DigitalUM :: Browsing by Subject "Glioma"

Browsing by Subject "Glioma"

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Open Access
BPTF promotes glioma development through USP34-mediated de-ubiquitination of FOXC1
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Pan, Yanling; Yuan, Feng; Lin, Zhiren; Li, Yijie
Glioma is the most prevalent malignant tumor of the brain, and the study of the molecular mechanisms associated with its development has important clinical significance. Our previous study found that BPTF promotes the malignant phenotype of glioma and is significantly associated with poor prognosis; the downstream regulatory mechanisms are explored in this study. Western blot and immuno-histochemical staining were used to detect protein expression in cells or tissues. BPTF knockdown as well as FOXC1-overexpressing lentiviruses were used in combination for the construction of the U251 cell model, leading to functional rescue experiments. CCK8 assay, flow cytometry, scratch assay, and Transwell assay were used to detect cell proliferation, apoptosis, and migration, respectively. Finally, immuno-precipitation assays, combined with western blot (WB), were used to detect the interaction between proteins as well as the level of ubiquitination modification. The obtained results suggested that BPTF knockdown may inhibit the malignant behavior of glioma cells by downregulating FOXC1 expression. Moreover, FOXC1 expression was significantly higher in glioma tissues than in normal brain tissues and was significantly associated with higher tumor stage and worse patient prognosis. Finally, the mechanism of FOXC1 regulation by BPTF was found to result from the affected protein stability of FOXC1 through USP34-mediated de-ubiquitylation. In conclusion, the BPTF/FOXC1 axis was identified as a key promotor in glioma development and may be a potential target in the inhibition of glioma development.
Open Access
Expression and prognostic value of PIM-1 kinase in gliomas
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Li, Zelin; Wang, Hu; Wang, Guangxiu; Wang, Chen; Zhang, Anling; Mo, Lidong; Jia, Zhifan; Tong, Xiaoguang; Biología Celular e Histología
Objective. This study aimed to explore the correlation of PIM-1 with the clinicopathological features and prognosis of patients. Methods. The MTERF3 mRNA and protein expression levels in tissues were detected by western blot and immunohistochemistry. The expression and survival of PIM-1 in patients with glioma were analysed using the Gene Expression Profiling Interactive Analysis database, the Gene Expression Database of Normal and Tumor Tissues 2, and the Chinese Glioma Genome Atlas database. The relationship between PIM-1 expression and immune cells and chemokines was analysed using the Tumor Immune Estimation Resource Version 2.0 tool and the Tumor and Immune System Interactions Database. A Kaplan–Meier plot was used to estimate the correlation between PIM-1 expression and the survival of patients with glioma. Results. The expression of PIM-1 was upregulated in glioma and was positively correlated with tumour grade. The expression of PIM-1 was significantly inhibited on the second day after transfection (p<0.05), and the inhibition was most obvious on the sixth day (p<0.01). The results of the co-expression pattern of PIM-1 showed that the expression of 5,012 genes was positively correlated with PIM-1, while the expression of 3,651 genes was negatively correlated with PIM-1. Macrophages (p<0.001), myeloid dendritic cells (p<0.001), NK cells (p<0.001), CD4 T cells (p<0.001), cancer-associated fibroblasts (p<0.001), and neutrophils (p<0.001) were positively correlated with the expression of PIM-1 in low-grade glioma. Conclusion. PIM-1 is overexpressed in glioma and is related to the prognosis of glioblastoma multiforme, and PIM-1 may be a prognostic biomarker and therapeutic target for glioma.
