Telomerase activity and expression of the telomerase catalytic subunit, hTERT, in meningioma progression

2000 ◽  
Vol 92 (5) ◽  
pp. 832-840 ◽  
Author(s):  
Matthias Simon ◽  
Tjoung-Won Park ◽  
Sven Leuenroth ◽  
Volkmar H. J. Hans ◽  
Thomas Löning ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Benign Tumors ◽  
Human Telomerase Reverse Transcriptase ◽  
Content Type ◽  
Brain Invasion ◽  
Amplification Protocol ◽  
Human Telomerase ◽  
Fine Print

Object. In recent reports, 6 to 19% of meningiomas have been classified as atypical or anaplastic/malignant. Some atypical and anaplastic meningiomas appear to arise from benign tumors by progression. Telomerase activation has recently been associated with malignant progression of human tumors. The authors have investigated a series of benign, atypical, and anaplastic/malignant meningiomas for telomerase activity and expression of the telomerase catalytic subunit human telomerase reverse transcriptase (hTERT).Methods. A quantitative telomeric repeat amplification protocol was used to detect telomerase enzyme activity in seven (21%) of 34 benign, but in nine (75%) of 12 atypical and in seven (100%) of seven anaplastic/malignant meningiomas. Very high levels of telomerase activity were observed only in highly aggressive tumors. Messenger (m)RNA expression of the catalytic subunit hTERT was found in 11 (33%) of 33 benign, 12 (92%) of 13 atypical, and all seven anaplastic/malignant tumors. All telomerase-positive lesions were also positive for hTERT mRNA, whereas no telomerase activity was detected in six (21%) of 29 hTERT-positive tumors. This indicates that upregulation of hTERT is the rate-limiting step for telomerase activation in the majority of meningiomas. Expression of telomerase and hTERT was seen in all four tumors with gross brain invasion. All recurrent tumors or meningiomas recurring during follow up expressed hTERT.Conclusions. The results are consistent with a role for telomerase activation during the development of malignancy in meningiomas. Hence, expression of telomerase activity and hTERT might prove to be potentially useful markers for the evaluation of these tumors.

scholarly journals Induction of apoptotic endonuclease EndoG with DNA-damaging agents initiates alternative splicing of telomerase catalytic subunit hTERT and inhibition of telomerase activity hTERT in human CD4+ and CD8+ T-lymphocytes

2017 ◽  
Vol 63 (4) ◽  
pp. 296-305 ◽  
Author(s):  
D.D. Zhdanov ◽  
D.A. Vasina ◽  
V.S. Orlova ◽  
E.V. Orlova ◽  
D.V. Grishin ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
T Lymphocytes ◽  
Splice Variants ◽  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Human Telomerase Reverse Transcriptase ◽  
Dna Damages ◽  
Dna Damaging Agents ◽  
Cd8 T Lymphocytes ◽  
Human Telomerase

Activity of telomerase catalytic subunit hTERT (human Telomerase Reverse Transcriptase) can be regulated by alternative splicing of its mRNA. At present time exact mechanism of hTERT splicing is not fully understood. Apoptotic endonuclease EndoG is known to participate this process. EndoG expression is induced by DNA damages. The aim of this work was to investigate the ability of DNA-damaging agents with different mechanism of action to induce EndoG expression and inhibit telomerase activity due to the activation of hTERT alternative splicing in normal activated human CD4+ and CD8+ T-lymphocytes. All investigated DNA-damaging agents were able to induce EndoG expression. Cisplatin, a therapeutic compound, producing DNA cross-links induced the highest level of DNA damages and EndoG expression. Incubation of CD4+ and CD8+ T-cells with cisplatin caused the changes in proportion of hTERT splice variants and inhibition of telomerase activity.

Surgical management of brain-stem tumors in children: results and statistical analysis of 75 cases

1993 ◽  
Vol 79 (6) ◽  
pp. 845-852 ◽  
Author(s):  
Alain Pierre-Kahn ◽  
Jean-François Hirsch ◽  
Mathieu Vinchon ◽  
Christine Payan ◽  
Christian Sainte-Rose ◽  
...  
Keyword(s):  
Brain Stem ◽  
Malignant Tumors ◽  
Benign Tumors ◽  
Patient Age ◽  
Content Type ◽  
Patient Âgé ◽  
Significant Difference ◽  
Brain Stem Tumors ◽  
Subtotal Removal ◽  
Fine Print

