 7, 606–619.
109. Katso, R.; Okkenhaug, K.; Ahmadi, K.; White, S.; Timms, J.; Waterfield, M.D. Cellular Function of Phosphoinositide 3-Kinases: Implications for Development, Immunity, Homeostasis, and Cancer. Annu. Rev. Cell Dev. Biol. 2001, 17, 615–675.
110. Porta, C.; Paglino, C.; Mosca, A. Targeting PI3K/Akt/mTOR Signaling in Cancer. Front. Oncol. 2014, 4, 64.
111. Yang, J.; Nie, J.; Ma, X.; Wei, Y.; Peng, Y.; Wei, X. Targeting PI3K in cancer: Mechanisms and advances in clinical trials. Mol. Cancer 2019, 18, 26.
112. Brennan, C.W.; Verhaak, R.G.W.; McKenna, A.; Campos, B.; Noushmehr, H.; Salama, S.R. The somatic genomic landscape of glioblastoma. Cell 2013, 155, 462–477.
113. Koul, D. PTEN Signaling pathways in glioblastoma. Cancer Biol. Ther. 2008, 7, 1321–1325.
114. Gallia, G.L.; Tyler, B.M.; Hann, C.L.; Siu, I.M.; Giranda, V.L.; Vescovi, A.L. Inhibition of Akt inhibits growth of glioblastoma and glioblastoma stem-like cells. Mol. Cancer Ther. 2009, 8, 386–393.
115. Kim, Y.C.; Guan, K.-L. mTOR: A pharmacologic target for autophagy regulation. J. Clin. Investig. 2015, 125, 25–32.
116. Bava, S.V.; Puliyappadamba, V.T.; Deepti, A.; Nair, A.; Karunagaran, D.; Anto, R.J. Sensitization of taxol-induced apoptosis by curcumin involves down-regulation of nuclear factor-κB and the serine/threonine kinase Akt and is independent of tubulin polymerization. J. Biol. Chem. 2018, 293, 12283.
117. Carballo, G.B.; Honorato, J.R.; De Lopes, G.P.F. A highlight on Sonic hedgehog pathway. Cell Commun. Signal. 2018, 16, 11.
118. Robbins, D.J.; Fei, D.L.; Riobo, N.A. The Hedgehog signal transduction network. Sci. Signal. 2012, 5, re6.
119. Melamed, J.R.; Morgan, J.T.; Ioele, S.A.; Gleghorn, J.P.; Sims-Mourtada, J.; Day, E.S. Investigating the role of Hedgehog/GLI1 signaling in glioblastoma cell response to temozolomide. Oncotarget 2018, 9, 27000–27015.
120. Ulasov, I.V.; Nandi, S.; Dey, M.; Sonabend, A.M.; Lesniak, M.S. Inhibition of Sonic hedgehog and Notch pathways enhances sensitivity of CD133(+) glioma stem cells to temozolomide therapy. Mol. Med. 2011, 17, 103–112.
121. Takezaki, T.; Hide, T.; Takanaga, H.; Nakamura, H.; Kuratsu, J.-I.; Kondo, T. Essential role of the Hedgehog signaling pathway in human glioma-initiating cells. Cancer Sci. 2011, 102, 1306–1312.
122. Takebe, N.; Miele, L.; Harris, P.J.; Jeong, W.; Bando, H.; Kahn, M. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: Clinical update. Nat. Rev. Clin. Oncol. 2015, 12, 445–464.
123. Rossi, M.; Magnoni, L.; Miracco, C.; Mori, E.; Tosi, P.; Pirtoli, L. β-catenin and Gli1 are prognostic markers in glioblastoma. Cancer Biol. Ther. 2011, 11, 753–761.
124. Honorato, J.R.; Hauser-Davis, R.A.; Saggioro, E.M.; Correia, F.V.; Sales-Junior, S.F.; Soares, L.O.S. Role of Sonic hedgehog signaling in cell cycle, oxidative stress, and autophagy of temozolomide resistant glioblastoma. J. Cell. Physiol. 2020, 235, 3798–3814.
125. Zhou, A.; Lin, K.; Zhang, S.; Ma, L.; Xue, J.; Morris, S.-A. Gli1-induced deubiquitinase USP48 aids glioblastoma tumorigenesis by stabilizing Gli1. EMBO Rep. 2017, 18, 1318–1330.
126. Ruiz i Altaba, A.; Stecca, B.; Sánchez, P. Hedgehog–Gli signaling in brain tumors: Stem cells and paradevelopmental programs in cancer. Cancer Lett. 2004, 204, 145–157.
127. Cheng, J.; Gao, J.; Tao, K. Prognostic role of Gli1 expression in solid malignancies: A meta-analysis. Sci. Rep. 2016, 6, 22184.