Open Access
GPBAR1 promotes proliferation and is related to poor prognosis of high-grade glioma via inducing MAFB expression
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Sun, Suohui; Guo, Hui; Liang, Nan; Wu, Tao; Zhang, Chunpu; Li, Huaqing
Background. Glioma is the most prevalent brain tumors with extremely poor prognosis, but the prognostic biomarkers of high-grade (grade III and IV) gliomas (HGG) are still insufficient. Materials and methods. In our study, we investigated the expression of GPBAR1 in HGG by qRT-PCR and immunohistochemistry (IHC), and evaluated the clinical significance of GPBAR1 with univariate and multivariate analyses. By retrieving the data from TCGA, we screened the genes significantly associated with GPBAR1, and identified the correlation between GPBAR1 and MAFB. By experiments in vitro, we showed the pivotal role of MAFB in GPBAR1-induced proliferation of HGG. Results. GPBAR1 expression in HGGs was significantly higher than that in normal brain tissues. GPBAR1 was an independent prognostic biomarker of HGG. GPBAR1 promoted the proliferation of HGG by inducing MAFB expression. MAFB was also a prognostic biomarker of HGG, and patients with coexpression of MAFB and GPBAR1 had worse prognosis. Conclusions. GPBAR1 promoted the proliferation of HGG by inducing MAFB expression. Both GPBAR1 and MAFB were prognostic biomarkers of HGG, and patients with co-expression of MAFB and GPBAR1 had worse prognosis than those with only GPBAR1 or MAFB expression.
Open Access
Histopathological findings in the peritumoral edema area of human glioma
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Wang, Xingfu; Liu, Xueyong; Chen, Yupeng; Lin, Guoshi; Mei, Wenzhong; Chen, Jianwu; Liu, Ying; Lin, Zhixiong; Zhang, Sheng
Peritumoral brain edema (PTBE) is considered to be one of the main biological behaviors of brain glioma. However, the histopathological features of PTBE remain imprecisely defined. We analyzed the histopathological characteristics in the PTBE area of 22 cases of glioma. Microscopically, the pre-existing basic structure in the edema area was still preserved but there were varying degrees of loose tissue. The main components of the edema tissue were scattered invasive tumor cells, reactive cells, and various blood vessel patterns. Invasive tumor cell density was significantly higher in high-grade glioma than in low-grade glioma, and the density was significantly higher in the area near compared to the area far from the glioma. The Ki-67 proliferative index of the invasive tumor cells was higher in high-grade glioma than in low-grade glioma, but the index was not different in the area near compared to the area far from the glioma. The microvessel pattern in PTBE was primarily branching capillary. The microvessel densities (MVDs) of CD34+ and CD105+ were higher in high-grade glioma and the area near the glioma than in low-grade glioma and the area far from the glioma. Compared to CD34+, the MVD of CD105+ exhibited a more significant downward trend in terms of distance from the glioma. The most obvious types of reactive cells were reactive astrocytes and activated microglia. The reactive astrocytes were positive for nestin. The activated microglia emerged in the area near the glioma in most cases and in the area far from the glioma in more than half of the cases. In addition, several cases displayed focal collections of small lymphocytes around small blood vessels and tumor cells arranged around a neuronal cell, and a limited number of cases displayed giant dysmorphic neurons in an edematous cortex. Our data indicate that PTBE is a consequence of tissue reconstruction resulting from tumor cell invasion and is an appropriate niche for the growth and spread of glioma cells.