A study was made of 75 children treated between 1970 and 1990, with partial, subtotal, or total removal of three intrinsic and 72 exophytic or surface brain-stem tumors. In all cases, the goal of surgery was to remove as much tumor as possible. Extent of removal was defined according to data obtained from postoperative computerized tomography or magnetic resonance imaging, and was considered partial when only a small amount of tumor was removed, subtotal when a few cubic millimeters of tumor was left, and total when no residual tumor was seen on postoperative radiological investigations. An ultrasonic aspirator was used for the 43 most recent operations. Among tumor removals without the aspirator, 24 (75%) were partial, eight (25%) subtotal, and none total; with the use of the aspirator, the number of partial removals decreased to 44.5% while that of subtotal and total removals increased to 32% and 23.5%, respectively. There were 69 gliomas (92%) and 47 benign tumors (62.6%). Forty-nine patients were irradiated postoperatively, and 14 of the 23 patients whose benign tumors were removed totally or subtotally did not undergo irradiation. This study showed that: 1) the overall prognosis of patients with malignant tumors was poor and was not improved by surgery; 2) the survival rate of those with benign tumors was significantly (p < 0.01) lower after partial removal than after total or subtotal removal (52% and 94%, respectively, at 5 years); 3) comparison of means and proportions (Student's and chi-squared tests) between benign and malignant tumors showed a significant difference relating to patient age (p < 0.03), peritumoral hypodensity (p < 0.001), and preoperative duration of symptoms (p < 0.001); 4) stepwise logistic regression analysis confirmed that two of these three variables were related to malignancy: namely, patient age at surgery (p < 0.03) and presence of peritumoral hypodensity (p < 0.001); and 5) routine postoperative irradiation was contraindicated after total or subtotal removal of benign tumors.

Factors associated with survival in patients with meningioma

1998 ◽  
Vol 88 (5) ◽  
pp. 831-839 ◽  
Author(s):  
Bridget J. McCarthy ◽  
Faith G. Davis ◽  
Sally Freels ◽  
Tanya S. Surawicz ◽  
Denise M. Damek ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Proportional Hazards Model ◽  
Malignant Tumors ◽  
Age At Diagnosis ◽  
Benign Tumors ◽  
Content Type ◽  
Cancer Data ◽  
Fine Print

Object. To explore factors affecting the survival rate in patients with meningiomas, the authors used the National Cancer Data Base (NCDB), which includes tumors from approximately 1000 hospitals participating in the American College of Surgeons tumor registry program. Methods. Analysis included over 9000 cases diagnosed from 1985 to 1988 and 1990 to 1992. Survival estimates were computed and prognostic factors were identified using a proportional hazards model. The overall 5-year survival rate was 69% and it declined with patient age. This rate was 81% in patients aged 21 to 64 years and 56% for patients 65 years of age or older. When patients were grouped by the histological type of their tumors, those with benign tumors had an overall 5-year survival rate of 70%, whereas the overall 5-year survival rates in patients with atypical and malignant meningiomas were 75% and 55%, respectively. Prognostic factors for benign tumors included age at diagnosis, tumor size, whether treated surgically, hospital type, and radiation therapy; for malignant tumors, the prognostic factors included: age at diagnosis, whether treated surgically, and radiation therapy. These factors were statistically significant. The 5-year rate for recurrence of symptoms (regardless of the method of treatment) was 19.2% for those with benign tumors and 32.4% for those with malignant tumors. In patients whose benign tumor had been completely removed, the 5-year rate of tumor recurrence was 20.5%. Conclusions. Although not population-based, the NCDB has the potential for providing pertinent information regarding patient characteristics and methods of treatment for benign, as well as malignant, brain tumors.

Selective Apoptosis and Growth Impairment of Cancer Cells Induced by Human Telomerase Reverse Transcriptase (hTERT) Targeting Artificial MicroRNA

2021 ◽  
Vol 13 (9) ◽  
pp. 1644-1656
Author(s):  
Hongjun Lin ◽  
Pengliang Xin ◽  
Huangen Li ◽  
Mingqing Tang
Keyword(s):  
Reverse Transcriptase ◽  
Cancer Cells ◽  
Telomerase Activity ◽  
Telomerase Reverse Transcriptase ◽  
Human Telomerase Reverse Transcriptase ◽  
Reverse Transcription Pcr ◽  
Angiogenesis Assay ◽  
Amplification Protocol ◽  
Huvec Cells ◽  
Human Telomerase