128. Hui, C.-C.; Angers, S. Gli Proteins in Development and Disease. Annu. Rev. Cell Dev. Biol. 2011, 27, 513–537.
129. Scales, S.J.; De Sauvage, F.J. Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol. Sci. 2009, 30, 303–312.
130. Stecca, B.; Ruiz i Altaba, A. Context-dependent regulation of the GLI code in cancer by HEDGEHOG and non-HEDGEHOG signals. J. Mol. Cell Biol. 2010, 2, 84–95.
131. Tu, Y.; Niu, M.; Xie, P.; Yue, C.; Liu, N.; Qi, Z. Smoothened is a poor prognosis factor and a potential therapeutic target in glioma. Sci. Rep. 2017, 7, 42630.
132. Jeng, K.-S.; Sheen, I.S.; Leu, C.-M.; Tseng, P.-H.; Chang, C.-F. The Role of Smoothened in Cancer. Int. J. Mol. Sci. 2020, 21, 6863.
133. Elamin, M.H.; Shinwari, Z.; Hendrayani, S.-F.; Al-Hindi, H.; Al-Shail, E.; Khafaga, Y. Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells. Mol. Carcinog. 2010, 49, 302–314.
134. Puliyappadamba, V.T.; Hatanpaa, K.J.; Chakraborty, S.; Habib, A.A. The role of NF-κB in the pathogenesis of glioma. Mol. Cell. Oncol. 2014, 1, e963478.
135. Mitchell, S.; Vargas, J.; Hoffmann, A. Signaling via the NFκB system. Wiley Interdiscip. Rev. Syst. Biol. Med. 2016, 8, 227–241.
136. Xia, Y.; Shen, S.; Verma, I.M. NF-κB, an active player in human cancers. Cancer Immunol. Res. 2014, 2, 823–830.
137. Sun, S.-C. The non-canonical NF-κB pathway in immunity and inflammation. Nat. Rev. Immunol. 2017, 17, 545–558.
138. Shoichi, N.; Kazuo, W.; Masanori, K.; Akira, T.; Shunro, E.; Toshiro, K. Aberrant nuclear factor-κB activity and its participation in the growth of human malignant astrocytoma. J. Neurosurg. 2002, 96, 909–917.
139. Wang, H.; Wang, H.; Zhang, W.; Huang, H.J.; Liao, W.S.L.; Fuller, G.N. Analysis of the activation status of Akt, NFκB, and Stat3 in human diffuse gliomas. Lab. Investig. 2004, 84, 941–951.
140. Raychaudhuri, B.; Han, Y.; Lu, T.; Vogelbaum, M.A. Aberrant constitutive activation of nuclear factor κB in glioblastoma multiforme drives invasive phenotype. J. Neuro-Oncol. 2007, 85, 39–47.
141. Atkinson, G.P.; Nozell, S.E.; Harrison, D.K.; Stonecypher, M.S.; Chen, D.; Benveniste, E.N. The prolyl isomerase Pin1 regulates the NF-kappaB signaling pathway and interleukin-8 expression in glioblastoma. Oncogene 2009, 28, 3735–3745.
142. Kim, S.-H.; Ezhilarasan, R.; Phillips, E.; Gallego-Perez, D.; Sparks, A.; Taylor, D. Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent Manner. Cancer Cell 2016, 29, 201–213.
143. Xu, R.X.; Liu, R.Y.; Wu, C.M.; Zhao, Y.S.; Li, Y.; Yao, Y.Q. DNA Damage-Induced NF-κB Activation in Human Glioblastoma Cells Promotes miR-181b Expression and Cell Proliferation. Cell. Physiol. Biochem. 2015, 35, 913–925.
144. Smith, D.; Shimamura, T.; Barbera, S.; Bejcek, B.E. NF-κB controls growth of glioblastomas/astrocytomas. Mol. Cell. Biochem. 2008, 307, 141–147.
145. Jiang, Z.; Zheng, X.; Rich, K.M. Down-regulation of Bcl-2 and Bcl-xL expression with bispecific antisense treatment in glioblastoma cell lines induce cell death. J. Neurochem. 2003, 84, 273–281.
146. Mitsiades, N.; Mitsiades, C.S.; Poulaki, V.; Chauhan, D.; Richardson, P.G.; Hideshima, T. Biologic sequelae of nuclear factor–κB blockade in multiple myeloma: Therapeutic applications. Blood 2002, 99, 4079–4086.
147. Zou, T.; Rao, J.N.; Guo, X.; Liu, L.; Zhang, H.M.; Strauch, E.D. NF-κB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion. Am. J. Physiol. Cell Physiol. 2004, 286, C1009–C1018.
148. Jeremias, I.; Kupatt, C.; Baumann, B.; Herr, I.; Wirth, T.; Debatin, K.M. Inhibition of Nuclear Factor κB Activation Attenuates Apoptosis Resistance in Lymphoid Cells. Blood 1998, 91, 4624–4631.