Open Access
Knockdown of ADAMDEC1 inhibits the progression of glioma in vitro
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Liu, Xueliang; Huang, Hao; Li, Xuehan; Zheng, Xiaomei; Zhou, Chong; Xue, Bin; He, Jimin; Zhang, Ye; Liu, Liang
Background. Glioma is one of the most lethal malignant tumors all over the world. The prognosis of patients with high-grade glioma remains very poor. Therefore, it is urgent to find a novel strategy for the treatment of glioma. It has been reported that ADAMDEC1 could regulate the progression of multiple diseases, including cancers. However, the role of ADAMDEC1 during the tumorigenesis of glioma remains largely unknown. Methods, Gene expression of ADAMDEC1 in glioma tissues or in cells was detected by qRT-PCR. Western blot was performed to measure the protein expressions of p53, active caspase3, active caspase9, CDK2 and Cyclin A in glioma cells. Cell proliferation was detected by CCK-8 assay. Cell apoptosis or cycle was tested by flow cytometry. Transwell was used to test the invasion of glioma cells. Results. The expression of ADAMDEC1 in glioma tissues or cells was significantly upregulated. In addition, downregulation of ADAMDEC1 notably inhibited the proliferation and induced apoptosis of glioma cells through upregulation of active caspase 3 and active caspase 9. Besides, silencing of ADAMDEC1 obviously induced G1 arrest in glioma cells via modulation of cell cycle-related proteins. Finally, knockdown of ADAMDEC1 significantly inhibited the migration and invasion of glioma cells. In contrast, overexpression of ADAMDEC1 promoted cell proliferation, migration and invasion of glioma cells. Conclusion. Downregulation of ADAMDEC1 could significantly inhibit the tumorigenesis of glioma in vitro, which may serve as a novel target for the treatment of glioma
Open Access
Murine monoclonal antibodies cytotoxic to human glioma cells in vitro
(Murcia : F. Hernández, 1992) Sánchez-Gómez, M.V.; Conde Guerri, B.; Sinués Porta, E.; Matute, C.
Six monoclonal antibodies (mABs) against human glioma cells (T2) were produced. T2 cells grown as solid tumors in nude mice, were dissociated and used to imrnunize Balblc rnice. After fusion of spleenocytes with myeloma cells, eight hybrids secreting mABs were selected according to their ability to react immunohistochernically with T2 cells, but not with normal adult human brain. Cytotoxicity of mABs was tested using (3~)-thymidinien corporation assays in vitro. Four mABs showed complement-mediated cytotoxicity for T2 cells, other human glioma cells (TI), and a human melanoma cell line. Incubation with one antibody, mAb2A1, lowered (3~)-thymidinein corporation in the T2 and T1 cells to ca. lo%, and in melanoma cells to ca. 35% of control levels. Another antibody, mAb3B2, displayed a similar cytotoxicity for T2 and T1 cells, but did not show measurable cytotoxicity for melanoma cells and rat primary astrocyte cultures. Moreover, this antibody did not crossreact with haematopoietic cells from patients bearing CNS tumors or normal subjects. MAb3B2, therefore, appears to recognize and epitope associated to human gliomas, will be a useful glioma tumor marker and may have some potential therapeutical value.
Open Access
NCAPD3 is a prognostic biomarker and is correlated with immune infiltrates in glioma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Qu, Linzhuo; Che, Huiying; Zhao, Jingyu; Lu, Xin; Ren, Zijun; Wu, Yu; Liu, Qian; Guan, Hongjian
Non-SMC Condensin II Complex Subunit D3 (NCAPD3) has been linked with the genesis and progression of multiple human cancers. Nevertheless, the scientific value and molecular process of NCAPD3 in glioma remain unclear. We explored the level of NCAPD3 expression in pan-cancer by multiple online databases. And we focused on the level and prognostic value of NCAPD3 expression in glioma by immuno-histochemistry (IHC) and survival analysis. Meanwhile, we verified the relationship between NCAPD3, biological function and immune infiltration in glioma by Linkedomics and SangerBox databases. The expression of NCAPD3 was increased in a variety of cancers, including glioma. Its high expression was strongly related to WHO grade (P=0.002) and programmed cell death ligand 1 (PD-L1) expression of glioma (P=0.001). Patients with a high level of NCAPD3 expression had a lower overall survival (OS) in glioma than patients with a low level of NCAPD3 expression. Multivariate statistical analyses showed NCAPD3 expression (P=0.040), WHO grade P<0.001), 1p/19q codeletion (P<0.001), recurrence (P<0.001), age (P=0.023), and chemotherapy status (P=0.001) were meaningful independent prognostic factors in patients with glioma. Furthermore, bioinformatics analysis proved that NCAPD3 has been linked to immune infiltration in glioma. High level of NCAPD3 expression may serve as a promising prognostic biomarker and correlate with dendritic cell infiltration, representing a potential immunotherapy target in glioma
Open Access
Nestin+cells forming spheroids aggregates resembling tumorspheres in experimental ENU-induced gliomas
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) García Blanco, Alvaro; Bulnes, Susana; Pomposo, Iñigo; Carrasco, Alex; Lafuente, José Vicente
Nestin+cells from spheroid aggregates display typical histopathological features compatible with cell stemness. Nestin and CD133+cells found in glioblastomas, distributed frequently around aberrant vessels, are considered as potential cancer stem cells. They are possible targets for antitumoral therapy because they lead the tumorigenesis, invasiveness and angiogenesis. However, little is known about their role and presence in low-grade gliomas. The aim of this work is to localize and characterize the distribution of these cells inside tumors during the development of experimental endogenous glioma. For this study, a single dose of Ethyl-nitrosourea was injected into pregnant rats. Double immunofluorescences were performed in order to identify stem-like and differentiated cells. Low-grade gliomas display Nestin+cells distributed throughout the tumor. More malignant gliomas show, in addition to that, a perivascular location with some Nestin+cells co-expressing CD133 or VEGF, and the intratumoral spheroid aggregates of Nestin/CD133+ cells. These structures are encapsulated by welldifferentiated VEGF/GFAP+cells. Spheroid aggregates increase in size in the most malignant stages. Spheroid aggregates have morphological and phenotypic similarities to in vitro neurospheres and could be an in vivo analogue of them. These arrangements could be a reservoir of undifferentiated cells formed to escape adverse microenvironments.
Open Access
NRF2, DJ1 and SNRX1 and their prognostic impact in astrocytic gliomas
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Haapasalo, Joonas A.; Nordfors, Kristiina; Granberg, Kirsi J.; Kivioja, Tomi; Nykter, Matti; Haapasalo, Hannu K.; Soini, Ylermi
Nuclear factor erythroid 2-related factor 2 (NRF2), DJ1 and sulfiredoxin 1 (SRXN1) are transcription factors which protect cells from the oxidative damage caused by reactive oxygen species and, on the other hand, are associated with resistance to cancer treatments. The immunohistochemical expression of NRF2, DJ1 and SRNX1 was assessed in human grade II-IV astrocytic gliomas. Their association to clinicopathologic and essential molecular factors was evaluated. The RNA expression levels and genetic alterations were analyzed from publicly available datasets. All studied molecules were commonly expressed. The cytoplasmic NRF2 expression was higher in tumors with a higher malignancy grade, whereas the nuclear and cytoplasmic DJ1 expression was associated with a lower grade. The presence of the isocitrate dehyrdogenase 1 mutation (IDH1) was associated with an increasing cytoplasmic and nuclear expression of NRF2 and a nuclear DJ1 expression. When primary grade IV astrocytomas were compared to secondary glioblastomas, nuclear DJ1 was associated with secondary tumors. In grade II-IV tumors, the cytoplasmic NRF2 expression was associated with a poor prognosis, whereas nuclear NRF2 and both cytoplasmic and nuclear DJ1 were associated with a better patient prognosis. Recurrent homozygous deletions of DJ1 were observed, especially in the IDH wild-type samples. When only the glioblastomas were evaluated, nuclear NRF2 and SRNX1 predicted better survival. As a conclusion, NRF2, DJ1 and SNXR1 can be used as prognosticators in gliomas.