Human telomerase reverse transcriptase (hTERT) is a promising cancer target, and amiRNA particle displays the siRNA’s specificity and miRNA’s safety, suggesting that cancers can be treated more effective and safely by hTERT targeting amiRNA particles. Hela, NCI-H446, U2-OS and Huvec cells were transfected by hTERT targeting amiRNA particles. hTERT expression, telomerase activity and cell viability were evaluated by quantitative reverse transcription-PCR (qRT-PCR), western blot (WB), telomeric repeat amplification protocol (TRAP) assays, MTT method, transwell protocol, fluorescence-activated cell sorting (FACS) technologies, angiogenesis assay, and xenograft tumor models. Results: hTERT expression and telomerase activity in Hela and NCIH446 were significantly inhibited by amiRNA. Anti-proliferation and pro-apoptosis effects were only observed in transfected Hela and NCI-H446 cells, but anti-migration and anti-angiogenesis effects were presented in transfected Huvec cells. More interestingly, low to 1.56 nM amiRNA can inhibit the proliferation of Hela cells by 80.99±5.24%. Conclusion: amiRNA selectively and effectively impairs the growth, and assists the apoptosis of telomerase-positive cancer cells.

Linear accelerator surgery for meningiomas

2005 ◽  
Vol 103 (2) ◽  
pp. 206-209 ◽  
Author(s):  
William A. Friedman ◽  
Gregory J. Murad ◽  
Patrick Bradshaw ◽  
Robert J. Amdur ◽  
William M. Mendenhall ◽  
...  
Keyword(s):  
Local Control ◽  
Linear Accelerator ◽  
Malignant Tumors ◽  
Local Control Rate ◽  
Benign Tumors ◽  
Content Type ◽  
Single Center Experience ◽  
Study Interval ◽  
Radiation Induced ◽  
Fine Print

Object. In this paper the authors review the results of a single-center experience in the use of linear accelerator (LINAC) surgery for radiosurgical treatment of meningiomas. Methods. A retrospective analysis of all patients treated with LINAC surgery for meningiomas between May 1989 and December 2001 was performed. All patients participated in follow-up review for a minimum of 2 years, and no patients were excluded. Two hundred ten patients were treated during the study interval. The actuarial local control rate for benign tumors was 100% at both 1 and 2 years, and 96% at 5 years. The actuarial local control rate for atypical tumors was 100% at 1 year, 92% at 2 years, and 77% at 5 years; and that for malignant tumors was 100% at both 1 and 2 years, and only 19% at 5 years. Of the 210 patients 13 (6.2%) experienced temporary radiation-induced complications, and only five (2.3%) experienced permanent complications. In all patients with a permanent complication the histological characteristics of the meningioma were malignant. Conclusions. Linear accelerator surgery produced high local control rates and very low rates of permanent morbidity in patients harboring benign meningiomas.

Telomerase activity in primary and secondary glioblastomas multiforme as a novel molecular tumor marker

2000 ◽  
Vol 93 (4) ◽  
pp. 618-625 ◽  
Author(s):  
Kunyu Harada ◽  
Kaoru Kurisu ◽  
Hidetoshi Tahara ◽  
Eiji Tahara ◽  
Toshinori Ide ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Telomerase Activity ◽  
Htert Expression ◽  
Chain Reaction ◽  
Content Type ◽  
Significant Difference ◽  
Polymerase Chain ◽  
Human Telomerase ◽  
Secondary Glioblastomas ◽  
Fine Print

Object. Telomerase activity is responsible for cell immortality. To examine the role of telomerase in the carcinogenesis of human glioblastomas multiforme (GBMs), the authors studied telomerase activity, telomerase component expression, and telomere lengths in 42 GBM samples.Methods. In all samples, EGFR and MDM2 amplifications and overexpressions were examined using Southern and Northern blot analyses. The p53 mutation was analyzed using polymerase chain reaction—single strand conformational polymorphism and by direct sequence analysis. Specimens of tissues were immunostained with p53, EGFR, and MDM2 antibodies. Allelic loss on chromosomes 17p and 10 was assessed by loss of heterozygosity (LOH) assays. Telomerase activity, expression of its components (human telomerase reverse transcriptase [hTERT], human telomerase RNA component [hTERC], and telomerase-associated protein [TEP1]), and telomere lengths were analyzed using the telomeric repeat amplification protocol (TRAP)—hybridization protection assay, reverse transcription—polymerase chain reaction, and Southern blot analysis. According to the results of assessments of EGFR and MDM2 amplifications, p53 mutation, LOHs in chromosomes 17p and 10, and the clinical course of the disease, the 42 samples were classified into 22 primary and 20 secondary glioblastomas.Twenty-six (61.9%) of all 42 samples demonstrated detectable telomerase activity during the TRAP assay. Secondary GBMs displayed significantly higher levels of telomerase activity and hTERT expression than primary GBMs. Tumors with a p53 gene mutation demonstrated significantly higher telomerase activity than those without a p53 mutation. Four samples with a codon 175 mutation demonstrated an exceptionally high amount of telomerase activity. In secondary GBMs, the increase in telomerase activity and the hTERT expression level correlated with the increased frequency of p53 mutations. There was no significant difference in telomere length between primary and secondary GBMs.Conclusions. These results suggest that telomerase activity and p53 mutations both play important roles in the multistep carcinogenesis of GBMs. Telomerase activity and hTERT expression may be considered as novel distinctive factors in human GBMs.

