Significance of p53 and CD31 in astrogliomas

Khattab, Abdul-Zaher M.; Ahmed, Magdy I.; Fouad, Mohamed; Essa, Waleed A.

doi:10.1007/s12032-008-9094-7

Cited by 12 publications

(9 citation statements)

References 27 publications

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“…In addition to its role in determining tumor cell survival and growth, MAPK signaling can influence tumorigenesis (30), and through this, some cannabinoids have also been shown to be antiangiogenic and antiinvasive (31). Our data support this, as the lessening of the red, bloody hue of the tumor mass in the brain sections also correlated with a reduction in the endothelial maker of angiogenesis/neovascularization CD31 (32). It is intriguing to speculate at this time, that in addition to hindering tumor growth through an antiproliferative effect, the treatment was also reducing cancer development by inhibiting tumor angiogenesis.…”

Section: Discussionsupporting

confidence: 70%

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model

Scott

Dalgleish

Liu

2014

Molecular Cancer Therapeutics

133

104

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High-grade glioma is one of the most aggressive cancers in adult humans and long-term survival rates are very low as standard treatments for glioma remain largely unsuccessful. Cannabinoids have been shown to specifically inhibit glioma growth as well as neutralize oncogenic processes such as angiogenesis. In an attempt to improve treatment outcome, we have investigated the effect of D 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) both alone and in combination with radiotherapy in a number of glioma cell lines (T98G, U87MG, and GL261). Cannabinoids were used in two forms, pure (P) and as a botanical drug substance (BDS). Results demonstrated a duration-and dose-dependent reduction in cell viability with each cannabinoid and suggested that THC-BDS was more efficacious than THC-P, whereas, conversely, CBD-P was more efficacious than CBD-BDS. Median effect analysis revealed all combinations to be hyperadditive [T98G 48-hour combination index (CI) at FU 50 , 0.77-1.09]. Similarly, pretreating cells with THC-P and CBD-P together for 4 hours before irradiation increased their radiosensitivity when compared with pretreating with either of the cannabinoids individually. The increase in radiosensitivity was associated with an increase in markers of autophagy and apoptosis. These in vitro results were recapitulated in an orthotopic murine model for glioma, which showed dramatic reductions in tumor volumes when both cannabinoids were used with irradiation (day 21: 5.5 AE 2.2 mm 3 vs. 48.7 AE 24.9 mm 3 in the control group; P < 0.01). Taken together, our data highlight the possibility that these cannabinoids can prime glioma cells to respond better to ionizing radiation, and suggest a potential clinical benefit for glioma patients by using these two treatment modalities. Mol Cancer Ther; 13(12); 2955-67. Ó2014 AACR.

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Section: Discussionsupporting

confidence: 70%

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model

Scott

Dalgleish

Liu

2014

Molecular Cancer Therapeutics

133

104

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“…The pan-endothelial marker CD34 was expressed in the significant portion of giant cell GBM (73%) as well as non-giant cell GBM (56%) with the strong widespread staining in 55% and 25% of tumors, respectively [ 60 ]. The significant relationship between the expression of pan-endothelial marker CD31 and tumor grade was found in the study with 45 astrocytomas where the highest expression was observed in GBM samples (P = 0.001) [ 61 ]. Another study examined the degree of angiogenesis in GBM measured by microvessel density (MVD) using both pan-endothelial marker CD31 and marker CD105/endoglin, which preferentially react with active endothelial cells in angiogenic tissue [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