Open Access
Overexpression of lncRNA IRAIN restrains the progression and Temozolomide resistance of glioma via repressing IGF-1R-PI3K-NF-κB signaling pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Guo, Aishun; Fang, Guixia; Lin, Zhenrong; Zheng, Shuishun; Zhuang, Zhijun; Lin, Ruisheng; Lin, Yanling
Background. Increasing studies have found that long noncoding RNAs (lncRNAs) contribute to regulating tumor progression. This study explores the expression characteristics, effects, and related mechanisms of lncRNA IGF1R antisense imprinted nonprotein coding RNA (IRAIN) in glioma. Methods. Quantitative real-time PCR (qRT-PCR) was implemented to testify the IRAIN profile in glioma tissues and paracancerous tissues, and the link between the IRAIN level and the clinicopathological indicators of glioma was analyzed. IRAIN overexpression and knockdown cell models were constructed in glioma cells. Cell proliferation was verified by the colony formation experiment, while flow cytometry was implemented to monitor apoptosis. Transwell assay was performed to examine cell invasion and migration. Western blot (WB) was adopted to compare the profiles of the apoptosis-related proteins (Bax, Bcl2, and Caspase3) and IGF-1R-PI3K-NF-κB pathway. Results. IRAIN was down-regulated in glioma tissues (compared with adjacent normal tissues), and the low IRAIN expression was significantly linked with the larger tumor volume and higher pathological stages. Functionally, overexpressing IRAIN abated glioma cell proliferation, invasion, and migration, promoted apoptosis, and attenuated IGF-1R-PI3K-NF-κB expression and temozolomide (TMZ) resistance, which was also confirmed in the xenograft tumor experiment. The WB result showed that overexpressing IRAIN inactivated the IGF-1R-PI3K-NF-κB pathway. Additionally, the IGF-1R knockdown model was established in U251 cells. Si-IGF-1R induced cell proliferation inhibition, promoted cell death, and reduced cell migration and TMZ resistance, whereas SiIGF-1R+IRAIN group showed no additional effects on glioma cells compared with the Si-IGF-1R group. Conclusion. IRAIN repressed glioma development and TMZ resistance by inactivating the IGF-1R-PI3KNF-κB axis.
Open Access
p53 mutation and protein alteration in 50 gliomas. Retrospective study by DNA-sequencing techniques and immunohistochemistry
(Murcia : F. Hernández, 1997) von Eckardstein, K.; Gries, H.; Bolik, E.; Cervós-Navarro, J.; Tschairkin, I.N.; Patt, Stephan
Alterations of the p53 protein, which is a 53 kD phosphoprotein and gene product of the p53 gene, has been found to play a major role in the genesis of a variety of human malignancies including tumors of the central nervous system. We investigated 50 tumor specimens from primary central nervous system neoplasms. Tissue samples were screened for mutations by the single-strand conformation polymorphism method and detected mutations were sequenced. Al1 tissue specimens were stained immuno- ' histochemically for p53 protein, which when altered accumulates in the nucleus due to prolonged halflife. Mutations were found in six cases, including one pilocytic astrocytoma World Health Organisation (WHO) grade 1, two astrocytomas WHO grade 11, two anaplastic astrocytomas WHO grade 111, and one primitive neuroectodermal tumor (PNET). In terms of relative frequency mutations were found mostly in the group of anaplastic astrocytomas WHO grade 111. Interestingly, no mutations were found in the group of investigated glioblastomas. P53 immunopositivity did not correlate with the mutations found, whereas the staining index was significantly higher in the cases with detected mutations than in those without. When p53 alteration is seen as an indicator for different pathogenic pathways in glioma formation, this study gives evidence for a difference between anaplastic astrocytoma and glioblastoma. However, since there was a great overlap in p53 immunopositivity and p53 mutation in tumors of different WHO grades and entities, it seems that p53 will not act as a marker molecule neither for tumor entities nor for tumor malignancy.
Open Access
Plexin-mediated neuronal development and neuroinflammatory responses in the nervous system
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Dai, Lu; Shen, Kai-Feng; Zhang, Chun-Qing
Plexins are a large family of single-pass transmembrane proteins that mediate semaphorin signaling in multiple systems. Plexins were originally characterized for their role modulating cytoskeletal activity to regulate axon guidance during nervous system development. Thereafter, different semaphorin-plexin complexes were identified in the nervous system that have diverse functions in neurons, astrocytes, glia, oligodendrocytes, and brain derived-tumor cells, providing unexpected but meaningful insights into the biological activities of this protein family. Here, we review the overall structure and relevant downstream signaling cascades of plexins. We consider the current knowledge regarding the function of semaphorin-plexin cascades in the nervous system, including the most recent data regarding their roles in neuronal development, neuroinflammation, and glioma.