First experience in using Novalis shaped beam radiosurgery in Korea

2004 ◽  
pp. 341-345
Author(s):  
Choong Jin Whang ◽  
Gi Taek Yee ◽  
Chan Young Choi ◽  
Moon-Jun Sohn ◽  
Dong Joon Lee
Keyword(s):  
Stereotactic Radiosurgery ◽  
Malignant Tumors ◽  
Benign Tumors ◽  
Tumor Control ◽  
Pineal Tumor ◽  
Content Type ◽  
Shaped Beam ◽  
Acoustic Neuromas ◽  
Fractionated Stereotactic Radiosurgery ◽  
Fine Print

Object. The role of radiosurgery has become increasingly important in the treatment of intracranial lesions. In this study the authors evaluated the efficacy of the Novalis shaped beam radiosurgery system (dedicated linear accelerator) for various brain and spinal lesions. Methods. Between November 2000 and October 2003 the authors treated 356 cases of various intracranial and extracranial lesions with Novalis shaped beam radiosurgery. Of these 356 cases, 109 cases were followed for more than a 2-year period. Fifty patients underwent fractionated stereotactic radiosurgery. Twenty patients (40%) harbored benign tumors (two acoustic neuromas, seven meningiomas, five pituitary adenomas, four optic gliomas, and two craniopharyngiomas), 18 patients (36%) harbored malignant tumors (16 glioblastoma multiforme [GBM], and two metastases), and the others included five with brainstem gliomas, one chordoma, five gliomas, and one with an arteriovenous malformation (AVM). Eighteen of 20 patients with benign tumors had good tumor control. Of 59 patients treated with single-dose stereotactic radiosurgery, 24 had benign intracranial tumors (12 acoustic neuromas, 11 meningiomas, and one pituitary adenoma), 20 had malignant tumors (two GBMs and 18 metastases), and the others were eight AVMs, two glomus jugulare tumors, three lymphomas, one pineal tumor, and one spinal tumor. Conclusions. Stereotactic radiosurgery and fractionated stereotactic radiosurgery using the Novalis shaped beam radiosurgery system are effective and safe noninvasive treatment modalities for various intracranial and extracranial lesions.

scholarly journals Functional Regions of Human Telomerase Reverse Transcriptase and Human Telomerase RNA Required for Telomerase Activity and RNA-Protein Interactions

2001 ◽  
Vol 21 (5) ◽  
pp. 1888-1897 ◽  
Author(s):  
François Bachand ◽  
Chantal Autexier
Keyword(s):  
Reverse Transcriptase ◽  
Rna Binding ◽  
Telomerase Activity ◽  
Catalytic Subunit ◽  
Telomerase Rna ◽  
Dna Repeats ◽  
Human Telomerase Reverse Transcriptase ◽  
Template Sequence ◽  
Human Telomerase

ABSTRACT Telomerase is a specialized reverse transcriptase (RT) that is minimally composed of a protein catalytic subunit and an RNA component. The RNA subunit contains a short template sequence that directs the synthesis of DNA repeats at the ends of chromosomes. Human telomerase activity can be reconstituted in vitro by the expression of the human telomerase protein catalytic subunit (hTERT) in the presence of recombinant human telomerase RNA (hTR) in a rabbit reticulocyte lysate (RRL) system. We analyzed telomerase activity and binding of hTR to hTERT in RRL by expressing different hTERT and hTR variants. hTRs containing nucleotide substitutions that are predicted to disrupt base pairing in the P3 helix of the pseudoknot weakly reconstituted human telomerase activity yet retained their ability to bind hTERT. Our results also identified two distinct regions of hTR that can independently bind hTERT in vitro. Furthermore, sequences or structures between nucleotides 208 and 330 of hTR (which include the conserved CR4-CR5 domain) were found to be important for hTERT-hTR interactions and for telomerase activity reconstitution. Human TERT carboxy-terminal amino acid deletions extending to motif E or the deletion of the first 280 amino acids abolished human telomerase activity without affecting the ability of hTERT to associate with hTR, suggesting that the RT and RNA binding functions of hTERT are separable. These results indicate that the reconstitution of human telomerase activity in vitro requires regions of hTERT that (i) are distinct from the conserved RT motifs and (ii) bind nucleotides distal to the hTR template sequence.

Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth

2000 ◽  
Vol 92 (2) ◽  
pp. 306-314 ◽  
Author(s):  
Ian E. McCutcheon ◽  
Keith E. Friend ◽  
Tammy M. Gerdes ◽  
Bing-Mei Zhang ◽  
David M. Wildrick ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Cells ◽  
Malignant Tumors ◽  
Xenograft Model ◽  
Benign Tumors ◽  
Athymic Mice ◽  
Orthotopic Model ◽  
Content Type ◽  
Human Meningioma ◽  
Fine Print

Object. Although human meningioma cells have been heterotopically implanted in nude mice, introducing these cells into intracranial locations seems more likely to reproduce normal patterns of tumor growth. To provide an orthotopic xenograft model of meningioma, the authors implanted a controlled quantity of meningioma cells at subdural and intracerebral sites in athymic mice.Methods. Malignant (one tumor), atypical (two tumors), or benign (three tumors) meningiomas were placed into primary cell cultures. Cells (106/10 µl) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal white matter or subdural space of athymic mice. Survival curves were plotted for mice receiving tumor cells of each histological type and according to injection site. Other mice were killed at intervals and their heads were sectioned whole. Hematoxylin and eosin staining of these sections revealed the extent of tumor growth.Conclusions. The median length of survival for mice with malignant, atypical, or benign tumors was 19, 42, or longer than 84 days, respectively. Atypical and malignant tumors were invasive, but did not metastasize extracranially. Malignant tumors uniformly showed leptomeningeal dissemination and those implanted intracerebrally grew locally and spread noncontiguously to the ventricles, choroid plexus, convexities, and skull base. Tumors formed in only 50% of mice injected with benign meningioma cells, whereas injection of more aggressive cells was uniformly successful at tumor production. The three types of human meningiomas grown intracranially in athymic mice maintained their relative positions in the spectrum of malignancy. However, atypical meningiomas became more aggressive after xenografting and acquired malignant features, implying that there had been immune constraint in the original host. Tumor cells injected into brain parenchyma migrated to more optimal environments and grew best there. This model provides insights into the biology of meningiomas and may be useful for testing new therapies.

The extended frontal approach to tumors of the anterior, middle, and posterior skull base

1992 ◽  
Vol 76 (2) ◽  
pp. 198-206 ◽  
Author(s):  
Laligam N. Sekhar ◽  
Anil Nanda ◽  
Chandra N. Sen ◽  
Carl N. Snyderman ◽  
Ivo P. Janecka
Keyword(s):  
Skull Base ◽  
Malignant Tumors ◽  
Muscle Flap ◽  
Benign Tumors ◽  
Low Grade ◽  
En Bloc ◽  
Content Type ◽  
Temporalis Muscle Flap ◽  
Cerebrospinal Fluid Leaks ◽  
Fine Print

✓ The extended frontal approach is a modification of the transbasal approach of Derome. The addition of a bilateral orbitofrontal or orbitofrontoethmoidal osteotomy improves the exposure of midline lesions of the anterior, middle, and posterior skull base, while minimizing the need for frontal lobe retraction. The authors present a 5-year experience with 49 patients operated on via the extended frontal approach. In seven patients, the extended frontal approach was used alone; in the remaining 42, it was combined with other skull base approaches. Highly malignant tumors were removed en bloc, whereas benign tumors and low-grade malignancies were removed either en bloc or piecemeal. Reconstruction was usually performed using fascia lata, a pericranial flap, and/or autologous fat. A temporalis muscle flap or a distant microvascular free flap was required for some patients. One patient died 1 month postoperatively due to superior mesenteric artery thrombosis. Three patients had postoperative infections, two had cerebrospinal fluid leaks requiring reoperation, and four had brain contusions or hematomas. All but two patients recovered to their preoperative functional level. After an average follow-up period of 26 months (range 6 to 56 months), 64% of patients with benign lesions, 64% of patients with low-grade malignancies, and 44% of patients with high-grade lesions were alive with no evidence of disease.

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