IDH1 mutation is associated with lower expression of VEGF but not microvessel formation in glioblastoma multiforme

et al. 2018

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IntroductionGlioblastoma multiforme (GBM) represents the most malignant primary brain tumor characterized by pathological vascularization. Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) were observed in GBM. We aimed to assess the intra-tumor hypoxia, angiogenesis and microvessel formation in GBM and to find their associations with IDH1 mutation status and patients prognosis.Methods52 patients with a diagnosis of GBM were included into the study. IDH1 R132H mutation was assessed by RT-PCR from FFPE tumor samples obtained during surgery. The expression of markers of hypoxia (HIF2α), angiogenesis (VEGF), tumor microvascularity (CD31, CD34, vWF, CD105), and proliferation (Ki-67) were assessed immunohistochemically (IHC). IDH1 mutation and IHC markers were correlated with the patient survival.Results20 from 52 GBM tumor samples comprised IDH1 R132H mutation (38.5%). The majority of mutated tumors were classified as secondary glioblastomas (89.9%). Patients with IDH1 mutated tumors experienced better progression-free survival (P = 0.037) as well as overall survival (P = 0.035) compared with wild type tumors. The significantly lower expression of VEGF was observed in GBM with IDH1 mutation than in wild type tumors (P = 0.01). No such association was found for microvascular markers. The increased expression of newly-formed microvessels (ratio CD105/CD31) in tumor samples was associated with worse patient’s progression-free survival (P = 0.026).SummaryNo increase in HIF/VEGF-mediated angiogenesis was observed in IDH1-mutated GBM compared with IDH1 wild type tumors. The histological assessment of the portion of newly-formed microvessels in tumor tissue can be used for the prediction of GBM patient’s prognosis.

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“…This sub-population may also have an enhanced proliferative capacity and it has been proposed that this T cell population may enhance susceptibility to autoimmune disease (48). Furthermore, some CD31-expressing tumour cells are less apoptotic and associated with a poorer prognosis for the patient (49, 50).…”

Section: Discussionmentioning

confidence: 99%

CD31 Is Required on CD4+ T Cells To Promote T Cell Survival during Salmonella Infection

Ross

Coughlan

Flores‐Langarica

et al. 2011

The Journal of Immunology

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Haematopoietic cells constitutively express CD31/PECAM1 a signalling, adhesion receptor associated with controlling responses to inflammatory stimuli. Although expressed on CD4+ T cells, its function on these cells is unclear. To address this we have used a model of systemic Salmonella infection that induces high levels of T cell activation and depends upon CD4+ T cells for resolution. Infection of CD31-deficient (CD31KO) mice demonstrates that these mice fail to control infection effectively. During infection, CD31KO mice have diminished numbers of total CD4+ T cells and IFN-γ-secreting Th1 cells. This is despite a higher proportion of CD31KO CD4+ T cells exhibiting an activated phenotype, and an undiminished capacity to prime normally and polarize to Th1. Reduced numbers of T cells reflected the increased propensity of naive and activated CD31KO T cells to undergo apoptosis after infection compared to wild-type (WT) T cells. Using adoptive transfer experiments we show that loss of CD31 on CD4+ T cells alone is sufficient to account for the defective CD31KO T cell accumulation. These data are consistent with CD31 helping to control T cell activation as in its absence T cells have a greater propensity to become activated, resulting in increased susceptibility to become apoptotic. The impact of CD31 loss on T cell homeostasis becomes most pronounced during severe, inflammatory and immunological stresses such as those caused by systemic Salmonella infection. This identifies a novel role for CD31 in regulating CD4 T cell homeostasis.

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Significance of p53 and CD31 in astrogliomas

Abstract: The estimation of p53 and CD31 could be used as good tools to assess the grade, prognosis, and aggressiveness of the astroglial tumors. Thus, the two markers can be used as adjunct to the diagnosis and stratification of the high grade from the low-grade intrinsic brain astrogliomas.

Cited by 12 publications

References 27 publications

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model

The Combination of Cannabidiol and Δ9-Tetrahydrocannabinol Enhances the Anticancer Effects of Radiation in an Orthotopic Murine Glioma Model

IDH1 mutation is associated with lower expression of VEGF but not microvessel formation in glioblastoma multiforme

CD31 Is Required on CD4+ T Cells To Promote T Cell Survival during Salmonella Infection

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