Open Access
Roles of microRNAs during glioma tumorigenesis and progression
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Wang, Shuwei; Yin, Yutong; Liu, Shuang
Glioma is the most common and aggressive type of brain tumor. It has a poor prognosis and a high recurrence rate. Despite continued advances in surgery, chemotherapy and radiotherapy, the clinical outcomes remain dismal. MicroRNAs (miRNAs) play important roles in the initiation and progression of a multitude of tumors. Until now, the molecular mechanism that is responsible for glioma tumorigenesis and progression remains unclear. Increasing evidence has shown that miRNAs play an important role in glioma. In this review, we focus on the current advances in determining the role of miRNAs in regulating tumorigenesis and the progression of glioma. In addition, the relevant roles of miRNAs about
Open Access
SOX10 and Olig2 as negative markers for the diagnosis of ependymomas: An immunohistochemical study of 98 glial tumors
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Švajdler, Marián; Rychlý, Boris; Mezencev, Roman; Fröhlichová, Lucia; Bednárová, Antónia; Pataky, František; Daum, Ondřej
SOX10 belongs to the family of transcription factors essential for the development of neural crest, peripheral nervous system and melanocytes. It is presently used in histopathology as a marker of melanocytic differentiation. SOX10 is expressed in normal brain tissue in oligodendrocytes, but the information about SOX10 expression in primary tumors of the central nervous system is quite limited. In this study, we examined the expression of SOX10 and Olig2 by immunohistochemistry in a series of 98 glial tumors and explored their specificity and sensitivity for differential diagnosis of ependymal vs non-ependymal tumors. In addition, we examined the expression of EMA and CD99 in ependymal tumors. SOX10 and Olig2 staining were scored as negative if no positive cells or only a few positive cells (typically up to 1-3%) were found. In all other instances, SOX10 or Olig2 staining was scored as positive. Out of 44 examined ependymal tumors none was found to express SOX10 and 7 specimens showed only a few SOX10-positive cells that likely corresponded to entrapped nonneoplastic oligodendrocytes. In contrast, non-ependymal tumors expressed SOX10 in 26/54 (48%) specimens. Olig2 was positive in 5 out of 44 ependymomas (11%) and 50 out of 54 (93%) non-ependymal tumors (astrocytomas and oligodendrogliomas). EMA and CD99 expression was found in 33/44 (75%) and 11/44 (25%) of ependymomas, respectively. SOX10-positivity rules out the diagnosis of ependymoma among other glial tumors with high confidence.
Open Access
SPHK2 protein expression, Ki-67 index and infiltration of tumor-associated macrophages (TAMs) in human glioma
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Liu, J.; Zhou, Q.; Wu, C.P.; Xu, Y.W.; Liu, W.L.; Zhao, H.F.; Li, W.P.
Introduction. Sphingosine kinases (SPHKs), the Ki-67 index and tumor-associated macrophages (TAMs) are associated with diverse human malignancies, including glioma. SPHK2, a subtype of SPHKs, has not been assessed in glioma or correlated with the Ki-67 index or TAM infiltration. We tested the hypothesis that expression of SPHK2 correlates with the Ki-67 index and TAM infiltration in patients with glioma. Materials and method. Western blot analysis was performed on protein lysates prepared from human astrocyte (HA) and glioma cell lines. Immunofluorescence was used to determine the subcellular location of SPHK2 protein in glioma cells. Next, immunohistochemistry was employed to analyze the correlations among SPHK2, Ki-67, CD68, and CD206 in 11 non-neoplastic brain tissues and 60 glioma tissues. All slides were evaluated under ×400 magnification, and the ratio of positively stained cells to the total number of cells was calculated for analysis. Results. SPHK2, CD68 and CD206 were all increased in glioma tissues compared to non-neoplastic brain tissues, but there were no differences between WHO grades of glioma. Ki-67 was highest in WHO grade IV tumors and lowest in non-neoplastic brain tissues, and all between-group differences were statistically significant. Moreover, SPHK2 expression was positively correlated with the Ki-67, CD68 and CD206 indexes. Finally, the CD68 and CD206 indexes were both associated with the Ki-67 index. Conclusion. SPHK2 protein expression, the Ki-67 index and TAM infiltration in human glioma tissue were reported in this study for the first time. SPHK2 was positively associated with TAM infiltration and glioma proliferation. Mechanistically, SPHK2 may promote glioma growth by stimulating TAMs to polarize M2-type macrophages.
Open Access
Suicide gene therapy with Herpes simplex virus thymidine kinase and ganciclovir is enhanced with connexins to improve gap junctions and bystander effects
(Murcia : F. Hernández, 2003) Nicholas, T.W.; Read, S.B.; Burrows, F.J.; Kruse, C.A.
Connexins are proteins that form gap junctions between cells in various mammalian tissues. Because of their role in intercellular communication, connexins are important in the bystander cell death seen in Herpes simplex virus-thymidine kinase (HSV-TK) gene therapy for brain tumors. A selective review of connexin transduction/transfection studies with particular emphasis to central nervous system tumor cells is presented. In addition, specific references to studies with cell types that demonstrate low gap junction intercellular communication are presented. Data are included with the HT-29 colorectal tumor cell line to support the concept that enhancing gap junction protein expression in otherwise low gap junction communicating HT-29 cells increases bystander cell death and reduces tumor burden beyond what might be expected from HSV-TK and ganciclovir (GCV) treatment alone. Maximum in vitro bystander cell death was always produced when GCV treated co-cultures of TKtransduced and non-TK-transduced HT-29 cell lines were also transduced with connexin-43. When connexin was present in only one group of cells in the co-culture, there was more bystander cell death observed with connexin transduced into the non- TK-transduced cells, rather than the TK-transduced cells. The data presented reinforces conclusions made from earlier findings from cell line mixing experiments in which the non- TKtransduced cell population determined the level of bystander cell death (Burrows et al., 2002).
Open Access
Tau, downstream of IDH mut, inhibits the EGFR/NF-kB/TAZ mesenchymal axis, normalizing the vasculature and impairing glioma aggressiveness
(American Association for the Advancement of Science, 2021-01-22) Gargini, Ricardo; Segura Collar, Berta; Herránz, Beatriz; García Escudero, Vega; Romero Bravo, Andrés; Núñez, Felipe J.; García Pérez, Daniel; Gutiérrez Guamán, Jacqueline; Ayuso Sacido, Ángel; Seoane, Joan; Pérez Núñez, Ángel; Sepúlveda Sánchez, Juan M.; Hernández Laín, Aurelio; Castro, María G.; García Escudero, Ramón; Ávila, Jesús; Sánchez Gómez, Pilar; Farmacología; Facultades de la UMU::Facultad de Medicina
Mutant IDH1/2 gliomas represent a more indolent form of cancer. However, how this group of tumors progress, in a microenvironment-dependent manner, is still a pending question. Here we describe that the expression of Tau, a gene classically associated with neurodegenerative diseases, is epigenetically controlled by the balance between wild-type and mutant IDH1/2 in gliomas. Moreover, Tau is almost absent from tumors with EGFR mutations, whereas its expression is inversely correlated with overall survival in gliomas carrying wild-type or amplified EGFR. We demonstrate that the overexpression of Tau, through the stabilization of microtubules, impairs the mesenchymal/pericyte transformation of EGFRamp/wt glioma cells through the blockade of the EGFR-NFκB-TAZ axis. However, mutant EGFR induces a constitutive activation of this pathway, which is no longer sensitive to Tau. By inhibiting the phenotypic plasticity of EGFRamp/wt glioma cells, Tau protein inhibits angiogenesis and favors vascular normalization, decreasing tumor aggressiveness.
Open Access
The antitumor action of cannabinoids on glioma tumorigenesis
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Zogopoulos, Panagiotis; Korkolopoulou, Penelope; Patsouris, Efstratios; Theocharis, Stamatios
Cannabinoids are a class of chemical compounds with a wide spectrum of pharmacological effects, mediated by two specific plasma membrane receptors (CB1 and CB2). Recently, CB1 and CB2 expression levels have been detected in human tumors, including those of brain. Cannabinoids-endocannabinoids exert anti-inflammatory, anti-proliferative, anti-invasive, anti-metastatic and pro-apoptotic effects in different cancer types, both in vitro and in vivo in animal models, after local or systemic administration. We present the available experimental and clinical data, to date, regarding the antitumor action of cannabinoids on the tumorigenesis of gliomas.
Open Access
The long non-coding RNA PANDAR regulates cell proliferation and epithelial-to-mesenchymal transition in glioma
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Guo, Jianfeng; Xiao, Deyong; Lin, Zhijing; Sui, Chengzhi
Glioma is one of the most aggressive intracranial tumors in the central nervous system. The long non-coding RNA P21-associated ncRNA DNA damage activated (PANDAR) has been reported to be an oncogene or tumor suppressor in several cancers. However, the prognostic value and biological function of PANDAR in glioma have not been described. Here, we report that expression of PANDAR is significantly upregulated in glioma tissues and cell lines. PANDAR expression was correlated with tumor size (p=0.044) and World Health Organization (WHO) grades (p=0.005), as shown by chi-squared test. Moreover, significant upregulation of PANDAR was found to correlate with poor prognosis in glioma, as shown using Kaplan-Meier method and Cox multivariate survival analysis. Furthermore, PANDAR knockdown suppressed cell proliferation, G1/S transition, migration and invasion, and promoted apoptosis in glioma cell lines (U251 and U87). PANDAR knockdown decreased expression of CDK4, Bcl-2, N-cadherin and Vimentin, but increased E-cadherin expression in glioma cells. In conclusion, our data suggest PANDAR as a potential prognostic biomarker and therapeutic candidate for glioma.
Open Access
The role of the Ki-67 labelling index as an independent prognostic factor in indonesian glioma patients
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Dwianingsih, Ery Kus; Pranacipta, Sofia; Theresia, Emilia; Safitri, Sekar; Hartanto, Rachmat Andi; Malueka, Rusdy Ghazali
Introduction. Gliomas are the most common type of brain tumor. However, interpreting glioma morphology is subjective, and identifying mitosis can be challenging. This can impact the determination of the patient's tumor grade, therapy, and prognosis. In addition, the Ki-67 expression level, which reflects the tumor cells' ability to proliferate, is closely related to the patient’s survival. This study aims to find a correlation between Ki-67 expression and the overall survival (OS) of glioma patients in the Indonesian population. Methods. Ninety-one glioma patients from Sardjito General Hospital were collected for formalin-fixed embedded paraffin (FFPE) samples, and the Ki-67 labeling index (LI) was calculated by determining the percentage of labeled nuclei per 1000 cells using a 40x objective lens in a randomized area (average method). The OS was calculated from the day of pathology diagnosis until death or the last follow-up (for censored cases). Kaplan-Meier survival analysis was used to analyze the OS. Results. Individuals aged ≥60 with high-grade tumors, infratentorial gliomas, and a Ki-67 LI ≥10% had a shorter OS. The p-values associated with these factors were 0.001, 0.018, and 0.006, respectively. In multivariate analysis, age and tumor grade did not significantly correlate with OS. Conclusion. Glioma patients with a Ki-67 LI ≥10% have a significantly shorter OS than those with a lower Ki-67 LI, indicating that Ki-67 LI is an independent prognostic factor in Indonesian glioma patients.